Longitudinal changes in ventricular size and function are associated with death and transplantation late after the Fontan operation.

BACKGROUND: Cross-sectional studies have reported that ventricular dilation and dysfunction are associated with adverse clinical outcome in Fontan patients; however, longitudinal changes and their relationship with outcome are not known. METHODS: This was a single-center retrospective analysis of Fontan patients with at least 2 cardiovascular magnetic resonance (CMR) scans without intervening interventions. Serial measures of end-diastolic volume index (EDVI), end-systolic volume index (ESVI), ejection fraction (EF), indexed mass (massi), mass-to-volume ratio, and end-systolic wall stress (ESWS) were used to estimate within-patient change over time. Changes were compared for those with and without a composite outcome (death, heart transplant, or transplant listing) as well as between patients with left (LV) and right ventricular (RV) dominance. RESULTS: Data from 156 patients were analyzed with a mean age at 1st CMR of 17.8 ± 9.6 years. 490 CMRs were included with median of 3 CMRs/patient (range 2-9). On regression analysis with mixed effects models, volumes and ESWS increased, while mass, mass-to-volume ratio, and EF decreased over time. With a median follow-up of 10.2 years, 14% met the composite outcome. Those with the composite outcome had a greater increase in EDVI compared to those without (4.7 vs. 0.8 ml/BSA1.3/year). Compared with LV dominance, RV dominance was associated with a greater increase in ESVI (1.4 vs. 0.5 ml/BSA1.3/year), a greater decrease in EF (- 0.61%/year vs. - 0.24%/year), and a higher rate of the composite outcome (21% vs. 8%). CONCLUSIONS: Ventricles in the Fontan circulation exhibit a steady decline in performance with an increase in EDVI, ESVI, and ESWS, and decrease in EF, mass index, and mass-to-volume ratio. Those with death or need for heart transplantation have a faster increase in EDVI. Patients with rapid increase in EDVI (> 5 ml/BSA1.3/year) may be at a higher risk of adverse outcomes and may benefit from closer surveillance. RV dominance is associated with worse clinical outcomes and remodeling compared to LV dominance.

Characterization of Circulating and Urinary Biomarkers in the Fontan Circulation and Their Correlation With Cardiac Imaging.

Several circulating biomarkers have been found to play a role in the surveillance and risk stratification of heart failure without congenital heart disease, but these have not been widely studied in patients with single ventricles palliated with a Fontan operation. Imaging predictors of worse outcomes in this population include ventricular dilation and dysfunction. Patients who weighed >30 kg with a Fontan circulation referred for cardiac magnetic resonance imaging were invited to participate in the study. Blood and urine samples were obtained at the time of imaging and multiple conventional and novel biomarkers were measured. A total of 82 patients with a median age of 18 years were enrolled. Among the novel biomarkers, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T had the strongest correlation with ventricular dilation and dysfunction. NT-ProBNP >100 pg/ml has a sensitivity of 91% for the detection of significant ventricular dilation (end-diastolic volume >120 ml/body surface area1.3) and 82% for detection of ejection fraction <50%. The urinary neutrophil gelatinase-associated lipocalin-2 to creatinine ratio correlated with ejection fraction and estimated glomerular filteration rate. In conclusion, abnormalities in biomarkers of heart failure are common in ambulatory, largely asymptomatic patients with Fontan circulation. NT-ProBNP may serve as a sensitive marker for the identification of patients with significant ventricular dilation or dysfunction. Further work is needed to understand how these easily measured circulating biomarkers may be integrated into clinical care.