Muscle Pathology Associated With Cardiac Function in Duchenne Muscular Dystrophy.

Cardiac complications are the leading cause of death in patients with Duchenne muscular dystrophy (DMD). Two-dimensional echocardiography is the current standard for monitoring of LV systolic function in these patients, but it might not detect early systolic dysfunction. The current study examined the use of speckle tracking echocardiography (STE) to detect early signs of cardiac dysfunction in DMD patients. A retrospective review of charts and offline strain analysis of transthoracic echocardiographic studies of DMD patients at our institution from April 2014 to January 2015 were performed and compared to age-matched healthy male subjects. Nineteen DMD patients (age range 12.6±3.1years) with normal ejection fraction and shortening fraction were compared with sixteen controls. The global circumferential strain was lower in DMD patients compared with controls (-14.7±4.7 vs. -23.1±2.9%, respectively, p value: 0.001). Circumferential strain measured at basal, mid-ventricular and apical parasternal short-axis views was lower in DMD patients compared with controls. Segmental circumferential strain was lower in DMD patients in most segments compared with controls. The global longitudinal strain was lower in DMD patients compared with controls (-13.6±5 vs. -18.8±3%, respectively, p value: 0.001). Segmental longitudinal strain measured in various segments was lower in DMD patients compared with controls. DMD patients can have occult cardiovascular dysfunction as shown by reduction in circumferential and longitudinal strain measurements with STE despite normal standard echocardiographic parameters. The clinical significance of early detection of cardiac dysfunction in these patients warrants further studies.

Validity of resting myotonometric assessment of lower extremity muscles in chronic stroke patients with limited hypertonia: A preliminary study

Coagulation system activated in Duchenne muscular dystrophy patients with cardiac dysfunction

On the basis of strong research evidence, Duchenne muscular dystrophy (DMD), the most common severe childhood form of muscular dystrophy, is an X-linked recessive disorder caused by out-of-frame mutations of the dystrophin gene. Thus, it is classified asa dystrophinopathy. The disease onset is before age 5 years. Patients with DMD present with progressive symmetrical limb-girdle muscle weakness and become wheelchair dependent after age 12 years. (2)(3). On the basis of some research evidence,cardiomyopathy and congestive heart failure are usually seen in the late teens in patients with DMD. Progressive scoliosis and respiratory in sufficiency often develop once wheelchair dependency occurs. Respiratory failure and cardiomyopathy are common causes of death, and few survive beyond the third decade of life. (2)(3)(4)(5)(6)(7). On the basis of some research evidence, prednisone at 0.75 mg/kg daily (maximum dose, 40 mg/d) or deflazacort at 0.9 mg/kg daily (maximum dose, 39 mg/d), a derivative of prednisolone (not available in the United States), as a single morning dose is recommended for DMD patients older than 5 years, which may prolong independent walking from a few months to 2 years. (2)(3)(16)(17). Based on some research evidence, treatment with angiotensin-converting enzyme inhibitors, b-blockers, and diuretics has been reported to be beneficial in DMD patients with cardiac abnormalities. (2)(3)(5)(18). Based on expert opinion, children with muscle weakness and increased serum creatine kinase levels may be associated with either genetic or acquired muscle disorders (Tables 1 and 3). (14)(15)

