Results:

Observational study: The study cohort included 195 HF patients—48 with no systolic dysfunction, 57 with mild to moderate dysfunction, and 90 with severe LV systolic dysfunction. In subjects with no systolic dysfunction, there was a strong correlation between heart rate increase and peak VO₂ (linear regression r² = 0.420, ANOVA F value <0.01), but this relationship was much less obvious in HF patients (r² = 0.366, ANOVA F value <0.01 for mild to moderate LV systolic dysfunction and r² = 0.179, ANOVA F value <0.01 for severe LV systolic dysfunction). They found that linear mixed model with random intercepts and slopes for each group when compared to the mixed model with only random intercepts fit the observation study better (likelihood ratio test χ² = 19.0 m; p < 10^–4). Patients with chronotropic incompetence had lower exercise time (477, 95% confidence interval [CI 425, 539] vs. 382, 95% CI [342, 422] s; p < 0.001), pVO₂ (16.3, 95% CI [14.9, 17.7] vs. 15.9, 95% CI [14.8, 17] ml/kg/min; p < 0.001) despite similar left ventricular ejection fraction, comorbidities, and medications. The findings of the observational study, therefore, suggest that there is a weak association between exercise capacity and rise in heart rate.

Rate-Adaptive pacing versus fixed-rate pacing—

1. Interventional study 1—increasing exercise heart rate: The study cohort was 79 patients; 53 in sinus rhythm and 26 with atrial fibrillation. In subjects with sinus rhythm, adaptive rate pacing led to higher heart rate at submaximal (p = 0.003) and maximal exercise (p < 0.001), but no changes in cardiopulmonary stress test variables including pVO₂ (p = 0.350), and exercise time (p = 0.644). There was no heterogeneity or change in exercise response between those patients with significant chronotropic incompetence at baseline (chronotropic index <0.8; n = 66) versus those without (n = 13). In patients with atrial fibrillation, rate-adaptive pacing led to higher heart rate at anerobic threshold (p = 0.035) and peak exercise (p < 0.001). This was associated with a small increase in pVO₂ (15.3, 95% CI [13.8, 16.7] vs. 14.2, 95% CI [12.7, 15.8] ml/kg/min; p = 0.058). There was no change in other variables including exercise time.
2. Interventional study 2—lowering exercise heart rate: The study cohort was comprised of 40 patients: 26 with sinus rhythm and 14 with atrial fibrillation. In patients with sinus rhythm, the use of ivabradine resulted in heart rate at rest (p < 0.001), submaximal exercise (p = 0.035), and at peak (p < 0.001) with no effect of or rise in heart rate. They found no change in overall exercise time and peak pVO₂ (p = 0.588). In patients in atrial fibrillation, reducing pacemaker base rate resulted in a longer exercise time (434, 95% CI [308, 61] vs. 482, 95% CI [356, 609] s; p = 0.042, with no change in pVO₂ (p = 0.207).