Intrahepatic Transcriptomics Differentiate Advanced Fibrosis and Clinical Outcomes in Adults With Fontan Circulation.

BACKGROUND: The molecular mechanisms underlying Fontan-associated liver disease (FALD) remain largely unknown. OBJECTIVES: This study aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. METHODS: This retrospective cohort study included adults with the Fontan circulation. Baseline clinical, laboratory, imaging, and hemodynamic data as well as a composite clinical outcome (CCO) were extracted from medical records. Patients were classified into early or advanced fibrosis. RNA was isolated from formalin-fixed paraffin-embedded liver biopsy samples; RNA libraries were constructed with the use of an rRNA depletion method and sequenced on an Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were performed with the use of DESeq2 and Metascape. RESULTS: A total of 106 patients (48% male, median age 31 years [IQR: 11.3 years]) were included. Those with advanced fibrosis had higher B-type natriuretic peptide levels and Fontan, mean pulmonary artery, and capillary wedge pressures. The CCO was present in 23 patients (22%) and was not predicted by advanced liver fibrosis, right ventricular morphology, presence of aortopulmonary collaterals, or Fontan pressures on multivariable analysis. Samples with advanced fibrosis had 228 upregulated genes compared with early fibrosis. Samples with the CCO had 894 upregulated genes compared with those without the CCO. A total of 136 upregulated genes were identified in both comparisons and were enriched in cellular response to cytokine stimulus or oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-ß signaling pathway, and vasculature development. CONCLUSIONS: Patients with FALD and advanced fibrosis or the CCO exhibited upregulated genes related to inflammation, congestion, and angiogenesis.

A new algorithm DEtectS critical Congenital Heart Disease at different altitudes: ANDES-CHD study.

BACKGROUND: Neonatal pulse oximetry screening (POS) algorithms for critical congenital heart disease (CCHD) have contributed towards decreasing neonatal mortality but cannot be applied at high altitudes. New POS algorithms at high altitudes are needed. METHODS: This observational, prospective study included newborns born at different altitudes from 0 to 4380 meters above the sea level in Peru. Healthy newborns underwent neonatal preductal and postductal oximetry, echocardiography and telephonic follow-up up to 12 months of age. Newborns with CCHD underwent preductal and postductal oximetry at the time of telemedicine evaluation while located at the high-altitude hospital where they were born, and their diagnoses were confirmed with echocardiography locally or after arriving to the referral center. Two new algorithms were designed using clinically accepted neonatal oximetry cutoffs or the 5th and 10th percentiles for preductal and postductal oximetry values. RESULTS: A total of 502 healthy newborns and 15 newborns with CCHD were enrolled. Echocardiography and telephonic follow-up were completed in 227 (45%) and 330 healthy newborns (65%), respectively. The algorithm based on clinically accepted cutoffs had a sensitivity of 92%, specificity of 73% and false positive rate of 27% The algorithm based on the 5th and 10th percentiles had a sensitivity of 80%, specificity of 88% and false positive rate of 12%. CONCLUSIONS: Two algorithms that detect CCHD at different altitudes had adequate performance but high false positive rates.

Cardiovascular Fellowship Training in Cardio-Obstetrics: JACC Review Topic of the Week.

The United States has the highest maternal mortality in the developed world with cardiovascular disease as the leading cause of pregnancy-related deaths. In response to this, the emerging subspecialty of cardio-obstetrics has been growing over the past decade. Cardiologists with training and expertise in caring for patients with cardiovascular disease in pregnancy are essential to provide effective, comprehensive, multidisciplinary, and high-quality care for this vulnerable population. This document provides a blueprint on incorporation of cardio-obstetrics training into cardiovascular disease fellowship programs to improve knowledge, skill, and expertise among cardiologists caring for these patients, with the goal of improving maternal and fetal outcomes.

The 2022 FASEB Virtual Catalyst Conference on the Cardiac Interatrial Septum and Stroke Risk, December 7, 2022.

