Cancer and Heart Failure: Understanding the Intersection

Abstract

Heart disease and cancer are the two leading causes of death, together accounting for almost 50 % of deaths in the US.1 Unfortunately, the tremendous success in improving cancer survival is often attenuated by downstream cardiovascular complications from cancer therapy.Acute cardiac toxicity may limit the ability to use life-saving cancer therapy and chronic toxicity limits overall survival. As novel agents with more specific targets become available, unanticipated cardiac complications arise. The spectrum of cardiac toxicities is broad, ranging from ischaemia and arrhythmias to hypertension, left ventricular dysfunction (LVD) and the development of clinical heart failure (HF).Notably, there is increasing evidence that suggests an underlying relationship between cancer and the heart, independent of cancer therapies' effect on left ventricular ejection fraction (LVEF) and heart rate. 2,3 HF caused by chemotherapy portends a worse prognosis compared with idiopathic and ischaemic cardiomyopathy, 4 highlighting the need for enhanced understanding and management. Definitions of Cancer Therapy-related Cardiac ToxicityThere is currently no universally accepted definition of cancer therapyrelated cardiac toxicity; however, several definitions pertaining to specific agents have been proposed. A recent consensus defines cancer therapy-related cardiac dysfunction (CTRCD) as a decrease in LVEF of >10 % to a value of <53 %. 5 The Cardiac Review and EvaluationCommittee involved in trials with trastuzumab defines cardiotoxicity as a decrease in LVEF that is either global or more severe in the septum and decline in LVEF of at least 5 % to <55 % with signs or symptoms of HF, or a decline of at least 10 % to <55 % without HF signs or symptoms. 6According to the Food and Drug Administration, anthracycline cardiotoxicity is defined as a >20 % decrease in LVEF when the baseline LVEF is normal, or >10 % decrease when baseline LVEF is abnormal. In contrast to topoisomerase II-alpha, which is located on rapidly dividing cells, topoisomerase II-beta, located on cardiac myocytes is the proposed mechanism behind the cardiotoxicity. 9 Anthracycline use has been shown to result in LVD with an incidence of 1-5 %, ranging from acute to late onset. 10 Anthracycline-induced HF is thought to be cumulative and dose-dependent, with an incidence reaching 5 % at a total doxorubicin dose of 450 mg/m 2 . 11 However, examination of endomyocardial biopsies reveals histopathological changes with doses as low as 240 mg/m 2 , suggesting that subclinical cardiotoxity may be present as early as the first dose. 12 HER2-targeted AgentsTrastuzumab, a monoclonal antibody targeted against humanised epidermal growth factor receptor 2 (HER2) has played a pivotal role in breast cancer patients whose tumours overexpress HER2. Under normal circumstances, in cardiac myocytes, the HER2 signalling pathway is responsible for adaptation to stress. 8 The incidence of LVD with trastuzumab ranges from 2 % to 28 %, 10 with a 1.7-4.1 % incidence of HF. 13 Other HER2-targeted a...

Development and progression of cancer cachexia: Perspectives from bench to bedside

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