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2.
J Cardiovasc Electrophysiol ; 34(2): 403-411, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36434796

RESUMO

BACKGROUND AND OBJECTIVE: Cardiac tamponade during ablation procedures is a life-threatening complication. While the incidence and management of tamponade in atrial fibrillation ablation have been extensively described, the data on tamponade during ventricular ablations are very limited. The purpose of this study is to shed light on the incidence, typical perforation sites, and optimal management as observed through real-life data in a tertiary referral center for ventricular ablation. METHODS AND RESULTS: Consecutive patients with structural heart disease undergoing ventricular tachycardia ablation from 2008-2020 were analyzed. Of the 1078 patients undergoing 1287 ventricular ablation procedures, 20 procedures (1.5%) were complicated by cardiac tamponade. In all but one patient, the tamponade was treated with emergent pericardial drainage, while nine patients eventually underwent surgical repair. The perforation occurred during transseptal or subxiphoid puncture in six patients, during ventricle mapping in two patients, and during ablation in five patients (predominantly basal left ventricle). Steam pop as definite perforation cause could only be established in two patients. Regardless of the management of the complication, all patients survived to discharge. CONCLUSION: Cardiac tamponade during ventricular ablation occurred in 1.5% of the procedures. In nine patients cardiac repair was necessary. Perforation was mostly associated with subxiphoid puncture or ablation of the basal left ventricle.


Assuntos
Fibrilação Atrial , Tamponamento Cardíaco , Ablação por Cateter , Humanos , Tamponamento Cardíaco/epidemiologia , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/terapia , Incidência , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/cirurgia , Ventrículos do Coração , Punções/efeitos adversos , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Resultado do Tratamento
3.
J Interv Cardiol ; 2022: 6829725, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935125

RESUMO

Background: Catheter ablation of ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) is an effective tool to prevent VT recurrences. Chronic total occlusion (CTO) represents a clinically relevant entity in ICM patients and is an independent predictor of ventricular arrhythmia and mortality. The effects of CTO on the outcome of VT ablation are not well-studied. Objective: This analysis aimed to identify the impact of CTO, revascularized, or not revascularized, on the outcome of VT ablation. Methods and Results: Of 385 consecutive subjects with ICM-VT who underwent catheter VT ablation for monomorphic VT at Heart Center Leipzig between 2008 and 2017, 108 patients without CTO and 191 patients with CTO were included in the analysis. Within a median follow-up time of 557 days (IQR 149, 1095), VT recurred in 77 (40%) patients in the CTO and 40 (37.0%) in the non-CTO cohort (p = 0.62). In a multivariable model, a 10% stepwise change in LVEF as well as ICD on admission was associated with VT recurrence (HRadj 1.82, 95% CI 1.04-3.18 and HRadj 1.35, 95% CI 1.23-1.61, respectively). Of the CTO cohort before ablation, 45% had received revascularization, which was independently associated with a higher risk for VT recurrence (HR 2.12, 95% CI 1.35-3.34) as compared to nonrevascularized CTO. Conclusion: In ICM patients with and without CTO, VT ablation was associated with equal effectiveness with regard to VT recurrence. However, in revascularized CTO patients, the risk of recurrence of VT after ablation was significantly increased.


Assuntos
Cardiomiopatias , Ablação por Cateter , Isquemia Miocárdica , Taquicardia Ventricular , Cardiomiopatias/complicações , Cardiomiopatias/cirurgia , Ablação por Cateter/métodos , Humanos , Isquemia Miocárdica/complicações , Isquemia Miocárdica/cirurgia , Recidiva , Taquicardia Ventricular/complicações , Taquicardia Ventricular/cirurgia , Resultado do Tratamento
4.
Herzschrittmacherther Elektrophysiol ; 33(2): 217-223, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35277790

