Cardiovascular mortality and chronotropic incompetence in systolic heart failure: the importance of a reappraisal of current cut-off criteria

Aims: An independent role for the exercise-induced heart rate (HR) response-and specifically the chronotropic incompetence (CI)-in the prognosis of heart failure (HF) is still debated. The multicentre study reported here sought to investigate the prognostic values of HR and CI variables on cardiovascular mortality in a large cohort of systolic HF patients.

Methods and results: A total of 1045 HF patients were recruited and prospectively followed in three Italian HF centres. The study endpoint was cardiovascular mortality. Besides a full clinical examination, each patient underwent a maximal cardiopulmonary exercise test at study enrolment. The age-predicted peak HR (%pHR) and the peak HR reserve (%pHRR) according to different cut-off values (60-80% of the maximum predicted) were adopted to identify the presence of CI. The median follow-up was 876 days (interquartile range 386-1590 days). Cardiovascular death occurred in 145 cases (13.8%). Besides LVEF, peak oxygen uptake, ventilation vs. carbon dioxide production slope, and beta-blocker therapy, the multivariate analysis showed that both %pHR and %pHRR were able to predict prognosis when considered as continuous variables. Conversely, the presence of CI was associated with the study endpoint only when the 70% (%pHR <70%, hazard ratio 1.80, confidence interval 1.24-2.61, P = 0.002; %pHRR <70%, hazard ratio 1.77, confidence interval 1.09-2.86, P = 0.020) or the 65% cut-off values (%pHR <65%, hazard ratio 2.04, confidence interval 1.34-3.10, P = 0.001; %pHRR <65%, hazard ratio 1.54, confidence interval 1.03-2.32, P = 0.038) were adopted.

Conclusions: Our findings demonstrated an additive role of CI in stratifying cardiovascular mortality. Both the 65% and the 70% cut-off values, regardless of the method (%pHR and %pHRR), allow identification of HF patients with the worst prognosis, thus supporting such definitions of CI in HF.