ORIGINAL ARTICLE 

Annals of Nuclear Medicine Vol. 1O, No. 2, 225-230, 1996 

Myocardial defect detected by 123I-BMIPP scintigraphy and left ventricular dysfunction in patients with idiopathic dilated cardiomyopathy 

Yasunori HASHIMOTO, Hiroshi YAMABE and Mitsuhiro YOKOYAMA 

First Department of Internal Medicine, Kobe University School of Medicine 

The present study examined the role of myocardial fatty acid in patients with idiopathic cardiomyopathy (DCM) by means of 123I-B-methyl-p-iodophenyl pentadecanoic acid (123I-BMIPP) scintigraphy. Thirteen patients underwent 123I-BMIPP imaging, 201Tl imaging and echocardiography. All patients showed defective myocardial uptake of 123I-BMIPP and 201Tl. The left ventricular end-diastolic dimension (64.1 +- 7.3 mm vs. 55.6 +- 1.5 mm, p < 0.05) and end-systolic dimension (52.4 +- 8.0 mm vs. 40.6 +- 2. 1 mm, p < 0.01 ) were significantly larger in the large defect group (123I-BMIPP defect score (DS) > 8) than the small defect group (DS < 7). The % fractional shortening ((%FS) was also significantly smaller (18.6 +- 3.8% vs. 27.0 +- 3.3%, p < 0.01) in the large defect group. The 123I-BMIPP DS correlated statistically with %FS (r = 0.75, p < 0.01), while the 201Tl DS did not (r = 0.41 , ns). We conclude that the patients with DCM revealed a 123I-BMIPP uptake defect and the defect reflected the degree of left ventricular dysfunction. 

Key words : DCM, 123I-BMIPP, 201Tl, echocardiography, left ventricular function 

INTRODUCTION 

IDIOPATHIC DILATED CARDIOMYOPATHY (DCM) is manifested by marked chamber dilation, diffusely reduced wall motion of the left ventricle and congestive heart failure; it has a poor prognosis. Although the pathogenesis of DCM has not been identified, previous myocarditis, microvascular dysfunction, toxins and myocardial metabolic disturbance have been suggested.1 Calcium overload,2,3 a decreased number of preceptors4 and inappropriate ventricular afterloading5 are deterioration factors in ventricular dysfunction. Recent investigations have elucidated the disturbed myocardial metabolism of DCM including the involvement of glucose6 and palmitate.7 123I-B-methyl-p-iodophenyl pentadecanoic acid (123I-BMIPP) is a new tracer used to assess myocardial fatty acid metabolism. 123I-BMIPP is appropriate for use with single photon emission computed tomography (SPECT) because of its long-lasting accumulation in the myocardium and its high uptake ratio.8-10 123I-BMIPP scintigraphy has provided fatty acid assessment in cardiomyopathic rats11,12 and hypertensive rats13 as well as in human hypertrophic cardiomyopathy.14 Few studies have investigated DCM with 123I-BMIPP scintigraphy. The present study was designed further to elucidate the characteristics of 123I-BMIPP SPECT, and to investigate echocardiographic left ventricular dysfunction in patients with DCM using 123I-BMIPP SPECT. 

