1 HLHS was present in 45 patients, complex double-outlet r
2 HLHS-iPSC-derived cardiomyocytes are characterised by a
3 We studied LV myocardial samples from
32 HLHS and 17 structurally normal midgestation fetuses.
4 nts using a sequential sampling strategy (
33 HLHS kindreds, 102 BAV kindreds).
5 All HLHS probands had aortic valve hypoplasia and dysplasia;
6 rformed in kindreds ascertained by either
an HLHS or BAV proband.
7 tablish for the first time that AVS, COA
and HLHS can share a common pathogenetic mechanism at the mo
8 atients, in comparison with those managed
as HLHS, have not been reported.
9 nd evaluate the genetic relationship
between HLHS and bicuspid aortic valve (BAV).
10 nd BAV exhibit complex inheritance, and
both HLHS and BAV kindreds are enriched for BAV.
11 ant mice and identification of genes
causing HLHS.
12 All patients had
classic HLHS, defined as a right ventricular dependent circulati
13 ween these loci was examined in the
combined HLHS and BAV cohort and associations between loci were d
14 PVD flow analysis and postnatally
confirmed HLHS were studied.
15 tality were high (48%) compared with
control HLHS patients, regardless of prenatal diagnosis and desp
16 associations between prenatal diagnosis,
CSC HLHS volume, and mortality were also examined.
17 ical mortality was associated with lower
CSC HLHS volume (odds ratio per 10 patients, 0.88; 95% confi
18 redicting which fetuses with AS will
develop HLHS is essential to optimize patient selection for feta
19 er between fetuses that ultimately
developed HLHS and those that maintained a biventricular circulati
20 uctures became evident in fetuses
developing HLHS.
21 with AS who are at high risk for
developing HLHS.
22 weight, gestational age, prenatal
diagnosis,
HLHS variant, associated diagnoses, ascending aortic siz
23 e midgestation aortic stenosis with
evolving HLHS from March 2000 to January 2013.
24 e studied hypoxia-associated injury in
fetal HLHS and human pluripotent stem cells during cardiac dif
25 The hypoplastic LV in
fetal HLHS samples demonstrates hypoxia-inducible factor-1alph
26 Compared with controls, the LV in
fetal HLHS samples had higher nuclear expression of hypoxia-in
27 uced pluripotent stem cells (iPSC) from
five HLHS patients and two unaffected controls, differentiate
28 bidirectional cavopulmonary anastomosis
for HLHS reduces second-stage mortality and improves interme
29 reveal novel genetic insights important
for HLHS pathology and shed new insights into the role of th
30 and improves hospital survival after NP
for HLHS.
31 atients who underwent stage I operations
for HLHS at our institution between 1983 and 1993, we identi
32 However, palliation
for HLHS is a three-stage process and final judgment regardi
33 After staged reconstruction
for HLHS, neo-aortic root dilation and neo-AR progress over
34 The sibling recurrence risk
for HLHS was 8%, and for CVM was 22%.
35 , 840 patients underwent stage I surgery
for HLHS.
36 Identifying the best treatment
for HLHS requires integrating individual patient risk factor
37 heart and transplantation as treatments
for HLHS have been compared in treatment-received analyses,
38 tients with available follow-up data, 17
had HLHS and 6 had a biventricular circulation.
39 nstrate linkage to multiple loci
identifying HLHS as genetically heterogeneous.
40 In HLHS, serial MRI shows the adaptation of the systemic RV
41 In HLHS, the pulmonary valve functions as the neo-aortic va
42 After reconstruction of the aortic arch
in HLHS, the diameter of the arch continues to increase thr
43 The recurrence risk ratio of BAV
in HLHS families (8.05) was nearly identical to that in BAV
44 is a contributor to transcriptome changes
in HLHS patient RVs.
45 receptors was significantly downregulated
in HLHS-iPSC-derived cardiomyocytes alongside NOTCH target
46 of left- and right-sided valve dysplasia
in HLHS probands and the increased prevalence of BAV in fam
47 y of transcripts differentially expressed
in HLHS patient hearts have validated Rbfox2 binding sites.
48 contributing to aberrant gene expression
in HLHS patients.
49 3.2 and 3.1, respectively, was identified
in HLHS kindreds.
