Imaging of microvascular disease

Microvascular Function ◽

Maximal Increase ◽

Asymptomatic Subjects ◽

Beside obstructive disease of the epicardial coronary arteries dysfunction of the coronary microvasculature has emerged in the past 20 years as an additional mechanism of myocardial ischaemia. The coronary microvasculature cannot be directly visualized in vivo, therefore, both invasive and non-invasive techniques, have been developed to assess parameters that depend directly on coronary microvascular function. Studies at the microcirculatory level entail the use of vasodilators to obtain near-maximal vasodilation. The ratio of the maximal increase of blood flow above its resting value the coronary flow reserve (CFR) allows to gain an insight into the integrated circulatory function. The diagnostic accuracy of imaging techniques can be exploited to detect impairments of myocardial perfusion in asymptomatic subjects with cardiovascular risk factors. The assessment of the coronary microvascular function has provided novel details on the pathophysiological role of coronary microvascular dysfunction in the development of myocardial ischaemia bearing also important prognostic implications.

Coronary microvascular function in athletes with abnormal exercise test results

Netherlands Heart Journal ◽

10.1007/s12471-019-01336-6 ◽

2019 ◽

Vol 27 (12) ◽

pp. 621-628

Author(s):

D. A. J. P. van de Sande ◽

P. C. Barneveld ◽

J. Hoogsteen ◽

P. A. Doevendans ◽

H. M. C. Kemps

Keyword(s):

Coronary Flow Reserve ◽

Myocardial Ischaemia ◽

Coronary Flow ◽

A Priori ◽

Microvascular Function ◽

Endothelin 1 ◽

Flow Reserve ◽

Abstract Aims In asymptomatic athletes, abnormal exercise test (ET) results have a poor positive predictive value. It is unknown whether abnormal ET results in the absence of obstructive coronary artery disease (CAD) are related to coronary microvascular dysfunction. It is also unknown whether they should be considered false-positive ET results or a consequence of physiological adaptation to sport. In our study, we evaluated whether athletes with abnormal ET results and documented myocardial ischaemia in the absence of obstructive CAD have an attenuated microvascular function and whether coronary microvascular dysfunction is related to endothelial dysfunction. Methods and results Nine athletes with concordant abnormal ET and myocardial perfusion scintigraphy (MPS) results without obstructive CAD were compared with age- and gender-matched individuals with a low-to-intermediate a priori risk of CAD. Coronary flow reserve was assessed by Rubidium-82 positron emission tomography (PET) imaging. Endothelin‑1 concentrations were measured to evaluate endothelial function. Coronary flow reserve was significantly lower in athletes (3.3 ± 0.8 versus 4.2 ± 0.6, p = 0.014 respectively). Endothelin‑1 levels were significantly higher in athletes (1.3 ± 0.2 pg/ml versus 1.0 ± 0.2 pg/ml, p = 0.012 respectively). There was no correlation between endothelin‑1 concentrations and mean global coronary flow reserve (r = 0.12). Conclusion Athletes with abnormal ET and MPS outcomes indicative for myocardial ischaemia and no obstructive CAD have a lower coronary flow reserve compared with non-athletes with low-to-intermediate a priori risk of CAD, suggesting an attenuated coronary microvascular function. Higher endothelin‑1 concentrations in athletes suggest that endothelial-dependent dysfunction is an important determinant of the attenuated microvascular function.

Abstract P278: Coronary Microvascular Dysfunction Is Associated With Augumented Autophagy-lysosomal Signaling In Mice With Hypercholesterolemic Diet

Hypertension ◽

10.1161/hyp.78.suppl_1.p278 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Yun-Ting Wang ◽

Wei Zhao ◽

Ashton A Huckaby ◽

Xiang Li ◽

Yang Zhang

Keyword(s):

