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Muscular dystrophies and cardiomyopathies
D. Harrington / International Journal of Cardiology 87 (2003) 133 – 134
lar systolic abnormalities may occur in patients with MP-CMD. Long term follow-up by serial echocardiographic studies is required to determine the clinical significance of these findings.
[8] [9]
[10]
Acknowledgements [11]
We would like to thank our families for full participation in our study. HT has been supported by the Association Francaise contre les Myopathies (AFM), France.
[12]
[13]
[14]
References [1] Straub V, Campbell KP. Muscular dystrophies and the dystrophin– glycoprotein complex. Curr Opin Neurol 1997;10:168–75. [2] Towbin JA. The role of cytoskeletal proteins in cardiomyopathies. Curr Opin Cell Biol 1998;10:131–9. [3] Lim LE, Campbell KP. The sarcoglycan complex in limb–girdle muscular dystrophy. Curr Opin Neurol 1998;11:443–52. [4] Melacini P, Fanin M, Duggan DJ et al. Heart involvement in muscular dystrophy due to sarcoglycan gene mutations. Muscle Nerve 1999;22:473–9. [5] Coral-Vazquez R, Cohn RD, Moore SA et al. Disruption of the sarcoglycan–sarcospan complex in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy. Cell 1999;98:465–74. [6] Ervasti JM, Campbell KP. A role for the dystrophin–glycoprotein complex as a transmembrane linker between laminin and actin. J Cell Biol 1993;122:809–23. ˇ ˇ [7] Topaloglu H, Kale G, Yalnizoglu D et al. Analysis of ‘pure’ congenital muscular dystrophies in thirty-eight cases. How different
[15]
[16]
[17]
[18] [19]
[20]
133
is the classical type 1 from the occidental type cerebromuscular dystrophy? Neuropediatrics 1994;25:94–100. Voit T. Congenital muscular dystrophies: 1997 update. Brain Dev 1998;20:65–74. ˇ H et al. Mutations in the Helbling-Leclerc A, Zhang X, Topaloglu laminin a2-chain gene (LAMA2) cause merosin deficient congenital muscular dystrophy. Nat Genet 1995;11:216–8. Tome FMS, Evangelista T, Leclerc A et al. Congenital muscular dystrophy with merosin deficiency. CR Acad Sci Paris III 1994;317:351–7. Brockington M, Sewry CA, Herrmann R et al. Assignment of a form of congenital muscular dystrophy with secondary merosin deficiency to chromosome 1q42. Am J Hum Genet 2000;66:428–35. Cormand B, Avela K, Pihko H et al. Assignment of the muscle– eye–brain disease gene to 1p32–p34 by linkage analysis and homozygosity mapping. Am J Hum Genet 1999;64:126–35. ˇ H et al. Clinical and histopathological Talim B, Kale G, Topaloglu study of merosin-deficient and merosin-positive congenital muscular dystrophy. Pediatric Develop Pathol 2000;3:168–76. Muntoni E, Philpot J, Spyrou N, Camici P, Dubowitz V. Cardiac involvement in merosin-negative congenital muscular dystrophy. Dev Med Child Neurol (abstract) 1995;72:90. Spyrou N, Philpot J, Foale R, Camici PG, Muntoni F. Evidence of left ventricular dysfunction in children with merosin-deficient congenital muscular dystrophy. Am Heart J 1998;136:474–6. Alehan FK, Ozkutlu S, Alehan D. Effects of respiration on left ventricular diastolic function in healthy children. Eur Heart J 1996;17:453–6. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072–83. Workshop report. 41st ENMC International workshop on congenital muscular dystrophy. Neuromusc Disord 1996; 6:295–306. ¨ ˇ H, C ˇ C¸il E, Topaloglu ¸ aglar M, Ozme S¸. Left ventricular structure and function by echocardiography in congenital muscular dystrophy. Brain Devel 1994;16:301–3. Dougherty AH, Naccarelli GV, Gray EL, Hicks CH, Goldstein RA. Congestive heart failure with normal systolic function. Am J Cardiol 1984;54:778–82.
