I. General Principles
1. Why Is Follow-up Necessary? A Cardiologist’s Point of View
1.1 History and Future Tasks for Surgical Management of Congential Heart Disease (CHD) Patients
The first successful open heart surgery in Japan was reported in 1956 for tetralogy of Fallot (TOF) repair. Artificial heart lung machines and cardioplegic methods were introduced and modified in the 1970s and 1980s. Ultrafiltration and other devices followed in the 1980s and 1990s.2 With these strides, the outcome of open cardiac surgery markedly improved, even in newborns and infants. Use of autologous tissues was promoted eagerly in this country, particularly for reconstruction of the right ventricular outflow tract until the 2000s; it provided excellent results in the short and intermediate terms.3,4 The majority of children repaired at that time are now reaching adulthood, including those with complex CHD.5 Nowadays, the main topic in congenital heart surgery is better quality of life (QOL) in the longer term. The way ahead is not only hopeful for future circumstance as a whole, but encouraging for patients with severe CHD surviving longer and eventually requiring palliative and end-of-life care.6
1.2 Pathophysiology of Repaired CHD: Residual Lesions, Sequelae, and Complications
CHD patients are often classified according to their anatomical complexity, namely, simple, moderate, and complex (severe) as described in the Table 6.7
Table 6. Classification of Congenital Heart Disease According to Complexity
| Simple |
| Native disease |
| Isolated small ASD |
| Isolated small VSD |
| Isolated mild pulmonic stenosis |
| Repaired conditions |
| Previously ligated or occluded ductus arteriosus |
| Repaired secundum or sinus venosus ASD without significant residual shunt or chamber enlargement |
| Repaired VSD without significant residual shunt or chamber enlargement |
| Moderate |
| Aorto-left ventricular fistula |
| Anomalous pulmonary venous connection, partial or total |
| Anomalous coronary artery arising from the pulmonary artery |
| Anomalous aortic origin of a coronary artery from the opposite sinus |
| AVSD (partial or complete, including primum ASD) |
| Congenital aortic valve disease |
| Congenital mitral valve disease |
| Coarctation of the aorta (isolated) |
| Ebstein malformation |
| Infundibular right ventricular outflow tract obstruction |
| Unrepaired secundum ASD with right ventricular volume overload |
| Persistent patent ductus arteriosus with ventricular volume overload |
| Pulmonary valve regurgitation (moderate or greater) |
| Pulmonary valve stenosis (moderate or greater) |
| Peripheral pulmonary stenosis |
| Sinus of Valsalva aneurysm/sinus of Valsalva–ventricle fistula |
| Sinus venosus type ASD |
| Subvalvar aortic stenosis (excluding HCM) |
| Supravalvar aortic stenosis |
| Straddling atrioventricular valve |
| Repaired tetralogy of Fallot |
| VSD with associated abnormality and/or with ventricular volume overload |
| Severe/Complex |
| Cyanotic congenital heart defect (unrepaired or palliated, all forms) |
| Double-outlet right ventricle/double-outlet left ventricle |
| Eisenmenger syndrome |
| Fontan circulation |
| Interrupted aortic arch/coarctation complex |
| Mitral atresia, hypoplastic left heart syndrome |
Functionally single ventricle (including double inlet left ventricle, tricuspid atresia, any other anatomic abnormality with a
functionally single ventricle) |
| Pulmonary atresia with or without VSD |
| TGA (classical or d-TGA; ccTGA or l-TGA) |
| Truncus arteriosus |
Other malformations with abnormal atrioventricular and ventriculoarterial connections (i.e., crisscross heart, visceral
heterotaxy, ventricular inversion, etc.) |
ASD, atrial septal defect; AVSD, atrioventricular septal defect; cc, congenitally corrected; d-, dextro-loop (the aorta rightward to the pulmonary trunk); HCM, hypertrophic cardiomyopathy; l-, levo-loop (the aorta leftward to the pulmonary trunk); TGA, transposition of the great arteries; VSD, ventricular septal defect. (Modified from Stout KK, et al. 2019.7)
Even in simpler cases of adult CHD (ACHD), patients could be at high risk of cardiovascular morbidity because lifestyle-associated diseases are common.8 Patients undergoing TOF repair (i.e., CHD of a moderate degree) have significant cardiovascular problems.9 As for complex CHD, perioperative survival has dramatically improved for the Fontan type procedure, but its late mortality is still high.10 Further technical advances or technological devices may emerge in the near future.11
Cardiovascular problems after repair are summarized as follows: (1) residual lesions (pulmonary stenosis, ventricular septal defect, etc), (2) sequelae (pulmonary valve regurgitation in repaired TOF, conduit stenosis due to prosthesis–patient mismatch, etc), and (3) complications (arrhythmias, protein-losing enteropathy, etc).
These post-repaired pathophysiologies can trigger heart failure and/or arrhythmia(s), leading to unexpected hospitalization and even premature death under physical or psychological stress.
Regarding management of heart failure, established guidelines for nonACHD patients, although evidence-based, may not be applicable to ACHD patients. Most ACHD patients possess quite unique circulations such as that in repaired TOF or the Fontan circulation. Classification based on left ventricular ejection fraction would be insufficient and unsuitable for CHD. Although left ventricular dysfunction, whether systolic or diastolic, is of ultimate importance,12 the right heart is similarly diseased in this setting and even right heart failure kicks off the process of overall deterioration. Cardiac resynchronization therapy (CRT) has not been standardized in CHD patients with a single ventricular physiology or in those with systemic right ventricle (RV).13 Arrhythmia management needs catheter ablation techniques in adult cardiology despite experience being limited in the CHD field. Pacemaker implantation is similarly useful for conduction disorders and dissynchronized ventricular contraction, as well as implantable cardioverter defibrillators (ICD).14,15 When considering ventricular pacing in patients with single ventricular physiology or the systemic RV, ventricular pacing sites should be carefully chosen.13,16 Other than arrhythmia, pulmonary hypertension (PH) is an issue. The survival rate has drastically improved in patients with primary PH, but a management strategy for secondary PH in ACHD has not been established.17 Management strategy for aortopathy also remains uncharted in the ACHD population.18 Lifestyle-related diseases, such as metabolic disorders, are known as higher risks of death.19 Central nervous system-associated lesions or psychological disorders are emerging issues in terms of their effect on QOL.20,21
1.3 A Guide for Long-Term Follow-up of Patients With Repaired CHD
Follow-up of patients with repaired CHD is necesary for their mental and physical development. Initial surgical repair, however successful the procedure had been, does not necessarily guarantee optimal outcome in the long term. Prosthesis–patient mismatch is an example. Thus, regular follow-up is mandatory. Patients need cooperative support from their family or guardian throughout their childhood; it is essential to communicate with them in a comprehensive way. Physical exercise should be appropriate and regular for patients to stay physically fit and psychologically healthy, except for those with unstable hemodynamics and/or at risk of dangerous arrhythmias. Physicians should consider the concept of “transition care” of adolescents. Towards adulthood, the follow-up strategy should include understanding their own disease, how to self-manage their condition, and how to avoid lifestyle-related disease. Teams specialized in ACHD are indispensable for better long-term outcomes in these unique patients.22
2. Why Is Follow-up Necessary? A Cardiac Surgeon’s Point of View
Most cases of congenital heart disease (CHD) require surgery, either reparative or palliative. Despite considerable strides in technology, prostheses are not perfectly durable. The materials, when deteriorated significantly, can become a hemodynamic impediment, eventually leading to surgical or interventional revision. For successful reoperations, knowledge regarding the previous procedures is helpful. Adult patients with CHD might have survived with some old-fashioned repairs. Follow-up is essential for the optimal therapeutic strategy going forward.
2.1 Durability of Prosthetic Materials
The quality of artificial materials has developed markedly, but they are still obviously foreign substances in the patient’s body, inevitably possessing drawbacks. They are susceptible to infection, degenerate/calcify in due course, and have no potential for growth. These are the essential elements that will determine subsequent reoperation.23
2.1.1 Surgical Patches
Surgical patches are standard use when closing a septal defect or enlarging a stenotic channel. Autologous pericardium is a popular material, either fresh or glutaraldehyde-treated. The latter will calcify in the longer term and the former is not applicable as a patch facing a high-pressured chamber. Artificial materials are usually heterologous pericardium or synthetic fibers (polyester, polytetrafluoroethylene (PTFE), etc.).
Autologous collagen tissues are derived from disseminated living cells. Other materials are under development by means of tissue engineering.
2.1.2 Prosthetic Valves
An artificial valve is meticulously chosen in terms of its merits and downside (Table 7). Prosthetic dysfunction, particularly valve stenosis, occurs because of pannus formation, thrombosis, or prosthesis–patient mismatch.24–28
Table 7. Artificial Valves in Congenital Heart Disease
| Bioprosthetic valves |
| Bioprosthetic valves degenerates rather rapidly in children, young adults, and pregnant females |
| - Porcine aortic valve (glutaraldehyde-treated) |
| - Bovine pericardial leaflets |
| Calcification-resistant treatment |
| Device in stent-fixation |
| Stentless valve |
| - Valve for transcatheter delivery |
| - Patch with a monocusp |
| Autologous pericardium |
| Heterologous pericardium |
| Mechanical valves |
| Bi-leaflet architecture |
| Management for anticoagulation is a vital issue |
| Expanded polytetrafluoroethylene (PTFE) valves |
Use of a trifoliate valved PTFE graft is popular for reconstruction of the right ventricular outflow tract (RVOT),
exclusively in Japan |
| A patch with a monocusp also utilized for reconstruction of the RVOT |
| Homograft (aortic or pulmonary, cryo-preserved) |
| Used for reconstruction of the RVOT, for aortic root replacement, and for treatment of severe infective endocarditis |
| Autograft (pulmonary) |
| Ross procedure, Ross-Konno procedure |
Aortic valve replacement (AVR) in small patients often requires enlargement of the aortic annulus. Use of a pulmonary autograft is an attractive procedure for AVR (i.e., the Ross procedure) in small children or female patients who intend to have their own babies, although it could turn a solitary valve issue into a problem of dual structures.29–36 Reconstruction of the aortic valve leaflets (i.e., the Ozaki procedure) sounds favorable in the shorter term, but results in the longer term need to be clarified in the pediatric population.37–41
a) Right Heart
The tricuspid or pulmonary valve often requires surgery in CHD (Table 8).42 A bioprosthesis is a common choice for right heart procedures, but on rare occasions, a mechanical valve is used with intense management against thrombosis.43–49 Use of a homograft or a conduit containing a hand-made PTFE valve is on the list for pulmonary valve replacement.50–54
Table 8. Replacement of the Right Heart Valves in Congenital Heart Disease
| Pulmonary valve replacement |
| Pulmonary regurgitation |
| - Repaired tetralogy of Fallot |
| - Repaired congenital pulmonary stenosis |
| External conduit failure (after the Rastelli procedure) |
| - Repaired tetralogy of Fallot with pulmonary atresia |
| - Repaired truncus arteriosus |
| - Repaired transposition of great arteries (type 3) |
| Pulmonary arterial revision (after the Ross procedure) |
| Infective endocarditis |
| Tricuspid valve replacement |
| Congenital tricuspid disease |
| - Ebstein malformation |
| - Tricuspid valve dysplasia |
| Secondary tricuspid regurgitation |
| - Previous intraventricular maneuvers through the tricuspid orifice |
| Infective endocarditis |
b) Left Heart
Table 9 shows replacement using an artificial valve for the left heart system.
Table 9. Replacement of the Left Heart Valves in Congenital Heart Disease
| Congenital aortic valve disease |
| - Ross procedure, Ross-Konno procedure |
| - Aortic valve replacement |
| Without annular enlargement |
| With annular enlargement |
| Konno procedure |
| Manouguian method |
| Nick’s method |
| Congenital mitral valve disease |
| Atrioventricular septal defect |
| - Regurgitation through the left atrioventricular valve |
| Systemic tricuspid valve regurgitation |
| - Congenitally corrected transposition of the great arteries |
| - Transposition of the great arteries repaired by intra-atrial redirection of blood |
| Systemic atrioventricular valve regurgitation (univentricular physiology) |
| - Common atrioventricular valve |
| - Tricuspid valve |
2.1.3 Tube Grafts
A synthetic graft with a large caliber is used for the aorta or the pulmonary trunk, whereas a small-caliber (mainly PTFE) tube graft is used for construction of a systemic-to-pulmonary shunt or other small pathways. The PTFE size is indicated by the internal diameter nowadays.55–57
Neointimal proliferation is frequent in tube grafts. A conduit made of the bovine jugular vein (Contegra) often forms a pseudo-aneurysm at the anastomosis.58–62 Tissue engineering, including iPS (induced pluripotent stem cells) technology, is endeavoring to achieve an ideal product for the future.
2.2 Developments in Surgical Procedures
Technological advances have also occurred in cardiopulmonary bypass equipment. Together with developed cardioplegic techniques, long and complicated surgery has become feasible in the CHD field. Furthermore, surgical skills have become sophisticated. Primary anatomical repair has been promoted in small infants in some malformations. A staged approach is sensibly established in others. Tremendous variations in strategies and actual methods require us to develop precise understanding and deep insight for the optimal management of each patient.
2.2.1 Biventricular Repair
Japanese surgeons have been keen to minimize postoperative pulmonary regurgitation after repair of tetralogy of Fallot, aiming for preserved function of the right ventricle.63–67
Anatomical repair is standard, when feasible, for complete transposition translocating the coronary arteries.68–80 Radical repair is also used for congenitally corrected transposition of the great arteries.81–100 In these malformations, conventional repair in which the circulation was functionally repaired placing the morphologically right ventricle as a systemic chamber used to be the only choice.
The atrioventricular valves are repaired, where possible, particularly in children and adolescents. The so-called cone procedure was invented for Ebstein malformation.101–103 The Ross procedure and its variant are appealing for use in children and females of reproductive age.31,104–114
2.2.2 Reconstruction of the Right Ventricular Outflow Tract
Use of a valved PTFE graft is popular exclusively in Japan. In other Western countries, manufactured products are preferred for standardized quality. An alternative is using a homograft, which is not necessarily superior to synthetic grafts; infection is relatively common on implanted tissue. Transcatheter pulmonary valve replacement is to be promoted still further, which will affect the choice of surgical conduit (type and size) thereafter.
The right ventricular outflow tract was enthusiastically reconstructed without use of an external conduit in Japan.54,63,64,115 This method has several technical variants: direct anastomosis between the right ventricle and the pulmonary artery (the Barbero-Marcial method and the Lecompte maneuver) or interposition of an autologous tissue flap.116 The characteristic orientation of the structures must be clarified prior to reoperation.
2.2.3 Univentricular Repair
The original Fontan procedure has been modified historically, transformed from atriopulmonary connection to a lateral tunnel or extracardiac total cavopulmonary connection.117–120 The Fontan circulation is unphysiological by any means with persistently high central venous pressure (CVP). Congestion of the tissues and bodily organs is the rule, affecting their function.10,121–125 On top of consequent functional issues (Fontan-associated liver disease (FALD), protein-losing enteropathy, arrhythmias, etc.), surgical interventions may become necessary for regurgitation across the atrioventricular/aortic valve and for stenosis/thrombosis of the Fontan pathway (from the vena cava to the pulmonary artery).126–130 These are mechanical factors that elevate CVP.
A one-and-a half ventricular repair provides an intermediate circulation, forming a spectrum of hemodynamics between biventricular and the Fontan physiology. Some patients will be eventually converted to the Fontan circulation.
2.2.4 Palliative Procedures
Patients remain palliated when the aforementioned definitive procedures are not feasible. Pulmonary hypertension and long-standing cyanosis should be monitored carefully because they lead to inefficient hemodynamics and malfunctioning organs.
The pulmonary artery can become significantly distorted or aneurysmal long after banding of the pulmonary trunk. A systemic-to-pulmonary shunt may be obstructed or even occluded. The Glenn circulation can promote pulmonary arteriovenous fistula. Systemic-to-pulmonary collaterals grow because of prolonged cyanosis; they are a cause of hemoptysis.
Surgical implantation of a pacemaker would be necessary, by placing epicardial leads, when a transvenous approach turns out to be less than ideal. Surgical standby is recommended, when a transvenous lead has to be extracted.
3. Evaluation and Management for Re-Intervention After Definitive Repair
3.1 Electrocardiogram-Related Examination
3.1.1 Resting Electrocardiogram
The ECG at rest gives information regarding abnormal rhythm, cardiac overload, and orientation of the conduction system.
The earliest activation of atrial rhythm is estimated from P wave morphology. The P wave amplitude increases with atrial overload, and decreases with the progression of atrial remodeling.131 P wave duration correlates with right atrial dimension in Fontan patients.132
QRS duration is known to be a risk factor for ventricular arrhythmias and sudden cardiac death in congenital heart disease (CHD) patients such as those with repaired tetralogy of Fallot (TOF).133–137 In patients with the Fontan circulation, QRS duration corelates with ventricular volume, aerobic capacity and hemodynamic deterioration during tachycardia.138–140 Fractionated QRS complex, which is defined as the presence >2 notches on the R/S wave in >2 contiguous leads, is a marker of poor prognosis and a risk of sudden death not only in the general adult population, but also in CHD patients.134,137,141–143
Resting ECGs are recommended for the patients with moderate or complex CHD, at every outpatient clinic or once every 3–6 months.
3.1.2 Ambulatory Holter Monitoring
Indications for ambulatory Holter monitoring include clinical evaluation of arrhythmias, measurement of cardiac autonomic nervous activities (heart rate turbulence), assessment of inhomogeneous repolarization (QT dynamics, T wave alternans), and evaluation of unexplained syncope, dizziness, palpitation or chest pain.144 When 24-hour Holter monitoring does not establish a diagnosis, an event monitor or a loop recorder (nonimplantable type) is useful and should be considered; they can record arrhythmic circumstances over a long period.
How efficient ambulatory Holter monitoring is as a predictor of sudden cardiac death in CHD patients remains contentious.133,145 Measurement of autonomic nervous activity has not proven to be useful as a predictor of sudden cardiac death. There is a substantial discrepancy between hemodynamic conditions and activity of the autonomic nervous system. This is because many postoperative patients with CHD have their heart partly denervated and their lungs restricted due to multiple thoracic surgeries.146
3.1.3 Exercise Stress Electrocardiogram
The exercise stress test aims to evaluate arrhythmias, ischemia, therapeutic effect and pacemaker status. Heart rate, arrhythmias, conduction abnormalities, ST change and QT morphologies are examined in this test. Heart rate dynamics during and after exercise reflect sinus nodal function in addition to activity of the cardiac autonomic nerves, and can reveal concealed sinus nodal dysfunction.147,148
3.1.4 Signal-Averaged Electrocardiogram (SAE)
The SAE is an examination in which a large number of electrical signals are averaged to weigh low-amplitude activity at the end of the QRS complex. This activity reflects depolarization of ventricular regions with a slow conduction (late potential). The recorded segment, therefore, indicates a substrate of ventricular tachyarrhythmia, which is a predictor of sudden cardiac death.149 Such late potentials, even if detected, would be less indicative of significant problems in patients with bundle branch block. Bundle branch block is common in CHD. The SAE is, therefore, useful only in a selected group of patients with CHD.149,150
3.1.5 Implantable Cardiac Monitor (ICM)
ICMs are covered by national medical insurance in Japan for unexplained syncope and for the detection of atrial fibrillation in patients diagnosed with cryptogenic stroke. In the JCS/JHRS 2019 guideline on nonpharmacotherapy of cardiac arrhythmias,151 ICM is recommended for patients with recurrent, infrequent, or unexplained syncope, and for those having syncope with high-risk factors suggesting a cardiogenic cause but without an identified cause or therapy for syncope after several evaluations (Class I, Evidence B). The ICM has been adapted for the diagnosis of syncope and detection of arrhythmias in CHD.152–154 Indications for ICM in CHD patients follow the above-mentioned guideline.151
3.2 Echocardiography
Diagnostic imaging modalities are essential tools for morphological and functional assessments of the heart in adult congenital heart disease (ACHD) patients. Echocardiography remains the first-line examination, being capable of advanced evaluation for clarifying pathophysiology, and also guiding catheter interventions.155–160 It is simple, portable, noninvasive, and repeatable; and universally available at outpatient clinics in Japan.
Echocardiography provides comprehensive information, but an obvious limitation is that the quality of the investigation is highly operator-dependent. ACHD requires special expertise. Unusual geometry and regional incoordination of the heart make assessment of ventricular volume and function rather complicated,161 particularly in patients with a morphologically right ventricle as a systemic chamber or in those with univentricular physiology. On such occasions, a multimodal approach using cardiac magnetic resonance, computed tomography, and catheter examination is recommended to precisely understand the morphology, function, and pathophysiology (Table 10).162,163
Table 10. Comparison of Imaging Modalities
| |
Echocardiography |
MRI |
CT |
Scintigraphy |
| Availability |
++++ |
++ |
++ |
+++ |
| Portability |
++++ |
− |
− |
− |
| Radiation exposure |
− |
− |
++++ |
++++ |
| Safety with pacers |
++++ |
+ |
+++ |
+++ |
| Metal artifact |
+ |
+++ |
+ |
− |
| Spatial resolution (mm) |
<1 |
<1–2 |
<1 |
5–10 |
| Time resolution (ms) |
20 |
30 |
75–175 |
− |
| RV volume/function |
++ |
++++ |
+++ |
+ |
| RV pressure |
+++ |
+ |
+ |
− |
| Regurgitation severity |
++/+++ |
+++ |
− |
− |
| LV volume/function |
+++ |
++++ |
+++ |
++ |
| Myocardial viability |
+ |
++++ |
+ |
+++ |
| Coronary artery |
++ |
+++ |
++++ |
− |
| Residual shunt |
+++ |
+++ |
+ |
− |
CT, computed tomography; LV, left ventricle; MRI, magnetic resonance imaging; RV, right ventricle. (Modified from Valente AM, et al. 2014162 and Cohen MS, et al. 2016.163)
Recent advances in 3D echocardiography have enabled physicians to evaluate chamber volumes more accurately. Doppler tissue imaging and speckle tracking imaging also provide key information on cardiac mechanics, which make it possible to detect cardiac dysfunction early. These advanced techniques give additional insights, over conventional variables, when discussing interventions for ACHD patients.
Transesophageal echocardiography (TEE) has an advantage in certain circumstances in adults, because of its excellent image quality. It is well-suited for cardiac monitoring during procedures such as closure of atrial septal defect164 (Table 11), although the procedure requires sedation or general anesthesia.165 Intracardiac echocardiography can be used as an alternative, but at greater expense. TEE is definitely contraindicated in those with an aortic vascular ring.166,167
Table 11. Recommended Indications for TTE/TEE in ACHD
| Recommendation |
COR |
LOE |
| Pre-/intra-operative TEE is recommended to guide surgical/catheter repair of ASD164,165 |
I |
B |
| TEE is recommended to evaluate for coexistence of PAPVC in ASD cases166 |
I |
B |
Patients with ACHD should undergo TTE for initial assessment, with serial assessment
based on anatomic and physiological severity and clinical status |
I |
C |
ACHD, adult congenital heart disease; ASD, atrial septal defect; COR, class of recommendation; LOE, level of evidence; PAPVC, partial anomalous pulmonary venous connection; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography.
3.3 CT/MRI
Computed tomography (CT) and magnetic resonance imaging (MRI) are useful in adult congenital heart disease (ACHD) patients.
3.3.1 CT
CT is advantageous for high spatial resolution (∼0.5 mm) and short scanning duration. On the other hand, contrast medium must be given carefully in patients with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2.168 CT scanning is highly recommended for the following morphologies or conditions: (1) coronary arterial impediments, and after the arterial switch or Ross procedure; (2) assessment of the right ventricular (RV) outflow tract prior to surgical/percutaneous pulmonary valve replacement; (3) surgical evaluation before reopening the chest, such as adhesion between the heart and the sternum or calcified tissues (previous conduit, surgical membrane, etc.), (4) thrombus in the atria, the Fontan route, or a pulmonary stump if any.160,169
3.3.2 MRI
The advantages of MRI in CHD are as follow: temporal (time) resolution and signal contrast compared with noncontrast CT scan, with no radiation exposure. Non-contrast MRI is good for quantitative assessment of ventricular geometry, contraction, and leakage through the valves. Myocardial ischemia, fibrosis and tissue infiltration are also assessed.
The AHA/ACC ACHD guideline in 2018 strongly recommended assessing RV size and function using MRI.7 MRI screening is also useful in complex CHD. Late gadolinium enhancement detects focal myocardial fibrosis, but this does not necessarily predict cardiac events in the CHD cohort. Nephrogenic systemic fibrosis is a serious complication after contrast MRI, so gadolinium injection should be avoided in patients with eGFR <30 mL/min/1.73 m2.170
MRI scan is contra-indicated in those with a pacemaker of a nonMR compatible type or an implantable cardioverter defibrillator.
3.4 Cardiac Catheterization
Noninvasive examinations such as echocardiography, cardiac CT and MRI have made remarkable strides, but cardiac catheterization remains essential in patients with congenital heart disease (CHD). Central venous pressure (CVP) can be directly measured only by the transcatheter approach; CVP is known to be a primary prognostic marker for patients in the longer term after the Fontan type procedure.171 Not only diagnostic catheterization but also concomitant transcatheter interventions are becoming increasingly important.
3.4.1 Indication of Cardiac Catheterization
Catheterization is an invasive examination with a risk of complications, so its indication should be rigorous. Most CHDs can be morphologically diagnosed by noninvasive examinations. The purpose of cardiac catheterization, therefore, is usually focused on hemodynamic evaluation and simultaneous interventional procedures. Whenever properly indicated, it should be done without hesitation following noninvasive tests.
3.4.2 Approach
The patient’s age affects the choice of puncture sites. The so-called femoral approach is always the case in children, whereas other approaches can be utilized in adults. Left heart catheterization can be done through the radial or brachial artery, and right heart catheterization through the internal jugular vein or brachial vein. Any approach requires careful planning in terms of the anatomy of the vessels and heart. Venous or arterial pathways and intracardiac channels could have been modified greatly by previous cardiovascular surgery. It is essential to check surgical records and catheterization reports of previous procedures.
3.4.3 Right Heart Catheterization
Right heart catheterization is crucial for assessing hemodynamics in CHD. Pulmonary hypertension is a frequent comorbidity,172 and cardiac catheterization is fundamental for its evaluation.173
3.4.4 Left Heart Catheterization and Coronary Angiography
Echocardiography, CT, and MRI are often substituted for left ventriculography, aortography, or coronary angiography. CT precisely illustrates abnormal origins and courses of the coronary arteries in many cases, which is why coronary angiography is not recommended as a routine examination (Class III). In some patients, nonetheless, coronary angiography is quite informative beyond CT resolution; for example, anastomotic stenosis at the coronary arterial origin would be better demonstrated by catheter angiography after the arterial switch procedure.174
3.4.5 Endomyocardial Biopsy
Endomyocardial biopsy is rarely required in patients with postoperative CHD.
3.4.6 Catheter Intervention
Transcatheter closure of atrial septal defect or patent ductus arteriosus is carried out routinely in the cardiac catheterization room, as is percutaneous pulmonary angioplasty. Interventional closure of ventricular septal defect needs more evidence before becoming established in Japan. Transcatheter pulmonary valve replacement will be introduced in the near future.
Electrophysiological study and catheter ablation are common practices for arrhythmias in the CHD field. Recent advances in technology and devices, such as 3D mapping systems, have contributed to notable results in anti-arrythmic treatments in patients with repaired CHD.175
3.5 Biomarkers
Heart failure (HF) occurs against a variety of pathological backgrounds in patients with congenital heart disease (CHD). Single ventricular physiology is an example. Other causes include the morphologically right ventricle (RV) as a systemic chamber, pulmonary hypertension and left ventricular function affected by right ventricular enlargement/dysfunction. The first step in correct diagnosis is to clarify the exact pathophysiology. It is also important to evaluate the current cardiac status of the patient, implement medical treatments, and predict a probable prognosis. In many cases nowadays, quantitative data are provided by CT, MRI, and cardiac catheterization, and patients are eventually referred for medical management. Biomarkers have an equally important role.176 Because the pathophysiology is diverse in cases of HF in patients with CHD, a combination of biomarkers should be measured when determining the characteristics of the heart condition (Table 12).
Table 12. Biomarkers for Heart Failure of Atrioventricular Septal Defect (ACHD)
| Natriuretic peptides |
| Brain natriuretic peptide (BNP) |
| N terminal-pro Brain natriuretic peptide (NT-proBNP) |
| Atrial natriuretic peptide (ANP) |
| Renin-Angiotensin system and Catecholamines |
| Renin |
| Angiotensin I |
| Angiotensin II |
| Norepinephrine |
| Cytokines |
| Interleukin-6 (IL6) |
| Soluble tumor necrosis factor-α (sTNF-α) |
| Myocardial injury markers |
| High sensitive toroponin T (hs-TnT) |
| Toroponin I |
| Others |
| Endothelin-1 (ET-1) |
| Hepatocyte growth factor (HGF) |
| Angiopoietin-2 (Ang-2) |
| Growth differentiation factor 15 (GDF15) |
| Galectin-3 |
3.5.1 Biomarkers Indicating HF in Biventricular Physiology (Table 12)
a) HF of the Systemic RV
This category includes congenitally corrected transposition of the great arteries (nonsurgical cases or after functional repair) and complete transposition of the great arteries (after intra-atrial redirection of blood). In these cases, brain (B-type) natriuretic peptide (BNP) and NT-proBNP are associated with functional class, RV contractility and peak oxygen uptake.177–182 There is also a report mentioning that the level of atrial natriuretic peptide (ANP) is relevant to the clinical stage of HF.183 BNP ≥36 pg/dL and ANP ≥75 pg/dL is useful for predicting right (systemic) ventricular dysfunction.177,183 Quality of life was not associated with these markers, so clinical use may be limited in that regard.184 Some reports describe the concentrations of renin–angiotensin system (RAS) hormone and catecholamine as related to RV contractility, but only weakly correlated with the clinical stage of HF.185–187
No biomarker that predominantly reflects the function of the pulmonary ventricle (the morphologically left ventricle) of these complex conditions has been finalized.
b) HF of the Pulmonary RV
This category includes a group of patients with volume or pressure overload to the RV, such as atrial septal defect (ASD), repaired tetralogy of Fallot (TOF), pulmonary arterial hypertension (PAH), and pulmonary stenosis. In these patients, BNP is generally elevated.188–192 It has been reported that the norepinephrine concentration significantly correlates with functional class and peak oxygen uptake, but not with other catecholamines or RAS hormone.189
BNP increase reflects RV enlargement, which is useful for management of ASD and repaired TOF.193,194 BNP decreases in proportion to the improvement in RV volume when the ASD is closed or a competent pulmonary valve is placed.195 BNP rises when RV function is deteriorating in PAH; the mortality rate increases markedly when BNP >150 pg/mL. This has further prognostic value when combined with the norepinephrine concentration.196
A systematic review also confirmed that BNP and NT-proBNP are useful when predicting the prognosis of CHD with PAH.192 The BNP level decreases on pulmonary vasodilators and nitric oxide nhalation.197 It should be noted that obesity and renal dysfunction, relatively common in adult CHD patients, may also affect the BNP level.198,199
During the course of pregnancy in adult CHD patients, the serum BNP and NT-proBNP levels do fluctuate, probably reflecting changes in volume overload to the atria and the ventricles. Its significance has yet to be fully clarified.
A recent report described high-sensitivity troponin T, soluble suppression of tumorgenesis-2, homoarginine, and B7-H3 are useful markers for predicting the prognosis of HF.200–204
3.5.2 Biomarkers for HF in the Fontan Circulation
It remains unclear how clinically significant biomarkers are in patients undergoing the Fontan type procedure. For biventricular physiology, prognostic predictors can be interleukin-6 (IL6), norepinephrine, high-sensitivity C-reactive protein (hs-CRP), BNP, and endothelin-1 (ET-1). In single ventricular physiology, it has been reported that only BNP and ET-1 predominantly have prognostic value.205
The feature of the main ventricular chamber, either morphologically left or right, may affect the behavior of biomarkers; analagous to the systemic ventricular morphology in biventricular physiology. The type of Fontan pathway, either atriopulmonary connection (APC) or total cavopulmonary connection (TCPC), is also influential. BNP is usually lower in TCPC. BNP is released from the atrial myocardium, so its serum level is generally higher in APC patients who have an enlarged right atrium. Even without marked enlargement, the BNP level is elevated (≈50–70 pg/mL), to say nothing of severe dilatation (>200 pg/mL).206 According to a previous report, the BNP value can predict prognosis if combined with the norepinephrine level.206 In another study of TCPC, serum BNP correlated with ventricular factors (volume, end-diastolic pressure, cardiac index), but was not a prognostic predictor.207
Norepinephrine and angiotensin II have been inversely correlated with ventricular contractility, as has ANP with the cardiac index.206 In patients with single ventricular physiology with a morphologically left chamber, prognostic predictors include BNP, norepinephrine, hs-CRP, soluble tumor necrosis factor (sTNF)-RI, IL-6, and ET-1. As for those with a morphologically right chamber, no biomarker has been attributed to this clinical aspect.205
Any of the conventional biomarkers would not figure as a criterion for HF by itself in the clinical setting. The cohort of patients is heterogeneous. Brand-new substances have been reported more recently, such as galectin-3 and growth differentiation factor-15, which may have promise as prognostic predictors. A large cohort study addressing these is anticipated in the near future.208,209
3.5.3 Biomarkers for HF in Patients With Unrepaired Circulation or Residual Cyanosis
This group comprises patients with single ventricular physiology who have not achieved the Fontan circulation (unoperated, shunt palliated, pulmonary artery banded, and remaining with the Glenn physiology), as well as those with Eisenmenger syndrome (ES). It is debatable whether cyanosis affects the BNP and NT-proBNP levels. A report found no correlation between hypoxemia and serum values in a pediatric population.210 Another study in adult patients described that serum levels were higher in those with hypoxemia than in those without, regardless of body fluid status.211
In patients with single ventricular physiology of a nonFontan circulation, ventricular end-diastolic pressure increases with age. Change in BNP reflects this phenomenon. For example, when an end-diastolic pressure of <12 mmHg, the average BNP level was 108 pg/mL; when ≥12 mmHg, the value increased to 234 pg/mL.212 Absolute values do not mean anything. The optimal judgement should be based on multifactorial characteristics of each individual patient. In particular, consecutive changes are suggestive of worsening or improvement of the patient’s condition.
In ES, the BNP level increases with age, but does not correlate with functional class or 6-minute walking distance.213 These are obviously of practical use as prognostic predictors. It is known that mortality and morbidity increase beyond serum BNP of 50 pg/mL.214 Prognosis is bleak when the value is rising consecutively.213 There are also reports stating that hs-TnT is a predictive marker for death in ES.215
4. Pathophysiology
4.1 Heart Failure
4.1.1 Pathology
4.1.1.1 Causes and Major Pathologies
Postoperative management for heart failure (HF) is clinically crucial in terms of prognosis and quality of life. Survival rate is nowadays as high as 95% after surgery for congenital heart disease (CHD). HF is generally caused by myocardial disorder, loading issues (hemodynamic), or rhythm disturbance. These abnormalities, either alone or in combination, suppress the pump function (systolic and diastolic) of the heart, resulting in congestion of the lungs and systemic organs. Hypoperfusion of the tissues becomes obvious, and thereby symptoms of HF appear such as dyspnea, edema, fatigability, and decreased exercise tolerance.
The postoperative status is roughly classified into 3 patterns: (1) almost normal structure and function of the heart, as represented by a repaired ventricular or atrial septal defect, (2) inevitable residual lesions after surgical repair because of intrinsic problems of the malformed heart, and (3) essentially abnormal circulation that functionally maintains blood supply to the body just sufficient to survive. HF is a concern mainly in patterns (2) and (3) in the longer term (Table 13). In patients with tetralogy of Fallot or its relatives, right HF progresses because of volume or pressure overload to the right ventricle (RV). Pulmonary valve insufficiency is almost always the case long after enlargement of the pulmonary annulus using a transannular patch or after reconstruction of the right ventricular outflow tract using an external conduit. Residual pulmonary stenosis at any level naturally imposes pressure overload to the RV. In some patients with Ebstein malformation or atrioventricular septal defect, HF progresses due to ventricular volume overload caused by residual/recurrent regurgitation across the atrioventricular valve. In those with a systemic pumping chamber of the morphologically RV, regurgitation across the morphologically tricuspid valve acts as functional mitral insufficiency. The systemic RV will likely malfunction with age; the chamber hardly tolerates high pressure of the systemic circulation for long. The Fontan circulation is another form of right HF; no pumping chamber is present for the pulmonary circulation. On the other hand, a solitary pumping chamber for the systemic circulation does not respond well to raised afterload.216 All these loading issues need to be recognized precisely when discussing progressive HF in the longer term after surgery for CHD.
Table 13. Pathology and Causes of HF After Surgery for Congenital Heart Disease
| |
Lesion |
Primary cause of HF |
Postoperative
residual disease
present |
Tetralogy of Fallot, disorders requiring RV outflow
tract repair or reconstruction |
Pulmonary artery stenosis,
pulmonic regurgitation
Aortic sclerosis |
RV volume/pressure overload
LV pressure/volume overload |
| Ebstein malformation, AV septal defect |
AV valve regurgitation |
Ventricular volume overload |
| Aortic coarctation and interruption |
Residual aortic stenosis
Aortic sclerosis |
Ventricular pressure overload |
| Left-to-right shunts |
Pulmonary hypertension |
RV pressure overload |
Residual atypical
circulation |
Univentricular circulation |
Fontan circulation |
|
Atrial switch operation for complete transposition of
the great arteries
Corrected transposition of the great arteries |
Systemic RV |
RV pressure overload |
Ebstein malformation, pure pulmonary atresia
Hypoplastic heart syndrome |
Diastolic failure
(Systolic failure) |
Ventricular dysfunction |
AV, atrioventricular; HF, heart failure; LV, left ventricular; RV, right ventricular.
These postoperatively troublesome hemodynamic issues are based on intrinsic functional disorders of the cardiovascular system. Abnormal preoperative physiology persisting is also modifying the circumstances. Surgical interventions induce further ischemic and reperfusion injury. These factors introduce direct insults to the ventricle itself, eventually exacerbating HF. Aortic coarctation and interruption of the aortic arch are examples often mentioned. The aortic media is abnormal, and the aortic wall is sclerotic. Even after relieving the morphological obstruction, the aortic wall remains stiff, which means that ventricular afterload is not normalized after ‘repair’.217 Other examples are Ebstein malformation, critical pulmonary stenosis, and pulmonary atresia with intact ventricular septum (pure pulmonary atresia). These diseases involve an intrinsically malformed RV. The diastolic function has been, is, and would be grossly impaired. The right ventricular myocardium is not necessarily remodeled towards normal performance after successful repair.
Loading abnormalities and myocardial damage relay, in turn, stress responses to HF; neurohumoral factors are activated and the oxidative process increases. Vascular endothelia behave abnormally, and the levels of inflammatory cytokines rise, causing injury to ventricular myocytes.146,218,219 Neurohumoral factors are known to play a central role in this cascade for HF in adult cardiology. It remains unclear, in the CHD field, how and to what extent these pathways are influential in promoting HF.220
Hemodynamic and myocardial impediments also produce dyssynchronized ventricular contraction, either electrically or mechanically. This is a phenomenon noted in nonCHD HF, and surely applies to CHD.218,221 The pathological paradigm of HF process after surgery for CHD seems similar to that observed in nonCHD HF, such as ischemic heart diseases in adults. Persistent loading abnormalities are probably more dominant in CHD though.
HF is usually progressive. Guidelines for diagnosis and treatment of acute and chronic HF in adults set the problem into 4 stages: Stage A, the high-risk stage without organic heart disease (pre-HF); Stage B, the stage with organic heart disease but without symptoms of HF (juxta-HF); Stage C, the stage with organic heart disease and symptoms of HF; and Stage D, the stage with refractory HF. This grading aims at optimal timing of therapeutic interventions, which are recommended at an earlier stage in patients at a high risk of progressive HF (according to evidence), even if they are asymptomatic.222 In view of the aforementioned pathological backgrounds, any patient with CHD is classified as Stage B or higher, suggesting that meticulous monitoring is important and that timely intervention is to be arranged as necessary.
