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1.
J Cardiovasc Electrophysiol ; 34(1): 90-98, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36217994

RESUMO

INTRODUCTION: Phrenic nerve (PN) injury is a rare but severe complication of radiofrequency (RF) pulmonary vein isolation (PVI). The objective of this study was to characterize the typical intracardiac course of the PN with a three-dimensional electroanatomic mapping system, to quantify the need for modification of the ablation trajectory to avoid delivering an ablation lesion on sites with PN capture, and to identify very circumscribed areas of common PNC on the routine ablation trajectory of a RF-PVI, allowing fast and effective PN screening for everyday usage. METHODS: We enrolled 137 consecutive patients (63 ± 9 years, 64% men) undergoing PVI. A detailed high output (20 mA) pace-mapping protocol was performed in the right (RA) and left atrium (LA) and adjacent vasculature. RESULTS: The right PN was most commonly captured in the superior vena cava at a lateral (50%) or posterolateral (23%) position before descending along the RA either straight (29%) or with a posterolateral bend (20%). In the LA, beginning deep within the right superior pulmonary vein (RSPV), the right PN is most frequently detectable anterolateral (31%), then descends to the lateral proximal RSPV (23%), and further towards the lateral antral region (15%) onto the medial LA wall (12%). To avoid delivering an ablation lesion on sites with PN capture, modification of ablation trajectory was necessary in 23% of cases, most commonly in the lateral RSPV antrum (81%). No PN injury occurred. CONCLUSION: PN mapping frequently reveals the close proximity of the PN to the ablation trajectory during PVI, particularly in the lateral RSPV antrum. Routine PN pacing should be considered during RF PVI procedures.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Traumatismos dos Nervos Periféricos , Veias Pulmonares , Masculino , Humanos , Feminino , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Nervo Frênico/lesões , Veias Pulmonares/cirurgia , Veia Cava Superior/cirurgia , Átrios do Coração/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/prevenção & controle
2.
Europace ; 25(1): 65-73, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35852306

RESUMO

AIMS: The cornerstone of pulmonary vein (PV) isolation (PVI) is a wide-area circumferential ablation (WACA) resulting in an antral PVI area. Pulsed-field ablation (PFA) is a new nonthermal 'single-shot' PVI technique resulting in well-characterized posterior isolation areas. However, information on circumferential PVI area is lacking. Thus, we sought to characterize the circumferential antral PVI areas after PFA-PVI. METHODS AND RESULTS: Atrial fibrillation (AF) patients underwent fluoroscopy-guided PVI with a pentaspline PFA catheter. Ultra-high-density voltage maps using a 20-polar circular mapping catheter were created before and immediately after PVI to identify and quantify (i) insufficient isolation areas per antral PV segment (10-segment model) and (ii) enlarged left atrial (LA) isolation areas (beyond the antral PV segments) per LA region (8-region model). The PFA-PVI with pre- (5469 ± 1822 points) and post-mapping (6809 ± 2769 points) was performed in 40 consecutive patients [age 62 ± 6 years, 25/40 (62.5%) paroxysmal AF]. Insufficient isolation areas were located most frequently in the anterior antral PV segments of the left PVs (62.5-77.5% of patients) with the largest extent (median ≥0.4 cm2) located in the same segments (segments 2/5/8). Enlarged LA isolation areas were located most frequently and most extensively on the posterior wall and roof region (89.5-100% of patients; median 1.1-2.7 cm2 per region). CONCLUSION: Fluoroscopy-guided PFA-PVI frequently results in insufficient isolation areas in the left anterior antral PV segments and enlarged LA isolation areas on the posterior wall/roof, which both may be extensive. To optimize the procedure, full integration of PFA catheter visualization into three-dimensional-mapping systems is needed.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Pessoa de Meia-Idade , Idoso , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Átrios do Coração , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Catéteres , Resultado do Tratamento
3.
Europace ; 25(3): 1126-1134, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36610064

