A recently published study(1) compared the clinical features and exercise capacity among patients with heart failure with preserved ejection fraction (HFpEF) who were in sinus rhythm (SR) or atrial fibrillation AF. Previous studies have shown that in HFrEF, patients with AF have worse exercise capacity compared to those in sinus rhythm (SR) suggesting that rhythm control improves exercise capacity. However, it’s unclear whether the presence of AF in patients with HFpEF compromises exercise performance. Results of this study suggest that AF identifies HFpEF patients with more advanced disease and significantly reduced exercise capacity.

This study involved patients enrolled in the RELAX study which was a multicenter randomized (1:1) placebo-controlled trial testing the impact of chronic PDE5 (phosphodiesterase 5) inhibition (sildenafil) on exercise capacity in patients with HFpEF. Inclusion criteria for Relax trial were objective evidence of HF, LVEF?50%, reduced exercise capacity as demonstrated by reduced (?60% predicted) peak oxygen consumption (peak VO2) at screening cardiopulmonary exercise testing (CPXT) and evidence of elevated filling pressures . 216 patients with HFpEF (mean age, 69±10 years; 48% women) of whom 79 (37%) had AF, 124 (57%) were in SR, and 13 (6%) were in other rhythms (excluded from this analysis) were enrolled. Patients underwent baseline transthoracic echocardiography. Plasma biomarkers were measured which included markers of neurohumoral activation, cardiac injury or inflammation, renal function, and fibrosis. Cardiopulmonary exercise testing, resting HR, Peak HR, HR recovery, chronotropic response, peak VO2, peak respiratory exchange ratio, peak oxygen pulse, peak circulatory power, ventilatory anaerobic threshold, peak systolic blood pressure were measured. Symptom-limited CPXT with simultaneous expired ventilator gas analysis was performed by treadmill or bicycle ergometry.

HFpEF patients in AF were older and exhibited worse LV systolic and diastolic function at rest, more severe neurohumoral activation( BNP, endothelin, troponin, NT-pro BNP, p<0.001) and greater impairment of exercise capacity(9.0±3.0 vs 10.1± 3.0, p=0.02) compared with SR patients. Peak VO 2 was lower in AF (p=0.008). However there was no difference in chronotropic response in both groups(37± 23 vs 42± 20, p =0.17). Ventilatory efficiency was lower in AF, suggesting greater impairment of pulmonary perfusion during exercise. Peak exercise systolic blood pressure (138±30 vs 163± 29, p<0.0001), circulatory power(1644 vs 2109 mm Hg ml/kg per min, p<0.0001), and circulatory stroke work ( 15.5 vs 19 mm Hg ml/kg per bpm, p<0.0001) were lower and peak O2 pulse (10.5 vs 11.6, p=0.04) was lower in AF suggesting impaired systolic reserve function. These findings demonstrate that mechanisms beyond altered chronotropic response mediate the more impaired exercise tolerance in patients with HFpEF and AF and suggest that AF is a marker of a more advanced HFpEF phenotype.

This study showed that in patients with HFpEF, AF is associated with decreased exercise capacity, greater impairment of LV systolic and diastolic function and neurohormonal activation. In HFpEF who are already ?-blockers , there is chronotropic incompetence in both AF and SR. Additional studies are needed to assess whether rhythm control or different rate control strategies are beneficial in HFpEF.

Reference: 1. Zakeri R, Borlaug BA, McNulty SE et al. Impact of Atrial Fibrillation on Exercise Capacity in Heart Failure With Preserved Ejection Fraction: A RELAX Trial Ancillary Study. Circulation Heart failure 2014;7:123-30.