Predictors of liver cirrhosis and hepatocellular carcinoma among perioperative survivors of the Fontan operation.

OBJECTIVE: Fontan-associated liver disease (FALD) is widely recognised as a common complication in patients long after the Fontan operation. However, data on the predictors of FALD that can guide its screening and management are lacking. The present study aimed to identify the predictors of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) in post-Fontan patients. METHODS: This was a multi-institutional retrospective cohort study. Clinical data of all perioperative survivors of Fontan operation before 2011 who underwent postoperative catheterisation were collected through a retrospective chart review. RESULTS: A total of 1117 patients (538 women, 48.2%) underwent their first Fontan operation at a median age of 3.4 years. Postoperative cardiac catheterisation was conducted at a median of 1.0 year. During a median follow-up period of 10.3 years, 67 patients (6.0%) died; 181 (16.2%) were diagnosed with liver fibrosis, 67 (6.0%) with LC, 54 (4.8%) with focal nodular hyperplasia and 7 (0.6%) with HCC. On multivariable analysis, high central venous pressure (CVP) (HR, 1.28 (95% CI 1.01 to 1.63) per 3 mm Hg; p=0.042) and severe atrioventricular valve regurgitation (HR, 6.02 (95% CI 1.53 to 23.77); p=0.010) at the postoperative catheterisation were identified as independent predictors of LC/HCC. CONCLUSIONS: Patients with high CVP and/or severe atrioventricular valve regurgitation approximately 1 year after the Fontan operation are at increased risk of developing advanced liver disease in the long term. Whether therapeutic interventions to reduce CVP and atrioventricular valve regurgitation decrease the incidence of advanced liver disease requires further elucidation.

Single-stage arterial switch operation conversion with dextro-transposition of the great arteries and pulmonary arterial hypertension due to baffle leak after a Senning procedure.

Patients who have undergone an atrial switch operation for dextro-transposition of the great arteries (dTGA) sometimes suffer from right ventricular dysfunction, tricuspid regurgitation, arrhythmias, or baffle leaks. We report the first case of single-stage arterial switch operation conversion in an adult patient with dTGA and pulmonary arterial hypertension (PAH) due to a baffle leak after a Senning procedure. Perioperative mechanical circulatory support was required for 3 weeks. Although chronic kidney disease persisted, her left ventricular function and pulmonary hypertension improved over the first postoperative year. This is a rare case, and we believe that the patient's PAH might have helped the left ventricle withstand systemic pumping for over two decades. Learning objective: Patients with dextro-transposition of the great arteries may face problems after an atrial switch operation because their right ventricle is responsible for systemic pumping. Staged arterial switch operation conversion is a strategy that can combat these problems but increases the risk of perioperative mortality. Pulmonary arterial hypertension allows for single-stage arterial switch operation, but the operative risk may be higher.

Outcomes of Restrictive Cardiomyopathy in Japanese Children　- A Retrospective Cohort Study.

BACKGROUND: There has been no nationwide survey on the prognosis of pediatric restrictive cardiomyopathy (RCM) in Japan; therefore, this retrospective multicentered study was designed to investigate the long-term survival rate of pediatric patients with RCM in Japan.Methods and Results: A multicentered, retrospective observational study was performed between 1990 and 2014 and included patients diagnosed with RCM who were aged <18 years from 18 Japanese institutions. A total of 54 patients were diagnosed with RCM. The median age at diagnosis was 4.4 years, and the median duration of observation was 2.2 years at the time of this study. Of these patients, 54% had symptoms, including heart failure. Twelve patients died without heart transplantation, mostly due to heart failure. The median time to death from diagnosis was 2.5 years. Freedom from death at 1, 5, and 10 years was 91%, 68%, and 62%, respectively. Death occurred within 5 years of diagnosis in most patients. Twenty-two patients underwent heart transplantation. Freedom from heart transplantation at 1, 5, and 10 years was 77%, 58%, and 53%, respectively. Freedom from death or heart transplantation at 1, 5, and 10 years was 72%, 40%, and 34%, respectively. The presence of symptoms was a risk factor for death or transplantation. CONCLUSIONS: The prognosis of pediatric RCM is poor, and the heart transplantation rate is low in Japan.

Predictors of long-term mortality among perioperative survivors of Fontan operation.

