Chemotherapy Induced Cardiomyopathy: Pathogenesis, Monitoring and Management

Abstract

The survival rate of cancer patients has greatly increased over the last 20 years. However, to achieve this result, a considerable price has been paid in terms of the side effects associated with the intensive anticancer treatment. The most common adverse effect is cardiotoxicity which may compromise the clinical effectiveness of chemotherapy, affecting the patient's survival and quality of life independently of the oncological prognosis. There are 2 types of cardiac toxicities, type I which is more serious and result in permanent damage to the myocardium and type II which is usually reversible. Chemotherapies varies in their incidence of inducing cardiomyopathy, and the onset which may occur acutely (during or shortly after treatment), sub-acutely (within days or weeks after completion of chemotherapy) or chronically (weeks to months after drug administration). 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 congestive heart failure (CHF). The risk for such effects depends upon: cumulative dose, rate of drug administration, mediastinal radiation, advanced age, younger age, female gender, pre-existing heart disease and hypertension. Serial measurements of LVEF and fractional shortening are the most common indices monitored to assess left ventricular systolic function and cardiotoxicity. This can be achieved by 2-dimensional, M-mode and color Doppler echocardiographic examination; also Cardiac troponins as a biological marker for myocardial damage can be used for monitoring in patients received anthracyclines. Angiotensin-converting enzyme (ACE) inhibitors (ACEIs) have been shown to slow the progression of left ventricular dysfunction in several different clinical settings, including anthracycline-induced cardiomyopathy. Carvedilol and probably with anti-oxidants like Probucol and vitamin E benefits also.KeywordsAnthracyclines; Cardiomyopathy; Chemotherapy

Cardio-Oncology: An Ongoing Evolution

“…Anthracyclines are common perpetuators of type 1 cardiotoxicity, while trastuzumab can cause type 2 cardiotoxicity. Risk factors for both type 1 and type 2 cardiotoxicity include age as well as previous cardiac disease [20]. Beyond this classification scheme, cardiotoxicity can also be defined as acute or chronic in nature.…”

Gemcitabine induced cardiomyopathy: a case of multiple hit cardiotoxicity

“…The mechanism of cardio‐toxicity here involves disruption of topoisomerase‐II‐mediated DNA repair and generation of oxygen‐derived free radicals 4, 5, 6, 7. Serial echocardiograms during several years after doxorubicin administration showed stable LVEF.…”

“…The patient was then exposed to R‐DHAP, of which, cisplatin has been shown to cause congestive heart failure, particularly in the elderly. Its mode of toxicity involves crosslinking with purine bases on the DNA and thus interfering with DNA repair mechanisms, causing DNA damage and cell apoptosis 4, 6…”

Matrix metalloproteinases 2 and 9 in rabbits with doxorubicin-induced cardiomyopathy

“…Hematological, gastrointestinal, cutaneous, and renal alterations are all anticipated in subjects undergoing anthracycline therapy (Speyer et al 1988, Steinherz et al 1991, Shakir & Rasul 2009, Gava et al 2013. Because MMP are found throughout the body and are involved with several biological events (Armstrong and Jude 2002), the plasma activity of these enzymes are likely influenced by their contribution in all these tissues, and not only related to the degradation of cardiac ECM.…”

“…Several cellular mechanisms are implicated in this cardiotoxicity, including necrosis and apoptosis. It is believed that the accumulation of doxorubicin within the mitochondria results in the production of free radicals and peroxidation reactions (Speyer et al 1988, Steinherz et al 1991, Shakir & Rasul 2009.…”