Monitoring for Chemotherapy-Related Cardiotoxicity in the Form of Left Ventricular Systolic Dysfunction: A Review of Current Recommendations

Abstract

Cardiotoxicity is a well-established complication of multiple cancer therapeutics, and the one of the most prominent effects that limits the use of these agents is in the form of left ventricular dysfunction, otherwise known as chemotherapy-induced cardiomyopathy (CIMP). Because CIMP can worsen patient outcomes and interfere with a patient's life-saving cancer treatments, it is important to implement a monitoring strategy for patients undergoing potentially cardiotoxic treatments. Efforts have been made by multiple societies to provide recommendations for screening and monitoring for CIMP in at-risk patients, with slight variations between guideline documents and expert consensuses. Most of the recommendations for monitoring for CIMP are specific to anthracyclines and the human epidermal growth factor receptor 2-antagonist trastuzumab, with very limited guidance for other cardiotoxic agents such as Tyr kinase inhibitors and proteasome inhibitors, which we cover in this article. Echocardiography remains the mainstay for imaging surveillance because of its safety profile and widespread availability, but the accuracy of cardiac magnetic resonance imaging (CMR) makes it an important modality when there are discrepancies in left ventricular ejection fraction assessment. Subclinical cardiotoxicity may be detected using laboratory biomarkers such as cardiac troponin and brain natriuretic peptide as well as myocardial deformation (strain) imaging by echocardiography or CMR. Specific recommendations for timing and frequency of laboratory biomarker assessment remain up for debate, but myocardial deformation imaging should be performed with every echocardiogram or CMR assessment. Future studies are needed to evaluate the efficacy of established surveillance recommendations and to develop specific recommendations for novel cancer therapeutics.

Doxorubicin plus lurbinectedin in patients with advanced endometrial cancer: results from an expanded phase I study

“…Of note, the absence of cardiac events related to changes in left ventricular ejection fraction either during dose escalation or in the expansion cohort suggest that lurbinectedin does not increase ventricular dysfunction over doxorubicin. 18 Due to the incidence of febrile neutropenia, the use of growth colony-stimulating factors is mandatory for further studies.…”

Cardiotoxicity Induced by Protein Kinase Inhibitors in Patients with Cancer

“…Protein KIs can be classified into several families depending on the structure and ligand: epidermal growth factor receptor (EGFR) inhibitors; vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors; v-raf murine sarcoma viral oncogene homolog B (BRAF) 1/2 inhibitors; mitogen-activated protein kinase kinases 1 and 2 (MEK) inhibitors; anaplastic lymphoma kinase (ALK) inhibitors; Bruton tyrosine kinase (BTK) inhibitors; phosphoinositide 3-kinase (PI3K) inhibitors; cyclin-dependent kinase (CDK) 4/6 inhibitors; Janus kinases (JAK) inhibitors; BCR-ABL tyrosine kinase inhibitors; FMS-like tyrosine kinase-3 (FLT3) inhibitors; and stem cell factor receptor/platelet-derived growth factor receptor (KIT/PDGFRA) inhibitors ( Figure 1 and Figure 2 ). Specified molecular targets and therapeutic indications currently available in the European Union are presented in Table 1 [ 5 , 10 ].…”

“…However, in the case of inhibitors with lower or unclear risk (e.g., imatinib), monitoring is required only in patients with predisposing conditions or symptoms suggesting cardiac disease. Initiation of treatment in patients with LVEF <50% should be avoided, and discontinuation of treatment is necessary in case of LVEF reduction [ 10 , 117 , 118 , 119 ].…”

Pediatric Chemotherapy Drugs Associated With Cardiotoxicity

“…Clinicians have developed an accurate, reproducible, and minimally invasive imaging modality called the ECHO. ECHO has now become the mainstay imaging modality for serial monitoring of the heart for potential cardiotoxic effects from chemotherapy [ 73 ]. The 2D-ECHO is the most widely used imaging technique for evaluating cardiotoxicity in children, before, during, and after chemotherapeutic treatment.…”