High Prevalence of Abnormal Hemoglobin A1c in the Adolescent and Young Adult Fontan Population.

Little is known about diabetes risk in adolescents and young adults with Fontan palliation. We sought to understand the prevalence of abnormal hemoglobin A1c (HbA1c) in the adolescent and young adult population with Fontan palliation. Between 2015 and 2021, 78 Fontan patients > 10 years of age were seen in our single ventricle clinic; 66 underwent screening with HbA1c. 50% of the study cohort (n = 33) had HbA1c ≥ 5.7%; 2% (n = 1) had HbA1c ≥ 6.5%. There was no correlation between BMI and HbA1c, with no difference in the prevalence of overweight or obesity (BMI ≥ 85th percentile) between those with and without abnormal HbA1c (31% versus 27%, p = 0.69). While 20% of the cohort had a family history of diabetes, there was no difference in family history between those with and without abnormal HbA1c (21% versus 19%, p = 0.85). There were no differences in other risk factors and characteristics (race, glomerular filtration rate, liver function, liver elastography, hematocrit, and years from Fontan surgery) between those with and without abnormal HbA1c. Our results highlight the importance of recognizing that abnormal HbA1c is highly prevalent in the Fontan population. Whether abnormal HbA1c in this population correlates with atherosclerotic cardiovascular disease in adulthood is not known. The mechanism for an abnormal HbA1c in the adolescent and young adult Fontan population remains unclear and further studies are needed.

Ventricular arrhythmias following transcatheter pulmonary valve replacement with the harmony TPV25 device.

BACKGROUND: Transcatheter pulmonary valve replacement (TPVR) with the Harmony valve (Medtronic, Inc.) was recently approved to treat postoperative native outflow tract pulmonary regurgitation. While the 22 mm Harmony valve Early Feasibility Study demonstrated ventricular tachycardia (VT) in only 5% of patients, little is known about ventricular arrhythmias after TPVR with the larger 25 mm valve (TPV25). METHODS: A single center review was performed of patients with TPV25 implant from 2020 to 2021. Demographic, cardiac, procedural, and postimplant cardiac telemetry data were collected and compared between patients who did and did not have peri-implant ventricular arrhythmia. RESULTS: Thirty patients underwent TPV25 at a median age of 30 years. On postimplant telemetry, VT events were documented in 12 patients (40%); 11 nonsustained VT (NSVT) (median 3 episodes per patient and 6 beats per episode, maximum 157 episodes) and 1 sustained VT (3%), with Torsades de Pointes secondary to a short coupled premature ventricular contraction (PVC). VT events were associated with annular valve positioning (p < 0.001) and increased postimplant PVC burden (p < 0.0001), but there was no association between VT and other demongraphic, historical, or procedural factors. The frequency of NSVT events fell from 3/h from 0 to 12 h postimplant to 0.5/hr from 12 to 24 h (p < 0.001). CONCLUSION: VT occurred commonly (40%) in the first 24 h after TPV25 implant, with self-limited NSVT in 11 of 12 patients and 1 patient with cardiac arrest secondary to Torsades de Pointes. VT only occurred with annular valve positioning. Larger, longer-term studies are needed to determine risk factors for and natural history of post-TPVR VT.

Substantial Cardiovascular Morbidity in Adults With Lower-Complexity Congenital Heart Disease.