RESUMO

AIMS: Transseptal puncture (TP) for left-sided catheter ablation procedures is routinely performed under fluoroscopic or echocardiographic guidance [transoesophageal echocardiography (TEE) or intracardiac echocardiography (ICE)], although three-dimensional (3D) mapping systems are readily available in most electrophysiology laboratories. Here, we sought to assess the feasibility and safety of a right atrial (RA) 3D map-guided TP. METHODS AND RESULTS: In 104 patients, 3D RA mapping was performed to identify the fossa ovalis (FO) using the protrusion technique. The radiofrequency transseptal needle was visualized and navigated to the desired potential FO-TP site. Thereafter, the interventionalist was unblinded to TEE and the potential FO-TP site was reassessed regarding its convenience and safety. After TP, the exact TP site was documented using a 17-segment-FO model. Reliable identification of the FO was feasible in 102 patients (98%). In these, 114 3D map-guided TP attempts were performed, of which 96 (84%) patients demonstrated a good position and 18 (16%) an adequate position after TEE unblinding. An out-of-FO or dangerous position did not occur. A successful 3D map-guided TP was performed in 110 attempts (97%). Four attempts (3%) with adequate positions were aborted in order to seek a more convenient TP site. The median time from RA mapping until the end of the TP process was 13 (12-17) min. No TP-related complications occurred. Ninety-eight TP sites (85.1%) were in the central portion or in the inner loop of the FO. CONCLUSION: A 3D map-guided TP is feasible and safe. It may assist to decrease radiation exposure and the need for TEE/ICE during left-sided catheter ablation procedures.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Humanos , Estudos de Viabilidade , Cateterismo Cardíaco/métodos , Átrios do Coração , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Punções , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Resultado do Tratamento
4.
Europace ; 23(12): 2010-2019, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34463710

RESUMO

AIMS: Atrial cardiomyopathy (ACM) is associated with new-onset atrial fibrillation, arrhythmia recurrence after pulmonary vein isolation (PVI) and increased risk for stroke. At present, diagnosis of ACM is feasible by endocardial contact mapping of left atrial (LA) low-voltage substrate (LVS) or late gadolinium-enhanced magnetic resonance imaging, but their complexity limits a widespread use. The aim of this study was to assess non-invasive body surface electrocardiographic imaging (ECGI) as a novel clinical tool for diagnosis of ACM compared with endocardial mapping. METHODS AND RESULTS: Thirty-nine consecutive patients (66 ± 9 years, 85% male) presenting for their first PVI for persistent atrial fibrillation underwent ECGI in sinus rhythm using a 252-electrode-array mapping system. Subsequently, high-density LA voltage and biatrial activation maps (mean 2090 ± 488 sites) were acquired in sinus rhythm prior to PVI. Freedom from arrhythmia recurrence was assessed within 12 months follow-up. Increased duration of total atrial conduction time (TACT) in ECGI was associated with both increased atrial activation time and extent of LA-LVS in endocardial contact mapping (r = 0.77 and r = 0.66, P < 0.0001 respectively). Atrial cardiomyopathy was found in 23 (59%) patients. A TACT value of 148 ms identified ACM with 91.3% sensitivity and 93.7% specificity. Arrhythmia recurrence occurred in 15 (38%) patients during a follow-up of 389 ± 55 days. Freedom from arrhythmia was significantly higher in patients with a TACT <148 ms compared with patients with a TACT ≥148 ms (82.4% vs. 45.5%, P = 0.019). CONCLUSION: Analysis of TACT in non-invasive ECGI allows diagnosis of patients with ACM, which is associated with a significantly increased risk for arrhythmia recurrence following PVI.


Assuntos
Fibrilação Atrial , Cardiomiopatias , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Feminino , Humanos , Masculino , Veias Pulmonares/cirurgia , Recidiva , Resultado do Tratamento
5.
Europace ; 22(5): 732-738, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32142124

RESUMO

AIMS: Transseptal puncture (TP) for left atrial (LA) catheter ablation procedures is routinely performed under fluoroscopic guidance. To decrease radiation exposure and increase safety alternative techniques are desirable. The aim of this study was to assess whether right atrial (RA) electroanatomic 3D mapping can reliably identify the fossa ovalis (FO) in preparation of TP. METHODS AND RESULTS: Between May 2019 and August 2019, electroanatomic RA mapping was performed before TP in 61 patients with paroxysmal or persistent atrial fibrillation. Three electroanatomic methods for FO identification, mapping catheter-induced FO protrusion, electroanatomic-guided analysis, and voltage mapping, were evaluated and compared with transoesophageal echocardiography (TOE). Mapping catheter-induced FO protrusion was feasible in 60 patients (98%) with a mean displacement of 6.8 ± 2.5 mm, confirmed by TOE, and proofed to be the most valuable and easiest marker for FO identification. Electroanatomic-guided analysis localized the FO midpoint consistently in the lower half (43 ± 7%) and posterior (18.2 ± 4.4 mm) to a line between coronary sinus and vena cava superior. Analysis of RA voltage maps during sinus rhythm (n = 40, low-voltage cut-off value 1.0 and 1.5 mV) allowed secure FO recognition in 33% and 18%, only. A step-by-step approach, combining FO protrusion (first step) with anatomy criteria in case of protrusion failure (second step) would have allowed for the correct localization of a TP site within the FO in all patients. CONCLUSION: Right atrial electroanatomic 3D mapping prior to TP proofed to be a simple tool for FO identification and may potentially be of use in the safe and radiation-free performance of TP prior to LA ablation procedures.


