Reducing Pulmonary Capillary Wedge Pressure During Exercise Does Not Improve Exercise Capacity in Heart Failure With Preserved Ejection Fraction

Background: Exercise intolerance is a defining characteristic of heart failure with preserved ejection fraction (HFpEF). A marked rise in pulmonary capillary wedge pressure (PCWP) during exertion is pathognomonic for HFpEF and is thought to be a key cause of exercise intolerance. If true, acutely lowering PCWP would improve exercise capacity. To test this hypothesis, we evaluated peak exercise capacity with and without nitroglycerin (NTG) to acutely lower PCWP during exercise in patients with HFpEF. Methods: In a preliminary analysis of a clinical trial, 15 patients with HFpEF (69±6 years, 60% female) underwent 2 upright, seated cycle exercise tests dosed with sublingual NTG or placebo control (CON), every 15 minutes in a single-blind, cross-over design. A right heart catheter was used to measure end-expiratory PCWP and cardiac output (Qc, direct Fick). Oxygen uptake was measured using breath-by-breath system. Measures were made at rest, 20W, and peak exercise. Results: PCWP increased from 6.0±2.4 to 33.7±7.4 mmHg from rest to peak exercise with placebo. With NTG, PCWP increased significantly less from 4.5±3.1 to 26.3±5.9 mmHg (drug x exercise p = 0.019). There was no change in peak VO 2 with NTG (CON: 1.25±0.36 vs NTG: 1.26±0.41 L/min, drug x exercise p = 0.986, Figure ). Peak Qc was similar between conditions (Qc: CON 10.4±2.3 vs 10.8±3.2 L/min). During submaximal exercise, PCWP was lower with NTG with no difference in VO 2 (PCWP: CON 21.2±6.5 vs NTG 16.6±6.4 mm Hg, VO 2 CON:0.87±0.17 vs NTG 0.86±0.17 L/min) but with a lower stroke volume (NTG: 90±18 vs CON: 98±21 ml). Conclusions: Sublingual nitroglycerin effectively lowered PCWP during submaximal and maximal exercise. Despite this reduction in PCWP, peak VO 2 was not changed. These results suggest acutely lowering PCWP is insufficient to improve exercise capacity and raises the possibility that high PCWP during exercise is a secondary phenomenon rather than a primary cause of exercise intolerance in patients with HFpEF.