AIMS: The criteria for 'good' Fontan haemodynamics have been poorly defined in relation to long-term outcomes. The aim of this study was to identify the risk factors for mortality among haemodynamic parameters obtained early after the Fontan operation. METHODS AND RESULTS: Clinical data of all perioperative survivors of the Fontan operation performed before 2011, from nine institutions, were collected through a retrospective chart review. In total, 1260 patients were included. The median age at the time of Fontan operation was 3.6 years. Post-operative cardiac catheterization was conducted in 1117 patients at a median period of 1.0 years after the operation. During the median follow-up period of 10.2 years, 107 patients died. The mortality rates at 10, 20, and 25 years after the operation were 5%, 12%, and 22%, respectively. On multivariable analysis, older age at the time of the operation {≥15 years, hazard ratio (HR) [95% confidence interval (CI)]: 3.2 (1.7-5.9)} and haemodynamic parameters obtained at post-operative catheterization, such as low ejection fraction [<30%, HR (95% CI): 7.5 (3.2-18)], low systemic oxygen saturation [<80%, HR (95% CI): 3.8 (1.6-9.1)], high central venous pressure [≥16 mmHg, HR (95% CI): 2.3 (1.3-3.9)], and low mean systemic arterial pressure [<60 mmHg, HR (95% CI): 3.0 (1.4-6.2)] were identified as independent predictors of mortality. The predictive model based on these parameters had a c-index of 0.75 at 10 years. CONCLUSIONS: Haemodynamic parameters obtained at a median period of 1.0 years, post-operatively, can accurately identify patients with a high mortality risk, who may need intensive management to improve long-term outcomes.

Outcomes of hypertrophic cardiomyopathy in Japanese children: a retrospective cohort study.

There has been no multicenter study on the prognosis of pediatric hypertrophic cardiomyopathy (HCM) in Japan. Therefore, we conducted a retrospective multicenter observational study on the long-term survival rate in patients diagnosed with HCM under the age of 18 between 1990 and 2014. Twenty institutions participated. A total of 180 patients were identified. The median age at diagnosis was 5.8 years old and median duration of observation was 8.3 years. Although six patients (3%) deteriorated into the dilated phase of HCM, no patient received heart transplantation. Freedom from death at 1, 5, 10, and 20 years were 97%, 92%, 84%, and 80%, respectively. There were 26 deaths. Among them, 11 patients died suddenly, presumably due to arrhythmia, and 15 patients died of heart failure. The presence of heart failure symptoms and a greater cardiothoracic ratio were significant risk factors for heart failure-related death. There were no significant risk factors identified for arrhythmia-related death. In conclusion, the prognosis of pediatric HCM in Japan is good and similar to those reported in population-based studies in the United States and Australia. Significant risk factors for heart failure-related death were identified in pediatric patients with HCM in Japan.

Outcomes of Dilated Cardiomyopathy in Japanese Children　- A Retrospective Cohort Study.

BACKGROUND: There has been no nationwide survey on the prognosis of pediatric dilated cardiomyopathy (DCM) in Japan. Therefore, we designed this retrospective multicenter study to investigate the long-term survival rate in pediatric patients with DCM in Japan.Methods and Results:In this multicenter retrospective observational study, data were reviewed for 106 patients aged <18 years who had been diagnosed with DCM at any 1 of 18 Japanese institutions between 1990 and 2014. The median age at diagnosis was 2.0 years and the median duration of observation was 3.3 years. Most DCM patients were diagnosed because of symptoms of heart failure. On echocardiography, the median left ventricular end-diastolic dimension z score was 5.4 and fractional shortening was 0.10. Freedom from death or transplantation rates at 1, 3, 5, 10, and 20 years after diagnosis were 76%, 66%, 64%, 58%, and 43%, respectively. Freedom from death rates at 1, 5, 10, and 20 years after diagnosis were 81%, 75%, 72%, and 53%, respectively. The incidence of heart transplantation at 1, 5, 10, and 20 years after diagnosis was 6%, 15%, 20%, and 20%, respectively, suggesting that only 15% of patients in Japan underwent heart transplantation within 5 years of diagnosis. CONCLUSIONS: In Japan, the prognosis of pediatric DCM is poor and the rate of heart transplantation is low.

[Medium-remote Term Results of the Atrioventricular Valve Replacement with Mechanical Valve for Functional Single Ventricles].

