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BACKGROUND: Atrial arrhythmias are common in patients with implantable cardioverter-defibrillator (ICD). External shocks and internal cardioversion through commanded ICD shock for electrical cardioversion are used for rhythm-control. However, there is a paucity of data on efficacy of external versus internal cardioversion and on the risk of lead and device malfunction. We hypothesized that external cardioversion is noninferior to internal cardioversion for safety, and superior for successful restoration of sinus rhythm. METHODS: Consecutive patients with ICD undergoing elective cardioversion for atrial arrhythmias at 13 centers were randomized in 1:1 fashion to either internal or external cardioversion. The primary safety end point was a composite of surrogate events of lead or device malfunction. Conversion of atrial arrhythmia to sinus rhythm was the primary efficacy end point. Myocardial damage was studied by measuring troponin release in both groups. RESULTS: N=230 patients were randomized. Shock efficacy was 93% in the external cardioversion group and 65% in the internal cardioversion group (P<0.001). Clinically relevant adverse events caused by external or internal cardioversion were not observed. Three cases of pre-existing silent lead malfunction were unmasked by internal shock, resulting in lead failure. Troponin release did not differ between groups. CONCLUSIONS: This is the first randomized trial on external vs internal cardioversion in patients with ICDs. External cardioversion was superior for the restoration of sinus rhythm. The unmasking of silent lead malfunction in the internal cardioversion group suggests that an internal shock attempt may be reasonable in selected ICD patients presenting for electrical cardioversion. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03247738.
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Arritmias Cardíacas/terapia , Fibrilação Atrial/terapia , Desfibriladores Implantáveis , Cardioversão Elétrica/métodos , Idoso , Idoso de 80 Anos ou mais , Falha de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
AIMS: Catheter ablation (CA) of ventricular arrhythmias is one of the most challenging electrophysiological interventions with an increasing use over the last years. Several benefits must be weighed against the risk of potentially life-threatening complications which necessitates a steady reevaluation of safety endpoints. Therefore, the aims of this study were (i) to investigate overall in-hospital mortality in patients undergoing such procedures and (ii) to identify variables associated with in-hospital mortality in a German-wide hospital network. METHODS AND RESULTS: Between January 2010 and September 2018, administrative data provided by 85 Helios hospitals were screened for patients with main or secondary discharge diagnosis of ventricular tachycardia (VT) or premature ventricular contractions (PVCs) in combination with an arrhythmia-related CA using ICD- and OPS codes. In 5052 cases (mean age 60.9 ± 14.3 years, 30.1% female) of 30 different hospitals, in-hospital mortality was 1.27% with a higher mortality in patients ablated for VT (1.99%, n = 2, 955) compared to PVC (0.24%, n = 2, 097, P < 0.01). Mortality rates were 2.06% in patients with ischaemic heart disease (IHD, n = 2, 137), 1.47% in patients with non-ischaemic structural heart disease (NIHD, n = 1, 224), and 0.12% in patients without structural heart disease (NSHD, n = 1, 691). Considering different types of hospital admission, mortality rates were 0.35% after elective (n = 2, 825), 1.60% after emergency admission/hospital transfer <24 h (n = 1, 314) and 3.72% following delayed hospital transfer >24 h after initial admission (n = 861, P < 0.01 vs. elective admission and emergency admission/hospital transfer <24 h). In multivariable analysis, a delayed hospital transfer >24 h [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.59-3.28, P < 0.01], the occurrence of procedure-related major adverse events (OR 6.81, 95% CI 2.90-16.0, P < 0.01), Charlson Comorbidity Index (CCI, OR 2.39, 95% CI 1.56-3.66, P < 0.01) and its components congestive heart failure (OR 8.04, 95% CI 1.71-37.8, P < 0.01), and diabetes mellitus (OR 1.59, 95% CI 1.13-2.22, P < 0.01) were significantly associated with in-hospital death. CONCLUSIONS: We reported in-hospital mortality rates after CA of ventricular arrhythmias in the largest multicentre, administrative dataset in Germany which can be implemented in quality management programs. Aside from comorbidities, a delayed hospital transfer to a CA performing centre is associated with an increased in-hospital mortality. This deserves further studies to determine the optimal management strategy.
