Keywords
noncompaction cardiomyopathy - spongy myocardium - left ventricular noncompaction
cardiomyopathy
Introduction
Noncompaction cardiomyopathy (NCCM) is a rare disorder that is considered to be an
unclassified cardiomyopathy according to the European Society of Cardiology (ESC)
Working Group on Myocardial and Pericardial Diseases and the World Health Organization
(WHO), or a genetic cardiomyopathy according to the American Heart Association (AHA).[1]
[2]
[3]
Noncompaction cardiomyopathy mainly involves the left ventricle (left ventricular
noncompaction [LVNC]), and, less frequently, both ventricles (NCCM); when it involves
the right ventricle, which is rare, it shows a worse prognosis. There is a high rate
of intrauterine and early neonatal deaths and the prognosis is particularly serious
for hydropic fetuses. Noncompaction cardiomyopathy can be diagnosed in utero, and
the main diagnostic tool is echocardiography.[4]
Left ventricular noncompaction has been diagnosed and described during the fetal life
in very few case reports: only one study shows the echocardiography myocardial evaluation
during the antenatal diagnosis, and recently, a small case series of nine cases was
published.[5] We report a case of antenatal diagnosis of LVNC with no other cardiac or extracardiac
anomalies at 26 weeks of gestation.
Case Description
A 23-year-old patient, para 1, with a silent medical history, underwent a combined
test during the first trimester, resulting in low risk for trisomy 21. The second
trimester ultrasound, at 21 weeks, showed no cardiac anomalies in the 4 chambers,
in the long axes, and in the 3-vessel views. At 26 weeks and 4 days, an ultrasound
scan showed normal fetal biometry with the presence of cardiomyopathy, characterized
by the heart circumference occupying more than ⅓ of the thoracic circumference: cardio-thoracic
ratio > 95th centile. Both ventricles appeared dilated with ventricular cavity biometry > 95th percentile, with thickened and irregular walls on the endocardial side, especially
in the apical area ([Figs. 1] and [2]). A color Doppler exam showed the presence of trabecular accentuation, protruding
in the ventricular cavities due to the presence of color signal in the myocardial
thickness. The absence of other structural cardiac anomalies was confirmed, and the
Doppler velocimetry of the heart appeared normal, with no tricuspid valve regurgitation.
Due to the new diagnosis, the second trimester ultrasound images were revised, and
a quantitative evaluation of the fetal cardiac biometry was made according to the
Shapiro Tables (1998). This evaluation, though limited, allowed to verify that the
cardiac structures showed a normal biometry with non-harmonic values between them.
The results of an invasive antenatal diagnosis and of infection investigations were
negative. An echocardiography was performed on both parents with negative results.
The medical history of the family was unremarkable, with no signs of cardiomyopathy.
Fig. 1 Both ventricles appear dilated with enlarged ventricular cavity biometry. Cardiac
walls appear thickened and irregular on the endocardial side, especially in the apical
area. First magnification.
Fig. 2 Both ventricles appear dilated with enlarged ventricular cavity biometry. Cardiac
walls appear thickened and irregular on the endocardial side, especially in the apical
area. Second magnification.
The patient was monitored until the onset of tricuspid valve regurgitation, which
led to a cesarean delivery at 31 weeks of gestation. The newborn died 3 days later.
The autopsy confirmed the absence of cardiac and extracardiac anomalies. The diagnosis
was idiopathic NCCM or “spongy myocardium.”
Discussion
Noncompaction cardiomyopathy refers to an uncommon structural abnormality of the heart's
ventricular myocardium characterized by an abnormally thick layer of left ventricular
trabeculations, as well as hypoplasia of the papillary muscles. It is a rare pathology
with great etiology and clinical management difficulties. It is associated with a
variable clinical phenotype including heart failure, thromboembolism, and sudden death.[6] Noncompaction cardiomyopathy is a relatively recent addition to the diagnostic catalogue.
Currently, it is controversial whether NCCM is a distinct cardiomyopathy or a morphological
characteristic shared by different heart diseases.
