Table 2.
Studies on coronary microvascular function in HFpEF.
| Study Design | Study Population | Method (Measurement) | Stimulus | Microvascular Function Assessed | Outcome (SD/IQR) | Outcome Adjusted for Confounders |
|---|---|---|---|---|---|---|
| Heart-autopsy | ||||||
| Retrospective [12] | Deceased: HFpEF (n = 124); Controls (no HF) (n = 104) |
Histology: microvessels/mm2 (microvascular density) | Rarefaction | Microvascular density: 961 (800–1370) vs. 1316 (1148–1467), p < 0.0001 | Not performed, unmatched population | |
| Invasive coronary function assessment | ||||||
| Retrospective [14] | CAG after positive stress test: HFpEF > 65 (n = 32); HFpEF < 65 (n = 24); Controls (n = 31) |
Invasive CFR and IMR | Adenosine | Hyperaemia | CFR: 1.94 ± 0.28 vs. 1.83 ± 0.32 vs. 3.24 ± 1.11, p ≤ 0.04 IMR: 39.2 ± 6.8 vs. 27.2 ± 6.4 vs. 18.3 ± 4.4, p ≤ 0.03 |
Age, sex, HT, DM, CKD, AF, BMI, LVMI. Unmatched controls |
| Retrospective [9] | HFpEF (n = 162) | Invasive CFR and coronary blood flow (CBF) | Adenosine, acetylcholine | Hyperaemia | No absolute values reported. Mortality is increased in coronary MVD (HR 2.8–3.5). | Age, sex, BMI, DM, HT, hyperlipidaemia, smoking, Hb, creatinine, uric acid |
| Retrospective [32] | HFpEF (n = 22); no HFpEF (n = 29) |
Invasive CFR and CBF | Adenosine, acetylcholine | Hyperaemia | CFR: 2.5 ± 0.6 vs. 3.2 ± 0.7, p = 0.0003 Median CBF % increase: 1 (−35;34) vs. 64 (−4;133), p = 0.002 |
Age, sex |
| Prospective [33] | HFpEF with obstructive epicardial CAD (n = 38); HFpEF without epicardial CAD (n = 37) | CAG (CFR, coronary reactivity, IMR) and MRI | Adenosine, acetylcholine | Hyperaemia | CFR: 2.0(1.2–2.4) vs. 2.4(1.5–3.1), p = 0.06. IMR: 18(12–26) vs. 27(19–43), p = 0.02. 24% microvascular spasm due to Acth. | Clinical characteristics are compared between groups based on coronary results. |
| Prospective (cross-sectional) [13] | Clinical indication for CAG: HFpEF (n = 30); Controls (n = 14) |
Invasive CFR and IMR | Adenosine | Hyperaemia | CFR: 2.55 ± 1.60 vs. 3.84 ± 1.89, p = 0.024 IMR: 26.7 ± 10.3 vs. 19.7 ± 9.7, p = 0.037 |
Exploratory analysis on age, BMI, GFR, BNP, echocardiographic data, hemodynamic data. Unmatched controls |
| Retrospective [34] | Patients with angina presented to the ER: HFpEF (n = 155); Controls (n = 135) | Total myocardial blush grade score (TMBGS) | None, nitroglycerin | Blood flow | TMBGS: 5.6 ± 1.22 vs. 6.1 ± 1.26, p = 0.02 | Not performed, unmatched population |
| Non-invasive coronary assessment | ||||||
| Prospective [35] | HFpEF (n = 19); Matched healthy controls (n = 19) |
PET (C-acetate-11): myocardial blood flow (MBF) and myocardial oxygen consumption (MVO2) | Dobutamine | Blood flow, hyperaemia, diffusion | MBF increase: 78% vs. 151%, p = 0.0480 MVO2 increase: 59% vs. 86%, p = 0.0079 Absolute values during stress test not significantly different. |
LVH, Hb. Healthy controls were matched for age and sex. |
| Retrospective [36] | Indication for cardiac PET: HFpEF (n = 78); HT without HF (n = 112); No HF no HT (n = 186) | PET (Rb-82): global myocardial flow reserve (MFR) | Dipyridamole | Hyperaemia | MFR: 2.16 ± 0.69 vs. 2.54 ± 0.80 vs. 2.89 ± 0.70, p ≤ 0.001 | Age, sex, BMI, smoking, DM, HT, hyperlipidaemia, HT, AF, statin use. Controls matched for HT. |
| Retrospective [37] | Suspected CAD: Cohort without HF (n = 201) | PET (Rb-82): (CFR) | Regadenoson or dipyridamole | Hyperaemia | 18% of the patients had a HFpEF event during follow-up. Independent HR with CFR <2.0 of 2.47 (1.09–5.62) | In entire cohort: AF, CKD, troponin, LVEF, CFR, E/e’ septal |
| Prospective [38] | HFpEF (n = 25); LVH (n = 13); Controls (n = 18) |
MRI (CFR) | Adenosine | Hyperaemia | CFR: 2.21 ± 0.55 vs. 3.05 ± 0.74 vs. 3.83 ± 0.73, p ≤ 0.002 | BNP, LVEF, E/e’, LA dimension |
| Retrospective [39] | HFpEF without events (n = 137), with events (n = 26) | MRI (CFR) | Adenosine | Hyperaemia | CFR: 2.67 ± 0.64 vs. 1.93 ± 0.38 | Not performed |
| Prospective [40] | HFpEF (n = 6); Post MI (n = 6); Healthy controls (n = 20) | MRI: intravascular volume of basal septum (IVV) | Gadofosveset | Permeability | IVV: 0.155 ± 0.033 vs. 0.146 ± 0.038 vs. 0.135 ± 0.018, p = 0.413 | Not performed, unmatched controls |
| Prospective [10] | HFpEF (n = 202) | Echocardiography (CFR) | Adenosine | Hyperaemia | CFR: 2.13 ± 0.51 | Age, sex, BMI, AF, DM, CAD, smoking, LV mass, 6MWT, KCCQ, urinary albumin-creatinine ratio. No controls. |
| Prospective [41] | HFpEF (n = 77); Healthy controls (n = 30) |
Echocardiography (CFR) | Adenosine | Hyperaemia | CFR: 1.7 ± 0.2 (with MVD) vs. 3.1 ± 0.4 (no MVD) vs. 3.4 ± 0.3 (control) | Age, LAVI, LVMI, LVEF, E/e’, 6MWT distance |
Abbreviations: AF, atrial fibrillation; BMI, body mass index; CAD, coronary artery disease; CAG, coronary angiography; CFR; coronary flow reserve; CKD, chronic kidney disease; CMD, coronary microvascular dysfunction; DM, diabetes mellitus; ER, emergency room; GFR, glomerular filtration rate; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HR, hazard ratio; HT, hypertension; IMR, index of microcirculatory resistance; LAVI; left atrial volume index; LV, left ventricle/ventricular; LVEDI, left ventricular end-diastolic volume indexLVEF, left ventricular ejection fraction; LVMI, left ventricular mass index; MFR, myocardial flow reserve; MVD, microvascular disease; PET, positron emission tomography; SR, sinus rhythm.