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Ablação por Cateter , Taquicardia Ventricular , Idoso , Feminino , Alemanha/epidemiologia , Mortalidade Hospitalar , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirurgia , Resultado do TratamentoRESUMO
Aims: Atrial fibrillation (AFib) and atrial flutter (AFlut) are common arrhythmias with increased use of invasive procedures. A steady re-evaluation of relevant safety endpoints is recommended and both quality management and pay-for-performance programs are evolving. Therefore, the aims of this study were (i) to investigate and report overall in-hospital mortality and mortality of invasive arrhythmia-related procedures and (ii) to identify mortality predictors in a German-wide hospital network. Methods and results: Administrative data provided by 78 Helios hospitals between 2010 and 2017 were examined using International Statistical Classification of Diseases and Related Health Problems- and Operations and Procedures-codes to identify patients with AFib or AFlut as main discharge diagnosis or secondary diagnosis combined with invasive arrhythmia-related interventions. In 161 502 patients, in-hospital mortality was 0.6% with a significant decrease from 0.75% to 0.5% (P < 0.01) during the observational period. In multivariable analysis, age [odds ratio (OR) 2.69, 95% confidence interval (CI) 2.36-3.05; P < 0.01], high centre volume (OR 0.57, 95% CI 0.50-0.65; P < 0.01), emergency hospital admission (OR 1.57, 95% CI 1.38-1.79; P < 0.01), and Charlson Comorbidity Index (CCI, OR 4.95, 95% CI 4.50-5.44; P < 0.01) were found as independent predictors of in-hospital mortality. Mortality rates were 0.05% for left atrial catheter ablation (CA, n = 21 744), 0.3% for right atrial CA (n = 9972), and 0.56% for implantation of a left atrial appendage occluder (n = 2309), respectively. Conclusion: We analysed for the first time in-hospital mortality rates of patients with atrial arrhythmias in a German-wide, multi-centre administrative dataset. This allows feasible, comparable, and up-to-date performance measurement of clinically important endpoints in a real-world setting which may contribute to quality management programs and towards value-based healthcare.
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Fibrilação Atrial/mortalidade , Flutter Atrial/mortalidade , Mortalidade Hospitalar , Adulto , Fatores Etários , Idoso , Fibrilação Atrial/cirurgia , Flutter Atrial/cirurgia , Ablação por Cateter , Comorbidade , Bases de Dados Factuais , Serviço Hospitalar de Emergência , Feminino , Alemanha/epidemiologia , Hospitais com Alto Volume de Atendimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Pulmonary vein isolation (PVI) has become a widely accepted therapy in patients suffering from symptomatic atrial fibrillation (AF). HYPOTHESIS: AF-free survival differs in patients with left common pulmonary vein (LCPV) after PVI with second-generation cryoballoon. METHODS: We included patients scheduled for first PVI for paroxysmal or persistent AF. Symptomatic and/or documented arrhythmia episodes (>30 seconds) were defined as AF recurrence, excluding a 3-month blanking period. RESULTS: We observed a LCPV in 37 of 270 consecutive patients (13.7%). Analyses were performed in a 1:1 propensity score matched cohort of 68 patients. During a median follow-up of 77.0 weeks, 37 patients (54.4%) had recurrent AF. The prevalence of LCPV was numerically higher in patients with AF recurrence (62.2% vs 35.5%, P = 0.051) and Kaplan-Meier analysis showed lower AF-free survival in patients with existence of a LCPV (P = 0.028). At 1-year follow-up, 70.6% of patients without versus 55.1% of patients with LCPV were free of AF. Multivariate Cox regression analysis revealed presence of a LCPV (hazard ratio [HR]: 2.996), chronic heart failure (HR: 3.423), and mitral regurgitation > I° (HR: 2.571) as predictors of AF recurrence. CONCLUSION: Patients with LCPV had significantly reduced AF-free survival after ablation with the second-generation cryoballoon, despite similar acutely successful PVIs.
