Treatment of coronary microvascular dysfunction

Merz, C. Noel Bairey; Pepine, Carl J.; Shimokawa, Hiroaki; Berry, Colin

doi:10.1093/cvr/cvaa006

Cited by 149 publications

(132 citation statements)

References 133 publications

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“…Exploitation of ACE2 by coronavirus is important in predicting potential pathology as ACE2 is particularly highly expressed in pericytes, in addition to type II alveolar epithelial cells, according to the single-cell human heart atlas. 16 High expression of ACE2 in pericytes could lead to development of microvascular dysfunction, 17 explaining greater propensity for acute coronary syndromes (ACS). 5 Moreover, ACE2 expression is up-regulated in failing human hearts, suggesting a plausible explanation for a higher infectivity of virus and a higher mortality in patients with heart failure.…”

Section: Properties Of Sars-cov-2mentioning

confidence: 99%

COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options

Guzik

Mohiddin

Dimarco³

et al. 2020

Cardiovascular Research

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The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) —a homologue of ACE—to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin–angiotensin–aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

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Section: Properties Of Sars-cov-2mentioning

confidence: 99%

COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options

Guzik

Mohiddin

Dimarco³

et al. 2020

Cardiovascular Research

Self Cite

1,287

1,347

View full text Add to dashboard Cite

show abstract

“…The exploitation of ACE2 by coronavirus may impair the renin-angiotensin-aldosterone system (RAAS). Furthermore, ACE2 is highly expressed on failing human hearts and pericytes, which could lead to the development of microvascular dysfunction [ 22 ], and explain the greater propensity for ACS [ 23 , 24 ]. Therefore, careful attention must be paid to the exacerbation of COVID-19 in patients with highly expressed ACE2.…”

Section: Covid-19 and Vascular Endothelial Dysfunctionmentioning

confidence: 99%

Endothelial glycocalyx damage as a systemic inflammatory microvascular endotheliopathy in COVID-19

Yamaoka‐Tojo

2020

Biomedical Journal

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In atherosclerosis patients, vascular endothelial dysfunction is commonly observed alongside damage of the vascular endothelial glycocalyx, an extracellular matrix bound to and encapsulating the endothelial cells lining the blood vessel wall. Although atherosclerotic risk factors have been reported in severe patients with coronavirus disease 2019 (COVID-19), the exact mechanisms are unclear. The mortality associated with the COVID-19 outbreak is increased by comorbidities, including hypertension, diabetes, obesity, chronic obstructive pulmonary disease (COPD), and cardiovascular disease. Besides, older individuals and smokers have significantly worse outcomes. Interestingly, these comorbidities and risk factors are consistent with the pathophysiology that causes vascular endothelial glycocalyx damage. Moreover, vascular glycocalyx dysfunction causes microvascular leakage, which results in interstitial pulmonary abnormal shadows (multiple patchy shadows with a ground glass inter-pneumonic appearance). This is frequently followed by severe acute respiratory distress syndrome (ARDS), closely related to coagulo-fibrinolytic changes contributing to disseminated intravascular coagulation (DIC) and Kawasaki disease shock syndrome, as well as inducing activation of the coagulation cascade, leading to thromboembolism and multiple organ failure. Notably, SARS-CoV-2, the causative virus of COVID-19, binds to ACE2, which is abundantly present not only in human epithelia of the lung and the small intestine, but also in vascular endothelial cells and arterial smooth muscle cells. Moreover, COVID-19 can induce severe septic shock, and sepsis can easily lead to systemic degradation of the vascular endothelial glycocalyx. In the current review, we propose new concepts and therapeutic goals for COVID-19-related vascular endothelial glycocalyx damage, based on previous vascular endothelial medicine research.

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“…It is worthy of attention whether they re ect systemic or local process and ischaemic or in ammatory process. Also, since ACE2 (a homologue of ACE) is expressed in cardiomyocytes, direct cardiomyocyte infection by SARS-CoV-2 may be a possibility [17,22 ]. Pulmonary congestion indirectly indicated left heart insu ciency, which is usually manifested as blurred hilar shadows and dilated PVs on CT images.…”

Section: Discussionmentioning

confidence: 99%

Role of pulmonary circulation assessment in CT imaging in evaluating the severity and tendency of severe and critical COVID-19 pneumonia

liu

Pan

et al. 2020

Preprint

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Objective: To investigate the value of changes of pulmonary circulation in CT imaging in evaluating the severity and tendency of 2019 novel coronavirus disease (COVID-19) pneumonia.Methods: This retrospective study analyzed 99 severe and critical COVID-19 pneumonia patients including the 47 improved cases and 52 dead cases. Demographic data, laboratory findings, comorbidities, and CT imaging features including the diameters of pulmonary vein (PV), pulmonary artery (PA) and ascending aorta were collected and assessed.Results: The PV diameters of the deceased patients were larger than recovered patients in the severe phase. Compared with the severe phase in the improvement group, the diameters of the pulmonary veins during the improved phase were smaller, and the total CT scores were significantly decreased (p < 0.001). Instead, there was no significant difference in the ratio of main PA to aorta diameter between the recovered group and the deceased group, nor did the self control of the recovered group and the deceased group (p > 0.05). Construction of a ROC curve yielded an optimal cut-off value of the PV diameters for prediction of survival (p < 0.05).Conclusion: The changes of the PV diameters might indirectly reflect the activity of pulmonary inflammation and cardiac insufficiency. Pulmonary manifestations of severe and critical COVID-19 pneumonia might be related to myocardial injury and cardiac insufficiency, expecially accompanied by dilated PVs. Evaluation of changes in pulmonary circulation by chest CT images may be considered as a useful tool for determining the severity, fatal outcome and tendency of COVID-19.Key words: COVID-19, pneumonia, pulmonary circulation, Computed Tomography

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Treatment of coronary microvascular dysfunction

Cited by 149 publications

References 133 publications

COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options

COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options

Endothelial glycocalyx damage as a systemic inflammatory microvascular endotheliopathy in COVID-19

Role of pulmonary circulation assessment in CT imaging in evaluating the severity and tendency of severe and critical COVID-19 pneumonia

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