Reduced Sympathetic Reserve Detectable by Heart Rate Response after Dipyridamole in Anginal Patients with Normal Coronary Arteries.

Background . Patients with ischemia and normal coronary arteries (INOCA) may show abnormal cardiac sympathetic function, which could be unmasked as a reduced heart rate reserve (HRR) during dipyridamole stress echocardiography (SE). Objectives . To assess whether HRR during dipyridamole SE predicts outcome. Methods . Dipyridamole SE was performed in 292 patients with INOCA. HRR was measured as peak/rest heart rate and considered abnormal when ≤1.22 (≤1.17 in presence of permanent atrial fibrillation). All-cause death was the only endpoint. Results . HRR during SE was normal in 183 (63%) and abnormal in 109 patients (37%). During a follow-up of 10.4 ± 5.5 years, 89 patients (30%) died. The 15-year mortality rate was 27% in patients with normal and 54% in those with abnormal HRR ( p < 0.0001). In a multivariable analysis, a blunted HRR during SE was an independent predictor of outcome (hazard ratio 1.86, 95% confidence intervals 1.20-2.88; p = 0.006) outperforming inducible ischemia. Conclusions . A blunted HRR during dipyridamole SE predicts a worse survival in INOCA patients, independent of inducible ischemia.