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Lymphatic congestion is known to play an important role in the development of late Fontan complications. This study aimed to (1) develop a gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) contrast three-dimensional heavily T2-weighed MR technique that can detect abnormal lymphatic pathway in the abdomen while simultaneously evaluating hepatocellular carcinoma (HCC) and to (2) propose a new classification of abnormal abdominal lymphatic pathway using a non-invasive method in adults with Fontan circulation. Twenty-seven adults with Fontan circulation who underwent Gd-EOB-DTPA abdominal MR imaging were prospectively enrolled in this study. We proposed MR lymphangiography that suppresses the vascular signal on heavily T2-weighted imaging after EOB contrast. The patients were classified as follows: grade 1 with almost no lymphatic pathway, grade 2 with a lymphatic pathway mainly around the bile duct and liver surface, and grade 3 with a lymphatic pathway mainly around the vertebral body and inferior vena cava. The grade 3 group showed the lowest oxygen saturation level, highest central venous pressure, highest incidence of massive ascites, HCC, and focal nodular hyperplasia. This group also tended to have patients with the oldest age and highest cardiac index; however, the difference was not statistically significant. As for the blood test, the grade 3 group showed the lowest platelet count and serum albumin level and the highest fibrosis-4 index. A novel technique, Gd-EOB-DTPA MR lymphangiography, can detect abnormal abdominal lymphatic pathways in Fontan circulation, which can reflect the severity of failing Fontan.

ObjectiveFontan-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.MethodsThis 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.ResultsA 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.ConclusionsPatients 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.

Patients with heart failure (HF) reportedly have activated platelets with increased platelet distribution width (PDW) and mean platelet volume (MPV), which lead to thrombotic events. These platelet indices are easily measured by routine blood tests and have been proposed as potential markers of cardiac events. We performed the present study to clarify whether platelet indices correlate to the severity of HF and to the prognosis of patients with congenital heart disease (CHD). We performed a retrospective single-center study including 400 patients with CHD [median age, 34 years (range 12-76); 49% males] hospitalized between 2014 and 2017. We assessed their clinical data, correlation between platelet indices and severity of HF, and prognosis of HF-related hospitalization and thrombus formation. In multivariate analysis, a significant correlation was found between PDW and logBNP (log-transformed brain natriuretic peptide; r = 0.30, p 0.001), as well as between MPV and logBNP (r = 0.24, p 0.001). After treatment for heart failure, a significant reduction was found in PDW (average value before treatment: 14.2; after: 13.2, p = 0.017). In multivariate logistic regression analysis, PDW [hazard ratio (HR) 1.365; 95% confidence interval (CI) 1.005-1.768] and MPV (HR 1.472; 95% CI 1.055-2.052) were predictors of HF-related hospitalization. Similarly, PDW (HR 1.998; 95% CI 1.461-2.630) and MPV (HR 1.792; 95% CI 1.155-2.781) were predictors of thrombus formation. Platelet volume indices correlate to severity of heart failure and have prognostic value for both cardiac and thrombotic events in patients with CHD.

The progression of atrial fibrosis long after Fontan surgery is unclear. This study aimed to evaluate the degree of atrial fibrosis long after the classic Fontan procedure and to investigate the factors associated with atrial fibrosis.We obtained atrial free wall specimens resected at Fontan conversion from 43 patients (Fontan group) and studied the degree of atrial fibrosis, along with its association with atrial tachycardia/fibrillation (AT/AF) and other clinical parameters, compared with those of the control group without heart disease (n=6).The time after the initial Fontan procedure was 19.9 (15.9-25.3) years. Atrial fibrosis (%) was more common in the Fontan group than in the control group [24.3 (20.9-35.0)% vs. 6.2 (5.6-7.5)%, p0.001]. The severity of atrial fibrosis was mild in 16% (n=7), moderate in 54% (n=23), and severe in 30% (n=13) of cases. Atrial fibrosis (%) was more common in the persistent/permanent AT/AF group than in the no AT/AF (p0.001) and paroxysmal AT/AF (p0.001) groups. The maximum atrial diameter on computed tomography (CT) (mm) significantly correlated with atrial fibrosis (%) (r=0.52, p0.001). The maximum diameter of the right atrium (≥75 mm) on CT was a significant risk factor for severe atrial fibrosis on multivariate logistic analysis (hazard ratio=10.22, 95% confidence interval=1.04-254.8, p=0.04).Atrial fibrosis was prominent long after classic Fontan surgery, especially in patients with non-paroxysmal AT/AF and dilated right atrium.