4.1.1.2 Types of HF
a) Ventricular Morphology
HF is classified as right or left according to the failing circulation, either pulmonary or systemic. These 2 types differ from the viewpoint of pathology and symptoms. Right ventricular failure is more common in repaired CHD than in nonCHD. Many patients with CHD have right ventricular lesions (Table 13). It is important to recognize that right ventricular failure affects the systolic as well as diastolic function of the left ventricle, and vice versa, because of ventricular interaction.223 They are a counterpart in biventricular physiology. As for the Fontan circulation, which is a unique pathological condition in CHD, ventricular failure represents a phenotype of bilateral HF.
b) Systolic and Diastolic Dysfunction
From another viewpoint, HF is classified into 2 categories: HF with reduced ejection fraction (HFrEF) and that with preserved EF (HFpEF), the latter is defined as a state in which HF symptoms appear with preserved EF and impaired diastolic function. ‘Preserved EF’ is a qualitative phrase; it does not define the level of ‘preservation’. Both the HFrEF and HFpEF categories could contain patients with ‘moderately’ reduced EF. In recent guidelines for the diagnosis and treatment of acute and chronic HF in adults, HF with moderately reduced EF (HFmrEF) has been added under its own heading.224 Classifying in this way has clinical significance, because underlying mechanisms, pathological processes, and response to treatments differ greatly among the subgroups.
HFrEF is generally the case after surgery for CHD presenting ventricular dilatation and reduced EF. Recent reports indicate that HFpEF is also found in those with CHD.12,225,226 HFpEF in CHD is on either the right or the left side. Left HFpEF (1) occurs mainly in young children approximately 1 year of age, (2) is frequent in specific diseases, such as tetralogy of Fallot, aortic coarctation/interruption, and totally anomalous pulmonary venous connection, (3) shows concentric hypertrophy and diastolic dysfunction without ventricular dilatation, (4) accompanying hypertension, and (5) imbalance of the activation of the renin-angiotensin-aldosterone and natriuretic peptide systems.225 When evaluating ventricular pressure and volume in detail, the chambers prove to be stiff in the systolic and diastolic phases. At the same time, the arteries are also stiff; arterial elastance is elevated at rest,226 and functional reserve is decreased for both systolic and diastolic flow. These changes are associated with an imbalance in oxygen supply and demand for coronary perfusion.226
Left HFpEF and pulmonary hypertension can induce right heart HFpEF, particularly in tetralogy of Fallot, aortic coarctation/interruption, and complete transposition of the great arteries.12 Right HFpEF, rather than HFrEF, is associated with hepatic congestion, lower exercise tolerance, and a high incidence of unscheduled hospitalization.12 This means that HFpEF is an important criterion in the CHD field. A pathophysiologic status equivalent to constrictive pericarditis is a potential cause for the impediments. Such constriction could be promoted by pericardial incision and adhesion. For more detailed understanding, further evidence needs to be accumulated.227
4.1.2 Pharmacological Therapy
Heart failure (HF) is a clinical syndrome presenting dyspnea, malaise, swelling and/or decreased exercise capacity. The symptoms originate from loss of compensation in the pumping performance of the heart which is structurally and/or functionally abnormal.228 In adult cardiology practice, HF is classified according to left ventricular ejection fraction (LVEF). When the LVEF <40%, that is termed HF with reduced LVEF (HFrEF), but HF with preserved LVEF (HFpEF) when ≥50%. Between 40% and 49%, it is called HF with mid-range EF (HFmrEF). Patients with CHD after surgical repair have various diseases and conditions. It is wise to take individual factors as well as the LVEF criteria into consideration.
The systemic ventricle would be of a morphologically right pattern in patients with transposition of the great arteries (TGA) undergoing intra-atrial redirection of blood or in those with congenitally corrected TGA (ccTGA) undergoing a conventional strategy. In such circumstances, the EF of the morphologically RV is to be discussed instead of the LVEF.
There is not much evidence for treatments for patients with CHD. Pharmacological therapy is based on general guidelines for HF in adults.
4.1.2.1 Patients With HFrEF (Including Systolic Dysfunction of the Systemic RV)
In adult cardiology, HFrEF is attributed to impaired activation of the sympathetic nervous system and the renin–angiotensin–aldosterone (RAA) system, resulting in the left ventricle (LV) progressively enlarging and becoming less contractile. The JCS 2017/JHFS 2017 Guideline228 mentions that pharmacological treatments have improved the prognosis of HFrEF in cohorts of general adult cardiology by inhibiting these neurohormonal systems.
In CHD, pharmacological therapy does not seem to improve the prognosis of those with HFrEF. Still, a general guideline with evidence in adult cardiology is the only one to follow at present. The recommendations are also considered valid, to some extent, for pharmacological therapies in patients with the systemic RV, in those with the Fontan circulation, and even in the pediatric population.
a) Angiotensin-Converting Enzyme (ACE) Inhibitors
In randomized clinical trials, ACE inhibitors decreased cardiovascular events and improved the prognosis in asymptomatic adults with HFrEF. These agents, therefore, should be used in CHD patients with HFrEF. The Fontan circulation is an exception. In that particular postoperative status, systemic vascular resistance may become undesirably low with cardiac output unnecessarily increased.171 ACE inhibitors should be discontinued in such cases.
b) Angiotensin II Receptor Blockers (ARBs)
Similar to ACE inhibitors, ARBs improve the prognosis and suppress cardiovascular events in adults with HFrEF. ARBs have not been found superior to ACE inhibitors.229 ARBs would be a secondary choice when ACE inhibitors are not continued because of side effects such as cough.
c) Mineralocorticoid Receptor Antagonists (MRAs)
MRAs improve the prognosis of adults with HFrEF when given together with ACE inhibitors or β-blockers. MRAs are often used in combination with ARBs as well. The serum potassium level should be monitored meticulously.
d) β-Blockers
β-Blockers are well known to improve prognosis in either asymptomatic or symptomatic patients with HFrEF in randomized clinical trials.230 β-Blockers act dose-dependently. Starting at a low dose, they should be gradually increased, paying attention to exacerbation of HF, hypotension, and bradycardia.
4.1.2.2 Patients With HFpEF
No pharmacological therapies have been proven to improve prognosis of HFpEF in adults without CHD. In those with CHD undergoing cardiac surgery, the constrictive nature of the pericardium would be a pathophysiology for HFpEF. This cohort of patients can also be complicated with pulmonary hypertension. Pharmacological therapy is aimed at mitigating symptoms, rather than improving prognosis.
a) Diuretics
Diuretics reduce symptoms; making patients less dyspneic on exertion, and less edematous. Loop diuretics are used in most patients. Vasopressin V2 receptor antagonists block the corresponding receptors in the collecting duct. They inhibit water reabsorption and promote water diuresis. The agents improve congestion without hyponatremia.
b) Pulmonary Vasodilators
Pulmonary vasodilators could improve exercise tolerance in patients with the Fontan circulation or Eisenmenger syndrome.
4.1.2.3 Acute Decompensated HF
In acute decompensated HF, the purpose of treatments is to improve symptoms and increase survival. HF in CHD is mainly characterized by right-sided HF because of the abnormally formed structures.
a) Diuretics
Diuretics reduce symptoms of HF caused by fluid retention. Loop diuretics are fast-acting and frequently used. When one-shot intravenous treatment is not effective, continuous intravenous injection should be attempted. Thiazide diuretics are combined if loop diuretics alone are not sufficiently effective.
b) Vasodilators
Vasodilators reduce the afterload of the LV, correct fluid distribution, and increase cardiac output. They are used for acute left HF associated with elevated blood pressure in adult cardiology. Acute decompensated HF in CHD is not always accompanied by hypertensive status. The pathological condition needs to be identified precisely in each patient.
c) Inotropic Drugs
Inotropic drugs are indicated in patients whose hypotension and peripheral circulatory insufficiency are resistant to other treatments. Inotropic drugs are effective in improving hemodynamics and clinical findings in the shorter term. On the other hand, they can increase the incidence of fatal ventricular arrhythmias, myocardial ischemia, myocardial damage, and might result in a poorer prognosis in the longer term.231
4.1.3 Nonpharmacological Therapy
a) Reoperations and Catheter Interventions
Quite a few cases of HF in patients with CHD are associated with valve issues and structural abnormalities. They are sequelae and residual lesions. Timely surgical or transcatheter treatment for these problems is essential to alleviate symptoms and to mitigate their progression. Risks for interventions become greater when surgical or transcatheter procedures are carried out once cardiac dysfunction is established.
b) Treatment of Arrhythmias
Brady- and tachyarrhythmias are complications frequently seen late after cardiac surgery. They trigger deterioration of HF.232,233 Implantation of a permanent pacemaker is indicated for bradyarrhythmias according to the guideline on nonpharmacotherapy of cardiac arrhythmias.151 Unique issues in the field of CHD, particularly technical problems, should be noted. For example, it is anatomically challenging to accommodate a pacemaker system using endocardial leads in patients with the tricuspid valve replaced or after the Fontan type procedure using an extracardiac conduit (the so-called extracardiac total cavopulmonary connection). Usually, epicardial leads are chosen in such circumstances. The transvenous approach is technically feasible in patients with unrepaired and cyanotic CHD. Its downside is an increased risk of infective endocarditis or systemic thromboembolism. Use of epicardial leads also has a downside in patients with prolonged cyanosis; collateral vessels are abundant causing surgical procedures to be complicated by bleeding. It is necessary to contemplate risks and benefits on a case-by-case basis.
Leadless pacemakers may be practical in anatomically complicated CHD. An occluded superior vena cava is an example, tricuspid regurgitation is another. The potential of infective endocarditis does not increase. Ventricular contraction, however, is not synchronized with atrial contraction. Atrial fibrillation could be the sole reasonable indication. Inappropriate positioning of ventricular pacing likely induces ventricular dysfunction due to dyssynchrony of the chambers.
Catheter ablation treats tachyarrhythmias well, although may not be entirely curative because of complex anatomy and associated multiple arrhythmic substrates.151 A permanent pacemaker is a practical measure when anti-arrhythmic drugs suppress tachyarrhythmia into bradycardia. Implantable cardioverter-defibrillators are used to minimize the occurrence of sudden cardiac death. Subcutaneous implantable defibrillators are among the options of choice, unless bradyarrhythmias are present, in patients with CHD after surgical repair who are at high risk for infective endocarditis.
c) Exercise Therapy/Cardiac Rehabilitation
It has been reported that more than one-third of patients with CHD have impaired exercise tolerance.234,235 There are no randomized controlled trials clarifying the efficacy of exercise therapy in this field. Reports on a small number of cases are available, describing that the 6-minutes walking distance was extended after exercise therapy and that maximal oxygen uptake improved.234,236
d) Home Oxygen Therapy
Home oxygen therapy (HOT) has not been shown to be effective in prognosis, exercise tolerance, or quality of life, including for Eisenmenger syndrome. HOT relieves symptoms of severe HF or hypoxemia.237
e) Treatment of Sleep-Disordered Breathing
It has been reported that sleep-disordered breathing (SDB) is often associated with CHD.238 In patients with obstructive sleep apnea syndrome (OSAS), continuous positive airway pressure has been established.239 Its clinical relevance remains unknown in terms of prognosis in patients with HF and OSAS. SDB practical guidelines are to be referred to for treatments in patients with CHD.239 The Fontan circulation is an exception. It has been reported that central venous pressure increases with positive airway pressure ventilation.240,241
4.1.4 Cardiac Dyssynchrony and Cardiac Resynchronization Therapy (CRT)
4.1.4.1 Cardiac Dyssynchrony
There are 3 types of cardiac dyssynchrony that can be present: atrioventricular, intraventricular and interventricular. In the general adult population, LV intraventricular dyssynchrony is the most common.242 The other types of dyssynchrony also need attention in CHD patients in whom the ventricular morphology is heterogenous.
QRS duration can become longer (wider) during childhood, because of atrioventricular conduction disturbance, or bundle branch block, to say nothing of ventricular pacing. As a result, cardiac dyssynchrony progresses and heart function deteriorates over time. We should bear that in mind and keep the QRS duration short (narrow).
4.1.4.2 Atrioventricular Dyssynchrony
Atrial contraction contributes to the stroke volume of the ventricle up to 20–30% at rest in the failing heart. Impaired atrioventricular conduction reduces cardiac output and systolic blood pressure.243,244
This type of dyssynchrony is dealt with by adjusted atrioventricular interval (AVI). The AVI should be optimal when the A wave terminates coincidentally with closure of the AV valve detected on the basis of trans-systemic AV valve flow.243,245,246 CHD patients may require extraordinary AVI settings compared with the general adult population, because the atrial lead is not always located as normally anticipated and intra-atrial conduction is considerably delayed around surgical scars or fibrosis of the atrial tissues. Prior to setting AVI in CHD, it is necessary to check the electrocardiogram, chest X-ray, and previous operative records.247
4.1.4.3 Intraventricular Dyssynchrony
We can apply the CRT method for general adult cardiology to CHD patients with a systemic LV showing LV intraventricular dyssynchrony.248 The circumstances are different for those with right ventricular (RV) conduction delay and RV intraventricular dyssynchrony, because the architecture and contractile sequence of the RV differ from those of the LV. CRT for the RV appears to be less effective than for the LV.248
There have been several reports stating the results of CRT for the systemic RV and subpulmonary RV. Further accumulation of cases is mandatory to establish better treatment strategies.249–252
4.1.4.4 Interventricular Dyssynchrony
Single ventricular physiology is the most unique circumstance in CHD. In this setting, an unrestrictive ventricular septal defect (VSD) often exists between the dominant ventricle and the rudimentary chamber. The interventricular dyssynchrony is distinctive, the so-called swinging biventricular motion. When the 2 ventricles contract in different cyclic patterns, blood flow goes back and forth from one ventricle to the other through the VSD, which results in low cardiac output.249,253
With the biventricular physiology, the interaction between the LV and RV plays an important role. Hemodynamics stay efficient when the LV and RV are well synchronized.254
4.1.4.5 Indications for CRT
The type of systemic ventricle is important for successful CRT; that is, LV, RV, or a solitary ventricular chamber (single ventricular physiology).13,255,256 Dyssynchrony of the subpulmonary ventricle is another aspect to consider.250,252 Indications for CRT and the choice of pacing sites should be determined by the ventricular morphology and the type of ventricular dyssynchrony.13,249,257 In patients with a systemic RV or single ventricular physiology, the ventricular dyssynchrony is distinct. There is little evidence for CRT in this cohort, and thus the level of recommendation is low. Still, earlier CRT implantation is advised, because dyssynchrony is quite disadvantageous hemodynamically in this group compared with the systemic LV group.
The recommendations for CRT in CHD patients are reprinted from the JCS/JHRS 2019 guideline on nonpharmacotherapy of cardiac arrhythmias151 (Table 14).
Table 14. Class of Recommendations and Levels of Evidence for CRT in CHD Patients
| |
COR |
LOE |
GOR
(MINDS) |
LOE
(MINDS) |
CRT is recommended for patients with a systemic left ventricle, NYHA class II–IV symptoms, systemic
LVEF ≤35%, complete left bundle branch block with QRS duration ≥120 ms, and sinus rhythm |
I |
B |
A |
II |
CRT should be considered for patients with a systemic right ventricle, NYHA class II–IV symptoms,
systemic right ventricular ejection fraction ≤35%, right ventricular dilatation, and complete right bundle
branch block with QRS duration ≥120 ms |
IIa |
C |
B |
IVb |
CRT should be considered for patients with congenital heart disease, NYHA class I–IV symptoms,
systemic ventricular ejection fraction ≤35%, and an intrinsically narrow QRS complex in those
undergoing new or replacement device implantation with anticipated requirement for ventricular pacing
≥40% (single-site pacing from the systemic ventricular apex/mid-lateral wall can be considered an
alternative) |
IIa |
C |
C1 |
IVb |
CRT should be considered for patients with a single ventricular physiology, NYHA class II–IV symptoms,
systemic ventricular ejection fraction ≤35%, ventricular dilatation, and QRS duration ≥120 ms due to
intraventricular conduction delay that produces a complete RBBB or LBBB morphology |
IIa |
C |
B |
IVb |
CRT may be considered for patients with congenital heart disease, NYHA class I–IV symptoms,
systemic ventricular ejection fraction ≥35%, and an intrinsically narrow QRS complex in those
undergoing new or replacement device implantation with anticipated requirement for ventricular pacing
≥40% (single-site pacing from the systemic ventricular apex/mid-lateral wall can be considered an
alternative) |
IIb |
C |
C2 |
IVb |
CRT may be considered for patients undergoing cardiac surgery with NYHA class I–IV symptoms,
QRS duration ≥120 ms, complete bundle branch block morphology ipsilateral to the systemic ventricle,
and progressive systolic ventricular dysfunction and/or dilatation (especially if epicardial access is
required to implement CRT) |
IIb |
B |
C1 |
IVb |
CRT may be considered for patients with a systemic right ventricle undergoing cardiac surgery for
tricuspid valve regurgitation with NYHA class I–IV symptoms, QRS duration ≥120 ms, and complete
RBBB |
IIb |
B |
C1 |
IVb |
CRT may be considered for patients with congenital heart disease with severe subpulmonary right
ventricular dilatation and dysfunction, NYHA class II–IV symptoms, and complete RBBB with QRS
duration ≥150 ms |
IIb |
C |
C2 |
V |
CRT may be considered for patients with NYHA class IV symptoms and severe systemic ventricular
dysfunction, in an attempt to delay or prevent cardiac transplantation or mechanical support |
IIb |
C |
C1 |
VI |
CRT is not recommended for patients whose comorbidities and/or frailty limit survival with good
functional capacity to <1 year |
III |
C |
C2 |
VI |
COR, class of recommendation; CRT, cardiac resynchronization therapy; GOR, grade of recommendation; LBBB, left bundle branch block; LOE, level of evidence; NYHA, New York Heart Association; RBBB, right bundle branch block.
(From JCS/JHRS 2019 Guideline on Non-Pharmacotherapy of Cardiac Arrhythmias. 2021.151)
4.2 Pulmonary Hypertension
4.2.1 Pathogenesis and Classification of Pulmonary Hypertension in the Longer Term After Congenital Heart Surgery
At the 6th World Symposium on Pulmonary Hypertension (held in Nice, France, 2018), pulmonary hypertension (PH) was redefined as mean pulmonary arterial pressure (mPAP) >20 mmHg. PVR (pulmonary vascular resistance) ≥3 Wood units (WU) was added as a condition for precapillary PH. The PH classification is now divided into 5 groups based on the same concept as before.258 Congenital heart disease (CHD)-PH can be distributed in any of these groups. The most characteristic pattern is the pulmonary arterial hypertension (PAH) (group 1 PH) associated with high pulmonary blood flow through a systemic-to-pulmonary (left-to-right) shunt. Three subcategories were initially set as shunt-associated PAH (sPAH). Another subcategory has been added for idiopathic PAH (IPAH) with coincidental (small/restrictive) shunts; we now have 4 subcategories of CHD-PAH259 (Table 15).
Table 15. Clinical Categories of PAH in the Distant Postoperative Period of Congenital Heart Disease
| 1. Congenital heart disease (shunt)-associated PAH |
| 1.1 Residual PAH after shunt closure (without significant shunt) |
| 1.1.1 Residual or worsening PAH immediately after surgery |
| 1.1.2 PAH manifests (develops) in the postoperative distant phase |
| 1.2 Idiopathic PAH with coincidental (small/restrictive) shunt |
| 1.3 PAH due to unrepaired large (nonrestrictive) shunt (has not yet become ES) |
| 1.4 ES |
ES is defined as the end stage of large shunt-associated PAH. The patient with ES has PAH equivalent to
systemic blood pressure due to a markedly elevated PVR and a substantial right–left (reverse) shunt, resulting in
hypoxemia and cyanosis |
| 2. Fontan circulatory failure (failing-Fontan) due to increased PVR |
In patients with Fontan circulation, an increase in PVR causes an increase in pulmonary arterial and venous
pressures, resulting in circulatory failure manifested by systemic edema, protein-losing enteropathy, plastic bronchitis,
and markedly impaired exercise capacity (≥WHO-FC III) |
ES, Eisenmenger syndrome; PAH, pulmonary arterial hypertension; PVR, pulmonary vascular resistance; WHO-FC, World Health Organization functional class.
(Summarized from Simonneau G, et al. 2013.259)
sPAH with unrepaired large (nonrestrictive) defects primarily causing high pulmonary blood flow is divided into 2 subcategories (1.3 and 1.4 in Table 15) based on whether or not Eisenmenger syndrome (ES) is present. ES is defined as a condition in which a marked increase in PVR leads to severe PH and a substantial amount of reverse (pulmonary-to-systemic or right-to-left) shunt through the defect, resulting in hypoxemia and cyanosis.260 Traditionally, surgical repair of the defect has been contraindicated in patients with ES, which remains as a rule even now, despite more than 10 different PAH drugs being available. On the other hand, the so-called “Treat and Repair” strategy (shunt closure after successful PH control by aggressive use of PAH drugs) increasingly attracts attention for patients with unrepaired shunt-sPAH that has not yet reached the ES stage. There have been many reports of improved prognosis and quality of life (QOL) in successful cases.261–266 Even in some cases of ES, PH control by drug therapy (Treat) may result in closure (Repair), and this “Treat and Repair” approach has been taken up as a notable topic.261,262,264
In the case of CHD-PAH with coincidental/small defects (1.2 in Table 15), the fundamental nature of the disease is considered as IPAH, and closure of the defect is contraindicated in the guidelines because the defect is expected to function as a safety valve against right heart failure.259 Because of the excellent results of IPAH treatment in Japan,267,268 nonetheless, some centers with fair experience in IPAH control may proceed to closure of the coincidental/small defects (from the viewpoint of therapeutic reasons such as reducing the volume overload onto the pulmonary artery and the ventricle, or preventing paradoxical emboli) when the safety valve is dispensable.
The remaining group (1.1 in Table 15) represents the sPAH cases with shunts closed. This group includes cases in which the residual PH gradually worsens in the longer term after the procedure, and cases in which PH seemingly disappeared after surgery but recurred long after. Either way, there is no difference in treatment once PH is detected. The pathophysiological process and consequence of pulmonary vascular occlusive lesions varies depending on the primary CHD and the presence or absence of chromosomal abnormalities such as trisomy 21.269 The guidelines for treatment of this type of sPAH do not differ from case to case. The patients are treated according to the guidelines of IPAH. Severity of PH, residual cardiac function, and the type and stage of heart failure are the most important factors when choosing treatments. Various defects and shunts have been previously undetected, but can be found by transthoracic and transesophageal echocardiography, as well as recent high-resolution computed tomography scans and cardiac magnetic resonance imaging (MRI), especially in patients who were operated before the advent of color Doppler echocardiography in the early 1980s. Particularly in 1970s and earlier, artificial cardiopulmonary support was not ideally available, and surgical interventions may have damaged cardiac function. How to decide on interventional treatment of the defects or the communication is crucial for postoperative sPAH with residual shunts.
Failure of the Fontan circulation (failing Fontan) because of elevated PVR is another condition that is difficult to determine how to incorporate into the PH classification (2 in Table 15). Increased PVR elevates pulmonary arterial pressure (i.e., systemic venous pressure), which inevitably leads to Fontan circulatory failure in the longer term after the definitive procedure. It has been reported that bosentan, an endothelin receptor antagonist (ERA), improves exercise tolerance and hemodynamics in patients with failing Fontan.270 Overexpression of endothelin-1 and its receptors has been demonstrated.271,272 On the other hand, PVR in the Fontan circulation decreases in response to nitric oxide inhalation,273 and exercise capacity improves on sildenafil administration because of the improved ventilatory efficiency.274 At the 5th World Symposium on Pulmonary Hypertension (held in Nice, France, 2013), Fontan circulatory failure was introduced into the section on PH group 1 (PAH).259 ERAs and phosphodiesterase-5 inhibitors (PDE-5I) are potentially effective in reducing PVR and improving exercise capacity in failing Fontan patients.275–277 These reports may entitle elevated PVR in the Fontan circulation as a PH category, although it is not included currently in the PH classification. In this guideline, Fontan circulatory failure is introduced and listed as a PH analog in Table 15.
4.2.2 Drug Therapy
4.2.2.1 Basics of Drug Administration for CHD-PAH
sPAH shows histopathological changes similar to IPAH in the pulmonary arteries. Also, sPAH responds to PAH drugs (pulmonary vasodilators) as anticipated when the drug therapy for IPAH is referred. Currently available for use in Japan are oral ERAs (bosentan, ambrisentan, macitentan), oral PDE-5Is (sildenafil, tadalafil), an oral soluble guanylate cyclase stimulator (riociguat), and prostacyclin derivatives (PC) (intravenous epoprostenol, intravenous/transdermal treprostinil, inhaled iloprost, oral beraprost, and oral selexipag).173
4.2.2.2 Pharmacotherapy Guidelines for CHD-PAH
a) Residual sPAH After Shunt Closure (Without a Significant Shunt) (1.1 in Table 15)
The pathophysiology and response to drugs of sPAH after shunt closure are considered identical to those of IPAH, although PH progresses slower than in IPAH because the high pulmonary blood flow that predisposed to PH has disappeared. A report described that achieving mPAP <42.5 mmHg on combined therapy was important for long-term prognosis in IPAH.268 Another report recommended PVR <7.5 WU (or mPAP <35 mmHg) to maintain reasonable right ventricular function in the normal heart.278 Setting strict criteria, mPAP <35 mmHg and PVR <7.5 WU are the hemodynamic target (Class IIa, Level C).
Good results have been achieved for IPAH control in Japan, mainly thanks to combination therapy.173,267,268,279 Oral drugs are used in combination aggressively from the beginning for this type of sPAH280 (Class IIa, Level C). Even after the shunt is closed, meticulous attention should be paid to the risk of transvenous infection associated with injection of drugs. The choice should be primarily combined oral medication (Class IIa, Level B).
When drugs are given in combination, each agent is expected to be as effective as if used in isolation173 (Class IIa, Level B). Beraprost is an exception; it is not recommended as a first-line agent, and should be used only for a combination purpose (Class IIb, Level C).
Inhaled iloprost is not recommended as a first- or second-line agent (Class IIb, Level C) because the need for repeated inhalation maneuvers (6–9 times per day) results in poor drug compliance. Inhaled iloprost should be considered as an additional medication in cases of inadequate improvement on combined oral drugs, low residual right heart function, and regurgitation ≥3rd degree across the right atrioventricular valve (morphologically tricuspid valve in most instances) (Class IIa, Level C).
Intravenous/transdermal infusion of a PC is rarely used as a first- or second-line treatment for sPAH, either, from the viewpoint of QOL and inducible infection (Class IIb, Level C). Only in cases of severe PH (WHO functional class ≥III) with severe right heart failure, is the substance used as a first-line therapy (Class I, Level C). In less severe cases, it should be the 3rd or subsequent adjunctive agent (Class IIa, Level C). Cardiovascular and other surgical procedures are another setting in which PC injectables are used without hesitation when PH abruptly worsens (e.g., PH crisis) in the perioperative period (Class I, Level C). In such a circumstance, the injectable PC is often reduced or discontinued once the acute phase is over. When choosing an injectable PC, it is preferable to start with transdermal treprostinil,281 which has a low risk of blood infection (Class IIa, Level C). On the other hand, epoprostenol would be the preferred choice for intravenous use (Class IIa, Level B) in terms of a risk of infective endocarditis that cannot be ignored in CHD. Epoprostenol, which has a strongly alkaline solution for injection, has a lower risk of blood infection than treprostinil, which is in a weakly acidic solution.282–284
b) sPAH With a Large (Nonrestrictive) Shunt (1.3 and 1.4 in Table 15)
If a shunt is found to be large (nonrestrictive) in the longer term after the initial repair, it poses a problem of high pulmonary flow for the control of sPAH, and impairs ventricular function. If the hemodynamically significant shunt is left untreated, use of PAH drugs may not only result in an inadequate antihypertensive effect, but also worsen the prognosis by inducing heart failure. In such a case, we need to evaluate whether the shunt can be closed. As shown in “Treat and Repair”,278 it is important to assess whether expected residual PH can be controlled after closure of the shunt, and whether cardiac function can withstand the procedural stress of closure of the shunt either during or after the procedure. It is advisable to consult a specialist with considerable expertise in the treatment of CHD-PAH, asking for an opinion particularly on “Treat and Repair” (Class IIa, Level C). In patients with a predominantly right-to-left shunt, it should be carefully determined whether the cyanotic shunt is caused by ES, a structural/anatomical reason, or cardiac function. The background is crucial in choosing the optimal strategy for drug therapy. Thus, it is advised to seek a correct diagnosis from an experienced team (Class IIa, Level C).
Inadvertent combination therapy of PAH drugs can induce a sudden decrease in PVR and high pulmonary blood flow, leading to inadequate or unfavorable PH control. The heart will be volume overloaded, subsequently resulting in rapid progression of heart failure and/or worsening of atrioventricular regurgitation. This sequence will eventually lead to a poorer prognosis after all. Closure of the shunt is no longer indicated when cardiac function has been impaired consequent to inappropriate medication. Administration of drugs should be supervised by an experienced team (Class IIa, Level C).
Evaluation of hemodynamics (by right heart catheter) and cardiac function (on cardiac MRI or echocardiography) should be carried out 3–6 months after the commencement of PAH drugs; this will clarify whether and when the shunt is to be closed (Class IIa, Level C). In the presence of a significant shunt, aggressive combination therapy is only pertinent when closure of the shunt will most likely be suitable (Class IIa, Level C). PAH treatment (Treat) is regarded as appropriate when it increases pulmonary blood flow without impairing cardiac function, without raising pulmonary arterial pressure, or without making PVR >7.5 WU (Repair criteria) (Class IIb, Level C). Such a response to administered drugs seemingly warrants closure of the shunt (Repair). Evaluation of drug effects is highly dependent on the circumstances of each individual case. We must continue to rely on the judgment of highly experienced experts.
4.2.3 Unique Pathology in PH in CHD
The mechanisms and classification of PH vary in CHD,285 but increased pulmonary blood flow via a left-to-right shunt is the most common mechanism.286,287 High pulmonary blood flow, when persistent, would make pulmonary resistance (Rp) higher with time, eventually progressing to Eisenmenger syndrome.288 Rp <4 WU is an indication for surgical closure. On the other hand, Rp >8 WU is regarded as a criterion of contraindication, leaving a borderline area in between. Aggressive drug therapy using pulmonary vasodilators has been introduced, followed by surgical or transcatheter closure of the shunt. This approach may alter the conventional indication of treatment. PH with a left-to-right shunt is classified as Group 1 in the criteria.
PH caused by left heart obstructive disease (e.g., pulmonary venous obstruction, congenital mitral stenosis or diastolic dysfunction of the left ventricle) is classified as Group 2.289 PH associated with hypoplastic pulmonary arteries or segmental defect of the pulmonary vascular beds (e.g., ventricular septal defect with pulmonary atresia and major aortopulmonary collateral arteries) is classified as Group 5.
PH after surgical repair is occasionally multifactorial in patients with complex CHD. A comprehensive strategy for treatment should be sought, combining administration of pulmonary vasodilators and subsequent surgical or catheter interventions.
4.3 Arrhythmias and Sudden Death
4.3.1 Pathophysiology
A congenitally abnormal conduction system in CHD causes either brady- or tachyarrhythmias, together with unique and acquired hemodynamic abnormalities (Figure 1).137,151,290 Arrhythmias are increasingly found over time, because of aging of the damaged tissues and prolonged hemodynamic issues (Figure 2).137
4.3.1.1 Bradyarrhythmias
a) Congenital Abnormalities of the Conduction System
i) Atrial Situs
Left isomerism of the atrial appendages has a high incidence of bradyarrhythmia.291–293 Histopathologically, a solitary and hypoplastic sinus node is found in 44% of patients with left isomerism. The structure is absent in 56% in this setting.294 Such structural abnormalities clinically present as concealed sinus nodal dysfunction that becomes more obvious with age.292 The AV node is not connected to the conduction bundles in 56% of cases of left isomerism, and AV block occurs often in this group.293,294
ii) AV Connection
AV connection is related to the development of the AV conduction system. Discordant AV connection, as seen in congenitally corrected transposition of the great arteries (ccTGA), may have the AV node anteriorly in isolation, posteriorly in isolation, or duplicated. The developmental process determines where the AV node is located, partly depending on the alignment between the interatrial and interventricular septa. When duplicated anteriorly and posteriorly, the circumstance is morphologically called dual AV nodes, or electrophysiologically named as ‘twin’ AV nodes (Figure 3).295,296 The posterior AV node is found at the apex of Koch’s triangle. The anterior AV node is located at the lateral junction between the mitral valve and pulmonary trunk. The conduction bundle courses anterior to the pulmonary valve before reaching the ventricular septum.296 Because of the abnormally long and tortuous pathway of the conduction bundle, AV block, either congenital or progressive, occurs frequently.297 When AV connection is discordant in situs inversus, AV block occurs much less often; usually, the posterior AV node meets with the short and straight AV bundle.298
b) Acquired Factors
i) Postoperative AV Block
Postoperative AV block often recovers during the perioperative period. When complete AV block is prolonged, future prognosis can be poor.299,300 In such cases, complete heart block can recur decades after and pose a risk of sudden cardiac death.301–303 When we encounter AV block in the long term after surgery without any anatomic or hemodynamic reason being detected, it is probably late recurrence of surgical block that seemed transient at the time.
In patients undergoing intra-atrial redirection of blood (the Mustard or Senning procedure), sinus nodal dysfunction occurs late after surgery, related to the complicated incisions and the suture lines onto the atria. Cumulative freedom from sinus nodal dysfunction has been reported as 46% and 40% at 20 years after the Mustard and the Senning procedures, respectively.304
ii) Overload to the Atria and the Ventricles
Myocardial remodeling due to right atrial or right ventricular overload causes sinus nodal and AV nodal dysfunction. Sinus nodal dysfunction has been observed in approximately 40% of patients with atriopulmonary connection (APC) Fontan, a representative of disease associated with right atrial pressure overload.305,306 In patients with tetralogy of Fallot (TOF) showing both right atrial and right ventricular overload, both sinus nodal dysfunction and AV block are observed in a certain proportion.307–309
iii) Aging
The aging process affects the conduction system as is the case in general adult cardiology. Sinus nodal dysfunction increases with age in left isomerism, as does AV block in discordant AV connection.81,292 The lesions producing atrial and ventricular overload and responsible for bradyarrhythmia also get worse with age, eventually inducing further disturbance of the conduction system.310
4.3.1.2 Supraventricular Tachycardia (SVT)
a) Congenital Abnormalities in the Conduction System
i) Atrial Situs
Patients with isomerism frequently experience SVT because of their unique atrial morphology.293 The crista terminalis, which serves as an electrical barrier during intra-atrial reentrant tachycardia (IART), is bilaterally present in the atria in 87% of patients with right isomerism, while entirely absent in 88% of those with left isomerism.311 Accordingly, the incidence of IART is much higher with right isomerism.312 In contrast, it is low with left isomerism, and nonreentrant atrial tachycardia (AT) and atrial fibrillation (AF) increases as sinus nodal dysfunction progresses with age.292
ii) Accessory Pathway
In Ebstein malformation, accessory pathways are almost always found in the region showing plastering of the leaflets of the tricuspid valve where the RV is atrialized and very thin with abnormal tissues.313,314 Such accessory pathways are often multiple, broad conducting, and slow conducting. Common patterns on electrocardiogram are wide QRS atrioventricular reciprocating tachycardia (AVRT) with an anterograde conduction through an accessory pathway and wide QRS tachycardia during AF (known as pseudo-ventricular tachycardia).151
The Ebstein malformation is a well-known lesion coexisting with discordant AV connection (ccTGA), seen in 20% of these patients. There is a high incidence of accessary pathways.81
iii) ‘Twin’ AV Nodes
Dual AV nodes are common in isomerism of the atrial appendages and occasionally found in AV discordance. Twin AV nodes are almost the rule (100%) of right isomerism, and less common in left isomerism (32%).294 Each of the dual AV nodes may be connected to its own bundle. When the bundles are conjoined within the ventricular septum, a connecting sling is formed.294,315 Such sling formation could accommodate a supraventricular tachycardia (SVT) circuit involving the dual AV nodes (twin AV node reciprocating tachycardia).315 Right isomerism with balanced ventricles shows frequent episodes of SVT. SVT of this type should respond well to appropriate treatments without contributing to deaths.316
Adenosine-sensitive focal junctional tachycardia has also been reported in complex CHD. It remains unclear how common this arrhythmia is, or how bleak its prognosis. Another question is whether the sling forms part of the circuit or not.316,317
b) Acquired Factors
i) Atrial Overload
Overload to the atrium causes remodeling of its tissues, producing an arrhythmic substrate.318
The APC Fontan procedure imposes considerable burden to the right atrium; cumulative freedom from SVT can be <30% at 30 years after the procedure.305,306,319 The Fontan circulation by total cavopulmonary connection is not SVT-free; long after surgery, SVT can occur, particularly in patients with regurgitation across the AV valve or in those undergoing surgical maneuvers around the pulmonary veins.312
Patients with repaired TOF or the Ebstein malformation are liable to develop atrial tachycardia through pressure or volume overload to the right atrium.307,313
ii) Surgical Procedures
The incisional line to the atrial wall can form an electrical barrier and become an arrhythmic substrate for IART.318
Patients undergoing intra-atrial redirection of blood (the Mustard or the Senning procedure) have complicated incisional scars and suture lines on the atria. IART often develops late after the procedure, associated with the insult to the atrial tissues. Stitches are always found at the isthmus between the annulus of the tricuspid valve and the inferior vena cava (IVC). The commonest reentrant circuit is around the tricuspid valve (TV). Atrial tachycardia is also possible that is not dependent on the TV–IVC isthmus.320
iii) Aging
As is often the case in general adult cardiology, SVT increases with age, including AF. The chronic overload to the right atrium induces myocardial remodeling that is responsible for the development of SVT.321 In a multicenter study of repaired TOF, the incidence of AT (including AF) increased with age, being noted in >50% at the age of 55 years or older. The incidence of AF alone increased beyond that of AT in patients >45 years old.307 Similarly, in those with functionally repaired TGA, the incidence of SVT increases with time; cumulative freedom from SVT is almost 0% at 50 years after surgery.310
4.3.1.3 VT/VF
Ventricular tachycardia (VT) or ventricular fibrillation (VF) occurs less frequently than SVT. They are, of course, the principal cause of sudden cardiac death.
a) Diseased Subpulmonary RV
Reentrant VT is seen in patients with a diseased subpulmonary RV; the reentrant circuit is related to an incisional line onto the RV wall.322
The RV of repaired TOF is representative of a diseased subpulmonary chamber. Various reports have discussed VT/VF late after surgery in this setting. Pulmonary regurgitation and its volume overload to the RV are known to be the major factor of VT/VF. Wide QRS duration >180 ms and obvious RV dysfunction are the predictors of a dangerous arrhythmia.323,324 Some reports add that left ventricular parameters are similarly indicative of VT/VF, such as elevated end-diastolic pressure of the left ventricle.133,307,325 The incidence of VT/VF after repair of TOF is lower and the overall survival rate higher in Japan than has been reported in Europe or North America.326 This might be thanks to the sensible efforts of respectful Japanese surgeons; since the early 1970s, some surgeons have insisted that TOF should be repaired with only a small or no right ventriculotomy.326,327 Still, VT/VF and sudden death do occur in a certain percentage. Follow-up must be continued even in patients showing good progress.
b) Systemic RV
The systemic RV is typically seen in ccTGA and TGA repaired by means of intra-atrial redirection of blood. In these settings, the RV is progressively malfunctioning, and the risk of VT/VF increases with age.310,328 How VT/VF occurs remains controversial. A ventricular incision is not the case with the systemic RV. It is fundamentally different from the mechanism of VT/VF in the subpulmonary RV. Ventricular arrhythmia induced during electrophysiological study does not have clinical value as a predictor of appropriate ICD shock in TGA repaired by the atrial maneuver.329 ATs were detected prior to VT/VF in several reports.329–331 Presumably, the myocardium becomes ischemic because of rapid AT conducted to the ventricle, eventually evoking VT/VF.
c) Ebstein Malformation
VT/VF can occur with the Ebstein malformation. The abnormal tissue within the atrialized RV is likely an origin of VT/VF.313,332 Ventricular dysfunction is reportedly another association.333
d) The Fontan Circulation
VT/VF is relatively infrequent in the Fontan circulation, only seen in a few percent. Ventricular fibrosis usually accompanies it.334,335
4.3.1.4 Sudden Cardiac Death
Among the causes of deaths in CHD, the proportion of sudden cardiac death has decreased gradually. It was approximately 25% in reports in the 1990s vs. 7% in 2015.336–339 Arrhythmic events comprise 80% of the causes of sudden cardiac death. Otherwise, it is thrombosis/bleeding, aneurysm rupture, myocardial infarction and so on.337,338 In retrospective studies the predictors for sudden cardiac death in CHD are systemic ventricular dysfunction, wide QRS, and a history of SVT.137,338,340
4.3.2 Special Issues in CHD
4.3.2.1 Arrhythmogenicity in CHD
Arrhythmias are frequent in CHD. The arrhythmic background is rather heterogeneous, depending on the variety of anatomy, types of surgical procedures and their insults, and hemodynamic features of the underlying disease.
