Reducing pulmonary capillary wedge pressure may not improve exercise capacity in HFpEF
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Sublingual nitroglycerin reduced pulmonary capillary wedge pressure in patients with HF with preserved ejection fraction during exercise, but did not improve oxygen uptake or cardiac output, according to findings published in Circulation.
Satyam Sarma, MD, associate professor in the department of internal medicine at UT Southwestern Medical Center, and colleagues stated that these results indicate that reducing pulmonary capillary wedge pressure may not be sufficient to improve exercise capacity in HFpEF.
“The key takeaway is that very high increases in pulmonary capillary wedge pressure during exercise are not the primary reason for exercise intolerance in patients with HFpEF,” Sarma told Healio. “Our results suggest elevated exercise pulmonary capillary wedge pressure is likely a secondary phenomenon, possibly the result of stiff and noncompliant left ventricle, rather than a primary cause of exercise intolerance in patients with HFpEF.
“Resting pulmonary capillary wedge pressure is still an important marker of pulmonary congestion and lowering it should remain an important therapeutic goal,” Sarma told Healio. “On the other hand, our results suggest strategies that solely target exercise pulmonary capillary wedge pressure, and that do not also improve ventricular stiffening, are unlikely to improve exercise intolerance in patients with HFpEF.”
Sarma and colleagues enrolled 30 patients with HFpEF as part of an ongoing exercise clinical trial evaluating the mechanisms behind exercise intolerance in HFpEF (mean age, 70 years; 63% women). Participants underwent two rounds of upright, seated cycle exercise plus sublingual nitroglycerin or placebo every 15 minutes.
Pulmonary capillary wedge pressure, oxygen uptake and cardiac output were assessed at rest, 20 W and peak exercise during both placebo and nitroglycerin conditions.
When participants received placebo, mean pulmonary capillary wedge pressure increased from 8 mm Hg to 35 mm Hg from rest to peak exercise, according to the study.
Compared with placebo, mean pulmonary capillary wedge pressure rest with nitroglycerin was:
- –1 mm Hg at rest;
- –5 mm Hg at 20 W; and
- –7 mm Hg at peak exercise (P = .004).
Researchers reported that nitroglycerin did not significantly improve oxygen uptake at any point during the rounds of exercise (1.34 vs. 1.32 L per minute; P = .984).
In addition, nitroglycerin reduced mean stroke volume compared with placebo at rest (–8 mL) and 20 W (–7 mL) but not at peak exercise (0 mL), according to the study.
“Exercise intolerance remains a significant unmet need in patients with HFpEF,” Sarma told Healio. “There are many potential abnormalities in cardiac, vascular, pulmonary and skeletal muscle function that can contribute to exercise intolerance. We need to better understand these mechanisms for exercise intolerance and develop new phenotyping strategies to identify new therapeutic approaches.”
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