Reduced Myocardial Flow in Heart Failure Patients With Preserved Ejection Fraction

Abstract

Background— There remains limited insight into the pathophysiology and therapeutic advances directed at improving prognosis for patients with heart failure with preserved ejection fraction (HFpEF). Recent studies have suggested a role for coronary microvascular dysfunction in HFpEF. Rb-82 cardiac positron emission tomography imaging is a noninvasive, quantitative approach to measuring myocardial flow reserve (MFR), a surrogate marker for coronary vascular health. The aim of this study was to determine whether abnormalities exist in MFR in patients with HFpEF without epicardial coronary artery disease. Methods and Results— A total of 376 patients with ejection fraction ≥50%, no known history of obstructive coronary artery disease, and a confirmed diagnosis of heart failure (n=78) were compared with patients with no evidence of heart failure (n=298), further stratified into those with (n=186) and without (n=112) hypertension. Global and regional left ventricular MFR was calculated as stress/rest myocardial blood flow using Rb-82 positron emission tomography. Patients with HFpEF were more likely to be older, female, and have comorbid hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, anemia, and renal dysfunction. HFpEF was associated with a significant reduction in global MFR (2.16±0.69 in HFpEF versus 2.54±0.80 in hypertensive controls; P <0.02 and 2.89±0.70 in normotensive controls; P <0.001). A diagnosis of HFpEF was associated with 2.62 times greater unadjusted odds of having low global MFR (defined as <2.0) and remained a significant predictor of reduced global MFR after adjusting for comorbidities. Conclusions— HFpEF, in the absence of known history for obstructive epicardial coronary artery disease, is associated with reduced MFR independent of other risk factors.

INDIE-HFpEF (Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure With Preserved Ejection Fraction)

“…26 Finally, recent studies have shown impairment in coronary microvascular structure and function that are related in large part to abnormalities in NO-cGMP bioavailability in HFpEF, which may limit O 2 delivery and utilization in the heart as well as the periphery. 27-29 …”

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

“…5 Over 1000 PET-referred patients had a normal ejection fraction and no PET-evidence of epicardial coronary artery disease. Of these, 78 were retrospectively identified to have a previous diagnosis of HFpEF by chart review and were compared to 112 normotensive and 186 hypertensive controls.…”

“…The potential impact of diffuse microvascular endothelial inflammation on the functional and structural integrity of the microcirculation and the role that microcirculatory dysfunction itself may play in HFpEF pathophysiology are unclear. In this issue of Circulation Heart Failure , Srivaratharajah et al 5 add to a small but growing body of literature suggesting a role for microvascular dysfunction in the pathophysiology of HFpEF.…”

Percutaneous Pericardial Resection

“…This model has been shown to display several features of human HFpEF, including elevation in LVEDP, hypertension, oxidative stress, and coronary microvascular dysfunction. 18–20, 26–29 However, we did not perform experiments to demonstrate that these animals had diastolic dysfunction or true clinical heart failure, and further study is warranted in this regard.…”