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LV Noncompaction Echocardiography Conference Connie Tsao Jan 21, 2009.

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Presentation on theme: "LV Noncompaction Echocardiography Conference Connie Tsao Jan 21, 2009."— Presentation transcript:

1 LV Noncompaction Echocardiography Conference Connie Tsao Jan 21, 2009

2 Terms Left ventricular noncompaction in association with congenital abnormalities Isolated left ventricular noncompaction ▫Left ventricular hypertrabeculation ▫Persistent myocardial sinusoids ▫Spongy myocardium

3 Outline Definitions Embryology Pathophysiology Associations with other disease Isolated LV noncompaction Epidemiology Genetics Pathology Clinical Features Diagnosis ▫Echocardiography ▫Cardiovascular magnetic resonance Prognosis Management

4 Definition Congenital heart disease Myocardial wall distortion ▫Prominent trabeculae ▫Deep intertrabecular recesses Continuity between LV cavity and recesses Primary cardiomyopathy in 2006 World Heath Organization classification Ritter M et al, Mayo Clin Proc 1997

5 Early Embryology, <5 weeks N-Cadherin Neuregulin growth factors 3 weeks ↓N-Cadherin

6 Embryology, 5-8 weeks Vascular endothelial growth factor Angiopoietin-1

7 Srivastava D, Nature 2000; and RP, Nature Rev Genetics 2002

8 Pathogenesis of Noncompaction Arrest of endomyocardial morphogenesis Potential pathological processes preventing regression of sinusoids (Weiford et al, Circ 2004) : ▫Pressure overload ▫Ischemia Not proven

9 History First described in association with other congenital abnormalities ▫Obstruction of LVOT/RVOT  Pulmonary atresia with intact ventricular septum ▫Complex cyanotic congenital heart disease ▫Anomalous coronary arteries Intertrabecular recesses communicate with ventricular cavity and coronary circulation Lauer RM et al, NEJM 1964 Dusek J et al, Arch Pathol 1975

10 Ebstein Anomaly and Noncompaction Bagur RH, et al. Circ 2008

11 … in association with other disease Neuromuscular disorders Metabolic disease Genetic syndromes ▫Barth syndrome  X-linked, dilated CMP, neutropenia, skeletal myopathy, mitochondrial abnormalities, lactic acidosis  G4.5 gene in Xq28: encodes tafazzins proteins: acyltransferase functions in mitochondria, expressed in heart/muscle cells ▫Charcot-Marie-Tooth ▫Nail-patella

12 Similar phenotypes Dilated cardiomyopathy HCM Restrictive cardiomyopathy Left-dominant arrhythmogenic cardiomyopathy ▫42 patients with unexplained IL TWI, arrhythmia of LV origin, and/or LDAC or familial myocardial fibrosis ▫5 patients fulfilled echocardiographic criteria for LVNC Sen-Chowdhry S et al., JACC 2008

13 1 st Report of Isolated Noncompaction


15 Epidemiology of Isolated LV Noncompaction Children  Adults, elderly 0.05% (Ritter M et al, Mayo Clin Proc 1997) ▫37,555 echocardiograms  17 cases ▫Prominent, excessive trabeculations 0.014% (Oechslin EN et al, JACC 2000) ▫242,857 echocardiograms  34 cases ▫Noncompacted/compacted ≥ 2:1 Men >> women

16 Genetics Sporadic or familial Familial in 18-50% (Oechslin et al, JACC 2000, Chin et al, Circ 1990, Xing et al, Mol Genet Metab 2006) Autosomal dominant with incomplete penetrance > X-linked or autosomal recessive G4.5 gene of Xq28 region (Bleyl SB et al, Am J Med Genet 1997) : taffazin α-dystrobrevin gene (Ichida F et al, Circ 2001) ▫Links cytoskeleton of myocytes to extracellular matrix LIM domain binding protein 3/ZASP Sarcomere genes: β myosin heavy chain (MYH7), α cardiac actin (ACTC), cardiac troponin T (TNNT2) (Klaassen S et al., Circ 2008)

