Europace Advance Access originally published online on March 8, 2007
Europace 2007 9(4):256-257; doi:10.1093/europace/eum013
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LETTER TO THE EDITOR
The letter of Finsterer and Stollberger was shown to the authors who replied
yna Markiewicz-
oskot
Department of Pediatric Cardiology
Medical University of Silesia
Medyków 16
40-752 Katowice
Poland
Department of Biochemistry
Medical University of Silesia
Narcyzów 1
41-200 Sosnowiec
Poland
oskot
Department of Pediatric Cardiology
Medical University of Silesia
Medyków 16
40-752 Katowice
Poland
aw Szydowski
Department of Pediatric Cardiology
Medical University of Silesia
Medyków 16
40-752 Katowice
Poland
a W
glarz
Department of Biochemistry
Medical University of Silesia
Narcyzów 1
41-200 Sosnowiec
Poland
Department of Biochemistry
Medical University of Silesia
Narcyzów 1
41-200 Sosnowiec
Poland
Tel: +48 32 207 18 55 Fax: +207 18 61 E-mail address: ejaniszewska{at}slam.katowice.pl
We would like to express our gratitude and appreciation to the authors of the article ‘Genetic background of the left venricular hypertrabeculation/noncompation with stroke’ for fruitful comments of our manuscript.1
We agree with Finsterer et al. that in a single patient ventricular non-compaction is an acquired phenomenon. In our case of a 3-year-old girl with both chambers affected and heart failure, the disorder has not disappeared after treatment. Two-dimensional echocardiograms disclosed numerous prominent trabeculations in both ventricles with deep intertrabecular recesses and thickened endocardium. The echocardiographic images were diagnostic2 of a restrictive filling pattern.
Mitral inflow velocities demonstrated a decrease in E/A ratio, consistent with restrictive left ventricular physiology. The left and right atria were enlarged. (LA-20 mm, Ao-14 mm). Left ventricular systolic function was depressed, with an ejection fraction (EF) of 48–50%. During follow-up, the EF of the left ventricle increased to 60–65% and now to 75%. But the ventricular morphology and restrictive filling pattern did not change during follow-up.
The girl had presented with an ischaemic stroke (right medial cerebral artery territory) when she was over 9-months-old. Non-compaction of the ventricles with quite good systolic function had been recognized before the cerebral event. The girl had no history of ventricular arrhythmias or atrial fibrillation and acetylsalicylic acid was used to prevent thromboembolism.
Oral anticoagulation (acenocoumarol) was initiated after the stroke and heart failure. More recently, when the ventricular systolic function improved, the patient was changed back to acetylsalicylic acid. Pignatelli et al. reported a study of 36 children with ventricular non-compaction, who were treated with aspirin therapy without systemic embolism.3
The girl had regular neurological and cardiological follow-up at intervals of 4-6 months. She had no concomitant congenital heart disease, clinical evidence of skeletal myopathy or facial dysmorphism, and there was nothing to suggest a neuromuscular disorder.
In clinical conclusion, this case shows that non-compaction with severe biventricular hypertrophy may be underdiagnosed or misdiagnosed as hypertrophic, dilated or restrictive cardiomyopathy.
We agree with the statement that the genetic background of left ventricular non-compaction (LVNC) is far more heterogeneous than mentioned.1,4 In our study, we focused on cardiac implications in LVNC. We discussed some, mostly mutated, genes which are associated with non-compaction.1 Mutations in LMNA gene encoding two ubiquitously expressed nuclear proteins, lamins A and C, give rise to seven different pathologies affecting specific tissues. Three of these disorders affect cardiac and/or skeletal muscles with atrioventricular conduction disturbances, dilated cardiomyopathy, and sudden cardiac death as common features.1
One of the genes responsible for non-compaction, tafazzin (G 4.5) is localized on chromosome Xq28 and expressed at high levels in cardiac and skeletal muscle. Its role in the mitochondria is maintaining the levels of cardiolipin, promoting differentiation and maturation of osteoblasts, and preventing adipocytes from maturing.5 This gene is localized in the proximity of other genes responsible for myopathies such as Emery–Dreifuss muscular dystrophy or Barth syndrome.6 Mutations in the gene G4.5 result in a wide spectrum of severe infantile cardiomyopathic phenotypes, including isolated LVNC, as well as Barth syndrome with dilated cardiomyopathy (DCM).7
Ichida et al.8 identified a Cys118-to-Arg (C118R) missense mutation in the exon 4 of the tafazzin gene in a 5-month-old male with isolated LVNC associated with a dilated, mildly hypertrophic heart, with poor systolic function and clinical heart failure. Neutropenia and 3-methylglutaconicaciduria were also identified.
