COVID-19 Vaccination and Atrial fibrillation: When Pandemics CollideJason S. Chinitz, MD1,2,3 and Laurence M. Epstein, MD1,2,41Northwell, New Hyde Park, NY2Northwell Cardiovascular Institute3South Shore University Hospital, Bay Shore, NY4North Shore University Hospital, Manhasset, NYShort title : COVID-19 Vaccination and Atrial fibrillationKey Words : Atrial Fibrillation, Atrial Arrhythmias, COVID-19, COVID-19 VaccinationFinancial support : none.Conflicts of Interest :Jason Chinitz, MD: Consultant for Boston Scientific, Biosense Webster, MedtronicLaurence Epstein, MD: none.Address for Correspondence :Jason Chinitz, MDNorthwell, 2000 Marcus Ave, Suite 300New Hyde Park, NY [email protected] the wake of the coronavirus disease 2019 (COVID-19) pandemic, accelerated research and development efforts were made to create a new class of vaccinations to mitigate the unprecedented global health burden. However, the rapid development and approval process was a factor in prompting vaccine hesitancy, based partially on concerns regarding the safety of the vaccine. Adding to the hesitancy, reports of adverse reactions became widely disseminated in medical literature, as well as in social media. However, the lack of long-term data and controlled studies have limited interpretation of the true COVID-19 vaccine risk profile, and has hampered the effort to combat misinformation.Cardiac complications are the most frequently reported adverse reaction following COVID-19 vaccination.1 Case series have attributed exacerbations of various chronic cardiac diseases to COVID-19 vaccination, including hypertension, coronary artery disease, and arrhythmias.2 In the WHO database, palpitation and tachycardia were reported frequently across all age groups and gender following vaccination, including many cases of atrial fibrillation.2 The Vaccine Adverse Event Report System (VAERS) database of the Food and Drug Administration reported over 2600 cases of atrial fibrillation following COVID-19 vaccination, only 315 of which were reported as new-onset.3 These reports, however, are generally anecdotal, denominators are not considered, and causality cannot be inferred. Any association is further confounded when evaluating the vaccine’s effects in populations in whom cardiovascular disease is the most common comorbidity, as the prevalence of heart rhythm abnormalities is already high. In this circumstance, patients and clinicians may tend to inappropriately attribute an arrhythmia occurrence to a history of vaccination. Indeed, the majority of adverse medical outcomes that occur following vaccination may have little to do with the vaccine itself, even when the temporal relationship is suggestive.Tachycardia and arrhythmias may occur as an inflammatory or stress-related response to vaccination. Inflammatory reactions such as myocarditis and pericarditis have been shown to occur at higher rates following COVID-19 vaccination.4 A potential mechanism of post-COVID-19 vaccine adverse events has been attributed to an immune response to the detection of mRNA as an antigen, particularly in genetically predisposed individuals; in these cases, immunization may activate inflammatory cascades, leading to systemic reactions including myocarditis and potentially atrial and ventricular arrhythmias.5 Atrial fibrillation and ventricular arrhythmias have been long associated with inflammatory conditions, and are relatively common in patients with pericarditis and myocarditis.6 Accordingly, an increase in arrhythmia burden after vaccination is biologically plausible, regardless of whether the vaccine itself is pro-arrhythmic.For practicing cardiologists, atrial fibrillation can reasonably be considered a disorder of pandemic proportions. Driven by both modifiable and non-modifiable risk factors, and more ubiquitous screening and detection modalities, the incidence of AF has been reported to be 31% higher in 2017 compared to 1997, and predictive models suggest AF will impact nearly 8 million Americans by 2050.7,8Furthermore, AF burden is progressive in at least 25% of patients, including progression from paroxysmal to persistent AF in 8-15% of patients per year.9 AF interventions, particular AF ablation, have been shown to reduce the rate of progression to persistent AF markedly.10Though increasing AF burden in an individual patient may be attributed to the natural history of the disease, cardiovascular risk factors are commonly implicated as drivers of AF progression. Interestingly, the pandemic itself may have also contributed to the increasing prevalence of AF, as we have reported high rates of AF, nearly two-thirds of which was new onset, in large numbers of hospitalized patients with COVID-19.11 However, in most patients with AF who have various cardiac risk factors, identification of extrinsic factors such as a novel vaccination that may contribute directly to AF onset and progression is challenging, and non-randomized studies can be misleading due to unrecognized confounders.In the study reported in this issue of the Journal of Cardiovascular Electrophysiology by Deshmukh et al,12arrhythmia burden was extracted retrospectively in large databases of patients with CIEDs, to evaluate any temporal association between COVID-19 vaccination and AF progression. Insurance claims were used to identify patients receiving COVID-19 vaccination, and long-term trends in arrhythmia burden, occurring before and after vaccination were analyzed, and compared to similar populations not undergoing vaccination. Though the AF burden was found to increase in the 3 months following vaccination, similar increases in AF burden were observed in patients who did not receive vaccination over the same time frame, and sustained increases in arrhythmia burden were noted over the course of a year, in both populations. These findings implicate disease progression, and not the vaccine itself, as the primary driver of AF events occurring following vaccination. This manuscript’s first conclusion citing an increase in the burden of arrhythmia events in the 3 months following COVID-19 vaccination, particularly in males over 70 years in whom the prevalence of AF is already highest, is therefore potentially misleading, as a subsequently reported comparison between matched vaccinated and un-vaccinated populations yielded no statistically significant difference in AF burden.There are two primary lessons to take from this research.AF is a common and progressive disease, which is best understood in populations that have devices capable of long-term arrhythmia monitoring. Beyond observed and predicted increases in AF prevalence and incidence over time, AF burden in individual patients is progressive over time. This study further demonstrates this trend in a population with underlying cardiovascular disease who have CIEDs, regardless of whether they had a vaccination or not.Exacerbations of chronic medical disease, such as atrial fibrillation, are seen following vaccinations, and may be in-part related to the vaccine\RL’s induced inflammatory response. However, in this study, arrhythmia burden did not appear to accelerate more quickly in patients who received vaccinations relative to those who did not get vaccinated, and no long-term difference in atrial or ventricular arrhythmia burdens were noted between these populations.A risk versus benefit analysis must always be performed when evaluating any therapy, including with vaccines. While this study does not report on the benefits of the vaccine, it does provide some reassurance in recommending COVID-19 vaccination to our patients at risk for arrhythmias, who are also at high risk of complications from COVID-19 infection. Furthermore, the progressive nature of AF in patients with cardiovascular disease, who are at highest risk of AF-related morbidity and mortality, further justifies current trends towards early AF intervention.
