Prognostic significance of impaired chronotropic response to pharmacologic stress Rb-82 PET

An impaired chronotropic response to exercise is an accepted risk marker but the relationship between heart rate reserve (HRR) with pharmacologic stress is less well-established. The primary aim of this analysis was to evaluate the prognostic significance of HRR in patients undergoing rest/stress myocardial perfusion positron emission tomography (PET) in estimating coronary artery disease (CAD) mortality. This subset analysis from the PET Prognosis Multicenter Registry includes a total of 2,398 patients undergoing rest/stress Rb-PET from three participating sites. The HRR from rest to peak stress was categorized into tertiles of a parts per thousand currency sign4, 5-14, and a parts per thousand yen15 beats per minute (bpm). At stress, the % abnormal myocardium was categorized as < 5 %, 5-9.9 %, and a parts per thousand yen10 %. We estimated CAD mortality using univariable and multivariable Cox proportional hazard models. CAD mortality was 12.8 %, 3.4 %, and 0.8 %, respectively, for HRR measurements of a parts per thousand currency sign4, 5-14, and a parts per thousand yen15 bpm (P < 0.0001). In a multivariable model, the HRR was independently predictive of CAD mortality (P < 0.0001) with adjusted hazard ratios elevated 3.5- and 8.4-fold for HRR of 5-14 and a parts per thousand currency sign4 versus a parts per thousand yen15 bpm. In a multivariable model, both the HRR and stress MPI % abnormal myocardium were independently and highly predictive of CAD mortality. Moreover, the net reclassification improvement was 0.18 for the HRR when compared to a model including risk factors, symptoms, rest HR, and PET variables (P = 0.0008). For those with a parts per thousand yen10 % abnormal myocardium on stress PET, there was a graded relationship between HRR and CAD mortality with adjusted hazards exceeding 50-fold for measurements of 5-14 and a parts per thousand currency sign4 bpm (P < 0.0001) compared to stress MPI with < 5 % abnormal myocardium and a HRR a parts per thousand yen15 bpm. A diminished HRR to vasodilator stress is a novel but increasingly important predictor of CAD mortality. HRR measurements of a parts per thousand currency sign4, 5-14, and a parts per thousand yen15 bpm were independently predictive of CAD mortality and underscore the importance of optimizing readily available novel markers of risk as highly relevant to identifying high and low risk patient subsets.