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. 2022 Feb 9;12(2):278. doi: 10.3390/biom12020278

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.