Calcium （Ca2+） is an important intracellular messenger that regulates myocyte contraction via excitation-contraction （E-C） coupling and gene transcription underlying cardiac hypertrophy. The mechanisms of E-C coupling in immature hearts are believed to be different from those in adult hearts because of the structural immaturity of the sarcoplasmic reticulum （SR） and T-tubules in an immature heart; however, the details of these mechanisms are not completely understood. Neuronal Ca2+ sensor-1 （NCS-1） is an EF-hand Ca2+-binding protein, which is an important regulator of neuronal functions. Although NCS-1 is expressed in high levels in immature hearts, only little is known about its cardiac functions. In this study, two novel functions of NCS-1 in cardiac tissue was discovered by characterizing the cardiac phenotypes of knockout （Ncs1－/－） mice. NCS-1 was found to be a regulator of contraction in immature hearts and that of hypertrophy in adult hearts. NCS-1 promotes Ca2+ release from the inositol trisphosphate receptors （IP3Rs）, followed by Ca2+/calmodulin-dependent protein kinase II signaling, which results in a large increase in the SR Ca2+ content in an immature heart. In addition, NCS-1 expression increased during the early stages of hypertrophy in the adult heart; and phenylephrine-induced cardiac hypertrophy was largely attenuated in Ncs1－/－ hearts. Our results revealed a novel mechanism of E-C coupling in immature hearts and another regulatory mechanism involved in the progression of receptor stimulation-elicited cardiac hypertrophy.
Loeys-Dietz syndrome（LDS）is an autosomal dominant genetic disorder characterized by vascular（arterial tortuosity, aneurysms and/or dissections）, craniofacial（hypertelorism, bifid uvula/cleft palate, craniosynostosis）, and skeletal manifestations（pectus excavatum or pectus carinatum, scoliosis, joint laxity, arachnodactyly, talipes equinovarus）; however, not all symptoms are always present in patients. Clinical features possibly overlap with Marfan syndrome, but the most characteristic feature of LDS is aggressive and widespread arterial aneurysms throughout the arterial tree, which needs frequent echocardiography or CT/MRA examinations and early therapeutic intervention. LDS is best managed with a multidisciplinary team of specialists, including pediatric and adult cardiologists, cardiothoracic surgeons, orthopedists and medical geneticists. The genes responsible for LDS are TGFBR1 and TGFBR2, and SMAD3 and TGFB2 are also involved in LDS-related phenotypes. These genes are all related to the TGF-β signaling pathway.
The practice of congenital heart disease（CHD）is a field in which we often have to face death. In the past, the death was a matter of God or Buddha, but it becomes a matter of medical science through the advance of medical technology. Accordingly, we are now required to have knowledge of thanatology in order to provide terminal care as satisfactory as possible to dying patients and families. For this purpose, we have to understand the psychological sequence of dying and death. This sequence includes shock, denial, anger, depressive feelings, and others, which are considered normal reactions to protect the mind of suffering people. Knowing their psychological status, we listen to their narrative story, which often includes personal emotions and wishes, and we give support with sympathy, accordingly. By doing this, we hope that they would pass through the painful process as comfortable as possible.Children start understanding death in the first 1-3 grades of primary school, but their apparent reaction to death is much different from that of adults. We have to watch carefully those children who are facing dying or death and give warm and continuous support.Now, the number of adult CHD（ACHD）patients and mortality is increasing. Their deaths are a major issue of thanatology and cause grief of parents and/or adult siblings of the ACHD patient, family, wife, and children of the ACHD patient, if any. We now have to start to prepare for this new very serious problem.
