Hypertrophy regression with N-acetylcysteine in hypertrophic cardiomyopathy (HALT-HCM) a randomized, placebo-controlled, double-blind pilot study

Ali J. Marian, Yanli Tan, Lili Li, Jeffrey Chang, Petros Syrris, Manouchehr Hessabi, Mohammad H. Rahbar, James T. Willerson, Benjamin Y. Cheong, Chia Ying Liu, Neal S. Kleiman, David A. Bluemke, Sherif F. Nagueh

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Rationale:Hypertrophiccardiomyopathy(HCM)isageneticparadigmofcardiachypertrophy.Cardiachypertrophy and interstitial fibrosis are important risk factors for sudden death and morbidity in HCM. Oxidative stress is implicated in the pathogenesis of cardiac hypertrophy and fibrosis. Treatment with antioxidant N-acetylcysteine (NAC) reverses cardiac hypertrophy and fibrosis in animal models of HCM. Objective: To determine effect sizes of NAC on indices of cardiac hypertrophy and fibrosis in patients with established HCM. MethodsandResults:HALT-HCM(HypertrophyRegressionWithN-AcetylcysteineinHypertrophicCardiomyopathy) is a double-blind, randomized, sex-matched, placebo-controlled single-center pilot study in patients with HCM. Patients with HCM, who had a left ventricular wall thickness of ≥15 mm, were randomized either to a placebo or to NAC (1:2 ratio, respectively). NAC was titrated ≤2.4 g per day. Clinical evaluation, blood chemistry, and 6-minute walk test were performed every 3 months, and electrocardiography, echocardiography, and cardiac magnetic resonance imaging, the latter whenever not contraindicated, before and after 12 months of treatment. Eighty-five of 232 screened patients met the eligibility criteria, 42 agreed to participate; 29 were randomized to NAC and 13 to placebo groups. Demographic, echocardiographic, and cardiac magnetic resonance imaging phenotypes at the baseline between the 2 groups were similar. WSE in 38 patients identified a spectrum of 42 pathogenic variants in genes implicated in HCM in 26 participants. Twenty-four patients in the NAC group and 11 in the placebo group completed the study. Six severe adverse events occurred in the NAC group but were considered unrelated to NAC. The effect sizes of NAC on the clinical phenotype, echocardiographic, and cardiac magnetic resonance imaging indices of cardiac hypertrophy, function, and extent of late gadolinium enhancement-a surrogate for fibrosis-were small. Conclusions: Treatment with NAC for 12 months had small effect sizes on indices of cardiac hypertrophy or fibrosis. The small sample size of the HALT-HCM study hinders from making firm conclusions about efficacy of NAC in HCM.

Original languageEnglish (US)
Pages (from-to)1109-1118
Number of pages10
JournalCirculation Research
Volume122
Issue number8
DOIs
StatePublished - 2018

Keywords

  • Acetylcysteine cardiomyopathy
  • Cardiac fibrosis hypertrophy
  • Hypertrophic death
  • Sudden

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Hypertrophy regression with N-acetylcysteine in hypertrophic cardiomyopathy (HALT-HCM) a randomized, placebo-controlled, double-blind pilot study'. Together they form a unique fingerprint.

Cite this