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Congenital Heart Disease: Review of Literature
Congenital Heart Disease: Review of Literature
Introduction:
Congenital heart diseases (CHD) are serious and common conditions that
have significant impact on morbidity, mortality, and health-care costs in children
and adults , these are abnormalities of the heart's structure and function caused
by abnormal or disordered heart development before birth (Go et al.,2013).
More patients with CHD reach adulthood, creating what is called patients
with grownup congenital heart disease (GUCH), Those patients need long-term
expert medical care and healthcare related costs are high. Therefore, the global
health burden as a result of CHD increases quickly (Van der Linde et al., 2011).
There is additionally expanding acknowledgement of neuro-developmental
issues in adolescent among CHD survivors (Massaro et al., 2008).
Definition :
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When circling occurs, so the future LV left ward and the future RV right
ward. With a specific end goal to make the systemic and respiratory flows
independentally, the first single chamber heart starts to be apportioned. The
improvement of endo cardial pads at both atrioventricular and conotruncal
intersections begins at 26 days and prompts the septation of the heart
(Sadeghpour et al., 2014).
By the fifth week, the superior and inferior cushions fused with one another,
forming a right (tricuspid) and left (mitral) atrioventricular orifice. At 30 days the
atria start septation with the slipping development of the of the septum primum,
The ostium primum is therefore closed because of the combination of the septum
primum along side the endocardial pads. In the mean time, the ostium secundum,
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shape up of the septum primum. Toward the end of the procedure, the septum
secundum becomes descending and lies at the right half of the septum primum,
however an interatrial hole stays until birth (i.e., the foramen ovale) (Bird et al.,
2008). The dilation of right and left conus swellings resulted in the
interventricular septum formation (two primitive ventricles) with the opposition
of the medial walls. The bulbus cordis divides into subaortic and subpulmonary
muscular conuses at the distal portion of the cardiac tube, So the subpulmonary
conus stretches and the subaortic conus resorbs, permitting the aorta to exchange
posteriorly and attach to the other side (Bird et al., 2008).
The aortopulmonary septum is made by the edges isolating the fourth (up
and coming aortic arch) and the sixth (forth coming pulmonary supply routes)
aortic curves. At that point, the truncus edges are designed in the zone where the
semilunar valves are proposed to be molded, in this manner producing the septum
at the middle of the ascending aortic trunk and the main pulmonary artery
(Abdulla et al., 2004).
Atria :
More than one source share formation of the atria, trabeculated portions are
shape up by the primitive atria, while the smooth posterior parts of the RA and
LA are created by the union of the venous vessels. The back side of the left atrial
chamber is made by a mix of the pulmonary veins; On the other hand, the sinus
venosus give rise to posterior smooth part of the right atrium. At that point the
embryonic sinuatrium is separated into the LA and RA by developing downward
from the roof of the septum primum toward the atrioventricular (AV) canal,
fusing with the cushions (Abdulla et al., 2004). The endocardial cushions (EC)
anteriorly and posteriorly fuse together splitting the AV canal into tricuspid and
mitral inlets. The inferior part of the atrial septum and superior part of the
ventricular septum and portions of the septal leaflet of the tricuspid valve and
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also, the anterior leaflet of the mitral valve are formed by EC. The posterior
leaflet of the mitral valve pre-dominantly develops from a piece of the AV
myocardium that protrudes into the lumen of the ventricle (Bonow et al., 2011).
Ventricles :
Pulmonary Veins :
The pulmonary veins are recorded as channels entering the atrial part
neighboring the atrioventricular intersection. After the conclusion of the
interventricular correspondence, it exchange to the top of the left chamber
(Ariane et al., 2012).
Great Arteries:
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left fourth one. At that point, the proximal part of the right subclavian artery is
framed by the right fourth arch (Sadeghpour et al., 2014).
