ANTHRACYCLIN-INDUCED CARDIOMYOPATHY
Andi Cahyadi, dr.
Resident of Pediatric, School of Medicine, Airlangga University
Surabaya, Indonesia
Chemotherapy is a well-established therapeutic approach for several malignancies1-3, but its clinical efficacy is often limited by its related cardiotoxicity, which leads to cardiomyopathy, possibly evolving into heart failure2 4 5. Cardiotoxicity may compromise the clinical effectiveness of chemotherapy, affecting survival, quality of life and prognosis2 4 6. Cardiomyopathy can occur years after completion of chemotherapy and it is important to recognize earlier, as complete recovery of cardiac function2 5-12. Dilated cardiomyopathy is the most common form of cardiomyopathy, caused by idiopathic cardiomyopathy of above 60%, followed by familial cardiomyopathy, active myocarditis and other causes such as cardiotoxic agents (doxorubicin)2 13 The most common cardiotoxic agent is athracycline derivate, such as doxorubicin (adriamicin, ADR).
The increasing number of patients treated by chemotherapy and to the availability of new, more aggressive antineoplastic drugs (combination and progressively higher cumulative doses), the incidence of cardiotoxicity is continuously growing4 10. For all cancers incidence increases with increasing age, therefore, it may have concomitant risk factor for cardiac diseases2 4 14. Within the first 30 years after diagnosis, 75% of childhood cancer survivors will suffer from a chronic health condition such as cardiovascular related14. Incidence of cardiotoxicity depends on different risk factors.5 15
Anthracyclines remain among the most widely prescribed and effective anticancer agents.14 Unfortunately, life-threatening cardiotoxicities continue to compromise their usefulness16. Anthracyclines are incorporated in more than 50% of regimens in childhood cancer such as rhabdomyosarcoma protocol, contributing to the 75% overall survival rates1 14.
The probability of developing congestive heart failure (CHF) at a cumulative doxorubicin (anthracycilne derivate) of 300 mg/M2 was between 0.7- 3.4%, rose to 1.3-6.1% at dose of 450 mg/M2, and rose steeply at higher doses. The occurrence of CHF seems to be in the range of 1-5%, and asymptomatic decrease in left ventricular function is in the range of 5-20%2. Toxicity can occur early within 1 year or late particularly among children2. The mortality rate is 20-30% and cardiac failure begin 1-2 months after treatment though the interval can be as long as 2 years3.
Cardiac events associated with chemotherapy may consist of mild blood pressure changes, thrombosis, electrocardiographic (ECG) changes, arrhythmias, myocarditis, pericarditis, myocardial infarction, cardiomyopathy, cardiac failure (left ventricular failure), and CHF. The risk for such effects depends upon: cumulative dose, rate of drug administration, mediastinal radiation, advanced age or younger age, female gender, pre-existing heart disease and hypertension2. Conversely, cardiotoxicity remains a major limitation in standard and high-dose chemotherapy, strongly impacting the quality of life and the overall survival, regardless of the oncologic prognosis4.
Differences between pediatric, adult, and elderly patients and the lack of uniformity in detecting and reporting cardiac events make such estimates even more difficult.16 To detect cardiac damage, the adopted diagnostic approach is the estimation of left ventricular ejection fraction by echocardiography. Noninvasive or systemic markers that can predict or track anthracycline cardiotoxicity are needed, both for clinical monitoring and as surrogate end in research. This approach shows early prediction of cardiomyopathy, when the possibilities of appropriate treatments could still improve the patient’s outcome.
Early onset chronic of cardiotoxic effect of antracycline could happen although drug monitoring has been done regularly. Identification of those patients at higher risk will be one key strategy to reduce the morbidity and mortality from cardiotoxicity using serial echocardiography. It is difficult to judge continued or discontinued antineoplastic drug while cardiomyopathy occurred. Long-term outcome should be taken into account because the incidence of cardiac abnormalities can still be progressive despite chemotherapy has been completed. It is important to consider that the approach of cardiologists to the definition of disease is quite different from that of the oncologists.
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