As long-term surgical outcome of congenital heart disease has continued to improve, most pediatric patients with congenital heart disease are able to reach adulthood. However, adult congenital heart disease (ACHD) patients have increased risk of arrhythmia, valvular diseases, infectious endocarditis, and heart failure. The end-stage ACHD patients with advanced heart failure may require mechanical circulatory support to improve the heart failure symptoms or to recover from circulatory collapse, and may eventually aim to heart transplant or destination therapy. In general, long-term mechanical support for dilated cardiomyopathy or ischemic cardiomyopathy has been achieved with left ventricular assist device with excellent survival outcomes and improved quality of life. However, the ventricular assist device for end-stage ACHD patients can be challenging due to patient-specific anatomical feature, multiple histories of surgical and catheter-based interventions and possible multiple end-organ dysfunctions, and offered less frequently compared to non-ACHD patients. The Interagency Registry for Mechanically Assisted Circulatory Support data published recently showed that ACHD patients receiving long-term mechanical circulatory support consisted1 % of all registrants and had higher mortality after mechanical support than non-ACHD patients. However, the ACHD patients supported with left ventricular assist device had similar survival with non-ACHD patients and a large proportion of the mortality difference between ACHD and non-ACHD patients seemed to result from operative and perioperative factors. Therefore, the ventricular assist device therapy can be an excellent treatment for selected ACHD patients. In this paper, we describe the current status of ventricular assist device support for end-stage ACHD patients and consideration to the future.

Background In complex congenital heart disease, supraventricular arrhythmia develops long term after surgical repair. The arrhythmia could have pharmacological tolerance and sometimes be fatal. We report our experiences with puncturing tough or calcified surgical repair material to access the pulmonary venous atrium for the purpose of the management of arrhythmia in complex congenital heart disease with surgical correction. Methods From June 2016, subsequent 9 patients underwent the procedure. Their age at the procedure ranged from 11 to 43 years old (median 26.4 years old). Surgical procedures were Mustard procedure (XenomedicaⓇ) in 6, lateral tunnel total cavo-pulmonary connection with autologous pericardium in 2, and extra-cardiac total cavo-pulmonary connection with expanded polytetrafluoroethylene (ePTFE) tube in 1. Results Multi-planar reconstruction imaging by cardiac computed tomography was done for making plans before the procedures. Under intracardiac echocardiography guidance, an 8 French steerable sheath was perpendicularly adjusted to target objects. The sharpened edge of 0.014 inch guide wire penetrated with gentle forward force. Subsequently, the puncture site was dilated from a small balloon to a large one step by step. In all patients, penetration was successfully completed. Catheter ablation was achieved in 8 patients and a pacemaker was implanted through the re-canalized superior caval vein in 1 patient. No complications were recorded. Conclusion The trans-catheter puncture of the synthetic or calcified material is safe and feasible, although careful planning is required with imaging. A steerable sheath could easily be controlled to the make appropriate angle to the target object for preventing slippage and conveying effective force.

Progression to acute kidney injury (AKI) under treatment in adult congenital heart disease (ACHD) patients with heart failure is associated with poor prognosis, early detection and interventions are necessary. We aimed to explore the utility of urinary liver-type fatty acid binding protein (L-FABP) in ACHD patients hospitalized for acute decompensated heart failure (ADHF). We prospectively evaluated hemodynamic, biochemical data, and urinary biomarkers including urinary L-FABP in ACHD patients hospitalized in our institution from June 2019 to March 2022. The primary outcomes were the development of AKI and death. AKI was defined as serum creatinine level increased by 0.3 mg/dl or more within 5 days after hospitalization. A total of 104 ADHF patients aged 31 (36-51) years were enrolled. 26 cases (25% of ADHF patients) developed AKI during hospitalization and 4 died after hospital discharge. Serum creatinine (sCr), serum total bilirubin, brain natriuretic peptide (BNP), and urinary L-FABP in AKI patients were significantly higher than in non-AKI patients, whereas systemic oxygen saturation of the peripheral artery (SpO

Recently, targeted therapy has been developed for idiopathic pulmonary arterial hypertension (IPAH). Studies evaluating the prognosis of IPAH have been conducted in adults. However, there is no nationwide survey of pediatric patients with IPAH regarding the long-term prognosis in Japan. Therefore, we investigated the clinical outcomes of Japanese pediatric patients with IPAH and risk factors for a poor prognosis. This multi-center, retrospective cohort study included pediatric patients with IPAH under the age of 15 years, who were gleaned from the nationwide network of Japanese Society of Pediatric Cardiology and Cardiac Surgery (JSPCCS). The questionnaire was sent to members of JSPCCS in 2015. Patients who were diagnosed with IPAH from 1994 to 2014 were included. The primary endpoint was death or lung transplantation. Ninety-five patients were finally enrolled. Both the mean age at diagnosis and the mean follow-up duration were 7 years. Ninety-five percent of patients had received targeted therapy for IPAH during follow-up. The overall 1, 3, 5, and 10-year event free rate, estimated using Kaplan-Meier survival estimate, was 96, 91, 83, and 74%, respectively. The prognosis was significantly poorer in patients with increased right ventricular systolic pressure (RVp), mean pulmonary artery pressure (mPAP) (≥ 52 mmHg), cardiothoracic ratio (≥ 55%), and levels of B-type natriuretic peptide (BNP) during follow-up (≥ 300 pg/mL) than in those without these parameters. In conclusion, in Japanese children with IPAH, the event-free rate for death or lung transplantation was found to be good. Greater RVp, mPAP, BNP levels during follow-up, and cardiothoracic ratio may be predictive indicators for a poor prognosis.