BACKGROUND: Although lower-complexity cardiac malformations constitute the majority of adult congenital heart disease (ACHD), the long-term risks of adverse cardiovascular events and relationship with conventional risk factors in this population are poorly understood. We aimed to quantify the risk of adverse cardiovascular events associated with lower-complexity ACHD that is unmeasured by conventional risk factors. METHODS: A multitiered classification algorithm was used to select individuals with lower-complexity ACHD and individuals without ACHD for comparison among >500 000 British adults in the UK Biobank. ACHD diagnoses were subclassified as isolated aortic valve and noncomplex defects. Time-to-event analyses were conducted for the primary end points of fatal or nonfatal acute coronary syndrome, ischemic stroke, heart failure, and atrial fibrillation and a secondary combined end point for major adverse cardiovascular events. Maximum follow-up time for the study period was 22 years with retrospectively and prospectively collected data from the UK Biobank. RESULTS: We identified 2006 individuals with lower-complexity ACHD and 497 983 unexposed individuals in the UK Biobank (median age at enrollment, 58 [interquartile range, 51-63] years). Of the ACHD-exposed group, 59% were male, 51% were current or former smokers, 30% were obese, and 69%, 41%, and 7% were diagnosed or treated for hypertension, hyperlipidemia, and diabetes mellitus, respectively. After adjustment for 12 measured cardiovascular risk factors, ACHD remained strongly associated with the primary end points, with hazard ratios ranging from 2.0 (95% CI, 1.5-2.8; P<0.001) for acute coronary syndrome to 13.0 (95% CI, 9.4-18.1; P<0.001) for heart failure. ACHD-exposed individuals with ≤2 cardiovascular risk factors had a 29% age-adjusted incidence rate of major adverse cardiovascular events, in contrast to 13% in individuals without ACHD with ≥5 risk factors. CONCLUSIONS: Individuals with lower-complexity ACHD had a higher burden of adverse cardiovascular events relative to the general population that was unaccounted for by conventional cardiovascular risk factors. These findings highlight the need for closer surveillance of patients with mild to moderate ACHD and further investigation into management and mechanisms of cardiovascular risk unique to this growing population of high-risk adults.

General principles of heart failure management in adult congenital heart disease.

The population of adults with congenital heart disease is now an estimated 1.4 million in the United States alone and growing. Unfortunately, survival to adulthood does not equate to a normal life expectancy, and heart failure (HF) has now emerged as the leading cause of death for the adult congenital heart disease (ACHD) patient. As this population continues to grow in number and advance in age, the prevalence of heart failure in the adult with congenital heart disease (ACHD-HF) will undoubtedly continue to increase. However, much of our current understanding of mechanism, diagnosis, and management of ACHD-HF remains limited. We aim to review the current understanding of the proposed definitions, mechanisms, clinical impact, and general management considerations of ACHD-HF while also recognizing the large number of knowledge gaps that persist.

Incidence, risk factors, and outcomes of acute kidney injury in adults undergoing surgery for congenital heart disease.

BACKGROUND: Acute kidney injury after cardiac surgery is a frequent and serious complication among children with congenital heart disease (CHD) and adults with acquired heart disease; however, the significance of kidney injury in adults after congenital heart surgery is unknown. The primary objective of this study was to determine the incidence of acute kidney injury after surgery for adult CHD. Secondary objectives included determination of risk factors and associations with clinical outcomes. METHODS: This single-centre, retrospective cohort study was performed in a quaternary cardiovascular ICU in a paediatric hospital including all consecutive patients ⩾18 years between 2010 and 2013. RESULTS: Data from 118 patients with a median age of 29 years undergoing cardiac surgery were analysed. Using Kidney Disease: Improving Global Outcome creatinine criteria, 36% of patients developed kidney injury, with 5% being moderate to severe (stage 2/3). Among higher-complexity surgeries, incidence was 59%. Age ⩾35 years, preoperative left ventricular dysfunction, preoperative arrhythmia, longer bypass time, higher Risk Adjustment for Congenital Heart Surgery-1 category, and perioperative vancomycin use were significant risk factors for kidney injury development. In multivariable analysis, age ⩾35 years and vancomycin use were significant predictors. Those with kidney injury were more likely to have prolonged duration of mechanical ventilation and cardiovascular ICU stay in the univariable regression analysis. CONCLUSIONS: We demonstrated that acute kidney injury is a frequent complication in adults after surgery for CHD and is associated with poor outcomes. Risk factors for development were identified but largely not modifiable. Further investigation within this cohort is necessary to better understand the problem of kidney injury.

Generation of two induced pluripotent stem cell lines from patients with Down syndrome.