There is emerging evidence that the cardiac interatrial septum has an important role as a thromboembolic source for ischemic strokes. There is little consensus on treatment of patients with different cardiac interatrial morphologies or pathologies who have had stroke. In this paper, we summarize the important background, diagnostic, and treatment considerations for this patient population as presented during the Federation of American Societies for Experimental Biology (FASEB) Virtual Catalytic Conference on the Cardiac Interatrial Septum and Stroke Risk, held on December 7, 2022. During this conference, many aspects of the cardiac interatrial septum were discussed. Among these were the embryogenesis of the interatrial septum and development of anatomic variants such as patent foramen ovale and left atrial septal pouch. Also addressed were various mechanisms of injury such as shunting physiologies and the consequences that can result from anatomic variants, as well as imaging considerations in echocardiography, computed tomography, and magnetic resonance imaging. Treatment options including anticoagulation and closure were addressed, as well as an in-depth discussion on whether the left atrial septal pouch is a stroke risk factor. These issues were discussed and debated by multiple experts from neurology, cardiology, and radiology.

Clinical and invasively-measured predictors of high exercise capacity in Fontan patients.

INTRODUCTION: Fontan patients have variable exercise capacity. Contemporary understanding as to which factors predict high tolerance is limited. METHODS: Records from the Ahmanson/University of California, Los Angeles Adult Congenital Heart Disease Center were reviewed for adult Fontan patients who underwent CPET. Patients were considered "high performers" if their maximum oxygen uptake (VO2 max/kg)-predicted was greater than 80%. Cross-sectional clinical, hemodynamic, and liver biopsy data was gathered. High-performers were compared to control patients across these parameters via associations and regression. RESULTS: A total of 195 adult patients were included; 27 patients were considered "high performers". They had lower body mass indices (BMI, p < 0.001), mean Fontan pressures (p = 0.026), and cardiac outputs (p = 0.013). High performers also had higher activity levels (p < 0.001), serum albumin levels (p = 0.003), non-invasive and invasive systemic arterial oxygen saturations (p < 0.001 and p = 0.004), lower New York Heart Association (NYHA) heart failure class (p = 0.002), and were younger at Fontan completion (p = 0.011). High performers had less severe liver fibrosis (p = 0.015). Simple regression found Fontan pressure, non-invasive O2 saturation, albumin level, activity level, age at Fontan surgery, NYHA class, and BMI to predict significant changes in VO2 max/kg %-predicted. These associations persisted in multiple regression for non-invasive O2 saturation, NYHA class II, activity level, and BMI. CONCLUSIONS: Thin Fontan patients who exercise more had better exercise capacity, Fontan hemodynamic profiles, and less liver fibrosis.

Intrahepatic transcriptomics differentiate advanced fibrosis and clinical outcomes in adults with the Fontan circulation.

Background: The molecular mechanisms underlying Fontan associated liver disease (FALD) remain largely unknown. We aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. Methods: This retrospective cohort study included adults with the Fontan circulation at the Ahmanson/UCLA Adult Congenital Heart Disease Center. Clinical, laboratory, imaging and hemodynamic data prior to the liver biopsy were extracted from medical records. Patients were classified into early (F1-F2) or advanced fibrosis (F3-F4). RNA was isolated from formalin-fixed paraffin embedded liver biopsy samples; RNA libraries were constructed using rRNA depletion method and sequencing was performed on Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were carried out using DESeq2 and Metascape. Medical records were comprehensively reviewed for a composite clinical outcome which included decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, protein-losing enteropathy, chronic kidney disease stage 4 or higher, or death. Results: Patients with advanced fibrosis had higher serum BNP levels and Fontan, mean pulmonary artery and capillary wedge pressures. The composite clinical outcome was present in 23 patients (22%) and was predicted by age at Fontan, right ventricular morphology and presence of aortopulmonary collaterals on multivariable analysis. Samples with advanced fibrosis had 228 up-regulated genes compared to early fibrosis. Samples with the composite clinical outcome had 894 up-regulated genes compared to those without it. A total of 136 up-regulated genes were identified in both comparisons and these genes were enriched in cellular response to cytokine stimulus, response to oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-beta signaling pathway, and vasculature development. Conclusions: Patients with FALD and advanced liver fibrosis or the composite clinical outcome exhibit up-regulated genes including pathways related to inflammation, congestion, and angiogenesis. This adds further insight into FALD pathophysiology.

Predictors of arrhythmia during pregnancy in adults with congenital heart disease.