The underlying malformations are classified as simple, moderate and severe/complex (see I-1, Table 6).7 Such structural complexity accords with the clinical manifestation of the patient’s impediments. How to treat arrhythmias effectively in CHD requires insight into the structural and functional abnormalities.
4.3.2.2 Sudden Death
A risk of sudden death reflects the underlying malformations. The more complex the structural abnormalities are, the higher the risk of sudden cardiac death becomes.340 In published data from 2000 to 2015, Eisenmenger syndrome produced the highest incidence of sudden cardiac death (4.8/1,000 person-years), followed by TGA repaired by intra-atrial redirection of blood (2.4/1,000 person-years), the so-called Fontan circulation (2.1/1,000 person-years), ccTGA (2.0/1,000 person-years), AVSD repaired (1.8/1,000 person-years), complicated malformations biventricularly repaired (1.3/1000 person-years), and TOF repaired (1.0/1,000 person-years).340
As is the case in general adult cardiology, it is important to identify high-risk patients at an earlier stage and to intervene appropriately to minimize the occurrence of unfortunate events. There has been no randomized controlled trial investigating the risks of sudden cardiac death in CHD, partly because CHD is so heterogeneous. Thus, the level of evidence remains low. Guidelines and recommendations have yet to be developed for primary prevention of sudden cardiac death.
4.3.3 Pharmacological Treatments of Arrhythmia
Cardioversion should be used to terminate acute tachycardia that is hemodynamically agitating and unstable. For hemodynamically tolerated tachycardia, antitachycardia pacing or pharmacological therapy should be introduced after detailed assessment of the complexity of CHD, ventricular function, sinus/atrioventricular nodal function and risk of thromboembolism.
4.3.3.1 Supraventricular Tachycardia (Table 16)
Table 16. Recommendation of Pharmacological Therapy for SVT
| |
COR |
LOE |
| Synchronized cardioversion is recommended for hemodynamically unstable SVT |
I |
C |
| Intravenous adenosine is recommended for AVRT and AVNRT unless contraindicated |
I |
C |
| Class III drugs should be considered for prevention of SVT recurrence |
IIa |
C |
Rate control using β-blockers should be considered in patients with failed rhythm
control |
IIa |
C |
| Anticoagulation therapy should be considered for AF or AT |
IIa |
C |
Oral Class I drugs or calcium-channel blocker are not recommended for SVT in patients with
reduced cardiac function and moderate or severe complex CHD |
III |
C |
AF, atrial fibrillation; AT, atrial tachycardia; AVRNT, atrioventricular nodal reentrant tachycardia; AVRT, atrioventricular reciprocating tachycardia; CHD, congenital heart disease; COR, class of recommendation; LOE, level of evidence; SVT, supraventricular tachycardia.
a) Urgent Management
Adenosine is to be administrated to terminate paroxysmal supraventricular tachycardia (PSVT) that is dependent on AV nodal reentry. Before giving the agent, the team needs to stand-by for cardiopulmonary resuscitation. When adenosine is contraindicated or ineffective, PSVT may be terminated by verapamil or diltiazem. The physician should realize that these drugs can suppress cardiac function.
AT (including atrial flutter and IART) should be terminated by synchronized cardioversion in patients with moderate or severe complex CHD. Patients with AF or AT for >48 h should be anticoagulated for ≥3 weeks prior to cardioversion.341 An intravenous or oral Class I agent may terminate AT in patients with simple CHD and normal cardiac function.
b) Long-Term Management
Rhythm control seems hemodynamically superior to heart rate control for PSVT in the CHD field. Class III drugs should be considered for prevention of SVT if catheter ablation proves ineffective or is unfeasible.175,342
Class I drugs may be considered in patients with simple CHD and normal cardiac function (Table 17).
Table 17. Vaughan-Williams Classification
| Class |
Mechanism |
Examples |
| Ia |
Na channel block
Prolong activation time |
Procainamide, disopyramide, cibenzoline,
pirmenol |
| Ib |
Na channel block
Shorten action potential |
Mexiletine, lidocaine, aprindine |
| Ic |
Na channel block
Not affecting action potential |
Propafenone, flecainide, pilsicainide |
| II |
β-receptor block |
Metoprolol, bisoprolol, acebutolol, propranolol,
carteolol, pindolol |
| III |
K channel block |
Amiodarone, sotalol, nifekalant |
| IV |
Ca channel block |
Verapamil, bepridil, diltiazem |
Rate control together with anticoagulation therapy would be considered appropriate if rhythm control is unsuccessful.
4.3.3.2 Ventricular Tachycardia (Table 18)
Table 18. Recommendation of Pharmacological Therapy for VT
| |
COR |
LOE |
| Synchronized cardioversion is recommended for hemodynamically stable or unstable VT |
I |
C |
Intravenous Class I or III drugs should be considered for acute termination if
cardioversion is not possible |
IIa |
C |
Antiarrhythmic drugs should be considered to reduce frequency of VT in patients under ICD
therapy |
IIa |
C |
β-blockers should be considered for nonsustained VT lacking increased risk of
sudden death |
IIa |
C |
Antiarrhythmic drugs are not recommended as stand-alone therapy in high-risk patients
for sudden death |
III |
C |
COR, class of recommendation; ICD, implantable cardioverter defibrillator; LOE, level of evidence; VT, ventricular tachycardia.
a) Urgent Management
Idiopathic VT in patients whose hemodynamics are normal is managed according to the guideline for the structurally normal heart. Synchronized cardioversion is recommended for terminating VT related to CHD. Class III or I drugs may be chosen when cardioversion is unsuccessful or unfeasible.
b) Long-Term Management
Antiarrhythmic drugs are not recommended as a solitary measure for VT in patients with a structurally abnormal heart because they may induce a risk of sudden death. They are not evidently superior to intracardiac defibrillator (ICD) therapy. They could suppress cardiac function significantly, and create even further arrhythmogenicity. Antiarrhythmic drugs are therapeutic under ICD treatment, reducing both the number of episodes and the symptoms of VT. The β-blockers should only be used for nonsustained VT which does not bear a risk of sudden death.
4.3.3.3 Anticoagulation Therapy
Thromboembolic complications of the cerebrovascular system are morbid in patients with loss of sinus rhythm.343 Anticoagulation therapy should be considered for AF or AT, including atrial flutter, defined as CHADS2
score ≥1 (Table 19).341 Most patients with AT or AF also suffer from heart failure.
Table 19. CHADS
2 Score
| |
Condition |
Points |
| C |
Congestive heart failure |
1 |
| H |
Hypertension |
1 |
| A |
Age ≥75 years |
1 |
| D |
Diabetes mellitus |
1 |
| S2 |
Prior stroke or TIA |
2 |
TIA, transient ischemic attack. (From JCS/JHRS 2020 Guideline on Pharmacotherapy of Cardiac Arrhythmias. 2022.341)
Oral anticoagulation before and after cardioversion is effective for preventing strokes in patients with CHD.344 Anticoagulation for 3 weeks before and 4 weeks after cardioversion is advised in patients with AT or AF lasting ≥48 h. Direct oral anticoagulants (DOAC) should be carefully used in those with renal dysfunction.345,346
4.3.4 Nonpharmacological Treatments
Nonpharmacological treatments for arrhythmia and sudden death in adult CHD are broadly classified into catheter ablation, cardiac implantable electrical devices (CIEDs), and surgical treatments.
4.3.4.1 Catheter Ablation
Catheter ablation is a therapy to electronically inactivate the tissue that causes arrhythmia. In addition to radiofrequency ablation,347 which has evolved from direct current ablation,348,349 there are cryoablation,350 laser ablation,351 and chemical ablation.352 More recently, electroporation, a new energy source, has been reported.353 Balloon catheter ablation is another type of device specifically introduced for pulmonary vein isolation.354–356 Computer-generated 3D imaging systems, such as CARTO (Biosense Webster), EnSite NavX (Abbott), and RHYTHMIATM (Boston) have been developed to navigate the catheter against cardiovascular morphologies other than normal. Niobe (Stereotaxis), which allows for the remote manipulation of catheters using a strong magnetic field from outside the body, is useful in patients with complicated malformations.357
a) Atrioventricular Reciprocating Tachycardia and Atrioventricular Nodal Reentrant Tachycardia
AVRT is a reentrant tachycardia that propagates between the atrium and the ventricle via the AV node and an accessory pathway. Patients with the Ebstein malformation,358,359 discordant AV connection (as seen in ccTGA) and heterotaxy syndrome, are known to possess accessory pathways at a high incidence.360,361 The Wolffe-Parkinson-White (WPW) syndrome occurring after reparative cardiac surgery has been reported as caused by electrical junction of the atrial and ventricular tissues.362 The details of AVNRT associated with congenital malformations are not well known.363,364 Ablation therapy has been used to treat both fast and slow conduction pathways that form a reentrant circuit. The anatomy of the AV node is highly variable in CHD, and it is difficult to accurately locate the site of a slow conduction pathway. In this respect, cryothermal mapping has been applied clinically, which is a method of determining the site of ablation by repeated freezing and rewarming.365
b) Atrial Tachycardia
A common arrhythmia is AT that occurs after cardiac repair. AT episodes increase according to the surgical insults to the atria, severe postoperative overload to the atria, and prolonged term after surgery.366–368 Ablation therapy plays an important role in the treatment of AT associated with CHD, as drug therapy alone is mostly insufficient. Also, the side effects of drugs are often unacceptable, producing hypotension and cardiac dysfunction. Arrhythmia mapping systems are useful tools that integrate 3D images of the heart with electrophysiological information on the arrhythmias.318,369,370 When all types of AT are induced and sustained steadily during a catheter ablation procedure, the propagation patterns of the tachycardia can be precisely identified.371 For uninducible or nonsustained tachycardia, it is recommended to extensively ablate low voltage areas or a narrow conduction channel, which are caused by abnormal myocardial tissues and detected by the arrhythmia mapping system.372 Although there have been significant technical advances in catheter ablation, the recurrence rate after AT ablation associated is relatively high in CHD. Commonly, a hybrid treatment of medication, pacing, and surgery is frequently carried out.
c) Atrial Fibrillation (AF)
AF is a common arrhythmia in the normal heart without organic heart disease. Most cases of lone AF originate from the pulmonary venous sleeves, and pulmonary vein isolation (PVI) plays a primary role in catheter ablation therapy.373,374 In contrast, AF in CHD is usually associated with organic changes of the atria; commonly originating from pathologically damaged atrial myocardia other than that around the pulmonary veins.375 Having said that, the pulmonary venous region is not entirely unrelated to AF even in CHD. Some reports describe that PVI before device closure of the atrial septal defect reduces the recurrence rate of AF in the longer term.376 There are also reports mentioning PVI in other cardiac malformations and postoperative AF.377,378
d) Ventricular Tachycardia and Ventricular Fibrillation
Incisions and suture lines onto the ventricles are indispensable in certain surgical repairs, but they cause postoperative ventricular arrhythmias. Some VTs are induced reproducibly and mappable with stable hemodynamics during tachycardia. As is the case with AT ablation, the origin and reentry circuit are identified, and the origin is ablated and the circuit is blocked.379,380 The ventricular muscle is thicker than the atrial structure. Scar tissue may surround and guard the target lesions. These features can cause ablation of the origin or the circuit to be incomplete. That is why VT ablation in CHD is more refractory than in normally structured hearts. VT associated with CHD should, in principle, be treated by placing an implantable cardioverter-defibrillator (ICD), as used in the treatment strategy for VT associated with other organic heart diseases.
4.3.4.2 Cardiac Implantable Electric Devices
CIED include transvenous pacemakers, leadless pacemakers, biventricular pacemakers (cardiac resynchronization therapy), transvenous implantable defibrillators, subcutaneous implantable defibrillators, and insertable cardiac monitors. WCDs (wearable cardioverter defibrillators) are just as important as ICD, but are not included in this CIED criterion.
a) Pacemaker
A pacemaker with atrial antitachycardia function is used for patients with bradyarrhythmia who also have episodes of AT or AF. The types of CHD that are suitable are: inherent sinus nodal dysfunction or AV conduction disturbance, and acquired dysfunction of the heart rhythm induced by cardiac surgery. A congenitally malfunctioning sinus node is often seen in left isomerism (polysplenia) and left juxtaposition of the atrial appendages, whereas acquired sinus nodal insufficiency is common after intra-atrial redirection of blood, the Fontan-type procedure, or the Glenn procedure. Congenital impairment of AV conduction is well known in ccTGA or AV septal defect, whereas acquired AV block is caused by maneuvers to the ventricular septum (e.g., closure of VSD and relief of obstruction across the left ventricular outflow tract). A variety of indications are listed for pacemaker implantation; that is, subjective symptoms associated with bradycardia, decreased cardiac function because of bradycardia or AV dissociation, ventricular arrhythmias, escape rhythm with wide QRS complexes, advanced AV block with no postoperative recovery expected, AV conduction disturbances with an average daytime heart rate <50 beats/min, sinus dysfunction with a mean daytime heart rate <40 beats/min, cardiac pauses >3 s, rate maintenance required, and refractory SVT that is responsive to atrial antitachycardia pacing.175,381 Pacemaker implantation for CHD has some limitations. Epicardial leads are more realistic rather than transvenous leads under certain circumstances. Venous access to the heart mass may be unfeasible. An intracardiac shunt may persist, which could pose a problem of venous thrombosis and eventual systemic embolism. Recently, a small leadless pacemaker that is implanted within the heart cavity using a catheter through the femoral vein has been developed.382
b) Implantable Cardioverter Defibrillator (ICD)
The ICD is a device that automatically provides antitachycardia pacing, cardioversion, and defibrillation in the event of a fatal ventricular arrhythmia. For patients with CHD who have limited access routes to the heart or persistent intracardiac shunts, placement of epicardial leads has been the method of choice for the purpose of sensing. The shock coils are located on the epicardium or under the skin. A subcutaneous implantable cardioverter-defibrillator (SICD) does not require the chest to be opened. Both the defibrillator device set in the left axilla and the defibrillation lead at the anterior chest wall are implanted under the skin. The downside of this product is that pacing for bradycardia and antitachycardia pacing are not applicable.383,384 Indications for ICDs include secondary prevention to minimize recurrent lethal episodes in patients with a history of resuscitation from VF or VT, and primary prevention in those without lethal events but at risk of sudden cardiac death (Table 20).151 Because only a small number of CHD cases have been accumulated in the literature, indications have yet to be clarified on a scientific evidence basis.
Table 20. Recommendations and Evidence Levels for ICD for CHD
| |
COR |
LOE |
GOR
(MINDS) |
LOE
(MINDS) |
ICD is recommended for CHD patients who are survivors of cardiac arrest due to VF or
hemodynamically unstable VT with irreversible cause |
I |
B |
A |
IVa |
ICD is recommended for patients with CHD and symptomatic sustained VT (catheter ablation or
surgical repair may offer a possible alternative in carefully selected patients) |
I |
B |
A |
IVa |
ICD should be considered for patients with CHD who have recurrent syncope of undetermined origin,
and the presence of either ventricular dysfunction with systemic ventricular ejection fraction ≤35% or
inducible ventricular arrhythmias in electrophysiological study |
IIa |
B |
B |
IVa |
ICD should be considered for patients with repaired tetralogy of Fallot and >3 risk factors for sudden
cardiac death (left ventricular systolic or diastolic dysfunction, non-sustained VT, QRS duration ≥180 ms,
extensive RV scarring, or inducible sustained ventricular arrhythmias in electrophysiological study) |
IIa |
B |
B |
IVb |
ICD should be considered for patients with CHD, and ventricular dysfunction with systemic ventricular
ejection fraction ≤35%, non-sustained VT, and NYHA class II or III symptoms |
IIa |
C |
C1 |
IVb |
ICD may be considered for CHD patients after surgical revascularization for an anomalous origin of
the coronary artery with a history of VF |
IIb |
C |
C1 |
V |
| ICD is not recommended for CHD patients with a predicted life expectancy ≤12 months |
III |
C |
C2 |
VI |
ICD is not recommended for CHD patients who do not give consent or cannot cooperate with treatment
because of significant psychiatric illness or other causes |
III |
C |
C2 |
VI |
ICD is not recommended for CHD patients with VT or VF due to an obvious acute cause (e.g., acute
ischemia, electrolyte imbalance, or drugs) that is determined to be preventable by treating the cause |
III |
C |
C2 |
VI |
ICD is not recommended for CHD patients with frequent VT or VF that is uncontrollable with
antiarrhythmic medications or catheter ablation |
III |
C |
C2 |
VI |
ICD is not recommended for NYHA Class IV patients with drug-refractory congestive heart failure who
are not candidates for cardiac transplantation, CRT, or insertion of a LVAD |
III |
C |
C2 |
VI |
ICD requiring endocardial leads is not recommended for CHD patients with intracardiac shunts (risk
assessment with respect to hemodynamic circumstances, concomitant anticoagulation, shunt closure
before endocardial lead placement, or alternative approaches for lead access should be individualized) |
III |
B |
D |
IVb |
CHD, congenital heart disease; COR, class of recommendation; GOR, grade of recommendation; ICD, implantable cardioverter defibrillator; LOE, level of evidence; LVAD, LV assist device; NYHA, New York Heart Association; VF, ventricular fibrillation; VT, ventricular tachycardia.
(From JCS/JHRS 2019 Guideline on Non-Pharmacotherapy of Cardiac Arrhythmias. 2021.151)
4.3.4.3 Antiarrhythmic Surgery
Surgical treatment consists of direct maneuvers against the causes of arrhythmia and secondary effects by means of repairing underlying hemodynamic impediments. The surgical treatments of AF have been studied in an extensive series of adult patients with organic heart disease. Based on the results, these procedures have been indicated as Class I; the antiarrhythmic procedures are carried out in conjunction with cardiac surgery for other lesions.151 In CHD, direct antiarrhythmic maneuvers have been introduced and modified; for example, the so-called right atrial maze procedure, division of an accessory pathway, ablation of arrhythmic substrates for VT, and left atrial manipulation for AF.130 The sites and the techniques of intraoperative ablation should be properly arranged in light of the substrates and nature of the tachycardia targeted for treatment. Electrophysiological studies should be conducted preoperatively whenever possible.
4.4 Metabolic Syndrome
4.4.1 Overview
Patients with CHD increasingly survive into adulthood and can then suffer from common adult comorbidities, such as hypertension, diabetes mellitus, dyslipidemia, obesity, and renal impairment. In general, these metabolic disorders are closely associated with progressive atherosclerosis even in children and adolescents.385,386 Coronary arterial disease naturally affects long-term outcomes in adult CHD (ACHD) patients,387 so proper evaluation and management are essential in this growing field.
4.4.1.1 Hypertension
a) Features
Hypertension in ACHD is prevalent, being seen in 24–47%.388–391 Similar to the general population, male sex,388 and older age391 are major risk factors. On top of these, there are several unique pathogeneses. Cyanotic CHD often promotes renal impairment,392,393 and nearly 60% of patients with coarctation of the aorta (CoA) develop hypertension.394–396 Arterial compliance is low in CoA, and does not become normal even after successful repair.
b) Management (Table 21)
Table 21. Recommendations for the Management of Metabolic Syndrome and CKD in ACHD
| |
COR |
LOE |
Comprehensive approach, including appropriate food restriction, physical exercise,
and smoking cessation for the management of metabolic syndrome and CKD is
recommended |
I |
A |
Yearly measurement of office blood pressure and/or monitoring of ambulatory/home blood
pressure is recommended |
I |
C |
DM screening is recommended every 3 years for patients aged over 45 years or for
patients aged under 45 years with BMI ≥25 kg/m2 and other DM risk factors |
I |
C |
Among the screening tests for DM, OGTT is recommended in addition to measurement of
blood sugar or HbA1c as necessary |
I |
A |
For the screening of dyslipidemia, collecting blood samples in the fasting state every 5
years is recommended |
I |
C |
Of the measurement of serum LDL-cholesterol, HDL-cholesterol, and triglyceride, the non-HDL
cholesterol level is recommended for the screening of dyslipidemia |
I |
A |
| Yearly measurement of height, weight, and BMI is recommended |
I |
C |
Active screening for CKD is recommended, especially in cyanotic ACHD and patients with
Eisenmenger syndrome |
I |
C |
ACHD, adult congenital heart disease; BMI, body mass index; CKD, chronic kidney disease; COR, class of recommendation; DM, diabetes mellitus; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LOE, level of evidence; OGTT, oral glucose tolerance test.
How to manage hypertension in ACHD follows the general adult guidelines for hypertension.397 The guideline for the management of hypertension published by the Japanese Society of Hypertension (JSH) in 2019 describes office blood pressure ≥140/90 mmHg as hypertensive. Blood pressure should be measured or monitored annually in the clinic or at home (Class I).398 When secondary hypertension is suspected on medical interview, physical examination, and general laboratory examinations, it is important to investigate specific risk factors in ACHD; sleep apnea syndrome,238 repaired coarctation of the aorta (CoA) and recurrent hypertension,399 and use of nonsteroidal anti-inflammatory drugs. In patients with cyanotic malformations, it may be worth screening for renal impairment, pheochromocytoma, and paraganglioma.400
Urinalysis, blood glucose levels, hematocrit, lipid panel, basic metabolic panel, and calcium levels are informative. Sarcopenia is not rare in ACHD.235,401 Cystatin C is useful, therefore, for calculating the estimated glomerular filtration rate (eGFR).
It remains unclear which level of blood pressure is an appropriate target for reducing future cardiovascular events. According to the current guidelines for treating heart failure, target systolic blood pressure is 110–130 mmHg for patients with heart failure with reduced ejection fraction and <130 mmHg for patients with heart failure with preserved ejection fraction.238,397
Lifestyle should be modified; controlled sodium intake, food restriction, healthy body mass index (BMI), and smoking cessation. Management for cardioprotection is reasonable using angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers in combination with mineralocorticoid receptor blockers.
4.4.1.2 Diabetes Mellitus
a) Features
It has been reported that diabetes mellitus (DM) occurs in ACHD as frequently as in the general population.388 In another study, fasting glucose was elevated more commonly in the ACHD group compared with the general population cohort (40.4% vs. 9.2%).389 The proportion of patients developing DM between 30 and 45 years old is greater in ACHD than in the general population, with a hazard ratio of 1.35. Furthermore, the phenomenon is more prominent for cyanotic ACHD than noncyanotic ACHD, the hazard ratio being 1.93.402
Nearly 40% of ACHD patients have impaired glucose tolerance, which in turn promotes low high-density lipoprotein cholesterol level.390,403,404 Fasting hypoglycemia is associated with poor prognosis.405 In patients with trisomy 21, type 1 DM is not rare, seen in 1.4–10.6%.406
b) Management
DM screening in ACHD is recommended for patients over 45 years old, or in those with increased BMI of over 25 kg/m2. Even when blood sugar profiles appear normal, DM screening should be carried out every 3 years.398,407 An oral glucose tolerance test has diagnostic benefit.408 Management of DM in ACHD follows the general strategy for treatment of DM.408 Lifestyle should be modified prior to administration of drugs. In the current guidelines for the treatment of heart failure,238,409 sodium-glucose co-transporter 2 (SGLT2) inhibitors are recommended in patients with heart failure and DM.410 They are also the clinical choice in those with DM and at risk of heart failure.411 These experiences may be valid for ACHD. In contrast, use of thiazolidinediones is contraindicated in heart failure patients,238,409,411 and should be prescribed very carefully in the ACHD cohort.
4.4.1.3 Lipid Abnormalities
a) Features
Dyslipidemia is seen in 27–60%.389–391 A Japanese study described mean total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglyceride levels within the normal range in 224 patients with ACHD.412 Similar results were shown by other investigators.413 Cholesterol levels are lower in patients with cyanotic ACHD than in those with noncyanotic types.414,415
b) Management
Diagnosis and management of dyslipidemia in ACHD follows the guidelines for the general population.416 Medication would be considered when lifestyle modification is ineffective. The role of conventional medical therapy remains uncertain in ACHD.
In the arterial switch procedure, the sympathetic nerves are transected,417 so the vasomotor function of the coronary arteries becomes abnormal,418 and the carotid intima–media thickness increases.419 Atherosclerotic events are a higher risk under this circumstance. Atorvastatin and ramipril decrease the serum markers of vascular inflammation in normotensive CoA patients in whom these markers are abnormal.420,421 Otherwise, routine use of statins is not recommended in ACHD; heart failure alone is not a definite indication for statins.422
4.4.1.4 Obesity
a) Features
BMI of 25–30 kg/m2
is seen in 23–32%,388,390,423 and BMI ≥30 kg/m2
in 8.8–21%.388–390,423,424 Physical exercise may be strictly restricted by medical staff or by patients themselves.425 The metabolic response to surgical stress can be profound and abnormal, induced by use of cardiopulmonary bypass particularly in neonatal surgery.414,426 These are factors for increasing body weight. Adult patients with moderate or complex malformations are paradoxically more underweight rather than obese.423,424,427
b) Management
Body height, weight, and BMI should be measured annually (Class I).398 Lifestyle modification, calorie restriction, and appropriate physical exercise should be planned comprehensively to avoid obesity. Rapid increase in body weight is known to promote coronary artery disease.428 Careful attention should be paid to the growth trajectory of body weight in childhood. The so-called obesity paradox may apply in ACHD,423 and thus it is also essential to monitor the baseline body weight and consecutive changes. Hypoalbuminemia is an indicator of malnutrition, illustrating a less ideal prognosis of heart failure429 also in ACHD.430,431
4.4.1.5 Chronic Kidney Disease
a) Features
Renal impairment is frequent in ACHD, of whom approximately 50% demonstrate decreased eGFR (<90 mL/min/1.73 m2).432 This is particularly the case in cyanotic ACHD and affects two-thirds of patients with Eisenmenger syndrome.432 In patients with the Fontan circulation, 10% have renal function impaired by the age of 13 years and >50% by 26 years old.433 A moderate or severe degree of impairment (eGFR <60 mL/min/1.73 m2) is significantly higher in ACHD than in the general population, with a hazard ratio of 18 in noncyanotic and 35 in cyanotic ACHD.432 Proteinuria and albuminuria are also common in ACHD.393,434
There are a variety of reasons for renal impairment in ACHD, including cyanosis,393 history of multiple use of cardiopulmonary bypass,435,436 repeated use of diuretics or contrast medium,432 elevated central venous pressure,437 and low cardiac output.432
Renal impairment impacts on outcome of ACHD. Moderate or severe GFR reduction (<60 mL/min/1.73 m2) provides a 6-year mortality rate nearly 5-fold higher than normal GFR does, and 3-fold higher than mild GFR reduction (60 to 89 mL/min/1.73 m2).432
b) Management (Table 21)
Based on practice guidelines,438 eGFR of 90 mL/min/m2
is the cutoff value of impaired renal function in ACHD. Renal impairment is so common in ACHD that routine screening of renal function is recommended (Class I). Patients with reduced volume of skeletal muscles or sarcopenia are common. Cystatin C is useful for calculating the eGFR.439 Particularly, the Fontan patients have a lower index of lean body mass than a control group. The eGFR value derived from cystatin C is likely associated with their prognosis.393,440 The renal resistive index is another useful indicator for predicting prognosis of Fontan patients.441 The index could be assessed noninvasively by ultrasound, and reflects renal impairment. Management of renal impairment specific to ACHD patients has yet to be established. Lifestyle modification is fundamental. Atherosclerotic risk factors are to be managed appropriately. Use of drugs should be reviewed meticulously, because of the effects on renal function.398
4.5 Aortopathy
4.5.1 Pathophysiology
4.5.1.1 Causes of Aortopathy
Atherosclerosis and endothelial dysfunction make the arteries stiff. The mechanism is identical between non-CHD and CHD. Stiff arteries prove to be the cause of aortic aneurysm/dissection, afterload mismatch, coronary arterial malperfusion, and hypertension. Increase in the ascending aortic diameter is approximately 0.02–0.07 mm/year in healthy normal adults.442 Histologically, cystic medial necrosis is identified within the middle layer of the aortic wall. The medial tissue of the ascending aorta shows degeneration with fibrosis, fragmentation of the elastic fibers, and loss of smooth muscle cells.443 In adult CHD or even younger, such aortopathy is commonly observed444 (Table 22).
Table 22. Aortopathy in CHD (Excluding Marfan Syndrome)
| Bicuspid aortic valve (after Ross procedure) |
| Aortic coarctation |
| Truncus arteriosus |
| VSD with pulmonary atresia |
| TOF |
| DORV |
| TGA |
| Single ventricle |
| Fontan circulation |
| HLHS |
CHD, congenital heart disease; DORV, double outlet right ventricle; HLHS, hypoplastic left heart syndrome; TGA, transposition of the great arteries; TOF, tetralogy of Fallot; VSD, ventricular septal defect. (Reproduced from Guidelines for Management of Congenital Heart Diseases in Adults [JCS 2017]. 2018.444)
Marfan syndrome is well-known as an abnormal aortic wall of genetic cause. The aortic root is progressively dilated as a result of degenerative microfibril architecture and consequently loss of integrity of the extracellular matrix. Fibrillin-1 (FBN1) mutations, abnormal transformation of growth factor-β signaling, and dysregulated matrix metalloproteinases have been implicated in Marfan syndrome.445
4.5.1.2 Diagnosis and Treatment of Aortopathy
Computed tomography and magnetic resonance imaging are useful to illustrate the entire aorta. There is no guideline for regularly checking up how stiff or distensible the aortic walls are in CHD.
How to treat CHD with aortic disease is not evidence-based as yet. Clinically, β-blockers and/or angiotensin II receptor blockers (ARB) are often prescribed for Marfan syndrome. Randomized control studies are currently in progress in this respect. Hopefully, some evidence will be achieved in the near future in terms of medication for aortopathy in CHD. Surgical indication for the dilated ascending aorta seems different from that for the usual aortic aneurysms. In general, adult CHD guidelines recommend aortic replacement when the aortic channel is >55 mm in diameter, rather than the 50 mm as set for standard aortic surgery. The speed of enlargement (e.g., increase >5 mm/year) is another factor to take into consideration. The dilated aorta in Marfan syndrome should have a separate criterion (>45 mm diameter or may be even 40 mm).
4.5.2 How Unique Is Aortopathy in CHD?
CHD aortic disease is recognized with the bicuspid aortic valve (BAV), aortic coarctation, and conotrucal abnormalities. The histological findings are basically similar to Marfan syndrome, such as cystic medial necrosis, and generally milder than seen in the genetic syndrome. In general, a markedly dilated sinus of Valsalva is typical in Marfan syndrome, whereas the whole ascending aorta is large beyond the Valsalva sinus in BAV. Aortic dissection and/or aneurysm are much less frequent in CHD. Abnormal hemodynamics, volume and/or pressure overloads, and shared stress onto the aortic wall are other components that significantly influence the development of aortic disease in CHD.
Risk factors for aortopathy in TOF are male sex, right aortic arch, pulmonary atresia, cyanosis, late repair, creation of a central/ Blalock-Taussig shunt, long duration of a shunt-palliated circumstances, and so on.446 Volume overload to the aorta is seen in pulmonary atresia, and after construction of a shunt. Aortic root dilatation leads to secondary aortic regurgitation. When the aorta becomes significantly stiff, the so-called ventricular–aortic decoupling can occur because of afterload mismatch.
5. Infective Endocarditis
Infective endocarditis (IE) is a significant concern in the life-long care of congenital heart disease (CHD). It is a frequent and mortal event. Its incidence is 5.1 to 8.6/100,000 per year447–449 for the general population, 44/100,000 per year in CHD children, and 110/100,000 per year for adult CHD.450 Predicted risk of IE in CHD is as high as 2.4% by the fifth decade, and 4.7%450 by the seventh decade, with a high mortality of 1.9 to 9%.451,452 Surgical treatment is required in 67% once IE occurs.453 In recent years, knowledge has been accumulated regarding timing for surgery from the viewpoint of preventing embolism.454 Early intervention is superior for patients with cerebral infarction,455 while early intervention should be avoided for cerebral hemorrhage.454,456 IE is increasing worldwide nowadays, especially in the elderly.449 As CHD patients are getting older day by day, IE is potentially increasing in the ACHD field. Therefore, guidance to the patients is important, prophylactic antibiotics should be administered appropriately, IE should be diagnosed early, and therapeutic intervention is to be carried out at the optimal timing. Currently, guidelines for IE are at domestic levels in each country. Each guideline has been revised, and reports are being published on changing epidemiology.449,457 This guideline, focusing on the adult patients with CHD, is based on recommendations by the Japanese Circulation Society Guidelines for IE and CHD,444,458,459 and has been modified according to recent evidence.
5.1 Disease Classification Based on IE Morbidity and Mortality
IE is not rare in CHD. It can be lethal, remaining as a challenge in adult CHD care. In particular, previous history of IE, prosthetic valves placed, and extremely complex CHD are risk factors, with cumulative incidence rates of 8.8%, 6.0%, and 1.3%, respectively, over ten years.460 The hazard ratio is as high as 65.4 for prior IE, and 19.1 for prosthetic valves, compared with background-matched controls.460 Risk of IE may be equivalent to that in general population, or regarded as high according to underlying diseases and history of treatments.461 From a practical viewpoint, patients are classified into 2 groups; high-risk group of those who are liable to suffer from severe consequences due to IE (including mortal events), and a moderate-risk group of those without such pessimistic prospects (Table 23). This stratification and grouping is useful when looking for recommendations for antibiotics prophylaxis.458 Our guideline458 recommends prophylaxis in both high- and moderate-risk groups.
Table 23. Risks of IE Long After Congenital Heart Surgery and Recommendations and Level of Evidence for Prophylactic Antibiotic Therapy at Invasive Procedures
| |
COR |
LOE |
GOR
(MINDS) |
LOE
(MINDS) |
High-risk group (susceptible to IE and liable to get into severe problems)
Prophylactic antibiotics should be given at high-risk procedures
Patients with;
• a bioprosthetic/mechanical valve, or an annuloplasty ring
• a previous episode of IE
• unrepaired cyanotic CHD (univentricular physiology, transposition of the
great arteries, tetralogy of Fallot, etc.), including use of a palliative shunt
or a conduit
• CHD repaired (either surgical or interventional) using a prosthetic material
within 6 months after the procedure
• CHD of any types repaired using a prosthetic material and having a
residual shunt or valvular regurgitation (lifelong)
• coarctation of the aorta |
I |
B |
A |
II |
Moderate-risk group
(susceptible to IE but unlikely to get into severe problems)
Antibiotics should be sensibly considered at high-risk procedures
Patients with;
• CHD other than a high-risk or a low risk circumstance
• Congenital valvar disease, including bicuspid aortic valve
• obstructive hypertrophic cardiomyopathy
• mitral prolapse with regurgitation |
IIa |
C |
B |
III |
Low-risk group
(equivalent to the healthy population)
Routine antibiotic prophylaxis is not recommended
Patients with;
• a solitary ASD
• VSD or PDA closed more than6 months ago with no residual shunt
• subsequent to coronary arterial bypass
• isolated mitral prolapse without regurgitation
• innocent heart murmur (either physiological or functional)
• an episode of Kawasaki disease without valvar dysfunction |
III |
C |
C2 |
IVa |
ASD, atrial septal defect; CHD, congenital heart disease; COR, class of recommendation; GOR, grade of recommendation; IE, infective endocarditis; LOE, level of evidence; PDA, patent ductus arteriosus.
The following factors are added to the original Table 29 in the Guideline:
Recommendation grades and evidence classification by Minds.
Types of artificial materials for the valvar procedures.
The element for unrepaired cyanotic CHD.
The bicuspid aortic valve is included in the congenital valvar malformation.
(Modified from the JCS 2017 Guideline for Prevention and Treatment of Infective Endocarditis. 2019.458)
European and American guidelines recommended prophylactic administration of antimicrobial agents only in the high-risk group.457 With new findings in prognosis after IE in hand,460,461 they are modifying their risk stratification. The cohort of patients with congenital valve disease (including bicuspid aortic valve) is currently in their moderate-risk criterion.461–463 Still, these patients are to be in the list of antibacterial prophylaxis. Their amendment goes along the Japanese guideline for prevention and treatment of infective endocarditis (JCS 2017).458 Our present guideline follows the preceding recommendation that prophylactic use of antimicrobial agents is appropriate in those with a moderate risk as well as in those with a high risk (Table 23).
5.2 Recommendations for Prophylactic Antibiotics During Invasive Procedures in Terms of IE Risk Stratification
Invasive procedures are classified as risk factors of IE (Table 24).
Table 24. Situations and Procedures at Risk
| 1. High-risk procedures |
• Dental procedure: All invasive dental procedures that induce bacteremia with bleeding (oral surgery such as
tooth extraction, periodontal surgery, implant surgery, scaling, infected root tube treatment, etc.) |
| • Otorhinolaryngeal procedure: Tonsillectomy / adenoidectomy |
| • Cardiovascular procedure: Implantation of pacemakers and implantable cardioverter-defibrillators |
| 2. Moderate to high-risk procedures |
• Surgical procedure for local infected site: Abscess drainage and endoscopic examination and treatment of
infected foci (including biliary obstruction) |
| • Cardiovascular procedure: prosthetic valves or devices in the cardiovascular system |
| • Transurethral prostate resection: especially inpatient with prosthetic valve |
| 3. Moderate risk procedures |
• Gastrointestinal procedure: Sclerotherapy for esophageal varices, esophageal stricture dilatation, mucosal
biopsy and polypectomy by colonoscope or rectoscope, biliary surgery |
• Urinary or genital procedure: Urethral dilatation, vaginal delivery, and vaginal hysterectomy, removal of uterine
contents, therapeutic abortion, insertion, and removal of intrauterine contraceptive devices |
| • Cardiovascular procedure: Cardiac catheterization and percutaneous intravascular intervention |
| • Skin incision for surgery (especially in cases of atopic dermatitis) |
| 4. Low-risk procedures |
• Dental procedure: Local infiltration anesthesia from non-infected sites, orthodontic procedures, and pulp
extraction procedures |
| • Respiratory procedure: Bronchoscopy and laryngoscopy, endotracheal intubation (nasal and oral) |
| • Otolaryngological procedure: Tube insertion for tympanic chamber perforation |
| • Gastrointestinal procedure: Transthoracic echocardiography, Upper gastric endoscopy (including biopsy) |
• Urology and genital procedure: urethral catheter insertion, transurethral endoscopy (cystourethroscopy,
pyeloureteroscopy) |
| • Cardiovascular procedure: insertion of central venous catheter |
(Charted from the JCS 2017 Guideline for Prevention and Treatment of Infective Endocarditis. 2019.458)
Prophylactic administration of antibiotics is strongly recommended during invasive procedure for patients in the high-risk group of IE. It is not unreasonable to use for those in the moderate-risk group, but unnecessary for those in the low-risk group.458 Our stance is more proactive for prophylaxis, in contrast to the Western guidelines. They are reluctant basically; recommending it only for the high-risk group464 or even not recommending it in principle.465 IE-related mortality is higher in Japan even in the moderate-risk group.451 Difference between the moderate- and the high-risk groups is unclear, and their cut-off line has changed over time.461 Of course, routine use of prophylactic antibiotics for all cases and for all invasive procedures does not sound sensible. Use of antibiotics has negative aspects, causing side effects and producing resistant strains. Some invasive procedures do not bear much opportunity for the germs to get into the blood stream. Scientific evidence should be respected for the benefits of anti-microbial agents.
5.3 Oral Hygiene and Others
Oral hygiene is an issue to minimize IE.466 Appropriate brushing, flossing, and regular dental check-up are recommended. Piercing and tattoos are not an excellent idea. Skincare guidance is advised for atopic dermatitis.444
5.4 Diagnosis
The modified Duke criteria467 are referred in the adult CHD (level C). Complications in this field are: valvar regurgitation, heart failure, perivalvar abscess, prosthetic valve failure, systemic embolism, cerebral embolism, arrhythmia, abscess formation, and mycotic aneurysm. These are found in 50% of patients (level C).451 Trans-thoracic echocardiography does not clarify the circumstance entirely. Infected tissues are often masked by prosthetic materials. Trans-esophageal echocardiography (Class I), contrast multi-slice CT (Class IIa), and brain MRI (Class IIb) provide informative data.458 Ga-scintigraphy is additionally used (Class IIb).458 F-FDG PET/CT is useful in patients with prosthetic materials463 (class IIa).458
5.5 Treatment
For treatment, the IE guidelines of the Japanese Circulation Society should be referred.458 Surgical therapy is indicated in patients with heart failure, infection inadequately controlled, abscess formation, and impending embolism. On the other hand, surgery barely happens when patients present intracranial hemorrhage, coma, severely disabling stroke, or other severe comorbidities that pose a risk of surgical complications to the central nervous system.458 It is often difficult to cure IE solely with antibiotics. This is particularly true for patients palliated by a shunt and those repaired using internal or external conduits. In such instances, surgical intervention should be arranged at the earliest opportunity.454,455 Cerebro-neurological complications can occur perioperatively, embolic episodes may precede in case surgery is delayed, and antibacterial therapy must be continued for a certain period of time postoperatively. These three aspects need to be balanced, seeking for the optimal strategy.
