Cardiac function and the effect of heart failure treatment in patients with genotype-positive dilated cardiomyopathy

Dilated and non-dilated left ventricular cardiomyopathy (DCM/NDLVC) are commonly caused by pathogenic genetic variants. Heart failure (HF) treatment recommendations for genotype-positive patients with early disease are lacking.

We aimed to assess HF outcome in HF treated and not treated DCM/NDLVC genotype-positive patients in early disease stages.

Genotype-positive DCM/NDLVC patients were enrolled in an observational study. We recorded the use of HF medication and analyzed echocardiographic examinations at baseline and last follow-up. Patients were stratified according to left ventricular ejection fraction (LVEF) as preserved (≥50%), mildly reduced (40-49%), and reduced (<40%). HF outcome was defined as decline of LVEF <40% in patients with preserved/mildly reduced LVEF at baseline. In patients with mildly reduced LVEF, all echocardiographic examinations were analyzed by mixed model regression analyses stratified by HF treated and untreated. Genotype-specific analyses were performed for high-risk and low-risk genotypes.

712 patients were followed for 3.1 years (mean age 40 years, 52% females, 20% probands). In 407 patients with preserved/mildly reduced LVEF, 24 (6%) patients declined to LVEF <40%. In 130 patients with mildly reduced LVEF, HF treatment was associated with a 1.8 percentage points (95% CI, 0.7 to 2.9; P=0.01) higher LVEF, and 2.4 percentage points (95% CI, 0.3 to 4.4; P=0.02) higher LVEF in high-risk genotypes.

In genotype-positive DCM/NDLVC patients with mildly reduced LVEF, we found a 1.8 percentage points higher LVEF in those receiving HF treatment. This should be considered when planning larger trials for guideline-directed HF treatment.