Top Things to Know: Elucidating the Clinical Implications and Pathophysiology of Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction

Published: July 11, 2022

  1. Heart failure with preserved ejection fraction (HFpEF) is one of the leading causes of pulmonary hypertension (PH) in the world.
  2. The definition of PH-HFpEF varies, and the modality of evaluation and prevalence is not consistent, however, PH may be present in a substantial proportion of the population, ranging from 36-83%.
  3. The variability in how PH-HFpEF is defined and diagnosed impacts the lack of clear incidence and prevalence data, and longitudinal data with standardized phenotyping.
  4. The reported prevalence of PH-HFpEF varies widely depending on the population (clinical trial participants vs. hospital-based cohorts), diagnostic approach (echocardiography or right heart catheterization) and how it is defined.
  5. This scientific statement clarifies key knowledge gaps associated with PH-HFpEF and suggests specific scientific research priorities for addressing identified gaps.
  6. Obesity and metabolic syndrome together account for up to 50% of patients with PH due to left heart disease with some data suggesting that the metabolic syndrome and associated inflammation may contribute to pulmonary vascular disease. The specific effects of age, sex, race, and comorbid conditions on PH risk in patients with HFpEF requires further study.
  7. Cancer and cancer therapies are associated with increased risk of cardiovascular disease, including HFpEF, due to effects on diastolic and microvascular dysfunction among other mechanisms.
  8. Little is known about pathophysiological processes and cellular/molecular mechanisms involved in the regulation of PH-HFpEF. What little that is known suggests pulmonary vascular pathology in PH-HFpEF is multifactorial and involves complex systemic alterations.
  9. The management of PH-HFpEF is challenging because of the lack of proven PH therapies in the setting of HFpEF.
  10. Successful randomized controlled trials (RCTs) in PH-HFpEF will likely require novel RCT designs such as umbrella trials, bucket trials, and adaptive trials This call to action encourages the scientific community to prioritize the study of PH-HFpEF, which requires collaboration, data sharing, and supportive clinical trial design.


Brittain EL, Thenappan T, Huston JH, Agrawal V, Lai Y-C, Dixon D, Ryan JJ, Lewis EF, Redfield MM, Shah SJ, Maron BA; on behalf of the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Lifestyle and Cardiometabolic Health; and Stroke Council. Elucidating the clinical implications and pathophysiology of pulmonary hypertension in heart failure with preserved ejection fraction: a call to action: a science advisory from the American Heart Association [published online ahead of print July 11, 2022]. Circulation. doi: 10.1161/CIR.0000000000001079