Editorial to "Atrial fibrillation and the risk of 30-day incident thromboembolic events and mortality in adults ≥50 years with COVID-19".

Abstract

Atrial fibrillation (AF) is associated with a 2- and 1.5-fold increased risk of all-cause mortality in women and men, respectively. AF was also associated with 5- to 8-folds increased risk of stroke and systemic embolization. These associations were observed in patients without respiratory infectious diseases. As the World Health Organization announced coronavirus disease 2019 (COVID-19) as a public health emergency on January 30th 2020, such viral respiratory illness has caused over one million deaths worldwide since then. During this pandemic emergency, cardiac arrhythmia including AF has been a common cardiovascular manifestation described in patients with COVID-19 infection. In patients with COVID-19, whether AF is also a risk factor for increased all-cause mortality remains unclear. Since the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might cause excessive inflammation, platelet activation, endothelial dysfunction, and stasis, patients with COVID-19 caused by this virus might have high risk of thrombosis both in the venous and arterial circulations.1 The thromboembolism risk caused by COVID-19 in patients with AF comparing to AF patients without COVID-19 remains to be explored. By using a global research network and propensity score matched over 13,000 adults with COVID-19, Harrison et al in this issue reported that the survival probability was significantly lower in adults with COVID-19 and AF compared to matched adults without AF (risk ratio 1.61), and risk of thromboembolic events was also higher in patients with AF (risk ratio 1.41).2 These findings indicated that AF remains a risk marker for increased all-cause mortality and thromboembolic events. Furthermore, the survival probability was significantly lower for adults with AF and COVID-19 compared to adults with AF while without COVID-19. Interestingly, there was no significant difference in risk of thromboembolic events between AF patients with and without COVID-19. The authors recommended that AF might be an important risk factor for inclusion in risk modeling and subsequent stratification of adults with COVID-19, and a target for intervention strategies. This study firstly elucidated the association of AF on mortality and thromboembolic events in patients with COVID-19. However, several limitations of this study remain to be investigated. Firstly, the 30-day mortality rates were extremely high (82.7% in non-AF cohort and 88.3% in AF cohort) comparing to those reported by Wang et al (4.3%)3, Shi et al (13.7%)4, and Inciardi et al (26%)5. This finding indicated that the current cohort might be representative of COVID-19 disease patients with severe illness. Whether such association also applied to COVID-19 patients of less severity remain to be explored. Secondly, the mechanisms of increased mortality and thromboembolism events with AF in patients with COVID-19 in this cohort remain unclear. AF is associated with in-hospital mortality in patients with acute myocarditis. In patients with COVID-19, evidence of myocardial injury was associated with higher mortality rate (51.2%) compared with those without myocardial injury (4.5%).4 Therefore, it is speculated that elevated serum levels of Inflammatory cytokines including C-reactive protein, interleukin-6, and tumor necrosis factor-α caused by SARS-CoV-2 might mutually contribute to myocardial injury, AF genesis, thromboembolic events, and mortally. With the findings from this study, optimal management of AF in patients with COVID-19 might be necessary to improve outcomes of patients with COVID-19 and AF. A major concern in this scenario is that all antiarrhythmic drugs (AADs) for rate/rhythm control may have significant side effects due to drug-drug interactions with emerging COVID-19 pharmacotherapy, leading to increased risk for bradycardia or tachyarrhythmias. Furthermore, drug-drug interaction between anti-coagulants and COVID-19 pharmacotherapy might lead to inadequate coagulation or bleeding events. Guideline for the management of AF in patients with COVID-19 has been published, which includes considerations of important potential drug-drug interactions of anticoagulants and AADs with emerging COVID-19 pharmacotherapies.6 Clinicians should be aware of the indications/contraindications and major drug-drug interactions among AADs, anticoagulants, and emerging COVID-19 treatments in AF patients with COVID-19 to improve their clinical outcomes. This study was supported in part by grants from Taichung Veterans General Hospital, Taiwan (TCVGH-NHRI10603, TCVGH-1067310C, TCVGH-FCU1068205, TCVGH-YM1060201, TCVGH-VTA106PREM1, TCVGH-1033103C, TCVGH-1033105C, TCVGH-1043109C, TCVGH-1053108C, TCVGH-VHCY1068606, and TCVGH-VHCY1078603) and the National Science Council, Taiwan (102-2314-B-075A-009-MY2, 104-2314-B-367-001, and 105-2314-B-075A-016-MY3). None.