Many common medications, despite being effective for the targeted condition, come with concerns about cardiotoxicity. These toxic effects commonly manifest as arrhythmias (especially QT prolongation with the potential to lead to torsades de pointes) but also as bradyarrhythmias, Afib/atrial flutter, atrial tachycardia, atrioventricular nodal reentrant tachycardia, monomorphic ventricular tachycardia (VT), and Brugada syndrome. The consequences of these developments can range from uncomfortable symptoms to sudden cardiac death.
The potential for toxic effects on the heart is well known with anticancer treatments, but dozens of other types of medication can cause problems as well. An American Heart Association (AHA) scientific statement detailing drug-induced arrhythmias pointed to multiple drug classes as culprits, including antiarrhythmics, antimicrobials, psychotropic medications, methadone, neurological drugs, and many others.1
Twelve-lead ECG can play a key role in monitoring patients for treatment-related cardiotoxicity. An ECG provides a fast and easy way to pick up early signs of subclinical cardiac damage before more overt effects become detectable.
Harming the Heart While Fighting Cancer
Great strides have been made with regard to cancer treatment in recent decades, but many anticancer therapies can also harm the heart. This conundrum is a major focus of the burgeoning field of cardio-oncology. Left Ventricular (LV) dysfunction, for instance, has been associated with anthracyclines and trastuzumab. The AHA scientific statement notes that thalidomide, used in newly diagnosed multiple myeloma, may cause or exacerbate sinus bradycardia or atrioventricular (AV) block.
Patients with a high cardiovascular risk are more likely to experience cardiotoxic effects from anthracycline chemotherapy and other types of anticancer treatments, including vascular endothelial growth factor inhibitors, BCr-Abl and Raf-MEK tyrosine kinase inhibitors, proteasome inhibitors, and gonadotrophin-releasing hormone receptor agonists, according to a review in European Heart Journal Supplements.2
The AHA notes that arrhythmias that may be sparked by anticancer therapies include monomorphic ventricular tachycardia, torsades de pointes associated with QT prolongation, and afib/atrial flutter.
The 12-lead ECG can be part of a strategy to mitigate these risks. A study in Cardio-Oncology showed that irregular ECG changes—specifically, a decrease in the sum of absolute QRS amplitudes in the six limb leads and an increase in corrected QT interval—could be detected before changes on echocardiography and were associated with a greater risk of developing cardiomyopathy in children treated with anthracyclines.3
Multiple cardiology and oncology societies have highlighted the utility of ECG and other noninvasive modalities, such as echocardiography, cardiac MRI, nuclear imaging, and cardiac biomarkers, in managing cardiovascular risks associated with anticancer therapies. In 2016, the European Society of Cardiology (ESC) recommended performing an ECG for all cancer patients before and during treatment to detect signs of cardiotoxicity, such as "resting tachycardia, ST-T wave changes, conduction disturbances, QT interval prolongation, or arrhythmias."4
2020 guidance from the European Society for Medical Oncology (ESMO) points out that many anticancer therapies, including arsenic trioxide, histone deacetylase inhibitors, tyrosine kinase inhibitors, and cyclin-dependent kinase 4/6 inhibitors, come with the risk of QT prolongation.5 Patients receiving one of these agents, ESMO says, should be monitored periodically with ECG for QT prolongation and arrhythmia, particularly at baseline and after steady-state drug levels are obtained. ECG monitoring is also warranted if doses are adjusted, new medications are added, or electrolyte abnormalities develop.
Irregular ECG Findings from Cardiovascular Drugs
Medications meant to treat heart conditions can also come with cardiotoxic effects that can be detected on ECG.
Multiple antiarrhythmic drugs, for example, have been known to induce or worsen monomorphic VT, Brugada syndrome, torsades de pointes, QT interval shortening, bradyarrhythmias, and afib/atrial flutter, according to the AHA scientific statement.
