This document discusses left ventricular noncompaction cardiomyopathy (LVNC), a rare genetic heart condition where the heart muscle does not compact properly during fetal development. It begins by defining LVNC and describing its increasing recognition due to advances in diagnostic imaging. The document then discusses the embryological development of the heart and how a disruption in the normal compaction process can lead to LVNC. It outlines the characteristic features of LVNC seen on imaging studies and potential genetic associations. The document concludes by discussing the challenges in diagnosing and managing LVNC.

1. Noncompaction
Cardiomyopathy
“A DIAGNOSTICALLY CHALLENGING CARDIOMYOPATHY”

2. LV Non Compaction
• Noncompaction of the left ventricular
myocardium (LVNC) is being increasingly
recognized and its diagnosis has moved from the
autopsy table or previously poorly recognized
entity to a widely recognized cardiomyopathy.
• Lot of research work- publications recently
• Advances in non invasive diagnostic
technologies- better delineation of morphology

3. Isolated left ventricular noncompaction in an autopsy specimen, shown in short-axis view. Note the compacted
epicardial layer and noncompacted endocardial layer with marked hypertrabeculation and deep recesses.
William D. Edwards, MD, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Characterized by:
An altered myocardial wall with prominent trabeculae and deep intertrabecular
recesses resulting in thickened myocardium with two layers consisting of
compacted and noncompacted myocardium.
Continuity between the left ventricular cavity and the deep intratrabecular
recesses, which are filled with blood from the ventricular cavity without evidence of
communication to the epicardial coronary artery system.

4. 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

5. HISTORY
• Dusek first described the postnatal persistence of
spongy myocardium in 1975 pathologically,
• Engberding and Bender made the first clinical
recognition with two-dimensional (2D)
echocardiography in 1984
• Three decades later, with only morphologic
assessment available and no definitive genetic
pathway, isolated left ventricular noncompaction
(LVNC) remains a diagnostic and management
challenge.
Dusek J et al, Arch Pathol 1975

6. CASE SCENARIO
• 26 YEARS OLD FEMALE PRESENTED WITH
PROGRESSIVELY INCRAESING DYSPNEA FOR
PAST 3 YAERS
• CLASS 3 PRESENTLY
• INTERMITTENT EPISODES OF PND
• SENT TO US FOR ECHOCARDIOGRAPHY

7. ECHOCARDIOGRAPHY

14. MRI

17. TREATMENT
• BETA BLOCKERS
• DIURETICS
• ACE-INHIBITORS
• ANTICOAGULATION

18. Noncompaction
Cardiomyopathy
“A DIAGNOSTICALLY CHALLENGING CARDIOMYOPATHY”

19. Outline
Definitions
Pathomorphogenesis
Associations with other disease
Isolated LV noncompaction
Epidemiology
Genetics
Clinical Features
Diagnosis
Echocardiography
Cardiovascular magnetic resonance
Management
Prognosis

20. Types
Left ventricular noncompaction in
association with congenital
abnormalities
Isolated left ventricular noncompaction
AKA
▫ Hypertrabeculation Syndrome
▫ Persistent myocardial sinusoids
▫ Spongy myocardium

21. 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

22. EMBRYOLOGY and PATHO-MORPHOGENESIS
• Because myocardial noncompaction represents a
congenital anomaly of the ventricular myocardium,
insight into the underlying pathomorphogenesis can
be helpful in clarifying diagnostic criteria and
understanding its clinical presentation and course.
• Need to review the literature on normal and
abnormal myocardial development in an attempt to
characterize the disease as a morphogenetic entity.

23. Early Embryology, <5 weeks
N-Cadherin
Neuregulin growth factors
3 weeks
↓N-Cadherin
The majority of cardiomyocytes originate from the anterolateral mesoderm soon
after gastrulation.
Soon after their specification, the cardiac myocytes migrate along the ventral
midline of the embryo, begin to express Ncadherin, and differentiate into an
epithelium.
A small population of these cells then downregulates Ncadherin and dissociates
from the epithelium to form the endocardium.
The majority of epithelial cells, in turn, will give rise to the myocardium.
At 3 weeks of human gestation, the myocardium and the endocardium fuse into a
single beating cardiac tube .
During the early developmental stages, the heart tube is still without epicardial overlay.
As an adaptation to improve nourishment of the rapidly growing heart, the
myocardium forms a loose network of interwoven fibers separated by deep recesses that
link the myocardium with the left ventricular cavity. This formation of ventricular
trabeculae is restricted to the free wall and the lower part of the ventricular septum,
sparing the regions of the atrioventricular canal and outflow tract septum . Neuregulin
growth factors secreted from the endocardium and their myocardial receptors ErbB2 and
ErbB4 are required for the development of the trabeculae .
The resulting increase in surface facilitates myocardial supply by exchange diffusion . It
is likely that during this developmental period the trabeculae generate much of the
contractile force of the heart .

