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

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

CHIP was detected in 40 (36.4%) patients in our cohort. The most commonly mutated genes were , , and . With a median follow-up of 55.2 months, patients carrying CHIP had a significantly higher heart failure hospitalization rate (adjusted HR: 3.060; 95% CI: 1.090-8.589;  = 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.