The Role of Cardioprotection in Cancer Therapy Cardiotoxicity: JACC: CardioOncology State-of-the-Art Review

Abstract

Cardiotoxicity is a relatively frequent and potentially serious side effect of traditional and targeted cancer therapies. Both general measures and specific pharmacologic cardioprotective interventions as well as imaging- and biomarker-based surveillance strategies to identify patients at high risk have been tested in randomized controlled trials to prevent or attenuate cancer therapy-related cardiotoxic effects. Although meta-analyses including early trials suggest an overall beneficial effect, there is substantial heterogeneity in results. Recent randomized controlled trials of neurohormonal inhibitors in patients receiving anthracyclines and/or human epidermal growth factor receptor 2-targeted therapies have shown a lower rate of cancer therapy-related cardiac dysfunction than previously reported and a modest or no sustained effect of the interventions. Data on preventive cardioprotective strategies for novel cancer drugs are lacking. Larger, prospective multicenter randomized clinical trials testing traditional and novel interventions are required to more accurately define the benefit of different cardioprotective strategies and to refine risk prediction and identify patients who are likely to benefit.

Keywords: ACE, angiotensin-converting enzyme; ADT, androgen deprivation therapy; ARB, angiotensin receptor blocker; CMR, cardiovascular magnetic resonance; CTRCD, cancer therapy–related cardiac dysfunction; GLS, global longitudinal strain; GnRH, gonadotropin-releasing hormone; HER2 therapy; HER2, human epidermal growth factor receptor 2; LV, left ventricular; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonist; RR, risk ratio; anthracycline; cardiomyopathy; prevention.

Graphical abstract

Central Illustration

Selected Cardiotoxicities and Potential Preventive Strategies Several classes of anticancer therapies, including anthracyclines, human epidermal growth factor receptor 2 (HER2)–targeted therapy (eg, trastuzumab), radiotherapy, and fluoropyrimidines may cause cardiotoxicity. Whereas the principal cardiotoxic problem associated with anthracyclines and HER2-targeted therapy is left ventricular dysfunction, fluoropyrimidines have been associated with vasospasm and subsequent myocardial ischemia. Radiotherapy may cause a variety of cardiovascular diseases, including ischemic heart disease, valvular and pericardial disease, and cardiomyopathy. Preventive strategies include treatment of modifiable cardiovascular risk factors, modification of cancer treatments, and potentially preventive cardioprotective interventions, but there is need for additional research.