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INTRODUCTION: Catheter ablation for atrial fibrillation (AF) is a common therapeutic strategy for patients with either paroxysmal AF (PAF) or persistent AF (persAF), but long-term ablation success rates are imperfect. Maintenance of sinus rhythm immediately before ablation with antiarrhythmic drug (AAD) therapy has been associated with improved outcomes in patients undergoing ablation. Amiodarone has superior efficacy relative to other AADs. Whether failure of amiodarone to maintain sinus rhythm before ablation for either PAF or persAF is associated with poor outcomes is unknown. METHODS: A total of 307 patients who received amiodarone in a 1-year window before undergoing catheter ablation for AF were included. Patients were divided into amiodarone success (n = 183) and amiodarone failure (n = 124) groups based on the response to pre-ablation amiodarone treatment. Analysis of procedural outcomes as a function of response to amiodarone therapy was performed. Patients were followed for at least 12 months postablation, to assess outcomes (adverse events and arrhythmia recurrence). Procedural success was defined by the absence of documented arrhythmia (>30 s) without any antiarrhythmic agents beyond a 90-day blanking period. RESULTS: Following ablation for either PAF or persAF, freedom from any recurrent atrial arrhythmia at 1 year was 57.7% for the entire cohort. One-year freedom from recurrent arrhythmia in the amiodarone success group was comparable to that in the amiodarone failure group (55.7% vs. 60.5%; p = .54). Success rates following ablation did not vary by the response to amiodarone when analyzed for PAF or persAF subgroups. CONCLUSION: Failure to restore and maintain sinus rhythm with amiodarone before ablation for either PAF or persAF is not a predictor of ablation procedural failure. Amiodarone failure alone should not deter practitioners from considering ablation therapy for patients with AF.
Assuntos
Técnicas de Ablação , Amiodarona , Fibrilação Atrial , Ablação por Cateter , Humanos , Amiodarona/uso terapêutico , Fibrilação Atrial/cirurgia , Antiarrítmicos/uso terapêutico , Ablação por Cateter/efeitos adversosRESUMO
BACKGROUND: Studies have identified significant sex-based differences and disparities in the clinical presentation and treatment of atrial fibrillation (AF). Studies have shown women are less likely to be referred for catheter ablation, are older at the time of ablation, and are more likely to have recurrence after ablation. However, in most studies investigating AF ablation outcomes, the female cohorts were relatively small. The impact of sex on the outcome and safety of ablation procedures is still unclear. OBJECTIVE: To investigate sex-based differences in outcomes and complications after AF catheter ablation, with a significant female cohort METHOD: In this retrospective study, patients undergoing AF ablation from January 1, 2014, to March 31, 2021, were included. We investigated clinical characteristics, duration and progression of AF, number of EP appointments from diagnosis to ablation, procedural data, and procedure complications. RESULTS: Total of 1346 patients underwent first catheter ablation for AF during this period, including 896 (66.5%) male and 450 (33.4%) female patients. Female patients were older at the time of ablation (66.2 vs. 62.4 years; p < .001). Women had higher CHA2 DS2 -VASc (congestive heart failure, hypertension, age, diabetes, stroke, vascular disease, sex category) scores (3 vs. 2; p < .001) than men, expectedly, as the female sex warrants an additional point. 25.3% female patients had PersAF at the time of diagnosis versus 35.3% male patients (p < .001). At the time of ablation, 31.8% female patients had PersAF as compared to 43.1% male patients (p < .001), indicating progression of PAF to PersAF in both sexes. Women tried more AADs than men before ablation (1.13 vs. 0.98; p = .002). Male and female patients had no statistically significant difference in (a) arrhythmia recurrence at 1-year post ablation (27.7% vs. 30%; p = .38) or (b) procedural complication rate (1.8% vs. 3.1%; p = .56). CONCLUSION: Female patients were older and had higher CHA2 DS2 -VASc scores compared to males at the time of AF ablation. Women tried more AADs than men before ablation. One-year arrhythmia recurrence rates and procedural complications were similar in both sexes. No sex-based differences were observed in safety and efficacy of ablation.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Humanos , Masculino , Feminino , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Fatores de Tempo , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , RecidivaRESUMO
