Background Clonal hematopoiesis of indeterminate potential (CHIP), commonly involving TET2 and DNMT3A mutations, is increasingly recognized as a cardiovascular risk factor, but its prognostic role in severe aortic valve stenosis (AVS) remains unclear. This study aimed to systematically evaluate the impact of CHIP on survival in AVS patients undergoing valve replacement. Methods A systematic search of PubMed, Embase, Web of Science, and Scopus through May 2025 identified observational studies of CHIP in AVS patients undergoing valve replacement. Eligible studies used validated genomic sequencing methods to identify CHIP and reported mortality outcomes. Two reviewers independently extracted study characteristics, outcomes, and related variables. Pooled hazard ratios (HRs) were calculated, with subgroup analyses by mutation type and geographic region, and meta-regression to assess effect modifiers. Risk of bias was assessed using the Newcastle–Ottawa Scale, and sensitivity and publication bias analyses were also assessed. Results Five studies with 1,175 patients were included. CHIP showed a non-significant trend toward increased all-cause mortality (HR = 1.58; 95% CI: 0.97–2.57; P = 0.0687; I2 = 64.8%). When defined by TET2 mutations, CHIP was significantly associated with worse survival (HR = 1.91; 95% CI: 1.43–2.56; P < 0.001, I2 = 0%), whereas DNMT3A mutations were not. In Western cohorts, CHIP was significantly associated with increased mortality (HR = 1.65; 95% CI: 1.28–2.12; P < 0.0001; I2 = 38.7%). Meta-regression identified body mass index (BMI) as a significant modifier of the CHIP–mortality association (P = 0.0069). Conclusions CHIP, particularly TET2-related mutations, is associated with poorer survival in patients with severe AVS undergoing valve replacement. In Western populations, CHIP was significantly associated with increased mortality. Higher BMI further strengthened this association across all patients. These findings indicate that CHIP may be a potential marker for risk stratification and preventive strategies, but confirmation in larger and more diverse cohorts is required. Graphical Abstract

Impact of clonal hematopoiesis of indeterminate potential on prognosis in patients with severe aortic valve stenosis: a meta-analysis

期刊论文
发表日期：

2025年12月15日

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Huang Sun,
Ruijie Li,
Xingyu Cao,
Huawei Wang,
Peng Ding,
Yan Ang,
Xiying Guo

摘要

Background

Clonal hematopoiesis of indeterminate potential (CHIP), commonly involving TET2 and DNMT3A mutations, is increasingly recognized as a cardiovascular risk factor, but its prognostic role in severe aortic valve stenosis (AVS) remains unclear. This study aimed to systematically evaluate the impact of CHIP on survival in AVS patients undergoing valve replacement.

Methods

A systematic search of PubMed, Embase, Web of Science, and Scopus through May 2025 identified observational studies of CHIP in AVS patients undergoing valve replacement. Eligible studies used validated genomic sequencing methods to identify CHIP and reported mortality outcomes. Two reviewers independently extracted study characteristics, outcomes, and related variables. Pooled hazard ratios (HRs) were calculated, with subgroup analyses by mutation type and geographic region, and meta-regression to assess effect modifiers. Risk of bias was assessed using the Newcastle–Ottawa Scale, and sensitivity and publication bias analyses were also assessed.

Results

Five studies with 1,175 patients were included. CHIP showed a non-significant trend toward increased all-cause mortality (HR = 1.58; 95% CI: 0.97–2.57; P = 0.0687; I² = 64.8%). When defined by TET2 mutations, CHIP was significantly associated with worse survival (HR = 1.91; 95% CI: 1.43–2.56; P < 0.001, I² = 0%), whereas DNMT3A mutations were not. In Western cohorts, CHIP was significantly associated with increased mortality (HR = 1.65; 95% CI: 1.28–2.12; P < 0.0001; I² = 38.7%). Meta-regression identified body mass index (BMI) as a significant modifier of the CHIP–mortality association (P = 0.0069).

Conclusions

CHIP, particularly TET2-related mutations, is associated with poorer survival in patients with severe AVS undergoing valve replacement. In Western populations, CHIP was significantly associated with increased mortality. Higher BMI further strengthened this association across all patients. These findings indicate that CHIP may be a potential marker for risk stratification and preventive strategies, but confirmation in larger and more diverse cohorts is required.

Graphical Abstract