Relationship between myocardial collagen and echo amplitude in non-fibrotic hearts

The aim of the study was to investigate the relationship between myocardial collagen and regional echo amplitude in humans with non-fibrotic myocardium. The ratio of myocardial collagen to total myocardial protein was determined as the hydroxyproline/leucine ratio in endoniyocardial biopsies obtained from the right ventricular side of the interventricular septum in orthotopically transplanted hearts. Regional echo amplitude was measured in the interventricular septum. Patients were studied prospectively. Twenty-five patients (five female, 20 male) who had undergone orthotopic cardiac transplantation were studied 355 to 2939 days (1009±718, mean±SD) post-transplantation at the time of annual cardiac catheterization and endomyocardial biopsy. Patient ages varied from 22 to 62 years (46±11). Donor ages were 14 to 47 years (25±8) and the ischaemic time, 90 to 245 min (151±42). Cardiac transplantation was performed for end-stage cardiac failure in all patients. The aetiology of cardiac failure was valvular heart disease in three, dilated cardiomyopathy in eight and ischaemic heart disease in the remainder. Echo amplitude studies were performed within 24 h of endomyocardial biopsy. All but one patient were on an immunosuppressive regime consisting of cyclosporine A and azathioprine with additional steroids in three. The remaining patient, who was the longest surviving patient in the study group, had never been treated with cyclosporine. This patient was maintained on steroids and azathioprine alone. No patient had clinical or histological evidence for acute cardiac rejection and all were clinically well. Five patients had angiographic evidence of coronary artery disease. All subject studies were performed at Harefield Hospital. Echo amplitude analysis was performed at the Royal Brompton Hospital. Myocardial collagen analysis was performed in the Biochemistry Unit at the National Heart and Lung Institute. End-diastolic echo amplitude was measured in the interventricular septum. A micro-analytical technique was used to measure the myocardial hydroxyproline/leucine ratio. There was a weak but significant correlation between the estimate of myocardial collagen measured by the hydroxyproline/leucmne ratio and end-diastolic echo amplitude (r = 0.41, P = 0.04, y = 3.66x + 4.24). If the five patients with angiographically documented coronary artery disease were excluded from analysis the correlation was substantially improved (r = 0.51, P = 0.02, y=4.19x+3.89). These findings suggest that the variation in collagen in the myocardium is responsible for approximately 20% of the observed variation in myocardial backscatter signal in non-fibrotic hearts. This supports clinical studies which have shown increases in myocardial ultrasonic backscatter in conditions where myocardial fibrosis occurs and also indicates the importance of myocardial collagen in determining the ultrasonic backscatter signal in normal hearts.