50 , the Rbfox2 nonsense mutation identified
in HLHS patients truncates the protein, impairs its subcell
51 binding protein Rbfox2, which is mutated
in HLHS patients, is a contributor to transcriptome changes
52 The staged palliation
in HLHS may be a risk factor particularly for reduced left
53 The systemic right ventricle (RV)
in HLHS is subject to significant changes in volume loading
54 dence for involvement of NOTCH signalling
in HLHS pathogenesis, reveal novel genetic insights importa
55 We conclude that,
in HLHS after the Norwood operation, the right ventricle to
56 e for Rbfox2 in controlling transcriptome
in HLHS.
57 Further, fetuses that developed a
marked HLHS phenotype had elevated serum titers of anti-beta-ad
58 olume CSC may significantly improve
neonatal HLHS survival.
59 However, the genetic basis
of HLHS and its relationship to BAV remains unclear.
60 e editing in mice as being digenic causes
of HLHS.
61 Familial clustering
of HLHS and bicuspid aortic valve (BAV) has been observed,
62 Efforts to improve prenatal diagnosis
of HLHS and subsequent delivery near a large volume CSC may
63 Prenatal diagnosis
of HLHS was associated with improved preoperative clinical
64 peptide ligand during the differentiation
of HLHS-iPSC restored their cardiomyocyte differentiation c
65 cyte proliferation with cardinal features
of HLHS.
66 Issues surrounding the genetics
of HLHS, developmental outcomes, and quality of life are ad
67 Heritability (h2)
of HLHS and associated CVM was estimated using maximum-like
68 ming left ventricle (one of the hallmarks
of HLHS).
69 The heritability
of HLHS alone and with associated CVM were 99% and 74% (p <
70 The high heritability
of HLHS suggests that it is determined largely by genetic f
71 is, to our knowledge, the first isolation
of HLHS mutant mice and identification of genes causing HLH
72 ly, we examine new results for palliation
of HLHS.
73 Whole exome sequencing
of HLHS fibroblasts identified deleterious variants in NOTC
74 Neonatal mortality in the subgroup
of HLHS patients with intact or highly restrictive atrial s
75 he art in our understanding and treatment
of HLHS during the stages of care: 1) pre-Stage I: fetal an
76 Surgical treatment
of HLHS involves either transplantation (Tx) or staged pall
77 ommended action after prenatal diagnosis,
on HLHS mortality has been poorly investigated.
78 rized based on postnatal management as BV
or HLHS.
79 ge of maternal autoantibodies and a
prenatal HLHS phenotype in exposed fetuses.
80 Mutations from
seven HLHS mouse lines showed multigenic enrichment in ten hum
81 f aortic valve abnormalities, both
signature HLHS defects.
82 a combined cohort provide evidence that
some HLHS and BAV are genetically related.
83 s. 36%) and hypoplastic left heart
syndrome (
HLHS) (47% vs. 13%).
84 surgery for hypoplastic left heart
syndrome (
HLHS) and assess current outcome for this condition.
85 se loci for hypoplastic left heart
syndrome (
HLHS) and evaluate the genetic relationship between HLHS
86 a (COA) and hypoplastic left heart
syndrome (
HLHS) are congenital cardiovascular malformations that a
87 n (S1P) for hypoplastic left heart
syndrome (
HLHS) has improved coincident with application of treatm
88 fetus with hypoplastic left heart
syndrome (
HLHS) have been correlated with restrictive interatrial
89 liation for hypoplastic left heart
syndrome (
HLHS) have improved in recent years; however, certain ri
90 nfants with hypoplastic left heart
syndrome (
HLHS) include increased inspired nitrogen (hypoxia) and
91 Hypoplastic left heart
syndrome (
HLHS) is a fatal congenital heart disease in which the l
92 Hypoplastic left heart
syndrome (
HLHS) is a severe cardiac malformation characterized by
93 Hypoplastic left heart
syndrome (
HLHS) is among the most severe forms of congenital heart
94 eration for hypoplastic left heart
syndrome (
HLHS) is critical to early survival.
95 Hypoplastic left heart
syndrome (
HLHS) is frequently diagnosed prenatally, but this has n
96 tified by a hypoplastic left heart
syndrome (
HLHS) proband.
97 sis (AS) to hypoplastic left heart
syndrome (
HLHS) requires identification of fetuses with salvageabl
98 ildren with hypoplastic left heart
syndrome (
HLHS) undergoing staged surgical reconstruction, to asse
99 rtality for hypoplastic left heart
syndrome (
HLHS) using intention-to-treat analysis.
