A 34-year-old man diagnosed with advanced non-Hodgkin lymphoma undergoes doxorubicin-containing chemotherapy with good clinical response. Several weeks after the last chemotherapy cycle, the patient comes to the office with progressive exertional dyspnea. He has difficulty sleeping flat at night and needs to use multiple pillows to fall asleep. The patient is a lifetime nonsmoker and has no family history of heart disease. Blood pressure is 124/72 mm Hg, pulse is 86/min, and respirations are 16/min. Oxygen saturation on room air is 96%. Which of the following is most likely responsible for this patient's current symptoms?

Question

A 34-year-old man diagnosed with advanced non-Hodgkin lymphoma undergoes doxorubicin-containing chemotherapy with good clinical response.  Several weeks after the last chemotherapy cycle, the patient comes to the office with progressive exertional dyspnea.  He has difficulty sleeping flat at night and needs to use multiple pillows to fall asleep.  The patient is a lifetime nonsmoker and has no family history of heart disease.  Blood pressure is 124/72 mm Hg, pulse is 86/min, and respirations are 16/min.  Oxygen saturation on room air is 96%.  Which of the following is most likely responsible for this patient's current symptoms?

Quizplus · Accepted Answer

11ec160b_3b76_dec6_9249_c3b73c04f36a_MD0001_00 Anthracyclines (eg, daunorubicin, doxorubicin) are chemotherapeutic agents associated with severe cardiotoxicity that manifests as dilated cardiomyopathy. The toxicity is dependent on the cumulative dose of anthracycline; affected patients develop symptoms of heart failure (eg, dyspnea on exertion, orthopnea, peripheral edema) anywhere from several weeks to years following treatment. Anthracyclines exert their antitumor effect by binding to the topoisomerase II enzyme in cancer cells to create DNA cleavage complexes that break DNA and cause cell death. Anthracycline cardiotoxicity results from a similar anthracycline-topoisomerase II complex that forms in healthy cardiomyocytes. In addition, anthracycline can form iron-containing complexes that produce DNA-damaging free radicals, which likely also plays a role in cardiotoxicity. The most effective method of preventing anthracycline-induced cardiomyopathy is the administration of dexrazoxane, a chelating agent thought to both block the formation of iron-associated free radicals and inhibit the formation of anthracycline-topoisomerase II complexes in healthy cardiomyocytes. (Choice B) Focal myocardial scarring commonly results following a myocardial infarction. (Choice C) Hypertrophic cardiomyopathy is an autosomal dominant disorder often caused by mutation of the beta-myosin heavy chain. (Choice D) Pericardial thickening and fibrosis usually follow cardiac surgery, radiation therapy, or viral infections of the pericardium. (Choice E) Restrictive cardiomyopathy often occurs as the initial cardiac manifestation of infiltrative disease (eg, hemochromatosis, amyloidosis, sarcoidosis) or may occur with radiation therapy. (Choice F) Right ventricular pressure overload can occur with acute pulmonary embolism. Although this patient with malignancy is at increased risk for venous thromboembolic disease, orthopnea is not explained by acute pulmonary embolism and is more consistent with heart failure. Educational objective: Anthracycline chemotherapeutic agents (eg, doxorubicin, daunorubicin) cause cardiotoxicity mainly through the formation of anthracycline-topoisomerase II DNA cleavage complexes that affect healthy cardiomyocytes. The cardiotoxicity is dependent on the cumulative dose of anthracycline received, and it manifests as dilated cardiomyopathy. __________ References: Anthracycline chemotherapy and cardiotoxicity. (http://www.ncbi.nlm.nih.gov/pubmed/28185035)

A 34-Year-Old Man Diagnosed with Advanced Non-Hodgkin Lymphoma Undergoes Doxorubicin-Containing