Coronary “Microvascular Dysfunction”: Evolving Understanding of Pathophysiology, Clinical Implications, and Potential Therapeutics

Abstract

Until recently, it has been generally held that stable angina pectoris (SAP) primarily reflects the presence of epicardial coronary artery stenoses due to atheromatous plaque(s), while acute myocardial infarction (AMI) results from thrombus formation on ruptured plaques. This concept is now challenged, especially by results of the ORBITA and ISCHEMIA trials, which showed that angioplasty/stenting does not substantially relieve SAP symptoms or prevent AMI or death in such patients. These disappointing outcomes serve to redirect attention towards anomalies of small coronary physiology. Recent studies suggest that coronary microvasculature is often both structurally and physiologically abnormal irrespective of the presence or absence of large coronary artery stenoses. Structural remodelling of the coronary microvasculature appears to be induced primarily by inflammation initiated by mast cell, platelet, and neutrophil activation, leading to erosion of the endothelial glycocalyx. This leads to the disruption of laminar flow and the facilitation of endothelial platelet interaction. Glycocalyx shedding has been implicated in the pathophysiology of coronary artery spasm, cardiovascular ageing, AMI, and viral vasculitis. Physiological dysfunction is closely linked to structural remodelling and occurs in most patients with myocardial ischemia, irrespective of the presence or absence of large-vessel stenoses. Dysfunction includes the impairment of platelet and vascular responsiveness to autocidal coronary vasodilators, such as nitric oxide, prostacyclin, and hydrogen sulphide, and predisposes both to coronary vasoconstriction and to a propensity for microthrombus formation. These findings emphasise the need for new directions in medical therapeutics for patients with SAP, as well as a wide range of other cardiovascular disorders.

Microvascular reperfusion of fibrinolysis followed by percutaneous coronary intervention versus primary percutaneous coronary intervention for ST-segment-elevation acute myocardial infarction

“…Third, in the first 6 hours of myocardial reperfusion, chemo-attractants released from injured endothelial cells and cardiomyocytes draw neutrophils into the infarct zone, which then migrate into the myocardial tissue over the next 24 hours. This process causes vascular plugging and the release of degradative and proteolytic enzymes and reactive oxygen species ( 26 , 27 ). This acute inflammatory response may have caused a higher caIMR in the PPCI group.…”

Hypertension Related Co-Morbidities and Complications in Women of Sub-Saharan Africa: A Brief Review

“…44,45 Current Research Diverse comorbidities as risk factors for arterial dysfunction in women include chronic hypertension, diabetes, hyperlipidemia, obesity, HDP, and menopause. 46,47 These factors contribute to arterial damage, accelerate atherosclerosis, and increase the risk of CVD. 48 Additionally, patients with obesity have elevated lipopolysaccharidebinding protein levels, potentially due to chronic inflammation altering intestinal flora and gut permeability to lipopolysaccharide, which can destroy endothelial cells.…”

The evolving role of cardiopulmonary exercise testing in ischemic heart disease – state of the art review

“…The process starts with endothelial dysfunction (ED) and if left unabated will lead to functional and structural changes in the microcirculation resulting in increased microvascular resistance (index of microcirculatory resistance -IMR) with subsequent decrease in coronary flow reserve (CFR) resulting in coronary microvascular dysfunction (CMD). Over time, the large coronary vessels also become involved resulting in nonobstructive CAD (NOCAD) as well as obstructive CAD (OCAD) with ED and CMD predictive of CV events regardless of the degree of large vessel obstruction [78][79][80][81]. The net effect of the functional and structural changes in the micro and macrovascular circulation will limit blood flow and oxygen delivery to the myocardium resulting in supply demand mismatching above a limiting work threshold referred to as the ischemic or inducible threshold (IT) [82,83].…”