cardiotoxicity
{{Short description|Poisoning of heart electrophysiology or muscle}}
Cardiotoxicity is the occurrence of heart dysfunction as electric or muscle damage, resulting in heart toxicity.{{Citation |last=Sishi |first=Balindiwe J. N. |title=Chapter 10 - Autophagy Upregulation Reduces Doxorubicin-Induced Cardiotoxicity |date=2015-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780128010334000102 |work=Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging |pages=157–173 |editor-last=Hayat |editor-first=M. A. |place=Amsterdam |publisher=Academic Press |language=en |doi=10.1016/b978-0-12-801033-4.00010-2 |isbn=978-0-12-801033-4 |access-date=2022-07-06|url-access=subscription }} This can cause heart failure, arrhythmia, myocarditis, and cardiomyopathy in patients.{{Cite journal |last=Herrmann |first=Joerg |date=August 2020 |title=Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia |journal=Nature Reviews Cardiology |language=en |volume=17 |issue=8 |pages=474–502 |doi=10.1038/s41569-020-0348-1 |issn=1759-5002 |pmc=8782611 |pmid=32231332}} 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){{cite journal |pages=675–83 |doi=10.1161/CIRCULATIONAHA.109.902221 |title=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. |year=2010 |last1=Huang |first1=C. |last2=Zhang |first2=X. |last3=Ramil |first3=J. M. |last4=Rikka |first4=S. |last5=Kim |first5=L. |last6=Lee |first6=Y. |last7=Gude |first7=N. A. |last8=Thistlethwaite |first8=P. A. |last9=Sussman |first9=M. A. |journal=Circulation |volume=121 |issue=5 |pmid=20100968 |pmc=2834271 }}{{cite journal | title = Anthracycline Cardiotoxicity: Prevalence, Pathogenesis and Treatment|vauthors=Volkova M, Russell R | journal = Curr Cardiol Rev| year = 2011 | volume = 7| issue = 4| pages = 214–220| doi = 10.2174/157340311799960645 | pmid = 22758622| pmc = 3322439 }} treatment and/or radiotherapy;{{Cite journal |last=Suchorska |first=Wiktoria M. |date=2020-01-01 |title=Radiobiological models in prediction of radiation cardiotoxicity |journal=Reports of Practical Oncology & Radiotherapy |language=en |volume=25 |issue=1 |pages=46–49 |doi=10.1016/j.rpor.2019.12.001 |issn=1507-1367 |pmc=6931197 |pmid=31889920}} complications from anorexia nervosa; adverse effects of heavy metals intake;{{Cite journal |last1=Nigra |first1=Anne E |last2=Ruiz-Hernandez |first2=Adrian |last3=Redon |first3=Josep |last4=Navas-Acien |first4=Ana |last5=Tellez-Plaza |first5=Maria |year=2016 |title=Environmental Metals and Cardiovascular Disease in Adults: A Systematic Review beyond Lead and Cadmium |journal=Current Environmental Health Reports |volume=3 |issue=4 |pages=416–433 |doi=10.1007/s40572-016-0117-9 |issn=2196-5412 |pmc=5801549 |pmid=27783356}} the long-term abuse of or ingestion at high doses of certain strong stimulants such as cocaine;{{Cite journal |last1=Pergolizzi |first1=Joseph V |last2=Magnusson |first2=Peter |last3=LeQuang |first3=Jo Ann K |last4=Breve |first4=Frank |last5=Varrassi |first5=Giustino |title=Cocaine and Cardiotoxicity: A Literature Review |journal=Cureus |year=2021 |volume=13 |issue=4 |pages=e14594 |doi=10.7759/cureus.14594 |doi-access=free |issn=2168-8184 |pmc=8136464 |pmid=34036012}} or an incorrectly administered drug such as bupivacaine.{{cite journal | vauthors = de La Coussaye JE, Eledjam JJ, Brugada J, Sassine A | title = [Cardiotoxicity of local anesthetics] | journal = Cahiers d'Anesthésiologie | volume = 41 | issue = 6 | pages = 589–598 | date = 1993 | pmid = 8287299 }}
