Personalized Approach to Cancer Treatment-Related Cardiomyopathy

Abstract

Purpose of review: Cancer treatment-related cardiotoxicity (CTRC) represents a significant cause of morbidity and mortality worldwide. The purpose of our review is to summarize the epidemiology, natural history, and pathophysiology of cardiotoxicity-related to cancer treatment. We also summarize appropriate screening, surveillance, and management of CTRC. While cardiotoxicity is characteristically associated with anthracyclines, HER2-B antagonists, and radiation therapy (XRT), there is growing recognition of toxicity with immune checkpoint inhibitors (ICI), tyrosine kinase inhibitors, and proteasome inhibitors.

Recent findings: Patients at risk for cardiotoxicity should be screened based on available guidelines, generally with serial echocardiograms. The role of medical heart failure (HF) therapies is controversial in patients with asymptomatic left ventricular dysfunction but may be considered in some instances. Once symptomatic HF has developed, treatment should be in accordance with ACC/AHA guidelines. The goal in caring for patients receiving cancer treatment is to optimize cardiac function and prevent interruptions in potentially lifesaving cancer treatment.

Keywords: Cancer therapeutics–related cardiac dysfunction; Cardio-oncology; Cardiomyopathy; Chemotherapy; Heart failure; Immune checkpoint inhibitor.

Fig. 1

Pathophysiology of anthracycline induced cardiotoxicity. Cardiotoxicity is generally thought to occur due to inhibition of topoisomerase II-ß. Inhibition of this enzyme leads to impaired ability to repair double stranded breaks, mitochondrial dysfunction, and the generation of reactive oxygen species (ROS) (adapted from J Am Coll Cardiol. 2014 Sep 2;64(9):938–45)

Fig. 2

Pathophysiology of radiation-induced cardiotoxicity. Radiation is thought to result in micro and macrovascular damage which results in impaired myocardial perfusion, myocardial fibrosis, and progressive systolic/diastolic dysfunction. Radiation may also lead to epicardial coronary disease, resulting in further impairment of myocardial performance (adapted from J Am Coll Cardiol. 2019 Aug 20;74(7):905–927)

Fig. 3

Risk factors for cancer treatment associated cardiotoxicity proposed in the ASCO clinical guidelines for the prevention and monitoring of cardiac dysfunction in cancer survivors (adapted from J Oncol Pract. 2017 Apr;13(4):270–275)

Fig. 4

ACC/AHA stages of heart failure (adapted from J Am Coll Cardiol. 2013 Oct 15;62(16):e147–239)

Figure 5

Cardiac MRI in a 61 year old male with Immune Checkpoint Inhibitor myocarditis due to nivolumab. The patient was recieving ICI for Hodgkin’s Lymphoma. There is inferior and septal myocardial edema (solid arrow) on T2 mapping (A) and patchy replacement fibrosis (dashed arrow) on late gadolinium enhancement images (B) in a non – coronary distribution suggesting an inflammatory cardiomyopathy.

Fig. 6

Management algorithm for screening (a) and surveillance (b) in patients receiving anthracycline or HER2B antagonist therapy as proposed in the American Society of Echocardiography (ASE) guidelines (adapted from J Am Soc Echocardiogr. 2014 Sep;27(9):911–39)

Fig. 7

Screening algorithm for cardiac dysfunction in patients receiving cardiac radiation exposure (XRT). Screening is generally recommended at 10 years in low-risk patients and every 5 years following exposure in higher risk individuals (adapted from J Am Soc Echocardiogr. 2013 Sep;26(9):1013–32)

Fig. 8

Adapted from J Am Coll Cardiol. 2017 Aug 8;70(6):776–803