Background: Conotruncal anomalies can cause severe cyanosis that requires intervention in the neonatal and early infantile period. Objectives: To evaluate the effectiveness and outcomes of using balloon pulmonary valvuloplasty （BVP） as an initial palliative procedure in such cases, particularly in those with subarterial ventricular septal defects. Materials and Methods: Between August 2002 and December 2012, 9 infants （8 males and 1 female） with conotruncal anomalies （3 with tetralogy of Fallot, 4 with double outlet right ventricle, and 2 with congenitally corrected transposition of the great arteries） underwent BVP. Echocardiographic and catheterization data, as well as the patients’ clinical course, were retrospectively examined. Results: The mean balloon to annulus ratio （B/A ratio） was 1.08 ± 0.15. Moreover, the mean systemic oxygen saturation increased from 75% ± 6% before BVP to 87% ± 7% after BVP （p <0.001）； however, no significant changes in peak velocity and peak pressure gradient at the right ventricular outflow tract were noted, and only minimal pulmonary regurgitation occurred. All the patients, except for 1 with tracheomalacia, were discharged without the need for home oxygen therapy. One patient subsequently required pulmonary arterial banding due to pulmonary over-circulation. No deaths were noted, and definitive repair was achieved in all the patients. Conclusion: As an initial palliative procedure, BVP involving a relatively smaller balloon size is less invasive, and provides appropriate pulmonary blood flow and bridge to the definitive surgery.
Background: Secondary hypertension is more common in children than in adults. Although the number of patients with renal artery stenosis is relatively small, renal artery stenosis is an important clinical condition because of the potential for a complete cure. Methods: We reviewed the clinical outcomes of patients with renovascular hypertension who underwent percutaneous transluminal angioplasty or surgery at a single center between 2005 and 2011. The hypertensive response was defined as （1）cured： normal blood pressure with no antihypertensive treatment, （2）improved： improved blood pressure with identical or reduced treatment, （3）unchanged： no change in blood pressure despite angiographic success, or （4）failed. Results: The first surgical or endovascular intervention was performed between 1.8 and 13 years of age. Nineteen renal angioplasty procedures and four surgeries were done. The outcomes were as follows： cured in one patient who underwent surgery, improved in 14 patients who underwent renal angioplasty and three who underwent surgery, unchanged in four patients who underwent renal angioplasty, and failed in one patient who underwent renal angioplasty. Conclusions: The results as a whole were satisfactory. The treatment of small children and patients with double renal arteries is difficult because of their small vessels.
Background: Detecting rate of congenital heart defects（CHD）with biventricular heart has been still low, while univentricular heart has been rather easily detected through a fetal four chamber view（4CV）. The observation of ventricular outflow tract is a crucial step to successful detection of biventricular heart defects. Objects: To evaluate the occurrence rate of the right aortic arch（RAA）among fetal diagnosed heart defects and assess the usefulness of RAA in the fetal screening. Materials and Methods: Total of 3,557 fetuses were enrolled in the present study, in which fetal echocardiography was performed from 1993 to 2010. Records on video tapes and medical records were retrospectively reviewed. Results: The incidence of RAA was 12.9％ among fetuses with CHD. The incidence of CHD was 81.0％ among fetuses with RAA. Cono-tranchal anomaly were most often associated with RAA, 38.2％in tetralogy of Fallot, 18.9％ in double outlet right ventricle, 24.1％ in transposition of great arteries. Among genetic syndromes, 22q11.2 deficiency syndrome was highly associated with RAA（75.0％）, although trisomy 13（0％）, trisomy 18（5.8％）, trisomy 21（5.4％）were rarely associated with RAA. Conclusion: It is suggested that RAA is a useful marker of CHD in fetal screening, especially for cono-truncal anomaly which is technically difficult to detect through 4CV. Furthermore, RAA might be a new and useful marker for cardiac defects in genetic syndrome because it is rarely associated with trisomy and, highly with 22q11.2 deficiency syndrpome.
Background: Amplatzer® Duct Occluder （ADO） was introduced in our hospital in 2010. This study aimed to analyze role of transcatheter coil occlusion for patent ductus arteriosus （PDA） before and after introduction of the ADO. Subjective and Methods: Group A （14 patients） who received coil occlusion in the era before introduction of ADO （2007-2009）, group B （12 patients） and group C （13 patients） underwent transcatheter occlusion of the PDA in the era after introduction of ADO （2010-2012） using coil for group B and ADO for group C, respectively. Age, body weight, and narrowest PDA diameter were analyzed. PDA morphology was determined using the Krichenko classification. Results: Age and body weight were comparable among groups A （7 ± 16 years, 18.3 ± 17.9 kg）, B （8 ± 15 years, 18.4 ± 12.4 kg）, and C （23 ± 33 years, 22.4 ± 21.3 kg）, while the narrowest PDA diameter was significantly different between groups B （1.4 ± 0.7 mm） and C （2.8 ± 2.0 mm）. The narrowest PDA diameter in group B tended to be small and could be corrected using a single coil in most patients. In one group B patient whose PDA was typed with the diameter >2 mm, ADO was not used as the length of the PDA was too long. Conclusion: Following the introduction of ADO, transcatheter coil occlusion was utilized only to correct the PDA with a diameter of ≤2 mm, and most cases required only a single coil. However, we suggest that coil occlusion should be utilized to treat long such as type D even if whose diameter is >2 mm.
