Cardiac Arrhythmias and Autonomic Dysfunction Associated With COVID-19

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EP LAB DIGEST. 2025;25(1):22-23.

Interview With Rakesh Gopinathannair, MD, MA, FAHA, FHRS 

EP Lab Digest talks with Rakesh Gopinathannair, MD, MA, FAHA, FHRS, about “Cardiac Arrhythmias and Autonomic Dysfunction Associated With COVID-19,” a new scientific statement from the American Heart Association.¹ In the interview, we discuss the significance of COVID-associated arrhythmias and autonomic dysfunction, pathophysiological mechanisms, clinical management strategies, and future research directions. 

This new scientific statement addresses both immediate and long-term cardiovascular impacts of COVID-19. How does this statement reflect the latest understanding of the relationship between COVID-19, cardiac arrhythmias, and autonomic dysfunction in patients during recovery?
The pandemic phase is behind us, but COVID-19 is still around and we are now in an endemic phase where there are still infections and new strains being identified. The severity of infections has gone down substantially and only a small fraction of patients now end up in the hospital. However, we continue to see arrhythmias, post-acute sequelae SARS-CoV-2 (PASC), of which autonomic dysfunction is a major concern. We still see those patients. The writing group felt that there was sort of a gap between the acute phase and how these arrhythmias are happening during follow-up, how surveillance is being performed, what kinds of drugs are being used, and types of interactions with cardiac drugs, etc. We also dedicated a section in the scientific statement to address the pathophysiology as well as the treatment strategies for COVID-associated autonomic dysfunction.

One of the main focuses of the scientific statement is what happens to these survivors. Interestingly, there were a lot of papers focusing on arrhythmias and cardiovascular manifestations when we were in the pandemic phase, but there has not been a lot of follow-up information on these patients. We reviewed and summarized all the available data, focusing on the patients who survived. What we noted was that of the patients who developed COVID-associated arrhythmias during the pandemic phase, their arrhythmic risk continued to remain higher during longer-term follow-up. A couple of large registry studies found there was at least a 2.5-times increase in atrial arrhythmias compared to those patients who did not get COVID. There was also about a 1.5 times higher risk of ventricular arrhythmias in these COVID survivors during follow-up.

So, arrhythmic manifestations continue to happen in these patients. This calls for heightened surveillance, evaluation of how clinically significant these are, and appropriate treatment for what the guidelines advocate for the specific arrhythmia. What we noted was that the arrhythmic risk seems to be on the higher side during follow-up. Major ventricular arrhythmias and sudden cardiac death incidence have abated; however, residual myocardial inflammation and associated arrhythmias are still being seen. 

The other major change is that, when compared to the medications we used during the pandemic phase, we are now mostly using oral therapy to reduce the severity of the COVID infection and prevent patients from going to the hospital. There are important drug interactions that physicians and practitioners need to be aware of when using Paxlovid (Pfizer, Inc), especially in cardiac patients. There are interactions with antiarrhythmic drugs, anticoagulants, and certain antibiotics. So, in a patient who has heart disease or heart failure, they need to make sure that there are no significant contraindications for Paxlovid. New strains are being identified and we are in a situation where we are not trying to avoid COVID, but instead living with it.

The scientific statement discusses various pathophysiological mechanisms for the cardiac arrhythmias observed in COVID-19 patients. Could you elaborate on the most significant mechanisms identified?
The mechanisms typically differ for different arrhythmias. A lot of these data comes from the early and late pandemic phase. In the acute phase, there were various mechanisms including a hyperadrenergic state, inflammation associated with the infection, as well as direct viral injury. These were thought to contribute to atrial and ventricular arrhythmias. Prior studies have shown that there was cardiac infiltration by the SARS-CoV-2 virus; however, the risk of arrhythmias could have been driven primarily by the inflammatory response rather than direct viral injury. As we know, the COVID virus gets into the body through the ACE receptors, which are plentiful in the heart. So, that may explain some predilection to cardiac arrhythmias. In the follow-up period of those with prior COVID infection who developed arrhythmias later, mechanisms are a bit unclear. One possibility is that the prior inflammation could lead to scar formation or fibrosis that could result in atrial and ventricular arrhythmias. Autonomic dysfunction, especially a hyperadrenergic state, could persist into recovery in some people. This could be a manifestation of a long COVID kind of scenario, and that could also contribute to arrhythmias. Especially for atrial arrhythmias and ventricular arrhythmias, if you developed these arrhythmias during the acute phase, there is a much higher risk of them developing during recovery and long-term follow-up. In terms of slow heart rates and incidence, it is a little less understood how it happens, but it is possible that they could be secondary to some myocardial injury and inflammatory damage to the pacemaker cells. Antiviral drugs used to treat COVID, especially remdesivir in hospitalized patients, was associated with almost a 20% increased risk of bradycardia. The other concern is with Paxlovid and other drugs, if you are not careful about drug interaction, they could prolong QT interval and lead to potentially dangerous ventricular arrhythmias. This is a summary of what we know. Again, exact mechanisms for specific patients are not yet well understood and we need more research on that.

