Coronarographic evaluation of dystrophic cardiomiopathy (author's transl)]

A 22 year old man with Duchenne's progressive muscular dystrophy is presented. Because of electro-and vectorcardiographic features compatible with ischemic heart disease, coronary angiography was performed in order to rule out obstructive coronary disease, which has been excluded in our case. The coronary tree presented the same characteristics of idiopathic primitive cardiomyopathy. The authors assert that the coronary arteriography is a necessary complement to the diagnosis of Duchenne's muscular dystrophy.     

Coronary arterioluminal communications in routine angiography

Visualization of the left ventricular cavity from coronary arterioventricular communications is rarely encountered in routine coronary angiography. We report 14 patients, of 5,500 consecutive cardiac catheterizations, in whom these communications were evident during coronary angiography. All 14 patients had angina pectoris; in each the arterioluminal communication originated from the left anterior descending coronary artery. Two patients had evidence of anterior wall ischemia despite a normal left anterior descending coronary artery, suggesting that a possible steal phenomenon is responsible for the myocardial ischemia. Cathet. Cardiovasc. Diagn. 43:29–32, 1998. © 1998 Wiley-Liss, Inc.     

A case of facioscapulohumeral muscular dystrophy complicated with complete A-V block

Myocardial involvement and serious electrocardiographic abnormalities are rare in patients with facioscapulohumeral (FSH) muscular dystrophy. We reported a case of FSH muscular dystrophy complicated with complete A-V block. The case was that of a 48 year-old male with the complaints of exertional dyspnea. His chest X-ray showed cardiomegaly, and the electrocardiogram recorded on admission showed complete A-V block. On the His bundle electrogram, complete A-H block and prolongation of H-V intervals were noted. Therefore, a permanent pacemaker was implanted, and he has been doing well for over 10 years after implantation. Although it is well known that serious electrocardiographic abnormalities are not infrequently associated with Duchenne's progressive muscular dystrophy (DMD), there are few reports about pacing therapy for patients with muscular dystrophy. Because the daily activity of patients with rapidly progressive type of muscular dystrophy such as DMD is at a very low level, they do not require pacing therapy. Whereas in patients with the FSH type of muscular dystrophy, which is a slowly progressive type, their daily activity is maintained at a high level. Therefore, pacing therapy should be recommended if the FSH type of muscular dystrophy is accompanied with serious bradyarrhythmias.     

Therapeutic trials on progressive muscular dystrophy.

The special medical care in the National Sanatorium prolonged the life span of the patients with progressive muscular dystrophy from 15.8 years to 20.4 years over the last 20 years. Various new drug trials for muscular dystrophy have been implemented in the last 12 years in Japan. Bestatin and Loxistatin, protease inhibitors, showed definite improvement on dystrophic mice or hamsters, animal models of muscular dystrophy. However clinical application of these drugs failed to prove the effects on patients with Duchenne muscular dystrophy. The difficulty of clinical evaluation and judgement of effects in progressive neurological diseases is discussed.     

Hemodynamic study in a case of progressive muscular dystrophy involving the heart

A case of progressive muscular dystrophy with cardiac involvement was studied by right heart catheterization. The data obtained suggested left ventricular failure as the primary hemodynamic disturbance. The pertinent clinical, pathologic and electrocardiographic features of the cardiac myopathy of progressive muscular dystrophy are briefly reviewed.     

Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS

Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscular dystrophy (GRMD) dogs with left ventricular dysfunction (measured by echocardiography) and in isolated coronary arteries. eNOS and nNOS proteins in carotid arteries were measured by western blot and cyclic guanosine monophosphate (cGMP) content was analyzed by radioimmunoassay. Compared with controls, GRMD dogs had an impaired vasodilator response to acetylcholine. In isolated coronary artery, acetylcholine-elicited relaxation was nearly absent in placebo-treated GRMD dogs. This was explained by reduced nNOS and eNOS proteins and cGMP content in arterial tissues. Chronic bradykinin infusion (1 μg/min, 4 weeks) restored in vivo and in vitro vascular response to acetylcholine to the level of control dogs. This effect was NO-mediated through upregulation of eNOS and nNOS expression. In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin.     

Cardiac involvement in Emery Dreifuss muscular dystrophy: a case series

Three patients with Emery Dreifuss muscular dystrophy are reported. Emery Dreifuss muscular dystrophy is an X linked muscular dystrophy, in which locomotor involvement is characteristically mild and slowly progressive. The effect on the heart becomes apparent in the teenage years and is characterised by cardiac conduction defects and infiltration of the myocardium by fibrous and adipose tissue. It first affects the atria, which results in atrial paralysis; treatment with ventricular pacing is usually needed. Female carriers can develop heart problems and are at risk of sudden death. Relatives of affected patients should be offered screening with electrocardiography and echocardiography.     

