The prevalence and prognostic impact of additive abnormal stress exercise markers in patients with normal stress myocardial perfusion imaging.

Background: While the rate of ischemia on stress myocardial perfusion imaging (MPI) has decreased over the last two decades, many symptomatic patients remain at an intermediate to high risk for cardiac events. Exercise workload, heart rate (HR) response, HR recovery, hemodynamic gain index, and blood pressure response to exercise have established prognostic value in isolation; however, the utility of these markers in patients with normal myocardial perfusion and no ischemic electrocardiogram ST segment depression (normal stress MPI) is unknown.

Methods: We performed a retrospective, single-center analysis of abnormal stress exercise markers in 892 patients who had a normal stress MPI from 2015 to 2017. We measured the prevalence and relative risk for death or non-fatal myocardial infarction associated with additive abnormal stress exercise markers.

Results: The mean age of patients was 61 years (55% male). Most patients (82.6%) had possible cardiac symptoms. At least one abnormal marker was found in 65.1% patients, and 9.6% had three or more markers. After adjustment for traditional risk factors, there was a 36% stepwise increase in the risk for events with each additional marker present, and patients with three or more markers were at the highest risk for events (HR: 2.44 [1.09-5.48], P = .031).

Conclusions: Patients with normal stress MPI have a high burden of abnormal stress exercise markers, which confer a stepwise increase in the risk for adverse events. This prognostic information highlights an added value of exercise testing for risk stratification in patients with normal stress MPI and may suggest symptom etiology in the absence of ischemia.