BACKGROUND: There are limited data describing the experience of radiofrequency (RF) vs. cryoballoon (CB) ablation for atrial fibrillation (AF) among elderly patients in the United States. METHODS: We conducted a retrospective analysis of patients ≥75 years of age undergoing index RF vs. CB ablation between January 2014 and May 2020 at our center. The choice of ablation technique was left to the operator's discretion. Major complications and efficacy, defined as freedom from any atrial tachyarrhythmia (ATA) lasting ≥30 s after one year of follow-up, were assessed in patients with index RF vs. CB ablation. RESULTS: In our cohort of 186 patients, the median age was 78 (76-81) years, 54.8% were men, and 39.2% had persistent AF. The median CHA2DS2-VASc score was 4 (3-4), while the median duration of AF was 3 (1-7) years. The majority (n = 112, 60.2%) underwent RF ablation. The median procedure time was significantly lower in CB group (197 vs 226.5 min, p=<0.01). The incidence of complications was similar in the two sub-groups (RF: 1.8% vs. CB: 2.7%, p = 0.67). Similarly, arrhythmia-free survival rate on antiarrhythmic drugs at 1-year follow-up remained statistically comparable (63.4% vs. 68.9%, p = 0.33) between patients receiving RF vs. CB ablation. CONCLUSION: The safety and efficacy of RF vs. CB ablation for AF remained comparable in our cohort of patients older than 75 years. CB ablation was associated with a shorter procedure time.
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Coronavirus disease 2019 (COVID-19) is a global pandemic that is wreaking havoc on the health and economy of much of human civilization. Electrophysiologists have been impacted personally and professionally by this global catastrophe. In this joint article from representatives of the Heart Rhythm Society, the American College of Cardiology, and the American Heart Association, we identify the potential risks of exposure to patients, allied healthcare staff, industry representatives, and hospital administrators. We also describe the impact of COVID-19 on cardiac arrhythmias and methods of triage based on acuity and patient comorbidities. We provide guidance for managing invasive and noninvasive electrophysiology procedures, clinic visits, and cardiac device interrogations. In addition, we discuss resource conservation and the role of telemedicine in remote patient care along with management strategies for affected patients.
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Arritmias Cardíacas/etiologia , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Eletrocardiografia , Pandemias , Pneumonia Viral/epidemiologia , Guias de Prática Clínica como Assunto , American Heart Association , Arritmias Cardíacas/terapia , COVID-19 , Cardiologia , Reanimação Cardiopulmonar , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Humanos , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , SARS-CoV-2 , Sociedades Médicas , Telemedicina , Triagem , Estados UnidosRESUMO
BACKGROUND: Data related to electrophysiologic characteristics of atypical atrial flutter (AFL) following atrial fibrillation (AF) ablation and its prognostic value on repeat ablation success are limited. METHODS: We studied consecutive patients who underwent a repeat left atrial (LA) ablation procedure for either recurrent AF or atypical AFL, at least 3 months after index AF ablation, between January 2012 and July 2019. The demographics, clinical history, procedural data, complications, and 1-year arrhythmia-free survival rates were recorded for each subject after the first repeat ablation. RESULTS: A total of 336 patients were included in our study. Among these 336 patients, 102 underwent a repeat ablation procedure for atypical AFL and 234 underwent a repeat ablation procedure for recurrent AF. The mean age was 63.7 ± 10.7 years, and 72.6% of patients were men. The atypical AFL cohort had significantly higher LA diameters (4.6 vs. 4.4 cm, p = .04) and LA volume indices (LAVi; 85.1 vs. 75.4 ml/m2 , p = .03) compared to AF patients at repeat ablation. Atypical AFL patients were more likely to have had index radiofrequency (RF) ablation (as opposed to cryoballoon) than recurrent AF patients (98% vs. 81%, p = .01). Atypical AFLs were roof-dependent in 35.6% and peri-mitral in 23.8% of cases. Major complications at repeat ablation occurred in 0.9% of the total cohort. Arrhythmia-free survival at one year was significantly higher in the recurrent atypical AFL compared to the recurrent AF cohort (75.5 vs. 65.0%, p = .04). CONCLUSION: In our series, roof-dependent flutter is the most common form of atypical atrial flutter post AF ablation. Patients developing atypical AFL after index AF ablation have greater LA dimensions than patients with recurrent AF. The success rate of first repeat ablation is significantly higher among patients with recurrent atypical AFL as compared to recurrent AF after index AF ablation.