Background Bevacizumab, a monoclonal antibody inhibitor of vascular endothelial growth factor (VEGF), can cause commonly left ventricular systolic dysfunction.The current role of echocardiography global longitudinal strain (GLS) in diagnosing subclinical cardiac damage caused by anticancer drugs is well-established. However, there is currently no data on the possible role of myocardial work indices (MWI) and left atrial (LA) strain in the early detection of bevacizumab-induced cardiac dysfunction. Purpose Our study aimed to explore the effectiveness of MWI derived from pressure–strain analysis and LA strain for early detection of cardiac dysfunction in patients with colorectal cancer treated with bevacizumab. Methods We included 42 patients (65.1 ± 7.5 years/old, 70% male) with metastatic colorectal cancers undergoing bevacizumab in combination with non-anthracycline-based chemotherapy (5-fluorouracil/ folinic acid plus oxaliplatin, FOLFOX i.v.). Patients underwent evaluation by 2D/3D echocardiography, measuring left ventricular ejection fraction (LVEF), LA Volume index (LAVi), GLS and MWI [global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE)] and LA reservoir longitudinal strain at baseline, after three and six moths post bevacizumab initiation. Results At six months, 8 patients (19% of patients) developed subclinical cardiac dysfunction or mild asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), defined as a relative decrease ≥15% in GLS from baseline, without a significant reduction in LVEF (threshold of 50%). In all patients, after bevacizumab initiation, GWE decreased and GWW increased significantly, both at three and six months (p <0.05), while there was no difference in the other echocardiographic parameters. There was no significant difference between baseline values of MWI and LA strain in patients who developed cardiotoxicity and those who did not. However, patients who developed cardiotoxicity showed significantly reduced values of GWE (p=0.001) and LA strain (p=0.001) compared to those who did not develop cardiotoxicity, at both three and six months. Patients who developed CTRCD at six months showed significantly reduced GWE (p=0.001) and LA strain (p=0.001) compared to baseline values, at both three months and six months. Conclusion MWI changes during bevacizumab therapy are significant and occur early (reduced GWE, increased GWW). GWE and LA strain appeared to decrease early in patients who developed subclinical cardiac dysfunction, even before a ≥15% decrease in GLS from baseline. An approach that includes both GLS, MWI and LA strain could be useful for the early identification of subclinical cardiotoxicity. Including more patients might help identify a possible MWI and LA strain cutoff that predicts, even earlier than GLS, subclinical cardiotoxicity in patient with metastatic colorectal cancers undergoing bevacizumab.GWE & LAstrain in pts with/without CTRCD MWI & LA strain in pts developing CTRCD

Duchenne muscular dystrophy (DMD) is a progressive, incurable X-linked neuromuscular disease caused by mutations in the dystrophin gene, resulting in functional dystrophin deficiency. Currently, cardiovascular complications are the leading cause of death in patients with DMD. Glucocorticoids are considered the gold standard treatment for children with DMD. Long-term glucocorticoid therapy can delay the loss of independent ambulation, improve lung function, and extend lifespan. However, the effects of glucocorticoids on cardiac function in patients with DMD remain controversial. This scoping review aims to summarize and analyze published clinical studies investigating the effects of glucocorticoids on cardiac function in children with DMD. A comprehensive search was conducted using PubMed, Web of Science, and Embase databases with relevant search terms. s and full texts of retrieved studies were reviewed. The studies were categorized into four themes: glucocorticoid use, Types of glucocorticoids, administration methods, and timing of glucocorticoid initiation. A total of 21 studies were included. Of these, 18 studies investigated the effects of glucocorticoids on cardiac function in patients with DMD, and the study of Koeks et al. reported both effective and non-effective outcomes of glucocorticoids on cardiac function stratified by age group, respectively. One study examined the impact of different glucocorticoid types, one study assessed the effects of glucocorticoid administration methods and one study evaluated the timing of glucocorticoid initiation. Among the 21 studies, 13 studies (n = 1814 patients) indicated that glucocorticoids could delay the progression of cardiac dysfunction in patients with DMD. Six studies (n = 6294 patients) reported no significant effects of glucocorticoids on cardiac function, while one study (n = 111 patients) suggested that early glucocorticoid therapy increased the risk of cardiomyopathy.Conclusion: It has been suggested that corticoids may delay the deterioration of cardiac function in patients with DMD. However, limited data exist on the long-term effects of early glucocorticoid therapy on cardiac function, leading to inconclusive findings. Prospective longitudinal studies are needed to determine the optimal timing, dose regimen, and long-term impact of glucocorticoid therapy in patients with DMD.What is Known:• The effects of glucocorticoids on cardiac function in patients with DMD remain controversial.What is New:• Glucocorticoids can delay the deterioration of cardiac function in DMD patients. However, prospective longitudinal studies are still needed to determine the optimal timing, dose regimen, and long-term effect of glucocorticoid therapy in DMD patients.