We prospectively investigated the relation of adaptation, timing of atrioventricular valve replacement (AVVR), valve type, size, durability of replacement valve, and preoperative cardiac function with prognosis of AVVR. The subjects included 26 patients[ 15.5 years old( day 2-43 years)] with functional single ventricle who underwent AVVR at our institution between August 1996 and January 2014. Of these patients, 24 had regurgitation, whereas 2 had stenosis. Of 7 patients who died, 3 were infants who died in the postoperative acute phase, and all of them had severe heart failure at the preoperative stage. The 5-year survival rate was 67% as assessed by Kaplan-Meier curve. On univariate analysis of the preoperative data, pulmonary artery pressure (PAP), pulmonary capillary wedge pressure, age at operation, body height, and body weight were significant risk factors for death;of these, only PAP remained in the last model for multiple regression analysis. AVVR for regurgitation is supposed to reduce cardiac volume load and help improve prognosis. Atrioventricular valve plasty or replacement should be performed prior to the development of severe heart failure.

Efficacy and Safety of Low-Dose Amiodarone Therapy for Tachyarrhythmia in Congenital Heart Disease.

Amiodarone (AMD) is a class III anti-arrhythmic drug that is highly effective for tachyarrhythmia treatment. AMD is widely used in adults with congenital heart disease (CHD); however, higher doses of AMD (> 200 mg/day) can cause various non-cardiac side effects. The purpose of this study was to assess the efficacy, safety, and adverse events of low-dose AMD (≤ 200 mg/day) for tachyarrhythmia in patients with CHD. We retrospectively studied 80 patients with CHD and tachyarrhythmia who received oral low-dose AMD (≤ 200 mg/day) from January 2004 to March 2016. Low-dose AMD therapy was used to treat supraventricular tachycardia (SVT) in 51 patients and ventricular tachycardia (VT) in 29 patients. After a mean follow-up of 2.9 years for SVT and 3.2 years for VT, 36% and 65% of the patients with SVT and VT, respectively, were free from a first tachyarrhythmia recurrence for 3 years. The incidence of AMD-induced side effects was 23%, and all these cases consisted of thyroid dysfunction. Low-dose AMD was effective for the treatment of tachyarrhythmia in patients with CHD and had a relatively low incidence of side effects. These findings suggest that low-dose AMD is useful and effective for decreasing the frequency of tachyarrhythmia in patients with CHD and has a low incidence of side effects.

Mechanisms of Left Ventricular Dysfunction Assessed by Layer-Specific Strain Analysis in Patients With Repaired Tetralogy of Fallot.

BACKGROUND: Left ventricular (LV) dysfunction in patients with repaired tetralogy of Fallot (rTOF) is an important risk factor for adverse outcomes. The aim of this study was to assess the details and time course of such LV dysfunction using layer-specific strain analysis by echocardiography.Methods and Results:The 66 patients with rTOF (mean age, 16.3±9.3 years) were divided into 3 groups (T1: 4-10 years, T2: 11-20 years, T3: 21-43 years), and 113 controls of similar age (mean age, 17.2±9.3 years) were divided into 3 corresponding groups (C1, C2, and C3). Layer-specific longitudinal strain (LS) and circumferential strain (CS) of 3 myocardial layers (endocardial, midmyocardial, and epicardial) were determined by echocardiography. Basal and papillary endocardial CS values were decreased in T1 compared with C1. With the exception of papillary epicardial CS, basal/papillary CS and LS of all 3 layers decreased in T2 compared with C2. Excepting papillary epicardial CS, all other values were decreased in T3 compared with C3. CONCLUSIONS: Potential myocardial damage was found in the endocardium at the basal and papillary levels of the LV in young patients with rTOF, extending from the endocardium to the epicardium and from the base to the apex. This is the possible time course of LV dysfunction in patients with rTOF.

Idiopathic mitral valve chordae rupture in an infant: importance of rapid diagnosis and surgery.

Mitral valve chordae rupture in infancy is a rare, but life-threatening disease. The progression of acute cardiac failure has been reported, with emergency surgery being required in most cases. Mitral valve chordae rupture typically occurs at the age of 4-6 months. Echocardiography is needed to diagnose this disease, and accurate diagnosis is difficult for general pediatricians. We herein describe the case of an acutely ill 4-month-old infant, who was saved and discharged without neurological sequelae due to the early diagnosis of mitral valve chordae rupture, life support, and surgery. We confirm the importance of acute pre-surgery treatment and immediate surgery for the survival and good outcome of infants.

Outcome of univentricular repair in patients with Down syndrome.

