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Left ventricular noncompaction and myocardial fibrosis: a case report.
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PMID:  20843341     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Left ventricular noncompaction (LVNC) is a rare congenital abnormality. It is currently classified as a genetic cardiomyopathy and results from early arrest of endomyocardial morphogenesis. The pathophysiology of left ventricular dysfunction, which becomes apparent beyond the 4th decade of life, is unclear.
CASE REPORT: We report a case of 60-year-old woman who presented with shortness of breath and showed noncompacted endocardium on echocardiography. Cardiac catheterization and viral studies were unremarkable. Histology revealed endomyocardial fibrosis without disarray. She was subsequently diagnosed with LVNC and treated with medications.
DISCUSSION: Cardiologists and other physicians should be aware of LVNC due to its high likelihood of misdiagnosis and associated high complication rates. Early diagnosis, intervention and screening among family members can decrease the morbidity and mortality associated with LVNC.
Authors:
Jagadeesh K Kalavakunta; Hemasri Tokala; Aparna Gosavi; Vishal Gupta
Publication Detail:
Type:  Journal Article     Date:  2010-09-15
Journal Detail:
Title:  International archives of medicine     Volume:  3     ISSN:  1755-7682     ISO Abbreviation:  Int Arch Med     Publication Date:  2010  
Date Detail:
Created Date:  2010-09-27     Completed Date:  2011-07-14     Revised Date:  2011-11-21    
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Nlm Unique ID:  101317943     Medline TA:  Int Arch Med     Country:  England    
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Languages:  eng     Pagination:  20     Citation Subset:  -    
Affiliation:
Department of Internal Medicine: Division of Cardiology, Michigan State University/Kalamazoo Center for Medical Studies/Borgess Medical Center, Kalamazoo, MI, USA. vishalgupta@borgess.com.
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Journal ID (nlm-ta): Int Arch Med
ISSN: 1755-7682
Publisher: BioMed Central
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Copyright ©2010 Kalavakunta et al; licensee BioMed Central Ltd.
open-access:
Received Day: 15 Month: 2 Year: 2010
Accepted Day: 15 Month: 9 Year: 2010
collection publication date: Year: 2010
Electronic publication date: Day: 15 Month: 9 Year: 2010
Volume: 3First Page: 20 Last Page: 20
Publisher Id: 1755-7682-3-20
PubMed Id: 20843341
DOI: 10.1186/1755-7682-3-20

Left ventricular noncompaction and myocardial fibrosis: a case report
Jagadeesh K Kalavakunta1 Email: jkalavakunta@gmail.com
Hemasri Tokala1 Email: hemasrit@gmail.com
Aparna Gosavi2 Email: agosavi03@yahoo.com
Vishal Gupta1 Email: vishalgupta@borgess.com
1Department of Internal Medicine: Division of Cardiology, Michigan State University/Kalamazoo Center for Medical Studies/Borgess Medical Center, Kalamazoo, MI, USA
2Department of Internal Medicine: Division of Cardiology, University of Missouri-Columbia, MO, USA

Background

Noncompaction of the ventricular myocardium, also called left ventricular noncompaction (LVNC), is a rare congenital abnormality seen in only 0.05% of adults [1]. It is characterized by spongy myocardium and results from arrest of the compaction of the loosely interwoven meshwork of myocardial fibers during endomyocardial morphogenesis between 5-8 weeks of fetal life. With the advent of new diagnostic imaging techniques, more cases of LVNC are being detected. Early diagnosis is crucial due to associated high morbidity and mortality.


Case Report

A 60-year-old Caucasian woman with a frequent history of asthma, presented to the hospital with several weeks of progressively worsening shortness of breath. She provided a history of intermittent chest pain which, at one time, was relieved with nitroglycerin and morphine, given in the emergency department. As the patient continued having increasing shortness of breath despite adjustments in her asthma medications, she was admitted for further workup. Pertinent positives in her review of systems included decreased appetite, paroxysmal nocturnal dyspnea, orthopnea, lower extremity swelling and intermittent chest pain. The patient denied fever, chills, or cough. Her past medical history was significant for type 2 diabetes, asthma, and osteoarthritis. Medications included theophylline, prednisone, furosemide (Lasix), fluticasone & salmeterol (Advair) and albuterol. She quit smoking 20 years ago and denied alcohol or intravenous drug abuse. Family history was negative for coronary artery disease at an early age. The physical examination was significant for tachycardia, raised jugular venous pressure, lower extremity edema and expiratory wheezes upon chest examination.

