Maude Abbott Pediatric Cardiovascular Symposium
Moderator: Glenn Taylor
Section 3 -
Glenn P. Taylor
Department of Laboratory Medicine and Pathobiology
University of Toronto
Department of Pediatric Laboratory Medicine
Hospital for Sick Children
Toronto , ON
Ventricular noncompaction, also called ventricular hypertrabeculation, persistent spongy myocardium,
dysplastic cardiac development and other designations, is a pathologically, diagnostically and clinically
controversial entity characterized by aberration of the trabecular morphology of the heart ventricles,
chiefly the left
The ventricular dysmorphology occurs with otherwise structurally normal heart,
designated isolated ventricular noncompaction, and in the presence of
significant congenital heart anomalies. Occasional reports from the early part of last century included
descriptions corresponding to ventricular noncompaction, but only in the last 30 years, predominantly in
the last 10, has there been detailed clinicopathologic investigation of this condition . Contemporary
reports generally restrict discussion to noncompaction without associated congenital heart malformations.
Despite growing appreciation of ventricular noncompaction, its status as a specific entity remains
uncertain, as reflected by its listing in the "unclassified cardiomyopathy" group of the 1995 WHO/ISFC
classification of cardiomyopathies 
Ventricular noncompaction is characterized by excessively prominent ventricular trabeculae with deep
intertrabecular recesses that do not communicate with the coronary circulation. The abnormality chiefly
affects the apical and mid-ventricular portions of the left ventricle free wall, although the right
ventricle may be involved as well rarely the septum. Both anatomical and echocardiographic features have
been proposed, but the definitive diagnostic criteria remain debated
Most of the recent literature on the morphology of noncompaction concerns imaging studies,
particularly echocardiography, and relates to the left ventricle. Echocardiographic findings used to
diagnose isolated left ventricular noncompaction include:
A recent magnetic resonance imaging study concluded that a diastolic noncompacted-to compacted ratio
> 2.3 reliably identified left ventricular noncompaction .
- Multiple prominent ventricular trabeculations with deep intertrabecular recesses demonstrating
continuity with the ventricular cavity by colour Doppler imaging .
- More than three prominent trabeculae apical to the papillary muscles .
- The above with the left ventricle demonstrating a two layered myocardium having a ratio of
thickness of noncompacted-to-compacted myocardium > 1.4 .
- A two-layered myocardium with the end systolic thickness of the noncompacted subendocardial
layer more than twice the thickness of the compacted subepicardial layer .
Burke and colleagues have to date reported the most detailed anatomical pathology review of
ventricular noncompaction . Of the 14 hearts examined, 12 were from infants, 1 from an adolescent and
1 from a young adult. One heart was an explant. Ten cases had associated, but generally minor, cardiac
anomalies. Nine of the individuals presented with sudden death. Only one heart had normal weight for
age, the others were up to three times heavier than expected. The hearts were selected on the basis of
two key gross features: 1) poorly developed left ventricle papillary muscles and 2) in the midventricle
to apex a two layered myocardium having a prominent "spongy" inner zone of irregular trabeculae and
recesses and a compacted outer layer that was 50% or less of the full thickness of the ventricle.
Microscopy in some cases demonstrated the endocardial-lined recesses extending to within 1 mm of the
epicardium. Additional findings included endocardial fibroelastosis and subendocardial replacement
fibrosis of varying extent. Right ventricle involvement, defined as a noncompacted zone greater than 75%
of the thickness of the ventricle, occurred in 6 cases.
Similar anatomic findings have been reported in other series, although papillary muscle abnormalities
have not been generally emphasized . Gross variants include hemangioma-like "spongy" myocardium and
thinned myocardium with excessive luminal surface trabeculations and cords . Thrombi may develop in
the deep recesses and be potential sources of systemic thromboembolism. Noncompaction affects the right
ventricle in less than half of cases and only rarely the interventricular septum. The differential
diagnosis, both anatomically and with imaging studies, must consider enlarged trabeculae associated with
ventricular hypertrophy and sometimes dilated cardiomyopathy, endomyocardial fibroelastosis, mural
thrombi and prominent trabeculae (although usually less than 3), cords and false tendons often seen in
normal hearts .
