Ten-year outcomes in adult patients with congenital heart disease and implantable cardioverter-defibrillators.

BACKGROUND: Adult congenital heart disease (ACHD) patients may be at risk of sudden cardiac death and be candidates for an implantable cardioverter-defibrillator (ICD). We evaluated the long-term rates of ventricular arrhythmias requiring treatment and mortality in these patients. METHODS: A single-center retrospective case-series identified ACHD patients with an ICD and were evaluated for the primary outcome of appropriate ICD intervention or ablation for ventricular tachyarrhythmias. Secondary endpoints were mortality and complication rates. Survival analyses to generate Kaplan-Meier curves for the primary and secondary outcomes were performed. RESULTS: There were 125 adult patients (median age 35.5 years, 68.8% male) with congenital heart disease and an ICD. The median follow-up was 6.4 years (interquartile range 2.8-9.1 years). Transposition of the Great Arteries (TGA) was present in 62 patients (49.6%) and Tetralogy of Fallot (ToF) in 33 (26.4%). The indication for an ICD was primary prevention in 90 patients (72%) and secondary prevention in 35 patients (28%). The primary endpoint occurred in 44 patients (35.2%). Time dependent analyses demonstrated a continual risk of the primary outcome (event rates of 23.8% at 5 years, 45.5% at 8 years, 47.9% at 10 years; p < 0.001). Death occurred in 20 patients (16.0%) and was most commonly from congestive heart failure (CHF). CONCLUSIONS: Long-term follow-up of ACHD patients with an ICD experience a persistent risk of ventricular arrhythmias. Mortality was most commonly attributed to CHF. These data provide insight into the clinical course and may guide shared clinical decision making in this complex patient population.

Cardiac Denial and Expectations Associated With Depression in Adults With Congenital Heart Disease.

Depression in adults with congenital heart disease is highly prevalent and strongly associated with adverse prognosis. Better management of risk factors for depression may improve clinical outcomes in this population. We conducted a single-site, cross-sectional study of 78 adults with congenital heart disease followed at Washington University School of Medicine. Data considered in the analyses included retrospectively obtained clinical information and patients' self-assessed psychosocial functioning and health status. To identify the clinical and psychosocial variables associated with depression, we built a stepwise multivariate model to measure the relative contribution of these variables to depression status. The prevalence of depression in our sample was 26%. Our model accounted for approximately 67% of the variability in depression scores. The final model consisted of the Cardiac Denial of Impact Scale, expectations domain of Barriers to Care, and the energy and social domains of the Rand 36-Item Short Form Health Survey. Clinical variables did not predict variability in depression scores. In conclusion, greater cardiac denial and negative expectations of the healthcare team were associated with increased depression symptoms in ACHD.

Contributors to disease-specific health knowledge in adults with congenital heart disease: A correlational study.

OBJECTIVE: Growth in the adults with congenital heart disease (ACHD) population represents a challenge to the health care infrastructure. As patients with chronic disease are increasingly held accountable for their own care, contributors to disease-specific health knowledge, which are known to correlate with patients' participation in care, merit investigation to design patient-focused interventions. DESIGN: We conducted a single-site, cross-sectional study of ACHD patients. Investigators retrospectively gathered clinical data as well as psychometric and health status assessments completed at the time of enrollment. OUTCOME MEASURES: We investigated the impact of clinical and psychological variables on Leuven Knowledge Questionnaire for Congenital Heart Diseases health knowledge composite scores (HKCS). Variables with significant associations were considered in a stepwise multivariable regression model to determine which combination of variables jointly explained variability in HKCS. RESULTS: Overall HKCS was associated with the number of prior cardiac surgeries (r = 0.273; 95% CI: 0.050-0.467; P = .016), perceived stress (r = 0.260; 95% CI: 0.033-0.458; P = .024), SF-36 emotional well-being (r = -0.251; 95% CI: -0.451, -0.024; P = .030), history of noncardiac surgery (P = .037), cirrhosis (P = .048), and presence of implantable cardioverter-defibrillator (P = .028). On multivariable modeling, only the number of cardiac surgeries was found to correlate with HKCS. CONCLUSIONS: While univariate correlations were found between HCKS and several other clinical and psychological variables, only number of prior cardiac surgeries independently correlated with disease-specific health knowledge in ACHD patients. These results suggest that clinical and psychological variables are not impediments to disease-specific health knowledge.

Effects of eplerenone on markers of myocardial fibrosis, 6-minute walk distance, and quality of life in adults with tetralogy of Fallot and complete transposition of the great arteries.