At the earliest stages of heart formation (cardiac crescent), two pools of cardiac
precursors exist. The first heart field (FHF) contributes to the left ventricle (LV), and the
second heart field (SHF) contributes to the right ventricle (RV) and later to the outflow tract
(OT), sinus venosus (SV), and left and right atria (LA and RA, respectively).V,
ventricle. b, Maturation of the heart. The cardiac cushions (CC) will give rise to the
atrioventricular valves. The ventricular septum (VS) arises from myocardium from the left and
right ventricles. Atrial septation (AS) occurs by the growth of two septa: the primary septum
(green) and the secondary septum (pink). Outflow tract septation separates the common
outflow tract (OT) into the aorta (AO, connected to the left ventricle) and the pulmonary artery
(PA, connected to the right ventricle)
Incidence of CHD :
The incidence of CHD is about 4–6/1000 live births and the true prevalence
could be 40/1000 if bicuspid aortic valve is included(Wren et al., 2012). Nearly
33% to 50% of these defects are critical, requiring intervention in the first year
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Although antenatal detection of CHD has improved over the past decade,
though recent studies suggest that greater than 60% remain undiagnosed (Chew
et al., 2006)
At present, around 20% of cases with CHD can be referred to known causes
for example, hereditary disorders and teratogens, however almost no is thought
about the etiology of most cases (about 80%). It is for the most part of CHD
lesions with obscure etiology follows a multi-factorial inheritance model, which
involves both genetic and environmental factors in disease development (Blue et
al., 2012).
Chromosome defect :
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Mendelian syndromes :
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Table (B): Microdeletions and single gene disorders associated with CHD (Pierpont
et al., 2007)
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The best recorded maternal risk element is maternal diabetes, with a reported
fivefold extended risk of CHD from pregestational diabetes (Wren et al., 2003).
Other environmental factors have been associated with an increased risk of CHD
in table (D)
Table (D): Environmental risk factors associated with CHD (Jenkins et al.,
2007)
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Classification of CHD:
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Fig: (B): CHD subtypes according to presence of cyanosis (Piers et al., 2012).
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Clinical manifestations:
Clinical presentation may vary from the incidental finding of a heart murmur
in an otherwise healthy neonate to cyanosis or life threatening arrhythmias or
cardiovascular collapse, including congestive heart failure or shock (Silberbach
and Hannon., 2007).
The clinical marker for the debilitating heart defects in the newborn might
be obscure. Ordinary heart murmur is not useful in this circumstance. It is
imperative for pediatricians to recognize the infant that " not doing well " and
having a high index of suspicion, and distinguishing the requirement for fast heart
assessment and guideline inherent cardiovascular issue which needs early
intercession. They incorporate cyanosis, un-explained acidosis, tachypnea
without lung issues, and so forth. Beginning assessment would incorporate
evaluation of oxygen saturation, blood gas investigation and blood pressure in all
extremities (Keane et al., 2006).
Some neonate with critical CHD might exhibit clinical symptoms first few
hours to days of life when PDA is closed. At this time, the babies would show
serious acidosis / cyanosis / shock even sudden death might occur (Krishnan.,
2002).
Radiological findings:
Boat shaped heart; which could be found in the TOF / PA and it’s variations
(Yee., 2007).
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Another specific element called the "egg on string" appearance can be seen in
TGA (Keane et al., 2006).
Rather than these established elements, the majority of critical CHD that
need early mediation have no specific discoveries beside cardiomegaly,
change of pulmonary vascular checking and un-pretentious finding of venous
congestion (Fleisher et al., 2006).
2. Electrocardiography (ECG) :-
3. Echocardiography:-
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4. Cardiac catheterization:-
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Endocarditis can occur at any time when microbes enter circulation system.
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Pulmonary hypertension
Arrhythmia
Stroke
Prevention:
Treatment:
Which treatment is used, and how well the baby responds to it, depends on
the condition. Many defects need to be followed carefully. Some will heal over
time, while others will need to be treated. Some congenital heart diseases can be
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treated with medication alone. Others need to be treated with one or more heart
surgeries (Leonar and Lilly., 2011).
Children with CHD are about 50% more likely to receive special education
services compared to children without birth defects (Riehle-Colarusso et al.,
2015).
Survival of infants with CHDs relies on how severe the defect is, the time
when it is diagnosed, and how it is treated. About 97% of babies born with a
non-critical CHD are expected to survive to one year of age. About 95% of babies
born with a noncritical CHD are expected to survive to 18 years of age. About
75% of babies born with a critical CHD are expected to survive to one year of
age, when about 69% of these are expected to survive to 18 years of age (Oster
et al., 2013).