Editorial comment
Muscular dystrophies and cardiomyopathies Derek Harrington* Kent Sussex Hospital, Mount Ephraim, Tunbridge Wells, Kent TN4 8 AT, UK
Received 10 June 2002; accepted 5 July 2002
*Tel.: 144-1892-672-986; fax: 144-1892-528-381.
Associations between diseases of cardiac and skeletal muscle are increasingly recognised [1]. Some
0167-5273 / 02 / $ – see front matter 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 02 )00319-4
134
D. Harrington / International Journal of Cardiology 87 (2003) 133 – 134
patients with muscular dystrophy have significantly impaired left ventricular function and suffer from chronic heart failure. Patients with chronic heart failure develop a wide range of secondary skeletal muscular changes which may have an important role in the pathogenesis of their condition [2]. To date, detailed echocardiographic studies of patients with skeletal muscle disease have been rarely performed. Ceviz et al. in this issue of the International Journal of Cardiology have performed such a study [3]. They describe a comparison of echocardiograms in 42 patients with merosin-positive congenital muscular dystrophy with healthy controls. The study is inevitably small and many of the differences noted relatively minor. Of interest, however, is the observation that three patients had significantly impaired systolic function with a calculated left ventricular ejection fraction of ,55%. What then is the significance of studies such as these? The first is the obvious impact on the care of patients with abnormal systolic function. ACE inhibitors are known to reduce morbidity in patients with even asymptomatic left ventricular dysfunction [4], the same may also be true for b-blockers. Patients at risk of developing a cardiomyopathy should thus undergo echocardiography to exclude significant systolic dysfunction. Importantly, also, symptoms such as exercise intolerance and fatigue should not simply be ascribed to the myopathy, as identical symptoms may be a result of a cardiomyopathy for which different treatment exists. The second point is, I think, more intriguing. The abnormalities observed in patients with muscular disease (atrophy, increased fatigue and reduced oxidative capacity) mirror the changes observed with chronic heart failure patients with primarily cardiac disease. The symptoms experienced by the two patient groups are similar and patients with myopathy suffer breathlessness and fatigue irrespective of the presence any cardiomyopathy. Myopathy patients
may thus provide an insight into the role of the muscle changes seen in chronic heart failure. We performed a small study of patients with mitochondrial myopathy who had markedly impaired skeletal muscular oxidative capacity [5]. Despite normal echocardiograms they had cardiopulmonary exercise tests which were identical to those seen in moderately severe chronic heart failure. Treatments directed at correcting the skeletal muscle abnormality may thus lead to symptomatic improvement in patients with primarily left ventricular systolic dysfunction. Ceviz et al. are to be congratulated for their study. The recognition of a cardiomyopathy as a part of the clinical syndrome of merosin-positive congenital muscular dystrophy has important implications for the care of this patient group. The wider link between cardiac and skeletal muscle diseases and the interplay between the two in generating symptoms requires further study. It is possible that such studies will benefit both patients with skeletal muscle disease and the much larger number of patients with persistently symptomatic left ventricular dysfunction.
References [1] Sachdev B, Elliot PM, McKenna WJ. Cardiovascular complications of neuromuscular disorders. Curr Treat Options Cardiovasc Med 2002;4(2):171–9. [2] Harrington D, Coats AJS. In: Poole-Wilson PA, Chatterjee K, Coats AJS, Collucci WS, Massie BM, editors, Skeletal muscle. Heart failure scientific principles and clinical practice, London: Churchill Livingstone, 1997. [3] Lim LE, Campbell KP. The sarcoglycan complex in limb–girdle muscular dystrophy. Curr Opin Neurol 1998;11:443–52. [4] SOLVD Investigators. Effect of Enalapril on mortality and development of heart failure in asymptomatic patients with reduced left ventricular ejection fraction. New Engl J Med 1992;327:685. [5] Harrington D, Chambers JS, Anker SD, Morgan-Hughes J, PooleWilson PA, Coats AJS. Similarities between exercise capacity and ventilation in patients with mitochondrial myopathy and chronic heart failure. J Am Coll Cardiol 1998;31(Suppl. 4A):331A.
lar systolic abnormalities may occur in patients with MP-CMD. Long term follow-up by serial echocardiographic studies is required to determine the clinical significance of these findings.
