Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction

Abstract

Background: When advanced, heart failure with preserved ejection fraction (HFpEF) is readily apparent. However, diagnosis of earlier disease may be challenging because exertional dyspnea is not specific for heart failure, and biomarkers and hemodynamic indicators of volume overload may be absent at rest.

Methods and results: Patients with exertional dyspnea and ejection fraction >50% were referred for hemodynamic catheterization. Those with no significant coronary disease, normal brain natriuretic peptide assay, and normal resting hemodynamics (mean pulmonary artery pressure <25 mm Hg and pulmonary capillary wedge pressure [PCWP] <15 mm Hg) (n=55) underwent exercise study. The exercise PCWP was used to classify patients as having HFpEF (PCWP ≥25 mm Hg) (n=32) or noncardiac dyspnea (PCWP <25 mm Hg) (n=23). At rest, patients with HFpEF had higher resting pulmonary artery pressure and PCWP, although all values fell within normal limits. Exercise-induced elevation in PCWP in HFpEF was confirmed by greater increases in left ventricular end-diastolic pressure and was associated with blunted increases in heart rate, systemic vasodilation, and cardiac output. Exercise-induced pulmonary hypertension was present in 88% of patients with HFpEF and was related principally to elevated PCWP, as pulmonary vascular resistances dropped similarly in both groups. Exercise PCWP and pulmonary artery systolic pressure were highly correlated. An exercise pulmonary artery systolic pressure ≥45 mm Hg identified HFpEF with 96% sensitivity and 95% specificity.

Conclusions: Euvolemic patients with exertional dyspnea, normal brain natriuretic peptide, and normal cardiac filling pressures at rest may have markedly abnormal hemodynamic responses during exercise, suggesting that chronic symptoms are related to heart failure. Earlier and more accurate diagnosis using exercise hemodynamics may allow better targeting of interventions to treat and prevent HFpEF progression.

Figures

Figure 1

[A] Pulmonary capillary wedge pressure (PCWP) increased to a greater extent in HFpEF (red) compared with non-cardiac dyspnea (NCD, green) with leg elevation and during exercise. PCWP returned to baseline almost immediately in recovery. [B] Left ventricular end-diastolic (LVEDP) and [C] mean pulmonary artery (PA) pressures also rose with exercise more dramatically in HFpEF (p values for exercise change between groups).

Figure 2

Increases in heart rate (ΔHR), cardiac index (ΔCI) and systemic arterial vasodilation (ΔSVRI) with exercise were impaired in HFpEF (red) compared with non-cardiac dyspnea (NCD, green). Systolic blood pressure (ΔSBP) increased to greater extent in HFpEF, while pulmonary vasodilation (ΔPVRI) was similar.

Figure 3

[A,B] Exercise changes in PCWP (ΔPCWP) were highly correlated with the corresponding changes in right atrial pressure (ΔRA) and pulmonary artery systolic pressure (ΔPASP). [C] Peak exercise PCWP (PCWPEX) and PASP (PASPEX) were strongly associated. [D] Clinical measures (BNP, E/e’) and diagnostic algorithms (ESC) did not robustly distinguish HFpEF from NCD. In contrast, PCWP with leg raise and exercise PASP showed excellent discrimination between HFpEF and NCD. Panel [E] shows receiver-operating characteristic curves using PCWP>15mmHg to define HFpEF. See text for details.