Thus, this rare disorder is considered to be an unclassified cardiomyopathy according
to the ESC Working Group on Myocardial and Pericardial Diseases and the WHO (it is
not clear whether it is a separate cardiomyopathy or merely a morphological trait
shared by many phenotypically distinct cardiomyopathies), or a genetic cardiomyopathy
according to the AHA[1]
[2]
[3] Echocardiography is the main method for detecting NCCM.[4]
Left ventricular non-compaction comprises the majority of the cases, but NCCM can
also be seen in the right ventricle or in both ventricles.[5]
Left ventricular noncompaction affects the left ventricular myocardial structure by
the compaction process interruption between the 5th and the 8th gestational week.[7] At this time, the myocardium is widely formed by trabeculae because the coronary
system is not yet developed and the wide intertrabecular spaces allow the blood flow
to spread to the myocardial developing tissues. Between the 5th and the 8th week, the trabeculae regress following the myocardial fiber compaction. This process
occurs from the basis to the cardiac apex, while the coronary system develops, supporting
the growing myocardial tissue. According to the pathogenetic theory, myocardial morphogenesis
interruption occurs, preventing the trabecular regression and muscle tissue compaction,
although the coronary system is normally developed. This leads to a gradual myocardial
fiber compaction failure, determining an excessive trabecular formation with deep
ventricular wall recesses. These remarkable trabeculations, especially in the ventricular
vertex, are responsible for the anomalous aspect of the ventricular cavity.[7]
[8]
[9]
Histopathology has shown a continuity between the endothelium of the intertrabecular
recesses and that of the endocardium, distinguishing LVNC from persistent sinusoids.
Other findings have included loosely organized myocytes and endocardial and subendocardial
replacement fibrosis, suggestive of ischemic necrosis. Left ventricular dilatation
and ischemia are frequently present, and thrombus formation in the recesses may occur,
which may be associated with possible thromboembolic events. Since there is no gold
standard for the diagnosis, the sensitivity and specificity of the morphologic criteria
are uncertain. The Jenni et al[10] criteria are the most widely accepted. These criteria were developed based upon
the echocardiographic appearance with pathologic confirmation in seven patients with
LVNC; the criteria were validated in a second population.[10]
In conclusion, the diagnosis of LVNC is based on these morphologic and echocardiographic
criteria:
-
Thickened myocardium with a two-layered structure consisting of a thin compacted epicardial
layer/band (C) and a much thicker, non-compacted endocardial layer (N) or trabecular
meshwork with deep endomyocardial spaces; N/C ratio of 2:0 at end-systole in the parasternal
short-axis view
-
Hypoplasia of the papillary muscles;
-
Noncompaction anomalies involving the lateral, inferior and apical myocardial segments;
-
Color Doppler evidence of flow within the deep intertrabecular recesses;[8]
[10]
-
Trabeculae and intertrabecular recesses are covered by the endocardium, filled with
blood with no communication with the coronary circulation.[8]
The clinical relevance of NCCM associated to other cardiac anomalies is still not
well defined. One hypothesis, based on recent research, says that families affected
by LVNC show mutations of the sarcomeric protein coding genes and myosin heavy chain
in continuum with hypertrophic, restrictive cardiomyopathy and, more rarely, with
dilated cardiomyopathy.[11]
[12]
Left ventricular noncompaction is almost invariably associated with other congenital
cardiac malformations, including atrioventricular canal defects, double-outlet right
ventricle, valvular atresia, ventricular septal defect, and transposition of the great
arteries.[13]
The clinical presentation varies from no symptoms to heart failure, embolism, arrhythmia,
mitral insufficiency, conduction disorders and sudden death.[14] Patients (fetus, child or adult) who show heart failure symptoms tend to have a
diminished ventricular function and a poor prognosis; those identified with family
screening or with echocardiography usually have a less serious disease, no symptoms
and a good prognosis in adult life. Noncompaction cardiomyopathy cases diagnosed in
utero are very few, with almost no data about long-term follow-ups.[8]
A retrospective study of autopsied fetuses and neonates with NCCM showed that heart
failure, including heart block, is a common cause of death. NCCM is often associated
with various cardiovascular malformations, but even in isolation it can be the basis
for severe cardiac failure, and biventricular endocardial fibroelastosis in NCCM suggests
a global pathologic process.[6]
The differential diagnosis of LVNC is based on: false tendons, remarkable trabeculae
as normal variants, apical hypertrophic cardiomyopathy, dilated cardiomyopathy with
no spongy myocardium, Fabry disease, right arrhythmogenic ventricular dysplasia, and
endocardial fibroelastosis. Patients with LVNC should be submitted to screening for:
congenital cardiac defects, genetic anomalies, and neuromuscular and metabolic diseases.[8]
[12]
Final Considerations
Ultrasound technical improvements and the progress in the training of ultrasound operators
have augmented the cardiac structure detection during fetal echocardiography. For
this reason, NCCM should be considered for a differential diagnosis in cases of dilated
cardiomyopathy.[15] The actual debate of a defined separation between LVNC and other overlapping forms
of cardiomyopathies is still under discussion, requiring further studies.[9] We hypothesize that LVNC belongs to the group of cardiomyopathies in which every
entity shows aspects that can overlap with the others and may share a common genetic
basis. This possibility gives new research perspectives on the etiopathogenetic mechanisms
of genetic myocardial diseases.