Laboratory tests revealed elevated brain natriuretic peptide at 1020 pg/ml (normal <100 pg/ml), and negative cardiac enzymes with troponin levels consistently below 0.01 ng/ml (normal 0.00-0.03 ng/ml). Electrocardiogram revealed sinus tachycardia, left atrial enlargement, poor R wave progression and nonspecific ST-T wave changes in all leads specifically T wave inversion in the lateral leads (Figure 1). Chest x-ray showed cardiomegaly with pulmonary vascular congestion. Pulmonary embolism was ruled out by spiral computer tomography (CT) scan. A 2D echocardiogram with albumin echo contrast showed left ventricular (LV) ejection fraction of 25-30% with moderate to severe global hypokinesis of the left ventricle and moderately enlarged left atrium. It also showed a normal sized ventricle with multiple trabeculation in the mid LV cavity and apex suggesting either an apical form of hypertrophic cardiomyopathy or LVNC (Figure 2). She underwent cardiac catheterization which revealed normal coronary arteries. In view of the normal coronaries and severe global hypokinesis, further workup was done to rule out other causes of cardiomyopathy. Viral cultures were negative for enteric cytopathic human orphan [ECHO] and coxsackie viruses. To further elucidate the cause of the cardiomyopathy, LV endomyocardial biopsy was performed. Histology showed myocardial fibrosis suggestive of cardiomyopathy, possibly secondary to LVNC (Figure 3).


Discussion

Left ventricular noncompaction is a rare cause of cardiomyopathy, and patients present with systolic dysfunction commonly of the left, and sometimes of the right ventricle. The incidence of LVNC in clinical practice is low because it is an under-recognized phenomenon and most cases are diagnosed as idiopathic cardiomyopathy. Age of onset and degree of clinical symptoms depend on the extent of the noncompacted cardiac segments [2].

The exact pathophysiology of the ventricular dysfunction is not known. Jenni, et al, suggested subendocardial hypoperfusion and microcirculatory dysfunction in development of ventricular dysfunction and arrhythmogenesis [3]. Echocardiography is the reference standard for diagnosing LVNC, although it can be well defined by CT scan, positron emission tomography and magnetic resonance imaging [4-8]. Echocardiogram shows a two-layered hypokinetic myocardium with thin, compacted epicardium, thick, noncompacted endocardium, and a noncompaction (NC) to compaction (C) ratio >2, and blood flowing directly from the ventricular cavity in to the deep intertrabecular recess [2,9]. In this case the NC/C was >2 with multiple trabeculations and it could be classified into the prominent trabeculation morphological group of LVNC [10].

LVNC is genetically heterogeneous, with predominance of autosomal dominant inheritance, and is currently classified under cardiomyopathies as a genetic disease [11]. LVNC leading to myocardial fibrosis has not been well defined in the literature [12]. The etiology of the fibrosis is unclear, but it explains the LV dysfunction associated with LVNC. Recent studies have reported a significant prevalence of mitochondrial myopathy and genetic mutations in patients with LVNC. Myopathies with cardiac involvement have also been implicated in LVNC, including Barth syndrome, Emery-Dreifuss muscular dystrophy, and myotubular myopathy [13,14]. Genetic mutations, especially the alpha-dystrobrevin gene, Cypher/ZASP and gene G4.5 of the Xq28 chromosome region and loss of the cardiac-specific gene CSX have been well described in the literature as causes of LVNC [15-17]. These genetic mutations and myopathies may eventually lead to fibrosis of the myocardium causing severe LV dysfunction. This process may take several years, thus explaining why heart failure in patients with LVNC usually occurs beyond the 4th decade of life. LVNC is misdiagnosed or missed in a majority of the cases due to its varied presentation and is not associated with any specific histological finding [18]. In a small case series, Burke, et al, found that LVNC was associated with endocardial fibroelastosis and anastomosing or polypoid endocardial trabeculations [19]. In our case, biopsy showed myocardial fibrosis without any disarray. Absence of disarray in the histology excluded hypertrophic cardiomyopathy in this case.

Clinical manifestation of LVNC ranges from absence of symptoms to disabling congestive heart failure, arrhythmias, such as atrial fibrillation, ventricular tachyarrhythmias, and sudden cardiac death, and thromboembolic events [20]. LVNC association with neuromuscular disorders is commonly seen with Barth syndrome and mitochondrial disorders [21]. With its varied presentation and genetic association, patients diagnosed with LVNC warrant genetic counseling, DNA diagnostics, and cardiological family screening to make an early diagnosis and prevent complications [22].

