Impact of Carrying DNMT3A or TET2 Mutations on Plaque Characteristics and Prognosis in Patients With STEMI Based on OCT.

Abstract

Background: Clonal hematopoiesis of indeterminate potential is a novel, nontraditional risk factor linked to coronary heart disease. DNMT3A and TET2 are the 2 most prevalent clonal hematopoiesis of indeterminate potential-associated driver genes. This study aims to evaluate their effects on plaque characteristics and prognosis in patients with ST-segment-elevation myocardial infarction.

Methods: Consecutive patients with ST-segment-elevation myocardial infarction (May 2017-May 2019) undergoing routine optical coherence tomography were enrolled. Targeted deep exome sequencing of peripheral blood (custom panel targeting DNMT3A and TET2) identified mutations (with a threshold variant allele frequency ≥2%). The primary end point was major adverse cardiovascular events, defined as a composite end point that includes all-cause death, nonfatal myocardial infarction, nonfatal stroke, and revascularization due to clinical ischemic events.

Results: Among 628 patients, 12.3% were identified as carriers of DNMT3A or TET2 gene mutations. Patients with DNMT3A/TET2 mutations were older (62.5 versus 55.6 years; P<0.001), while the 2 groups showed comparable prevalence rates of hypertension (48.1% versus 43.2%), diabetes (22.1% versus 22.3%), and dyslipidemia (53.2% versus 61.7%). Carriers demonstrated greater plaque vulnerability characteristics on optical coherence tomography, including a higher macrophage proportion, smaller minimal lumen area, thinner fibrous cap, and higher lipid index. During a median follow-up of 2.4 years (interquartile range 2.0-3.0), major adverse cardiovascular events rates were significantly higher in the mutation group (39.5% versus 19.9%; P<0.001). Both DNMT3A/TET2 mutations (adjusted hazard ratio, 1.91 [95% CI, 1.19-3.07]; P=0.008) and TET2 mutations specifically (adjusted hazard ratio, 3.57 [95% CI, 1.78-7.17]; P<0.001) independently predicted major adverse cardiovascular events occurrence in patients with ST-segment-elevation myocardial infarction.

Conclusions: Patients with ST-segment-elevation myocardial infarction and DNMT3A/TET2 mutations exhibit vulnerable characteristics in their coronary plaques, along with an increased risk of experiencing major adverse cardiovascular events. Moreover, carrying TET2 mutations confers a worse prognosis compared with solely having DNMT3A mutations.