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Fibrilação Atrial , Flutter Atrial , Ablação por Cateter , Veias Pulmonares , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Flutter Atrial/diagnóstico por imagem , Flutter Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Átrios do Coração , Humanos , Masculino , Pessoa de Meia-Idade , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Transesophageal echocardiography (TEE) is variably performed before atrial fibrillation (AF) ablation to evaluate left atrial appendage (LAA) thrombus. We describe our experience with transitioning to the pre-ablation cardiac computed tomography (CT) approach for the assessment of LAA thrombus during the COVID-19 pandemic. METHODS: We studied consecutive patients undergoing AF ablation at our center. The study cohort was divided into pre- versus post-COVID groups. The pre-COVID cohort included ablations performed during the 1 year before the COVID-19 pandemic; pre-ablation TEE was used routinely to evaluate LAA thrombus in high-risk patients. Post-COVID cohort included ablations performed during the 1 year after the COVID-19 pandemic; pre-ablation CT was performed in all patients, with TEE performed only in patients with LAA thrombus by CT imaging. The demographics, clinical history, imaging, and ablation characteristics, and peri-procedural cerebrovascular events (CVEs) were recorded. RESULTS: A total of 637 patients (pre-COVID n = 424, post-COVID n = 213) were studied. The mean age was 65.6 ± 10.1 years in the total cohort, and the majority were men. There was a significant increase in pre-ablation CT imaging from pre- to post-COVID cohort (74.8% vs. 93.9%, p ≤ .01), with a significant reduction in TEEs (34.6% vs. 3.7%, p ≤ .01). One patient in the post-COVID cohort developed CVE following negative pre-ablation CT. However, the incidence of peri-procedural CVE between both cohorts remained statistically unchanged (0% vs. 0.4%, p = .33). CONCLUSION: Implementation of pre-ablation CT-only imaging strategy with selective use of TEE for LAA thrombus evaluation is not associated with increased CVE risk during the COVID-19 pandemic.