6. Physical Exercise and Congenital Heart Disease
Children grow both mentally and physically healthy when developing physical strength based on good cardiopulmonary function. This is important for daily management and school life even if children have congenital heart disease (CHD). Physical exercise has proven to be important not only for development of the respiratory and the circulatory systems at the growth stage, but also for mature adults in terms of the metabolic system,468,469 the immune system, and mental health.470 In this respect, lifestyle guidance is one of the major roles of pediatric or adult cardiologists and adult CHD specialists in the long-term management of patients. On the other hand, there are many exercise-related heart accidents.471–474 It is necessary to contemplate proper types and amounts of exercise for daily medical care.
6.1 Evaluation of Exercise Tolerance
It is ideal if exercise time and maximal oxygen uptake (peak V̇O2) can be measured in a cardiopulmonary exercise test combined with exhaled gas analysis using a treadmill or ergometer. Exercise stress testing is feasible in healthy children aged 5 years or older, providing objectively useful information for lifestyle guidance and management at school. Not all hospitals can carry out exercise stress tests, so an alternative would be a 6-minute walk test in patients whose clinical condition has deteriorated.475,476 This test is of practical use in patients whose pulmonary hypertension or heart failure is too severe to pursue maximal exercise load. Another observational method is to score the activity level of daily life for quantitative evaluation, as proposed in Health-Behavior Scale-Congenital Heart Disease.477
Exercise ability has 2 aspects: aerobic exercise ability is known as physical strength and the other ability is skills, which are basically independent of physical strength. The latter is important in daily life on top of physical fitness,478 though cannot be evaluated objectively on a universal consensus at present.
6.2 Exercise Tolerance in CHD Patients
Patients undergoing repair of simple CHD, such as ventricular or atrial septal defect (VSD, ASD), show good exercise tolerance equivalent to that of healthy subjects. In adults with untreated ASD, exercise tolerance is usually around 60% of normal, depending on patient’s age, systemic-to-pulmonary blood flow ratio, and right ventricular pressure. Exercise tolerance should gradually improve and eventually reach the normal range in the longer term after surgical repair.479–481 In patients whose VSD is hemodynamically insignificant (surgical closure not indicated) or has spontaneously closed, peak V̇O2
is equivalent to normal. In those in whom the VSD has been surgically closed, exercise capacity is not worse than that of the normal population.482
Most patients with repaired tetralogy of Fallot are unaware of limited capacity in their daily lives; their exercise tolerance is as low as around 70% of normal. The discrepancy indicates that subjective symptoms are not always pertinent as an indicator for planning therapeutic interventions.483 Exercise tolerance is associated with many determinant factors: aging, higher age at repair, variability of heart rate, impaired respiratory function, pulmonary regurgitation, and biventricular dysfunction among others.484
In Ebstein malformation, not a few reports describe that the peak V̇O2
value is 50–60% of normal when surgical intervention is decided.485–487 Functional class improves after surgery, whereas peak V̇O2
does not improve drastically. In most patients, the value remains within a subnormal range.485 This is an obvious contrast to the favorable recovery after repair of ASD, despite the fact that the hemodynamic background is volume overload to the right heart in both diseases.486 Impaired exercise tolerance is almost always the case in asymptomatic children with Ebstein malformation. Lower oxygen saturation and reduced left ventricular volume correlate with exercise intolerance.487
The Fontan circulation has factors intricately associated with declining exercise tolerance.206,488 Its first line is low cardiac output with heart rate ineffectively responding to physical exercise. Behind this interrelated are imbalanced activity of the cardiac sympathetic nerves, vascular dysfunction, disorder of neurohumoral factors, diastolic dysfunction of the ventricles, and impaired baro-/chemical receptors. It is repeatedly reported that peak V̇O2
is around 60% of normal in Fontan patients. Heart rate is 10% higher than normal at rest, while the maximal rate is lower.
6.3 Exercise and Arrythmias
Supraventricular or ventricular extrasystoles are known to decrease or even disappear as exercise intensity increases in children and young adults without heart disease. CHD patients are different, particularly postoperative patients. These arrhythmias can get worse quantatively and/or qualitatively during exercise. Before they participate in athletics and extra physical activities, the potential for arrhythmias should be scrutinized by exercise stress test or Holter ECG; that is, whether arrhythmias will occur and how significant they would be. In particular, exercise stress test is strongly recommended for adult patients with complex CHD who have survived surgical repair in childhood; they have arrhythmic episodes rather frequently. The investigation should be arranged before participating in exercise activities (Class IIb). Significant arrhythmias do not necessarily correlate with exercise intolerance. The settings in the exercise stress test do not necessarily reflect all activities in daily life of the patients, either. Nobody can perfectly predict cardiac accidents.324 The best thing clinicians can do is to meticulously consider for each patient whether or not certain exercise activities are suitable on the basis of the patient’s condition and objective data from investigations.
In addition, automated external defibrillators (AED) should be better distributed widely. It is wise to provide focused training for staff (cardiopulmonary resuscitation training including use of AED) at schools and offices.473
6.4 Indices of Cardiopulmonary Exercise Testing
6.4.1 Heart Rate
The heart rate response during exercise is determined mainly by body temperature, sinus nodal function, and autonomic nervous activity of the heart. In some occasions, in turn, sinus nodal dysfunction is diagnosed because of poor heart rate increase during exercise. Sinus nodal function tends to decline in left isomerism (polysplenia), after extensive surgical manipulation of the atria such as the Senning procedure, and when the right atrium is markedly enlarged because of tricuspid regurgitation.489 Poor heart rate increase during exercise is a comprehensible marker for predicting future cardiac accidents in adult CHD patients as seen in adults with acquired heart disease. Delayed settlement of heart rate in the early stage of exercise recovery is similarly indicative of abnormal heart rhythm regulation.490 Denervation is unavoidable after surgery. CHD surgery requires a thoracotomy and causes direct injury to the heart. Autonomic nervous activity of the heart is often impaired to a varying degree.491,492 When the parasympathetic nervous function is damaged exclusively, heart rate may not increase as expected during the initial stage of exercise or during light exercise. Interpreting heart rate variability is not quite straightforward for evaluating the postoperative condition of patients after CHD surgery. Heart rate does not increase ideally after reconstruction of the right ventricular outflow tract or the Fontan type procedure, and at the same time the pattern of heart rate restoration in the early stage of motor recovery is abnormal.493,494
6.4.2 Blood Pressure
Blood pressure (BP) is determined by peripheral vascular resistance and cardiac output. Maximal systolic BP is closely related to maximal cardiac output during exercise. When cardiac output does not increase on exercise, systolic BP increases only a little or even decreases. Following repair of complex CHD, increase in BP could be poor due to residual hemodynamic abnormalities. Exercise-induced hypotension is a high risk for ventricular fibrillation.495 In patients with repaired aortic coarctation, the BP difference should be measured between the upper and lower limbs at rest, and also immediately after maximal exercise load. The difference may grow during exercise even if there was no hypertension at rest.396,496–498 This phenomenon is known to reveal residual stenosis. Furthermore, hypertension on exercise occurs in those without residual or recurrent aortic obstruction, in particular when repair of coarctation is carried out late. The configuration of the aortic arch may or may not affect hypertension on exercise.499 Residual coarctation, even if mild, appears to be a risk factor for elevated BP during exercise.500 Antihypertensive therapy is reasonable for such masked hypertension from the viewpoint of preventing damage to the organs. A standard for treatment has not been established for how BP on exercise should be taken into account. When myocardial hypertrophy is present in patients without significant stenosis through the aortic pathway, the remedy would consist of appropriate lifestyle guidance (regulated salt intake, obesity control, etc.) and antihypertensive therapy (Class IIb).
6.4.3 Peak Oxygen Uptake (V̇O2)
Peak V̇O2
is a useful indicator of cardiopulmonary reserve in patients with heart disease (Table 25). Peak V̇O2
is defined as oxygen uptake at the maximal exercise load judged by the following criteria: (1) gas exchange ratio at maximal load (=carbon dioxide excretion/oxygen intake) ≥1.09 (≥1.05 for young children),501 with the anticipated normal value being around 1.20; (2) heart rate reaching the estimated maximal value; and (3) Borg score of 18–19. The absolute value of peak V̇O2
fluctuates according to the loading method and protocol. A value for normal is set at each institution/hospital, and patients’ peak V̇O2
is indicated as a percentage of the standard value.
Table 25. Main Indices of the Cardiopulmonary Exercise Test
| Indices |
Definition |
| Peak oxygen uptake (peak V̇O2) |
Maximum oxygen uptake obtained from maximum exercise |
| Anaerobic threshold (AT) |
Oxygen uptake above which aerobic energy production is supplemented by
anaerobic mechanisms |
| V̇E/V̇CO2 slope |
Ventilatory efficiency for carbon dioxicide during exercise |
Peak V̇O2
is prognostic; <14 mL/kg/min is an index determining indication for heart transplantation in adults.502 In adults with repaired tetralogy of Fallot or the Fontan circulation, peak V̇O2
indicates how well their hemodynamics are working at the time of investigation and whether potential future risks would be expected.503–505 The situation is slightly different in pediatric patients; future cardiac accidents may not be predicted well by peak V̇O2. Whether the value 14 mL/kg/min sets a reasonable criterion for heart transplantation remains uncertain in pediatric CHD.501,506
Some patients with heart failure demonstrate low peak V̇O2
with relatively long duration of exercise. This is probably because the limited cardiac output is distributed efficiently to working muscles during exercise. Other patients have normal peak V̇O2
with impaired ventricular ejection fraction at rest. Peripheral tissue perfusion is adjusted by vascular endothelial function, which regulates blood flow distribution and increases oxygen extraction in the skeletal muscles. Thus, the peak V̇O2
value can appear reasonably high for the low cardiac output.507 This adaptative mechanism will increase the oxygen debt in the organs during exercise.
Patients are not always keen to achieve their maximal exercise load. Forcing them to do so could be dangerous on some occasions depending on their diseases, their condition, and age. In this respect, the anaerobic threshold (AT) is a useful index for estimating exercise tolerance objectively on submaximal load (Table 25). The AT indicates the range of aerobic exercise.508 The AT point appears at heart rate 120–130 beats/min on exercise in healthy subjects. AT is important for instructing daily physical activity and determining the optimal load in cardiac rehabilitation. The amount of load 30–60 s before reaching the threshold for anaerobic metabolism is a guideline for rehabilitation.
On top of these objective and numerical indicators, functional classifications that have been used conventionally are similarly useful for predicting prognosis and assessing patient’s quality of life. A multifaceted approach is the way to go.509
6.4.4 Ventilatory Efficiency (V̇E)
This index indicates how effective ventilation is based on changes in ventilation volume with respect to carbon dioxide (CO2) production (Table 25). There is a linear correlation between CO2
excretion and ventilation during exercise and the slope of this line is named as the V̇E/V̇CO2
slope. The minimal V̇E/V̇CO2
value or that at the AT point also represents the efficiency of ventilation. Either of these are normally <30. They are more sensitive than peak V̇O2
as prognostic markers in patients with heart failure, being used for predicting cardiac accidents in adult CHD patients.510 In heart failure and abnormal pulmonary circulation, the V̇E/V̇CO2
value rises and the slope becomes steeper, because the proportion of dead space ventilation goes up during exercise and a greater ventilation volume is needed for excreting CO2. It is known that attenuated ventilation efficiency is also associated with increased sensitivity of central and peripheral chemoreceptors. In patients with CHD, V̇E/V̇CO2
is a complicated product affected also by hypoxemia, abnormally developed respiratory system (alveoli, airways, and the thoracic muscles), and unique hemodynamics.510–513
6.5 Cardiac Rehabilitation
Many reports have stated that cardiac rehabilitation is of practical use in pediatric and adult CHD patients.514–518 Early participation in physical exercise promotes aerobic exercise capacity, and the effect lasts for some time. Physical exercise and recreational activities are also advantageous for mental health and self-establishment.519,520 With this in mind, participating in athletic activities is encouraged unless medically contraindicated.521 Home cardiac rehabilitation is effective for adult CHD patients. Exercise should be arranged at a permissible level.522 Regular guidance and monitoring are therefore advised.
7. Pregnancy and Delivery in Congenital Heart Disease
Evaluation of the CHD patient’s condition is important because management of medication or re-intervention may be needed after definitive repair.
Patients with simple CHD should be able to conceive and give birth as in the general population. Among patients at a moderate or severe risk, including those who have undergone surgical repair of complex cardiac malformations, maternal or fetal complications may emerge during pregnancy and after delivery. In recent years, there has been an increasing number of female patients with complex CHD who wish to have children. Fontan patients were not expected to have the opportunity of reproduction in the past, but the dream has come true.523,524 Still, pregnancy is a condition of considerably high-risk for both the mother and the fetus. It is necessary to evaluate cardiac function precisely prior to pregnancy, to consider interventions and reparative surgery before conception in case they are needed, to select an appropriate contraceptive method, and possibly to choose termination of pregnancy when carrying on is medically unreasonable. It has been reported that the risks of fetal miscarriage, low birth weight and other fetal risks are also higher in patients who have undergone CHD repair compared with normal healthy subjects.525 The most important thing is to have a counseling session, together with the obstetrician, for each patient and her spouse before she gets pregnant where the feasibility and downsides of the reproduction process can be discussed.526
During pregnancy and around childbirth, bodily regulation changes drastically in the maternal circulatory, respiratory, hematological, endocrinological, and autonomic nervous systems.527 It is important to determine how these changes will affect the anatomy and inherent pathology of the underlying heart disease, and what risks the changes might pose to the mother and fetus.528 The high-risk diseases listed in Table 26 are those for which pregnancy should be avoided.523 They are also high-risk for the fetus. These diseases may lead to lethal complications such as heart failure, arrhythmia, thromboembolism, and aortic dissection during pregnancy and after delivery. Female patients with heart disease should be informed that there is still insufficient evidence on how significantly pregnancy affects the long-term prognosis of their heart diseases.529
Table 26. Modified WHO Classification of Maternal Cardiovascular Risk: Application
| Conditions in which pregnancy risk is WHO I |
| • Uncomplicated, small or mild |
| - pulmonary stenosis |
| - patent ductus arteriosus |
| - mitral valve prolapse |
• Successfully repaired simple lesions (atrial or ventricular septal defect, patent ductus arteriosus, anomalous pulmonary venous
drainage) |
| • Atrial or ventricular ectopic beats, inolated |
| Conditions in which pregnancy risk is WHO II or III |
| WHO II (if otherwise well and uncomplicated) |
| • Unoperated atrial or ventricular septal defect |
| • Repaired tetralogy of Fallot |
| • Most arrhythmias |
| WHO II–III (depending on individual) |
| • Mid left ventricular impairment |
| • Hypertrophic cardiomyopathy |
| • Native or tissue valvular heart disease not considered WHO I or IV |
| • Marfan syndrome without aortic dilatation |
| • Aorta <45 mm in aortic disease associated with bicuspid aortic valve |
| • Repaired coarctation |
| WHO III |
| • Mechanical valve |
| • Systemic right ventricle |
| • Fontan circulation |
| • Cyanotic heart disease (unrepaired) |
| • Other complex congenital heart disease |
| • Aortic dilatation 40–45 mm in Marfan syndrome |
| • Aortic dilatation 45–50 mm in aortic disease associated with bicuspid aortic valve |
| Conditions in which pregnancy risk is WHO IV (pregnancy contraindicated) |
| • Pulmonary arterial hypertension of any cause |
| • Severe systemic ventricular dysfunction (LVEF <30%, NYHA III–IV) |
| • Previous peripartum cardiomyopathy with any residual impairment of left ventricular function |
| • Severe mitral stenosis, severe symptomatic aortic stenosis |
| • Marfan syndrome with aorta dilated >45 mm |
| • Aortic dilatation >50 mm in aortic disease associated with bicuspid aortic valve |
| • Native severe coarctation |
LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; WHO, World Health Organization.
(Modified from the JCS 2018 Guideline on Indication and Management of Pregnancy and Delivery in Women with Heart Disease. 2019.523)
8.1 Transitional Care
Adults with congenital heart disease (CHD) are increasing markedly in number; the majority have undergone successful treatments during infancy and childhood.444 These patients should be under consecutive care, because they commonly possess medical issues such as residua, sequelae, or other complications in the longer term after repair. Care include not only the physical aspect but also psychological and social issues; these situations are changing drastically during the process of growth from childhood to adulthood.
It is stated that “the goal of transition in health care for young adults needing special medical support is to maximize their lifelong function and potential abilities through the provision of high-quality, developmentally appropriate health care services that continue uninterrupted as the individual moves from adolescence to adulthood”.530 It is essential for such patients to decide by themselves which medical treatments they will undergo as independent individuals. During transition, it is expected that key people for their health care should gradually move from parents, caretakers, or medical personnel to the maturing patient themselves.531
8.2 History of Transitional Care
The concept of transitional care had been recognized as crucial in the USA in children with chronic diseases.532 A Consensus Statement was published as early as 2002, from 4 American societies: American Academy of Pediatrics, American Academy of Family Physicians, American College of Physicians-American Society of Internal Medicine.530 As for CHD, the issue was described in ACC/AHA 2008 Guidelines for the management of adults with congenital heart disease,533 and also in AHA 2011 Best practices in managing transition to adulthood for adolescents with congenital heart disease.534
In our country, recognition of transitional care commenced in the field of CHD. JCS 2011 Guideline for management of congenital heart disease in Adults535 was the primary publishment, followed by a 2014 report from a working group of the Japan Pediatric Society.531 More recently, in 2017, a statement was published by JCS and other seven Japanese Societies/Associations.536
8.3 What to Consider for Transitional Care
As mentioned above, the fundamental factor is to realize that the growing patient should become independent and make their own choices. In this respect, the report from a Working Group of the Japan Pediatric Society reinforces (1) the principle of self-decision, (2) an understanding of the disease and its complications according to the patient’s age, and (3) medical treatments appropriate and matched for the patient’s maturing personality.531 For a smooth transition, patients should be supported in terms of a self-decision process that is continuous from childhood to adolescence. This activity is not confined to patient education, but includes the patient’s family, a multidisciplinary professional team, and social organization.536 The whole process cannot be achieved without institutional communication between pediatric and adult departments, establishment of specialists’ institutions for adult CHD, education of multidisciplinary professionals, and development of a social system or construction of a national network for medical collaboration.
8.4 Current Status and Challenges of Transitional Care
Transitional care is not developing quickly, despite recognition of its importance. There has been a report that only 50% of patients with complex CHD successfully transitioned to an adult program.536 Obstacles are composed of many factors; such as the social system, institutional conflicts, cultural diversity, and psychological aspects.444,537 These are multiplied by another factor, that is, patients, families, and medical professionals. Listed in Table 27 are the challenges of transition in CHD.444 A program for transitional education seems to be functioning, and a special outpatient clinic is another example of successful establishment of transitional care.538–541 These trials are being imported to Japan, and hopefully will develop still further.
Table 27. Challenges of Transition in CHD
| • Patient education towards adult medical care |
| • Recruting clinicians and cardiologists interested in ACHD care |
| • Pooling knowledge and experience of CHD among clinicians |
| • Seamless collaboration between pediatric and adult cardiologists |
| • Preparing medical facilities for ACHD patients care and improving medical care system by using network information |
| • Clarifying long-term outcome and life history of CHD |
| • Building consensus on transition among staff at children’s hospital |
• Providing measures against limiting patient’s social independence: more opportunities for education and
employment |
| • Improving counseling services provided to ACHD patients for pregnancy, labor, and genetic conditions |
| • Improving lack of knowledge about psychophysiological problems and mental retardation in ACHD among medical staff |
• Research in social insurance (e.g., health insurance, disability certificate, pension, and publicly funded health care) and
welfare in adulthood and accumulation of its knowledge |
| • Maximal use of existing medical resources |
ACHD, adult congenital heart disease; CHD, congenital heart disease. (Translated from Guidelines for Management of Congenital Heart Diseases in Adults [JCS 2017]. 2018.444)
8.5 Timing of Transition
The American guideline indicates that the transition to adult medicine should be started at age 12 and completed by age 21 years.533 Young teenagers begin with understanding their own diagnoses, treatments used thus far, and limited physical excise if any. Older teenagers can learn how important their transitional care is, what their medical details are, what lifestyle issues they have, the impact of pregnancy and delivery, life-long prognosis, choices for future occupation, and so on. The timing for dealing with these matters is, of course, depending on patients’ development, personal maturity, and their heart condition.542 In the Japanese population, the social and cultural environment is different from that of the USA, and therefore the optimal timing for transition needs to be determined for each individual.
One reasonable way to promote transition to an adult cardiology department or an adult CHD unit is to confirm patients’ understanding of their disease using a checklist. Patients’ medical data need to be transferred securely and in detail. It is a good idea to share outpatient clinic data between the pediatric and adult doctors for a certain period of time when seeing patients with complex heart problems. A specialist nurse can be of a practical help for a patient to smoothly adapt to the transitional period.536
9. Medical Care System for Adults With Congenital Heart Disease
9.1 Need for Medical Care System and Its Current Status for Adult Congenital Heart Disease (ACHD) Patients
In the 1990s and 2000s, the number of adult patients with complex CHD markedly increased, making it challenging for pediatricians and pediatric cardiac surgeons to treat all ACHD patients. ACHD requires not only management skills in pediatric care but also knowledge and experience in general adult practice. The pathophysiology and complications of ACHD are rather specific, and a comprehensive approach is to be sought.543 In Europe and the USA, pediatric and adult cardiology have been successfully unified in the ACHD field.544–546
In Japan, the number of ACHD patients exceeded 400,000 in 2007,5 and has been increasing by 10,000 per year. In 2008, the Health and Labor Sciences Research Grants-in-Aid for Intractable Diseases Policy Research Project started a program to establish a system for regional and comprehensive ACHD care, in which ACHD care centers, core hospitals, and children’s hospitals collaborated regionally in order to provide lifelong care for CHD patients. A regional ACHD care center is a facility with a dedicated ACHD team consisting of ACHD specialists, pediatric and adult cardiologists, obstetricians, and cardiac surgeons. The team should be able to manage all aspects of ACHD: physical investigations, surgery, catheter intervention, general adult diseases, special conditions of pregnancy and childbirth, as well as psychological and welfare issues. Comprehensive ACHD care system leads to lower mortality rates in ACHD patients.22,547 In 2019, the Japanese Society of Adult Congenital Heart Disease (JSACHD) launched a board certification system for ACHD specialists; on this basis, the JSACHD accredited 40 regional and 41 collaborative training facilities (centers). As of 2021, 170 certified provisional ACHD specialists are engaged in ACHD care and specialist training. This is a nationwide program, although there are still regional and inter-institutional disparities.
It should be noted that some patients do not receive the recommended or required medical care in the longer term after repair. A background reason for this may be that an appropriate facility with a specialist is not conveniently available. Another reason is that patients or their families have been told the condition is “surgically cured”; they did not think that they needed further medical check-up any longer.548 Reportedly, patients who are lost to follow-up or are referred to regional ACHD care centers from non-CHD/ACHD-specialist facilities have a higher risk of requiring additional invasive treatments.549–551 In each region, closer cooperation is necessary between medical providers. Additionally, the transitional care system needs attention and revision. Patient education, when commenced during the transitional period, leads to a constructive circumstance in which they are more receptive to ongoing consultations and adjustments in lifestyle.540,552
9.2 How to Utilize the Medical Care System
To improve the medical care system, it is essential for healthcare professionals, patients, and their families to share data on the system efficiently.
• For information on the ACHD care system in each region, refer to the website of JSACHD (http://www.jsachd.org/) and the website of the Japanese Network of Cardiovascular Departments for ACHD (https://www.jncvd-achd.jp/).
• In regions with insufficient ACHD care systems, consider referring patients to the cardiology department of a regional core hospital with sufficient referral information, including surgical records.
• The referral should best be made to a hospital where ACHD specialists and pediatric cardiologists are available.
• Facilities that provide specialized treatment for ACHD should list, on their websites, the number of ACHD specialists, pediatric cardiologists, adult cardiologists, and cardiac surgeons, information regarding the CHD/ACHD specialized outpatient clinic, the number of CHD/ACHD outpatients and inpatients, achievement in CHD/ACHD cardiac surgery and interventions, and the results of medical treatments for special refractory conditions such as pulmonary hypertension and the Fontan circulation.
10. Cardiac Transplantation
As complex congenital heart disease (CHD) patients increasingly survive corrective surgery, the number of adults with CHD (ACHD) is rising. A significant proportion of those with ACHD develop advanced heart failure and are considered for heart transplantation. Mostly the indications for heart transplantation are systemic ventricular failure and the so-called Fontan failure (Table 28).7 Although the outcome after heart transplantation for failed-Fontan patients has improved in the current era,553 the final surgical option is often judged as out of indication in this cohort, because other organs, the liver and the kidney particularly, most likely fail before decompensation of the systemic circulation.
Table 28. Indications for Heart Transplantation in ACHD Patients
| 1. |
New York Heart Association functional class IV HF not amenable to palliative or corrective surgery |
| 2. |
Severe symptomatic cyanotic heart disease not amenable to palliation |
| 3. |
Post-Fontan procedure with refractory HF, persistent protein-losing enteropathy, and/or plastic bronchitis despite optimal
medical and surgical therapy |
| 4. |
Pulmonary hypertension with the potential risk of developing fixed, irreversible elevation of PVR that could preclude heart
transplantation in the future |
ACHD, adult congenital heart disease; HF, heart failure; PVR, pulmonary vascular resistance. (Produced from Stout KK, et al. 2019.7)
The average waiting time for heart transplantation is longer than 4 years in Japan. Since 1999, heart transplantation for CHD has taken place only twice out of 452. More than 95% of recipients are waiting with a left ventricular assist device (LVAD). Currently, 4 patients with complex CHD and biventricular physiology are on the waiting list with LVAD support. In the USA and Europe, patients with single-ventricular physiology have a higher incidence of adverse events during LVAD support.554 The mortality rate of patients with CHD on the waiting list has been higher than that of those without. In 2018, UNOS (United Network for Organ Sharing) changed the donor allocation system (Table 29)555 to give priority to CHD patients (New status 4) and to the patients with single-ventricular physiology on LVAD support (New status 2). The Japanese donor allocation system is to be revised.556
Table 29. Change in Heart Allocation Criteria Resulting in a New 6-Tiered System
| Old |
New |
Listing criteria |
| Status 1A |
Status 1 |
• VA-ECMO |
| • Non-dischargeable, surgically implanted, nonendovascular biventricular support device |
| • MCSD with life-threatening ventricular arrhythmia |
| Status 2 |
• IABP |
| • Non-dischargeable, surgically implanted, nonendovascular LVAD |
| • VT or VF without mechanical support |
| • MCSD with device malfunction or failure |
| • TAH, BiVAD, RVAD, or VAD for patients for single ventricular physiology |
| • Percutaneous endovascular MCSD |
| Status 3 |
• Dischargeable LVAD for discretionary 30 days |
| • Multiple inotropes or single high-dose inotrope with continuous hemodynamic monitoring |
| • Single inotrope with continuous monitoring |
• VA-ECMO after 7 days; IABP or percutaneous endovascular circulatory support device
after 14 days |
| • Non-dischargeable, surgically implanted, nonendovascular LVAD after 14 days |
| • Mechanical support device with complication |
| Status 1B |
Status 4 |
Dischargeable LVAD without discretionary 30 days |
| • Inotropes without hemodynamic monitoring |
| • Retransplant |
• Diagnosis of CHD, ischemic heart disease with intractable angina, hypertrophic CM,
restrictive CM, amyloidosis |
| Status 2 |
Status 5 |
• On waitlist for at least 1 other organ at the same hospital |
| Status 6 |
• All other active candidates |
BiVAD, biventricular assist device; CHD, congenital heart disease; CM, cardiomyopathy; IABP, intra-aortic balloon pumping; LVAD, left ventricular assist device; MCSD, mechanical circulatory support device; RVAD, right ventricular assist device; TAH, total artificial heart; VAD, ventricular assist device; VA-ECMO, venoarterial extracorporeal membrane oxygenation; VF, ventricular fibrillation; VT, ventricular tachycardia. (From Liu J, et al. 2021.555 Copyright 2020 The Authors. Transplantation Direct. Published by Wolters Kluwer Health, Inc.)
For candidates with abnormal arrangement of the great arteries and/or unusual systemic venous drainage, the transplant procedure is complicated. Particularly, anastomosis of abnormal venae cavae to the normal donor heart is technically demanding and has higher morbidity and mortality.557 In Japan, to date there has been only one heart transplantation for a patient with single-ventricular physiology.558 There is no established surgical method for these vascular abnormalities. For the treatment of endstage heart failure with ACHD, the clinician should be familiar with the wide spectra of CHD morphology and treatment strategies. It is necessary to solve the problem with mechanical circulatory support for failing-Fontan patients and revise the donor allocation system.559
In Japan, heart and lung transplantation has occurred on only 3 occasions: 1 for Eisenmenger syndrome and the other 2 for restrictive cardiomyopathy with highly elevated pulmonary vascular resistance. The number of candidates for heart and lung transplantation appears to have decreased, thanks to earlier diagnosis of these diseases. Because heart and lung transplantation carries high mortality risk, its indication must be carefully decided.
11. Palliative Care
11.1 Need of Palliative Care
Palliative care is a crucial part of integrated and patient-centered health services. Grief/pain may be related to physical, psychological, social, or spiritual issues560 (Figure 4), and relieving serious grief and pain is an ethical responsibility worldwide. Palliative care services are needed and should be available at all levels of care, regardless of the cause of suffering (whether it is cardiovascular disease, cancer, or any other disease/condition)560 (Figure 5). The goal of palliative care is to achieve the optimal quality of life for patients and their families. Care must be multidisciplinary. Over the past decade, this field has grown and changed substantially. Palliative care plans are now more evidence-based. We have new models for care delivery. Innovative payment mechanisms have been introduced. Above all, the public and professionals are increasingly aware that palliative care plays an important role.
11.2 Palliative Care in Adult Congenital Heart Disease (ACHD)
The essential components of palliative care are effective control of symptoms and appropriate communication with patients, families, and other people involved in the patient’s care. As disease progresses, continuity of care becomes increasingly important; services need to be well coordinated, and information must be shared promptly and efficiently among professionals in the medical community as well as in the hospitals and hospices. In Japan, various supports are available for CHD/ACHD patients: medical care, education, social security, welfare, and employment support are provided. These are all applicable to palliative care and should be noted for each ACHD patient. An advised care pattern for ACHD is summarized in the Table 30 and Figure 6561 according to heart failure stage.562
Table 30. Care for Adult Congenital Heart Disease According to Heart Failure Stage
Heart failure
stage |
Stage B/C |
Stage D |
| Palliative care |
Recognition of condition |
| Social security services |
| Advance care planning |
| Transfer/transition |
End-of-life care |
| Employment support |
11.3 Advance Care Planning
Planning ahead for the end of life is sometimes called as advance care planning. It involves observation, discussion, and intent consideration of the patient’s wishes for care during the final months of life. The medical team should realize that there may be some treatments which the patient will not undergo. By planning ahead, patients can let people know their view of life, longings and feelings while they are still able to communicate with the people surrounding them. Sharing patients’ choices and wishes with their families should assist future decisions regarding care of these patients. Patients with cognitive impairment need special assistance when deciding which medical care they would prefer. The optimal clinical treatment is to be set for each patient through meticulous discussion among caregivers.
12. Nursing
Postoperative congenital heart disease (CHD) patients need multifaceted treatments depending on their condition and the clinical course of their diseases, to say nothing of daily management of disease. It is crucial to understand how to adapt to social life, when to decide reoperation, and how to deal with end-of-life care. From a psychological viewpoint, adult CHD (ACHD) patients seemingly feel more anxiety than depression in Japan.563 Their problem-solving ability appears lower, as does their self-esteem.564 They are liable to psychologically depend on parents and others. Because of this, they readily experience great difficulties in life events and changes in the condition of their diseases. In order for them to cope with such difficulties, nurses play an important role in coordinating multiple teams. Nurses can assist patients to adjust and enhance their conditions, either physical or mental, and can guide them to their desired lives, as far as possible, in accordance with their developmental stage.
12.1 Promoting Understanding of Diseases and Self-Care
Lifestyle-related diseases should be prevented whenever possible; this is also the rule for ACHD patients. A unique aspect in ACHD is that care patterns are diverse depending on the condition of each patient and the status of their disease. Thus, self-care management can become confusing. Behavior modification is essential, and each patient has a different personality. Nutrition and fluid management should be adjusted individually according to the pathological condition of their disease against deterioration in cardiac function. Working style needs to be reconsidered, and how to spend free time is another factor, in line with their prospective course and treatment plan. Appropriate self-care may be disturbed by conflicts arising from childcare, a desire to be highly recognized at work, and the relationship with friends. These are issues commonly featuring in adulthood.
In recent years, as it has become necessary to think about diseases and lifestyles and promote patients’ understanding,565 self-administered checklists are used to prompt patients to think about their own diseases and lifestyles. Nurses support patients through the outpatient service for transitional care. Thoughtful interviews are carried out before and after medical examinations.
12.2 Supporting Decision Making
CHD patients may have residual or recurrent impediments of a moderate or severe degree7 after previous surgery. Most of them need to repeatedly make serious decisions about treatments. Reoperation, catheter intervention, anti-arrhythmic therapy, and heart failure treatment can be invasive. Planning for end-of-life medical treatment is another decision. Life-related choices are social aspects such as academic progress and professional career, marriage, pregnancy, and childbirth. Here, nurses play a practical role in providing systematic information and efficient communication to assist in coming to a consensus, as well as in coordinating the medical teams. Eventually, patients and their families are convinced that they can make the optimal decision.
12.3 Support From Family
ACHD patients are often accompanied by their parents for their regular medical check-ups. When making a decision on treatment, patients may have different opinions from their families’, and the process of decision making can take time. Family members have lived with anxiety regarding the patient’s disease and condition for a long time from their birth to adulthood. Generously understanding these circumstances, nurses can support both patients and their families. It is ideal for patients to independently make decisions.
12.4 Consultation and Coordination
Patients and families may consult with nurses about nonmedical issues. For example, medical expenses, welfare systems, school life, employment, friends and family relationships, pregnancy and contraception, and childcare are issues they usually hesitate to ask to the doctors,566 as well as the benefit of psychological therapy on the outcomes of heart failure treatments in CHD. Coordinating various specialists is another important task for the nurses so that the team effectively and flexibly collaborates with the multiple members such as psychiatrists, clinical psychologists, dentists, and social workers.567
12.5 Nursing Consultation and Outpatient Care Service
As of 2020, outpatient consultations for CHD, for either disease management or medical treatment, do not generate additional medical fees. Desirably, outpatient care consultations for those with cardiovascular diseases should yield a financial benefit of its own. Currently, better systems are being devised at various facilities for outpatient care service in ACHD. Nurses can contribute to such progress through their practical knowledge and research results, which must be accumulated and shared as evidence.
II. Specific Lesions
1. Patent Arterial Duct, Atrial Septal Defect, and Ventricular Septal Defect
1.1 Atrial Septal Defect (ASD)
Surgical closure of ASD, which was initially introduced in 1955, is now an established procedure that is secure and provides excellent results. Catheter intervention has developed remarkably over the past 2 decades. Percutaneous transvenous closure of an ASD is currently the standard approach in a large proportion of patients. In a sense, use of the Amplatzer Septal Occluder and Occlutech Figulla Flex II has taken over the surgical approach in a certain cohort of patients; already more than 15,000 patients with ASD in Japan have been treated.
Transesophageal echocardiography is informative for clarifying the precise morphology of the rim of the ASD when an interventional approach is being considered. As standard practice, an ASD suitable for device closure should have a circumferential edge of ≥5 mm width all around except for on the aortic side.527 An indication recently extended allows more generous conditions, such as a circumferential edge grossly defective around the aortic aspect or the postero-inferior rim, for successful closure achievement.568
Essentially, complications are infrequent after transcatheter closure. Clinical issues are less common in the early postprocedural period of catheter intervention compared with surgical treatment. Occasionally, an occluder can migrate from its proper position (≈0.5%) or perforate/erode the heart structure (≈0.2%).527,568 The latter is particularly serious, although thus far no report has been made regarding death related to the transcatheter technique in the Japanese registry. Erosion usually starts within 72 h of placement of an occluder; pericardial effusion and cardiac tamponade can progress acutely. Such impediments need to be identified on transthoracic echocardiography in a timely fashion. Dyspnea is an important clinical symptom, as well as chest pain, which is related to damage to the tissues. In a small number of patients, these phenomena are noted several months to several years after the interventional procedure.569
Risk factors for perforation or erosion are: (1) use of an over-sized device (an occluder diameter >150% of the defect), (2) a large defect extending towards the aortic root without a sufficient circumferential edge, and (3) marked malalignment of the rim of the ASD.570,571 In these circumstances, the occluding device irritates the aortic wall and the atrial tissues mechanically and repeatedly. Either of the 2 types of devices available in Japan causes this significant complication.572,573 There has not been a comparative study of these products.570,574 A brand-new device (Gore Cardioform ASD Occluder) made of extended polytetrafluoroethylene was introduced in August 2021.
It has been reported that the atrial septum seems more deviated in older patients.571 Septum primum may be posteriorly malaligned (towards the left atrium) in relation to septum secundum. In such circumstances, the size of the ASD tends to be measured inaccurately. Although rare, bacterial infection onto the device through the blood stream needs attention.575,576 Residual pulmonary hypertension is another issue the cardiologist needs to keep in mind; combination of therapy using a pulmonary arterial vasodilator and interventional closure of the ASD is an ambitious approach in those with high pulmonary resistance.265
Regular follow-up is sensible in the longer term after either surgical or interventional treatment. Checking would include: residual shunt, volume-overload to the right ventricle (RV), tricuspid insufficiency, estimated RV systolic pressure, atrial arrhythmia, and mitral insufficiency. In particular, atrial fibrillation is a crucial phenomenon to be noted in adults;577 some investigators state that interventional closure is superior to conventional surgery in this respect, but others are not so sure because these 2 groups of patients are not scientifically comparable in the strictest sense. Those undergoing surgical closure usually have a larger ASD and the preoperative shunt across it is greater than in those undergoing interventional closure. Atrial arrhythmia occurs more often in the early postoperative phase following surgical closure.376 It is known that surgical incision to the right atrium predisposes to re-entrant circuits. Surgical insults can induce the post-pericardiotomy syndrome or constrictive pericarditis.577
Whether atrial arrhythmia is potentially present or not should be investigated before ASD closure (either surgical or interventional). Electrophysiological ablation is efficient for atrial fibrillation prior to ASD closure, maintaining sinus rhythm for long after the procedure.376 Prophylactic surgical ablation is feasible at surgical closure of the ASD; re-entrant circuits around the ASD, the tricuspid valve annulus, and the atriotomy to the right atrium are blocked. Atrial arrhythmia developing after ASD closure requires an electrophysiological study and ablation after the procedure.
Diastolic function of the left ventricle (LV) matters in older patients. By closing the defect, their LV end-diastolic pressure rises considerably, which may lead to congestive heart failure.578,579 During transcatheter closure, it is wise to monitor pulmonary arterial wedge pressure, evaluating a potential risk of clinical deterioration.
For regular follow-up in the longer term, chest X-ray, ECG, and echocardiography are fundamental (once a year to several years). In those showing arrhythmic episodes, Holter and exercise testing should be arranged.
Sinus–venosus-type ASD is treated surgically. Partially anomalous pulmonary venous connection is a very common association in this variant form. Stenosis might progress across the pulmonary venous or the superior caval venous channel after repair. CT or MRI will be informative to clarify such situations.580,581
1.2 Ventricular Septal Defect (VSD)
Surgical closure of a VSD is safely carried out nowadays; early mortality is reported as ≤1–2% and outcome appears excellent in the longer term.527,577
Transcatheter closure of a VSD is used in other Western countries, but has not been approved in Japan (as of 2022). The interventional approach has not been statistically compared with the conventional results by surgery. Only a few reports are available regarding long-term results after transcatheter closure.582
Transcatheter closure can induce atrioventricular block, tricuspid regurgitation, or aortic regurgitation (AR),583 but these are also issues after surgical closure. In particular, AR is not extremely rare in patients with VSD at the conal septum. Tricuspid regurgitation is commoner in those with a perimembranous VSD. In addition, residual shunt, LV dysfunction, pulmonary hypertension, and postoperative formation of a double-chambered RV are on the list of sequelae.
