Whole-exome sequencing uncovers the genetic complexity of bicuspid aortic valve in families with early-onset complications.

Bicuspid aortic valve (BAV) is the most common congenital heart lesion with an estimated population prevalence of 1%. We hypothesize that specific gene variants predispose to early-onset complications of BAV (EBAV). We analyzed whole-exome sequences (WESs) to identify rare coding variants that contribute to BAV disease in 215 EBAV-affected families. Predicted damaging variants in candidate genes with moderate or strong supportive evidence to cause developmental cardiac phenotypes were present in 107 EBAV-affected families (50% of total), including genes that cause BAV (9%) or heritable thoracic aortic disease (HTAD, 19%). After appropriate filtration, we also identified 129 variants in 54 candidate genes that are associated with autosomal-dominant congenital heart phenotypes, including recurrent deleterious variation of FBN2, MYH6, channelopathy genes, and type 1 and 5 collagen genes. These findings confirm our hypothesis that unique rare genetic variants drive early-onset presentations of BAV disease.

Mortality and morbidity after combined heart and liver transplantation in the failing Fontan: An updated dual center retrospective study.

INTRODUCTION: As the adult Fontan population with Fontan associated liver disease continues to increase, more patients are being referred for transplantation, including combined heart and liver transplantation. METHODS: We report updated mortality and morbidity outcomes after combined heart and liver transplant in a retrospective cohort series of 40 patients (age 14 to 49 years) with Fontan circulation across two centers from 2006-2022. RESULTS: The 30-day, 1-year, 5-year and 10-year survival rate was 90%, 80%, 73% and 73% respectively. Sixty percent of patients met a composite comorbidity of needing either post-transplant mechanical circulatory support, renal replacement therapy or tracheostomy. Cardiopulmonary bypass time > 283 min (4.7 h) and meeting the composite comorbidity were associated with mortality by Kaplan Meier analysis. CONCLUSION: Further study to mitigate early mortality and the above comorbidities as well as the high risk of bleeding and vasoplegia in this patient population is warranted.

Experiences and Attitudes Toward Telemedicine in an Adult Congenital Heart Disease Clinic: Lessons Learned from the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has driven a broader adoption of telemedicine (TM). We aim to describe adult congenital heart disease (ACHD) patient experiences with TM and explore factors associated with positive attitude toward future TM visits. This is a cross-sectional, single-center study in an outpatient ACHD clinic from February to June, 2022. Between-group comparisons were made using Wilcoxon-Rank Sum, Chi-Square, or Fisher-Exact tests. Univariate logistic regression was performed for variables that could correlate with a "positive" attitude toward future TM visits. Significance was determined using an alpha level of 0.05. Of 262 patients (median age 33 years, 55% female, 81% White), 115 (44%) had a prior TM visit and 110 (96%) reported a positive experience. There were 64 (24%) with a positive attitude toward future TM visits. Concerns include lack of cardiac testing and limited quality of visit. Patients with visits every 3-6 months (Odds Ratio [OR] 2.44; p < 0.01) and prior TM visit (OR 1.89; p = 0.03) had higher odds of a positive attitude toward future TM, whereas males had lower odds (OR 0.53; p = 0.04). Age, annual income, disease complexity, distance from clinic, and employment status were not associated. There is high rate of satisfaction with TM among ACHD patients but only one-quarter indicated interest in using TM in the future. Factors associated with interest in TM visits are identified, and together with patient feedback, can be used to understand potential role of TM for the ACHD population in the post-pandemic era.

Prolonged labor and adverse cardiac outcomes in pregnant patients with congenital heart disease.

