TY - JOUR
T1 - Hypertrophy regression with N-acetylcysteine in hypertrophic cardiomyopathy (HALT-HCM) a randomized, placebo-controlled, double-blind pilot study
AU - Marian, Ali J.
AU - Tan, Yanli
AU - Li, Lili
AU - Chang, Jeffrey
AU - Syrris, Petros
AU - Hessabi, Manouchehr
AU - Rahbar, Mohammad H.
AU - Willerson, James T.
AU - Cheong, Benjamin Y.
AU - Liu, Chia Ying
AU - Kleiman, Neal S.
AU - Bluemke, David A.
AU - Nagueh, Sherif F.
N1 - Funding Information:
This work was supported, in part, by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute (R34 HL105563, R01 HL088498, and 1R01HL132401), Leducq Foundation (14 CVD 03), the Ewing Halsell Foundation, George and Mary Josephine Hamman Foundation, and TexGen Fund from Greater Houston Community Foundation.
Publisher Copyright:
© 2018 American Heart Association, Inc.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Acetylcysteine cardiomyopathy
KW - Cardiac fibrosis hypertrophy
KW - Hypertrophic death
KW - Sudden
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U2 - 10.1161/CIRCRESAHA.117.312647
DO - 10.1161/CIRCRESAHA.117.312647
M3 - Article
C2 - 29540445
AN - SCOPUS:85052091909
VL - 122
SP - 1109
EP - 1118
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 8
ER -