All these possible complications should be evaluated regularly on echocardiography. Prolapse or deformity of the aortic valve leaflets could have been present preoperatively in those who have AR progression.584–586 Once AR becomes significant after VSD closure, the indication for aortic valve surgery would be equivalent to that for ordinary isolated AR. Atrioventricular conduction can worsen even long after VSD closure.
Medical check-up is recommended to be 1–3 years after VSD closure, unless a residual shunt, a residual lesion or pulmonary hypertension is present. Annual check-up would be reasonable when these impediments or LV dysfunction are obvious.
Surgical closure of a residual shunt should be considered according to the indication for untreated VSD.587
Residual pulmonary hypertension is a significant factor for less than ideal prognosis. Closure of a residual shunt, if any, might improve the difficult situation. Use of a pulmonary arterial vasodilator would be another treatment to consider, although no concrete evidence has been established in terms of long-term prognosis.
Physical exercise needs to be limited when impediments such as pulmonary arterial hypertension, impaired LV function, or a residual shunt are prominent, posing significant overload to the heart. In patients with a residual shunt, even small, prophylactic treatment should be carefully applied in order to prevent bacterial endocarditis.
1.3 Patent Arterial Duct (PDA)
Patients with a PDA are treated, the majority during infancy and childhood, by either transcatheter technique or surgery. The former uses coils, the Amplatzer Duct Occluder, or Vascular Plug, and the latter includes ligation, clipping and division. Devices recently available are all MRI compatible. Early and late results are excellent after either interventional or surgical closure.588–590
Annual follow-up should not be necessary in surgical patients with no residual lesions. On rare occasions, there may be recurrent nerve palsy. A residual shunt may be detected, making a continuous murmur, after interventional closure or surgical ligation and reoperation or re-intervention is recommended.591,592 Some investigators suggest that further treatment is not mandatory for a small residual shunt with no audible murmur.593,594 Even so, prophylactic care is essential to avoid bacterial endocarditis.
Residual pulmonary hypertension should be followed up long-term.595
2. Atrioventricular Septal Defect
Atrioventricular septal defect (AVSD) was previously unified as endocardial cushion defect; reportedly seen in 0.04–0.05% of live births, in 3–5% of congenital heart disease (CHD), and in approximately 20% of patients with trisomy 21. The septum is lacking between the right atrium and the left ventricle (LV). Subtypes include the so-called complete form, incomplete or partial form, and intermediate form.596 This septal malformation can coexist with abnormal ventriculo-arterial connection. Visceral heterotaxy often shows AVSD as a part of combined structural abnormalities.597
2.1 Morphology
AVSD does not have independent bilateral atrioventricular (AV) junctions. The AV valves commonly possess 5 leaflets. The LV outflow is anteriorly deviated, and the LV is geometrically deformed (short inlet vs. long outlet). The AV node and the proximal conduction bundle are inferiorly deviated. These features are the rule throughout the subtypes.598
In complete AVSD, the common AV valve has bridging leaflets (anterior and posterior) and mural leaflets. The bridging leaflets are floating at the AV junction. The so-called Rastelli types (A, B, and C) depend on the feature of an anterior bridging leaflet and the pattern of its tendinous cords.599 In typical incomplete AVSD, the bridging leaflets are conjoined (connecting tongue) providing the bilateral orifices. The middle part is attached to the crest of the ventricular septum (no interventricular communication is present). As for intermediate AVSD, a connecting tongue is imperfectly fused with the crest of the ventricular septum. Interventricular communication is restrictive.
When the sizes of the ventricles are disproportionate, it is described as unbalanced AVSD.
2.2 Surgical Repair
Complete AVSD promotes early, severe pulmonary hypertension (PH). Intracardiac repair is arranged early in infancy. In babies with complicating factors, the pulmonary trunk is initially banded, followed by definitive repair around 1 year of age. When repairing complete or intermediate AVSD, the common AV valve is separated, the interventricular communication is closed, the fissure within the left AV valve is fixed, and the atrial septation is completed. These repairs are achieved using separate atrial and ventricular patches or a continuous patch. More recently, a modified one-patch method was introduced in which interventricular communication was closed by fixing the common valve down onto the crest of the ventricular septum. Results in the longer term (>5–15 years) have yet to be clarified for this method.600 Repair of incomplete AVSD is simpler.
2.3 Management
Regular and life-long follow-up is recommended, paying attention to residual shunts, AV valve deterioration, ventricular dysfunction, PH, obstruction across the LV outflow tract, and rhythm disturbance. The left AV valve could become not only regurgitant but also stenotic. Atrial fibrillation and PH are consequences. Conduction is delayed progressively in some patients. Regular evaluation by standard ECG and Holter recording has clinical utility.
2.3.1 Limitation in Exercise
There is no need to limit physical exercise unless significant lesions remain after repair. Mild left AV valve regurgitation does not warrant a reduced program for physical exercise at school, either, unless there are clinical symptoms, prominent LV enlargement, impaired LV contraction, PH, or arrhythmia. Exercise should be under supervision when these features are noted or the left AV valve is significantly regurgitant.
2.3.2 Pulmonary Hypertension
Secondary PH will usually not progress in those undergoing repair during infancy. Trisomy 21, nonetheless, is a known risk factor that can promote pulmonary vascular changes.601 In the adult CHD cohort, mortality is reportedly 4-fold higher in patients with PH compared with those without.602
2.3.3 Pregnancy
In a 2005 study, NYHA class worsened in 23% of pregnant women with AVSD, residual AV valve regurgitation became severer in 17%, and arrhythmia newly appeared in 19%.603 Maintaining pregnancy is unrealistic when systemic ventricular function is markedly impaired or AV valve regurgitation is severe.
2.4 Repeated Invasive Treatments
Approximately 15% of patients will undergo reoperations in the longer term, because of left AV valve regurgitation (66–77%), residual shunt (10–19%), or obstruction across the LV outflow tract (4–9%). On rarer occasions, there can be bradycardia because of sinus nodal dysfunction or AV block (2.7–7%), left AV valve stenosis, and right AV valve regurgitation.604–608 Repeated reoperation may be needed. Freedom from reoperation is 88–91% (at 10 years), 83–89% (at 20 years), and 78% (at 30 years) in those with complete AVSD.609,610 The results are comparable in incomplete or intermediate AVSD: 81–84% (at 10 years), 78.6% (at 15 years), and 75% (at 30 years).611,612
2.4.1 Left AV Valve Regurgitation
This condition caused reoperation in 7–14% of repaired patients.604,605,609,613 The functional issue is related to the morphological characteristics of the valve. Risk factors for reoperation are: dysplasia of the valve leaflets, a recurrent fissure between the bridging leaflets,613,614 imbalanced small LV, dual orificial valve, and moderate valve leakage at discharge after the initial repair.615,616
Reoperation is considered appropriate, in children, when left AV valve regurgitation is moderate or severe associated with clinical symptoms (Class I, Level C). In adults, surgical indication is based on that for acquired mitral valve insufficiency.617,618 The ESC 2010 Guidelines for the management of grown-up congenital heart disease155 and the AHA/ACC 2018 Guidelines for the management of adults with congenital heart disease are also referred to.7 Significant regurgitation accompanying LV enlargement or impaired contraction is submitted for reoperation, irrespective of clinical symptoms (Class I, Level B) (Table 31).
Table 31. Indication for Intervention in Patients With Repaired AVSD
| |
COR |
LOE |
| Residual shunt |
Closure of residual shunts is recommended when there is a net left-to-right shunt (Qp/Qs
≥1.5), PA systolic pressure >50% systemic and pulmonary vascular resistance <one-third
systemic |
I |
C |
Closure of reisidual shunts mey be considered when there is a net left-to-right shunt (Qp/Qs
≥1.5), if PA systolic pressure is ≥50% systemic, and/or pulmonary vascular
resistance >one-third systemic |
IIb |
C |
Closure of residual shunts in patients with repaired AVSD should not be performed with
PA systolic pressure >two-thirds systemic, pulmonary vascular resistance >two-thirds
systemic, or a net right-to-left shunt |
III |
C |
| AV valve regurgitation |
Symptomatic patients with moderate to severe AV valve regurgitation should undergo valve
surgery, preferably AV valve repair |
I |
C |
Asymptomatic patients with moderate or severe left-sided AV valve regurgitation and
LVESD ≥45 mm and/or impaired LV function (LVEF <60%) should undergo valve surgery
when other causes of LV dysfunction are excluded |
I |
B |
Surgical repair should be considered in asymptomatic patients with moderate or
severe left-sided AV valve regurgitation who have signs of volume overload of the LV and
a substrate of regurgitation that is very likely to be amenable for surgical repair |
IIa |
C |
AV, atrioventricular; AVSD, atrioventricular septal defect; COR, class of recommendation; LOE, level of evidence; LV, left ventricle; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; PA, pulmonary artery.
Repair vs. replacement of the valve is always disputed; the former sounds favorable in terms of functional or vital prognosis605,613 and is recommended (Class I, Level C). Reparative techniques include annular plication, fixation at the fissure, augmentation of the leaflets, and use of artificial cords.619 Further reoperation is carried out in 11–22%; replacement at the third surgery seems less ideal,615,616 but the procedure would be the only solution if repair does not work. A mechanical prosthesis is usually a practical choice, particularly in children (Class IIa, Level C). With growth, patient–prosthesis mismatch will require upsizing of the valve.620 A bioprosthesis is preferred in females at reproductive age.
2.4.2 Residual Shunts
Residual shunts are often treated at an earlier stage after the initial repair. Indication for reoperation is comparable to that for residual ASD and VSD in their isolated forms.
2.4.3 Obstruction Across the LV Outflow Tract (Subaortic Stenosis)
Reoperation is carried out to relieve subaortic stenosis in 1–3.7%.604,609,621,622 The LV has a disproportionally long outlet in AVSD, and an obstructive muscular bar can be present. The anterior bridging leaflet may be tethered across the outflow.623 Fibromuscular membranes and anomalous fibrous tissues at the LV outflow, if any, should be removed. When the subaortic pathway has a tunnel-like formation, enlargement of the channel is insufficient only through the aortic valve, and obstruction recurs in 15–29%. In such circumstances, the modified Konno procedure is the procedure of choice.621,623
Mean pressure gradient >50 mmHg across the LV outflow, together with clinical symptoms, is an indication for reoperation (Class I, Level C). When the LV is enlarged, hypertrophied, or impaired, reoperation should be considered even in the absence of clinical symptoms (Class IIa, Level C) (Table 32).
Table 32. Indications for Intervention in Repaired AVSD Patients With Subaortic Stenosis
| |
COR |
LOE |
| Symptomatic patients should undergo surgery when: |
| mean Doppler gradient ≥50 mmHg or severe AR |
I |
C |
Operation for LVOTO is reasonable in patients with mean Doppler gradient <50 mmHg if
symptoms are present, or if concomitant moderate-to-severe Left AVVR or AR are
present |
IIa |
C |
| Asymptomatic patients should be considered for surgery when: |
| LVEF is <50% (gradient may be <50 mmHg due to low flow) |
IIa |
C |
| AR is severe and LVESD ≥50 mm (or 25 mm/m2 BSA) and/or LVEF <50% |
IIa |
C |
| mean Doppler gradient is ≥50 mmHg and marked LVH |
IIa |
C |
mean Doppler gradient is ≥50 mmHg and blood pressure response is abnormal on
exercise testing |
IIa |
C |
| Asymptomatic patients may be considered for surgery when: |
mean Doppler gradient is ≥50 mmHg, LV is normal, exercise testing is normal, and surgical
risk is low |
IIb |
C |
Progression of AR is documented and AR becomes more than mild (to prevent further
progression) |
IIb |
C |
AR, aortic regurgitation; AVSD, atrioventricular septal defect; AVVR, atrioventricular valve regurgitation; BSA, body surface area; COR, class of recommendation; LOE, level of evidence; LV, left ventricle; LVESD, left ventricular end-systolic dimension; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; LVOTO, left ventricular outflow tract obstruction.
2.4.4 Bradycardia
AV block and sinus nodal dysfunction are not rare as a cause of bradycardia of a severe degree. It is important to know that AV block can progress late after the initial repair. A pacemaker was implanted in 3.6–7% of patients in the longer term.606–608 Furthermore, AV block can occur at or after surgical revision.
3. Totally Anomalous Pulmonary Venous Connection
Totally anomalous pulmonary venous connection (TAPVC) is an entity of cyanotic heart disease, seen in 1.5–2.5% of newborns.624 Soon after birth, pulmonary venous obstruction (PVO) becomes obvious, leading to hypoxemia, pulmonary congestion, pulmonary hypertension (PH), and respiratory distress. Urgent surgery is often needed during the neonatal period. Without surgical treatment, the natural prognosis is extremely poor,625 with 75–95% dying before 12 months of age.
3.1 Features
3.1.1 Morphology
The Darling classification626 is commonly used depending on where pulmonary venous (PV) drainage returns: type I to the superior vena cava region, type II to the right atrial cavity, type III to the inferior vena cava region, and type IV as a mixed pattern of these three. Type I is commonest (seen in ≈45%), followed by type II (25%) and III (25%). Type IV is uncommon. Significant PVO is almost always the case preoperatively in type III, seen in 50% of type I and rarer in type II.627 TAPVC can coexist with other abnormalities such as visceral heterotaxy.628
3.1.2 Surgery
Conventional repair for type I or III provides a good long-term outcome (survival rate >95%). A common chamber that receives all the PVs is anastomosed to the posterior wall of the left atrium (LA). To repair type II, the intra-atrial septa are incised, and a baffle is attached, draining the PVs to the LA cavity.629 When a common PV chamber is not well formed (as seen in type IV or right isomerism), the so-called ‘primary suture-less technique’ may be chosen in which no stitches are placed directly to the PV intima. The outcome of this recent device seems promising.630
The channel causing severe PVO can be stented, temporarily improving pulmonary congestion and delaying the need for a surgical procedure. This technique may be beneficial in a high-risk group of patients in whom preoperative condition is critical. Also, low birth weight infants and those with visceral heterotaxy could be candidates for the strategy, aiming at better overall results.631
3.2 Complications and Management
3.2.1 Pulmonary Venous Stenosis
PV stenosis complication appears in 7–20% of patients after TAPVC repair,632,633 seemingly more frequent in those with Darling classification type IV, hypoplastic common PV chamber, atrial isomerism, and single ventricular physiology.633,634 The stenosis has 2 patterns: tissue hyperplasia at the anastomotic site, and the other is an intrinsic disorder of the PVs. The latter is difficult to treat. Postoperative stenosis usually progresses early, requiring reoperation within 4–6 weeks in the majority. It is rare to find progressive stenosis beyond 12 months.626,627
Pulmonary congestion and PH should improve following TAPVC repair. When dyspnea and pulmonary congestion persist, it is essential to rule out PV stenosis. Echocardiography is useful to monitor the situation consecutively. A flow pattern through the PVs is informative, although echocardiography can underestimate the degree of obstruction because of flow-distribution imbalance. Magnetic resonance imaging may overestimate in this respect. Geometry at the surgical anastomosis is also illustrated on computed tomography (slightly over-estimating). Catheter evaluation can supplement needed data by measuring the pulmonary arterial wedge pressure and by injecting contrast medium.
Once PV stenosis is diagnosed, early surgical revision should be contemplated (Class IIb, Level C). Conventionally, thickened intimal tissues were resected with the PVs augmented using a patch. This has improved survival of patients, but the stenosis resolves in only 40% (Level C).635,636 Since the late 1990s, a suture-less technique has been widely used in which the anastomotic stenosis is cut open longitudinally and augmented using an autologous pericardial flap without direct suturing to the PV intima.637 This has improved overall results (Class IIb, Level C).638 Balloon dilatation or stenting is considered as a temporary measure. Stenosis may not recur when enlarged >7 mm diameter.639 Use of a drug-eluting vs. a bare-metal stent remains contentious.639,640
3.2.2 Pulmonary Hypertension
Yamaki et al investigated 60 pediatric patients with simple TAPVC histopathologically, reporting proliferation of the medial smooth muscles of the pulmonary arteries and veins. They concluded that PH should regress unless PVO remains.641 PH persists in those with lymphatic ectasia, PV atresia, or diffuse PV stenosis.642 Their prognosis is poor. A postoperative RV/LV systolic pressure ratio >0.5 is another sign of poorer prognosis.643 Use of pulmonary vasodilators is not recommended, because pulmonary congestion tends to worsen. When the PV stenosis is untreatable, lung or lung–heart transplant is the only solution (Class I, Level C).
3.2.3 Arrhythmia
Supraventricular tachycardia is uncommon.644 On the other hand, in 2007 Tanel et al reported sinus nodal dysfunction was seen on exercise testing in approximately 30% of patients who had undergone TAPVC repair 11 years prior to testing.645 Concealed rhythm disturbance may be revealed on 12-lead electrocardiogram (ECG), Holter, and exercise ECG in the longer term (Level C).
4. Pulmonary Stenosis and Obstruction Across the Right Ventricular Outflow Tract
Pulmonary stenosis (PS) is seen in 8% of all congenital heart disease (CHD), comprising 3 groups: (1) PS at the valve level, (2) above the valve, and (3) below the valve. Valvar PS is the commonest (80–90%). PS can be an isolated lesion, or a part of combined malformations. Clinical symptoms vary; from a sick infant requiring invasive treatment to an asymptomatic adult. Regardless of the level of obstruction, significant and prolonged stenosis will promote RV fibrosis, elevated end-diastolic pressure of the right ventricle (RV), and eventually raised right atrial (RA) pressure. It is known that vital prognosis is poor when treatment is introduced too late.551 It is appropriate to carry out interventional or surgical treatment before the RV is irreversibly impaired. After the initial procedure, pulmonary regurgitation would need attention in the long run.
Dysplasia of the pulmonary valve is common in Noonan syndrome, and supravalvar PS can be a phenotype of Williams syndrome or Alagille syndrome. These patients should be managed not only for the PS but also from the bodily disorder point of view.
This chapter describes PS at the 3 levels in terms of postoperative management. PS in tetralogy of Fallot (TOF) or pulmonary atresia with intact ventricular septum is not included.
4.1 Valvar PS
The cardiologist may come across patients with residual or recurrent PS who underwent valvotomy/valvuloplasty in childhood or adults with native and untreated PS. Severe PS in infants is successfully ballooned or surgically repaired with good results in general. Re-intervention is needed in 9% of those initially undergoing balloon valvuloplasty.646 Residual PS of a mild degree does not affect prognosis even without treatment. Moderate PS needs more attention because the stenosis can get worse. Vital prognosis is basically good, but ventricular arrhythmia is a potential issue to minimize by treating the PS.647
4.1.1 Diagnosis
The leaflets of the pulmonary valve are often thickened, opening insufficiently with doming, and flow accelerates across the valve orifice. Transthoracic echocardiography may not be able to distinguish valvar from supravalvar PS. Transesophageal echocardiography, CT, and cardiac MRI can provide a good view of the valve, as can cardiac catheterization. Echo-Doppler measurement would indicate mild PS when the estimated maximum pressure gradient (maxPG) is <36 mmHg (max. flow velocity <3.0 m/s), moderate PS with maxPG 36–64 mmHg (3.0–4.0 m/s), and severe PS with maxPG >64 mmHg (>4.0 m/s).7,618 Regurgitant flow across the tricuspid valve is an important measure to estimate systolic RV pressure.
4.1.2 Treatments
Balloon dilatation has established good results in the adult population when using a dual-balloons technique or the Inoue balloon.648,649 The less invasive nature of balloon valvuloplasty is attractive enough to make this approach the first choice. Surgery is indicated when it is not feasible or is unsuccessful because of a narrow pulmonary valve annulus. Surgical procedures securely relieve the obstruction, but pulmonary regurgitation has been documented in 20% of patients in the longer term.646 Technical options include valvotomy, resection of redundant valve tissues, patch enlargement of the pulmonary valve annulus, and pulmonary valve replacement using a bioprosthesis (Figure 7).
Balloon valvuloplasty is recommended in patients with moderate or severe PS and clinical symptoms (Class I). With no symptoms, the recommendation is Class IIa. A surgical approach is indicated in those with severe PS and clinical symptoms in whom balloon treatment is not feasible or successful (Class I). When PS is moderate, the recommendation is Class IIa618 (Table 33). With moderate PS and no clinical symptoms, surgery is not an immediate indication. RV systolic pressure >80 mmHg, however, remains as a parameter recommending surgery (Class I) if a balloon procedure has been unsuccessful.444 This is because a hemodynamic impediment is expected on exercise beyond this level.650
Table 33. Recommendations for Intervention in Pulmonary Valve Stenosis
7,527,618
| Recommendations |
COR |
LOE |
| Severe PS |
Pulmonary arterial balloon valvuloplasty is recommended in the presence of the following:
• Heart failure
• Cyanosis from right to left shunt via ASD/VSD
• Exercise intolerance |
I |
B |
Surgical repair is indicated in the case of balloon valvuloplasty being anatomically
unsuitable or failure if in the presence of following:
• Heart failure
• Cyanosis from right to left shunt via ASD/VSD
• Exercise intolerance |
I |
B |
| • Pulmonary arterial balloon valvuloplasty if anatomically suitable |
IIa |
C |
• In asymptomatic severe pulmonary stenosis, Surgical repair is indicated in
the case of balloon valvuloplasty being anatomically unsuitable or failure if in the
presence of following:
• RV systolic pressure ≥80 mmHg
• Decreasing RV function
• Progression of tricuspid regurgitation
• Right to left shunt via ASD/VSD |
I |
C |
| Moderate PS |
Pulmonary arterial balloon valvuloplasty is recommended in the presence of the following:
• Heart failure
• Cyanosis from right to left shunt via ASD/VSD
• Exercise intolerance |
I |
B |
Surgical repair is indicated in the case of balloon valvuloplasty being anatomically
unsuitable or failure if in the presence of following:
• Heart failure
• Cyanosis from right to left shunt via ASD/VSD
• Exercise intolerance |
IIa |
C |
ASD, atrial septal defect; COR, class of recommendation; LOE, level of evidence; PS, pulmonary stenosis; RV, right ventricle; VSD, ventricular septal defect.
4.2 Pulmonary Regurgitation (PR)
After surgical relief of isolated valvar PS, follow-up is needed for PR, RV volume overload, RV dysfunction, and exercise tolerance. The ventricular response to PR is different in this setting from that after TOF repair.527,651 The suggested parameters for pulmonary valve replacement in repaired TOF are not applied to those with isolated valvar PS.7,652 Pulmonary valve replacement is recommended for those with moderate or severe PR and RV enlargement associated with symptoms (dyspnea, chest pain, decreased exercise tolerance, etc.)653 (Class I). Even without symptoms, pulmonary valve replacement can be indicated (Class IIb) if the RV is progressively enlarged, dysfunctioning, or exercise tolerance is decreasing (Table 34).7,527,618
Table 34. Recommendations for Isolated PR After Repair of PS
| Recommendations |
COR |
LOE |
Pulmonary valve replacement for symptomatic isolated moderate or greater PR with RV
enlargement or dysfunction |
I |
C |
Pulmonary valve replacement for asymptomatic isolated moderate or greater
PR with progressive RV enlargement or dysfunction |
IIb |
C |
COR, class of recommendation; LOE, level of evidence; PR, pulmonary regurgitation; PS, pulmonary stenosis; RV, right ventricle.
(Produced from JCS/JSCS/JATS/JSVS 2020 Guideline on the Management of Valvular Heart Disease. 2020,618 Stout KK, et al. 20197 and Baumgartner H, et al. 2021.527)
4.3 Supravalvar PS and Pulmonary Arterial Stenosis
Some syndromic features need attention. Scientific evidence has yet to be accumulated for treating pulmonary arterial stenosis. The optimal strategy is determined mainly by symptoms, impediments in the pulmonary circulation, and the degree of pressure load to the RV.7
Stenosis at the peripheral pulmonary arterial level can be difficult to detect on echocardiography, but MRI and CT can provide a morphological diagnosis. Functional information can be obtained by MRI or lung perfusion scintigraphy. A vessel lumen diameter <50%, RV systolic pressure >50 mmHg, and/or an abnormal pattern of pulmonary venous return are indicators for repair, irrespective of the presence or absence of clinical symptoms (Class IIa).652 Balloon dilatation,654 placement of a stent, and surgical pulmonary arterial reconstruction are options of choice.
4.4 Obstruction Across the RV Outflow Tract and Double-Chambered RV
The double-chambered RV is caused by hypertrophic muscular bands at the subvalvar level.655 The obstruction is progressive, and a ventricular septal defect (VSD) usually coexists (including those that have been spontaneously occluded).656 Severity of obstruction is classified according to that seen in valvar PS. Pressure measurement by catheter is essential; an estimated pressure gradient on echocardiography is often not sufficiently reliable. The hypertrophied muscular bands are identified on cardiac MRI and CT. The structure is to be excised surgically, and the VSD is closed if still patent.657 Postoperative outcome is excellent.655–657 Transcatheter techniques are not effective, because the intima is quite thickened, fibrosed, and tough.656 Surgery is the choice when the RV outflow tract is moderately or severely obstructed, posing heart failure, cyanosis, or exercise intolerance (Class I).
5. Ebstein Malformation
Ebstein malformation is a rare form of disease (0.5% of congenital heart disease), initially reported by Wilhelm Ebstein in 1866.658 Clinical status varies, from being critically ill since birth to remaining asymptomatic throughout life.659,660
5.1 Morphological Features
The malformation arises during formation of the right ventricular (RV) wall. Tricuspid regurgitation is clinically most prominent; the septal and inferior leaflets show downward displacement with the area described as the atrialized portion of the RV. The RV cavity can be smaller than usual, which causes dysfunction of the RV and its severity determines the clinical presentation. Often, a right-to-left shunt remains at the atrial level. Noncompaction of the left ventricle (LV) can coexist, which is a detrimental factor in terms of prognosis. When the atrialized RV is markedly large, the anterior wall of the RV is limited in motion and accordingly RV performance decreases.661 In the severest form, fetal death occurs. In a critically ill newborn, the lungs are grossly hypoplastic with significant respiratory impediment. On the other hand, untreated adult patients are not extremely rare.659,660
5.2 Surgical Repair
In a small number of neonatal patients, RV function can be restored, achieving biventricular physiology. In most sick neonates, however, the final goal is likely the Fontan circulation. The intractable RV has to be extensively plicated in order to avoid interfering with LV function.662
Tricuspid valve repair/replacement is the surgical plan of choice together with plication of the RV in children with mild or moderate symptoms and coexisting atrial septal defect (ASD) or arrhythmia.101,663,664 When the anterior leaflet is sufficiently large, the Carpentier method (the so-called sliding technique) and its derivatives are feasible with good outcome.101 Replacement is not attractive in children, particularly in those with prolonged RV dysfunction.663 No significant difference has been detected statistically between tricuspid valve repair and replacement in the setting of adults.46
Among various surgical procedures for Ebstein malformation, the cone procedure has expanded the surgical indications.102 This technique, first reported in 1993, has become the standard method for repairing the tricuspid valve, contributing to better outcomes.103,665 Because of this stride forward brought by the cone procedure, surgery is nowadays encouraged earlier. Repair at an earlier stage is considered beneficial, avoiding paradoxical embolism through an interatrial communication. The strategy might mitigate further deterioration of the RV function.103
In patients with a significantly small RV cavity, tricuspid valve repair is combined with the bidirectional Glenn procedure.666,667 In those with atrial flutter or fibrillation, antiarrhythmic maneuvers are to be used.
(1) Tricuspid valve repair/replacement and ASD closure (if applicable) are recommended (Class I, Level C) when:
• symptomatic, exercise tolerance decreased
• cyanotic
• an episode of paradoxical embolism
• progressive increase in cardio-thoracic ratio (CTR) on chest X-ray
• RV enlargement/contractility worsening.
(2) Concomitant antiarrhythmic procedure (by an experienced congenital heart surgeon) recommended (Class I, Level C) when:
• supraventricular and ventricular tachycardia resistant to catheter ablation
• pre-excitation syndrome resistant to catheter ablation.
(3) Reoperation recommended (Class I, Level C) when:
• symptomatic, exercise tolerance decreasing, NYHA III–IV
• RV enlargement/contractility worsening with recurrent TR or progressive supraventricular/ventricular tachycardia
• bioprosthetic failure causing stenosis and regurgitation
• bioprosthetic stenosis (mean pressure gradient >12–15 mmHg)
• milder stenosis but symptomatic or exercise tolerance decreasing.
(4) Types of procedures
For repairing Ebstein malformation in adults, techniques of choice are the Carpentier technique, the cone procedure, tricuspid valve replacement, and their modifications. The cone procedure seems promising in terms of a lower reoperation-rate in the longer term.665
• Following successful surgery, exercise tolerance increases and supraventricular arrhythmia remarkably decreases. Age, sex and the degree of cardiac enlargement affects how much exercise tolerance will improve.667
• After closure of the ASD, cyanosis and paradoxical embolism are no longer expected.
• Repair of the tricuspid valve surpasses replacement in children from the viewpoint of long-term outcome, while equivalent in adult patients.
• It is fundamental to monitor the postoperative function of the repaired/replaced tricuspid valve.
• The inevitable surgical scar on the right atrium could become a new source of atrial arrhythmia.
• Ventricular arrhythmia and ventricular performance need life-long follow-up.
5.3 Prognosis Long After Surgery
Survival rate is approximately 90% at 10–15 years after Ebstein repair. Causes of death include heart failure, arrhythmia, and sudden death.101,663,664 Quality of life improves postoperatively.668,669 Reoperation was seen in >40% before the advent of the cone procedure.664 The type of artificial valve, whether mechanical or biological, does not affect durability of the prosthesis in the tricuspid position.669,670 Mechanical valves seem more prone to complications such as thromboembolism, infective endocarditis, and hemorrhagic events associated with anticoagulation.671 Based on this, a biological valve tends to be chosen.
Function of the tricuspid valve deteriorates postoperatively over time in many patients. A malfunctioning tricuspid valve can induce LV dysfunction.668 To minimize this unfavorable interventricular interaction, tricuspid valve surgery should be carried out before the LV starts to deteriorate.
Wolff-Parkinson-White (WPW) syndrome is a well-known coexisting abnormality (seen in ≈30%), causing atrioventricular (AV) re-entrant tachycardia. Other types of arrhythmias also need attention; namely, re-entrant tachycardia within the atria or around the AV node, ectopic atrial tachycardia, atrial fibrillation, ventricular tachycardia, and bradytachycardia syndrome.672
5.4 Medical Management
It is reasonable to follow up patients with a clinical condition every 6 or 12 months. There is no need to limit physical exercise unless signs of heart failure are obvious, although competitive athletic activity should be avoided7.
A pregnant patient with Ebstein malformation should undergo counselling with a specialist physician of adult congenital heart disease. Pregnancy and delivery are basically feasible under appropriate guidance, and are particularly well tolerated when NYHA class is I–II. Catheter ablation is highly recommended prior to pregnancy, if arrhythmic episodes have been noted before. If the patient is cyanotic, fetal death or a low birth weight infant may occur.673 Approximately 6% of fetuses could have congenital heart disease.46
A prophylactic protocol for infective endocarditis is recommended in either repaired or unrepaired patients, particularly after tricuspid valve replacement.
5.5 Invasive Treatments in the Longer Term (Table 35)527
Table 35. Recommendations of Indications for Intervention in Ebstein Anomaly
| |
COR |
LOE |
| Indication for surgical intervention |
| Severe tricuspid regurgitation and symptoms with reduced exercise capacity |
I |
C |
| Surgery performed by experienced congenital heart surgeons |
I |
C |
Closure of atrial communication at the timing of tricuspid valve repair if right ventricular
function is well preserved |
I |
C |
| Progression of symptoms (surgery should be considered before deterioration of RV function) |
IIa |
C |
| Indication for catheter intervention |
Ablation therapy following electrophysiologic testing in patients with symptomatic arrhythmia
or pre-excitation on the ECG, or surgical treatment if heart surgery for other lesions |
I |
C |
Atrial communication closure in patients who experience paradoxical embolism and are
expected to tolerate it hemodynamically after careful evaluation |
IIa |
C |
Atrial communication closure for the patients with desaturation (resting SpO2 <90%) who
are expected to tolerate it hemodynamically after careful evaluation |
IIa |
C |
COR, class of recommendation; LOE, level of evidence; RV, right ventricle; SpO2, percutaneous oxygen saturation. (Produced from Baumgartner H, et al. 2021.527)
5.5.1 Tachyarrhythmia
Various types of tachyarrhythmia seen in Ebstein malformation are usually treated prior to or at the time of Ebstein repair,674–676 because these influence postoperative outcomes, even sudden death. When occurring or recurring after surgery, further interventional treatments are to be considered (Class IIa, Level C). Residual accessory pathways are successfully ablated in 70–80%.677,678 The technique can be more demanding than in the usual WPW ablation, because of the surgically modified geometry of the right heart on top of the initial structural abnormalities in this particular disease. Catheter ablation to the AV junction is rather challenging after tricuspid valve replacement. If redo surgery is to be carried out, intra-operative ablation or the so-called RA maze maneuver should be considered (Class IIa, Level C).678
5.5.2 Pacemaker Implantation
A pacemaker is indicated in patients with postoperative AV block or sinus nodal dysfunction. In those with a replaced tricuspid valve, a lead may not sit well onto the RV. Alternatively, a lead tip could be delivered to the LV musculature through the coronary sinus.679
5.5.3 Surgical Revision
Not much evidence has accumulated regarding reoperations. Redo for progressive tricuspid valve regurgitation was carried out in 20% at 10 years after initial tricuspid valve repair, and the majority required a prosthetic valve.668 In another 3% (at 10 years), problems other than tricuspid valve regurgitation were treated.668 The cone procedure might decrease the reoperation rate after initial repair,680 but it remains unknown whether the method is feasible as redo surgery.
When RV function is significantly impaired, tricuspid valve surgery does not improve the overall circumstances. The bidirectional Glenn procedure would be the option in such cases.668 It will be crucial how to evaluate volume overload to the RV and its contractility in relation to progressive tricuspid valve regurgitation before RV function starts to decline.665
6. Tetralogy of Fallot
Tetralogy of Fallot (TOF) is the commonest of the cyanotic congenital heart diseases, seen in 0.18–0.26 of 1,000 births,681–683 and 3–6% of congenital heart disease (CHD).684–686 The most recent figure is 0.046% of live births by population-based estimates in North America,687 indicating no differences between ethnic groups. Long survivors are rare without surgical treatment; survival rates are 64% at 1 year and 23% at 10 years.688
Surgical treatments comprise palliative procedures and intracardiac repair. The latter, usually described as definitive, eliminates cyanosis and intracardiac shunts, and drastically improves quality of life as well as long prognoses. Surgical modifications have been proposed to provide better results and fewer complications. On the other hand, some impediments can progress even after definitive repair.
6.1 Morphological Features
Pulmonary stenosis and ventricular septal defect (VSD) with overriding aorta are 3 morphological features of TOF, together with the 4th, which is secondary right ventricular (RV) hypertrophy.
The subvalvar or infundibular region is almost always obstructed, and the obstruction frequently extends to the level of the pulmonary valve and the pulmonary arteries. Obstruction below the pulmonary valve is associated with anterior deviation of the outlet (infundibular) septum. The annulus of the pulmonary valve usually has a small diameter, and is quite often bifoliate or even unifoliate. Supravalvar stenosis may be the case. The pulmonary arteries can be narrow at the bifurcation or more peripherally. Such stenoses are localized or diffuse; they can be even entirely hypoplastic in some extreme examples.
The VSD in TOF is commonly of a perimembranous form.689 The outlet septum is anteriorly deviated, and the defect is immediately below the aortic valve. The orientation is described as malalignment. A VSD can be an outlet (juxta-arterial) variant in some patients. The aortic valve is larger than normal in association with anterior deviation of the outlet septum and aortic overriding.
How to distinguish TOF from double outlet right ventricle with subaortic VSD and pulmonary stenosis remains contentious. Some apply the so-called 50% rule strictly, and others note fibrous continuity between the aortic valve and the mitral valve as a feature of TOF irrespective of aortic overriding >50%.
6.2 Intracardiac Repair
Intracardiac repair consists of VSD closure and relief of obstruction across the RV outflow tract. The VSD is approached through an incision to the RV or the right atrium (RA). A trans-pulmonary artery approach is another option in certain types of TOF. As for RV outlet tract enlargement, the infundibular muscular bands are to be resected. A narrow pulmonary valve annulus and the pulmonary artery may need extensive incisions and patch augmentation.
6.3 Management After Repair
It is important to plan how much exercise and daily activity should be limited. In children, a plan for physical education at school should be developed. Asymptomatic patients with pulmonary regurgitation (PR) but no RV outlet tract obstruction, no RV dilatation, no impaired RV contraction, and no arrhythmia can participate in an ordinary program for physical education but not competitive sports activity with hard training (Level C). When the RV is significantly dilated or markedly malfunctioning, physical exercise is to be limited (Class IIa, Level C). Hazardous supraventricular or ventricular tachycardia is also taken into consideration.
Regular medical check-up is recommended annually or biennially even without obvious clinical symptoms (Class C). More frequent consultation would be sensible if the condition of the heart seems unstable on medical treatments.
6.4 Impediments After Repair
Repair of TOF is not a complete cure. Residua and sequelae include PR, tricuspid regurgitation, aortic regurgitation, obstruction across the RV outlet tract, atrial/ventricular arrhythmia, ventricular dysfunction, and bacterial endocarditis. Dilatation of the aorta is an additional issue nowadays.
6.4.1 Pulmonary Regurgitation
A certain degree of PR is inevitable if the leaflets or the annulus of the pulmonary valve had been incised at repair. Some investigators report moderate or severe PR in 40–85% at 5–10 years after repair.690 Color flow mapping and/or pulse Doppler illustrate PR in most patients. PR imposes a volume burden to the RV, becoming less contractile. Clinical symptoms are usually obscure during childhood and adolescence, but can become prominent in adults over 20 years after repair.691–693 Exercise intolerance and signs of heart failure are noted. Dangerous arrhythmia, such as ventricular tachycardia, can be lethal.
Significant dilatation and dysfunction of the RV are more commonly seen in those who underwent repair associated with PR in late childhood or adolescence. An extensive incision to the RV musculature and/or excessive enlargement of the pulmonary valve annulus is a surgical factor that affects the RV through PR. Once the RV is distended because of volume overload through PR, the RV contracts inefficiently.
Pulmonary valve replacement after TOF repair is a safe procedure with a low mortality rate in adults.694–697 A bioprosthesis is generally chosen. It will become stenosed or regurgitant because of tissue calcification and degeneration several to 10 years after replacement. According to UK data, reoperation was needed in 8% at 10 years and in 11% at 15 years among 2,733 patients undergoing pulmonary valve replacement.698
Timely replacement of the pulmonary valve will off-load the RV, and the RV parameters change favorably.694,695,699–701 NYHA class improves,694,702 but better exercise tolerance may not be proven objectively.697,703–706 Moreover, risks of ventricular tachycardia and sudden death do not appear to be minimized by pulmonary valve replacement alone.707–709
Cardiac MRI is a great technique to evaluate the geometry and function of the RV, obtain quantitative data on PR, and assess myocardial damage.710–715 The geometry of the RV should normalize when a competent pulmonary valve is placed in patients with RV end-diastolic volume <150–170 mL/m2
or RV end-systolic volume <82–90 mL/m2.713,716,717 CT is another modality with a high spatial resolution, which is applicable in those with a pacemaker or an implantable cardioverter defibrillator (ICD). A downside is exposure to radiation or use of a contrast medium.718,719
The optimal timing for implanting a competent pulmonary valve remains controversial. Attention must be given not only to the RV but also the left ventricle (LV). Deaths seem more frequent with an impaired LV.325 Under current opinions, pulmonary valve replacement is indicated when the following factors are noted together with significant PR:527,720,721 (i) signs of right heart failure or exercise intolerance (Class I, Level B), (ii) moderate or severe dilatation/dysfunction of the RV (Class IIa, Level B), and (iii) worsening arrhythmia either atrial or ventricular (Class IIa, Level C) (Table 36).