Background: Reduction of the fast pathway effective period has been reported in adult patients with successful slow pathway disconnection. However in children, the effect of slow pathway ablation on fast pathway refractoriness has not been well documented. Method: Medical charts of children without congenital heart diseases who received radiofrequency catheter ablation for the treatment of atrioventricular nodal reentrant tachycardia （AVNRT） during April 2011 and August 2013 were retrospectively reviewed. Fast pathway effective refractory periods before and after slow pathway ablation were compared. Result: Eight children were included in the study. Slow pathways were successfully disconnected in all children without any complications, and none of them showed any evidence of recurrence during the follow-up period. Fast pathway effective refractory period was significantly shortened after slow pathway disconnection （403.8 ± 101.6 ms vs. 300.0 ± 96.2 ms，p <0.001）. Conclusions: Effective refractory period of fast pathway was reduced significantly after slow pathway disconnection in children with AVNRT.
Background: Patients with Kawasaki disease（KD）who show non-responsiveness to initial intravenous immunoglobulin treatmen（t IVIG）are at high risk of coronary artery abnormalit（y CAA）. Kobayashi et al. reported a useful prediction score for determining non-responders to the initial IVIG（Kobayashi score）; however, some patients are non-responders despite having low scores. We investigated the characteristics of these non-responders. Methods: Clinical findings of nine non-responders and 114 responders with low Kobayashi scores（4 points or fewer）were compared. Results: The incidence of non-responders who were 6 months old or younger was significantly higher than responders（44% vs. 12%; p =0.026）. Although both groups of patients were admitted at the same illness day, non-responders showed a significantly higher incidence of two or fewer principal KD symptoms at admission compared with responders（56% vs. 15%; p =0.009）. Conclusions: Even in patients with low Kobayashi scores, those who are 6 months old or younger are potential non-responders. Those who have two or fewer principal KD symptoms at admission and show a rapid increase in the number of symptoms are also potential non-responders. Careful observation for symptoms of non-responsiveness after initial IVIG is required for these patients.
Objectives: We herein report a case of a series of prenatally diagnosed vascular rings with right aortic arch with aberrant left subclavian artery （RAA with ALSA） and left ductus arteriosus, describing the clinical outcomes after birth. The aim of this study was to uncover the most appropriate prenatal diagnostic and postnatal follow-up methods for vascular rings with RAA with ALSA. Methods: Among 1,695 pregnant females examined from January 2001 to December 2011, eleven patients had a prenatal diagnosis of vascular rings with RAA with ALSA. The diagnosis was confirmed by postnatal echocardiography or computed tomography and/or based on the surgical findings. This was a retrospective analysis of these 11 cases. Results: Of the 11 cases with a prenatal diagnosis of RAA with ALSA, five were born in our hospital. Two of the 11 postnatal developed respiratory symptoms requiring surgery at one month and at one year and five months after birth, respectively. The former case had a diagnosis of double aortic arch （DAA） based on the surgical findings after birth. The remaining nine cases were asymptomatic. Only one case with RAA with ALSA was found to have VSD and a chromosome 22q11.2 deletion after birth. The others had no structural anomalies or major cardiac defects. Conclusions: In addition to using the three-vessel trachea view, it is important to identify the cervical vessels arising from the aortic arch during the differentiation of RAA with ALSA and DAA on fetal echocardiography, paying special attention to detect cases with a DAA with a very diminutive aortic arch. The delivery should be planned in perinatal institutions when it is difficult to differentiate DAA from RAA with ALSA. Because some cases with vascular rings with RAA with ALSA develop symptoms long after birth, meticulous follow-up and appropriate explanation to the family are recommended.
