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.