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.{{Cite journal |last1=Huang |first1=Mei-Zhou |last2=Li |first2=Jian-Yong |date=January 2020 |title=Physiological regulation of reactive oxygen species in organisms based on their physicochemical properties |url=https://onlinelibrary.wiley.com/doi/10.1111/apha.13351 |journal=Acta Physiologica |language=en |volume=228 |issue=1 |pages=e13351 |doi=10.1111/apha.13351 |pmid=31344326 |issn=1748-1708|url-access=subscription }}
Other mechanisms of cardiotoxicity include inflammatory,{{Cite journal |last1=Tousif |first1=Sultan |last2=Singh |first2=Anand P. |last3=Umbarkar |first3=Prachi |last4=Galindo |first4=Cristi |last5=Wheeler |first5=Nicholas |last6=Toro Cora |first6=Angelica |last7=Zhang |first7=Qinkun |last8=Prabhu |first8=Sumanth D. |last9=Lal |first9=Hind |date=2023-02-03 |title=Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation |journal=Circulation Research |language=en |volume=132 |issue=3 |pages=267–289 |doi=10.1161/CIRCRESAHA.122.321504 |issn=0009-7330 |pmc=9898181 |pmid=36625265}} DNA damaging, and disrupted cell signaling. DNA damage and disrupted cellular signaling are the proposed mechanism for many cardiotoxic chemotherapeutics.{{Cite journal |last1=Babiker |first1=Hani M |last2=McBride |first2=Ali |last3=Newton |first3=Michael |last4=Boehmer |first4=Leigh M. |last5=Drucker |first5=Adrienne Goeller |last6=Gowan |first6=Mollie |last7=Cassagnol |first7=Manouchkathe |last8=Camenisch |first8=Todd D. |last9=Anwer |first9=Faiz |last10=Hollands |first10=James M. |date=June 2018 |title=Cardiotoxic effects of chemotherapy: A review of both cytotoxic and molecular targeted oncology therapies and their effect on the cardiovascular system |url=https://linkinghub.elsevier.com/retrieve/pii/S1040842817303566 |journal=Critical Reviews in Oncology/Hematology |language=en |volume=126 |pages=186–200 |doi=10.1016/j.critrevonc.2018.03.014|pmid=29759560 |url-access=subscription }}
Regardless of the mechanism, clinical manifestations include heart failure, arrhythmia, myocarditis, and cardiomyopathy that can be permanent. 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 =
- 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 =
- Antipsychotics such as thioridazine which can prolong QT interval {{Cite journal |last1=Li |first1=Xiao-Qing |last2=Tang |first2=Xin-Ru |last3=Li |first3=Li-Liang |date=2021-10-19 |title=Antipsychotics cardiotoxicity: What's known and what's next |journal=World Journal of Psychiatry |volume=11 |issue=10 |pages=736–753 |doi=10.5498/wjp.v11.i10.736 |doi-access=free |issn=2220-3206 |pmc=8546771 |pmid=34733639}}
- Antibiotics such as Erythromycin and levofloxacin due to QT prolongation {{Cite journal |last1=Goldstein |first1=E. J. C. |last2=Owens |first2=R. C. |last3=Nolin |first3=T. D. |date=2006-12-15 |title=Antimicrobial-Associated QT Interval Prolongation: Pointes of Interest |url=https://academic.oup.com/cid/article-lookup/doi/10.1086/508873 |journal=Clinical Infectious Diseases |language=en |volume=43 |issue=12 |pages=1603–1611 |doi=10.1086/508873 |pmid=17109296 |issn=1058-4838|url-access=subscription }}
= Environmental toxins =
- Heavy Metals like lead and mercury{{Cite journal |last1=Ferreira |first1=Gonzalo |last2=Santander |first2=Axel |last3=Chavarría |first3=Luisina |last4=Cardozo |first4=Romina |last5=Savio |first5=Florencia |last6=Sobrevia |first6=Luis |last7=Nicolson |first7=Garth L. |date=October 2022 |title=Functional consequences of lead and mercury exposomes in the heart |url=https://linkinghub.elsevier.com/retrieve/pii/S0098299721001084 |journal=Molecular Aspects of Medicine |language=en |volume=87 |pages=101048 |doi=10.1016/j.mam.2021.101048|pmid=34785060 |hdl=11449/222852 |hdl-access=free }}
