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Cardiotoxicity

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Cardiotoxicity is the occurrence of heart dysfunction as electric or muscle damage, resulting in heart toxicity.[1] This can cause heart failure, arrhythmia, myocarditis, and cardiomyopathy in patients.[2] Some effects are reversible, while in others, permanent damage requiring further treatment may arise. The heart becomes weaker and is not as efficient in pumping blood. Cardiotoxicity may be caused by chemotherapy (a usual example is the class of anthracyclines)[3][4] treatment and/or radiotherapy;[5] complications from anorexia nervosa; adverse effects of heavy metals intake;[6] the long-term abuse of or ingestion at high doses of certain strong stimulants such as cocaine;[7] or an incorrectly administered drug such as bupivacaine.[8]

Mechanism

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Many mechanisms have been used to explain cardiotoxicity. While many times, differing etiologies share the same mechanism, it generally depends on the agent inducing cardiac damage. For example, the primary mechanism is thought to be oxidative stress on cardiac myocytes.[8] It is thought that reactive oxygen species (ROS) overwhelm the antioxidant defenses of cardiac cells, causing direct cellular damage. This oxidative damage can disrupt mitochondrial function, therefore disrupting energy production in the heart muscle itself, leading to energy depletion via depleted ATP and promoting cell death through apoptosis or necrosis.[9]

Other mechanisms of cardiotoxicity include inflammatory,[10] DNA damaging, and disrupted cell signaling. DNA damage and disrupted cellular signaling are the proposed mechanism for many cardiotoxic chemotherapeutics.[11]

Regardless of the mechanism, clinical manifestations include heart failure, arrhythmia, myocarditis, and cardiomyopathy that can be permanent.[12] These conditions can greatly alter mortality and morbidity in patients meaning careful monitoring is necessary in patients exposed to cardiotoxic agents.

Inciting agents

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The list of inciting agents is vast and involves various classes of medication as well as environmental agents. The effects of the cardiotoxic substances vary and are not all identical.

Chemotherapy drugs [13]

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  • Anthracyclines such as doxorubicin also referred to as "The Red Devil"
  • Alkylating Agents such as cyclophosphamide
  • HER2 Inhibitors
  • Tyrosine Kinase Inhibitors
  • Antimetabolites
  • Proteasome Inhibitors

Other medications

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  • Antipsychotics such as Haloperidol which can prolong QT interval [14]
  • Antibiotics such as Erythromycin and levofloxacin due to QT prolongation [15]

Environmental toxins

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  • Heavy Metals like lead and mercury[16]
  • Pesticides such as organophosphates [17]

Abused substances [18]

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  • Alcohol: Chronic heavy consumption leading to alcoholic cardiomyopathy
  • Recreational Drugs: Cocaine, Methamphetamine

Others

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  • Biological Toxins such as Diphtheria toxin [19]
  • Radiation Therapy is known to cause radiation-induced heart disease (RIHD) [20]


These agents can lead to varying degrees of cardiotoxicity, and their effects may be dose-dependent and influenced by individual factors such as pre-existing cardiovascular disease and genetic predispositions that can foster greater sensitivity to any cardiac damage.

Treatment

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The most likely effective treatment is to stop exposure to the inciting agent as soon as possible whether a pharmacologic or environmental agent. While some may fully recover from cardiotoxicity caused from exposure, many are left with permanant damage that may need further management. The management varies on the damage sustained, but generally follows guidelines for each condition such as heart failure, arrhythmias, and myocarditis. [21]

Patients taking anthracyclines can take Dexrazoxane as a cardioprotective agent to prevent extensive cardiac damage. [22]

