Prognostic Contribution of Exercise Capacity, Heart Rate Recovery, Chronotropic Incompetence, and Myocardial Perfusion Single-Photon Emission Computerized Tomography in the Prediction of Cardiac Death and All-Cause Mortality

Abstract

Chronotropic incompetence, measured by the percentage (%) of heart rate (HR) reserve achieved (%HR reserve), abnormal HR recovery, reduced exercise capacity (EC), and myocardial perfusion single-photon emission computerized tomography (SPECT MPS) abnormalities are known predictors of all-cause mortality (ACM) and cardiac death (CD). The aim of this study was to determine if EC, %HR reserve, and HR recovery add incremental value to MPS in the prediction of ACM and CD. A total of 11,218 patients without valvular disease and not on β blockers underwent symptom-limited exercise MPS. %HR reserve was (peak HR - rest HR)/(220 - age - rest HR) × 100, with %HR reserve <80 defined as low. HR recovery was peak HR - recovery HR. An HR recovery <22 beats/min at 2 minutes after peak exercise was considered abnormal. Poor EC was defined as exercise duration ≤6 minutes (7 metabolic equivalents). Summed stress scores (SSSs) were calculated using a 20-segment, 5-point MPS model. Statistical analysis was performed using Cox regression models. There were 445 deaths (148 CD) during a mean follow-up of 3.2 ± 2.5 years. In multivariate analysis, the independent predictors of ACM were age, χ(2) = 154.81; EC, χ(2) = 74.00; SSS, χ(2) = 32.99; %HR reserve, χ(2) = 24.74; abnormal electrocardiogram at rest, χ(2) = 23.13; HR recovery, χ(2) = 18.45; diabetes, χ(2) = 17.75; and previous coronary artery disease, χ(2) = 11.85 (p ≤0.0006). The independent predictors of CD were SSS, χ(2) = 54.25; EC, χ(2) = 49.34; age, χ(2) = 46.45; abnormal electrocardiogram at rest, χ(2) = 30.60; previous coronary artery disease, χ(2) = 20.69; Duke treadmill score, χ(2) = 19.50; %HR reserve, χ(2) = 11.43; diabetes, χ(2) = 10.23 (all p ≤0.0014); and HR recovery, χ(2) = 5.30 (p = 0.0214). The exercise variables showed increases in Harrell's C static and net improvement reclassification, with EC showing the strongest incremental improvement in predicting ACM and CD (respective C-index 76.5% and 83.3% and net reclassification index 0.3201 and 0.4996). In conclusion, EC, %HR reserve, and HR recovery are independent predictors of ACM and CD and add incremental prognostic value to extent and severity of MPS.