Assuntos
Fibrilação Atrial , Septo Interatrial , Ablação por Cateter , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Septo Interatrial/diagnóstico por imagem , Septo Interatrial/cirurgia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Humanos , Projetos Piloto , Punções , Resultado do Tratamento
6.
Europace ; 22(2): 240-249, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31782781

RESUMO

AIMS: Presence of arrhythmogenic left atrial (LA) low-voltage substrate (LVS) is associated with reduced arthythmia freedom rates following pulmonary vein isolation (PVI) in persistent atrial fibrillation (AF). We hypothesized that LA-LVS modifies amplified sinus-P-wave (APW) characteristics, enabling identification of patients at risk for arrhythmia recurrences following PVI. METHODS AND RESULTS: Ninety-five patients with persistent AF underwent high-density (>1200 sites) voltage mapping in sinus rhythm. Left atrial low-voltage substrate (<0.5 and <1.0 mV) was quantified in a 10-segment LA model. Amplified sinus-P-wave-morphology and -duration were evaluated using digitized 12-lead electrocardiograms (40-80 mm/mV, 100-200 mm/s). 12-months arrhythmia freedom following circumferential PVI was assessed in 139 patients with persistent AF. Left atrial low-voltage substrate was most frequently (84%) found at the anteroseptal LA. Characteristic changes of APW were related to the localization and extent of LA-LVS. At an early stage, LA-LVS predominantly located to the LA-anteroseptum and was associated with APW-prolongation (≥150 ms). More extensive LA-LVS involved larger areas of LA-anteroseptum, leading to morphological changes of APW (biphasic positive-negative P-waves in inferior leads). Severe LA-LVS involved the LA-anteroseptum, roof and posterior LA, but spared the inferior LA, lateral LA, and LA appendage. In this advanced stage, widespread LVS at the posterior LA abolished the negative portion of P-wave in the inferior leads. The delayed activation of the lateral LA and LA appendage produced the late positive deflections in the anterolateral leads, resulting in the "late-terminal P"-pattern. Structured analysis of APW-duration and -morphology stratified patients to their individual extent of LA-LVS (Grade 1: mean LA-LVS 4.9 cm2 at <1.0 mV; Grade 2: 28.6 cm2; Grade 3: 42.3 cm2; P < 0.01). The diagnostic value of APW-duration for identification of LA-LVS was significantly superior to standard P-wave-amplification (c-statistic 0.945 vs. 0.647). Arrhythmia freedom following PVI differed significantly between APW-predicted grades of LA-LVS-severity [hazard ratio (HR) 2.38, 95% confidence interval (CI) 1.18-4.83; P = 0.015 for Grade 1 vs. Grade 2; HR 1.79, 95% CI 1.00-3.21, P = 0.049 for Grade 2 vs. Grade 3). Arrhythmia freedom 12 months after PVI was 77%, 53%, and 33% in Grades 1, 2 and 3, respectively. CONCLUSION: Localization and extent of LA-LVS modifies APW-morphology and -duration. Analysis of APW allows accurate prediction of LA-LVS and enables rapid and non-invasive estimation of arrhythmia freedom following PVI.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Liberdade , Humanos , Veias Pulmonares/cirurgia , Recidiva , Resultado do Tratamento
7.
Europace ; 20(2): 279-287, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28011800

RESUMO

Aims: The number of pulmonary vein isolation (PVI) ablation procedures is steadily increasing worldwide resulting in a substantial radiation exposure to patients and operators. The aim of our study was to reduce radiation exposure during these procedures to a critical amount without compromising patient safety. Methods and results: First, we assessed radiation exposure for primary PVI procedures over time (2005-2015) at the University Heart Center Freiburg-Bad Krozingen. Second, we prospectively evaluated in 52 patients, the efficacy and safety of a novel radiation reduction program (particularly applying an enhanced fluoroscopy pulse dose-reduction and optimized 3D-mapping system use). In 2035 primary PVI procedures, radiation exposure, assessed as estimated effective dose (eED in mSv, dose area product * 0.002 * conversion factor for females), fluoroscopy-time, and procedure-time decreased significantly from 2005 to 2015 (e.g. eED decreased from 9.3 (interquartile range (IQR) 6.4-13.4) mSv to 0.9 (IQR 0.5-1.6) mSv, p for trend <0.001). Importantly, application of the enhanced radiation reduction program further reduced eED to 0.4 mSv (IQR 0.3-0.6, P < 0.001 vs. control), a value not significantly different from slow-pathway ablation procedures (P = 0.41). Multiple linear regression analysis identified the radiation reduction program as the only independent variable associated with a decrease in radiation exposure. Conclusion: Radiation exposure during PVI decreased over the last decade and can further be reduced significantly by the implementation of an enhanced radiation reduction program.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Doses de Radiação , Exposição à Radiação/prevenção & controle , Radiografia Intervencionista , Idoso , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/fisiopatologia , Exposição à Radiação/efeitos adversos , Radiografia Intervencionista/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
8.
J Cardiovasc Electrophysiol ; 25(5): 479-484, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24384060