24. Embryology, 5-8 weeks
Vascular endothelial growth factor
Angiopoietin-1
Once the myocardium has become covered with epicardium, the coronary vasculature develops.
In the subepicardial space, an endothelial network is formed that gradually covers the heart and
develops microvessels within the myocardium [62]. Arteriogenesis of the coronary arteries
includes the formation of media from smooth muscle cells that originate from epitheliumderived
cells . As soon as a continuity has been established by connection of the vessels to the aortic root
as well as to the right atrium, the initial embryonic means of myocardial nourishment by diffusion
from the cardiac lumen switches to the permanent form of active circulation through coronary
vessels . At the same time—between 5 and 8 weeks of embryonic life—gradual compaction of the
spongy meshwork of fibers and intertrabecular recesses occurs. This process results in the normal
prominent outer compact layer of the mature myocardium
with only few residual trabeculae remaining present subendocardially. Similar to the direction of
coronary arterial development, the recession of the trabeculae proceeds from the epicardium to
the endocardium and from the base of the heart to the apex

25. Srivastava D, Nature 2000; and RP, Nature Rev Genetics 2002

26. • In patients with myocardial noncompaction, the normal
process of myocardial compaction has undergone a
premature arrest.
• The fact that a normally developed myocardium is of
immense importance for the viability of the rapidly
developing embryo, may explain why primary
myocardial noncompaction is such a rare disease.
• Failure of normal progression of myocardial
morphogenesis results in the persistence of the early
embryonic, largely trabeculated myocardium in certain
ventricular regions.
• Referring to the prominent spongious layer of the
myocardium in these cases, the disease has also been
termed “spongy myocardium.”

27. • Histologically, patchy areas with loosely organized, wavy to angulated
myocardial fibers that are thinner than normal, with a reduced content of
myofibrils, and central cytoplasmic clearing can be found in these ventricles.
• Secondary to the premature arrest of myocardial maturation the inner,
trabeculated, myocardial layer remains abnormally thick with a reduced
thickness of the outer, compact, myocardial layer.
• Therefore, the noncompacted subendocardial myocardial layer is always
much thicker than the outer compacted myocardium in primary myocardial
noncompaction.
• This results in the typical echocardiographic picture of multiple prominent
trabeculations with deep intertrabecular recesses invaginating deeply into
the outer one third of the ventricular myocardium.
• Magnetic resonance imaging (MRI) provides a good correlation with
echocardiography for localization and extent of noncompaction and can be
useful in cases with poor echocardiographic image quality.

28. • Corresponding to the course of normal cardiovascular
morphogenesis, a stop of progression of normal myocardial
maturation will lead to different extensions of myocardial
noncompaction.
• Because the inner part of the ventricular apex is always last
to complete the compaction process, and minor
trabeculations remain present in this segment even in the
normal heart, primary myocardial noncompaction
always affects the left ventricular apex.
• However, the abnormal myocardium can extend toward
the ventricular base and involve additional regions of the
left ventricle, such as inferior and lateral wall segments.
• Although the disease process typically occurs in
the left ventricle, involvement of the right ventricle
has been described in less than half of patients.
• Because of the difficulty in distinguishing normal variants
of the highly trabeculated right ventricle with its per se
thinner compact myocardial layer from the pathological
noncompacted ventricle, several authors dispute the
existence of right ventricular noncompaction

30. Compaction continues into
the postnatal period with
continued growth and
increasing systemic
pressures.
The final process is development
of the spiral pattern of the
myocardial fibers, which is
responsible for the twisting
nature of contraction.
Without the completion of
compaction, there is
myocardial dysfunction
secondary to the failure of
the efficient rotational
ventricular system to
develop for contractile
performance.
This concept has been
demonstrated
by abnormal speckle tracking

31. … 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

32. 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

33. 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

34. 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)
• Systematic review by Bhatia et al. identified a familial
occurrence rate of 30% in family members that were
screened based on an index case
• There are multiple genetic proposals for the phenotypic
development of noncompaction. None of them have been
consistently identified to be the single gene abnormality
causing LVNC.

35. Genes Identified.The identified genes are as
follows:
• Fbkp1a/Notch pathway.
• G4.5 gene/TAZ protein.
• 14-3-3 deletion.
• ZASP protein.
• TNNT2 protein.
• MYH7 protein.
• TPM1 protein.
• MYBPC3 protein.
• ACTC1 protein.

