Heart Failure with Recovered Ejection Fraction in Patients with Vinculin Loss-of-function Variants

Abstract

Predictors of myocardial recovery in heart failure (HF) are poorly understood. We explored if vinculin (VCL) variants are associated with myocardial recovery in dilated cardiomyopathy (DCM). Six infants with DCM with a VCL loss-of-function (LOF) variant were identified. Median age at diagnosis was 2 months, median LV ejection fraction was 24%, and median LV end-diastolic diameter z-score was 10.8. All patients received HF medications. Five patients (83%) showed normalization of LV function at a median age of 2.7 years. One patient progressed to end-stage HF requiring heart transplant. This case series identified a unique phenotype of HF with reduced ejection fraction at presentation that evolved to HF with recovered EF in over 80% of infant DCM cases with LOF VCL variants. These findings have prognostic implications for counseling and management of VCL-associated DCM and highlight a possible genetic basis for HF with recovered ejection fraction.

Keywords: Dilated cardiomyopathy; HFrEF; HFrecEF; Heart failure; Myocardial recovery; Vinculin.

Fig. 1

Left ventricular ejection fraction (LVEF) from diagnosis to last follow-up (n=84 echocardiograms from 6 patients). LVEF normalized in all patients except patient V who showed a progressive decline in LVEF

Fig. 2

Family pedigrees of patients harboring VCL variants. a Patient Ia, Ib - VCL, c.1639C>T, (p.Arg547X); b patient II—VCL, c.3115C>T, (p.Gln1039X); c patient III—VCL, c.2949del, (p.Lys983fs); d patient IV - VCL, c.670_671insG, (p.Glu224fs); e patient V—VCL, c.313C>T, (p.Arg105X). Square = male, circle = female; white = unaffected, black = DCM, grey = mild phenotype (arrhythmias or mild cardiac dysfunction); + genotype-positive for VCL variant, − genotype-negative for VCL variant