Skip to main content
Top
Published in: Clinical Research in Cardiology 4/2012

01-04-2012 | Original Paper

Cardiovascular magnetic resonance imaging (CMR) reveals characteristic pattern of myocardial damage in patients with mitochondrial myopathy

Authors: Ali Yilmaz, Hans-Jürgen Gdynia, Matthias Ponfick, Sabine Rösch, Alfred Lindner, Albert C. Ludolph, Udo Sechtem

Published in: Clinical Research in Cardiology | Issue 4/2012

Login to get access

Abstract

Background

Mitochondrial myopathy comprises various clinical subforms of neuromuscular disorders that are characterised by impaired mitochondrial energy metabolism due to dysfunction of the mitochondrial respiratory chain. No comprehensive and targeted cardiovascular magnetic resonance (CMR) studies have been performed so far in patients with mitochondrial disorders. The present study aimed at characterising cardiac disease manifestations in patients with mitochondrial myopathy and elucidating the in vivo cardiac damage pattern of patients with different subforms of mitochondrial disease by CMR studies.

Methods and results

In a prospective study, 37 patients with mitochondrial myopathy underwent comprehensive neurological and cardiac evaluations including physical examination, resting ECG and CMR. The CMR studies comprised cine-CMR, T2-weighted “edema” imaging and T1-weighted late-gadolinium-enhancement (LGE) imaging. Various patterns and degrees of skeletal myopathy were present in the participants of this study, whereas clinical symptoms such as chest pain symptoms (in eight (22%) patients) and various degrees of dyspnea (in 16 (43%) patients) were less frequent. Pathological ECG findings were documented in eight (22%) patients. T2-weighted “edema” imaging was positive in one (3%) patient with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) only. LGE imaging demonstrated the presence of non-ischemic LGE in 12 (32%) patients: 10 out of 24 (42%) patients with CPEO (chronic progressive external ophthalmoplegia) or KSS (Kearns-Sayre syndrome) and 2 of 3 (67%) patients with MELAS were LGE positive. All 10 LGE-positive patients with CPEO or KSS demonstrated a potentially typical pattern of diffuse intramural LGE in the left-ventricular (LV) inferolateral segments.