Ventricular dysfunction is common among patients with repaired cyanotic congenital heart disease. To date, no pharmacologic intervention has been demonstrated to be beneficial in this setting. To begin addressing this knowledge gap, we conducted a single-center prospective, randomized, open-label pilot study to investigate the effects of eplerenone on serologic markers of collagen turnover and inflammation, 6-minute walk distance, and quality of life in patients with tetralogy of Fallot (TOF) or transposition of the great arteries with a systemic right ventricle (transposition of the great arteries [TGA]). Patients were randomized to a 3-month drug-free period at the beginning of the treatment period or at the end. All patients received 12 months of eplerenone therapy during the treatment period. Twenty-six patients were enrolled in the trial; 17 completed the study protocol: 8 with TOF and 9 with TGV. Eplerenone had no effect on serum levels of procollagen 1 N-terminal peptide (PINP), procollagen 3 N-terminal peptide (PIIINP), or galectin-3 (G3). Similarly, eplerenone had no effect on 6-minute walk distance or quality of life. In conclusion, PINP and PIIINP levels are as high as or higher in patients with TOF and TGA than in patients with normal cardiac anatomy and heart failure, whereas G3 levels are lower. Eplerenone is well tolerated by adults born with congenital heart disease.

Clinical and Psychological Drivers of Perceived Health Status in Adults With Congenital Heart Disease.

The factors having the greatest impact on self-reported health status in adults with congenital heart disease (ACHD) remain incompletely studied. We conducted a single-site, cross-sectional study of ACHD patients followed at the Center for ACHD at Washington University School of Medicine, including retrospectively gathered clinical data and psychometric and health status assessments completed at the time of enrollment. To identify primary drivers of perceived health status, we investigated the impact of the demographic, clinical, and psychological variables on self-reported health status as assessed using the Rand 36-Item Short Form Health Survey. Variables with significant associations within each domain were considered jointly in multivariable models constructed via stepwise selection. There was domain-specific heterogeneity in the variables having the greatest effect on self-reported health status. Depression was responsible for the greatest amount of variability in health status in all domains except physical functioning. In the physical functioning domain, depression remained responsible for 5% of total variability, the third most significant variable in the model. In every domain, depression more strongly influenced health status than did any cardiac-specific variable. In conclusion, depression was responsible for a significant amount of heterogeneity in all domains of self-perceived health status. Psychological variables were better predictors of health status than clinical variables.

Effect of Ambrisentan on Exercise Capacity in Adult Patients After the Fontan Procedure.

The Fontan operation is a common end point for children born with a single functional ventricle. Fontan patients typically experience physiological deterioration leading to transplant or death in their third or fourth decades of life. This deterioration is partially attributable to progressive increases in pulmonary vascular resistance (PVR) and as such endothelin receptor antagonists, which are known to decrease pulmonary vascular resistance, have been proposed as potentially beneficial in this population. We conducted a single-center, randomized, double-blind, placebo-controlled, crossover study of 12 weeks of ambrisentan therapy (10 mg per day) versus placebo to test the hypothesis that endothelin receptor antagonism will improve cardiopulmonary exercise test parameters and 36-item short form (SF-36) assessed quality of life in adult Fontan patients. Twenty-eight patients entered the trial, 19 patients completed the protocol. Ambrisentan therapy improved peak oxygen consumption by 1.7 ml/kg/min in patients who achieved a respiratory exchange ratio of >0.95 (p = 0.05) and decreased the slope of the ventilatory equivalent ratio for oxygen (-2.8, p = 0.019) in all completers. It did not change SF-36 physical function score compared with placebo (p = 0.28). Ambrisentan therapy resulted in a decrease in (-1.4 g/dl, p <0.001) with no change in liver or renal function. Therapy was generally well tolerated, with no greater rate of side effects than placebo. In conclusion, ambrisentan is well tolerated and improves exercise capacity in adult Fontan patients.

Cardiac Denial and Psychological Predictors of Cardiac Care Adherence in Adults With Congenital Heart Disease.

The current study examined cardiac denial and psychological predictors (i.e., depression, anxiety) of health outcomes including medical nonadherence and physical health in a sample of 80 adults with congenital heart disease (ACHD). Results indicated that denial of impact was elevated in this patient group compared with reference groups, and denial was negatively associated with depression and anxiety at ps < .01. Results indicated that depression, anxiety, and denial predicted unique variance in medical nonadherence, and gender moderated the relationships between these psychological factors and nonadherence. For depression, men and women showed similar relationships between depression and nonadherence at high levels of depression; however, at low levels of depression (i.e., a more normal mood state), men were less adherent compared with women. For anxiety, men and women did not differ in adherence at low levels of anxiety; however, men experiencing high anxiety were less adherent compared with women experiencing high anxiety. Implications of this study are discussed including the role of gender and denial and the impact of denial functioning to reduce negative affect. Depression was the only significant predictor of physical functioning. Results of this study suggest that psychological interventions aimed at depression and anxiety may function differently across gender to improve patient medical adherence and improve physical functioning in ACHD.

