Drug Proarrhythmia

Last Updated: September 18, 2020

Disclosure: No relevant disclosures. Consultant for Medtronic at modest level.
Pub Date: Tuesday, Sep 15, 2020
Author: John D. Fisher, MD, FAHA
Affiliation: Montefiore Medical Center, Albert Einstein College of Medicine

Health care providers will be very happy to see the AHA Scientific Statement on drug-induced arrhythmias (proarrhythmia).1 Tisdale and colleagues, mostly members of the AHA Clinical Pharmacology Committee, have produced a unique and useful document.

It has been estimated that >250,000 deaths yearly are caused by medical errors in the United States.2 Not all of these are medication errors, and the methodology and numbers have been disputed,3 but most practitioners would agree that avoiding drug-related arrhythmias is a major challenge.

Another challenge is to present the problem of proarrhythmia in an engaging format, rather than a dry listing. The AHA Scientific Statement has risen to that challenge. The Statement is organized into three sections. First is a text of modest length. This is followed by extensive tables, with links to sites with even greater detail. Finally, there is a brief supplemental section with illustrations.

The first or textual portion covers well known examples of proarrhythmia, but also calls attention to medications that may not be considered by cardiologists, or subtle interactions that may occur with seemingly innocuous drug combinations or effects. Some features of the Statement:

  1. Topics are organized by site, e.g. sinus node, atrium, AV node, His-Purkinje system, ventricle.
  2. Bradycardias as well as tachycardias considered as drug-induced arrhythmias.
  3. Clinical circumstances likely to produce proarrhythmia, and estimated risks are considered.
    1. Example: a “benign” drug tolerated by a patient unless the potassium level declines to a certain level; and what happens then to change from benign to malignant.
  4. Mechanisms for proarrhythmia such as effects on autonomics and channels.
  5. Effects of non-cardiac drugs: anti-neoplastics, immunologics, neuro-psychologics, etc.
  6. Timing of effects: immediate or delayed for days, weeks or the addition of other factors (the “time bomb” effect).
  7. Downstream effects.
    1. Example: amiodarone may be well-tolerated until it produces hyperthyroidism which in turn causes atrial fibrillation.
    2. After heart transplant, atropine (“paradoxically”) or adenosine can cause profound bradycardia.
  8. Drug metabolism.
    1. What can slow metabolism resulting in increased blood levels, e.g. renal failure or drug-drug interaction.
    2. Many effects mediated by cytochrome P450 system, phosphodiesterases, etc.
  9. Reversible and non-reversible proarrhythmia.
    1. 50% with drug-induced bradycardia may require permanent pacing. Why? Unmasked inevitable bradycardia, or created a lasting change in cellular function?
  10. How to avoid proarrhythmia. Pulls together many of the points above. As always, “avoidance” is the mainstay when possible.
  11. Unsolved mysteries.
    1. Why does drug-induced bradycardia often become permanent even after the drug has been stopped? (see above).
    2. Why can ivabradine cause atrial fibrillation?
    3. Others.
  12. The tables: The major table is organized with intuitive headings: Drug Class, (Individual sample) Drug, Incidence (of proarrhythmia), and Mechanism (of proarrhythmia). The drugs include those most familiar to cardiologists, and samples of important but less familiar drugs.

Altogether, the Scientific Statement is an up-to-date easy to read summary of the complex world of proarrhythmia. The emphasis on general principles makes it is a useful guide in clinical as well as educational situations. The Statement is not an exhaustive compendium of all known, suspected or possible drug-related proarrhythmias, but handy links are provided for that level of detail.


Tisdale JE, Chung MK, Campbell KB, Hammadah M, Joglar JA, Leclerc J, Rajagopalan B; on behalf of the American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology and Council on Cardiovascular and Stroke Nursing. Drug-induced arrhythmias: a scientific statement from the American Heart Association [published online ahead of print September 15, 2020]. Circulation. doi: 10.1151/CIR.0000000000000905


  1. Tisdale JE, Chung MK, Campbell KB, Hammadah M, Joglar JA, Leclerc J, Rajagopalan B; on behalf of the American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology and Council on Cardiovascular and Stroke Nursing. Drug-Induced Arrhythmias: A Scientific Statement from the American Heart Association. Circulation. 2020;141:e000–e000.
  2. Makary MA, Daniel M. Medical error: the third leading cause of death in the United States. BMJ. 2016;353:i2139:1-5.
  3. Harkanen M, Vehvilainen-Julkunen K, Rafferty AM, Franklin BD. Medical administration errors and mortality: incidents reported in England and Wales between 2007-2016. Res Social Admin Pharm. 2019;15:858-863.

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-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association --