Prognostic Value of Heart Rate Reserve in Patients with Permanent Atrial Fibrillation during Dipyridamole Stress Echocardiography

In patients in sinus rhythm, a blunted heart rate reserve (HRR) during dipyridamole stress echocardiography (SE) is a prognostically unfavorable sign of cardiac autonomic dysfunction. In this study we sought to assess the prognostic meaning of HRR in patients with permanent atrial fibrillation (AF). The study population was made by 301 patients (176 men, age 73 ± 8 years) with suspected (n = 200) or known (n = 101) coronary artery disease and permanent AF who underwent high-dose dipyridamole SE. HRR was calculated on an average of 5 consecutive beats as the peak/rest ratio of HR from 12-lead EKG. During a median follow-up time of 77 months (first quartile 44, third quartile 115 months), 111 (37%) patients died. Receiver operating characteristics analysis identified HRR <=1.17 as the best predictor of mortality. At multivariable analysis, HRR <=1.17 (HR 1.75, 95% CI 1.17 to 2.62; p = 0.006) independently predicted mortality together with age (HR 1.09, 95% CI 1.06 to 1.13; p <0.0001), rest wall motion score index (HR 1.69, 95% CI 1.01 to 2.83; p = 0.04), and systemic hypertension (HR 1.76, 95% CI 1.06 to 3.00; p = 0.04). The annual mortality was 5.1% in the overall population, 7.0% in the 140 (46%) patients with abnormal HRR and 3.5% in the 161 (54%) patients with normal HRR. The 8-year mortality was 48% in patients with abnormal HRR and 18% in those with normal HRR (p <0.0001). In conclusion, patients with suspected or known coronary artery disease with permanent AF with a blunted HRR have an increased mortality. HRR outweighs inducible ischemia for prediction of survival. The assessment of HRR should become an integral part of dipyridamole SE reading also in AF.