BACKGROUND Sarcopenia is one of the important predictors of heart failure (HF) in patients with cardiac problems. Skeletal muscle pump is important to maintain Fontan circulation. We aimed to quantify the volume of the psoas major muscle (PMM) and investigate whether it is relevant to HF hospitalization in adults with Fontan circulation. METHODS A total of 154 adults with Fontan circulation, and 30 age-matched adults were studied retrospectively. We identified secondary sarcopenia by measuring the PMM volume, using non-contrast abdominal computed tomography. RESULTS PMM indexed volume in Fontan patients was lower than controls (206.4+/-18.0 cc/m2 vs 288.0+/-61.1 cc/m2, p

PURPOSE The native T1 value at 3T MRI is a sensitive marker for diffuse fibrosis or damage in various organs including the heart, liver, and pancreas. Despite the fact that Fontan-associated liver disease (FALD) is a crucial issue in adults with Fontan circulation, there are only a few studies with liver T1 mapping in children and adolescents. We investigated the potential of the liver native T1 mapping in detecting FALD in adult patients. METHODS We prospectively enrolled 16 consecutive adults with Fontan circulation (age 31.3 ± 8.5 years), who were in New York Heart Association Functional class II-IV. Twenty with tetralogy of Fallot (TOF), and 20 age-matched controls also underwent cardiac magnetic resonance (CMR) imaging at 3T. Myocardial T1 mapping with a Modified Look-Locker Inversion recovery sequence was applied to liver T1 mapping. Patients in the Fontan group underwent the right heart catheter and liver function tests, including those for fibrotic markers. RESULTS Liver native T1 values in the Fontan group were significantly higher than that in TOF and controls (P < 0.001). In the Fontan group, the liver native T1 value was significantly correlated with age, γ-glutamyltransferase, model for end-stage liver disease XI score, and albumin-bilirubin score (P = 0.01, 0.01, 0.044, 0.001). However, it demonstrated no correlation with central venous pressure, pulmonary vessel resistance, or fibrotic markers. CONCLUSION Liver native T1 value derived from CMR may be a non-invasive adjunctive and/or screening marker to detect FALD.

Although arterial switch operations (ASOs) have been performed globally to repair d-transposition of the great arteries (d-TGA) in neonates and infants, few studies have been reported regarding the influence of the hemodynamics of patients with d-TGA who have undergone ASO on the development of neo-aortic valve regurgitation (AR). We aimed to investigate the relationship between the hemodynamics and development of AR after ASO in patients with d-TGA by catheter evaluation. This observational study screened 114 consecutive patients who underwent ASO for d-TGA or Taussig–Bing anomaly and who subsequently underwent catheter evaluations in our institution. We reviewed their records for the past 20 years and collected their first catheterization data post-ASO in early childhood. Thirty-six post-ASO patients who underwent catheter evaluations in both the early surgical and long-term phases were finally analyzed. Patients were divided into the following groups according to the presence of significant AR in the long-term phase: the AR group (n = 9 with AR ≥ grade II by the Sellers classification) and the non-AR group (n = 27 with AR

To employ quantitative analysis in the vorticity and helicity of the aortic root and the ascending aorta (AAo) in adults with tetralogy of Fallot (TOF), and to evaluate aortopathy and the relevant factors. Prospectively, 51 consecutive adults with TOF underwent 4 dimensional flow magnetic resonance imaging study for the assessment of vorticity and helicity of the aortic root and AAo, wall shear stress (WSS), viscous energy loss (EL), and the left ventricular outflow tract – aortic root (LVOT-Ao) angle. Patients were divided into the two groups: dilated aortic root and/or AAo (indexed diameter > 25 mm/cm2), Group A (15 patients); non-dilated aortic patients, Group B (36 patients). Ten age-matched controls were also enrolled. Group A showed more acute LVOT-Ao angle, higher incidence of aortic regurgitation, and initial anatomy of pulmonary atresia, compared to Group B (P

This study aimed to summarize cases of successful pregnancy and delivery in patients with transposition of the great arteries (TGA) after atrial switch operation (ASO), to provide management, clinical experience, and maternal and fetal outcomes.During a 16-year period (2004-2019), we experienced 30 pregnancies in 15 patients after ASO at our institution. We retrospectively reviewed the medical records of the patients.In 30 pregnancies, there were 21 (70%) live births, five (17%) miscarriages, and four (13%) artificial abortions. There were no maternal or neonatal deaths. Cardiac complications occurred in nine (43%) patients: deterioration of right ventricular (RV) function in one, symptomatic heart failure (HF) in three, supraventricular tachyarrhythmia requiring electrical cardioversion in two, sick sinus syndrome that required pacemaker implantation in two, and hemoptysis in one. Obstetric complications occurred in five (24%). Neonatal complications were premature births (delivery at37 weeks of gestation) in 15 (71%), and birthweight2500 g in 18 (86%). The mode of delivery consisted of vaginal delivery (VD) in five (24%), and cesarean section (CS) in 16 (76%).A high incidence of preterm CS and cardiac complications including deterioration of RV function was observed in patients who had undergone ASO for TGA.

