Assessment of Exercise Intolerance and Evaluation for HFpEF: A Literature Review of Pathophysiology, Diagnosis, and Management
Ali Moradi, Kurt Ramey, Kutiba Tabbaa, Abdullah Sahyouni, Kevin Sanchez Garcez, Shivanshu Kumar, Elaine Pan, Grant Barton, Olugbenga Oyesanmi, Robert SubbiondoHeart failure with preserved ejection fraction (HFpEF) is a type of heart failure in which the ejection fraction remains within the normal range (≥50%); however, patients still experience typical symptoms of heart failure. One of the most common manifestations in this population is exercise intolerance, which in some cases may be the only presenting symptom. Exercise intolerance refers to a reduced capacity to perform physical activity. Several processes, including impaired cGMP–PKG signaling, increased collagen deposition, endothelial dysfunction, increased arterial stiffness, pulmonary hypertension, and vascular remodeling, contribute to the pathophysiology of HFpEF. The disruption of these fundamental physiological processes significantly impairs exercise capacity, leading to attenuated increases in heart rate, stroke volume, and/or contractility, along with abnormal ventricular–vascular coupling during exertion. When EI is suspected, a spectrum of diagnostic modalities—from simple, low-cost tools such as the 6 min walk test to advanced imaging—can be used to evaluate its presence and its association with HFpEF. When EI in HFpEF is diagnosed, management should focus on addressing this limitation to improve quality of life and reduce morbidity and mortality. Exercise training and pharmacological therapies, such as SGLT2 inhibitors, may be beneficial in this population. In conclusion, EI is a common manifestation of HFpEF that significantly impacts patients’ quality of life. Understanding its underlying mechanisms and addressing it appropriately are essential to improving patient outcomes.