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Definition of PAH:
Pulmonary arterial hypertension is defined as an elevated mean pulmonary
arterial pressure (mPAP) of 25 mmHg or higher and a pulmonary wedge pressure
of 15 mmHg or lower (Simonneau et al., 2009 and Sanli et al., 2012).
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2. Alveolar hypoxia
b. Airway obstruction
1). Kyphoscoliosis
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3. Pulmonary venous hypertension: mitral stenosis, cor triatriatum, total anomalous pulmonary
venous return with obstruction, chronic left heart failure, left-sided obstructive lesions
(aortic stenosis, coarctation of the aorta). Rarely, congenital pulmonary vein stenosis causes
incurable pulmonary hypertension.
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may be associated with degradation of the extracellular matrix and the release of
growth factors which, in turn, induce smooth muscle hypertrophy and
proliferation, with migration into the pulmonary vasculature ( Diller and
Gatzoulis, 2007).
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Each cell type (endothelial, smooth muscle, and fibroblast) in the pulmonary
vascular wall plays a specific role in the response to injury (Jeffery and Morrell,
2002). A feature common to all forms of PAH remodeling is the distal extension
of smooth muscle into small peripheral, normally nonmuscular, pulmonary
arteries within the respiratory acinus. The cellular processes underlying
muscularization of this distal part of the pulmonary arterial tree are incompletely
understood. In addition, a hallmark of severe pulmonary hypertension is the
formation of a layer of myofibroblasts and extracellular matrix between the
endothelium and the internal elastic lamina, termed the neointima (Humbert et
al., 2004).
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Endothelial cells:
Inflammatory cells:
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Indeed, in addition to its role in coagulation, the platelet stores and releases
important contributors to pulmonary vasoconstriction and remodeling such as
thromboxane A2, platelet activating factor, serotonin (5-hydroxytryptamine [5-
HT]), platelet-derived growth factor (PDGF), TGF-ß, and VEGF. In most cases,
however, it remains unclear whether thrombosis and platelet dysfunction are
causes or consequences of the disease (Herve et al., 2001).
Molecular mechanisms
Pulmonary vasoconstriction is believed to be an early component of the
pulmonary hypertensive process. Excessive vasoconstriction has been related to
abnormal function or expression of potassium channels, as well as to endothelial
dysfunction. Endothelial dysfunction leads to chronically impaired production of
vasodilators such as nitric oxide (NO) and prostacyclin along with prolonged
overexpression of vasoconstrictors such as endothelin (ET)-1, which not only
affect vascular tone, but also promote vascular remodeling and, therefore,
represent logical pharmacological targets figure (D) It appears that most stimuli
that acutely enhance vasoconstriction ultimately also cause cell proliferation
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Potassium channels :
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Serotonin:
TGF-ß superfamily:
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Angiogenesis:
Although the isoform VEGF-A has been most extensively studied in the
context of pulmonary hypertension and has been proposed to play a protective
role, a study identified a pathogenic role for VEGF-B. Animal studies have
emphasized the positive effects of VEGF in models of pulmonary hypertension.
Indeed, cell-based VEGF gene transfer has proved an effective method of
preventing the development and progression of pulmonary hypertension.
Vascular endothelial growth factor would minimize progression of the disease by
preventing loss of existing vessels or by inducing the development of new blood
vessels within the lung (Campbell et al., 2001).
Various other growth factors including PDGF, basic fibroblast growth factor,
insulin-like growth factor-1, and epidermal growth factor have also been
implicated in the development of remodeling and all have been reported to be
increased in the pulmonary hypertensive lung. The mechanism that leads to
induction of these growth factors in the pulmonary vasculature is unclear, though
reactive oxygen species have been implicated because hydrogen peroxide
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Proteolysis:
Elastase activity:
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Clinical Manifestations
Natural history:
The two most frequent causes of death are progressive RV failure and
sudden death (probably secondary to arrhythmias).
Physical examination:
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In these patients with moderate-to-large defects, the increase in PVR is mild-to-moderate, systemic-to-
pulmonary shunt is still largely present and no cyanosis is present at rest.
