Abstract 4337342: Relationship Between Circulating Cardiac Troponin I Levels and Coronary Flow Reserve in a Porcine Model of Chronic Coronary Artery Disease

Abstract

Introduction: Recent clinical data have revealed a role for circulating cardiac troponin I (cTnI) concentrations as a prognostic tool in patients with stable coronary artery disease (CAD). However, the mechanisms underlying cTnI elevations in this population are poorly understood. We utilized a porcine model of chronic CAD to test the hypothesis that cTnI elevations reflect episodic demand-induced ischemia distal to a coronary stenosis and are therefore associated with more severe impairments in regional coronary flow reserve (CFR). Methods: Juvenile swine (n=66) were instrumented with fixed 1.5mm stenoses on the left anterior descending (LAD) and/or left circumflex (LCx) coronary arteries and followed for up to 5 months. Circulating cTnI concentrations were quantified with a porcine-specific high-sensitivity assay (Life Diagnostics) at a total of 98 timepoints across the study population. At the time of blood sampling, coronary stenosis severity was assessed via angiography and myocardial blood flow was quantified with fluorescent microspheres at rest and during intravenous administration of adenosine (0.9 mg/kg/min) to assess regional CFR. Results: cTnI was detectable in 72 of 98 samples (73%) and averaged 14.1±2.7 ng/L across the study population, which consisted of animals with a mean stenosis severity of 84±2% and mean CFR of 2.7±0.2 in the stenotic territory (vs. 5.3±0.2 in the remote territory; p<0.001). Statistically significant correlations were not observed between cTnI and stenosis severity (r=0.14; p=0.15) or between cTnI and CFR (r=-0.12; p=0.24). Stenosis severity (82±2 vs. 83±3%; p=0.76) and CFR (2.7±0.2 vs. 2.6±0.2; p=0.60) did not differ between animals above vs. below the median cTnI value (3.1 ng/L). Similarly, between-group differences in cTnI were absent when animals were stratified by stenosis severity or CFR ( Figure ). Conclusion: In swine with chronic CAD, cTnI is measurable in the majority of subjects but circulating levels are not related to angiographic stenosis severity or regional CFR. These results suggest that demand-induced ischemia may not be a primary determinant of cTnI release in this population and support investigation of alternative causes of myocardial injury in stable CAD.