RESUMO

OBJECTIVES: This study analyzes the incidence, characteristics, and ECG morphology of ventricular tachycardia (VT) in post-infarction patients undergoing epicardial VT ablation. BACKGROUND: Ablation of recurrent VTs in patients with ischemic cardiomyopathy is typically performed endocardially. In rare cases, epicardial access is required to achieve non-inducibility. METHODS AND RESULTS: The study evaluated the baseline characteristics, procedural data, and ECG morphology of clinical VT in patients undergoing epicardial VT ablation. From the initial 491 patients with coronary heart disease (CHD) and recurrent VTs undergoing ablation at the Heart Center of Leipzig, Germany, between 2012 and 2020, only 39 patients required an additional epicardial access. In 17 patients, the VTs were associated with infarction scar, while the remaining patients had concomitant CHD without infarction-associated scar and were excluded from the analysis. A propensity match study was performed at a 1:2 ratio for these 17 patients, with 34 patients of the initial cohort as a control group to evaluate the differences in baseline characteristics, procedural data, and ECG morphology of the VTs. The specific VT morphology of negative concordance and superior axis in patients with inferior scar as well as the history of VT ablation were independent predictors of the need for epicardial access. CONCLUSIONS: In addition to previous endocardial ablation, VT ECG morphology with negative concordance and superior axis in post-infarction patients with inferior scar predicted the need for epicardial VT ablation.


Assuntos
Ablação por Cateter , Taquicardia Ventricular , Ablação por Cateter/métodos , Cicatriz/complicações , Cicatriz/diagnóstico , Cicatriz/cirurgia , Eletrocardiografia/métodos , Humanos , Infarto/complicações , Infarto/cirurgia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/cirurgia , Resultado do Tratamento
5.
JACC Case Rep ; 3(16): 1756-1759, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34825204

RESUMO

A 25-year-old male patient with highly symptomatic, monomorphic, premature ventricular contractions presented for repeat ablation after failed endocardial ablation. Three weeks after excessive endocardial and epicardial ablation on the left ventricular summit, the patient was admitted again with tamponade following a pseudoaneurysm on the ablation site. (Level of Difficulty: Advanced.).

6.
Europace ; 23(12): 1980-1988, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34405874

RESUMO

AIMS: Epicardial ablation has risen to an essential part of the treatment of ventricular tachycardias (VTs). In this study, we report the efficacy, risks, and current trends of epicardial ablation in structural heart disease as reported in a tertiary single centre over a 12-year period. METHODS AND RESULTS: Two hundred and thirty-six patients referred for VT ablation underwent a successful epicardial access and were included in the analysis (89% non-ischaemic cardiomyopathy, 90% males, mean age 60 years, mean left ventricular ejection fraction 38.4%). After performing epicardial ablation the clinical VTs were eliminated in 87% of the patients and 71% of the cohort achieved freedom from VT during 22-month follow-up. Twelve patients (5%) suffered major procedure-related complications. Until the end of follow-up 47 (20%) patients died, 9 (4%) underwent a left ventricular assist device implantation and 10 (4%) patients received a heart transplantation. Antiarrhythmic drugs at baseline and during follow-up were independent predictors of VT recurrence. Atrial fibrillation, renal dysfunction, worse New York Heart Association class, and antiarrhythmic drugs at follow-up were associated with worse survival in our cohort. CONCLUSION: In this large tertiary single-centre experience, percutaneous epicardial access was feasible in the large majority of the cohort with acceptably low complications rates. A combined endo-/epicardial approach resulted in 87% acute and 71% long-term success. Further studies are needed to clarify the role of routine combined endo-/epicardial ablation in these complex cardiomyopathies.


