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.

Objectives: 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 an unfavorable clot phenotype 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.

Conclusions: This is the first study to demonstrate that prothrombotic fibrin clot properties, which might be related to enhanced NETosis, are associated with anticoagulation failure in patients with LVT complicating acute MI.