Editorials
Current Status and Future Direction of Cardiac Resynchronization Therapy for Congenital Heart Disease and Pediatric Patients
2014 Volume 78 Issue 7 Pages 1579-1581
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2014 Volume 78 Issue 7 Pages 1579-1581
Device therapy, including implantable cardioverter-defibrillator, cardiac resynchronization therapy (CRT), and CRT-D (CRT with a defibrillator), is currently considered an effective alternative for drug-resistant heart failure (HF) and prevention of sudden cardiac death (SCD). Several multicenter clinical trials have demonstrated that these therapies can improve left ventricular (LV) function and NYHA functional class and reduce all-cause mortality rate from HF and SCD.1,2 Following its inclusion in the Governmental Health Insurance System, the use of device therapy for HF has increased exponentially in Japan. However, data on use of device therapy in congenital heart disease (CHD) and pediatric patients are scarce. In this issue of the Journal, Suzuki et al report for the first time the number of such cases and application of each type of device.3 Considering the rapidly growing number of adult patients with CHD and improvement in the life expectancy of these patients, the report includes important information on the current status and issues to overcome for wider use of the technology. The article focuses on the application of CRT in CHD and the pediatric field.
Article p 1710
Prevalence of CRT UseThe nationwide questionnaire survey3 provided several important data regarding current trends in CRT use in pediatric patients (<16 years of age). First, the number of children on CRT increased to 8–16 cases/year in 2008–2012. Also, DDD pacemakers, instead of CRT-P (CRT with a biventricular pacemaker) or CRT-D, were used for CRT in approximately two-thirds of patients younger than 5 years, despite interventricular delay being unable to be set in the former device. The wide use of DDD is probably because of the prohibition imposed by the Government on the use of the CRT-P in most children’s hospitals that do not meet the institutional criteria. One advantage of CRT with a DDD pacemaker is its small size for children, although a Y-connector, which takes additional subcutaneous space, should be used for simultaneous biventricular pacing (Figure A).
(A) Examples of conventional DDD, CRT with a biventricular pacemaker (CRT-P), and CRT with a defibrillator (CRT-D) for size comparison. The DDD device (Left) is smaller than the others but a Y-connector is necessary for simultaneous biventricular pacing, which occupies considerable subcutaneous space. Interventricular delay cannot be set in the DDD device, compared with the CRT-P (Middle) and CRT-D devices (Right), although the last one is much larger than the others. (B) Chest X-ray films of a 16-month-old patient, weighing 6.7 kg, with autoantibody-associated congenital complete heart block. Severe heart failure developed 11 months after implantation of right ventricular single-site pacemaker (Left). The child was transferred to Tsukuba University Hospital with intratracheal intubation, because the hospital admitting the patient did not meet the institutional criteria for CRT-P use. Heart failure resolved completely 8 months after pacemaker upgrade to CRT-P (Right). Cardiothoracic ratio decreased from 70 to 55%, and QRS duration shortened from 150 to 120 ms. Serum BNP fell from 6,520 before CRT to 28 pg/ml after CRT.
Second, the underlying cardiac diseases are largely different from those in adults, in whom dilated cardiomyopathy (DCM) and ischemic heart disease are the main indications. A review of studies with enough number of pediatric patients4–7 showed that the majority of patients had CHD, followed by cardiomyopathy and congenital heart block (CHB), and only a small number had left bundle branch block (LBBB) and other conduction disorders, in contrast to adults (Table).
| Dubin et al4 (2005) | Khairy et al5 (2006) | Cecchin et al6 (2009) | Janousek et al7 (2009) | |
|---|---|---|---|---|
| n | 103 | 13 | 60 | 109 |
| Age, years, median (range) | 12.8 (0.25–55.4) | 6.5 (0.8–15.5) | 15.0 (0.42–47) | 16.9 (0.24–73.8) |
| Cardiac diagnosis | ||||
| CHD, n (%) | 73 (71) | 10 (77) | 46 (77) | 87 (80) |
| Systemic LV | 49 | 6 | 26 | 47 |
| Systemic RV | 17 | 4 | 7 | 36 |
| Single-ventricle | 7 | 0 | 13 | 4 |
| Cardiomyopathy, n (%) | 16 (16) | 3 (23) | 10 (17) | 10 (9) |
| CHB, n (%) | 14 (13) | 1 (7) | 4 (7) | 12 (11) |
| Conduction disorders, n (%) | ||||
| AVB | ND | 10 (77) | 41 (68) | 84 (77) |
| LBBB | ND | ND | 10 (17) | 10 (9) |
| RBBB | ND | ND | 4 (7) | 5 (5) |
| Non-specific IVCD | ND | 3 (23) | 5 (8) | 10 (9) |
| QRS duration (ms) | ||||
| Pre-CRT | 166±33 | ND | Mean 149 | Median 160 |
| Post-CRT | 126±24 | ND | Mean 120 | Median 130 |
| Systemic ventricular EF (%) | ||||
| Pre-CRT | 26.2±11.6 | 31.4±13.5 | Median 35, 8–57 | Median 27 |
| Post-CRT | 39.9±14.8 | 50.6±15.2 | Median 44, 13–73 | Median 38.5 |
| NYHA | ||||
| Pre-CRT | Class III or IV in 39 (38%) | ND | Class II (42%), III (25%), IV (7%) | Median Class 2.5 |
| Post-CRT | ND | ND | Improved in 39/45 (87%) | Median Class 1.5 |
| Non-responders, n (%) | 11/89 (12) | ND | 6/45 (13) | 15/94 (16) |
AVB, atrioventricular block; CHB, congenital heart block; CHD, congenital heart disease; CRT, cardiac resynchronization therapy; IVCD, intraventricular conduction delay; LBBB, left bundle branch block; LV, left ventricle; ND, not described; RBBB, right bundle branch block; RV, right ventricle.
