Predictors of the identification of clinically relevant genetic variants in dilated cardiomyopathy in a sample of the brazilian population

Abstract Introduction Dilated cardiomyopathy is associated with clinically relevant variants in up to 40% of cases. The Madrid Genotype Score optimises the yield of genetic testing by evaluating variables such as the absence of left bundle branch block (LBBB), absence of hypertension, low voltage on ECG, family history of dilated cardiomyopathy, and skeletal myopathy. However, it was developed in an European population. Purpose To evaluate the effectiveness of the Madrid Genotype Score and assess predictors for the identification of clinically relevant variants in a Brazilian cohort of patients with dilated cardiomyopathy. Methods This observational, retrospective study assessed clinical characteristics and complementary test results of patients with dilated cardiomyopathy who underwent genetic testing. Patients with a left ventricular ejection fraction 50% and a diagnosis age greater than 14 years were included. They were divided into two groups: presence or absence of clinically relevant variants. The Madrid Genotype Score was applied to all patients, and univariate and multivariate regressions were performed to identify statistically significant predictors. Results A total of 749 patients were evaluated, of whom 441 (58.9%) were male. Clinically relevant variants were identified in 168 (22.4%) patients. The yield by Madrid Genotype Score in this population showed an increased likelihood of identifying clinically relevant variants with higher scores, albeit at a lower rate than in the original population (Figure 1.A). In multivariate regression, the following independent variables were associated with the identification of clinically relevant variations: non-Black (OR: 2.1, CI: 1.02–4.2), NYHA III-IV (OR: 1.8, CI: 1.01–3.3), absence of left bundle branch block (OR: 3.9, CI: 2.1–7.4), and presence of atrial fibrillation (OR: 1.9, CI: 1.03–3.86) (Figure 1.B). The ROC curve demonstrated a predicted probability of 0.697 (Figure 1.C). Conclusions The Madrid Genotype Score increased the predictive effectiveness for identifying clinically relevant variations in a sample of the Brazilian population with dilated cardiomyopathy, albeit at a lower rate than in the original study. Predictors for the presence of clinically relevant variants included the absence of LBBB, more severe symptoms (NYHA III-IV), presence of atrial fibrillation, and non-Black. These findings suggest potential genetic differences between Brazilian and European populations with dilated cardiomyopathy.Figure 1