Prothrombotic fibrin clot phenotype as a risk factor for persistent left ventricular thrombus following acute myocardial infarction

Abstract Background Left ventricular thrombus (LVT) occurs in up to 15% of ST-segment elevation myocardial infarction (MI) patients and may persist in 30% despite anticoagulation. We hypothesized that formation of dense and poorly lysable fibrin clots may contribute to this phenomenon. Purpose We investigated whether unfavorable fibrin clot properties and their determinants are associated with resolution of LVT on anticoagulation. Methods We included 149 consecutive patients with LVT during acute MI referred for diagnostic work-up. Three months after MI we determined plasma fibrin clot permeability (Ks), clot lysis time (CLT) and plasminogen activator inhibitor-1 (PAI-1), along with citrullinated histone H3 (citH3), a marker of NETosis. LVT resolution was assessed on enrollment (after 3 months of anticoagulation mostly with direct oral anticoagulants n=121, 82%) and 3 months thereafter. Results Patients with LVT visible at 3 months (n=75, 50.3%) were characterized by lower Ks (-15.5%) and longer CLT (+30%), along with higher PAI-1 (+42.4%) and citH3 (+33.3%), without differences in the type of anticoagulation. At 6 months post MI on continued anticoagulation, LVT was visible in 44 (29.7%) of patients, who had more prothrombotic fibrin clot properties as compared with individuals with resolved LVT. Lower Ks and longer CLT were associated with LVT persistence at 3 and 6 months, irrespective of potential confounding factors. Conclusion This is the first study to demonstrate that prothrombotic fibrin clot properties, in part related to enhanced NETosis, are associated with anticoagulation failure in patients with LVT following acute MI. This indicates that a subset of LVT patients should receive more effective antithrombotic therapies.