The role of heart rate on functional capacity in chronic heart failure: association or contribution?

A key feature of chronic heart failure (CHF) is an inability of the heart rate (HR) to increase in proportion to the level of physical exertion, known as chronotropic incompetence (CI). Increases in HR during exercise contribute to an increase in cardiac output and hence greater blood supply to exercising peripheral muscles. It is generally assumed therefore that a limitation to heart rate rise might contribute to exercise intolerance. Whether CI is a causal factor in CHF has been a long-standing topic of debate and conflicting opinions. This thesis comprises a series of studies aiming to clarify the role of HR on exercise capacity in CHF. The observational study demonstrated a relationship between exercise capacity and heart rate rise, both of which are reduced in the context of heart failure. I have identified an association between the degree of CI and the extent of exercise capacity reduction in CHF, however this relationship is weaker with more severe CHF. I have also shown in two randomised controlled interventional double-blind crossover trials that increasing or decreasing the heart rate response in patients with CHF, does not result in any changes in exercise capacity. Finally, in a double blind case-control study, I have demonstrated a marked difference in heart rate related contractility in CHF compared to controls. This suggests that correcting CI may improve exercise capacity in controls by increasing cardiac output via increases in contractility, and this might not be the case in CHF. Based on these novel findings, I conclude that in patients with CHF, CI is a marker of reduced exercise tolerance in CHF, and cannot be considered to be a causal factor. Aggressively correcting CI should therefore not be pursued as part of the the symptomatic treatment of patients with moderate to severe heart failure in either sinus rhythm or atrial fibrillation. Instead the chronotropic adaptation seen with worsening heart failure should be optimised, with the aim to maintain the exertional heart rate rise between 50 to 110 beats per minute.