Assuntos
Ablação por Cateter , Cardiopatias , Taquicardia Ventricular , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Feminino , Cardiopatias/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Volume Sistólico , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/cirurgia , Resultado do Tratamento , Função Ventricular Esquerda
7.
J Cardiovasc Electrophysiol ; 32(10): 2675-2683, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34411387

RESUMO

INTRODUCTION: This study sought to examine gender differences in patients with structural heart disease (SHD) referred for ablation of ventricular tachycardia (VT). BACKGROUND: Female patients are often underrepresented in large studies. Significant differences in the clinical presentation, treatment, and prognosis of female patients have been described in previous studies. METHODS AND RESULTS: We investigated 88 female patients with SHD undergoing VT ablation (mean age 59 years, 56% nonischemic cardiomyopathy, mean left ventricular ejection fraction 35%, 82% in electrical storm). A case-control study with 88 male patients was performed and the results regarding clinical and procedural characteristics, acute and long-term results of the two groups were compared. The female patients had more arrhythmogenic substrate, as they more commonly presented with electrical storm (p = .016) and had a higher number of inducible VT morphologies during the procedure (p = .018). Moreover, the female patients were less likely to have an optimized heart failure medical treatment at baseline (p = .030) and required more time from the first manifestation of the VT to ablation referral (p = .034). Although fewer epicardial ablations were performed in female patients (p = .019), the two groups showed similar results regarding VT noninducibility as ablation endpoint (p = .844), major procedure-related complications (p = .719) and freedom from VT during follow-up (p = .268). Moreover, the overall mortality in the two groups was similar (p = .176). Advanced NYHA class was associated with worse transplant and assist-device-free survival in the female group. CONCLUSION: Female patients presenting for VT ablation had more arrhythmogenic substrate and were less likely to have an optimized heart failure medical treatment. Nevertheless, the procedural acute and long-term outcomes between the two genders were similar.


Assuntos
Ablação por Cateter , Cardiopatias , Taquicardia Ventricular , Estudos de Casos e Controles , Ablação por Cateter/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores Sexuais , Volume Sistólico , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirurgia , Resultado do Tratamento , Função Ventricular Esquerda
8.
Herzschrittmacherther Elektrophysiol ; 32(3): 353-358, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34269843

RESUMO

INTRODUCTION: Ablation of ventricular tachycardias (VTs) in patients with structural heart disease (SHD) has been associated with advanced heart failure and poor survival. METHODS AND RESULTS: This matched case-control study sought to assess the difference in survival after left ventricular assist device (LVAD) implantation and/or heart transplantation (HTX) in SHD patients undergoing VT ablation. From the initial cohort of 309 SHD patients undergoing VT ablation (187 ischemic cardiomyopathy, mean age 64 ± 12 years, ejection fraction of 34 ± 13%), 15 patients received an LVAD and nine patients HTX after VT ablation during a follow-up period of 44 ± 33 months. Long-term survival after LVAD did not differ from the matched control group (p = 0.761), although the cause of lethal events was different. All post-HTX patients survived during follow-up. CONCLUSION: In this matched case-control study on patients with SHD undergoing VT ablation, patients that received LVAD implantation had similar survival compared to the control group after 4­year follow-up, while the patients with HTX had a significantly better outcome.


Assuntos
Ablação por Cateter , Cardiopatias , Transplante de Coração , Taquicardia Ventricular , Idoso , Estudos de Casos e Controles , Humanos , Pessoa de Meia-Idade , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirurgia , Resultado do Tratamento
9.
J Cardiovasc Electrophysiol ; 32(3): 766-771, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33428325

RESUMO

INTRODUCTION: This study sought to examine the feasibility and outcome of ablation of ventricular tachycardias (VTs) in a contemporary cohort of geriatric patients with structural heart disease (SHD). BACKGROUND: Geriatric patients are often underrepresented in large studies. As frailty is becoming an increasing problem, we need to examine the best course of action for this population. METHODS AND RESULTS: We investigated 68 SHD-patients ≥ 75 years old undergoing VT-ablation (men 88%, ischemic cardiomyopathy 77%, electrical storm 72%, mean left ventricular ejection fraction 31%) and divided the cohort into two groups: 75-79 years old (n = 51) and ≥80 years old (n = 17). The two groups showed similar results regarding noninducibility as ablation endpoint (p = .693), major procedure-related complications (p = .488), and VT-recurrence (p = .882) during the 39-month follow-up. At the end of the follow-up, 10 patients in the octogenarian group (59%) versus 16 patients of the other group (31%) died. CONCLUSION: Geriatric patients with SHD including octogenarians showed similar results regarding procedural endpoints, freedom of VT, and major procedure-associated complications after VT-ablation. When ablation is indicated, age alone should not be an inhibiting factor to treat these patients.


