Resting heart rate and risk of adverse cardiovascular outcomes in asymptomatic aortic stenosis: The SEAS study

BackgroundAn elevated resting heart rate (RHR) may be an early sign of cardiac failure, but its prognostic value during watchful waiting in asymptomatic aortic stenosis (AS) is largely unknown.MethodsRHR was determined by annual ECGs in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study of asymptomatic mild-to-moderate AS patients. Primary endpoint in this substudy was major cardiovascular events (MCEs) and secondary outcomes its individual components. Multivariable Cox-models using serially-measured RHR were used to examine the prognostic impact of RHR per se.Results1563 patients were followed for a mean of 4.3 years (6751 patient-years of follow-up), 553 (35%) MCEs occurred, 10% (n = 151) died, including 75 cardiovascular deaths. In multivariable analysis, baseline RHR was independently associated with MCEs (HR 1.1 per 10 min− 1 faster, 95% CI: 1.0-1.3) and cardiovascular mortality (HR 1.3 per 10 min− 1 faster, 95% CI: 1.0-1.7, both p ≤ 0.03). Updating RHR with annual in-study reexaminations, time-varying RHR was highly associated with excess MCEs (HR 1.1 per 10 min− 1 faster, 95% CI: 1.1-1.3) and cardiovascular mortality (HR 1.4 per 10 min− 1 faster, 95% CI: 1.2-1.7, both p ≤ 0.006). The association of RHR with MCEs and cardiovascular mortality was not dependent on atrial fibrillation status (both p ≥ 0.06 for interaction).ConclusionsRHR is independently associated with MCEs and cardiovascular death in asymptomatic AS (Clinicaltrials.gov; unique identifier NCT00092677).