The c.1617del variant of TMEM260 is identified as the most frequent single gene determinant for Japanese patients with a specific type of congenital heart disease.

Although the molecular mechanisms underlying congenital heart disease (CHD) remain poorly understood, recent advances in genetic analysis have facilitated the exploration of causative genes for CHD. We reported that the pathogenic variant c.1617del of TMEM260, which encodes a transmembrane protein, is highly associated with CHD, specifically persistent truncus arteriosus (PTA), the most severe cardiac outflow tract (OFT) defect. Using whole-exome sequencing, the c.1617del variant was identified in two siblings with PTA in a Japanese family and in three of the 26 DNAs obtained from Japanese individuals with PTA. The c.1617del of TMEM260 has been found only in East Asians, especially Japanese and Korean populations, and the frequency of this variant in PTA is estimated to be next to that of the 22q11.2 deletion, the most well-known genetic cause of PTA. Phenotype of patients with c.1617del appears to be predominantly in the heart, although TMEM260 is responsible for structural heart defects and renal anomalies syndrome (SHDRA). The mouse TMEM260 variant (p.W535Cfs*56), synonymous with the human variant (p.W539Cfs*9), exhibited truncation and downregulation by western blotting, and aggregation by immunocytochemistry. In situ hybridization demonstrated that Tmem260 is expressed ubiquitously during embryogenesis, including in the development of cardiac OFT implicated in PTA. This expression may be regulated by a ~ 0.8 kb genomic region in intron 3 of Tmem260 that includes multiple highly conserved binding sites for essential cardiac transcription factors, thus revealing that the c.1617del variant of TMEM260 is the major single-gene variant responsible for PTA in the Japanese population.

Functional characterization of variants found in Japanese patients with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant form of vascular dysplasia. Genetic diagnosis is made by identifying loss-of-function variants in genes, such as ENG and ACVRL1. However, the causal mechanisms of various variants of unknown significance remains unclear. In this study, we analyzed 12 Japanese patients from 11 families who were clinically diagnosed with HHT. Sequencing analysis identified 11 distinct variants in ACVRL1 and ENG. Three of the 11 were truncating variants, leading to a definitive diagnosis, whereas the remaining eight were splice-site and missense variants that required functional analyses. In silico splicing analyses demonstrated that three variants, c.526-3C > G and c.598C > G in ACVRL1, and c.690-1G > A in ENG, caused aberrant splicing, as confirmed by a minigene assay. The five remaining missense variants were p.Arg67Gln, p.Ile256Asn, p.Leu285Pro, and p.Pro424Leu in ACVRL and p.Pro165His in ENG. Nanoluciferase-based bioluminescence analyses demonstrated that these ACVRL1 variants impaired cell membrane trafficking, resulting in the loss of bone morphogenetic protein 9 (BMP9) signal transduction. In contrast, the ENG mutation impaired BMP9 signaling despite normal cell membrane expression. The updated functional analysis methods performed in this study will facilitate effective genetic testing and appropriate medical care for patients with HHT.

α/ß- and ß-Blocker Exposure in Pregnancy and the Risk of Neonatal Hypoglycemia and Small for Gestational Age.

BACKGROUND: α/ß- and ß-blockers are essential in pregnant women's perinatal congenital heart disease management. Nevertheless, data on the effects of α/ß- and ß-blockers on pregnant women and fetuses are limited. We examined the risks of neonatal hypoglycemia and small for gestational age (SGA) associated with maternal exposure to α/ß- and ß-blockers.Methods and Results: All consecutive pregnant women with heart disease admitted to our hospital between January 2014 and October 2020 were included. Of 306 pregnancies (267 women), 32 were in the α/ß-blocker group, 11 were in the ß-blocker group, and 263 were in the control group. All 32 pregnancies in the α/ß-blocker group were treated with carvedilol. In the ß-blocker group, 4 women were treated with bisoprolol, 3 were treated with propranolol, 2 were treated with atenolol, 1 was treated with metoprolol, and 1 was treated nadolol. The incidence of neonatal hypoglycemia was higher in pregnant women taking carvedilol than in the control group (P=0.025). SGA was observed significantly more frequently in pregnant women taking ß-blockers than in the carvedilol and control groups (P<0.001). CONCLUSIONS: Carvedilol administration during pregnancy was associated with neonatal hypoglycemia; however, it did not occur in a time- or dose-dependent manner. Routine monitoring of blood glucose levels in newborns exposed to α/ß- and ß-blockers is essential.