Assuntos
Ablação por Cateter , Cardiopatias , Taquicardia Ventricular , Idoso , Idoso de 80 Anos ou mais , Ablação por Cateter/efeitos adversos , Cardiopatias/diagnóstico , Cardiopatias/cirurgia , Humanos , Masculino , Recidiva , Volume Sistólico , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirurgia , Resultado do Tratamento , Função Ventricular Esquerda
10.
Europace ; 22(11): 1672-1679, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32830252

RESUMO

AIMS: Ablation of ventricular tachycardias (VTs) in patients with structural heart disease has been established in the past decades as an effective and safe treatment. However, the prognosis and long-term outcome remains poor. METHODS AND RESULTS: We investigated 309 patients with ischaemic cardiomyopathy (ICM) and non-ischaemic cardiomyopathy (NICM) (186 ICM, 123 NICM; 271 males; mean age 64.1 ± 12 years; ejection fraction 34 ± 13%) after ≥1 VT ablations over a mean follow-up period of 34 ± 28 months. Electrical storm was the indication for 224 patients (73%), whereas 86 patients (28%) underwent epicardial as well as endocardial ablation. During follow-up, 132 patients (43%) experienced VT recurrence and 97 (31%) died. Ischaemic cardiomyopathy and NICM patients showed comparable results, regarding procedural endpoints, complications, VT recurrence and survival. The Cox-regression analysis for all-cause mortality revealed that the presence of higher left ventricular end-diastolic volume (LVEDV; P < 0.001), male gender (P = 0.018), atrial fibrillation (AF; P < 0.001), chronic obstructive pulmonary disease (COPD; P = 0.001), antiarrhythmic drugs during the follow-up (P < 0.001), polymorphic VTs (P = 0.028), and periprocedural complications (P = 0.001) were independent predictors of mortality. CONCLUSION: Ischaemic cardiomyopathy and NICM patients undergoing VT ablation had comparable results regarding procedural endpoints, complications, VT recurrence and 3-year mortality. Higher LVEDV, male gender, COPD, AF, polymorphic VTs, use of antiarrhythmics, and periprocedural complications are strong and independent predictors for increased mortality. The PAINESD score accurately predicted the long-term outcome in our cohort.


Assuntos
Ablação por Cateter , Cardiopatias , Isquemia Miocárdica , Taquicardia Ventricular , Idoso , Antiarrítmicos/uso terapêutico , Ablação por Cateter/efeitos adversos , Cardiopatias/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/tratamento farmacológico , Taquicardia Ventricular/cirurgia , Resultado do Tratamento
11.
Europace ; 21(9): 1392-1399, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31102521

RESUMO

AIMS: We sought to investigate the overlap between late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR) and electro-anatomical maps (EAM) of patients with non-ischaemic dilated cardiomyopathy (NIDCM) and how it relates with the outcomes after catheter ablation of ventricular arrhythmias (VA). METHODS AND RESULTS: We identified 50 patients with NIDCM who received CMR and ablation for VA. Late gadolinium enhancement was detected in 16 (32%) patients, mostly in those presenting with sustained ventricular tachycardia (VT): 15 patients. Low-voltage areas (<1.5 mV) were observed in 23 (46%) cases; in 7 (14%) cases without evidence of LGE. Using a threshold of 1.5 mV, a good and partially good agreement between the bipolar EAM and LGE-CMR was observed in only 4 (8%) and 9 (18%) patients, respectively. With further adjustments of EAM to match the LGE, we defined new cut-off limits of median 1.5 and 5 mV for bipolar and unipolar maps, respectively. Most VT exits (12 out of 16 patients) were found in areas with LGE. VT exits were found in segments without LGE in two patients with VT recurrence as well as in two patients without recurrence, P = 0.77. In patients with VT recurrence, the LGE volume was significantly larger than in those without recurrence: 12% ± 5.8% vs. 6.9% ± 3.4%; P = 0.049. CONCLUSIONS: In NIDCM, the agreement between LGE and bipolar EAM was fairly poor but can be improved with adjustment of the thresholds for EAM according to the amount of LGE. The outcomes were related to the volume of LGE.


