Abstract 12714: Impact of Reduced Left Ventricular Filling Pressure on Diastolic Function During Exercise in Patients With HFpEF

Abstract

Background: During exercise, patients with heart failure with preserved ejection fraction (HFpEF) have an exaggerated increase in pulmonary capillary wedge pressure (PCWP) and left atrial-left ventricular pressure gradient (E wave velocity), as well as a blunted increase in early diastolic recoil (e’ velocity). It is unknown if non-invasive markers of diastolic function improve when exercise PCWP is acutely ameliorated. Methods: Patients with invasively proven HFpEF (n = 34, 71±6 years, 59% female, PCWP > 25 or Δ15 mm hg at peak exercise) underwent 2 seated cycle exercise tests with sublingual nitroglycerin (NTG) and placebo (PLB) in a cross-over design. PCWP (right heart catheter), tissue Doppler velocities of the mitral annulus (e’) and mitral inflow velocities (E) were measured at rest and during 20-watt submaximal steady state exercise. Differences between placebo and GTN conditions were assessed by repeated measures mixed model. Results: PCWP was 7.6±3.9 mmHg at rest and 21.1±7.8 mmHg with sub-maximal exercise and was decreased by 14% and 24% respectively by NTG (Drug effect p < 0.001, Figure ). Mean E’ was 6.2±1.5 cm/sec at rest and 8.8±1.7 cm/sec during exercise and was decreased by 6% and 8% respectively by NTG (p = 0.003), but augmentation during exercise was unchanged (NTG +36%, PLB +41%, p = 0.211). The E wave velocity was 69.6±21.2 cm/sec rest and 101.9±31.3 cm/sec during exercise and was decreased by 12% and 11% with NTG respectively (p <0.001), but augmentation during exercise was unchanged (NTG +48%, PLB +46%, p = 0.507). Conclusions: NTG significantly and acutely lowered exercise PCWP in patients with HFpEF but did not improve diastolic function as assessed by echocardiography. The symmetrical slowing of E wave velocity and e’ with reduced PCWP demonstrate that higher preload helps maintain diastolic recoil and early diastolic filling for patients with HFpEF. Therapies that reduce preload in HFpEF may result in apparently worsened markers of diastolic function.