David N. Rosenthal

It has been 50 years since Francis Fontan pioneered the operation that today bears his name. Initially designed for patients with tricuspid atresia, this procedure is now offered for a vast array of congenital cardiac lesions when a circulation with 2 ventricles cannot be achieved. As a result of technical advances and improvements in patient selection and perioperative management, survival has steadily increased, and it is estimated that patients operated on today may hope for a 30-year survival of >80%. Up to 70 000 patients may be alive worldwide today with Fontan circulation, and this population is expected to double in the next 20 years. In the absence of a subpulmonary ventricle, Fontan circulation is characterized by chronically elevated systemic venous pressures and decreased cardiac output. The addition of this acquired abnormal circulation to innate abnormalities associated with single-ventricle congenital heart disease exposes these patients to a variety of complications. Circulatory failure, ventricular dysfunction, atrioventricular valve regurgitation, arrhythmia, protein-losing enteropathy, and plastic bronchitis are potential complications of the Fontan circulation. Abnormalities in body composition, bone structure, and growth have been detected. Liver fibrosis and renal dysfunction are common and may progress over time. Cognitive, neuropsychological, and behavioral deficits are highly prevalent. As a testimony to the success of the current strategy of care, the proportion of adults with Fontan circulation is increasing. Healthcare providers are ill-prepared to tackle these challenges, as well as specific needs such as contraception and pregnancy in female patients. The role of therapies such as cardiovascular drugs to prevent and treat complications, heart transplantation, and mechanical circulatory support remains undetermined. There is a clear need for consensus on how best to follow up patients with Fontan circulation and to treat their complications. This American Heart Association statement summarizes the current state of knowledge on the Fontan circulation and its consequences. A proposed surveillance testing toolkit provides recommendations for a range of acceptable approaches to follow-up care for the patient with Fontan circulation. Gaps in knowledge and areas for future focus of investigation are highlighted, with the objective of laying the groundwork for creating a normal quality and duration of life for these unique individuals.

CONTEXT: Although beta-blockers improve symptoms and survival in adults with heart failure, little is known about these medications in children and adolescents. OBJECTIVE: To prospectively evaluate the effects of carvedilol in children and adolescents with symptomatic systemic ventricular systolic dysfunction. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, double-blind, placebo-controlled study of 161 children and adolescents with symptomatic systolic heart failure from 26 US centers. In addition to treatment with conventional heart failure medications, patients were assigned to receive placebo or carvedilol. Enrollment began in June 2000 and the last dose was given in May 2005 (each patient received medication for 8 months). INTERVENTIONS: Patients were randomized in a 1:1:1 ratio to twice-daily dosing with placebo, low-dose carvedilol (0.2 mg/kg per dose if weight <62.5 kg or 12.5 mg per dose if weight > or =62.5 kg), or high-dose carvedilol (0.4 mg/kg per dose if weight <62.5 kg or 25 mg per dose if weight > or =62.5 kg) and were stratified according to whether each patient's systemic ventricle was a left ventricle or not. MAIN OUTCOME MEASURES: The primary outcome was a composite measure of heart failure outcomes in patients receiving carvedilol (low- and high-dose combined) vs placebo. Secondary efficacy variables included individual components of this composite, echocardiographic measures, and plasma b-type natriuretic peptide levels. RESULTS: There was no statistically significant difference between groups for the composite end point based on the percentage of patients who improved, worsened, or were unchanged. Among 54 patients assigned to placebo, 30 improved (56%), 16 worsened (30%), and 8 were unchanged (15%); among 103 patients assigned to carvedilol, 58 improved (56%), 25 worsened (24%), and 20 were unchanged (19%). The rates of worsening were lower than expected. The odds ratio for worsened outcome for patients in the combined carvedilol group vs the placebo group was 0.79 (95% CI, 0.36-1.59; P = .47). A prespecified subgroup analysis noted significant interaction between treatment and ventricular morphology (P = .02), indicating a possible differential effect of treatment between patients with a systemic left ventricle (beneficial trend) and those whose systemic ventricle was not a left ventricle (nonbeneficial trend). CONCLUSIONS: These preliminary results suggest that carvedilol does not significantly improve clinical heart failure outcomes in children and adolescents with symptomatic systolic heart failure. However, given the lower than expected event rates, the trial may have been underpowered. There may be a differential effect of carvedilol in children and adolescents based on ventricular morphology. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00052026.

BACKGROUND: Options for mechanical circulatory support as a bridge to heart transplantation in children with severe heart failure are limited. METHODS: We conducted a prospective, single-group trial of a ventricular assist device designed specifically for children as a bridge to heart transplantation. Patients 16 years of age or younger were divided into two cohorts according to body-surface area (cohort 1, <0.7 m(2); cohort 2, 0.7 to <1.5 m(2)), with 24 patients in each group. Survival in the two cohorts receiving mechanical support (with data censored at the time of transplantation or weaning from the device owing to recovery) was compared with survival in two propensity-score-matched historical control groups (one for each cohort) undergoing extracorporeal membrane oxygenation (ECMO). RESULTS: For participants in cohort 1, the median survival time had not been reached at 174 days, whereas in the matched ECMO group, the median survival was 13 days (P<0.001 by the log-rank test). For participants in cohort 2 and the matched ECMO group, the median survival was 144 days and 10 days, respectively (P<0.001 by the log-rank test). Serious adverse events in cohort 1 and cohort 2 included major bleeding (in 42% and 50% of patients, respectively), infection (in 63% and 50%), and stroke (in 29% and 29%). CONCLUSIONS: Our trial showed that survival rates were significantly higher with the ventricular assist device than with ECMO. Serious adverse events, including infection, stroke, and bleeding, occurred in a majority of study participants. (Funded by Berlin Heart and the Food and Drug Administration Office of Orphan Product Development; ClinicalTrials.gov number, NCT00583661.).