Heart rate and its reduction in chronic heart failure and beyond.

Heart rate (HR) is associated with cardiovascular outcomes in all the stages of the cardiovascular continuum as well as in patients with pulmonary, cerebrovascular, and renal disease, sepsis, cancer, and erectile dysfunction. In patients with cardiovascular disease, but also in the general population, increased HR represents an important indicator of mortality with each acceleration of HR over 70 b.p.m. increasing the risk. In patients in sinus rhythm with chronic heart failure with reduced ejection fraction (HFrEF), a HR >70 b.p.m. increased the risk of hospitalization, and >75 b.p.m. the risk of cardiovascular death as shown in the Systolic Heart Failure Treatment with the I Inhibitor Ivabradine Trial (SHIFT). Reducing HR with ivabradine by 11 b.p.m. (placebo-controlled) reduced the primary composite endpoint (cardiovascular death and hospitalization for worsening heart failure). Ivabradine was well tolerated showing benefit irrespective of age or diabetes status, and also in the presence of low systolic blood pressure and severe heart failure (SHIFT trial). Therefore, HR qualifies as a modifiable risk factor in heart failure. In patients with stable coronary disease, HR is a risk marker but HR reduction with ivabradine does not improve outcomes. The role of selective HR lowering remains unclear in patients with pulmonary, renal, cerebrovascular, and other diseases, as the potential benefit of interventions on HR has not been explored in these conditions. Future studies should scrutinize if HR reduction improves outcomes, defining HR as a potential risk factor and therapeutic target in other conditions beyond heart failure.