Recognizing Left-Ventricular Noncompaction in Children as a Mechanism for Heart
Failure: The University of Louisville Experience
Authors:
Bibhuti B Das, Walter Sobczyk, Bradley B. Keller
Departments of Pediatrics, Division of Pediatric Cardiology
University of Louisville School of Medicine, Louisville, Kentucky, USA
Key words:
Left ventricular noncompaction cardiomyopathy,
Ventricular noncompaction, ventricular hypertrabeculation
Corresponding Author:
Bibhuti B Das, M.D.
Division of Pediatric Cardiology
Department of Pediatrics
University of Louisville
571 South Floyd Street, Suite 334
Louisville, KY 40202, USA
E-mail: bdas99@hotmail.com
Tel: 502-852-3876, Fax: 502-852-3877
1
Abstract
Background and objective: Left ventricular noncompaction (LVNC) is an uncommon form of
cardiomyopathy but increasingly recognized in children. We sought to determine the spectrum of
clinical presentations and outcomes of children diagnosed with isolated LVNC in a single center.
Methods: Case records of children diagnosed with isolated LVNC between 2004 and 2010 were
reviewed. Diagnosis of LVNC was based on echocardiographic criteria published in literature.
Results: Thirty patients (20 males) were diagnosed with LVNC at an average age of 12.5±6.3
years (range, birth to 20 years) included in the study. Clinical presentations included heart failure
in 10 (33.3%), chest pain in seven (23.3%), ventricular arrhythmias in seven (23.3%),
neuromuscular disorder in four (13.3%) and two (6.6%) with heart murmur.
Conclusions: LVNC in children is a heterogeneous condition. Long-term follow-up is indicated
once LVNC is diagnosed for the development of LV dysfunction and cardiac arrhythmias.
2
Noncompaction of the left ventricular myocardium (LVNC) is a rare congenital cardiomyopathy
characterized by a thin compacted epicardial (C) and a thickened endocardial layer with
prominent trabeculations and deep intertrabecular recesses (NC). Clinical manifestations may
range from being asymptomatic to heart failure, arrhythmias, sudden death, and systemic
thromboembolism. The anatomic findings of LVNC may be present at birth; however, its clinical
implications vary, and diagnosis may occur at any age. The clinical manifestations are not
sufficient to establish the diagnosis; echocardiography is the diagnostic tool that makes it
possible to document ventricular noncompaction. Five sets of diagnostic criteria form the basis
for echocardiographic diagnosis of LVNC, namely those by Jenni et al [1], Chin et al [2],
Pignatelli et al [3], Strollberger et al [4] and Belanger et al [5] respectively.
In a prospective study evaluating 5220 consecutive children for echocardiographic
assessment, a prevalence of 1.26% has been reported. [6] Recently, this condition has been
classified under the category of genetic cause of primary cardiomyopathy by the American Heart
Association. [7] In the past decade, increased awareness of this entity has led to its increasing
diagnosis in the pediatric population, although data remain limited. The biggest challenge is
differentiation of isolated LVNC from normal anatomic variants such as aberrant bands, since
incidence of LV false tendons/aberrant bands in normal heart is relatively high (40.8%). [8] The
aim of the current study was to review a single-center experience in the diagnosis and
management of children with LVNC over a six year period in order to identify common features
and echocardiography imaging measurement standards for LVNC diagnosis.