Ventricular noncompaction is most widely believed to be a failure in the normal condensation of
ventricular myocardium that occurs during embryogenesis when development of the coronary circulation
supersedes perfusion of the myocardium by intracavitary diffusion . Additional cardiac anomalies may
accompany this aberrant development, including of the coronary arteries and conotruncal derivatives. In
approximately 20% of cases of Ebstein malformation of the tricuspid valve, a right ventricle myocardial
developmental abnormality, the left ventricle shows noncompaction-type changes.
About half of reported pediatric cases of isolated noncompaction have
familial association, whereas in adults familial recurrence is reported in less than 20% of cases. There
is genetic heterogeneity. Ventricular noncompaction occurs in some cases of Barth syndrome, an X-linked
disorder involving Xq28. Other X-linked cases without Barth syndrome have been mapped to the same
genetic region. The candidate gene is tafazzin (G4.5). Emery-Dreifuss
muscular dystrophy and myotubular myopathy also map to the Xq28 region. Familial association in adults
is more often autosomal dominant. Genetic abnormalities involving 18q12.1-q12.2 (alpha-dystrobrevin
gene), del(5)(q35.1-35.3) (cardiac specific homeobox, CSX)
and 11p15 have been identified . Other
syndromes associated with ventricular noncompaction include Noonan, Roifman, Melnick-Needles and
Nail-Patella. About a third of the reported affected children demonstrate characteristic facial
Stollberger and Finisterer argue that, at least for the adult population, other etiologies than
aberrant embryonic development should also be considered for ventricular noncompaction, and that it may
represent a morphologic endpoint of different pathogenetic mechanisms . Supporting the possibility
for acquired etiologies of noncompaction are serial echocardiographic
observations of the development of noncompaction in apparently originally normal hearts. As well,
ventricular noncompaction has been documented with aortic stenosis, pulmonary atresia with intact
ventricular septum and other congenital cardiac anomalies that promote high intracavitary ventricular
pressures. This suggests that the noncompaction-like appearance in these settings might instead
represent hypertrophic and ischemic consequences of the hemodynamic challenge rather than a primary
Ventricular noncompaction has been considered rare, with a reported incidence of 0.014% for isolated
noncompaction in a prospective echocardiographic study of adult patients . Other echocardiography
studies with mixed age populations report prevalence from 0.05% to 0.24%. Two large retrospective
echocardiography studies of pediatric populations similarly determined noncompaction accounts for
approximately 10% of diagnosed cardiomyopathies (hypertrophic cardiomyopathy, in comparison, accounted
for approximately 25% of pediatric cardiomyopathy)
The prevalence of ventricular noncompaction
in these studies was about 0.12%. The pediatric groups show an approximate 60% male predominance,
similar to the sex distribution over all age groups noted in a review of published cases . Diagnosis
has been made antenatally and in the aged.
The major clinical consequences of isolated ventricular noncompaction are heart failure, dysrhythmias,
and thromboembolic events. Decreased systolic function is reported in the majority of patients, but
impaired diastolic function and restrictive-type dysfunction also occur. The cardiac rhythm disorders
include ventricular arrhythmias, supraventricular tachycardias, atrial fibrillation,
Wolff-Parkinson-White syndrome, complete heart block and bundle branch block. Sudden death is a
well-appreciated occurrence in patients with ventricular noncompaction. In the adult population,
thromboembolic events such as cerebrovascular accidents are reported to occur in approximately 20 to 40%
In children, where noncompaction is more likely to be secondary than in the adult population, other
cardiac malformations and syndromic manifestations contribute to the clinical concerns. Stollberger and
Finisterer have stressed, at least for the adult population, the importance of neuromuscular disease such
as Becker's muscular dystrophy, myotonic dystrophy and various metabolic myopathies, that affect up to
80% of patients with ventricular noncompaction.
The prognosis for patients with ventricular noncompaction has been considered poor, with 50% to 60% of
patients dying or undergoing cardiac transplantation within 5 to 6 years  A recent pediatric series
reported unfavourable outcome at 3 years from diagnosis in 27% of patients . Despite these studies,
asymptomatic patients with ventricular noncompaction and patients demonstrating waxing and waning of
symptoms are reported. Treatment for noncompaction includes management of heart failure, antiarrhythmic
drugs and anticoagulation. Biventricular pacemakers and implantable defibrillators may be considered.
Heart transplantation has been performed. Screening of first degree relatives for noncompaction and
investigation of patients with noncompaction for neuromuscular disorders have been advocated.
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