Exercise Lower-body Negative Pressure in Heart Failure With Preserved Ejection Fraction

Inclusion Criteria for the HFpEF Group: * Adults with a clinical diagnosis of HFpEF (LV ejection fraction ≥50%) measured in the year prior to Visit 1 (and confirmed at Visit 1), who are New York Heart Association Functional Class II-III (mild-moderate symptoms), ambulatory, receiving guideline-directed medical therapy unchanged for ≥2 months, and clinically stable for ≥3 months. * Symptom(s) of heart failure requiring treatment within the year prior to Visit 1 * NT-proBNP \>50 pmol/L (sinus rhythm) or \>150 pmol/L (atrial fibrillation in year prior) * Diastolic dysfunction based on at least one of the following echocardiographic findings: * Left atrial enlargement (diameter \>4 cm or volume index \>28 mL/m2); or * e' \<10 cm/s (lateral) or \<8 cm/s (septal), or * E/e' \>10 (lateral), or \>15 (septal) Inclusion Criteria for the Healthy Control Group: \- Healthy sedentary or recreationally active adults from the community Exclusion Criteria for the HFpEF Group: * Any prior measurement demonstrated LV ejection fraction ≤40% * Primary pulmonary, metabolic, renal, hepatic, neuromuscular, or malignant disease * Primary pulmonary vascular, complex congenital, or \> mild valvular heart disease * Documented infiltrative cardiomyopathy * Documented valvular or coronary disease requiring intervention * Myocarditis, pericardial effusion, acute coronary syndrome, or revascularization in the last 3 months * Resting seated systolic blood pressure \>160 mmHg or \<100 mmHg * Jugular venous pressure \>12 cm * Inferior vena cava \>2 cm with no inspiratory collapse, or severe right ventricular dysfunction by echo * Ambulatory supplemental oxygen * Current or recent participation in \>150 min. per week of moderate intensity exercise * Current or recent (within the past 6 months) smoking * Body mass index \>35 kg/m2 * Contraindication to exercise or otherwise unable to perform cycle ergometry * Poor echocardiographic imaging windows Exclusion Criteria for the Healthy Control Group * Current or recent participation in \>150 min. per week of moderate intensity exercise * History of any cardiovascular condition or cardioactive drug use * History of any respiratory condition including asthma * History of any metabolic condition including diabetes * Non-sinus rhythm * Echocardiographic evidence of significant left ventricular hypertrophy, valvular abnormalities, left ventricular ejection fraction \<50%, or diastolic dysfunction as described in HFpEF inclusion criteria. * Seated blood pressure ≥140/90 mmHg * Any other chronic systemic illness * Current or recent (within the past 6 months) smoking * Body mass index \>35 kg/m2 * Contraindication to exercise or otherwise unable to perform cycle ergometry * Poor echocardiographic imaging windows