Zakeri, R., Borlaug, B. A., McNulty, S., Mohammed, S. F., Lewis, G. D., Semigran, M. J., Deswal, A., Lewinter, M., Hernandez, A. F., Braunwald, E., Redfield, M. M. Impact of Atrial Fibrillation on Exercise Capacity in Heart Failure with Preserved Ejection Fraction: A RELAX Trial Ancillary Study Circ Heart Fail. 2013;NA(NA):NA.

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. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867.