Assuntos
Cardiomiopatia Dilatada/diagnóstico por imagem , Técnicas Eletrofisiológicas Cardíacas/métodos , Imagem Cinética por Ressonância Magnética/métodos , Taquicardia Ventricular/diagnóstico por imagem , Complexos Ventriculares Prematuros/diagnóstico por imagem , Adulto , Idoso , Cardiomiopatia Dilatada/fisiopatologia , Ablação por Cateter , Meios de Contraste , Feminino , Gadolínio , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/cirurgia , Resultado do Tratamento , Complexos Ventriculares Prematuros/fisiopatologia , Complexos Ventriculares Prematuros/cirurgia
12.
Oncotarget ; 9(75): 34079-34089, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30344923

RESUMO

Wilms tumour (WT), the most frequent malignant childhood renal tumour, shows a high degree of genetic and epigenetic heterogeneity. Loss of imprinting on chromosome 11p15 is found in a large fraction of cases and mutations in a few genes, including WT1, CTNNB1, WTX, TP53 and, more recently, SIX1, SIX2 and micro RNA processing genes (miRNAPGs), have been observed. However, these alterations are not sufficient to describe the entire spectrum of genetic defects underlying WT development. We inspected data obtained from a previously performed genome-wide single nucleotide polymorphism (SNP) array analysis on 96 WT samples. By selecting focal regions commonly involved in chromosomal anomalies, we identified genes with a possible role in WT development, based on the prior knowledge of their biological relevance, including MYCN, DIS3L2, MIR562, HACE1, GLI3, CDKN2A and CDKN2B, PALB2, and CHEK2. The MYCN hotspot mutation c.131C>T was detected in seven cases (7.3%). Full sequencing of the remaining genes disclosed 16 rare missense variants and a splicing mutation. Most of these were present at the germline level. Promoter analysis of HACE1, CDKN2A and CDKN2B disclosed partial methylation affecting HACE1 in a consistent fraction of cases (85%). Interestingly, of the four missense variants identified in CHEK2, three were predicted to be deleterious by in silico analyses, while an additional variant was observed to alter mRNA splicing, generating a functionally defective protein. Our study adds additional information on putative WT genes, and adds evidences involving CHEK2 in WT susceptibility.

13.
Herzschrittmacherther Elektrophysiol ; 29(3): 259-263, 2018 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-30076446

RESUMO

The precise target location for radiofrequency energy delivery was initially determined through electrophysiological signals and with the help of fluoroscopy. The introduction of the 3D mapping system CARTO® (Biosense Webster Inc., Diamond Bar, CA, USA) in recent years for radiofrequency ablation of arrhythmias has provided new therapeutic options. These improvements have led to reduced procedural and fluoroscopic times. The introduction of new software and technology has also improved clinical outcome and helped to understand the substrate of complex arrhythmias. This article provides an overview of the development of the CARTO® system and presents new features of the system.


