Central Cardiac Limit to Aerobic Capacity in Patients With Exertional Pulmonary Venous Hypertension

Abstract

Background The mechanism of functional limitation in heart failure with preserved ejection fraction (HFpEF) remains controversial. We examined the contributions of central cardiac and peripheral mechanisms and hypothesized that the pulmonary vascular response to exercise is an important determinant of aerobic capacity among patients with exertional pulmonary venous hypertension (ePVH). Methods and Results We compared 31 ePVH patients (peak VO2<80% predicted and peak pulmonary arterial wedge pressure≥20 mmHg) with 31 age and gender matched controls (peak VO2>80% predicted) who underwent invasive cardiopulmonary exercise testing for unexplained exertional intolerance. ePVH patients had lower peak cardiac output (73±14 vs 103±18 % predicted; p<0.001) compared to controls, related both to impaired chronotropic response (peak HR 111±25 vs 136±24 bpm; p<0.001) and to reduced peak stroke volume index (47±10 vs 54±15 mL/min/m2; p=0.03). Peak systemic O2 extraction was not different between groups (arterial-mixed venous oxygen content difference: 13.0±2.1 vs 13.4±2.4 mL/dL; p=0.46). ePVH patients had higher resting (150±74 vs 106±50 dyne.s.cm−5; p=0.009), peak (124±74 vs 70±41 dyne.s.cm−5; p<0.001) and isoflow pulmonary vascular resistance (PVR; 124±74 vs 91±33 dyne.s.cm−5 at CO~10.6L/min; p=0.04). PVR decreased with exercise in all control subjects but increased in 36% (n=11) of ePVH patients. Abnormal pulmonary vascular response was not associated with peak VO2. Conclusion Reduced cardiac output response, rather than impaired peripheral O2 extraction, constrains oxygen delivery and aerobic capacity in ePVH. Pulmonary vascular dysfunction is common in patients with ePVH at rest and with exercise.

Exercise Intolerance in Heart Failure With Preserved Ejection Fraction

“…Importantly, their patients' resting PCW was elevated and increased during exercise along with the pulmonary artery pressure. Consistent with the study by Santos et al, 4 the reduction in VO 2 in patients with HFpEF was because of an inadequate increase in cardiac output, attributable to both lower stroke volume and heart rate at peak exercise. There was no difference in peak CaO 2 −CvO 2 .…”

“…4,5 Both groups performed upright cardiopulmonary exercise testing with hemodynamic monitoring in patients with preserved ejection fraction, elevated pulmonary capillary wedge pressure (PCW), and exercise intolerance. Santos et al 4 found that the major contributor to exercise disability was a limitation of cardiac output, indicating a cardiac cause.…”

“…4,5 Both groups performed upright cardiopulmonary exercise testing with hemodynamic monitoring in patients with preserved ejection fraction, elevated pulmonary capillary wedge pressure (PCW), and exercise intolerance. Santos et al 4 found that the major contributor to exercise disability was a limitation of cardiac output, indicating a cardiac cause. This finding is consistent with a similar study by Abudiab et al 1 In contrast, Dhakal et al 5 found that a peripheral limitation was the most important cause of reduced aerobic capacity, whereas impaired cardiac output had less impact.…”

Exercise Intolerance in Heart Failure with Preserved Ejection Fraction

“…Santos et al 11 and Abudiab et al 12 suggested that the major contributor to exercise inability in HFpEF patients is the reduced cardiac output relative to metabolic needs, indicating a cardiac cause. Extensive fibrosis and titin hypophosphorylation 7 is thought to create stiffness in the LV of patients with HFpEF, contributing to the cardiac limitations in exercise capacity.…”

High intensity exercise training in heart failure: Understanding the exercise “overdose”

“…Most recent studies, especially performed in subjects with HF and preserved ejection fraction, have definitively changed this paradigm by looking at the variety of complex mechanisms that limit the oxygen (O 2 ) transport chain from air to mithocondria [5][6][7] and, through this, discerning how the physical therapeutic approach may work. 8 According to the Fick principle, VO 2 depends on cardiac output (CO) times O 2 artero-venous difference (A-VO 2 diff) and reflects the product of the integrated biological response of the heart and peripheral mechanisms involved in O 2 delivery (convection), diffusion and extraction during exercise.…”