Cardiotoxicity Explained

Cardiotoxicity is the occurrence of heart dysfunction as electric or muscle damage, resulting in heart toxicity. This can cause heart failure, arrhythmia, myocarditis, and cardiomyopathy in patients.[1] Some effects are reversible, while in others, permanent damage requiring further treatment may arrise. 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)[2] [3] treatment and/or radiotherapy;[4] complications from anorexia nervosa; adverse effects of heavy metals intake;[5] the long-term abuse of or ingestion at high doses of certain strong stimulants such as cocaine;[6] or an incorrectly administered drug such as bupivacaine.[7]

Mechanism

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. 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.[8]

Other mechanisms of cardiotoxicity include inflammatory,[9] DNA damaging, and disrupted cell signaling. DNA damage and disrupted cellular signaling are the proposed mechanism for many cardiotoxic chemotherapeutics.[10]

Regardless of the mechanism, clinical manifestations include heart failure, arrhythmia, myocarditis, and cardiomyopathy that can be permanent.[11] These conditions can greatly alter mortality and morbidity in patients meaning careful monitoring is necessary in patients exposed to cardiotoxic agents.

Inciting agents

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 [12]

Other medications

Environmental toxins

Abused substances [17]

Others

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

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. [20]

Patients taking anthracyclines can take Dexrazoxane as a cardioprotective agent to prevent extensive cardiac damage. [21]

See also

Notes and References

  1. Herrmann . Joerg . August 2020 . Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia . Nature Reviews Cardiology . en . 17 . 8 . 474–502 . 10.1038/s41569-020-0348-1 . 1759-5002 . 8782611 . 32231332.
  2. 675–83 . 10.1161/CIRCULATIONAHA.109.902221 . 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. . 2010 . Huang . C. . Zhang . X. . Ramil . J. M. . Rikka . S. . Kim . L. . Lee . Y. . Gude . N. A. . Thistlethwaite . P. A. . Sussman . M. A. . Circulation . 121 . 5 . 20100968 . 2834271 .
  3. Anthracycline Cardiotoxicity: Prevalence, Pathogenesis and Treatment. Volkova M, Russell R . Curr Cardiol Rev. 2011 . 7. 4. 214–220. 10.2174/157340311799960645 . 22758622. 3322439 .
  4. Suchorska . Wiktoria M. . 2020-01-01 . Radiobiological models in prediction of radiation cardiotoxicity . Reports of Practical Oncology & Radiotherapy . en . 25 . 1 . 46–49 . 10.1016/j.rpor.2019.12.001 . 1507-1367 . 6931197 . 31889920.
  5. 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 . 10.1007/s40572-016-0117-9 . 2196-5412 . 5801549 . 27783356.
  6. Pergolizzi . Joseph V . Magnusson . Peter . LeQuang . Jo Ann K . Breve . Frank . Varrassi . Giustino . Cocaine and Cardiotoxicity: A Literature Review . Cureus . 2021 . 13 . 4 . e14594 . 10.7759/cureus.14594 . free . 2168-8184 . 8136464 . 34036012.
  7. de La Coussaye JE, Eledjam JJ, Brugada J, Sassine A . [Cardiotoxicity of local anesthetics] . Cahiers d'Anesthésiologie . 41 . 6 . 589–598 . 1993 . 8287299 .
  8. Huang . Mei-Zhou . Li . Jian-Yong . January 2020 . Physiological regulation of reactive oxygen species in organisms based on their physicochemical properties . Acta Physiologica . en . 228 . 1 . e13351 . 10.1111/apha.13351 . 31344326 . 1748-1708.
  9. 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 . en . 132 . 3 . 267–289 . 10.1161/CIRCRESAHA.122.321504 . 0009-7330 . 9898181 . 36625265.
  10. 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 . en . 126 . 186–200 . 10.1016/j.critrevonc.2018.03.014. 29759560 .
  11. Herrmann . Joerg . August 2020 . Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia . Nature Reviews Cardiology . en . 17 . 8 . 474–502 . 10.1038/s41569-020-0348-1 . 1759-5002 . 8782611 . 32231332.
  12. Jain . Diwakar . Aronow . Wilbert . 2019-01-01 . Cardiotoxicity of cancer chemotherapy in clinical practice . Hospital Practice . en . 47 . 1 . 6–15 . 10.1080/21548331.2018.1530831 . 30270693 . 2154-8331.
  13. 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 . 10.5498/wjp.v11.i10.736 . free . 2220-3206 . 8546771 . 34733639.
  14. Goldstein . E. J. C. . Owens . R. C. . Nolin . T. D. . 2006-12-15 . Antimicrobial-Associated QT Interval Prolongation: Pointes of Interest . Clinical Infectious Diseases . en . 43 . 12 . 1603–1611 . 10.1086/508873 . 17109296 . 1058-4838.
  15. 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 . en . 87 . 101048 . 10.1016/j.mam.2021.101048. 34785060 .
  16. 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 . en . 353 . 1–14 . 10.1016/j.taap.2018.06.004. 29885332 . 2018ToxAP.353....1G .
  17. 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 . en . 309 . 9 . H1453–H1467 . 10.1152/ajpheart.00554.2015 . 0363-6135 . 4666974 . 26386112.
  18. Sagar . Sandeep . Liu . Peter P . Cooper . Leslie T . February 2012 . Myocarditis . The Lancet . en . 379 . 9817 . 738–747 . 10.1016/S0140-6736(11)60648-X . 5814111 . 22185868.
  19. 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 . en . 93 . 9 . 737–753 . 10.1139/cjpp-2015-0006 . 26030720 . 0008-4212.
  20. Fanous . Ibrahim . Dillon . Patrick . August 2016 . Cancer treatment-related cardiac toxicity: prevention, assessment and management . Medical Oncology . en . 33 . 8 . 84 . 10.1007/s12032-016-0801-5 . 27372782 . 1357-0560.
  21. 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 . en . 41 . 12 . 2248–2257 . 10.1200/JCO.22.02423 . 0732-183X . 10448941 . 36669148.

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