Assuntos
Ablação por Cateter , Imageamento Tridimensional , Arritmias Cardíacas , Eletrofisiologia Cardíaca , Fluoroscopia , Humanos , Resultado do Tratamento
16.
J Electrocardiol ; 50(4): 510-512, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28347478

RESUMO

A 76-year-old woman, affected by drugs resistant focal atrial tachycardia, underwent a catheter ablation procedure in our Hospital. During ablations we observed on the surface ECG a progressive modification of the second component of the P wave (delayed and then negative in inferior leads). These findings demonstrated, compared to the beginning of the procedure, a different propagation of the activation wave from the right to the left atrium, helped to identify the true origin of a focal atrial tachycardia. Moreover, this case underlined the importance of the Bachmann's bundle for the impulse propagation through the interatrial septum in normal hearts.


Assuntos
Ablação por Cateter , Átrios do Coração/fisiopatologia , Átrios do Coração/cirurgia , Taquicardia Supraventricular/fisiopatologia , Taquicardia Supraventricular/cirurgia , Idoso , Ecocardiografia , Eletrocardiografia , Feminino , Septos Cardíacos/fisiopatologia , Humanos
17.
J Cardiovasc Med (Hagerstown) ; 18(7): 528-533, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27828828

RESUMO

BACKGROUND: Atrial fibrillation transcatheter ablation (TCA) is, within available atrial fibrillation rhythm control strategies, one of the most effective. To potentially improve ablation outcome in case of recurrent atrial fibrillation after a first procedure or in presence of structural myocardial disease, isolation of the pulmonary veins may be associated with extensive lesions within the left atrium. To avoid rare, but potentially life-threatening, complications, thorough knowledge and assessment of left atrium anatomy and its relation to structures in close proximity are, therefore, mandatory. Aim of the present study is to describe, by cardiac computed tomography, the anatomic relationship between aortic root, left coronary artery and left atrium in patients undergoing atrial fibrillation TCA. METHODS AND RESULTS: The cardiac computed tomography scan of 21 patients affected by atrial fibrillation was elaborated to segment left atrium, aortic root and left coronary artery from the surrounding structures and the following distances measured: left atrium and aortic root; left atrium roof and aortic root; left main coronary artery and left atrium; circumflex artery and left atrium appendage; and circumflex artery and mitral valve annulus. Above all, the median distance between left atrium and aortic root (1.9, 1.5-2.1 mm), and between circumflex artery and left atrium appendage ostium (3.0, 2.1-3.4 mm) were minimal (≤3 mm). None of measured distances significantly varied between patients presenting paroxysmal versus persistent atrial fibrillation. CONCLUSION: The anatomic relationship between left atrium and coronary arteries is extremely relevant when performing atrial fibrillation TCA by extensive lesions. Therefore, at least in the latter case, preablation imaging should be recommended to avoid rare, but potentially life-threatening, complications with the aim of an as well tolerated as possible procedure.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Vasos Coronários/diagnóstico por imagem , Átrios do Coração/cirurgia , Tomografia Computadorizada Multidetectores , Idoso , Pontos de Referência Anatômicos , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Feminino , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Valor Preditivo dos Testes , Fatores de Risco , Resultado do Tratamento
18.
Oncotarget ; 7(8): 8908-15, 2016 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-26802027

RESUMO

Approximately half of children suffering from recurrent Wilms tumor (WT) develop resistance to salvage therapies. Hence the importance to disclose events driving tumor progression/recurrence. Future therapeutic trials, conducted in the setting of relapsing patients, will need to prioritize targets present in the recurrent lesions. Different studies identified primary tumor-specific signatures associated with poor prognosis. However, given the difficulty in recruiting specimens from recurrent WTs, little work has been done to compare the molecular profile of paired primary/recurrent diseases. We studied the genomic profile of a cohort of eight pairs of primary/recurrent WTs through whole-genome SNP arrays, and investigated known WT-associated genes, including SIX1, SIX2 and micro RNA processor genes, whose mutations have been recently proposed as associated with worse outcome. Through this approach, we sought to uncover anomalies characterizing tumor recurrence, either acquired de novo or already present in the primary disease, and to investigate whether they overlapped with known molecular prognostic signatures. Among the aberrations that we disclosed as potentially acquired de novo in recurrences, some had been already recognized in primary tumors as associated with a higher risk of relapse. These included allelic imbalances of chromosome 1q and of chromosome 3, and CN losses on chromosome 16q. In addition, we found that SIX1 and DROSHA mutations can be heterogeneous events (both spatially and temporally) within primary tumors, and that their co-occurrence might be positively selected in the progression to recurrent disease. Overall, these results provide new insights into genomic and genetic events underlying WT progression/recurrence.