[8] [9]
[10]
Acknowledgements [11]
We would like to thank our families for full participation in our study. HT has been supported by the Association Francaise contre les Myopathies (AFM), France.
[12]
[13]
[14]
References [1] Straub V, Campbell KP. Muscular dystrophies and the dystrophin– glycoprotein complex. Curr Opin Neurol 1997;10:168–75. [2] Towbin JA. The role of cytoskeletal proteins in cardiomyopathies. Curr Opin Cell Biol 1998;10:131–9. [3] Lim LE, Campbell KP. The sarcoglycan complex in limb–girdle muscular dystrophy. Curr Opin Neurol 1998;11:443–52. [4] Melacini P, Fanin M, Duggan DJ et al. Heart involvement in muscular dystrophy due to sarcoglycan gene mutations. Muscle Nerve 1999;22:473–9. [5] Coral-Vazquez R, Cohn RD, Moore SA et al. Disruption of the sarcoglycan–sarcospan complex in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy. Cell 1999;98:465–74. [6] Ervasti JM, Campbell KP. A role for the dystrophin–glycoprotein complex as a transmembrane linker between laminin and actin. J Cell Biol 1993;122:809–23. ˇ ˇ [7] Topaloglu H, Kale G, Yalnizoglu D et al. Analysis of ‘pure’ congenital muscular dystrophies in thirty-eight cases. How different
[15]
[16]
[17]
[18] [19]
[20]
133
is the classical type 1 from the occidental type cerebromuscular dystrophy? Neuropediatrics 1994;25:94–100. Voit T. Congenital muscular dystrophies: 1997 update. Brain Dev 1998;20:65–74. ˇ H et al. Mutations in the Helbling-Leclerc A, Zhang X, Topaloglu laminin a2-chain gene (LAMA2) cause merosin deficient congenital muscular dystrophy. Nat Genet 1995;11:216–8. Tome FMS, Evangelista T, Leclerc A et al. Congenital muscular dystrophy with merosin deficiency. CR Acad Sci Paris III 1994;317:351–7. Brockington M, Sewry CA, Herrmann R et al. Assignment of a form of congenital muscular dystrophy with secondary merosin deficiency to chromosome 1q42. Am J Hum Genet 2000;66:428–35. Cormand B, Avela K, Pihko H et al. Assignment of the muscle– eye–brain disease gene to 1p32–p34 by linkage analysis and homozygosity mapping. Am J Hum Genet 1999;64:126–35. ˇ H et al. Clinical and histopathological Talim B, Kale G, Topaloglu study of merosin-deficient and merosin-positive congenital muscular dystrophy. Pediatric Develop Pathol 2000;3:168–76. Muntoni E, Philpot J, Spyrou N, Camici P, Dubowitz V. Cardiac involvement in merosin-negative congenital muscular dystrophy. Dev Med Child Neurol (abstract) 1995;72:90. Spyrou N, Philpot J, Foale R, Camici PG, Muntoni F. Evidence of left ventricular dysfunction in children with merosin-deficient congenital muscular dystrophy. Am Heart J 1998;136:474–6. Alehan FK, Ozkutlu S, Alehan D. Effects of respiration on left ventricular diastolic function in healthy children. Eur Heart J 1996;17:453–6. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072–83. Workshop report. 41st ENMC International workshop on congenital muscular dystrophy. Neuromusc Disord 1996; 6:295–306. ¨ ˇ H, C ˇ C¸il E, Topaloglu ¸ aglar M, Ozme S¸. Left ventricular structure and function by echocardiography in congenital muscular dystrophy. Brain Devel 1994;16:301–3. Dougherty AH, Naccarelli GV, Gray EL, Hicks CH, Goldstein RA. Congestive heart failure with normal systolic function. Am J Cardiol 1984;54:778–82.
