Heart-autopsy |
Prospective | [22] |
Retrospective | [12 | n = 321 |
Controls without HF, matched for age, sex, HT, and DM (n = 173) |
Peripheral arterial tonometry (endoPAT): (RHI) |
Ischemia |
Hyperaemia |
] |
Deceased:
HFpEF (n = 124);
Controls (no HF) (n = 104) |
Histology: microvessels/mm | 2 | (microvascular density)Log RHI: 0.53 ± 0.20 vs. 0.64 ± 0.20, p < 0.001 |
|
Rarefaction |
Microvascular density: 961 (800–1370) vs. 1316 (1148–1467), | p | < 0.0001 |
Not performed, unmatched population |
Prospective | [10] |
n = 202 |
No controls |
79 | endoPAT (RHI) |
] | Ischemia |
[ | Hyperaemia |
Log RHI: no absolute values reported. Correlation with CFR of R 0.21, p = 0.004 |
Invasive coronary function assessment |
80] |
Serum cholesterol panel |
Skin, eye, heart |
Function decreases with higher serum low-density lipoprotein cholesterol levels |
Retrospective | [23] |
n |
Retrospective | [14] | = 159 |
No controls |
endoPAT (RHI) |
Ischemia |
Hyperglycaemia | [81][82 | CAG after positive stress test: HFpEF > 65 ( | Hyperaemia |
] | n = 32);
HFpEF < 65 (n = 24);
Controls (n = 31) | Log RHI: 0.50 ± 0.09. Event free 0.52 ± 0.09 vs. Events 0.46 ± 0.08, |
Invasive CFR and IMR |
Adenosinep |
Hyperaemia < 0.001 |
CFR: 1.94 ± 0.28 vs. 1.83 ± 0.32 vs. 3.24 ± 1.11, |
Glucose tolerance test, fasting glucose, HbA1c |
Skin, eye, heart |
Function decreases with higher plasma glucose levels | 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 |
Prospective (cross-sectional) | [24] |
Hypertension | [34][36][69][83][84 | n = 62 |
Controls matched for age, sex, HT, DM, dyslipidaemia and CAD (n = 64) |
endoPAT (RHI) |
Ischemia |
Hyperaemia |
RHI: 2.01 [1.64–2.42] vs. 1.70 [1.55–1.88], |
Retrospective | [9] | ] | p | < 0.001 |
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 |
24-h systolic blood pressure shows the highest correlation |
Skin, eye, skeletal muscle, heart |
Function decreases with higher systolic blood pressure and by duration of hypertension |
Prospective | [25] |
Retrospective | [30] | n = 42 |
HFpEF (n = 22);
no HFpEF (nHFrEF (n = 46) |
endoPAT (RHI) |
= 29) |
Invasive CFR and CBFIschemia |
Hyperaemia |
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), pRHI: 1.77 [1.67–2.16] vs. 1.53 [1.42–1.94], | p | = 0.014. |
= 0.002 |
Dietary intake | [85] |
Caffeine | Age, sex |
Skin |
Function is temporarily increased |
Prospective | [26] |
n = 26 |
Healthy controls, matched for age and sex ( |
Prospective | [31] | n = 26) |
endoPAT (RHI) |
HFpEF with obstructive epicardial CAD (n = 38); HFpEF without epicardial CAD (nIschemia |
= 37) |
Dietary intake | [86 | CAG (CFR, coronary reactivity, IMR) and MRI | Hyperaemia |
][ | Adenosine, acetylcholine | RHI interpretation from boxplots: 1.9 [1.6–2.9] vs. 1.8 [2.0–3.3], p = 0.036. No effect of exercise |
Hyperaemia |
87] | 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. |
High-fat diet |
Skin, heart |
Function is temporarily decreased |
Prospective | [27] |
Prospective (cross-sectional) | [13] |
Physical inactivity | n = 21 |
[29][88][89][90] | Clinical indication for CAG: HFpEF (n = 30);
Controls (n = 14)HT controls without HF (n = 19)
|
24-h accelerometer, physical activity questionnaire | Healthy controls (n = 10) |
endoPAT (RHI) |
Ischemia |
Hyperaemia |
Skin, eye, skeletal muscle | Log RHI: 0.85 ± 0.42 vs. 0.92 ± 0.38 vs. 1.33 ± 0.34, p = n.s. between HFpEF and HT controls |
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 |
Function decreases with more physical inactivity. |
Skin-arm |
Retrospective | [32] |
Obesity | [8][69][91][92] | 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 |
Waist circumference is more correlated than BMI or BSA. |
Skin, eye, skeletal muscle, heart |
Function decreases with increasing level of obesity |
Prospective | [28] |
n = 45 |
HT controls, matched for age, sex and diabetic status (n = 45) |
Laser Doppler flowmetry (LDF), power spectral density (PSD) of the LDF signal |
None, ischemia |
Vasomotion, hyperaemia |
Sex | [93][94] | LDF PSD: lower in HFpEF, no absolute numbers reported, | p | < 0.05. |
| Peak blood flow (PU): 135 [104–206] vs. 177 [139–216], p = 0.03 |
Non-invasive coronary assessment |
|
Skin, eye, skeletal muscle, heart |
Effect on function depends on other confounders. |
Prospective | [11] |
HFpEF with CAD n = 12 |
Prospective | [33] |
HFpEF (n = 19);
Matched healthy controls (n = 19)HFrEF with CAD (n = 12)
CAD without HF (n = 12) |
PET (C-acetate-11): myocardial blood flow (MBF) and myocardial oxygen consumption (MVOLaser Doppler imaging (LDI) coupled with transcutaneous iontophoresis of vasodilators |
2 | acetylcholine, sodium nitroprusside |
Hyperaemia |
)Vasodilation due to Acth: No absolute values reported. p |
Dobutamine |
Blood flow, hyperaemia, diffusion |
MBF increase: 78% vs. 151%, p = 0.0480
MVO2 increase: 59% vs. 86%, p = 0.0079
= 0.00099 (HF vs. controls).
Vasodilation due to nitroprusside: p = 0.006 (HF vs. controls) |
Absolute values during stress test not significantly different. |
LVH, Hb. Healthy controls were matched for age and sex. |
Muscle-leg |
Retrospective | [34] |
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. |
Prospective | [16] |
n = 22 |
Healthy controls, age-matched (n = 43). |
Histology (skeletal muscle biopsy of thigh) |
|
Capillary density |
Capillary-to-fibre ratio: 1.35 ± 0.32 vs. 2.53 ± 1.37, p = 0.006 |
Prospective | [29] |
n = 7 |
No controls. |
Near-infrared spectroscopy: index for skeletal muscle haemoglobin oxygenation of thigh |
|
Diffusion |
Muscle deoxygenation overshoot was decreased after priming exercise, p = 0.041 |