ライフサイエンスコーパス: ARVC

1 ARVC desmosomal mutation carriers (n = 84) were evaluate

2 ARVC is a familial arrhythmogenic disease characterized

3 ARVC is a potentially lethal genetic cardiovascular diso

4 ARVC is a primary disease of the myocardium characterize

5 ARVC is characterized pathologically by fibrofatty infil

6 ARVC was diagnosed in 35 patients at initial evaluation

7 ARVC was suspected in all 8 cats examined with echocardi

8 ARVC-derived desmoplakin mutants DSP-1-V30M and DSP-1-S2

9 demonstrated pronounced RV lesions in all 12 ARVC cats, including marked myocardial injury (myocyte d

10 Myocarditis was present in 10 of the 12 ARVC cats.

11 on could abolish all Epi-LAVA in 4 ICM and 2 ARVC patients, whereas all patients with NICM required e

12 Among 70 patients who fulfilled the 2010 ARVC/D Revised Task Force Criteria and underwent baselin

13 In 21 (91%) of 23 ARVC patients, RV EVM was abnormal, with a total of 45 e

14 3' untranslated region were sequenced in 38 ARVC families.

15 in 15 (83%) ICM, 2 (13%) NICM, and 11 (73%) ARVC patients, contributing to a potential reduction in

16 ns (ICM: 20 of 71 [28%], NICM: 3 of 39 [8%], ARVC: 25 of 63 [40%]) successfully eliminated the Epi-LA

17 Apoptosis was detected in 9 ARVC cats (mean apoptotic index, 28+/-23% RV, 21+/-19% L

18 Eighty-two additional ARVC cases were obtained from published reports, and add

19 (P=0.013) than those who developed HF after ARVC/D presentation.

20 All ARVC samples but no control samples showed a marked redu

21 ardiomyopathy established the North American ARVC Registry and enrolled patients with a diagnosis of

22 In the North American ARVC Registry, the majority of ventricular arrhythmias i

23 lators (ICDs) enrolled in the North American ARVC Registry.

24 The overall yield of mutations among ARVC cases was 58% versus 16% in controls.

25 ical from mechanical tissue substrates among ARVC clinical stages.

26 In addition, a family member may have an ARVC gene defect and have development of the disease or

27 ate ARVC gene because of its proximity to an ARVC locus at position 2q32 and the connection of the ti

28 utation and endurance training to trigger an ARVC-like phenotype.

29 (n = 45), athletes without TWI (n = 35), and ARVC patients (n = 35).

30 g inherited cardiac disorders in general and ARVC specifically.

31 lly compared in 60 subjects: 30 asymptomatic ARVC gene carriers and 30 healthy controls.

32 latent electrical substrate in asymptomatic ARVC gene carriers that is shared by patients with ARVC

33 itizing medical surveillance in asymptomatic ARVC gene carriers.

34 Management of asymptomatic ARVC gene carriers is challenging because of variable pe

35 Patients with clinical HF before ARVC/D diagnosis (n=31) were older (P=0.005) and met few

36 as Naxos disease, which is characterized by ARVC and a cutaneous disorder.

37 a cardiocutaneous syndrome characterized by ARVC and abnormalities of hair and skin.

38 rdiomyopathy gene titin (TTN) as a candidate ARVC gene because of its proximity to an ARVC locus at p

39 right ventricular dysplasia/cardiomyopathy (ARVC) is a genetic disease caused by mutations in desmos

40 right ventricular dysplasia/cardiomyopathy (ARVC), in which the right ventricle is "replaced" by fib

41 imaging in arrhythmogenic RV cardiomyopathy (ARVC) may be inadequate because of the complex contracti

42 genic right ventricular (RV) cardiomyopathy (ARVC) is a cardiomyopathy characterized pathologically b

43 ythmogenic right ventricular cardiomyopathy (ARVC) (13%); and hypertrophic cardiomyopathy (HCM) (6%).

