© 2005 European Society of Cardiology
Rapid progression from hypertrophic cardiomyopathy to heart failure in a patient with Becker's muscular dystrophy
a Seonam University College of Medicine Namwon, South Korea
b Department of Cardiology and Pathology, Chonnam National University Hospital 8 Hakdong, Dongku, Gwangju 501-757, South Korea
* Corresponding author. Department of Cardiology, Chonnam National University Hospital, 8 Hakdong, Dongku, Gwangju 501-757, South Korea. Tel.: +82 62 220 4764; fax: +82 62 227 7174. E-mail address: cecilyk{at}hanmail.net
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Abstract |
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 Top Abstract 1. Introduction2. Case report3. DiscussionReferences |
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We describe the case of a 17-year-old boy with Becker*s muscular dystrophy (BMD) presenting with rapid progression from hypertrophic cardiomyopathy to heart failure within 2 years. Initial echocardiogram showed severe hypertrophy of left ventricle (LV) and right ventricle (RV) with normal chamber size, and preserved LV systolic function. Microscopic study of cardiac muscle obtained by endomyocardial biopsy of the interventricular septum showed severe hypertrophy of the muscle fibers and interstitial fibrosis. Follow-up echocardiogram 2 years after the first examination exhibited marked dilated LV and RV with severe LV global hypokinesia. Follow-up endomyocardial biopsy demonstrated increased interstitial cellular matrix. Immunohistochemical staining for dystrophin revealed significant loss of dystrophin along the sarcoplasmic membrane of the right biceps brachii muscle, compatible with BMD.
Key Words: Becker's muscular dystrophy • Hypertrophic cardiomyopathy • Heart failure
Received November 6, 2003; Revised May 28, 2004; Accepted July 14, 2004
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1. Introduction |
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TopAbstract1. Introduction2. Case report3. DiscussionReferences |
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Duchenne's and Becker's X-linked muscular dystrophies involve cardiac and skeletal muscle. Cardiac involvement may precede skeletal-muscle symptoms and is often unrelated to the extent of musculoskeletal involvement. Myocardial involvement is less frequent among patients with BMD as compared with those with Duchenne muscular dystrophy [1]. Since muscular disability in BMD progresses very slowly, myocardial involvement may become a life-threatening problem [2]. Cases of BMD with cardiac involvement usually have dilated cardiomyopathy (DCM) and few have hypertrophic cardiomyopathy (HCM). It is known that progression of HCM to dilated, or burnt out, cardiomyopathy occurs in 10–15% of patients [3]. However, to the best of our knowledge, there has been no documented case of BMD with HCM rapidly progressing to heart failure.
We report a patient with BMD presenting with rapid progression from HCM to heart failure.
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2. Case report |
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TopAbstract1. Introduction2. Case report3. DiscussionReferences |
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A 17-year-old boy with normal intelligence presented to our hospital due to orthopnea, progressive muscle weakness, and cramping myalgia for the previous 2 weeks.
His mother had been diagnosed with DCM without muscular disease but there was no other history of either neuromuscular disorders or cardiac events in father, sister, any male siblings, any male maternal uncles or male cousins.
He had been examined for abnormal liver function test at the age of 11. The elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) had been 202, 201, 946, and 764 U/l, respectively. Transthoracic echocardiogram (TTE) demonstrated no abnormal findings on his heart. A muscle biopsy from the right gastrocnemius muscle showed some degenerating myofibers and a liver biopsy showed nonspecific reactive change.
