ABSTRACT NUMBER: ESOC2026A1347 PREVALENCE AND PROGNOSTIC ROLE OF CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL (CHIP) IN ISCHEMIC STROKE PATIENTS: ASSOCIATION WITH CARDIOEMBOLIC SUBTYPE AND INCREASED INFARCT VOLUME

Abstract Background and aims Clonal Hematopoiesis of Indeterminate Potential (CHIP) is an age-related condition from somatic hematopoietic mutations associated with increased cardiovascular and cerebrovascular risk. However, its prevalence, etiological distribution, and prognostic impact in acute ischemic stroke remain unclear. This study investigated these aspects in a stroke cohort. Methods In this prospective observational study, consecutive patients >60 years with a non-lacunar first ischemic stroke were enrolled and underwent complete etiological evaluation and targeted sequencing of 13 CHIP-associated genes during hospitalization. CHIP was defined by presence of ≥1 mutation with Variant Allele Frequency (VAF)≥2%. Outcomes included NIHSS at onset and discharge, infarct volume at 24–72 hours and 3-months mRS. Results Seventy-eight patients (50% female; median age 72) were included. Stroke subtypes were cardioembolic 46%, atherothrombotic 44%, and cryptogenic 10%. CHIP was identified in 21 (27%) patients with the most frequent mutations DNMT3A (48%), TET2 (19%), and SRSF2 (9.5%). Cardioembolic stroke was associated with CHIP (p=0.031), and TET2 mutations were detected only in this etiological subgroup. CHIP with VAF>4%, multiple CHIP mutations and presence of TET2 were associated with higher infarct volume (p=0.07, 0.02 and 0.02). Additionally, there was a trend toward higher NIHSS and poorer 3-months mRS in CHIP patients. However, in multivariable regression analysis, cardioembolic stroke subtype was the main predictor of NIHSS at onset, infarct volume and 3-months mRS. Conclusions CHIP was frequent, particularly in cardioembolic stroke. CHIP with VAF>4%, TET2 and multiple CHIP mutations were associated with larger infarcts, but cardioembolic stroke remained the main predictor of clinical outcomes. Conflict of interest All authors declare no conflicts of interest