Escobar-Lopez, LuisOchoa, Juan PabloRoyuela, AnaVerdonschot, Job A JDal Ferro, MatteoEspinosa, Maria AngelesSabater-Molina, MariaGallego-Delgado, MariaLarrañaga-Moreira, Jose MGarcia-Pinilla, Jose MBasurte-Elorz, Maria TeresaRodríguez-Palomares, José FCliment, VicenteBermudez-Jimenez, Francisco JMogollón-Jiménez, María VictoriaLopez, JavierPeña-Peña, Maria LuisaGarcia-Alvarez, AnaLópez-Abel, BernardoRipoll-Vera, TomasPalomino-Doza, JulianBayes-Genis, AntoniBrugada, RamonIdiazabal, UxuaMirelis, Jesus GDominguez, FernandoHenkens, Michiel T H MKrapels, Ingrid P CBrunner, Han GPaldino, AlessiaZaffalon, DeniseMestroni, LuisaSinagra, GianfrancoHeymans, Stephane R BMerlo, MarcoGarcia-Pavia, Pablo2023-03-172023-03-172022-09-20J Am Coll Cardiol. 2022 Sep 20;80(12):1115-1126http://hdl.handle.net/20.500.12105/15675Although 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. This study sought to develop and externally validate a score that predicts the probability for a positive genetic test result (G+) in DCM/LVSD. 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. 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). The Madrid Genotype Score is an accurate tool to predict a G+ result in DCM/LVSD.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Cardiomyopathy, DilatedVentricular Dysfunction, LeftCohort StudiesGenotypeHumansRisk FactorsAttribution-NonCommercial-NoDerivatives 4.0 Internacional361091068012111510.1016/j.jacc.2022.06.0401558-3597Journal of the American College of Cardiologyopen access