Duchenne progressive muscular dystrophy (DMD) is characterized by progressive degeneration of skeletal and cardiac muscles with fibrotic tissue replacement and fatty infiltration[1]. Resulting myocardial dysfunction has been estimated to be responsible for death in 20% of human DMD patients[2, 3].

Echocardiography is one of the useful noninvasive methods used to assess cardiac function in patients and animals with Duchenne's cardiomyopathy[4‐9]. It is possible that the recognition of earlier subclinical cardiac systolic or diastolic dysfunction could allow for an early medical approach, thus improving long-term cardiovascular outcomes. Several studies have demonstrated the usefulness of tissue Doppler imaging (TDI) to detect subclinical myocardial systolic and diastolic dysfunction in patients with normal conventional echocardiographic parameters[10]. These studies have also confirmed that myocardial velocities, myocardial wall-thickening velocities, myocardial velocity gradients and strain during systole and early diastole in the left ventricular free wall were reduced in patients[11‐15] and dogs with DMD[16, 17]. However, strain measurements derived from TDI involve several disadvantages including angle-dependence and the limitations of an available cardiac region for an assessment. Since it has been reported that the distribution of myocardial lesions detected by magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) varied among DMD patients[18‐20], TDI might underestimate the severity of myocardial dysfunction in certain patients.

Two-dimensional speckle tracking echocardiography (STE) is a new approach designed to assess left ventricular function in humans and animals[21, 22]. STE has no angle-dependence and allows the assessment of any region of the heart. Usefulness of STE analysis in human patients with idiopathic dilated cardiomyopathy to detect systolic and diastolic dysfunction has been described in several reports. STE provides several advantages over TDI, in for example, estimation for the increase in LV filling pressure[23‐25]. In addition, STE has the ability to detect regional myocardial dysfunction[22]. We hypothesized that STE could detect early myocardial lesions in patients with Duchenne's cardiomyopathy without clinical signs. To our knowledge, there have been no reports assessing the cardiac function of Duchenne's cardiomyopathy using STE.

Canine X-linked muscular dystrophy in Japan (CXMD_J) is a Beagle-based dog colony established by artificially inseminating frozen semen from spontaneous Golden retriever muscular dystrophy. CXMD_J has been reported to be comparable to human patients and dogs with DMD[9, 26‐28]. The purpose of the present study was to assess left ventricular regional myocardial dysfunction using STE in affected and carrier CXMD_J dogs without overt clinical signs of heart failure.

In the present study, no significant difference was found in any parameters using conventional echocardiography among the 3 groups, which indicated no apparent LV dilation or systolic dysfunction with normal FS in affected and carrier dogs.

SrR_E has been reported to show a significant correlation with LV relaxation[38, 39]. A significant difference in SrR_E was observed in posterior segments at the Ct level in carrier and affected dogs. SrR_E tended to decrease in other LV segments. The results of segmental STE analysis suggest an impairment of LV relaxation in the basal inferoposterior segments of CXMD_J - affected dogs prior to a detectable decrease in global indices of cardiac function. In previous studies, pathological lesions were frequently observed in the posterior and lateral wall of the left ventricle in patients and dogs with DMD[9, 40, 41]. Previous reports have indicated that TDI-derived parameters also identified myocardial dysfunction in the LV free wall[11, 14‐17, 42], which supported our results.

Circumferential strain parameters in affected dogs were not significantly changed in the present study. In contrast, Mertens et al. reported significant decreases in TDI-derived strain indices in the apical, mid and basal level of LV long-axis views in DMD patients[15]. One possible explanation for this difference is more advanced disease in the previously reported population, supported by the presence of obvious LV dilation in the patients of that study. A second possibility is different measurement techniques. Mizuguchi et al. have suggested that LV systolic dysfunction may begin with reduced longitudinal shortening that is compensated by augmented circumferential shortening in early stages. Therefore, one could hypothesize that STE performed using long-axis views is a more sensitive method than with short-axis views, although it was not evaluated in the present study.

E wave velocity in carrier dogs was significantly increased compared with normal dogs. Increased E wave was noticed in dogs with overt and occult dilated cardiomyopathy (DCM), which may suggest diastolic dysfunction[43]. However, in the present study, the other measured parameters derived from transmitral flow, such as DcT and A wave velocity, were all within the reference range and no statistical significance was found among groups. In addition, the TMF pattern was not the typical restrictive pattern (i.e. E/A>2 as well as short DcT) in any individual carrier dogs[43, 44]. The clinical relevance of this finding is uncertain given the relatively small magnitude of difference and the large amount of overlap in values among groups. In addition, higher value of E/SrR_E in carrier dogs might be influenced by the increased E wave. E' measured using TDI was significantly reduced in affected dogs compared with normal dogs. This is similar to a previous report of reduced peak E' velocity in patients with DMD[13].

Duchenne's cardiomyopathy in a carrier female was previously reported, though it was found to be mild compared with that in an affected male[45, 46]. In the present study, there was significant difference in segmental assessment of SrR_E between normal and carrier female dogs as well as affected dogs. Since our carrier females were young to middle-aged, it is possible that follow-up evaluation would reveal myocardial impairment.

In the present study, low dose of acepromazine was used for sedation. The influence of sedation was seen in EDVI, and A wave velocity of TMF. Schaefer et al. demonstrated increased A waves of TMF and myocardial velocity using TDI under anesthesia in normal mice, while increased heart rates were observed at the same time[47]. They speculated that changes in heart rates constituted one of the factors causing increased A wave velocity. Since changes in A waves in our study were accompanied by decreased heart rates, there might have been a relationship. Although further study is needed, parameters influenced by sedation appeared to be less important in the overall interpretation of our results. Additionally, proportions of sedated dogs in each group were similar.

There were several limitations in the present study. First, the number of dogs available for each group was limited and age distribution was relatively wide in all groups because of the difficulty in maintaining a sufficient number of CXMD_Js. Second, body weight in affected dogs was significantly lower than in normal dogs. However, we consider that this difference would be less likely to affect our results. Third, one carrier dog had mild MR. A report described mitral valve prolapse in DMD patients, and MR was considered to be responsible for LV dilation[48]. In the present study, because LV dilation was not observed in that carrier dog, MR was more likely caused by myxomatous degeneration of the mitral valve, the most common acquired heart disease in dogs. In this case, MR was considered to be too mild to likely affect our results. Fourth, the accuracy of strain measurement depends on the quality of 2-dimensional echocardiography and frame rate. The mean frame rates per cardiac cycle in normal, carrier and affected dogs were 57.4, 49.4 and 45.1, respectively. The frame rate per cardiac cycle was relatively low due to the relatively higher heart rate compared with humans (about 70-110 frames when the human heart rate was considered to be 60 bpm [49]). This may affect the accuracy of tracking quality, especially in early diastolic parameters. Further investigation using newer methods might detect change more precisely[50]. Finally, given the characteristics of this disease, differences in the sex ratio among the groups were unavoidable. Since significant differences between males and females in some STE parameters have been reported in a human study[51], the results could have been influenced by gender. Since the number of normal dogs was small when categorized by gender, further studies using a greater number of dogs are warranted. In addition, there should be some differences in expression of the disease among the affected dogs, and CXMDJ might have less severe disease compared to the human patients.

The myocardial strain rate by STE served to detect the impaired cardiac diastolic function in CXMD_J without any obvious LV dilation or clinical signs. The radial strain rate may be a useful parameter to detect early myocardial impairment in CXMD_J.