Genetic testing in hypertrophic cardiomyopathy (HCM) is central to cascade screening and risk stratification but may require prioritization due to financial and logistical constraints. This retrospective multicenter analysis included 466 patients with HCM. The study was published in the Journal of The American Heart Association. Genotype positivity, defined as pathogenic or likely pathogenic variants in nine major sarcomere-encoding genes, was identified in 30.3% of patients.

Candidate electrocardiographic (ECG) variables were selected using multivariable logistic regression with bootstrap aggregation. Genotype-positive patients more frequently exhibited atrial fibrillation, intraventricular conduction disturbance, lower prevalence of high voltage, and abnormal T-wave inversion in precordial leads. These parameters were incorporated into a novel Mayo-ECG score.

The Mayo-ECG score stratified genotype positivity from 7.1% (score ≤−1) to 91.4% (score ≥4). Discriminative performance was higher than the conventional Mayo score (area under the receiver operating characteristic curve [AUC] 0.81 [95% CI 0.77–0.85] versus 0.76 [95% CI 0.71–0.81]; P=0.005), with improved model fit (Akaike’s information criterion 439 versus 479). Internal cross-validation demonstrated consistent calibration.

Limitations include lack of external validation, retrospective design, limited ECG parameters, potential referral bias, and restriction to sarcomeric genes.

In this cohort, integrating ECG variables improved genotype prediction in HCM. Prospective validation in diverse populations is needed to confirm broader clinical utility.