Simple Summary In this study, the induced pluripotent stem cell-derived cardiomyocyte model from a patient with long QT syndrome harboring a heterozygous Nav1.5 R1623Q mutation exhibited prolonged field potential duration corrected by Fridericia’s formula (FPDcF, analogous to QTcF). FPDcF was shortened with mexiletine treatment and increased the frequency of arrhythmia-like EAD events following E4031, an Ikr blocker, administration. These characteristics partly reflect the patient phenotypes. As the R1623Q mutation is related to severe congenital LQT syndrome in fetuses and neonates, the effect of the neonatal variants on the electrophysiological properties of the R1623Q mutant was examined using an automated patch-clamp system. Our results demonstrated that both R1623Q and neonatal R1623Q delayed inactivation of INa and increased late Na current. We speculated that neonatal Nav1.5 ameliorates QTc prolongation. Developmental switching of neonatal/adult Nav1.5 isoforms might play a role in the mechanisms underlying severe long QT syndrome in fetuses and neonates. Abstract The SCN5A R1623Q mutation is one of the most common genetic variants associated with severe congenital long QT syndrome 3 (LQT3) in fetal and neonatal patients. To investigate the properties of the R1623Q mutation, we established an induced pluripotent stem cell (iPSC) cardiomyocyte (CM) model from a patient with LQTS harboring a heterozygous R1623Q mutation. The properties and pharmacological responses of iPSC-CMs were characterized using a multi-electrode array system. The biophysical characteristic analysis revealed that R1623Q increased open probability and persistent currents of sodium channel, indicating a gain-of-function mutation. In the pharmacological study, mexiletine shortened FPDcF in R1623Q-iPSC-CMs, which exhibited prolonged field potential duration corrected by Fridericia’s formula (FPDcF, analogous to QTcF). Meanwhile, E4031, a specific inhibitor of human ether-a-go-go-related gene (hERG) channel, significantly increased the frequency of arrhythmia-like early after depolarization (EAD) events. These characteristics partly reflect the patient phenotypes. To further analyze the effect of neonatal isoform, which is predominantly expressed in the fetal period, on the R1623Q mutant properties, we transfected adult form and neonatal isoform SCN5A of control and R1623Q mutant SCN5A genes to 293T cells. Whole-cell automated patch-clamp recordings revealed that R1623Q increased persistent Na+ currents, indicating a gain-of-function mutation. Our findings demonstrate the utility of LQT3-associated R1623Q mutation-harboring iPSC-CMs for assessing pharmacological responses to therapeutic drugs and improving treatment efficacy. Furthermore, developmental switching of neonatal/adult Nav1.5 isoforms may be involved in the pathological mechanisms underlying severe long QT syndrome in fetuses and neonates.

A wide variety of pathologies are involved in heart failure in patients with congenital heart disease (CHD). Specific causes of heart failure after the Fontan procedure include not only single-ventricle circulation, but also the function of the right ventricle as the systemic ventricle, atrioventricular or semilunar valve stenosis or regurgitation, pulmonary hypertension, and left ventricular dysfunction secondary to right ventricular enlargement or dysfunction. As heart failure can occur post-Fontan, for a variety of reasons, clarification of the pathophysiology is the first step in management and treatment. At the same time, it is important to understand each patient's current condition and treatment plan to make an accurate prognosis. Because of the wide variety of pathophysiologies in post-Fontan CHD patients, however, no single biomarker is useful in all situations. Relevant biomarkers must be selected according to each patient's disease state, and combinations of multiple biomarkers should also be considered. In this review, the author describes the clinical importance of various biomarkers for patients who have undergone a Fontan procedure.

