Cardiac Remodeling in Subclinical Hypertrophic Cardiomyopathy: The VANISH Randomized Clinical Trial

Area of Science:

• Cardiology
• Genetics
• Pharmacology

Background:

• Early-stage sarcomeric hypertrophic cardiomyopathy (HCM) involves cardiac remodeling.
• Genetic testing identifies individuals at risk for subclinical HCM.
• Valsartan has shown potential in managing cardiac remodeling in HCM.

Purpose of the Study:

• To evaluate valsartan's efficacy in modifying disease development in subclinical HCM.
• To characterize short-term phenotypic progression in sarcomere variant carriers with subclinical HCM.

Main Methods:

• A multicenter, double-blind, placebo-controlled trial (VANISH) with 2-year follow-up.
• Included sarcomere variant carriers with early phenotypic manifestations but no left ventricular hypertrophy (LVH).
• Primary outcome: composite z score of cardiac remodeling parameters; secondary outcomes: phenotypic progression markers.

Main Results:

• Valsartan showed no statistically significant effect on cardiac remodeling compared to placebo (composite z score change: -0.01; P=.92).
• Modest 2-year phenotypic progression observed, with a mild increase in left atrial volume (3.5 mL/m2; P=.002).
• Nine participants (26%) developed increased left ventricular wall thickness, with 6 (18%) progressing to overt HCM. Higher baseline left atrial volume index and interventricular septum thickness were associated with HCM development.

Conclusions:

• Valsartan did not demonstrate efficacy in slowing the progression of subclinical HCM in this exploratory cohort.
• Minimal cardiac remodeling changes were observed, yet a significant proportion progressed to overt disease.
• Baseline interventricular septum thickness and left atrial volume index predict disease transition, emphasizing the need for longitudinal monitoring and further research into disease penetrance factors.