Description: Rationale: There is mounting evidence of a higher incidence of coronary heart disease in cytomegalovirus-seropositive individuals. Objective: The aim of this study was to investigate whether acute myocardial infarction triggers an inflammatory T-cell response that might lead to accelerated immunosenescence in cytomegalovirus-seropositive patients. Methods and Results: Thirty-four patients with acute myocardial infarction undergoing primary percutaneous coronary intervention were longitudinally studied within 3 months after reperfusion (Cohort A). In addition, 54 patients with acute myocardial infarction and chronic myocardial infarction were analyzed in a cross-sectional study (Cohort B). Cytomegalovirus-seropositive patients demonstrated a greater fall in the concentration of terminally differentiated CD8 effector memory T cells (T EMRA ) in peripheral blood during the first 30 minutes of reperfusion compared with cytomegalovirus-seronegative patients (–192 versus –63 cells/μL; P =0.008), correlating with the expression of programmed cell death-1 before primary percutaneous coronary intervention ( r =0.8; P =0.0002). A significant proportion of T EMRA cells remained depleted for ≥3 months in cytomegalovirus-seropositive patients. Using high-throughput 13-parameter flow cytometry and human leukocyte antigen class I cytomegalovirus-specific dextramers, we confirmed an acute and persistent depletion of terminally differentiated T EMRA and cytomegalovirus-specific CD8 + cells in cytomegalovirus-seropositive patients. Long-term reconstitution of the T EMRA pool in chronic cytomegalovirus-seropositive postmyocardial infarction patients was associated with signs of terminal differentiation including an increase in killer cell lectin-like receptor subfamily G member 1 and shorter telomere length in CD8 + T cells (2225 versus 3397 bp; P 〈0.001). Conclusions: Myocardial ischemia and reperfusion in cytomegalovirus-seropositive patients undergoing primary percutaneous coronary intervention leads to acute loss of antigen-specific, terminally differentiated CD8 T cells, possibly through programmed cell death-1–dependent programmed cell death. Our results suggest that acute myocardial infarction and reperfusion accelerate immunosenescence in cytomegalovirus-seropositive patients.

Description: Rationale: Inflammation in the setting of acute myocardial infarction (MI) has been linked to risk stratification; however, the release kinetics of inflammatory biomarkers in patients with acute MI has been difficult to establish. Objective: The aim of this study was to determine the kinetics of changes in the levels of several biomarkers specifically linked to inflammation after transcoronary ablation of septal hypertrophy, a procedure that mimics acute MI. Methods and Results: We analyzed release kinetics of C-reactive protein, high-sensitivity C-reactive protein, interleukin-6, soluble CD40 ligand, and peripheral blood leukocyte subsets in patients (n=21) undergoing transcoronary ablation of septal hypertrophy. Blood samples were collected before transcoronary ablation of septal hypertrophy and at various times after transcoronary ablation of septal hypertrophy. Serum levels of C-reactive protein were increased at 24 hours (1.0 mg/dL [interquartile range [IQR], 0.7–1.75] versus 0.2 mg/dL [IQR, 0.1–1.05] at baseline [BL]; P 〈0.001), whereas high-sensitivity C-reactive protein increased as early as 8 hours (2.68 mg/L [IQR, 1.23–11.80] versus 2.17 mg/L [IQR, 1.15–5.06] at BL; P =0.002). Interleukin-6 was significantly increased at 45 minutes (2.59 pg/mL [IQR, 1.69–5.0] versus 1.5 pg/mL [IQR, 1.5–2.21] at BL; P =0.002), and soluble CD40 ligand was significantly decreased at 60 minutes (801.6 pg/mL [IQR, 675.0–1653.5] versus 1750.0 pg/mL [IQR, 1151.0–2783.0] at BL; P =0.016). Elevated counts of polymorphonuclear neutrophils were detectable at 15 minutes, with a significant increase at 2 hours (6415 cells/μL [IQR, 5288–7827] versus 4697 cells/μL [IQR, 2892–5620] at BL; P =0.004). Significant monocytosis was observed at 24 hours (729 cells/μL [IQR, 584–1344] versus 523 cells/μL [IQR, 369–701] at BL; P =0.015). Conclusions: Interleukin-6 and neutrophil granulocytes showed a continuous rise at all prespecified time points after induction of MI. Our results provide valuable additional evidence of the diagnostic value of inflammatory biomarkers in the setting of early acute MI.