lv noncompaction
DESCRIPTION
LV Noncompaction. Echocardiography Conference Connie Tsao Jan 21, 2009. Terms. Left ventricular noncompaction in association with congenital abnormalities Isolated left ventricular noncompaction Left ventricular hypertrabeculation Persistent myocardial sinusoids Spongy myocardium. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/1.jpg)
LV NoncompactionEchocardiography Conference
Connie TsaoJan 21, 2009
![Page 2: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/2.jpg)
Terms•Left ventricular noncompaction in
association with congenital abnormalities•Isolated left ventricular noncompaction
▫Left ventricular hypertrabeculation▫Persistent myocardial sinusoids▫Spongy myocardium
![Page 3: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/3.jpg)
Outline• Definitions• Embryology• Pathophysiology• Associations with other disease • Isolated LV noncompaction• Epidemiology• Genetics• Pathology• Clinical Features• Diagnosis
▫ Echocardiography▫ Cardiovascular magnetic resonance
• Prognosis• Management
![Page 4: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/4.jpg)
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
![Page 5: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/5.jpg)
Early Embryology, <5 weeksAnterolateral
mesoderm
Epithelium
Endocardium Myocardium
N-Cadherin
Cardiac Tube
Trabeculations
Neuregulin growth factors
3 weeks
↓N-Cadherin
![Page 6: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/6.jpg)
Embryology, 5-8 weeksEndocardium
Sub-epicardial space
Microvessels coronary
circulation
Vascular endothelial growth factorAngiopoietin-1
Compaction• Base apex
• Epi- endocardium• Intratrabecular
recesses myocardial capillaries
![Page 7: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/7.jpg)
Srivastava D, Nature 2000; and RP, Nature Rev Genetics 2002
![Page 8: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/8.jpg)
Pathogenesis of Noncompaction•Arrest of endomyocardial morphogenesis•Potential pathological processes
preventing regression of sinusoids (Weiford et
al, Circ 2004):▫Pressure overload▫Ischemia
•Not proven
![Page 9: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/9.jpg)
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 circulationLauer RM et al, NEJM 1964Dusek J et al, Arch Pathol 1975
![Page 10: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/10.jpg)
Ebstein Anomaly and Noncompaction
Bagur RH, et al. Circ 2008
![Page 11: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/11.jpg)
… 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
![Page 12: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/12.jpg)
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
![Page 13: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/13.jpg)
1st Report of Isolated Noncompaction
![Page 14: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/14.jpg)
![Page 15: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/15.jpg)
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
![Page 16: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/16.jpg)
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)
![Page 17: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/17.jpg)
Pathology
Ritter et al, Mayo Clin Proc 1997Jenni R et al, Heart 2001
Kaneda et al, Circ 2005
![Page 18: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/18.jpg)
Cross sectionAzan stain, fibrosis Van Gieson elastin stain
Ritter et al, Mayo Clin Proc 1997
Kaneda et al, Circ 2005
![Page 19: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/19.jpg)
Clinical Features•Heart failure
▫Dyspnea▫Chest pain
•Arrhythmia▫Atrial fibrillation▫Ventricular tachycardia
•Thromboembolism▫CVA/TIA▫Pulmonary embolism
![Page 20: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/20.jpg)
Heart FailureDiastolic Systolic• 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
![Page 21: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/21.jpg)
Microvascular dysfunctionThallium CMR- increased T2 signal
Hamamichi Y et al, Int J Cardiovas Imag 2001
Ichida F et al, JACC 1999
![Page 22: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/22.jpg)
PET
Jenni R et al, Heart 2001
Jenni R et al, JACC 2002
![Page 23: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/23.jpg)
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
![Page 24: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/24.jpg)
LVH, T-wave abnormalities
McCrohon, J. A. et al. Circulation 2002;106:e22-e23
![Page 25: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/25.jpg)
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 1990Ritter M et al., Mayo Clin Proc 1997Oechslin E et al, JACC 2000
![Page 26: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/26.jpg)
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
![Page 27: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/27.jpg)
Oechslin et al, JACC 2000
![Page 28: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/28.jpg)
Weiford et al, Circ 2004
![Page 29: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/29.jpg)
Imaging for diagnosis
![Page 30: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/30.jpg)
Chow C et al, Circ 2007
![Page 31: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/31.jpg)
Diagnosis- Echocardiography I
• X/Y ≤ 0.5• Apex at end-diastole
▫ Subcostal▫ Apical 4Ch
0.59+0.05 0.20±0.040.92+0.07
Chin TK et al, Circ 1990
![Page 32: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/32.jpg)
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
![Page 33: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/33.jpg)
Noncompacted/ Compacted Ratio Mean±SD
Noncompacted/ Compacted RatioRange
Noncompaction (n=34)
3.5±0.8 2.3-5
Dilated CMP (n=10)
0.8±0.4 0.4-2.0
Hypertensive heart dz (n=9)
1.1±0.5 0.4-2.0
• 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
![Page 34: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/34.jpg)
Jenni R et al, Heart 2001
![Page 35: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/35.jpg)
Jenni R et al, Heart 2001
![Page 36: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/36.jpg)
Weiford et al, Circ 2004 Ichida F et al, JACC 1999
![Page 37: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/37.jpg)
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
![Page 38: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/38.jpg)
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
![Page 39: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/39.jpg)
Frischknecht B et al, J Am Soc Echocardiogr 2005
![Page 40: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/40.jpg)
Frischknecht B et al, J Am Soc Echocardiogr 2005
![Page 41: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/41.jpg)
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
![Page 42: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/42.jpg)
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
![Page 43: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/43.jpg)
Routine 2D TTE With Definity
Chow et al, Circ 2007
![Page 44: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/44.jpg)
•7 patients with clinical noncompaction by echo or CMR (5M, 14-46 years)▫At least 1 of following: similar appearance in 1st
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
![Page 45: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/45.jpg)
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
![Page 46: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/46.jpg)
• 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
![Page 47: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/47.jpg)
CMR criteria• NC/C ratio >2.3 in
diastole▫Sensitivity 86%▫Specificity 99%▫PPV 75%▫NPV 99%
![Page 48: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/48.jpg)
![Page 49: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/49.jpg)
![Page 50: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/50.jpg)
![Page 51: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/51.jpg)
![Page 52: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/52.jpg)
Oechslin et al, JACC 2000
![Page 53: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/53.jpg)
Weiford et al, Circ 2004
![Page 54: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/54.jpg)
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
![Page 55: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/55.jpg)
• 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
![Page 56: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/56.jpg)
Management• Screening 1st 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
![Page 57: LV Noncompaction](https://reader033.vdocuments.site/reader033/viewer/2022061615/568166ea550346895ddb3118/html5/thumbnails/57.jpg)
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