As also shown in the Table, patients eligible for CRT can be divided into 3 groups: (1) systemic LV failure, (2) systemic right ventricular (RV) failure, and (3) HF with a single-ventricular physiology. Group 1 includes HF after corrective surgery for CHD, such as tetralogy of Fallot with right bundle branch block (RBBB), and that associated with RV single-site pacing for congenital or surgical atrioventricular block (AVB). The latter has gathered much interest since Tantengco et al8 reported its adverse effects on LV function. Group 2 includes HF developing with aging rather than complex CHD (eg, corrected transposition of the great arteries, complete transposition of the great arteries corrected by atrial switch operation). Group 3 is unique to the pediatric field (ie, HF most typically develops after Fontan type surgery for single ventricle or hypoplastic right/left heart syndrome). It is remarkable that CRT can correct HF even in patients with such complex CHD.9
Patient Selection and Prediction of RespondersEven in adults with DCM, establishment of CRT eligibility criteria is still challenging but often includes NYHA functional class III or IV, ejection fraction <35%, and QRS duration >120 ms under optimal pharmacotherapy. Unfortunately, not all those who meet these criteria respond well to CRT and the non-response rate is up to 30%. The selection of pediatric patients for CRT is more difficult because of differences in the type of cardiac anomaly, ventricular morphology, conduction system and postoperative status. However, the lower rate of non-responders to CRT (12–16%) relative to adult patients is encouraging (Table). In the nationwide survey reported here,3 the overall response rate was 83%, including those with single-ventricular physiology, similar to previous studies.4–7
In pediatrics, CRT for CHD typically started as an upgraded pacemaker in patients with a preexisting conventional pacemaker. Tantengco et al showed that long-term RV apical pacing from a young age can induce LV dysfunction,8 which attracted a lot of interest because many pediatric cardiologists were aware of the phenomenon in patients with CHB. The authors suggested biventricular pacing from early stage to prevent late-onset HF. In fact, Moak et al demonstrated that patients who developed DCM after conventional pacing for CHB showed reverse ventricular remodeling as well as clinical improvement following upgrading to atriobiventricular pacing.10 Figure B shows a 1-year-old patient with autoantibody-related CHB who had major improvement following upgrading to CRT-P.
Echocardiography is frequently used to detect mechanical dyssynchrony, and many parameters have been proposed for that purpose in children with CHD.11 However, a multicenter prospective study conducted recently in Japan (the J-CRT study)12 did not find a single echocardiographic criterion that could significantly predict the response to CRT; rather, the response to therapy correlated with a combination of parameters of dyssynchrony between the septum and LV free wall measured by M-mode and tissue Doppler imaging, as well as LBBB on ECG. These results could not necessarily be applied to the field of CHD where RBBB instead of LBBB is a common cause of wide QRS and various ventricular morphologies are included. Thus, the indications for CRT should be assessed in individual patients with CHD. Recently, Seo et al demonstrated the usefulness of 3-dimensional speckle-tracking echocardiography in determining intraventricular regional mechanical activation, based on comparison with electrical voltage mapping.13 This new imaging method seems promising and should be tried in CHD patients with various ventricular morphologies, including single ventricles.
Implantation IssuesConsideration of CRT use in pediatric or CHD patients is limited by various factors. Small body size is an obstacle for implantation of the generator, especially with CRT-D (Figure A). Transvenous lead implantation is precluded by complex venous anatomies, venous obstruction because of previous surgeries, and intracardiac shunt with right-to-left shunt. In the present nationwide survey,3 approximately 90% of Japanese patients underwent CRT-P or CRT with a DDD pacemaker using epicardial leads. Lead dislodgement or fracture may also occur as the patient grows. Furthermore, inappropriate shock is a problem when a CRT-D is implanted in children.
CRT is a promising tool for CHD and pediatric patients with pharmacotherapy-resistant HF, with a lower failure rate compared with adult patients. However, there are currently no guidelines for selection of patients and devices and these are not easy to establish because of the heterogeneity of the disease. Also, the majority of children’s hospitals in Japan are currently not allowed to use CRT-P or CRT-D devices because they do not meet the institutional criteria for such use.14 Revision of the criteria to allow wider use of these devices in children’s hospitals should further reduce the mortality of CHD and pediatric patients.
