Exercise unmasks the limited multi-organ reserve characteristic of heart failure with preserved ejection fraction (HFpEF). Using invasive cardiopulmonary exercise testing (iCPET), metabolite profiling and genomics, the investigators characterised seven exercise physiologic deficits in HFpEF patients: reduced exercise stroke volume and heart rate, a steep PCWP/cardiac-output slope, elevated pulmonary vascular resistance, pulmonary mechanical limitation, impaired peripheral oxygen extraction, and the obesity-related exaggerated metabolic cost of exercise. They mapped the distribution and the functional and prognostic significance of these deficits and linked them to molecular (metabolite and genetic) signatures — a step toward more targeted HFpEF phenotyping and risk assessment.
Background: Exercise unmasks limitations in multi-organ system reserve capacity characteristic of heart failure with preserved ejection fraction (HFpEF). However, the metabolic and genetic underpinnings of exercise deficits, and their cumulative contribution to HFpEF severity and prognosis, remain incompletely understood.Methods: We used invasive cardiopulmonary exercise testing (iCPET), metabolite profiling, and genomics to simultaneously characterize seven exercise physiologic deficits in HFpEF patients: reduced exercise stroke volume and heart rate, steep pulmonary capillary wedge pressure/cardiac output (PCWP/CO) slope, elevated pulmonary vascular resistance, pulmonary mechanical limitation to exercise, impaired peripheral oxygen extraction, and obesity-related exaggerated metabolic cost of initiating exercise. We first mapped the distribution, functional, and prognostic significance of these exercise deficits. We then applied LASSO regression to identify metabolite signatures of e
