Graphical Abstract.

In a primary prevention cohort of 94 LMNA genotype–positive patients without VA at baseline, VA incidence was as high as 20% after 4.6 years follow up. Individual patient disease progression by ECG and echocardiography was a strong predictor of subsequent VA, suggesting additional value to the previously described risk factors in current guidelines for primary preventive ICD implantation. Threshold values of LVEF <44% and PR interval >280 ms indicated transition to a more arrhythmogenic phenotype. ECG, electrocardiogram; ICD, implantable cardioverter defibrillator; LVEF, left ventricular ejection fraction; VA, ventricular arrhythmia.