THALLIUM UPTAKE AND MORPHOLOGIC CORRELATES IN CHRONIC ISCHEMIC HEART DISEASE: EVIDENCE FOR MYOCARDIAL REMODELING IN NON-INFARCTED MYOCARDIUM Thallium is a clinically important tracer for assessment of both regional blood flow and myocardial viability. However, in some patients with chronic ischemic heart disease, the severity of left ventricular dysfunction at rest may be disproportionate to the extent of ischemic myocardial injury as assessed by thallium. In 13 patients with chronic ischemic heart disease (mean LVEF=14+6% at rest), enlisted for cardiac transplantation, we examined the relation between pre-transplantation quantitative thallium uptake and post-transplantation extent and distribution of collagen replacement in infarct and non-infarct myocardium, segmental wall thickness, and severity of coronary artery narrowing. Structurally normal hearts of 13 age-matched adults were used as controls. Histologic assessment of myocardial fibrosis in 104 mid left ventricular segments stained with picrosirius red showed an inverse relationship between volume fraction of collagen and wall thickness (r=-0.70, p<0.001). Volume fraction of collagen was significantly higher in irreversible (30.9+15.8%) compated to reversible (20.2+12.6%, p<0.001) or normal thallium segments (15.0+8.7%, p<0.001). The higher collagen content in irreversible thallium segments was associated with lower wall thickness and more severe cross-sectional coronary artery narrowing when compared to reversible and normal thallium segments. Significant differences also exist in the magnitude of thallium uptake among segments with and without an infarct. Mean volume fraction of collagen was significantly lower in non-infarcted segments (13+6%) when compared to infarct segments (36+13%, p<0.001) but higher when compared to structurally normal, control hearts (4+2%, p<0.001). These histomorphologic data suggest that in patients with chronic ischemic heart disease and severe left ventricular dysfunction, there is an overall good relationship between patterns of thallium uptake and the magnitude of collagen replacement, segmental wall thickness, and severity of cross-sectional coronary artery narrowing. The finding of scattered areas of microscopic and patchy replacement fibrosis in non-infarcted myocardial segments provides an potential explanation for the observed disproportionalety between severity of left ventricular contractile dysfunction at rest and the extent of ischemic myocardial injury assessed by thallium. - left ventricular ejection fraction (LVEF), single photon emission computerized tomography (SPECT) - Human Subjects