Functional Rescue of Dystrophin-deficient mdx Mice by a Chimeric Peptide-PMO

Background/Objectives: Duchenne Muscular Dystrophy (DMD) is a prevalent fatal genetic disorder, and heart failure is the leading cause of mortality. Peak left ventricular (LV) circumferential strain (Ecc), twist, and circumferential-longitudinal shear angle (θCL) are promising biomarkers for the improved and early diagnosis of incipient heart failure. Our goals were as follows: 1) to characterize a spectrum of functional and rotational LV biomarkers in boys with DMD compared with healthy age-matched controls; and 2) to identify LV biomarkers of early cardiomyopathy in the absence of abnormal LVEF or LGE. Methods: Boys with DMD (N = 43) and age-matched healthy volunteers (N = 16) were prospectively enrolled and underwent a 3T CMR exam after obtaining informed consent. Breath-held MRI tagging was used to estimate left ventricular Ecc at the mid-ventricular level as well as the twist, torsion, and θCL between basal and apical LV short-axis slices. A two-tailed t-test with unequal variance was used to test group-wise differences. Multiple comparisons were performed with Holm-Sidak post hoc correction. Multiple-regression analysis was used to test for correlations among biomarkers. A binomial logistic regression model assessed each biomarker's ability to distinguish the following: (1) healthy volunteers vs. DMD patients, (2) healthy volunteers vs. LGE(-) DMD patients, and (3) LGE(-) DMD patients vs. LGE(+) DMD patients. Results: There was a significant impairment in the peak mid-wall Ecc [-17.0 ± 4.2% vs. -19.5 ± 1.9%, p < 7.8 × 10-3], peak LV twist (10.4 ± 4.3° vs. 15.6 ± 3.1°, p < 8.1 × 10-4), and peak LV torsion (2.03 ± 0.82°/mm vs. 2.8 ± 0.5°/mm, p < 2.6 × 10-3) of LGE(-) DMD patients when compared to healthy volunteers. There was a further significant reduction in the Ecc, twist, torsion, and θCL for LGE(+) DMD patients when compared to LGE(-) DMD patients. In the LGE(+) DMD patients, age significantly correlated with LVEF (r2 = 0.42, p = 9 × 10-3), peak mid-wall Ecc (r2 = 0.27, p = 0.046), peak LV Twist (r2 = 0.24, p = 0.06), peak LV torsion (r2 = 0.28, p = 0.04), and peak LV θCL (r2 = 0.23, p = 0.07). In the LGE(-) DMD patients, only the peak mid-wall Ecc was significantly correlated with age (r2 = 0.25, p = 0.006). The peak LV twist outperformed the peak mid-wall LV Ecc and EF in distinguishing DMD patients from healthy volunteer groups (AUC = 0.88, 0.80, and 0.72), as well as in distinguishing LGE(-) DMD patients from healthy volunteers (AUC = 0.83, 0.74, and 0.62). The peak LV twist and peak mid-wall LV Ecc performed similarly in distinguishing the LGE(-) and LGE(+) DMD cohorts (AUC = 0.74, 0.77, and 0.79). Conclusions: The peak mid-wall LV Ecc, peak LV twist, peak LV torsion, and peak LV θCL were significantly impaired in advance of the decreased LVEF and the development of focal myocardial fibrosis in boys with DMD and therefore were apparent prior to significant irreversible injury.

Holter electrocardiogram should be systematic in Duchenne muscular dystrophy

D.P.15 Quantitative T2 relaxation times in lower leg of Duchenne and Becker muscular dystrophy patients

The prevalence and associated factors of myocardial involvement in Duchenne muscular dystrophy patients in the first decade of life.

We examined the association of activities of daily living (ADL), mobility and balance ability, and symptoms of Parkinson's disease (PD) with the masses and amounts of intramuscular non-contractile tissue of the trunk and lower extremity muscles in patients with PD. The subjects were 11 community-dwelling patients with PD. ADL were assessed using the Functional Independence Measure. Mobility capacity was assessed based on measurement of maximal walking speed and timed up-and-go time, while balance ability was evaluated based on measurement of one-legged stance time. The symptoms of PD were assessed based on measurement of the Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale. Muscle thickness (MT) and echo intensity (EI) of the trunk and lower extremity muscles were also measured using an ultrasound imaging device. Partial correlation analysis revealed an association between reduced ADL and increased EI of the lumbar erector spinae muscle; reduced mobility capacity and increased EI of the rectus abdominis and gluteus minimus muscles; and reduced balance ability and decreased MT of the lumbar erector spinae muscle and increased EI of the lumbar erector spinae, semitendinosus, and tibialis posterior muscles. Partial correlation analysis also showed an association between symptoms of severe PD and decreased MT of the tibialis anterior muscles and increased EI of the lumbar erector spinae, gluteus minimus, and tibialis posterior muscles. The properties of the trunk and lower extremity muscles may be critical for ADL, mobility and balance ability, and symptoms of PD in patients with PD.