BACKGROUND: Patients with congenital heart disease are at high risk for peripartum cardiac morbidity, yet data on the impact of duration of labor on cardiac outcomes are limited. Prolonged labor is a known risk factor for maternal morbidity, but the impact of prolonged labor on cardiac outcomes in patients with congenital heart disease has not been evaluated. OBJECTIVE: This study aimed to evaluate the association between prolonged labor (≥24 hours) and adverse peripartum maternal cardiac outcomes in pregnant patients with congenital heart disease. STUDY DESIGN: This was a retrospective cohort study of pregnant patients ≥18 years with congenital heart disease who received prenatal care and delivered at an academic institution between 1998 and 2020 with a singleton gestation. Pregnancies that ended <20 weeks' gestation and patients who underwent an outright cesarean delivery without exposure to labor were excluded. The primary outcome was a composite adverse maternal cardiac outcome that occurred intrapartum or up to 6 weeks postpartum, defined as the occurrence of 1 or more of the following events: heart failure or clinical volume overload requiring diuresis, pulmonary edema, arrhythmia requiring treatment, thromboembolic complications including deep vein thrombosis or pulmonary embolism, transient ischemic attack, stroke, endocarditis, myocardial infarction, aortic dissection, cardiac arrest, or cardiac death. Outcomes were compared between patients with prolonged labor (≥24 hours) and those without prolonged labor (<24 hours). An interaction between prolonged labor and cesarean delivery was evaluated. RESULTS: A total of 229 patients were included. The median duration of labor was 14 hours, and 18% of patients labored for ≥24 hours. Overall, 11.8% experienced the composite cardiac outcome with a significantly higher rate in the prolonged labor group (22% vs 9.6%; P=.03). After adjusting for confounders, including nulliparity, labor induction, gestational age, and World Health Organization class, there was a 2.7-fold increase in the odds of the composite cardiac outcome for patients who experienced prolonged labor (adjusted odds ratio, 2.7; 95% confidence interval, 1.1-7.1). There was no significant difference in cardiac outcome between those who had a vaginal delivery and those who had a cesarean delivery during labor (10.0% vs 16.1%; P=.18). There was, however, a significant interaction between prolonged labor and cesarean delivery; after adjustment for confounders, patients who underwent a cesarean delivery after prolonged labor had a 6.8-fold increase in the odds of experiencing the composite cardiac outcome when compared with those who underwent a cesarean delivery without prolonged labor (30.8% vs 7.1%; adjusted odds ratio, 6.8; 95% confidence interval, 1.4-32.5), most commonly, heart failure or volume overload requiring diuresis. CONCLUSION: In a cohort of pregnant patients with congenital heart disease, prolonged duration of labor ≥24 hours was significantly associated with an increased risk for an adverse peripartum cardiac outcome, especially among those who underwent a cesarean delivery after that time. These findings suggest that close attention should be paid to the duration of labor, and those who require a cesarean delivery after a prolonged labor should be monitored closely for signs of volume overload and other adverse cardiac events.

Novel Approaches to the Failing Congenital Heart.

PURPOSE OF REVIEW: Heart failure is the leading cause of morbidity and mortality in adults with congenital heart disease and is characterized by a variety of underlying mechanisms. Here, we aim to elaborate on the medical and technological advancements in the management of heart failure in adult patients with congenital heart disease and highlight the use of imaging modalities to guide therapy. RECENT FINDINGS: There have been several advances over the past decade with angiotensin receptor neprilysin and sodium-glucose cotransporter-2 inhibitors, atrioventricular valve clips, transcatheter pulmonary valves, catheter ablation, and cardiac resynchronization therapy, as well as the introduction of lymphatic interventions. Expanded use of echocardiography, cardiac magnetic resonance imaging, and cardiac computed tomography has guided many of these therapies. Significant innovations in the management of heart failure in adults with congenital heart disease have evolved with advancements in imaging modalities playing a critical role in guiding treatment therapies.

Laparoscopic Surgery Requiring Abdominal Insufflation in Patients With Congenital Heart Disease.

OBJECTIVE: To determine if patients with congenital heart disease are undergoing laparoscopic surgery requiring abdominal insufflation and to compare the outcomes of these procedures with those who underwent an open surgical approach. DESIGN, SETTING, PARTICIPANTS: This was a retrospective study using the National Inpatient Sample from 2006 to 2014. Individuals with congenital heart disease who underwent at least one of six selected surgical procedures (laparoscopic or open) were included in the study. Subgroup analysis was performed on patients with Fontan palliation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was to determine the frequency with which congenital heart disease patients undergo laparoscopic surgery requiring abdominal insufflation compared with open surgery. Secondary outcomes included all-cause in-hospital mortality and in-hospital length of stay. Of the 5,527 patients included, nearly half underwent laparoscopic surgery (46.3%), and 128 (2.3%) had single-ventricle circulation. All-cause mortality was significantly higher for those who underwent open surgery compared with the laparoscopic approach (3.6% v 0.9%; odds ratio [OR], 4.0 [2.6-6.3]; p < 0.0001). Subgroup analysis of patients with Fontal palliation older than five years showed 30 (42%) underwent laparoscopic surgery and there was no mortality difference between the laparoscopic and open approaches (OR, 1.4 [0.2-21.3], p = 0.8). Length of stay was significantly shorter for patients undergoing laparoscopic compared with open surgery (median three days [interquartile range, two-five] v six days [three-13], p < 0.0001). CONCLUSIONS: Individuals with congenital heart disease are being offered laparoscopic surgery that requires abdominal insufflation. All-cause mortality and length of stay were higher for patients who underwent open surgical operations.

