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. 2025 Jan 8;4(2):101532.
doi: 10.1016/j.jacadv.2024.101532. eCollection 2025 Feb.

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

Chi-Yuan Yao  1   2   3 , Tsung-Yu Ko  1   3 , Li-Tan Yang  1 , Masaaki Takeuchi  4 , Chih-Fan Yeh  1 , Mao-Shin Lin  1 , Ying-Hsien Chen  1 , Ching-Ying Kuo  5 , Chia-Lang Hsu  6   7   8 , Wen-Chien Chou  1   2   3 , Hsien-Li Kao  1   3
Affiliations

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

Chi-Yuan Yao et al. JACC Adv. .

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: CHIP was detected in 40 (36.4%) patients in our cohort. The most commonly mutated genes were DNMT3A, TET2, and ASXL1. 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; P = 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.

Keywords: aortic stenosis; clonal hematopoiesis; inflammation; left ventricular remodeling; transcatheter aortic valve implantation.

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Conflict of interest statement

This research work was supported by 10.13039/501100006737National Taiwan University Hospital (NTUH-112-S0227) and 10.13039/501100001868National Science Council, Taiwan (project number: 111-2314-B-002-267-, 113-2314-B-002-107-MY2). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Characterization of the Clonal Hematopoiesis of Indeterminate Potential (CHIP) Variants Identified in the Patients With Severe Aortic Stenosis (A) Number of genetic variants identified across various genes included in our sequencing panel. (B) Distribution of variant allele frequency of the genetic variants identified in this study.
Figure 2
Figure 2
Kaplan-Meier Analysis of Heart Failure Hospitalization in the AS Patients of this Study AS patients harboring CHIP had significantly higher HFH rate than those without. (5-year HFH rate: 22.7% vs 11.7%; adjusted HR: 3.060; 95% CI: 1.090-8.589; P = 0.034).
Central Illustration
Central Illustration
The Prevalence and Clinical Impact of CHIP in Patients With Severe AS In this study, 36.4% of the 110 severe AS patients undergoing transcatheter aortic valve implantation (TAVI) were found to harbor CHIP. The presence of CHIP is a strong predictor for a higher HFH rate post-TAVI.
See this image and copyright information in PMC

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