BACKGROUND: Risk prediction of arrhythmia during pregnancy in adult congenital heart disease (ACHD) patients is currently lacking, and the impact of preconception catheter ablation on future antepartum arrhythmia has not been studied. METHODS: We conducted a single-center, retrospective cohort study of pregnancies in ACHD patients. Clinically significant arrhythmia events during pregnancy were described, predictors of arrhythmia were analyzed, and a risk score devised. The impact of preconception catheter ablation on antepartum arrhythmia was assessed. RESULTS: The study included 172 pregnancies in 137 patients. Arrhythmia events occurred in 25 (15%) of pregnancies, with 64% of events occurring in the second trimester and sustained supraventricular tachycardia being the most common rhythm. Univariate predictors of arrhythmia were history of tachyarrhythmia (OR 20.33, 95% CI 6.95-59.47, p < 0.001, Fontan circulation (OR 11.90, 95% CI 2.60-53.70, p < 0.001), baseline physiologic class C/D (OR 3.72, 95% CI 1.54-9.01, p = 0.002) and history of multiple valve interventions (OR 3.10, 95% CI 1.20-8.20, p = 0.017). Three risk factors (excluding multiple valve interventions) were used to formulate a risk score, with a cutoff of ≥2 points predicting antepartum arrhythmia with sensitivity and specificity of 84%. While recurrence of the index arrhythmia was not observed following successful catheter ablation, preconception ablation did not impact odds of antepartum arrhythmia. CONCLUSIONS: We provide a novel risk stratification scheme for predicting antepartum arrhythmia in ACHD patients. The role of contemporary preconception catheter ablation in risk reduction needs further refinement with multicenter investigation.

Vascular malperfusion and abruption are prevalent in placentas from pregnancies with congenital heart disease and not associated with cardiovascular risk.

Congenital heart disease (CHD) in pregnancy is associated with an increased risk of adverse maternal, obstetric, and neonatal outcomes, plausibly through mechanisms involving abnormal placental development and function. This retrospective study aims to elucidate how maternal CHD influences placental health. Demographic and clinical information were collected via electronic medical record review, and placentas underwent histopathological evaluation. Fifty-three singleton pregnancies were included: 35 participants (66%) were classified as lower cardiovascular risk (modified World Health Organization Classification (mWHO) I, II, II-III), and 18 (34%) were classified as higher cardiovascular risk (mWHO III, IV). 12 participants (23%) had a fetus with small for gestational age (SGA). Maternal vascular malperfusion (53%) and placental abruption (11.6%) were common in this cohort, with prevalence above baseline risk. Participants at higher cardiovascular risk had higher rates of SGA (p = 0.04), subchorionic hematomas (p = 0.01) and birth weight:placental weight < 10th percentile (p = 0.04), but did not differ in rates of maternal vascular malperfusion (p = 0.15) compared to those at lower cardiovascular risk. In pregnancies with maternal CHD, SGA and histologic evidence of maternal vascular malperfusion and placental abruption were common, though patients at higher cardiovascular risk did not show evidence of worsened placental health compared to those at lower risk.

Postural orthostatic tachycardia syndrome and orthostatic hypotension in post-acute sequelae of COVID-19 during pregnancy: a case report.

Background: Patients with post-acute sequelae of COVID-19 (PASC) often experience the addition of new symptoms after recovery from COVID-19 illness. These may include orthostatic intolerance and autonomic dysfunction, and postural orthostatic tachycardia syndrome has been described to occur in a proportion of patients with PASC. Case summary: In this report, we present a 32-year-old pregnant woman (G3P2) who experiences severe orthostatic symptoms as part of her PASC syndrome, which is decoupled from normal physiologic changes of pregnancy. At 25 weeks of gestation, she was evaluated for increasing episodes of dyspnoea, marked tachycardia with minimal exertion, intermittent non-exertional chest pain, and presyncope. This patient had a moderate course of COVID-19 at 12 weeks of gestation, for which she received monoclonal antibody therapy (casirivimab/imdevimab). The patient then had complete resolution of COVID-19 symptoms and felt well for 1 month prior to developing orthostatic symptoms at 25 weeks of gestation. Evaluation with a NASA Lean Test revealed marked orthostatic tachycardia, as well as delayed orthostatic hypotension. Given her COVID-19 illness 4 months prior, PASC involving autonomic dysfunction was diagnosed. Discussion: Patients with orthostatic symptoms in PASC should be carefully evaluated with dedicated active stand tests, such as the NASA Lean Test, to characterize the autonomic response to standing. In pregnant patients, an understanding of normal pregnancy physiology is crucial to correctly identify abnormal findings in such tests.