Assuntos
Biomarcadores Tumorais/genética , Aberrações Cromossômicas , Proteínas de Homeodomínio/genética , Mutação/genética , Recidiva Local de Neoplasia/genética , Ribonuclease III/genética , Tumor de Wilms/genética , Criança , Pré-Escolar , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 3/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Tumor de Wilms/patologia
19.
J Transl Med ; 13: 297, 2015 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-26364058

RESUMO

BACKGROUND: Heart failure (HF) is characterized by a series of adaptive changes in energy metabolism. The use of metabolomics enables the parallel assessment of a wide range of metabolites. In this study, we appraised whether metabolic changes correlate with HF severity, assessed as an impairment of functional contractility, and attempted to interpret the role of metabolic changes in determining systolic dysfunction. METHODS: A 500 MHz proton nuclear magnetic resonance ((1)H-NMR)-based analysis was performed on blood samples from three groups of individuals: 9 control subjects (Group A), 9 HF patients with mild to moderate impairment of left ventricle ejection fraction (LVEF: 41.9 ± 4.0 %; Group B), and 15 HF patients with severe LVEF impairment (25.3 ± 10.3 %; Group C). In order to create a descriptive model of HF, a supervised orthogonal projection on latent structures discriminant analysis (OPLS-DA) was applied using speckle tracking-derived longitudinal strain rate as the Y-variable in the multivariate analysis. RESULTS: OPLS-DA identified three metabolic clusters related to the studied groups achieving good values for R(2) [R(2)(X) = 0.64; R(2)(Y) = 0.59] and Q(2) (0.39). The most important metabolites implicated in the clustering were 2-hydroxybutyrate, glycine, methylmalonate, and myo-inositol. CONCLUSIONS: The results demonstrate the suitability of metabolomics in combination with functional evaluation techniques in HF staging. This innovative tool should facilitate investigation of perturbed metabolic pathways in HF and their correlation with the impairment of myocardial function.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Metabolômica , Idoso , Feminino , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Espectroscopia de Prótons por Ressonância Magnética
20.
Brain Imaging Behav ; 8(2): 311-22, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23975276

RESUMO

The volume, diversity and velocity of biomedical data are exponentially increasing providing petabytes of new neuroimaging and genetics data every year. At the same time, tens-of-thousands of computational algorithms are developed and reported in the literature along with thousands of software tools and services. Users demand intuitive, quick and platform-agnostic access to data, software tools, and infrastructure from millions of hardware devices. This explosion of information, scientific techniques, computational models, and technological advances leads to enormous challenges in data analysis, evidence-based biomedical inference and reproducibility of findings. The Pipeline workflow environment provides a crowd-based distributed solution for consistent management of these heterogeneous resources. The Pipeline allows multiple (local) clients and (remote) servers to connect, exchange protocols, control the execution, monitor the states of different tools or hardware, and share complete protocols as portable XML workflows. In this paper, we demonstrate several advanced computational neuroimaging and genetics case-studies, and end-to-end pipeline solutions. These are implemented as graphical workflow protocols in the context of analyzing imaging (sMRI, fMRI, DTI), phenotypic (demographic, clinical), and genetic (SNP) data.


Assuntos
Algoritmos , Genômica/métodos , Internet , Neuroimagem/métodos , Software , Fluxo de Trabalho , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Dor Crônica/complicações , Dor Crônica/patologia , Biologia Computacional/métodos , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Disseminação de Informação/métodos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/patologia , Masculino , Pessoa de Meia-Idade
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