Increased Body Mass Index Is Associated with Congestive Heart Failure and Mortality in Adult Fontan Patients.

OBJECTIVE: Obesity affects adults with congenital heart disease (CHD). The effect of an increased body mass index (BMI) with respect to morbidity and mortality has not been evaluated in adults with complex CHD. Our objective was to evaluate the effects of increased BMI on heart failure and mortality in univentricular patients who had undergone Fontan palliation. METHODS: A query of Fontan patients' first appointments at the Washington University Center for Adults with CHD between 2007 and 2014 yielded 79 patients. BMI status as normal (<25 kg/m(2) ), overweight (≥25, <30 kg/m(2) ), and obese (≥30 kg/m(2) ) was established at the patient's first appointment. We analyzed demographics, diuretic requirements, New York Heart Association (NYHA) class, and laboratory values using Student's two-sample t-test and Fisher's exact test. Mortality was assessed via survival curves, and hazard ratios were compiled with proportional hazard modeling. RESULTS: The recent average BMI was significantly greater in patients with NYHA classes II-IV (29.3 ± 9 kg/m(2) ) compared with asymptomatic patients (24.8 ± 5.1 kg/m(2) , P = .006). Additionally, the average BMI of patients with a high diuretic requirement (≥40 mg/day IV furosemide equivalent) was obese, at 32.15 ± 9.1 kg/m(2) , compared with 25.91 ± 7.3 kg/m(2) for those on no or lower doses of diuretics (P = .009). Eighteen of the 79 patients met an endpoint of death, hospice placement, or cardiac transplant by the study conclusion. Kaplan-Meier analysis from time of first appointment until recent follow-up revealed a significant association between time to combined endpoint and BMI class. Cox proportional hazard modeling with age adjustment yielded a hazard ratio of 3.2 (95% CI 1.096-9.379) for obesity upon first presentation to an adult CHD clinic. CONCLUSIONS: In patients with univentricular hearts and Fontan palliation, obesity is associated with symptomatic heart failure and mortality.

Contraceptive Use and Unintended Pregnancy in Women With Congenital Heart Disease.

OBJECTIVE: To identify patterns of contraceptive use and pregnancy in an academic adult congenital cardiology practice. METHODS: In this cross-sectional study, from October 2013 through March 2014, 100 women with congenital heart disease aged 18-45 years were recruited from an academic congenital heart disease clinic and administered a survey regarding pregnancy history, contraception use, and understanding of pregnancy-related and contraceptive-related risk. The primary outcome was current use of long-acting reversible contraception, including intrauterine devices or subdermal implants. RESULTS: Of 83 sexually active women, 63 (75.9%, 95% confidence interval [CI] 65.3-85.1) reported currently using any contraceptive method, including 30 of 83 (36.1%, 95% CI 25.9-47.4) using tier I methods (typical-use failure rates of less than 1% per year) and 20 of 83 (24.1%, 95% CI 15.4-34.7) using tier II methods (typical-use failure rates of 6-12% per year). Nine of 83 (10.8%, 95% CI 5.1-19.6) reported currently using long-acting reversible contraception. Sixty-four of 141 total pregnancies (45.4%, 95% CI 31.9-58.9) were self-reported by participants as "unexpected" rather than "planned." Only one (1.6%, 95% CI 0-4.6) of the 64 unintended pregnancies occurred when the woman was using a tier I method of contraception at the time of conception. CONCLUSION: Most women with congenital heart disease of childbearing age are sexually active. The high incidence of unintended pregnancy in this group may be related to underuse of highly effective methods of contraception. Specific counseling on tier I methods may reduce unintended pregnancies in women with congenital heart disease. LEVEL OF EVIDENCE: III.

Cardiovascular disease in late survivors of tetralogy of fallot: a tertiary care center experience.