Down syndrome (DS) is caused by trisomy of Homo sapiens chromosome 21 (HSA21) and is by far the most common chromosomal disorder accompanied by neurodevelopmental disorders and congenital heart disease. Here, we generated two induced pluripotent stem cell (iPSC) lines from two patients with DS. These two lines exhibited normal morphology, trisomy 21 karyotype, pluripotency and differentiation capability into derivatives of three germ layers. The patient-specific iPSC lines arean invaluable resource in research to model DS-related cellular and molecular pathologies and test possible therapeutic strategies for DS.

Durability of Pulmonary Valve Replacement with Large Diameter Stented Porcine Bioprostheses.

There is limited information about durability of large diameter porcine bioprostheses implanted for pulmonary valve replacement (PVR). We studied patients who underwent surgical PVR from 2002-2019 with a stented porcine bioprosthetic valve (BPV) with a labeled size ≥27 mm. The primary outcome was freedom from reintervention. During the study period, 203 patients underwent PVR using a porcine BPV ≥27 mm, 94% of whom received a Mosaic valve (Medtronic Inc., Minneapolis, MN). Twenty patients underwent reintervention from 3.4-12.0 years after PVR: 5 surgical and 15 transcatheter PVR procedures. The indication for reintervention was regurgitation in 13 patients, stenosis in 2, mixed disease in 4, and endocarditis in 1. Estimated freedom from reintervention was 97±1% at 5 years and 82±4% at 10 years, and freedom from prosthesis dysfunction (moderate or severe regurgitation and/or a maximum Doppler gradient ≥50 mm Hg) over time was 91±2% at 5 years and 74±4% at 10 years. Younger age and smaller true valve diameter were associated with shorter freedom from reintervention, but valve oversizing was not. The durability of large stented porcine bioprostheses in the pulmonary position is generally excellent, particularly in adolescents and adults, similar to various other types of BPV. In the current study, relative valve size was not associated with valve longevity, although the low event-rate in this population was a limiting factor.

Tetralogy of Fallot and Aortic Dissection: Implications in Management.

We present the case of a 61-year-old man with tetralogy of Fallot postrepair and mechanical aortic valve replacement with an aortic root/ascending/arch aneurysm with chronic type A aortic dissection. He underwent uncomplicated aortic root and total arch replacement. Continued surveillance for aortic aneurysm is necessary in the tetralogy of Fallot population. (Level of Difficulty: Intermediate.).

Race and Genetics in Congenital Heart Disease: Application of iPSCs, Omics, and Machine Learning Technologies.

Congenital heart disease (CHD) is a multifaceted cardiovascular anomaly that occurs when there are structural abnormalities in the heart before birth. Although various risk factors are known to influence the development of this disease, a full comprehension of the etiology and treatment for different patient populations remains elusive. For instance, racial minorities are disproportionally affected by this disease and typically have worse prognosis, possibly due to environmental and genetic disparities. Although research into CHD has highlighted a wide range of causal factors, the reasons for these differences seen in different patient populations are not fully known. Cardiovascular disease modeling using induced pluripotent stem cells (iPSCs) is a novel approach for investigating possible genetic variants in CHD that may be race specific, making it a valuable tool to help solve the mystery of higher incidence and mortality rates among minorities. Herein, we first review the prevalence, risk factors, and genetics of CHD and then discuss the use of iPSCs, omics, and machine learning technologies to investigate the etiology of CHD and its connection to racial disparities. We also explore the translational potential of iPSC-based disease modeling combined with genome editing and high throughput drug screening platforms.

Waitlist and post-transplant outcomes for eisenmenger syndrome: A comparison of transplant strategies.

