Incidence and treatment of arrhythmias secondary to coronavirus infection in humans: A systematic review

Abstract

Background: The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide resulting in significant morbidity and mortality. Arrhythmias are prevalent and reportedly, the second most common complication. Several mechanistic pathways are proposed to explain the pro-arrhythmic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A number of treatment approaches have been trialled, each with its inherent unique challenges. This rapid systematic review aimed to examine the current incidence and available treatment of arrhythmias in COVID-19, as well as barriers to implementation.

Methods: Our search of scientific databases identified relevant published studies from 1 January 2000 until 1 June 2020. We also searched Google Scholar for grey literature. We identified 1729 publications of which 1704 were excluded.

Results: The incidence and nature of arrhythmias in the setting of COVID-19 were poorly documented across studies. The cumulative incidence of arrhythmia across studies of hospitalised patients was 6.9%. Drug-induced long QT syndrome secondary to antimalarial and antimicrobial therapy was a significant contributor to arrhythmia formation, with an incidence of 14.15%. Torsades de pointes (TdP) and sudden cardiac death (SCD) were reported. Treatment strategies aim to minimise this through risk stratification and regular monitoring of corrected QT interval (QTc).

Conclusion: Patients with SARS-CoV-2 are at an increased risk of arrhythmias. Drug therapy is pro-arrhythmogenic and may result in TdP and SCD in these patients. Risk assessment and regular QTc monitoring are imperative for safety during the treatment course. Further studies are needed to guide future decision-making.

Keywords: COVID-19; arrhythmia; coronavirus; long QT syndrome; sudden cardiac death.

Figure 1

Pathogenesis of arrhythmias in SARS‐CoV‐2. Cleavage of viral S protein via an enzyme TMPRSS2 results in fusion of viral and host membrane leading to entry of virus into host cytoplasm. Direct infiltration of myocytes ensues which has been established in 35% of SARS‐CoV patients., , Due to the genomic similarity between SARS‐CoV and SARS‐CoV‐2, direct invasion by SARS‐CoV‐2 may also occur. Indirect myocardial injury results from systemic inflammatory response syndrome (SIRS). The sum of microvascular and macrovascular dysfunction, increased thrombogenicity, acidosis and hypoxia as well as the imbalance of T‐helper 1 and 2 responses leads to an intense release of cytokines and chemokines, particularly interleukin 1 (IL‐1), interleukin 6 (IL‐6) and tumour necrosis factor‐alpha (TNF‐α). The heightened catecholaminergic response amplifies this process. In fact, hyper‐inflammation due to high levels of IL‐6 results in hERG potassium channel blockade and QT prolongation, facilitating formation of unstable arrhythmias. Traditional cardiovascular risk factors such as type II diabetes mellitus, hypertension and hypercholesterolaemia, as well as comorbidities such as ischaemic heart disease and chronic renal failure, also contribute to arrhythmia formation by altering cardiac structure and also responsible for clinically severe disease., Another potential contributor for arrhythmia formation in the setting of COVID‐19 is the common SCN5A‐encoded Nav1.5 sodium channel variant p.Ser1103Tyr‐SCN5A which results in a lack of ‘repolarisation reserve’. ACE‐2, angiotensin‐converting enzyme 2; hERG, human ether‐a‐go‐go–related gene; p.Ser1103Tyr‐SCN5A, SCN5A‐encoded Nav1.5 sodium channel variant; QTc, corrected QT; RNA, Ribonucleic acid; S protein, Spike protein; TMPRSS2, enzyme transmembrane protease serine 2

Figure 2

Literature search results