3
Material and methods
We retrospectively reviewed 30 children with LVNC evaluated at our center for congenital heart
disease between January of 2005 and December 2010. During this period there were total 20,000
patients had scheduled routine outpatient visits. Medical records were reviewed to document
clinical presentation, including symptoms, primary diagnosis, New York Heart Association
classification (NYHA) for functional status, presence of arrhythmias, associated neurological
findings and presence of positive family history. Holter monitor and 12-lead ECGs were
examined for arrhythmias. Nonsustained ventricular tachycardia was considered to be more than
three premature ventricular contractions lasting up to 30 seconds. A ventricular tachycardia run
of more than 30 seconds was defined as sustained ventricular tachycardia. [9]
Multiple echocardiographic studies were performed in each patient during follow-up to
establish the diagnosis of LVNC in most of the cases. The inclusion criteria for isolated LVNC
were: (1) absence of coexisting cardiac structural abnormalities; (2) prominent LV trabeculations
(>3 in any imaging plane) (Figure-1A & B); (3) recesses supplied by intraventricular blood on
color Doppler (Figure-1C); and (4) a two-layered structure of the endocardium with a NC to C
ratio >2 (Figure-1A & B). Echocardiograms were analyzed for LV ejection fraction and mitral
inflow velocity for determination of E/A. Diastolic function was graded as normal (E/A 1.01.49), abnormal relaxation (E/A <1) and restrictive pattern (E/A ≥1.5) using previously described
criteria. [10]
The distributions of prominent trabeculations in LV were analyzed from apical 4 and 2
chambers and parasternal short axis images (Figure 1-A &B, Figure 2-C). Each echocardiogram
was carefully examined for false tendon/aberrant bands which often gives a trabeculated
4
appearance to LV myocardium. False tendon/aberrant bands were defined as linear cord like
fibromuscular structures with free intracavitary course and connected to papillary muscles,
ventricular walls or both, with a thickness ≤2 mm. [11-12] The false tendons/aberrant bands were
identified appropriately from different views including apex (Figure-2A) and parasternal shortaxis view (Figure-2B) and excluded from the measurement of NC to C ratio. More than 3
prominent trabeculations with the same signal intensity like myocardium, protruding from the
LV wall, apically to the papillary muscles, visible in one imaging plane and with communication
of the intertrabecular spaces to the LV cavity are considered abnormal (Figure-2C). [13] The
position, orientation and point of insertion of the trabeculation were carefully analyzed to
differentiate between normal and pathological trabeculation.
Clinical follow-up was obtained on all patients based on notes from the last visit to
outpatient clinic in the patient’s charts. This study was reviewed and approved by the
Institutional Review Board of the University of Louisville. For statistical analysis, data were
summarized as mean ± standard deviation. The risks for unfavorable clinical events were shown
as % value.
Results
Thirty pediatric patients with a mean age 12.5± 6.3 years (range, birth to 20 years) were
studied (Table-1). Twenty (66.6%) were male and 10 (33.4%) were female. The prevalence of
isolated LVNC was 0.15 % (30 patients from 20,000 visits in 6 years) based on our study. The
characteristics of patient at presentation and follow-up were summarized in Table-2. Heart
failure was most common presentation (33.3%) in the current study. Five of the 10 patients
showed clinical and echocardiographic improvements during follow-up. Other five patients were
5
in chronic heart failure and developed progressive exertional dyspnea. Two of these five patients
had NYHA functional status class I-II and remaining 3 had class III-IV. These five patients with
heart failure remained on treatment with diuretics, ACE inhibition, digoxin, and +/- betablocking agents. One patient underwent orthotopic heart transplantation secondary to
uncontrolled intractable ventricular tachycardia. One patient died due to chronic heart failure at
age nine years.
In 10% of patients ECG showed WPW pattern and two of them had atrial tachycardia
required complete electrophysiology study and underwent radiofrequency ablation. Premature
ventricular contractions (PVCs) were seen in 26.6% on 12-lead ECG. 24 hour Holter monitor
was available in 26 patients and in 23% patients had ventricular tachyarrhythmia. One patient
who had LVNC with central hypoventilation syndrome had prolonged sinus pauses up to seven
seconds on Holter. Seven patients (23.3%) presented with chest pain and were evaluated with
exercise stress test. No exercise induced arrhythmia or ischemia noted. We did not find any
incidence of familial LVNC in this study. Four patients had neurological abnormalities including
developmental delay, hypotonia, seizures, and in one of them absence corpuscallosum. We did
not have genetic evaluation in any of these patients.
Echocardiographic data were shown in Table-3. Isolated LVNC was diagnosed based on
echocardiographic maximal NC to C ratio >2 in the parasternal short axis view. Decreased LV
ejection fraction (<50%) was noted in 13.3 %. Diastolic dysfunction was noted in 6 patients and
4 of them had impaired relaxation and two of them had restrictive pattern. The noncompacted
segment was localized to apex in 19 of 30 patients (63%) and involved apex and lateral wall in
nine patients (30%). There was diffuse global involvement of LV with noncompaction in two
patients. Out of 30 patients with LVNC, seven had dilated form and two had hypertrophic form
6
and remaining 21 had normal LV size. There was only one patient with evidence of LV
thrombus on two-dimensional echocardiogram.