The human LMNA gene, when mutated, has been shown to cause at least seven human diseases: dilated cardiomyopathy, an Emery–Dreifuss muscular dystrophy, a limb girdle muscular dystrophy, a familial partial lipodystrophy, Charcot–Marie–Tooth disease type II, mandibuloacral dysplasia, and a Hutchinson–Gilford Progeria.9 LMNA mutations have been associated with familial or sporadic dilated cardiomyopathy (DC), with or without conduction system disease.9,10
In 2004, Sasse-Klaassen et al.,11 discovered novel gene locus for autosomal dominant LVNC. They mapped a locus for autosomal dominant LVNC to a 6.8-megabase region on human chromosome 11p15. Identification of the disease gene will allow genetic screening and provide fundamental insight into the understanding of myocardial morphogenesis.11
Our findings are in agreement with those of Stollberger et al.12 who stated that: (i) non-compaction has a higher prevalence than previously thought, which seems to increase further with the improvement in cardiac imaging; (ii) because non-compaction is most frequently diagnosed on echocardiography, echocardiographers should be aware and trained to recognize this abnormality; (iii) non-compaction is frequently associated with other cardiac and extracardiac, particularly neuromuscular disorders; (iv) there are indications that the cause of non-compaction is usually genetic and quite heterogeneous; and (v) controversies exist about diagnostic criteria, nomenclature, prognosis, origin, pathogenesis, and the necessity to classify non-compaction as a distinct entity and cardiomyopathy by the World Health Organization.12
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oskot G, Moric-Janiszewska E, oskot M, Szydowski L, Wglarz L, Hollek A. Isolated ventricular noncompaction—clinical study and genetic review. Europace 2006; 8: 1064–7.[2] Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA. Echocardiographic and pathoanatomical characteristics of isolated noncompaction: a step towards classification as a distinct cardiomyopathy. Heart 2001; 86: 666–71.
[3] Pignatelli RH, McMahon CJ, Dreyer WJ, Denfield SW, Price J, Belmont JW, et al. Characterization of left ventricular noncompation in children. A relatively common form of cardiomyoathy. Circulation 2003; 108: 2672–8.
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[8] Ichida F, Tsubata S, Bowles KR, Haneda N, Uese K, Miyawaki T, et al. Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation 2001; 103: 1256–63.
[9] Taylor MR, Robinson ML, Mestroni L. Analysis of genetic variations of lamin A/C gene (LMNA) by denaturing high performance liquid chromatography. J Biomol Screen 2004; 9: 625–8.
[10] Hermida-Prieto M, Monserrat L, Castro-Beiras A, Laredo R, Soler R, Peteiro J, et al. Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations. Am J Cardiol 2004; 94: 50–4.[CrossRef][Web of Science][Medline]
[11] Sasse-Klaassen S, Probst S, Gerull B, Oechslin E, Nurnberg P, Heuser A, et al. Novel gene locus for autosomal dominant left ventricular noncompaction maps to chromosome 11p15. Circulation 2004; 109: 2720–3.
[12] Stollberger C and Finsterer J. Left ventricular hypertrabeculation/noncompaction. J Am Soc Echocardiogr 2004; 17: 91–100.[CrossRef][Web of Science][Medline]
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