Coronary Microvascular Dysfunction Is Associated With Myocardial Ischemia and Abnormal Coronary Perfusion During Exercise

Rahman, Haseeb; Ryan, M. J.; Lumley, Matthew; Modi, Bhavik; McConkey, Hannah; Ellis, Howard; Scannell, Cian M.; Clapp, Brian; Marber, Michael; Webb, David J.; Chiribiri, Amedeo; Perera, Divaka

doi:10.1161/circulationaha.119.041595

Cited by 138 publications

(130 citation statements)

References 44 publications

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“…Investigation of such interaction of obstructive CAD with CMD, by combining a chronic proximal coronary artery stenosis [37,55] with the current model of comorbiditiesinduced CMD, should be the topic of future studies. Such studies should then also include the assessment of flow distribution across the left ventricular wall, as the presence of a coronary artery stenosis causes a regional flow redistribution away from the subendocardium towards the subepicardium [17], whereas comorbidities in the absence of obstructive CAD appear to result in more diffuse and transmurally homogeneous reductions in myocardial blood flow [5,38,50].…”

Section: Methodsological Considerationsmentioning

confidence: 99%

“…Our finding of a reduction in CFR due to an increase in basal coronary flow, rather than a decrease in maximal flow, is also in good agreement with observations in a variety of patient groups. Thus, in INOCA patients with functional CMD [50], in patients with residual CMD after undergoing percutaneous coronary intervention for obstructive CAD [27], and in patients with diabetes mellitus [46], an increase in basal coronary blood flow per gram of myocardium [50] or increases in basal coronary flow velocity [27,46], as compared to healthy individuals, appears primarily responsible for the reduction in CFR. Moreover, patients with a reduced CFR and an increased basal blood flow demonstrate an increased cardiovascular mortality risk compared to patients with normal basal coronary blood flow and CFR [24].…”

Section: Coronary Microvascular Dysfunctionmentioning

confidence: 99%

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Perturbations in myocardial perfusion and oxygen balance in swine with multiple risk factors: a novel model of ischemia and no obstructive coronary artery disease

et al. 2020

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Comorbidities of ischemic heart disease, including diabetes mellitus (DM), hypercholesterolemia (HC) and chronic kidney disease (CKD), are associated with coronary microvascular dysfunction (CMD). Increasing evidence suggests that CMD may contribute to myocardial 'Ischemia and No Obstructive Coronary Artery disease' (INOCA). In the present study, we tested the hypothesis that CMD results in perturbations in myocardial perfusion and oxygen delivery using a novel swine model with multiple comorbidities. DM (streptozotocin), HC (high-fat diet) and CKD (renal embolization) were induced in 10 female swine (DM + HC + CKD), while 12 healthy female swine on a normal diet served as controls (Normal). After 5 months, at a time when coronary atherosclerosis was still negligible, myocardial perfusion, metabolism, and function were studied at rest and during treadmill exercise. DM + HC + CKD animals showed hyperglycemia, hypercholesterolemia, and impaired kidney function. During exercise, DM + HC + CKD swine demonstrated perturbations in myocardial blood flow and oxygen delivery, necessitating a higher myocardial oxygen extraction-achieved despite reduced capillary density-resulting in lower coronary venous oxygen levels. Moreover, myocardial efficiency was lower, requiring higher oxygen consumption for a given level of myocardial work. These perturbations in myocardial oxygen balance were associated with lower myocardial lactate consumption, stroke volume, and LVdP/dt max , suggestive of myocardial ischemia and dysfunction. Further analyses showed a reduction in adenosine-recruitable coronary flow reserve, but this was exclusively the result of an increase in basal coronary blood flow, while maximal coronary flow per gram of myocardium was maintained; the latter was consistent with the unchanged arteriolar wall/lumen ratio, arteriolar density and peri-arteriolar collagen content. However, isolated small arteries displayed selective blunting of endothelium-dependent vasodilation in response to bradykinin in DM + HC + CKD swine, suggesting that changes in coronary microvascular function rather than in structure contributed to the perturbations in myocardial oxygen delivery. In conclusion, common comorbidities in swine result in CMD, in the absence of appreciable atherosclerosis, which is severe enough to produce perturbations in myocardial oxygen balance, particularly during exercise, resembling key features of INOCA.

