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 1 – Flowchart of the systematic review. Number of articles excluding duplicates = 809 Excluded by the title and according to inclusion and exclusion criteria = 411 Number of articles for reading the abstract = 398 Number of articles for reading in full text = 123 Number of articles elegible for the analysis = 20 Number of articles used in the meta-analysis = 21 Additional article identified through review of references = 1 Excluded by the abstract and according to inclusion and exclusion criteria = 275 Excluded after full-text reading and according to inclusion and exclusion criteria and after assessment of methodological quality = 102 were selected, including 14 prospective and 7 retrospective studies, comprising 14,901 patients (age, 45 ± 16 years; 62.8%males). 11-14,17-33 The main characteristics of the included studies are shown in Table 2. Myocardial fibrosis The systematic review selected 5 articles that correlated the presence of fibrosis on cardiac MRI with severe arrhythmic outcomes. One of them was excluded from the meta-analysis because all the patients who had events had myocardial fibrosis using the MRI, making it impossible to calculate the measure of effect. 24 Among the four remaining studies involving 2549 patients, the presence of fibrosis was correlated with events equivalent to SD in two studies; 14,29 however, this only occurred in the univariate analysis of the other two. 32,33 In the meta-analysis, we found a significant probability of severe arrhythmic outcomes in the presence of this variable (RR, 3.43; 95% CI, 1.95-6.03). We highlighted the absence of heterogeneity in the Forest plot and the RR, which was the highest among all the other markers evaluated (Figures 2A and 3). The funnel plot for myocardial fibrosis is shown in figure 2B. Meta-analysis of classic RMs As shown in Figure 3, the following classic RMs demonstrated an association with the outcomes studied: family history of SD (13 studies – 9815 patients; RR, 1.75; 95% CI, 1.39‑2.20); severe left ventricular hypertrophy (11 studies – 5501 patients; RR, 1.86; 95%CI, 1.26-2.74); unexplained syncope (12 studies – 10064 patients; RR, 2.27; 95% CI, 1.69-3.07); NSVT on 24‑hour Holter monitoring (14 studies – 9421 patients; RR, 2.79; 95% CI, 2.29-3.41); and ABPRE (6 studies – 3061 patients; RR, 1.53; 95% CI, 1.12-2.08). In our analysis, the only RISK MARKER that showed no correlation with serious arrhythmic outcomes was LVOTO (5 studies – 4762 patients; RR, 1.72; 95% CI, 0.97-3.02). This may have been influenced by the small number of studies involved in the combined analysis. It should be emphasized that the inclusion of this marker in the stratification of SD has always been a matter of debate. When we evaluated the heterogeneity in all the RMs, we observed that only severe left ventricular hypertrophy was significant (I 2 = 75%, p < 0.01), although we emphasize that the random effect model used in the meta-analysis already had mitigated this aspect. The Egger´s test also points to a publication bias for this RISK MARKER (p = 0.002) We did not observe any publication bias by Egger's test or by the funnel plot for the other classic RMs. Based on these results, it seems plausible that all classic RMs can still be used in SD stratification in HCM, except for LVOTO. Discussion This systematic review and meta-analysis shows the importance of a broad approach in SD risk stratification in patients with HCM, including myocardial fibrosis assessment. The evaluation of patients with HCMmay include multiple complementary examinations in an attempt to predict SD. 283