Calmodulinopathy in Japanese Children　- Their Cardiac Phenotypes Are Severe and Show Early Onset in Fetal Life and Infancy.

BACKGROUND: Cardiac calmodulinopathy, characterized by a life-threatening arrhythmia and sudden death in the young, is extremely rare and caused by genes encoding calmodulin, namely calmodulin 1 (CALM1), CALM2, and CALM3.Methods and Results: We screened 195 symptomatic children (age 0-12 years) who were suspected of inherited arrhythmias for 48 candidate genes, using a next-generation sequencer. Ten probands were identified as carrying variants in any of CALM1-3 (5%; median age 5 years), who were initially diagnosed with long QT syndrome (LQTS; n=5), catecholaminergic polymorphic ventricular tachycardia (CPVT; n=3), and overlap syndrome (n=2). Two probands harbored a CALM1 variant and 8 probands harbored 6 CALM2 variants. There were 4 clinical phenotypes: (1) documented lethal arrhythmic events (LAEs): 4 carriers of N98S in CALM1 or CALM2; (2) suspected LAEs: CALM2 p.D96G and D132G carriers experienced syncope and transient cardiopulmonary arrest under emotional stimulation; (3) critical cardiac complication: CALM2 p.D96V and p.E141K carriers showed severe cardiac dysfunction with QTc prolongation; and (4) neurological and developmental disorders: 2 carriers of CALM2 p.E46K showed cardiac phenotypes of CPVT. Beta-blocker therapy was effective in all cases except cardiac dysfunction, especially in combination with flecainide (CPVT-like phenotype) and mexiletine (LQTS-like). CONCLUSIONS: Calmodulinopathy patients presented severe cardiac features, and their onset of LAEs was earlier in life, requiring diagnosis and treatment at the earliest age possible.

A rare combination of post-ductal coarctation of the aorta and adjunct tortuous aneurysm: a neonate with Posterior fossa anomalies, Haemangiomas of the head and neck, Arterial, Cardiovascular, and Eye anomalies and ventral developmental defect syndrome.

A 4-day-old girl with Posterior fossa anomalies, Haemangiomas of the head and neck, Arterial, Cardiovascular, and Eye anomalies and ventral developmental defect syndrome comprising a facial haemangioma, aortic coarctation at the aortic arch, torturous aortic aneurysm distal to coarctation, and ductus arteriosus originating proximal to the coarctation is presented. The aortic arch was successfully reconstructed without cardiopulmonary bypass, and she is currently doing well after 4 years and 8 months.

Thrombus in the left atrial appendage: a case report of neonate.

A Japanese girl first pointed out the mass in the left atrial appendage by the echocardiography on the 3rd day of life. At 30th day of life, the mass in the left atrial appendage was excised en bloc successfully under cardiopulmonary bypass because it appeared mobile. Its pathologic finding revealed an old organised thrombus. She is doing well with no episode of thrombus formation or thromboembolism, 2 years postoperatively.

A survey of the 3-decade outcome for patients with giant aneurysms caused by Kawasaki disease.

BACKGROUND: Our purpose was to determine the outcome in patients with a more-than-20-year history of giant coronary aneurysms (GAs) caused by Kawasaki disease (KD). METHODS: Between 2010 and 2011, the incidence and outcome of cardiac events (CEs) in patients with GA was surveyed by questionnaire by the Kinki area Society of KD research. Death, acute myocardial infarction (AMI), coronary artery bypass grafting (CABG), percutaneous coronary catheter intervention, syncope, and ventricular tachycardia were considered as CEs. Survival rate and CE-free rate were analyzed by the Kaplan-Meier method. RESULTS: We enrolled 245 patients (187 were male, 58 were female), 141 with bilateral GA and 104 with unilateral GA. The interval between the onset of acute KD to the time of survey ranged from 0.2 to 51 years, and the median was 20 years. Death, AMI, and CABG occurred in 15 (6%), 57 (23%), and 90 patients (37%), respectively. The CE-free rate and the survival rate at 30 years after KD were 36% (95% CI 28-45) and 90% (95% CI 84-94), respectively. The 30-year survival rate for bilateral GA was 87% (95% CI 78-93), and for unilateral GA, it was 96% (95% CI 85-96; hazard ratio 4.60, 95% CI 1.27-29.4, P = .027). The 30-year survival rate in patients with AMI was 49% (95% CI 27-71), and the 25-year survival rate in patients undergoing CABG was 92% (95% CI 81-98). CONCLUSIONS: The outcome differed significantly between bilateral GA and unilateral GA. The results focus attention on the need to preserve myocardial perfusion, especially in high-risk patients with bilateral GA. An understanding of the optimal CABG would be useful in bilateral GA.