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Fibrilação Atrial/cirurgia , Criocirurgia/instrumentação , Veias Pulmonares/cirurgia , Idoso , Fibrilação Atrial/diagnóstico por imagem , Angiografia Coronária , Ecocardiografia , Feminino , Fluoroscopia , Alemanha , Humanos , Masculino , Pontuação de Propensão , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Relaxin-2 (RLX) is a peptide hormone that exerts beneficial anti-fibrotic and anti-inflammatory effects in diverse models of cardiovascular disease. The goal of this study was to determine the effects of RLX treatment on the susceptibility to atrial fibrillation (AF) after myocardial infarction (MI). METHODS: Mice with cryoinfarction of the left anterior ventricular wall were treated for two weeks with either RLX (75 µg/kg/d) or vehicle (sodium acetate) delivered via subcutaneously implanted osmotic minipumps. RESULTS: RLX treatment significantly attenuated the increase in AF-inducibility following cryoinfarction and reduced the mean duration of AF episodes. Furthermore, epicardial mapping of both atria revealed an increase in conduction velocity. In addition to an attenuation of atrial hypertrophy, chronic application of RLX reduced atrial fibrosis, which was linked to a significant reduction in atrial mRNA expression of connective tissue growth factor. Transcript levels of the pro-inflammatory cytokines interleukin-6 and interleukin-1ß were reduced in RLX treated mice, but macrophage infiltration into atrial myocardium was similar in the vehicle and RLX treated groups. CONCLUSION: Treatment with RLX in mice after MI reduces susceptibility to AF due to anti-inflammatory and anti-fibrotic properties. Because to these favorable actions, RLX may become a new therapeutic option in the treatment of AF, even when complicating MI.
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Anti-Inflamatórios/uso terapêutico , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Átrios do Coração/efeitos dos fármacos , Infarto do Miocárdio/complicações , Relaxina/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Fibrilação Atrial/fisiopatologia , Cardiomegalia/etiologia , Cardiomegalia/fisiopatologia , Cardiomegalia/prevenção & controle , Feminino , Átrios do Coração/fisiopatologia , Masculino , Camundongos , Relaxina/administração & dosagemRESUMO
BACKGROUND: During aging a mosaic of normal cells and cells with mitochondrial deficiency develops in various tissues including the heart. Whether this contributes to higher susceptibility for arrhythmia following myocardial infarction (MI) is unknown. METHODS AND RESULTS: Myocardial cryoinfarction was performed in 12-month-old transgenic mice with accelerated accumulation of deletions in mitochondrial DNA. Occurrence and pathogenesis of arrhythmia was investigated after two weeks. Holter-ECG recordings revealed higher rates of premature ventricular complexes (incidence > 10/24 h: 100% vs. 20%; p = 0.048) and more severe spontaneous arrhythmia during stress test in mutant mice with MI as compared to control mice with MI. Mice with mitochondrial dysfunction exhibited longer spontaneous AV-blocks (467 ± 26 ms vs. 377 ± 24 ms; p = 0.013), an increased probability for induction of ventricular tachycardia during in vivo electrophysiological investigation (22% vs. 9%; p = 0.044), and a reduced conduction velocity in the infarct borderzone (38.5 ± 0.5 cm/s vs. 55.3 ± 0.9 cm/s; p = 0.001). Furthermore, mutant mice exhibited a significant reduction of the phospho-Cx43/Cx43 ratio in right (0.59 ± 0.04 vs. 0.85 ± 0.01; p = 0.027) and left ventricular myocardium (0.72 ± 0.01 vs. 0.86 ± 0.02; p = 0.023). CONCLUSIONS: Aging-related cardiac mosaic respiratory chain dysfunction facilitates the occurrence of spontaneous and inducible cardiac arrhythmia after myocardial infarction and is associated with slowing of electrical impulse propagation in the infarct borderzone.