RESUMO

BACKGROUND: Transseptal puncture (TP) is a prerequisite for LA ablations. LA access can be gained by catheter probing in case of PFO (trans-PFO method) or puncture of the interatrial septum (IAS) using a transseptal needle. A 2nd access can again be gained via PFO, a 2nd TP or catheter probing of the previous puncture site (probe-TS method). This study investigates the risk factors and complications related to the mode of transseptal access. METHODS AND RESULTS: From August 2010 to August 2012, a total of 544 LA ablations, were performed. The mode of LA access was either a double TP or a single TP followed by the probe-TS or the trans-PFO method, respectively. TP was always guided by TEE and was successfully performed without complications in all cases. In contrast, 6/410 patients (1.5%) in whom catheter probing was performed (probe-TS, n = 4, trans-PFO, n = 2) had a dissection of the superior IAS originating from inside the oval fossa (n = 5) or perforation above the oval fossa (n = 1). Perforation into the pericardial space occurred in 4/6 patients, leading to one cardiac tamponade. In 5/6 patients, LA ablation was successfully completed, after repeated TP, despite effective anticoagulation. Patients with complications had the following characteristics: LA size 46 ± 4 mm, persistent AF (5/6), a repeat transseptal procedure (3/6) and a right-sided pouch (RSP, 5/6). CONCLUSIONS: Interatrial septum dissection/perforation, occasionally with perforation into the pericardial space, is an unreported complication of TP, especially with the catheter-probing techniques. An RSP is an unrecognized risk factor in this context and can be visualized by TEE.


Assuntos
Fibrilação Atrial/cirurgia , Flutter Atrial/cirurgia , Septo Interatrial , Cateterismo Cardíaco/métodos , Ablação por Cateter/métodos , Átrios do Coração/cirurgia , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Flutter Atrial/diagnóstico , Flutter Atrial/fisiopatologia , Septo Interatrial/diagnóstico por imagem , Septo Interatrial/lesões , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Cateteres Cardíacos , Tamponamento Cardíaco/etiologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/instrumentação , Ecocardiografia Doppler em Cores , Ecocardiografia Transesofagiana , Feminino , Forame Oval Patente/diagnóstico por imagem , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Traumatismos Cardíacos/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Punções , Radiografia Intervencionista , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
9.
J Cardiovasc Electrophysiol ; 25(3): 266-70, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24172190

RESUMO

BACKGROUND: Thrombi form mainly in the left rather than the right atria of patients with atrial fibrillation (AF), the reason of this predilection being unknown. OBJECTIVE: The purpose of this study was to investigate whether atrial-specific differences in endothelial damage, leukocyte activation, platelet stimulation, and tissue factor activity occur in patients with AF. METHODS: Twenty-two patients (16 men, 6 women; age 56 ± 8 years; 16 paroxysmal AF, 6 persistent AF) with AF undergoing pulmonary vein isolation were investigated. Blood samples from the left and the right atrium were obtained at the start of the procedure. Microparticles (MPs) released by apoptotic/stimulated cells were measured by capture assays. Their procoagulant abilities were quantified by functional prothrombinase and tissue factor assays and their cellular origin were determined (endothelium, platelet, leukocyte). Platelet reactivity was evaluated by whole blood flow cytometry for expression of platelet P-selectin (CD62P), active glycoprotein IIb/IIIa receptor (PAC-1). Platelet aggregation was evaluated using ADP, TRAP and collagen-induced whole blood aggregometry. RESULTS: There were no atrial-specific differences in the levels of total procoagulant MPs, leukocyte-derived-MPs or platelet-derived MPs. Conversely, endothelial-derived MPs and tissue factor activity and collagen-induced platelet aggregation were slightly elevated in the right atrium (P < 0.05). CONCLUSIONS: Our data show no evidence for increased thrombogenic status in the left atrium that would account for its greater propensity for thrombus formation in patients with AF.


