As cancer treatment continues to advance, there have been drawbacks that often come with progress. Toxicities from effective cancer treatments may lead to damaging acute and chronic effects in patients.

As various treatments to address cardiotoxicity in cancer patients are researched, it is believed that patients with these comorbidities should be closely monitored and managed by cardio-oncology teams that include multiple specialists.

 

Cardiotoxicity explained

Adverse events involving the cardiovascular system are one of the greatest barriers in successful cancer treatment. These complications are not only linked to older chemotherapy drugs like anthracyclines but also to emerging targeted therapies and immunotherapies.

This cardiotoxicity can result from:

• Direct effects on cardiac myocytes that impair function or protective mechanisms

• Vascular endothelial damage

• Alterations in the hemodynamic flow

• Changes in thrombogenicity

Such cardiotoxicity can present acutely and limit the dosage of cancer treatments. It can also present decades after treatment, possibly resulting in greater cardiovascular disease and death.

Medical societies have published guidelines on cardiovascular monitoring of patients who have been administered cardiotoxic cancer therapies, along with recommendations on how to treat cardiac toxicities. But evidence to support these guidelines is lacking and discrepancies abound, according to a statement published by the Journal of the American Heart Association (JAHA).

Alexandre J, Cautela J, Ederhy S, et al. Cardiovascular toxicity related to cancer treatment: A pragmatic approach to the American and European cardio-oncology guidelines. J Am Heart Assoc. 2020;9(18):e018403.

 

 

Anthracyclines to blame?

Various factors that complicate the successful treatment of cardiotoxicity were highlighted in a Notice of Special Interest from the National Cancer Institute and National Heart, Lung, and Blood Institute intended (in part) to foster collaboration and innovation when addressing anticancer-treatment-related cardiotoxicity.

Notice of special interest (NOSI): Improving outcomes in cancer treatment-related cardiotoxicity. NIH. November 4, 2021.

 

“Given the heterogeneity among patients with respect to cardiotoxicity risk, the timing of onset, clinical presentation, and outcome, understanding and translating mechanisms and biomarkers into individualized cardio-oncology risk stratification, early detection, prevention, monitoring, and management during cancer treatment and survivorship care is of utmost importance, and are currently lacking,” the authors wrote.

“Current guidelines addressing cancer treatment-related cardiotoxicity are broad, based mainly on anthracyclines, and suffer from a poor level of evidence for individual risk evaluation, prevention, monitoring, and management strategies for new and emerging cancer treatment approaches,” the authors added.

Anthracyclines are considered the top culprit in relation to chemotherapy-induced cardiotoxicity. These agents result in hypokinetic cardiomyopathy that progresses to heart failure, a complication first described in 1967, according to research published by Frontiers in Cardiovascular Medicine.

Cardinale D, Iacopo F, Cipolla CM. Cardiotoxicity of anthracyclines. Front Cardiovasc Med. 2020;7:26.

It should be stressed, however, that newer anticancer treatments may also play a role.

 

With immune checkpoint inhibitors or chimeric antigen receptor T-cell therapies, for instance, inflammation and immune mechanisms should be considered in relation to cardiotoxicity.

Some targeted therapies can mediate corrected QT interval prolongation, ventricular arrhythmias, and cardiac arrest, according to an article published by Nature Reviews Cardiology.

Herrmann J. Adverse cardiac effects of cancer therapies: Cardiotoxicity and arrhythmia. Nat Rev Cardiol. 2020;17(8):474–502.

 

 

Monitoring and treatment

According to the Mayo Clinic, such a team should include cardiologists, oncologists, hematologists and other specialists to provide coordinated and comprehensive care, evaluate the patient’s condition, and develop a treatment plan.

Cardio-oncology clinic - overview. Mayo Clinic.

 

Regarding treatment, let’s focus on two relevant scenarios, espoused by the JAHA statement, which synthesized guidelines from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Society of Cardiology.

Anthracycline use. Anthracyclines should be avoided in patients with a left ventricular ejection fraction (LVEF) < 40% unless there are no alternatives. In patients with an LVEF ≥ 40% but < 50%, as well as those taking multiple cardiotoxic cancer treatments with a normal LVEF and related cardiovascular risk factors, anthracyclines may be employed with a cardioprotective strategy (eg, ACEs, ARBs, β‐blockers).

LVSD and HF. The JAHA statement recommended that the cardio-oncologic evaluation for left ventricular systolic dysfunction (LVSD) and early cancer-therapy-related cardiotoxicity include measurements of blood pressure, blood glucose, ECG, transthoracic echo (TTE) to determine LVEF, left ventricular contrast with 2D echo, and cardiac magnetic resonance imaging if the TTE results are suboptimal. Patients should be advised to maintain a healthy diet and exercise, as well as to actively manage modifiable risk factors.

In patients with a drop in LVEF of 10% to < 50% or an absolute drop of 20%, beta-blockers and ACEIs should be initiated. In patients with symptomatic heart failure (HF) with reduced ejection fraction, cancer treatment should be withheld.

Specifically, with trastuzumab-related cardiac dysfunction, HF treatment can be ceased following normalization of function.