Differential prognostic impact of heart rate in younger and older patients with chronic heart failure

Abstract

Background: In patients with chronic heart failure (HF), high heart rate (HR) is a marker of poor prognosis, and HR reduction is associated with improved outcomes. However, these data are based on trials including relatively young patients (typically less than 75 years), and there is little information regarding the prognostic role of HR in older HF patients. Accordingly, the aim of the present study was to compare the relationship between HR and outcomes in younger (age <75 years) and older (age ≥75 years) patients with chronic HF. Methods: Patients enrolled in the randomized, controlled multicenter Trial of Intensified Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) with sinus rhythm and without any device (pacemaker, defibrillator) throughout the trial were included in this post-hoc analysis. The effects of baseline HR (≥70 vs. <70 beats per minute (bpm) on 18 months outcomes (survival, HF hospitalization-free survival) were compared between younger (n=141, age 69±4 years) and older (n=186, age 82±4 years) patients. Results: Younger patients with higher baseline HR (n=86; HR 81±7 bpm) had worse left ventricular ejection fraction (LVEF; p=0.01), worse NYHA class (p=0.006) and higher N-terminal-pro-B-type natriuretic peptide (NT-proBNP; p=0.003) than those with lower HR (n=55; HR 62±5 bpm) but groups did not differ in terms of management strategy allocation (NT-proBNP-guided vs. symptom-guided). Survival and HF hospitalization-free survival at 18 months were worse in those with higher compared to those with lower HR [hazard ratio = 4.01 (95% CI, 1.17 -13.69), p= 0.02 and hazard ratio=2.35 (95% CI, 1.01-5, 50), p= 0.04; respectively], even after adjustment for LVEF, NYHA class, and NT-proBNP. In contrast, older patients with lower (n=77; HR 61±6 bpm) and higher (n=109; HR 83±9 bpm) baseline HR did not differ in terms of LVEF, NYHA class, NT-proBNP, and management strategy, and outcomes did not differ between those with higher and lower HR [for survival hazard ratio= 0.87 (95% CI, 0.47-1.61), p= 0.66 and HF hospitalization-free survival hazard ratio =0.84 (95% CI, 0.52-1.34), p= 0.46]. In older patients, the relationship between HR and outcomes was similar across LVEF categories (>45% and ≤45%) and was not influenced by betablocker use (p value for interaction > 0.33 for all endpoints). Conclusion: In accordance with previous data, we observed better outcomes in younger patients with chronic HF with lower HR compared to those with higher HR. In contrast, an association between HR and outcomes was not seen in older patients with chronic HF.