A 45-year-old woman receiving her sixth cycle of doxorubicin-based chemotherapy reports exertional dyspnoea. Endomyocardial biopsy shows myofibrillar loss and vacuolar degeneration without inflammation. The characteristic feature of this cardiomyopathy is:

• A It resolves completely on stopping the drug
• B It is idiosyncratic and unrelated to cumulative dose
• C It is dose dependent and largely irreversible ✓
• D It results from coronary artery vasospasm

Explanation

Anthracycline cardiomyopathy is a type I injury caused by free radical generation and topoisomerase II beta inhibition in cardiac myocytes. Risk rises steeply with cumulative dose, classically above 450 to 550 mg per square metre of doxorubicin, and the damage is characteristically irreversible. This distinguishes it from trastuzumab cardiotoxicity, which is dose independent and usually reversible. Dexrazoxane, an iron chelator, reduces risk when cumulative exposure must exceed standard limits.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

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