ABC | Volume 112, Nº3, March 2019

Original Article Role of Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Systematic Review and Updated Meta-Analysis of Risk Markers for Sudden Death Marcelo Imbroinise Bittencour t, Samária Ali Cader, Denizar Vianna Araúj o, Ana Luiza Ferreira Salles, Felipe Neves de Albuquerque , Pedro Pimenta de Mello Spinet i, Denilson Campos de Albuquerqu e, R icardo Mourilhe-Roch a Hospital Universitário Pedro Ernesto da Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ – Brazil Mailing Address: Marcelo Imbroinise Bittencourt • Rua Dona Maria, 71 BL 1 Apto 902. Postal Code 20541-030, Vila Isabel, Rio de Janeiro, RJ – Brazil E-mail: mib@cardiol.br , marceloibittencourt@gmail.com Manuscript received April 04, 2018, revised manuscript July 05, 2018, accepted July 05, 2018 DOI: 10.5935/abc.20190045 Abstract Background: Hypertrophic cardiomyopathy (HCM) is associated with sudden death (SD). Myocardial fibrosis is reportedly correlated with SD. Objective: We performed a systematic review with meta-analysis, updating the risk markers (RMs) in HCM emphasizing myocardial fibrosis. Methods: We reviewed HCM studies that addressed severe arrhythmic outcomes and the certain RMs: SD family history, severe ventricular hypertrophy, unexplained syncope, non-sustained ventricular tachycardia (NSVT) on 24-hour Holter monitoring, abnormal blood pressure response to exercise (ABPRE), myocardial fibrosis and left ventricular outflow tract obstruction (LVOTO) in the MEDLINE, LILACS, and SciELO databases. We used relative risks (RRs) as an effect measure and random models for the analysis. The level of significance was set at p < 0.05. Results: Twenty-one studies were selected (14,901 patients aged 45 ± 16 years; men, 62.8%). Myocardial fibrosis was the major RISK MARKER (RR, 3.43; 95% CI, 1.95-6.03). The other RMs, except for LVOTO, were also predictors: SD family history (RR, 1.75; 95% CI, 1.39-2.20), severe ventricular hypertrophy (RR, 1.86; 95% CI, 1.26-2.74), unexplained syncope (RR, 2.27; 95% CI, 1.69-3.07), NSVT (RR, 2.79; 95% CI, 2.29‑3.41), and ABPRE (RR, 1.53; 95% CI, 1.12-2.08). Conclusions: We confirmed the association of myocardial fibrosis and other RMs with severe arrhythmic outcomes in HCM and emphasize the need for new prediction models in managing these patients. (Arq Bras Cardiol. 2019; 112(3):281-289) Keywords: Cardiomyopathy, Hypertrophic, Familial;Endomyocardial Fibrosis; Risk Factors; Death, Sudden,Cardiac; Review; Meta-Analsis. Introduction Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease characterized by ventricular hypertrophy in the absence of other conditions that cause heart overload. 1-3 It is the most common genetic disease, with a prevalence rate estimated at 1:500, affecting both men and women. Its presentation can vary from asymptomatic to more severe complications, such as sudden death (SD), which has an incidence rate of 1% per year. HCM is mainly responsible for SD in young and competitive athletes. 5-7 There is a discussion regarding how we should stratify SD and indicate implantable cardioverter-defibrillator (ICD) for the purpose of primary prevention of this disease. Strategies have been proposed to identify these patients, and classic risk markers (RMs), such as family history of SD, severe ventricular hypertrophy, unexplained syncope, non-sustained ventricular tachycardia (NSVT) on 24‑hour Holter monitoring, and abnormal blood pressure response to exercise (ABPRE), have been evaluated in several clinical studies. 13 As such, the pathophysiology of SD in HCM is not fully understood. Some factors seem to be involved, including the development of myocardial fibrosis. Studies that investigated myocardial fibrosis using magnetic resonance imaging (MRI) have shown correlations with severe outcomes. In a recent study, Chan et al. 14 found that a percentage of fibrosis > 15% of the left ventricular mass was associated with a twofold increase in the risk of SD in patients considered initially at low risk. 1 However, the detection of myocardial fibrosis using cardiac MRI continues to generate discussions among experts and is now considered only a risk modifier, as evidenced by the American College of Cardiology Foundation / American Heart Association Task Force on Practice Guidelines. 1 The reassessment of RMs, considering the presence of myocardial fibrosis, is fundamental to improve risk stratification. We performed a systematic review andmeta-analysis of observational studies that examined RMs in HCM, emphasizing the presence of fibrosis using cardiac MRI, to evaluate their statistical power in predicting SD. 281