Table 36. Indication for Pulmonary Valve Replacement
| |
COR |
LOE |
| Symptoms of right heart failure |
I |
B |
| Exercise intolerance |
I |
B |
| Moderate RV dilatation |
IIa |
B |
| RV dysfunction |
IIa |
B |
| Progressive and symptomatic atrial and/or ventricular arrhythmia |
IIa |
C |
COR, class of recommendation; LOE, level of evidence; RV, right ventricle.
Percutaneous transcatheter replacement of the pulmonary valve is successfully carried out in Western countries in patients with an external conduit for reconstruction of the RV outflow tract.704,722 There is even a report describing that a channel other than an external conduit can accommodate transcatheter valve. In that article, the RV outlet tract was constructed without a conduit in more than 50% of 774 patients undergoing implantation of a Sapien valve, and the overall success rate was 97.4%, with 14 patients requiring urgent surgery to relieve acute complications.723 Further development is ongoing in this area.
6.4.2 Obstruction Across the RV Outflow Tract
Significant pressure overload to the RV leads to progressive fibrous changes of its musculature. The RV functions better when the obstruction is appropriately treated.724 Surgical or interventional procedures are recommended for relief of such obstructions if the RV systolic pressure is >70% of that of the LV, or there is a pressure gradient >50–60 mmHg across the RV outflow tract (Class IIa, Level C).527,720 These values could be smaller in criteria for an interventional approach; namely, RV vs. LV systolic pressure is half to two-thirds, or the pressure gradient is 20–30 mmHg across the stenosis.725
Stenoses at the peripheral pulmnonary arteries are not uncommon. They can be present unilaterally or bilaterally at the intrapericardial pulmonary arteries or the intrapulmonary portions beyond the hilum of the lungs. Transcatheter intervention is a practical choice, by simple balloon dilatation or by placing a stent (Class IIb, Level C).527,720 An indication criterion is a pulmonary flow ratio <0.4 on the stenotic side compared with the other side on lung perfusion scintigraphy (Class IIb, Level C),726 or imbalance of lung perfusion worse than 35% vs. 65%.725
6.4.3 Arrhythmia
Silka et al reported that 1.5 of 1,000 TOF patients died suddenly per year after definitive repair.337 Others describe a similar figure of 0.35% per year.727 Ventricular arrhythmia is detected in a certain percentage of patients, which can lead a sudden death (Level B).325,728,729 A report has described that ventricular arrhythmia occurred in 44% of post-repair patients; higher age at repair correlated with a higher incidence of such dangerous arrhythmia. Duration of follow-up, postoperative hemodynamics, or the year when repair was carried out were not influential factors.730 In the past, sudden death appeared to occur in 5% of patients in the long term after TOF repair. More recently, the figure has been <1% in those who underwent definitive surgery during their infancy or early childhood.731 Dangerous arrhythmias can be detected and treated more efficiently nowadays, contributing to an improved prognosis still further.732
An odds ratio was determined for ventricular tachycardia by analyzing 7,218 patients; a QRS 1 ms wider increases the odds ratio to 1.031.733 Another clinical analysis showed that sudden death was obviously commoner in those who experienced transient AV block lasting more than 3 days immediately after repair.303
As for the types of definitive repair, some investigators mentioned that transatrial closure of VSD was beneficial for less potential of lethal arrhythmia or RV dysfunction in the long term.734 Also, supraventricular arrhythmia may be minimized.735 Others are skeptical about this hopeful perspective.736 According to multi-institutional joint research in Japan, AV block without a pacemaker implanted and an episode of ventricular tachycardia were major risks for poorer prognoses. Overall, serious arrhythmias were less frequent in the Japanese cohort than seen in those in Western countries.326 Sudden death cannot be attributed to one specific issue. Lethal arrhythmias could have an intimate background of structural problems (such as significant obstruction across the RV outflow tract and PR), or functional deterioration (either LV or RV).733,737 Taking these into consideration, proper treatments should be arranged. Ventricular tachycardia with moderate LV or RV dysfunction warrants electrophysiological examination, antiarrhythmic medication, and catheter ablation (Class IIa, Level B).227,706,732 ICD implantation must be considered when sustained ventricular tachycardia or transient cardiac arrest is recorded. A large French study of 165 repaired TOF patients undergoing ICD implantation demonstrated that QRS fragmentation was the only factor predicting future indication of the device (Class IIa, Level B).14,738 This phenomenon was revisited by analyzing another registry’s data.739
6.4.4 Aortic Valve Insufficiency
The annular diameter of the aortic valve is natively larger than normal in TOF. The dimension does not become normal even after definitive repair. The aortic valve is liable to become regurgitant with age.446 Surgical indication for aortic valve replacement should conform to a similar circumstance in the normally structured heart.740
6.4.5 Tricuspid Valve Insufficiency
Tricuspid valve may leak also after TOF repair. One mechanism for this is surgical modification. A surgical patch is attached to close the VSD adjacent to the septal leaflet of the tricuspid valve when the defect is of a perimembranous type. Together with overriding of the aorta, the leaflets of the tricuspid valve are susceptible to adhering to the patch, eventually malfunctioning. Another cause of tricuspid regurgitation is dilatation of the annular attachment of the valve. Prolonged PR enlarges the RV cavity as well as the tricuspid annulus. Tricuspid valve repair is carried out in a standard way: attaching a ring for annuloplasty, and fixing the commissure between the septal and the anterior leaflets if needed.
6.4.6 Infective Endocarditis
A long-term observation study up to 30 years described that bacterial endocarditis occurred in 1.3%.741 The AHA/ACC guideline 2007 for prevention of infective endocarditis recommends caution when using antibacterial agents (either oral or injectable) in a selected cohort of patients when they undergo invasive procedures (Class IIa, Level C).742 The cohort includeds those undergoing surgery for CHD in whom an artificial membrane or material placed has not been covered with endothelium and a residual lesion is present adjacent to the prosthesis. Patients after TOF repair may fulfill the high-risk criteria, because of a VSD patch, reconstructed RV outlet, PR, stenosis across the RV outflow tract, a residual VSD communication, etc. Invasive procedures include dental treatments to the gingiva, roots of the teeth, or perforated oral mucosa, and also surgery to the airway, the skin, the skeletal tissues, or other organs infected.
7. Double Outlet Right Ventricle
The term ‘double outlet right ventricle (DORV)’ is used for an entity of malformation as well as for a manner of ventriculo-arterial connection in sequential segmental analysis. When cardiac architecture is complex with an abnormal ventricular inlet, the Fontan type procedure is usually chosen. This chapter describes DORV in the setting of situs solitus and concordant atrioventricular (AV) connection.
7.1 Morphological Features
The so-called 150% rule is applied practically; when “a%” of the circumference of the pulmonary valve and “b%” of the aortic circumference are related to the RV musculature, a+b >150 is a definition of DORV.743 As an embryological explanation, the subarterial conus is bilaterally present for this malformation.744 These 2 aspects can coexist in typical examples, but not always.
As the norm, the pulmonary trunk is left-anterior to the aortic root. When transposed (TGA), the aorta (Ao) is usually right-anterior to the pulmonary arterial (PA) trunk. DORV could have the Ao to the right of the PA trunk (side-by-side), right-anterior (oblique), or anterior (TGA equivalent). Rotation of the arteries extends into an L-loop arrangement in which the aortic root is even leftward of the PA trunk. Such 360-degree spatial variations greatly affect the proximal courses of the coronary arteries.745
In the side-by-side arrangement (the Ao is on the right with the PA trunk on the left), interventricular communication is referred to in relation to the great arteries; namely, 4 types: subaortic, subpulmonary, doubly-committed, and noncommitted743 (Figure 8746). These morphological orientations influence the hemodynamic features, from noncyanotic to severely cyanotic circulations.
In the TGA pattern, the aortic orifice is remote from the ventricular septum; accordingly, termed subpulmonary or noncommitted ventricular septal defect (VSD) type, and is also called “DORV of a TGA type” or “false Taussig-Bing malformation” (the classical form of Taussig-Bing malformation having the great arteries side-by-side with a subpulmonary VSD), leading to confusion in nomenclature.
Another factor in the hemodynamic variations is deviation of the outlet septum. Without deviation, both the aortic and pulmonary valves are unobstructed, and the amount of pulmonary flow increases. Pulmonary perfusion will decrease if the outlet septum obviously deviates towards the pulmonary channel (similar to tetralogy of Fallot). The other way round, it is the aortic pathway that becomes obstructed, and coexisting coarctation of the aorta is not rare.747
Other complicating factors include multiple VSDs, hypoplastic LV, mitral stenosis, straddling or overriding of an AV valve, and ASD.748–751 These can militate against biventricular repair of DORV, particularly when combined.
Types of reparative procedures are the main topic of concern in a surgical database. In this respect, DORV is classified under 4 headings: equivalent to simple VSD physiology, equivalent to tetralogy of Fallot, akin to TGA, and others.752,753
7.2 Biventricular Repair
7.2.1 Surgical Procedures
When DORV is anatomically repaired, a tunnel pathway is constructed from the LV to Ao through the interventrcular communication within the RV. Its procedural counterpart is to secure blood flow from the RV to the PA. The interventricular communication may be enlarged or the outlet septum may be partly resected to make sure that the LV–Ao channel stays unobstructed. Some reports indicate that such myotomy/myectomy is used in 45–63% of repaired DORV.749,751,752 As for the RV–PA channel, the RV outflow or the RV–PA junction is incised, if needed. In more complicated circumstances, use of an external conduit or the Lecompte maneuver would be the surgical option of choice.
In the subaortic VSD type, the LV–Ao tunnel is usually short. In doubly-committed VSD type, dual pathways, one for the LV–Ao and the other for the RV–PA, need to be designed in a balanced way. In the noncommitted VSD type, the intraventricular tunnel becomes long. Tension apparatus of the tricuspid valve and other intracardiac structures could interfere with placement of a baffle for rerouting. If not feasible without postoperative sequelae, the Fontan strategy would be an alternative. In the subpulmonary VSD type, the arterial switch procedure is popular combined with intraventricular rerouting in those without pulmonary stenosis.754 This provides an unobstructed LV–Ao channel; a relatively short intraventricular tunnel and natively small aortic valve should pose no problem, because the neo-aortic valve is a native pulmonary valve that has been widely patent. Some surgeons prefer a technique for intraventricular rerouting in the subpulmonary VSD type with the Ao–PA side-by-side.755 Other options include use of a Damus-Kaye-Stansel (DKS) anastomosis,756 the REV procedure,757 and the half-turned truncal switch procedure.758 The latter two procedures are applied in those with pulmonary stenosis.
Functional biventricular repair, such as use of intra-atrial redirection of blood,759 is no longer performed.
7.2.2 Surgical Outcomes
Surgical outcomes are the result of various factors, such as the detailed features within the morphological spectra, the nature of the surgical procedures, and the era of repair. An overview in heterogeneous groups reported a survival rate of 87–88% at 5 years,750,760,761 or 81% at 8 years.751
7.3 Management in the Longer Term
Exercise is not limited in those who have reasonable heart function and no obvious residua or sequelae. Annual follow-up would be sensible using standard echocardiography and electrocardiography. Anticoagulation and prophylactic antibacterial agents are to be administered on a standard guideline basis for the surgical prosthetic materials used.
Follow-up should be more frequent in those with progressive sequelae; Holter monitoring, exercise testing, and cardiac MRI are of practical use. As indicated in a guideline by the Japanese Circulation Society,762 sudden death is mostly related to ventricular arrhythmia. Such lethal events are associated with significant degrees of ventricular hypertrophy, the pressure gradient across the ventricular outflow tracts, myocardial ischemia, regurgitation through the semilunar valves, and miscellaneous arrhythmia. This suggests that lifestyle and exercise protocol should be advised on these findings.
7.3.1 LV–Ao Channel
The channel from the LV to the Ao is obstructed in 0–10% (which could be an underestimate because of the limited periods for observation).748,751,753,760,763–765 The major mechanisms are overgrowth of fibrous tissues, narrowing of the interventricular communication, and intimal proliferation in the tunnel. Hemodynamic turbulence is generated, leading to thickening and degeneration of the aortic valve, eventually resulting in aortic regurgitation. Aortic valve insufficiency needs attention also when the arterial switch procedure or the DKS anastomosis has been carried out.
7.3.2 RV–PA Channel
Obstruction across the RV outflow requires incision to the RV or resection of the obstructive RV muscles. Pulmonary valve replacement for regurgitant burden remains infrequent in DORV. Pulmonary valve replacement may be challenging after the REV procedure; a rigid artificial valve might not sit ideally adjacent to the sternum. A malfunctioning conduit (stenosed or regurgitant) is replaced. Pulmonary stenosis after the arterial switch procedure is treated according to the level of obstruction (subpulmonary, valvar or supravalvar). The coronary artery crossing the RV outflow tract influences the method used for enlargement.745
7.3.3 Intraventricular Baffle
A complicated suture line can leave a hemodynamically significant leak between the coarsely trabeculated RV and a long baffle. The tricuspid valve leaflets and their tension apparatus could adhere to the baffle, causing progressive tricuspid regurgitation. The baffle material can harbor bacterial infection which is far from easy to eradicate.
7.4 Invasive Treatments After DORV Repair
The reoperation rate varies from 13% to 54% among a limited number of reports.751,753,754,764,766,767 As for a narrow LV–Ao pathway, a systolic pressure gradient 50 mmHg would be the usual criterion for reoperation (Class IIa, Level C).763 From a technical viewpoint, the lesion should be approached not only via the tricuspid valve but also through a RV incision and the aortic valve.
In the subaortic VSD type, obstruction and regurgitation across the RV–PA channel and a residual shunt are keys. In the doubly-committed VSD type, the baffle design is not uniform. Both the LV–Ao and RV–PA channels need attention. In the subpulmonary VSD type, the arterial switch maneuver has issues regarding aortic regurgitation, RV–PA stenosis, and stenosis of the coronary arteries. When the intraventricular tunnel technique is chosen, the pathway is rather long. The baffle-related issues need to be sorted out.
The noncommitted VSD type repaired by biventricular repair gets into more trouble. The LV outflow tract becomes narrow in many cases,751,768 and its enlargement is far from perfect, because of intracardiac features. The presence of a large noncontractile baffle will negatively affect ventricular performance. Furthermore, tricuspid regurgitation often requires replacement of the valve.
Nonsurgical invasive therapy remains uncharted. Obstruction across the RV outflow tract, pulmonary valve regurgitation, and arrhythmia are treated by catheter intervention similar to those in tetralogy of Fallot.769–771 Some case reports are available.772,773 Placement of a stent at the stenosed LV–Ao tunnel is a very rare occurrence thus far.774
8. Transposition of the Great Arteries
8.1 Intra-Atrial Redirection of Blood
Intra-atrial redirection of blood was reported in 1959 by Senning775 (using own atrial tissues) and in 1964 by Mustard et al776 (using a baffle made of an artificial material) for functional biventricular repair of transposition of the great arteries (TGA). These techniques were routinely used in 1970s, eventually replaced with anatomical repair, the arterial switch procedure firstly reported in 1976 by Jatene et al.777 Nowadays, functional procedures are rarely used; only in very exceptional cases such as a patient with a significantly abnormal pulmonary valve.
8.1.1 Postoperative Failure of the Systemic Ventricle
Following the intra-atrial redirection procedure, the systemic ventricle is morphologically of the right. The pumping chamber is quite likely to deteriorate and its inlet valve often becomes regurgitant. These are impediments that worsen with age. Tricuspid regurgitation (TR) is functionally equivalent to mitral regurgitation; a severe degree of TR requires repair or replacement of the valve.778 Such TR is not as frequent as seen in congenitally corrected TGA. Once ventricular function is impaired, β-blockers and/or angiotensin-converting enzyme inhibitors are given, according to usual practice in patients with a systemic ventricle morphologically of the left. It remains unknown, however, whether the morphological right ventricle (RV) would respond similarly and favorably to ordinary anti-heart failure drugs.779,780 In the case of intractable circulatory failure even on catecholamines, an auxiliary artificial heart or heart transplantation is to be considered. Cardiac resynchronization therapy is attempted for interventricular incoordination by means of biventricular pacing.
The pathways within the atria are so complicated after the functional repair that obstruction frequently occurs across the venous channel either from the vena cava to the mitral valve or from the pulmonary veins to the tricuspid valve. Leakage through the suture line for the intra-atrial baffle is another issue. Both may be successfully treated by balloon dilatation or placement of a stent.
8.1.2 Postoperative Arrhythmia
Intra-atrial rerouting imposes a certain burden on the atrial tissues; the suture line for fixing the baffle is long and complicated. Sinus nodal dysfunction can be induced postoperatively,781 and supraventricular tachycardia, such as atrial fibrillation or atrial tachycardia, is not rare in the longer term.782 Tachyarrhythmia after extensive atrial surgery is often drug resistant. Radiofrequency ablation is attempted.783 The intra-atrial baffle is oriented in various ways. Without preoperative cardiac CT imaging, it is quite difficult to locate the catheter ablation tips at appropriate sites. In addition, following the Mustard procedure, the intra-atrial baffle is usually thickened and calcified. Often the transvenous approach to the functionally left atrial cavity is rather demanding.
8.2 The Arterial Switch Procedure
This radical procedure took over from intra-atrial rerouting repair by the mid 1980s. Surgical results have improved markedly since the procedure became standard in the early neonatal period and the Lecompte maneuver (the pulmonary arterial (PA) trunk is mobilized anteriorly to the ascending aorta) was introduced. Survival rate is nowadays 97% at 25 years.784 Early death is seemingly associated with myocardial ischemia. Other complications in the longer term include neo-aortic valve insufficiency, obstruction across the RV outflow tract, and arrhythmia.784–797
8.2.1 Aortic Regurgitation (AR)
a) Frequency and Mechanism
AR is seen in 5–40% cases after the arterial switch procedure. Reports have described a mild degree in 61% at 20 years after the repair vs. moderate or severe in 22%.74,798–803
Progressive AR is attributed to enlargement of the aortic root throughout childhood.803 The wall of the neo-aortic root is composed of PA tissues by nature. The root tends to dilate more than expected with ordinary growth.791,804,805 Other factors include the presence of a ventricular septal defect (VSD), previous PA banding, preoperative obstruction across the left ventricular (LV) outflow tract, surgical modification of the Valsalva sinus associated with coronary arterial translocation, and a marked mismatch between the diameters of the reconstructed root and the distal ascending aorta.74,790,797–804,806,807
b) Medical Follow-up
Follow-up at regular outpatient clinic is based on symptoms and ECG, chest X-ray, or echocardiography. Chronic AR, when mild, may stay silent for a long period; the LV compensates the reflux with its overall performance maintained.808 More precisely, the LV myocardium potentially has a perfusion defect, and flow reserve is decreased through the coronary arteries.809–813 Moderate or severe AR can promote distention and dysfunction of the LV within a relatively short period. General symptoms occur, such as chest pain, palpitation, faintness, and dyspnea on exertion. Exercise testing and echocardiography are useful for consecutive evaluation of LV function.
Mild AR with neither symptoms nor LV dilatation would require annual medical check-ups. Moderate AR with mild LV dilatation or extrasystoles would require meticulous assessment of cardiac function on echocardiography every 6–12 months, and coronary angiography to assess for potential issues. Patients with severe LV dilatation/dysfunction, angina or dyspnea are at a high risk of poor prognosis. Aortic valve replacement (AVR) should be considered carefully (Class IIa, Level C).814,815 When severe AR coexists with other sequelae, strict and regular evaluation is mandatory. The neo-aortic root becomes larger disproportionally during the early postoperative phase (first several years). A severely dilated aortic root (aortic root diameter ≥55 mm in adults816) is an indication for surgical treatment (Class IIa, Level C).
c) Invasive Treatments
AR after the arterial switch procedure is treated by AVR (Class IIa, Level C).807,817–819 A bioprosthesis is chosen for females of reproductive age. Otherwise, a mechanical valve is used. A reasonable outcome is anticipated in the longer term after AVR.807 Significant AR with the aortic root dilated is an indication for the Bentall procedure. When the aortic root is significantly large but AR is mild or less, aortic root replacement may be feasible with the valve spared (the David maneuver).820–822
8.2.2 Obstruction Across the RV Outflow Tract and Pulmonary Stenosis
a) Frequency and Mechanism
This is a common sequela seen in 3–30%.784–798,823–827 PS is present at the level of the pulmonary valve, the subpulmonary region, the pathway above the valve (the anastomotic site), the intrapericardial PA, or the peripheral PA. These can be in combination. The Lecompte maneuver stretches the reconstructed PA. The materials used for PA augmentation can be thickened and shrunken. In some patients, the native aortic valve (the RV outflow channel) has an intrinsically small diameter. Such a valve annulus as well as the surgical anastomosis may not grow proportionally following the arterial switch procedure.
This postoperative sequela increases over time, and additionally, the degree of obstruction gradually becomes worse. A multi-institutional study827 demonstrated that surgical or percutaneous re-intervention for obstructed RV outflow tract was carried out in 12% of patients undergoing the neonatal arterial switch. Freedom from re-intervention was 94% and 83% at 1 year and 10 years, respectively, after the initial procedure.
b) Medical Follow-up
Follow-up at regular outpatient clinic is based on symptoms and examinations (ECG, chest X-ray, or echocardiography). Mild obstruction usually does not present symptoms; the RV adapts generously to chronic pressure-load via compensatory hypertrophy. Exercise tolerance and overall ventricular performance stay within their normal ranges. RV systolic pressure may not be elevated by unilateral stenosis of the PA. Significant obstruction has the potential to cause RV distension and dysfunction, or ventricular extrasystoles within a relatively short period of time. Palpitations, dyspnea on exertion, and hepatomegaly are warning signs. Exercise testing, echocardiography, and lung perfusion scintigraphy are useful for clarifying the circumstances of RV outflow obstruction.828
Mild obstruction with neither symptoms nor RV dilatation would require annual medical check-up (Level C). Moderate obstruction with RV dilatation or extrasystoles at rest/on exertion (moderate risk group) would warrant meticulous assessment on echocardiography every 6–12 months (Level C). Patients with severe obstruction (pressure gradient ≥50 mmHg or the ratio of systolic RV pressure to systolic LV pressure ≥0.7) should be submitted for interventional treatments (Level C). Surgical revision is appropriate also in females who are intending to get pregnant, in those who want to participate in competitive sports, and in those with significant pulmonary valve regurgitation (Class IIa, Level C).
c) Invasive Treatments
The surgeon augments the stenosed portion of the PA using a patch. A narrow pulmonary valve annulus is split at the RV–PA junction. These maneuvers provide good results with low recurrence rates (Class IIa, Level B).786,823,824 Percutaneous balloon dilatation seems less radical than surgical revision, but can be repeated, particularly for milder obstructions (Level B). Once effective, the site becomes nicely large in proportion to body growth.829–831 Following the Lecompte method, the site of the PA stenosis is often adjacent and adherent to the anterior aspect of the reconstructed proximal ascending aorta. If balloon dilatation tears the arterial walls too extensively, the consequence is iatrogenic creation of an aorto-pulmonary window. In this respect, enhanced CT is informative for clarifying the orientation of the structures and nature of the lesion.
Use of stents appears promising, compared with simple balloon dilatation;832 the stenosed channels become wider, the pressure gradient less, and the RV/aortic systolic pressure ratio smaller (Level C). Stent fracture is not rare in those with a stenotic PA bent by the adjacent ascending aorta, because the pulsatile aortic wall compresses the stent from behind. The stent, in turn, should not compress the coronary arteries. The coronary arterial course can be visualized on enhanced CT, in relation to the prospective stent placement (Level C).
8.2.3 Coronary Arterial Obstruction
a) Frequency and Mechanism
Translocation of the coronary arteries is a minute and technically demanding maneuver. If the vessel not fully patent at its origin or at its proximal course after re-implantation, myocardial ischemia should cause serious problems either in the early stage or in the longer term. A considerable number of reports have described coronary arterial obstruction in the longer term. Deaths are common within 1 year postoperatively.833 Coronary or aortic root angiography in the longer term will reveal coronary arterial lesions in 3.6–17.4% of patients at a later stage.786,788,791,809,834 That figure jumps to 40% in those with signs of myocardial ischemia. Even in those without evidence of ischemia, stenosis is observed in 7%.791 The obstructive conditions can change long after in the postoperative course.835 Various degrees of stenotic change are detectable in as high as 89% of asymptomatic patients, using intravascular ultrasound examination.836
The proximal part of the coronary artery is easily distorted, twisted, or stretched during surgery. The intima is liable to get injured at the orifice and inside the proximal stem, eventually leading to fibrous proliferation and afferent intimal thickening, which induce mechanical obstruction of the vascular lumen. Such pathological changes are progressive.834 Peripheral obstruction of the coronary arteries is rare.
Hearts with TGA often show abnormal architecture of the coronary arteries. A solitary stem for the whole system is not extremely rare. A branch may go through between the pulmonary trunk and the mitral valve.791,837,838 In some patients, the right or the left coronary artery courses between the aorta and the PA trunk. An intramural portion may be present within the aortic wall for the proximal stem. Translocation of such coronary arteries is technically challenging.
b) Medical Follow-up
Strict check-up is mandatory in patients with chest pain, other cardiac symptoms, and signs of myocardial ischemia on echocardiography or exercise ECG. Scintigraphy and selective coronary angiography should be arranged for these patients.
Even when the degree of coronary arterial insufficiency is unclear, the vessel could have a potential obstruction or narrowing. The left coronary artery is known to possess a smaller diameter than normal. Perfusion defect to the LV muscles is found in a relatively high percentage in the longer term.809–813 Noninvasive evaluation alone is often inadequate for precise diagnosis. Angiography and other invasive methods are needed, particularly in adults (Class IIb, Level C).
Invasive treatments are indicated in patients with symptoms or proven evidence of myocardial ischemia, to say nothing of those with a history of myocardial infarction. Surgery or catheter intervention should not be delayed for severe stenosis at the main stem and impending disruption of collateral flow (Class IIa, Level C).839
c) Invasive Treatments
Percutaneous balloon dilatation of the coronary arteries and/or placement of stent is effective on many occasions. The alternative is surgery for coronary arterial bypass or patch augmentation of the orifices.839–845 Experience in these invasive treatments remains limited, and conclusions on the outcome in the longer term are yet to be made.
8.2.4 Arrhythmia
Atrial arrhythmia is seen in approximately 5%,846,847 which is less than in those undergoing functional repair by intra-atrial rerouting.845,848,849 A Japanese multi-institutional study showed various types of arrhythmias in 9.6% of 624 patients (who underwent the arterial switch procedure between 1976 and 1995 and survived ≥1 year), including complete atrioventricular block, sinus nodal dysfunction and other bradycardic disturbance, supraventricular tachycardia, atrial fibrillation, and ventricular tachycardia.846 Postoperative arrhythmia is regarded as a risk factor for mortal or morbid events in the longer term. Arrhythmic status will become worse in half of patients once this complication occurs. Coexistent ventricular septal defect may be an unfavorable factor for complete atrioventricular block and other arrhythmias.
9. Congenitally Corrected Transposition of the Great Arteries and Discordant Atrioventricular Connection
Ventricular septal defect (VSD), pulmonary stenosis, and other cardiac lesions often coexist with congenitally corrected transposition of the great arteries (ccTGA). For the status of functional repair, frequently achieved are closure of the VSD, interposition of an external conduit from the morphologically left ventricle (LV) to the pulmonary artery (PA), and tricuspid valve replacement. The systemic ventricle of the morphologically right ventricle (RV) can fail at a certain stage of life. The tricuspid valve deteriorates over time, causing significant tricuspid regurgitation (TR). Tachyarrhythmia is often the case. Surgical revision is probable. With the status of anatomical repair, in contrast, the reoperation rate appears lower, particularly when the arterial switch maneuver is combined with intra-atrial redirection of blood.
9.1 Morphological Features
The atrioventricular (AV) connection is discordant; that is, the right atrium is connected to the morphologically LV with the left atrium to the morphologically RV. The ventriculo-arterial connection is also discordant; the PA trunk arises from the morphologically LV with the aorta from the RV. This combination corrects the hemodynamics in a functional way. That is why the malformation is called as ‘congenitally corrected transposition of the great arteries’. The PA trunk is located right-posteriorly, wedged in between the right and the left AV valves. Fibrous continuity is obvious between the pulmonary valve and the mitral valve. The aorta sits left-anteriorly supported by a conus below.
In addition to segmental discordances, commonly coexisting malformations are VSD (60–80%), pulmonary stenosis/atresia (30–50%), and abnormal AV valves (14–56%).81,850,851 The outflow to the PA is usually obstructed at the valve or subvalvar level. Subvalvar stenosis may be caused by a membranous sac from the ventricular septum or fibrous tissue in continuity with the inlet valves. In those with an atretic pulmonary outflow, the aorta almost always overrides the VSD. This geometric feature accommodates a subaortic stenosis when the VSD is small. As for the inlet valves, Ebstein malformation is common for the morphologically tricuspid valve in this setting. Straddling is occasionally seen in either the mitral or the tricuspid valve. The conduction system is abnormally structured, associated with the distorted arrangement of the atria and the ventricles. AV block is a frequent finding. In some patients, AV nodes persist anteriorly and posteriorly, forming the so-called ‘sling’ of the conduction bundle.852,853
The overall circulation may be balanced reasonably well by combined hemodynamic abnormalities, and surgical intervention may not be indicated for the time being. In such circumstances, the morphologically RV is not pressure-offloaded. Coordination between the ventricles remains as it should be for efficient function in this particular malformation. When these coexisting malformations are absent, the patient and the medical team are understandably reluctant to pursue surgery. Functional repair is achieved, in childhood or later, when the VSD needs to be closed, the tricuspid valve needs to be replaced, or the LV–PA channel needs to be reconstructed using a conduit.90,854 The natural prognosis and the status of functional repair are not always encouraging; problems are progressive failure of the systemic RV, TR (functionally mitral regurgitation), and tachyarrhythmia.851,855–858 In anatomical repair, the morphologically LV is placed as a systemic chamber instead.859–862 The LV must have been kept as a high-pressured chamber before the radical repair. The morphologically RV, rather pessimistic for maintenance of the systemic circulation for long, is placed as a pulmonary ventricle.
9.2 Prognosis in the Nonsurgical Group
Without VSD or pulmonary stenosis, the prognosis of ccTGA depends on deterioration of the AV block and TR. Patients can remain well up to 60–70 years old without AV block or TR. A multi-institutional study by Graham et al81 reported that 67% of ccTGA patients with coexisting malformations and 25% with no coexisting issues had episodes of heart failure by 45 years old. The systemic ventricle was failing in 70% of the former and in 55% of the latter. TR was present in 82% and 84%, respectively. LV failure was in 25% of the former vs. only 7% of the latter. The Toronto Children’s Hospital group described854 survival rates as 75% at 20 years, 60% at 30 years, <50% at 40 years, and 15% at 60 years. AV block occurred in 2% per year.
9.3 Surgical Repair
9.3.1 Functional Repair
The morphologically RV sits as a systemic chamber after functional biventricular repair, which is a conventional definitive procedure. Pulmonary stenosis, if coexistent, would require use of an external conduit, although could be treated by pulmonary valvotomy or enlargement of the pulmonary valve annulus in some patients. An external conduit usually stenoses eventually, requiring reoperation after 10–15 years. It is a paradoxical phenomenon that successful relief of pulmonary stenosis may promote TR. In contrast, in some patients without pulmonary stenosis, TR can regress after banding of the PA trunk because of a shift of the ventricular septum towards the morphologically RV. A significantly regurgitant tricuspid valve should be replaced, because repair of the valve is usually unsuccessful. Replacement should be arranged before the systemic RV is irreversibly impaired. A preoperative RV ejection fraction <40–43% leads to a poorer prognosis.89,863,864
Patients with a discordant AV connection can have more complicated circumstances such as ventricular disproportion and abnormal inlet valves. Those patients are to be treated by a single ventricular strategy. The Fontan circulation would be somewhat efficient up to the mid-term in this setting.865,866
9.3.2 Anatomical Repair
The morphologically LV serves as a systemic chamber. Anatomical repair was introduced in early 1990s.859 The discordant AV connection is corrected by intra-atrial rerouting (either the Mustard or the Senning maneuver), together with amendment of the discordant ventriculo-arterial connection. The latter part is achieved by the arterial switch procedure in patients without pulmonary stenosis (the so-called double switch procedure), and intraventricular rerouting with reconstruction of the RV–PA pathway using an external conduit in those with pulmonary channel obstruction.859–862 Intraventricular rerouting requires a sufficiently large VSD and RV volume, because the tunnel starts at the VSD and occupies space within the RV cavity. Anatomical repair demands the LV to remain high-pressured prior to surgery. When low-pressured, the LV needs to be preconditioned by banding of the PA trunk. This procedure for such training purpose may induce LV dysfunction, rather than preconditioning, after early adolescence. In adults, anatomical repair is only considered in those with pulmonary stenosis (naturally pressure-loaded LV). There have been reports describing anatomical repair as not providing better results compared with the Fontan circulation in the intermediate term in adults.865,866
9.4 Prognosis in the Longer Term After Repair
A recent study86 compared the long-term results after heart transplantation, the Fontan-type procedure, functional repair, and anatomical repair in ccTGA. Up to 15 years of follow-up, systemic LV failure was rare after anatomical repair. Systemic RV failure and TR occurred mainly after 12 years or more.
9.4.1 Functional Biventricular Repair
RV dysfunction, TR, AV block, conduit stenosis, and pulmonary regurgitation progress with time. The survival rate is 55–85% at 10 years. Causes of death are surgical death at reoperation, RV failure, sudden death, and arrhythmia. Average age at death is around 40 years old in ccTGA patients with associated intracardiac malformations.81,86,90,854 Reoperations are needed in one-third of patients at 10 years after tricuspid valve replacement or conduit placement. Conduit revision is usually needed every 10–20 years. The types of conduits available have changed remarkably and will change still further with continuing innovation in medical technology. TR becomes worse after initial functional repair using a conduit, particularly in patients with VSD and pulmonary stenosis, probably because the ventricular septum deviates in a geometrically unfavorable fashion.90,489,867,868 A similar mechanism applies to the circumstances after revision of a conduit that lowers the systolic LV pressure. The morphologically LV can intrinsically tolerate a certain degree of pressure load, which means that moderate conduit stenosis is even beneficial after functional repair in terms of tricuspid valve function. Complete AV block is strongly related to heart failure and sudden death. Tachyarrhythmia reflects impaired function of the systemic ventricle, appearing increasingly with time. Heart transplantation would be the last method for intractable ventricular failure even on optimal medical therapy, cardiac resychronization therapy, and conventional surgical treatments.868–871
9.4.2 Anatomical Repair
The morphologically LV functions well as a systemic chamber, with the survival rate being 90–100% at 10 years and 75–80% at 15 years.85,872–876 Postoperative NYHA functional class is I or II in the majority of the patients. Residual TR was a risk factor for late death. The arterial switch procedure combined with intra-atrial rerouting provides better results in the longer term compared with functional biventricular repair. The group of patients undergoing intraventricular rerouting and use of a RV–PA conduit may have more sequelae than the arterial switch group; pulmonary stenosis, subaortic stenosis, RV failure (the pulmonary ventricle), and arrhythmia require interventional therapy. On the basis of a domestic analysis,85 freedom from reoperation was 84.4% (the arterial switch group) and 89.6% (the intraventricular rerouting group) at 10 years after anatomical repair.
9.5 Postoperative Management
Angiotensin converting enzyme inhibitors and β-blockers are not unreasonable to prescribe for TR and systemic RV failure. Disappointingly, no positive data have been obtained in large-scale trials in this respect.187,877–880 Some physicians prefer to use anticoagulants and antiplatelet agents as a precaution against thrombosis within a systemic RV that is quite trabeculated and ready to fail. Warfarin must be given after replacement with a mechanical valve. Anticoagulation therapy is also pertinent for supraventricular tachycardia that is sustained or not entirely suppressed.
The systemic LV can fail, particularly after banding of the pulmonary trunk for preconditioning followed by anatomical repair. LV function should be monitored consecutively. Intra-atrial rerouting maneuvers can induce supraventricular arrhythmia, or the venous pathways constructed within the atria can become narrow related to intimal proliferation or body growth. It is also wise to consider prevention of infective endocarditis.
Pregnancy should only proceed under the guidance of a specialist in adult congenital heart disease. Heart function and residual issues need to be clarified by echocardiography and MRI in advance. Exercise testing with analysis of expired gas is informative. In general, exercise tolerance of ≤75% of the anticipated value indicates unsuitable conditions for pregnancy.528
9.6 Investigations for Follow-up
Investigations listed below should be considered during follow-up.
• Electrocardiogram: paying attention to progressive AV block
• Chest X-ray: checking for enlarged cardiac silhouette, pulmonary congestion
• Echocardiography: to monitor ventricular function, TR, LV pressure, PA pressure (in a qualitative way)881
• Cardiac MRI: not applicable in patients with a conventional pacing system;882 can evaluate function of the systemic RV better than echocardiography (particularly for meso-cardia or dextrocardia); can calculate the regurgitant fraction, which indicates the severity of valve insufficiency in a quantitative way; can illustrate cardiac segments in 3-D or 4-D883–885
• CT: can evaluate RV function, stenosis of the LV–PA conduit, calcification of native tissues or artificial materials, and coronary arterial lesions in 3D
• Cardiac catheterization: can precisely evaluate ventricular function, regurgitation across the AV valves, pulmonary stenosis, and coronary arterial stenosis
• Nuclear medicine: evaluates myocardial ischemia, and autonomic nerve function886,887
9.7 Repeated Invasive Treatments in the Longer Term (Table 37527)
Table 37. Recommendations for Intervention in ccTGA
| |
COR |
LOE |
Tricuspid valve replacement in symptomatic patients with severe TR and preserved RVEF
(EF >40%) |
I |
C |
Tricuspid valve replacement in asymptomatic patients with severe TR and progressive RV
dilation and preserved RVEF (EF >40%) |
IIa |
C |
Biventricular pacing in patients with complete AV block or 40% ventricular pacing
requirement |
IIa |
C |
Tricuspid valve replacement in asymptomatic patients with severe TR, progressive RV
dilation, and reduced RVEF (EF <40%) |
IIb |
C |
Main pulmonary artery banding in symptomatic patients with severe TR, progressive RV
dilation, and reduced RVEF (EF <40%) who are not amenable to medical treatment |
IIb |
C |
AV, atrioventricular; ccTGA, congenitally corrected transposition of the great arteries; COR, class of recommendation; EF, ejection fraction; LOE, level of evidence; RV, right ventricle; TR, tricuspid valve regurgitation.
(Produced from Baumgartner H, et al. 2021.527)
9.7.1 Catheter Intervention
Percutaneous balloon dilatation is carried out for stenosis at the bifurcation of the PA trunk. Enlargement of the pulmonary valve annulus may cause AV conduction disturbance, because the nonbranching bundle is often coursing anterior to the pulmonary valve.
9.7.2 Antiarrhythmic Interventions
Catheter ablation is attempted for supraventricular and ventricular tachycardia; for the time being, it is effective. Arrhythmia often recurs (Level C). Complete AV block needs pacemaker implantation to avoid sudden death (Class IIa, Level C). In patients with RV dysfunction, AV synchronization (DDD pacing) is recommended (Class IIa, Level B).888 In those presenting ventricular tachycardia, an implantable cardioverter defibrillator is indicated.255 Cardiac resynchronization therapy (CRT) improves the QRS interval, as well as the geometry and ejection fraction of the systemic ventricle. The effect on the systemic ventricle of right morphology is less impressive compared with that of the left.889,890 CRT may work better together with PA banding in patients after functional biventricular repair.891
9.7.3 Surgical Revision
Significant or progressing TR after functional biventricular repair requires replacement of the valve (Class IIa, Level C).7 Repair is seldom achieved successfully. Surgical intervention to the valve should be arranged before irreversible myocardial changes of the RV are initiated (Class IIa, Level C). Re-replacement might be necessary in due course. A radical revision from the status of functional biventricular physiology to anatomical repair sounds attractive, but no successful achievement has been reported in adults.874,892,893 Banding of the PA trunk will no longer precondition the morphologically LV appropriately. Nonetheless, banding itself, not aiming at further radical procedures, improves TR in a selected number of patients and could be supplementary to medical treatments when the patient’s condition is severely deteriorating (Class IIb, Level C).
Following anatomical repair, the vena caval channels may need surgical enlargement. A RV–PA conduit would need replacement or other types of revision. Results after these reoperations are seemingly promising. It should be noted that aortic valve regurgitation increases gradually with growth in some patients.