Assuntos
Fibrilação Atrial/diagnóstico , Endotélio Vascular/patologia , Átrios do Coração/patologia , Ativação Plaquetária/fisiologia , Trombose/diagnóstico , Fibrilação Atrial/sangue , Micropartículas Derivadas de Células/metabolismo , Micropartículas Derivadas de Células/patologia , Endotélio Vascular/metabolismo , Feminino , Átrios do Coração/metabolismo , Humanos , Leucócitos/metabolismo , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Tromboplastina/metabolismo , Trombose/sangue
10.
J Cardiovasc Electrophysiol ; 25(7): 701-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24575734

RESUMO

INTRODUCTION: Pulmonary vein reconnection (PVR) is an important cause of AF recurrence after ablation. With the advent of force sensing catheters, catheter-tissue contact can be determined quantitatively. Since contact force (CF) plays a major role in determining the characteristics of RF lesion, we prospectively assessed the mechanisms of PVR with regard to catheter-contact and lesion distances in patients undergoing AF ablation. METHODS AND RESULTS: Forty symptomatic AF patients underwent wide circumferential PV isolation (PVI) with SmartTouch™ CF catheter. The exact locations of acute PVI and spontaneous or adenosine-provoked PVR were annotated on CARTO. One thousand nine hundred and twenty-six RF lesions isolated 153 PVs. PVR occurred in 35 (23%) PVs: 22 (63%) adenosine-provoked and 13 (37%) spontaneous. CF was significantly lower at PVR versus PVI sites for RF lesions within 6 mm from these sites: mean CF 5 versus 11 g (P < 0.0001) and force-time integral (FTI) 225 versus 415 gs (P < 0.0001); 86% of PVR occurred with a mean CF < 10 g (FTI < 400 gs); and the remaining 14% occurred at ablation sites with a long interlesion distance (≥5 mm) despite mean CF ≥ 10 g. Eighty percent of PVR sites were located anteriorly. There were no significant differences in regard to arrhythmia freedom between the patients without (69%) versus with PVR (67%; P = 1.0). CONCLUSIONS: Acutely durable PVI can be achieved when RF lesions are delivered with a mean CF ≥ 10 g and an interlesion distance <5 mm. The majority of PVR occur anteriorly due to inadequate CF or long interlesion distances.


Assuntos
Fibrilação Atrial/cirurgia , Cateterismo Cardíaco/efeitos adversos , Ablação por Cateter/efeitos adversos , Veias Pulmonares/cirurgia , Adenosina , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Cateterismo Cardíaco/instrumentação , Cateterismo Cardíaco/métodos , Cateteres Cardíacos , Ablação por Cateter/instrumentação , Ablação por Cateter/métodos , Técnicas Eletrofisiológicas Cardíacas , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Veias Pulmonares/fisiopatologia , Recidiva , Fatores de Tempo , Transdutores de Pressão , Resultado do Tratamento
11.
J Immunol ; 189(4): 1868-77, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22772448

RESUMO

The proteasome is responsible for the generation of most epitopes presented on MHC class I molecules. Treatment of cells with IFN-γ leads to the replacement of the constitutive catalytic subunits ß1, ß2, and ß5 by the inducible subunits low molecular mass polypeptide (LMP) 2 (ß1i), multicatalytic endopeptidase complex-like-1 (ß2i), and LMP7 (ß5i), respectively. The incorporation of these subunits is required for the production of numerous MHC class I-restricted T cell epitopes. The structural features rather than the proteolytic activity of an immunoproteasome subunit are needed for the generation of some epitopes, but the underlying mechanisms have remained elusive. Experiments with LMP2-deficient splenocytes revealed that the generation of the male HY-derived CTL-epitope UTY(246-254) was dependent on LMP2. Treatment of male splenocytes with an LMP2-selective inhibitor did not reduce UTY(246-254) presentation, whereas silencing of ß1 activity increased presentation of UTY(246-254). In vitro degradation experiments showed that the caspase-like activity of ß1 was responsible for the destruction of this CTL epitope, whereas it was preserved when LMP2 replaced ß1. Moreover, inhibition of the ß5 subunit rescued the presentation of the influenza matrix 58-66 epitope, thus suggesting that a similar mechanism can apply to the exchange of ß5 by LMP7. Taken together, our data provide a rationale why the structural property of an immunoproteasome subunit rather than its activity is required for the generation of a CTL epitope.


