THE HEART OF THE MATTER: ANTHRACYCLINE-INDUCED CARDIOTOXICITY

Abstract

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Cardiotoxicity is a well-known complication of anthracycline chemotherapy. The incidence has been reported as high as 9% in solid cancer patients and up to 18% in acute myeloid leukemia (AML) patients [1].Unfortunately, anthracycline-induced cardiotoxicity (AIC) in AML patients represents a unique and high-risk subset of patients that are largely underrepresented in the literature.We report a case of a patient with AML who was admitted for induction chemotherapy with Cytarabine and Daunorubicin. Two weeks later she developed cardiogenic shock and was transferred to the ICU. A literature review reveals gaps in current research and suggests AML patients are at particularly high risk for developing AIC. CASE PRESENTATION: Ms. D was a 64 year-old female with AML admitted for induction chemotherapy with high dose Cytarabine and Daunorubicin. Eighteen days after receiving treatment she developed hypoxic respiratory failure with pulmonary edema and an echocardiogram showed a newly reduced ejection fraction of 30%. Heart catheterization revealed a depressed cardiac index. She was started on inotropic support with improved lactate clearance and cardiac function; however, given her poor overall prognosis, she was determined to not be a candidate for mechanical circulatory support. Congruent with the patient's wishes, she was placed on comfort measures and died 12 hours later. DISCUSSION: AIC is generally defined as >10% reduction in left ventricular ejection fraction (LVEF) with a final LVEF < 50% [2]. Pathogenesis is multifactorial and involves reactive oxygen species generation and defective mitochondrial biogenesis with a predilection for cardiac myocytes due to their high mitochondrial content [3]. Patient risk factors for AIC include age >65 or <18 years old, female sex, pre-existing cardiac disease and genetic factors [1]. In studies of solid cancer and lymphoma regimens, AIC is dose-dependent [1]. For unclear reasons, AML patients seem to experience unexpectedly high rates of AIC after induction. Medications to reduce the risk of AIC include chelation therapy with dexrazoxane, prolonged infusion times, liposomal preparations and pre-treatment with enalapril and carvedilol [3]. These interventions have failed to show consistent benefit in AML patients [1]. CONCLUSIONS: We present a case of AIC in an AML patient who's only known risk factor was female sex. This case and review of the literature suggests that AML patients are at an increased risk for developing AIC. More research is needed to determine effective preventative strategies for AML patients receiving anthracycline chemotherapy. REFERENCE #1: Neuendorff NR, Loh KP, Mims AS, Christofyllakis K, Soo WK, Bölükbasi B, Oñoro-Algar C, Hundley WG, Klepin HD. Anthracycline-related cardiotoxicity in older patients with acute myeloid leukemia: a Young SIOG review paper. Blood Adv. 2020 Feb 25;4(4):762-775. doi: 10.1182/bloodadvances.2019000955. PMID: 32097461; PMCID: PMC7042993. REFERENCE #2: Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, Habib G, Lenihan DJ, Lip GYH, Lyon AR, Lopez Fernandez T, Mohty D, Piepoli MF, Tamargo J, Torbicki A, Suter TM; ESC Scientific Document Group. 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). Eur Heart J. 2016 Sep 21;37(36):2768-2801. doi: 10.1093/eurheartj/ehw211. Epub 2016 Aug 26. Erratum in: Eur Heart J. 2016 Dec 24;: PMID: 27567406. REFERENCE #3: Volkova M, Russell R 3rd. Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment. Curr Cardiol Rev. 2011 Nov;7(4):214-20. doi: DISCLOSURES: No relevant relationships by Robert McLeroy, source=Web Response No relevant relationships by Matthew Middendorf, source=Web Response No relevant relationships by Sarah Schulte, source=Web Response