Abstract 13671: Lymphocyte Depletion Post STEMI Confers Poor Prognosis: a Potential Role for T Lymphocytes and the Key Chemokine Fractalkine in Myocardial Ischemia/Reperfusion Injury
Introduction: We have previously shown depletion of circulating T lymphocytes (T cells) following primary percutaneous coronary intervention (PPCI) for STEMI. The goal of this study was to assess the prognostic significance of lymphocyte depletion, characterize the cells involved, and explore potential mechanisms.
Methods and Results: Lymphocyte counts were retrospectively analyzed in 1377 consecutive STEMI patients treated with PPCI and discharged alive. Lymphopenia post PPCI was associated with lower survival at 3 years (79.3% vs 95.6%, lowest vs. highest tertile, p<0.001), independent of age and sex (hazard ratio 2.4, 95% CI 1.4-4.1).
For cell characterization studies, arterial blood from 52 STEMI patients undergoing PPCI was sampled at 0, 15, 30, 90min and 24hrs after reperfusion. Absolute numbers of different leucocyte subpopulations were quantified by flow cytometry and are presented as % change ± SEM. Total T cells fell by -36±3% between 0 and 90 minutes (p<0.0001), before recovery by 24 hours. CD8 T cells declined by -48±4% and CD4 cells by -26±3%. Within each of these, the highly differentiated subsets (effector memory and TEMRA) showed greater decline than the less differentiated naïve and central memory cells. Monocytes (-16±4%) and natural killer (NK; -56±4%) cells also fell, while granulocytes did not. The fall in T cells between 15 and 30 minutes correlated with development of microvascular obstruction (MVO) on cardiac MRI (r=0.568, p<0.001).
The populations with the largest drops (highly differentiated T cells, and NK cells) expressed high levels of the chemokine receptor CX3CR1. Moreover, serum concentration of the CX3CR1 ligand fractalkine, a key chemokine in leucocyte migration, fell to 59±7% of baseline at 15 minutes, increased to 139±10% at 90 minutes, then returned towards baseline at 24 hours (p<0.001). As such, dynamic changes in cell counts can be seen to follow changes in serum fractalkine concentration.
Conclusions: Lymphopenia following STEMI treated by PPCI is associated with a poorer prognosis. T cell counts drop after PPCI, and their early decline correlates with development of MVO, a known poor prognostic feature. We hypothesize that fractalkine contributes to leucocyte shifts, which in turn may influence the extent of MVO.
Author Disclosures: S. Boag: None. E. Shmeleva: None. N. Howard: None. R. Das: None. M. Egred: None. A. Zaman: None. A. Bagnall: None. W. Owens: None. B. Keavney: None. I. Spyridopoulos: None.
- © 2014 by American Heart Association, Inc.