Prognostic Relevance of Left Atrial Dysfunction in Heart Failure With Preserved Ejection Fraction

Abstract

Background: Left atrial (LA) size is an established marker of risk for adverse outcomes in heart failure with preserved ejection fraction (HFpEF). However, the independent prognostic importance of LA function in HFpEF is not known.

Methods and results: We assessed LA function measured by speckle-tracking echocardiography in 357 patients with HFpEF enrolled in the Treatment Of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial who were in sinus rhythm at the time of echocardiography. Lower peak LA strain, indicating LA dysfunction, was associated with older age, higher prevalence of atrial fibrillation and left ventricular (LV) hypertrophy, worse LV and right ventricular systolic function, and worse LV diastolic function. At a mean follow-up of 31 months (interquartile range, 18-43months), 91 patients (25.5%) experienced the primary composite end point of cardiovascular death, HF hospitalization, and aborted sudden death. Lower peak LA strain was associated with a higher risk of the composite end point (hazard ratio, 0.96 per unit of reduction in strain; 95% confidence interval, 0.94-0.99; P=0.009) and of HF hospitalization alone (hazard ratio, 0.95 per unit of reduction in strain; 95% confidence interval, 0.92-0.98; P=0.003). The association of LA strain with incident HF hospitalization remained significant after adjustment for clinical confounders, but not after further adjustment for LV global longitudinal strain and the E/E' ratio, parameters of LV systolic and diastolic function, respectively.

Conclusions: LA dysfunction in HFpEF is associated with a higher risk of HF hospitalization independent of potential clinical confounders, but not independent of LV strain and filling pressure. Impairment in LV systolic and diastolic function largely explains the association between impaired LA function and higher risk of HF hospitalization in HFpEF.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.

Keywords: atrial strain; diastolic heart failure; echocardiography; prognosis.

© 2016 American Heart Association, Inc.

Figures

Figure 1

Two-dimensional speckle tracking imaging in the apical four-chamber view in a HFpEF patient with impairment of LA function (decreased peak LA strain).

Figure 2

Distribution of peak LA strain in the HFpEF study population (A) overall and (B) by LA size.

Figure 3

Scatter plot and Pearson's correlation of peak LA strain and (A) global longitudinal strain and (B) E/E′ in the study population overall.

Figure 4

Forest plot graph demonstrating the association of LA function (reservoir, conduit and pump) with (A) the primary endopoint and (B) HF hospitalization. *Multivariable analysis is adjusted for age, sex, race, enrollment region (Americas versus Russia/Georgia), randomization strata, history of atrial fibrillation, heart rate, New York Heart Association class, history of stroke, creatinine, hematocrit, LVEF, left atrial volume index, and randomized treatment assignment. *Hazard Ratio: per unit of SD

Figure 4

Forest plot graph demonstrating the association of LA function (reservoir, conduit and pump) with (A) the primary endopoint and (B) HF hospitalization. *Multivariable analysis is adjusted for age, sex, race, enrollment region (Americas versus Russia/Georgia), randomization strata, history of atrial fibrillation, heart rate, New York Heart Association class, history of stroke, creatinine, hematocrit, LVEF, left atrial volume index, and randomized treatment assignment. *Hazard Ratio: per unit of SD