Utility of urinary liver-type fatty acid-binding protein as a prognostic marker in adult congenital heart patients hospitalized for acute heart failure.

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 (SpO2) and estimated glomerular filtration ratio in AKI patients were lower than non-AKI patients. There was no difference in the intravenous diuretic dose on admission and during hospitalization between the two groups. In the receiver operating characteristic (ROC) analysis, the maximum area under the curve (AUC) of urinary biomarkers in AKI patients was urinary L-FABP (AUC = 0.769, p < 0.001) with a cutoff value of 4.86 µg/gCr. Urinary L-FABP level on admission was associated with a predictor for AKI development during hospitalization after adjusting for sCr, BNP and SpO2. Urinary L-FABP was a useful predictor for the development of AKI in ACHD patients hospitalized for ADHF. Monitoring of urinary L-FABP allows us to detect a high-risk patient earlier than the conventional biomarkers.

Abdominal lymphatic pathway in Fontan circulation using non-invasive magnetic resonance lymphangiography.

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.

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.

Platelet volume indices correlate to severity of heart failure and have prognostic value for both cardiac and thrombotic events in patients with congenital heart disease.

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.

Biomarkers for heart failure and prognostic prediction in patients with Fontan circulation.

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.

Management of pregnancy and delivery in women with transposition of the great arteries after atrial switch operation: A 16-year single-center experience.

AIM: 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. METHODS: 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. RESULTS: 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 at <37 weeks of gestation) in 15 (71%), and birthweight <2500 g in 18 (86%). The mode of delivery consisted of vaginal delivery (VD) in five (24%), and cesarean section (CS) in 16 (76%). CONCLUSION: A high incidence of preterm CS and cardiac complications including deterioration of RV function was observed in patients who had undergone ASO for TGA.

Predictors of neo-aortic valve regurgitation in the long term after arterial switch operation.

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 < grade II). In the long-term phase, the diastolic blood pressure was significantly lower and the ascending aortic diameter was significantly larger in the AR group than in the non-AR group (p = 0.004 and p = 0.006, respectively). The systolic blood pressure (SBP) and pulse pressure (PP) were similar in both groups. Meanwhile, in the early surgical phase, SBP and PP were significantly higher in the AR group than in the non-AR group (p = 0.029 and p = 0.002, respectively). The receiver operating characteristic curve for late AR showed that the area under the curve for SBP and PP in the early surgical phase were 0.746 and 0.853, respectively. Even though sensitivity analysis was performed, SBP or PP greater than the cutoff value in the early surgical phase was identified as predictors for late AR. Our results suggested that high SBP or PP in the early surgical phase could influence the development of AR in the long term after ASO.

Outcomes of idiopathic pulmonary arterial hypertension in Japanese children: a retrospective cohort study.

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.

Diagnosing Atrial Septal Defect from Electrocardiogram with Deep Learning.

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.

Aortic Vorticity, Helicity, and Aortopathy in Adult Patients with Tetralogy of Fallot: Pilot Study Using Four-Dimensional Flow Magnetic Resonance Images.

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 < 0.0001, 0.02, 0.043). Group A showed greater clockwise vorticity at the level of Valsalva, AAo, and proximal arch, sagittal vorticity, AAo helicity, WSS, and EL than in Group B (P < 0.001, < 0.001, < 0.001, 0.045, 0.049, 0.02, 0.026). More acute LVOT-Ao angle correlated with the diameter of the aortic root and AAo, AAo vorticity, helicity, WSS, and EL (P = 0.004, 0.023, 0.045, 0.004, 0.0004, 0.017). On a univariate logistic analysis, more acute LVOT-Ao angle, AAo vorticity, AAo helicity, and maximum WSS were relevant factors of AAo dilatation (P = 0.02, 0.02, 0.045, 0.03, 0.046). On a multivariate logistic analysis, more acute LVOT-Ao angle was the most important factor of AAo dilatation (odds ratio 0.66, 95% CI 0.46-0.95, P < 0.024). TOF adults presenting dilated AAo have greater vorticity, helicity, and acute LVOT-Ao angle. Flow eccentricity and these flow hemodynamic parameters may be adjunctive predictions of aortopathy in this population.

Pregnancy and Delivery in Patients With Repaired Congenital Heart Disease　- A Retrospective Japanese Multicenter Study.