36. • The current genes available for testing are
variants of established dilated cardiomyopathy
and hypertrophic cardiomyopathy genes.
• Oechslin and Jenni have proposed an acquired
pathogenesis in patients with prior normal
cardiac structure and function that develop
LVNC later in life.
• This supports the hypothesis that LVNC
may represent a morphologic continuum
of genetic cardiomyopathies, including
dilated and hypertrophic
cardiomyopathies

37. Clinical features
• Depending on the exact time of failure of normal progression of
the myocardial maturation process, the hearts of patients with
primary myocardial noncompaction show different extensions
of the abnormally thickened trabeculated myocardial layer
within the ventricle.
• The amount of normal myocardium will determine the
functional relevance of the disease, thus explaining the highly
variable clinical course.
• The more severe cases present during the first years of life, and
myocardial noncompaction was initially described as a
cardiomyopathy of children.
• It is likely that the most severe forms are lethal at an
early stage of embryonic development.
• At the other end of the spectrum are patients with very
localized forms of myocardial noncompaction that can be
asymptomatic for prolonged periods, with the diagnosis only
being made at an old age

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

39. 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

40. 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

41. 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

42. DIAGNOSTIC APPROACH

43. • There is much debate regarding the diagnostic
criteria for LVNC and the predilection for
overdiagnosis.
• ECHO vs CMR vs MDCT –NO GOLD
STANDARD
• No lab tests/ genetic tests confirmatory
of LVNC
• Multiple modalities may be required for
complete assessment.

44. Two-Dimensional Echocardiography.
• The traditional diagnostic study for evaluation of
LVNC is echocardiography.
• It is still the most common initial test that
identifies the characteristic findings of LVNC
and may lead to further evaluation.
• There are three proposed diagnostic criteria that
are most utilized in the literature. These criteria
are :
1. Chin et al
2. Jenni et al
3. Stollberger et al

46. 1990-First diagnostic criteria
• LVNC
 X (distance between epicardial surface and trough
of the intertrabecular recesses)
 Y (distance between epicardial surface and peak
of the trabeculations)
If X/Y< 0.5
if it progressively decreased from the papillary
muscles toward the apex
Chin TK, Perloff JK, Williams RG, Jue K, Mohrmann R. Isolated noncompaction of
left ventricular myocardiu. A study of eight cases. Circulation 1990;82:507–13.

47. Diagnosis- Echocardiography I
• X/Y ≤ 0.5
• Apex at end-diastole
▫ PSAX
▫ Apical 4Ch
0.59+0.05 0.20±0.040.92+0.07
Chin TK et al, Circ 1990

48. Diagnosis- Echocardiography 2nd
criteria
• 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
• Absence of any other cardiac
anomaly.
Jenni R et al, Heart 2001

50. 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

51. 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

53. Frischknecht B et al, J Am Soc Echocardiogr 2005

54. Frischknecht B et al, J Am Soc Echocardiogr 2005

55. End-Systole VS End-Diastole????
First, the observation that delineation, hence
measurements, of the compacted and noncompacted
layers of the myocardium are more precise at end-
diastole than at end-systole. End diastole
measurement is consistent with the American
Society of Echocardiography’s convention of
chamber and wall thickness measurements, which are
performed at end-diastole.
• Second, a ratio based on measurement of wall thickness
at end systole by definition incorporates the
influence of the contractile state of the
compacted myocardium. Since noncompacted
myocardium shows little systolic thickening, the ratio of
NC/C can change significantly depending on the extent
of systolic thickening of compacted myocardium.

56. 2014-Latest:All 4 criteria to be fulfilled
LVNC
1. >3 Prominent trabeculous formations along the left
ventricular endocardial border visible in end-diastole,
distinct from papillary muscles, false tendons or aberrant
bands
2. Trabeculations move synchronously with the compacted
myocardium
3. Trabeculations form the noncompacted part of a two-
layered myocardial structure, best visible at end-systole
4. Perfusion of the intertrabecular spaces from the
ventricular cavity is present at end-diastole on colour
Doppler echocardiography or contrast echocardiography
Refinement of echocardiographic criteria for left ventricular noncompaction Claudia
Stöllberger,Birgit Gerecke,Josef Finsterer,Rolf Engberding.International Journal of
Cardiology 165 (2013) 463–467
They suggested that measurement of
the myocardial layers is not
feasible due to the lack of uniformly
accepted standards for measurements.

59. 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

60. Echocardiographic criteria of Chin et al, Jenni et al and
Stöllberger et al were used for identification of LVNC in HF and
control groups.
There was meager correlation among the 3 sets of
echocardiographic criteria, with only 30% of patients satisfying
all of them.
Additionally, 8% of controls met at least 1 of the diagnostic
criteria for LVNC.
This information raises the concern that the current
echocardiographic criteria are too sensitive, particularly in
individuals of African heritage, resulting in overdiagnosis of
LVNC (false positive).