Cardiac Function ◽

Signaling Pathway ◽

Microvascular Function ◽

Chow Diet ◽

Flow Reserve ◽

Hypercholesterolemic Diet ◽

Early Effects ◽

Accumulating evidence indicates coronary microvascular dysfunction (CMD) contributes to myocardial ischemia with or without epicardial coronary atherosclerosis. However, it remains unknown which molecular pathway is associated with compromised coronary microvascular function preceding the development of myocardial ischemic injury. Recent studies suggest that autophagy-lysosomal signaling pathway is involved in the regulation of endothelial homeostasis under various metabolic stresses such as hypercholesterolemia. In this study, the early effects of hypercholesterolemia on the function and integrity of coronary microcirculation were studied in mice and the expressions of various molecular markers of autophagy-lysosome pathway were also determined in the coronary circulation. Mice were fed a hypercholesterolemic paigen diet (PD) for 8 weeks and coronary microvascular function was determined by measuring coronary flow reserve (CFR) under baseline and hyperemic conditions. The effects of PD on cardiac function or remodeling were also assessed by echocardiograph or immunohistochemistry studies. In PD-fed hypercholesterolemic mice, hyperemia-induced increase in CFR was significantly abrogated compared to that in normal chow diet-fed (ND) control mice (PD: 1.583±0.4193 vs. ND: 3.087±0.586) (n=7-8). The diet-induced hypercholesterolemia did not lead to cardiac dysfunction (EF%, PD: 59.870±7.549 vs ND: 64.040±9.088) or hypertrophic remodeling (LV mass (mg), PD: 92.240±14.410 vs ND: 96.030±25.07). PD increased mild cardiac inflammation and fibrosis but did not resulted in rarefaction in the myocardium. In small coronary arterial wall, PD induced endothelial inflammasome activation and inflammation, which was accompanied by upregulation of autophagy and lysosome signaling pathway. In conclusion, hypercholesterolemic diet induces CMD without alterations in cardiac function or remodeling. These alterations in coronary microvascular function represent the early effects of diet-induced hypercholesterolemia, which may be ameliorated with activation of autophagy and lysosome signaling pathways.

Evaluation of Non-invasive Imaging Parameters in Coronary Microvascular Disease: A Systematic Review

10.21203/rs.3.rs-97536/v1 ◽

2020 ◽

Author(s):

Floor Groepenhoff ◽

R.G.M. Klaassen ◽

G.B. Valstar ◽

S.H. Bots ◽

N.C. Onland-Moret ◽

...

Keyword(s):

Systematic Review ◽

Angina Pectoris ◽

Imaging Technique ◽

Imaging Techniques ◽

Microvascular Disease ◽

Current Evidence ◽

Non Invasive ◽

Positron Emission

Abstract Background: Coronary microvascular dysfunction (CMD) is an important underlying cause of angina pectoris. Currently, no diagnostic tool is available to directly visualize the coronary microvasculature. Invasive microvascular reactivity testing is the diagnostic standard for CMD, but several non-invasive imaging techniques are being evaluated. However, evidence on reported non-invasive parameters and cut-off values is limited. Thus, we aimed to provide an overview of reported non-invasive parameters and corresponding cut-off values for CMD.Methods: Pubmed and EMBASE databases were systematically searched for studies enrolling patients with angina pectoris without obstructed coronary arteries, investigating at least one non-invasive imaging technique to quantify CMD. Methodological quality assessment of included studies was performed using QUADAS-2.Results: Thirty-six studies were included. Nine cardiac magnetic resonance (CMR) studies reported MPRI (n = 9) and nine positron emission tomography (PET) and transthoracic echocardiography (TTE) studies reported CFR. Mean MPRI ranged from 1.47 ± 0.36 to 1.83 ± 0.50 in patients and from 1.50 ± 0.47 to 2.23 ± 0.37 in healthy controls. Reported mean CFR in PET and TTE ranged from 1.39 ± 0.31 to 2.85 ± 1.35 and 1.69 ± 0.40 to 2.40 ± 0.40 for patients, and 2.68 ± 0.83 to 4.32 ± 1.78 and 2.65 ± 0.65 to 3.31 ± 1.10 for controls, respectively.Conclusions: This systematic review summarized current evidence on reported parameters and cut-off values to diagnose CMD for various non-invasive imaging modalities. Nonetheless, standardization of methodology and reporting of outcome measures is required to provide clinically applicable reference values.