Assuntos
Apresentação de Antígeno/imunologia , Cisteína Endopeptidases/química , Cisteína Endopeptidases/imunologia , Complexo de Endopeptidases do Proteassoma/química , Complexo de Endopeptidases do Proteassoma/imunologia , Animais , Antígenos Virais/imunologia , Western Blotting , Eletroforese em Gel Bidimensional , Epitopos de Linfócito T/imunologia , Humanos , Imunoprecipitação , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção
12.
J Cardiovasc Electrophysiol ; 24(12): 1328-35, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23889915

RESUMO

INTRODUCTION: Irrigated tip radiofrequency (RF) catheter ablation is the most frequently used technology for pulmonary vein isolation (PVI). The purpose of this study was to compare the efficiency and the safety of 2 different open irrigated tip RF ablation catheters. METHODS AND RESULTS: A total of 160 patients with symptomatic AF (29% persistent, 68% male, 61 ± 10 years) were randomized to circumferential PVI using 2 different irrigated tip catheters: (1) the novel Thermocool SF(®) with a porous tip (56 holes) or (2) the Thermocool(®) catheter with 6 irrigation holes at the distal tip in both power- and temperature-controlled modes. PVI procedural time and RF duration were significantly shorter with SF(®) versus Thermocool(®) catheter: 104.5 versus 114 minutes (P = 0.023) and 35.4 minutes versus 39.9 minutes (P < 0.001), respectively. Similarly, the total fluoroscopy time and dose were shorter with SF(®) versus. Thermocool(®) catheter: 21 minutes versus 24 minutes (P = 0.02) and 1014.5 µGy*m(2) versus 1377 µGy*m(2) (P < 0.0001), respectively. Irrigation volume was lower with SF(®): 600 mL versus 1100 mL, (P < 0.0001) and the rates of complications were not significantly different (0.6% vs 0.49%, P = 0.66). At 20.5 ± 7.5 months follow-up, there were no significant differences with regard to arrhythmia freedom between SF(®) (59.2%) and TC® groups (59.3%), (P = 0.61). CONCLUSIONS: Using the novel irrigated tip SF catheter, PVI is achieved within a shorter ablation and procedural durations. The underlying mechanisms and potential differences in RF lesion size remain to be elucidated.


Assuntos
Fibrilação Atrial/cirurgia , Cateteres Cardíacos , Ablação por Cateter/instrumentação , Veias Pulmonares/cirurgia , Irrigação Terapêutica/instrumentação , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Desenho de Equipamento , Feminino , Fluoroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Porosidade , Estudos Prospectivos , Veias Pulmonares/fisiopatologia , Doses de Radiação , Radiografia Intervencionista/métodos , Fatores de Tempo , Resultado do Tratamento
13.
J Electrocardiol ; 44(3): 346-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21419423

RESUMO

BACKGROUND: Risk stratification of asymptomatic individuals with type 1 electrocardiogram (ECG) phenotype of Brugada syndrome (BS) still remains controversial. This study investigated the long-term prognosis of asymptomatic subjects with spontaneous or drug-induced type 1 ECG pattern of BS. METHODS AND RESULTS: Data from 33 apparently healthy individuals (30 males; age, 43.6 ± 13.4 years) with spontaneous (n = 12) or drug-induced (n = 21) type 1 ECG pattern of BS were retrospectively analyzed. Thirteen subjects (39.4%) displayed a positive family history of BS and/or sudden cardiac death. Electrophysiologic study was performed in 16 subjects, and programed right ventricular stimulation induced polymorphic ventricular tachycardia in 9 (56.3%) of them. A cardioverter defibrillator was implanted in 6 cases. During a mean follow-up period of 5.3 ± 2.8 years, all subjects remained asymptomatic. None of them had syncope or cardioverter defibrillator discharges due to ventricular arrhythmias. CONCLUSIONS: Asymptomatic individuals with spontaneous or drug-induced type 1 ECG phenotype of BS display a benign clinical course during long-term follow-up.


Assuntos
Síndrome de Brugada/induzido quimicamente , Síndrome de Brugada/fisiopatologia , Eletrocardiografia/métodos , Adulto , Síndrome de Brugada/terapia , Desfibriladores Implantáveis , Feminino , Seguimentos , Humanos , Masculino , Fenótipo , Prognóstico , Estudos Retrospectivos , Medição de Risco
15.
J Cardiovasc Electrophysiol ; 21(2): 120-5, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19793145

RESUMO

BACKGROUND: Pulmonary vein (PV) isolation using a balloon-mounted cryoablation system is a new technology for the percutaneous treatment of atrial fibrillation (AF). Complete PV occlusion during balloon ablation has been shown to predict successful electrical isolation. The aim of this study was to correlate mechanical PV occlusion with changes in a pressure curve recorded at the distal tip of the cryoballoon catheter. METHODS AND RESULTS: We analyzed 51 PVs in 12 patients (61 +/- 6 years old) with paroxysmal AF. At first, PV occlusion via the cryoballoon was documented by changes in the pressure curve. Once the PV is occluded, the pressure curve registered in the vein converts from a left atrial pressure curve to a pulmonary artery pressure curve: the PV wedge curve. Occlusion was then confirmed by transesophageal echocardiography (TEE). Following 2 cryoablation applications, electrical PV isolation was assessed with a circumferential mapping catheter. Under the exclusive guidance of changes in the pressure curve at the tip of the cryoballoon, mechanical occlusion confirmed by TEE was achieved in 47 of 51 PVs (92%). Three PVs required further TEE guidance to achieve occlusion. All 50 occluded veins were electrically isolated after cryoablation. One right inferior vein, which could not be occluded with the balloon, displayed conduction post cryoablation and was isolated by focal ablation. CONCLUSIONS: Occlusion and electrical isolation of PVs during cryoballoon ablation can be predicted by the appearance of a PV wedge curve at the tip of the catheter. This new straightforward parameter may facilitate the procedure.