BACKGROUND: End-stage Eisenmenger syndrome (ES) due to unrepaired atrial septal defect (ASD) or ventricular septal defect (VSD) is an indication for lung transplantation (LTx) or heart-lung transplantation (HLTx). Limited evidence exists as to the optimal transplant strategy for this unique population. AIM: To describe waitlist characteristics and post-transplant outcomes in patients with ES-ASD or ES-VSD. METHODS: Using the ISHLT Registry, data were extracted for all ES-ASD or ES-VSD patients who underwent transplantation between 1987 and 2018. Additional data were sought for patients listed for LTx or HLTx in the OPTN Registry during the same period. Early era was defined as 1987-2004, and current era was defined as 2005-2018. RESULTS: In the current era, patients with ES-ASD or ES-VSD represented a lessening proportion of all LTx and HLTx. Compared to LTx for other indications, the odds of transplantation were significantly less for both ES-ASD 0.18 [0.07-0.50] and ES-VSD 0.03 [0.004-0.22]. In the early era, an equivalent survival was observed for ES-ASD who underwent HLTx versus LTx (p = 0.47), and superior survival for ES-VSD (p = 0.015). In contrast, ES-ASD patients who underwent LTx from the current era displayed better survival compared with HLTx, 10-year survival 52% vs 30% p = 0.036. Similar survival were observed for ES-VSD for both transplant strategies (p = 0.68). CONCLUSION: LTx shows superior survival outcomes in the current era for ES ASD patients, and equivalent outcomes for ES-VSD. In the current era, ES-ASD or ES-VSD patients were less likely to be transplanted than other candidates for LTx.

A 40-Year-Old Man With Tricuspid Atresia, Status Post-Fontan, With Severe COVID-19 Pneumonia and Pneumothorax.

We report a case of COVID-19 in an adult single-ventricle patient post-Fontan-to our knowledge, the first report in this population documenting the use of the latest management recommendations for this novel disease. Additionally, this patient had significant pre-existing ventricular dysfunction, valvular disease, and comorbidities including HIV. (Level of Difficulty: Advanced.).

Cardiac assessment in duchenne and becker muscular dystrophies.

Mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophies. In addition to muscle disease, there nearly always is an associated cardiomyopathy in Duchenne or Becker muscular dystrophy. In these muscular dystrophies, the severity of cardiomyopathy and congestive heart failure may not parallel the severity of skeletal muscle disease. Loss of normal dystrophin function in the heart produces four-chamber dilation and reduction in left ventricular function that develop after the onset of muscle weakness. Arrhythmias affecting both atrial and ventricular rhythms occur and may be life threatening. The degree to which hypoventilation and pulmonary dysfunction are present also directly affect cardiac function in muscular dystrophy. Care guidelines recently were issued to outline surveillance and treatment strategies for the younger patient with Duchenne muscular dystrophy. Herein, we review those guidelines, and additionally, provide recommendations for monitoring and treating cardiac disease in the populations of advanced Duchenne and Becker muscular dystrophies.

Extended cardiac ambulatory rhythm monitoring in adults with congenital heart disease: Arrhythmia detection and impact of extended monitoring.

BACKGROUND: Arrhythmias are a leading cause of death in adults with congenital heart disease (ACHD). While 24-48-hour monitors are often used to assess arrhythmia burden, extended continuous ambulatory rhythm monitors (ECAM) can record 2 weeks of data. The utility of this device and the arrhythmia burden identified beyond 48-hour monitoring have not been evaluated in the ACHD population. Additionally, the impact of ECAM has not been studied to determine management recommendations. OBJECTIVE: To address the preliminary question, we hypothesized that clinically significant arrhythmias would be detected on ECAM beyond 48 hours and this would lead to clinical management changes. METHODS: A single center retrospective cohort study of ACHD patients undergoing ECAM from June 2013 to May 2016 was performed. The number and type of arrhythmias detected within and beyond the first 48 hours of monitoring were compared using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Three hundred fourteen patients had monitors performed [median age 31 (IQR 25-41) years, 61% female). Significant arrhythmias were identified in 156 patients (50%), of which 46% were noted within 48 hours. A management change based on an arrhythmia was made in 49 patients (16%). CONCLUSIONS: ECAM detects more clinically significant arrhythmias than standard 48-hour monitoring in ACHD patients. Management changes, including medication changes, further testing or imaging, and procedures, were made based on results of ECAM. Recommendations and guidelines have been made based on arrhythmias on 48-hour monitoring; the predictive ability and clinical consequence of arrhythmias found on ECAM are not yet known.