MRI-based in vivo detection of coronary microvascular dysfunction before alterations in cardiac function induced by short-term high-fat diet in mice

Scientific Reports ◽

10.1038/s41598-021-98401-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Grzegorz Kwiatkowski ◽

Anna Bar ◽

Agnieszka Jasztal ◽

Stefan Chłopicki

Keyword(s):

Endothelial Dysfunction ◽

Cardiac Function ◽

High Fat Diet ◽

High Fat ◽

Short Term ◽

Systemic Insulin Resistance ◽

AbstractEndothelial dysfunction is one of the hallmarks of vascular abnormalities in metabolic diseases and has been repeatedly demonstrated in coronary and peripheral circulation in mice fed high-fat diet (HFD), particularly after long-term HFD. However, the temporal relationship between development of coronary microvascular endothelial dysfunction and deterioration in diastolic and systolic cardiac function after short-term feeding with HFD has not yet been studied. This study aimed to correlate the changes in coronary microvascular endothelial function and global cardiac performance indices in vivo after short-term feeding with HFD in mice. Short-term feeding with a HFD (60% fat + 1% cholesterol) resulted in severely impaired coronary microvascular function, as evidenced by the diminished effect of nitric oxide synthase inhibition (by L-NAME) assessed using T1 mapping via in vivo MRI. Deterioration of coronary microvascular function was detected as early as after 7 days of HFD and further declined after 8 weeks on a HFD. HFD-induced coronary microvascular dysfunction was not associated with impaired myocardial capillary density and was present before systemic insulin resistance assessed by a glucose tolerance test. Basal coronary flow and coronary reserve, as assessed using the A2A adenosine receptor agonist regadenoson, were also not altered in HFD-fed mice. Histological analysis did not reveal cardiomyocyte hypertrophy or fibrosis. Increased lipid accumulation in cardiomyocytes was detected as early as after 7 days of HFD and remained at a similar level at 8 weeks on a HFD. Multiparametric cardiac MRI revealed a reduction in systolic heart function, including decreased ejection rate, increased end-systolic volume and decreased myocardial strain in diastole with impaired ejection fraction, but not until 4 weeks of HFD. Short-term feeding with HFD resulted in early endothelial dysfunction in coronary microcirculation that preceded alteration in cardiac function and systemic insulin resistance.

Evaluation of non-invasive imaging parameters in coronary microvascular disease: a systematic review

BMC Medical Imaging ◽

10.1186/s12880-020-00535-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

F. Groepenhoff ◽

R. G. M. Klaassen ◽

G. B. Valstar ◽

S. H. Bots ◽

N. C. Onland-Moret ◽

...

Keyword(s):

Systematic Review ◽

Angina Pectoris ◽

Imaging Technique ◽

Imaging Techniques ◽

Microvascular Disease ◽

Current Evidence ◽

Non Invasive ◽

Positron Emission

Abstract Background Coronary microvascular dysfunction (CMD) is an important underlying cause of angina pectoris. Currently, no diagnostic tool is available to directly visualize the coronary microvasculature. Invasive microvascular reactivity testing is the diagnostic standard for CMD, but several non-invasive imaging techniques are being evaluated. However, evidence on reported non-invasive parameters and cut-off values is limited. Thus, we aimed to provide an overview of reported non-invasive parameters and corresponding cut-off values for CMD. Methods Pubmed and EMBASE databases were systematically searched for studies enrolling patients with angina pectoris without obstructed coronary arteries, investigating at least one non-invasive imaging technique to quantify CMD. Methodological quality assessment of included studies was performed using QUADAS-2. Results Thirty-seven studies were included. Ten cardiac magnetic resonance studies reported MPRI and nine positron emission tomography (PET) and transthoracic echocardiography (TTE) studies reported CFR. Mean MPRI ranged from 1.47 ± 0.36 to 2.01 ± 0.41 in patients and from 1.50 ± 0.47 to 2.68 ± 0.49 in controls without CMD. Reported mean CFR in PET and TTE ranged from 1.39 ± 0.31 to 2.85 ± 1.35 and 1.69 ± 0.40 to 2.40 ± 0.40 for patients, and 2.68 ± 0.83 to 4.32 ± 1.78 and 2.65 ± 0.65 to 3.31 ± 1.10 for controls, respectively. Conclusions This systematic review summarized current evidence on reported parameters and cut-off values to diagnose CMD for various non-invasive imaging modalities. In current clinical practice, CMD is generally diagnosed with a CFR less than 2.0. However, due to heterogeneity in methodology and reporting of outcome measures, outcomes could not be compared and no definite reference values could be provided.

