Effect of clonal hematopoiesis on plaque morphology and prognosis in patients with acute myocardial infarction.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is related to cardiovascular disorders and poor prognosis. However, the relationship between CHIP and clinical outcome as well as pathological phenotype of patients with acute myocardial infarction was unknown. Herein, we aimed to investigate the associations between CHIP mutation stratified by variant allele frequency (VAF) from 0.5% to 2% and the incidence of major adverse cardiovascular events (MACE) as well as the characteristics of culprit lesions in patients with ST-segment elevation myocardial infarction (STEMI).

Methods: Targeted deep sequencing with a unique molecular identifier (UMI) was used to examine CHIP with VAFs greater than 0.5%, 1%, and 2% in prospective cohort including a total of 1403 patients with STEMI, and MACE including all-cause death, myocardial infarction, stroke, and unplanned revascularization during follow-up was recorded. In addition, the morphology of culprit plaques detected by optical coherence tomography (OCT) in 355 patients with de novo lesions were evaluated via image analysis.

Results: The CHIP mutation frequency in each VAF stratification increased with increasing age. Patients with either TET2 or ASXL1 CHIP mutations presented significantly greater mortality than those without for VAF > 2%, 1%, and 0.5% (17.1% vs. 10.1%, p = 0.0001; 17.0% vs. 10.3%, p = 0.0464; and 17.8% vs. 9.8%, p = 0.0025 for VAF > 2%, 1%, and 0.5%, respectively). For other MACE including myocardial infarction, stroke and unplanned revascularization, no significant difference was observed. Simultaneous assessment of CHIP and systemic inflammation revealed combined effects on all-cause mortality, depicted by significant higher risk for patients with high-sensitivity C-reactive protein level > 5.8 mg/L and concomitant CHIP. Moreover, subgroup analysis revealed that patients with CHIP mutations got greater clinical benefit of ticagrelor and statin than those without CHIP. Additionally, patients with TET2/ASXL1 VAFs of > 0.5% and 1% were significantly prone to exhibit a greater prevalence of ruptured fibrous cap in culprit lesions than those without (33 [70.2%] vs. 145 [47.1%], p = 0.0031; 16 [72.7%] vs. 162 [48.6%], p = 0.0287).

Conclusions: TET2/ASXL1 CHIP mutations with VAF > 2% combined with high inflammatory status were indicative of high mortality in patients with STEMI. Additionally, TET2/ASXL1 mutation with a VAF > 0.5% favored the recognition of vulnerable plaque features in patients with STEMI.