Variations in collagen content of asynergic left ventricular segments in explanted hearts of men with ischemic cardiomyopathy

Abstract

Transmural left ventricular (LV) biopsies obtained at the time of coronary artery surgery have been used to evaluate the histomorphologic features of viable myocardium in patients with ischemic cardiomyopathy. 1–16 Usually, 1 or 2 biopsies are obtained from the center of the LV region supplied by the left anterior descending coronary artery. The biopsy specimens (1.2 to 1.5 mm in diameter) are subsequently used for quantifi cation of collagen using grids with visual point counting. 1–16 The degree of myocardial fi brosis in these biopsy samples has been correlated with the results of various noninvasive tests used for assessment of preoperative regional myocardial viability. However, it is unclear whether the data obtained from these transmural biopsy samples would uniformly refl ect the overall histomorphologic features of the entire LV region as evaluated by noninvasive imaging techniques. In this study, we determined the extent of variation in volume fraction of collagen of 2-mm-wide (biopsy-equivalent) consecutive transmural sections of mid-LV anterior wall from explanted hearts of men with chronic ischemic heart disease. Moreover, we examined the variability of fi brosis in normal, ischemic, and scarred myocardium as assessed by thallium.  The 13 men with ischemic cardiomyopathy awaiting cardiac transplantation were prospectively enrolled in a study determining the relation of thallium uptake to myocardial fi brosis. 17 Patients’ ages ranged from 41 to 62 years (mean 54). All patients had severe (New York Heart Association functional class III to IV) heart failure and/or angina pectoris and multivessel coronary artery disease, and were listed as stable outpatients at the time of enrollment. Patients with recent acute myocardial infarction or unstable angina were excluded from the study. Cardiac transplantation was performed at a mean of 6 2 months after the nuclear imaging studies. The explanted hearts were fi rst fi xed in formaldehyde. The left ventricle was then sliced transversely at a mean thickness of 8 mm/slice from apex to base. A mid-LV slice was divided into 8 large segments. The 2 large segments representing the anterior wall were then embedded in paraffi n, cut at a thickness of 5 m and stained with picrosirius red. These segments were further divided into consecutive 2-mmwide transmural sections. Percent collagen was then quantifi ed using a computerized image analysis system (Quantimet 520, Cambridge, Massachusetts) in the large segments and in each small section, as previously described. 18 All patients underwent stress-redistribution-reinjection thallium single-photon emission computed tomography. Short-axis tomograms at the mid left ventricle, corresponding to that used for the histomorphologic study, from the 3 sets of thallium images (stress, redistribution, and reinjection) were analyzed objectively, using a semiautomated quantitative circumferential profi le as previously described. 19 Briefl y, for each patient, an operator-defi ned region of interest was drawn around the LV activity of each short-axis slice on the corresponding stress, redistribution, and reinjection images. As with the histologic assessment, the myocardial activity was divided into 8 segments of equal arcs, beginning at the center of the anterior LV wall and proceeding clockwise. Mean counts per pixel within the 2 anterior wall segments (anteroseptal and anterolateral) on stress, redistribution, and reinjection images were computed. The myocardial segment with the highest thallium activity on the stress tomogram was used as the normal reference segment. The same segment in redistribution and reinjection thallium