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Anticancer Drug Induced Cardiotoxicity
editThe cardiotoxicity of anticancer drugs has been well documented, with an entire sub-speciality of cardio-oncology dedicated towards investigating and treating this serious side effect. The two most well known anti-cancer drug families that cause cardiotoxicity are anthracyclines and monoclonal antibodies targeting HER2.
Pathophysiology
editThe current mechanism of anthracycline-induced cardiotoxicity is unknown and is under active research. However, multiple theories exist. One highly support mechanism of anthracycline-induced cardiotoxicity is thought to be related to the production of superoxide anion radicals.[1] Other proposed mechanisms include interference with cardiac ATP production, mitochondria-related stress, and lipid peroxidation.
On the other hand, the mechanism of HER2 antibody cardiotoxicity is known. [2] HER2 is a protein that occurs on the cell membranes of HER2 positive breast cancer cells, of which these antibodies target. However, HER2 is also expressed on cardiac myocytes. It is hypothesized that the HER2 expressed in cardiac cells have a cardioprotective mechanism, and the targeting of these proteins in this context leads to cardiotoxicity associated with HER2 monoclonal antibodies.[3]
Clinical Manifestation and Epidemiology
editThe cardiotoxicity of anthracyclines can be classified into three categories: early, early onset chronic, and late onset chronic. Early cardiotoxicity is rare, but manifests as arrthymias, myocarditis, and pericarditis. This type of toxicity occurs directly after treatment with anthracycline. Early onset chronic cardiotoxicity is defined as cardiotoxicity manifesting within one year of the completion of treatment, while late onset chronic cardiotoxicity occurs after one year. [4] The cardiotoxicity of anthracyclines is dose dependent on total exposure. At total exposure levels lower than 400 mg/m2, the incidence of heart failure is between 3%-5%. at a cumulative dose of 700 mg/m2, the heart failure incidence is at 48%.[5]
Cardiotoxicity involving HER2 monoclonal antibodies manifests as decrease left ventricular ejection fraction and resulting heart failure.[6] The cardiotoxicity of HER2 monoclonal antibodies is dose-independent .[7]
Treatments
editThe immediate intervention for the development of cardiotoxicity is discontinuation of the drug. Preventative measures for anthracycline induced cardiomyopathy include Dexrazoxane, which is the only preventative drug approved by the FDA for prevention of anthracycline cardiomyopathy. Overall, there are no specific treatments targeted towards the cardiotoxicity of anti-cancer drugs. Rather, treatment is centered on treatment of resultant heart failure that occurs, which often takes the form of ACE inhibitors and beta blockers.
Antiarrhymatic Cardiotoxicity
editAntiarrhythmics are broad class of drugs that are used treat heart rhythm irregularities. [8] Utilizing the Vaughan-Williams (VW) system, antiarrhymatic drugs are classified into four main classes based on their mechanism of action. Class I antiarrhymatics lead to blockage of sodium channels. Class II antiarrhymatics are beta-adrenoceptor blockers. Class III antiarrhymatics act as potassium channel blockers, while Class IV antiarrhymatics are non-dihydropyridine calcium channel blockers.
Pathophysiology
editThe pharmacological cardiotoxicity of anti-arrhythmic compounds is related to their electrophysiological mechanism. In particular, because antiarrhythmic drugs act on the opening/closing of ion channels, the modification of the electrical currents can lead to adverse cardiac events such torsade de pointes or ventricular fibrillation.
Clinical Manifestation and Epidemiology
editThe manifestation of antiarrhythmic cardiotoxicity may manifest as worsening of the pre-existent arrhythmia or the development of a new arrhythmia.
Female sex at birth has been associated with an increased risk of the development of new arrhythmia, and other risk factors include increased age, kidney disease, drug-drug interactions, and other underlying heart issues.[9]
Treatment
editLike with anticancer drugs, the most common intervention for the development of cardiotoxicity is discontinuation of the causative drug. Individual risk factors, such as risk of arrhymia re-emergence, are considered when deciding final courses of action. Adjacent devices, such as pacemakers, or ablation therapy may also be considered as alternatives to medical to treat the primary arrhythmia.
References
edit- ^ Raj, Shashi; Franco, Vivian I.; Lipshultz, Steven E. (2014-04-22). "Anthracycline-Induced Cardiotoxicity: A Review of Pathophysiology, Diagnosis, and Treatment". Current Treatment Options in Cardiovascular Medicine. 16 (6): 315. doi:10.1007/s11936-014-0315-4. ISSN 1534-3189.
- ^ Keefe, Deborah L. (2002-10). "Trastuzumab‐associated cardiotoxicity". Cancer. 95 (7): 1592–1600. doi:10.1002/cncr.10854. ISSN 0008-543X.
{{cite journal}}: Check date values in:|date=(help) - ^ Copeland-Halperin, Robert S.; Liu, Jennifer E.; Yu, Anthony F. (2019-07). "Cardiotoxicity of HER2-targeted therapies". Current Opinion in Cardiology. 34 (4): 451. doi:10.1097/HCO.0000000000000637. ISSN 0268-4705.
{{cite journal}}: Check date values in:|date=(help) - ^ Volkova, Maria; Russell, Raymond. "Anthracycline Cardiotoxicity: Prevalence, Pathogenesis and Treatment". Current Cardiology Reviews. 7 (4): 214–220. doi:10.2174/157340311799960645.
- ^ Johnson, Mark; Keyes, Daniel (2024), "Anthracycline Toxicity", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 38261713, retrieved 2024-11-12
- ^ "Cardiotoxicity and the Evolving Landscape of HER2-Targeted Breast Cancer Treatment". American College of Cardiology. Retrieved 2024-11-12.
- ^ Zhang, Li; Wang, Yan; Meng, Wenjing; Zhao, Weipeng; Tong, Zhongsheng (2022-08-22). "Cardiac safety analysis of anti-HER2-targeted therapy in early breast cancer". Scientific Reports. 12 (1): 14312. doi:10.1038/s41598-022-18342-1. ISSN 2045-2322.
- ^ King, Gregory S.; Goyal, Amandeep; Grigorova, Yulia; Patel, Preeti; Hashmi, Muhammad F. (2024), "Antiarrhythmic Medications", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 29493947, retrieved 2024-11-15
- ^ academic.oup.com https://academic.oup.com/europace/article/20/5/731/4846844. Retrieved 2024-11-15.
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