Impaired Exercise Capacity in Heart Failure Not Caused by Chronotropic Incompetence

Chronotropic incompetence (CI) does not contribute to impaired exercise capacity in chronic heart failure (CHF), according to new data published in the Journal of the American College of Cardiology.

This finding refutes previous assertions that CI contributes to impaired exercise capacity in CHF.

Researchers conducted 3 investigations to determine the role of limited heart rate (HR) on exercise capacity in CHF. The first was a retrospective observational cohort study to assess the relationship between heart rate rise (HRR) and exercise capacity, specifically in the context of left ventricular systolic dysfunction (LVSD) and peak oxygen consumption (pVo₂).

The latter 2 investigations were interventional randomized crossover studies to determine if increasing HRR increases exercise capacity and if reducing HRR reduces exercise capacity.

There were a total 195 patients in the observational study; 48 were included in the “no LVSD” group, 57 in the “mild-moderate LVSD” group, and 90 in the “severe LVSD” group. A strong correlation between HRR and pVo₂ (linear regression: r²=0.420; ANOVA [analysis of variance] F value <0.01) was seen in patients with no LVSD, but this was not the case in patients with CHF (r²=0.366; ANOVA F value <0.01 for mild-moderate LVSD and r²=0.179; ANOVA F value <0.01 for severe LVSD).

Lower exercise time, pVo₂ and anaerobic threshold were seen in patients with chronotropic index <0.8 in the HF cohort (P<.001 for all), despite similar EF, comorbidities, and medications.

In the first interventional study, which increased exercise, 79 patients were enrolled—53 with sinus rhythm (SR) and 26 patients with atrial fibrillation (AF). In patients with SR, rate-adaptive pacing led to higher HR at submaximal and maximal exercise (P=.003 and P<.001, respectively).

However, there were no changes in cardiopulmonary exercise test variables, including pVo₂ (P=.350), exercise time (P=.644), anaerobic threshold (P=.075), VE/Vco₂ slope (to peak: P=.533; to anaerobic threshold: P=.353), respiratory exchange ratio (P=.806), mean oxygen pulse (P=.605), end-tidal oxygen tension (P=.287), or perceived exertion level (for shortness of breath: P=.458; leg weakness: P=.494).

All patients had peak exertional HR <90% peak predicted HR, and there was no heterogeneity in change in exercise response between those patients with significant chronotropic index at baseline vs those without.

In the second interventional study, which lowered exercise HR, 40 patients were enrolled—26 with SR and 14 with AF. The use of ivabradine in patients with SSR resulted in a HR reduction at rest (P<.001), submaximal exercise (P=.035), and at peak (P<.001) with no effect on HRR (48 beats/min; P=.588).

In addition, there was no change in overall exercise time (P=.396), oxygen pulse (P=.286), PETo₂ (P=.560), and oxygen consumption at anaerobic threshold and at peak (P=.700 and .588, respectively).

“The findings from our observational data stimulated the hypotheses for the subsequent intervention studies; that CI is not a contributor to exercise intolerance in unselected patients with CHF,” researchers wrote.

“The first of the interventional studies demonstrated that increasing PHR [peak heart rate] to ‘correct’ CI does not improve oxygen consumption, exercise time, or symptoms in CHF,” they added. “In our second interventional study, we found that reducing RHR [resting heart rate] did not result in worsening exercise capacity in either the SR or AF cohorts.”

Having a lower RHR in AF actually resulted in higher HRR and longer exercise time, researchers pointed out, which suggests an increase in metabolic efficiency and reached a greater workload for similar oxygen consumption.

Researchers concluded that further studies are necessary to define the “optimum HR range” for patients with HF and to determine the role, if any, medications and/or pacemaker settings will play in improving exercise tolerance.

Reference

Jamil HA, Gierula J, Paton MF, et al. Chronotropic incompetence does not limit exercise capacity in chronic heart failure. J Am Coll Cardiol. 2016;67(16):1885-1896. doi: 10.1016/j.jacc.2016.02.042.