European Society of Cardiology guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1-epidemiology, pathophysiology, and diagnosis

Abstract

Aims: Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular disease (CVD) in association with COVID-19.

Methods and results: A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, reported here, focuses on the epidemiology, pathophysiology, and diagnosis of cardiovascular (CV) conditions that may be manifest in patients with COVID-19. The second part, which will follow in a later edition of the journal, addresses the topics of care pathways, treatment, and follow-up of CV conditions in patients with COVID-19.

Conclusion: This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities.

Keywords: ACE2; Arrhythmias; Biomarkers; COVID-19; Cardiogenic shock; Myocardial injury; Myocarditis; Non-invasive imaging.

Graphical Abstract

Figure 1

Critical role of ACE2 in the regulation of SARS-CoV-2 infection in ACE2-expressing cells^a (A) and ACE2 reduced surface expression by ADAMTS17 (B). (A) SARS-CoV-2 spike protein (S1) is primed by the serine protease transmembrane protein serine 2, which enables its interaction with the membrane bound form of ACE2. This is required for virus internalization and subsequent replication. Other receptors can also facilitate the entry of SARS-CoV-2, e.g. neuropilin 1. (B) Membrane bound ACE2 may be shed from the cell membrane by ADAMTS17 producing soluble ACE2. This mechanism may limit viral invasion. ACE2, angiotensin-converting enzyme 2; ADAMTS17, a disintegrin and metalloproteinase with thrombospondin motifs 17; NRP1, neuropilin-1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; S1, spike protein 1; TMPRSS2, transmembrane protease serine 2. ^aThis includes type 2 pneumocytes, cardiomyocytes, pericytes, endothelium, and possibly other cell types.

Figure 2

Cardiovascular involvement in COVID-19—key manifestations and hypothetical mechanisms. SARS-CoV-2 anchors on transmembrane angiotensin-converting enzyme 2 to enter the host cells including type 2 pneumocytes, macrophages, endothelial cells, pericytes, and cardiac myocytes, leading to inflammation and multiorgan failure. In particular, the infection of endothelial cells or pericytes could lead to severe microvascular and macrovascular dysfunction. Furthermore, in conjunction with the immune over-reactivity, it can potentially destabilize atherosclerotic plaques and explain the development of the acute coronary syndrome. Infection of the respiratory tract, particularly of type 2 pneumocytes, by severe acute respiratory syndrome coronavirus 2 is manifested by the progression of systemic inflammation and immune cell overactivation, leading to a ‘cytokine storm’, which results in an elevated level of cytokines such as IL-6, IL-7, IL-22, and CXCL10. Subsequently, it is possible that activated T cells and macrophages may infiltrate infected myocardium, resulting in the development of fulminant myocarditis and severe cardiac damage. This process could be further intensified by the cytokine storm. Similarly, the viral invasion could cause cardiac myocyte damage directly leading to myocardial dysfunction and contribute to the development of arrhythmia. CXCL10, C-X-C motif chemokine ligand 10; IL-6, interleukin 6; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 3

Considerations in patients with suspected (or at risk for) cardiogenic shock and possible COVID-19 infection. COVID-19, coronavirus disease 2019; HF, heart failure; MI, myocardial infarction; PPE, personal protective equipment. ^aConsider also myocarditis as potential cause.

Figure 4

Temporal changes in high-sensitivity cardiac troponin I concentrations from illness onset in patients hospitalized with COVID-19. Differences between survivors and non-survivors were significant for all time points shown. Reprinted from Zhou et al., Copyright (2020), with permission from Elsevier.

Figure 5

High-sensitivity cardiac troponin T/I concentrations should be interpreted as quantitative variables. ARDS, acquired respiratory distress syndrome; HF, heart failure; PE, pulmonary embolism; ULN, upper limit of normal (assay-specific).

Figure 6

Haemodynamic determinants of natriuretic peptides. ANP, atrial natriuretic peptide; BNP, B-type natriuretic peptide; LV, left ventricular; NT-proBNP, N-terminal proBNP; RV, right ventricular.

Figure 7

Potential mechanisms underlying elevations in cardiac troponin and myocardial injury in patients with COVID-19. ACE2, angiotensin-converting enzyme 2; ↑, elevation.