In cases with small defects (usually VSD ,1 cm and ASD ,2 cm of effective diameter assessed by
echocardiography), the clinical picture is very similar to idiopathic PAH.
In these cases, CHD has been corrected but PAH is either still present immediately after surgery or has
recurred several months or years after surgery in the absence of significant post-operative residual
congenital lesions or defects that originate as a sequelae to previous surgery.
PVR: pulmonary vascular resistance; VSD: ventricular septal defect; ASD: atrial septal defect; CHD: congenital
heart disease.
Class II Patients with PHT resulting in slight limitation of physical activity. They are
comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or
near syncope.
Class III Patients with PHT resulting in marked limitation of physical activity. They are
comfortable at rest. Less-than-ordinary physical activity causes undue dyspnea or fatigue, chest
pain, or near syncope.
Class IV Patients with PHT with inability to carry out any physical activity without symptoms.
These patients manifest signs of right heart failure. Dyspnea and/or fatigue may even be present
at rest. Discomfort is increased by any physical activity.
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Diagnosis of PAH
Laboratory studies:
Chest radiography
The radiographic findings are variable, and the chest radiograph may be
remarkably normal for some patients. Right atrial and right ventricular
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Electrocardiogram
Echocardiography
Cardiac catheterization
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Lung biopsy
Treatment of PAH
Early diagnosis and treatment for a large systemicto- pulmonary shunt is
critical for preventing Eisenmenger syndrome. The treatment options for patients
with PAH associated with congenital heart disease are limited to palliative
measures and heart-lung transplantation for highly selected patients with
Eisenmenger syndrome. The treatment may include the use of supplemental
oxygen, digitalis, diuretics, vasodilators and anticoagulants, or lung
transplantation and repair of the congenital heart defect(s), or heart-lung
transplantation (Jung, 2007).
General Management :
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Conventional treatment:
Anticoagulation
Anticoagulation with warfarin (Coumadin) is widely recommended in
patients with thromboembolic disease and may be beneficial in those with
pulmonary hypertension from other causes, with significant improvement in
survival. An International Normalized Ratio (INR) of 2.0 to 2.5 is the goal of
therapy. Unlike the approach for patients with a prosthetic mechanical heart
valve, concomitant use of aspirin is not recommended because it may increase
effects of warfarin. Some recommend antiplatelet drugs (aspirin) instead of
warfarin to prevent microembolism in the pulmonary circulation (Park, 2008c).
Therapy of PAH:
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There are no data to support the use of calcium channel blockers in patients
with PAH-CHD and their use must be avoided. In particular, their use is
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Prostanoids (Prostacyclins):
Therapy with prostacyclin and its analogues has been extrapolated for use in
children. Long-term IV epoprostenol has improved survival for children with
PAH with a 4-year survival rate of 94% in IPAH, and a 10-year treatment success
rate (freedom from death, transplantation, or atrial septostomy) of 37% (Ivy,
2012).
Recently, the use of specific closed hub systems has been shown to decrease
the infection rate. Although uncommon, children with a dramatic sustained
response to epoprostenol may be weaned to oral or inhaled therapy if
hemodynamics return to near normal values (Ivy, 2012).
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Although bosentan is not approved for use in children with PAH in the US,
several studies have suggested safety and a delay in disease progression (Hislop
et al., 2011). A specific pediatric formulation has been recently approved in
Europe (Ivy et al., 2010).
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Studies in children suggest that some patients treated with bosentan may
show additional improvement on transition to ambrisentan (Ivy et al., 2010).
Phosphodiesterase-5 inhibitors
Novel Therapies:
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Other targets in the future may include blockade of stem cell populations
contributing to the fibroproliferative process, such as fibrocytes (Yeager et al.,
2011).