Assuntos
Fibrilação Atrial/cirurgia , Determinação da Pressão Arterial/métodos , Cateterismo/métodos , Criocirurgia/métodos , Sistema de Condução Cardíaco/cirurgia , Veias Pulmonares/cirurgia , Fibrilação Atrial/diagnóstico , Determinação da Pressão Arterial/instrumentação , Cateterismo/instrumentação , Criocirurgia/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
Europace ; 12(2): 271-4, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19897501

RESUMO

AIMS: The present study investigated whether several ECG markers of ventricular repolarization are associated with ventricular tachycardia/fibrillation (VT/VF) inducibility in subjects with type 1 ECG pattern of Brugada syndrome (BS). METHODS AND RESULTS: The clinical data of 23 individuals (19 males, age 42.69 +/- 14.63) with spontaneous (n = 10) or drug-induced (n = 13) type 1 ECG pattern of BS who underwent programmed ventricular stimulation were analysed. Sustained VT/VF was induced in 17 subjects (74%) and was significantly associated with the presence of spontaneous type 1 ECG of BS (P = 0.012). Among the studied ECG repolarization markers, subjects with inducible VT/VF displayed an increased T(peak)-T(end) interval in leads V(2) (88.82 +/- 15.70 vs. 78.33 +/- 4.08 ms, P = 0.02) and V(6) (76.33 +/- 10.08 vs. 66.66 +/- 5.16 ms, P = 0.04) and a greater T(peak)-T(end)/QT ratio in lead V(6) (0.214 +/- 0.028 vs. 0.180 +/- 0.014, P = 0.009) compared with those without arrhythmias. Ventricular tachycardia/fibrillation inducibility was not associated with arrhythmic events during a mean follow-up period of 4.61 +/- 2.14 years (P = 0.739). CONCLUSION: The T(peak)-T(end) interval and T(peak)-T(end)/QT ratio were associated with VT/VF inducibility in BS. The utility of T(peak)-T(end)/QT ratio as a new marker of arrhythmogenesis in BS requires further studies, including a large number of patients.


Assuntos
Síndrome de Brugada/fisiopatologia , Eletrocardiografia , Taquicardia Ventricular/epidemiologia , Taquicardia Ventricular/fisiopatologia , Adulto , Ajmalina/efeitos adversos , Antiarrítmicos/efeitos adversos , Biomarcadores , Síndrome de Brugada/induzido quimicamente , Feminino , Flecainida/efeitos adversos , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fibrilação Ventricular/epidemiologia , Fibrilação Ventricular/fisiopatologia
18.
Acta Cardiol ; 65(2): 171-6, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20458824

RESUMO

OBJECTIVE: The present study aimed to evaluate the diagnostic value of specific ECG markers in the differentiation of common type atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT) via a concealed accessory pathway. METHODS: One hundred and ten ECGs with paroxysmal narrow QRS complex, short RP tachycardia were evaluated. Subjects with overt ventricular pre-excitation during sinus rhythm were excluded from the study. The mechanism of arrhythmia was established during the electrophysiological study and confirmed by the efficacy of radiofrequency ablation. RESULTS: Of the 110 patients, 74 displayed common type AVNRT and 36 AVRT. Predictors of AVNRT were the presence of pseudo r'-waves in lead V1 [sensitivity 39.19%; specificity 97.14%; positive predictive value (PPV) 96.67%; negative predictive value (NPV) 43.04%] and pseudo S-waves in inferior leads (sensitivity 28.38%; specificity 94.29%; PPV 91.30%; NPV 38.37%). In the setting of visible P-waves, an RP interval < or =90 ms favoured the diagnosis of AVNRT (sensitivity 57.14%; specificity 80.65%). Predictors of AVRT were QRS alternans (sensitivity 50%; specificity 89.19%; PPV 69.23%; NPV 78.57%) as well as ST-segment alterations during tachycardia. The overall sensitivity, specificity, PPV and NPV of ST-segment depression for discriminating AVRT from AVNRT were 97.22%, 58.11%, 53.03%, 97.73%, respectively. Similarly, the sensitivity, specificity, PPV and NPV of ST-segment elevation in lead aVR were 94.44%, 58.11%, 52.31%, and 95.56%, respectively. Multiple logistic regression analysis showed that ST-segment depression [(odds ratio (OR): 12.67, 95% confidence interval (CI): 1.77-90.81, P = 0.011)] and QRS alternans (OR: 9.43, 95% CI: 1.38-64.37, P = 0.022) displayed the highest predictive ability favouring the diagnosis of AVRT. CONCLUSIONS: Twelve-lead ECG parameters may help to differentiate the mechanism of supraventricular tachycardia prior to the ablation procedure.


