Transcript LV Noncompaction

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
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 weeks
N-Cadherin
↓N-Cadherin
3 weeks
Neuregulin growth factors
Embryology, 5-8 weeks
Vascular endothelial growth factor
Angiopoietin-1
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 circulation
Lauer RM et al, NEJM 1964
Dusek 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
Kaneda et al, Circ 2005
Ritter et al, Mayo Clin Proc 1997
Jenni R et al, Heart 2001
Cross section
Azan stain, fibrosis
Kaneda et al, Circ 2005
Van Gieson elastin stain
Ritter et al, Mayo Clin Proc 1997
Clinical Features
• Heart failure
▫ Dyspnea
▫ Chest pain
• Arrhythmia
▫ Atrial fibrillation
▫ Ventricular tachycardia
• Thromboembolism
▫ CVA/TIA
▫ Pulmonary embolism
Heart Failure
Diastolic
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 dysfunction
Thallium
Hamamichi Y et al, Int J Cardiovas Imag 2001
CMR- increased T2 signal
Ichida F et al, JACC 1999
PET
Jenni R et al,
JACC 2002
Jenni R et al,
Heart 2001
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 1990
Ritter M et al., Mayo Clin Proc 1997
Oechslin E et al, JACC 2000
Clinical Manifestations
• Largest comprehensive
study in adults to date
• Review of all
echocardiograms 1/8412/98
• 34 adults with
noncompaction
Oechslin et al, JACC 2000
Oechslin et al, JACC 2000
Weiford et al, Circ 2004
Imaging for diagnosis
Chow C et al, Circ 2007
Diagnosis- Echocardiography I
0.92+0.07
• X/Y ≤ 0.5
• Apex at end-diastole
▫ Subcostal
▫ Apical 4Ch
Chin TK et al, Circ 1990
0.59+0.05
0.20±0.04
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 Ratio
Range
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
JACC 2005
• 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)
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