Clinical Implications of Electrocardiographic Left Ventricular Strain and Hypertrophy in Asymptomatic Patients with Aortic Stenosis: The Simvastatin and Ezetimibe in Aortic Stenosis Study

BACKGROUND: The prognostic impact of electrocardiographic left ventricular (LV) strain and hypertrophy (LVH) in asymptomatic aortic stenosis (AS) is not well described. METHODS AND RESULTS: Data were obtained in asymptomatic patients randomized to simvastatin/ezetimibe combination vs. placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Primary endpoint was the first of myocardial infarction, non-hemorrhagic stroke, heart failure, aortic valve replacement (AVR) or cardiovascular death. Predictive value of electrocardiographic LV strain (defined as T-wave inversion in leads V(4-6)) and LVH (assessed by Sokolow-Lyon voltage criterion (R(V5-6)+S(V1) =35 mV) and Cornell voltage-duration criteria ((RaVL+S(V3)+[6 mV in women]) × QRS-duration =2440 mV msec), was evaluated by adjusting for other prognostic covariates. 1,533 patients were followed 4.3±0.8 years (6,592 patient-years of follow-up), 627 cardiovascular events occurred. Electrocardiographic strain was present in 340 (23.6%) patients; LVH by Sokolow-Lyon voltage in 260 (17.1%) and in 220 (14.6%) by Cornell voltage-duration product. In multivariable analyses, electrocardiographic LV strain was associated with 3.1-fold higher risk of in-study myocardial infarction (95% confidence interval [CI], 1.4 to 6.8, p=0.004). Similarly, electrocardiographic LVH by both criteria predicted, compared to no electrocardiographic LVH, 5.8-fold higher risk of heart failure (95% CI, 2.0 to 16.8), 2.0-fold higher risk of AVR (95% CI, 1.3 to 3.1, both p=0.001) and 2.5-fold higher risk of a combined endpoint of myocardial infarction, heart failure or cardiovascular death (95% CI, 1.3 to 4.9, p=0.008). CONCLUSIONS: Electrocardiographic LV strain and LVH were independently predictive of poor prognosis in asymptomatic AS. CLINICAL TRIAL REGISTRATION: http://www.ClinicalTrials.gov; NCT00092677.