cardiotoxicity of chemotherapy
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Cardiotoxicity of Chemotherapy:
Case StudyKrystal PerezCardiac Stress Lab Intern
Beth Israel Deaconess Medical CenterNovember 8, 2016
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No relevant disclosures
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Anthracyclines• Treat hematologic malignancies and solid tumors via selective transport to nuclei of proliferating cells and binding to DNA to stop further proliferation.
• Doxorubicin used most often due to efficacy in solid tumor treatment
• Used in combination with other drugs• Types of cancer used for: breast cancer, small lung cancer, ovarian cancer
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Cardiac Effects: CHF/LV Dysfunction
• Dose-Related Response • High dosage correlates with LV dysfunction due to
increased myocardial cell death • Schedule of delivery: rapid vs continuous infusion of drug
• Drug combination: when taken with other drugs can increase toxicity
• Doxorubicin combined with Paclitaxel can cause CHF in 20% of patient
• Time between administration of both drugs influence incidence rates
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Monoclonal Antibodies• Treat hematologic malignancies and solid tumors
• Antibodies that bind to specific receptors with that limit tumor growth.
• Trastuzumab: antibody that selectively binds to HER2 which is overexpressed in 25-33% of breast cancer cases
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Cardiac Effects: CHF/LV Dysfunction
• Drug combination: increased incidence of CHF when used with other chemotherapeutic drugs that are administered in close proximity.
• Rose from 7% to 27% incidence • Lead to cardiac dysfunction but have high reversibility potential.
• Mechanism for dysfunction is unknown• Shows lower morbidity and mortality than
anthracycline-induced dysfunction.• Cardiac events range from HTN, Arrhythmias, and CHF depending on the monoclonal antibody used.
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Antimetabolites• Treat solid tumors by mimicking purines/pyrimadines/folic acid and inducing cell death by interfering with DNA synthesis and inhibiting enzymes used in nucleic acid production.
• 5-Fluourouracil (5-FU) widely used in sold tumor treatment in many cancers (breast, ovarian, colon-rectal, adrenal, liver, etc).
• Among the first effective chemotherapy agents.
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Cardiac Effects: Ischemia• Most commonly causes cardiac ischemia but is usually reversible with cessation.
• Dose-response relationship – high doses proportional to greater incidence.
• Schedule of administering drug – rapid vs continuous infusion
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Radiation• High-energy radiation administered internally or externally to kill cancer cells and shrink tumors.
• Used in at some point in time during most cancer treatments.
• Cancer cells are killed by damaging their DNA or creating free radicals within cell that lead to DNA damage.
• Normal cell DNA is damaged in the process so proper placement of radiation is crucial.
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Cardiac Effects: Wide Range of CVD
• Location: the closer to the heart, the more potential damage to the hear.
• Thorax :• Pericardium – pericarditis (short-term) or pericardial effusion• Myocardium – fibrosis causing perfusion defects• Valves: thickening• Coronary Artery – endothelium damage
• Most common cardiac effect is cardiomyopathy.• Dose-related response: major cardiac events rate increase with increased dose by 7.4%.
• Type of cancer: excess risk of ischemic heart disease for women with left-sided breast cancer
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Treatments• Anthracycline-induced CHF/LV Dysfunction:
• Dexrazoxane: iron chelator – reduces free iron in myocytes caused by anthracyclines
• Questionable efficacy of cancer treatment• Beta blockers and ACE inhibitors
• Monoclonal Antibody-incuded CHF/LV Dysfunction: • Cessation• Beta blockers and ACE inhibitors
• Antimetabolite-induced Ischemia: • Cessation• Calcium channel blockers and oral nitrates to resolve symptoms• Capecitabine alternative
• Radiation-induced CAD:• Better radiation field direction• Subcarinal block• CABG/Angioplasty• NSAIDS, Diuretics, ACE Inhibitors, Beta Blockers
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Difference in Treatment
• Revascularization for treatment-induced MI’s are not ideal due to possibility of bleeding diathesis.
• Stent placement can stop treatment regimens and prolong the process cause medications required can cause bleeding.
• Especially the cause with DES
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Monitoring Cardiotoxicity of Chemotherapy
• Echocardiogram to measure LV dysfunction periodically
• Limit:• Decreased LVEF generally occurs late in history of treatment-
related injury• LV dysfunction is only measureable after enough cardiac
damage has occurred to cause functional impairment. • Positive ECHO can mean irreversible damage especially in the
case of anthracycline-induced cardiomyopathy• Not ideal for asymptomatic patients
• Research show 33% of Patients with preserved LVEF had underlying systolic and and diastolic cardiac dysfunction
• 47% of CHF is diastolic in nature, occurring with a preserved LVEF
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Monitoring Cardiotoxicity of Chemotherapy
• Cardiac biomarkers like Troponin I and BNP as an indication for a cardiac event due to high correlation with subsequent cardiac systolic and diastolic dysfunction before reduction in LVEF is seen.
