What about chronotropic incompetence in heart failure with mildly reduced ejection fraction? Clinical and prognostic implications from the MECKI score data-set

Aims: Chronotropic incompetence (CI) is a strong predictor of outcome in heart failure with reduced ejection fraction (HFrEF), however no data on its clinical and prognostic impact in heart failure with mildly reduced ejection fraction (HFmrEF). Therefore, the study aims to investigate, in a large multicenter HFmrEF cohort, the prevalence of CI as well as its relationship with exercise capacity and its prognostic role over the cardiopulmonary exercise testing (CPET) parameters. Methods: Within the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) database, we analyzed data of 864 HFmrEF out of 1164 stable outpatients who performed a maximal CPET at the cycle ergometer and who had no significant rhythm disorders or comorbidities. The primary study endpoint was cardiovascular (CV) death. All-cause death was also explored. Results: CI prevalence differed depending on the method (peak heart rate, pHR% versus pHR reserve, pHRR%) and the cut-off adopted (pHR% from ≤75% to ≤60% and pHRR%≤65% to ≤50%), ranging from 11% to 62%. A total of 84 (9.7%) CV deaths were collected, with 39 (4.5%) occurring within 5 year. At multivariate analysis, both pHR% [Hazard Ratio 0.97(0.95-0.99), p < 0.05] and pHRR% [Hazard Ratio 0.977(0.961-0.993), p < 0.01) were associated with the primary end-point. A pHR%≤75% and a pHRR%≤50% represented the most accurate cut-off values in predicting the outcome. Conclusions: The study suggests an association between blunted exercise-HR response, functional capacity, and CV death risk among patients with HFmrEF. Whether the CI presence might be adopted in daily HFmrEF management needs to be addressed in larger prospective studies.