Abnormal right ventricular-pulmonary artery coupling with exercise in heart failure with preserved ejection fraction

Abstract

Background: Exercise intolerance is common in people with heart failure and preserved ejection fraction (HFpEF). Right ventricular (RV) dysfunction has been shown at rest in HFpEF but little data are available regarding dynamic RV-pulmonary artery (PA) coupling during exercise.

Methods and results: Subjects with HFpEF (n = 50) and controls (n = 24) prospectively underwent invasive cardiopulmonary exercise testing using high-fidelity micromanometer catheters along with simultaneous assessment of RV and left ventricular (LV) mechanics by echocardiography. Compared with controls at rest, subjects with HFpEF displayed preserved RV systolic and diastolic mechanics (RV s' and e'), impaired LV s' and e', higher biventricular filling pressures, and higher pulmonary artery pressures. On exercise, subjects with HFpEF displayed less increase in stroke volume, heart rate, and cardiac output (CO), with blunted increase in CO relative to O₂ consumption (VO₂). Enhancement in RV systolic and diastolic function on exercise was impaired in HFpEF compared with controls. Exercise-induced PA vasodilation was reduced in HFpEF in correlation with greater venous hypoxia. Elevations in biventricular filling pressures and limitations in CO reserve were strongly correlated with abnormal enhancement in ventricular mechanics in the RV and LV during stress.

Conclusions: In addition to limited LV reserve, patients with HFpEF display impaired RV reserve during exercise that is associated with high filling pressures and inadequate CO responses. These findings highlight the importance of biventricular dysfunction in HFpEF and suggest that novel therapies targeting myocardial reserve in both the left and right heart may be effective to improve clinical status.

Keywords: Diastolic function; Exercise; Haemodynamics; Heart failure; Heart failure with preserved ejection fraction; Pulmonary hypertension; Right ventricular function.

Figure 1

Baseline, low-level exercise (20 W), and peak exercise haemodynamics shown in heart failure with preserved ejection fraction subjects (red) and controls (black) for cardiac output (A), stroke volume (B), heart rate (C), cardiac output reserve relative to oxygen consumption (ΔCO/ΔVO₂) (D), and arterial-venous oxygen contents and difference (AVO₂diff) (E and F). P-value refers to group–exercise interaction comparison (RMANOVA) characterizing exercise reserve. *P < 0.01 between groups for single time point comparisons.

Figure 2

When compared with controls (black), subjects with heart failure with preserved ejection fraction (red) displayed impaired pulmonary vasodilation, with less reduction in pulmonary vascular resistance (A), greater reduction in pulmonary artery compliance (B), and steeper slope of pulmonary artery pressure-flow relationship (C). In heart failure with preserved ejection fraction subjects, pulmonary vascular resistance increased with decreasing mixed venous oxygen saturation (pulmonary artery), whereas no such relationship was observed in controls (D).

Figure 3

(A–D) Compared with controls (black), subjects with heart failure with preserved ejection fraction (red) showed less increase in left and right ventricular systolic velocities (LV S′, RV S′) during exercise that were correlated with reduced diastolic reserve in the respective chambers (LV/RV E′).

Figure 4

Compared with controls (black), subjects with heart failure with preserved ejection fraction displayed less increase in left ventricular (A) and right ventricular (C) diastolic mechanics (E′ velocities) at low level (20 W) and peak exercise. Impaired enhancement in diastolic mechanics was associated with greater increases in pulmonary capillary wedge pressure (B) and right atrial pressure (D).