Adolescents and adults with Fontan circulation: insights from the PREpArE-Fontan registry.

The Patient Registry for Adolescents and Adults with Stable Fontan Circulation aims to describe a contemporary cohort of Fontan patients who could be eligible for a clinical trial investigating macitentan, an endothelin receptor antagonist. This international, non-interventional, multicentre, cross-sectional, observational registry enrolled patients with "stable" Fontan circulation ≥10 years following extra-cardiac conduit or lateral tunnel procedure. Main exclusion criteria were NYHA functional class IV, reoperation of Fontan circulation, or signs of disease worsening. Patient characteristics at enrolment are described; available data were collected during a single registration visit. Of the 266 screened patients, 254 were included in this analysis. At enrolment, median (interquartile range) age was 24 (20;30) years, 37%/63% of patients were from the USA/Europe, 54% were male, 54%/47% had undergone extra-cardiac conduit/lateral tunnel procedures, and 95% were in NYHA functional class I or II. History of arrhythmia was more common in older patients and patients with lateral tunnel; overall prevalence was 19%. Most laboratory values were within the normal range but mean creatinine clearance was abnormally low (87.7 ml/min). Angiotensin-converting enzyme inhibitors were used by 48% of patients and their use was associated with creatinine clearance <90 ml/min (p = 0.007), as was Fontan completion at an older age (p = 0.007). 53.4% of patients had clinical characteristics that could potentially meet an endothelin receptor antagonist trial's eligibility criteria. The PREpArE-Fontan registry describes a cohort of patients who could potentially participate in an endothelin receptor antagonist trial and identified early subtle signs of Fontan failure, even in "stable" patients.

Mechanisms for heart failure in systemic right ventricle.

There are two predominant scenarios where the right ventricle acts as the systemic ventricle, namely congenitally corrected transposition of the great arteries (CC-TGA) and patients with D-transposition of the great arteries (D-TGA) who have undergone an atrial switch operation. There is evidence that having a right ventricle in the systemic position predisposes to the development of heart failure. In this review, we aim to explore the proposed mechanisms and pathophysiology for heart failure in patients with a systemic right ventricle in these two subsets of patients.

Assessment and management of heart failure in the systemic right ventricle.

Transposition of the great arteries (TGA) is a common congenital cardiac malformation, in which many patients survive into adulthood. From the 1960s through much of the 1980s, the majority of those with D-TGA were repaired with an atrial switch procedure, in which the right ventricle (RV) remains the systemic ventricle. Congenitally corrected TGA patients often remain with a systemic RV. In these patients, heart failure risks result from residual sequelae of childhood repair, which often include tricuspid regurgitation, RV failure, and atrial and ventricular arrhythmias. Imaging techniques, including echocardiography, cardiac magnetic resonance imaging, multi-detector computed tomography, and radionuclide ventriculography focus on evaluation of anatomy and function as both diagnostic and prognostic tools. Biomarkers are used for risk stratification. Structural and surgical interventions are targeted for palliation and prevention of further decompensation in conjunction with pharmacologic, ablative, and device-based therapies for acute and chronic management of heart failure.

Successful in vitro fertilization in women with Fontan physiology.