A case of Toriello-Carey syndrome with severe congenital tracheal stenosis.

Toriello-Carey syndrome is rare condition characterized by agenesis of the corpus callosum, the Pierre Robin sequence, and facial anomalies such as telecanthus, short palpebral fissures, and a small nose with anteverted nares [Toriello and Carey, 1988]. In addition, tracheal and laryngeal anomalies are common complications in patients with Toriello-Carey syndrome, and these anomalies can lead to death [Kataoka et al., 2003]. Congenital tracheal stenosis is a life-threatening condition with high mortality. Even if surgery is successful, several serious complications can result in a high risk of mortality. We describe a case of a Japanese boy with Toriello-Carey syndrome who had severe congenital tracheal stenosis, in whom surgical tracheal plasty was avoided because of adequate respiratory care, allowing the patient to be alive at 18 months of age.

Persistent truncus arteriosus with double aortic arch and mitral stenosis.

This report describes a case involving the rare combination of persistent truncus arteriosus type A2, double aortic arch, and mitral stenosis. At the age of 26 days, the patient underwent division of the right-sided aortic arch with tracheal compression and bilateral pulmonary banding. Fontan completion was successfully achieved after separation of the pulmonary artery from the arterial trunk, atrial septostomy, and modified Blalock-Taussig shunt at the age of 7 months and bilateral bidirectional Glenn anastomosis at the age of 1 year and 3 months. At this writing, the patient is doing well 2 years and 6 months after Fontan completion.

Novel operative technique for Scimitar syndrome: Posterior flap technique.

Various surgical techniques have been reported for Scimitar syndrome, because of the heterogenous anatomy of the disease. We developed a novel surgical method to repair Scimitar syndrome, in which, a new pulmonary venous route is constructed behind the inferior vena cava using autologous flaps of the inferior vena cava and the interatrial septum. An adult case of Scimitar syndrome was repaired by this method with good results.

Kommerell's diverticulum of retroesophageal aberrant brachiocephalic artery with right aortic arch in an adult.

A retroesophageal aberrant brachiocephalic artery is a very rare congenital aortic arch anomaly. We herein presented a 29-year-old man with right aortic arch, retroesophageal aberrant left brachiocephalic artery, left ligamentum arteriosus, and absent left internal carotid artery. Graft replacement of the descending aorta and anatomical reconstruction of left brachiocephalic artery was successfully performed using a midline sternotomy approach without blood transfusion. We discuss the surgical management for Kommerell's diverticulum.

Midterm Outcomes After Surgical Management for Mitral Valve Regurgitation in Infancy.

BACKGROUND: Mitral valve repair is preferred for pediatric mitral valve disease. However, it is technically difficult because of complex lesions, poor surgical exposure, and tissue fragility, especially in infants. We investigated the midterm outcomes of mitral valve surgery for mitral regurgitation in infancy. METHODS: We retrospectively reviewed 18 patients (aged <12 months old) undergoing mitral valve surgery for mitral regurgitation at our institution between October 2005 and March 2019. The patients had 10 acquired and 8 congenital valve lesions as follows: torn chordae (n = 6), leaflet prolapse (n = 4), posterior leaflet hypoplasia (n = 3), anterior leaflet cleft (n = 2), infective endocarditis (n = 1), papillary muscle rupture (n = 1), and hammock valve (n = 1). RESULTS: All patients initially underwent mitral valve repair. There was no operative mortality, and 1 case of late death. The median follow-up period was 7 years and 9 months. Reoperation was performed in 3 patients, re-repair (twice) in 1 patient with a hammock valve, and mitral valve replacement in 2 patients. Fifteen patients had at most mild mitral regurgitation at the last follow-up. A transmitral mean pressure gradient of over 5 mm Hg was observed in 3 cases, including the patient with a hammock valve. Postoperative mitral annular diameter increased within the normal range in all patients. Survival and reoperation-free rates at 5 and 10 years were 94.4% and 83.0%, respectively. CONCLUSIONS: Mitral valve repair for mitral regurgitation in infancy is safe and feasible with satisfactory midterm outcomes, even under serious preoperative conditions.

A neonate of coronary artery fistula from left circumflex to coronary sinus.

The patient was a neonate with a large coronary artery fistula (CAF) between the left circumflex artery and coronary sinus in whom an intractable progressive heart failure with myocardial ischemia developed within 24 h after birth. He survived the surgical intervention and is doing well. This is the first report of coronary fistula presenting with cardiogenic shock on the first day of life. Additionally, this is the fourth case of the CAF between the left circumflex artery and coronary sinus in children, and the first case in a newborn.

Posterior mitral leaflet extension using autologous pericardium to repair a hammock mitral valve associated with severe mitral valve regurgitation in a 4-month-old boy.

