Drug-Induced Cardiotoxicity
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Direct answer
Drug-induced cardiotoxicity is damage to the myocardium, conduction system, coronary arteries or pericardium caused by medicines or drugs of abuse. Anthracyclines cause a dose-dependent cardiomyopathy that is often irreversible, trastuzumab causes left ventricular dysfunction that usually recovers after stopping, and fluorouracil causes coronary vasospasm. Monitoring with serial ejection fraction, troponin and ECG allows drugs to be held before heart failure develops.
What you must remember
- Anthracyclines: doxorubicin causes dose-dependent cardiomyopathy that is often irreversible, with risk rising steeply above a cumulative dose of about 400 mg per square metre.
- Trastuzumab: causes left ventricular systolic dysfunction that is usually reversible on stopping, and the risk is higher when it is given with an anthracycline.
- Fluorouracil and capecitabine: cause coronary vasospasm, presenting as chest pain, ST elevation or myocardial infarction.
- Cocaine: causes coronary vasoconstriction, myocardial infarction, arrhythmias and aortic dissection; benzodiazepines are the first-line sedative and pure beta-blockers are avoided in acute toxicity.
- Immune checkpoint inhibitors: cause myocarditis that can be fulminant, with heart block and cardiogenic shock, and needs early high-dose corticosteroids.
- Clozapine and QT drugs: clozapine causes myocarditis, while QT-prolonging antipsychotics and class IA and III antiarrhythmics cause torsades de pointes.
- Thiazolidinediones and NSAIDs: cause sodium and fluid retention that can precipitate heart failure.
- Cyclophosphamide: high-dose therapy causes haemorrhagic myocarditis.
Monitoring a patient on cardiotoxic chemotherapy
A 50-year-old woman with HER2-positive breast cancer is planned for doxorubicin followed by trastuzumab. Her cardiac risk is assessed before the first dose.
- Set the baseline. An echocardiogram measures ejection fraction and an ECG records the QTc, alongside a review of hypertension, coronary disease and earlier anthracycline exposure.
- Track the cumulative dose. The total anthracycline dose is recorded at every cycle, and dexrazoxane may be given to reduce cardiomyopathy when the dose is high.
- Repeat the surveillance. Ejection fraction is rechecked during and after therapy, and troponin and natriuretic peptides can flag injury earlier than echocardiography.
- Act on a fall. Trastuzumab is held when ejection fraction falls substantially, commonly by about 10 points to below the normal range, and restarted once function recovers.
- Treat the failure. Standard heart failure therapy with an ACE inhibitor or ARB, a beta-blocker and diuretics is started as needed.
- Recognise acute toxicity. Chest pain during a fluorouracil infusion prompts stopping the drug, an ECG and troponin, and coronary care if ischaemia is confirmed.
Where the exam tries to catch you
Cardiotoxicity questions test whether the damage is reversible and what to do first.
- Trap: permanently stopping trastuzumab after an ejection fraction fall Correct: trastuzumab dysfunction is often reversible, so holding, re-evaluating and restarting once function recovers is the usual course.
- Trap: treating anthracycline cardiomyopathy as reversible Correct: it is typically irreversible, so dose limits and early detection matter more than later treatment.
- Trap: giving a pure beta-blocker first for cocaine-associated chest pain Correct: unopposed alpha stimulation can worsen coronary spasm, so benzodiazepines come first.
Frequently asked questions
Which chemotherapy drug causes dose-dependent cardiomyopathy?
Anthracyclines, such as doxorubicin and daunorubicin, cause dose-dependent cardiomyopathy. The damage is often irreversible, so cumulative dose tracking and echocardiographic surveillance are central to safe use.
Which chemotherapy drug causes coronary vasospasm?
Fluorouracil, and its oral prodrug capecitabine, can cause coronary vasospasm and myocardial infarction. Chest pain during the infusion should prompt stopping the drug and checking an ECG and troponin.
How is cocaine-associated chest pain managed initially?
Cocaine-associated chest pain is managed with standard acute coronary care, with benzodiazepines to control sympathetic drive. Pure beta-blockers are avoided in the acute phase because unopposed alpha stimulation can worsen coronary spasm.
Which checkpoint inhibitor toxicity is life-threatening?
Myocarditis from immune checkpoint inhibitors is life-threatening and can be fulminant, with heart block and cardiogenic shock. Early recognition, high-dose corticosteroids and withholding the drug are the core steps in management.