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Apêndice Atrial , Fibrilação Atrial , COVID-19 , Ablação por Cateter , Trombose , Idoso , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Ecocardiografia Transesofagiana , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Trombose/diagnóstico por imagem , Trombose/epidemiologia , TomografiaRESUMO
INTRODUCTION: Atrial fibrillation (AF) ablation is successful in 60%-80% of optimal candidates, with many patients requiring repeat procedures. We performed a detailed examination of electrophysiologic findings and clinical outcomes associated with first repeat AF ablations in the era of contact force-sensing radiofrequency (RF) catheters. METHODS: We retrospectively studied patients who underwent their first repeat AF ablations for symptomatic, recurrent AF at our center between 2013 and 2019. All repeat ablations were performed using contact force-sensing RF catheters. Pulmonary vein (PV) reconnections at repeat ablation and freedom from atrial arrhythmia 1 year after repeat ablation were evaluated. We further assessed these findings based on AF classification at the time of presentation for repeat ablation, index RF versus cryoballoon (CB) ablation, and duration (≥3 versus <3 years) between index and repeat procedures. RESULTS: Among 300 patients, there were 136 (45.3%) who presented for their first repeat ablations in persistent AF. During repeat ablation, at least one PV reconnection was found in 257 (85.6%) patients, while 159 (53%) had three to four reconnections. There was a similar distribution of reconnections among patients with persistent versus paroxysmal AF (mean: 2.7 ± 1.3 vs. 2.9 ± 1.2; p = .341), index RF versus CB ablation (mean: 2.8 ± 1.3 vs. 2.9 ± 1.2; p = .553), and ≥3 versus <3 years between index and repeat procedures (mean: 3.0 ± 1.1 vs. 2.7 ± 1.3; p = .119). At repeat ablation, the PVs were re-isolated in all patients, and additional non-PV ablation was performed in 171 (57%) patients. Freedom from atrial arrhythmia at 1-year follow-up after repeat ablation was 66%, similar among those with persistent versus paroxysmal AF (65.4% vs. 66.5%; p = .720), index RF versus CB ablation (66.7% vs. 68.9%; p = .930), and ≥3 versus <3 years between index and repeat ablations (64.4% vs. 66.7%; p = .760). Major complications occurred in a total of 4 (1.3%) patients. CONCLUSION: In a contemporary cohort of patients receiving their first repeat AF ablations using contact force-sensing RF catheters, PV reconnections were common, and freedom from atrial arrhythmia was 66% at 1-year follow-up. The distributions of PV reconnections and rates of freedom from atrial arrhythmia were similar, based on persistent versus paroxysmal AF at presentation for repeat ablation, index RF versus CB ablation, and duration between index and repeat procedures. The incidence of major complications was very low.
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Fibrilação Atrial , Ablação por Cateter , Criocirurgia , Veias Pulmonares , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Humanos , Veias Pulmonares/cirurgia , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The effects of atrial fibrillation (AF) catheter ablation on the left atrium (LA) are poorly understood. OBJECTIVES: To examine short- and long-term associations of AF catheter ablation with LA function using cardiac magnetic resonance (CMR). METHODS: Fifty-one AF patients (mean age 56 ± 8 years) underwent CMR at baseline, 1 day (n = 17) and 11 ± 2 months after ablation (n = 38). LA phasic volumes, emptying fractions (LAEF), and longitudinal strain were measured using feature-tracking CMR. LA fibrosis was quantified using late gadolinium enhancement (LGE). RESULTS: There were no acute changes in volume; however, active, total LAEF, and peak LA strain decreased significantly compared to the baseline. During long-term follow-up, there was a decrease in maximum but not minimum LA volume (from 99 ± 5.2 ml to 89 ± 4.7 ml; p = .009) and a decrease in total LAEF (from 43 ± 1.8% to 39 ± 2.0%; p = .001). In patients with AF recurrence, LA volumes were unchanged. However, total LAEF decreased from 38 ± 3% to 33 ± 3%; p = .015. Patients without AF recurrence had no changes in LA functional parameters during follow-up. The amount of LA LGE at long-term follow-up was higher compared to the baseline, however, was significantly less compared to immediately post-procedure (37 ± 1.9% vs. 47 ± 2.8%; p = .015). A higher increase in LA LGE extent compared to the baseline was associated with a greater decrease in total LAEF (r = -.59; p < .001). CONCLUSIONS: LA function is impaired acutely following AF catheter ablation. However, long-term changes of LA function are associated positively with the successful restoration of sinus rhythm and inversely with increased LA LGE.
