Impaired Myocardial Oxygen Availability Contributes to Abnormal Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction

Abstract

BackgroundHypertension is a frequent risk factor for the development of heart failure with preserved ejection fraction (HFPEF). Progressive extracellular matrix accumulation has been presumed to be the fundamental pathophysiologic mechanism that leads to the transition to impaired diastolic reserve. However, the contribution of other mechanisms affecting active and passive components of diastolic function has not been comprehensively assessed. In this study, we investigated the potential role of impaired myocardial oxygen delivery in the pathophysiology of HFPEF.Methods and ResultsPatients with HFPEF, those with controlled hypertension, and healthy controls underwent simultaneous right‐heart catheterization, echocardiography, and paired arterial and coronary sinus blood gas sampling at rest and during supine‐cycle ergometry. Despite a lower workload (HFPEF vs control, hypertension: 43±8 versus 114±12, 87±14 W; P<0.001 and P<0.05, respectively), peak exercise pulmonary capillary wedge pressure was markedly higher in HFPEF patients compared with healthy and hypertensive controls (32±2 versus 16±1 and 17±1 mm Hg, both P<0.001). During exercise, the transcardiac oxygen gradient increased significantly in all groups; however, the peak transcardiac oxygen gradient was significantly lower in HFPEF patients (P<0.05). In addition, the left ventricular–work corrected transcardiac oxygen gradient remained significantly lower in HFPEF patients compared with controls (P<0.001).ConclusionThe current study provides unique data suggesting that the abnormal diastolic reserve observed during exertion in HFPEF patients may, in part, be explained by impaired myocardial oxygen delivery due possibly to microvascular dysfunction. Further studies are required to confirm the structural and functional basis of these findings and to investigate the influence of potential therapies on this abnormality.

Sodium Nitrite Improves Exercise Hemodynamics and Ventricular Performance in Heart Failure With Preserved Ejection Fraction

“…However, elegant work from van Heerebeek et al (12) showed that cGMP limitation in HFpEF is not related to excessive breakdown but rather inadequate production, suggesting that NO-cGMP-providing therapies may be the more effective approach. A major barrier in managing many patients with HFpEF is related to the fact that the increase in cardiac filling pressures and PA pressure is confined to exercise, whereas hemodynamics at rest may be more normal (1)(2)(3)(4)(5)(6)(7)(8). Thus, an agent that enhances NO-cGMP signaling preferentially during exercise would be expected to provide more targeted hemodynamic improvements precisely at the time of greatest need.…”

“…limitations in the periphery(1)(2)(3)(4)(5)(6)(7)(8)10,11,(24)(25)(26). The subjects enrolled in the current study displayed many of these hemodynamic abnormalities, with a slight increase in resting RAP, PA pressure, and PCWP and dramatic increases during exercise that were coupled to limitations in CO reserve and abnormal pulmonary vascular function.…”

Reduced Myocardial Flow in Heart Failure Patients With Preserved Ejection Fraction

“…A review by Paulus and Tschöpe 6 further supports this view by proposing that coronary artery microvascular inflammation and dysfunction as a downstream consequence of a proinflammatory cascade leads to hypertrophy and myocyte stiffening, resulting in HFpEF. After this, van Empel et al 8 showed that measured exercise transcardiac oxygen gradient was significantly lower in HFpEF patients compared with healthy and hypertensive controls, suggesting impaired myocardial oxygen delivery (presumably because of microvascular dysfunction, although epicardial coronary arteries were not assessed) in this group. To further validate this possibility, we proposed examining MFR in a cohort of patients who had undergone clinically indicated PET scans at our institution.…”

Zooming in on the Microvasculature in Heart Failure With Preserved Ejection Fraction

“…van Empel performed assessment of rest and exercise transcardiac O 2 gradients, invasive hemodynamics and echocardiography in nine HFpEF patients without coronary disease and hypertensive (n=7) and healthy (n=12) controls 11 . The increase in the transcardiac O 2 gradient with stress was blunted in HFpEF as compared to either control group, consistent with impaired O 2 extraction and microcirculatory dysfunction as outlined above 7 .…”