Conclusions

Cardiac involvement is a frequent finding in patients with mitochondrial myopathy. A potentially characteristic pattern of diffuse intramural LGE in the LV inferolateral segments was identified in patients suffering from the subforms CPEO or KSS.
Literature
1.
go back to reference Chinnery PF, Turnbull DM (2001) Epidemiology and treatment of mitochondrial disorders. Am J Med Genet 106:94–101PubMedCrossRef Chinnery PF, Turnbull DM (2001) Epidemiology and treatment of mitochondrial disorders. Am J Med Genet 106:94–101PubMedCrossRef
2.
go back to reference Ito T, Hattori K, Tanaka M, Sugiyama S, Ozawa T (1990) Mitochondrial cytopathy. Jpn Circ J 54:1214–1220PubMedCrossRef Ito T, Hattori K, Tanaka M, Sugiyama S, Ozawa T (1990) Mitochondrial cytopathy. Jpn Circ J 54:1214–1220PubMedCrossRef
4.
go back to reference Lev D, Nissenkorn A, Leshinsky-Silver E et al (2004) Clinical presentations of mitochondrial cardiomyopathies. Pediatr Cardiol 25:443–450PubMedCrossRef Lev D, Nissenkorn A, Leshinsky-Silver E et al (2004) Clinical presentations of mitochondrial cardiomyopathies. Pediatr Cardiol 25:443–450PubMedCrossRef
5.
go back to reference Darin N, Oldfors A, Moslemi AR, Holme E, Tulinius M (2001) The incidence of mitochondrial encephalomyopathies in childhood: clinical features and morphological, biochemical, and DNA abnormalities. Ann Neurol 49:377–383PubMedCrossRef Darin N, Oldfors A, Moslemi AR, Holme E, Tulinius M (2001) The incidence of mitochondrial encephalomyopathies in childhood: clinical features and morphological, biochemical, and DNA abnormalities. Ann Neurol 49:377–383PubMedCrossRef
6.
go back to reference Holt IJ, Harding AE, Morgan-Hughes JA (1988) Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331:717–719PubMedCrossRef Holt IJ, Harding AE, Morgan-Hughes JA (1988) Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331:717–719PubMedCrossRef
7.
8.
go back to reference Goto Y, Nonaka I, Horai S (1990) A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348:651–653PubMedCrossRef Goto Y, Nonaka I, Horai S (1990) A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348:651–653PubMedCrossRef
9.
go back to reference Lestienne P, Ponsot G (1988) Kearns-Sayre syndrome with muscle mitochondrial DNA deletion. Lancet 1:885PubMedCrossRef Lestienne P, Ponsot G (1988) Kearns-Sayre syndrome with muscle mitochondrial DNA deletion. Lancet 1:885PubMedCrossRef
10.
go back to reference Wallace DC, Zheng XX, Lott MT et al (1988) Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease. Cell 55:601–610PubMedCrossRef Wallace DC, Zheng XX, Lott MT et al (1988) Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease. Cell 55:601–610PubMedCrossRef
11.
go back to reference Anan R, Nakagawa M, Miyata M et al (1995) Cardiac involvement in mitochondrial diseases. A study on 17 patients with documented mitochondrial DNA defects. Circulation 91:955–961PubMed Anan R, Nakagawa M, Miyata M et al (1995) Cardiac involvement in mitochondrial diseases. A study on 17 patients with documented mitochondrial DNA defects. Circulation 91:955–961PubMed
12.
go back to reference Channer KS, Channer JL, Campbell MJ, Rees JR (1988) Cardiomyopathy in the Kearns-Sayre syndrome. Br Heart J 59:486–490PubMedCrossRef Channer KS, Channer JL, Campbell MJ, Rees JR (1988) Cardiomyopathy in the Kearns-Sayre syndrome. Br Heart J 59:486–490PubMedCrossRef
13.
go back to reference Guenthard J, Wyler F, Fowler B, Baumgartner R (1995) Cardiomyopathy in respiratory chain disorders. Arch Dis Child 72:223–226PubMedCrossRef Guenthard J, Wyler F, Fowler B, Baumgartner R (1995) Cardiomyopathy in respiratory chain disorders. Arch Dis Child 72:223–226PubMedCrossRef
14.
go back to reference Holmgren D, Wahlander H, Eriksson BO, Oldfors A, Holme E, Tulinius M (2003) Cardiomyopathy in children with mitochondrial disease; clinical course and cardiological findings. Eur Heart J 24:280–288PubMedCrossRef Holmgren D, Wahlander H, Eriksson BO, Oldfors A, Holme E, Tulinius M (2003) Cardiomyopathy in children with mitochondrial disease; clinical course and cardiological findings. Eur Heart J 24:280–288PubMedCrossRef
15.
go back to reference Wortmann SB, Rodenburg RJ, Backx AP, Schmitt E, Smeitink JA, Morava E (2007) Early cardiac involvement in children carrying the A3243G mtDNA mutation. Acta Paediatr 96:450–451PubMedCrossRef Wortmann SB, Rodenburg RJ, Backx AP, Schmitt E, Smeitink JA, Morava E (2007) Early cardiac involvement in children carrying the A3243G mtDNA mutation. Acta Paediatr 96:450–451PubMedCrossRef
16.
go back to reference Jose T, Gdynia HJ, Mahrholdt H et al (2011) CMR gives clue to “ragged red fibers” in the heart in a patient with mitochondrial myopathy. Int J Cardiol 149(1):e24–7 Jose T, Gdynia HJ, Mahrholdt H et al (2011) CMR gives clue to “ragged red fibers” in the heart in a patient with mitochondrial myopathy. Int J Cardiol 149(1):e24–7
17.
go back to reference Goldberg LR, Jessup M (2006) Stage B heart failure: management of asymptomatic left ventricular systolic dysfunction. Circulation 113:2851–2860PubMedCrossRef Goldberg LR, Jessup M (2006) Stage B heart failure: management of asymptomatic left ventricular systolic dysfunction. Circulation 113:2851–2860PubMedCrossRef
