Temporal changes in biomarkers and their relationships to reperfusion and to clinical outcomes among patients with ST segment elevation myocardial infarction

Abstract

Coronary plaque rupture mediating acute ST segment elevation myocardial infarction (STEMI) is associated with a systemic inflammatory response. Whether early temporal changes in inflammatory biomarkers are associated with angiographic and electrocardiographic markers of reperfusion and subsequent clinical outcomes is unclear. In the APEX-AMI biomarker substudy, 376 patients with STEMI had inflammatory biomarkers measured at the time of hospital presentation and 24 h later. The primary outcome was the 90-day composite of death, shock, or heart failure. Secondary reperfusion outcomes were (1) worst least residual ST segment elevation (ST-E: <1 mm, 1 to <2 mm, ≥2 mm) and (2) post-percutaneous coronary intervention (PCI) TIMI flow grade (0/1/2 vs 3) and TIMI myocardial perfusion grade (TMPG 0/1 vs 2/3). The 90-day incidence of death, shock or heart failure was 21.3 % in this cohort. Electrocardiographic reperfusion (worst residual ST-E <1 mm, 1 to<2 mm, ≥2 mm) was associated with differences in 24 h change in N-terminal proB-type natriuretic peptide (NT-proBNP) (1192.8, 1332.5, 1859.0 ng/mL; p = 0.043) and the pro-inflammatory cytokines Interleukin (IL)-6 (14.0, 13.6, 22.1 pg/mL; p = 0.016), IL-12 (-0.5, -0.9, -0.1 pg/mL; p = 0.013), and tumor necrosis factor α (TNFα) (1.0, 0.6, 3.6 pg/mL; p = 0.023). Angiographic reperfusion (TMPG 0/1 vs 2/3) was associated with changes in median NT-proBNP (2649.3, 1382.7 ng/mL; p = 0.002) and IL-6 (28.7, 15.1; p = 0.040). After adjustment for baseline covariates, the 24 h change in the pro-inflammatory cytokine TNFα [hazard ratio (HR) 0.49; 95 % CI 0.26-0.95; p = 0.035] and the anti-inflammatory cytokine IL 10 (HR 1.41; 95 % CI 1.06-1.87; p = 0.018) were independently associated with the primary composite outcome. Successful coronary reperfusion was associated with less systemic inflammatory response and greater temporal inflammatory changes were independently associated with higher 90-day composite of death, shock, or heart failure. These findings provide support for an association between success of reperfusion, an acute STEMI inflammatory response and subsequent clinical outcomes.

Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs

“…These cascade reactions in the early phase of reperfusion contribute largely to myocardial necrosis (summarized in [46,47]) and intervening clinically at this phase could provide cardioprotection. On the other hand, progressive reperfusion contributes towards cardiac tissue repair also known as cardiac remodeling.…”

“…However, the process of cardiac remodeling by itself carries deleterious effects and is the leading cause for heart failure after myocardial infarction. Effectively regulating the process of tissue repair could substantially reduce the deleterious effects of remodeling [47]. The current study aimed to attenuate I/R injury by pharmacologically intervening with Dex during the early reperfusion phase.…”

Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association

“…36 There is growing recognition of the cytokine cascade, chemokine response, and inducible NO synthase expression associated with coronary plaque rupture. 26,[41][42][43][44][45][46] As previously described, putative mechanisms also are associated with a "wet and warm" CS presentation wherein a systemic inflammatory response syndrome and vasodilation can occur after an MI. 26,47 This phenotype is characterized by systemic inflammatory response syndrome features, lower systemic vascular resistance, and a higher risk of sepsis and mortality.…”

Circulating plasma dipeptidyl dipeptidase 3 and the prognosis of cardiogenic shock

“…Biological pathways that affect systemic inflammation, neurohormonal modulation, and extracellular matrix remodelling are all altered in cardiogenic shock . Multiple studies have demonstrated the marked change in inflammatory markers and downstream mediators after myocardial infarction . Vasopressin and angiotensin II levels increase in the setting of cardiogenic shock, altering fluid and salt homeostasis .…”

“…1,3 Multiple studies have demonstrated the marked change in inflammatory markers and downstream mediators after myocardial infarction. 4,5 Vasopressin and angiotensin II levels increase in the setting of cardiogenic shock, altering fluid and salt homeostasis. 1 Alterations of the renin-angiotensin system also affects extracellular remodelling pathways.…”