Clinical research
European Heart Journal (2006) 27, 1855–1860
doi:10.1093/eurheartj/ehl112
Congenital heart disease
Complications of non-compaction of the left
ventricular myocardium in a paediatric population:
a prospective study
´zek1, James J. Joyce5, Thomas Rau2, Barbara F. Finckh3, Florian Weiss4,
Christian Lilje1,5*, Vit Ra
Christian R. Habermann4, Janet C. Rice6, and Jochen Weil1
1
¨ts-Klinikum Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany;
Departments of Kinderkardiologie, Universita
¨ts-Klinikum Hamburg-Eppendorf, Hamburg, Germany;
Experimentelle & Klinische Pharmakologie & Toxikologie, Universita
3
¨ts-Klinikum Hamburg-Eppendorf, Hamburg, Germany; 4 Diagnostische Radiologie,
Clinical Pathology/Pediatrics, Universita
¨ts-Klinikum Hamburg-Eppendorf, Hamburg, Germany; 5 Section of Pediatric Cardiology, Tulane University Health
Universita
Sciences Center, New Orleans, LA, USA; and 6 Department of Biostatistics, Tulane University School of Public Health &
Tropical Medicine, New Orleans, LA, USA
2
Received 28 September 2004; revised 5 April 2006; accepted 1 June 2006; online publish-ahead-of-print 3 July 2006
KEYWORDS
Aims Non-compaction of the left ventricular myocardium (NCVM) is reportedly exceedingly rare and
associated with a high morbidity and mortality. A different genetic background has been suggested
for NCVM with [non-isolated NCVM (ni-NCVM)] and without [isolated NCVM (i-NCVM)] other congenital
heart defects. We prospectively evaluated both the NCVM subgroups regarding frequency of occurrence
and cardiovascular complications in a paediatric population.
Results In a prospective, single-centre study, 66/5220 consecutive patients (1.26%) were diagnosed (25
i-NCVM, 41 ni-NCVM). The median age was 4 years (range 0–21), the median follow-up 12 months (range
0–51). The occurrence of congestive heart failure (CHF) at follow-up was 68.0%. CHF was as frequently
seen in i-NCVM and ni-NCVM patients (77.5 vs. 62.1%, P ¼ 0.322). The occurrence of arrhythmias (20.0%)
and thrombo-embolic events (13.9%) was not different between subgroups. The cardiomyopathy related
mortality was 7.1%, with three and one deaths in the i-NCVM and ni-NCVM groups, respectively
(P ¼ 0.126).
Conclusion When prospectively evaluated, NCVM appears to have been previously under-diagnosed.
Whereas arrhythmias and thrombo-embolic events were rare, CHF was frequently found. An equally
aggressive anticongestive treatment regimen would seem indicated for both the NCVM subgroups.
Introduction
Non-compaction of the left ventricular myocardium (NCVM)
is a distinct, not yet classiﬁed congenital cardiomyopathy.1
It is characterized by numerous, excessively prominent ventricular trabeculations and deep intertrabecular recesses.2
Recently, this entity has been increasingly recognized, but
study-based data are limited. Supposedly, it is extremely
rare and associated with a high morbidity and mortality.2–6
Although congestive heart failure (CHF) universally is a
common ﬁnding, observations regarding other cardiovascular complications are less consistent.
Early in gestational life, the myocardium is loosely compacted. Blood ﬂow in this avascular sponge-like meshwork
of interwoven myocardial ﬁbres with intertrabecular
recesses is provided from the ventricular cavity.
Compaction of the ventricular myocardium occurs during
* Corresponding author. Tel: þ49 40 42803 3718; fax: þ49 40 42803 6826.
E-mail address: [email protected]
gestational weeks 5–8, progressing from the epicardium
towards the endocardium and from the base towards the
apex. Simultaneously, the intertrabecular spaces are
reduced to capillaries.2,7 NCVM is believed to represent an
arrest in this gradual morphogenetic process.2,7,8
The ontogenetic determinants for this arrest are unknown.
