COVID-19 and the CHA₂DS₂-VASc Score: Is It Time to Refine?

The CHADS₂ (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack [TIA]) score, and its subsequent modification, the CHA₂DS₂-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack [TIA], vascular disease, age 65 to 74 years, sex category score), have been used over the past years to objectively predict the risk of stroke in patients with non-valvular atrial fibrillation (NVAF).^1,2 Specifically, the CHA₂DS₂-VASc schema, a refined 2006 Birmingham/NICE stroke risk stratification schema, is regarded as an improvement of the CHADS₂ schema in predicting stroke and thromboembolism (TE) because it incorporates new data such as female gender, age, and vascular disease as risk factors for stroke or TE. Also, the CHA₂DS₂-VASc schema simplified stroke and TE stratification based on a point-based system, resulting in low event rates recorded in low-risk subjects and a small proportion of subjects classified into the intermediate-risk category. For this reason, the CHA₂DS₂-VASc has been widely accepted by the AHA, ACC, and other societies as an objective tool for stroke and TE risk stratification and choice of antithrombotic therapy. Therefore, as new risk factors for stroke or TE in patients with NVAF are defined, they should be considered in refining risk stratification.

Since after the first report in Wuhan, China, coronavirus disease-19 (COVID-19), caused by the SARS-CoV-2 virus, is now recognized as a disease that affects extrapulmonary organs.³ Particularly, the heart has been recognized as a common target of the SARS-CoV-2 virus partly because of increased expression of the ACE2 receptors in cardiomyocytes, a receptor used by the virus to enter cells. Cardiac arrhythmias, including new-onset atrial fibrillation associated with poorer outcomes, are prevalent in COVID-19 patients, occurring in up to 44% of intensive care unit (ICU) patients.⁴ Malaty et al⁵ summarized more recent studies discussing the incidence and treatment of arrhythmias secondary to COVID-19, although the exact pathways leading to these arrhythmias remain unknown at large. Plausible mechanisms include direct cardiomyocyte injury, pericardial edema, myocardial fibrosis or scars caused by ischemic injury, and proinflammatory cytokines predisposing to arrhythmias.⁶ Also, COVID-19 is a hypercoagulable state causing widespread arterial and venous thromboembolism. The mechanisms of coagulopathy in COVID-19 include cytokine storm, complement activation, viral-induced coagulation activation, and endothelial injury/endothelitis.⁷ Thrombosis in the coronary arteries can lead to tissue ischemia and arrhythmias. These cardiovascular complications caused by COVID-19 can linger for months to years and can even cause permanent structural damage to the heart, thereby predisposing to arrhythmias. In this light, COVID-19 can be regarded as an independent risk factor for developing arrhythmias including atrial fibrillation, as well as an independent risk factor for stroke and TE irrespective of the presence of AF. A study involving 414 hospitalized patients with COVID-19 showed that during a median follow-up of 28 days, AF was the most frequent incident sustained arrhythmia.⁸ Meanwhile, other studies have shown poorer outcomes in hospitalized patients with AF and high CHA₂DS₂-VASc scores. Specifically, Ip et al⁹ showed that the presence of AF led to 2.38 times greater risk of mortality when compared to COVID-19 patients with normal sinus rhythm. Colon et al¹⁰ showed that COVID-19 positive individuals with new-onset atrial tachyarrhythmia had a higher mortality rate after multivariable adjustment. Harrison et al¹¹ reported that the survival probability was significantly lower in adults with COVID‐19 and AF when compared to matched adults without AF and that the risk of developing TE within 30 days is significantly higher in COVID-19 patients with AF when compared with those without AF. This finding suggests that AF is a risk marker for increased TE in COVID-19 and, conversely, that COVID-19 is a risk factor of TE in patients with AF. With these findings in mind, we start to see a clear association between severe COVID-19, ie, disease with laboratory evidence of coagulopathy and requiring hospitalization, and NVAF/TE. Therefore, it begs the question of whether it is time to start considering incorporating severe COVID-19 into the CHA₂DS₂-VASc schema.

To establish severe COVID-19 as an independent risk factor of stroke in patients with NVAF, more data will need to be collected and analyzed. It will be interesting to see the associations that come to light especially between COVID-19 and specific subgroups such as pregnant patients and those with underlying thrombophilia. In a pandemic such as COVID-19, many individuals are affected within a relatively short period hence providing us with an appropriate volume of relevant clinical data needed to make prompt changes to current practice. As our understanding of the long-term complications of COVID-19 continues to evolve and as more people are affected and hospitalized, more convincing associations will come to light. Because prophylactic or therapeutic antithrombotic therapy which can mitigate stroke is part of the treatment regimen of hospitalized COVID-19 patients barring absolute contraindications, appropriately adjusting for antithrombotic therapy will need to be done when interrogating whether severe COVID-19 is an independent or combination risk factor for stroke in patients with NVAF.

So, just as the 2006 Birmingham/NICE stroke risk stratification schema was refined by incorporating additional new relevant risk factors, we should consider refining the CHA₂DS₂-VASc scheme to include severe COVID-19 as a risk factor of stroke or TE in patients with NVAF.