Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association

Abstract

Many widely used medications may cause or exacerbate a variety of arrhythmias. Numerous antiarrhythmic agents, antimicrobial drugs, psychotropic medications, and methadone, as well as a growing list of drugs from other therapeutic classes (neurological drugs, anticancer agents, and many others), can prolong the QT interval and provoke torsades de pointes. Perhaps less familiar to clinicians is the fact that drugs can also trigger other arrhythmias, including bradyarrhythmias, atrial fibrillation/atrial flutter, atrial tachycardia, atrioventricular nodal reentrant tachycardia, monomorphic ventricular tachycardia, and Brugada syndrome. Some drug-induced arrhythmias (bradyarrhythmias, atrial tachycardia, atrioventricular node reentrant tachycardia) are significant predominantly because of their symptoms; others (monomorphic ventricular tachycardia, Brugada syndrome, torsades de pointes) may result in serious consequences, including sudden cardiac death. Mechanisms of arrhythmias are well known for some medications but, in other instances, remain poorly understood. For some drug-induced arrhythmias, particularly torsades de pointes, risk factors are well defined. Modification of risk factors, when possible, is important for prevention and risk reduction. In patients with nonmodifiable risk factors who require a potentially arrhythmia-inducing drug, enhanced electrocardiographic and other monitoring strategies may be beneficial for early detection and treatment. Management of drug-induced arrhythmias includes discontinuation of the offending medication and following treatment guidelines for the specific arrhythmia. In overdose situations, targeted detoxification strategies may be needed. Awareness of drugs that may cause arrhythmias and knowledge of distinct arrhythmias that may be drug-induced are essential for clinicians. Consideration of the possibility that a patient’s arrythmia could be drug-induced is important.

Use of Disproportionality Analysis to Identify Previously Unknown Drug-Associated Causes of Cardiac Arrhythmias Using the Food and Drug Administration Adverse Event Reporting System (FAERS) Database

“…Also, this substantial number of unknown drug associations is likely due to much of the arrhythmia literature and databases focusing on QTc-prolongation and TdP with the exception of a recent review of drug-induced arrhythmias. 1,[5][6][7]17 A recent review from the American Heart Association only included information on 5 of the top 10 medications reported across the 6 arrythmias in our study: rofecoxib (under a class category and not specifically mentioned), digoxin, alendronate, dronedarone, and zoledronic acid. 17 The results of this retrospective pharmacovigilance disproportionality analysis display the significance of post-marking surveillance for arrhythmias.…”

“…20,21,[23][24][25][26] The ROR was determined using the formula: ROR ¼ (n11 Â n00)/(n10 Â n01), where n11 ¼ arrhythmia reports for drug of interests, n01 ¼ arrhythmia reports not including the drug of interest; n10 ¼ reports not including arrhythmia for the drug of interest; n00 ¼ reports including neither arrhythmia nor the drug of interest. 17,19 Using this formula resulted in the ratios of the odds of the reported event of interest A for the drug B to the odds of event of interest A in the absence of drug B. 19 ROR > 1 was considered to have greater odds of being proarrhythmogenic than other ADRs.…”

“…[14][15][16] A newly published review of drug-induced arrhythmias did add further to the literature by including a section on atrioventricular nodal reentrant tachycardia. 17 Antineoplastic agents are a class of medications with mounting evidence of bradyarrhythmias that may further exacerbate cardiotoxicities already caused by atrioventricular nodal blocking agents. 14 A recent review of oncology literature has linked multiple chemotherapeutic agents to various cardiac arrhythmias ranging from sinus bradycardia to sudden cardiac death.…”

Stroke in SARS-CoV-2 Infection: A Pictorial Overview of the Pathoetiology

“…As discussed in earlier sections, patients with COVID-19 are prone to cardiovascular damage and newonset arrhythmia as a consequence of comorbidities and infection. Drugs that have been associated with the induction of AF and the possible mechanisms are comprehensively reviewed by previous studies (322)(323)(324). Based on these studies, drug-induced AF is believed to have the following principal mechanisms: alterations in autonomic tone through either adrenergic or vagal stimulation, changing the atrial automaticity and conduction, direct cardiovascular toxicity such as coronary vasoconstriction/ischemia and electrolyte disturbances, local or systemic inflammation, oxidative stress, hyperthermia (322)(323)(324).…”

Arrhythmias in cancer: rhythm is gonna get you!

“…chemotherapy, targeted therapies, immunotherapies), radiotherapy with chest irradiation involving cardiac tissue and supportive medications, such as antiemetics. Certain anticancer agents have been associated with pro‐arrhythmic properties, with QT prolongation being the most typical one 5–7 . Anticancer drugs may further predispose to arrhythmias by causing other forms of CV disease such as ventricular dysfunction and heart failure or myocardial ischaemia as part of their cardiotoxicity profile or by inducing electrolyte and metabolic disorders due to gastrointestinal and other toxicities.…”