Clinical research in cardiology : official journal of the German Cardiac Society · 2025
Impact of clonal hematopoiesis of indeterminate potential on prognosis in patients with severe aortic valve stenosis: a meta-analysis.
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Sun Huang, Li Ruijie, Cao Xingyu, Wang Huawei, Ding Peng, Ang Yan, Guo Xiying
Аннотация
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.
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.