Treatment is symptomatic, including consideration of heart transplantation. Medical treatment depends mainly upon the clinical presentation. Cardiac resynchronization therapy (CRT) or placement of an implantable cardioverter-defibrillators (ICD) should be considered when the LV ejection fraction ≤35% and prior to heart transplantation. In one study, the largest cohort of LVNC patients showed the effectiveness of ICD for secondary or primary prevention of sudden cardiac death, and improvement of New York Heart Association (NYHA) class in patients with LV ejection fraction ≤35% or LVNC with CRT [23]. There are no concrete guidelines for anticoagulation therapy as a primary prevention of thromboembolism among LVNC patients. Many authors believe that it should be considered among LVNC patients with atrial fibrillation, severe LV dysfunction, or a history of thromboembolism. In our case, implantation of an ICD, warfarin anticoagulation was offered to the patient but she refused.

Prognosis, in general, is poor and improves significantly with heart transplantation. A larger case series of 34 patients with long-term follow-up of 44 months, showed mortality of 35%, and with sudden cardiac death accounting for 50% of fatalities [2]. In the same study, 24% of patients had thromboembolic events and 41% had ventricular tachyarrhythmias. A recent similar study showed lower mortality and fewer complications [24]. This variation is secondary to the inclusion of milder/preclinical cases in the later study, along with advancement in the echocardiographic technology that facilitate earlier diagnosis. Heart transplantation is considered only when medical therapy fails to control the progression of heart failure. Our patient responded well to treatment with angiotensin-converting enzyme inhibitors and beta blockers.


Conclusion

Cardiologists and other physicians should be aware of LVNC due to its high likelihood of misdiagnosis and consequent high complication rates. Early diagnosis and intervention, and screening among family members can decrease the morbidity and mortality associated with LVNC.


Consent

Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


Competing interests

The authors declare that they have no competing interests.


Authors' contributions

All the four authors contributed to the conception, design, analysis and preparation of the manuscript. All authors read and approved the final manuscript.