Two years before admission, at the age of 15, he had visited an emergency room due to chest pain and dizziness experienced while playing football. He had been found to have ventricular tachycardia (VT). After VT was converted to sinus rhythm, biventricular hypertrophy with QRS widening was documented on the electrocardiogram (ECG). TTE showed severe hypertrophy of left ventricle (LV) and right ventricle (RV) with LV end diastolic dimension 50 mm, LV end systolic dimension 33 mm, LV posterior wall thickness 23.8 mm, interventricular septum thickness 25.0 mm, and ejection fraction (EF) of LV 62.4%, compatible with hypertrophic cardiomyopathy (Fig. 1A). However, no evidence of systolic anterior motion of mitral valve leaflets or left ventricular outflow tract obstruction was demonstrated in TTE. Microscopic study of cardiac muscle from the endomyocardial biopsy of intraventricular septum showed severe hypertrophy of the muscle fibers and interstitial fibrosis (Fig. 2A). After administration of amiodarone and angiotensin converting enzyme inhibitor (ACEI), VT, chest pain, and dypnea did not recur for 2 years.
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On physical examination, his general appearance was chronically ill looking and the jugular vein was dilated. Fine crackles were audible in both lower lung fields and no murmur was audible. He showed generalized atrophy in upper and lower extremities. On manual muscle testing, he was found to have normal muscle power in all muscle groups and normal deep tendon reflexes.
A chest roentgenogram revealed severe cardiomegaly and pulmonary congestion. Follow-up echocardiogram 2 years after the first examination exhibited marked dilated LV, RV, and global hypokinesia with LV diastolic dimension 65.1 mm, systolic dimension 59.5 mm, LV posterior wall thickness 16.2 mm, interventricular septum thickness 15.0 mm, and LVEF 22.8% (Fig. 1B). Follow-up endomyocardial biopsy demonstrated that increased interstitial cellular matrix (Fig. 2B). The biopsy findings from biceps brachii, gastrocnemius, and sural nerve showed dystrophic change on microscopic examination, i.e., anisocytosis of muscle fibers, endomysial fibrosis, internal migration of nuclei, cytoplasmic vacuolation and regenerating fibers (Fig. 3A). Sarcoplasmic infiltration of lymphocytes and myophagocytosis were noted in a myofiber but no ragged red fiber or inclusion body was observed (Fig. 3B).
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Immunohistochemical staining for dystrophin revealed significant loss of dystrophin along the sarcoplasmic membrane of the right biceps brachii muscle, compatible with BMD (Fig. 4). However, 17 sets of Exon deletion in dystrophin gene using electrophoresis of multiplex PCR products in peripheral blood cells were not detected.
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An electromyogram revealed polyradiculoneuropathy and myopathic changes with brief potentials of small amplitude on muscles of the lower limb.
On admission, the laboratory findings demonstrated moderate elevation in CK and CK-MB 956/28 U/l, myoglobin 500 ng/ml, AST 213 U/l, and LDH 1842 U/l.
The patient was given an ACEI and β-blocker in addition to diuretics, including an aldosterone antagonist. However, the clinical signs of impending congestive heart failure and myalgia were markedly increased. The patient has been put onto the waiting list for cardiac transplantation.
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3. Discussion |
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TopAbstract1. Introduction2. Case report3. DiscussionReferences |
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BMD is an allelic X-linked recessive disorder that is characterized by progressive muscle wasting [4]. The gene involved is extremely large and complex and encodes a 427-kDa protein named dystrophin, which is localized mainly at the surface membrane of striated muscle fibers and probably links the cytoskeleton to the basal lamina via the dystrophin-associated glycoprotein complex [5,6]. In mild BMD, myocardial damage may develop because the patients, who are unaware of possible cardiac involvement, are still able to perform strenuous muscle exercise and, through pressure or volume overload, may induce mechanical stress, which is harmful for dystrophin-deficient myocardial cells [4]. Immunostaining for dystrophin in skeletal muscle specimens has been documented to be more sensitive than gene analysis [2]. Several reports demonstrated the deletion of several exons in dystrophin gene in BMD [4,7]. Exon deletion was not found in this case. The dystrophin gene is expressed in the skeletal and cardiac muscles, smooth muscles, brain, and other organs. Dystrophin is expressed as similar isoforms in skeletal and cardiac muscles, which suggests that the cardiac involvement of patients with BMD may be produced by the same mechanism as in skeletal muscular dystrophy [2]. In this case, the patient showed generalized atrophy in upper and lower extremities and had the elevated muscle enzyme and abnormal EMG finding (myopathic changes with brief potentials of small amplitude on muscles of the lower limb ). Although we could not confirm Beckers MD by Western blot or Immunoblot and family history, it was possible to confirm Beckers MD by immunohistochemical staining for dystrophin; which showed significant loss of dystrophin along the sarcoplasmic membrane of the right biceps brachii muscle.