PURPOSE: Patients with single ventricle anatomy palliated with Fontan operation are at risk for thromboembolism, arrhythmia, and heart failure rendering pregnancy high risk or even contraindicated. Infertility and high rates of first trimester miscarriage are not uncommon. In vitro fertilization (IVF) with or without gestational surrogacy can be an option, but poses risks during ovarian stimulation, oocyte retrieval, and the post-procedural period. We present six cases of women with complex congenital heart disease status post Fontan operation who underwent successful IVF. METHODS: Case series from a single-center tertiary care setting. RESULTS: Indications for referral were cardiac or fertility concerns for pregnancy of the congenital cardiologist. One woman had mild volume overload after oocyte retrieval requiring furosemide and one experienced post-operative colitis. There were no thrombotic complications. CONCLUSIONS: A multidisciplinary team-based approach can result in successful oocyte retrieval and IVF in women with complex congenital heart disease and Fontan physiology.

Pulmonary arterial hypertension in adults with systemic right ventricles referred for cardiac transplantation.

BACKGROUND: Systemic right ventricular (RV) failure may progress necessitating referral for orthotropic heart transplantation (OHT). Pulmonary hypertension (PH) frequently coexists in adult congenital heart disease and can complicate the assessment for OHT. METHODS: Single-center case series of six patients (median age 34.9 years [IQR, 31.9-42.4]) with systemic RV physiology with PH referred for OHT evaluation from 2008 to 2017. RESULTS: One-third (n = 6) of 18 patients with systemic RV physiology referred for OHT evaluation had pulmonary arterial hypertension (PAH) defined as mean pulmonary artery pressure (mPAP) > 25 mm Hg and pulmonary vascular resistance (PVR) > 3 Wood Units. Two of the six patients were considered OHT-ineligible due to PH and comorbidities. Of the remaining four, two had pre-capillary PH and underwent heart-lung transplant (HLTx). The other two demonstrated reversibility of PVR with vasodilator testing and underwent OHT alone, one of whom died post-transplant from PH crisis. CONCLUSIONS: Pulmonary arterial hypertension is common in systemic RV patients referred for OHT. Systemic RV dysfunction places these patients at risk for post-capillary PH but pre-capillary PH can exist. Despite management with selective pulmonary vasodilators and afterload reduction, criteria for listing patients for HLTx vs OHT are not known and need further elucidation.

Psychological distress in adults with congenital heart disease: focus beyond depression.

BACKGROUND: Adults with congenital heart disease face psychological challenges although an understanding of depression vs. anxiety symptoms is unclear. We analyzed the prevalence of elevated symptoms of anxiety and depression and explored associations with demographic and medical factors as well as quality of life. METHODS: Adults with congenital heart disease enrolled from an outpatient clinic completed the Hospital Anxiety and Depression Scale and two measures of quality of life: the Linear Analogue Scale and the Satisfaction with Life Scale. Medical data were obtained by chart review. RESULTS: Of 130 patients (median age = 32 years; 55% female), 55 (42%) had elevated anxiety symptoms and 16 (12%) had elevated depression symptoms on subscales of the Hospital Anxiety and Depression Scale. Most patients with elevated depression symptoms also had elevated anxiety symptoms (15/16; 94%). Of 56 patients with at least one elevated subscale, 37 (66%) were not receiving mental health treatment. Compared to patients with 0 or 1 elevated subscales, patients with elevations in both (n=15) were less likely to be studying or working (47% vs. 81%; p=0.016) and reported lower scores on the Linear Analogue Scale (60 vs. 81, p<0.001) and the Satisfaction with Life Scale (14 vs. 28, p<0.001). CONCLUSIONS: Among adults with congenital heart disease, elevated anxiety symptoms are common and typically accompany elevated depressive symptoms. The combination is associated with unemployment and lower quality of life. Improved strategies to provide psychosocial care and support appropriate engagement in employment are required.

Diagnosis and Management of Noncardiac Complications in Adults With Congenital Heart Disease: A Scientific Statement From the American Heart Association.

Life expectancy and quality of life for those born with congenital heart disease (CHD) have greatly improved over the past 3 decades. While representing a great advance for these patients, who have been able to move from childhood to successful adult lives in increasing numbers, this development has resulted in an epidemiological shift and a generation of patients who are at risk of developing chronic multisystem disease in adulthood. Noncardiac complications significantly contribute to the morbidity and mortality of adults with CHD. Reduced survival has been documented in patients with CHD with renal dysfunction, restrictive lung disease, anemia, and cirrhosis. Furthermore, as this population ages, atherosclerotic cardiovascular disease and its risk factors are becoming increasingly prevalent. Disorders of psychosocial and cognitive development are key factors affecting the quality of life of these individuals. It is incumbent on physicians who care for patients with CHD to be mindful of the effects that disease of organs other than the heart may have on the well-being of adults with CHD. Further research is needed to understand how these noncardiac complications may affect the long-term outcome in these patients and what modifiable factors can be targeted for preventive intervention.