44 ythmogenic right ventricular cardiomyopathy (ARVC) and pure fat replacement of the right ventricle is

45 ythmogenic right ventricular cardiomyopathy (ARVC) can be challenging because the clinical presentati

46 ythmogenic right ventricular cardiomyopathy (ARVC) has a prevalence of at least 1 in 1000, is a leadi

47 ythmogenic right ventricular cardiomyopathy (ARVC) has been suggested, the arrhythmogenic substrate f

48 ythmogenic right ventricular cardiomyopathy (ARVC) have recently been updated, the diagnosis remains

49 ythmogenic right ventricular cardiomyopathy (ARVC) in asymptomatic gene carriers.

50 ythmogenic right ventricular cardiomyopathy (ARVC) in relation to diagnostic criteria and genotype.

51 ythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous condition caused by

52 ythmogenic right ventricular cardiomyopathy (ARVC) is a genetically transmitted disease.

53 ythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease of unknown etiology that

54 Arrhythmic right ventricular cardiomyopathy (ARVC) is a hereditary heart muscle disease that causes s

55 ythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death, but it

56 ythmogenic right ventricular cardiomyopathy (ARVC) is a phenotype caused by mutations in desmosomal c

57 ythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disorder resulting from

58 ythmogenic right ventricular cardiomyopathy (ARVC) is a primary myocardial disease of incompletely re

59 ythmogenic right ventricular cardiomyopathy (ARVC) is a significant cause of sudden cardiac death in

60 ythmogenic right ventricular cardiomyopathy (ARVC) is an autosomal dominant heart muscle disorder tha

61 ythmogenic right ventricular cardiomyopathy (ARVC) is an inheritable myocardial disorder associated w

62 ythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disorder characterized by

63 ythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disorder mainly caused by

64 ythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by ve

65 ythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder associated with arrhythmi

66 ythmogenic right ventricular cardiomyopathy (ARVC) is an inherited genetic myocardial disease charact

67 ythmogenic right ventricular cardiomyopathy (ARVC) is associated with sudden cardiac death.

68 ythmogenic right ventricular cardiomyopathy (ARVC) is fibrofatty scar replacement.

69 ythmogenic right ventricular cardiomyopathy (ARVC) patients.

70 ythmogenic right ventricular cardiomyopathy (ARVC) patients.

71 ythmogenic right ventricular cardiomyopathy (ARVC) phenotype manifestation; however, research is hamp

72 ythmogenic right ventricular cardiomyopathy (ARVC).

73 ythmogenic right ventricular cardiomyopathy (ARVC).

74 ythmogenic right ventricular cardiomyopathy (ARVC).

75 ythmogenic right ventricular cardiomyopathy (ARVC).

76 ythmogenic right ventricular cardiomyopathy (ARVC).

77 ythmogenic right ventricular cardiomyopathy (ARVC).

78 ythmogenic right ventricular cardiomyopathy [ARVC]) with sustained VT underwent combined endo- and ep

79 g intense exertion occurred in 61% of cases; ARVC and left ventricular fibrosis most strongly predict

80 vide evidence that titin mutations can cause ARVC, a finding that further expands the origin of the d

81 the desmosomal plakophilin-2 gene can cause ARVC.

82 nd desmocollin 2 (DSC2), respectively, cause ARVC.

83 WT)) or a truncated (PG(TR)), known to cause ARVC, in the heart; and PG null (PG(-)/(-)) embryos.

84 cardiac desmosomes, have been shown to cause ARVC.

85 In a cohort of well-characterized ARVC subjects, neither beta-blockers nor sotalol seemed

86 We studied 23 consecutive ARVC patients (16 males; mean age, 38+/-12 years) who un

87 an age 36 years [22-52]) from 44 consecutive ARVC families undergoing comprehensive genetic screening

88 We studied 69 consecutive ARVC/D patients (47 males; median age 35 years [28-45])

89 Compared with 20 healthy controls, ARVC patients had longer ventricular activation duration

90 Definite ARVC or post-inflammatory cardiomyopathy was diagnosed i

91 diagnosis in 10 of 11 subjects with definite ARVC on the basis of clinical criteria and correctly rul

92 leven of the 23 patients (48%) with definite ARVC would not have been in this group if CMR had not be

93 ts, respectively, all of whom had definitive ARVC.