MATERIALS AND METHODS 

Subjects: Thirteen patients with DCM (age 49 +- 16 years; ten males and three females) were selected for the study. The diagnosis of DCM was made by the criteria of the collaborative research project of the committees for Idiopathic Cardiomyopathy of the Ministry of Health and Welfare and of the Japanese Circulation Society. Ten of the patients had a history of congestive heart failure. The other three did not have a history of manifest congestive heart failure in spite of ventricular dysfunction. Twelve of the patients underwent coronary angiography, and none showed any coronary artery disease. A 38-year-old female patient did not undergo coronary angiography be-cause she did not show any clinical signs of coronary artery disease. Twelve patients had taken medication for heart failure; eleven patients had diuretics, nine had digitalis, four had angiotensin converting enzyme inhibitor and two had B-blocker. Informed consent to the 123I-BMIPP scintigraphy was obtained from all patients. 
SPECT imaging; All patients underwent both a 121I-BMIPP scintigraphy and a 201Tl scintigraphy under the resting condition. The average interval between the scintigraphies was 7 days, and their order was random. Patients fasted and discontinued medication 12 hours before each scintigraphy. 111 MBq of 123I-BMIPP or 111 MBq of 201TI was injected intravenous]y, with the subject at rest in the upright position. The SPECT images were acquired 20 minutes after 123I-BMIPP injection, and 5 minutes after 201Tl injection in the supine position with a rotating gamma camera (ZLC75ECT, Siemens, German) and a computer analyzer (Scintipack 2400, Shimadzu, Japan). Both image sequences consisted of 32 projections with a 64 x 64 matrix acquired for 40 seconds (123I-BMIPP) and 30 seconds (201Tl) over a 180' circular orbit, from 60' left posterior oblique to 30' right anterior oblique. Contiguous transaxial tomographic images were obtained with a filtered back projection algorithm. Thereafter, long-axial, short-axial and horizontal-axial tomographic images were reconstructed from the transaxial tomographic images. In order to assess the myocardial uptake defects, we selected two short-axial slices (one each of the basal and apical part) and one long axial slice. Each short-axial slice was divided into 6 segments. The long-axis image was used for assessment of the apex. Thirteen segments were assessed in this way. The defects were graded visually on a scale of 0 to 2 (0: nearly normal, 1: mild to moderate, 2: severe). The grading was done by three skilled investigators. The total defect score (DS) was calculated as the summation of all the defect grades. 
We then retrospectively divided the patients into two groups according to their DS from the 123I-BMIPP image: the large defect group (DS > 8, n = 8) and the small defect group (DS < 7, n = 5). In addition, the defect pattern of the serial tomographic images was divided into two categories, i.e., a scattered patchy pattern of which the defect's size did not exceed a segment and a regional pattern of which the defect's size exceeded a segment. 
Echocardiography: All patients underwent M-mode and two-dimensional echocardiography with an ultra-sonoscope (SSH-140A, SSH-160A, Toshiba, Japan). The end-diastolic dimension (LVDd) and the end-systolic dimension (LVDs) of the left ventricle and percent fractional shortening (%FS) were measured with an M-mode strip chart averaging 5 sequential beats. The regional wall motion of the left ventricle was assessed visually with two-dimensional echocardiography. We compared the echocardiographic images and the scintigraphic image of each segment, and then examined the relationship between left ventricular wall motion and the myocardial defect of 123I-BMIPP. 
Statistical analysis: Values are expressed as the mean +- standard deviation. The comparison between the two groups was done by one-way analysis of variance test. A p value less than 0.05 was considered significant. 