Background: Efficient and durable intervention for residual pulmonary artery （PA）stenosis is important for the establishment of excellent Fontan circulation. However, optimal patch material for surgical PA plasty has not been clearly defined. We hypothesized that the internal thoracic artery （ITA） was the optimal viable material for surgical PA plasty. Methods: Since 2007, four infants with single ventricle physiology developed residual PA stenosis and surgically intervened with ITA patch. The diagnosis was HLHS in 2 cases and pulmonary atresia and single ventricle in 2. They underwent surgical PA plasty with fresh autologous ITA patch for residual PA stenosis at 5-15 months of age after previous palliative surgery. Concomitant procedures were bidirectional Glenn shunt as a second palliation in 3 cases and intrapulmonary artery septation as a third palliation in 1. Intraoperatively, the dilated ITA was harvested with skeletonized fashion, and longitudinally opened. Under cardiopulmonary bypass, stenotic lesion of the PA was augmented with the ITA patch using 8-0 polypropylene continuous sutures. Results: All patients were subsequently completed extracardiac TCPC at 20-25 months of age without further intervention. Operative findings at TCPC shows smooth PA endothelium with elasticity at the site of ITA patch plasty, revealing less degeneration and less inflammation. Neither mortality nor re-intervention was noted at 22-45 months of the follow-up period. Post-TCPC cineangiography revealed balanced and developed PA configuration without residual stenosis. Conclusions: The ITA patch seems to be one of the materials for surgical PA patch plasty in Fontan candidates in the infantile period.
We report two cases of patients with dilated cardiomyopathy （DCM） who were successfully treated for severe heart failure by plasma exchange （PE）.
Case 1 was a 1-year-old girl who was treated using mechanical ventilation and infusions of catecholamine and diuretics for severe heart failure. Although her cardiac function improved with catecholamine infusion, this was catecholamine-dependent and the dosage could not be reduced. As an alternative therapy, PE was performed on the 99th hospital day. Cardiac function gradually improved after PE, and catecholamine infusion was discontinued with additional administration of pimobendan and denopamine. In addition, the carvedilol dosage was increased.
Case 2 was a 1-year-old girl who was treated with infusions of catecholamine and diuretics for intractable heart failure. Cardiac function marginally improved with the maximum dose of catecholamine. Based on our experience with case 1, we performed an earlier initiation of PE, on the 41st hospital day before a reduction in the catecholamine dose. After PE, cardiac function gradually improved and catecholamine infusion could be discontinued. The carvedilol dosage was also increased.
In both cases, clinical symptoms improved from NYHA class IV to II, and they were discharged without significant sequelae on the 210th and 137th hospital days, respectively.
Infantile DCM is a life threatening condition with poor prognosis, and often requires heart transplantation as an ultimate therapy. Under difficult circumstances related to heart transplantation in Japan, PE could be considered a potential rescue therapy in patients with intractable heart failure not stabilized by medical therapy alone.
We report three cases of congenital pulmonary vein stenosis （CPVS）. All 3 cases had some cardiac anomalies, such as atrial septal defect, persistent left superior vena cava, patent ductus arteriosus, and patent foramen ovale. Patients experienced tachypnea and retractive breath in early infancy. We could easily diagnose CPVS used by Doppler echocardiography and contrast three-dimensional CT scan. One of the patients underwent sutureless repair for CPVS, but he had re-stenotic changes at the operative site. Pathological examination of two patients showed myofibroblast proliferation in the pulmonary veins. Imatinib administration failed to regress the myofibroblast proliferation in a child with postoperative pulmonary vein stenosis. All three patients died of progressive pulmonary venous stenosis.
CPVS is a progressive disease, and the prognosis for infants with bilateral CPVS is very poor. Postnatal progression of CPVS may be caused by abnormal myofibroblast proliferation in the pulmonary veins.
