Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk of diastolic dysfunction in a cardio-oncology cohort

Background/Introduction Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to increase all-cause mortality and risk of adverse cardiovascular outcomes, including cardiomyopathy and immune-checkpoint inhibitor associated myocarditis, in patients with solid malignancies [1, 2]. Immune cells in heart failure patients with CHIP mutations have increased effector functions [3]. Diastolic dysfunction is a subset of heart failure with preserved ejection fraction (HFpEF) characterized by impaired relaxation and increased stiffness of the left ventricle [4]. Although its pathophysiology remains incompletely understood, inflammatory mechanisms have been shown to be a key contributor [4]. It is unclear whether cancer patients with CHIP are at increased risk for diastolic dysfunction. Purpose Given the enhanced inflammatory profile associated with CHIP mutations in heart failure and the association between inflammatory mechanisms and diastolic dysfunction, our study aimed to evaluate the risk of diastolic dysfunction in patients with solid malignancies with and without CHIP. Methods In a single-center retrospective cohort study, we enrolled 236 patients undergoing treatment for solid tumors between 2018-2023 who were referred to cardio-oncology or seen by the cardiology service. We evaluated for CHIP status as well as starting point for time of death by blood draw at time of enrollment. Chart review was performed to extract relevant parameters. Diastolic dysfunction was determined using echocardiography criteria. Kaplan-Meier (KM) survival curves stratified by CHIP and a competing risk model for the outcome of diastolic dysfunction were generated. Results 90 patients in the cohort had CHIP mutations. Patients with CHIP were more likely to have coronary artery disease (CAD) (p-value <0.001) and HFpEF (p-value 0.007) (Table). CHIP was an independent risk factor for diastolic dysfunction (p-value 0.021) (Figure A). There was a significant difference between CHIP and non-CHIP patients for the outcome of diastolic dysfunction in KM analyses (p-value 0.00013) (Figure B). Patients with CHIP had a shorter time to diastolic dysfunction compared to non-CHIP patients (median time of 17.5 days (Q1 6.25, Q3 25.75) and 18.0 days (Q1 12.0, Q3 27.0) respectively). Conclusions CHIP is associated with an increased risk of developing diastolic dysfunction in cancer patients. Our study has several implications for the care of such patients. Given that diastolic dysfunction, which can frequently present asymptomatic, is associated with incident heart failure and decreased survival, early identification through imaging and intervention can improve cardiovascular outcomes. Further studies are warranted to understand how CHIP plays a role in the pathophysiology of diastolic dysfunction and to identify effective treatment strategies.TableFigure