Increasing burden of atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) was found to be associated with lower left atrial compliance and mechanics, according to a study published in the Journal of the American College of Cardiologists.

Patients with HFpEF (n=285) and control individuals (n=146) were recruited at the Mayo Clinic between 2000 and 2015. All participants underwent invasive hemodynamic exercise testing. Healthy controls had normal resting and exercise pulmonary capillary wedge pressure, left ventricular ejection fraction >49%, and no history of AF. Patients with HFpEF were classified according to the stage of AF progression: no AF (65%), paroxysmal AF (ie, sinus rhythm but no history of AF, 18%), and permanent AF (17%). Participants in the different cohorts (healthy controls and the 3 HFpEF groups) differed significantly (P ≤.05) in age, body mass index, hemoglobin levels, rates of diabetes, rates of hypertension, laboratory results, chest radiography results, prescribed medications, left and right ventricle structure and function (except left ventricular end-diastolic dimension), and ventriculoatrial remodeling and independence.

Patients with vs without HFpEF had higher left ventricle masses with worse diastolic function and stiffness. As the degree of AF increased among patients with HFpEF, systolic function decreased.

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Patients with permanent AF had the largest heart volumes. A 2-fold greater atrial volume was observed among patients with permanent AF compared with the other HFpEF cohorts and a 4-fold greater volume than controls. Patients with permanent AF had the highest resting biventricular filling pressures coupled with the weakest cardiac output and stroke volume.

The 10-year survival was lowest for patients with permanent AF (38%), followed by patients with paroxysmal AF (62%), patients with no AF (73%), and healthy controls (94%). The hazard ratio (HR) of survival per increase in AF stage was 1.95 (95% CI, 1.56-2.45; P <.001). Progression from paroxysmal to permanent AF after 10 years was common (52%). AF progression was associated with impaired left atrial strain (HR, 6.8; 95% CI, 3.3-14.1; P <.0001), poor left atrial compliance (HR, 6.0; 95% CI, 2.9-12.7; P <.0001), and elevated pulmonary capillary wedge pressure (HR, 5.3; 95% CI, 2.8-10.3; P <.0001).

A potential limitation of this study was that some healthy controls had dyspnea of noncardiac origin, which may have skewed observations and comparisons.

“These unique pathophysiologic differences suggest that patients with permanent AF may respond differently to treatment and ought to be considered as a separate phenotype,” concluded the study authors.


Reddy Y N V, Obokata M, Verbrugge F H, et al. Atrial dysfunction in patients with heart failure with preserved ejection fraction and atrial fibrillation. J Am Coll Cardiol. 2020;76:1051-1064.