Arginase inhibition restores in vivo coronary microvascular function in type 2 diabetic rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00560.2010 ◽

2011 ◽

Vol 300 (4) ◽

pp. H1174-H1181 ◽

Cited By ~ 47

Author(s):

Julia Grönros ◽

Christian Jung ◽

Jon O. Lundberg ◽

Ruha Cerrato ◽

Claes-Göran Östenson ◽

...

Keyword(s):

Vascular Function ◽

Wistar Rats ◽

Diabetic Rats ◽

Microvascular Function ◽

Vascular Integrity ◽

Gk Rats ◽

Type 2 Diabetic ◽

Nitric oxide (NO) is crucial for maintaining normal endothelial function and vascular integrity. Increased arginase activity in diabetes might compete with NO synthase (NOS) for their common substrate arginine, resulting in diminished production of NO. The aim of this study was to evaluate coronary microvascular function in type 2 diabetic Goto-Kakizaki (GK) rats using in vivo coronary flow velocity reserve (CFVR) and the effect of arginase inhibition to restore vascular function. Different groups of GK and Wistar rats were given vehicle, the arginase inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA), l-arginine, and the NOS inhibitor NG-monomethyl -l-arginine (l-NMMA). GK rats had impaired CFVR compared with Wistar rats (1.31 ± 0.09 vs. 1.87 ± 0.05, P < 0.001). CFVR was restored by nor-NOHA treatment compared with vehicle in GK rats (1.71 ± 0.13 vs. 1.23 ± 0.12, P < 0.05) but remained unchanged in Wistar rats (1.88 ± 0.10 vs. 1.79 ± 0.16). The beneficial effect of nor-NOHA in GK rats was abolished after NOS inhibition. CFVR was not affected by arginine compared with vehicle. Arginase II expression was increased in the aorta and myocardium from GK rats compared with Wistar rats. Citrulline-to-ornithine and citrulline-to-arginine ratios measured in plasma increased significantly more in GK rats than in Wistar rats after nor-NOHA treatment, suggesting a shift of arginine utilization from arginase to NOS. In conclusion, coronary artery microvascular function is impaired in the type 2 diabetic GK rat. Treatment with nor-NOHA restores the microvascular function by a mechanism related to increased utilization of arginine by NOS and increased NO availability.

Clinico-pathophysiological considerations in coronary microvascular disorders

Vessel Plus ◽

10.20517/2574-1209.2021.68 ◽

2022 ◽

Author(s):

Sarena La ◽

Rosanna Tavella ◽

Sivabaskari Pasupathy ◽

John F. Beltrame

Keyword(s):

Coronary Arteries ◽

Myocardial Ischaemia ◽

Pain Perception ◽

Microvascular Angina ◽

Common Clinical Presentation ◽

Microvascular Spasm ◽

Underlying Mechanisms ◽

Microvascular Resistance

Around half of the patients undergoing an elective coronary angiogram to investigate typical stable angina symptoms are found to have non-obstructive coronary arteries (defined as < 50% stenosis). These patients are younger with a female predilection. While underlying mechanisms responsible for these presentations are heterogeneous, structural and functional abnormalities of the coronary microvasculature are highly prevalent. Thus, coronary microvascular dysfunction (CMD) is increasingly recognised as an important consideration in patients with non-obstructive coronary arteries. This review will focus on primary coronary microvascular disorders and summarise the four common clinical presentation pictures which can be considered as endotypes - Microvascular Ischaemia (formerly “Syndrome X”), Microvascular Angina, Microvascular Spasm, and Coronary Slow Flow. Furthermore, the pathophysiological mechanisms associated with CMD are also heterogenous. CMD may arise from an increased microvascular resistance, impaired microvascular dilation, and/or inducible microvascular spasm, ultimately causing myocardial ischaemia and angina. Alternatively, chest pain may arise from hypersensitivity of myocardial pain receptors rather than myocardial ischaemia. These two major abnormalities should be considered when assessing an individual clinical picture, and ultimately, the question arises whether to target the heart or the pain perception to treat the anginal symptoms.

