CHIP was found in 39.6% of early AVS patients and independently increased AVS progression risk (HR 1.82) and mortality (24% vs. 13.7%) over 4 years.
Does the presence of Clonal Hematopoiesis of indeterminate potential (CHIP) predict disease progression and mortality in patients with lower grade aortic valve stenosis?
CHIP is highly prevalent in early-stage aortic valve stenosis and serves as an independent blood-based biomarker predicting disease progression and increased mortality.
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Abstract Introduction Aortic valve stenosis (AVS) initiates as clinically inapparent calcification or mild stenosis, progression to severe aortic stenosis is associated with significant increases in morbidity and mortality. Biomarkers that identify patients at risk for progression are currently lacking. Clonal Hematopoiesis of indeterminate potential (CHIP) has been associated with adverse outcomes in cardiovascular disease, its effect on progression risk and mortality in patients with lower grade AVS is unknown. Purpose This study aims to evaluate the influence of CHIP on progression risk and subsequent outcomes in a prospective cohort of patients with lower grade AVS. Methods 270 patients were recruited in the study at diagnosis of AVS and followed up prospectively, blood was collected at study inclusion. A targeted NGS capture panel for 48 CH associated driver genes was used to diagnose CH with a minimal Variant Allele Frequency (VAF) of 0.5%, CHIP was defined according to the WHO definition (VAF ≥2% after preprocessing and variant calling). Progression was defined as an increment in AVS grading from mild stenosis or AV sclerosis to at least moderate AVS, progression from moderate to severe AVS or progression requiring valve replacement. Maximum follow up was 4 years, statistical analyses were conducted using SPSS 29.0.2.0. and R 4.4.2. Kaplan Meier log-rank and Cox regression were performed for univariate and multivariable survival analyses. Results 597 candidate driver mutations in 34 genes were detected in 224 patients (83%), 39.6% of patients fulfilled diagnostic criteria for CHIP. DNMT3A (40,4%) and TET2 (30%) were the most frequently mutated genes (Fig. 1). Patients with and without CHIP did not differ significantly with respect to age, sex, comorbidities and extent of AVS at baseline. During a median echocardiographic follow up of 647 days CHIP (+) patients showed significantly higher AVS progression rates (progression-free survival: 45.9% vs. 60.7%, p0.001, Median progression free survival: 806 vs. 1301 days) (Fig. 2a). Multivariable Cox regression showed CHIP to be the only independent risk factor to be significantly associated with AVS progression (adj. p=0.019; HR: 1.822, 95% CI: 1.236-2.685) (Fig. 2c). Within the follow-up period, 31% of CHIP (+) patients progressed to severe AVS or required valve replacement, compared to 24.6% of CHIP (-) patients. Mortality was significantly increased in CHIP (+) patients (24% vs. 13.7%, p=0.029) (Fig. 2b), with maximum VAF as a continuous variable correlating with mortality risk (p=0.012). Conclusion CHIP is highly prevalent in early-stage AVS and serves as an independent predictor of progression risk and mortality. CHIP-positive patients exhibited enhanced risk of AVS progression, suggesting a potential mechanistic role in disease pathology. These findings highlight CHIP as a blood-based biomarker for AVS risk stratification even in the context of other classical cardiovascular risk factors.
Jamin et al. (Sat,) reported a other. CHIP was found in 39.6% of early AVS patients and independently increased AVS progression risk (HR 1.82) and mortality (24% vs. 13.7%) over 4 years.