In the case of HCM that has progressed to DCM, patients have a chronically increased serum level of LDH1 and CKMB. This may represent a chronic insult and destruction of the myocardial cells. In the present case, such increases in the serum levels of these enzymes were evident.
Cardiomyopathy has been the presenting symptom of Becker's muscular dystrophy in rare instances, and cardiac failure is not necessarily a late feature of this disorder [5]. Hayashi et al. [1] reported BMD associated with hypertrophic cardiomyopathy. Patients with BMD-related cardiomyopathy typically survive into their 30s, when they succumb to complications of cardiomyopathy or may receive heart transplants [8].
The features of this patient's cardiomyopathy are different from the typical dilated cardiomyopathy of Becker's MD. We cannot exclude the combination of another genetic abnormality with the genetic abnormality due to BMD. This case suggest that patients with BMD should be prospectively studied to pick up early manifestations of cardiomyopathy, possibly by measuring b-type natriuretic peptide levels. Once cardiomyopathy is diagnosed by echocardiography, regular cardiology follow up is recommended with consideration for beta blocker and ACE inhibitor therapy earlier rather than later, as the medications may be tolerated better early and may have protective benefits [8].
In Becker's muscular dystrophy or female carriers of Duchenne muscular dystrophy, it is not known whether therapy to decrease myocardial wall stress is beneficial in preventing or delaying progression to cardiac failure. Once heart failure is established, conventional therapy is indicated. Orthotopic cardiac transplantation has been reported [9].
In the present case, the patient had been found to have VT and biventricular hypertrophy with QRS widening was documented on the ECG. Serious ventricular arrhythmias have been documented in patients with BMD and are believed to play a role in sudden death. The use of anti-arrhythmic drugs is recommended and an implantable cardioverter-defibrillator could be useful for recurrent drug refractory ventricular tachycardia [10].
This case study describes a patient with BMD-related cardiomyopathy in which a rapid progression from HCM to DCM-like state was documented.
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References |
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TopAbstract1. Introduction2. Case report3. DiscussionReferences |
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- Hayashi Y., Ikeda U., Ogawa T., et al. Becker-type muscular dystrophy associated with hypertrophic cardiomyopathy. Am. Heart J. (1994) 128:1265–1266.
- Melacini P., Fanin M., Danieli G.A., et al. Myocardial involvement is very frequent among patients affected with subclinical Becker's muscular dystrophy. Circulation (1996) 94:3168–3175.
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- Muntoni F., Cau M., Ganau A., et al. Deletion of the dystrophin muscle-promoter region associated with X-linked dilated cardiomyopathy. N. Engl. J. Med. (1993) 329:921–925.
[Free Full Text] - Yu Y., Yamabe H., Fujita H., et al. Cardiac involvement in a family with Becker muscular dystrophy. Intern. Med. (1995) 34:919–923.[CrossRef][Web of Science][Medline]
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- Case records of the Massachusetts general hospital: weekly clinicopathological exercises: case 22-1998: a 22-year-old man with a cardiac transplant and creatine kinase elevation. N. Engl. J. Med. (1998) 339:182–190.
[Free Full Text] - Munoz J., Sanjuan R., Morell J.S., Ibanez M. Ventricular tachycardia in Duchenne's muscular dystrophy. Int. J. Cardiol. (1996) 54:259–262.[CrossRef][Web of Science][Medline]
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