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]

Contents

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. [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. [2] 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

Source: [12]

Other medications

Environmental toxins

Abused substances

Source: [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 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. [20]

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

See also

Related Research Articles

<span class="mw-page-title-main">Cardiomyopathy</span> Disease of the heart muscle

Cardiomyopathy is a group of primary diseases of the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. An irregular heart beat and fainting may occur. Those affected are at an increased risk of sudden cardiac death.

<span class="mw-page-title-main">Premature ventricular contraction</span> Skipped beat with ventricular origin

A premature ventricular contraction (PVC) is a common event where the heartbeat is initiated by Purkinje fibers in the ventricles rather than by the sinoatrial node. PVCs may cause no symptoms or may be perceived as a "skipped beat" or felt as palpitations in the chest. PVCs do not usually pose any danger.

<span class="mw-page-title-main">Coxsackie B virus</span> Virus that causes digestive upset and sometimes heart damage

Coxsackie B is a group of six serotypes of coxsackievirus (CVB1-CVB6), a pathogenic enterovirus, that trigger illness ranging from gastrointestinal distress to full-fledged pericarditis and myocarditis.

<span class="mw-page-title-main">Long QT syndrome</span> Medical condition

Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainting, drowning, seizures, or sudden death. These episodes can be triggered by exercise or stress. Some rare forms of LQTS are associated with other symptoms and signs including deafness and periods of muscle weakness.

<span class="mw-page-title-main">Cardiac muscle</span> Muscular tissue of heart in vertebrates

Cardiac muscle is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of the heart. The cardiac muscle (myocardium) forms a thick middle layer between the outer layer of the heart wall and the inner layer, with blood supplied via the coronary circulation. It is composed of individual cardiac muscle cells joined by intercalated discs, and encased by collagen fibers and other substances that form the extracellular matrix.

<span class="mw-page-title-main">Myocarditis</span> Inflammation of the heart muscle

Myocarditis is defined as inflammation of the myocardium. Myocarditis can progress to inflammatory cardiomyopathy when there are associated ventricular remodeling and cardiac dysfunction due to chronic inflammation. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The duration of problems can vary from hours to months. Complications may include heart failure due to dilated cardiomyopathy or cardiac arrest.

<span class="mw-page-title-main">Dilated cardiomyopathy</span> Condition involving an enlarged, ineffective heart

Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Complications can include heart failure, heart valve disease, or an irregular heartbeat.

<span class="mw-page-title-main">Doxorubicin</span> Chemotherapy medication

Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used together with other chemotherapy agents. Doxorubicin is given by injection into a vein.

<span class="mw-page-title-main">Anthracycline</span> Class of antibiotics

Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from Streptomyces peucetius bacterium. These compounds are used to treat many cancers, including leukemias, lymphomas, breast, stomach, uterine, ovarian, bladder cancer, and lung cancers. The first anthracycline discovered was daunorubicin, which is produced naturally by Streptomyces peucetius, a species of Actinomycetota. Clinically the most important anthracyclines are doxorubicin, daunorubicin, epirubicin and idarubicin.

Tachycardia-induced cardiomyopathy (TIC) is a disease where prolonged tachycardia or arrhythmia causes an impairment of the myocardium, which can result in heart failure. People with TIC may have symptoms associated with heart failure and/or symptoms related to the tachycardia or arrhythmia. Though atrial fibrillation is the most common cause of TIC, several tachycardias and arrhythmias have been associated with the disease.

<span class="mw-page-title-main">Restrictive cardiomyopathy</span> Medical condition

Restrictive cardiomyopathy (RCM) is a form of cardiomyopathy in which the walls of the heart are rigid. Thus the heart is restricted from stretching and filling with blood properly. It is the least common of the three original subtypes of cardiomyopathy: hypertrophic, dilated, and restrictive.

<span class="mw-page-title-main">Dexrazoxane</span> Chemical compound

Dexrazoxane hydrochloride, sold under the brand name Zinecard among others, is a cardioprotective agent. It was discovered in 1972. The IV administration of dexrazoxane is in acidic condition with HCl adjusting the pH.

Loeffler endocarditis is a form of heart disease characterized by a stiffened, poorly-functioning heart caused by infiltration of the heart by white blood cells known as eosinophils. Restrictive cardiomyopathy is a disease of the heart muscle which results in impaired diastolic filling of the heart ventricles, i.e. the large heart chambers which pump blood into the pulmonary or systemic circulation. Diastole is the part of the cardiac contraction-relaxation cycle in which the heart fills with venous blood after the emptying done during its previous systole.