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Fibrilação Atrial , Ablação por Cateter , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Meios de Contraste , Gadolínio , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
AIMS: The exact circuit of atrioventricular nodal re-entrant tachycardia (AVNRT) remains elusive. To assess the location and dimensions of the AVNRT circuit. METHODS AND RESULTS: Both typical and atypical AVNRT were induced at electrophysiology study of 14 patients. We calculated the activation time of the fast and slow pathways, and consequently, the length of the slow pathway, by assuming an average conduction velocity of 0.04 mm/ms in the nodal area. The distance between the compact atrioventricular node and the slow pathway ablating electrode was measured on three-dimensionally reconstructed fluoroscopic images obtained in diastole and systole. We also measured the length of the histologically discrete right inferior nodal extension in 31 human hearts. The length of the slow pathway was calculated to be 10.8 ± 1.3 mm (range 8.2-12.8 mm). The distance from the node to the ablating electrode was measured in five patients 17.0 ± 1.6 mm (range 14.9-19.2 mm) and was consistently longer than the estimated length of the slow pathway (P < 0.001). The length of the right nodal inferior extension in histologic specimens was 8.1 ± 2.3 mm (range 5.3-13.7 mm). There were no statistically significant differences between these values and the calculated slow pathway lengths. CONCLUSION: Successful ablation affects the tachycardia circuit without necessarily abolishing slow conduction, probably by interrupting the circuit at the septal isthmus.
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Ablação por Cateter , Taquicardia por Reentrada no Nó Atrioventricular , Taquicardia Ventricular , Nó Atrioventricular/diagnóstico por imagem , Nó Atrioventricular/cirurgia , Fascículo Atrioventricular , Eletrocardiografia , Frequência Cardíaca , Humanos , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Taquicardia por Reentrada no Nó Atrioventricular/cirurgiaRESUMO
INTRODUCTION: Advanced interatrial block (IAB) on a 12-lead electrocardiogram (ECG) is a predictor of stroke, incident atrial fibrillation (AF), and AF recurrence after catheter ablation. The objective of this study was to determine which features of IAB structural remodeling is associated with left atrium (LA) magnetic resonance imaging structure and function. METHODS/RESULTS: We included 152 consecutive patients (23% nonparoxysmal AF) who underwent preprocedural ECG and cardiac magnetic resonance (CMR) in sinus rhythm before catheter ablation of AF. IAB was defined as P-wave duration ≥120 ms, and was considered partial if P-wave was positive and advanced if P-wave had a biphasic morphology in inferior leads. From cine CMR and late gadolinium enhancement, we derived LA maximum and minimum volume indices, strain, LA fibrosis, and LA dyssynchrony. A total of 77 patients (50.7% paroxysmal) had normal P-wave, 52 (34.2%) partial IAB, and 23 (15.1%) advanced IAB. Patients with advanced IAB had significantly higher LA minimum volume index (25.7 vs 19.9 mL/m2 , P = .010), more LA fibrosis (21.9% vs 13.1%, P = .020), and lower LA maximum strain rate (0.99 vs 1.18, P = .007) than those without. Advanced IAB was independently associated with LA (minimum [P = .032] and fibrosis [P = .009]). P-wave duration was also independently associated with LA fibrosis (ß = .33; P = .049) and LA mechanical dyssynchrony (ß = 2.01; P = .007). CONCLUSION: Advanced IAB is associated with larger LA volumes, lower emptying fraction, and more fibrosis. Longer P-wave duration is also associated with more LA fibrosis and higher LA mechanical dyssynchrony.