Quality Indicator Completion Rates for Adults with Tetralogy of Fallot.

Quality indicators for adult congenital heart disease (ACHD) were recently published due to a lack of consensus regarding delivery of care to adults with congenital heart disease (CHD). The objective of this study was to examine adherence to quality indicators for the care of patients with tetralogy of Fallot. Adults with tetralogy of Fallot seen in outpatient cardiology clinics at a tertiary care facility between July 2014 and June 2015 were included, and electronic medical records for each visit were reviewed. Completion rates for eight proposed quality indicator metrics were recorded and results for ACHD and non-ACHD cardiologists were compared. A total of 96 eligible patients completed 179 cardiology visits (134 ACHD and 45 non-ACHD). The quality indicator completion rates were over 80% for 7 of the 8 indicators. Metric 5 (cardiac magnetic resonance imaging every five years) had the lowest completion rate at 38.7%. Compared to non-ACHD cardiologists, ACHD cardiologists had higher completion rates for QRS assessment (88.1% vs. 75.6%, p = 0.04), echocardiogram by CHD expert (97.8% vs. 80.0%, p < 0.001), and infective endocarditis counseling (95.9% vs. 77.4%, p = 0.001). In this single center study, there was a wide range of quality indicator completion rates for tetralogy of Fallot. Routine cardiac MRI by an expert in CHD was identified as an area for improvement. There were significant differences in quality indicator completion between ACHD and non-ACHD cardiologists.

Single-center outcomes of combined heart and liver transplantation in the failing Fontan.

Long-term outcomes of the Fontan operation include Fontan failure and liver disease. Combined heart-liver transplantation (CHLT) is an option for select patients although limited data exist on this strategy. A retrospective review of Fontan patients 18 years or older referred for cardiac transplant evaluation between 2000 and 2013 at the Hospital of the University of Pennsylvania was performed. All patients were considered for potential CHLT. Clinical variables such as demographics, perioperative factors, and short-term outcomes were reviewed. Of 17 referrals for cardiac transplantation, seven Fontan patients underwent CHLT. All patients who underwent CHLT had either advanced fibrosis or cirrhosis on liver biopsy. There were no perioperative deaths. The most common postoperative morbidity was acute kidney injury. Short-term complications include one episode of acute liver rejection but no cardiac rejection greater than 1R. CHLT is an acceptable therapeutic option for patients with failing Fontan physiology who exhibit concomitant advanced liver fibrosis. However, optimal patient selection is currently undefined, and long-term outcomes are not known.

Adult CHD: the ongoing need for physician counselling about heredity and contraceptive options.

Purpose Current guidelines recommend that patients with CHD receive age-appropriate counselling on reproduction, pregnancy, and risk of heredity. Our aim was to examine patient knowledge of reproductive health and explore the association between patient knowledge of CHD transmission risk and earlier physician counselling in adults with CHD. METHODS: We performed a cross-sectional survey of patients with CHD aged 18 years and older in a paediatric hospital. RESULTS: Of the 100 patients who completed the questionnaire, most did not report counselling on heredity (66%) or contraception (71%). Of the 54 women, 25 (46%) identified their contraceptive options correctly; 42 (78%) women were classified as being at significantly increased risk for an adverse outcome during pregnancy, and of these 20 (48%) identified this risk correctly. Of all patients surveyed, 72% did not know that having CHD placed them at increased risk for having a child with CHD. On multivariate analysis, factors associated with correct knowledge about risk of recurrence were correct identification of CHD diagnosis (p=0.04) and patient-reported counselling (p=0.001). CONCLUSIONS: Knowledge about heredity, pregnancy risk, and contraceptive options is inadequate among adults with CHD followed-up in a paediatric subspecialty clinic. The majority of patients did not report a history of counselling about reproductive health. There is a strong correlation between history of counselling by the patient's cardiologist and correct knowledge about recurrence risk, suggesting that effective reproductive counselling can positively impact this knowledge gap.