Accelerated coronary vascular disease in the heart transplant patient: coronary arteriographic findings

Annual coronary arteriograms have been obtained from all heart transplant recipients at Stanford University Medical Center since 1969. Angiographic lesions in 81 transplant patients exhibiting coronary vascular disease were classified into three categories: type A, discrete or tubular stenoses; type B, diffuse concentric narrowing; and type C, narrowed irregular vessels with occluded branches. The 81 arteriograms showing transplant coronary vascular disease were contrasted with 32 from nontransplant patients with coronary artery disease analyzed in a similar fashion. The nontransplant angiograms showed 178 lesions, all of type A (discrete or tubular) morphology, 75% of which were located in primary epicardial coronary vessels and 25% in secondary branch vessels. In the patients with transplant coronary vascular disease, 349 (76%) of 461 lesions were type A: 57% in primary vessels, 42% in secondary branches and 1.4% in tertiary branches. Of the 112 type B and C lesions (diffuse narrowing, tapering and obliteration), 25% were in primary vessels, 44% in secondary vessels and 31% in tertiary branches (p less than 0.05 for patients with transplant coronary vascular disease versus patients with nontransplant coronary artery disease). Total vessel occlusion was found in proximal or middle vessel segments in 96% and distally in 4% of patients with "ordinary" coronary artery disease versus 49% distally in patients with transplant coronary disease (p less than 0.002). In the presence of total vessel occlusion, collateral vessels were poor or absent in 92% of transplant versus 7% of nontransplant patients with coronary disease (p less than 0.002). Therefore, coronary artery disease in transplant patients represents a mixture of typical atheromatous lesions and unique transplant-related progressive distal obliterative disease that occurs without collateral vessel development.     

The two brothers' case of dilated cardiomyopathy with benign Duchenne type of progressive muscular dystrophy (Becker's type)]

The presence of myocardial involvement is rare in benign Duchenne type of progressive muscular dystrophy (Becker's muscular dystrophy). We describe two brothers suffering from Becker's muscular dystrophy, both of whom presented with dilated cardiomyopathy. The first case is a 39-year-old male who had suffered from gait disturbance from the age of 17. When 37 years old, he was found to have heart disease. When he first came to our hospital, pseudohypertrophy of the calves was present. Chest radiography, electrocardiogram, ultrasonocardiography and clinical feature indicated Becker's muscular dystrophy with dilated cardiomyopathy. The second case is the younger brother of the 37-year old male. He suffered from leg weakness. He came to our hospital with the chief complaint of discomfort of the anterior chest. Pseudohypertrophy of the calves was present. Chest radiography, electrocardiogram, ultrasonogram indicated dilated cardiomyopathy.     

Non-invasive mechanical ventilation as an alternative respiratory support during gastrostomy tube placement,in a patient with Duchenne muscular dystrophy, 24/24 hours ventilation dependent

Patients with Duchenne muscular dystrophy may benefit from gastrostomy tube feeding due to progressive dysphagia and malnutrition. However, due to concomitant pathologies, they are often at high risk for anesthesiologic complications. We describe how the non-invasive mechanical ventilation has been an alternative successful respiratory support option during the gastrostomy tube placement in a patient with Duchenne muscular dystrophy, on continuous NIV treatment. This report confirms how the use of NIV can support alveolar ventilation, before, during and after mini-invasive procedures, and prevent respiratory complications.Key words: Duchenne muscular dystrophy, percutaneous endoscopic gastrostomy, NIV treatment     

A 17-year-old Male with Duchenne muscular dystrophy complicated with dilated cardiomyopathy and large left ventricular mural thrombosis

Background Heart failure is one of the main causes of death due to progressive muscular dystrophy of Duchenne muscular dystrophy (DMD) in the majority of the cases. There is high incidence of arterial thromboembolism in DMD patients with severe heart failure. However, it has been receiving little attention whether anticoagulative therapy in DMD patients with severe heart failure in sinus rhythm should be performed. Herein we present a case of DMD patients, with severe heart failure in sinus rhythm, who pres...     

A case of fascioscapulohumeral muscular dystrophy misdiagnosed as Becker's muscular dystrophy for 20 years

A 60-year-old man diagnosed clinically with Becker's muscular dystrophy 20 years ago by another physician presented with gradually progressive proximal muscle weakness since teenage years. Family history revealed a strong paternal familial inheritance pattern of similar distribution of weakness-face, forearm flexion, knee extension and foot dorsiflexion. Work-ups revealed B12 deficiency and allele 1 deletion in fascioscapulohumeral muscular dystrophy (FSHD) DNA testing. FSHD is the third most common muscular dystrophy. Clinical diagnosis is made from the distinctive pattern of weakness, autosomal-dominant inheritance, and confirmed by genetic testing. This case strongly demonstrates the importance of a thorough and careful clinical evaluation even in a case with a long standing diagnosis.     

Noninvasive ventilation during gastrostomy tube placement in patients with severe duchenne muscular dystrophy: case reports and review of the literature

Individuals with Duchenne muscular dystrophy may benefit from gastrostomy tube feeding due to progressive dysphagia and malnutrition. However, due to their severely impaired pulmonary function, these individuals are at risk of severe complications when they are sedated or undergo anesthesia for the procedure. We previously described a technique of noninvasive positive pressure ventilation to provide respiratory support during gastrostomy tube placement in such patients, but this technique had risks and limitations. In this case report, we examine two alternative techniques we used to provide respiratory support successfully to patients with severe muscular dystrophy and malnutrition who underwent percutaneous endoscopic gastrostomy tube placement. We then review the literature and discuss the potential benefits, risks, and limitations of the above techniques and of other options for gastrostomy placement in people with severe muscular dystrophy.     