- Pesticides such as organophosphates {{Cite journal |last1=Georgiadis |first1=Nikolaos |last2=Tsarouhas |first2=Konstantinos |last3=Tsitsimpikou |first3=Christina |last4=Vardavas |first4=Alexandros |last5=Rezaee |first5=Ramin |last6=Germanakis |first6=Ioannis |last7=Tsatsakis |first7=Aristides |last8=Stagos |first8=Dimitrios |last9=Kouretas |first9=Demetrios |date=August 2018 |title=Pesticides and cardiotoxicity. Where do we stand? |url=https://linkinghub.elsevier.com/retrieve/pii/S0041008X18302606 |journal=Toxicology and Applied Pharmacology |language=en |volume=353 |pages=1–14 |doi=10.1016/j.taap.2018.06.004|pmid=29885332 |bibcode=2018ToxAP.353....1G |url-access=subscription }}
= Abused substances =
- Alcohol: Chronic heavy consumption leading to alcoholic cardiomyopathy
- Recreational Drugs: Cocaine, Methamphetamine
= Others =
- Biological Toxins such as Diphtheria toxin {{Cite journal |last1=Sagar |first1=Sandeep |last2=Liu |first2=Peter P |last3=Cooper |first3=Leslie T |date=February 2012 |title=Myocarditis |journal=The Lancet |language=en |volume=379 |issue=9817 |pages=738–747 |doi=10.1016/S0140-6736(11)60648-X |pmc=5814111 |pmid=22185868}}
- Radiation Therapy is known to cause radiation-induced heart disease (RIHD) {{Cite journal |last1=Slezak |first1=Jan |last2=Kura |first2=Branislav |last3=Ravingerová |first3=Táňa |last4=Tribulova |first4=Narcisa |last5=Okruhlicova |first5=Ludmila |last6=Barancik |first6=Miroslav |date=September 2015 |title=Mechanisms of cardiac radiation injury and potential preventive approaches |url=http://www.nrcresearchpress.com/doi/10.1139/cjpp-2015-0006 |journal=Canadian Journal of Physiology and Pharmacology |language=en |volume=93 |issue=9 |pages=737–753 |doi=10.1139/cjpp-2015-0006 |pmid=26030720 |issn=0008-4212|url-access=subscription }}
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 permanent 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.{{Cite journal |last1=Fanous |first1=Ibrahim |last2=Dillon |first2=Patrick |date=August 2016 |title=Cancer treatment-related cardiac toxicity: prevention, assessment and management |url=http://link.springer.com/10.1007/s12032-016-0801-5 |journal=Medical Oncology |language=en |volume=33 |issue=8 |page=84 |doi=10.1007/s12032-016-0801-5 |pmid=27372782 |issn=1357-0560|url-access=subscription }}
Patients taking anthracyclines can take Dexrazoxane as a cardioprotective agent to prevent extensive cardiac damage.{{Cite journal |last1=Chow |first1=Eric J. |last2=Aggarwal |first2=Sanjeev |last3=Doody |first3=David R. |last4=Aplenc |first4=Richard |last5=Armenian |first5=Saro H. |last6=Baker |first6=K. Scott |last7=Bhatia |first7=Smita |last8=Blythe |first8=Nancy |last9=Colan |first9=Steven D. |last10=Constine |first10=Louis S. |last11=Freyer |first11=David R. |last12=Kopp |first12=Lisa M. |last13=Laverdière |first13=Caroline |last14=Leisenring |first14=Wendy M. |last15=Sasaki |first15=Nao |date=2023-04-20 |title=Dexrazoxane and Long-Term Heart Function in Survivors of Childhood Cancer |journal=Journal of Clinical Oncology |language=en |volume=41 |issue=12 |pages=2248–2257 |doi=10.1200/JCO.22.02423 |issn=0732-183X |pmc=10448941 |pmid=36669148}}
See also
References
{{Reflist}}
{{Toxins}}
{{Authority control}}