Surviving Cancer without a Broken Heart

Abstract

Chemotherapy-associated myocardial toxicity is increasingly recognized with the expanding armamentarium of novel chemotherapeutic agents. The onset of cardiotoxicity during cancer therapy represents a major concern and often involves clinical uncertainties and complex therapeutic decisions, reflecting a compromise between potential benefits and harm. Furthermore, the improved cancer survival has led to cardiovascular complications becoming clinically relevant, potentially contributing to premature morbidity and mortality among cancer survivors. Specific higher-risk populations of cancer patients can benefit from prevention and screening measures during the course of cancer therapies. The pathobiology of chemotherapy-induced myocardial dysfunction is complex, and the individual patient risk for heart failure entails a multifactorial interaction between the selected chemotherapeutic regimen, traditional cardiovascular risk factors, and individual susceptibility. Treatment with several specific chemotherapeutic agents, including anthracyclines, proteasome inhibitors, epidermal growth factor receptor inhibitors, vascular endothelial growth factor inhibitors, and immune checkpoint inhibitors imparts increased risk for cardiotoxicity that results from specific therapy-related mechanisms. We review the pathophysiology, risk factors, and imaging considerations as well as patient surveillance, prevention, and treatment approaches to mitigate cardiotoxicity prior, during, and after chemotherapy. The complexity of decision-making in these patients requires viable discussion and partnership between cardiologists and oncologists aiming together to eradicate cancer while preventing cardiotoxic sequelae.

Figure 1

Proposed Protocol for Early Detection of Subclinical LV Dysfunction and Management of Cardiotoxicity in Patients Receiving Anthracyclines. ^*Approved by the FDA in acquired immune deficiency syndrome (AIDS)–related Kaposi sarcoma, advanced/refractory ovarian cancer, multiple myeloma after failure of at least 1 prior therapy, and metastatic breast cancer., ACEi/BB, angiotensin-converting enzyme inhibitor/β-blocker; cTn, cardiac troponin; CTRCD, cancer therapeutics–related cardiac dysfunction; D/C, Discontinue; DOX, doxorubicin; DRZ, dexrazoxane; EF, ejection fraction; GLS, global longitudinal strain; HF, heart failure; LVEF, left ventricular ejection fraction.

Figure 2

Risk Stratification, Preventive Therapy, and Surveillance of Trastuzumab-treated Patients. Blue arrows symbolize cardio-oncological chronological point of intervention. *Dependent on the availability of alternative therapies and following cardio-oncology team discussion. Holding trastuzumab and re-challenge following EF normalization (LVEF>50%) is one potential strategy. ^†LVEF should be assessed using 2D Simpson’s LVEF or preferably 3D-based LVEF. ^‡One risk stratification criterion required. ^§dLVEF>10%: reduction in LVEF>10% and LVEF<50%. AC, anthracyclines; dLVEF, difference in left ventricular ejection fraction; EF, ejection fraction; GLS, global longitudinal strain; HsTnI, high-sensitivity troponin I; LV, left ventricular; RT, radiation therapy.

Figure 3

Risk Stratification, Preventive Therapy, and Surveillance of Immune Checkpoint Inhibitor-treated Patients. Blue arrow symbolizes cardio-oncological chronological point of intervention. *Dependent on the availability of alternative therapies and following oncologist consultation; †LVEF should be assessed using 2D Simpson’s LVEF or preferably 3D-based LVEF; ‡dLVEF>10% to LVEF<50%. ATG, antithymocyte globulin; dLVEF, difference in left ventricular ejection fraction; dGLS, difference in global longitudinal strain; EF, ejection fraction; GLS, global longitudinal strain; HsTnI, high-sensitivity troponin I; ICPi, immune checkpoint inhibitors; LVEF, left ventricular ejection fraction.