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Envelhecimento , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Mitocôndrias Cardíacas , Doenças Mitocondriais/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Doenças Mitocondriais/complicações , Infarto do Miocárdio/complicaçõesRESUMO
BACKGROUND: Generalized tonic-clonic seizures (GTCS) frequently lead to emergency inpatient referrals. Laboratory blood values are routinely performed on admission to detect underlying causes and metabolic or cardiac complications. Our goal was to assess the nature and frequency of complications occurring in association with GTCS. METHODS: We retrospectively extracted data from emergency protocols and discharge letters of adult patients admitted to the Department of Epileptology between 01/2010 and 06/2015. Inclusion criteria were diagnosis of GTCS and admission via emergency services. Exclusion criteria were status epilepticus prior to admission to hospital and non-generalized seizures. RESULTS: A total of 223 patients (of 986 screened cases) were included. Overall, 1.8% required intubation while 1.3% had less severe respiratory problems. In 5.6% of patients, a transient hypoxemia was measured. Hypertensive urgencies affected 7.8% of the patients, sinus tachycardia occurred in 41.2%. Troponin I (cTNI) was determined in 75 patients and was increased in 12% of these cases. Occurrence of elevated cTNI levels was significantly correlated with patient's age. Four patients were diagnosed with NSTEMI and one patient with STEMI. Creatine kinase (CK) was increased in 59.4% of the patients, with <5-fold increases in 47%, <10-fold in 5.8% and >10-fold increases in 4.3%. Rhabdomyolysis with an >50 fold increase in CK was detected in 1.9% of patients. Prolonged disturbances of consciousness affected 5% of cases while agitation, delirium, and psychotic episodes occurred in 6.3%. Minor traumatic injuries affected 45.7% of patients. CONCLUSIONS: Troponin elevations in association with GTCS are one of the more common complications after emergency admissions especially in older patients. In our selected patient population, serious complications such as intracranial hemorrhage, myocardial infarction and acute renal failure occurred in <1% of GTCS only.
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Biomarcadores/metabolismo , Doenças Cardiovasculares/fisiopatologia , Convulsões/complicações , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Estudos Retrospectivos , Troponina I/metabolismo , Adulto JovemRESUMO
BACKGROUND: The wearable cardioverter defibrillator (WCD) has emerged as a valuable tool to protect patients with increased risk of sudden cardiac death (SCD). We sought to characterize WCD patients and to analyze predictors of ventricular arrhythmia (VA) occurrence and WCD shock delivery. METHODS AND RESULTS: One hundred fourteen patients with WCD use were included in the study. Indications were mainly ischemic cardiomyopathy (ICM; 31.6%), non-ICM (45.6%) and explantation of implantable cardioverter defibrillator due to device infection (11.4%). We observed sustained VA in 9.6% of the study population and 6.1% received an appropriate shock. VA occurred in 16.7% of ICM, 3.8% of non-ICM and 15.4% of patients with device infection. CONCLUSIONS: Our data demonstrate a very high rate of sustained VA in patients at risk for SCD during WCD use. ICM patients, including those with recent MI, bore the highest risk.
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Cardiomiopatias/fisiopatologia , Morte Súbita Cardíaca/prevenção & controle , Cardioversão Elétrica/instrumentação , Dispositivos Eletrônicos Vestíveis , Adulto , Idoso , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Visually guided laserballoon (LB) ablation has recently been introduced for pulmonary vein (PV) isolation (PVI). We analyzed efficacy and safety results of the newly introduced LB ablation technique in patients with persistent and longstanding persistent atrial fibrillation (AF), and compared this with an established standard method using the cryoballoon (CB). METHODS: A total of 35 patients with symptomatic persistent AF underwent LB ablation and were followed-up for 1 year. Results were compared to 35 patients who underwent CB ablation at the same institution and case matched for age, sex, CHA2 DS2 -VASc score, and left atrial volume. RESULTS: Complete isolation of all PVs was achieved in 68.6% in the LB and 97.1% in the CB group (P < 0.01). No significant differences were found for AF-free survival after 12 months in the complete cohort of all patients (LB: 53.3% vs CB: 70.4%; P = n.s.) and after excluding patients without complete PVI (LB: 57.8% vs CB: 72.5%; P = n.s.). LB ablation resulted in longer procedure (158.5 ± 37.9 minutes vs 110.9 ± 26.5 minutes; P < 0.01) and fluoroscopy durations (28.4 ± 11.1 minutes vs 23.5 ± 9.4 minutes; P = 0.04.), and a trend toward more major complications (14.3% vs 2.9%; P = n.s.). Procedure durations and complications declined over time and were level with CB-treated patients when reaching the last quartile of the LB patients. CONCLUSION: PVI in patients with persistent AF using the LB or the CB resulted in comparable success rates. Initial prolongations in procedure and safety parameters as a result of a learning curve effect for the LB have to be considered before starting to use this technique.
