Right heart dysfunction in heart failure with preserved ejection fraction

Abstract

Aim: Right heart function is not well characterized in patients with heart failure and preserved ejection fraction (HFpEF). The goal of this study was to examine the haemodynamic, clinical, and prognostic correlates of right ventricular dysfunction (RVD) in HFpEF.

Methods and results: Heart failure and preserved ejection fraction patients (n = 96) and controls (n = 46) underwent right heart catheterization, echocardiographic assessment, and follow-up. Right and left heart filling pressures, pulmonary artery (PA) pressures, and right-sided chamber dimensions were higher in HFpEF compared with controls, while left ventricular size and EF were similar. Right ventricular dysfunction (defined by RV fractional area change, FAC <35%) was present in 33% of HFpEF patients and was associated with more severe symptoms and greater comorbidity burden. Right ventricular function was impaired in HFpEF compared with controls using both load-dependent (FAC: 40 ± 10 vs. 53 ± 7%, P < 0.0001) and load-independent indices (FAC adjusted to PA pressure, P = 0.003), with enhanced afterload-sensitivity compared with controls (steeper FAC vs. PA pressure relationship). In addition to haemodynamic load, RVD in HFpEF was associated with male sex, atrial fibrillation, coronary disease, and greater ventricular interdependence. Over a median follow-up of 529 days (IQR: 143-1066), 31% of HFpEF patients died. In Cox analysis, RVD was the strongest predictor of death (HR: 2.4, 95% CI: 1.6-2.6; P < 0.0001).

Conclusion: Right heart dysfunction is common in HFpEF and is caused by both RV contractile impairment and afterload mismatch from pulmonary hypertension. Right ventricular dysfunction in HFpEF develops with increasing PA pressures, atrial fibrillation, male sex, and left ventricular dysfunction, and may represent a novel therapeutic target.

Keywords: Atrial fibrillation; Gender; Haemodynamics; Heart failure; Pulmonary hypertension; Ventricular function.

Figure 1

(A) Distribution of right ventricular function (fractional area change fractional area change %) in controls and heart failure and preserved ejection fraction. (B) Stress-shortening relation of right ventricular fractional area change % to pulmonary artery pressure in controls and heart failure and preserved ejection fraction. If right ventricular dysfunction in heart failure and preserved ejection fraction were purely due to afterload-mismatch all fractional area change pulmonary artery pressure coordinates in heart failure and preserved ejection fraction and controls would fall along a single regression slope. The lower and steeper slope in heart failure and preserved ejection fraction indicates impaired contractility and heightened afterload-sensitivity in addition to more severe pulmonary hypertension. (C) Differential relation of right ventricular fractional area change % to systemic arterial blood pressure (SBP, left ventricular afterload) and pulmonary artery pressure (right ventricular afterload, B) in heart failure and preserved ejection fraction and controls. See text for details. Solid lines: linear regression, Interrupted lines: 95% CI bands; r, Pearson's correlation coefficient.

Figure 2

(A) Correlations (with regression line and 95% confidence intervals) between right ventricular function (right ventricular fractional area change %) and myocardial systolic tissue velocities at left ventricular lateral mitral annulus (left), interventricular septum (middle) or right ventricular lateral tricuspid annulus in controls (black) and heart failure patients (red). (2) Comparison of tissue velocities between controls, heart failure and preserved ejection fraction with (+) or without (−) right ventricular dysfunction by ANOVA and Tukey's post hoc test (*P < 0.05 vs. controls, ^#P < 0.05 vs. RVD (−).

Figure 3

(A) Impact of gender on right ventricular and Right atrial function and right ventricular haemodynamic load in heart failure and preserved ejection fraction patients (red) and controls. *P < 0.05 vs. females. (B) Distinct relations between right ventricular function and afterload in male and female heart failure and preserved ejection fraction patients.

Figure 4

(A) Impact of atrial fibrillation on haemodynamic parameters and right ventricular function in heart failure and preserved ejection fraction and controls (RA, right atrial, PA, pulmonary artery, SR, sinus rhythm). Differences tested with ANOVA and Tukey's post hoc test, *P < 0.05 vs. Con, ^§P < 0.05 vs. heart failure and preserved ejection fraction in sinus rhythm. (B) The impact of atrial fibrillation on maximal systolic tissue velocities of mitral and tricuspid annulus by tissue Doppler imaging. (C) Distinct relations between right ventricular function and afterload in heart failure and preserved ejection fraction in sinus rhythm and in atrial fibrillation.

Figure 5

Kaplan–Meier plots of survival in the heart failure and preserved ejection fraction group according to right ventricular function (factional area change). Significance tested with the log-rank test.