Which chemotherapeutic agent is most commonly associated with dilated cardiomyopathy leading to congestive heart failure?

• A. Bleomycin
• B. Vincristine
• C. Cisplatin
• D. Doxorubicin

Answer: (D)

This item centers on chemotherapy-induced cardiomyopathy, specifically the dose-dependent dilated form that leads to heart failure. Doxorubicin, an anthracycline, is classic for this toxicity. It damages cardiac myocytes mainly through reactive oxygen species production and free radical injury; this oxidative stress disrupts mitochondrial function and cellular membranes. Additionally, it interferes with topoisomerase II beta in heart cells, promoting apoptosis. The result is a progressive, dilated cardiomyopathy with systolic failure that correlates with the cumulative dose received. Clinically, this risk is mitigated by watching the total lifetime dose and, in some cases, using protective strategies like dexrazoxane, which chelates iron and reduces ROS.

Other chemotherapeutic agents listed have different toxicity profiles and do not classically cause this cardiomyopathy. Bleomycin is notorious for pulmonary fibrosis; vincristine causes neurotoxicity, including peripheral neuropathy; cisplatin mainly causes nephrotoxicity and ototoxicity, with less emphasis on cardiomyopathy.

So the agent most consistently linked to dilated cardiomyopathy and congestive heart failure is the one from the anthracycline family, doxorubicin.