Clonal Hematopoiesis Is Associated With Adverse Clinical Outcomes and Left Ventricular Remodeling in Aortic Stenosis

Abstract

Background: Clonal hematopoiesis of indeterminate potential (CHIP) has been linked to intensified systemic inflammation and represents a novel risk factor for atherosclerotic cardiovascular diseases, including aortic stenosis (AS). Objectives: This study aimed to assess the clinical impact of CHIP in a cohort of severe AS patients undergoing transcatheter aortic valve implantation (TAVI). Methods: We enrolled 110 severe AS patients in this retrospective study. Targeted next-generation sequencing was employed to detect somatic mutations with a variant allele frequency >2% in 16 genes most frequently associated with CHIP. Correlative analyses on clinical, laboratory, and echocardiographic parameters were also performed. The primary endpoint was post-TAVI heart failure hospitalization. Multivariate Cox regression model was used to account for confounding effects of relevant clinical factors. Results: = 0.034) than those without CHIP. Additionally, patients harboring CHIP had higher serum ferritin levels, as well as echocardiographic evidence of left ventricular hypertrophy and diastolic dysfunction. Conclusions: Our study supports the adverse clinical impact of CHIP in AS patients undergoing TAVI, which could be attributed to systemic inflammation and maladaptive LV remodeling. Prospective trials are anticipated to validate our findings and provide further evidence that CHIP holds the potential of being an actionable therapeutic target in AS.