Journal Article

The Design of the Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) Trial

Solomon, Scott D., MacRae, Calum A., Desai, Akshay S., Shi, Ling, Ho, Carolyn Y., McMurray, John J.V., Cirino, Allison L., Day, Sharlene M., Colan, Steven D., Orav, E. John, Lipshultz, Steven E., Braunwald, Eugene

2017

Overview

Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations, resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of sudden cardiac death and heart failure. Studies in mouse models of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human studies using ARBs for HCM have targeted heterogeneous adult cohorts with well-established disease. The VANISH trial is testing the safety and feasibility of disease-modifying therapy with an ARB in genotyped HCM patients with early disease. A randomized, placebo-controlled, double-blind clinical trial is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM and no/minimal symptoms, or those with early phenotypic manifestations but no LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily (depending on age and weight) or placebo. The primary endpoint is a composite of 9 z-scores in domains representing myocardial injury/hemodynamic stress, cardiac morphology, and function. Total z-scores reflecting change from baseline to final visits will be compared between treatment groups. Secondary endpoints will assess the impact of treatment on mutation carriers without LVH, and analyze the influence of age, sex, and genotype. The VANISH trial is testing a new strategy of disease modification for treating sarcomere mutation carriers with early HCM, and those at risk for its development. In addition, further insight into disease mechanisms, response to therapy, and phenotypic evolution will be gained.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Adolescent / Adult / Angiotensin / Angiotensin II Type 1 Receptor Blockers - therapeutic use / Animal models / Cardiomyopathy / Cardiomyopathy, Hypertrophic - drug therapy / Cardiomyopathy, Hypertrophic - genetics / Cardiomyopathy, Hypertrophic - pathology / Child / Clinical trials / Control methods / Disease control / Double-Blind Method / Electrocardiography / Evolutionary design method / Fibrosis / Genotype / Health risks / Heart / Heart diseases / Heart failure / Humans / Hypertrophy / Hypertrophy, Left Ventricular - etiology / Middle Aged / Mutation / Patients / Sarcomeres - genetics / Studies / Therapy / Valsartan - therapeutic use / Ventricle / Young Adult