A heterogeneous genetic background is suspected. Mutations
in the gene G4.5 on the Xq28 chromosomal region and in the
gene Cypher/ZASP have been linked to infantile cardiomyopathies, including some familial forms of isolated NCVM
(i-NCVM).9–13 Mutations in the gene a-dystrobrevin on the
18q12 chromosome and distal 5q35 deletion (CSX gene)
were identiﬁed in familial NCVM associated with structural
congenital heart defects (CHD), i.e. non-isolated NCVM
(ni-NCVM).10,14,15 G4.5 mutations were not found in
ni-NCVM.10 It only rarely caused i-NCVM in adults.16 Instead,
autosomal-dominant adult forms of i-NCVM have been linked
to chromosome 11p15 and lamin A/C gene mutations.16,17
In light of the above scarce and somewhat inconclusive
data, and a suspected different genetic background for
& The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: [email protected]
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Heart defects, congenital;
Cardiomyopathy;
Heart failure, congestive;
Echocardiography;
Non-compaction
1856
i-NCVM and ni-NCVM as outlined above, we sought to
prospectively characterize both entities in a paediatric
population regarding their frequency of occurrence and
cardiovascular complications.
C. Lilje et al.
multicentre study on dilated cardiomyopathy and myocarditis
(www.uni-essen.de/kinderklinik/downloads/protokoll.pdf). The procedures followed were in accordance with institutional guidelines.
All patients/patient representatives gave informed consent.
Statistical analysis
Methods
Study sample, design, and diagnostic criteria
Results
Patient characteristics
Sixty-six out of 5220 patients (1.26%) met the criteria for
NCVM and were included for further follow-up. The
median age at diagnosis was 4 years (0–21). There were 32
female and 34 male patients (48.5 vs. 51.5%). The median
follow-up was 12 months (0–51). i-NCVM was found in 25
patients, ni-NCVM in 41 patients. Age at diagnosis, gender
ratio, and severity of NCVM were not different between
the subgroups (Table 1).
Diagnostic methods and morphology
The degree of LV non-compaction was mostly moderate and
not different between i-NCVM and ni-NCVM patients
(Table 1). Autopsy ﬁndings, obtained in two neonatal
cases, corresponded closely to echocardiographic ﬁndings.
Mild subendocardial ﬁbrosis was noted in one of them. The
ﬁbrotic changes predominately involved the LV apex as a
thin layer of thickened endocardium, but was also found in
focal areas of the LV-free wall. In both cases, the recesses
were covered by endothelium that was in continuity with
the ventricular endocardium. The myocyte fascicles were
found to be loosely organized, the myocyte ﬁbres abnormally thin and angulated, the number of ﬁlaments
reduced. One specimen was remarkable for moderate mitochondrial proliferation. Right ventricular biopsies were performed in 14 i-NCVM patients. No proof of an infectious or
Table 1 Patient characteristics at diagnosis
Figure 1 Method of determining X-to-Y ratio according to Chin et al.,2
X represents the distance between the epicardial surface and the trough of
the recesses and Y represents the distance between the epicardial surface
and the peak of the trabeculations. X-to-Y ratios were measured at the
level of the apex, papillary muscles, and mitral valve.
Frequency of
occurrence
Age (years)
median (range)
Gender ratio (%)
(female:male)
NCVM grading
Mild
Moderate
Severe
i-NCVM
(n ¼ 25)
ni-NCVM
(n ¼ 41)
P-value
0.5%
0.8%
3 (0–21)
8 (0–20)
0.43
52:48 (13:12)
46:54 (19:22)
0.66
5 (20.0%)
17 (68.0%)
3 (12.0%)
8 (19.4%)
28 (68.3%)
5 (12.2%)
0.97
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Between September 1999 and May 2002, we evaluated all consecutive patients who were sent for echocardiography. The study
design was observational, single-centre, and prospective. The
diagnosis of NCVM was made by transthoracic echocardiography
in accordance with suggested criteria.2,4–6,18,19 Concurrence of
two independent observers was required to conﬁrm the diagnosis.
Hypertrabeculation of the left ventricular (LV) with an apical
X-to-Y ratio of 0.33 was a prerequisite, where X represents the distance between the epicardial surface and the trough of the recess
and Y represents the distance between the epicardial surface and
the peak of the trabeculations (Figure 1).2 To quantitate the magnitude of the myocardial non-compaction, X-to-Y ratios were
measured at the level of the apex, papillary muscles, and mitral
valve. NCVM was graded as mild (apical affection only with an
X-to-Y ratio of 0.33–0.26), moderate (two level affection or an
apical X-to-Y ratio of 0.25–0.20), or severe (three level involvement
or an apical X-to-Y ratio of ,0.20).
