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

BACKGROUND: An 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.

METHODS: RHR 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.

RESULTS: 1563 patients were followed for a mean of 4.3years (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 10min(-1) faster, 95% CI: 1.0-1.3) and cardiovascular mortality (HR 1.3 per 10min(-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 10min(-1) faster, 95% CI: 1.1-1.3) and cardiovascular mortality (HR 1.4 per 10min(-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).

CONCLUSIONS: RHR is independently associated with MCEs and cardiovascular death in asymptomatic AS (Clinicaltrials.gov; unique identifier NCT00092677).