94 into mice resulted in an exercise-dependent ARVC phenotype.

95 values of isoproterenol testing to diagnose ARVC were 91.4%, 88.9%, 43.2%, and 99.1%, respectively.

96 of 8.5% of RV free wall was used to diagnose ARVC with 94% sensitivity (95% confidence interval [CI]:

97 EAM-guided biopsy diagnosed ARVC in 11 (46%), myocarditis in 8 (33%), and idiopathic

98 amined the contribution of CMR to diagnosing ARVC using the rTFC in a pediatric population.

99 lement of the rTFC contributed to diagnosing ARVC was determined using a c-statistics model.

100 Different ARVC stages were characterized by distinct RV deformatio

101 viduals from Naxos and 43 autosomal dominant ARVC probands were homozygous for the normal allele.

102 ost likely cause for the genesis of dominant ARVC due to mutations in PKP2.

103 right ventricular cardiomyopathy/dysplasia (ARVC) genetic test and to determine genetic associations

104 right ventricular cardiomyopathy/dysplasia (ARVC/D) is controversial.

105 right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation

106 right ventricular cardiomyopathy/dysplasia (ARVC/D) varies depending on study cohort and is not well

107 right ventricular cardiomyopathy/dysplasia (ARVC/D).

108 al RV deformation has been reported in early ARVC without structural abnormalities.

109 ed modified diagnostic criteria for familial ARVC and 7 were obligate gene carriers, suggesting that

110 hout the proposed modifications for familial ARVC; and 2) gene-carrier status in 35 individuals from

111 Fibrofatty ARVC was characterized by right ventricular myocardial t

112 n, but was less extensive than in fibrofatty ARVC and FaRV.

113 Patients with fibrofatty ARVC were younger than those with FaRV (31+/-14 versus 4

114 ach from 25 hearts with typical (fibrofatty) ARVC, 7 hearts with fat replacement of the right ventric

115 with ATWI fulfilled diagnostic criteria for ARVC after further evaluation.

116 Diagnostic criteria for ARVC are nonspecific in such individuals.

117 ients with no or only minor CMR criteria for ARVC diagnosis.

118 eason, international diagnostic criteria for ARVC were proposed by an expert consensus panel in 1996.

119 sess the accuracy of diagnostic criteria for ARVC when applied to athletes exhibiting electrocardiogr

120 k Force and modified diagnostic criteria for ARVC.

121 more accurate set of diagnostic criteria for ARVC.

122 itional patients met diagnostic criteria for ARVC.

123 dies of 142 pediatric patients evaluated for ARVC between 2005 and 2009 were reviewed.

124 ed plakoglobin signal level was specific for ARVC, we analyzed myocardium from 15 subjects with hyper

125 a sensitive and specific diagnostic test for ARVC, we performed immunohistochemical analysis of human

126 y sensitive and specific diagnostic test for ARVC.

127 uable component of the diagnostic workup for ARVC when performed with a dedicated protocol by special

128 Survival free from ARVC diagnosis was significantly lower in the positive i

129 rcise-induced arrhythmogenic remodeling from ARVC and post-inflammatory cardiomyopathies.

130 rcise-induced arrhythmogenic remodeling from ARVC and post-inflammatory cardiomyopathy.

131 METHODS AND We studied 20 genotyped ARVC patients with a broad spectrum of disease using ele

132 Hence, ARVC is the first identified disease of disrupted differ

133 heart-biopsy samples from the Johns Hopkins ARVC registry.

134 icted DP-deficient mice as a model for human ARVC.