17 Pathology Ritter et al, Mayo Clin Proc 1997 Jenni R et al, Heart 2001 Kaneda et al, Circ 2005

18 Cross section Azan stain, fibrosisVan Gieson elastin stain Ritter et al, Mayo Clin Proc 1997Kaneda et al, Circ 2005

19 Clinical Features Heart failure ▫Dyspnea ▫Chest pain Arrhythmia ▫Atrial fibrillation ▫Ventricular tachycardia Thromboembolism ▫CVA/TIA ▫Pulmonary embolism

20 Heart Failure DiastolicSystolic Restrictive hemodynamics on catheterization Initial presentation as restrictive cardiomyopathy Pathophysiology ▫Abnormal relaxation ▫Decreased compliance due to volume of trabeculations No significant epicardial coronary disease Subendocardial hypoperfusion  chronic microvascular ischemia Ichida F et al, JACC 1999; Sen-Chowdhry et al, Curr Opin Card 2008

21 Microvascular dysfunction ThalliumCMR- increased T2 signal Hamamichi Y et al, Int J Cardiovas Imag 2001 Ichida F et al, JACC 1999

22 PET Jenni R et al, Heart 2001 Jenni R et al, JACC 2002

23 Electrophysiology Atrial fibrillation Ventricular tachycardia ECG: Left or right axis deviation PR prolongation Left ventricular hypertrophy LBBB, RBBB, IVCD Repolarization abnormalities In pediatric population: ▫Sinus bradycardia ▫WPW Duru F et al, J Cardiovasc Electrophysiol 2000

24 LVH, T-wave abnormalities McCrohon, J. A. et al. Circulation 2002;106:e22-e23

25 Thromboembolism Stroke TIA Pulmonary embolus Mesenteric infarction Reported 21-38% Etiology ▫Stasis of blood in deep recesses/trabeculations ▫Atrial fibrillation Chin TK et al, Circ 1990 Ritter M et al., Mayo Clin Proc 1997 Oechslin E et al, JACC 2000

26 Oechslin et al, JACC 2000 Clinical Manifestations Largest comprehensive study in adults to date Review of all echocardiograms 1/84- 12/98 34 adults with noncompaction

27 Oechslin et al, JACC 2000

28 Weiford et al, Circ 2004

29 Imaging for diagnosis

30 Chow C et al, Circ 2007

31 Diagnosis- Echocardiography I X/Y ≤ 0.5 Apex at end-diastole ▫Subcostal ▫Apical 4Ch 0.59+0.050.20±0.040.92+0.07 Chin TK et al, Circ 1990

32 Diagnosis- Echocardiography II Compacted and noncompacted layers of ventricular wall ▫Thickened endocardial layer ▫Prominent trabeculations ▫Deep recesses ▫Ratio noncompacted to compacted >2:1 ▫End-systole Trabecular meshwork in apex or midventricular segments of inferior and lateral wall Jenni R et al, Heart 2001

33 Noncompacted/ Compacted Ratio Mean±SD Noncompacted/ Compacted Ratio Range Noncompaction (n=34) 3.5±0.82.3-5 Dilated CMP (n=10)0.8±0.40.4-2.0 Hypertensive heart dz (n=9) 1.1±0.50.4-2.0 All p <0.001 vs. noncompaction group Autopsy validation in 7 of 34 noncompaction patients Autopsy validation in all dilated cardiomyopathy patients Jenni R et al, Heart 2001



36 Weiford et al, Circ 2004Ichida F et al, JACC 1999

37 Diagnosis- Echocardiography III >3 trabeculations protruding from LV wall ▫Apical to papillary muscles ▫On single image plane Intertrabecular spaces in continuity with ventricular cavity ▫Visualized on color doppler Stollberger C et al, Am J Cardiol 2002

38 Validation of Jenni criteria Blinded retrospective review of records comparing patients with: ▫LVNC (n=19) ▫Dilated cardiomyopathy (n=31) ▫Hypertensive heart disease (n=22) ▫Chronic severe valvular disease (n=86)  Mitral regurgitation (n=22)  Aortic regurgitation (n=20)  Aortic stenosis (bi- and tri-leaflet valves, n=44) Frischknecht B et al, J Am Soc Echocardiogr 2005



