Heart rate and its reduction in chronic heart failure and beyond

Abstract

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.

Circadian‐timed quick‐release bromocriptine lowers elevated resting heart rate in patients with type 2 diabetes mellitus

“…There was no such B‐QR impact to reduce RHR in subjects with baseline RHR below 70 BPM. That is, the B‐QR influence to reduce RHR was only observable if the RHR was elevated to a range above 70 BPM, a threshold that has in previous studies been associated with increased risk of insulin resistance, metabolic syndrome, type 2 diabetes and adverse CVD outcomes . The B‐QR‐induced reduction in RHR was accompanied also by a concurrent reduction in BP, suggesting an influence to reduce central elevated sympathetic drive to the cardiovascular system .…”

“…It is important to appreciate in general and relative to the present investigation in particular that a large body of evidence indicates that while tachycardia is usually defined as heart rate ≥100 BPM, RHR thresholds substantially lower than this traditional tachycardia criterion are also associated with significant increased cardiovascular risks . Accumulating evidence from a multitude of large longitudinal epidemiological studies and clinical trials indicate that chronically elevated RHR over a threshold of approximately the >70‐80 BPM range is significantly associated with and is a predictor of increased cardiometabolic risk (insulin resistance, metabolic syndrome, type 2 diabetes and CVD) as well as both cardiovascular and all‐cause mortality and such associations have been reported in general healthy populations as well as in those with hypertension, coronary artery disease or heart failure .…”

“…While clinically RHR between 60 and 100 beats per minute (BPM) is considered the “normal” range for RHR and RHR ≥100 is used as the criteria for defining tachycardia, a large body of evidence from epidemiological and clinical studies suggests that increasing RHR within the “normal” range is associated with increased cardiometabolic risk, particularly above 70‐80 beats per minute (BPM). Such elevated RHR has been associated with insulin resistance, altered beta cell function, impaired glucose regulation and increased risk of developing type 2 diabetes mellitus as well as increased cardiovascular disease (CVD) risk and mortality …”

Ivabradine in Cancer Treatment-Related Left Ventricular Dysfunction

“…Moreover, a recent prospective study showed that heart rate is associated with mortality in patients with different types of cancer, irrespective of other comorbidities, particularly infections and anemia [13]. Heart rate therefore has been seen as a potential modifiable risk factor [14] that, based on these findings, can be treated pharmacologically. Unlike BB, ivabradine reduces the heart rate without causing ­hypotension and improves diastolic function, which seems to precede CTrLVD [15].…”

Utility of photoplethysmography for heart rate estimation among inpatients

“…HR estimation using PPG has been validated among patients in sinus rhythm but a paucity of data exists to support its use in cardiac arrhythmias . With an increasing prevalence of atrial fibrillation (AF) among hospitalised patients, attaining recommended HR targets with titration of chronotropic therapies has prognostic implications especially among patients with heart failure . Furthermore, early detection of significant brady or tachyarrhythmia among inpatients not on continuous telemetry monitoring may facilitate timely intervention .…”