10. Coarctation of the Aorta and Interrupted Aortic Arch
Hypertension remains as a concern even after these lesions are successfully treated by surgical or interventional procedures. Invasive therapy is often repeated long after the initial repair, for restenosis, aneurysm or dissection around the primary lesion. In addition, aortic valve disease is potentially present. The ascending aorta and the intracranial arteries also need attention for aneurysmal change.396,894–897
10.1 Morphological Features
The aortic channel is commonly coarctated adjacent to the arterial duct. The aortic arch is entirely nonconfluent when the structure is interrupted. Aortic coarctation is isolated (simple coarctation) or combined with intracardiac malformations (coarctation complex). The latter is commoner in Japan. Interrupted aortic arch is almost always found together with intracardiac abnormalities.
Ventricular septal defect (VSD) is the most intimate association, followed by bifoliate aortic valve (seen in >50%). Aortic valve stenosis, subaortic stenosis, and mitral valve problems are not rare. Other complex abnormalities can coexist (e.g., transposition of the great arteries, double outlet right ventricle, common arterial trunk, etc.). Cystic medial necrosis is frequently seen in histological specimens from the aortic wall.443
10.2 Initial Repair
Reconstruction of the aortic arch was first performed around 1950. Orthodox techniques include end-to-end direct anastomosis (with resection of the coarctated part and the ductal tissue), patch augmentation, interposition of an artificial graft, and the so-called subclavian flap method (plasty using a flap prepared from a proximal portion of the left subclavian artery). After 1990, repair was increasingly carried out during the neonatal period or early infancy, enabled by modified techniques; namely, an extended aortic arch reconstruction (an oblique anastomosis between the inner curvature of the aortic arch and the descending aorta) or a side-to-end direct anastomosis between the ascending and descending aorta.
Coexisting intracardiac malformations are repaired simultaneously with reconstruction of the aortic pathway in many patients. As an alternative approach, aortic arch reconstruction is carried out concomitantly with pulmonary arterial banding during the newborn period, followed by second-stage intracardiac repair in late infancy. A staged approach is considered reasonable in those with low body weight, very poor preoperative condition or extremely complicated intracardiac abnormalities.
Primary balloon dilatation of the coarctated aorta, attempted some time ago in place of surgery, turned out to produce an aneurysm around the treated area in a relatively large proportion of patients.898
10.3 Management After Initial Repair
Attention is paid postoperatively to restenosis, aneurysmal formation (either true or pseudo-aneurysm), dissection or rupture of the aorta, residual hypertension, arteriosclerotic changes (cerebrovascular or coronary arterial disease), aortic valve disease and infective endocarditis.
Restenosis is diagnosed by detecting a pressure difference between the upper and lower limbs, as well as hypertension of the upper body. Also, it is wise to note if blood pressure pulse waves show phasic delay, lower pulse pressure, and lower wave height. Even in those with no pressure difference between the upper/lower limbs at rest, exercise may reveal a growing pressure gradient and markedly elevated blood pressure of the upper body. Hypertension on exercise alone, however, may not always indicate restenosis of the aortic channel.499
Life expectancy is not normalized by repair of aortic coarctation; survival rates are 91%, 84%, and 72% at 10, 20, and 30 years, respectively, after surgical treatment at around 16 years of age. Earlier surgical treatment appears to be better; survival rates of 91% and 80% at 20 and 40–50 years, respectively, after repair at around 5 years of age. Residual hypertension is not entirely dismissed by surgery during infancy. Some investigators report that hypertension remains in one-third of patients undergoing invasive treatments, leading to left ventricular (LV) hypertrophy, myocardial infarction, and heart failure. Cardiovascular complications are the cause of death in 70% of patients dying late.396,896,899
An enlarged aortic arch shadow on chest X-ray is a crucial sign of aneurysmal formation. LV hypertrophy and ST-T change are noted on electrocardiography. On echocardiography, attention should be paid to the aortic valve, the subaortic region, the mitral valve, LV function, LV wall thickness, diameter of the aorta at the ascending, the arch, and the descending levels, and blood flow pattern/velocity across the aortic arch/the descending aorta. MRI and CT (with a contrast medium) are informative for morphological evaluation of the lesions, and stent fracture or migration. It is reported that intracranial aneurysm is present in approximately 10% of those with aortic obstruction. The incidence is higher in adolescents and adults than in small children. Systolic blood pressure correlates with LV mass. Hypertension of the upper body is associated with late complications. In this respect, mobile blood pressure monitoring and blood pressure measurement on exercise are of practical use. According to the findings, timely diagnosis and proper medication become feasible on the basis of hypertension guidelines.900
10.4 Repeated Invasive Treatments
10.4.1 Indication
Catheter evaluation (pressures and geometry) is the gold standard for revision to correct restenosis or aneurysm (Table 38).7 Re-intervention or re-operation is indicated when the systolic pressure gradient is ≥20 mmHg, <20 mmHg but with obviously impaired LV, aortic regurgitation or markedly developed collateral flow (Class I, Level B),396,901,902 fusiform aneurysm ≥50 mm diameter, an expanding saccular type or pseudo-aneurysm (Class I, Level B).903,904 Mean systolic pressure difference of 20 mmHg (Doppler-estimated) is another criterion to consider. Modern imaging by MRI and CT illustrates the obstruction as significant when the narrowest diameter of the aortic channel is <50% of the adjacent portion, or <50% of the aortic diameter at the diaphragm level.
Table 38. Recommendations for Late-Term Management and Timing of Intervention for Coarctation of Aorta and Interrupted Aortic Arch
| Recommendation |
COR |
LOE |
| Management |
Assessment for coarctation of aorta should be performed in young patients with hypertension
of the upper limbs or leg fatigue in exercising |
I |
B |
Contrast-enhanced cardiac MRI and/or CT for initial or post-surgical/catheter follow-up
examination in adult patients with coarctation of aorta |
I |
B |
>20 mmHg resting systolic blood pressure gradient between upper and lower limbs is
significant for the diagnosis of coarctation of aorta |
IIa |
C |
Exercise testing in the adult patients with coarctation of aorta to assess exercise-
induced hypertension |
IIb |
C |
| Treatment |
Surgical or catheter intervention in patients with pressure gradient of >20 mmHg between
upper and lower limbs |
I |
B |
| Surgical or catheter intervention in patients with coarctation of aorta and aortic aneurysm |
I |
B |
Catheter intervention in patients with coarctation of aorta and aortic stenosis of
≥50% but with mild pressure gradient (≤20 mmHg) |
IIa |
C |
Balloon angioplasty in patients with coarctation of aorta who need repair but stent placement
or surgical intervention is not an option |
IIb |
B |
COR, class of recommendation; CT, computed tomography; LOE, level of evidence; MRI, magnetic resonance imaging.
(Produced from Stout KK, et al. 2019.7)
10.4.2 Methods
A Heart Team composed of cardiologists, cardiac surgeons, anesthetists, and other experts should decide which invasive techniques are needed to solve the problem, considering the benefits and risks in each individual patient. If artificial materials are placed during the procedure, antiplatelet agents (e.g., aspirin) should be prescribed for at least 6 months afterwards.
a) Surgical Treatment
Aneurysm is removed and the aorta is reconstructed by interposing an artificial graft or anastomosing directly in an end-to-end fashion. Restenosis requires a similar maneuver or patch enlargement (Class I, Level B).902,905,906 The so-called extra-anatomical bypass is an alternative when a direct approach to the stenotic part is extremely challenging.
b) Catheter Intervention898,901,907–909
i) A localized restenosis without hypoplasia of the aortic isthmus is a good indication for balloon dilatation, regardless of the patient’s age (Class I Level C).
ii) Placement of a stent is pertinent in those who can accommodate a ≥20 mm-diameter stent (Class I, Level B).
iii) It is acceptable to consider use of a stent device that can be dilated afterwards up to the size of the aorta in adults (Class IIa, Level C).
iv) Use of a covered stent is an option of choice for treating an aneurysm when the so-called landing zone is sufficiently large on the proximal and distal sides of the lesion and the device causes no deleterious obstruction of the adjacent arterial branches. Covered stents available in Japan remain limited in terms of size. This technique may not be applicable for patients in a growth stage.
11. Persistent Truncus Arteriosus
Persistent truncus arteriosus is a rare form of heart malformation, seen in 1–4% of congenital heart disease. The hemodynamics rapidly change as pulmonary resistance falls soon after birth.
11.1 Morphology
Embryologically, a common arterial trunk persists because the arterial septum (between the aorta and the pulmonary trunk) is deficient. The trunk gives rise to the aorta, the coronary arteries, and the pulmonary arteries. Interruption of the aortic arch coexists in 10–15%. The outlet septum (conus septum) is also lacking; forming a ventricular septal defect of a juxta-arterial type. The semilunar valve is a solitary structure, either overriding the ventricles or more related to one of the ventricles. The valve is trifoliate, quadrifoliate, bifoliate or of other forms, often dysplastic, and either regurgitant or stenotic. Patterns of the coronary arterial origins are various.910,911 The aortic arch is frequently right-sided.
The Collet-Edwards classification is based on the configuration of the pulmonary arteries, and Van Praagh added a heading for interrupted aortic arch. DiGeorge or 22q11.2 micro deletion syndrome is a common association.912,913
Systemic, pulmonary, and coronary perfusions are all supplied via the trunk. When pulmonary resistance falls, pulmonary perfusion increases drastically causing fulminant ventricular volume overload. The truncal valve may start to deteriorate as blood flow significantly increases across the structure. Systemic and coronary perfusions decrease to a critical level. These sequential phenomena are against a fair prognosis. When left untreated, Eisenmenger syndrome is established at an early stage of life.
11.2 Clinical Course
Medical treatment is limited. A surgical plan is needed on a semi-urgent basis.
11.3 Surgical Procedures
11.3.1 Primary Repair
Primary repair is preferred during early infancy, usually by means of the Rastelli procedure using a right ventricle–pulmonary artery (RV-PA) conduit.914–919 A small homograft (10–12 mm diameter) is used in Western countries, but is not regularly available in Japan. Instead, a nonvalved tube or a bovine jugular vein with a venous valve is utilized. These conduits will become obstructed relatively early. The RV-PA channel may be reconstructed without use of a conduit, which has been a trend in Japan. The technique could delay reoperation for an obstructed RV-PA pathway,116,913,920–922 but would be deleterious for pulmonary regurgitation.
When detaching the pulmonary arteries from the trunk, the coronary arterial orifices must be secured. Type II or III truncus arteriosus is more demanding technically than type I in this respect.
11.3.2 Staged Repair
Repair in a staged fashion is chosen in infants with complicating factors. Initially, the pulmonary arteries are banded to regulate pulmonary perfusion. The so-called bilateral banding is popular particularly in Japan, carried out in 76% of patients undergoing staged repair between 2008 and 2018.922 A greater conduit can be placed for the RV-PA pathway at the second stage than at the primary repair in early infancy. Another ambitious approach is a palliative Rastelli procedure (without closing the ventricular septal defect) followed by completion of repair.923
11.3.3 Truncal Valve Regurgitation
Repair of the truncal valve is challenging when significantly dysplastic, particularly in neonates and infants. Primary repair could offload the valve. Still, replacement has been the only solution eventually in many patients.924–929 Replacement of the truncal valve is usually pessimistic during early infancy.930,931
11.4 Post-Repair Management
11.4.1 Outcome
Most deaths occur immediately after primary repair because of a pulmonary hypertensive crisis or impaired ventricular function. Beyond that period, outcome is fair; survival rate is 60–85% at either 10 or 20 years.915,916,918,932,933 Causes of death in the longer term include respiratory failure, infection, pulmonary hypertension, and sudden death. DiGeorge syndrome and a post-tracheostomy status are among the risk factors for late death.916,932 Pulmonary resistance remains relatively high in many patients and could be related to unfortunate results in the longer term.116 NYHA functional class is usually I or II. Interrupted aortic arch is a detrimental factor for early survival, but does not appear to have much effect in the long run.934–937
11.4.2 Reoperation and Catheter Intervention
a) Conduit Stenosis
Obstruction across the external conduit used for primary repair requires reoperation relatively early. A conduit with a 10–12 mm diameter may be renewed at 2 or 3 years after the initial repair. Overall, freedom from conduit replacement has been 45–55% at 5 years, 35–50% at 10 years, and 3–35% at 20 years.917,932,936,937 Use of a homograft is not necessarily superior to use of a xenograft from the viewpoint of long-term results.938 The pulmonary arteries are occasionally distorted after initial banding, which needs surgical revision.
Catheter intervention is carried out for degenerative or calcified tissues of the valve leaflets in the conduit or anastomotic obstruction. These will be effective, although transiently.932,938,939
b) The Truncal Valve
Surgery to the truncal valve is not infrequent after repair; freedom from reoperation being 80–83% at 10 years and 62–85% at 20 years.933,934,940 In patients in whom the valve was repaired at the initial definitive procedure, freedom from reoperation is lower: 20–40% at 10 years and 15–20% at 20 years.941–944 A quadrifoliate valve is another risk factor from a morphological aspect.945
c) The Trunk
The diameter of the trunk is greater than that of the normal aortic root. Even after successful repair, its configuration remains abnormal. The truncal wall is stiffer than the normal aortic wall, but fortunately, rupture or dissection of the neo-aortic root is rare.946,947 Deformity and stiffness of the trunk may be background mechanisms of progressive truncal valve regurgitation.948
12. Biventricular Repair Using an External Conduit
Repair using an external conduit, the so-called Rastelli-type procedure, was initially reported in late 1960s.949,950 It is applied in truncus arteriosus, transposition of the great arteries (type III), and other cyanotic heart diseases with pulmonary stenosis or atresia (Table 39).
Table 39. Indications for Repair Using an External Conduit
| a. TOF with pulmonary atresia (pulmonary atresia with VSD) ± major aortopulmonary collateral arteries (MAPCAs) |
| b. TOF or double outlet RV with abnormal coronary artery crossing in front of the RV outflow tract |
| c. TGA + VSD + pulmonary stenosis (LV outflow tract obstruction) |
| d. Truncus arteriosus (common arterial trunk) |
| e. Double outlet RV + pulmonary stenosis/atresia |
| f. Anatomical repair for congenitally corrected TGA or AV discordance + pulmonary stenosis/atresia |
| g. Aortic valve replacement using a pulmonary autograft (the Ross/Ross-Konno procedure) |
| h. Functional biventricular repair for congenitally corrected TGA or AV discordance+pulmonary stenosis/atresia (LV-PA conduit) |
AV, atrioventricular; LV, left ventricle; PA, pulmonary artery; RV, right ventricle; TGA, transposition of the great arteries; TOF, Tetralogy of Fallot; VSD, ventricular septal defect.
12.1 Conduit Materials
Conduits are made of an autologous or heterologous pericardium, an aortic or pulmonary homograft tissue, or synthetic materials such as a Dacron or a PTFE (Gore-Tex®) tube. As for a valve structure (either trifoliate, bifoliate or unifoliate), handmade leaflets are provided using autologous/heterologous pericardium or a PTFE membrane. Otherwise, a commercially available bioprosthesis or a homograft valve is available. Very occasionally, a mechanical valve is chosen. Use of a tube without a valve is less than ideal in terms of pulmonary regurgitation.50,115 A handmade PTFE conduit with bulging sinuses and triple PTFE leaflets (0.1 mm thick) has been rather popular in Japan.54,63,64 A cryopreserved homograft is conveniently and regularly used in other Western countries. A homograft may be decellularized to suppress immunoreactivity. In older children and adults, a stentless bioprosthesis is an option of choice.951–953 A bovine jugular vein with a venous valve (Contegra®) was recently approved in Japan.60,954
12.2 Fate of the Conduit
Biventricular repair became feasible in some complicated malformations using a valved conduit. The results are promising prognostically in the intermediate term. In the longer term, nevertheless, the conduit poses a hemodynamic impediment.
12.2.1 Conduit Failure
Prosthesis–patient mismatch induces stenosis in a relative sense. Proliferated pseudo-intima and calcified valve leaflets cause mechanical obstruction. The thoracic cage could compress the conduit lumen. The anastomosis between the conduit and the right ventricle or the pulmonary artery may be distorted as the thorax grows. Leaflets of a bioprosthetic valve become calcified and degenerative, resulting in stenosis and regurgitation. Autologous pericardial leaflets usually degenerate. In this respect, leaflets made of a 0.1-mm-thick PTFE membrane tolerate calcification and seemingly last longer.54,63,955
12.2.2 Re-Intervention
Use of a 10–12 mm diameter conduit is usually the only choice in neonates and infants. This warrants surgical exchange of the conduit in 2–3 years’ time. An 18-mm-diameter tube would not require reoperation until adulthood.63,64,916,956
Stenosis may not occur when no conduit is used. Some techniques (the Lecompte maneuver, for example) are dedicated to this purpose; in which the pulmonary artery is mobilized and directly attached to the right ventricular incision.116,957 Anteriorly, a patch with a monocusp is placed for augmenting the channel. Pulmonary regurgitation will be the main issue in the future.
12.3 Management in the Longer Term After Conduit Repair
Heart murmur, arrhythmia, and hepatomegaly need to be checked at physical examination. Chest X-ray, ECG (including Holter recording), and echocardiography should be carried out once every 6–12 months. Enhanced CT and cardiac MRI provide accurate 3D information in adults, supplementing echocardiographic resolution. Exercise testing has practical use for unmasking functional problems.
Once clinical symptoms appear or impediments progress, follow-up should be arranged more frequently. A therapeutic strategy is to be determined based on further investigations such as cardiac catheterization and angiography. For other organs, sequential blood tests and abdominal investigations (ultrasound, CT, hepatic scintigraphy, etc.) are informative.
An external conduit bears a high risk of infective endocarditis. Appropriate prophylactic treatments are strongly recommended at dental surgery. Whenever a patient with a conduit is febrile, infection of the prosthesis should be on the list of differential diagnoses. A bovine jugular venous prosthesis can get infected more often than others do.60,61
12.4 Pathophysiology of Conduit Malfunction
The right ventricle (RV) will get pressure overload by stenosis across the conduit as well as volume overload by regurgitation through it. Tricuspid insufficiency of a significant degree, if it coexists, will impose further volume load to the RV and the right atrium. These are obvious burdens for a heart that has experienced previous surgical insults. Incisional scars and overloaded musculature of the heart readily accommodate arrhythmic potential. Moreover, the overloaded RV deleteriously compresses the left ventricle, suppressing its performance for the systemic circulation. A severely obstructive conduit would produce systemic venous congestion and progressive dysfunction of the bodily organs.
12.5 Treatments for Conduit Failure
12.5.1 Medical Treatment
Prescribing oral diuretics is a basic medical treatment, but severe conduit failure cannot be dealt solely with medication. The proper way to go is timely surgical revision. Antiarrhythmic drugs are not unreasonable to administer in a standard fashion, but they may not be effective insofar as mechanical disorders remain. An electrophysiological study should be carried out to clarify the mechanisms of arrhythmias. Catheter ablation or surgical antiarrhythmic maneuvers are to be planned in conjunction with hemodynamic offloading of the heart. A Japanese national study regarding arrhythmia after conduit repair958 indicated that late death occurred in 9% of the cohort (including sudden death) and ventricular arrhythmia in 2%.
12.5.2 Catheter Intervention
Balloon dilation, placement of a stent, and transcatheter pulmonary valve replacement are among the therapeutic options. Pulmonary valve procedure will be introduced soon in Japan. At this moment, nonetheless, the technique is not permitted for a channel using a PTFE tube by the government. A procedure for dilating severely calcified lesions is considered a temporary measure. Surgical treatment should be arranged without delay.959,960 Excessive dilation can rupture the conduit. Another pitfall is to compress the coronary artery coursing behind the conduit, inducing acute coronary insufficiency.961,962 Complications of balloon rupture and stent fracture are not rare.
Catheter intervention is the first choice for peripheral pulmonary arterial lesions.
12.5.3 Reoperation
Surgical revision is a radical solution, upsizing the conduit. The conduit anastomoses (either proximal or distal) are made unobstructed, as well as relieving any obstruction within the RV. The handmade PTFE conduit is popular also for exchange of the conduit.50 A PTFE tube containing a bioprosthesis (either stented or stentless) is used in adult patients; its results appear to be equivalent to those of pulmonary homograft.952,953
The so-called Danielson method (the peel operation) is historical.963 Utilizing fibrous tissues behind the previous RV–pulmonary artery (PA) channel, a conduit is no longer placed at reoperation. To minimize pulmonary regurgitation, a prosthetic valve is attached nowadays if this technique is applied. Modification of this maneuver is used in patients in whom the previous conduit cannot be removed securely, such as in the case of extremely calcified artificial materials or when a coronary artery is adjacent to the conduit. Leaving some materials behind, a new RV-PA pathway is reconstructed using an anterior augmentation patch.964
A competent pulmonary valve might not have been provided in patients with low pulmonary arterial pressure.115 This is not positively supported under the current trend. In those with pulmonary hypertension or hypoplastic peripheral pulmonary arteries, a competent pulmonary valve is essential.
Peripheral stenosis of the PAs should be treated dominantly by catheter techniques. Direct surgical approaches are challenging. Cardiac resynchronization or other pacing therapy is another sensible idea by which catheter techniques can cooperate with surgical revision.
12.5.4 Indication for Reoperation
Indication for conduit replacement conforms to that for obstruction across the RV outflow tract in principle. Symptomatic patients are submitted for invasive treatments (Class I, Level C). Asymptomatic patients are also considered for such treatments when the features listed in Table 40 are noted (Class IIa, Level C).
Table 40. Indications for Conduit Revision
| a. RV/LV systolic pressure ratio >70% |
| b. RV-PA systolic pressure gradient >50 mmHg |
| c. Pulmonary regurgitation causing RV dilatation or impaired systolic function |
| RVEDVI >150–160 mL/m2 |
| RVESVI >80 mL/m2 |
| d. Impaired or deteriorating exercise tolerance |
| e. Significant tricuspid regurgitation |
| f. Other (hemodynamically relevant arrhythmias, planned surgery for lesions other than the RV-PA conduit, etc.) |
EDVI, end-diastolic volume index; ESVI, end-systolic volume index; LV, left ventricle; PA, pulmonary artery; RV, right ventricle.
12.6 Prognosis
12.6.1 After the Initial Conduit Procedure
Survival rate in the longer term after the initial repair is partly up to the nature of the disease. On the whole, the survival rate is 77% at 10 years and 60% at 20 years.115 Some reports recently described that outcome could be better; survival rate >90% at 20 years965 or even 95% at 15 years after a PTFE conduit procedure.50 A Japanese series documented 92% at 10 years and 88% at 20–25 years.958
Causes of death in the longer term include arrhythmia (sudden death),958 infective endocarditis,62 and complications at reoperation.115,966 Heart failure is unlikely to be a major cause of late death nowadays, because timely reoperation is carried out for conduit obstruction/regurgitation. Death from pulmonary hypertension is, in general, malformation-specific (e.g., major aortopulmonary collateral arteries or truncus arteriosus) rather than conduit-related. Cardiomegaly, RV hypertension, atrial arrhythmia, and NYHA functional class II or worse are detrimental factors prior to surgical revision. Accordingly, reoperation should not be delayed.958
Reoperation is inevitable when the initial repair was carried out during infancy; freedom from reoperation is 49% at 10 years and 33% at 20 years.967 Timing depends on the conduit size placed at the initial repair.
12.6.2 After Conduit Replacement
The results after conduit revision are fair; survival rates are 80% at 10 years and 60% at 20 years.115 NYHA functional class remains within I or II in many patients following reoperation done at optimal timing. A 3rd conduit procedure may not happen, in terms of channel obstruction, when an 18-mm diameter conduit or greater is used at reoperation in adults. Instead, pulmonary valve insufficiency could be the cause of repeated interventions. Follow-up and management after reoperation should stay the same as after the initial repair.
12.7 After Conventional Repair (Functional Biventricular Repair Using a LV-PA Conduit) for Congenitally Corrected Transposition of the Great Arteries (ccTGA)
Conventional repair used to be the only surgical choice, before 1990, for ccTGA with LV outflow tract obstruction or atrioventricular (AV) discordance with double outlet RV and pulmonary stenosis/atresia. A long conduit was placed from the LV apex to the PA behind the sternum or via the right thoracic cavity. A polyester tube was used together with a bioprosthesis. This conduit needs to be replaced when it becomes severely obstructed. Different from a RV-PA conduit, however, the indication for reoperation must be considered cautiously. If the morphological LV is perfectly pressure-offloaded, the geometry of the ventricles will change undesirably and the systemic AV valve (the morphologically tricuspid valve) could start to deteriorate. A modest degree of obstruction is intentionally left across the LV-PA channel to avoid this phenomenon.87,893,968,969 Surgical indication is, therefore, not straightforward.
12.8 After the Ross Procedure
The RV-PA channel functions relatively well in the longer term after the Ross procedure. Presumably, use of an autologous pericardium or a homograft is a favorable factor. On the other hand, a channel made of autologous tissues may not be suited for interventional catheter techniques. Surgical revision would be rational.
13. Fontan-Type Procedure
The Fontan-type procedure is a functional repair in patients whose malformations are unsuitable for biventricular repair. The procedure offloads the ventricle fully and resolves hypoxemia caused by a right-to-left shunt. The procedure was first achieved in a girl with tricuspid atresia by Fontan and Baudet, reported in 1971.970
13.1 Surgical Methods
Initially, atriopulmonary connection (APC) was popular, in which the pulmonary arteries (PAs) were directly anastomosed to the right atrium. Total cavopulmonary connection (TCPC) was the next stride forward advocated by de Leval et al in 1988, in which better fluid dynamics, fewer arrhythmias, and rarer thrombotic complications were expected.971 The TCPC was originally achieved by either a lateral tunnel technique or intra-atrial grafting. Subsequently, an extra-cardiac method was introduced by Marcelletti et al in 1990.972 Their variation has several advantages; such as a less arrhythmogenic nature with less damage to the atrial tissues.
13.2 Pathophysiology
The Fontan circulation is characterized by (1) raised central venous pressure (CVP) and congestion of the bodily organs, (2) lower cardiac output, and (3) mild hypoxemia.973 CVP must be raised to maintain lung perfusion, but it impedes perfusion of other organs (Figure 9).974 Absence of the pulmonary ventricle makes preload to the systemic ventricle inadequate, creating the status of chronic heart failure. This is particularly true for the systemic chamber that has suffered from longstanding hypoxemia and volume-overload prior to the Fontan procedure. Nonpulsatile flow is not ideal for the pulmonary circulation; production of nitric oxide from endothelial cells is diminished. A right-to-left shunt develops through progressive collateral formation between the systemic and pulmonary veins.
Exercise tolerance is suboptimal. Maximal oxygen uptake is up to 60–70% of normal.
13.3 Complications and Management
13.3.1 Cardiovascular Complications
a) Ventricular Malfunction
i) Systolic Dysfunction
Contractility is influenced by prolonged hypoxemia, preoperative volume overload, surgical insult, and conduction disturbance. The ventricle becomes dilated, less contractile, and occasionally asynchronous.
Standard medical treatment for chronic heart failure is applied: angiotensin-converting enzyme (ACE) inhibitors, β-blockers, and/or mineral corticoid receptor antagonists (MRA) are administered under proper fluid management (Class IIa, Level C).973,975
ii) Diastolic Dysfunction
The pulmonary circulation becomes less than ideal when the end-diastolic pressure of the ventricle increases.
Potential factors that induce ventricular hypertrophy should be removed, such as coarctation of the aorta or obstruction across the ventricular outflow tract (Class IIb, Level C).
iii) Heart Asynchrony
Ventricular pacing is a detrimental factor in patients with atrioventricular (AV) block.976 A wider QRS is associated with impaired exercise tolerance.138
Cardiac resynchronization therapy is attempted. In those with a degree of AV block, conduction duration is adjusted under monitoring by cardiac Doppler; A and E waves should be separated appropriately.246 Ventricular dyscoordination requires expertise. Pacing simulation on cardiac catheterization is helpful. In general, a longitudinal arrangement of electrodes benefits a solitary right ventricle, whereas biventricular activation is favorable for dual ventricles (Class IIb, Level C).249
b) Atrioventricular Valves
A solitary tricuspid or a common inlet valve is likely to leak as postoperative time increases.977 Insufficiency does not necessarily pose clinical symptoms. Optimal timing for commencing remediation needs careful attention.
ACE inhibitors are pertinent to start in those with moderate regurgitation across the AV valve (Class IIb, Level C). When severe, a surgical approach is preferred. An inlet valve other than a morphologically mitral form is often difficult to repair, and thus requires replacement (Class IIa, Level C). The surgeon should minimize the potential for AV block with any intracardiac maneuvers.
c) Vascular Abnormalities
i) The Great Arteries
The ascending aorta may be distended and less extensible. Medial necrosis of the vessel is related to an intrinsic disorder. Impaired glucose tolerance and hypertension are acquired issues that can decrease distensibility in the longer term.978 Such aortopathy, if manifested, is associated with exercise intolerance or a worse prognosis. Coarctation of the aorta, even without a pressure gradient during rest, can cause hypertension on exercise, eventually causing pressure overload to the systemic ventricle and its hypertrophy.
Residual coarctation is treated by catheter or surgical intervention. Pharmacotherapy for aortopathy remains uncharted.
ii) The Peripheral Arteries
The small arteries have reduced endothelial function. Exercise tolerance is suboptimal. Also, the coagulation–fibrinolysis system is affected.
Hypertension and elevated systemic vascular resistance are treated by vasodilators. Impaired glucose tolerance, which influences endothelial function, should be treated under consultation on lifestyle habits and physical exercise (Class IIb, Level C).
iii) Aortopulmonary Collateral Arteries
Collateral arteries develop from the subclavian or the intercostal arteries to the lungs. Additional blood supply through these abnormal vessels, when excessive, can cause hemoptysis or volume overload to the ventricle.
These troublesome complications are treated by catheter intervention embolizing the abnormal vessels (Class IIa, Level C).
iv) Systemic Venous to Pulmonary Venous Collaterals
Raised CVP can promote abnormal communications from the vena cava, the brachiocephalic vein or the hepatic vein to the pulmonary veins. This results in a degree of hypoxemia.
These communications are to be occluded surgically or interventionally when desaturation is obvious or a thromboembolic episode is documented (Class I, Level B). It should be noted that CVP could increase still further following occlusion of the collateral channels, leading to a less efficient Fontan circulation overall.979
d) Heart Failure
When focusing on patterns of failing conditions, 2 headings are useful: (1) early failure in which the patients do not adapt to the circulation soon after the Fontan-type procedure, and (2) late failure in which the once-adapted Fontan circulation becomes less efficient long afterwards.171,973 Usually, in the former there is reduced cardiac output with higher CVP, while in the latter there is increased cardiac output with higher CVP.171 Late failure may be a result of some complications of the bodily organs.
i) Low Cardiac Output With High CVP Type
Cardiopulmonary dysfunction is often the major issue soon after surgery. Features to be diagnosed are significant AV valve regurgitation, pump failure of the heart, raised systemic vascular resistance, and elevated pulmonary vascular resistance.
ACEI/ARB, β-blockers, and MRA are considered as anti-heart failure remedies (Class IIb, Level C).973,975 Pulmonary vasodilators are used in those with higher pulmonary vascular resistance (Class I, Level B). Patients with ventricular asynchrony are submitted for resynchronization. Significant inlet valve insufficiency may need repair or replacement. Heart transplantation is an alternative option for patients in whom all these treatments are considered far from effective.
ii) High Cardiac Output With High CVP Type
The ventricle often contracts reasonably well in late failure. Pulmonary vascular resistance remains unelevated. Systemic resistance is disproportionally low. Impaired hepatic function is deemed crucial for such vasodilation.
This circumstance is the opposite to early failure. The conventional treatments for heart failure could make the overall pathophysiology even worse. Pulmonary vasodilators would not work for the PAs; rather, inducing systemic hypotension. Oxygen inhalation is one step to go ahead. Systemic vascular resistance should be appropriately maintained as high by administering α-agonists (midodrine, norepinephrine, etc.) (Class IIb, Level C). These maneuvers adjust oxygen delivery and perfusion pressure to the organs.980 This type of circulatory failure has a bleak prognosis. Palliative care might be the way to go.981
iii) How to Prevent Late Failure
CVP needs to stay low during the asymptomatic stage to mitigate the potential of Fontan failure in the future.982 Body fluid management is fundamental. Meticulous attention should be paid to respiratory conditions, inlet valve, ventricular function, and collateral vessels. Then, pharmacological and/or nonpharmacological treatments will follow in a strategic way.
13.3.2 Arrhythmia
a) Tachycardia
Atrial tachycardia is common, seen in 60–80% of patients with APC and 5–33% of those with TCPC. Among the TCPC group, the surgical technique for the Fontan circulation using an extracardiac graft appears superior to that by means of intra-atrial rerouting.120 A background for atrial arrhythmia is surgical incisions to the atrial tissue, a dilated atrial wall or hypertrophy of the atrial muscles. Ventricular arrhythmia is less common (2–10%).
Tachyarrhythmia is more frequent in older patients, in those long after APC, and those with significant hemodynamic issues. Heart failure, if present, should be treated simultaneously with or prior to antiarrhythmic therapy.
β-blockers, sotalol, and amiodarone suppress tachyarrhythmias, although they may recur. Sotalol elongates the QT interval, and amiodarone can induce malfunction of the thyroid or the lungs (Class IIb, Level C).
Catheter ablation is the principal treatment measure (Class IIa, Level C), but the success rate is not as high as in non-Fontan patients. Arrhythmia can recur in approximately 50% of those with APC. Repeated ablations improve the overall success rate.983
Implantation of a pacemaker is challenging through a transvenous approach. Once a pacemaker is attached successfully, implantable cardioverter defibrillator and antitachycardia pacing function are sensible to use (Class IIb, Level C).984
b) Bradycardia
Sinus nodal dysfunction is relatively common, particularly after APC.
A pacemaker is implanted for sinus nodal dysfunction and complete AV block (Class I, Level B). It is essential to cease the bradycardia when diastolic dysfunction of the ventricle is obvious. Ventricular pacing sites should be chosen for better ventricular synchrony (Class IIa, Level C).249
13.3.3 Noncardiovascular Complications
a) Protein-Losing Enteropathy
i) Pathophysiology
Proteins escape from lymphatic fluid to the intestinal lumen when the abdominal lymphatic system becomes congested.
ii) Diagnosis
Serum albumin is often <3.5 g/dL. Tc-human serum albumin scintigraphy readily detects the proof that serum albumin is leaking into the intestine. Clinical symptoms include edema of the limbs, abdominal distension, diarrhea, and ascites, although they may not be remarkable.
iii) Epidemiology
PLE occurs in 5–15% of patients with the Fontan circulation, and 20 years ago the survival rate was estimated as 50% at 5 years after manifestation of PLE. That figure has come up to 80%, but complete remission is still rare.985
iv) Management (Table 41)
Table 41. Management of Major Problems Long After the Fontan Operation
| Pathophysiology |
Management strategy |
COR |
LOE |
| Nutrition, body composition |
| Obesity, cachexia, sarcopenia |
Nutritional education, exercise prescription |
IIa |
C |
| Cardiovascular disease |
| Impaired cardiac function (*) |
| Systolic dysfunction |
Heart failure therapy (β-blocker, ACEI/ARB, etc.) |
IIa |
C |
| Diastolic dysfunction |
Heart failure therapy (β-blocker, ACEI/ARB, etc.) |
IIb |
– |
| Dyssynchrony |
Cardiac resynchronization therapy |
IIa |
C |
| Atrioventricular dysfunction (**) |
| Regurgitation, stenosis |
Heart failure therapy, surgical repair (plasty, replacement) |
I |
C |
| Aortopathy |
(ACEI/ARB, surgical repair) |
IIb |
C |
| Endothelial dysfunction |
(Heart failure therapy, exercise prescription) |
IIb |
C |
| Cirrhotic hemodynamics |
(Diuretics, vasoconstriction therapy) |
IIb |
C |
| Arrhythmias |
| Sick sinus syndrome |
Pacemaker implantation |
I |
C |
| Supraventricular tachycardia |
Medication |
IIa |
C |
| (reentrant, automaticity) |
Digoxin, aprindine, β-blocker, sotalol, amiodarone |
|
|
| |
Antitachycardia pacing |
IIb |
C |
| |
Catheter ablation |
IIa |
C |
| |
Surgery (Maze, TCPC conversion) |
IIb |
C |
| Respiratory disease |
| Restrictive impairment |
(Respiratory training) |
|
|
| Pulmonary arteriovenous fistula (PAVF) |
Oxygen therapy, pulmonary artery dilators |
I |
C |
Maldistribution of hepatic vein flow to the pulmonary
circulation |
Surgical redirection of the Fontan route |
IIa |
C |
| Portosystemic shunt |
Catheter embolization |
IIa |
C |
| Discrete-type PAVF |
Catheter embolization |
IIa |
C |
| Fontan-associated liver disease (FALD) |
Consult with hepatologist |
IIa |
C |
| Phrenic nerve palsy |
Diaphragm plication |
IIb |
C |
| Plastic bronchitis |
Cast removal, intubation |
I |
C |
| |
Tissue plasminogen activator, steroid inhalation |
IIb |
C |
| Protein-losing enteropathy (PLE) |
| Inflammation, infection |
Anti-inflammation therapy |
I |
C |
| Hemodynamics (***) |
To eliminate factors raising CVP |
|
|
| Bradycardia, tachycardia |
Pacemaker implantation/antiarrhythmia drugs |
I |
C |
| Fontan route stenosis/obstruction |
Catheter or surgical intervention |
I |
C |
| Pulmonary vein obstruction |
Catheter or surgical intervention |
I |
C |
| Aortopulmonary collaterals, PAVF |
Catheter embolization |
IIa |
C |
| Ventricular dysfunction |
Refer to (*) |
IIa |
C |
| Atrioventricular valve dysfunction |
Refer to (**) |
I |
C |
| Excess fluid retention |
Fluid management, diuretics |
I |
C |
| FALD |
| Congestion |
Refer to (***) |
I |
C |
| Cirrhosis, Liver cancer |
Consult with hepatologist |
I |
C |
| Hemostatic problems |
| Thromboembolism |
| Fontan route stenosis/obstruction |
Antithromboembolic therapy, Catheter or surgical removal |
I |
C |
| Stroke |
Consult cerebrovascular neurologist |
I |
C |
| Hemorrhage |
| Hemoptysis |
Hemostatic therapy, coil embolization |
I |
C |
| Stroke |
Consult cerebrovascular neurologist |
I |
C |
ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin II receptor blocker; COR, class of recommendation; CVP, central venous pressure; LOE, level of evidence; TCPC, total cavopulmonary connection.
