Longitudinal Outcomes of Patients With Single Ventricle After the Fontan Procedure

Abstract

Background: Multicenter longitudinal objective data for survival into adulthood of patients who have undergone Fontan procedures are lacking.

Objectives: This study sought to describe transplant-free survival and explore relationships between laboratory measures of ventricular performance and functional status over time.

Methods: Exercise testing, echocardiography, B-type natriuretic peptide, functional health assessment, and medical history abstraction were repeated 9.4 ± 0.4 years after the Fontan Cross-Sectional Study (Fontan 1) and compared with previous values. Cox regression analysis explored risk factors for interim death or cardiac transplantation.

Results: From the original cohort of 546 subjects, 466 were contacted again, and 373 (80%) were enrolled at 21.2 ± 3.5 years of age. Among subjects with paired testing, the percent predicted maximum oxygen uptake decreased (69 ± 14% vs. 61 ± 16%; p < 0.001; n = 95), ejection fraction decreased (58 ± 11% vs. 55 ± 10%; p < 0.001; n = 259), and B-type natriuretic peptide increased (median [interquartile range] 13 [7 to 25] pg/mol vs. 18 [9 to 36] pg/mol; p < 0.001; n = 340). At latest follow-up, a lower Pediatric Quality of Life Inventory physical summary score was associated with poorer exercise performance (R² adjusted = 0.20; p < 0.001; n = 274). Cumulative complications since the Fontan procedure included additional cardiac surgery (32%), catheter intervention (62%), arrhythmia treatment (32%), thrombosis (12%), and protein-losing enteropathy (8%). Since Fontan 1, 54 subjects (10%) have received a heart transplant (n = 23) or died without transplantation (n = 31). The interval risk of death or/cardiac transplantation was associated with poorer ventricular performance and functional health status assessed at Fontan 1, but it was not associated with ventricular morphology, the subject's age, or the type of Fontan connection.

Conclusions: Interim transplant-free survival over 12 years in this Fontan cohort was 90% and was independent of ventricular morphology. Exercise performance decreased and was associated with worse functional health status. Future interventions might focus on preserving exercise capacity. (Relationship Between Functional Health Status and Ventricular Performance After Fontan-Pediatric Heart Network; NCT00132782).

Keywords: Fontan procedure; adult congenital heart disease; exercise; functional health status; single ventricle.

Figure 1. Laboratory testing of subjects enrolled in the Fontan 3 Study

Number of tests performed by enrolled subjects at Fontan 3 is shown in blue. Number of subjects with paired tests performed at both Fontan 1 and Fontan 3 are shown in white.

Central Illustration. Survival of Single Ventricle Patients after the Fontan Procedure

A) Transplant-free survival. Proportion of subjects in each of 3 competing mutually exclusive states: death, transplantation, and alive without transplantation for all 545 subjects. B) Transplant-free survival since Fontan 1 (with 95% confidence intervals) in all subjects with complete follow-up data. For improved resolution, the scale on the y-axis is limited to 0.85–1.0.