RESULTS 

Patients ' characteristics 
Table 1 lists the clinical manifestations of the patients. Five patients were New York Heart Association (NYHA) class I,4 patients were class II,3 patients were class III, and one patient was class IV. Echocardiography revealed that all 13 patients had a dilated left ventricle and all except one had reduced %FS. Defects in myocardial (123)I-BMIPP uptake were found in all 13 patients. The DS of the (123)I-BMIPP image was 8.8 +- 4.3 (3 to 16). (201)Tl perfusion defects were also found in all patients. The DS of the (201)Tl image was 9.1 +- 4.7 (4 to 20). There was no significant difference between the DS obtained from the (123)I-BMIPP image and that from the (201)Tl image. 
(123)I-BMIPP imaging and (201)Tl imaging 
Patients with the small defect group (n = 5) had a scattered patchy pattern. Patients with the large defect group (n = 8) had relatively large regional defects with or without patchy defects. The (123)I-BMIPP DS was 4.2 +- 0.8 in the small defect group and 11.6 +- 2.8 in the large defect group. The (201)Tl DS was 6.4 +- 1.8 in the small defect group and 10.8 +- 5.3 in the large defect group (p < 0.001). There was no difference between the small defect group and the large defect group in the patients' medication. Figure 1 shows representative cases. The upper panel shows the (123)I-BMIPP image of the small defect group and the lower panel shows that of the large defect group. 
The location and size of the defects were compared in the (123)I-BMIPP images and (201)Tl images. The two images were consistent in 4 patients, but they were mismatced in 9 patients. Of these 9 patients, 4 cases showed a larger defect in the (123)I-BMIPP image than in the (201)Tl image; while 3 cases showed a smaller defect in the (123)I-BMIPP image than in the (201)Tl image, and in 2 cases defect locations were different. The consistent type was prevalent in the large defect group, but the mismatch type was less frequent in the small defect group. 
Relationship between echocardiography and the scintigraphic images 
Echocardiography revealed left ventricular dilation (LVDd >= 55 mm) and/or systolic dysfunction (%FS < 30%) in all patients except one and the abnormal wall motion in all patients. Advanced wall motion abnormality (akinesis or dyskinesis) was found in 8 patients. The (123)I-BMIPP image of 6 of these 8 patients showed defects in the akinetic or dyskinetic segments. Figure 2 shows the statistically significant differences between the large defect group and the small defect group in LVDd, LVDs and %FS. The LVDd (64.1 +- 7.3 mm vs. 55.6 +- 1.5 mm, p < 0.05) and LVDs (52.4 +- 8.0 mm vs. 40.6 +- 2.1 mm, p < 0.01 ) were larger in the large defect group than in the small defect group. The %FS was also smaller (18.6 +- 3.8% vs. 27.0 +- 3.3%, p < 0.01 ) in the large defect group. When patients were divided into two groups according the (201)Tl DS, there was no statistical difference in these echocardiographic findings (Table 2). Figure 3 shows that the (123)I-BMIPP DS correlated significantly with %FS (r = 0.75, p < 0.01), but the (201)Tl DS did not correlate with it (r = 0.41 , ns). 
DISCUSSION 
The results of the present study indicate that the patients with DCM had a defective uptake of myocardial (123)I-BMIPP, and that the defect was related to left ventriculardysfunction. 
(123)I-BMIPP is a branched fatty acid. Most (123)I-BMIPP is trapped in the triglyceride fraction and a small percentage of (123)I-BMIPP is catabolized via ~oxidation in the cells.(8-10) The myocardial uptake of (123)I-BMIPP can be influenced by coronary flow, a decreased triglyceride pool, increased back diffusion from cells owing to re-duced ATP, or the decreased myocardium itself. All of the patients in the present study had an abnormal 123I-BMIPP image which was characterized by heterogeneity over the myocardium with patchy and/or regional lesions. This is consistent with the other studies with 11C-palmitate.7.15 These heterogeneous lesions of the myocardial metabolism may reflect the process of myocardial damage in DCM. The advanced wall motion abnormality corresponded with the defect in 123I-BMIPP uptake. This accords with the report by Ugolini et al.16 who used 123I-phenylpentadecanoic acid which can be catabolized via ~oxidation. 123I-BMIPP may therefore be valuable in the 
assessment of metabolic disorders in DCM, similar to the other tracers of physiological fatty acid. 
Myocardial ischemia has been a main subject of past studies on myocardial fatty acid metabolism. 11C-palmitate clearance, a function of fatty acid oxidation, deteriorated under ischemic and reperfused conditions. 17-19 The clearance correlates with the total amount of free fatty acid in the intercellular pool.20,21 Since most 123I-BMIPP is not rapidly catabolized in the mitochondria, our results do not directly indicate a decrease in the metabolic rate for fatty acid in DCM. It has been reported that the cellular ATP concentration correlates with 123I-BMIPP uptake,22 and that mitochondrial damage caused by adriamycin correlates with 123I-BMIPP uptake.23 These reports suggest that 123I-BMIPP uptake may reflect the state of energy production in the myocardium. The damage to myocardial cells in DCM may involve mitochondrial function, which decreases the oxidation of fatty acid. Reduced oxidative capacity can accelerate the depletion of the energy source for myocardial contraction. Impaired fatty acid metabolism may therefore be a cause as well as a result of myocardial dysfunction. This may be a reason why the 123I-BMIPP uptake defect is related to left ventricular dysfunction . 
 The second important finding in the present study was mismatched defects between the 123I-BMIPP image and the 201Tl image. In 9 of the 13 patients, the defect revealed by the 123I-BMIPP was not identical to the defect shown by the 201Tl image. Such a mismatched defect is more frequent in the small defect group, and this suggests a less severe myocardial abnormality. In a study with a hamster model of DCM, the 123I-BMIPP image showed a larger defect than did the 201Tl image,11,12 A study of spontaneously hypertensive rats reported that abnormal accumulation of 123I-BMIPP developed faster than that of 201Tl.13 A 201Tl defect indicates reduced coronary flow or myocardial mass. Since myocardial fibrosis develops into ventricular failure,24 a 201Tl image may indicate left ventricular dysfunction in DCM,25-27 but the 201Tl image in the present study did not accord with this concept. This may be related to the fact that the number of patients that we studied was small. There were 3 patients who had reverse mismatch of 123I-BMIPP and 201Tl defect, that is, the defect in the 201Tl image was more predominant than the 123I-BMIPP image. It is difficult to interpret the phenomenon of reverse mismatch. As we assessed the 123I-BMIPP image by SPECT, diffusely reduced accumulation of 123I-BMIPP as found in DCM may unmask a regional defect. 
 Clinical lmplications: Left ventricular systolic dysfunction is a major feature of DCM. Echocardiographic or angiographic ventriculography, and the histological finding in biopsied ventricular specimens such as myocardial degeneration and fibrosis, have characterized the myocardial damage in DCM. The present study showed that 123I-BMIPP scintigraphy provides new information on myocardial fatty acid metabolism which will be useful for the clinical assessment of patients with DCM, but the diagnostic value for prognosis and efficacy of treatment remains unclear. 

CONCLUSION 

SPECT with 123I-BMIPP showed defective uptake of myocardial fatty acid in patients with DCM and the defects' relationship with left ventricular dysfunction. 

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