Muscle degeneration without mechanical injury in sarcoglycan deficiency

In humans, mutations in the genes encoding components of the dystrophin-glycoprotein complex cause muscular dystrophy. Specifically, primary mutations in the genes encoding alpha-, beta-, gamma-, and delta-sarcoglycan have been identified in humans with limb-girdle muscular dystrophy. Mice lacking gamma-sarcoglycan develop progressive muscular dystrophy similar to human muscular dystrophy. Without gamma-sarcoglycan, beta- and delta-sarcoglycan are unstable at the muscle membrane and alpha-sarcoglycan is severely reduced. The expression and localization of dystrophin, dystroglycan, and laminin-alpha2, a mechanical link between the actin cytoskeleton and the extracellular matrix, appears unaffected by the loss of sarcoglycan. We assessed the functional integrity of this mechanical link and found that isolated muscles lacking gamma-sarcoglycan showed normal resistance to mechanical strain induced by eccentric muscle contraction. Sarcoglycan-deficient muscles also showed normal peak isometric and tetanic force generation. Furthermore, there was no evidence for contraction-induced injury in mice lacking gamma-sarcoglycan that were subjected to an extended, rigorous exercise regimen. These data demonstrate that mechanical weakness and contraction-induced muscle injury are not required for muscle degeneration and the dystrophic process. Thus, a nonmechanical mechanism, perhaps involving some unknown signaling function, likely is responsible for muscular dystrophy where sarcoglycan is deficient.     

Normal coronary arteries and isolated,regional, left ventricular dysfunction in myotonic dystrophy: a case report

Development of cardiomyopathy in myotonic dystrophy is rare. Regional ventricular abnormality in the presence of normal coronary vessels has not been reported in this condition. We describe a case of isolated, regional, left ventricular dysfunction with corresponding defects on nuclear perfusion imaging in a patient with classical myotonic dystrophy and normal coronary arteries.     

Adult-onset acid maltase deficiency. Case report of an adult with severe respiratory difficulty.

Pompe's disease (acid maltase deficiency) classically affects infants and children, with a few sporadic cases occurring in adults. An adult patient initially have progressive muscular weakness, exertional dyspnea, diaphragmatic paralysis, and objective evidence of restrictive respiratory disease. Muscle biopsy established the diagnosis of acid maltase deficiency. The patient's brother had died at the age of 44 years, after 23 years of a "progressive muscular dystrophy." Acid maltase deficiency should be considered in the differential diagnosis of progressive respiratory insufficiency associated with weakness.     

Early Myocardial Dysfunction and Benefits of Cardiac Treatment in Young X-Linked Duchenne Muscular Dystrophy Mice

Cardiovascular Drugs and Therapy - Duchenne muscular dystrophy (DMD) is associated with a progressive alteration in cardiac function. The aim of this study was to detect early cardiac dysfunction...     

Multiple fistulae of coronary arteries to both ventricles

A 74 year old man was found at necropsy to have multiple coronary arteriosystemic fistulae involving all three major coronary arteries and both ventricles. This is the second such case reported. All terminal branches of the coronary arteries entered the myocardium and numerous tiny vessels opened into the cardiac chambers. No coronary veins or coronary sinus were recognized. This vascular anomaly is considered to result from the abnormal persistence of intertrabecular spaces within the embryonic myocardium.     

Gene transfer establishes primacy of striated vs. smooth muscle sarcoglycan complex in limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy types 2E and F are characterized by skeletal muscle weakness and often cardiomyopathy and are due to mutations in the genes encoding beta- and delta-sarcoglycan. We previously demonstrated that loss of sarcoglycans in smooth muscle leads to constrictions of the microvasculature that contributes to the cardiac phenotype. It is unclear how vasculature abnormalities affect skeletal muscle. We injected recombinant beta- or delta-sarcoglycan adenoviruses into skeletal muscles of corresponding null mice. We hypothesized that the adenoviruses would not transduce vascular smooth muscle, and we would only target skeletal muscle. Indeed, sustained expression of intact sarcoglycan-sarcospan complex was noted at the sarcolemma, neuromuscular junction, myotendinous junction, and in peripheral nerve, but not in vascular smooth muscle. Gene transfer of the corresponding deleted sarcoglycan gene preserved sarcolemmal integrity, prevented pathological dystrophy and hypertrophy, and protected against exercised-induced damage. We conclude that vascular dysfunction is not a primary cause of beta- and delta-sarcoglycan-deficient muscular dystrophy. In addition, we show successful functional rescue of entire muscles after adenovirus-mediated gene delivery. Thus, virus-mediated gene transfer of sarcoglycans to skeletal muscle in combination with pharmacological prevention of cardiomyopathy constitute promising therapeutic strategies for limb-girdle muscular dystrophies.