18.
go back to reference Baccouche H, Mahrholdt H, Meinhardt G et al (2009) Diagnostic synergy of non-invasive cardiovascular magnetic resonance and invasive endomyocardial biopsy in troponin-positive patients without coronary artery disease. Eur Heart J 30:2869–2879PubMedCrossRef Baccouche H, Mahrholdt H, Meinhardt G et al (2009) Diagnostic synergy of non-invasive cardiovascular magnetic resonance and invasive endomyocardial biopsy in troponin-positive patients without coronary artery disease. Eur Heart J 30:2869–2879PubMedCrossRef
19.
go back to reference Yilmaz A, Kindermann I, Kindermann M et al (2010) Comparative evaluation of left and right ventricular endomyocardial biopsy: differences in complication rate and diagnostic performance. Circulation 122:900–909PubMedCrossRef Yilmaz A, Kindermann I, Kindermann M et al (2010) Comparative evaluation of left and right ventricular endomyocardial biopsy: differences in complication rate and diagnostic performance. Circulation 122:900–909PubMedCrossRef
20.
go back to reference Cerqueira MD, Weissman NJ, Dilsizian V et al (2002) Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 105:539–542PubMedCrossRef Cerqueira MD, Weissman NJ, Dilsizian V et al (2002) Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 105:539–542PubMedCrossRef
21.
go back to reference Rochitte CE, Oliveira PF, Andrade JM et al (2005) Myocardial delayed enhancement by magnetic resonance imaging in patients with Chagas’ disease: a marker of disease severity. J Am Coll Cardiol 46:1553–1558PubMedCrossRef Rochitte CE, Oliveira PF, Andrade JM et al (2005) Myocardial delayed enhancement by magnetic resonance imaging in patients with Chagas’ disease: a marker of disease severity. J Am Coll Cardiol 46:1553–1558PubMedCrossRef
22.
go back to reference Silva MC, Meira ZM, Gurgel GJ et al (2007) Myocardial delayed enhancement by magnetic resonance imaging in patients with muscular dystrophy. J Am Coll Cardiol 49:1874–1879PubMedCrossRef Silva MC, Meira ZM, Gurgel GJ et al (2007) Myocardial delayed enhancement by magnetic resonance imaging in patients with muscular dystrophy. J Am Coll Cardiol 49:1874–1879PubMedCrossRef
23.
go back to reference Francone M, Bucciarelli-Ducci C, Carbone I et al (2009) Impact of primary coronary angioplasty delay on myocardial salvage, infarct size, and microvascular damage in patients with ST-segment elevation myocardial infarction: insight from cardiovascular magnetic resonance. J Am Coll Cardiol 54:2145–2153PubMedCrossRef Francone M, Bucciarelli-Ducci C, Carbone I et al (2009) Impact of primary coronary angioplasty delay on myocardial salvage, infarct size, and microvascular damage in patients with ST-segment elevation myocardial infarction: insight from cardiovascular magnetic resonance. J Am Coll Cardiol 54:2145–2153PubMedCrossRef
24.
go back to reference Baccouche H, Yilmaz A, Alscher D, Klingel K, Val-Bernal JF, Mahrholdt H (2008) Images in cardiovascular medicine. Magnetic resonance assessment and therapy monitoring of cardiac involvement in Churg-Strauss syndrome. Circulation 117:1745–1749PubMedCrossRef Baccouche H, Yilmaz A, Alscher D, Klingel K, Val-Bernal JF, Mahrholdt H (2008) Images in cardiovascular medicine. Magnetic resonance assessment and therapy monitoring of cardiac involvement in Churg-Strauss syndrome. Circulation 117:1745–1749PubMedCrossRef
25.
go back to reference Yilmaz A, Gdynia HJ, Baccouche H et al (2008) Cardiac involvement in patients with Becker muscular dystrophy: new diagnostic and pathophysiological insights by a CMR approach. J Cardiovasc Magn Reson 10:50PubMedCrossRef Yilmaz A, Gdynia HJ, Baccouche H et al (2008) Cardiac involvement in patients with Becker muscular dystrophy: new diagnostic and pathophysiological insights by a CMR approach. J Cardiovasc Magn Reson 10:50PubMedCrossRef
26.
go back to reference Yilmaz A, Gdynia HJ, Ludolph AC, Klingel K, Kandolf R, Sechtem U (2010) Images in cardiovascular medicine. Cardiomyopathy in a Duchenne muscular dystrophy carrier and her diseased son: similar pattern revealed by cardiovascular MRI. Circulation 121:e237–e239PubMedCrossRef Yilmaz A, Gdynia HJ, Ludolph AC, Klingel K, Kandolf R, Sechtem U (2010) Images in cardiovascular medicine. Cardiomyopathy in a Duchenne muscular dystrophy carrier and her diseased son: similar pattern revealed by cardiovascular MRI. Circulation 121:e237–e239PubMedCrossRef
27.
go back to reference Cooper LT, Baughman KL, Feldman AM et al (2007) The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol 50:1914–1931PubMedCrossRef Cooper LT, Baughman KL, Feldman AM et al (2007) The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol 50:1914–1931PubMedCrossRef
Metadata
Title
Cardiovascular magnetic resonance imaging (CMR) reveals characteristic pattern of myocardial damage in patients with mitochondrial myopathy
Authors
Ali Yilmaz
Hans-Jürgen Gdynia
Matthias Ponfick
Sabine Rösch
Alfred Lindner
Albert C. Ludolph
Udo Sechtem
Publication date
01-04-2012
Publisher
Springer-Verlag
Published in
Clinical Research in Cardiology / Issue 4/2012
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-011-0387-z

Other articles of this Issue 4/2012

Clinical Research in Cardiology 4/2012 Go to the issue