Prognostic implications of stress modality on mortality risk and cause of death in patients undergoing office-based SPECT myocardial perfusion imaging

Background. Patients requiring vasodilator single-photon emission computed-tomography myocardial perfusion imaging (SPECT-MPI) have a higher mortality risk than those selected for exercise or vasodilator with low-level exercise SPECT-MPI. However, it is unknown whether the increased mortality is driven by cardiac deaths alone or cardiac and non-cardiac deaths. Methods. In a prospective cohort of 1,511 consecutive patients referred for SPECT-MPI, patients were classified according to stress test modality: exercise, adenosine with low-level exercise (AdenoEx), and adenosine. Subjects were followed for events of all-cause mortality and cause of death. Survival analyses using multivariate Cox regression and propensity score matching methods were performed. Results. During a follow-up of 4.9 +/- 0.9 years, a total of 68 (4.5%) deaths occurred: 50 non-cardiac and 18 cardiac. The adenosine group had the highest annual mortality (all-cause 3.65%, non-cardiac 2.36%, cardiac 1.29%), while exercise stress had the lowest mortality (all-cause 0.42%, non-cardiac 0.37%, cardiac 0.05%) and AdenoEx had an intermediate mortality (all-cause 1.3%, non-cardiac 0.91%, cardiac 0.39%); all P values <0.001. The majority of non-cardiac deaths were attributed to cancer. Using exercise stress as a reference standard, multivariable Cox regression analyses demonstrated that adenosine stress was independently predictive of all-cause mortality [HR 3.23 (CI 1.77-5.88); P < 0.001], non-cardiac death [HR 2.67 (CI 1.34-5.31); P = 0.005], and cardiac death [HR 6.30 (CI 1.55-25.56); P = 0.010] after adjusting for univariate predictors of mortality. These findings were consistent in the subgroups of patients with normal and abnormal MPI. AdenoEx was predictive of all-cause, non-cardiac, and cardiac deaths in univariate analysis, but it was not predictive by multivariate analysis. Propensity score matched cohort analysis showed that the adenosine stress group had the highest all-cause (P < 0.001), non-cardiac (P = 0.013), and cardiac deaths (P < 0.001), while the exercise stress group had the lowest mortality of any cause. Conclusions. The inability to perform any level of exercise during a SPECT-MPI stress is associated with high mortality risk, which is derived from both cardiac and non-cardiac deaths.