A study published in the Journal of the American College of Cardiology found that the Madrid Genotype Score is an accurate predictor of a positive genetic test for nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD).
To formulate the Madrid Genotype Score, a derivation cohort of 1015 patients with nonischemic DCM/LVSD were recruited between 2015 and 2020 at 20 hospitals in Spain. All participants received genetic testing and 2-dimensional echocardiography. A total of 18 prespecified easy to obtain clinical, electrocardiographic, and echocardiographic candidate features were tested for their power to predict nonischemic DCM/LVSD. The final score was tested using the validation cohort which comprised 647 unrelated probands from the Maastricht Cardiomyopathy Registry and 450 from the Trieste Cardiomyopathy registry.
The derivation sample included individuals with a mean age of 50.06 (SD, 14.49) years, 68.47% were men, 47.29% had a family history of DCM, 12.22% had a family history of sudden cardiac death (SCD), 52.8% had a DCM phenotype, and 47.2% had a LVSD phenotype.
In the univariate analysis, a positive genetic test result was associated with a younger age at diagnosis, hypertension, diabetes, smoking, hypercholesterolemia, skeletal muscle disease, DCM family history, first-degree relative with SCD, non-first-degree relative with SCD, left bundle branch block, limb lead QRS voltage, and precordial lead QRS voltage.
In the multivariate analysis, low limb lead QRS voltage (odds ratio [OR], 3.64; 95% CI, 2.30-5.76; P <.001), absence of left bundle branch block (OR, 3.55; 95% CI, 2.52-4.99; P <.001), skeletal muscle disease (OR, 3.11; 95% CI, 1.33-7.28; P =.009), family history of DCM (OR, 2.13; 95% CI, 1.58-2.87; P <.001), and absence of hypertension (OR, 2.09; 95% CI, 1.48-2.95; P <.001) remained significant predictors for a positive genetic test.
In the validation sample, all 5 of these predictors remained significantly associated with a positive genetic test (OR range, 2.09-5.15; all P £.022).
The estimated probability of a positive genetic test was calculated using a derived equation.
The equation had a C-statistic of 0.753 during calibration and 0.742 during optimization. After removing 134 probands for a sensitivity analysis, the equation had a C-statistic of 0.740 during calibration and 0.735 during optimization.
The utility of this score among the general population may be limited as the majority of the derivation cohort were recruited from Inherited Cardiac Diseases Units.
“The Madrid Genotype Score predicts a positive genetic test result in nonischemic DCM/LVSD with good precision and discrimination,” the study authors wrote. “Thus, it represents an easy-to-use tool to direct genetic testing toward patients and families with a higher probability of a positive genetic test result to improve the diagnostic yield of genetic testing.”
Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Escobar-Lopez L, Ochoa JP, Royuela A, et al. Clinical risk score to predict pathogenic genotypes in patients with dilated cardiomyopathy. J Am Coll Cardiol. Published online September 12, 2022. doi:10.1016/j.jacc.2022.06.040