CHF was graded as mild, moderate/severe, or terminal
(CHF-related death or transplant recipient) on the basis of a modiﬁed clinical score,20 the intensity of anticongestive therapy (no
medication, 1–2 drugs, 3 drugs), and the LV shortening fraction
by M-mode echocardiography (.27%, 20–27%, ,20%). Any structural CHD associated with the NCVM, including a muscular ventricular septal defect, qualiﬁed for the ni-NCVM group. Like in
the previous reports, arrhythmias were considered signiﬁcant,
if they were ventricular and qualiﬁed for a Lown class III.
Thrombo-embolic events were deﬁned by either visualization of
an intracardiac thrombus or typical neurological ﬁndings.
Initial evaluation included a medical history, a physical examination, a 12-lead electrocardiogram (ECG), and a transthoracic echocardiogram. Follow-up visits were scheduled at 3, 6, 12 months, and
6 monthly thereafter. Follow-up included an interval history, a
focused physical examination, a 12-lead ECG, and a transthoracic
echocardiogram. Holter monitoring, additional imaging studies like
transesophageal echocardiography, magnetic resonance imaging
(MRI), scintigraphy, or cardiac catheterization, and therapeutic
decisions were performed at the discretion of the primary cardiologist. Right ventricular biopsies were obtained in i-NCVM patients
with LV dilatation as part of an unrelated ongoing German
Descriptive statistics for continuous variables are presented as
median (range). Patient characteristics at diagnosis were calculated
by means of Mann–Whitney U test for continuous variables and x2
test for categorical variables. Cumulative event rates at 12
months follow-up were estimated by means of the Kaplan–Meier
and the Log-Rang (Mantel-Cox) methods. Ages at occurrence of
CHF were compared by means of the Kaplan–Meier method and
Mann–Whitney U test. Reported P-values are two-sided. A P-value
of ,0.05 was considered statistically signiﬁcant. All follow-up
data were analysed at 12 months after diagnosis using StatView
5.0 (SAS) and STATISTICA 6.0 (StatSoft).
Non-compaction of the ventricular myocardium
1857
inﬂammatory process was found in any of them. MRI did not
detect fatty deposits in the myocardium of the 13 patients
who were imaged.
Associated CHD
Ventricular septal defects were the single most frequent
lesions. They were found in 11 patients (26.8%) with 90.9%
of the defects being muscular. 73.2% of associated CHD
were found to be obstructive: 43.9% (18 patients) in the
left heart, 29.3% (12 patients) in the right heart, and 7.3%
(3 patients) on both sides. The left-sided obstructions comprised six patients with subaortic obstruction, six patients
with valvar aortic stenosis including three with a bicuspid
aortic valve, and six patients with coarctation of the
aorta. The right-sided obstructions comprised one patient
with Ebstein’s anomaly/pulmonary stenosis, four patients
with valvar pulmonary stenosis, ﬁve patients with
Tetralogy of Fallot, and two patients with pulmonary
atresia/intact ventricular septum.
Mortality
CHF
At diagnosis, CHF for the entire sample was found in 40.9% of
patients. At 12 months follow-up, CHF had been detected in
68.0% of patients. The occurrence of CHF was not different
between i-NCVM and ni-NCVM patients (77.5 and 62.1%,
respectively; P ¼ 0.322) (Figure 2). CHF was at least
severe in i-NCVM as in ni-NCVM patients at all times. The
median age at diagnosis of CHF was 2.0 years (0.0–21.0)
for i-NCVM patients vs. 8.5 years (0.0–18.0) for ni-NCVM
patients (P ¼ 0.186).
At 12 months follow-up, arrhythmias were found in four
patients (20.0%) (Table 3); they were pre-existing in two
patients. Their overall occurrence was not different in
i-NCVM and ni-NCVM patients (Table 2). Thrombo-embolic
events were detected in two patients (13.9%) (Table 3);
they were pre-existing in one patient. Although no such
events were observed in i-NCVM patients, their occurrence
was likewise not different between the groups (Table 2).
