No abstract

2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

Wytyczne ESC dotyczące postępowania w chorobach układu sercowo-naczyniowego podczas ciąży (2018) Grupa Robocza Europejskiego Towarzystwa Kardiologicznego ds. postępowania w chorobach układu sercowo-naczyniowego podczas ciąży

A wide range of cardiac symptoms have been observed in COVID-19 patients, often significantly influencing the clinical outcome. While the pathophysiology of pulmonary COVID-19 manifestation has been substantially unraveled, the underlying pathomechanisms of cardiac involvement in COVID-19 are largely unknown. In this multicentre study, we performed a comprehensive analysis of heart samples from 24 autopsies with confirmed SARS-CoV-2 infection and compared them to samples of age-matched Influenza H1N1 A (n = 16), lymphocytic non-influenza myocarditis cases (n = 8), and non-inflamed heart tissue (n = 9). We employed conventional histopathology, multiplexed immunohistochemistry (MPX), microvascular corrosion casting, scanning electron microscopy, X-ray phase-contrast tomography using synchrotron radiation, and direct multiplexed measurements of gene expression, to assess morphological and molecular changes holistically. Based on histopathology, none of the COVID-19 samples fulfilled the established diagnostic criteria of viral myocarditis. However, quantification via MPX showed a significant increase in perivascular CD11b/TIE2 + —macrophages in COVID-19 over time, which was not observed in influenza or non-SARS-CoV-2 viral myocarditis patients. Ultrastructurally, a significant increase in intussusceptive angiogenesis as well as multifocal thrombi, inapparent in conventional morphological analysis, could be demonstrated. In line with this, on a molecular level, COVID-19 hearts displayed a distinct expression pattern of genes primarily coding for factors involved in angiogenesis and epithelial-mesenchymal transition (EMT), changes not seen in any of the other patient groups. We conclude that cardiac involvement in COVID-19 is an angiocentric macrophage-driven inflammatory process, distinct from classical anti-viral inflammatory responses, and substantially underappreciated by conventional histopathologic analysis. For the first time, we have observed intussusceptive angiogenesis in cardiac tissue, which we previously identified as the linchpin of vascular remodeling in COVID-19 pneumonia, as a pathognomic sign in affected hearts. Moreover, we identified CD11b + /TIE2 + macrophages as the drivers of intussusceptive angiogenesis and set forward a putative model for the molecular regulation of vascular alterations.

Endothelial progenitor cells (EPC) are bone marrow derived cells with the potential to differentiate into mature functional endothelial cells. First clinical trials have been performed investigating the effects of EPC transplantation into cardiac ischemic areas after myocardial infarction, in patients with peripheral atherovascular disease or on endothelialisation of artificial heart valves. Next to EPC transplantation, the pharmacological mobilisation and functional modification of EPC may also play a major role in future therapies. Studies have raised the concern that patients with coronary heart disease or severe heart failure may suffer from decreased amounts and impaired function of peripheral circulating EPC. Drug induced mobilization of EPC and normalization of EPC function may therefore improve prognosis of certain cardiovascular diseases. The underlying molecular events of a disturbed mobilisation, differentiation, homing and/or function of EPC are not well understood. In the present review we will highlight the current knowledge of the role of EPC dysfunction in various cardiovascular diseases and focus on potential causally related molecular mechanisms, which might be novel drug targets.