OBJECTIVES Patients who have achieved Fontan circulation may require reoperation. We reviewed the outcomes of reoperation after Fontan completion and assessed the risk factors for poor outcomes. METHODS This was a retrospective study of 106 patients undergoing open-heart reoperations after Fontan completion in 2003 at a single institution. RESULTS The mean age at reoperation was 24.6 ± 8.3 years. A history of Fontan failure or end-organ dysfunction was noted in 30 patients. The reoperations included 73 total cavopulmonary connection conversions, 29 atrioventricular or semilunar valve operations (17 with total cavopulmonary connection conversions) and 4 other operations. Eight early deaths occurred. During a median follow-up of 5.5 (0.01–16.2) years, there were 3 late deaths and 9 second cardiac operations. The 10-year survival rate after reoperation was 89.8%, and the 5-year second cardiac operation-free survival was 84.3%. The 10-year survival rates were significantly lower in patients who underwent surgery before 2011 (75.8% vs 100%), had a history of Fontan failure or end-organ dysfunction (71.7% vs 97.3%), had preoperative central venous pressure >15 mmHg (64.9% vs 96.5%) and were operated on with deep hypothermic circulatory arrest (DHCA) (60.0% vs 91.3%). A history of Fontan failure or end-organ dysfunction, preoperative central venous pressure >15 mmHg and requirement of DHCA were identified as risk factors for mortality. CONCLUSIONS Reoperation after Fontan completion resulted in excellent mid-term outcomes. A history of failed Fontan circulation and the requirement of DHCA negatively affected survival outcomes.

Background:Although sleep apnea is an important disorder associated with cardiac events, data regarding its prevalence and risk factors in adult patients with congenital heart disease are limited.Methods:In this study, patients underwent a sleep study in the hospital. Indications for admission were classified as heart failure, diagnostic catheterisation, interventional catheterisation, or arrhythmia. The prevalence, characteristics, and risk factors of sleep apnea using a type-3 portable overnight polygraph in adult patients with congenital heart disease were evaluated.Results:There were 104 patients [median age: 36 (interquartile range: 28–48) years] who were admitted for heart failure 34% (n = 36), diagnostic catheterisation 26% (n = 27), interventional catheterisation 18% (n = 19), or arrhythmia 22% (n = 23). The prevalence of sleep apnea, defined as a respiratory disturbance index ≥5, was 63% (n = 63), with a distribution of 37%, 16%, and 10% for mild (5≤ respiratory disturbance index Conclusion:Our results showed a high prevalence of sleep apnea in adult patients with congenital heart disease. Its unique haemodynamics may be associated with a high prevalence of sleep apnea. Congestive heart failure and being overweight are important risk factors for sleep apnea. Management of heart failure and general lifestyle improvements will be important for controlling sleep apnea symptoms in these patients.

BackgroundAlthough sleep apnoea is an important disorder associated with cardiac events, data regarding its prevalence and risk factors in adult patients with CHD are limited.MethodsIn this study, patients underwent a sleep study in the hospital. Indications for admission were classified as heart failure, diagnostic catheterisation, interventional catheterisation, or arrhythmia. The prevalence, characteristics, and risk factors of sleep apnoea using a type 3 portable overnight polygraph in adult patients with CHD were evaluated.ResultsThis study comprised 104 patients of median age 36 years with interquartile range of 28–48 years, admitted for heart failure 34% (n = 36), diagnostic catheterisation 26% (n = 27), interventional catheterisation 18% (n = 19), or arrhythmia 22% (n = 23). The prevalence of sleep apnoea, defined as a respiratory disturbance index ≥5, was 63% (n = 63), with a distribution of 37, 16, and 10% for mild (5≤ respiratory disturbance index ConclusionOur results showed a high prevalence of sleep apnoea in adult patients with CHD. Its unique haemodynamics may be associated with a high prevalence of sleep apnoea. Congestive heart failure and being overweight are important risk factors for sleep apnoea. Management of heart failure and general lifestyle improvements are important for controlling sleep apnoea symptoms in these patients.

The recognition of fluid retention is critical in treating heart failure (HF). Bioelectrical impedance analysis (BIA) is a well-known noninvasive method; however, data on its role in managing patients with congenital heart disease (CHD) are limited. Here, we aimed to clarify the correlation between BIA and HF severity as well as the prognostic value of BIA in adult patients with CHD.This prospective single-center study included 170 patients with CHD admitted between 2013 and 2015. We evaluated BIA parameters (intra- and extracellular water, protein, and mineral levels, edema index [EI, extracellular water-to-total body water ratio]), laboratory values, and HF-related admission prevalence.Patients with New York Heart Association (NYHA) functional classes III-IV had a higher EI than those with NYHA classes I-II (mean ± SD, 0.398 ± 0.011 vs 0.384 ± 0.017, P .001). EI was significantly correlated with brain natriuretic peptide level (r = 0.51, P .001). During the mean follow-up period of 7.1 months, Kaplan-Meier analysis showed that a discharge EI 0.386, the median value in the present study, was significantly associated with a future increased risk of HF-related admission (HR = 4.15, 95% CI = 1.70－11.58, P .001). A body weight reduction during hospitalization was also related to EI reduction.EI determined using BIA could be a useful marker for HF severity that could predict future HF-related admissions in adult patients with CHD.