Discussion
We present the largest and the ﬁrst prospective study on
NCVM so far. It is one of the three investigations including
ni-NCVM patients. Since the initial report of Chin et al.2
on 8 patients, just about a dozen studies involving at
least that many patients have been published
(Table 3).4–6,12,16,19,21–24 Six of them comprised exclusively
adults.5,6,16,19,22,24 Unlike our study, two of them were
focused on genetics and coronary function. Two investigations addressed both the i-NCVM and ni-NCVM,12,21
whereas only one compared these groups.21
Imaging and morphology
Universally, echocardiography is considered the diagnostic
modality of choice.2,5,8,10,12,18,19,21,25 Colour Doppler was
particularly helpful in detecting intertrabecular perfusion
from the ventricular cavity. Our two autopsy ﬁndings, as in
the previous studies,5,26 conﬁrmed the echocardiographic
ﬁndings of NCVM. Subendocardial ﬁbrosis, if present, is not
a diagnostic criterion for NCVM but is probably an ominous
prognostic ﬁnding indicating ischaemic necrosis. In terms
of histology, a mild increase in mitochondrial size and
density has been described previously.8,9 To avoid falsepositive diagnoses, we chose a X-to-Y cut-off value of
0.33, which is equivalent to the suggested non-compacted
to compacted (N/C) ratio 2.5,12,18,19 However, diagnostic
criteria may need reﬁnement.25,27–29 We agree with
several more recent investigators that with modern
imaging technology, NCVM in children could reliably be diagnosed with an X-to-Y ratio well .0.33 (i.e. a N/C ratio , 2),
Table 2 Cardiovascular complications at follow-up
i-NCVM
Mortalitya
(n ¼ 25:41)
CHFb (n ¼ 23:37)
Arrhythmias
(n ¼ 23:37)
Thromb-embolic
events
(n ¼ 23:37)
ni-NCVM
P-value
All NCVM
3 (12.0%)
1 (2.1%)
0.126
4 (6.1%)
17 (77.5%)
1 (5.0%)
24 (62.1%)
3 (34.5%)
0.322
0.369
41 (68.0%)
4 (20.0%)
0 (0.0%)
2 (26.1%)
0.160
2 (13.9%)
P-values are given for NCVM subgroup comparison. Follow-up data were
analysed at 12 months after diagnosis (median follow-up). Numbers in
parenthesis (ﬁrst column) indicate i-NCVM vs. ni-NCVM patients in
whom information was available.
a
An additional death in the ni-NCVM group was unrelated to both NCVM
and CHF.
b
CHF comprises patients who died from terminal CHF or became transplant recipients (three CHF).
Figure 2 Kaplan–Meier estimate of cumulative freedom from CHF to
follow-up time. The overall outcome was similarly poor for both subgroups
(P ¼ 0.322). ni-NCVM patients experienced a more rapid decline early during
follow-up; there were few late new onset CHF cases. i-NCVM patients presented
with CHF more frequently; there was a slow but steady decline of freedom from
CHF during follow-up. Data were analysed at 12 months (median follow-up
time). CHF indicates congestive heart failure; i-NCVM, isolated NCVM;
ni-NCVM, non-isolated NCVM; x, event time; o, censored observation time.
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Five patients died during 12 months follow-up. One death in
the ni-NCVM group was unrelated to both the cardiomyopathy and CHF. The cardiomyopathy related mortality was
7.1%. Three patients (14.3%) died in the i-NCVM subgroup
and one patient (2.7%) died in the ni-NCVM subgroup
(P ¼ 0.126) (Table 2). All deaths in the i-NCVM patients
occurred within the ﬁrst 3 months following the diagnosis.
Arrhythmias and thrombo-embolic events
67%
20%
4.0%
45
45:0
3.8a
?
3.0%
73%
65%
?
53%
41%
24%
Frequency of occurrence
53%
47%
24%
91%
23%
0%
89%
2.8%
2.8%
35%
8%
0%
48%
rare
7.4%
63%
63%
38%
Three further studies did not in detail address cardiovascular complications.16,19,29
a
Mean+ SD.
b
An additional death in the ni-NCVM group was unrelated to both NCVM and CHF.
62
62:0
?
34
34:0
3.7a
SD + 3.3
46%
To quantify the degree of NCVM, different indices have been
applied at different or non-speciﬁed wall segments and at
different or non-speciﬁed points in time during the cardiac
cycle.2,10,18,25 In our study, the X-to-Y ratio was applied at
three levels with distinct threshold levels. We support
Borreguero et al.31 and Petersen et al.25 that measurements
should be taken in ventricular diastole rather than in systole
to enhance diagnostic sensitivity and speciﬁcity.
68%
20%
14%
50a
42a SD + 7
42a
?
17
17:0
2.5a
SD + 2.3
59%
3.0
?
22
22:0
3.9a
?