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Fibrilação Atrial , Bloqueio Interatrial , Idoso , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Fibrilação Atrial/diagnóstico por imagem , Meios de Contraste , Eletrocardiografia , Feminino , Fibrose , Gadolínio , Átrios do Coração/diagnóstico por imagem , Humanos , Bloqueio Interatrial/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Pacemaker battery depletion triggers alert for replacement notification and results in automatic reprogramming, which has been shown to be associated with relevant cardiorespiratory symptoms and adverse clinical events. OBJECTIVE: Determine if electrocardiogram (ECG) pacing features may be predictive of pacemaker battery depletion and clinical risk. METHODS: This is an ECG substudy of a cohort analysis of 298 subjects referred for pacemaker generator replacement from 2006 to 2017. Electronic medical record review was performed; clinical, ECG, and pacemaker characteristics were abstracted. We applied two ECG prediction rules for pacemaker battery depletion that are relevant to all major pacemaker manufacturers except Boston Scientific and MicroPort: (1) atrial pacing not at a multiple of 10 and (2) nonsynchronous ventricular pacing not at a multiple of 10, to determine diagnostic sensitivity, specificity, and risk in applicable ECG subjects. RESULTS: We excluded 32 subjects not at replacement notification or duplicate surgeries. Overall, 176 of 266 subjects (66.2%) demonstrated atrial pacing or nonsynchronous ventricular pacing on preoperative ECG. When utilizing both rules, 139 of 176 preoperative ECGs and 12 of 163 postoperative ECGs met criteria for battery depletion yielding reasonable sensitivity (79.0%), high specificity (92.6%), and a positive likelihood ratio of 11.6:1. These rules were associated with significant increase in cardiorespiratory symptoms (P < .001) and adverse clinical events (P < .025). CONCLUSIONS: The "Rules of Ten" provided reasonable sensitivity and specificity for detecting replacement notification in pacemaker subjects with an applicable ECG. This ECG tool may help clinicians identify most patients with pacemaker battery depletion at significant clinical risk.
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Fontes de Energia Elétrica , Eletrocardiografia/métodos , Falha de Equipamento , Marca-Passo Artificial , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeAssuntos
Fibrilação Atrial , Ablação por Cateter , Criocirurgia , Fibrilação Atrial/cirurgia , HumanosRESUMO
INTRODUCTION: Ablation of atrial vagal ganglia has been associated with improved pulmonary vein isolation (PVI) outcomes. Disruption of vagal reflexes results in heart rate (HR) increase. We investigated the association between HR change after PVI and freedom from atrial fibrillation (AF) at 1 year. METHODS AND RESULTS: Patients who underwent PVI for paroxysmal AF were identified from the Johns Hopkins Hospital AF registry. Electrocardiograms taken pre-PVI and post-PVI were used to determine the change in HR. Patients followed-up at 3, 6, and 12 months. Of 257 patients (66% male, age 59+/-11 years), 134 (52%) remained free from AF at 1 year. The average HR increased from 60.6 ± 11.3 beats per minute (bpm) pre-PVI to 70.7 ± 12.0 bpm post-PVI. Patients with recurrence of AF had lower post-PVI HR than those who remained free from AF (67.8 ± 0.2 vs 73.3 ± 13.0 bpm; P <.001). The probability of AF recurrence at 1-year decreased as the change in HR increased (estimated odds ratio [OR], 0.83; 95% confidence interval [CI, 0.74-0.93]; P = .002). HR increase more than 15 bpm was associated with the lowest odds of AF recurrence (estimated OR, 0.39; 95% [0.17-0.85]; P = .018) compared to HR decrease. CONCLUSIONS: Resting HR was found to increase after PVI. Increase in HR more than 15 bpm has a positive association with remaining free from atrial fibrillation at 1 year.
