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Cardiac Magnetic Resonance Aids in the Diagnosis of Mitochondrial Cardiomyopathy

2011; Lippincott Williams & Wilkins; Volume: 123; Issue: 6 Linguagem: Inglês

10.1161/circulationaha.110.973305

1524-4539

Sara L. Partington, Michael M. Givertz, Sanjay Gupta, Raymond Y. Kwong,

Advanced MRI Techniques and Applications

HomeCirculationVol. 123, No. 6Cardiac Magnetic Resonance Aids in the Diagnosis of Mitochondrial Cardiomyopathy Free AccessBrief ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplementary MaterialsFree AccessBrief ReportPDF/EPUBCardiac Magnetic Resonance Aids in the Diagnosis of Mitochondrial Cardiomyopathy Sara L. Partington, MD, Michael M. Givertz, MD, Sanjay Gupta, MBBS, MRCP and Raymond Y. Kwong, MD Sara L. PartingtonSara L. Partington From the Non-invasive Cardiovascular Imaging Program, Department of Medicine and Radiology (S.L.P., S.G., R.Y.K.), and the Cardiovascular Division, Department of Medicine (M.M.G., R.Y.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. , Michael M. GivertzMichael M. Givertz From the Non-invasive Cardiovascular Imaging Program, Department of Medicine and Radiology (S.L.P., S.G., R.Y.K.), and the Cardiovascular Division, Department of Medicine (M.M.G., R.Y.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. , Sanjay GuptaSanjay Gupta From the Non-invasive Cardiovascular Imaging Program, Department of Medicine and Radiology (S.L.P., S.G., R.Y.K.), and the Cardiovascular Division, Department of Medicine (M.M.G., R.Y.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. and Raymond Y. KwongRaymond Y. Kwong From the Non-invasive Cardiovascular Imaging Program, Department of Medicine and Radiology (S.L.P., S.G., R.Y.K.), and the Cardiovascular Division, Department of Medicine (M.M.G., R.Y.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Originally published15 Feb 2011https://doi.org/10.1161/CIRCULATIONAHA.110.973305Circulation. 2011;123:e227–e229A 29-year-old woman presented with symptoms of cough, shortness of breath, and wheezing. She was diagnosed with bronchitis, but did not improve with empirical therapy, including antibiotics, inhalers, and prednisone. She subsequently developed chest pain that was worse when lying down, and a chest X-ray demonstrated cardiomegaly. This radiographic finding prompted further investigations. Her past medical history was notable for respiratory distress at birth and small stature growing up. She was diagnosed with a heart murmur at age 15, but investigations performed at that time were unrevealing. She also suffered from hearing loss. In retrospect it was discovered that several members in her maternal family, including her mother, grandmother, and aunt, also suffered from hearing loss. In addition, her mother had type 2 diabetes and a history of stroke and seizures.On physical examination, she was a short, thin young woman with a body mass index of 17, wearing bilateral hearing aids. Her vital signs were normal. Cardiac auscultation revealed a 2/6 systolic ejection murmur. Laboratories revealed an elevated serum creatinine level of 1.36 mg/dL and a markedly elevated B-type natriuretic peptide level of 1417 pg/mL. The electrocardiogram was abnormal with evidence of right atrial enlargement, inferior Q waves, poor R wave progression, and inferolateral T wave inversions.Transthoracic echocardiography revealed severe, concentric left ventricular (LV) hypertrophy with a septal wall thickness of 17 mm (Figure 1). LV systolic function was hyperdynamic (Movie I of the online-only Data Supplement), while diastolic filling demonstrated a restrictive pattern. The right ventricle also demonstrated increased wall thickness but was of normal chamber size and function. There was a moderate-sized pericardial effusion measuring 1.8 cm inferiorly with no evidence of hemodynamic compromise.Download figureDownload PowerPointFigure 1. Transthoracic echocardiogram demonstrating the parasternal long (A) and short (B) axis images with increased LV mass and a moderate-sized pericardial effusion (arrow).A cardiac magnetic resonance (CMR) scan was performed for better assessment of cardiac morphology and to rule out an infiltrative process. CMR confirmed severe concentric