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Duchenne's progressive muscular dystrophy (DMD) is a genetic muscular disorder that causes degeneration and atrophy of skeletal and cardiac muscle. Histologic changes in the heart of patients with DMD include fibrosis, degeneration, and fatty infiltration. Fibrosis begins in the outer half of the left ventricular posterior wall, which is a relatively specific finding for DMD.1
Ultrasonography can be used to characterise changes in the myocardium at the cellular level. Unprocessed radiofrequency signals, redirected back to the transducer, provide quantitative information about intramural architecture in terms of ultrasonic integrated backscatter (IBS). Two of the IBS parameters can be measured: the magnitude of cyclic variation (CV) and IBS intensity. Changes in the CV are caused by variations in myocardial collagen, water content, myofibril orientation, and myocardial contractility. Myocardial IBS intensity is correlated with the collagen content or the degree of the fibrosis in the myocardium.2 3 In this study, we investigated whether myocardial ultrasound IBS is useful for the early detection of myocardial involvement in patients with DMD.
Twenty five patients with DMD were enrolled in this study. The mean patient age was 17.6 (2.7) years. Fourteen healthy individuals were included as an age matched control group. A previously described protocol was used for the measurement of myocardial IBS.4In the parasternal long axis view of the left ventricle, an elliptical shaped region of interest was positioned in the inner and outer halves of the left ventricular posterior wall, respectively. The CV of the inner and outer halves of the left ventricular posterior wall were calculated as the difference between the end diastolic (peak) and end systolic (nadir) IBS values (CVin and CVout, respectively). The difference in the CV (dif CV) was calculated by subtracting the CVout from the CVin. Mean values for the IBS intensity in the inner and outer halves of the left ventricular myocardium were automatically displayed (IBSin and IBSout, respectively). The corrected mean myocardial IBS values for the inner and outer halves of the left ventricular posterior wall (cIBSin and cIBSout, respectively) were measured by subtracting the mean IBS value for the left ventricular cavity near the left ventricular posterior wall from the IBSin and IBSout. The difference in the IBS intensity (dif IBS) was also calculated by subtracting the cIBSin from the cIBSout.
Comparison of the IBS parameters between patients with DMD and the control group is summarised in table 1. In the control group, CVin was significantly higher than CVout (9.6 (2.4) dBv 8.4 (1.9) dB, p < 0.01). The intensity of cIBSin was significantly lower than that of cIBSout (11.4 (3.5) dBv 14.3 (4.3) dB, p < 0.001).
Both CVin and CVout were significantly lower in patients with DMD than in the control group (6.1 (2.1) dB v 9.6 (2.4) dB for CVin, 4.5 (2.1) dB v 8.4 (1.9) dB for CVout, p < 0.001 for both). The intensities of cIBSin and cIBSout were significantly greater in patients with DMD than in the control group (15.3 (4.6) dB v 11.4 (3.5) dB for cIBSin, p < 0.01: 25.2 (6.3) dBv 14.3 (4.3) dB for cIBSout, p < 0.001). The dif IBS was also significantly greater in patients with DMD than in the control group (9.9 (5.0) dB v 2.9 (1.8) dB, p < 0.001).
When the normal range for the shortening fraction of the left ventricle was defined as the mean (2 SD), nine patients with DMD had a normal shortening fraction (28%). Both CVin and CVout were significantly lower in patients with DMD with normal shortening fraction than in the control group (7.6 (1.0) dB v 9.6 (2.4) dB for CVin, p < 0.05: 5.4 (1.4) dB v 8.4 (1.9) dB for CVout, p < 0.001). There was no significant difference in cIBSin intensity between the two groups. In contrast, cIBSout was significantly higher in patients with DMD than in the control group (22.8 (7.3) dB v 14.3 (4.2) dB, p < 0.005). The dif IBS was also significantly greater in patients with DMD than in the control group (8.9 (5.3 ) dBv 2.9 (1.8) dB, p < 0.001). These data indicate that IBS intensity was increased and the magnitude of CV was decreased in the outer half of the left ventricular posterior wall in patients with DMD, even in the setting of normal global cardiac function (shortening fraction). When the mean (2 SD) in the control group is considered the upper limit of normal for dif IBS, 6.5 dB> dif IBS is abnormally high. Among the nine DMD patients with a normal left ventricular shortening fraction, six patients had an increase in dif IBS.
Fibrotic changes do not always occur homogeneously throughout the ventricular wall in myocardial diseases. In the setting of idiopathic dilated cardiomyopathy, the endocardial half of the myocardium generally has more severe fibrosis. In contrast, cardiomyopathy caused by DMD is unique in that fibrosis begins in the outer half of the myocardium.1 Thereafter, small areas of fibrosis may be identified in the ventricular septum, near the right ventricular cavity. Eventually, there is a diffuse transmural fibrosis. The echo amplitude of the outer half of the left ventricular posterior wall is often increased on conventional two dimensional echocardiography in patients with DMD.5 We were able to evaluate quantitatively the characteristics of the myocardium in patients with DMD by analysing myocardial IBS.
Suwa and colleagues reported that patients with dilated cardiomyopathy who responded to β blocker treatment had a lower IBS intensity of the left ventricular posterior wall compared to non-responders.2 They concluded that left ventricular myocardial IBS intensity provides useful information for predicting the degree of myocardial fibrosis and the response to β blocker treatment in patients with dilated cardiomyopathy. We believe that measurements of IBS variables, especially the dif IBS, are useful for the early detection of the myocardial involvement in patients with DMD, even if conventional echocardiographic findings (such as shortening fraction) show normal values. Early detection of myocardial changes in patients with DMD might be important, because earlier treatment might be more effective in preventing the development of myocardial fibrosis.