Factors promoting higher CVP should be removed. Anti-inflammatory agents are given. A lymphatic duct might be occluded interventionally. Alimentary therapy is fundamental. Albumin or immunoglobulin is infused when applicable (Class IIa, Level C).
b) Thrombosis and Hemorrhage
i) Pathophysiology
The Fontan circulation fulfils the so-called Virchow’s triad. Thrombosis occurs either in the venous or arterial system. A residual interatrial communication, a constructed fenestration, and systemic venous to pulmonary venous collaterals can pass a thrombus causing cerebral infarction. Hemoptysis is a well-known bleeding event.986
ii) Diagnosis
Thrombus formed is demonstrated on transesophageal echocardiography, CT, or MRI, and 40% of patients with a thrombus remain asymptomatic.987 CT could indicate the bleeding point for hemoptysis.
iii) Epidemiology
Complications are seen in 6–7% of patients related to a hemostatic disorder. Thrombosis usually occurs within 1 year or beyond 15 years after the Fontan procedure.986 Bleeding episodes gradually increase in the longer term.986 Of bleeding complications, hemoptysis is most common, seen in 45%, followed by cerebral hemorrhage (10%).
iv) Background Factors
Heart failure, hepatic dysfunction, impaired glucose tolerance, and some ethnic origins affect disorders of the coagulation–fibrinolysis system.988,989 In Western countries, thrombus formation is significantly more frequent in untreated patients.990 In Japan, hemorrhagic complications are mentioned often in patients on anticoagulant agents.986
v) Prevention
A randomized study showed no statistical difference in thrombotic episodes during the early postoperative phase between use of aspirin or warfarin.991 This result cannot be extrapolated to therapy in the longer term. Prophylactic medication is recommended when (1) arrhythmic episodes are evident, (2) hemodynamics are not as efficient as they should be (impaired ventricular function, high CVP, obstruction across the inferior vena cava–PA pathway), (3) a dead cavity is present (e.g., blind-ended PA trunk), (4) a right-to-left shunt persists, and (5) prior thrombosis (Class IIb, Level C). It is sensible to commence anticoagulants properly when coagulability is activated; such as with injury, surgery, infection, worsening heart malfunction, or arrhythmia (Class IIb, Level C).
vi) Treatment
A large thrombus should be removed surgically in a timely fashion (Class IIb, Level C). Massive hemoptysis requires transfusion. The responsible bleeding vessels are to be embolized (Class IIb, Level C). Anticoagulants are temporarily discontinued, and a hemostatic is given.
c) Fontan-Associated Liver Disease (FALD)
i) Pathophysiology
FALD includes a series of diseases: liver congestion, hepatic nodules, liver cirrhosis, portal hypertension, and hepatic carcinoma.992 Liver fibrosis is seemingly a consequence of sinusoidal dilatation (stellate cells being activated by congestion) and microthrombosis.993 Cirrhosis and portal hypertension increase intrinsic substances that induce vasodilation, which leads to heart failure of a high cardiac output type.171,973
ii) Diagnosis
Hepatic echocardiography detects hyperechoic spots and a mass. A space-occupying lesion is readily visualized on CT and MRI. Liver congestion leads to higher levels of serum bilirubin and gamma-glutamyltranspeptidase (γ-GTP), whereas liver enzymes are not necessarily elevated. Serum albumin decreases when synthetic ability is deteriorating at the terminal stage. Liver fibrosis is definitively diagnosed by means of biopsy, but that is not a generalized practice. Practical evaluation of the severity of liver dysfunction is usually based on the Child-Pugh score or the MELD-XI score. Hepatic encephalopathy can happen at the end stage of FALD.980
iii) Epidemiology
Cirrhosis occurs in 1%, 6%, and 43% of patients at 10, 20, and 30 years, respectively, after the Fontan-type procedure. Once diagnosed, the survival rate is 57% and 35% at 1 year and 5 years, respectively.994 Liver cancer is seen in 1.6% and 5.7% of patients at 20 years and 30 years, respectively, after the Fontan type procedure. Beyond 30 years, the proportion increases more rapidly.995
iv) Management
It is essential to lower the CVP to minimize FALD (Class IIb, Level C). Systemic vascular resistance should be set appropriately high as is the case in hepatorenal syndrome (Class IIb, Level C).980
d) Pulmonary Arteriovenous Fistula (PAVF)
i) Pathophysiology
PAVF occurs on the PA side that receives diminished flow from the hepatic veins, presenting in a diffuse type, a discrete type or a mixed type. This complication is common with the Glenn physiology or after the Kawashima shunt (total cavopulmonary shunt). Such lesions can regress following completion of the Fontan circulation in childhood. Liver cirrhosis is another mechanism of PAVF.
ii) Diagnosis
Contrast echocardiography (infusing microbubbles into the PA) detects PAVF specifically. Thoracic CT may locate a lesion of a certain size. PAVF is found increasingly as the postoperative period gets longer, and is particularly frequent in left isomerism.996
iii) Management
Hepatic venous effluents can be redistributed appropriately by revision of the Fontan channel. Such reoperation is effective in some children (Class IIa, Level B).997 In those with PAVF of the discrete form, catheter embolization of the fistula is considered (Class I, Level B). Inhalation of oxygen or nitric oxide is used for hypoxia.
e) Plastic Bronchitis
i) Pathophysiology
High CVP is probably responsible for this complication. Casts can occlude the bronchi, which is lethal.
ii) Epidemiology
Seen in 1–2% of the Fontan patients. More common in childhood.
iii) Diagnosis
Productive cough and dyspnea. Definitively diagnosed by an obstructive cast with a crabmeat-like appearance.
iv) Management
Bronchoscopy is performed if a patient cannot cough out the casts in the airway. Hemodynamic status should be optimized. Steroid administration or use of aerosolized tissue plasminogen activator may be effective (Class IIb, Level C). There is a report describing percutaneous lymphatic embolization.998
13.4 Lifestyle and Exercise
Cardiovascular function is maintained at a reasonable level by preventing obesity, hypertension, and diabetes. Impaired glucose metabolism is common in domestic Fontan patients, seen in 40% of patients including 10% with established diabetes. They die early.19 Exercise intolerance is an obvious risk factor for bleak prognosis.999 Managing dietary and exercise habits is beneficial (Class IIa, Level C).488
14. Hypoplastic Left Heart Syndrome
Hypoplastic left heart syndrome (HLHS) comprises malformations with extremely small left heart structures. In the narrowest sense, HLHS is classified into 4 entities, based on a combination of aortic atresia or stenosis vs. mitral atresia or stenosis in hearts with situs solitus, concordant atrioventricular and ventriculoarterial connections, and no interventricular communication. Practically, some other forms are included, as variants, in those with abnormal segmental connections or septal defects.1000 This guideline includes both.
HLHS is seen in 1.4–3.8% of all congenital heart disease. Before the advent of fetal echo-screening, newborns with HLHS comprised 0.16–0.36 among 1,000 live births.1001 HLHS causes 23% of cardiac deaths within 1 week and 15% within 1 month.681,1001–1005
14.1 Morphological Features
One or multiple components of the left heart segments are hypoplastic, and the left heart system cannot maintain the systemic circulation. Conventional surgical or medical treatments cannot rescue the left heart function. Such hemodynamic implication is the essence of this clinical heading. Critical aortic stenosis, for example, is not included within the HLHS criteria, because surgical valvotomy or balloon valvuloplasty may work for biventricular physiology.
The pathogenesis of HLHS remains speculative; closure of the foramen ovale at an early fetal stage, undeveloped aortic and mitral valves, failure of myocardial growth at an early embryonic stage, and so on.
14.2 Surgical Treatment
HLHS is palliated by the Norwood procedure, which makes the right ventricle (RV) and the pulmonary trunk act as the left heart system, subsequently followed by establishment of the Fontan circulation. Otherwise, heart transplantation is an alternative.
14.2.1 Management Prior to the Norwood Procedure
Interatrial communication, if restricted, must be enlarged urgently by balloon technique (BAS) or surgery. When prenatal echocardiography shows restricted communication, the mother should be transferred to an institution where such urgent treatments are feasible for delivery of the baby (Class IIb, Level C). Prenatal MRI of the fetus would be informative; a nutmeg lung appearance1006 is a known deleterious factor for very poor prognosis. Fistula between the left ventricle (LV) and the coronary arteries affects ventricular function and atrioventricular conduction, particularly following the BAS maneuver. Extracorporeal circulatory assist device would better stand by on such an occasion.
The arterial duct must be kept patent on prostaglandin E1 continuous infusion. Even with cyanosis, oxygen inhalation is contraindicated.
Pulmonary flow may become excessive after birth. In order to raise the pulmonary vascular resistance, PaCO2
is maintained intentionally higher. Advanced management is carried out for respiration on lower oxygen concentration (fraction of inspiratory oxygen (FiO2) adjusted to 0.16–0.19 by mixing nitrogen gas with ordinary air).1007 A surgical maneuver for controlling flow to the lungs would be bilateral pulmonary arterial (PA) banding (Class IIa, Level C).
14.2.2 Perioperative Management of the Norwood Procedure
The Norwood procedure is primarily carried out during the neonatal period in many centers. The procedure may be arranged at a few or several months later if the bilateral PA have been banded as an initial palliation. Prostaglandin E1 needs to be given, or alternatively a stent is placed at the arterial duct until the Norwood procedure is completed. Over 4 months of age, the second-stage Norwood procedure can be achieved concomitantly with the bidirectional Glenn anastomosis (Class IIb, Level C). On the other hand, a longer interval between banding and the Norwood procedure may hinder PA growth.1008,1009
At the Norwood procedure, pulmonary flow is provided via a Blalock-Taussig (BT) shunt or a RV–PA conduit. The former has an advantage in terms of PA growth, whereas the latter is superior to a BT shunt because it avoids insufficient myocardial perfusion. Sano et al reported that 53% of patients with a BT shunt survived the Norwood procedure vs. 89% of those with a RV–PA conduit.1010 Pizarro et al1011 and Mair et al1012 described similar results.
Following the Norwood stage, the bidirectional Glenn procedure is usually arranged at 6 months of age or later. The Fontan completion is to be achieved after 1 year of age (Level C). At present, the survival rate of HLHS patients is 50–69% at 5 years (including those undergoing the Fontan completion). That figure should become more promising in the future.1013
14.3 Complications in the Longer Term After the Norwood Procedure
In many patients with HLHS, the native ascending aorta is quite narrow and coronary arterial perfusion is liable to become inadequate. Technical details for the Norwood procedure should be considered carefully to prevent reduced coronary arterial flow afterwards. Persistent myocardial ischemia should lead to dysfunction of the systemic ventricle and its inlet valve (morphologically tricuspid) regurgitation in the longer term.
The aortic pathway may be obstructed at some level. Also, the left PA is occasionally squeezed between the newly reconstructed ascending aorta and the trachea. For these obstructions, balloon dilatation or surgical augmentation is considered (Class IIb, Level C). Placing a stent is a sensible idea, but the stent could potentially compress the aortic pathway or the bronchial tree. Checking on CT or MRI is necessary from the viewpoint of 3D orientation.
A hypoplastic LV is a known potential abnormality of the conduction system. Atrioventricular block and other bradyarrhythmias can progress. Tachyarrhythmia is also possible in adults.1014
Other than heart problems, mild cognition disorder and maladaptation to social interactions have been recognized as issues of neural development and behavioral disorder in HLHS patients. Special support should be offered, such as physical, occupational, or language therapy, in a certain proportion of patients during their childhood and adolescence.1015,1016
15. Unrepaired and Cyanotic Patients
Some cyanotic patients remain unrepaired for certain reasons with or without previous palliative procedures. The degree of cyanosis varies, as do the hemodynamic features. Long-standing hypoxemia induces chronic damage to the bodily organs. Such visceral disorders, hemorrhagic episodes, and coagulation abnormalities are key issues for medical management (Table 42).
Table 42. Systemic Complications in Chronic Cyanosis
| 1. Polycythemia |
| Erythrocytosis |
| Hyperviscosity syndrome |
| 2. Bleeding and coagulation abnormalities |
| Thrombocytopenia |
| von Willebrand factor abnormality |
| Hemoptysis, Intrapulmonary hemorrhage |
| Cerebral thrombosis, thrombosis in the pulmonary arterial aneurysm |
| 3. Renal complication and uric acid metabolism |
| Proteinuria, glomerulosclerosis |
| Chronic renal failure |
| Hyperuricemia |
| 4. Coronary abnormalities and myocardial damage |
| Coronary dilatation, coronary tortuosity |
| Myocardial fibrosis |
| 5. Bone abnormalities |
| Clubbing, hyperplastic osteoarthritis |
| 6. Brain abscess |
15.1 Polycythemia
Prolonged hypoxemia induces an excessive level of erythropoietin secretion, eventually leading to polycythemia.1017 Decreased oxygen supply is partly compensated by increased number of red cells and a rightward shift of the oxygen dissociation curve. On the other hand, markedly increased erythrocytes cause headache, dizziness or visual disturbance.
The clinical status of a patient with such symptoms is called hyperviscosity syndrome;1018 usually the hematocrit is >65%. Iron deficiency and dehydration are modifying factors. The former can occur through hypermenorrhea or gastrointestinal bleeding, and the latter is associated with the use of diuretics. This syndrome used to be treated by phlebotomy to prevent imminent cerebral thrombosis,1019,1020 but the effect proved rather transient, even paradoxically inducing a more severe hyperviscosity status by worsening iron deficiency.1017 The primary remedy nowadays is to supplement iron and to infuse fluid (Class IIa).1021,1022
15.2 Hemorrhage and Coagulation Disorder
It is known that thrombocytopenia and decreased clotting factors are common in those with a cyanotic circulation.1023–1025 Nitric oxide, prostaglandin, and vascular endothelial growth factor (VEGF) are actively synthesized under hypoxic conditions, resulting in proliferation of the vessels to the organs and vasodilation of the small arteries. Bleeding tendency may emerge as nasal bleeding, intrapulmonary hemorrhage or hemoptysis; occasionally lethal.
Thrombosis or thromboembolism is another issue. A Blalock-Taussig shunt may be blocked; even the Glenn anastomosis and the pulmonary arteries. The kidney and the spleen may be infarcted.1026 Asymptomatic cerebral microthromboembolism can occur, to say nothing of noticeable ischemic brain stroke.343,1027,1028 Patients are at higher risk of these deleterious events when iron deficiency or dehydration is obvious. Together with bleeding tendency, it is not straightforward deciding whether antiplatelet or anticoagulant agents should be used (Class IIb).
15.3 Renal Complications
The glomerulus is swollen with its capillary dilated and mesangial matrix enhanced. These changes are in response to released platelet-derived growth factor, transforming growth factor β and VEGF.1029–1031 Proteinuria, hyperuricemia, and glomerulosclerosis are clinically detected.1031,1032 Proteinuria is seen in >60% of patients in their 30 s.1029 Microalbumin in the urine predicts subsequent cardiovascular events.1033,1034 The glomerulus is progressively sclerosed with deteriorating function; the so-called cyanotic nephropathy.432,1032,1035 Angiotensin converting enzyme inhibitor seems effective in this respect, although no large-scale study has been conducted to prove its effectiveness thus far (Class IIb).1032
Hyperuricemia is related to increased production of uric acid from the abundant red cells. The serum uric acid concentration gradually increases as renal function deteriorates with age. Approximately 20% of adult patients present gouty arthritis.1036 Uric acid levels are more likely to increase with the use of diuretics. Because there are not many reports of uric acid nephropathy, asymptomatic patients are often followed up without treatment. Treatment may be given in significantly elevated cases, such as >10 mg/dL, but there is no general guideline for cyanotic heart disease (Class IIb). There are many reports showing the relationship between serum uric acid levels and the prognosis of heart failure, and further studies will be conducted in the future.1037
15.4 Myocardial Damage
The coronary arteries are frequently dilated and tortuous in cyanotic heart disease.1038 This is a response to the chronically deficient oxygen supply to the myocardium. Myocardial infarction or angina is uncommon. Coronary perfusion in reserve is smaller than normal.1039 Proteins such as ZO-2 and PGC-1α remodel myocytes.1040,1041 Fibrosis is detectable on cardiac MRI more obviously in cyanotic than in noncyanotic patients.1042
15.5 Abnormal Ostosis
Clubbed fingers is a well-known phenomenon. The nails become hyperplastic, the connective tissues proliferate, and the collagen fibers accumulate.1043 Telangiectasia and lymphocytic infiltration are frequent findings. Chronic cyanosis promotes hypertrophic osteoarthritis as well.1043,1044 The periostea, synovia and surrounding tissues become inflamed, usually starting at the distal ends of a long bone; clinically, asymptomatic, aching, or exothermic. On roentgenogram, the periostea appear thickened and irregular. Nonsteroidal anti-inflammatory drug or steroids are given to those with significant osteoarthritis (Class IIb).1045
15.6 Brain Abscess
Brain abscess is a serious cerebral complication,1027 although it often presents as only mild and nonspecific symptoms such as headache, feeling unwell, and low-grade fever. Dental treatment can trigger this complication. Although CT and MRI have promoted earlier diagnosis, the mortality rate remains around 10%.1027 Ceftriaxone and metronidazole should be continued for 6–8 weeks (Class IIb).1046,1047 Brain surgery may be needed in some patients.
16. Aortic Stenosis and Regurgitation
Aortic stenosis (AS) is seen in 3–10% of congenital heart disease (CHD), subgroups being at the valve, below the valve, and above the valve. Stenosis at the valve level is common (60–75% of AS)1048 and a bicuspid valve is often the case. Subvalvar stenosis is usually caused by the formation of a fibrous or muscular ridge. Supravalvar stenosis may be a phenotype of a certain genetic disorder. Obstruction at any level will impose a pressure overload to the left ventricle (LV), resulting in its hypertrophy. Where severe, cardiac output decreases and clinical symptoms of heart failure appear. Surgical or interventional treatments are carried out as necessary at any stage of life from the newborn period to adulthood.
Aortic regurgitation (AR) occurs because either the valvar leaflets are abnormal or the aortic root is enlarged. A bicuspid, quadricuspid or even unicuspid valve can be the cause of the functional impairment of the valve. As for aortic root enlargement, it may represent a connective tissue disorder such as Marfan or Ehlers-Danlos syndrome, and other aortopathy, which are not uncommon in CHD. Hemodynamically, the LV is volume-overloaded and enlarged; eventually LV dysfunction and heart failure ensues.
16.1 Invasive Treatments
16.1.1 Open Aortic Valvotomy or Percutaneous Balloon Aortic Valvuloplasty
Critical aortic valve stenosis requires immediate treatment. Surgically, commissurotomy is carried out under direct vision with the aorta cross-clamped on cardiopulmonary bypass. Interventionally, a balloon is inflated at the aortic valve, which technique is obviously less invasive than the surgical procedure. On the other hand, obstruction remains when the valve orifice is inadequately opened. Acute AR, if newly created by dilating the valve more than optimal, is a troublesome complication. AS and AR can progress in the longer term, and therefore need to be checked regularly on echocardiography.
16.1.2 Aortic Valve Replacement (AVR)
The aortic valve with severe AS or significant AR needs to be replaced. In adults, the procedure is quite standard, but in children the use of a prosthetic material is less than ideal. Replacement should be very carefully indicated, using a mechanical valve or the Ross procedure (see below).
Several points should be noted after AVR: (1) prosthesis–patient mismatch as a result of body growth, (2) prosthetic failure (thrombosed valve, pannus formation, etc.), and (3) complications caused by anticoagulation and bacterial endocarditis. The first issue is essential to be checked in children. Also, pannus formation is much more common and quicker to develop in children and adolescents; a fibrous shelf forms above or below the artificial valve. Anticoagulation is known to be a key issue, particularly for a mechanical valve, which must not be thrombosed. At the same time, life-long anticoagulation keeps hemorrhagic complications at risk.1049,1050 A bioprosthesis has fewer problems regarding hemorrhagic or thromboembolic episodes, but is not as durable as a mechanical valve. Its leaflets are liable to become calcified and torn over 10–15 years in adults. Degeneration occurs much earlier in the younger population.
Taking these factors into account, coagulability is to be monitored, and function of both the prosthesis and the heart should be examined on echocardiography (Class I, Level C). Patients with markedly reduced cardiac performance prior to surgery should be followed up under strict care for a longer period (Class I, Level C).
16.1.3 The Ross Procedure
In this procedure, the patient’s own pulmonary valve is translocated to the aortic root, and the right ventricular (RV) outflow tract is reconstructed using an artificial conduit or a homograft. This procedure appears beneficial in small children or female patients of reproductive age. Postoperative autograft failure (AR), obstruction across the RV outflow tract, and pulmonary valve regurgitation are issues to be investigated regularly on echocardiography.
16.1.4 The Konno Procedure
This procedure is AVR with an extensive aortic root enlargement performed by incising the ventricular septum; it is quite effective when the aortic annulus is significantly small and/or subaortic stenosis is present. A combined patch is used to augment the ventricular septum, the aortic annulus, and the ascending aorta. Patch-related sequela should be checked, as well as the artificial valve-related issues mentioned above.
The Konno incision to the ventricular septum can be also applied in the Ross procedure; the so-called Ross–Konno procedure.
16.1.5 Resection of Subaortic Stenosis
The fibromuscular ridge is removed to treat subaortic stenosis. For muscular obstruction, part of the ventricular septum is resected. If the ventricular septum is perforated to the RV, the hole needs to be closed using a patch. This is called the modified Konno procedure, in which the aortic annulus is not incised and the aortic valve is not replaced.
Careful postoperative follow-up on echocardiography is recommended for checking residual or recurrent subaortic stenosis and progressive AR. A surgical maneuver to the ventricular septum can evoke AV block.
16.1.6 Repair of Supra-Aortic Stenosis
Supra-aortic stenosis can be repaired by patch augmentation, or may need replacement of the ascending aorta in those with a hypoplastic aortic root, as typically seen in Williams syndrome. It’s not rare for the stenotic lesion to involve the sinotubular junction. AR can progress after surgery because of changes in the geometry of the surgically modified aortic root.
16.2 Investigations for Follow-up
Regular echocardiography is recommended for assessing valve function and heart performance (Class I, Level C) (Table 43),618 but there is no consensus for how long; it depends on the functional and morphological problems of the valve (Table 44). Once a mechanical valve is suspected to be malfunctioning, fluoro-roentgenography is carried out to check the opening angle of the leaflets (Class I, Level C). Cardiac catheterization would be the method of choice for evaluating the hemodynamic significance of the lesions, when echocardiography does not explain the clinical picture precisely (Class IIa, Level C).
Table 43. Recommendations and Evidence for Follow-up Examination After Aortic/Mitral Valve Surgery
| |
COR |
LOE |
GOR
(MINDS) |
LOE
(MINDS) |
Periodical TTE is recommended for evaluating postoperative valve function
and cardiac function |
I |
B |
A |
II |
TTE is recommended for patients with any change in symptoms or physical
examination findings |
I |
C |
A |
III |
TEE is recommended in suboptimal evaluation with TTE or if further
examinations are required |
I |
B |
A |
II |
Fluoroscopic examination is recommended for patients with mechanical
valve and suspected valve dysfunction |
I |
C |
A |
III |
Assessment of severity and hemodynamics by cardiac catheterization is
reasonable for patients who are difficult to evaluate by echocardiography or
for patients showing discrepancy between clinical symptoms and
echocardiographic findings |
IIa |
C |
B |
III |
COR, class of recommendation; GOR, grade of recommendation; LOE, level of evidence; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography.
(Modified from JCS/JSCS/JATS/JSVS 2020 Guideline on the Management of Valvular Heart Disease. 2020.618)
Table 44. Frequency of Echocardiographic Examinations in Asymptomatic Patients With Heart Valve Disease
| |
Recommended interval
of follow-up TTE |
| Patients with severe stenosis/severe regurgitation |
Every 6–12 months |
| Patients with moderate stenosis/moderate regurgitation |
Every 1–2 years |
| Patients with mild stenosis/mild regurgitation |
Every 3–5 years |
| Patients after valve replacement without apparent valve dysfunction |
Every 1–2 years |
TTE, transthoracic echocardiography.
16.3 Medical Treatments
16.3.1 Antithrombotic Therapy
Warfarin is to be administrated after AVR with a mechanical prosthesis (Class I, Level C) (Table 45).618 Prothrombin time is targeted at 2.0–2.5 international normalized ratio (INR), unless other risk factors are obvious such as atrial fibrillation, severely impaired heart function, any thromboembolic episodes in the past, or unusual hypercoagulability. Some physicians recommend administering a low dose of aspirin (75–100 mg/day) concomitant with warfarin.1051 Antithrombotic agents are given only for the first 3–6 months after AVR with a bioprosthetic valve in those having no particular risk factors.
Table 45. Recommendations and Evidence for Long-Term Medical Therapy After Surgery
| |
COR |
LOE |
GOR
(MINDS) |
LOE
(MINDS) |
Oral anticoagulant therapy with warfarin is recommended lifelong for all
patients with a mechanical valve
Target INR of warfarin control
• Aortic position: INR 2.0–2.5
• Aortic position and thrombotic risks: INR 2.0–3.0
• Mitral position: INR 2.0–3.0 |
I |
B |
A |
II |
Warfarin control of INR 2.5–3.5 is reasonable for patients with a mechanical
valve and thrombotic event despite adequate anticoagulation therapy |
IIa |
C |
B |
III |
Aspirin combination therapy may be considered for patients with a mechanical
valve and thrombotic event despite adequate anticoagulation therapy |
IIb |
C |
C1 |
III |
| Single aspirin therapy is contraindicated for patients with a mechanical valve |
III |
B |
D |
II |
Direct oral anticoagulant usage is contraindicated for patients with a
mechanical valve |
III |
B |
D |
II |
Standard medical therapy for heart failure, including RAS inhibitor/β-blocker,
should be performed for patients with impaired cardiac function/heart failure |
I |
A |
A |
I |
COR, class of recommendation; GOR, grade of recommendation; INR, international normalized ratio; LOE, level of evidence; RAS, renin–angiotensin system.
(Modified from JCS/JSCS/JATS/JSVS 2020 Guideline on the Management of Valvular Heart Disease. 2020.618)
16.3.2 Treatment of Heart Failure
Cardioprotective agents are recommended, whenever appropriate, in those presenting significant cardiac dysfunction (Class I, Level A).
16.4 Invasive Treatments in the Longer Term
16.4.1 AS and AR
Recurrent aortic lesions are to be reoperated according to standard indications described in the valve disease guidelines (Table 46).618 In the setting of CHD, nevertheless, the initial surgery is commonly carried out at an earlier stage of life, which implies that the total number of surgical or interventional revisions will be greater in this cohort. A life-long strategy should be determined in each individual patient, contemplating impediments and benefits related to repeated procedures. The more frequently surgical procedures are repeated and the more severely the ventricles are impaired, the higher the mortality rate the patient will face.
Table 46. Recommendations and Evidence for Surgery for AR/AS Long-Term After Aortic Valve Surgery
| |
COR |
LOE |
GOR
(MINDS) |
LOE
(MINDS) |
| AR |
| Surgery is recommended for symptomatic patients with severe AR |
I |
B |
A |
II |
Surgery is recommended for asymptomatic patients with severe AR with
LVEF <50% |
I |
B |
A |
II |
Surgery is reasonable for asymptomatic patients with severe AR with
preserved LVEF (≥50%) but with LVESD >45 mm |
IIa |
B |
B |
II |
Surgery is reasonable for asymptomatic patients with severe AR with
preserved LVEF (≥50%) but with LVESD >45 mm |
IIb |
C |
C1 |
III |
| AS |
| Intervention is recommended for symptomatic patients with severe AS |
I |
B |
A |
II |
Intervention is recommended for asymptomatic patients with severe AS and
LV systolic dysfunction (LVEF <50%) |
I |
C |
A |
III |
Intervention is reasonable for asymptomatic patients with very severe AS
(Vmax ≥5 m/s, mPG ≥60 mmHg, or AVA ≤0.6 cm2) at low surgical risk |
IIa |
B |
B |
II |
AR, aortic regurgitation; AS, aortic stenosis; AVA, aortic valve area; COR, class of recommendation; GOR, grade of recommendation; LOE, level of evidence; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; mPG, mean pressure gradient.
(Modified from JCS/JSCS/JATS/JSVS 2020 Guideline on the Management of Valvular Heart Disease. 2020.618)
16.4.2 Prosthetic Valve Failure and Prosthesis–Patient Mismatch
A thrombosed mechanical valve requires a prompt response, either thrombolytic treatment or surgery (Class I, Level C) (Table 47).618 Early death (within 30 days) following urgent surgery is 10–15% for the whole cohort of patients, but <5% in those presenting NYHA I or II.1052,1053 As for thrombolytic therapy, Ozkan et al reported that early death within 30 days was 8%, hemodynamics improved in 70%, and embolic or hemorrhagic complications occurred in 14% before 2012.1054 Those results have been improved by means of slow venous injection of low-dose thrombolytic agents under echocardiographic monitoring; early death <2%, hemodynamic improvement >90%, and thrombotic or hemorrhagic complications <2%.1054 It is institutional policy or the patient’s decision whether the surgical approach or thrombolytic protocol is chosen.
Table 47. Recommendations and Evidence for Surgery in Patients After Valve Replacement
| |
COR |
LOE |
GOR
(MINDS) |
LOE
(MINDS) |
Low-dose thrombolytic therapy or urgent/emergency valve replacement is
recommended for symptomatic patients due to obstructive thrombosis of
left-sided prosthesis |
I |
C |
A |
III |
Surgical replacement is recommended for severe prosthetic valve stenosis
with heart failure symptoms |
I |
C |
A |
III |
Surgical replacement is recommended for severe prosthetic valve regurgitation
with heart failure symptoms or hemolysis |
I |
C |
A |
III |
COR, class of recommendation; GOR, grade of recommendation; LOE, level of evidence. (Modified from JCS/JSCS/JATS/JSVS 2020 Guideline on the Management of Valvular Heart Disease. 2020.618)
Stenosis or regurgitation across an artificial valve requires reoperation for re-replacement when signs of heart failure progress (Class I, Level C). Hemolysis is another reason for re-intervention; this phenomenon usually associated with perivalvar leaks (Class I, Level C). With no obvious clinical symptoms, the indication for reoperation should be considered carefully on an individual basis. This is particularly true for prosthesis–patient mismatch in children; no evident criteria have been established in this respect. A sensible plan for consecutive treatments is crucial, considering the risks and benefits brought by each procedure, in a prospective way.
16.4.3 Recurrent Subaortic Stenosis
Subaortic stenosis is known to recur in approximately 20%; freedom from reoperation being 85% at 15 years. The patient’s status should be regularly followed up after initial resection of the lesion, seeking change in the pressure gradient on echocardiography or in clinical symptoms; these may reach the criteria for reoperation in due course (Class IIa, Level C).
16.4.4 Obstruction Across the RV Outflow Tract
The RV outflow channel can be obstructed after the Ross procedure in which heterologous or autologous materials were used for reconstruction. A surgical or interventional treatment would be indicated when the pressure gradient across the RV outflow tract is >50 mmHg at rest, dyspnea on exertion or chest pain noted, and pre-syncopal or syncopal episodes are evident (Class IIa, Level C).
16.4.5 Infective Endocarditis
The patient’s own tissues of the repaired valve or the artificial materials used for replacement occasionally get infected. Active bacterial endocarditis is to be surgically treated when (1) medical managements cannot control heart failure, (2) embolic episodes repeatedly occur, and (3) the infection is expanding.458 A nonsurgical approach to these circumstances is pessimistic. The ‘Guideline for prevention and treatment of infective endocarditis (JCS 2017)’ are referred to.458
17. Mitral Stenosis and Regurgitation
Congenital mitral disease is a rare entity, seen in 0.6–1.2% of postmortem cases of congenital heart disease (CHD) and in 0.2–0.4% of a clinical series.1055 The lesion may coexist with other CHD, such as atrioventricular septal defect or tetralogy of Fallot.
A congenitally stenotic mitral valve is hypoplastic and dysplastic. The leaflets are often thickened with the papillary muscles fused, deformed, and abnormally attached. The so-called parachute mitral valve is well known. A hammock formation and a supra-annular membrane are other mechanisms of a stenotic orifice. When a mitral lesion coexists with aortic valve stenosis and coarctation of the aorta, Shone complex is suspected.
Regurgitation may be related to mitral prolapse as seen in Marfan, Ehlers-Danlos, and Loeys-Dietz syndromes. A cleft within a leaflet is another cause. Structural abnormality of the papillary muscles and the tendinous cords could cause insufficiency. A dual orificial valve and an abnormal hinge (Ebstein-like) can cause regurgitation as well.
17.1 Invasive Treatments
17.1.1 Repair
A supra-annular membrane is resected for supra-mitral stenosis. Stenosis across the valve requires commissurotomy, and papillotomy. These techniques provide good outcome, particularly in patients with an isolated mitral lesion.1056,1057 For regurgitation, fixation of a fissure, augmentation of the leaflets, annuloplasty, papillotomy, and artificial cords reconstruction are useful. Scientific evidence in children is not sufficient regarding how many times repair is feasible or how promising are the long-term results.99,1058–1060
Regular follow-up on echocardiography is mandatory; stenosis or regurgitation can recur and progress in childhood or even after reaching adulthood.
17.1.2 Mitral Valve Replacement (MVR)
Valve repair is a primary procedure by all means. This is particularly true in children. Replacement is an alternative only when the mitral lesion is significant and intractable by reparative methods. A mechanical valve is used in children, because a bioprosthesis degenerates quite rapidly (the tendency being more obvious at the mitral position than the aortic). Still, reoperation is not rare.28
Postoperatively, physicians need to check the following: (1) prosthesis–patient mismatch as a result of body growth, (2) artificial valve dysfunction (thrombosed valve or pannus formation), and (3) anticoagulation and bacterial endocarditis. To do so, regular investigation by echocardiography and blood samples is encouraged (Class I, Level C). In sicker patients whose preoperative heart function was poor, a more intense follow-up is recommended for a longer period (Class I, Level C).
17.2 Investigations for Follow-up
Regular echocardiography is recommended (Class I, Level C) (Table 43).618 Once a mechanical valve is suspected to be malfunctioning, fluoro-roentgenography is to be carried out to check the opening angle of the leaflets (Class I, Level C). Cardiac catheterization would be appropriate to evaluate how hemodynamically significant the lesion is, when echocardiography does not precisely explain the clinical picture (Class IIa, Level C).
17.3 Medical Treatments
17.3.1 Antithrombotic Therapy
Warfarin is to be administrated after MVR with a mechanical prosthesis (Class I, Level C) (Table 45).618 Prothrombin time is targeted at 2.0–3.0 international normalized ratio. Some physicians recommend administrating a low dose of aspirin (75–100 mg/day) concomitant with warfarin.1051 Antithrombotic agents are given only for the first 3–6 months after MVR with a bioprosthetic valve in those having no other risk factors.
17.3.2 Treatment of Heart Failure
Cardioprotective agents are recommended for those with significantly impaired heart function and pulmonary hypertension (Class I, Level A).
17.4 Invasive Treatments in the Longer Term
17.4.1 Mitral Stenosis or Regurgitation
Reoperation rate seems higher in the congenital mitral cohort than in the acquired adult cardiac surgery data base.99,1057–1060 Usually, standard indications described in the valve disease guidelines (Tables 47,48)618 are applied in the congenital setting. Replacement is more frequent at reoperation than at the initial surgery in which the surgeon strives to repair the valve in small children. A life-long strategy should be determined for each individual patient, contemplating impediments and benefits related to repeated procedures (either surgical or interventional).
Table 48. Recommendations and Evidence for Surgery for MR/MS Long-Term After Mitral Valve Surgery
| |
COR |
LOE |
GOR
(MINDS) |
LOE
(MINDS) |
| MR |
Mitral valve surgery is recommended for symptomatic patients with LVEF
>30% |
I |
B |
A |
II |
Mitral valve surgery is recommended for asymptomatic patients with LVEF
≤60% or LVESD ≥40 mm (LVESDI ≥24 mm/m2) |
I |
B |
A |
II |
Mitral valve surgery is reasonable for asymptomatic patients with LVEF
>60% and LVESD <40 mm (LVESDI <24 mm/m2) who have new onset of AF
or resting PASP >50 mmHg |
IIa |
B |
B |
II |
Mitral valve repair is reasonable for asymptomatic patients with LVEF >60%
and LVESD <40 mm (LVESDI <24 mm/m2) who have neither new onset of AF
nor resting PASP >50 mmHg, when durable repair is safely accomplished |
IIa |
C |
B |
III |
| MS |
| Surgery is recommended in symptomatic patients with moderate or severe MS |
I |
B |
A |
II |
Surgery is reasonable for asymptomatic patients with moderate or severe
MS who show symptoms or mPG >15 mmHg or pulmonary hypertension
(PASP >60 mmHg) during exercise |
IIa |
B |
B |
II |
Surgery may be considered for asymptomatic patients with moderate or
severe MS and new onset AF or history of embolism due to left atrial thrombus |
IIb |
C |
C1 |
III |
AF, atrial fibrillation; COR, class of recommendation; GOR, grade of recommendation; LOE, level of evidence; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; LVESDI, LVESD/body surface area; MR, mitral regurgitation; MS, mitral stenosis; PASP, pulmonary artery systolic pressure.
(Modified from JCS/JSCS/JATS/JSVS 2020 Guideline on the Management of Valvular Heart Disease. 2020.618)
17.4.2 Prosthetic Valve Failure and Prosthesis–Patient Mismatch
A thrombosed mechanical valve requires immediate thrombolytic treatment or urgent surgery (Class I, Level C). A stenotic or regurgitant artificial valve should be re-replaced as soon as signs of heart failure emerge (Class I, Level C) (Table 48).618 Hemolysis is another cause for re-intervention; this phenomenon is usually associated with a perivalvar leak (Class I, Level C). With no clinical symptoms, reoperation should be considered carefully on an individual basis. No clear indication has been established for prosthesis–patient mismatch in children.
17.4.3 Infective Endocarditis
Refer to the ‘Guideline for prevention and treatment of infective endocarditis (JCS 2017)’.458
17.4.4 Others
Complete AV block is a potential complication subsequent to MVR. Subaortic stenosis can also occur.
18. Coronary Arterial Malformation
Congenitally abnormal coronary arteries are seen in 0.21–5.79% of patients in investigated groups.1061 Their problems include sudden death as well as the surgical challenge of intracardiac repair.7,160,1062 This chapter focuses on isolated lesions of the vessels. Based on morphological features, Angelini classified this entity into (1) an origin and a proximal course, (2) structures of the vessel itself, and (3) a terminal portion.1063
18.1 Abnormal Origin
18.1.1 BWG Syndrome
Abnormal origin of the left coronary artery from the pulmonary artery (ALCAPA) is called as Bland-White-Garland (BWG) syndrome; the left main stem arises from the pulmonary trunk.160,1062 As pulmonary arterial pressure falls after birth, the left coronary artery is retrogradely perfused via the collateral vessels. The affected region becomes ischemic, leading to LV dilatation, impaired LV contraction, and mitral regurgitation. In the severest form, an infant without a surgical treatment would be in significant heart failure and at a risk of sudden death.1064 In a milder form, collaterals develop in time even without causing any clinical symptoms and the malformation is eventually diagnosed in adulthood. Deep Q wave in the aVL
lead is characteristic on ECG. Echocardiography is useful for general screening. Computed tomography (CT) coronary angiography and cardiac magnetic resonance imaging (MRI) are diagnostic.1062 The patient is submitted for surgery (Class I) as soon as diagnosed.7,527
Several variations of surgical repair have been reported. A radical method is translocation of the abnormal artery from the pulmonary arterial trunk to the aortic sinus. An alternative is construction of an intrapulmonary tunnel from the aortic root to the coronary arterial ostium (the Takeuchi method). An artificial graft or a roll of autologous tissues can be interposed outside the pulmonary arterial lumen. These repairs provide better LV contraction, normalized ventricular volume, and a less regurgitant mitral valve in most cases. It is contentious whether mitral valve repair should be carried out concomitantly or not.1065,1066
Early surgical death is seen in 0–16%, and survival rate is 86–100% at 10 years.1067 The reconstructed coronary arterial channel has the potential of obstruction. Function of the left ventricle and the mitral valve should be followed up regularly. Complications after the Takeuchi method are not uncommon, including pulmonary stenosis above the hinge of the pulmonary valve leaflets, coronary arterial obstruction at the intrapulmonary tunnel, leaking across the baffle suture line, pulmonary regurgitation, and aortic regurgitation. Reoperation rate is higher after the Takeuchi method than after direct coronary arterial translocation.1065,1066 In contrast, direct translocation in adults is not always straightforward, because mobilization needs to be more extensive and well-developed collaterals tend to induce more bleeding than in infants or children.
Postoperative CT coronary angiography, cardiac MRI, and myocardial perfusion scintigraphy are capable of clarifying residual issues of coronary arterial configuration and function.160,1062 It would be wise to collaborate with an experienced coronary arterial surgeon for further surgical revision, if indicated.
18.1.2 Origin From the Wrong Sinus
The left coronary artery originates from the right-facing sinus (together with the right artery) in rare instances. Its reversed pattern (the right from the left-facing sinus) can also happen. The wrongly arising vessel is readily squeezed between the aorta and the pulmonary trunk, causing ischemia. There is a great risk of sudden death on exercise in younger people.7,160,1062 The intramural course within the aorta and/or a slit-like ostium of the artery are also narrowed when aortic pressure is raised.
Once myocardial ischemia is proven in this malformation, timely surgery should be arranged (Class I).7,527 Following successful repair, regular check-up by echocardiography is appropriate.160 Further scrutiny is recommended when the patient is symptomatic or unstable clinically. The unrepaired abnormal right coronary artery may not be symptomatic to warrant surgical treatment. Still, close follow-up is recommended by echocardiography at least once every 2–5 years.160
18.2 Coronary Arterial Fistula
An abnormal communication is formed between the coronary artery and other parts of the heart (cardiac chambers, systemic or pulmonary veins, cardiac veins, or the pulmonary artery; found in 0.18% of adults who undergo coronary angiography1068). It can coexist with other congenital malformations.1069,1070 Fistulous sites are more common for the right coronary artery, and to the right heart chambers.1071 A small fistula scarcely causes any symptoms, but a large lesion can grow with time, resulting in myocardial ischemia, volume-overload to the ventricle, infective endocarditis, pulmonary hypertension, aneurysm, or thrombosis.1062
Surgical or catheter interventions are indicated to mitigate or prevent these impediments. Occlusion of a branch and myocardial infarction are well-known complications in the immediate and longer terms after invasive treatment. The therapeutic strategy is best decided by an experienced team having special knowledge in coronary arterial therapy.7 Regular follow-up is mandatory in either repaired or unrepaired patients. The post-procedural status should be scrutinized by CT, MRI, and perfusion scintigraphy when any sign of myocardial ischemia persists or newly develops.160