• Used to determine high risk patients before drug administration to start preventive measures beforehand.
• Limits:• BNP elevation can be due to non-cardiac events
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Monitoring Cardiotoxicity of Chemotherapy
• Global longitudinal strain (GLS) recently used to detect subtle changes in LV systolic function by assessing the longitudinal contraction of the myocardium to predict overall mortality and cardiac events.
• More sensitive predictor of cardiac events than LVEF.• Use as a comparative measure before, during and after treatments.
• Early reduction in GLS predicts subsequent chemotherapy-related cardiac dysfunction.
• Limits• Has not been tested on a larger population. • Price
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Stress Testing Cancer Survivors/Patients
• Hx of cancer should be mentioned in patient history and taken into account when determining relative risk levels despite years of remission.
• Pay attention to the treatment regimen because the type of drug and dosage can have an affect on patients despite symptoms.
• If a patient has CAD risk factors (HTN, HLD, Smoking, etc) along with the history of cancer, they have a higher chance of a positive stress test at a younger age than those without history of cancer.
• Cancer treatment cannot be identified as a direct reason for a positive stress test or cardiac events (MI/CHF), only a contributing factor.
• Determining stress test protocol using this additional information.
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Patient Information•53 yr old Male•Chief Complaint: CP and SOB•CAD Risk Factors:
• HLD, +Family Hx, Obesity (BMI: 31.7)•02.2016 – Colon Cancer•Labs: RBC 4.44, HgB 13.3•Walks occasionally and plays golf
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Medications •FOLFOX
• 955mg Leucovorin Calcium• 950mg Fluorouracil bolus• 2850mg Fluorouracil continuous infusion• 155mg Oxaliplatin
•40mg Prednisone•16mg Ondansetron•0.5mg Lorazepam tablets•Vitamins
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Pretest: HR 67, BP 128/86
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Bruce 5:01 min: HR 142, BP 158/78
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Bruce 5:36 min (Peak): HR 148
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Recovery 0:14 min: HR 133
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Recovery 1:43min: HR 81
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Recovery 15 min: HR 93, BP 128/82
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Diagnosis & Follow Up• + Ischemia via Stress Test• ECHO: EF = 55%, regional left systolic dysfunction,
dyskinesis of apex, hypokinesis of distal septal and anterior walls
• Cath (3 days later): • 80% Stenosis LAD DES • 50-60% stenosis Left Cx
• Labs (before Cath): Trop<0.01 x 4• Follow up:
• cardiac rehab for CAD • placed on Atorvastatin, Clopidogrel, Lisinopril, Metoprolol,
ASA
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Sources• Armstrong, Joshi, Ness, Marwick, Zhang, Srivastava, Griffin, Grimm, Thomas, Phelan, Collier,
Krull, Mulrooney, Green, Hudson, Robison, and Plana. "Comprehensive Echocardiographic Detection of Treatment-Related Cardiac Dysfunction in Adult Survivors Of Childhood Cancer: Results From the St. Jude Lifetime Cohort Study: Results From the St. Jude Lifetime Cohort Study." Journal of the American College of Cardiology 65.23 (2015): 2511-522.
• Thavendiranathan, Paaladinesh, Husam Abdel-Qadir, Hadas D Fischer, Ximena Camacho, Eitan Amir, Peter C Austin, and Douglas S Lee. "Breast Cancer Therapy-Related Cardiac Dysfunction in Adult Women Treated in Routine Clinical Practice: A Population-Based Cohort Study." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology 34.19 (2016): 2239-46. Web.
• Aleman, Berthe M P, Elizabeth C Moser, Janine Nuver, Thomas M Suter, Maja V Maraldo, Lena Specht, Conny Vrieling, and Sarah C Darby. "Cardiovascular Disease after Cancer Therapy." EJC Supplements : EJC : Official Journal of EORTC, European Organization for Research and Treatment of Cancer ... [et Al.] 12.1 (2014): 18-28. Web.
• Aarif Y Khakoo, and Edward Th Yeh. "Therapy Insight: Management of Cardiovascular Disease in Patients with Cancer and Cardiac Complications of Cancer Therapy." Nature Clinical Practice Oncology 5.11 (2008): 655. Web.
• Yeh, and Vejpongsa. "Subclinical Cardiotoxicity Associated With Cancer Therapy: Early Detection and Future Directions." Journal of the American College of Cardiology 65.23 (2015): 2523-525. Web.
• Yeh, Eth, At Tong, Dj Lenihan, Sw Yusuf, J. Swafford, C. Champion, Jb Durand, H. Gibbs, AA Zafarmand, and MS Ewer. "Cardiovascular Complications of Cancer Therapy - Diagnosis, Pathogenesis, and Management." Circulation 109.25 (2004): 3122-131. Web.