LV hypertrophy with an LV ejection fraction of 55% (Figure 2; Movie II of the online-only Data Supplement). Right ventricular dimensions and function were normal. T2-weighted imaging demonstrated high signal intensity globally with evidence of focal increased signal intensity in the subepicardial anterior and midwall anterolateral regions consistent with generalized edema with focal regions of increased edema (Figure 3A). On late gadolinium enhancement (LGE) imaging, extensive areas of hyperenhancement were seen in the basal to mid anterior and anterolateral walls corresponding to the focal regions of increased signal intensity on the T2-weighted images (Figure 3B). The territories of LGE are consistent with regions of edema or combined fibrosis and edema. Perfusion imaging revealed a circumferential global perfusion defect (worse with stress compared to rest) consistent with small vessel disease (Figure 4; Movies IIIA and IIIB of the online-only Data Supplement). These findings were suggestive of an infiltrative or myopathic process.Download figureDownload PowerPointFigure 2. CMR steady state free procession image of the left ventricle in the 2-chamber view in diastole (A) and systole (B), demonstrating LV hypertrophy and a moderate-sized pericardial effusion.Download figureDownload PowerPointFigure 3. CMR short axis images of the mid left ventricle. T2-weighted image (A) demonstrates bright myocardium globally as well as areas of brighter myocardium (arrows), suggesting global edema with areas of increased focal edema in the subepicardial anterior and midwall anterolateral regions. Late gadolinium enhancement (B) (arrow) corresponds with the territories of bright myocardium on T2-weighted imaging, suggesting edema or a combination of edema and fibrosis.Download figureDownload PowerPointFigure 4. CMR stress perfusion imaging (A) demonstrates a circumferential subendocardial region of hypoperfusion (arrow) with regadenoson (vasodilator) stress indicating a perfusion defect. CMR rest perfusion image (B) demonstrates a circumfrential subendocardial perfusion defect that is less severe than with stress, suggesting small vessel disease.The concomitant presence of hearing loss, low skeletal mass, cardiac hypertrophy, and pericardial effusion raised the possibility of a mitochondrial cardiomyopathy. Along with deafness, the maternal history of diabetes, seizures, and stroke-like syndrome also suggested this diagnosis. Additional laboratories revealed evidence of anaerobic metabolism with an elevated lactic acid level of 2.1 mmol/L and abnormal Krebs cycle metabolism with an elevated pyruvate level of 0.15 mmol/L. Fasting blood glucose was 118 mg/dL, and hemoglobin A1c was mildly elevated at 6.4%.The diagnosis of mitochondrial cardiomyopathy was confirmed, and other forms of infiltrative and inflammatory cardiomyopathies were ruled out by endomyocardial biopsy. Light microscopic evaluation revealed the hallmarks of mitochondrial myopathy, with myocyte hypertrophy, perinuclear vacuolar swelling (Figure 5A), and the absence of other infiltrative or inflammatory disorders. Electron microscopy (Figure 5B) revealed severe hyperplasia of the mitochondria, with marked variability in size, shape and morphology, including abnormalities in the structure of the cristae, along with an absence of specific findings of other cardiomyopathies.Download figureDownload PowerPointFigure 5. Endomyocardial biopsy. A, Light microscopic image showing myocyte hypertrophy and vacuolar change (H&E stain, 200× original magnification). B, Electron microscopic image demonstrating an excessive number of swollen mitochondria with variability in size and shape, and abnormal morphology. Images courtesy of Dr. Robert Padera, Department of Pathology, Brigham and Women's Hospital.This case highlights the important clinical and CMR characteristics in making the uncommon diagnosis of mitochondrial cardiomyopathy. The tissue-characterizing capability of CMR was effective in ruling out other causes of increased LV mass. Familial hypertrophic cardiomyopathy due to sarcomeric gene mutations can have LGE in variable locations and distributions, but most commonly at the junction of the interventricular septum and right ventricular wall,1 