23%
5.7
(0–15)
27
27:0
6
(up to 17)
7.4%
8.9a
?
8
8:0
?
(up to 5)
38%
Age (years)
Median (range)
n
i-NCVML: ni-NCVM
Follow-up (years)
Median (range)
Mortality þheart
transplants
Heart failure
Arrhythmias
Thrombo-embolic
events
Ichida et al.4
3.5
?
12
5:7
2.6a
?
0%
0.3
(0–17)
36
31:15
3.2
(0.5–12)
24%
4.0
(0–21)
66
25:41
1.0
(0–4.3)
7.1%b
?
Sto
¨llberger et al.22
Oechslin et al.5
Wald et al.23
Pignatelli et al.12
Lilje et al.
Ritter et al.6
Grading
Chin et al.2
Oezk utlu et al.21
likely as high as 0.5.12,25,29 Today, even fetal detection is
possible.26 Although NCVM of the right ventricle has been
reported in clinical and in autopsy series,6,12,26,29,30 sufﬁciently precise criteria for a reliable in vivo diagnosis are
lacking.
The prospectively evaluated frequency of occurrence of
NCVM in our study—even if considering i-NCVM patients
only—was startlingly higher than one would expect from
the early previous reports. Like for other studies, a referral
bias has to be accounted for in the setting of a large tertiary
care centre. Our institution serves an area of about 3.4
million people. Roughly, 35% of the population is 21
years of age. The low frequency of occurrence referred to
previously (0.014–0.045%) unanimously originates from
only two studies.6,18 Both studies exclusively addressed
adult i-NCVM patients. However, not all NCVM patients
survive through adulthood. In adults, echocardiographic
windows usually do not permit a similar ﬁne resolution of
myocardial structure as in paediatric patients. Even
though imaging technology has signiﬁcantly improved as
has the awareness of echocardiographers for the disease,
most investigators agree that NCVM is still underdiagnosed.8,18,27,32 It is missed in up to 90% pf patients.4,29
More recent data support a considerably higher frequency
of occurrence of i-NCVM,8,12,22,23,32 whereas no previous
data have been available for ni-NCVM.
Associated CHD
Only recently it has been increasingly recognized in paediatric
series that NCVM can also accompany diverse forms of structural CHD.8,29 Ventricular septal defects and outﬂow obstructive lesions were the most frequent associated entities. Both
associations have been observed previously.12,22,27,31 It is
easily conceivable that the deep intertrabecular recesses
present both in the right ventricle and in a non-compacted
LV interfere with the formation of an intact ventricular
septum leading to muscular septal defects. However, it is
not known whether the prominent trabeculations hinder
fetal blood ﬂow leading to hyperplasia and outﬂow obstruction. Or whether the outﬂow obstruction (in ni-NCVM)
accounts for the occurrence of at least some degree of noncompacted hypertrabeculation, which may be functionally
different from the hypertrabeculation in i-NCVM.
Mortality
As in the previous reports,2,4–6,12,23 the mortality in our
population was concerning. The difference between the subgroups, though not statistically signiﬁcant, was remarkable
in a setting of small numbers and a high-survival rate. For
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Table 3 Major clinical studies on NCVM
?
C. Lilje et al.
Murphy et al.24
1858
Non-compaction of the ventricular myocardium
1859
the i-NCVM patients, our ﬁndings were comparable to data
provided by Ichida et al.4 Mortality in Oezkutlu’s et al.21
was found to be lower, but it was even higher in the
studies by Chin et al.2 and Pignatelli et al.12 as well as in
the earlier adult populations.5,6 Paediatric non-survivors
are not accounted for in adult series (Table 3). Most previous
studies have a longer, but retrospective, follow-up period.
No previous data are available on the mortality in ni-NCVM.
ﬁnd evidence of fatty myocardial degeneration in any of
the patients studied by MRI. Interestingly, late potentials
and prolonged QT dispersion have been found in NCVM by
electrophysiological studies.33 In terms of thrombo-embolic
events, the non-laminar intertrabecular ﬂow and early CHF
certainly constitute the risk factors.
CHF
The prevalence of NCVM in a non-selected or even general
population cannot be determined from this study. A referral
bias has to be accounted for in the setting of a large tertiary
care centre. Screening for gene mutations was not part of
this observational study protocol. The degree to which
heart failure in the ni-NCVM group was due to the associated
CHD other than the NCVM could not be quantiﬁed. Holter
monitoring, transesophageal echocardiography, MRI, scintigraphy, and angiography for the detection of arrhythmias
and thrombo-emboli were done on clinical indication only.
