Impact of Atrial Fibrillation on Exercise Capacity in Heart Failure With Preserved Ejection Fraction

Abstract

Background Atrial fibrillation (AF) is common among patients with heart failure and preserved ejection fraction (HFpEF) but its clinical profile and impact on exercise capacity remains unclear. RELAX was a multicenter randomized trial testing the impact of sildenafil on peak VO2 in stable outpatients with chronic HFpEF. We sought to compare clinical features and exercise capacity among HFpEF patients who were in sinus rhythm (SR) or AF. Methods and Results RELAX enrolled 216 HFpEF patients with 79 (37%) in AF, 124 (57%) in SR and 13 in other rhythms. Participants underwent baseline cardiopulmonary exercise testing (CPXT), echocardiogram, biomarker and rhythm status assessment prior to randomization. AF patients were older than those in SR but had similar symptom severity, co-morbidities and renal function. Betablocker use and chronotropic indices were also similar. Despite comparable LV size and mass, AF was associated with worse systolic (lower EF, stroke volume and cardiac index) and diastolic (shorter deceleration time and larger left atria) function compared to SR. Pulmonary artery systolic pressure was higher in AF. AF patients had higher NT-proBNP, aldosterone, endothelin-1, troponin I and CITP levels suggesting more severe neurohumoral activation, myocyte necrosis and fibrosis. Peak VO2 was lower in AF, even after adjustment for age, sex, and chronotropic response, and VE/VCO2 was higher. Conclusions AF identifies an HFpEF cohort with more advanced disease and significantly reduced exercise capacity. These data suggest that evaluation of the impact of different rate or rhythm control strategies on exercise tolerance in HFpEF patients with AF is warranted.

Impact of Atrial Fibrillation on Exercise Capacity and Mortality in Heart Failure With Preserved Ejection Fraction: Insights From Cardiopulmonary Stress Testing

“…Most prior studies have shown that patients with AF have a higher peak HR, which is likely a result of activation of sympathetic compensatory mechanisms to low cardiac output 8, 9, 17. In contrast, only 1 study showed that peak HR was not different between AF and non‐AF in patients with HFpEF,25 similar to our study, suggesting that the implementation of a strict rate control strategy in these patients may inhibit the essential normal compensatory response required to maintain adequate perfusion at peak exercise.…”

“…Each of these mechanisms is of particular importance at peak exercise when maximal contractile reserve is used. As such, AF has been associated with exercise intolerance in patients with lone AF and more notably in those with associated heart disease 9, 23, 24, 25. Some studies have shown that peak VO 2 , a surrogate of maximal aerobic capacity,12 is 10% to 20% lower in patients with HFrEF with AF 6, 8, 9, 25.…”

“…As such, AF has been associated with exercise intolerance in patients with lone AF and more notably in those with associated heart disease 9, 23, 24, 25. Some studies have shown that peak VO 2 , a surrogate of maximal aerobic capacity,12 is 10% to 20% lower in patients with HFrEF with AF 6, 8, 9, 25. In addition, surrogates of cardiac output at peak exercise, such as oxygen pulse (a surrogate for stroke volume), circulatory power (a surrogate for cardiac power), and SBP, have been shown to be lower in patients with HFrEF with AF 8, 9, 20, 26.…”

Atrial remodelling in heart failure: recent developments and relevance for heart failure with preserved ejection fraction

“…Fibrosis is especially prevalent in atrial remodelling in patients with HFpEF 29. In the RELAX trial, HFpEF patients with AF (37%) had more advanced disease and a significantly reduced exercise capacitance, which might be also related to the development of tachy‐cardiomyopathy 53. Likewise, others reported that AF is independently associated with greater exertional intolerance, natriuretic peptide elevation, and left anterior descending artery remodelling in HFpEF 53, 54.…”

“…In the RELAX trial, HFpEF patients with AF (37%) had more advanced disease and a significantly reduced exercise capacitance, which might be also related to the development of tachy‐cardiomyopathy 53. Likewise, others reported that AF is independently associated with greater exertional intolerance, natriuretic peptide elevation, and left anterior descending artery remodelling in HFpEF 53, 54. Vice versa, in Framingham Heart Study participants, pre‐existing AF tended to be more strongly associated with new‐onset HFpEF (hazard ratio 2.34) than did HFrEF (hazard ratio 1.32), highlighting the relevance of atrial function in HFpEF 55…”