Clonal hematopoiesis of indeterminate potential (CHIP) was a risk factor for the development of cardiomyopathy during cancer therapy for the treatment of solid tumors, according to the results of a single-center study published as a letter in JACC: CardioOncology.
Among patients with solid tumors, the presence of CHIP — assessed using blood whole-exome sequencing — was an independent predictor for development of cardiomyopathy (hazard ratio [HR] = 2.01; 95% CI 1.03-3.93; p=0.042). Patients with CHIP also had significantly higher cumulative incidence of cardiomyopathy (38% vs. 25%; p<0.001) and shorter median time to cardiomyopathy (441 vs. 614 days; p<0.001) compared with patients with no CHIP.
Study researcher Jennifer M. Kwan, MD, PhD, of Yale University School of Medicine, told ASH Clinical News that data from the study lend support to screening for CHIP in patients diagnosed with cancer.
“This could potentially help identify higher-risk patients who may develop cardiomyopathy during cancer therapy or years beyond,” Dr. Kwan said. “These patients may want to start primary prevention, even before we start to see evidence that they have developed cardiotoxicity.”
There are currently no guidelines recommending standard CHIP evaluation in patients diagnosed with solid cancers, Dr. Kwan said. Previously, CHIP was shown to be a risk factor for systolic heart failure and, more recently, for diastolic heart failure. With this analysis, Dr. Kwan and colleagues were interested in characterizing associations between CHIP and cardiovascular risk factors in patients with cancer.
The prospective study enrolled 236 patients undergoing treatment for solid tumors and assessed CHIP status at time of enrollment. All enrolled patients had an inpatient or outpatient cardio-oncology consultation before enrollment.
CHIP was found in 38.0% of patients, which the researchers noted “was higher than expected in comparison to a general population of similar age but similar to previous series of cancer patients.”
About one-third (32.2%) of patients with CHIP had breast cancer, and about one-fifth (22.2%) had genitourinary cancer. Many patients had undergone potentially cardiotoxic therapies, including immune checkpoint inhibition (37.3%) and chest radiation therapy (48.7%).
At baseline, patients with CHIP had more than double the rate of heart failure with preserved ejection fraction (20.0% vs. 7.5%; p=0.007), but no greater incidence of obstructive coronary artery disease, heart failure with reduced ejection fraction, diabetes, hypertension, and hyperlipidemia.
In addition to presence of CHIP, treatment with an immune checkpoint inhibitor was an independent predictor of cardiomyopathy (HR=1.95; 95% CI 1.03-3.71; p=0.042).
Dr. Kwan said the study is limited by its single-center design.
“Patients were also referred to us from cardiology service or for concerns about cardiotoxicity,” Dr. Kwan said. “That leads to a potentially biased population of patients who were higher risk to begin with.”
However, Dr. Kwan noted that the increased risk for cardiomyopathy, even within this cardiology cohort, is still significant and something clinicians should monitor.
“As of right now, assessing for CHIP is not standardized and requires DNA sequencing,” Dr. Kwan noted. “There has been a lot of discussion around its standardization, and that needs to be done before we can roll out CHIP assessment to the entire cancer community.”
Moving forward, these findings will need to be validated, and more research is needed to assess whether patients with CHIP benefit from initiation of primary prevention that would help prevent future cardiomyopathy.
“These patients might also benefit from more frequent heart monitoring while undergoing chemotherapy or other oncologic therapies,” Dr. Kwan said. “More studies will be needed.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Leveille E, Cheheyeb RJ, Matute-Martinez C, et al. Clonal hematopoiesis is associated with cardiomyopathy during solid tumor therapy [published online ahead of print, 2024 July 2]. J Am Coll Cardiol CardioOnc. doi: 10.1016/j.jaccao.2024.05.013.
