Low Ventricular Chamber Stiffness Identifies a High-Risk Eccentric Remodeling Phenotype in the Fontan Circulation: A FORCE Registry Analysis.

BACKGROUND

Rising end-diastolic pressure in patients with a Fontan circulation has led to the hypothesis that circulatory failure is driven by progressive ventricular stiffening. However, end-diastolic pressure is influenced by loading conditions and extracardiac constraint and may not accurately reflect chamber stiffness. We aimed to characterize ventricular chamber stiffness using the end-diastolic pressure-volume relationship and examine its clinical and prognostic significance in patients with a Fontan circulation.

METHODS

In the FORCE registry (Fontan Outcomes Registry Using Clinical Examinations), chamber stiffness was quantified with the exponential coefficient β derived from single-beat end-diastolic pressure-volume relationship reconstruction using paired catheterization and cardiovascular magnetic resonance data. The β values were standardized as body surface area- and sex-based Z scores and related to clinical characteristics, ventricular remodeling, and a composite adverse outcome (death, transplantation listing, sustained atrial or ventricular arrhythmias, protein-losing enteropathy, or plastic bronchitis).

RESULTS

Among 814 patients (median age, 14.7 years), median β was 0.034 mL-1 (0.025-0.046). Lower β Z score was associated with dominant right ventricle, eccentric remodeling with reduced ejection fraction, increased collateral flow and intracardiac recirculation, greater symptom burden, and higher arrhythmia prevalence, despite similar filling pressures. Over a median follow-up of 2.7 years (0.9-6.1 years), lower β Z score independently predicted adverse outcomes (adjusted hazard ratio, 1.30 per 1-SD decrease [95% CI 1.04-1.61]). A β Z score <-0.71, β<0.025 mL-1, or body surface area-indexed end-diastolic volume >103 mL/m2 showed similarly modest discrimination for adverse outcomes overall (area under the curve, 0.59), with greater discrimination in dominant right ventricles.

CONCLUSIONS

Contrary to prevailing assumptions, lower rather than higher chamber stiffness was associated with adverse Fontan outcomes, identifying a high-compliance phenotype characterized by ventricular dilation and eccentric remodeling. These findings suggest that, in the contemporary FORCE cohort, Fontan failure might be more closely associated with this remodeling phenotype than with progressive stiffening.