Current Cardiology Reviews - Volume 7, Issue 4, 2011

In the last two decades, significant advances in cancer therapy development have lead to more effective chemotherapeutic and novel targeted therapies for cancer patients. Although this has resulted in a remarkable improvement in cure rates and cancer-related survival, it has also resulted in unwanted long term side effects in a growing population of survivors. In recent years, cardiac toxicity has been increasingly recognized as a potential complication of cancer therapy, and in some cases, risk factors have been identified. There are ongoing research efforts focused on the management, and more importantly the prevention of this serious complication. We are pleased to introduce this issue titled “Cancer Therapy Related Cardiotoxicity” with a focused update on the early recognition and management of this particularly concerning complication. Among the key clinical considerations, the authors describe the cardiotoxicity risk factors that should be recognized and considered when formulating a treatment plan for cancer patients. The authors discuss potential underlying pathophysiologic mechanisms which may result in better understanding of the cardiac manifestations resulting from various cancer treatments. In addition, they present modern diagnostic techniques as well as recommendations for a multidisciplinary approach between oncologists and cardiologist involved in the care of cancer patients.

Anthracyclines, such as doxorubicin and idarubicin, remain an important class of chemotherapeutic agents. Unfortunately, their efficacy in treating cancer is limited by a cumulative dose-dependent cardiotoxicity, which can cause irreversible heart failure. In this review, we discuss the pathogenesis and incidence of anthracycline-induced cardiotoxicity as well as methods to detect, prevent and treat the condition.

Cardiac toxicity of molecularly targeted cancer agents is increasingly recognized as a significant side effect of chemotherapy. These new potent therapies may not only affect the survival of cancer cells, but have the potential to adversely impact normal cardiac and vascular function. Unraveling the mechanisms by which these therapies affect the heart and vasculature is crucial for improving drug design and finding alternative therapies to protect patients predisposed to cardiovascular disease. In this review, we summarize the classification and side effects of currently approved molecularly targeted chemotherapeutics.

Chemotherapeutic agents reduce mortality and can prevent morbidity in a wide range of malignancies. These agents are, however, associated with toxicities of their own, and the treating physician must remain ever vigilant against the risk outgrowing the benefit of therapy. Thus, pre-treatment evaluation and monitoring for toxicity during and following administration is a fundamental tenet of oncologic practice. Among the most insidious and deadly toxicities of antitumor agents is cardiac toxicity, which in some cases may be irreversible. Early detection of cardiotoxicity allows the treating oncologist to redirect therapy or dose modify, taking into account the cost of a reduction in therapy against the potential of further injury to the patient. In these instances, the role of the cardiologist is to assist and advise the oncologist by providing diagnostic and prognostic information regarding developing cardiotoxicity. This review discusses noninvasive diagnostic options to identify and characterize cardiotoxicity and their use in prognosis and guiding therapy. We also review established protocols for cardiac safety monitoring in the treatment of malignancy.

Chemotherapy related cardiac dysfunction (CRCD) is a serious complication of anticancer therapy. CRCD can be classified into two types. Type I CRCD is exemplified by anthracyline- induced cardiac dysfunction and type II CRCD is exemplified by trastuzumab- induced cardiac dysfunction. The mechanism of cardiac toxicity in both types is not well defined. Certain risk factors may play a role in developing the cardiac injury, most importantly, the cumulative dose when dealing with anthracycline induced cardiotoxicity. Establishing an early diagnosis and initiating early treatment may be an important step in preventing irreversible cardiac injury especially in type I CRCD. Currently there are no guidelines developed specifically for the treatment of chemotherapy induced cardiomyopathy (CIC), however a few small studies support the use of neurohormonal antagonists in the treatment and prevention of CIC. Large multi- centers trials are needed to establish guidelines for CIC. Until then, we advocate following the American College of Cardiology/ American Heart Association (ACC/AHA) and Heart Failure Society of America (HFSA) guidelines. Additionally, a close collaboration between the patient's cardiologist and oncologist is strongly recommended in order to establish a long term plan for the patient.

Purpose: The purpose of this paper is to identify risk factors for cardiovascular disease in women with breast cancer and review healthy lifestyle behaviors as essential risk reduction strategies. Findings: Women with breast cancer account for 22% of the 12 million cancer survivors. Women diagnosed with breast cancer often present with modifiable and non-modifiable cardiovascular risk factors and/or pre-existing co-morbid illness. Any one or a combination of these factors may increase the risk of cardiovascular disease. There is strong evidence that healthy eating and routine physical activity can reduce cardiovascular disease. Exercise improves cardiovascular fitness, body composition and quality of life in breast cancer survivors and observational studies suggest a survival benefit. Clinical Implications: Lifestyle interventions including a healthy diet, regular physical activity, weight management and smoking cessation should be integrated into a survivorship care plan to reduce cardiovascular disease risk and promote better health for women with breast cancer.

Because of the paucity of large, randomized trials concerning the cardiac care of patients with cancer, treatment and prevention of chemotherapy-induced cardiotoxicity must rely on insights gained from small trials and case reports as well as the application of guidelines developed for the general population. In these clinical vignettes, we present patients referred by their oncologists to a cardiologist for specialized evaluation and management of cardiotoxicity with the goal of emphasizing the importance of identifying risk factors for cardiotoxicity, initiating evidence-based therapy, and establishing a close collaboration between oncologists and cardiologists.

Regulation of gene expression is central to cell growth, differentiation and diseases. Context specific and signal dependent regulation of gene expression is achieved to a large part by transcription factors. Cardiac transcription factors regulate heart development and are also involved in stress regulation of the adult heart, which may lead to cardiac hypertrophy. Hypertrophy of cardiac myocytes is an outcome of the imbalance between prohypertrophic factors and antihypertrophic factors. This is initially a compensatory mechanism but sustained hypertrophy may lead to heart failure. The growing knowledge of transcriptional control mechanisms is helpful in the development of novel therapies. This review summarizes the role of cardiac transcription factors in cardiac hypertrophy, emphasizing their potential as attractive therapeutic targets to prevent the onset of heart failure and sudden death as they can be converging targets for current therapy.

Atherosclerosis is a pathology characterized by low-grade vascular inflammation rather than a mere accumulation of lipids. Inflammation is central at all stages of atherosclerosis. Acute coronary syndrome significantly affects the concentration and composition of the lipids and lipoproteins in plasma. Plasma triglyceride and very low density lipoprotein levels increase, while high density lipoprotein, low density lipoprotein and total cholesterol levels decrease. Early treatment of hyperlipidemia provides potential benefits. However, post-event changes in lipid and lipoproteins lead to delays in the choice of the treatment. This review focuses on the mechanism and the clinical importance of the relevant changes.