Q&A: Considerations for arrhythmia risk management after COVID-19 infection
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Key takeaways:
- COVID-19 is linked to cardiac arrhythmia and autonomic dysfunction, even after infection resolves.
- Researchers issued a scientific statement detailing management strategies for patients.
SARS-CoV-2 infection and subsequent COVID-19 are linked to elevated risk for abnormal heart rhythms, and understanding underlying mechanisms and management strategies are clinically important objectives, researchers reported.
With that goal in mind, Rakesh Gopinathannair, MD, MA, FAHA, FHRS, and colleagues issued a scientific statement outlining the evidence-based guidance on the epidemiology, presentation and management of arrhythmias and autonomic dysfunction in patients with or recovering from COVID-19.
The American Heart Association Scientific Statement was issued on behalf of the AHA Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, Council on Basic CV Sciences, Council on CV and Stroke Nursing, Council on Genomic and Precision Medicine and Council on Hypertension, and published in Circulation.
Healio spoke with Gopinathannair, who is the cardiac electrophysiology lab director at Kansas City Heart Rhythm Institute, electrophysiology medical director, Research Medical Center, and professor of medicine at University of Missouri-Columbia and associate professor of medicine (adjunct) at University of Louisville, about COVID-19-related cardiac arrhythmias, its prevalence and important treatment considerations for clinicians.
Healio: What is the goal of this AHA Scientific Statement?
Gopinathannair: We have now moved from the pandemic phase of COVID-19 to an endemic phase. COVID-19-associated arrhythmias as well as autonomic dysfunction continued to persist. We felt that clinicians needed guidance to care for these patients in the acute as well as postinfectious phases of COVID-19. Therefore, the goal of this AHA Scientific Statement is to discuss common arrhythmic and autonomic manifestations of COVID-19, review pathophysiological mechanisms, clinical significance and treatment strategies of these manifestations. We address comparative data with other viral illnesses, review the association of COVID-19 vaccination and arrhythmias as well as risk for recurrent arrhythmias after recovery. Implications for long-term follow-up, monitoring and treatment strategies are summarized; knowledge gaps and areas for future research have been identified.
Healio: What is the prevalence of cardiac arrhythmias after COVID-19 infection and who is most at-risk?
Gopinathannair: Patients with underlying cardiac illness/cardiac risk factors are at an increased risk for COVID-19-associated arrhythmias.
Majority of the data on incidence/prevalence data comes from the pandemic phase, and data shows wide variability. Early in the pandemic, bradyarrhythmias have been reported in 22% to 36% of infected patients, whereas data from a large global research network showed bradycardia in only 4.5%. Use of remdesivir (Veklury, Gilead Sciences) was associated with bradycardia in 22% of patients. Only 0.13% to 0.3% of patients required pacemaker implantation.
Atrial fibrillation is the commonest cardiac arrhythmia noted — 18% to 22%, new onset in 4.5% to 13%. Patients with COVID-19 and AF tended to be older.
In patients with COVID-19 infection, the overall prevalence of ventricular arrhythmias is 0.1% to 8%. Ventricular arrhythmia was higher in more severe COVID-19 infections. Ventricular arrhythmia was significantly associated with increased mortality. The arrhythmic risk is likely lower during the current endemic phase with less virulent strains.
There is limited outpatient data on ventricular arrhythmia occurrence with COVID-19. One study evaluating arrhythmias 3 months after hospitalization for COVID-19 using 24-hour ambulatory monitoring found premature ventricular contractions in 18% and nonsustained ventricular tachycardia in 5% without sustained ventricular arrhythmias.
A study evaluating 13,790 hospitalized patients with COVID-19 showed that sudden cardiac arrest occurred in 1.8% of hospitalized patients with COVID-19 and in 10% of those who died.
A study evaluating long-term arrhythmic outcomes after COVID-19 infection in approximately 4.1 million patients in the U.S. Collaborative Network (TriNetX) showed higher incidence of atrial (2.4-fold) and ventricular arrhythmias (1.6-fold) at 1-year follow-up in people who had COVID-19. Similar results were shown in a large U.S. Veterans Affairs study. These findings support the need for continued arrhythmia surveillance after COVID-19.
Healio: By what mechanism does prior COVID-19 infection cause cardiac arrhythmias?
Gopinathannair: Mechanisms may differ for different arrhythmias. In the acute phase, various mechanisms including a hyperadrenergic state, and immune-mediated — inflammation and direct viral injury — can contribute to development of cardiac arrhythmias. Prior studies have shown cardiac infiltration by the SARS-CoV-2 virus. However, the risk of arrhythmias may be driven more by the inflammatory response than direct viral injury. The presence of high levels of ACE-2 receptors in the heart, which are needed for viral entry, also explain predilection to cardiac arrhythmias.
The mechanisms underlying arrhythmias in those with prior COVID-19 infection are less clear. Prior inflammation could lead to scar formation — fibrosis — that could result in AF and ventricular arrhythmias. Autonomic dysfunction, especially a hyperadrenergic state, could persist into recovery and may contribute to arrhythmias. Especially for AF and ventricular arrhythmias, development during acute hospitalization portends higher risk of recurrence during longer-term follow-up. The development of bradycardia and cardiac conduction system disturbances are poorly understood but could be secondary to myocardial injury and inflammatory damage to pacemaker cells. Antiviral drugs used for acute treatment can potentially prolong QT interval, which can lead to life-threatening cardiac arrhythmias.
Healio: What arrhythmias are most common?
Gopinathannair: Available data shows that AF is by far the most common cardiac arrhythmia. Among bradyarrhythmias, sinus bradycardia and atrioventricular block were the commonest.
Healio: For how long after COVID-19 infection does the elevated arrhythmia risk last and is risk modified by prior COVID-19 vaccination?
Gopinathannair: Based on available data, we know that elevated arrhythmic risk persists for at least 1 year following COVID-19 infection. Vaccine Adverse Event Reporting System (VAERS) database shows that overall incidence of AF after COVID-19 vaccination is less than what would be expected for the general population. There is currently no consistent evidence to demonstrate a higher risk for arrhythmia attributable to COVID-19 vaccination in the general population.
Healio: What are some of the drug-to-drug interactions that should be taken into consideration when caring for patients with COVID-19 and concomitant heart disease?
Gopinathannair: This is a very pertinent question. Currently, nirmatrelvir-ritonavir (Paxlovid, Pfizer) is commonly used to prevent progression to severe COVID-19 infection. Nirmatrelvir-ritonavir can interact with antiarrhythmics, anticoagulants, antibiotics and immunosuppressive drugs. Patients on class 1A and III antiarrhythmic drugs should be careful, as levels of these drugs can be elevated with nirmatrelvir-ritonavir use. Patients on warfarin should have frequent international normalized ratio checks while on nirmatrelvir-ritonavir. Dose adjustment and withholding may be needed for direct oral anticoagulants. Table 3 in the scientific statement details these interactions.
Healio: Anything else you would like to say?
Gopinathannair: Various arrhythmic manifestations have been associated with COVID-19, ranging from the benign to life-threatening. COVID-19 can precipitate autonomic dysfunction with risk for long-term symptoms. Although we are past the acute pandemic stage, with new, less infectious SARS-CoV-2 variants, newer drugs to treat acute COVID-19 infection, and widespread administration of vaccines, health care professionals must remain vigilant for arrhythmic and dysautonomic manifestations that may continue to occur with this novel disease.
For more information:
Rakesh Gopinathannair, MD, MA, FAHA, FHRS, can be reached at 2330 E. Meyer Blvd, Suite 509, Kansas City, MO 64132.
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