Cardiac fibrosis commonly refers to the excess deposition of extracellular matrix in the cardiac muscle, but the term may also refer to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts. Fibrotic cardiac muscle is stiffer and less compliant and is seen in the progression to heart failure. The description below focuses on a specific mechanism of valvular pathology but there are other causes of valve pathology and fibrosis of the cardiac muscle.

<span class="mw-page-title-main">Arrhythmia</span> Group of medical conditions characterized by irregular heartbeat

Arrhythmias, also known as cardiac arrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults – is called tachycardia, and a resting heart rate that is too slow – below 60 beats per minute – is called bradycardia. Some types of arrhythmias have no symptoms. Symptoms, when present, may include palpitations or feeling a pause between heartbeats. In more serious cases, there may be lightheadedness, passing out, shortness of breath, chest pain, or decreased level of consciousness. While most cases of arrhythmia are not serious, some predispose a person to complications such as stroke or heart failure. Others may result in sudden death.

sCAR-Fc is an experimental prophylactic treatment against coxsackievirus B3 (CVB) infections. Coxsackievirus B3 can cause cardiac damage, eventually resulting in a weakened and enlarged heart that is termed dilated cardiomyopathy. While many other treatments inhibit viral proliferation in myocytes, sCAR-Fc prevents the virus entering the cell by competitively binding to coxsackie virus and adenovirus receptors (CAR) on the membrane of myocytes.

Viral cardiomyopathy occurs when viral infections cause myocarditis with a resulting thickening of the myocardium and dilation of the ventricles. These viruses include Coxsackie B and adenovirus, echoviruses, influenza H1N1, Epstein–Barr virus, rubella, varicella, mumps, measles, parvoviruses, yellow fever, dengue fever, polio, rabies, and the viruses that cause hepatitis A and C, as well as COVID-19, which has been seen to cause this in persons otherwise thought to have a "low risk" of the virus's effects.

Neurocardiology is the study of the neurophysiological, neurological and neuroanatomical aspects of cardiology, including especially the neurological origins of cardiac disorders. The effects of stress on the heart are studied in terms of the heart's interactions with both the peripheral nervous system and the central nervous system.

<span class="mw-page-title-main">Bisantrene</span> Chemical compound

Bisantrene is an anthracenyl bishydrazone with anthracycline-like antineoplastic activity and an antimetabolite. Bisantrene intercalates with and disrupts the configuration of DNA, resulting in DNA single-strand breaks, DNA-protein crosslinking, and inhibition of DNA replication. This agent is similar to doxorubicin in chemotherapeutic activity, but unlike anthracyclines like doxorubicin, it exhibits little cardiotoxicity.

<span class="mw-page-title-main">Pharmacological cardiotoxicity</span>

Pharmacological cardiotoxicity is defined as cardiac damage that occurs under the action of a drug. This can occur both through damage of cardiac muscle as well as through alteration of the ion currents of cardiomyocytes.

References

  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. 1 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. 1 2 de La Coussaye JE, Eledjam JJ, Brugada J, Sassine A (1993). "[Cardiotoxicity of local anesthetics]". Cahiers d'Anesthésiologie. 41 (6): 589–598. PMID   8287299.
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  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. ↑ 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.
  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. doi: 10.5498/wjp.v11.i10.736 . ISSN   2220-3206. PMC   8546771 . PMID   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. 43 (12): 1603–1611. doi:10.1086/508873. ISSN   1058-4838. PMID   17109296.
  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. 87: 101048. doi:10.1016/j.mam.2021.101048. PMID   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. 353: 1–14. Bibcode:2018ToxAP.353....1G. doi:10.1016/j.taap.2018.06.004. PMID   29885332.
  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. 309 (9): H1453–H1467. doi:10.1152/ajpheart.00554.2015. ISSN   0363-6135. PMC   4666974 . PMID   26386112.
  18. ↑ 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.
  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. 93 (9): 737–753. doi:10.1139/cjpp-2015-0006. ISSN   0008-4212. PMID   26030720.
  20. ↑ 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.
  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. 41 (12): 2248–2257. doi:10.1200/JCO.22.02423. ISSN   0732-183X. PMC   10448941 . PMID   36669148.
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