The antiplatelet medication dipyridamole has been associated with monomorphic ventricular tachycardia and sinus bradycardia/AV block, and use of digoxin has been tied to monomorphic VT and bradyarrhythmias. Digoxin toxicity can induce paroxysmal atrial tachycardia with AV block, the AHA notes.
The number of drug classes that can cause arrhythmias is extensive. The National Heart, Lung, and Blood Institute notes that at least 50 medications have been shown to cause long QT syndrome, with the list including antihistamines, decongestants, diuretics, antibiotics, antidepressants, antipsychotics, and certain cholesterol-lowering drugs.6
Illicit drugs like cocaine and methamphetamine, along with derivatives like 3,4-methylenedioxymethylamphetamine (commonly known as MDMA, ecstasy, or molly), can cause a variety of arrhythmic complications as well. The potential cardiotoxic effects of cannabis, which is being legalized in an increasing number of U.S. states and other countries, are still being explored. Alcohol and caffeine may cause ECG irregularities as well.
In many cases, the most effective management of drug-induced arrhythmia is stopping the medication that's causing the problem, according to the AHA, but in some cases that might not be enough to ensure the issue is resolved. Patients with drug-induced Brugada syndrome, for example, should be screened with ambulatory ECG monitoring after discontinuation of the culprit agent to check for latent Brugada syndrome.
In addition, ECG can be useful for monitoring patients taking medications known to cause torsades de pointes. In hospitalized patients, a 12-lead ECG should be performed daily, and for those on long-term therapy, ECG readings should be obtained every 3 to 6 months, the AHA recommends. For patients receiving methadone to treat opioid addiction, an ECG should be performed at the start of therapy and again within 30 days for those with risk factors. After that, patients should be reevaluated annually or when the daily methadone dose is greater than 120 mg.
To learn more about the power of the ECG in today's clinical landscape, browse our Diagnostic ECG Clinical Insights Center.
Importance of ECG
The 12-lead ECG remains a key tool in monitoring patients for potential cardiotoxic effects of necessary medications.
Experts from the American College of Cardiology, describing the cost-effectiveness of monitoring for cardiotoxicity specifically related to cancer treatments, note the importance of taking baseline and serial 12-lead ECGs, calling this the "standard of care for cardiotoxicity monitoring," along with transthoracic echocardiography assessments.7
In a more general sense, the AHA says that "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." It's crucial for clinicians to be aware of which medications can cause arrhythmias.
References:
- Tisdale J E et al. Drug-induced arrhythmias: A scientific statement from the American Heart Association. Journal of the American Heart Association. Sep 2020; vol. 142 (iss.15): 214-233. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000905
- Habibian M and Lyon A R. Monitoring the heart during cancer therapy. European Heart Journal Supplements. Dec 2019; vol. 21 (iss. Supplement_M): 44-49. https://academic.oup.com/eurheartjsupp/article/21/Supplement_M/M44/5691328
- Desai L et al. Electrocardiograms for cardiomyopathy risk stratification in children with anthracycline exposure. Cardio-Oncology. Aug 2019; vol. 5 (iss. 10). https://cardiooncologyjournal.biomedcentral.com/articles/10.1186/s40959-019-0045-6
- Zamorano J L et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). European Heart Journal. Sept 2016; vol. 37 (iss. 36): 2768-2801. https://academic.oup.com/eurheartj/article/37/36/2768/2197413
- Curigliano G et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESCO consensus recommendations. European Society for Medical Oncology Annals of Oncology. Feb 2020; vol. 31 (iss. 2): 171-190. https://www.annalsofoncology.org/article/S0923-7534(19)36080-6/fulltext
- National Heart, Lung, and Blood Institute. Long QT Syndrome. https://www.nhlbi.nih.gov/health-topics/long-qt-syndrome
- Yu A F et al. Cost-effectiveness of cardiotoxicity monitoring, expert analysis. American College of Cardiology. Aug 2017. https://www.acc.org/latest-in-cardiology/articles/2017/08/14/07/23/cost-effectiveness-of-cardiotoxicity-monitoring
