Navigating COVID-Associated Arrhythmias and Autonomic Dysfunction

Over the years since the onset of the global coronavirus pandemic, more than 776 million individuals have been infected with SARS-CoV-2 worldwide.¹ The coronavirus infection (COVID-19) has been associated with arrhythmias and autonomic dysfunction.^2,3

The American Heart Association Scientific Statement on Cardiac Arrhythmias and Autonomic Dysfunction Associated with COVID-19 serves as a single document that addresses both arrhythmias and autonomic dysfunction associated with COVID-19 infection. In this document, the multidisciplinary writing group provides an appraisal of the existing evidence for insights on pathophysiologic mechanisms and clinical manifestation, pragmatic considerations for drug-drug interactions, and implications for management of applicable patients and directions for future research.

This valuable document underscores several important broad messages. Mechanistically, pathophysiologic contributions to COVID-associated arrhythmias and autonomic dysfunction are likely multifactorial, with potential contributions related to systemic COVID-19 infection (hypoxemia, acidosis, hemodynamic instability), direct injury to myocardial tissues, autonomic aberration, inflammatory response, and immune-related causes.

Severity of COVID-19 infection may modulate risk for a wide spectrum of arrhythmias during acute COVID-19 infection and prompt treatment of COVID-19 is a key part of acute management in these scenarios. Long-term management patients with AF diagnosed in the setting of COVID-19 infection, similar to the management of AF diagnosed in the setting of acute medical or surgical illness,^4,5 include patient counseling regarding likelihood for AF recurrence, arrhythmia surveillance with heart rhythm monitoring, and thromboembolic risk stratification for long-term anticoagulation consideration.

Pragmatic to clinical practice, the Scientific Statement highlights drug-drug interactions of COVID medication Paxlovid (nirmatrelvir-ritonavir) with antiarrhythmic and anticoagulant medications. Ritonavir (a component of Paxlovid) is an inhibitor of P-glycoprotein and hepatic CYP3A4 metabolism. The P-glycoprotein or the CYP3A4 pathways are implicated in the metabolism of many common antiarrhythmic and anticoagulant medications. This document provides useful guidance for dose adjustment, monitoring, discontinuation or avoidance of specific antiarrhythmic and/or anticoagulant in relation to Paxlovid treatment.

The content on long-term considerations, especially with expanded discussions on postacute sequelae of SARS-CoV-2 (PASC), further sets this Scientific Statement apart from other documents published in the early phase of the COVID-19 pandemic. PASC, also known as long COVID, is defined as ongoing, relapsing, or new symptoms or conditions present 30 or more days after infection.⁶ PASC is the focus of the ongoing National Institutes of Health's Researching COVID to Enhance Recovery (RECOVER) Initiative, which seeks to understand, treat, and prevent PASC (https://recovercovid.org/). The discussions on PASC in this Scientific Statement center on autonomic dysfunction following COVID infection (PASC-AD). Subtypes of PASC-AD are specifically considered, including postural orthostatic tachycardia syndrome, orthostatic hypotension, inappropriate sinus tachycardia, and normotensive patients with orthostatic intolerance without tachycardia. The document calls for better characterization of the presences and severity of autonomic dysfunction in PASC, advocating for more consistent and standardized autonomic testing. In consideration of existing data, the document suggests that assessment of autonomic dysfunction symptoms at initial encounter and over follow-up can be useful and can be accomplished with tools (the Composite Autonomic Symptom 31 [COMPASS-31] and the Vanderbilt Orthostatic Symptoms Score [VOSS]) now validated to assess autonomic dysfunction symptoms in PASC patients.^7,8 More data are needed to guide specific treatment strategies for PASC-AD; in the meantime, management of PASC-AD patients in accordance to existing autonomic disorder guidelines is suggested.

The AHA Scientific Statement on Cardiac Arrhythmias and Autonomic Dysfunction Associated with COVID-19 is informative, practical, and timely. The continued evolution of the SARS-CoV2 viral strains and the knowledge gaps identified in the document set the stage for future research. Studies to inform long-term surveillance and treatment strategies for individuals with COVID-associated arrhythmias or autonomic dysfunction are particularly needed. Data are anticipated from dedicated efforts such as the NIH RECOVER COVID initiatives (with specific ongoing RECOVER-AUTONOMIC clinical trials NCT06305793, NCT06305806, NCT06305780) and may serve to guide future practice.