and pericardial effusion is not a common finding. Fabry's disease specifically involves LGE in the inferolateral basal or mid basal segments.2 The CMR findings were not typical of an infiltrative cardiomyopathy. Cardiac amyloid shows diffuse subendocardial LGE not present in this patient. In addition, the gadolinium washout kinetics in blood compared to myocardium were not consistent with cardiac amyloidosis.1 Myocardial sarcoid does not typically result in generalized hypertrophy.3Mitochondrial disorders result in problems with oxidative phosphorylation, limiting the production of adenosine triphosphate. Mitochondrial diseases represent a heterogeneous group of disorders, but the brain, heart, and skeletal muscle are most commonly affected, because these systems are particularly vulnerable to defects in energy metabolism. Other multisystem abnormalities can occur, including sensorineural hearing loss, endocrine dysfunction (diabetes), and short stature. Although LV hypertrophy is not common in all forms of mitochondrial disease, in 1 large series of children with various subtypes of mitochondrial myopathies, 17% had an associated cardiomyopathy. The cardiomyopathy frequently results in concentric hypertrophy with significant variability in LV volume and function.4 Pericardial effusions are present in up to 1 quarter.The combination of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episode (MELAS), often accompanied by seizures, represents a clinically distinct subgroup of patients with mitochondrial disease. Symmetrical LV hypertrophy is prevalent among patients with MELAS.5 Although the genetic tests to confirm the diagnosis of MELAS are pending, our patient's clinical symptoms, laboratory work, and family history are suggestive of this diagnosis. Previous reports of CMR in MELAS also showed a pericardial effusion, increased signal with T2-weighted imaging, and LGE.6The presence of cardiomyopathy in patients with mitochondrial disease has prognostic implications because it is associated with increased mortality.4 The diagnosis can be made with a skeletal muscle biopsy and screening for cardiac involvement. Although in this case CMR was used to assess the etiology of cardiomyopathy in a patient without known mitochondrial disease, CMR could also be used to screen for myocardial involvement in patients with known mitochondrial myopathy. This case also illustrates the importance of taking a careful family history. Treatment consists of standard heart failure therapy, and dietary supplements that increase adenosine triphosphate production, such as creatine, carnitine, and coenzyme Q10.Our patient's presenting symptoms, which included cough, shortness of breath, and positional chest pain, were presumed to be due to myopericarditis, and her chest pain improved with nonsteroidal antiinflammatory therapy. Our patient was also treated with metoprolol, with consideration of coenzyme Q10 and carnitine supplementation. Genetic testing was negative for the known genes responsible for hypertrophic cardiomyopathy and dilated cardiomyopathy. Mitochondrial genome analysis is pending.DisclosuresNone.FootnotesGuest Editor for this article was Leon Axel, MD, PhD.The online-only Data Supplement is available with this article at http://circ.ahajournals.org/cgi/content/full/123/6/e227/DC1.Correspondence to Sara Partington, MD, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. E-mail [email protected]orgReferences1. Sechtem U, Mahrholdt H, Vogelsberg H. Cardiac magnetic resonance in myocardial disease. Heart. 2007; 93:1520–1527CrossrefMedlineGoogle Scholar2. DeCobelli F, Esposito A, Belloni E, Pieroni M, Perseghin G, Chimenti C, Frustaci A, Del Maschio A. Delayed-enhanced cardiac MRI for differentiation of Fabry's disease from symmetric hypertrophic cardiomyopathy. AJR Am J Roentgenol. 2009; 192:W97–W102CrossrefMedlineGoogle Scholar3. Smedema JP, Snoep G, van Kroonenburgh MPG, van Genus RJ, Dassen WRN, Gorgels AP, Crijns HJ. Evaluation of the accuracy of gadolinium-enhanced cardiovascular magnetic resonance in the diagnosis of cardiac sarcoidosis. J Am Coll Cardiol. 