See also

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References

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  1. ^ Sishi, Balindiwe J. N. (2015-01-01), Hayat, M. A. (ed.), "Chapter 10 - Autophagy Upregulation Reduces Doxorubicin-Induced Cardiotoxicity", Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, Amsterdam: Academic Press, pp. 157–173, doi:10.1016/b978-0-12-801033-4.00010-2, ISBN 978-0-12-801033-4, retrieved 2022-07-06
  2. ^ Herrmann, Joerg (August 2020). "Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia". Nature Reviews Cardiology. 17 (8): 474–502. doi:10.1038/s41569-020-0348-1. ISSN 1759-5002. PMC 8782611. PMID 32231332.
  3. ^ Huang, C.; Zhang, X.; Ramil, J. M.; Rikka, S.; Kim, L.; Lee, Y.; Gude, N. A.; Thistlethwaite, P. A.; Sussman, M. A. (2010). "Juvenile Exposure to Anthracyclines Impairs Cardiac Progenitor Cell Function and Vascularization Resulting in Greater Susceptibility to Stress-Induced Myocardial Injury in Adult Mice. Cardiotoxins are the second most toxic venom while neurotoxins are the first". Circulation. 121 (5): 675–83. doi:10.1161/CIRCULATIONAHA.109.902221. PMC 2834271. PMID 20100968.
  4. ^ Volkova M, Russell R (2011). "Anthracycline Cardiotoxicity: Prevalence, Pathogenesis and Treatment". Curr Cardiol Rev. 7 (4): 214–220. doi:10.2174/157340311799960645. PMC 3322439. PMID 22758622.
  5. ^ Suchorska, Wiktoria M. (2020-01-01). "Radiobiological models in prediction of radiation cardiotoxicity". Reports of Practical Oncology & Radiotherapy. 25 (1): 46–49. doi:10.1016/j.rpor.2019.12.001. ISSN 1507-1367. PMC 6931197. PMID 31889920.
  6. ^ Nigra, Anne E; Ruiz-Hernandez, Adrian; Redon, Josep; Navas-Acien, Ana; Tellez-Plaza, Maria (2016). "Environmental Metals and Cardiovascular Disease in Adults: A Systematic Review beyond Lead and Cadmium". Current Environmental Health Reports. 3 (4): 416–433. doi:10.1007/s40572-016-0117-9. ISSN 2196-5412. PMC 5801549. PMID 27783356.
  7. ^ Pergolizzi, Joseph V; Magnusson, Peter; LeQuang, Jo Ann K; Breve, Frank; Varrassi, Giustino (2021). "Cocaine and Cardiotoxicity: A Literature Review". Cureus. 13 (4): e14594. doi:10.7759/cureus.14594. ISSN 2168-8184. PMC 8136464. PMID 34036012.
  8. ^ a b de La Coussaye JE, Eledjam JJ, Brugada J, Sassine A (1993). "[Cardiotoxicity of local anesthetics]". Cahiers d'Anesthésiologie. 41 (6): 589–598. PMID 8287299.
  9. ^ Huang, Mei-Zhou; Li, Jian-Yong (January 2020). "Physiological regulation of reactive oxygen species in organisms based on their physicochemical properties". Acta Physiologica. 228 (1): e13351. doi:10.1111/apha.13351. ISSN 1748-1708. PMID 31344326.
  10. ^ Tousif, Sultan; Singh, Anand P.; Umbarkar, Prachi; Galindo, Cristi; Wheeler, Nicholas; Toro Cora, Angelica; Zhang, Qinkun; Prabhu, Sumanth D.; Lal, Hind (2023-02-03). "Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation". Circulation Research. 132 (3): 267–289. doi:10.1161/CIRCRESAHA.122.321504. ISSN 0009-7330. PMC 9898181. PMID 36625265.
  11. ^ Babiker, Hani M; McBride, Ali; Newton, Michael; Boehmer, Leigh M.; Drucker, Adrienne Goeller; Gowan, Mollie; Cassagnol, Manouchkathe; Camenisch, Todd D.; Anwer, Faiz; Hollands, James M. (June 2018). "Cardiotoxic effects of chemotherapy: A review of both cytotoxic and molecular targeted oncology therapies and their effect on the cardiovascular system". Critical Reviews in Oncology/Hematology. 126: 186–200. doi:10.1016/j.critrevonc.2018.03.014. PMID 29759560.
