Contribution of Central Abnormalities to Exertional Dyspnea and Ventilatory Response in Heart Failure with Preserved Ejection Fraction

Abstract

Introduction: Exercise intolerance is attributed to cardiac and peripheral abnormalities in heart failure with preserved ejection fraction (HFpEF). However, no study has evaluated the relationships between hemodynamics, dyspnea and ventilatory response in HFpEF. Methods and Results: Subjects with invasively-diagnosed HFpEF (n = 50) and participants with dyspnea but no identifiable cardiac pathology (controls, n = 24) underwent invasive catheterization at rest and during exercise with simultaneous expired gas analysis and spiroergometry. Compared to controls, subjects with HFpEF displayed higher exercise pulmonary capillary wedge pressures (PCWP) and pulmonary artery pressures, greater Borg perceived dyspnea and fatigue scores, and increased respiratory rate relative to exercise intensity (Figure). Exercise PCWP was directly correlated with Borg dyspnea and effort scores (r = 0.31 and r = 0.39, both P < .01). The ratio of dead space ventilation to tidal volume (VD/VT) was greater in HFpEF during exercise (0.25 ± 0.09 vs. 0.33 ± 0.11, P = .002), and this was correlated with exercise PA pressures (r = 0.42, P = .0003). Compared to controls, HFpEF subjects displayed lower increase in VT during peak exercise (ΔVT 831 ± 464 vs. 454 ± 233 ml, P = .001). Peak VT was inversely correlated with exercise PCWP (r = −0.38, P = .0007). Peak VO2 was markedly impaired in HFpEF subjects (8.1 ± 2.4 vs. 14.2 ± 4.0 ml/kg/min, P < .0001) and varied inversely with exercise PCWP (r = −0.65, P < .0001). Conclusions: Central hemodynamic derangements that develop during exercise in people with HFpEF are correlated with subjective symptoms of dyspnea, impaired tidal volume reserve, and increased dead space ventilation relative to tidal volume, supporting the relevance of central hemodynamics as a key mediator of disability in HFpEF and important therapeutic target.