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Background: Because ST segment depression has limited diagnostic performance at exercise electrocardiography (ECG), ST segment depression/heart rate (ST/HR) hysteresis and cardiopulmonary exercise test (CPET)-derived parameters have been proposed as alternatives to diagnose exercise-induced myocardial ischemia. We compared the diagnostic performance of such parameters. Methods: We studied 56 subjects (45 men, 11 women, age 59.7±13.6years) referred for suspected exercise-induced myocardial ischemia with an equivocal ECG exercise test. All subjects serially underwent CPET and a myocardial single-photon emission computerized tomography (SPECT) perfusion imaging (as the gold standard for ischemia). Maximum ST depression at peak exercise (ST-max), the ST/HR hysteresis, ΔVO2/ΔWR b–b1 slope, ΔVO2/ΔWR (aa1–bb1), VO2/HR flattening duration and other CPET parameters were derived in all subjects. Results: On the basis of SPECT, 23 subjects (41%) were considered ischemic and 33 subjects (59%) non-ischemic. ST/HR hysteresis was higher (0.026mV; 95% CI: 0.003 to 0.049 vs −0.016mV; 95% CI: −0.031 to −0.001mV) and ST-max was lower (−0.105mV; 95% CI: −0.158 to −0.052 vs 0.032mV; 95% CI: −0.001 to −0.066mV) in ischemic vs non-ischemic subjects (P=0.004 and P=0.001, respectively). Among CPET parameters, ΔVO2/ΔWR b–b1 slope was lower (9.4±3.8) and ΔVO2/ΔWR (aa1–bb1) was higher (2.1±2.6) in ischemic vs non-ischemic subjects (11.4±2.3, P=0.005, and 1.1±1.5, P=0.001, respectively). The ST/HR hysteresis had the highest area under the curve value, better (P<0.05) than any other parameters tested, thus showing the highest overall diagnostic performance. Conclusion: The ST/HR hysteresis is superior to CPET-derived parameters for detecting exercise-induced myocardial ischemia in patients with equivocal ECG exercise test results. [ABSTRACT FROM AUTHOR]