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Section: Methodsological Considerationsmentioning

confidence: 99%

Section: Coronary Microvascular Dysfunctionmentioning

confidence: 99%

Perturbations in myocardial perfusion and oxygen balance in swine with multiple risk factors: a novel model of ischemia and no obstructive coronary artery disease

et al. 2020

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“…However, this approach limited because the achievable maximal tachycardia is limited by Wenckebach block, thus affecting CFR determination. Supine exercise testing during coronary angiography with radial or brachial artery access is feasible and can provide clinically relevant information on disease mechanisms ( 95 ). Rahman et al.…”

Section: How To Assess Coronary Vascular Dysfunction In the Catheterimentioning

confidence: 99%

“…Rahman et al. ( 95 ) measured coronary flow velocity and pressure under resting conditions, during intravenous adenosine–mediated hyperemia (140 μg/kg/min), and during bicycle exercise using a supine ergometer in the catheterization laboratory. They found that in patients with angina without obstructive CAD (n = 85), CFR but not microvascular resistance identified patients with maladaptive physiological responses to exercise and subendocardial myocardial ischemia (n = 55; hyperemic subendocardial/subepicardial perfusion ratio <1.0, as revealed by stress perfusion cardiovascular magnetic resonance).…”

Section: How To Assess Coronary Vascular Dysfunction In the Catheterimentioning

confidence: 99%

Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease

Ford

Ong

Sechtem

et al. 2020

JACC: Cardiovascular Interventions

131

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Ischemic heart disease secondary to coronary vascular dysfunction causes angina and impairs quality of life and prognosis. About one-half of patients with symptoms and signs of ischemia turn out not to have obstructive coronary artery disease, and coronary vascular dysfunction may be relevant. Adjunctive tests of coronary vasomotion include guidewire-based techniques with adenosine and reactivity testing, typically by intracoronary infusion of acetylcholine. The CorMicA (Coronary Microvascular Angina) trial provided evidence that routine management guided by an interventional diagnostic procedure and stratified therapy improves angina and quality of life in patients with angina but no obstructive coronary artery disease. In this paper, the COVADIS study group provide a comprehensive review of why, how, and when coronary vascular dysfunction should be assessed invasively. They discuss the rationale through a shared understanding of vascular pathophysiology and clinical evidence. They propose a consensus approach to how an interventional diagnostic procedure is performed with focus on practical aspects. Finally, the authors discuss the clinical scenarios in patients with stable and acute coronary syndromes in which measurement of coronary vascular function may be helpful for patient care.

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“…We categorized those patients with microvascular dysfunction to the unclassified ischemic heart disease (IHD) group. In this report, among 154 patients with suspected angina having non-ACh-provoked epicardial coronary spasm ( [4,62,118,[126][127][128][129][130][131][132][133]. The ACh-provocation test can be useful to assess the reactivity (such as spasm) of not only of epicardial coronary arteries but also endothelium-dependent coronary microvessels.…”

Section: Significance Of Microvascular Spasm In Nonobstructive Coronamentioning

confidence: 99%

Role of acetylcholine spasm provocation test as a pathophysiological assessment in nonobstructive coronary artery disease

Kaikita

Yamamoto

Jinnouchi

et al. 2020

Cardiovasc Interv and Ther

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Coronary angiography (CAG) sometimes shows nonobstructive coronary arteries in patients with suspected angina or acute coronary syndrome (ACS). The high prevalence of nonobstructive coronary artery disease (CAD) in those patients has recently been reported not only in Japan but also in Western countries, and is clinically attracting attention. Coronary spasm is considered to be one of the leading causes of both suspected stable angina and ACS with nonobstructive coronary arteries. Coronary spasm could also be associated with left ventricular dysfunction leading to heart failure, which could be improved following the administration of calcium channel blockers. Because we rarely capture spontaneous attacks of coronary spasm with electrocardiograms or Holter recordings, an invasive diagnostic modality, acetylcholine (ACh) provocation test, can be useful in detecting coronary spasm during CAG. Furthermore, we can use the ACh-provocation test to identify high-risk patients with coronary spasm complicated with organic coronary stenosis, and then treat with intensive care. Nonobstructive CAD includes not only epicardial coronary spasm but also microvascular spasm or dysfunction that can be associated with recurrent anginal attacks and poor quality of life. ACh-provocation test could also be helpful for the assessment of microvascular spasm or dysfunction. We hope that cardiologists will increasingly perform ACh-provocation test to assess the pathophysiology of nonobstructive CAD.

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Coronary Microvascular Dysfunction Is Associated With Myocardial Ischemia and Abnormal Coronary Perfusion During Exercise

Cited by 138 publications

References 44 publications

Perturbations in myocardial perfusion and oxygen balance in swine with multiple risk factors: a novel model of ischemia and no obstructive coronary artery disease

Perturbations in myocardial perfusion and oxygen balance in swine with multiple risk factors: a novel model of ischemia and no obstructive coronary artery disease

Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease

Role of acetylcholine spasm provocation test as a pathophysiological assessment in nonobstructive coronary artery disease

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