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Fibrilação Atrial/cirurgia , Ablação por Cateter , Criocirurgia , Gânglios Parassimpáticos/cirurgia , Frequência Cardíaca , Veias Pulmonares/cirurgia , Nervo Vago/cirurgia , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Criocirurgia/efeitos adversos , Intervalo Livre de Doença , Feminino , Gânglios Parassimpáticos/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Veias Pulmonares/inervação , Recidiva , Reflexo , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Nervo Vago/fisiopatologiaRESUMO
Cellular reprogramming of somatic cells to patient-specific induced pluripotent stem cells (iPSCs) enables in vitro modelling of human genetic disorders for pathogenic investigations and therapeutic screens. However, using iPSC-derived cardiomyocytes (iPSC-CMs) to model an adult-onset heart disease remains challenging owing to the uncertainty regarding the ability of relatively immature iPSC-CMs to fully recapitulate adult disease phenotypes. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited heart disease characterized by pathological fatty infiltration and cardiomyocyte loss predominantly in the right ventricle, which is associated with life-threatening ventricular arrhythmias. Over 50% of affected individuals have desmosome gene mutations, most commonly in PKP2, encoding plakophilin-2 (ref. 9). The median age at presentation of ARVD/C is 26 years. We used previously published methods to generate iPSC lines from fibroblasts of two patients with ARVD/C and PKP2 mutations. Mutant PKP2 iPSC-CMs demonstrate abnormal plakoglobin nuclear translocation and decreased ß-catenin activity in cardiogenic conditions; yet, these abnormal features are insufficient to reproduce the pathological phenotypes of ARVD/C in standard cardiogenic conditions. Here we show that induction of adult-like metabolic energetics from an embryonic/glycolytic state and abnormal peroxisome proliferator-activated receptor gamma (PPAR-γ) activation underlie the pathogenesis of ARVD/C. By co-activating normal PPAR-alpha-dependent metabolism and abnormal PPAR-γ pathway in beating embryoid bodies (EBs) with defined media, we established an efficient ARVD/C in vitro model within 2 months. This model manifests exaggerated lipogenesis and apoptosis in mutant PKP2 iPSC-CMs. iPSC-CMs with a homozygous PKP2 mutation also had calcium-handling deficits. Our study is the first to demonstrate that induction of adult-like metabolism has a critical role in establishing an adult-onset disease model using patient-specific iPSCs. Using this model, we revealed crucial pathogenic insights that metabolic derangement in adult-like metabolic milieu underlies ARVD/C pathologies, enabling us to propose novel disease-modifying therapeutic strategies.
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Displasia Arritmogênica Ventricular Direita/metabolismo , Displasia Arritmogênica Ventricular Direita/patologia , Células-Tronco Pluripotentes Induzidas/patologia , Modelos Biológicos , Transporte Ativo do Núcleo Celular , Idade de Início , Apoptose/genética , Displasia Arritmogênica Ventricular Direita/genética , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Reprogramação Celular , Meios de Cultura/farmacologia , Corpos Embrioides/efeitos dos fármacos , Corpos Embrioides/fisiologia , Metabolismo Energético/genética , Ácidos Graxos/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Glucose/metabolismo , Glicólise , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Lipogênese/genética , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/patologia , PPAR alfa/metabolismo , PPAR gama/metabolismo , Fenótipo , Placofilinas/genética , Fatores de Tempo , beta Catenina/metabolismoRESUMO
INTRODUCTION: Catheter ablation is common for patients with symptomatic, drug-refractory atrial fibrillation (AF). Obesity is a known risk factor for incident AF. The impact of obesity on AF ablation outcomes is incompletely understood. We sought to determine the impact of elevated body mass index (BMI) on pulmonary vein isolation (PVI) procedural outcomes and associated complications. METHODS AND RESULTS: We evaluated patients undergoing PVI from 2001 to 2015, dividing them into four groups: normal weight (BMI ≥ 18.5 to < 25), overweight (BMI ≥ 25 to < 30), obese (BMI > 30 to < 40), and morbidly obese (BMI ≥ 40). Demographic and procedural characteristics, complications, and ablation outcomes were compared among groups. A total of 701 patients (146 time-matched controls, 227 overweight, 244 obese, and 84 morbidly obese) with complete demographic, procedural, and follow-up data were included. Increasing BMI correlated positively with HTN, OSA, CHA2 DS2 -VASC score, and persistent AF (P ≤ 0.001 for all associations). Radiofrequency application time and intraprocedural heparin dose increased with BMI (P ≤ 0.001). Arrhythmia recurrence at 1 year was 39.9% in controls, while higher in all high-BMI groups (overweight, 51.3%; obese, 57%; morbidly obese, 58.1 %; P = 0.007 for all versus controls). Impact of BMI on AF recurrence was not seen in persistent AF patients. Complication rates across groups were similar. CONCLUSIONS: AF recurrence after catheter ablation is higher in overweight, obese, and morbidly obese patients comparing to normal-weight controls, driven primarily by outcomes differences in paroxysmal AF patients. Complications were not associated with increased BMI.