135 inst desmoplakin (DP), responsible for human ARVC.

136 , thus recapitulating the phenotype of human ARVC.

137 itulated the clinical manifestation of human ARVC: ventricular dilation and aneurysm, cardiac fibrosi

138 scs in cardiomyocytes from four of six human ARVC cases show reduced or loss of iASPP.

139 In ARVC, 5 causative desmosomal genes have been identified,

140 Fat extent was 16.5% +/- 6.1 in ARVC and 4.6% +/- 2.7 in non-ARVC (P < .0001).

141 The findings suggest that adipocytes in ARVC, at least in part, originate from c-Kit+ CPCs.

142 rotecting against ventricular arrhythmias in ARVC, but no studies have provided data in a group rigor

143 of RV strain and dyssynchrony assessment in ARVC using feature-tracking CMR analysis.

144 ture ventricular contractions were common in ARVC patients with variable initiation sites in both ven

145 especially exertional dyspnea, are common in ARVC/D; yet, classic left-sided signs are typically abse

146 ological substrate properties that differ in ARVC patients compared with healthy controls.

147 globin signal level was reduced diffusely in ARVC samples, including those obtained in the left ventr

148 t a biologically plausible candidate gene in ARVC pathogenesis.

149 determine prevalence and predictors of HF in ARVC/D.

150 sonance (CE-CMR) for imaging scar lesions in ARVC patients.

151 powerful predictor of arrhythmic outcome in ARVC/D, independently of history and RV dilatation/dysfu

152 The finding of a deletion in plakoglobin in ARVC suggests that the proteins involved in cell-cell ad

153 To investigate the role of plakoglobin in ARVC, we generated an inducible cardiorestricted knockou

154 nisms responsible for disease progression in ARVC.

155 stic value of beta-adrenergic stimulation in ARVC.

156 genes for arrhythmic risk stratification in ARVC.

157 minant involvement of the right ventricle in ARVC.

158 nds tested previously for mutations in known ARVC genes and found an additional likely pathogenic var

159 ctively adjudicated for 289 patients meeting ARVC/D Task Force Criteria.

160 relevant cardiomyopathy that closely mimics ARVC in humans.

161 ow identification of RV scar lesions in most ARVC patients.

162 , with posterolateral RV wall being the most ARVC-specific area.

163 tic substrates by studying genotype-negative ARVC families.

164 e subsequently screened 73 genotype-negative ARVC probands tested previously for mutations in known A

165 s had definite, borderline, possible, and no ARVC, respectively, applying the rTFC.

166 finitive," "borderline," "possible," or "no" ARVC diagnostic groups based on the rTFC.

167 6.5% +/- 6.1 in ARVC and 4.6% +/- 2.7 in non-ARVC (P < .0001).

168 enic heterozygosity was identified in 16% of ARVC-causing desmosomal gene mutation carriers and was a

169 d missense mutations versus a similar 21% of ARVC cases.

170 by 0.5% of control individuals versus 43% of ARVC cases, while 16% of controls hosted missense mutati

171 rrect identification of 88%, 75%, and 63% of ARVC patients with no or only minor CMR criteria for ARV

172 Improved noninvasive assessment of ARVC and better understanding of the disease substrate a

173 The strong association of ARVC and left ventricular fibrosis with exercise-induced

174 These data suggest that the genetic basis of ARVC includes reduced penetrance with compound and digen

175 ent of the titin spring is a likely cause of ARVC and constitutes a novel mechanism underlying myocar

176 te CDH2 mutations as novel genetic causes of ARVC and contribute to a more complete identification of

177 The pathological characteristic of ARVC is myocyte loss with fibrofatty replacement.

178 dy sought to describe the clinical course of ARVC and occurrence of life-threatening arrhythmic event

179 are important contributors to a diagnosis of ARVC in children, using the rTFC.