Discussion
This retrospective study reports the presenting symptoms, echocardiographic,
demographic, and clinical characteristics of 30 patients with isolated LVNC. As shown in the
present series, the LV apex is almost universally involved; however the degree of noncompaction
varies. This has been postulated to be related to variations in the time course of ventricular
trabecular compaction in utero. [14] The salient feature of the current study is that we have
meticulously applied the definition of abnormal trabeculation (Figure-2C) as defined previously
[13]
while carefully exclude normal trabeculations [11-12] like false tendon and aberrant bands
(Figure-2A & B). In our study, most subjects with LVNC had normal LV size; with fewer
subjects displaying either the dilated or hypertrophic forms of LVNC. At least seven different
phenotypes of LVNC have been described in literature such as: LVNC with normal size, dilated
form of LVNC, hypertrophic form of LVNC, restrictive form of LVNC, biventricular LVNC,
LVNC with congenital heart disease, and undulating form of LVNC, likely reflecting variations
in the genetic defects in these patients as well as variations in secondary modifiers. [15]
Clinical presentation of patients with LVNC as illustrated in this and other studies can be
highly diversified. It ranges from asymptomatic with incidental findings of heart murmur to
symptomatic heart failure or fatal arrhythmia. In our cohort, heart failure is the most common
(33.3%) presenting symptom. Our experience is similar to the findings reported by Koh et al. [16]
The lower incidence of heart failure in some of the previous studies might be related to identification of asymptomatic individuals by screening. [17-18] The variable presentation supports the
7
recently proposed concept of LVNC being a continuum of disease, with milder forms having less
prominent trabeculations echocardiographically. In our study, patients who have global
involvement of myocardium with noncompaction are more likely develop chronic heart failure
than those who have noncompaction limited only to apex. While ventricular dysfunction has
been postulated to be related to reduce thickness of the compacted myocardial layer, findings of
several studies suggest possibility of myocardial ischemia as an alternative mechanism. [14]
Cardiac magnetic resonance has demonstrated subendocardial perfusion defects while
positron-emission tomography has shown impaired myocardial perfusion and decreased flow
reserve in areas of ventricular noncompaction in children. [19] In adults, decreased coronary flow
reserve has been shown to involve not only noncompacted but also normal myocardium,
suggesting a pathogenetic role of microcirculatory dysfunction. Various forms of arrhythmias,
including left bundle branch, second degree and complete heart block, sinus bradycardia,
premature atrial and ventricular contractions, atrial fibrillation, and ventricular tachycardia and
fibrillation, have been documented to occur in association with LVNC. In our study, arrhythmias
are noted in 13% of patients by Holter, similar to previous report of 14% of arrhythmia in
children with LVNC. [20] Wolff–Parkinson–White pattern in ECG is noted in three patients (10%)
in current study and is reported up to 17% of children with LVNC in literature. [21]
The incidence of thromboembolism is rare in children with LVNC. It has been proposed
that infrequent thrombi formation may be attributed to reasons including complete
endothelialization of the trabeculations and relative preservation of mobility of apical
myocardium in children compared to adults. [9] It remains controversial, however, whether
anticoagulation therapy should be routinely given to all of the patients or only to those with risk
factors such as ventricular dysfunction or atrial fibrillation.
8
The clinical course of patients with LVNC is highly variable. Significant improvement in
LV ejection fraction has been noted spontaneously during follow-up in five of our patients,
whether these patients represent transient form of cardiomyopathy and misclassified as
noncompaction or truly reversible form of LVNC is unknown. Reversible isolated LVNC in
adults and children are reported in the literature. [22-23] One of our patient required orthotopic
heart transplantation secondary to intractable ventricular arrhythmia and one patient died during
follow-up in spite of both carvedilol and amiodarone therapy. Although a mortality rate up to
52% has been reported, [24] the rate varies greatly among series. In our study, we have only 2
cases of death or transplantation. A recent published study has suggested that patients with
LVNC who present with hemodynamic instability and poor ventricular function have decreased
transplant-free survival, and most poor outcomes occur within the first year after presentation. [25]
Study limitations: Limitations to this study were mostly related to the retrospective nature
of the clinical study and echocardiographic review. Because the acquisition of appropriate
echocardiographic views was not performed on many subjects, LV segmental analysis was not
evaluated. Additionally, certain echocardiographic analytic tools that could potentially be
relevant were not reliably used on the entire study population. Ejection fraction was unavailable
in 15% patients, and on these patients ejection fraction was assumed based on fractional
shortening. Genetic assessment is not performed and family screening is not uniformly
documented in the chart.