OBJECTIVE: Total cavopulmonary connection (TCPC) is rarely performed for a functional single ventricle in children with Down syndrome; therefore, the postsurgical outcomes are not well known. We evaluated mortality and related factors after TCPC in children with Down syndrome. METHODS: Between January 2004 and March 2010 we identified 8 patients with Down syndrome among 235 patients who had undergone TCPC. The preoperative clinical course, preoperative data, and postoperative clinical course were evaluated. In addition, clinical parameters and postoperative clinical course were compared between children with Down syndrome (n = 8) and a non-Down syndrome group (n = 227). RESULTS: The median age at the time of TCPC was 4.1 years (range, 3.4-5.5 years), and the preoperative mean pulmonary artery pressure was 13.9 ± 1.81 mm Hg. We observed respiratory complications in 2 patients, surgical site infection in 3 patients, and chylothorax in 2 patients. No significant difference was observed in preoperative data and mortality rate (1 of 8 patients [12.5%] in the Down syndrome group; 5 of 227 patients [2.2%] in the non-Down syndrome group) between the groups of children with and without Down syndrome. However, when the postoperative clinical course was examined, the durations of intensive care unit stay (P = .009) and hospital stay (P = .007) were found to be significantly prolonged in the Down syndrome group. CONCLUSIONS: Patients with Down syndrome tend to show prolonged recovery after TCPC. However, as opposed to previous reports, the mortality rate of patients undergoing TCPC is lower with no significant difference from that of children without Down syndrome.

Outcome of implantable cardioverter defibrillator therapy for congenital heart disease.

BACKGROUND: The use of implantable cardioverter defibrillator (ICD) therapy for congenital heart disease (CHD) has been increasing, but few studies have reported on the efficacy of ICD therapy in Japanese CHD patients. METHOD: Twelve CHD patients (median age, 35 years) with first ICD implantation were examined. Median follow-up duration was 2.9 years. Demographic information, implant electrical parameters, appropriate and inappropriate discharge data and complications were recorded for all implants from 2003 to 2010. RESULTS: Implant indication was primary prevention in two patients and secondary prevention in 10. Overall four patients received one or more discharges; three patients (25%) with secondary prevention received nine appropriate discharges. Inappropriate discharge attributed to sinus tachycardia occurred in two patients (16.7%). Only one patient experienced the late complication of skin erosion at the generator implantation site. CONCLUSIONS: Patients with CHD experienced significant rates of appropriate discharges and lower complications. But given that the indications of ICD implantation were mostly for secondary prevention, the ratio of appropriate shocks might be lower than in previous studies. In the primary prevention patients, the benefit of ICD was not clear because no appropriate discharges were seen during follow up. Although ICD implantation for CHD is beneficial for preventing sudden cardiac death, careful decision making and a large, long-term prospective study is required for the determination of the efficacy of ICD therapy in Japanese patients with CHD.

Effect of carvedilol on heart failure in patients with a functionally univentricular heart.

BACKGROUND: The effect of carvedilol on heart failure (HF) in patients with a functionally univentricular heart (UVH) remains unclear. METHODS AND RESULTS: Carvedilol was used to treat HF in 51 patients with a UVH, classified into 3 groups: after the Fontan operation (F), after the bidirectional Glenn operation (G), and patients who had not undergone Fontan or Glenn operation (NF). Carvedilol therapy was started at a mean age of 10 ± 12 years (range: 1 month to 34 years). The initial and maximum doses of carvedilol were 0.04 ± 0.03 and 0.42 ± 0.29 mg · kg(-1) · day(-1), respectively. After a mean follow-up of 11 months, the cardiothoracic ratio improved from 60 ± 8 to 58 ± 8% (P<0.01), and the dosage of furosemide was reduced from 1.4 ± 0.9 to 0.7 ± 0.7 mg · kg(-1) · day(-1) (P < 0.01). The ejection fraction also improved from 35 ± 12 to 40 ± 11% (P < 0.05), and this improvement was prominent in the F group (from 35 ± 15 to 45 ± 9%; P < 0.05). Clinical signs, symptoms, and New York Heart Association functional class also improved. CONCLUSIONS: Carvedilol may play an important role in treating HF associated with a UVH.

Clinical characteristics and genetic background of congenital long-QT syndrome diagnosed in fetal, neonatal, and infantile life: a nationwide questionnaire survey in Japan.

