Genotyping permits family screening and affects risk stratification in patients with nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD), but its results are unfavorable in a sizable proportion of individuals, preventing its mainstream use. For a study, researchers sought to create and externally validate a score that estimated the likelihood that a genetic test result (G+) in DCM/LVSD would be positive.

In 1,015 genotyped DCM/LVSD patients of clinical, electrocardiographic, and echocardiographic data were gathered. The Madrid Genotype Score was produced by summing the independent predictors of G+ that were found using multivariable logistic regression analysis. About 1,097 genotyped patients from the Maastricht and Trieste registries made up the external validation sample.

Individuals from the derivation and validation cohorts had a G+ result in 377 (37%) and 289 (26%) patients. In the derivation cohort, skeletal myopathy (OR: 3.42; 95% CI: 1.60-7.31; P = 0.001), low electrocardiogram voltage in peripheral leads  (OR: 3.61; 95% CI: 2.38-5.49; P < 0.001), family history of DCM (OR: 2.29; 95% CI: 1.73-3.04; P < 0.001), absence of hypertension (OR: 2.28; 95% CI: 1.67-3.13; P < 0.001), and absence of left bundle branch block (OR: 3.58; 95% CI: 2.57-5.01; P < 0.001) were all independent predictors of a G+ result, as well as low electrocardiogram voltage in peripheral leads (OR: 3.61; 95% CI: 2.38-5.49; P < 0.001) and low electrocardiogram voltage overall. When all indicators were absent, the projected G+ score ranged from 3% to 79%, with just ≥4 predictors. A C-statistic of 0.74 (95% CI: 0.71-0.77) and a calibration slope of 0.94 (95% CI: 0.80-1.10) were given via internal validation. In the external validation cohort, the C-statistic was 0.74 (95% CI: 0.71-0.78).

A G+ result in DCM/LVSD may be accurately predicted using the Madrid Genotype Score.

Reference: jacc.org/doi/10.1016/j.jacc.2022.06.040