Body Mass Index, Valsartan, and Myocardial Remodeling in Early-Stage Hypertrophic Cardiomyopathy: A Secondary Analysis of the Randomized VANISH Trial.

BACKGROUND

Obesity is associated with adverse outcomes in overt hypertrophic cardiomyopathy, but the prevalence and impact of elevated body mass index (BMI) in early-stage hypertrophic cardiomyopathy is uncertain.

METHODS

In this post hoc analysis of the randomized VANISH (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) trial, participants were categorized according to baseline BMI (nonelevated or elevated [≥85th percentile if age <18 years; ≥25 kg/m2 if age ≥18 years]). Exercise capacity (peak oxygen uptake [milliliters per kilogram per minute]) and cardiac imaging parameters were evaluated by baseline BMI and 2-year change in BMI.

RESULTS

Among 171 (96%) participants (mean age, 23±10 years; 39% female sex; 97% White), 82 (48%) had nonelevated BMI and 89 (52%) had an elevated BMI. After covariate adjustment, higher baseline BMI was associated with lower peak oxygen uptake; lower left ventricular systolic and diastolic function; higher left ventricular mass; and higher atrial, ventricular, and extracellular volumes. Similarly, greater 2-year increases in BMI were associated with greater declines in peak oxygen uptake and greater increases in left ventricular mass. Participants with elevated BMI were more likely to develop late gadolinium enhancement over 2 years (adjusted odds ratio, 3.6 [95% CI, 1.1-11.9]; P=0.033). Valsartan appeared to modestly attenuate 2-year increases in body weight versus placebo (adjusted mean difference, -3.1% [95% CI, -6.2 to -0.1%]; P=0.042). Baseline BMI did not appear to modify the effect of valsartan on cardiac remodeling (Pinteraction=0.96).

CONCLUSIONS

Elevated BMI was common and associated with greater hypertrophic, eccentric, and fibrotic remodeling in early-stage hypertrophic cardiomyopathy. Two-year increases in BMI were associated with greater phenotypic progression. These findings suggest prevention and treatment of elevated BMI may attenuate hypertrophic cardiomyopathy progression.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01912534.