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Chemotherapy Induced Cardiac Toxicity Russell Huntsinger, MD Cardiologist. Title 1 Subtitle 2. What is Cardiac Toxicity?. Damage to the heart muscle by a toxin is called cardiac toxicity. They may cause arrhythmias May lead to heart failure
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Chemotherapy Induced Cardiac Toxicity Russell Huntsinger, MD Cardiologist Title 1 Subtitle 2
What is Cardiac Toxicity? • Damage to the heart muscle by a toxin is called cardiac toxicity. • They may cause arrhythmias • May lead to heart failure • Does not mean that that the heart has stopped or is about to stop • The heart muscle cannot pump with enough force to supply the body with blood containing essential oxygen and nutrients.
Chemotherapy Agents that Cause Cardiac Toxicity • Doxorubicin (Adriamycin) • Epirubicin • Idarubicin • Cyclophosphamide • Fluorouracil • Mitoxantrone
Anthracyclines • Are the most common cause of cardiac toxicity in cancer patients.
Anthracyclines • Used to treat a wide range of hematological and solid malignancies.
Chemotherapy drugs that have been reported to cause abnormalities in heart rhythm • Gemtuzumab ozogamicin • Paclitaxel • Idarubicin • Tyrosine kinase inhibitors • Monoclonal antibodies
Occurrence • Clinical heart failure generally occurs within a month to a year after anthracycline treatment. • May occur up to 6 -10 years or later.
How is it diagnosed • Heart sound – stethoscope • Chest X-ray • ECG • Echo • MUGA scan
What are the symptoms? • Fatigue • Shortness of breath on exertion • Discomfort lying in supine • Swelling of the ankles
Long cardiac toxicity can manifest as ventricular dysfunction and clinical heart failure.
Why? • It is thought that direct myocardial injury is from free radicals.
How Can Cardiac Toxicity be Prevented • Altering the amount of dose • Limit anthracyclines For example: • if doxorubicin is less than 550mg/m2, there is a less than 1% chance of cardiac toxicity. • If doxorubicin is between 560-1155 mg/m2, the risk increases to 30% Cur Med Chem. 2001;13:1649-1660.
Reported incidence of heart failure in adjuvant anthracycline therapy trials is 2% or less. • Recent studies have reported 10-50% occurrence of subclinical decline in left ventricular function > 10% points after anthracycline treatment. J Am Coll Cardiol 2007; 50:1435
Reducing Drug Cardiotoxicity • Structural modifications to the doxorubicin molecule (epirubicin). • Incorporation into liposomes (doxorubicin) • Development of structurally related drugs (mitoxantrone).
Method of Administration • Evidence that the method of drug administration may affect the risk of cardiac toxicity. • Rapid administration of drugs results in high blood levels, which may cause more heart damage than the same amount of drug given over a longer period of time. • Small doses of drug, more frequently can decrease the toxicity compared to large doses of drugs at longer intervals.
Advancements in chemotherapy administration • Liposomal anthracyclines are anthracycline encapsulated in a liposome. • By enclosing in lipose, it stays in body longer due to the immune system doesn’t target it for elimination and the liver doesn’t break it down as quickly. • Current studies indicate that the risk for heart problems is considerable lower with liposomal doxorubicin formulations than with conventional doxorubicin. Oncologist. 2003;8 Suppl 2:17-24.
Types of liposomal anthracyclines • Liposomal daunorubicin (DaunoXome) • Pegylated liposomal doxorubicin (Doxil) • Has been studied most extensively and has demonstrated the most significant reductions in heart problems • Has shown a similar anticancer effect to doxorubicin, but with less cardiac toxicity
Dexrazoxane (Zinecard) • Has been shown to prevent or reduce the severity of heart damage caused by doxorubicin. • Thought to protect the heart muscle by blocking the formation of oxygen free radicals.
Diagnostics • Performed through echocardiogram. • Abnormalities in diastolic dysfunction through Doppler. • Cardiac biomarkers such as troponin or B-type natriuretic peptide (BNP) in monitoring chemotherapy induced cardiotoxicity is still be studied.
How is it treated • Stopping or reducing the dose. • Diuretics • Digitalis drugs • ACE inhibitors • Beta-Blockers
Endomyocardial biopsy may be useful to help diagnosis anthracycline induced cardiotoxicity. • Histological scaling has correlated with left ventricular function on radionuclide ventriculogram. • Has limitations with availability of technique and high likelihood of missing the involved areas via biopsy. Dis Manage 2008; 11: 1-6
Survivorship and Cardiac Function • As effectiveness of cancer treatment continues to improve, the population of long term survivors of childhood cancer will grow – an increase of late onset of cardiomyopathy will occur. • Prognosis after heart failure is generally poor compared to that associated with idiopathic or ischemic cardiomyopathy.