Exercise-induced ventricular arrhythmia improves cardiovascular risk stratification beyond SCORE2 in a large primary-prevention population

Background Exercise-induced ventricular arrhythmia (EIVA) is frequently observed during exercise testing, yet its long-term prognostic significance in individuals without established cardiovascular disease remains uncertain and it is not routinely incorporated into clinical risk assessment. Purpose To determine whether EIVA provides incremental prognostic information beyond traditional risk factors in a large primary-prevention population undergoing exercise testing. Methods We analysed 36,914 adults who underwent exercise testing as part of a self-referred preventive health evaluation, excluding individuals with prior cardiovascular disease, active malignancy or exercise-induced ischemia. EIVA was defined as any ventricular ectopy (isolated or repetitive ventricular premature beats or non-sustained ventricular tachycardia) occurring during the exercise phase. The primary outcome was major adverse cardiovascular events (MACE). Time-to-event analyses were performed using Cox proportional hazards models adjusted for age, sex, systolic blood pressure, non-HDL cholesterol and smoking (SCORE2 components). Incremental prognostic value was assessed using likelihood-ratio testing, time-dependent discrimination at 5 years and net reclassification improvement (NRI). Prespecified subgroup analyses were performed by sex, BMI and exercise capacity (METS). Results The mean age was 49.1 ± 10.8 years, 36.8% were women. During a median follow-up of approximately 5 years, 686 MACE events occurred. EIVA was present in 3,927 participants (10.6%). Kaplan-Meier analysis demonstrated an early and progressive divergence in MACE-free survival. EIVA was independently associated with incident MACE (adjusted HR 1.31, 95% CI 1.08-1.59, p = 0.006) and significantly improved model fit beyond SCORE2 components (likelihood-ratio p = 0.007). At 5 years, the inclusion of EIVA resulted in a significant continuous NRI of 14% (95% CI 7-23%). Subgroup analyses revealed that the prognostic value of EIVA was most significant in individuals with BMI <30 kg/m² and those with reduced exercise capacity (METS <11). The association remained directionally consistent in women, with no significant interaction by sex. Conclusions In a large primary-prevention population, EIVA provides clinically meaningful prognostic information beyond established risk factors. Incorporation of EIVA into routine interpretation of exercise testing may enhance cardiovascular risk stratification and support more personalised preventive strategies.