ESC Working Group on Coronary Pathophysiology and Microcirculation position paper on ‘coronary microvascular dysfunction in cardiovascular disease’

Abstract

Although myocardial ischaemia usually manifests as a consequence of atherosclerosis-dependent obstructive epicardial coronary artery disease, a significant percentage of patients suffer ischaemic events in the absence of epicardial coronary artery obstruction. Experimental and clinical evidence highlight the abnormalities of the coronary microcirculation as a main cause of myocardial ischaemia in patients with ‘normal or near normal’ coronary arteries on angiography. Coronary microvascular disturbances have been associated with early stages of atherosclerosis even prior to any angiographic evidence of epicardial coronary stenosis, as well as to other cardiac pathologies such as myocardial hypertrophy and heart failure. The main objectives of the manuscript are (i) to provide updated evidence in our current understanding of the pathophysiological consequences of microvascular dysfunction in the heart; (ii) to report on the current knowledge on the relevance of cardiovascular risk factors and comorbid conditions for microcirculatory dysfunction; and (iii) to evidence the relevance of the clinical consequences of microvascular dysfunction. Highlighting the clinical importance of coronary microvascular dysfunction will open the field for research and the development of novel strategies for intervention will encourage early detection of subclinical disease and will help in the stratification of cardiovascular risk in agreement with the new concept of precision medicine.

L-Arginine-Nitric Oxide-Asymmetric Dimethylarginine Pathway and the Coronary Circulation: Translation of Basic Science Results to Clinical Practice

“…It is of note that these results are based on the effects of methylated L-arginines, because it is complicated to detect the level of NO in vivo. Inhibition of NO synthesis reduced CBF and enhanced the vulnerability of the myocardium to ischemia (Padro et al, 2020).…”

“…Coronary vascular resistance is the most important factor in determining CBF (Reitsma et al, 2007). Endothelium-derived vasoactive derivatives, metabolic factors, and neuro-hormones deliver the vasodilator and vasoconstrictor signals that should be balanced to maintain proper coronary vascular tone (Vanhoutte et al, 1986;Padro et al, 2020).…”

Potential Mechanisms of Cardiac Injury and Common Pathways of Inflammation in Patients With COVID-19

“…However, different possible mechanisms manifested in recent clinical and observational studies can be elaborated and further discussed ( Table 1). [10][11][12][13][14][15][16] Coronavirus-associated Acute Myocarditis Alhogbani 11 described the evidence from a coronavirus-associated acute myocarditis, manifested as myocardial edema and acute myocardial injury of the apical and lateral walls of the left ventricle. This regional myocardial injury may result from direct viral myocardial infection and inflammation.…”

“…Since ACE2 is also highly expressed in the heart, it is reasonable to hypothesize that COVID-19-induced cardiac injury might be mediated by ACE2. [12][13][14][15][16] ACE2 is a key counter regulatory enzyme that degrades angiotensin II to angiotensin-(1-7), thereby attenuating its effects on vasoconstriction, sodium retention, and fibrosis. Although angiotensin II is the primary substrate of ACE2, that enzyme also cleaves angiotensin I to angiotensin- (1)(2)(3)(4)(5)(6)(7)(8)(9) and also participates in the hydrolysis of other peptides.…”

Inside the heart of COVID-19

“…If we consider the severe metabolic demand and cardiac dysfunction observed particularly in patients with co-existent hypertension, diabetes, and cardiac disease, the use of ACE inhibitors or angiotensin II receptor antagonists might be justified and beneficial. 11 Experimental evidence, however, suggests that ACE2 used by SARS-CoV-2 to access host cells may be up-regulated by these medications, raising questions about the therapeutic use of renin-angiotensin-aldosterone system inhibitors if they promote increased ACE2 levels. Due to the crucial functional relevance of ACE2 to SARS-CoV-2, the possible effects of antihypertension therapeutics with angiotensin receptor blockers or ACE inhibitors in patients infected with COVID-19 have to be prudently deliberated.…”