BACKGROUND: Data on the clinical presentation and genotype-phenotype correlation of patients with congenital long-QT syndrome (LQTS) diagnosed at perinatal through infantile period are limited. A nationwide survey was conducted to characterize how LQTS detected during those periods is different from that in childhood or adolescence. METHODS AND RESULTS: Using questionnaires, 58 cases were registered from 33 institutions. Diagnosis (or suspicion) of LQTS was made during fetal life (n=18), the neonatal period (n=31, 18 of them at 0 to 2 days of life), and beyond the neonatal period (n=9). Clinical presentation of LQTS included sinus bradycardia (n=37), ventricular tachycardia/torsades de pointes (n=27), atrioventricular block (n=23), family history of LQTS (n=21), sudden cardiac death/aborted cardiac arrest (n=14), convulsion (n=5), syncope (n=5), and others. Genetic testing was available in 41 (71%) cases, and the genotype was confirmed in 29 (71%) cases, consisting of LQT1 (n=11), LQT2 (n=11), LQT3 (n=6), and LQT8 (n=1). Ventricular tachycardia/torsades de pointes and atrioventricular block were almost exclusively observed in patients with LQT2, LQT3, and LQT8, as well as in those with no known mutation. In LQT1 patients, clues to diagnosis were mostly sinus bradycardia or family history of LQTS. Sudden cardiac death/aborted cardiac arrest (n=14) was noted in 4 cases with no known mutations as well as in 4 genotyped cases, although the remaining 6 did not undergo genotyping. Their subsequent clinical course after aborted cardiac arrest was favorable with administration of beta-blockers and mexiletine and with pacemaker implantation/implantable cardioverter-defibrillator. CONCLUSIONS: Patients with LQTS who showed life-threatening arrhythmias at perinatal periods were mostly those with LQT2, LQT3, or no known mutations. Independent of the genotype, aggressive intervention resulted in effective suppression of arrhythmias, with only 7 deaths recorded.

Efficacy and safety of carvedilol for heart failure in children and patients with congenital heart disease.

There have been few reports describing the use of carvedilol in children or patients with congenital heart disease. Therefore, its optimal regimen, efficacy, and safety in these patients have not been adequately investigated. Subjects were 27 patients with two functioning ventricles, for whom carvedilol was initiated (from December 2001 to December 2005) to treat heart failure. All patients had failed to respond to conventional cardiac medication. They consisted of 12 males and 15 females, aged 23 days to 47 years (median age: 2 years). Heart failure due to ischemia (myocardial infarction, intraoperative ischemic event) or due to myocardial disease (cardiomyopathy, myocarditis), and heart failure with atrial or ventricular tachyarrhythmia represented 70% of all cases. Carvedilol was initiated at a dose of 0.02-0.05 mg/kg/day, which was increased by 0.05-0.1 mg/kg/day after 2 days, 0.1 mg/kg/day after 5 days, and 0.05-0.1 mg/kg/day every month thereafter with a target dose of 0.8 mg/kg/day. This study retrospectively assessed the efficacy and adverse reactions based on changes of symptoms, cardiothoracic ratio (CTR), left ventricular ejection fraction (LVEF), and human atrial natriuretic peptide (hANP)/b-type natriuretic peptide (BNP) blood levels. The mean follow-up period was 10.2 months (range: 1-46 months). Twenty-six (96.3%) patients showed improvement in symptoms and were discharged from the hospital. However, the remaining one patient failed to respond and died. Significant cardiovascular adverse reaction was seen in none of the patients. The mean CTR decreased from 61.8% +/- 5.3% before treatment to 57.6% +/- 7.4% after treatment (P < 0.05, n = 25), and the mean LVEF improved from 41.4% +/- 23.1% to 61.1% +/- 10.1% (P < 0.05, n = 10), respectively. Mean hANP and BNP levels showed a decrease from 239.1 pg/ml to 118.3 pg/ml and a significant decrease from 437.9 pg/ml to 120.5 pg/ml, respectively (P < 0.05, n = 10). Improvements in these data were also demonstrated when analyzed individually among the pediatric group (aged younger than 18) and the congenital heart disease group. Initiation of carvedilol at a lower dose with more gradual dose escalation, compared with previously reported regimens, might have efficacy with low incidence of adverse effects in pediatric patients and patients with congenital heart disease. Carvedilol may be effective in treating heart failure in children due to ischemia, myocardial disease, and complicated by tachyarrhythmia.