BACKGROUND: Although advances in cardiac surgery have led to an increased number of survivors with congenital heart disease (CHD), epidemiological data regarding the pregnancies and deliveries of patients with repaired CHD are scarce.Methods and Results:In this study, we retrospectively reviewed the clinical outcomes of pregnancies and deliveries of women with repaired CHD. Overall, 131 women with repaired CHD were enrolled and there were 269 gestations. All patients were classified as New York Heart Association (NYHA) Class I or II. The prevalence of cesarean sections was higher in patients with (CyCHD) than without (AcyCHD) a past history of cyanosis (51% vs. 19%, respectively; P<0.01). There were 228 offspring from 269 gestations and the most prevalent neonatal complication was premature birth (10%), which was more frequent in the CyCHD than AcyCHD group (15.7% vs. 5.6%, respectively; P<0.01). Five maternal cardiac complications during delivery were observed only in the CyCHD group (8%); these were classified as NYHA Class II and none was fatal. CONCLUSIONS: Delivery was successful in most women with repaired CHD who were classified as NYHA Class I or II, although some with CyCHD and NYHA Class II required more attention. Cesarean sections were more common in the CyCHD than AcyCHD group, and CyCHD may be a potential risk for preterm deliveries.

Liver Strain Using Feature Tracking of Cine Cardiac Magnetic Resonance Imaging: Assessment of Liver Dysfunction in Patients with Fontan Circulation and Tetralogy of Fallot.

We propose a novel method to quantify pulsatile liver deformation using the feature tracking method of cardiac cine magnetic resonance imaging (MRI) and investigate its association with liver dysfunction in long-term postoperative patients after Fontan and intracardiac repair for the tetralogy of Fallot (TOF). Standard cine MRI which was previously performed for cardiac evaluation of 85 patients who underwent Fontan operation (mean age, 22.9 years), 43 patients with TOF (mean age, 34.6 years), and 32 healthy controls (mean age, 42.3 years) were retrospectively analyzed. Pulsatile liver deformation in the craniocaudal direction was calculated using the feature tracking method of cardiac cine imaging derived from cine-balanced turbo field-echo sequences performed on a 1.5 Tesla MR scanner, and was defined as liver strain. The liver strain was compared across the three patient groups using one-way analysis of variance. Liver dysfunction by a liver strain were compared using the Mann-Whitney U test. Liver strain for patients who underwent Fontan operation and TOF patients was significantly lower than controls (Fontan, 13.3 ± 6.5%; TOF, 15.0 ± 11.2%; controls, 23.1 ± 10.2%, p < 0.0001). In Fontan and TOF patients, MELD score was significantly greater for patients with a liver strain < 15% than those with values > 15% (5.9 ± 5.8 vs. 2.9 ± 2.9, p < 0.001). Lower liver strain values were found in adolescent and adult patients after Fontan operation and TOF, and correlates with the severity of liver injury, expressed as MELD score. Our method can evaluate hepatic function in adult congenital heart disease, together with the assessment of cardiac function.

Clinical Significance of Central Venous Pressure During Exercise After Fontan Procedure.

Various late complications are associated with the Fontan procedure. In patients who undergo the Fontan procedure, the central venous pressure (CVP) tends to be higher than normal. However, the relationship between CVP (at rest and during exercise) and late complications associated with the Fontan procedure is unknown. Thirty-four patients who underwent the Fontan procedure were enrolled in this study. The median age was 19.3 years, and the median time after the Fontan procedure was 12.7 years. With exercise, the CVP increased from a median of 11 to 19 mmHg, and the cardiac index increased from a median of 2.1 to 4.4 l/min/m2. In 38% of the patients, CVP measured at the resting condition and during exercise differed. Laboratory results indicated no significant difference between the patients in the high-CVP group and low-CVP group at rest. In contrast, during exercise, brain natriuretic peptide (67 ± 38 vs. 147 ± 122 pg/ml, p < 0.05), gamma-glutamyl transpeptidase (63 ± 33 vs. 114 ± 30 IU/l, p < 0.05), type IV collagen 7S (6.7 ± 1.3 vs. 8.1 ± 1.3 ng/ml, p < 0.05), and creatinine (0.72 ± 3.14 vs. 0.83 ± 3.16 mg/dl, p < 0.05) levels were significantly higher in the high-CVP group than in the low-CVP group. Elevated CVP during exercise may be associated with long-term complications after the Fontan procedure; hence, CVP should be measured during exercise in patients who underwent the Fontan procedure to accurately predict the risk of developing such complications.

