Abstract 4867: Circulating Chemical and Cellular Injury/Repair Responses Are Linked to the Extent of Heart Injury in Human Myocardial Infarction
Introduction: Circulating injury and repair pathways in human myocardial infarction (MI) are incompletely understood. We investigated rheological and regenerative pathways acutely and in the longer term post-MI.
Methods: Blood constituents implicated in myocardial injury (e.g. red cell volume distribution width, hemoglobin) and repair (circulating CD34+ progenitor cells, serum vascular endothelial growth factor (VEGF), serum thymosin β4 and AcSDKP excreted in urine) were quantified in patients 2 days and 3 months after ST elevation MI (STEMI). Coronary collateral flow was measured invasively during emergency percutaneous coronary intervention. Cardiac function and remodeling were quantified by gadolinium contrast enhanced MRI at 1.5T at these time-points.
Results: Thirty-five consecutive STEMI patients (mean±SD age 58±10 years; 3(9%) women) were included. Mean (SD) thymosin β4 concentration was lower at day 2 compared to at 3 months post-MI (3.0±1.6 vs. 7.0±2.9 μg/L; P<0.0001). Two days post-MI, AcSDKP correlated negatively with white cell count (R=−0.54; P=0.024) and VEGF (R=−0.57; P=0.038). After adjustment for white cell count, AcSDKP two days post-MI negatively predicted left ventricular (LV) ejection fraction (R2=0.43; P=0.024) and positively predicted LV end-systolic volume index (R2=0.56; P=0.011) at 3 months. At follow-up, CD34+ count negatively predicted myocardial infarct mass (R2=0.29; P=0.015) and LV end-systolic volume index (R2=0.20; P=0.02). Delta CD34+ negatively predicted infarct mass (R2=0.13; P=0.049) at 3 months. Mean red cell volume at day 2 negatively predicted LV end-systolic volume index (R2=0.24; P=0.038) and infarct size (R2=0.13; P=0.045) at 3 months. In multivariable analyses, VEGF at day 2 predicted LV end-diastolic volume index at follow-up (coefficient of variation (95% CI) −0.021 (−0.038, −0.035); P=0.021). Coronary collateral supply was negatively predicted by hemoglobin (−0.04 (−0.06, −0.11); P=0.006) and positively predicted by red cell volume distribution width (0.06 (0.02, 0.10); P=0.004) and platelet count (0.001 (0.0001, 0.002); P=0.001) at day 2.
Conclusions: Circulating injury/repair responses predict coronary collateral recruitment and cardiac function and remodeling post-MI.