  12. ^ Herrmann, Joerg (August 2020). "Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia". Nature Reviews Cardiology. 17 (8): 474–502. doi:10.1038/s41569-020-0348-1. ISSN 1759-5002. PMC 8782611. PMID 32231332.
  13. ^ Jain, Diwakar; Aronow, Wilbert (2019-01-01). "Cardiotoxicity of cancer chemotherapy in clinical practice". Hospital Practice. 47 (1): 6–15. doi:10.1080/21548331.2018.1530831. ISSN 2154-8331. PMID 30270693.
  14. ^ Li, Xiao-Qing; Tang, Xin-Ru; Li, Li-Liang (2021-10-19). "Antipsychotics cardiotoxicity: What's known and what's next". World Journal of Psychiatry. 11 (10): 736–753. doi:10.5498/wjp.v11.i10.736. ISSN 2220-3206. PMC 8546771. PMID 34733639.
  15. ^ Goldstein, E. J. C.; Owens, R. C.; Nolin, T. D. (2006-12-15). "Antimicrobial-Associated QT Interval Prolongation: Pointes of Interest". Clinical Infectious Diseases. 43 (12): 1603–1611. doi:10.1086/508873. ISSN 1058-4838. PMID 17109296.
  16. ^ Ferreira, Gonzalo; Santander, Axel; Chavarría, Luisina; Cardozo, Romina; Savio, Florencia; Sobrevia, Luis; Nicolson, Garth L. (October 2022). "Functional consequences of lead and mercury exposomes in the heart". Molecular Aspects of Medicine. 87: 101048. doi:10.1016/j.mam.2021.101048. PMID 34785060.
  17. ^ Georgiadis, Nikolaos; Tsarouhas, Konstantinos; Tsitsimpikou, Christina; Vardavas, Alexandros; Rezaee, Ramin; Germanakis, Ioannis; Tsatsakis, Aristides; Stagos, Dimitrios; Kouretas, Demetrios (August 2018). "Pesticides and cardiotoxicity. Where do we stand?". Toxicology and Applied Pharmacology. 353: 1–14. Bibcode:2018ToxAP.353....1G. doi:10.1016/j.taap.2018.06.004. PMID 29885332.
  18. ^ Varga, Zoltán V; Ferdinandy, Peter; Liaudet, Lucas; Pacher, Pál (November 2015). "Drug-induced mitochondrial dysfunction and cardiotoxicity". American Journal of Physiology-Heart and Circulatory Physiology. 309 (9): H1453–H1467. doi:10.1152/ajpheart.00554.2015. ISSN 0363-6135. PMC 4666974. PMID 26386112.
  19. ^ Sagar, Sandeep; Liu, Peter P; Cooper, Leslie T (February 2012). "Myocarditis". The Lancet. 379 (9817): 738–747. doi:10.1016/S0140-6736(11)60648-X. PMC 5814111. PMID 22185868.
  20. ^ Slezak, Jan; Kura, Branislav; Ravingerová, Táňa; Tribulova, Narcisa; Okruhlicova, Ludmila; Barancik, Miroslav (September 2015). "Mechanisms of cardiac radiation injury and potential preventive approaches". Canadian Journal of Physiology and Pharmacology. 93 (9): 737–753. doi:10.1139/cjpp-2015-0006. ISSN 0008-4212. PMID 26030720.
  21. ^ Fanous, Ibrahim; Dillon, Patrick (August 2016). "Cancer treatment-related cardiac toxicity: prevention, assessment and management". Medical Oncology. 33 (8): 84. doi:10.1007/s12032-016-0801-5. ISSN 1357-0560. PMID 27372782.
  22. ^ Chow, Eric J.; Aggarwal, Sanjeev; Doody, David R.; Aplenc, Richard; Armenian, Saro H.; Baker, K. Scott; Bhatia, Smita; Blythe, Nancy; Colan, Steven D.; Constine, Louis S.; Freyer, David R.; Kopp, Lisa M.; Laverdière, Caroline; Leisenring, Wendy M.; Sasaki, Nao (2023-04-20). "Dexrazoxane and Long-Term Heart Function in Survivors of Childhood Cancer". Journal of Clinical Oncology. 41 (12): 2248–2257. doi:10.1200/JCO.22.02423. ISSN 0732-183X. PMC 10448941. PMID 36669148.
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