Coagulation factor XIII activity predicts left ventricular remodelling after acute myocardial infarction

Abstract

Aims: Acute myocardial infarction (MI) is the major cause of chronic heart failure. The activity of blood coagulation factor XIII (FXIIIa) plays an important role in rodents as a healing factor after MI, whereas its role in healing and remodelling processes in humans remains unclear. We prospectively evaluated the relevance of FXIIIa after acute MI as a potential early prognostic marker for adequate healing.

Methods and results: This monocentric prospective cohort study investigated cardiac remodelling in patients with ST-elevation MI and followed them up for 1 year. Serum FXIIIa was serially assessed during the first 9 days after MI and after 2, 6, and 12 months. Cardiac magnetic resonance imaging was performed within 4 days after MI (Scan 1), after 7 to 9 days (Scan 2), and after 12 months (Scan 3). The FXIII valine-to-leucine (V34L) single-nucleotide polymorphism rs5985 was genotyped. One hundred forty-six patients were investigated (mean age 58 ± 11 years, 13% women). Median FXIIIa was 118% (quartiles, 102-132%) and dropped to a trough on the second day after MI: 109% (98-109%; P < 0.001). FXIIIa recovered slowly over time, reaching the baseline level after 2 to 6 months and surpassed baseline levels only after 12 months: 124% (110-142%). The development of FXIIIa after MI was independent of the genotype. FXIIIa on Day 2 was strongly and inversely associated with the relative size of MI in Scan 1 (Spearman's ρ = -0.31; P = 0.01) and Scan 3 (ρ = -0.39; P < 0.01) and positively associated with left ventricular ejection fraction: ρ = 0.32 (P < 0.01) and ρ = 0.24 (P = 0.04), respectively.

Conclusions: FXIII activity after MI is highly dynamic, exhibiting a significant decline in the early healing period, with reconstitution 6 months later. Depressed FXIIIa early after MI predicted a greater size of MI and lower left ventricular ejection fraction after 1 year. The clinical relevance of these findings awaits to be tested in a randomized trial.

Keywords: Blood coagulation factor XIII; Cardiac magnetic resonance imaging; Healing and remodelling processes; ST-elevation myocardial infarction.

Figure 1

Study flow. cMRI, cardiac magnetic resonance imaging; FXIII, factor XIII.

Figure 2

Short‐term and long‐term changes of FXIII activity levels after myocardial infarction. FXIIIa significantly declined in the course of the first days after myocardial infarction and recovered within 2 months. After 12 months, the levels of FXIIIa were significantly higher compared with those on the first post‐MI measurement on Day 2. D, day; FXIII, factor XIII; Mo, month.

Figure 3

Relation of FXIIIa levels with indices of cardiac remodelling. Spearman correlation between FXIIIa levels measured within the first 7 to 9 days after myocardial infarction and repetitively measured cardiac MRI parameters. (A) Strength of correlation with LVEDVi and LVEF at baseline (i.e. within the first 96 h after MI; cMRI Scan 1), after 7–9 days (Scan 2), and after 12 months (Scan 3). (B) Strength of correlation with rIS at baseline (i.e. within the first 96 h after MI; cMRI Scan 1), after 7–9 days (Scan 2), and after 12 months (Scan 3); and with infarct expansion represented by the difference in rIS between Scan 2 and Scan 1. The colour represents the correlation coefficient, with bluish colours for positive and reddish colours for negative correlations. The area of the individual dot represents the number of patients in each separate analysis. LVEDVi, left ventricular end‐diastolic volume indexed to body surface area; LVEF, left ventricular ejection fraction; rIS, relative infarct size. * indicates P < 0.05, and ** P < 0.01.