Patients with tetralogy of Fallot can survive to late adulthood; however, there are few data on cardiovascular outcomes in this population. We conducted a single-center retrospective analysis of cardiovascular outcomes and risk factors in 208 patients with tetralogy of Fallot to better evaluate the burden of cardiovascular disease in this group. Descriptive statistics were used to determine the prevalence of relevant cardiovascular risk factors and outcomes, including a composite analysis of cardiovascular disease. Rates and mean values from the American Heart Association 2011 Heart Disease and Stroke Statistics Update were used as population estimates for comparison. In tetralogy of Fallot patients, cardiovascular disease prevalence was not different from that found in the general population (40% vs. 36%, P=0.3). However, there was significantly more cardiovascular disease in tetralogy of Fallot men aged 20 to 39 years (30% vs. 14%, P < 0.05) and in tetralogy of Fallot men aged 40 to 59 years (63% vs. 29%, P < 0.0001). This was due to higher prevalence of coronary disease (12% vs. 7%, P < 0.05) and heart failure (16% vs. 2%, P < 0.0001). In particular, the increased prevalence of heart failure (regardless of pulmonary valve disease) accounts for the frequency of cardiovascular disease in tetralogy of Fallot men aged 20 to 59 years. These data support the need to routinely screen young adult male survivors of tetralogy of Fallot for asymptomatic heart failure. Further studies are needed to determine the incidence, severity, and long-term effects of cardiovascular disease in the adult congenital heart disease population.

Heart Failure in Adults who had the Fontan Procedure: Natural History, Evaluation, and Management.

OPINION STATEMENT: Fontan type palliations are a group of operations employed in patients with only one functional ventricle. These procedures take the normally parallel pulmonary and systemic circulations and place them in series to reestablish separation between the two. The Fontan circulation established by such operations is a unique, artificial physiologic entity. Although the Fontan circulation supports patients for decades, patients eventually experience progressive heart failure. As this growing group of patients reaches adulthood, there is a need for general cardiologists as well as adult congenital heart disease specialists to be familiar with the long-term sequelae of the Fontan circulation. The purpose of the present review is to summarize the limited available data on heart failure of the Fontan, its natural history, evaluation, and management.

A unique case of two sources of right ventricle enlargement in tetralogy of Fallot.

The most common long-term sequelae of tetralogy of Fallot (TOF) are related to acquired late postsurgical pulmonary valve pathology. This is often in the form of pulmonic insufficiency (PI) ultimately leading to right ventricular (RV) enlargement and failure, which may necessitate pulmonary valve replacement. We present a case of severe PI in TOF with an incidental large circumflex to RV fistula and single-vessel coronary artery stenosis in a patient with an enlarged RV. The diagnostic dilemma was to determine whether the RV enlargement was caused by severe PI, shunting from the coronary fistula, or a combination of both.

Massive global right ventricular hypertrophy with both fixed and dynamic obstruction and pulmonary valve dysplasia.

Congenital pulmonary valvular dysplasia is an unusual condition typically associated with Noonan syndrome. Among its other cardiac manifestations, occasional patients with Noonan syndrome have been demonstrated to have hypertrophic nonobstructive cardiomyopathy, which may be biventricular. We report a unique case of pulmonary valvular dysplasia, dynamic right ventricular outflow tract obstruction and profound right ventricular hypertrophy with only mild left ventricular hypertrophy, in a patient without Noonan syndrome.

Role of protein binding in renal elimination of leptin.

OBJECTIVE: Leptin, a hormone produced by fat which signals to the brain the extent of fat stores, is known to be eliminated from circulation primarily by the kidney. The hormone circulates in both free and protein-bound forms, but there is little information concerning the inter-relationship of these forms of leptin, or which form is influenced by physiological processes such as renal elimination. We studied total, free and bound concentrations of leptin in ambulatory adults undergoing catheterization for diagnosis/management of congenital cardiac disease. DESIGN: Blood specimens were collected from both the arterial circulation and the renal vein, for determination of the fractional extraction of leptin resulting from a single pass through the kidney. PATIENTS: Thirteen subjects were studied. MEASUREMENTS: Total leptin concentrations were measured by radioimmunoassay, and free/protein-bound leptin concentrations were quantified by an high-performance liquid chromatography method. Adequacy of renal vein sampling was assessed by comparing the creatinine concentration of arterial and venous specimens. RESULTS: Mean fractional extraction of creatinine was 28 +/- 7% in the 13 subjects studied. Fractional extraction of total leptin was 18 +/- 8%, significantly less than that for creatinine. Fractional extraction of total leptin was not related to arterial leptin concentration or the fractional extraction of creatinine. Both free and bound fractions of leptin were significantly reduced by passage through the kidney, with fractional extractions of 22% and 25%, respectively. Efficiency of extraction was not influenced by the relative proportion of free or bound leptin fractions. Leptin-binding capacity (a measure of the concentrations of leptin-binding proteins) was not altered by passage through the kidney. CONCLUSIONS: Both free and bound leptin are metabolically active with regard to elimination. Protein-bound leptin equilibrates with the free leptin fraction in circulation as the result of a dynamic equilibrium. The data are consistent with either glomerular filtration or active uptake as mechanisms of elimination. Leptin-binding proteins are apparently neither eliminated or produced by the kidney.