DIAGNOSTIC METHODS MYOCARDIAL DISEASE Gallium-67 imaging in patients with dilated cardiomyopathy and biopsy-proven myocarditis

Current standards for detection of myocarditis in a clinical setting rely on endomyocardial biopsy for accurate diagnosis. With this technique a subset of patients with dilated cardiomyopathy show unsuspected myocarditis histologically. Endomyocardial biopsy, despite its specificity, may lack sensitivity due to sampling error if the inflammation is patchy or focal. Therefore, inflammationsensitive radioisotopic imaging may be a useful adjunct in the diagnosis of myocarditis. This study was designed to evaluate the applicability of gallium-67 (67Ga) myocardial imaging as an adjunct to endomyocardial biopsy in the diagnosis of myocarditis. Sixty-eight consecutive patients referred for evaluation of dilated cardiomyopathy underwent 71 parallel studies with 67Ga imaging and biopsies that served as the basis of comparison for this study. Histologic myocarditis was identified in 8% of biopsy specimens. Clinical and hemodynamic parameters could not be used to predict the presence of myocarditis. Five of six biopsy samples (87%) with myocarditis showed dense 67Ga uptake, whereas only nine of 65 negative biopsy samples (14%) were paired with equivocally positive 67Ga scans (p < .001). The single patient with myocarditis and no myocardial 67Ga uptake had dense mediastinal lymph node uptake that may have obscured cardiac uptake. The incidence of myocarditis on biopsy with a positive 67Ga scan was 36% (5/14); however, the incidence of myocarditis with a negative 67Ga scan was only 1.8% (1/57). Follow-up scans for three patients showed close correlation of 67Ga uptake with myocarditis on biopsy. In conclusion 67Ga may be a useful screening test for identifying patients with a high yield of myocarditis on biopsy, and serial scans may eliminate the need for frequent biopsies in patients with proven myocarditis. Circulation 70, No. 1, 58-62, 1984. DILATED CARDIOMYOPATHY is a clinical syndrome that frequently culminates in progressive congestive heart failure and premature death. The etiology of dilated cardiomyopathy is obscure by definition; consequently, current therapy is neither specific nor life prolonging. ' The recent development of safe techniques of endomyocardial biopsy has led to the realization that patients with dilated cardiomyopathy may have unsuspected myocarditis and that the inflammatory infiltrates are potentially reversible.2 Immunosuppressive therapy may ultimately lead to improvement of clinical symptoms and prognosis if the From the Departments of Medicine, Radiology, and Pathology, Loyola University Medical Center, Maywood, and Veterans Administration Medical Center, Hines, IL. Supported in part by the Earl M. Bane Charitable Trust and a grant from the Fraternal Order of Eagles. Address for correspondence: John B. O'Connell, M.D., Section of Cardiology, Loyola University Medical Center, 2160 South First Ave., Maywood, IL 60153. Received Jan. 4, 1984; revision accepted March 29, 1984. Presented in part at the 56th Annual Scientific Sessions of the American Heart Association, Anaheim, November 1983. 58 myocardium has not been irreversibly damaged. Although safe when performed by experienced hands, endomyocardial biopsy is not the ideal diagnostic tool because of its morbidity, cost, and potential for sampling error, which may cause low sensitivity when the inflammatory infiltrate is patchy or focala common finding in myocarditis. The ideal noninvasive screening test should have high sensitivity, low morbidity, and low cost. Inflammation-sensitive radioisotopic imaging has great potential for this role. Gallium-67 (67Ga) is a radioisotope that is routinely used to identify chronic inflammatory reactions with a reported sensitivity of 90%.3 We have previously described 67Ga uptake over the cardiac region in patients with pericardial inflammation,4 and more recently we have identified a subset of patients with dilated cardiomyopathy who have 67Ga uptake over the myocardium.5 Forty percent of these patients showed clinical and hemodynamic improvement after the initiation of immunosuppressive therapy.6 Changes in myocardial 67Ga avidity paralleled the clinical reCIRCULATION by gest on M ay 1, 2017 http://ciajournals.org/ D ow nladed from DIAGNOSTIC METHODS-MYOCARDIAL DISEASE sponse to immunosuppression. This study was designed to compare 67Ga imaging with endomyocardial biopsy in identification of inflammation in patients with dilated cardiomyopathy. Materials and methods Patients. All patients referred to Loyola University Medical Center for evaluation of dilated cardiomyopathy from January 1981 through December 1982 underwent endomyocardial biopsy and 67Ga scintigraphy within 72 hr of the biopsy. Diagnoses other than dilated cardiomyopathy were excluded by left ventricular and coronary angiography in all patients over 25 years of age. The criteria included a dilated, hypocontractile left ventricle with normal coronary arteries and no evidence of valvular or pericardial disease. All patients underwent two-dimensional and M mode echocardiographic and electrocardiographic examinations as well as gated blood pool imaging by standard techniques with technetium-99m---labeled red blood cells. Endomyocardial biopsy. Endomyocardial biopsy was performed by standard techniques with the Stanford bioptome (Scholten Surgical Supply, Redwood City, CA) through the right internal jugular vein.7 A minimum of four samples were obtained with attempts to vary the sampling site. Tissue was immediately immersed in paraformaldehyde. All specimens were embedded in paraffin and stained with hematoxylin-eosin and Masson's trichrome stains. A minimum of nine sections of each of the four specimens were reviewed. Myocarditis was considered to be present if more than five lymphocytes per high power field or focal clusters of lymphomononuclear cells were noted. Myocytic necrosis along with cellular infiltration aided the confirmation of the diagnosis -of myocarditis. 67Ga imaging. 67Ga imaging was routinely performed 72 hr after the intravenous injection of 8 mCi 67Ga citrate. Patients were scanned in the anterior, 45 and 60 degree left anterior oblique, and left lateral projections, with most of the liver excluded from the region of interest. Images were performed with a latest-generation, large-field-of-view gamma camera with a medium-energy collimator capable of detecting the 93, 185, and 300 keV 67Ga peaks to 625,000 counts. The images were then processed in a nuclear medicine computer with a 256 x 256 matrix and enhanced by less than 20% of the maximal pixel. Scans were interpreted by a nuclear medicine physician who was blinded to the clinical and pathologic data. Density of gallium uptake was compared with the density of the sternum. Scans were interpreted as positive if the density was equal to or greater than that of the sternum and equivocal if density was less than that of the sternum. Data analysis. Evidence of active myocarditis by endomyocardial biopsy was considered the standard to which 67Ga images were compared. Patient populations were compared by a chi-square analysis or unpaired Student's t test where appropriate; data are expressed as mean + SD.