61. Why is it so difficult to validate the diagnosis of LVNC with
certainty?
• Lack of awareness and meticulous imaging technique
• Failure to differentiate prominent physiologic trabeculations to
disease. The complex meshwork of muscle bundles of the apical- third
of the LV and muscle bundles aligning the border of the myocardium
are normal structures.
• These normal trabecular patterns can mimic LVNC. The current
echocardiographic diagnostic criteria often fail to distinguish the
boundary of normal morphologic features and disease.
• Lastly, the difficulty in diagnosing LVNC is due to the lack of clarity
between morphologic findings of “left ventricular noncompaction” and
the disease entity LVNC cardiomyopathy. The disease should not be
defined by the rigid criteria of measurements, such as ratios of the
bilayered myocardium. Clearly, we cannot identify a NC/C ratio equal
to 2 at end-diastole or end-systole as disease and a ratio of 1.9 as no
disease.
• There must be recognition that any NC/C ratio with normal LV
systolic and diastolic function and normal myocardial
mechanics should not be defined as a disease.
• This set of circumstances must be characterized as morphologic
findings that need close follow-up over time to determine if and when
there is a transition to disease phenotype (ie, LVNC cardiomyopathy).

63. Cardiac MRI
• The high resolution imaging of cardiac magnetic
resonance (CMR) has allowed improvement in
differentiating the noncompacted and
compacted myocardium.
• Key features of CMR in addition to the spatial
resolution are
the ability to image the apex well and
the use of late gadolinium enhancement for the
evaluation of fibrosis.

65. • In 2005, Petersen et al. compared the noncompacted to
compacted layers of myocardium on CMR of healthy volunteers
and patients with hypertrophic cardiomyopathy, dilated
cardiomyopathy, hypertensive heart disease, and aortic stenosis
and patients previously diagnosed with LVNC based on other
findings .
• They found that pathological noncompaction had a NC/C
>2.3 in end-diastole and that the specificity and
negative predictive values were both 99%.
• Later in 2010, Jacquier et al. proposed that the trabeculated
mass be taken into consideration when they found that the
percentage of trabeculated mass was three times higher in patients
with LVNC compared to other groups including controls.
• LV trabecular mass >20% of the global mass predicted
the diagnosis of LVNC with a sensitivity and specificity
of 93.7%. The advantage of this later method is not depending
on the evaluation of specific myocardial segments, but rather the
entire mass.

66. CARDIAC MRI
• Disadvantages of this modality include
the availability of MRI and
the time to complete the exam and required breath
holding that pose challenges to the patients.
There is also an inability to image patients with some
devices/implants.
CMR should play a major role in the evaluation
of patients with LVNC when
1. The diagnosis by echocardiogram is not confirmed;
2. A good quality echocardiogram cannot be obtained;
and/or
3. The degree of fibrosis may help delineate the severity
of disease.

67. MANAGEMENT
- no prospective studies/ large cohorts
• Screening 1st degree family members
• Treatment of heart failure
▫ Medical rx:
 Guideline based mx for heart failure
▫ Consideration of biventricular PPM/ICD
• Screening for arrhythmias
▫ Consideration of ICD
• Anticoagulation
▫ Atrial fibrillation and/or LVEF <40% / high CHADS2
score (The event rate of stroke is 1-2% per year or a total
risk thromboembolismof 21–38%)
• Heart transplantation

69. Oechslin et al, JACC 2000

70. 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

71. • 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

72. 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.
• Treatment based on clinical manifestations

74. • Although distribution and development of the main coronary arteries typically
are normal , there is increasing evidence of disturbances in microcirculation in
hearts with myocardial noncompaction.
• Keeping in mind the intimate relation of embryonic morphogenesis of the
myocardium and the coronary vasculature, this is not surprising.
• With MRI, positron emission tomography, and scintigraphy with thallium201,
areas of disturbed microcirculation and transmural perfusion defects
corresponding to the zones of noncompacted myocardium have been revealed.
•
• Coronary flow reserve has been found to be reduced in the noncompacted
segments but also in other segments with wall motion abnormalities.
• Postmortem analysis has shown subendocardial ischemic lesions and interstitial
fibrosis with necrotic myocytes within the trabeculae and compensatory
hypertrophy of other myocytes .
• From the available data, it is difficult to differentiate whether the persistence of
the embryonic pattern of trabeculated myocardium is secondary to a failure of
the coronary microcirculation to grow with the increasing ventricular mass or
whether the abnormal myocardial development did not allow normal progression
of coronary artery development.

75. 1st Report of Isolated Noncompaction

77. 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)

78. 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)

79. 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

80. Oechslin et al, JACC 2000

81. Weiford et al, Circ 2004

82. Jenni R et al, Heart 2001

83. Jenni R et al, Heart 2001

84. Weiford et al, Circ 2004