We successfully repaired a hammock mitral valve associated with severe mitral valve regurgitation in a 4-month-old boy using posterior leaflet extension along with glutaraldehyde-treated autologous pericardium and the splitting of bilateral papillary muscles. Surgical reinterventions were performed for the bilateral papillary muscles at 14 and 24 months postoperatively. The extended autologous pericardium was still pliable with mild mitral valve regurgitation at 26 months postoperatively.

Idiopathic Acute Mitral Regurgitation Due to Chordal Rupture in Infants: Surgical Management and Results.

OBJECTIVE: Emergency surgical treatment is required for idiopathic acute mitral regurgitation due to chordae rupture in infants. Nevertheless, mitral valve repair for such a patient population still remains challenging. We report our experience with mitral valve repair for idiopathic acute mitral regurgitation due to chordae rupture in infants. METHODS: From 2005 to 2017, six infants (four boys) were diagnosed with acute mitral regurgitation due to chordae rupture and underwent mitral valve repair. The median age, mean body weight, and median follow-up period were 5.5 months (range: 4-9 months), 6.8 kg (range: 5.5-8.0 kg), and 6.4 years (range: 6 months to 10 years), respectively. RESULTS: In all cases, surgical intervention was performed within 24 hours of admission. Artificial chordae reconstruction and paracommissural edge-to-edge repair were utilized in three and four cases, respectively, while Kay's annuloplasty was performed in all cases. Mean cardiopulmonary bypass time and aortic cross-clamp time were 117 minutes (range: 70-143 minutes) and 73 minutes (range: 35-108 minutes), respectively. No early or late deaths and reoperations had occurred during the follow-up period. Moreover, postoperative mitral regurgitation was significantly reduced, while no chronologic progression of mitral regurgitation was observed. CONCLUSIONS: The combination of various techniques, such as artificial chordae reconstruction, paracomissural edge-to-edge repair, and Kay's annuloplasty, can be a promising surgical option for idiopathic acute mitral regurgitation due to chordae rupture in infants.

Truncus Arteriosus With Major Aortopulmonary Collateral Arteries.

Truncus arteriosus with the absence of one branching pulmonary artery and presence of major aortopulmonary collateral arteries is rare. A small patient, with a birth weight of 2,219 g, was successfully repaired by a staged approach, after banding of the left pulmonary artery and unifocalization of major aortopulmonary collateral arteries.

The conversion to Rastelli's type operation from Patrick-McGoon's procedure of an adult with Taussig-Bing heart: a case report.

A 23-year-old female of Taussig-Bing heart with antero-posterior relation of the great arteries was underwent Patrick-McGoon's intraventricular rerouting at 6 years old of age. The left ventricular outflow obstruction (peak pressure gradient of 100 mmHg) developed, and severe aortic valve regurgitation following bacterial endocarditis was noted. The conversion to Rastelli's type operation and aortic valve replacement were performed successfully at 23 years old of age. She is doing well without any significant left or right ventricular outflow obstruction at 7 years postoperatively.

Mode of death and predictors of mortality in adult Fontan survivors: A Japanese multicenter observational study.

BACKGROUND: Mortality rates may be high in adult Fontan patients; however, the clinical determinants remain unclear. PURPOSE: We conducted a prospective multicenter study of adult Fontan survivors to determine the 5-year mortality rate and clarify the determinants. METHOD AND RESULTS: We followed 600 adult Fontan survivors from 40 Japanese institutions (307 men, 28 ±â€¯7 years old, follow-up: 18 ±â€¯6 years). The New York Heart Association (NYHA) functional class I and II was 51% and 42%, respectively. During the follow-up period of 4.1 ±â€¯1.6 years, 33 patients died, and the 5-year survival rate was 93.5%. The mode of death was heart failure in 11 patients (34%), arrhythmia or sudden death in 8 (24%), cancer in 5 (15%), perioperative problems and hemostatic problems in 4 each (12% for each), and infection in 1 (3%). Left isomerism, prior hospitalization, protein losing enteropathy (PLE), pulmonary arteriovenous fistulae, NYHA functional class, impaired hemodynamics, hyponatremia, hepatorenal dysfunction, and use of diuretics were associated with a high mortality rate (p < 0.05-0.0001). Further, PLE (hazard ratio [HR]: 14.4), left isomerism (HR: 3.5), and NYHA (HR: 2.4) independently predicted a high 5-year high mortality (p < 0.05 for all). The incidence of cancer-related mortality increased markedly with age >40 years. CONCLUSIONS: Majority of the Japanese adult Fontan survivors had good functional status, with an acceptable 5-year survival rate. However, the significant prevalence of non-cardiac mortality highlights Fontan pathophysiology as a multi-organ disease that requires a multidisciplinary management strategy to improve the long-term outcome.

