Negative Impact of TET2 Mutations on Long-Term Survival After Transcatheter Aortic Valve Replacement

Figures

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  Figure 1. Large Profile of CHIP in Our Patients Studied by Captured-Based High-Throughput Sequencing (A) Prevalence of clonal hematopoiesis of indeterminate potential (CHIP) according to age. (B) Proportion of common CHIP variants in individuals in whom a variant was identified (176 CHIP-positive patients, 392 variants). (C) Molecular landscape showing covariants in 176 CHIP-positive patients. Black boxes indicate several mutations within the same gene. Each column represents 1 patient.

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  Figure 2. Scatter Plot of VAF for Each CHIP-Driver Variant The number of variants identified for each gene is as follows: DNMT3A = 119, TET2 = 110, PPM1D = 25, ASXL1 = 27, Splicing = 30, TP53 = 16, CBL = 10, others = 55. Splicing includes SF3B1, SRSF2, and U2AF1. The median VAF is shown as horizontal line. Three values are not shown in this graph because of VAFs higher than 50% (1 DNMT3A, VAF 73%, and 2 TET2: VAF 64% and 75%). CHIP = clonal hematopoiesis of indeterminate potential; VAF = variant allele frequency.

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  Figure 3. Incidence of Deaths in CHIP-Positive (VAF ≥2%) Patients Depending on the Genes The bubble size represents the number of patients mutated for the gene on the horizontal axis (also given in absolute number). Genes for which there were fewer than 3 patients mutated were excluded. Abbreviations as in Figure 2.

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  Figure 4. Kaplan-Meier Survival Analyses of AVS Patients During 5 Years of Follow-Up After TAVR (A) Defined by different subgroups depending on the mutated genes. (B) Depending on the TET2-CHIP-driver gene. Patients with a VAF <2% or >10% were excluded, as well as patients who died in the first 30 days after the procedure. AVS = aortic valve stenosis; TAVR = transcatheter aortic valve replacement; CHIP = clonal hematopoiesis of indeterminate potential.

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  Figure 5. Circulating Concentrations of IL-1β, IL-6, IL-8, and TNF-α Cytokines Before TAVR in TET2-Positive (n = 8) and TET2-Negative Patients (n = 24) IL = interleukin; TAVR = transcatheter aortic valve replacement; TNF = tumor necrosis factor.