Assuntos
Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Taquicardia Reciprocante/diagnóstico , Adulto , Idoso , Algoritmos , Ablação por Cateter , Estudos de Coortes , Intervalos de Confiança , Diagnóstico Diferencial , Eletrocardiografia/métodos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Taquicardia Reciprocante/fisiopatologia
19.
J Cardiovasc Electrophysiol ; 20(11): 1197-202, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19563358

RESUMO

BACKGROUND: Pulmonary vein (PV) isolation using a balloon-mounted cryoablation system is a new technology for the percutaneous treatment of atrial fibrillation (AF). Transesophageal echocardiography (TEE) allows real-time visualization of cryoballoon positioning and successful vein occlusion via color Doppler. We hypothesized that PV mechanical occlusion monitored with TEE could predict effective electrical isolation. METHODS: We studied 124 PVs in 30 patients. Under continuous TEE assessment, a cryoballoon was placed in the antrum of each PV aiming for complete PV occlusion as documented by color Doppler. At the end of the procedure, PV electrical isolation was evaluated using a circumferential mapping catheter. RESULTS: Of the 124 PVs studied, 123 (99.2%) could be visualized by TEE: the antrum was completely visualized in 80 of them (64.5%), partially in 36 (29.0%), and only disappearance of proximal flow could be observed in the remaining 7 PVs (5.7%). Vein occlusion could be achieved in 111 of the 123 (90.2%) visualized PVs. Postinterventional mapping demonstrated electrical isolation in 109 of 111 occluded PVs (positive predictive value 98.2%) and only in 1 of 12 nonoccluded PVs (negative predictive value 91.7%, P < 0.001). After a mean follow-up of 7.4 +/- 3.7 months, 73.3% of patients remained in sinus rhythm without antiarrhythmic drugs. CONCLUSION: Color Doppler documented PV occlusion during cryoballoon ablation can predict effective electrical isolation.


Assuntos
Fibrilação Atrial/cirurgia , Cateterismo/métodos , Criocirurgia/métodos , Ecocardiografia Transesofagiana/métodos , Veias Pulmonares/cirurgia , Cirurgia Assistida por Computador/métodos , Cateterismo/tendências , Criocirurgia/tendências , Feminino , Sistema de Condução Cardíaco/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento
20.
Methods Mol Biol ; 564: 173-86, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19544023

RESUMO

In the last years, intracellular protein degradation by the proteasome has become a focus area of scientific interest. Here, we describe a proteomics approach for the molecular mapping of the constituents of the proteolytically active core particle, the constitutive 20S proteasome from mouse intestine. In addition to the proteomics workflow widely used for protein isolation, gel electrophoretic separation, in-gel digestion, and UV-MALDI mass spectrometry, high-resolution Fourier transform ion cyclotron resonance mass spectrometry using infrared-MALDI ionisation (IR-MALDI FTICR-MS) has been employed as an efficient method for protein identification by peptide mass fingerprint. The 20S proteasome subunits alpha1-alpha7 and beta1-beta7 were completely and unambiguously identified. In addition to subunits beta1 and beta2, the corresponding inducible subunits being part of the immuno-proteasome were identified. The subunit beta5i was found to completely replace the corresponding constitutive subunit, suggesting a high proteolytic activity of the intestinal proteasome leading to increased production of antigenic peptides. The high mass accuracy in the low ppm range and resolution of FTICR-MS provide direct identifications of individual proteins as mixtures such as components resulting from incomplete electrophoretic separation. In addition, the comparison of UV- and IR-MALDI FTICR-MS may provide details of fragmentation and rearrangement reactions that may occur under UV-MALDI ionisation conditions.


Assuntos
Intestinos/enzimologia , Complexo de Endopeptidases do Proteassoma/análise , Proteoma/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Animais , Eletroforese em Gel Bidimensional , Camundongos , Camundongos Endogâmicos BALB C , Fragmentos de Peptídeos/análise , Mapeamento de Peptídeos , Espectrofotometria Ultravioleta
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