Prognostic Value of Reduced Heart Rate Reserve during Exercise in Hypertrophic Cardiomyopathy

Sympathetic dysfunction can be evaluated by heart rate reserve (HRR) with exercise test. To determine the value of HRR in predicting outcome of patients with hypertrophic cardiomyopathy (HCM). We enrolled 917 HCM patients (age = 49 ± 15 years, 516 men) assessed with exercise stress echocardiography (ESE) in 11 centres. ESE modality was semi-supine bicycle in 51 patients (6%), upright bicycle in 476 (52%), and treadmill in 390 (42%). During ESE, we assessed left ventricular outflow tract obstruction (LVOTO), stress-induced new regional wall motion abnormalities (RWMA), and HRR (peak/rest heart rate, HR). By selection, all patients completed the follow-up. Mortality was the predetermined outcome measure Results: During ESE, RWMA occurred in 22 patients (2.4%) and LVOTO (≥50 mmHg) in 281 (30.4%). HRR was 1.90 ± 0.40 (lowest quartile ≤ 1.61, highest quartile > 2.13). Higher resting heart rate (odds ratio 1.027, 95% CI: 1.018-1.036, < 0.001), older age (odds ratio 1.021, 95% CI: 1.009-1.033, < 0.001), lower exercise tolerance (mets, odds ratio 0.761, 95% CI: 0.708-0.817, 0.001) and resting LVOTO (odds ratio 1.504, 95% CI: 1.043-2.170, 0.029) predicted a reduced HRR. During a median follow-up of 89 months (interquartile range: 36-145 months), 90 all-cause deaths occurred. At multivariable analysis, lowest quartile HRR (Hazard ratio 2.354, 95% CI 1.116-4.968 = 0.025) and RWMA (Hazard ratio 3.279, 95% CI 1.441-7.461 0.004) independently predicted death, in addition to age (Hazard ratio 1.064, 95% CI 1.043-1.085 0.001) and maximal wall thickness (Hazard ratio 1.081, 95% CI 1.037-1.128, < 0.001). A blunted HRR during ESE predicts survival independently of RWMA in HCM patients.