LV Noncompaction
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Transcript of LV Noncompaction
LV NoncompactionEchocardiography Conference
Connie TsaoJan 21, 2009
Terms•Left ventricular noncompaction in
association with congenital abnormalities•Isolated left ventricular noncompaction
▫Left ventricular hypertrabeculation▫Persistent myocardial sinusoids▫Spongy myocardium
Outline• Definitions• Embryology• Pathophysiology• Associations with other disease • Isolated LV noncompaction• Epidemiology• Genetics• Pathology• Clinical Features• Diagnosis
▫ Echocardiography▫ Cardiovascular magnetic resonance
• Prognosis• Management
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
Early Embryology, <5 weeksAnterolateral
mesoderm
Epithelium
Endocardium Myocardium
N-Cadherin
Cardiac Tube
Trabeculations
Neuregulin growth factors
3 weeks
↓N-Cadherin
Embryology, 5-8 weeksEndocardium
Sub-epicardial space
Microvessels coronary
circulation
Vascular endothelial growth factorAngiopoietin-1
Compaction• Base apex
• Epi- endocardium• Intratrabecular
recesses myocardial capillaries
Srivastava D, Nature 2000; and RP, Nature Rev Genetics 2002
Pathogenesis of Noncompaction•Arrest of endomyocardial morphogenesis•Potential pathological processes
preventing regression of sinusoids (Weiford et
al, Circ 2004):▫Pressure overload▫Ischemia
•Not proven
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
Ebstein Anomaly and Noncompaction
Bagur RH, et al. Circ 2008
… 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
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
1st Report of Isolated Noncompaction
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
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)
Pathology
Ritter et al, Mayo Clin Proc 1997Jenni R et al, Heart 2001
Kaneda et al, Circ 2005
Cross sectionAzan stain, fibrosis Van Gieson elastin stain
Ritter et al, Mayo Clin Proc 1997
Kaneda et al, Circ 2005
Clinical Features•Heart failure
▫Dyspnea▫Chest pain
•Arrhythmia▫Atrial fibrillation▫Ventricular tachycardia
•Thromboembolism▫CVA/TIA▫Pulmonary embolism
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
Microvascular dysfunctionThallium CMR- increased T2 signal
Hamamichi Y et al, Int J Cardiovas Imag 2001
Ichida F et al, JACC 1999
PET
Jenni R et al, Heart 2001
Jenni R et al, JACC 2002
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
LVH, T-wave abnormalities
McCrohon, J. A. et al. Circulation 2002;106:e22-e23
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
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
Oechslin et al, JACC 2000
Weiford et al, Circ 2004
Imaging for diagnosis
Chow C et al, Circ 2007
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
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
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
Jenni R et al, Heart 2001
Jenni R et al, Heart 2001
Weiford et al, Circ 2004 Ichida F et al, JACC 1999
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
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
Frischknecht B et al, J Am Soc Echocardiogr 2005
Frischknecht B et al, J Am Soc Echocardiogr 2005
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
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
Routine 2D TTE With Definity
Chow et al, Circ 2007
•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
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
• 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
CMR criteria• NC/C ratio >2.3 in
diastole▫Sensitivity 86%▫Specificity 99%▫PPV 75%▫NPV 99%
Oechslin et al, JACC 2000
Weiford et al, Circ 2004
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
• 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
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
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