Heart, Lung and Circulation

Evidence for an Acute Diffuse Fibrotic Response Throughout the Left Ventricle Following Acute Myocardial Infarction

      Introduction: A fundamental process in the development of ischaemic cardiomyopathy is left ventricular (LV) remodeling, characterised by structural and functional abnormalities throughout the entire myocardium. However, contributing factors and time-course of this process are not well understood.
      Methods: We assessed the temporal evolution of LV remodeling in patients 1–24, 52–243, and 180–7300 days post-acute myocardial infarction (MI) forming the acute (n = 25), subacute (n = 21), and chronic MI (n = 15) groups, respectively. Contrast-enhanced cardiac magnetic resonance imaging evaluated LV morphology and function, with post-contrast T1 mapping to semi-quantitatively assess myocardial fibrosis. Controls (n = 20) without prior MI were also scanned.
      Results: Age, gender, diabetic and hypertensive status were similar across all groups (p > 0.05). Compared with controls, LV ejection fraction (LVEF) was reduced, and indexed LV mass and LV end-diastolic volume were increased in all MI groups. Abnormalities of myocardium remote to the area of infarction were present immediately after acute infarction, with reduced systolic thickening compared to controls (60 ± 5% vs. 106 ± 8%, p = 0.009), and diffuse fibrosis suggested by lower T1 times compared to controls (437 ± 25 ms vs. 549 ± 27 ms, p = 0.02). These changes persisted at all stages post MI. T1 times correlated with acute and subacute LVEF (r = 0.43, p = 0.05; r = 0.50, p = 0.03, respectively) and systolic thickening in acute infarct (r = 0.46, p = 0.04) and subacute peri-infarct regions (r = 0.56, p = 0.02).
      Conclusion: Acute MI triggers immediate remodeling changes in the remote myocardium, characterised by diffuse fibrosis and systolic dysfunction that persist into chronic stages. This is the first demonstration in humans of an acute diffuse fibrotic response in the entire myocardium post-acute MI.