Delivery Timing and Associated Outcomes in Pregnancies With Maternal Congenital Heart Disease at Term.

Background Current recommendations for delivery timing of pregnant persons with congenital heart disease (CHD) are based on expert opinion. Justification for early-term birth is based on the theoretical concern of increased cardiovascular stress. The objective was to evaluate whether early-term birth with maternal CHD is associated with lower adverse maternal or neonatal outcomes. Methods and Results This is a retrospective cohort study of pregnant persons with CHD who delivered a singleton after 37 0/7 weeks gestation at a quaternary care center with a multidisciplinary cardio-obstetrics care team between 2013 and 2021. Patients were categorized as early-term (37 0/7 to 38 6/7 weeks) or full-term (≥39 0/7) births and compared. Multivariable logistic regression was conducted to calculate the adjusted odds ratio for the primary outcomes. The primary outcomes were composite adverse cardiovascular, maternal obstetric, and adverse neonatal outcome. Of 110 pregnancies delivering at term, 55 delivered early-term and 55 delivered full-term. Development of adverse cardiovascular and maternal obstetric outcome was not significantly different by delivery timing. The rate of composite adverse neonatal outcomes was significantly higher in early-term births (36% versus 5%, P<0.01). After adjusting for confounding variables, early-term birth remained associated with a significantly increased risk of adverse neonatal outcomes (adjusted odds ratio 11.55 [95% CI, 2.59-51.58]). Conclusions Early-term birth for pregnancies with maternal CHD was associated with an increased risk of adverse neonatal outcomes, without an accompanying decreased rate in adverse cardiovascular or obstetric outcomes. In the absence of maternal or fetal indications for early birth, induction of labor before 39 weeks for pregnancies with maternal CHD should be reserved for routine obstetrical indications.

Mechanical thrombectomy of COVID-19 DVT with congenital heart disease leading to phlegmasia cerulea dolens: a case report.

BACKGROUND: COVID-19 and Fontan physiology have each been associated with an elevated risk of venous thromboembolism (VTE), however little is known about the risks and potential consequences of having both. CASE PRESENTATION: A 51 year old male with tricuspid atresia status post Fontan and extracardiac Glenn shunt, atrial flutter, and sinus sick syndrome presented with phlegmasia cerulea dolens (PCD) of the left lower extremity in spite of supratherapeutic INR in the context of symptomatic COVID-10 pneumonia. He was treated with single session, catheter directed mechanical thrombectomy that was well-tolerated. CONCLUSIONS: This report of acute PCD despite therapeutic anticoagulation with a Vitamin K antagonist, managed with emergent mechanical thrombectomy, calls to attention the importance of altered flow dynamics in COVID positive patients with Fontan circulation that may compound these independent risk factors for developing deep venous thrombosis with the potential for even higher morbidity.

Orthotopic Heart and Combined Heart Liver Transplantation: the Ultimate Treatment Option for Failing Fontan Physiology.

Purpose of the Review: This is a comprehensive update on failing Fontan physiology and the role of heart and combined heart and liver transplantation in the current era. Recent Findings: Single ventricle physiology encompasses a series of rare congenital cardiac abnormalities that are characterized by absence of or hypoplasia of one ventricle. This effectively results in a single ventricular pumping chamber. These abnormalities are rarely compatible with long-term survival if left without surgical palliation in the first few years of life. Surgical treatment of single ventricle physiology has evolved over the past 60 years and is characterized by numerous creative innovations. These include the development of arteriopulmonary shunts, the evolution of partial cavopulmonary connections, and the eventual development of the "Fontan" operation. Regardless of the type of Fontan modification, the long-term consequences of the Fontan operation are predominantly related to chronic central venous hypertension and the multi-organ consequences thereof. Atrial arrhythmias can further compromise this circulation.Patients with single ventricle physiology represent a special sub-segment of congenital cardiac transplants and are arguably the most challenging patients considered for transplantation. Summary: This review describes in detail the challenges and opportunities of heart and liver transplantation in Fontan patients, as viewed and managed by the experienced team at the Ahmanson/UCLA Adult Congenital Heart Center.

