A dense fibrin network favours layered plaque formation in the infarct-related artery in patients with ST-segment elevation myocardial infarction

Background Layered plaques in epicardial coronary arteries are considered a signature of previous subclinical plaque destabilisation and subsequent healing; however, the mechanisms of their formation remain incompletely elucidated. Purpose We sought to investigate determinants of layered plaques in the infarct-related artery (IRA) with an emphasis on the coagulation system activity and endothelial and vascular dysfunction in patients after primary coronary angioplasty for ST-elevation myocardial infarction (STEMI). Methods Ninety-four STEMI patients were enrolled, including 72 males, with a median age of 61 (interquartile range 54-69) years. In all patients optical coherence tomography (OCT) of IRA was performed twice, first after restoration of epicardial blood flow following aspiration thrombectomy to assess the naive structure of the culprit vessel, and second after stent deployment to assess the procedural result. On admission, thrombin generation was assessed ex vivo by calibrated automated thrombogram including peak thrombin generation and endogenous thrombin potential. Plasma fibrin structure/function was assessed ex vivo by fibrin clot permeability (Ks), reflecting fibrin pore size, and clot lysis time (CLT), reflecting fibrin clot susceptibility to lysis. Endothelial and vascular function were assessed within 3 days using brachial artery flow-mediated dilatation (FMD) and nitroglycerine-mediated dilatation (NMD), respectively. Results The layered plaques in IRA were identified in 67 (71.3%) patients. Patients with layered plaques in IRA versus those without did not differ in terms of age, body mass index, ischaemia time, previous angina, cardiovascular risk factors, lipid profile and enzymatic infarct size but had higher plasma fibrinogen (3.64 [3.21-3.71] versus 3.36 [2.96-4.14] g/L, P=0.024, respectively). Women were more frequent in the group with layered plaques than in the group without (28% versus 8%, P=0.032, respectively). There were no significant differences in OCT characteristics of IRA, FMD, or NMD between the two groups. The presence of layered plaques in IRA was associated with a lower Ks (3.70 [3.01-4.40] versus 5.31 [4.39-6.36] x10-9 cm2, P<0.001) and a longer CLT (128 [107-165] versus 119 [97-141] min, P=0.019), but not with endogenous thrombin potential (P=0.157) or peak thrombin generation (P=0.258). Moreover, Ks correlated inversely with the number of layered plaques (Figure). On multivariable analysis, after adjustment for plasma fibrinogen, Ks (odds ratio [OR] 0.324, 95% confidence interval [CI] 0.176-0.599, P<0.001) was independently associated with the presence of layered plaques in IRA. Conclusions The layered plaques in IRA, identified in two-thirds of STEMI patients, were more common in women and were present irrespective of endothelial and vascular function. Layered culprit plaques in IRA were independently associated with a more compact fibrin network.Correlation plot