Congenital pulmonary vein stenosis is rare condition, and an isolated form of this condition characterized by no intra-cardiac anomalies is extremely rare. We report here a four-month-old male infant with bilateral pulmonary vein stenosis, who finally received a percutaneous stent implantation due to recurrent pulmonary vein stenosis after repeated surgical repair. Congenital isolated pulmonary vein stenosis is frequently lethal because of worsening pulmonary hypertension and cardiac failure. Surgical or transcatheter intervention is not a definite therapy due to recurrent stenosis. Although lung or cardiopulmonary transplantation might be recommended, there are limited cases in Japan. At present, percutaneous pulmonary vein stent implantation may be considered an important therapy as a bridge to cardiac transplantation.
We report two cases of interventional cardiac catheterization via a transhepatic approach. Patient 1 （age, 1 year; weight, 5.8 kg） had tetralogy of Fallot and underwent percutaneous transluminal angioplasty for left pulmonary artery stenosis. Patient 2 （age, 25 years; weight, 51 kg） had polysplenia, and underwent coil embolization for a tortuous patent ductus arteriosus. Because these patients had either bilateral femoral vein obstruction or interruption of the inferior vena cava, and both had right internal jugular vein obstruction, we chose a transhepatic approach. The procedures were performed under general anesthesia. Hepatic vein punctures were performed by hepatic surgeons with ultrasound guidance; access was obtained by a single needle puncture within 20 min in both patients. Stable manipulation of the catheter was achieved, and the intervention was successful without complications. After the intervention, the transhepatic tract was closed with oxidized cellulose （SURGICEL®） introduced through the sheath. No intrahepatic or retroperitoneal hemorrhage was observed in either patient. In patients with interruption of the inferior vena cava or obstruction of the femoral vein and obstruction of the jugular vein, the traditional venous access sites are unavailable. Cardiac catheterization via a transhepatic approach is a safe and effective option for this condition and can be performed in infants. Intraoperative hemostasis is important; furthermore, closure of the transhepatic tract with oxidized cellulose is a simple and useful procedure. To ensure patient safety, it is essential to involve physicians with expertise and familiarity with the puncture procedure and maintenance of hemostasis in the hepatic vein.
We report successful transcatheter aspiration of thrombi combined with percutaneous transluminal angioplasty （PTA）for an infant complicated by superior vena cava （SVC）obstruction in postoperative period presenting critical SVC syndrome. After fetal diagnosis of transposition of the great arteries with restrictive atrial communication, the patient was delivered in the 38th week and balloon atrial septostomy was performed immediately after birth. However, the patient experienced complications of persistent pulmonary hypertension （PPHN）and presented with severe cyanosis. Extracorporeal membrane oxygenation had been needed for two weeks to eliminate the PPHN. An arterial switch operation （ASO）was performed sixteen days after birth, while pleural effusion persisted after ASO. Severe chylothrax emerged on the thirty-sixth day of life, while central venous pressure was elevated acutely followed by severe edema in the head, neck, and upper limbs, which suggested SVC obstruction. After confirming the complete occlusion of SVC by venography, a Radifocus® guide wire was passed through the site of occlusion, over which PTA was performed. After PTA, venography showed residual stenosis and thrombi on the vessel wall. We advanced the sheath introducer from right juggler vein to the stenotic site and aspirated the thrombi using the sheath. After removing many thrombi, final venography showed no residual stenosis and thrombi. Fifty-six days after the thrombectomy, venography revealed sufficient patency of the SVC. SVC obstruction in early infancy may be difficult to maintain patency and may require frequent interventions. The combination of PTA and transcatheter thrombectomy may be feasible choices immediately after obstruction of the SVC.
We assessed the pulmonary vascular morphology by optical coherence tomography （OCT） in a 10-year-old boy with idiopathic pulmonary arterial hypertension. The thickness of the intima and media was 0.18 mm and 0.19 mm, respectively, in the distal pulmonary artery. The findings suggested that pulmonary artery lesions involved medial hypertrophy and intimal thickening （Heath-Edwards grade II or III）. Pulmonary arterial pressure was greater than aortic pressure. The patient had poor response to the acute vasodilator test using intravenous epoprostenol administration. The hemodynamic result was compatible with the OCT findings. We propose OCT as a useful tool in diagnosing pulmonary artery hypertension and may provide helpful information for the pulmonary arterial remodeling process, severity, therapeutic strategy, and prognosis.