Exercise haemodynamics in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Aims: Exercise right heart catheterization (RHC) is considered the gold-standard test to diagnose heart failure with preserved ejection fraction (HFpEF). However, exercise RHC is an insufficiently standardized technique, and current haemodynamic thresholds to define HFpEF are not universally accepted. We sought to describe the exercise haemodynamics profile of HFpEF cohorts reported in literature, as compared with control subjects. Methods and results: We performed a systematic literature review until December 2020. Studies reporting pulmonary artery wedge pressure (PAWP) at rest and peak exercise were extracted. Summary estimates of all haemodynamic variables were evaluated, stratified according to body position (supine/upright exercise). The PAWP/cardiac output (CO) slope during exercise was extrapolated. Twenty-seven studies were identified, providing data for 2180 HFpEF patients and 682 controls. At peak exercise, patients with HFpEF achieved higher PAWP (30 [29–31] vs. 16 [15–17] mmHg, P < 0.001) and mean right atrial pressure (P < 0.001) than controls. These differences persisted after adjustment for age, sex, body mass index, and body position. However, peak PAWP values were highly heterogeneous among the cohorts (I2 = 93%), with a relative overlap with controls. PAWP/CO slope was steeper in HFpEF than in controls (3.75 [3.20–4.28] vs. 0.95 [0.30–1.59] mmHg/L/min, P value < 0.0001), even after adjustment for covariates (P = 0.007). Conclusions: Despite methodological heterogeneity, as well as heterogeneity of pooled haemodynamic estimates, the exercise haemodynamic profile of HFpEF patients is consistent across studies and characterized by a steep PAWP rise during exercise. More standardization of exercise haemodynamics may be advisable for a wider application in clinical practice.