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 3 – Forest plot of the risk markers and the relative risk of severe arrhythmic outcomes:A: unexplained syncope; B: severe ventricular hypertrophy; C: family history of sudden death; D: non-sustained ventricular tachycardia; E: abnormal blood pressure response to exercise; F: left ventricular outflow tract obstruction. TE: estimated treatment effect; seTE: standard error of treatment estimate; RR: relative risk; 95%CI: 95% confidence interval. 0.1 0.5 2 1 10 0.1 0.5 2 1 10 0.1 0.5 2 1 10 0.82 2.27 7.8% 10.0% 11.3% 10.5% 13.5% 1.5% 9.6% 4.2% 9.9% 3.8% 14.9% 7.2% 3.4% 10.5% 8.7% 18.6% 0.6% 7.1% 1.9% 7.6% 1.6% 30.2% 41.1% 1.4% 100.0% 100.0% 2.08 4.30 3.80 0.70 1.75 0.93 1.11 1.81 2.33 5.60 0.84 2.44 2.27 0.3196 0.2753 0.3028 0.2064 1.1748 0.3340 0.6513 0.3239 0.6981 0.1620 0.4396 0.7497 0.73 1.46 1.34 0.56 0.10 0.59 0.84 1.72 –0.17 0.3975 0.53 0.4757 1.06 0.3260 1.28 0.8649 1.86 0.1994 0.57 0.0381 0.00 0.3680 0.35 0.6224 1.29 1.0189 1.28 0.7425 0.48 0.3196 0.63 0.2531 0.58 0.6796 –0.43 0.2108 1.20 0.1517 0.65 1.1806 0.88 1.1235 1.29 0.4302 0.05 0.4180 –0.26 0.5980 0.76 0.1475 0.57 0.4341 0.34 0.7495 –0.29 0.3890 –0.11 –0.36 –0.08 [1.21; 4.25] 1.70 0.8% 10.0% [0.78; 3.71] 1.88 6.0% 8.9% [1.00; 3.52] 1.79 9.6% 11.9% [1.09; 2.94] 0.65 1.3% 2.6% [0.17; 2.46] 3.31 13.9% 14.3% [2.19; 5.00] 1.91 26.8% 18.5% [1.42; 2.58] 2.40 0.4% 0.9% [0.24; 24.27] 3.62 0.5% 1.0% [0.40; 32.71] 1.05 3.3% 5.8% [0.45; 2.44] 0.77 3.5% 6.0% [0.34; 1.75] 2.14 1.7% 3.3% [0.66; 6.91] 1.76 28.4% 18.8% [1.32; 2.35] 1.40 3.3% 5.7% [0.60; 3.28] 0.75 1.1% 2.2% [0.17; 3.26] 0.90 0.9% 10.2% [0.42; 1.93] 3.61 1.2% 11.5% [1.91; 6.84] 6.40 0.2% 4.0% [1.17; 34.87] 1.76 3.3% 14.3% [1.19; 2.60] 1.00 91.2% 16.6% [0.93; 1.08] 1.42 1.0% 10.6% [0.69; 2.92] 3.65 0.3% 6.3% [1.08; 12.36] 3.60 0.1% 3.1% [0.49; 26.52] 1.62 0.2% 5.0% [0.38; 6.94] 2.90 0.6% 8.5% [1.14; 7.37] [1.21; 3.57] [2.38; 7.78] [2.54; 5.69] [0.07; 7.00] [0.91; 3.37] [0.26; 3.32] [0.59; 2.09] [0.46; 7.11] [1.69; 3.20] [2.37; 13.25] [0.19; 3.65] [2.05; 2.91] [1.69; 3.07] -- -- 100.0% 100.0% 1.06 1.86 [0.99; 1.14] [1.26; 2.74] -- -- 100.0% 100.0% 1.85 1.75 [1.58; 2.15] [1.39; 2.20] -- -- Elliott PM et al., 2006 Gimeno JR et al., 2009 Kofflard MJ et al., 2003 Maron BJ et al., 2007 Rubinshtein R et al., 2010 Spirito P et al., 2009 Syska P et al., 2010 Magnusson et al., 2016 Klopotoeski et al., 2015 Mahony et al., 2014 Debonmaire et al., 2015 Ismail et al., 2014 Elliott PM et al., 2006 Gimeno JR et al., 2009 Kofflard MJ et al., 1993 Maron BJ et al., 2007 Michaelides AP et al., 2009 Chan et al., 2014 Syska P et al., 2010 Magnusson et al., 2016 Klopotoeski et al., 2015 Mahony et al., 2014 Debonmaire et al., 2015 Ismail et al., 2014 Elliott PM et al., 2006 Elliott PM et al., 2000 Gimeno JR et al., 2009 Maron BJ et al., 2007 Rubinshtein R et al., 2010 Rubinshtein R et al., 2010 Spirito P et al., 2000 Syska P et al., 2010 Magnusson et al., 2016 Klopotoeski et al., 2015 Debonmaire et al., 2015 Ismail et al., 2014 Fixed effect model Random effects model Heterogeneity: I 2 = 55%, τ 2 = 0.1291, p = 0.01 Fixed effect model Random effects model Heterogeneity: I 2 = 75%, τ 2 = 0.236, p < 0.01 Fixed effect model Random effects model Heterogeneity: I 2 = 36%, τ 2 = 0.0504, p = 0.10 Study TE seTE Risk Ratio RR 95%-Cl Weight (fixed) Weight (random) Study TE seTE Risk Ratio RR 95%-Cl Weight (fixed) Weight (random) Study TE seTE Risk Ratio RR 95%-Cl Weight (fixed) Weight (random) A B C limitation, but it is important to remember that the systematic review with meta-analysis has the capacity of minimizing this problem, bringing information from observational studies to a higher level of evidence; (4) myocardial fibrosis was analyzed in a few studies and in a binary manner, not quantitatively, although the latter has been gaining attention in recent publications. 14 Although the study of Chan et al., 14 which was used in this meta-analysis, provided quantitative information, we used only the RR for the presence or absence of fibrosis. 14 Another relevant issue for discussion, although not addressed in this study, which can be considered a limitation, is the cost of cardiac MRI. No cost-effectiveness analysis aimed at the investigation of fibrosis using MRI in patients with HCM has been conducted yet. Despite these limitations, we rely on the findings of our study because of its methodology, consistency of results (absence of heterogeneity in most analyses), and especially the close and well-known association between myocardial fibrosis and arrhythmias. And with the purpose of studying this association, it is important to emphasize that we chose to include only studies that evaluated outcomes equivalent to SD. Conclusions In summary, although it is very difficult to make clinical decisions of great relevance to patients based solely on information from observational studies, it is important to 286