Coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction

Abstract

There are multiple proposed mechanisms for the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). We hypothesized that coronary microvascular dysfunction is common in these patients. In a prospective, observational study, patients undergoing cardiac catheterization with HFpEF [left ventricular (LV) ejection fraction ≥ 50% and with clinical HF] were compared with similar patients without HFpEF. Patients with ≥50% stenosis were excluded, and coronary flow reserve (CFR) and the index of microvascular resistance (IMR) were measured after adenosine administration using a guidewire, with CFR ≤ 2 and IMR ≥ 23 being abnormal. Baseline characteristics and CFR and IMR were compared in 30 HFpEF patients and 14 control subjects. Compared with control subjects, HFpEF patients were older (65.4 ± 9.6 vs. 55.1 ± 3.1 yr, P < 0.01), had higher numbers of comorbidities (4.4 ± 1.5 vs. 2.6 ± 1.9, P = 0.002), had higher median B-type natriuretic peptide [161 (interquartile range: 75-511) pg/dl vs. 37 (interquartile range: 18.5-111) pg/dl, P < 0.01], and had higher LV end-diastolic pressure (17.8 ± 4.2 vs. 8.4 ± 4.2, P < 0.01). HFpEF patients had lower CFR (2.55 ± 1.60 vs. 3.84 ± 1.89, P = 0.024) and higher IMR (26.7 ± 10.3 vs. 19.7 ± 9.7 units, P = 0.037) than control subjects. Most (71.4%) control subjects had normal coronary physiology, whereas 36.7% of HFpEF patients had both abnormal CFR and IMR and another 36.7% had either abnormal CFR or IMR. In conclusion, this is the first study that has reported invasively determined CFR and IMR in HFpEF patients. We demonstrated the presence of four distinct coronary physiology groups in HFpEF patients. Investigation into the potential mechanisms for these findings is needed. NEW & NOTEWORTHY In this prospective observational study of patients with heart failure with preserved ejection fraction (HFpEF), we found that patients with HFpEF had more abnormalities of coronary flow and resistance than asymptomatic control patients, indicating that coronary microvascular dysfunction may play a role in the HFpEF disease process.

Endothelium‐dependent and independent coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction

“…Recent studies, editorial commentaries and reviews have begun to embrace the potential importance of CMD in the pathophysiology of HFpEF . In an autopsy study, patients with HFpEF displayed a higher prevalence of microscopic hypertrophy, coronary microvascular rarefaction, and fibrosis than age‐matched controls .…”

“…endothelin), while endothelium‐independent dysfunction depends on vascular myocyte tone and other factors . Although a number of studies have revealed that endothelium‐independent CMD is present on average in patients with HFpEF, both non‐invasively and invasively, no study has yet specifically evaluated endothelium‐dependent coronary microvascular function. The current study confirms and extends upon these earlier studies by demonstrating impaired CFR as measured directly in a much larger cohort of patients, while demonstrating for the first time in HFpEF that coronary endothelium‐dependent vasodilatation is also impaired in a substantial proportion of patients.…”

“…While clinical cardiology originally focused on diseases of the large epicardial conduit arteries, myocardial perfusion is importantly determined by structure and function of the coronary microvasculature and capillaries . An increasing number of studies have shown that coronary microvascular dysfunction (CMD) plays an important role in many cardiovascular diseases, including heart failure with preserved ejection fraction (HFpEF) . In this patient cohort, CMD has been demonstrated histologically, via imaging techniques, and invasively .…”

Effect of tofogliflozin on cardiac and vascular endothelial function in patients with type 2 diabetes and heart diseases: A pilot study

“…However, change of %FMD was not associated with change of E/e ′ in the present study. It is possible that for the evaluation of endothelial function of small vessels, for example, the peripheral arterial tonometry ratio might be more suitable, as coronary microcirculation impairment participates in left ventricular diastolic dysfunction.…”

Coronary microvascular dysfunction in heart failure with preserved ejection fraction – adding new pieces to the jigsaw puzzle

“…A key point of the study is that CMD, similarly to HFpEF, can be manifold and the existence of different CMD forms in HFpEF should be identified in order to unravel its role and weight in the pathophysiology of HFpEF. Accordingly, Dryer et al . recently demonstrated the presence of four distinct coronary physiology groups in HFpEF patients combining invasive measurements of CFR and index of microvascular resistance.…”