Absent Pulmonary Valve Syndrome With Tricuspid Atresia, Ventricular Septal Defect, and Aneurysmal Dilated Pulmonary Artery: A Case Report of Successful Fontan Completion.

Of the associated cardiac defects with absent pulmonary valve, the combination of tricuspid atresia, ventricular septal defect, and aneurysmal dilatation of the pulmonary arteries is very rare. We report the case of a low-birth-weight girl (2,282 g) with this anomaly, which was prenatally diagnosed. Fontan completion was successfully achieved at 16 months of age, following staged palliative procedures including banding of the main pulmonary trunk and plication of the aneurysmal dilated central pulmonary artery.

Arrhythmia burden and related outcomes in Eisenmenger syndrome.

BACKGROUND: Patients with Eisenmenger syndrome have a shorter lifespan than the general population. A significant proportion develop arrhythmia and some, sudden death. OBJECTIVE: The aims of this study were to characterize the frequency, type and effects of arrhythmias in adult patients with Eisenmenger's syndrome and to identify risk factors for arrhythmias. METHODS: This retrospective study included patients aged ≥ 18 years of age with Eisenmenger's syndrome from three institutions. Arrhythmias were noted from electrocardiograms and Holter study reviews. RESULTS: A total of 167 patients, 96 females, 63 males (gender not available in 9 patients) were included in this study. The mean age was 38 ± 9 years (range: 18-63 years) with a majority in NYHA functional class II or III (57% and 32% respectively). Twenty-eight patients (17%) had significant tachyarrhythmia: paroxysmal supraventricular tachycardia (8 patients, 29%), atrial fibrillation (6 patients, 21%), atrial fibrillation and flutter (2 patients, 7%), nonsustained ventricular tachycardia (6 patients, 21%) and sustained ventricular tachycardia (6 patients, 21%). Among the entire study group, 26 patients (16%) were currently on antiarrhythmic therapy and 77 patients (49%) were on advanced therapies for pulmonary hypertension. Down syndrome was present in 78 patients (46%). There were 21 (13%) documented deaths, of which 8 (5%) were sudden death. Patients with arrhythmia were older [P = .01] and were more likely to have atrioventricular valvar regurgitation [Odds ratio: 4.33]. Advanced pulmonary hypertension therapy was associated with decreased all-cause mortality in logistic regression analysis [odds ratio: 0.31], while antiarrhythmic therapy was associated with sudden death [odds ratio: 6.24]. CONCLUSIONS: Arrhythmias are common among patients with Eisenmenger syndrome occurring in around 1 in 5 individuals and are associated with all-cause mortality and sudden death.

Ventricular Tachycardia Rotating a Scar of a Total Right Ventricular Exclusion.

We describe a 15-year-old postoperative girl who underwent surgical 3-dimensional mapping and ablation of hemodynamically unstable ventricular tachycardia (VT) with an on-pump beating heart surgical technique. She had previously received a tricuspid valve closure, entire right ventricular free wall resection, and finally Fontan operation with an extracardiac conduit to treat a severe Ebstein's anomaly. Activation mapping revealed a VT rotating around a large right ventricular free wall incisional scar with a narrow conduction channel between the scar and a tricuspid annulus (TA). A linear radiofrequency ablation connecting the scar and the TA terminated the VT.

Survey of the current status and management of Eisenmenger syndrome: a Japanese nationwide survey.

BACKGROUND: The management of Eisenmenger syndrome (ES) has dramatically changed since the advent of disease-targeted therapy (DTT). However, guidelines for ES management, including DTT, have not been established. We aimed to clarify the current incidence, underlying disease, and management of ES in Japan, using a nationwide survey. METHODS: A written questionnaire was sent to members of the Japanese Society for Adult Congenital Heart Disease, through which information was obtained from 86 institutions. RESULTS: A total of 251 patients with ES (80.5% cases≥20 years of age) were followed as of February 2012; DTT was performed in 124 (49.4%) patients. Unrepaired simple anatomy was reported as an underlying condition in 165 patients (65.7%). Among patients with ES, 55 (21.9%), 128 (51%), 53 (21.1%), and 12 (4.8%) were classified into functional classes I, II, III, and IV, respectively. DTT was routinely performed at 52 (60.5%) institutions, but there were variations in the DTT therapeutic strategy at these institutions. Combined therapy was more often used than monotherapy; an endothelin receptor antagonist was the most frequently prescribed medication. There were institutional differences regarding heart failure treatment and indications for anticoagulation. Digitalis and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were widely used, but beta-blockers were infrequently used to manage heart failure. CONCLUSIONS: This survey describes the current status, including prevalence and underlying disease, and variations in the practical management of ES in Japan. The results will help in the creation of future guidelines for ES management.