Assuntos
Angioplastia com Balão a Laser , Fibrilação Atrial/cirurgia , Criocirurgia/métodos , Veias Pulmonares/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Recent studies have demonstrated the feasibility of measuring heart rate turbulence (HRT) as a marker of baroreflex function in healthy mice. The aim of this investigation was to measure HRT in a mouse model with induced structural heart defects and to determine if there were threshold values of HRT for inducible ventricular tachycardias (VTs). METHODS AND RESULTS: HRT was measured during electrophysiological investigations 2 weeks after transverse aortic constriction (TAC, n = 13) or myocardial cryoinfarction (MCI, n = 14). Sham-operated mice served as controls (n = 8 for TAC controls and n = 9 for MCI controls). Mice with heart disease lacked an early acceleration (turbulence onset [TO]) in heart rate after extrastimulus pacing (heart disease: 0.39% [0.19%-0.59%] vs. all controls: -0.04% [-0.25-0.19%]; P < 0.01). At a cutoff value of >0.25%, TO could be used to classify mice with induced heart disease with a sensitivity of 64.0% and specificity of 88.2% (P < 0.01) but did not identify mice at higher risk of induced VTs. Animals that were susceptible to VTs (n = 8) had lower values for turbulence slope (TS) compared with noninducible mice (6.2 milliseconds/beat [3.1-9.5 milliseconds/beat] vs. 10.1 milliseconds/beat [7.2-14.2 milliseconds/beat]; P = 0.03). TS <7.8 milliseconds/beat identified mice with inducible VTs with a sensitivity of 75.0% and specificity of 75.8% (P = 0.02). CONCLUSION: Measurement of HRT is feasible in mouse models with induced structural heart disease. More abnormal values for TO were found in the presence of structural heart disease but did not predict susceptibility to VTs. Decreased TS was associated with VTs induced by programmed stimulation.
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INTRODUCTION: Right phrenic nerve palsy (PNP) is a typical complication of cryoballoon ablation of the right-sided pulmonary veins (PVs). Phrenic nerve function can be monitored by palpating the abdomen during phrenic nerve pacing from the superior vena cava (SVC pacing) or by fluoroscopy of spontaneous breathing. We sought to compare the sensitivity of these 2 techniques during cryoballoon ablation for detection of PNP. METHODS AND RESULTS: A total of 133 patients undergoing cryoballoon ablation were monitored with both SVC pacing and fluoroscopy of spontaneous breathing during ablation of the right superior PV. PNP occurred in 27/133 patients (20.0%). Most patients (89%) had spontaneous recovery of phrenic nerve function at the end of the procedure or on the following day. Three patients were discharged with persistent PNP. All PNP were detected first by fluoroscopic observation of diaphragm movement during spontaneous breathing, while diaphragm could still be stimulated by SVC pacing. In patients with no recovery until discharge, PNP occurred at a significantly earlier time (86 ± 34 seconds vs. 296 ± 159 seconds, P < 0.001). No recovery occurred in 2/4 patients who were ablated with a 23 mm cryoballoon as opposed to 1/23 patients with a 28 mm cryoballoon (P = 0.049). CONCLUSION: Fluoroscopic assessment of diaphragm movement during spontaneous breathing is more sensitive for detection PNP as compared to SVC pacing. PNP as assessed by fluoroscopy is frequent (20.0%) and carries a high rate of recovery (89%) until discharge. Early onset of PNP and use of 23 mm cryoballoon are associated with PNP persisting beyond hospital discharge.