In summary, LVNC cardiomyopathy in children is difficult to diagnose unless the physician
has a high level of suspicion during echocardiographic evaluation. Although an
echocardiographic maximal NC: C ratio >2 suggest the diagnosis of LVNC in children as
previously reported by our group, [24] additional echocardiographic parameters are needed to
9
distinguish between normal and noncompacted LV. In children with diagnosis of LVNC, longterm follow-up for development of LV dysfunction and cardiac arrhythmia is indicated.
10
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13
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14
Figure Legends
Figure-1: (A) Transthoracic two-dimensional apical 4 chamber and (B) 2 chamber images show
dilatation of left ventricle (LV), multiple trabecuale and recesses in apex and lateral wall of LV.
Figure-1C: Transthoracic two-dimensional study with color Doppler (parasternal short axis view
of left ventricle) shows penetration of color into the intertrabecular recesses
Figure-2: (A) Apical 4-chamber (focusing only left ventricle (LV) apex) and (B) parasternal
short-axis view demonstrating false tendons/aberrant bands. (C) Parastenal short-axis view of LV
at apex showing patological trabeculations diagnostic of LV noncompaction. Example of the
noncompaction (NC) and compaction (C) layer demonstrated.
15
Table 1: Demographic characteristics (n=30)
16
Male
Average age in years
20 (66.6%)
12.5 ± 6.3
Average age in yrs at diagnosis
8.3 ± 5.9
Average years of follow-up
5 ± 3.6
Age, years
Number
0–1
4 (13.3%)
2–5
3 (10%)
6–10
4 (16.6%)
11–15
5 (16.6%)
16-20
14 (46.6%)
Prevalence in our center
30/20,000/6 years
(0.15%)
Table-2: Clinical and electrocardiographic characteristics of patients at presentation and followup
Clinical findings
Heart failure at presentation
During follow-up:
-Subsequent improvement (5) (16.6%)
- Chronic heart failure (5) (16.6%)
- NYHA class I/II (2)
- NYHA class III/IV (3)
Abnormal ECG (during follow-up)
WPW pattern (3) (10%)
Long QT (1) (3.3%)
Bundle branch block (2) (6.6%)
Premature ventricular contraction (8) (26.6%)
Premature atrial contractions (3) (10%)
Chest pain at presentation
History of syncope at presentation
LVNC associated with neuromuscular disorder
Asymptomatic heart murmur
Cardiac rhythm in 24 hour Holter
Premature ventricular contractions
Sustained/nonsustained ventricular tachycardia
Atrial tachycardia
Sinus pause (prolonged up to 7 seconds)
17
10 (33.3%)
17 (56%)
7 (23.3%)
2 (6.6%)
4 (13.3%)
2 (6.6%)
10 (33.3%)
7 (23.3%)
2 (6.6%)
1 (3.3%)
Table-3: Echocardiographic findings at presentation and during follow-up
Systolic function
Decreased left ventricular ejection fraction (EF < 50%)
Diastolic function
Impaired relaxation
Restrictive pattern
Normal
Thrombus
Left ventricle
Valvular regurgitation
Mild mitral
Moderate mitral
Mild aortic
Mild tricuspid
Subtypes of LVNC
Dilated
Hypertrophic
Previously dilated LV with localized noncompaction at apex
and then LV become normal size and function
Normal LV size, thickness and function
Localization of noncompaction segment
Apex
Apex and lateral wall
Global
Ratio of Noncompacted to Compacted layer (NC:C)
18
10 (33.3%)
4 (13.3%)
2 (6.6%)
24 (80%)
1 (3.3%)
3 (10%)
2 (6.6%)
1 (3.3%)
5 (16.6%)
7 (23.3%)
2 (6.6%)
5 (16.6%)
16
19 (63.3%)
9 (30%)
2 (6.6%)
2.3 ± 0.26
RA
LA
RV
LV
NC
C
Figure-1A
19
LA
LV
NC
Figure- 1B
20
LV
Figure-1C
21
NC
Aberrant bands
Mitral valve
chordal
attachment
LV
(A)
Figure-2
22
C
LV
False
tendon
(B)
(C)