Transduction of Full-length Dystrophin to Multiple Skeletal Muscles Improves Motor Performance and Life Span in Utrophin/Dystrophin Double Knockout Mice

Objective: To explore the characteristics and changes of cardiac injury with age in Duchenne muscular dystrophy (DMD) and its clinical significance. Methods: A prospective cohort study was conducted. The 215 patients diagnosed with DMD in West China Second Hospital from January 2019 to November 2022 and aged from 6 to 18 years were enrolled. Their clinical data, myocardial injury markers, routine electrocardiogram, cardiac magnetic resonance (CMR) and echocardiography were collected. The patients were divided into five age groups: 6-<8, 8-<10, 10-<12, 12-<14 and 14-18 years of age, and matched with healthy boys respectively. Independent sample t test or Mann-Whitney U test was used to compare the clinical data and CMR indexes between DMD patients and controls in all age subgroups, and to compare the value of left ventricular ejection fraction (LVEF) measured by echocardiography and CMR in each subgroup of DMD patitents. Pearson correlation analysis or Spearman correlation analysis was used to explore the relation between the CMR indexes and age in DMD patients. Results: A total of 215 patients with DMD (all male) and 122 healthy boys were included in the study. There were 75 DMD patients and 23 controls in 6-<8 years of age group, 77 DMD and 28 controls in 8-<10 years of age group, 39 DMD and 23 controls in 10-<12 years of age group, 10 DMD and 31 controls in the 12-<14 years of age group, and 14 DMD and 17 controls in 14-18 years of age group. In the DMD patients, the older the age, the lower the levels of creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). In the 6-<8 years of age group, the CK level was 10 760 (7 800, 15 757) U/L, while in the group of 14-18 years of age, it was 2 369 (1 480, 6 944) U/L. As for CK-MB, it was (189±17) μg/L in the 6-<8 years of age group and (62±16) μg/L in the 14-18 years of age group. Cardiac troponin I remained unchanged in <12 years of age groups, but significantly increased in 12-<14 years of age group, reaching the highest value of 0.112 (0.006, 0.085) μg/L. In the DMD patients, the older the age, the higher the proportion of abnormal electrocardiogram (ECG). In the 6-<8 years of age group, the proportion is 29.3% (22/75), while in the 14-18 years of age group, it was 10/14. Correlation analysis showed that the left ventricular end-diastolic volume index was positively related with age (r=0.18, P=0.015), and the left ventricular stroke volume index and cardiac output index were negatively related with age (r=-0.34 and -0.31, respectively, both P<0.001). In the DMD patients, the older the age, the lower LVEF, with the LVEF decreasing to (49.3±3.1)% in the 14-18 years of age group. The LVEF of DMD cases was significantly lower than that of controls in the age subgroups of 8-<10, 10-<12, 12-<14 and 14-18 years of age groups ((57.9±5.2) % vs. (63.6±0.8)%, 60.7% (55.9%, 61.9%) vs. 63.7% (60.2%, 66.0%), 57.1% (51.8%, 63.4%) vs. 62.1 % (59.5%, 64.5)%, (49.3±3.1) % vs. (61.6±1.3)%, respectively; all P<0.01). In the DMD patients, the older the age, the higher the proportion of positive late gadolinium enhancement (LGE). In the 6-<8 years of age group, it was 22% (11/51), in the 12-<14 years of age group, it was 13/14, and in the 14-18 years of age group, all DMD showed positive LGE. The value of LVEF of DMD cases measured by echocardiography was significantly higher than that measured by CMR in 6-<8 years of age group and 8-<10 years of age group (63.2% (60.1%, 66.4%) vs. 59.1 % (55.4%, 62.9%), and (62.8±5.2) % vs. (57.9±5.2)%, all P<0.001). Conclusion: DMD patients develop cardiac injury in the early stage of the disease, and the incidence of cardiac damage gradually increases with both age and the progression of disease.

Identifying evidence of cardio-renal syndrome in patients with Duchenne muscular dystrophy using cystatin C