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Definition:
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Definitions
Strain (S)
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All walls −15.9 ± 6.0 −16.9 ± 6.6 −14.9 ± 5.2 −16.0 ± 6.1 <0.001
Anterior −15.2 ± 6.7 −19.9 ± 6.6 −15.0 ± 5.9 −11.6 ± 4.7 <0.001
Anteroseptal −16.0 ± 5.5 −14.6 ± 6.0 −15.8 ± 4.9 −17.6 ± 5.3 0.01
Inferoseptal −15.8 ± 5.4 −14.1 ± 5.6 −15.4 ± 4.7 −17.6 ± 5.3 0.004
Inferior −16.6 ± 5.8 −16.2 ± 5.8 −14.5 ± 4.8 −19.3 ± 5.6 <0.001
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Inferolateral −15.5 ± 6.0 −17.2 ± 6.5 −13.7 ± 5.2 −15.6 ± 5.7 <0.001
Anterolateral −16.9 ± 6.3 −20.3 ± 6.3 −15.2 ± 5.6 −15.6 ± 5.7 <0.001
(walls)
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Table (K): Mean left ventricular radial segmental strain values. (Sebastiaan et
al., 2014)
(levels)
All walls 35.4 ± 17.5 34.8 ± 17.8 38.5 ± 18.2 31.5 ± 15.2 <0.001
Anterior 40.4 ± 18.2 40.2 ± 18.1 46.1 ± 18.6 34.8 ± 14.2 0.001
Anteroseptal 38.1 ± 17.0 39.8 ± 18.1 42.4 ± 16.8 32.4 ± 14.4 0.09
Inferoseptal 33.0 ± 15.3 32.3 ± 16.0 34.2 ± 15.4 32.4 ± 14.4 0.16
Inferior 27.4 ± 15.9 27.9 ± 16.6 28.8 ± 16.1 25.4 ± 14.9 0.54
Inferolateral 33.8 ± 16.6 32.1 ± 15.5 36.1 ± 18.2 33.0 ± 15.7 0.008
Anterolateral 38.1 ± 17.6 37.5 ± 17.3 43.7 ± 18.0 33.0 ± 15.7 <0.001
(walls)
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(levels)
All walls −30.5 ± 6.0 −29.6 ± 6.3 −31.4 ± 5.7 −30.5 ± 5.9 <0.001
Anterior −29.2 ± 5.8 −28.7 ± 5.9 −30.7 ± 5.5 −28.0 ± 5.5 <0.001
Anteroseptal −31.2 ± 6.0 −29.7 ± 6.2 −32.4 ± 6.0 −31.4 ± 5.7 <0.001
Inferoseptal −31.0 ± 6.2 −29.6 ± 6.7 −31.8 ± 6.0 −31.4 ± 5.7 <0.001
Inferior −31.4 ± 5.7 −30.5 ± 6.1 −31.5 ± 5.5 −32.1 ± 5.4 0.054
Inferolateral −30.3 ± 6.0 −29.6 ± 6.3 −31.0 ± 5.5 −30.4 ± 6.1 0.01
Anterolateral −30.2 ± 6.1 −29.2 ± 6.5 030.9 ± 5.6 −30.4 ± 6.1 0.001
(walls)
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Clinical applications:
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that LS correlates with the global and regional extent (transmurality) of scar
tissue as evaluated by contrast-enhanced MRI (Becker et al., 2008, Roes et al.,
2009).
Taken together, these studies support the use of STE to identify and risk-
stratify atherosclerotic coronary disease with good accuracy and reproducibility.
Myocardial Infarction
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segments using strain and SR cutoffs of -13% and -0.8 s-1, respectively. DSI
and regional myocardial blood flow (contrast echo) predicted LV remodeling
(20% increase in end-diastolic diameter) in 10 patients 4 to 6 months after
reperfused ST-elevation myocardial infarction and correlated with an LV
functional improvement (ejection fraction increases 10%) in an additional 19
patients. (Korosoglou et al., 2008).
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The incremental value of strain rate imaging (SRI) parameters over low-
dose dobutamine wall motion scoring for predicting functional recovery 9 months
after revascularization was studied in 55 patients with a previous myocardial
infarction. Abnormal segments that recovered function (146 of 369 segments)
had lower wall motion score and strain and SRs (and SRI increments), with
similar sensitivity and specificity for predicting functional recovery; however, the
combination of wall motion score and SRI parameters increased the sensitivity
for prediction of functional recovery over wall motion scoring alone without a
change in specificity. (Hanekom et al., 2005)
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Limitations
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