Potential Value of Native T1 Mapping in Symptomatic Adults with Congenital Heart Disease: A Preliminary Study of 3.0 Tesla Cardiac Magnetic Resonance Imaging.

The native T1 value at 3.0 Tesla is a sensitive marker of diffuse myocardial damage. We evaluated the clinical usefulness of native T1 mapping in symptomatic adults with congenital heart disease (CHD), particularly in the systemic right ventricle (RV). Prospectively, 45 consecutive symptomatic adults with CHD were enrolled: 20 with systemic RV and 25 with tetralogy of Fallot underwent cardiac magnetic resonance (CMR) imaging at 3.0 Tesla. The Modified Look-Locker Inversion recovery sequence was used for T1 mapping. Cardiovascular events in the systemic RV were defined as heart failure and tachyarrhythmia. Brain natriuretic peptide (BNP) and indexed systemic ventricular end-diastolic volume were significantly higher in the systemic RV group. The native T1 value and extracellular volume (ECV) of the septal and lateral walls were higher in the systemic RV group, suggesting high impairment of the myocardium in the systemic RV group. There was a strong correlation between the native T1 value and ECV of the septum (r = 0.58, P = 0.03) and lateral wall (r = 0.56, P = 0.046) in the systemic RV group. Seven patients with systemic RV had cardiovascular events. In univariate logistic regression analysis, BNP and native T1 values of the insertion point were important for predicting cardiovascular events. The native T1 value at 3.0 Tesla may be a sensitive, contrast-free, and non-invasive adjunct marker of myocardial damage in CHD and predictive of cardiovascular events in the systemic RV.

Stroke volume ratio derived from magnetic resonance imaging as an indicator of interventricular dyssynchrony predicts future cardiac event in patients with biventricular Fontan circulation.

The prognostic factors in patients with biventricular heart who underwent Fontan surgery remain unclear. This study wanted to assess the hypothesis that interventricular dyssynchrony evaluated by cardiac magnetic resonance imaging (MRI) can predict future cardiac events in patients with biventricular heart who have undergone Fontan surgery. We prospectively enrolled consecutive patients with biventricular Fontan circulation from 2003 to 2016, and performed protocolized cardiac MRI. We determined the stroke volume ratio (SVr) using the following formula to assess interventricular dyssynchrony: (stroke volume (SV) of the two whole ventricles)/(SV of the right ventricle + SV of the left ventricle), by tracing cine MRI data. If interventricular dyssynchrony existed, blood flowed and returned to each ventricle through the ventricular septal defect; therefore, the SVr in this instance should be less than 1.0. We enrolled 40 patients. SVr ranged from 0.81 to 1.0 (median 0.95). Low SVr (< 0.95) was associated with worse New York Heart Association functional class, longer QRS duration, right bundle branch block, low biventricular indexed stroke volume, and low biventricular ejection fraction. During the follow-up period (median 53.5 months), 10 cardiac events occurred (six cases of acute exacerbation of heart failure, three cases of supraventricular tachycardia, and one case of exacerbation of protein-losing enteropathy). Univariate analysis showed four clinical predictors: SVr < 0.95 [hazard ratio (HR) 9.3, 95% confidential interval (CI) 1.7-171.5]; biventricular ejection fraction < 0.45 (HR 9.4, 95% CI 2.2-65.3); left ventricular indexed end-diastolic volume > 73 mL/m2 (HR 4.5, 95% CI 1.1-15.7); and the presence of the aorta directly arising from the right ventricular conus (HR 5.8, 95% CI 1.1-106). SVr derived from MRI can predict future cardiac events in Fontan patients with biventricular hearts.

Prevalence and risk factors of sleep apnea in adult patients with congenital heart disease.

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 <15), moderate (15≤ respiratory disturbance index <30), and severe (respiratory disturbance index ≥30) sleep apnea, respectively. A large majority of the sleep apnea cases were categorised as obstructive sleep apnea (92%, n = 58). The respiratory disturbance index ≥15 group had a significantly higher proportion of male patients and higher body mass index, noradrenaline level, and aortic blood pressure than the group without sleep apnea (respiratory disturbance index <5). Multivariable analysis showed that New York Heart Association class ≥II (OR, 4.36; 95% CI, 1.09-20.87) and body mass index ≥25 (OR, 4.29; 95% CI, 1.32-15.23) were independent risk factors for a respiratory disturbance index ≥15. 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.