Aim
Pharmacologic reduction of heart rate (HR) with betablockers (BB) and/or ivabradine has been associated with improved survival in patients with heart failure (HF) in sinus rhythm. We analyzed the impact of different HR reducing drug treatments on outcomes in an advanced heart failure (HF) cohort.


Methods
Consecutive patients with HF and sinus rhythm (SR) referred to a specialised tertiary HF service offering advanced therapy options including assist device and heart transplantation were prospectively enrolled from August 2015 until March 2018. Clinical characteristics were assessed at baseline. We performed a) linear regression analyses to examine the effect of the drug regimen (BB in submaximal dose [group 1], BB in maximum tolerated dose [group 2] or BB in maximum tolerated dose plus ivabradine [group 3] on resting HR, and b) cox regression analyses with the combined endpoint of death and/or heart transplantation over a mean follow-up period of 3.1 years.


Results
Of 278 patients included, 213 (76.6%) were male. Median age was 57.0 years (interquartile range 49.0-66.1). HF was more often due to non-ischemic than ischemic origin (59.7% vs. 40.3%), and 185 (73.7%) patients suffered from HFrEF. Most patients received treatment with a BB in submaximal [n=118, group 1], or maximum tolerated dose [n=136, group 2]. Patients treated with BB in maximum tolerated dose plus ivabradine [n=24, group 3] were younger (53.0 vs. 58.0 years) and had a lower left-ventricular ejection fraction on echocardiography (EF, 25 vs. 31%) than those without ivabradine. Upon regression analyses, higher resting HR was associated with an increased risk of death or heart transplantation (hazard ratio HR 1.03 [1.01, 1.06]). There were no significant differences between the 3 study groups concerning the disease-related endpoint.


Conclusion
Our prospective study underlines the importance of heart rate reduction in HF with SR but failed to demonstrate a better risk reduction in patients with uptitrated BB doses or on a combination of BB plus ivabradine.