COVID-19 and atrial fibrillation: Intercepting lines

Abstract

Almost 20% of COVID-19 patients have a history of atrial fibrillation (AF), but also a new-onset AF represents a frequent complication in COVID-19. Clinical evidence demonstrates that COVID-19, by promoting the evolution of a prothrombotic state, increases the susceptibility to arrhythmic events during the infective stages and presumably during post-recovery. AF itself is the most frequent form of arrhythmia and is associated with substantial morbidity and mortality. One of the molecular factors involved in COVID-19-related AF episodes is the angiotensin-converting enzyme (ACE) 2 availability. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 to enter and infect multiple cells. Atrial ACE2 internalization after binding to SARS-CoV-2 results in a raise of angiotensin (Ang) II, and in a suppression of cardioprotective Ang(1-7) formation, and thereby promoting cardiac hypertrophy, fibrosis and oxidative stress. Furthermore, several pharmacological agents used in COVID-19 patients may have a higher risk of inducing electrophysiological changes and cardiac dysfunction. Azithromycin, lopinavir/ritonavir, ibrutinib, and remdesivir, used in the treatment of COVID-19, may predispose to an increased risk of cardiac arrhythmia. In this review, putative mechanisms involved in COVID-19-related AF episodes and the cardiovascular safety profile of drugs used for the treatment of COVID-19 are summarized.

Keywords: COVID-19; COVID-19 drugs; atrial fibrillation; atrial remodeling; inflammation.

FIGURE 1

Pharmacological therapy of COVID-19. Antiviral (RNA polymerase and protease inhibitors, monoclonal antibodies), immunomodulatory (IL-1 and IL-6 antagonists, JAK inhibitors) or other drugs (antibiotics, tyrosine kinase inhibitors) are used either alone or in combination.

FIGURE 2

Pathophysiology of COVID-19-related atrial fibrillation (AF) events. Putative mechanisms include a reduced availability of angiotensin-converting enzyme 2, binding of viral spike protein to CD147 or sialic acid, enhancement of inflammatory signaling culminating in cytokine storm, endothelial damage, and increased adrenergic drive.