The Madrid Genotype Score accurately predicted a positive genetic test in patients with dilated cardiomyopathy, achieving an external validation C-statistic of 0.74 (95% CI: 0.71-0.78).
Observational (n=2,112)
Yes
Does the Madrid Genotype Score predict a positive genetic test result in patients with nonischemic dilated cardiomyopathy or isolated left ventricular systolic dysfunction?
The Madrid Genotype Score, using five simple clinical and electrocardiographic variables, accurately predicts the probability of a positive genetic test in patients with dilated cardiomyopathy, which may help prioritize genetic testing.
Effect estimate: C-statistic 0.74 (95% CI 0.71-0.78)
BACKGROUND: Although genotyping allows family screening and influences risk-stratification in patients with nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD), its result is negative in a significant number of patients, limiting its widespread adoption. OBJECTIVES: This study sought to develop and externally validate a score that predicts the probability for a positive genetic test result (G+) in DCM/LVSD. METHODS: Clinical, electrocardiogram, and echocardiographic variables were collected in 1,015 genotyped patients from Spain with DCM/LVSD. Multivariable logistic regression analysis was used to identify variables independently predicting G+, which were summed to create the Madrid Genotype Score. The external validation sample comprised 1,097 genotyped patients from the Maastricht and Trieste registries. RESULTS: A G+ result was found in 377 (37%) and 289 (26%) patients from the derivation and validation cohorts, respectively. Independent predictors of a G+ result in the derivation cohort were: family history of DCM (OR: 2.29; 95% CI: 1.73-3.04; P < 0.001), low electrocardiogram voltage in peripheral leads (OR: 3.61; 95% CI: 2.38-5.49; P < 0.001), skeletal myopathy (OR: 3.42; 95% CI: 1.60-7.31; 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). A score containing these factors predicted a G+ result, ranging from 3% when all predictors were absent to 79% when ≥4 predictors were present. Internal validation provided 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). The C-statistic in the external validation cohort was 0.74 (95% CI: 0.71-0.78). CONCLUSIONS: The Madrid Genotype Score is an accurate tool to predict a G+ result in DCM/LVSD.
Escobar-López et al. (2022) conducted an observational in Nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD) (n=2,112). Madrid Genotype Score was evaluated on Positive genetic test result (G+) (C-statistic 0.74, 95% CI 0.71-0.78). The Madrid Genotype Score accurately predicted a positive genetic test in patients with dilated cardiomyopathy, achieving an external validation C-statistic of 0.74 (95% CI: 0.71-0.78).