Purpose Dilated aortic root and ascending aorta (AAO) with progressive aortic regurgitation is a well-known sequela after arterial switch operation (ASO) in adults with transposition of the great arteries (TGA). We aimed to quantitatively assess aortic flow profiles in adults with TGA after ASO (Jatene procedure with LeCompte maneuver) using echo planar imaging (EPI) 4D flow MRI. Methods Prospectively, 9 consecutive adults (30.2 ± 6.6 years) after ASO (Jatene operation with LeCompte technique), 13 consecutive adults (34.3 ± 7.2 years) after the atrial switch operation with Senning procedure, and 8 age-matched control patients, who underwent turbo field echo (TFE) EPI 4D flow MRI (average scan time of approximately 4 min), were enrolled. Results TGA after ASO showed a markedly dilated sinus of Valsalva, compared to TGA after atrial switch operation (26.6. ± 4.9 vs. 18.6. ± 1.5 mm/cm2). Vorticity, helicity, wall share stress (WSS), and energy loss (EL) in the aortic root and the AAO in TGA were greater than in the controls. Vorticity, helicity, WSS, and EL in the aortic root and the AAO were also greater in TGA after ASO than after atrial switch operation. More acute aortic arch angle correlated with greater vorticity of the aortic root, and the significant diameter ratio of the sinus of Valsalva and the AAO was relevant to greater vorticity, helicity, and EL in TGA after ASO. Conclusions A non-physiological blood flow pattern of the aortic root was identified in TGA adults after the ASO (Jatene procedure with LeCompte maneuver). Missing spiral looping of the great arteries and the unique structure after the Jatene procedure may play an adjunctive role in promoting aortopathy. The evaluation of aortic flow profile using EPI 4D flow MRI may be useful for risk stratification for aortopathy in this population.

We used 4D-flow MRI to investigate circulation, an area integral of vorticity, in the main pulmonary artery (MPA) as a new hemodynamic parameter for assessing patients with a repaired Tetralogy of Fallot (TOF). We evaluated the relationship between circulation, right ventricular (RV) function and the pulmonary regurgitant fraction (PRF). Twenty patients with a repaired TOF underwent cardiac MRI. Flow-sensitive 3D-gradient sequences were used to obtain 4D-flow images. Vortex formation in the MPA was visualized, with short-axis and longitudinal vorticities calculated by software specialized for 4D flow. The RV indexed end-diastolic/end-systolic volumes (RVEDVi/RVESVi) and RV ejection fraction (RVEF) were measured by cine MRI. The PR fraction (PRF) and MPA area were measured by 2D phase-contrast MRI. Spearman ρ values were determined to assess the relationships between circulation, RV function, and PRF. Vortex formation in the MPA occurred in 15 of 20 patients (75%). The longitudinal circulation (11.7 ± 5.1 m2/s) was correlated with the RVEF (ρ = − 0.85, p = 0.0002), RVEDVi (ρ = 0.62, p = 0.03), and RVESVi (ρ = 0.76, p = 0.003) after adjusting for the MPA size. The short-axis circulation (9.4 ± 3.4 m2/s) in the proximal MPA was positively correlated with the MPA area (ρ = 0.61, p = 0.004). The relationships between the PRF and circulation or RV function were not significant. Increased longitudinal circulation in the MPA, as demonstrated by circulation analysis using 4D flow MRI, was related to RV dysfunction in patients with a repaired TOF.

The heart murmur associated with atrial septal defects is often faint and can thus only be detected by chance. Although electrocardiogram examination can prompt diagnoses, identification of specific findings remains a major challenge. We demonstrate improved diagnostic accuracy realized by incorporating a proposed deep learning model, comprising a convolutional neural network (CNN) and long short-term memory (LSTM), with electrocardiograms. This retrospective observational study included 1192 electrocardiograms of 728 participants from January 1, 2000, to December 31, 2017, at Tokyo Women's Medical University Hospital. Using echocardiography, we confirmed the status of healthy subjects—no structural heart disease—and the diagnosis of atrial septal defects in patients. We used a deep learning model comprising a CNN and LTSMs. All pediatric cardiologists (n = 12) were blinded to patient groupings when analyzing them by electrocardiogram. Using electrocardiograms, the model’s diagnostic ability was compared with that of pediatric cardiologists. We assessed 1192 electrocardiograms (828 normally structured hearts and 364 atrial septal defects) pertaining to 792 participants. The deep learning model results revealed that the accuracy, sensitivity, specificity, positive predictive value, and F1 score were 0.89, 0.76, 0.96, 0.88, and 0.81, respectively. The pediatric cardiologists (n = 12) achieved means of accuracy, sensitivity, specificity, positive predictive value, and F1 score of 0.58 ± 0.06, 0.53 ± 0.04, 0.67 ± 0.10, 0.69 ± 0.18, and 0.58 ± 0.06, respectively. The proposed method is a superior alternative to accurately diagnose atrial septal defects.