ACC/AHA/ASE/HRS/ISACHD/SCAI/SCCT/SCMR/SOPE 2020 Appropriate Use Criteria for Multimodality Imaging During the Follow-Up Care of Patients With Congenital Heart Disease: A Report of the American College of Cardiology Solution Set Oversight Committee and Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Pediatric Echocardiography.

The American College of Cardiology (ACC) collaborated with the American Heart Association, American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and the Society of Pediatric Echocardiography to develop Appropriate Use Criteria (AUC) for multimodality imaging during the follow-up care of patients with congenital heart disease (CHD). This is the first AUC to address cardiac imaging in adult and pediatric patients with established CHD. A number of common patient scenarios (also termed "indications") and associated assumptions and definitions were developed using guidelines, clinical trial data, and expert opinion in the field of CHD.1 The indications relate primarily to evaluation before and after cardiac surgery or catheter-based intervention, and they address routine surveillance as well as evaluation of new-onset signs or symptoms. The writing group developed 324 clinical indications, which they separated into 19 tables according to the type of cardiac lesion. Noninvasive cardiac imaging modalities that could potentially be used for these indications were incorporated into the tables, resulting in a total of 1,035 unique scenarios. These scenarios were presented to a separate, independent panel for rating, with each being scored on a scale of 1 to 9, with 1 to 3 categorized as "Rarely Appropriate," 4 to 6 as "May Be Appropriate," and 7 to 9 as "Appropriate." Forty-four percent of the scenarios were rated as Appropriate, 39% as May Be Appropriate, and 17% as Rarely Appropriate. This AUC document will provide guidance to clinicians in the care of patients with established CHD by identifying the reasonable imaging modality options available for evaluation and surveillance of such patients. It will also serve as an educational and quality improvement tool to identify patterns of care and reduce the number of Rarely Appropriate tests in clinical practice.

Utility of the long DrySeal sheath in facilitating transcatheter pulmonary valve implantation with the Edwards Sapien 3 valve.

OBJECTIVE: To assess the utility of the 65-cm-long Gore DrySeal sheath when compared to the standard 36-cm-long Edwards expandable sheath (e-sheath) for transcatheter pulmonary valve implantation (TPVI) with the Edwards Sapien 3 valve. METHODS: All patients who underwent TPVI with the Sapien 3 valve, excluding those performed via hybrid approach, at our center between September 2015 and November 2019 were retrospectively reviewed and compared between two groups. RESULTS: A total of 94 patients were enrolled; 29 patients underwent TPVI with the Sapien valve using the DrySeal sheath and 65 underwent TPVI using the e-sheath. The height and body weight of patients implanted using the DrySeal sheath ranged from 137 to 193 cm and from 33 to 129 kg, respectively. Valve delivery time was significantly shorter in the DrySeal group (median time 4 min 33 s vs. 9 min 6 s, p = .002). There were no complications in the DrySeal group (0/27). Nine procedural complications occurred in the e-sheath group (9/65), five of which were potentially directly related to sheath choice, including tricuspid valve injury in four and embolization of the tip of the e-sheath during retrieval of a ruptured balloon in one patient. CONCLUSIONS: TPVI with the Sapien 3 valve using the 65-cm-long DrySeal sheath facilitates faster and safer valve implantation when compared to the e-sheath.

Early Experience With Sacubitril/Valsartan in Adult Patients With Congenital Heart Disease.

BACKGROUND: Heart failure (HF) is the leading cause of hospitalizations and death in patients with adult congenital heart disease (ACHD). Sacubitril/valsartan is a new agent in the treatment of HF, but its effects have not been assessed in ACHD. METHODS: We retrospectively studied all 15 patients with ACHD at our center who were prescribed sacubitril/valsartan between June 2017 and June 2018. We assessed baseline characteristics and clinical and laboratory changes after initiation of sacubitril/valsartan. Adverse events, including renal function, medication intolerance, and worsening HF were documented. RESULTS: The median age was 53.2 (27.6-83.6) years, with a median follow-up duration of 69 (8-419) days. At baseline, all patients had refractory HF despite guideline-directed medical therapy, with ten (67%) patients as New York Heart Association (NYHA) class II, and five (33%) patients NYHA class III. The medication was discontinued in one (7%) patient secondary to worsening kidney function. No patients reported clinical deterioration; four NYHA class III patients with complex CHD, pulmonary hypertension, and cyanosis reported significant improvement to NYHA class II. Baseline creatinine was 1.1 (0.9-1.7) and two weeks after starting sacubitril/valsartan it was 1.3 (0.8-2.5, P = .22). CONCLUSIONS: Sacubitril/valsartan seems to be well tolerated in patients with ACHD who present with refractory HF symptoms. Patients with complex CHD associated with cyanosis and pulmonary hypertension could benefit the most, but larger studies are needed to assess the safety as well as the effectiveness of sacubitril/valsartan in this patient population.