PAF attenuates endothelium-dependent coronary arteriolar vasodilation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.270.6.h2094 ◽

1996 ◽

Vol 270 (6) ◽

pp. H2094-H2099 ◽

Cited By ~ 1

Author(s):

D. V. DeFily ◽

L. Kuo ◽

W. M. Chilian

Keyword(s):

Endothelial Dysfunction ◽

Platelet Activating Factor ◽

Canine Heart ◽

Activated Neutrophils ◽

Significant Attenuation ◽

Arteriolar Diameter

Platelet-activating factor (PAF) has been reported to play a role in neutrophil activation, microvascular permeability, and endothelial dysfunction in a variety of vascular preparations. Although a majority of the effects of PAF are thought to be mediated by the activation of neutrophils, it is unclear the extent to which the deleterious effects of PAF extend to coronary resistance vessels. Therefore, the purpose of this study was to determine whether PAF causes coronary arteriolar endothelial dysfunction in vivo and whether this dysfunction is independent of activated neutrophils. To test these hypotheses, we measured changes in coronary arteriolar diameter to endothelium-dependent and -independent dilators in vivo by measuring coronary microvascular diameters in a beating canine heart using intravital videomicroscopy following intracoronary infusion of PAF (20 ng.kg-1.min-1). Changes in coronary arteriolar diameter following incubation with PAF were also measured in isolated coronary arterioles. In vivo, incubation with PAF resulted in a significant attenuation of endothelium-dependent dilation to intracoronary acetylcholine (0.1 microgram.kg-1.min-1, 39 +/- 7 vs. 20 +/- 3% dilation) and serotonin (1 microgram.kg-1.min-1, 29 +/- 6 vs. 2 +/- 2% dilation). Papaverine-induced relaxation, however, was unchanged. Likewise, in vitro relaxation to serotonin (10 nM) was significantly reduced (38 +/- 4 vs. 3 +/- 5%) following treatment with PAF, whereas nitroprusside (10 nM)-induced relaxation was unchanged. Because PAF impaired endothelium-dependent arteriolar dilation both in vivo and in vitro, we conclude that the presence of activated neutrophils is not required for PAF-induced coronary microvascular dysfunction.

Effect of liraglutide on body weight and microvascular function in non-diabetic overweight women with coronary microvascular dysfunction

International Journal of Cardiology ◽

10.1016/j.ijcard.2018.12.005 ◽

2019 ◽

Vol 283 ◽

pp. 28-34 ◽

Cited By ~ 2

Author(s):

Hannah Elena Suhrs ◽

Kristoffer Flintholm Raft ◽

Kira Bové ◽

Steen Madsbad ◽

Jens Juul Holst ◽

...

Keyword(s):

Body Weight ◽

Microvascular Function ◽

Overweight Women

Myocardial ischaemia: definition and causes

ESC CardioMed ◽

10.1093/med/9780198784906.003.0327_update_001 ◽

2018 ◽

pp. 1325-1329

Author(s):

Filippo Crea ◽

Gaetano Antonio Lanza

Keyword(s):

Coronary Artery ◽

Myocardial Ischaemia ◽

Coronary Artery Spasm ◽

Chronic Stable Angina ◽

Oxygen Demand ◽

Myocardial Oxygen Demand ◽

Coronary Artery Dissection ◽

The Right

Myocardial ischaemia is caused by a mismatch between myocardial oxygen demand and myocardial blood flow supply, which results in reversible myocardial suffering and, when prolonged, in irreversible injury. The main causes of myocardial ischaemia include (1) atherosclerotic flow-limiting stenoses which are responsible for chronic stable angina; (2) coronary thrombus superimposed on an atherosclerotic plaque which is responsible for acute coronary syndromes; (3) coronary artery spasm which is responsible for vasospastic angina; and (4) coronary microvascular dysfunction which is responsible for microvascular angina and can also contribute to myocardial ischaemia in various clinical settings. Functional alterations (thrombus, spasm, and microvascular dysfunction) may act on angiographically normal coronary arteries or arteries presenting stenoses of variable severity. Less frequent coronary causes of myocardial ischaemia include spontaneous coronary artery dissection, myocardial bridge, coronary thromboembolism, an abnormal origin of the right or left coronary artery, and ascending aorta dissection involving coronary ostia. Finally, myocardial ischaemia can occur in the presence of severe left ventricular hypertrophy as observed in aortic stenosis and hypertrophic cardiomyopathy.