Effects of chronotropic incompetence on exercise capacity in people with heart failure versus age-matched controls

Chronotropic incompetence (CI) is an inability to adequately raise heart rate during physiological stress. We established CI prevalence and exercise capacity in heart failure versus healthy age-matched controls. We conducted a systematic search (1966-July 1, 2020) and meta-analysis of studies reporting peak VO2 in people with heart failure with reduced (HFrEF) and preserved (HFpEF) left ventricular ejection fraction and controls. Seventeen studies of 4410 participants were included, 4167 with heart failure and 243 age-matched controls. In both heart failure phenotypes, CI was more prevalent in HFrEF (51.7%) and HFpEF (55.8%) than in healthy controls (9%). Mortality was 24% higher in people with HFrEF and CI versus those with HFrEF and without CI; OR -1.24 (95% CI -2.20 to -0.28; p = 0.01). People with heart failure and CI had lower peak VO2 than those without CI (MD) -3.30 ml kg(-1) min(-1) (95% CI -4.25 to -2.35, p < 0.01), and this was primarily driven by the HFrEF sub-population (MD) -3.86 ml kg(-1) min(-1) (95% CI -4.83 to -2.89, p < 0.01). Maximum heart rate MD -37.51 beats min(-1) (95% CI -41.99 to -33.03, p < 0.01) and maximum-resting heart rate were lower MD -29.44 beats min(-1) (95% CI -34.55 to -24.33, p < 0.01) in people with heart failure with CI vs without CI. People with heart failure and CI demonstrated similar respiratory exchange ratios (RER) to people with heart failure but without CI; (MD) -0.02 (95% CI -0.03 to -0.01), p < 0.01, suggesting that poor effort was unlikely to explain CI. CI is more prevalent in heart failure than in age-matched controls and although it is associated with lower peak VO2 in HFrEF, it is unrelated to the lower peak VO2 in HFpEF. RER values suggest poor effort is unlikely to explain these findings.