Maternal Fontan procedure is a predictor of a small-for-gestational-age neonate: a 10-year retrospective study.

BACKGROUND: Women with single ventricle cardiac physiologic condition who have undergone Fontan procedures are surviving well into reproductive age and historically have been discouraged from pregnancy, despite the paucity of data regarding maternal and neonatal outcomes. OBJECTIVE: Our primary objective was to investigate, in a large cohort, the maternal and neonatal outcomes of pregnant women who have undergone the Fontan procedure and to understand maternal and neonatal sequelae of their pregnancies. STUDY DESIGN: This single-center retrospective cohort study involves pregnant women with a Fontan palliation who delivered at UCLA Medical Center over a 10-year period (2007-2017). All pregnancies were evaluated for differences in maternal and neonatal characteristics. RESULTS: We identified 37 distinct pregnancies in 24 women with a Fontan procedure. The physiologic pregnancy-related increase in cardiac output is blunted substantially in Fontan circulation. Third-trimester cardiac index positively correlated to birthweight z-score (R2=0.48; P=.038) but not to small for gestational age (R2=0.13; P=.339). The most common cardiac complications in pregnancies of >24 weeks gestation were sustained arrhythmia (37.5%) and decompensated heart failure (21%). The 37 pregnancies comprised 25 live births (67.6%), 1 fetal death (2.7%), 9 spontaneous abortions (24%), and 2 pregnancy terminations (5.4%). Of the live births, 60% were preterm at an average gestational age of 34.9±3.7 weeks. Newborn infants were delivered via cesarean in 53%, operative vaginal delivery in 28%, and spontaneous vaginal delivery in 20%. Forty percent of neonates were born small (<10th percentile) for gestational age; 44.0% of all neonates were admitted to the neonatal intensive care unit. CONCLUSION: Women with a single ventricle and Fontan circulation can have a successful pregnancy, although they are at increased risk for arrhythmias and heart failure. The decreased cardiac reserve in these pregnancies blunts the normal increase in maternal cardiac output, which is associated with preterm delivery and small-for-gestational-age neonates. Further studies are needed to determine to what extent the impaired rise in maternal cardiac output reduces uteroplacental perfusion, placental exchange, fetal growth, and onset of parturition.

Survival in patients with univentricular hearts: the impact of right versus left ventricular morphology.

Objective: Patients with univentricular hearts (UVH) have high mortality despite modern treatment, and better methods to identify patients at highest risk are needed. We wanted to improve risk stratification in patients with UVH by focusing on the prognostic significance of single right versus single left ventricular morphology (SRV vs SLV). Methods: All 395 patients with UVH operated at our centre were prospectively included from 1972 to 2016 (195 SRV, 166 SLV, 34 mixed or indeterminate ventricular morphology). Diagnoses, UVH morphology, types of all operations and time and causes of death or heart transplantation (HTX) were recorded. The primary endpoint was death or HTX. Results: Among the 111 non-Fontan patients, 88 died (SRV 62 vs SLV 20; p<0.0001), 32 due to heart failure (SRV 23 vs SLV 5; p=0.0012). Twenty-five years of cumulative SRV versus SLV survival among the 284 Fontan patients (41 deaths/HTX) was 66.9% vs 87.9% (p=0.0027), partly explained by more deaths/HTX due to heart failure among patients with SRV (p=0.0006). Survival in patients with SRV with and without hypoplastic left heart syndrome (HLHS) was similar. SRV versus SLV was a strong predictor of death/HTX in multivariable proportional hazards analyses (RR 3.3, 95% CI 1.6 to 6.6). Conclusion: SRV versus SLV is a strong short-term and long-term predictor of survival among patients with UVH, mainly explained by higher rates of death/HTX due to heart failure in the SRV group. Our findings apply to patients with SRV both with and without HLHS.