180 Timely diagnosis of ARVC is difficult as clinical findings may be subtle and

181 Once the diagnosis of ARVC is established, the single most important clinical

182 in strenuous exercise after the diagnosis of ARVC, hemodynamically tolerated sustained monomorphic ve

183 ve (sensitivity, 91.4%) for the diagnosis of ARVC, particularly in its early stages.

184 ry and enrolled patients with a diagnosis of ARVC.

185 ms better than RV volume in the diagnosis of ARVC.

186 the right ventricle.Phenotypic expression of ARVC is variable and a significant number of patients ma

187 sudden cardiac death, displaying features of ARVC.

188 frequently nonspecific clinical features of ARVC/D.

189 Forms of ARVC in which gene penetrance and disease expression are

190 ant implications for other dominant forms of ARVC, related cardiomyopathies, and other cutaneous dise

191 c modalities and advances in the genetics of ARVC/D.

192 Almost half of ARVC patients have a mutation in genes encoding cell adh

193 The phenotypic hallmark of ARVC is fibroadipocytic replacement of cardiac myocytes,

194 At autopsy, hearts of ARVC cats were characterized grossly by moderate-to-seve

195 This novel model of ARVC demonstrates for the first time how plakoglobin aff

196 duced pluripotent stem cell (hiPSC) model of ARVC.

197 molecular mechanism for the pathogenesis of ARVC and establish cardiac-restricted DP-deficient mice

198 ded further insights for the pathogenesis of ARVC and potential therapeutic interventions.

199 n molecular genetics and the pathogenesis of ARVC could afford the opportunity for a genetic-based di

200 dysfunction involved in the pathogenesis of ARVC remain poorly understood.

201 tein plakoglobin (PG) in the pathogenesis of ARVC.

202 esponsible mechanism for the pathogenesis of ARVC.

203 molecular mechanisms in the pathogenesis of ARVC.

204 have been implicated in the pathogenesis of ARVC.

205 w molecular insight into the pathogenesis of ARVC.

206 ns of this pathway to the pathophysiology of ARVC, not only through perturbation of cardiac patternin

207 were present in the early concealed phase of ARVC.

208 lar EVM characterized a low-risk subgroup of ARVC/D patients.

209 A subset of ARVC is categorized as Naxos disease, which is character

210 and cardiac dysfunction similar to those of ARVC patients.

211 This disease constitutes the triad of ARVC, diffuse nonepidermolytic palmoplantar keratoderma,

212 early diagnosis and noninvasive follow-up of ARVC patients.

213 is study evaluated the impact of exercise on ARVC cardiac manifestations in mice after adeno-associat

214 The p.C796R and other ARVC-related PKP2 mutations indicate loss of function ef

215 of clinical criteria and correctly ruled out ARVC in 10 of 11 subjects without ARVC, for a sensitivit

216 Radical mutations are high-probability ARVC-associated mutations, whereas rare missense mutatio

217 c locus for the triad of autosomal recessive ARVC, palmoplantar keratoderma, and woolly hair (Naxos d

218 rdiac death (SCD) in desmosomal gene-related ARVC.

219 important pathogenic pathway for Jup-related ARVC.

220 sults may not be generalizable to lower-risk ARVC/D cohorts.

221 Subclinical and electrical staged ARVC subjects already showed signs of local mechanical a

222 nt definitions of electrical and subclinical ARVC stages.

223 patients undergoing evaluation for suspected ARVC.

224 ricular contractions evaluation or suspected ARVC.

225 ound to be high in patients with symptomatic ARVC: new epsilon waves appeared in 3 of 18 (17%), super

226 ects with desmosomal mutations confirms that ARVC is a disease of the desmosome and cell junction.

227 ance of this decision reflects the fact that ARVC is a common cause of sudden death in young people a

228 Genetic variation among the ARVC susceptibility genes has not been systematically ex

229 enetic variation in healthy controls for the ARVC susceptibility genes.

230 ers of lipid droplets were identified in the ARVC-CMs that displayed the more severe desmosomal patho

231 fied widened and distorted desmosomes in the ARVC-hiPSC-CMs.