Introduction: Sarcopenia is one of the important predictors of heart failure (HF) in patients with cardiac problems. Hypothesis: Skeletal muscle pump is very important to maintain Fontan circulation. We aimed to quantify the volume of the psoas major muscle (PMM) and investigate whether it is relevant to HF hospitalization in adults with Fontan circulation. Methods: A total of 154 adults with Fontan circulation, and 30 age-matched adults were studied retrospectively. We identified secondary sarcopenia by measuring the PMM volume, using non-contrast abdominal computed tomography (CT). Results: PMM indexed volume in Fontan patients was lower than controls (206.4+/-18.0 cc/m2 vs 288.0+/-61.1 cc/m2, P Conclusions: PMM volume reduction has an adjunctive prediction of HF hospitalization in adults with Fontan circulation, particularly in Fontan females. Secondary sarcopenia may have a negative impact on the prognosis of HF in this population. The assessment of skeletal muscle mass also may be a comprehensive screening tool for multi-organ dysfunction in Fontan circulation.

Introduction and hypothesis: Flow hemodynamic parameters may relate to aortopathy in adults with tetralogy of Fallot. We aimed to employ quantitative analysis in the vorticity and helicity of the aortic root and the ascending aorta (AAo) in adults with tetralogy of Fallot (TOF), and to evaluate aortopathy and the relevant factors. Methods: Prospectively, 51 consecutive adults with TOF underwent 4 dimensional flow magnetic resonance imaging study for the assessment of vorticity and helicity of in the aortic root and AAo, wall shear stress (WSS), viscous energy loss (EL), and the left ventricular outflow tract - aortic root (LVOT-Ao) angle. Patients were divided into the two groups: dilated aortic root and/or AAo (indexed dimeter>25mm/cm2), Group A (15 patients); non-dilated aortic patients, Group B (36 patients). Ten age matched controls were also enrolled. Results: Group A showed acute LVOT-Ao angle, higher incidence of aortic regurgitation, and initial anatomy of pulmonary atresia, compared to Group B (P Conclusions: TOF Adults with TOF presenting dilated AAo have greater vorticity, helicity, and acute LVOT-Ao angle. Flow eccentricity correlates with vorticity and helicity, which may affect the aortopathy in adults with TOF. AAo vorticity and helicity are also relevant factors of aortic dilatation, and these flow hemodynamic parameters may be adjunctive predictions of aortopathy in this population.

The native TWe prospectively enrolled 16 consecutive adults with Fontan circulation (age 31.3 ± 8.5 years), who were in New York Heart Association Functional class II-IV. Twenty with tetralogy of Fallot (TOF), and 20 age-matched controls also underwent cardiac magnetic resonance (CMR) imaging at 3T. Myocardial TLiver native TLiver native T

Collection of peripheral blood from many patients over a long period of time has resulted in the establishment of a library composed of more than 4400 immortalized B cell lines, which have been used to identify mutated genes responsible for congenital heart defects (CHD). Because of the current progress in induced pluripotent stem cell (iPSC) technology and the ability of these iPSC lines to differentiate into cardiomyocytes, we started a project to establish an in vitro cardiac disease model using patient specific-iPSC-derived cardiomyocytes. As part of this project, we have established more than 20 iPSC lines from patients with CHD and from normal controls. All generated iPSC lines expressing pluripotent stem cell marker genes and proteins were alkaline phosphatase-positive. After reprogramming, the mutated genes were not altered and normal karyotypes were observed; Epstein–Barr viral genes were also not expressed. Most iPSC lines were confirmed to be able to differentiate into ectoderm, mesoderm and endoderm in vivo, indicating that we had successfully established iPSC lines. These iPSC lines were then induced to differentiate into cardiomyocytes. Most of these iPSC lines were observed to differentiate into beating cardiomyocytes, with some diversity in cardiomyocyte differentiation among the cell lines. In this study, we examined the effect of serial dilutions of agents on early stages of cardiomyocyte differentiation. In a floating culture system, varying concentrations of Activin A (0–10 ng/mL) and BMP4 (0–10 ng/mL) with FGF-2 (5 ng/mL) in StemPro 34 (ThermoFisher Scientific, Waltham, MA) medium were used to induce mesoderm formation. The optimum concentrations of the agents for cardiomyocyte induction in iPSC lines were varied; 0–5 ng/mL Activin A and 1.25–10 ng/mL BMP4 were generally effective. We further investigated some additives for enhancement of embryoid body (EB) formation, and hyaluronate and Matrigel (BD Biosciences, San Jose, CA) addition relatively improved EB formation. Induction of functioning cardiomyocytes was associated with the ability to form appropriately sized EB in floating culture. Thus, further studies are required to improve the cell differentiation ability in some iPSC lines for establishment of stable disease models using patient-specific iPSC-derived cardiomyocytes.