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Fibrilação Atrial/cirurgia , Criocirurgia/efeitos adversos , Diafragma/inervação , Monitorização Intraoperatória/métodos , Paralisia/diagnóstico , Traumatismos dos Nervos Periféricos/diagnóstico , Nervo Frênico/lesões , Veias Pulmonares/cirurgia , Respiração , Adulto , Idoso , Pontos de Referência Anatômicos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Estimulação Elétrica , Feminino , Fluoroscopia , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Palpação , Paralisia/diagnóstico por imagem , Paralisia/etiologia , Paralisia/fisiopatologia , Alta do Paciente , Traumatismos dos Nervos Periféricos/diagnóstico por imagem , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervo Frênico/fisiopatologia , Nervo Frênico/cirurgia , Valor Preditivo dos Testes , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
RATIONALE: The gap junctional protein connexin (Cx) 45 is strongly expressed in the early embryonic myocardium. In the adult hearts of mice and humans, the expression mainly is restricted to the cardiac conduction system. Cx45 plays an essential role for development and function of the embryonic heart because general and cardiomyocyte-directed deficiencies of Cx45 in mice lead to embryonic lethality attributable to morphological and functional cardiovascular defects. The function of Cx45 in the adult mouse has not yet been cleared. OBJECTIVE: To clarify the function of Cx45 in the adult mouse heart. METHODS AND RESULTS: To circumvent the embryonic lethality resulting from Cx45 deficiency, mice were generated in which deletion of Cx45 specifically was induced in cardiomyocytes of adult mice. These Cx45-deficient mice were viable but showed a decrease in atrioventricular nodal conductivity. In addition, the Cx30.2 protein that is coexpressed with Cx45 in the cardiac conduction system was posttranscriptionally reduced by 70% in mutant hearts. Furthermore, deletion of both Cx45 and Cx30.2 resulted in viable mice that, however, showed stronger impairment of atrioventricular nodal conduction than the single Cx45-deficient mice. CONCLUSIONS: Cx45 is required for optimal impulse propagation in the atrioventricular node and stabilizes the level of the coexpressed Cx30.2 protein in the adult mouse heart. In contrast to the embryo, Cx45 is not essential for the viability of adult mice.
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Nó Atrioventricular/embriologia , Nó Atrioventricular/metabolismo , Conexinas/fisiologia , Coração/embriologia , Coração/fisiologia , Animais , Conexinas/deficiência , Conexinas/genética , Sistema de Condução Cardíaco/embriologia , Sistema de Condução Cardíaco/metabolismo , Camundongos , Camundongos KnockoutRESUMO
Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and a major cause of stroke. In the mammalian heart the gap junction proteins connexin40 (Cx40) and connexin43 (Cx43) are strongly expressed in the atrial myocardium mediating effective propagation of electrical impulses. Different heterozygous mutations in the coding region for Cx40 were identified in patients with AF. We have generated transgenic Cx40A96S mice harboring one of these mutations, the loss-of-function Cx40A96S mutation, as a model for atrial fibrillation. Cx40A96S mice were characterized by immunochemical and electrophysiological analyses. Significantly reduced atrial conduction velocities and strongly prolonged episodes of atrial fibrillation were found after induction in Cx40A96S mice. Analyses of the gating properties of Cx40A96S channels in cultured HeLa cells also revealed significantly lower junctional conductance and enhanced sensitivity voltage gating of Cx40A96S in comparison to Cx40 wild-type gap junctions. This is caused by reduced open probabilities of Cx40A96S gap junction channels, while single channel conductance remained the same. Similar to the corresponding patient, heterozygous Cx40A96S mice revealed normal expression levels and localization of the Cx40 protein. We conclude that heterozygous Cx40A96S mice exhibit prolonged episodes of induced atrial fibrillation and severely reduced atrial conduction velocities similar to the corresponding human patient.