Editorial comment
Muscular dystrophies and cardiomyopathies Derek Harrington* Kent Sussex Hospital, Mount Ephraim, Tunbridge Wells, Kent TN4 8 AT, UK
Received 10 June 2002; accepted 5 July 2002
*Tel.: 144-1892-672-986; fax: 144-1892-528-381.
Associations between diseases of cardiac and skeletal muscle are increasingly recognised [1]. Some
0167-5273 / 02 / $ – see front matter 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 02 )00319-4
134
D. Harrington / International Journal of Cardiology 87 (2003) 133 – 134
patients with muscular dystrophy have significantly impaired left ventricular function and suffer from chronic heart failure. Patients with chronic heart failure develop a wide range of secondary skeletal muscular changes which may have an important role in the pathogenesis of their condition [2]. To date, detailed echocardiographic studies of patients with skeletal muscle disease have been rarely performed. Ceviz et al. in this issue of the International Journal of Cardiology have performed such a study [3]. They describe a comparison of echocardiograms in 42 patients with merosin-positive congenital muscular dystrophy with healthy controls. The study is inevitably small and many of the differences noted relatively minor. Of interest, however, is the observation that three patients had significantly impaired systolic function with a calculated left ventricular ejection fraction of ,55%. What then is the significance of studies such as these? The first is the obvious impact on the care of patients with abnormal systolic function. ACE inhibitors are known to reduce morbidity in patients with even asymptomatic left ventricular dysfunction [4], the same may also be true for b-blockers. Patients at risk of developing a cardiomyopathy should thus undergo echocardiography to exclude significant systolic dysfunction. Importantly, also, symptoms such as exercise intolerance and fatigue should not simply be ascribed to the myopathy, as identical symptoms may be a result of a cardiomyopathy for which different treatment exists. The second point is, I think, more intriguing. The abnormalities observed in patients with muscular disease (atrophy, increased fatigue and reduced oxidative capacity) mirror the changes observed with chronic heart failure patients with primarily cardiac disease. The symptoms experienced by the two patient groups are similar and patients with myopathy suffer breathlessness and fatigue irrespective of the presence any cardiomyopathy. Myopathy patients
may thus provide an insight into the role of the muscle changes seen in chronic heart failure. We performed a small study of patients with mitochondrial myopathy who had markedly impaired skeletal muscular oxidative capacity [5]. Despite normal echocardiograms they had cardiopulmonary exercise tests which were identical to those seen in moderately severe chronic heart failure. Treatments directed at correcting the skeletal muscle abnormality may thus lead to symptomatic improvement in patients with primarily left ventricular systolic dysfunction. Ceviz et al. are to be congratulated for their study. The recognition of a cardiomyopathy as a part of the clinical syndrome of merosin-positive congenital muscular dystrophy has important implications for the care of this patient group. The wider link between cardiac and skeletal muscle diseases and the interplay between the two in generating symptoms requires further study. It is possible that such studies will benefit both patients with skeletal muscle disease and the much larger number of patients with persistently symptomatic left ventricular dysfunction.
References [1] Sachdev B, Elliot PM, McKenna WJ. Cardiovascular complications of neuromuscular disorders. Curr Treat Options Cardiovasc Med 2002;4(2):171–9. [2] Harrington D, Coats AJS. In: Poole-Wilson PA, Chatterjee K, Coats AJS, Collucci WS, Massie BM, editors, Skeletal muscle. Heart failure scientific principles and clinical practice, London: Churchill Livingstone, 1997. [3] Lim LE, Campbell KP. The sarcoglycan complex in limb–girdle muscular dystrophy. Curr Opin Neurol 1998;11:443–52. [4] SOLVD Investigators. Effect of Enalapril on mortality and development of heart failure in asymptomatic patients with reduced left ventricular ejection fraction. New Engl J Med 1992;327:685. [5] Harrington D, Chambers JS, Anker SD, Morgan-Hughes J, PooleWilson PA, Coats AJS. Similarities between exercise capacity and ventilation in patients with mitochondrial myopathy and chronic heart failure. J Am Coll Cardiol 1998;31(Suppl. 4A):331A.