Cardiomyocytes derived from induced pluripotent stem cells (iPSC) are used to evaluate the function and risk factors of genetic variations linked to congenital and adult heart diseases in human beings. Our purpose in this study was to establish an in vitro cardiac disease model from an immortalized B-cell line stock using patient-specific iPSC-derived cardiomyocytes. Long QT syndrome (LQTS) 3 is caused by a gain-of-function mutation in the SCN5A gene, resulting in a prolonged QT interval as well as the development of early after-depolarizations (EADs). We generated LQT3-iPSC lines from immortalized B-cell lines transformed from peripheral blood obtained from a 24-day-old male (patient #1) and an 11-year-old female (patient #2), both diagnosed with type-3 LQTS due to SCN5A missense mutation (patient #1: exon 28, G4868A, R1623Q; patient #2: exon 20, G3578A, R1193Q). Several control iPSC lines were also created from samples collected from healthy candidates (26–36-year-old male and female). In both the generated patient iPSC lines, mutated genes were not altered after reprogramming, and normal karyotypes were observed. The pluripotency of all these iPSC lines was proven by in vivo teratoma formation and the expression of pluripotent stem cell marker genes and proteins. To evaluate the electrophysiological properties at the multicellular level, we studied the iPSC-derived cardiac cell layers with a microelectrode array mapping system (MED 64, Alpha MED Scientific Inc.). The recorded extracellular electrograms were analyzed to measure the field-potential duration (FPD), which was normalized to account for variations in beating frequency, using Fridericia’s correction (FPDcF, analogous to the QTc interval in the electrocardiogram). FPDcF was observed to be longer in LQT3 patient-derived specimens when compared to that in healthy control specimens (patient #1: P < 0.05, N = 17 and patient #2: P < 0.0001, N = 19 when compared to healthy control N = 39). Moreover, EADs were observed in both LQT3 patient specimens after 15–30 nM of E-4031 was added exclusively to patient samples. The results indicated that LQT3 patient iPSC-derived cardiac cells expressed prolonged QT duration (a common pathophysiological feature of LQTS) and EAD development with marked arrhythmogenicity in our in vitro disease model system.

Background Patients with congenital heart disease (CHD) reportedly have reduced exercise capacity. Underlying cardiac anatomy and a sedentary lifestyle are thought to be associated with exercise impairment. However, little has been reported regarding the relationship between quantitative body composition and exercise capacity. Bioelectrical impedance analysis (BIA) is a rapid and safe assessment method that has been widely used in clinical research. We hypothesized that bioelectrical impedance parameters are determinants of exercise capacity, and the skeletal muscle index (SMI) determined by BIA is a prognostic predictor in patients with CHD. Methods We conducted a retrospective single-center study of 305 consecutive patients with CHD [median age, 26 years (range 12–60]; 48% males] admitted between 2014 and 2017. The BIA parameters were reviewed, including the edema index (EI, extracellular water to total body water ratio), SMI (skeletal muscle mass/height2), mineral index (MI, mineral mass/height2), percent body fat (%BF), and exercise capacity [peak oxygen uptake (peakVO2)] via a cardiopulmonary exercise test. Results The multivariate analysis revealed a significant correlation between peakVO2 and EI (r = 0.55) and peakVO2 and SMI (r = 0.49). The receiver operating characteristic curve analysis showed that the EI cut-off for peakVO2 Conclusions SMI determined by BIA is a determinant of exercise capacity and can be used as a prognostic predictor in patients with CHD.

The aim of the study was to evaluate systemic right ventricular (RV) dyssynchrony in patients with congenitally corrected transposition of the great arteries (CCTGA) and transposition of the great arteries (TGA) with New York Heart Association functional class (NYHA FC)

Aim We investigated the clinical courses before and during pregnancy and after delivery in patients with repaired anomalous origin of the left coronary artery from the pulmonary artery to determine the impact of the hemodynamic changes and cardiac function on the selection of the appropriate mode of delivery. Methods Six patients who underwent coronary artery reimplantation delivered 10 infants. We scrutinized the patients' hemodynamic changes on echocardiographs and the plasma brain natriuretic peptide levels before and during pregnancy and after delivery, the perinatal outcomes and maternal and fetal events. Results All patients were asymptomatic and categorized as having New York Heart Association functional class I before pregnancy. In 8 of 10 pregnancies, vaginal deliveries were performed; two elective cesarean sections were performed because of symptomatic heart failure. The hemodynamic parameters were stable throughout pregnancy and postdelivery, and no maternal or fetal events occurred in the patients who underwent vaginal deliveries. One cesarean section patient developed significant heart failure during the late second and third trimesters, which was accompanied by hemodynamic changes, including increased brain natriuretic peptide levels, left ventricular diastolic dysfunction and worsening arrhythmias, and thrombosis and post-partum hemorrhage occurred postdelivery. The baby had intrauterine growth retardation and small for gestational age. None of the babies had congenital anomalies. Conclusion Pregnancy was safe in most of the asymptomatic patients long after anomalous origin of the left coronary artery from the pulmonary artery was repaired. Symptomatic heart failure might occur during pregnancy in patients with persisting myocardial damage. Pregnancy and delivery should be carefully managed.