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Fibrilação Atrial/genética , Fibrilação Atrial/fisiopatologia , Conexinas/genética , Sistema de Condução Cardíaco/fisiopatologia , Mutação/genética , Animais , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/metabolismo , Conexina 43/metabolismo , Conexinas/metabolismo , Eletrocardiografia , Fibrose Endomiocárdica/metabolismo , Fibrose Endomiocárdica/patologia , Fibrose Endomiocárdica/fisiopatologia , Mapeamento Epicárdico , Junções Comunicantes/genética , Células HeLa , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Humanos , Ativação do Canal Iônico , Camundongos , Camundongos Transgênicos , Transporte Proteico , Fatores de Tempo , Transfecção , Ultrassonografia , Proteína alfa-5 de Junções ComunicantesRESUMO
The cardiac intercalated disc harbors mechanical and electrical junctions as well as ion channel complexes mediating propagation of electrical impulses. Cardiac connexin43 (Cx43) co-localizes and interacts with several of the proteins located at intercalated discs in the ventricular myocardium. We have generated conditional Cx43D378stop mice lacking the last five C-terminal amino acid residues, representing a binding motif for zonula occludens protein-1 (ZO-1), and investigated the functional consequences of this mutation on cardiac physiology and morphology. Newborn and adult homozygous Cx43D378stop mice displayed markedly impaired and heterogeneous cardiac electrical activation properties and died from severe ventricular arrhythmias. Cx43 and ZO-1 were co-localized at intercalated discs in Cx43D378stop hearts, and the Cx43D378stop gap junction channels showed normal coupling properties. Patch clamp analyses of isolated adult Cx43D378stop cardiomyocytes revealed a significant decrease in sodium and potassium current densities. Furthermore, we also observed a significant loss of Nav1.5 protein from intercalated discs in Cx43D378stop hearts. The phenotypic lethality of the Cx43D378stop mutation was very similar to the one previously reported for adult Cx43 deficient (Cx43KO) mice. Yet, in contrast to Cx43KO mice, the Cx43 gap junction channel was still functional in the Cx43D378stop mutant. We conclude that the lethality of Cx43D378stop mice is independent of the loss of gap junctional intercellular communication, but most likely results from impaired cardiac sodium and potassium currents. The Cx43D378stop mice reveal for the first time that Cx43 dependent arrhythmias can develop by mechanisms other than impairment of gap junction channel function.
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Arritmias Cardíacas/metabolismo , Conexina 43/metabolismo , Junções Comunicantes/metabolismo , Miócitos Cardíacos/metabolismo , Potenciais de Ação , Fatores Etários , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatologia , Conexina 43/química , Conexina 43/genética , Eletrocardiografia Ambulatorial , Mapeamento Epicárdico , Genótipo , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Técnicas de Patch-Clamp , Fenótipo , Telemetria , Fatores de Tempo , Transfecção , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
The risk of atrioesophageal fistula after cryoballoon pulmonary vein isolation is thought to be much lower than after radiofrequency ablation, seeing that no data exist on this complication so far. We report for the first time on the occurrence of an atrioesophageal fistula 4 weeks after cryoballoon ablation at the site of the left inferior pulmonary vein. We suggest that even when using cryothermal ablation technique, an imaging modality to assess the proximity of esophagus and left atrium should be routinely performed to avoid this fatal complication.
Assuntos
Fibrilação Atrial/cirurgia , Cateteres Cardíacos , Criocirurgia/efeitos adversos , Criocirurgia/instrumentação , Fístula Esofágica/etiologia , Fístula/etiologia , Cardiopatias/etiologia , Veias Pulmonares/cirurgia , Idoso , Fibrilação Atrial/diagnóstico , Técnicas Eletrofisiológicas Cardíacas , Embolia Aérea/etiologia , Fístula Esofágica/diagnóstico por imagem , Fístula Esofágica/cirurgia , Fístula/diagnóstico por imagem , Fístula/cirurgia , Átrios do Coração/diagnóstico por imagem , Cardiopatias/diagnóstico por imagem , Cardiopatias/cirurgia , Humanos , Masculino , Estado Vegetativo Persistente/etiologia , Veias Pulmonares/diagnóstico por imagem , Reoperação , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
INTRODUCTION: In order to optimize power delivery into the myocardium during radiofrequency ablation (RFA) without overheating the electrode tip, active cooling of the tip electrode as well as electrode tips made of gold have evolved. Recently, an externally irrigated gold tip electrode ablation catheter has been developed to combine the advantages of these 2 technologies. We sought to investigate the procedural parameters tip temperature, delivered power and cooling flow requirements of the irrigated gold tip catheter in comparison to the conventional irrigated platinum iridium (Pt) tip catheter in pulmonary vein isolation (PVI) and cavotricuspid isthmus (CTI) ablation. METHODS AND RESULTS: Sixty patients referred for first PVI were randomized into ablation with irrigated gold tip catheter versus irrigated Pt tip catheter. Forty-nine patients received ablation of CTI following PVI. Mean and standard deviation from all measurements were calculated for each patient. During RFA of pulmonary veins, mean catheter tip temperature was significantly lower in the gold group (35.4 ± 0.9 °C vs 38.2 ± 0.8 °C, P < 0.001), and total amount of delivered energy was higher (1303.1 ± 81.1 W vs 1223.7 ± 115.6 W, P = 0.004). During CTI ablation, necessary saline flow was almost 2.5-fold lower in the gold group (22.5 ± 5.9 mL/min vs 52.5 ± 9.7 mL/min, P < 0.001), accompanied by significantly lower tip temperature (39.1 ± 0.6 °C vs 40.5 ± 1.4 °C, P < 0.001). CONCLUSION: The irrigated gold tip electrode allows to deliver significantly more energy at a lower electrode tip temperature in RFA of PV and CTI in comparison to the irrigated Pt tip electrode. The required saline flow during CTI ablation is much lower than in Pt.
Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/instrumentação , Catéteres , Ouro , Temperatura Alta , Platina , Veias Pulmonares/cirurgia , Irrigação Terapêutica/instrumentação , Valva Tricúspide/cirurgia , Veia Cava Inferior/cirurgia , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Desenho de Equipamento , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Veias Pulmonares/fisiopatologia , Resultado do Tratamento , Valva Tricúspide/fisiopatologia , Veia Cava Inferior/fisiopatologiaRESUMO
INTRODUCTION: Cardiogenic shock (CS) remains the leading cause of death in patients hospitalized for myocardial infarction (MI). Systemic inflammation with inappropriate vasodilatation is observed in many patients with CS and may contribute to an excess mortality rate. The purpose of this study was to determine the predictive role of serial measurements of Nt-proBNP, interleukin-6 (IL-6), and procalcitonin (PCT) for 30-day mortality in patients with CS due to MI. METHODS: The present study is a prospective single-center study including 87 patients with MI complicated by CS treated with acute revascularization and intraaortic balloon counterpulsation (IABP) support. Predictive values of plasma levels at admission (T0), after 24 hours (T1), and after 72 hours (T2) were examined according to 30-day mortality. RESULTS: Significant differences between survivors (n = 59) and nonsurvivors (n = 28) were seen for Nt-proBNP at T0, for IL-6 at T0 and T1, and for PCT at T1 and T2. According to ROC analyses, the highest accuracy predicting 30-day mortality was seen at T0 for IL-6, at T1 for PCT, and at T2 for PCT. In univariate analysis, significant values were found for Nt-proBNP at T1, and for IL-6 and PCT at all points in time. Within the multivariate analysis, age, creatinine, and IL-6 were significant determinants of 30-day mortality, in which IL-6 showed the highest level of significance. CONCLUSIONS: In patients with MI complicated by CS, IL-6 represented a reliable independent early prognostic marker of 30-day mortality. PCT revealed a significant value at later points in time, whereas Nt-proBNP seemed to be of lower relevance.
Assuntos
Calcitonina/sangue , Mortalidade Hospitalar , Interleucina-6/sangue , Infarto do Miocárdio/complicações , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Precursores de Proteínas/sangue , Choque Cardiogênico/sangue , Choque Cardiogênico/mortalidade , Injúria Renal Aguda/complicações , Idoso , Análise de Variância , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Creatinina/sangue , Feminino , Hemodinâmica , Humanos , Unidades de Terapia Intensiva , Balão Intra-Aórtico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/cirurgia , Revascularização Miocárdica , Estudos Prospectivos , Sensibilidade e Especificidade , Choque Cardiogênico/etiologia , Choque Cardiogênico/cirurgiaRESUMO
Transcatheter ablation of the pulmonary veins (PVs) has been established as a therapeutic option for patients with symptomatic atrial fibrillation. Cryothermal energy is an alternative energy source that has been developed to overcome some of the disadvantages of radiofrequency ablation. The major complication of the cryoballoon technique seems to be right-sided phrenic nerve injury (PNI) following ablation of the right superior PV. This case report describes a left-sided PNI after cryoballoon ablation of the left superior PV.