Atrial Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction and Atrial Fibrillation

Abstract

Background: Paroxysmal and permanent atrial fibrillation (AF) are common in heart failure with preserved ejection fraction (HFpEF).

Objectives: This study sought to determine the implications of left atrial (LA) myopathy and dysrhythmia across the spectrum of AF burden in HFpEF.

Methods: Consecutive patients with HFpEF (n = 285) and control subjects (n = 146) underwent invasive exercise testing and echocardiographic assessment of cardiac structure, function, and pericardial restraint.

Results: Patients with HFpEF were categorized into stages of AF progression: 181 (65%) had no history of AF, 49 (18%) had paroxysmal AF, and 48 (17%) had permanent AF. Patients with permanent AF were more congested with greater pulmonary vascular disease and lower cardiac output. LA volumes increased, while LA compliance, LA reservoir strain, and right ventricular function decreased with increasing AF burden. The presence of permanent AF was characterized by a distinct pathophysiology, with greater total heart volume caused by atrial dilatation, leading to elevated filling pressures through heightened pericardial restraint. Survival decreased with increasing AF burden. Ten-year progression to permanent AF was common, particularly in paroxysmal AF (52%), and the likelihood of AF progression increased with higher AF stage, poorer LA compliance, and lower LA strain.

Conclusions: LA compliance and mechanics progressively decline with increasing AF burden in HFpEF, increasing risk for new onset AF and progressive AF. These changes promote development of a unique phenotype of HFpEF characterized by heightened ventricular interaction, right heart failure, and worsening pulmonary vascular disease. Further study is required to identify therapeutic interventions targeting LA myopathy to improve outcomes in HFpEF.

Keywords: HFpEF; atrial fibrillation; exercise hemodynamics; left atrial strain; pericardial restraint.

FIGURE 1. Pericardial and Atrial Size Interaction Across the Spectrum of AF Risk in HFpEF

(A, B) Increasing total heart volume by both echocardiography and chest radiography was driven by atrial enlargement with increasing atrial fibrillation (AF) burden in heart failure with preserved ejection fraction (HFpEF). (C to F) Patients with greater AF burden displayed increased pericardial restraint with a higher exertional right atrial pressure (RAP), RAP/pulmonary capillary wedge pressure (PCWP) ratio, and lower left ventricular (LV) transmural pressure and enhanced diastolic ventricular interaction in the permanent AF HFpEF group. Par = paroxysmal; Perm = permanent.

FIGURE 2. Left Heart Filling Pressures, Pulmonary Vascular Load, and Cardiac Output Reserve Across AF Grades in HFpEF

Baseline (resting) PCWP was highest in the permanent AF HFpEF group, and the corresponding PCWP v-wave height (A) increased progressively across groups and (B) was associated with worse pulmonary arterial (PA) elastance. (C to E) There was progressive worsening of pulmonary vascular load measured at rest with increasing AF stages along with (F) decreased cardiac output (CO) reserve during exercise. PVR = pulmonary vascular resistance; Vo₂ = oxygen consumption; other abbreviations as in Figure 1.

FIGURE 3. LA Reservoir Dysfunction With Increasing AF Burden in HFpEF

Progressive impairment in (A) LA reservoir strain and (B) LA compliance with worsening AF stage. Abbreviations as in Figure 1.

FIGURE 4. Risk of Progression of AF Stratified by Baseline AF Burden

The risk of progressing to higher AF stage increased (A) with higher AF burden at index assessment and (B, C) in patients with more severe LA myopathy as evidenced by lower LA reservoir strain and compliance. For panels B and C, results are presented stratified by median LA reservoir strain and compliance. CI = confidence interval; HR = hazard ratio; other abbreviations as in Figure 1.

FIGURE 4. Risk of Progression of AF Stratified by Baseline AF Burden

The risk of progressing to higher AF stage increased (A) with higher AF burden at index assessment and (B, C) in patients with more severe LA myopathy as evidenced by lower LA reservoir strain and compliance. For panels B and C, results are presented stratified by median LA reservoir strain and compliance. CI = confidence interval; HR = hazard ratio; other abbreviations as in Figure 1.

CENTRAL ILLUSTRATION. Progressive LA Myopathy and AF Burden in Heart Failure With Preserved Ejection Fraction

Increasing atrial fibrillation (AF) burden in heart failure with preserved ejection fraction was associated with worsening left atrial (LA) mechanics, LA remodeling, central hemodynamics, right ventricular-pulmonary artery coupling, and pericardial restraint. LV = left ventricular; PVR = pulmonary vascular resistance.