232 nt decrease in the expression of PKP2 in the ARVC-hiPSC-CMs.

233 d prolonged field potential rise time in the ARVC-hiPSC-CMs.

234 SC-CMs were demonstrated to recapitulate the ARVC phenotype in the dish, provide mechanistic insights

235 d in clear RV dysfunction that resembled the ARVC phenotype (impaired global RV systolic function and

236 rol subjects, matched for age and sex to the ARVC group, were included for comparison purpose.

237 out the background noise associated with the ARVC genetic test.

238 on that showed complete segregation with the ARVC phenotype in 1 large family.

239 Thus, ARVC, at least in a subset, is a disease of desmosomes.

240 n TMEM43 and TGFB1 have been associated with ARVC.

241 to the specificity of their association with ARVC/D.

242 Clinical features of 12 domestic cats with ARVC (7 male; 1 to 20 years old, mean 7.3+/-5.2 years) w

243 When athletes were compared with ARVC patients, markers of physiological remodeling inclu

244 .686A>C, p.Gln229Pro) that cosegregated with ARVC in affected family members.

245 e sequencing was performed on 2 cousins with ARVC.

246 ere genotyped for 93 probands diagnosed with ARVC from the Netherlands and 427 ostensibly healthy con

247 At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudd

248 encoding plakoglobin in a German family with ARVC but no cutaneous abnormalities.

249 Thirty-six patients with ARVC (mean age +/- standard deviation, 46 years +/- 15;

250 s positive in 32 of 35 (91.4%) patients with ARVC and in 42 of 377 (11.1%) patients without ARVC (P<0

251 unction and RV dyssynchrony in patients with ARVC and provides incremental value over conventional ci

252 distribution differed between patients with ARVC and those without, with posterolateral RV wall bein

253 oncerns risk stratification in patients with ARVC and to place this literature in the framework of th

254 ere significantly higher among patients with ARVC compared with patients with RV outflow tract arrhyt

255 We investigated 100 white patients with ARVC for mutations in plakophilin-2.

256 Frequently, patients with ARVC have >1 genetic defect in the same gene (compound h

257 but because only 30% to 50% of patients with ARVC have 1 of these gene abnormalities, it is assumed t

258 Thirty-two consecutive patients with ARVC referred to CMR imaging were included.

259 ife-threatening arrhythmias in patients with ARVC spans from adolescence to advanced age, reaching it

260 ical course of 301 consecutive patients with ARVC using the Kaplan-Meier method adjusted to avoid the

261 f the study, ETT results of 25 patients with ARVC with histories of sustained ventricular arrhythmia

262 ene carriers that is shared by patients with ARVC with histories of ventricular arrhythmia.

263 broblasts were obtained from 2 patients with ARVC with plakophilin-2 (PKP2) mutations, reprogrammed t

264 In patients with ARVC, fat correlated to RV volume (R = 0.63, P < .0001),

265 of ventricular arrhythmias in patients with ARVC.

266 time experiences in caring for patients with ARVC.

267 ers and therapeutic targets in patients with ARVC.

268 in unrelated genotype-negative patients with ARVC.

269 an increased risk for MACE in patients with ARVC/D with advanced disease and a high risk for adverse

270 aphy in risk stratification in patients with ARVC/D, although our results may not be generalizable to

271 first-degree family members of a person with ARVC to have genetic testing but only if there is a know

272 If the affected family member (proband) with ARVC does not have a genetic defect identified, then it

273 N-cadherin were normal in all subjects with ARVC.

274 irst tested myocardium from 11 subjects with ARVC; of these samples, 8 had desmosomal gene mutations.

275 hat should not be considered synonymous with ARVC.

276 VC and in 42 of 377 (11.1%) patients without ARVC (P<0.0001).

277 ruled out ARVC in 10 of 11 subjects without ARVC, for a sensitivity of 91%, a specificity of 82%, a