Pregnancy in complex CHD: focus on patients with Fontan circulation and patients with a systemic right ventricle.

The majority of children with congenital heart disease (CHD) now survive into adulthood, and many women with CHD want to pursue pregnancy. Pregnancy represents a complex issue for the CHD care provider. It requires balancing the interests of the woman against the risk to her health during pregnancy, while also factoring in the long-term risks to her health and the risk to her fetus. Our knowledge about this subject has been historically limited by lack of data regarding the outcome of pregnancy in CHD; however, in recent years, more data have begun to emerge. In this review, we will summarise what is known about risk assessment in pregnant CHD patients. We provide a framework for healthcare providers managing pregnancy in this population, with focus on the systemic right ventricle and the Fontan operation.

Aortic dilatation and aortopathies in congenital heart disease.

PURPOSE OF REVIEW: The objective of this review is to summarize the recent data pertaining to aortic dilatation in congenital heart disease (CHD) and to discuss the current understanding of the pathophysiology and management of this disease. RECENT FINDINGS: Aortic dilatation is a common finding in CHD. However, acute aortic complications appear to be relatively rare. Multiple factors predispose this population to aortic dilatation, including underlying genetics, cellular-based mechanisms, and abnormalities in aortic mechanics and valve morphology. SUMMARY: Although aortic dilatation is common in CHD, data about adverse long-term outcomes are limited. Optimal disease-specific management strategies have yet to be developed, and further research is needed to guide care in this population.

Pregnancy-related cardiac outcomes among patients with congenital heart disease after formalization of a cardio-obstetrics program.

BACKGROUND: The prevalence of pregnant patients with congenital heart disease (CHD) is increasing, and these patients are at high risk for cardiac morbidity. OBJECTIVE: This study aimed to examine the pregnancy outcomes in patients with congenital heart disease before and after the establishment of formal cardio-obstetrics collaboration between adult congenital heart disease and maternal-fetal medicine programs. STUDY DESIGN: This was a retrospective cohort study of pregnant patients with congenital heart disease from 2002 to 2020 at a single urban academic institution in the United States. This study included patients with a singleton pregnancy who continued a pregnancy beyond 20 weeks of gestation. The primary outcome was a composite adverse maternal cardiac outcome, compared before (2002-2010) and after (2011-2020) the program. The secondary outcomes included gestational age at delivery, mode of delivery, rate of labor induction, use of diuresis after delivery, and a composite maternal morbidity outcome. RESULTS: The number of pregnant patients with congenital heart disease increased after formalization of the cardio-obstetrics program (200 [postprogram group] vs 84 [preprogram group]; 0.48% of all deliveries in the postprogram group vs 0.25% of all deliveries in the preprogram group; P<.001). The postprogram group was more likely to undergo labor induction than the preprogram group (126 [63%] vs 34 [41%], respectively; P<.001). There were fewer patients in the postprogram group than in the preprogram group who were New York Heart Association class II to IV (23 [12%] vs 17 [22%], respectively; P=.04) or with systemic ventricular dysfunction (8 [4%] vs 12 [16%], respectively; P=.001). There was no difference in the primary outcome (38 [19%] in the postprogram group vs 14 [17%] in the preprogram group; P=.64), even after adjusting for confounders, including New York Heart Association class >I and systemic ventricular dysfunction (adjusted odds ratio, 2.3; 95% confidence interval, 0.96-5.4). Patients in the postprogram group were more likely to receive diuresis after delivery than patients in the preprogram group, even in the absence of heart failure or pulmonary edema (9 [4.5%] vs 0 [0.0%], respectively; P=.04). CONCLUSION: In the period after the establishment of a formal cardio-obstetrics program between adult congenital heart disease and maternal-fetal medicine, the number of patients with congenital heart disease delivering at our institution increased significantly. Overall, fewer patients entered pregnancy with advanced-stage heart failure or systemic ventricular dysfunction, possibly suggesting improved prepregnancy cardiac care or improved preconception counseling. Composite maternal cardiac outcomes were similar, but the rates of postpartum diuresis increased significantly, suggesting increased attention to volume status in the postpartum period. Formalized collaboration between congenital heart disease and maternal-fetal medicine may help better optimize patients' care before conception, during pregnancy, and after delivery.