Chronotropic Incompetence and Exercise Capacity in HF
What is the role of heart rate on exercise capacity in heart failure (HF)?
The investigators conducted one observational (a retrospective cohort study) and two interventional randomized crossover studies to determine the impact of rise in heart rate on exercise capacity, and to determine the impact of changing heart rate on exercise capacity in systolic HF patients. They measured peak oxygen consumption (pVO2) to determine exercise capacity. The patients in the interventional studies had pacemakers or defibrillators. The first interventional study assessed whether rate-adaptive pacing increased exercise capacity, and the second study examined whether the heart rate lowering agent ivabradine (in HF patients with sinus rhythm) or pacemaker programming in patients (with atrial fibrillation) impaired exercise capacity. They analyzed the data using a linear mixed model with random intercepts and slope parameters, and compared data with the model only random intercepts using the likelihood ratio test.
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—
- 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.
- 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).
The authors concluded that chronotropic incompetence does not contribute to impaired exercise capacity in HF patients.
This is an important study because it refutes the fact that correcting chronotropic incompetence in HF improves exercise capacity. Further studies are needed to confirm whether modulating heart rate response with pacemaker settings can improve exercise tolerance.
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