Risk Estimates for Atherosclerotic Cardiovascular Disease in Adults With Congenital Heart Disease.

The adult with congenital heart disease (CHD) is at risk of developing atherosclerotic cardiovascular disease (ASCVD). We performed a cross-sectional study to describe established ASCVD risk factors and estimate 10-year and lifetime risk of ASCVD in adults over age 18 with CHD of moderate or great complexity using 3 validated risk assessment tools-the Framingham Study Cardiovascular Disease Risk Assessment, the Reynolds Risk Score, and the ASCVD Risk Estimator. We obtained extensive clinical and survey data on 178 enrolled patients, with average age 37.1 ± 12.6 years, 51% men. At least 1 modifiable ASCVD risk factor was present in 70%; the 2 most common were overweight/obesity (53%) and systemic hypertension (24%). Laboratory data were available in 103 of the 178 patients. Abnormal levels of glycated hemoglobin, high-sensitivity C-reactive protein, and high-density lipoprotein were each found in around 30% of patients. The 10-year ASCVD predicted risk using all 3 tools was relatively low (i.e., at least 90% of patients <10% risk), yet the median estimated lifetime risk was 36%. In conclusion, ASCVD risk factors are prevalent in adults with CHD. The risk estimation tools suggest that this population is particularly vulnerable to ASCVD with aging and should undergo guideline-based screening and management of modifiable risk factors.

Quality of Life of Adults With Congenital Heart Disease in 15 Countries: Evaluating Country-Specific Characteristics.

BACKGROUND: Measuring quality of life (QOL) is fundamental to understanding the impact of disease and treatment on patients' lives. OBJECTIVES: This study aimed to explore QOL in an international sample of adults with congenital heart disease (CHD), the association between patient characteristics and QOL, and international variation in QOL and its relationship to country-specific characteristics. METHODS: We enrolled 4,028 adults with CHD from 15 countries. QOL was assessed using a linear analog scale (LAS) (0 to 100) and the Satisfaction with Life Scale (SWLS) (5 to 35). Patient characteristics included sex, age, marital status, educational level, employment status, CHD complexity, and patient-reported New York Heart Association (NYHA) functional class. Country-specific characteristics included general happiness and 6 cultural dimensions. Linear mixed models were applied. RESULTS: Median QOL was 80 on the LAS and 27 on the SWLS. Older age, lack of employment, no marriage history, and worse NYHA functional class were associated with lower QOL (p < 0.001). Patients from Australia had the highest QOL (LAS: 82) and patients from Japan the lowest (LAS: 72). Happiness scores and cultural dimensions were not associated with variation in QOL after adjustment for patient characteristics and explained only an additional 0.1% of the variance above and beyond patient characteristics (p = 0.56). CONCLUSIONS: This large-scale, international study found that overall QOL in adults with CHD was generally good. Variation in QOL was related to patient characteristics but not country-specific characteristics. Hence, patients at risk for poorer QOL can be identified using uniform criteria. General principles for designing interventions to improve QOL can be developed.

Congenital Heart Defects in Adults : A Field Guide for Cardiologists.

Advances in cardiology and cardiac surgery allow a large proportion of patients with congenital heart defects to survive into adulthood. These patients frequently develop complications characteristic of the defect or its treatment. Consequently, adult cardiologists participating in the care of these patients need a working knowledge of the more common defects. Occasionally, patients with congenital heart defects such as atrial septal defect, Ebstein anomaly or physiologically corrected transposition of the great arteries present for the first time in adulthood. More often patients previously treated in pediatric cardiology centers have transitioned to adult congenital heart disease centers for ongoing care. Some of the more important defects in this category are tetralogy of Fallot, transposition of the great arteries, functionally single ventricle defects, and coarctation. Through this field guide, we provide an overview of the anatomy of selected defects commonly seen in an adult congenital practice using pathology specimens and clinical imaging studies. In addition, we describe the physiology, clinical presentation to the adult cardiologist, possible complications, treatment options, and outcomes.