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Clonal Hematopoiesis Is Associated With Adverse Clinical Outcomes and Left Ventricular Remodeling in Aortic Stenosis
Chi-Yuan Yao1, Tsung-Yu Ko2, Li-Tan Yang3
1Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Insights
Clonal hematopoiesis of indeterminate potential (CHIP) increases heart failure risk in severe aortic stenosis patients after TAVI. CHIP may be an actionable target for AS treatment.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Genetics
Background:
- Clonal hematopoiesis of indeterminate potential (CHIP) is linked to systemic inflammation and atherosclerotic cardiovascular diseases like aortic stenosis (AS).
- CHIP is an emerging risk factor for cardiovascular events.
Purpose of the Study:
- To assess the clinical impact of CHIP in patients with severe AS undergoing transcatheter aortic valve implantation (TAVI).
- To identify associations between CHIP and clinical, laboratory, and echocardiographic parameters.
Main Methods:
- Retrospective analysis of 110 severe AS patients undergoing TAVI.
- Targeted next-generation sequencing to detect CHIP-associated somatic mutations.
- Multivariate Cox regression analysis to determine the primary endpoint of post-TAVI heart failure hospitalization.
Main Results:
- CHIP was identified in 36.4% of patients, with DNMT3A, TET2, and ASXL1 as the most common mutations.
- CHIP was associated with a significantly higher rate of heart failure hospitalization (adjusted HR: 3.060; P = 0.034) over a median follow-up of 55.2 months.
- CHIP patients exhibited higher serum ferritin, left ventricular hypertrophy, and diastolic dysfunction.
Conclusions:
- CHIP adversely impacts clinical outcomes in AS patients undergoing TAVI, potentially due to inflammation and maladaptive left ventricular remodeling.
- Further prospective trials are needed to validate these findings and explore CHIP as a therapeutic target in AS.
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.
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