2005; 45:1683–1690CrossrefMedlineGoogle Scholar4. Holmgren D, Wåhlander H, Eriksson BO, Oldfors A, Holme E, Tulinius M. Cardiomyopathy in children with mitochondrial disease; clinical course and cardiological findings. Eur Heart J. 2003; 24:280–288CrossrefMedlineGoogle Scholar5. Anan R, Nakagawa M, Miyata M, Higuchi I, Nakao S, Suehara M, Osame M, Tanaka H. Cardiac involvement in mitochondrial diseases: A study on 17 patients with documented mitochondrial DNA defects. Circulation. 1995; 91:955–961LinkGoogle Scholar6. Jose T, Gdynia HJ, Mahrholdt H, Vöhringer M, Klingel K, Kandolf R, Bornemann A, Yilmaz A. CMR gives clue to "ragged red fibers" in the heart in a patient with mitochondrial myopathy.Int J Cardiol. 2009April1. [Epub ahead of print].MedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Cha M, Kim C, Park C, Hong Y, Shin J, Kim T, Cha Y and Park C (2022) Differential Diagnosis of Thick Myocardium according to Histologic Features Revealed by Multiparametric Cardiac Magnetic Resonance Imaging, Korean Journal of Radiology, 10.3348/kjr.2021.0815, 23:6, (581), . Lioncino M, Monda E, Caiazza M, Fusco A, Cirillo A, Dongiglio F, Simonelli V, Sampaolo S, Ruggiero L, Scarano G, Pota V, Frisso G, Mazzaccara C, D'Amati G, Nigro G, Russo M, Wahbi K and Limongelli G (2022) Cardiovascular Involvement in mtDNA Disease, Heart Failure Clinics, 10.1016/j.hfc.2021.07.003, 18:1, (51-60), Online publication date: 1-Jan-2022. Keogh M, Steele H and Chinnery P (2018) Mitochondrial Cardiovascular Diseases Cardiovascular Genetics and Genomics, 10.1007/978-3-319-66114-8_8, (239-258), . Kabunga P, Lau A, Phan K, Puranik R, Liang C, Davis R, Sue C and Sy R (2015) Systematic review of cardiac electrical disease in Kearns–Sayre syndrome and mitochondrial cytopathy, International Journal of Cardiology, 10.1016/j.ijcard.2014.12.038, 181, (303-310), Online publication date: 1-Feb-2015. Florian A, Ludwig A, Stubbe-Dräger B, Boentert M, Young P, Waltenberger J, Rösch S, Sechtem U and Yilmaz A (2015) Characteristic cardiac phenotypes are detected by cardiovascular magnetic resonance in patients with different clinical phenotypes and genotypes of mitochondrial myopathy, Journal of Cardiovascular Magnetic Resonance, 10.1186/s12968-015-0145-x, 17:1, Online publication date: 1-Dec-2015. Nakagawa H, Okayama S, Kamon D, Nakano T, Onoue K, Kawakami R, Horii M, Sakaguchi Y, Uemura S, Takemura G and Saito Y (2014) Refractory High Output Heart Failure in a Patient with Primary Mitochondrial Respiratory Chain Disease, Internal Medicine, 10.2169/internalmedicine.53.1386, 53:4, (315-319), . Raissuni Z, Ghannudi S, Doghmi N, Cherti M and Germain P (2014) Mitochondrial cardiomyopathy: An exceptional cause of cardiac hypertrophy, Diagnostic and Interventional Imaging, 10.1016/j.diii.2013.12.019, 95:6, (611-612), Online publication date: 1-Jun-2014. Raissuni Z, El Ghannudi S, Doghmi N, Cherti M and Germain P (2014) Cardiomyopathie mitochondriale : une cause exceptionnelle d'hypertrophie cardiaque, Journal de Radiologie Diagnostique et Interventionnelle, 10.1016/j.jradio.2013.10.008, 95:6, (606-608), Online publication date: 1-Jun-2014. Pfeffer G and Chinnery P (2011) Diagnosis and treatment of mitochondrial myopathies, Annals of Medicine, 10.3109/07853890.2011.605389, 45:1, (4-16), Online publication date: 1-Feb-2013. Lakdawala N and William Dec G (2013) Hypertrophic, Restrictive, and Infiltrative Cardiomyopathies Cardiovascular Therapeutics: A Companion to Braunwald's Heart Disease, 10.1016/B978-1-4557-0101-8.00017-5, (332-341), . Stalder N, Yarol N, Tozzi P, Rotman S, Morris M, Fellmann F, Schwitter J and Hullin R (2012) Mitochondrial A3243G Mutation With Manifestation of Acute Dilated Cardiomyopathy, Circulation: Heart Failure, 5:1, (e1-e3), Online publication date: 1-Jan-2012. Karamitsos T, Francis J and Neubauer S (2011) The Current and Emerging Role of Cardiovascular Magnetic Resonance in the Diagnosis of Nonischemic Cardiomyopathies, Progress in Cardiovascular Diseases, 10.1016/j.pcad.2011.08.007, 54:3, (253-265), Online publication date: 1-Nov-2011. February 15, 2011Vol 123, Issue 6 Advertisement Article InformationMetrics © 2011 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.110.973305PMID: 21321176 Originally publishedFebruary 15, 2011 PDF download Advertisement SubjectsCardiomyopathyComputerized Tomography (CT)Diabetes, Type 2EchocardiographyHeart Failure