100 Hypoplastic left heart
syndrome (
HLHS) with intact or very restrictive atrial septum is a
101 t resembles hypoplastic left heart
syndrome (
HLHS), a life-threatening CHD primarily affecting the le
102 e show that hypoplastic left heart
syndrome (
HLHS), a severe CHD, is multigenic and genetically heter
103 liation for hypoplastic left heart
syndrome (
HLHS), and strategies for selective cerebral perfusion (
104 lliation of hypoplastic left heart
syndrome (
HLHS), the NO, includes augmentation of the aortic arch
105 ruction for hypoplastic left heart
syndrome (
HLHS).
106 trategy for hypoplastic left heart
syndrome (
HLHS).
107 surgery for hypoplastic left heart
syndrome (
HLHS).
108 liation for hypoplastic left heart
syndrome (
HLHS).
109 , including hypoplastic left heart
syndrome (
HLHS).
110 gression to hypoplastic left heart
syndrome (
HLHS).
111 ildren with hypoplastic left heart
syndrome (
HLHS).
112 tcomes than hypoplastic left heart
syndrome (
HLHS).
113 requency of hypoplastic left heart
syndrome (
HLHS).
114 sis (AS) to hypoplastic left heart
syndrome (
HLHS).
115 84+/-12% at 10 years, which was better
than HLHS patients (log-rank P=0.04).
116 Previously, we identified
that HLHS and BAV exhibit complex inheritance, and both HLHS
117 Our data indicate
that HLHS-iPSC have a reduced ability to give rise to mesoder
118 These findings show
that HLHS can arise genetically in a combinatorial fashion, t
119 lence of BAV in family members suggests
that HLHS is a severe form of valve malformation.
120 ro cellular and functional correlates of
the HLHS phenotype.
121 Although the 3-stage treatment approach
to HLHS is now well founded, there is significant variation
122 rvention to prevent the progression of AS
to HLHS.
123 with progression of midgestation fetal AS
to HLHS.
124 nt in ten human chromosome regions linked
to HLHS.
125 alvageable left hearts who would progress
to HLHS if left untreated, a successful in utero valvotomy,
126 bility that all 24 fetuses would progress
to HLHS if left untreated.
127 wever, all of the fetuses that progressed
to HLHS had retrograde flow in the transverse aortic arch (
128 dysfunction are predictive of progression
to HLHS.
129 entify and expectantly manage the fetus
with HLHS and RAS.
130 In the fetus
with HLHS, a PVD forward/reverse VTI ratio of <5 is the stron
131 Infants
with HLHS born far from a CSC have increased neonatal mortali
132 Infants
with HLHS requiring catheter septostomy within the first 2 da
133 ized and paralyzed preoperative infants
with HLHS were evaluated in a prospective, randomized, crosso
134 in the right ventricle (RV) of infants
with HLHS, although the molecular mechanisms remain unknown.
135 Data on 231 infants
with HLHS, born between 1989 and 1994 and intended for surger
136 In preoperative infants
with HLHS, under conditions of anesthesia and paralysis, alth
137 C and neonatal mortality in 463 infants
with HLHS.
138 From 1990 to 2002, 33 newborns
with HLHS (11% of newborns with HLHS managed during this peri
139 dentifying the need for EAS in newborns
with HLHS and RAS.
140 tal condition, the outlook for newborns
with HLHS has been altered dramatically with staged reconstru
141 33 newborns with HLHS (11% of newborns
with HLHS managed during this period) underwent urgent/semiur
142 gest that low weight alone in a patient
with HLHS or an anatomic variant should not be considered a c
143 Patients
with HLHS and coexisting atrioventricular septal defect were
144 We reviewed patients
with HLHS between July 1992 and March 1999 to determine the i
145 Patients
with HLHS born before January 1995 who had the Fontan operati
146 iterature and a dataset of 231 patients
with HLHS born between 1989 and 1994.
147 graphic data of 59 consecutive patients
with HLHS operated on at our institution.
148 trategy for centers that treat patients
with HLHS should be guided by local organ availability, stage
149 intermediate-term survival for patients
with HLHS undergoing staged palliation increased significantl
150 itation is a common finding in patients
with HLHS undergoing staged surgical reconstruction and can r
151 e serial echocardiograms of 50 patients
with HLHS who underwent NO to determine the diameter of the r
152 autopsy specimens of 10 other patients
with HLHS who underwent NO were examined to determine the con
153 intermediate-term outlook for patients
with HLHS.
154 hemi-Fontan procedure from 24 patients
with HLHS; the first 10 had a Norwood operation with a system
155 In 38 probands
with HLHS, a 3-generation family history was obtained; using
156 We also identified one subject
with HLHS with SAP130 and PCDHA13 mutations.
157 ons are that 70% of newborns born today
with HLHS may reach adulthood.