References
Ritter M,Oechslin E,Sutsch G,Attenhofer C,Schneider J,Jenni R,Isolated noncompaction of the myocardium in adultsMayo Clin ProcYear: 199772263110.4065/72.1.269005281
Oechslin EN,Attenhofer Jost CH,Rojas JR,Kaufmann PA,Jenni R,Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosisJ Am Coll CardiolYear: 20003649350010.1016/S0735-1097(00)00755-510933363
Jenni R,Wyss CA,Oechslin EN,Kaufmann PA,Isolated ventricular noncompaction is associated with coronary microcirculatory dysfunctionJ Am Coll CardiolYear: 20023945045410.1016/S0735-1097(01)01765-X11823083
Conces DJ Jr,Ryan T,Tarver RD,Noncompaction of ventricular myocardium: CT appearanceAm J RoentgenolYear: 1991156717718
Daimon Y,Watanabe S,Takeda S,Hijikata Y,Komuro I,Two-layered appearance of noncompaction of the ventricular myocardium on magnetic resonance imagingCirc JYear: 20026661962110.1253/circj.66.61912074286
Senior R,Left ventricular contrast echocardiography: role for evaluation of function and structureEchocardiographyYear: 20021961562012401137
Hany TF,Jenni R,Debatin JF,MR appearance of isolated noncompaction of the left ventricleJ Magn Reson ImagingYear: 1997743743810.1002/jmri.18800702319090604
Bax JJ,Atsma DE,Lamb HJ,Rebergen SA,Bootsma M,Voogd PJ,Somer S,Schalij MJ,de Roos A,vander Wall EE,Noninvasive and invasive evaluation of noncompaction cardiomyopathyJ Cardiovasc Magn ResonYear: 2002435335710.1081/JCMR-12001330212234106
Jenni R,Oechslin E,Schneider J,Attenhofer Jost C,Kaufmann PA,Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathyHeartYear: 20018666667110.1136/heart.86.6.66611711464
Kohli SK,Pantazis AA,Shah JS,Adeyemi B,Jackson G,McKenna WJ,Sharma S,Elliott PM,Diagnosis of left-ventricular non-compaction in patients with left-ventricular systolic dysfunction: time for a reappraisal of diagnostic criteria?Eur Heart JYear: 200829899510.1093/eurheartj/ehm48117993472
Maron BJ,Towbin JA,Thiene G,Antzelevitch C,Corrado D,Arnett D,Moss AJ,Seidman CE,Young JB,Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and PreventionCirculationYear: 20061131807181610.1161/CIRCULATIONAHA.106.17428716567565
Finsterer J,Stollberger C,Feichtinger H,Histological appearance of left ventricular hypertrabeculation/noncompactionCardiologyYear: 20029816216410.1159/00006631612417817
Bleyl SB,Mumford BR,Brown-Harrison MC,Pagotto LT,Carey JC,Pysher TJ,Ward K,Chin TK,Xq28-linked noncompaction of the left ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individualsAm J Med GenetYear: 19977225726510.1002/(SICI)1096-8628(19971031)72:3<257::AID-AJMG2>3.0.CO;2-O9332651
Zambrano E,Marshalko SJ,Jaffe CC,Hui P,Isolated noncompaction of the ventricular myocardium: clinical and molecular aspects of a rare cardiomyopathyLab InvestYear: 20028211712211850525
Ichida F,Tsubata S,Bowles KR,Haneda N,Uese K,Miyawaki T,Dreyer WJ,Messina J,Li H,Bowles NE,Towbin JA,Novel gene mutations in patients with left ventricular noncompaction or Barth syndromeCirculationYear: 20011031256126311238270
Chen R,Tsuji T,Ichida F,Bowles KR,Yu X,Watanabe S,Hirono K,Tsubata S,Hamamichi Y,Ohta J,et al. Mutation analysis of the G4.5 gene in patients with isolated left ventricular noncompactionMol Genet MetabYear: 20027731932510.1016/S1096-7192(02)00195-612468278
Pauli RM,Scheib-Wixted S,Cripe L,Izumo S,Sekhon GS,Ventricular noncompaction and distal chromosome 5q deletionAm J Med GenetYear: 19998541942310.1002/(SICI)1096-8628(19990806)85:4<419::AID-AJMG21>3.0.CO;2-S10398271
Weiford BC,Subbarao VD,Mulhern KM,Noncompaction of the ventricular myocardiumCirculationYear: 20041092965297110.1161/01.CIR.0000132478.60674.D015210614
Burke A,Mont E,Kutys R,Virmani R,Left ventricular noncompaction: a pathological study of 14 casesHum PatholYear: 20053640341110.1016/j.humpath.2005.02.00415892002
Agmon Y,Connolly HM,Olson LJ,Khandheria BK,Seward JB,Noncompaction of the ventricular myocardiumJ Am Soc EchocardiogrYear: 19991285986310.1016/S0894-7317(99)70192-610511656
Stollberger C,Finsterer J,Blazek G,Left ventricular hypertrabeculation/noncompaction and association with additional cardiac abnormalities and neuromuscular disordersAm J CardiolYear: 20029089990210.1016/S0002-9149(02)02723-612372586
Hoedemaekers YM,Caliskan K,Michels M,Frohn-Mulder I,van der Smagt JJ,Phefferkorn JE,Wessels MW,ten Cate FJ,Sijbrands EJ,Dooijes D,Majoor-Krakauer DF,The importance of genetic counseling, DNA diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathyCirc Cardiovasc GenetYear: 2010323223910.1161/CIRCGENETICS.109.90389820530761
Kobza R,Steffel J,Erne P,Schoenenberger AW,Hürlimann D,Lüscher TF,Jenni R,Duru F,Implantable cardioverter-defibrillator and cardiac resynchronization therapy in patients with left ventricular noncompactionHeart RhythmYear: 2010 in press . 20493963
Murphy RT,Thaman R,Blanes JG,Ward D,Sevdalis E,Papra E,Kiotsekolglou A,Tome MT,Pellerin D,McKenna WJ,Elliott PM,Natural history and familial characteristics of isolated left ventricular non-compactionEur Heart JYear: 20052618719210.1093/eurheartj/ehi02515618076

Figures

[Figure ID: F1]
Figure 1 

A 12-lead electrocardiogram showing sinus tachycardia, left atrial enlargement, poor R wave progression and nonspecific ST-T wave changes and T wave inversion in the lateral leads.



[Figure ID: F2]
Figure 2 

Transthoracic echocardiogram (A, B, C, D) four chamber view with albumin contrast showing numerous trabeculations (white arrow) in the left ventricular apex, along with deep intertrabecular recesses. (RA- right atrium, LA- Left atrium, RV-right ventricle, LV- left ventricle).



[Figure ID: F3]
Figure 3 

Endomyocardial biopsy of the left ventricle (hematoxylin and eosin stain) showing the myocardial fibrosis (100×, 400×), along with the cardiac myocytes.



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