41 Accuracy of Combined Echocardiographic criteria 199 patients referred to heart failure clinic Compared with 60 normal controls Evaluated all 3 echo criteria 47 patients (24%) fulfilled any echo criteria ▫Chin et al, 19% ▫Jenni et al, 15% ▫Stollberger et al, 13% ▫Combined: 7% fulfilled all 3 criteria 5 controls (8%) fulfilled echo criteria ▫4 controls African-American Current criteria too sensitive? Kohli S et al, EHJ 2008

42 An underdiagnosed disease? 27 pediatric patients with noncompaction (Ichida F et al, JACC 1999) ▫Diagnosis missed in 89% patients ▫Alternative diagnoses: dilated cardiomyopathy, apical hypertrophic cardiomyopathy, restrictive cardiomyopathy, myocarditis 17 adults identified with noncompaction of 37,555 echos screened (Ritter M et al., Mayo Clin Proc 1997) ▫Onset of symptoms to diagnosis: 3.5±5.7 years

43 Routine 2D TTEWith Definity Chow et al, Circ 2007

44 7 patients with clinical noncompaction by echo or CMR (5M, 14-46 years) ▫At least 1 of following: similar appearance in 1 st degree relatives, assoc neuromuscular d/o, thromboembolic disease, regional WMA Comparison to: Healthy volunteers (n=45), athletes (n=25), HCM (n=39), dilated CMP (n=14), Hypertensive heart dz (n=17), AS (n=30) JACC 2005

45 Methods 17 segment model ▫Excluded true apex as thinner wall Noncompacted segment ▫2 myocardial layers with different tissue compaction ▫Segment of most pronounced trabeculations Ratio of noncompacted to compacted myocardium in diastole measured

46 Healthy volunteers: 91% subjects w/ NC in apex, 78% mid, 21% base. Most common anterior Similar distribution in other groups Noncompaction patients significantly greater # segments involved (10±3) than all other groups

47 CMR criteria NC/C ratio >2.3 in diastole ▫Sensitivity 86% ▫Specificity 99% ▫PPV 75% ▫NPV 99%





52 Oechslin et al, JACC 2000

53 Weiford et al, Circ 2004

54 Not so poor prognosis? 45 patients referred for cardiomyopathy ▫28M, 17F ▫37±17 yrs (13-83) ▫Majority in NYHA Class I-II CHF (64%) ▫20% NSVT, no sustained arrhythmias ▫Medical rx:  60% anticoagulation for EF <25% or thromboembolism  90% ACE-I  47% beta blockers ▫At 46 month followup, 97% mean survival from death or transplantation Murphy RT et al, EHJ 2005

55 65 pts with suspected noncompaction 74% symptom-based referral, 26% asymptomatic Followed for mean 46 ± 44 mos (6-193 mos) Non-symptom group more benign characteristics ▫Younger, fewer ECG abnormalities, greater LVEF, lower left atrial size No difference in extent of noncompaction No major CV events in asymptomatic group 31% symptomatic group  CV death, transplantation Independent predictors of CV death, transplantation: ▫NYHA III-IV, ventricular arrhythmias, LA size

56 Management Screening 1 st degree family members Treatment of heart failure ▫Medical rx:  Improved LVEF, decreased LVM in infant rx with carvedilol (Toyono M et al, Heart 2001) ▫Consideration of biventricular PPM/ICD Screening for arrhythmias ▫Consideration of ICD Anticoagulation ▫Atrial fibrillation and/or LVEF <40% Heart transplantation

57 Conclusions Rare congenital heart disease thought to result from an arrest in early cardiac embryogenesis ▫Genetic and sporadic forms Clinical manifestations: ▫Heart failure ▫Arrhythmias ▫Thromboembolism Diagnosis by echocardiography or CMR ▫Advances in imaging  increased recognition Variable prognosis, likely long natural history Treatment based on clinical manifestations

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