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Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Criocirurgia/efeitos adversos , Obesidade/complicações , Sobrepeso/complicações , Veias Pulmonares/cirurgia , Potenciais de Ação , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Índice de Massa Corporal , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Sobrepeso/diagnóstico , Veias Pulmonares/fisiopatologia , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure to clinical personnel. While the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. ACC leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. "Optimal Use of Ionizing Radiation in Cardiovascular Imaging - Best Practices for Safety and Effectiveness" is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. "Part I: Radiation Physics and Radiation Biology" addresses radiation physics, dosimetry and detrimental biologic effects. "Part II: Radiologic Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection" covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy). For each modality, it includes the determinants of radiation exposure and techniques to minimize exposure to both patients and to medical personnel.
Assuntos
Técnicas de Imagem Cardíaca/normas , Doenças Cardiovasculares/diagnóstico por imagem , Exposição Ocupacional/normas , Doses de Radiação , Exposição à Radiação/normas , Benchmarking/normas , Consenso , Medicina Baseada em Evidências/normas , Humanos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/prevenção & controle , Segurança do Paciente/normas , Valor Preditivo dos Testes , Exposição à Radiação/efeitos adversos , Exposição à Radiação/prevenção & controle , Medição de Risco , Fatores de RiscoRESUMO
The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure for clinical personnel. Although the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. The American College of Cardiology leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. Optimal Use of Ionizing Radiation in Cardiovascular Imaging: Best Practices for Safety and Effectiveness is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. Part I: Radiation Physics and Radiation Biology addresses the issue of medical radiation exposure, the basics of radiation physics and dosimetry, and the basics of radiation biology and radiation-induced adverse effects. Part II: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy) and will be published in the next issue of the Journal.
Assuntos
Técnicas de Imagem Cardíaca/normas , Doenças Cardiovasculares/diagnóstico por imagem , Doses de Radiação , Exposição à Radiação/normas , Benchmarking/normas , Consenso , Medicina Baseada em Evidências/normas , Humanos , Segurança do Paciente/normas , Valor Preditivo dos Testes , Exposição à Radiação/efeitos adversos , Exposição à Radiação/prevenção & controle , Medição de Risco , Fatores de RiscoRESUMO
Aims: Historical studies of ablation of atrioventricular nodal re-entrant tachycardia (AVNRT) have shown high long-term success rates and low complication rates. The potential impact of several recent practice trends has not been described. This study aims to characterize recent clinical practice trends in AVNRT ablation and their associated success rates and complications. Methods and results: Patients undergoing initial ablation of AVNRT between 1 July 2005 and 30 June 2015 were included in this study. Patient demographics and procedural data were abstracted from procedure reports. Follow-up data, including AVNRT recurrence and complications, was evaluated through electronic medical record review. In total, 877 patients underwent catheter ablation for AVNRT. By the last recorded year, three-dimension (3D) electroanatomical mapping (EAM) was used in 36.2%, 43.2% included anaesthesia, and 23.1% utilized irrigated catheters. Long-term procedural success was 95.5%. The use of anaesthesia, 3D EAM, and irrigated ablation catheters were not associated with differences in success. The presence of an atrial 'echo' or 'AH' jump at the end of an acutely successful procedure was not associated with long-term recurrence (P = 0.18, P = 0.15, respectively). Complications, including AV block requiring a pacemaker (0.4%), were uncommon. Conclusion: In a large, contemporary cohort, catheter ablation for AVNRT remains highly successful with low complications rates. The increased use of anaesthesia as well as modern mapping and ablation tools were not associated with changes in clinical outcomes. Further prospective evaluation of such contemporary practices is warranted given the lack of evidence to support their escalating use.