What specific arrhythmias are associated with COVID-19, and what key considerations should electrophysiologists take into account when developing treatment plans for patients experiencing arrhythmias post-COVID-19?
During the pandemic phase, bradyarrhythmias were reported in almost 20% to 30% of patients. But there are conflicting reports; some of the reports show much lower incidence. So, we are dealing with a lot of data, and how accurate they are is a little tough to say in that period. We talked about remdesivir use, which commonly causes bradycardia that resolves with drug withdrawal. If you look at the available data, only about 0.3% or so of patients had severe bradyarrhythmias that required pacemaker implantation. Regarding atrial arrhythmias, atrial fibrillation (AF) is by far the most common cardiac arrhythmia noted, with the incidence about 18% to 22%, with new-onset AF happening in approximately 5% to 13%. Typically, when looking at the risk factors, patients tended to be older and had underlying cardiac disease that contributed to AF.

Fortunately, ventricular arrhythmias were uncommon. In the early stages of the pandemic, it was higher. But if you look at follow-up studies, like at least a year out, they were much less, in the 1% to 2% range. However, ventricular arrhythmias were associated with poorer outcomes. Thankfully, the arrhythmic risk is much lower during the current endemic phase with the less virulent strains. Outpatient data on ventricular arrhythmia occurrence is not very well known. There was one study that looked at ventricular arrhythmias at 3 months after hospitalization for COVID using 24-hour ambulatory monitoring. They found that a higher percentage of patients had frequent premature ventricular beats and some nonsustained ventricular tachycardia, but there were no sustained arrhythmias. So, there could be some signs that they were having more arrhythmias, but nothing that could lead to sudden cardiac death. A large study that evaluated over 13,000 hospitalized COVID-19 patients showed that sudden cardiac death occurred in 1.8% of patients and in 10% of those who died. But again, in the long-term endemic phase, it is a little less clear who is experiencing sudden cardiac death and how that is related to COVID. We also talked about when following these patients over 1 year, a couple of large studies have shown that both atrial and ventricular arrhythmia incidence is significantly higher compared to those patients who did not get COVID infection. So again, it is important to understand this, as we think about longer term rhythm monitoring for surveillance.

The statement identifies important knowledge gaps concerning the long-term effects of COVID-19 on cardiac health. What specific areas of research do you believe are critical for improving our understanding of post-acute sequelae and their implications for clinical practice?
I think the long-term risk of arrhythmia still needs to be better understood. We have some data, but we need more. The use of wearables and other tools that we have at our disposal should be helpful in identifying these patients. In this scenario, it has not been very well studied, but I think if a patient already has a history of arrhythmia related to COVID infection, there is value in having some sort of rhythm monitoring to better understand recurrent arrhythmia that could be treated appropriately. 

Autonomic dysfunction continues to be a very challenging topic in the sense that its mechanisms are not well understood. There are several theories, including direct COVID infection, and some concern related to deconditioning, but it is not very clear. Symptoms typically happen weeks to months afterwards, such as fatigue, dizziness, a lot of nonspecific symptoms, brain fog, etc. Most people have either inappropriate sinus tachycardia or postural orthostatic tachycardia. The treatment strategies are not well understood and currently there is no specific treatment that can be recommended other than how we treat other patients with autonomic disorders per the current syncope/autonomic dysfunction guidelines. There is really a need to understand the long-term outcomes of these patients, because we are still seeing these patients and they recover at various times. Is it possible to make that recovery quicker? Those are some of the things that we need to understand better. 

The other “hot potato” item is the association between vaccines and heart rhythm issues. If you look at long-term data, or at least the available data on vaccines and arrhythmias, there is no clear evidence that vaccines cause a higher risk of arrhythmias compared to COVID infection. We still do not have a clear understanding of the long-term effects of myocardial inflammation and how that impacts patients down the road. It would be nice to have long-term rhythm monitoring in these patients to have a better idea. 

Lastly, I think COVID is here to stay, so we must stay up to date with the cardiovascular consequences of future infection. Even though the virulence has gone down and the infections have become milder, again, it is a respiratory virus, so we must be cognizant of potential cardiovascular and arrhythmic outcomes in these patients. 

The transcripts were edited for clarity and length.

Reference

1. Gopinathannair R, Olshansky B, Mina K, Chung MK, et al. Cardiac Arrhythmias and Autonomic Dysfunction Associated With COVID-19: a Scientific Statement From the American Heart Association. Circulation. 2024;150(21):e449-e465. Epub 2024 Oct 14. doi:10.1161/CIR.0000000000001290