Medication was initiated and modiﬁed according to the judgment of the primary cardiologist. Only two autopsies were
available. ni-NCVM patients generally had more frequent
follow-up appointments than i-NCVM patients. Incomplete
follow-up data tend to over-represent symptomatic
patients. The follow-up period was relatively short.
Conclusion
In paediatric patients, both i-NCVM and ni-NCVM appear to
have been previously under-diagnosed. As the diagnosis is
easily missed, familiarity with the characteristic imaging
features is mandatory. Two-dimensional echocardiography
including the LV apex assisted by colour Doppler is diagnostic. Arrhythmias and thrombo-embolic events in either
group were not nearly as frequent as observed in some previous retrospective (and mostly adult) studies. In contrast,
CHF was an overall very common ﬁnding. Eventual cumulative freedom from CHF was unusual and not different
between the NCVM subgroups. The mortality was concerning
in either subgroup. An equally aggressive anticongestive
treatment regimen would seem indicated for both NCVM
populations. However, i-NCVM and ni-NCVM may carry a
different cardiovascular risk, and the risk may be different
at different ages. Long-term prospective follow-up studies,
possibly including tissue velocity imaging, strain rate analysis, and screening for gene mutations, could help to further
characterize this risk.
Arrhythmias and thrombo-embolic events
Arrhythmias and thrombo-embolic events were observed
remarkably infrequently in our series compared to some
previous reports. They were generally more common in
adult series.5,6,22,24 Also, retrospective studies tend to
be biased towards pathologic ﬁndings. The early data of
Chin et al.2 were based on a small sample size. Our ﬁndings
are consistent with more recent reports on paediatric
patients.3,4,12,21,33 However, previous reports mostly analysed i-NCVM patients only. Besides, we did not routinely
screen our patients with Holter monitoring, transesophageal
echocardiography, MRI, or angiography unless clinical
suspicion was raised.
Why NCVM appears to be arrhythmogenic is not known.
The suggested conjectural analogy to arrhythmogenic right
ventricular dysplasia is appealing.2 However, we did not
Acknowledgements
The authors thank Bradley K. Taylor, Ph.D. and James L. Reynolds,
M.D. for valuable comments and for proofreading of the manuscript.
Conﬂict of interest: none declared.
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CHF is a common ﬁnding in most previous observations,
especially in paediatric studies (Table 3).2–6,12,22–24 It was by
far the most prominent complication in our study. The cumulative freedom from CHF by follow-up time was similarly
poor for both subgroups. Though not statistically different,
there was a tendency for i-NCVM patients to develop CHF at
younger ages than for ni-NCVM patients. ni-NCVM patients
were more likely to be evaluated early with a lesser chance
of a delayed diagnosis and anticongestive therapy. Besides,
there was possibly a more aggressive treatment bias towards
ni-NCVM patients and/or a higher recovery rate (e.g. after corrective surgery) in the latter group. Patients with asymptomatic or mild CHF likely presented late in either groups. An
at least equally high incidence of CHF in i-NCVM patients as
in ni-patients was also observed by Oezkutlu et al.,21 the
only other study separately analysing both groups.
Several mechanisms may lead to CHF in NCVM. Noncompacted myocardium is more dependent on aerobic
oxidation and more sensitive to oxygen deprivation and
toxic effects of catecholamines than compacted myocardium.7 Its myosin ATPase activity is lower resulting in a
lower contraction velocity.7 Abnormal LV wall motion appearances have been detected by tissue velocity echocardiography with strain rate imaging.28 They were even
suggested to be pathognomonic for NCVM. Besides, coronary
ﬂow may be affected by lacuno-vascular shunts7,19,33 and a
dysfunctional microcirculation. Segmental subendocardial
perfusion deﬁcits, possibly leading to subendocardial ﬁbrosis,
are detectable by MRI34,35 and have been reported as an
unfavourable early prognostic ﬁnding.36 On the other hand,
inﬂammatory processes were unlikely to be the cause of
CHF in our i-NCVM patients. Finally, as pointed out earlier,
emerging evidence suggests a different genetic background
for i-NCVM and ni-NCVM.8–17,27 These subgroups may thus
carry a potentially different risk for the development of CHF.
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1860
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