Abstract 13511: Cardiac Release Kinetics of Soluble Fms-Like Tyrosine Kinase 1 (sflt-1) And Hstroponin T Identify Sflt-1 as an Early Marker of Myocardial Ischemia in Acs
Recent experimental studies revealed that oxygen tension critically regulates differential splicing of the fms-like tyrosine kinase 1 (Flt-1) leading to hypoxia-induced up-regulation of the soluble form of Flt-1 (sFlt-1) from endothelial cells. In order to establish a role for sFlt-1 in myocardial hypoxia and to evaluate its potential diagnostic performance in the early diagnosis of ACS, we measured transcoronary concentration gradients of sFlt-1 and hsTNT as a sensitive marker of myocardial ischemia. Blood samples were simultaneously obtained from the aortic bulb (Ao) and the coronary venous sinus (CVS) of 56 patients with either stable coronary artery disease (CAD, n=30) or acute coronary syndrome (ACS, n=26). Transcoronary concentration gradients were expressed as the difference between CVS and Ao concentration (delta: [CVS]-[Ao]). Circulating sFlt-1 and hsTNT were significantly increased across the coronary circulation during myocardial injury. However, there was no significant correlation between transcoronary gradients of sFlt-1 and hsTNT. Detailed analysis of time from symptom onset to blood sampling disclosed a significant transcoronary gradient for sFlt-1 specifically within the first 3 hours after symptom onset, whereas hsTNT levels increased gradually up to 6-12 hours after symptom onset (figure). ROC curve analysis for sFlt-1 demonstrated an excellent diagnostic performance for early diagnosis of ACS (within 3hrs from symptom onset, AUC 0.869). Indeed, in patients presenting within 2 hours from symptom onset, sFlt-1 was elevated in the CVS despite still normal hsTNT levels. Thus, the positive transcoronary concentration gradient documents the release of sFLT-1 into the coronary circulation during myocardial ischemia. The cardiac release kinetics with a very early release of sFlt-1 suggest that sFlt-1 may reflect myocardial hypoxia and, thus, might be useful as an early diagnostic marker in patients with suspected ACS.
- © 2011 by American Heart Association, Inc.