ABC | Volume 112, Nº3, March 2019

Original Article Bittencourt et al Myocardial fibrosis in hypertrophic cardiomyopathy Arq Bras Cardiol. 2019; 112(3):281-289 Figure 2 – A. Forest plot of myocardial fibrosis and relative risk of the severe arrhythmic outcomes. B. Funnel plot of myocardial fibrosis to evaluate for publication bias. TE: estimated treatment effect; seTE: standard error of treatment estimate; RR: relative risk; 95%CI: 95% confidence interval. 0.0 0.2 0.4 0.6 0.8 0.5 1.0 1.0 2.0 5.0 Risk Ratio Standard Error 10.0 20.0 0.1 0.5 1 2 10 1.16 2.31 1.09 1.15 0.3564 1.0813 0.7688 0.7751 3.20 10.10 2.98 3.15 [1.59; 6.44] [1.21; 84.08] [0.66; 13.45] [0.69; 14.39] 65.1% 7.1% 14.0% 13.8% 65.1% 7.1% 14.0% 13.8% 3.43 100.0% -- -- 100.0% [1.95; 6.03] [1.95; 6.03] 3.43 Chan et al., 2014 Klopotowski et al., 2016 Ismail et al., 2014 O’ Hanlon R et al., 2010 Fixed effect model Random effects model Heterogeneity: I 2 = 0%, τ 2 = 0, p = 0.78 Study TE seTE Risk Ratio RR 95%-Cl Weight (fixed) Weight (random) A B A meta-analysis published by Briasoulis et al., 40 addressing only myocardial fibrosis, found similar results. However, one article used in the analyses did not allow a precise calculation of an effect measure because the group without fibrosis did not have any event. 24 Our option was to remove it, because we understood this would compromise the statistical analysis. It stands out that this meta-analysis included the article of Klopotowski et al. 29 with 328 patients and updated other RMs. We consider that this finding is of much clinical relevance, as the latest guidelines on the subject do not address the presence of fibrosis as an RM. In its latest document regarding the disease, the European Society of Cardiology based the indication of ICD placement on using a risk calculator (HCM‑Risk SCD) created to provide more accurate stratifications. 2 Based on a cohort, the derived model used the parameters of age, maximum ventricular thickness, LVOTO, left atrial diameter, family history of SD, presence of NSVT, and unexplained syncope. 30 Subsequent studies showed conflicting results regarding the calculator., Perhaps, the fact that it does not assess fibrosis may be a limitation. Regarding the other findings, we observed that all classic RMs correlated with the occurrence of the outcomes studied, except for LVOTO. In contrast to what has been observed in a previously published meta-analysis, our findings do not indicate that LVOTOmay be associated with severe arrhythmic outcomes. This was probably because of the smaller number of patients used in our analysis and the inclusion of two recent studies of which results do not indicate the association between this marker and SD. The methods that investigated possible publication bias only found significant result for severe left ventricular hypertrophy. However, the clinical relevance of this risk marker has already been documented in several studies and emphasized in the last guidelines. 1,2,11,18,43 The limitations of our study include: (1) the inclusion and exclusion criteria, diagnostic methods, and definitions varied discreetly among the different studies; (2) the data of the patients from the same institution may have overlapped, although this did not occur in most of the analyses; (3) the absence of randomized trials may also be considered a relative 285