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Sex Differences in HFpEF Pathophysiology
Study Questions:
How do sex differences contribute to exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF), as measured by various invasive hemodynamic and echocardiographic parameters?
Methods:
Patients were defined as having HFpEF based on exertional intolerance, EF ≥50%, and pulmonary capillary wedge pressure (PCWP) ≥15 mm Hg at rest or ≥25 mm Hg with exercise. Exclusions included more than mild valvular disease and significant pulmonary disease. All patients were undergoing clinically indicated exercise right heart catheterization (RHC) via supine cycle ergometry. Invasive hemodynamic measurements, mixed venous blood gases, and lactates were taken at rest and at peak. Transthoracic echocardiography (TTE) was obtained in 37% of patients, either on the day of exercise RHC or within 112 days.
Results:
A total of 161 subjects were included, of whom 114 (71%) were women. Women had higher PCWP indexed to peak exercise workload (p = 0.001), and lower systemic (p = 0.019) and pulmonary arterial compliance (p = 0.032) (ratio of stroke volume to systemic arterial and pulmonary pulse pressures) at peak exercise. They had a greater rise in lactate indexed to peak workload (p = 0.007). TTE measurements revealed higher E/e’ ratios at both rest and peak, along with higher EF and smaller ventricular dimensions.
Conclusions:
This study is the first to investigate gender differences in the hemodynamic exercise profiles of HFpEF patients. The authors identify cardiac, pulmonary, and systemic contributors to impaired exercise tolerance, which differ significantly between men and women. In particular, women had: 1) poorer diastolic reserve at peak exercise with a greater rise in PCWP for a given workload and higher E/e’ ratios, implying greater left ventricular filling pressures; 2) lower systemic and pulmonary arterial compliance, suggesting concomitant vascular abnormality; and 3) greater rise in lactate indexed to peak workload, suggesting poorer peripheral oxygen utilization.
Perspective:
This study provides a first glimpse of potential gender differences in HFpEF, with a focus on mechanisms contributing to exercise intolerance. It highlights the need to take gender into account in the design of studies of this disease, and the development of therapies aimed at physiologic targets like diastolic reserve or vascular compliance. Limitations include small sample size with a disproportionate number of women. Given the large number of variables and calculated parameters, it is also unclear how the authors addressed the problem of multiple comparisons.
Keywords: Blood Pressure, Cardiac Catheterization, Diagnostic Imaging, Diastole, Echocardiography, Ergometry, Exercise Tolerance, Heart Failure, Hemodynamics, Lactic Acid, Lung Diseases, Pulmonary Wedge Pressure, Sex Characteristics, Stroke Volume, Vascular Diseases, Workload
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