Circulation: Arrhythmia and Electrophysiology最新文献

{"title":"Cardiovascular Predictive Value and Genetic Basis of Ventricular Repolarization Dynamics.","authors":"J. Ramírez, S. van Duijvenboden, N. Aung, P. Laguna, E. Pueyo, A. Tinker, P. Lambiase, M. Orini, P. Munroe","doi":"10.1161/CIRCEP.119.007549","DOIUrl":"https://doi.org/10.1161/CIRCEP.119.007549","url":null,"abstract":"BACKGROUND\u0000Early prediction of cardiovascular risk in the general population remains an important issue. The T-wave morphology restitution (TMR), an ECG marker quantifying ventricular repolarization dynamics, is strongly associated with cardiovascular mortality in patients with heart failure. Our aim was to evaluate the cardiovascular prognostic value of TMR in a UK middle-aged population and identify any genetic contribution.\u0000\u0000\u0000METHODS\u0000We analyzed ECG recordings from 55 222 individuals from a UK middle-aged population undergoing an exercise stress test in UK Biobank (UKB). TMR was used to measure ventricular repolarization dynamics, exposed in this cohort by exercise (TMR during exercise, TMRex) and recovery from exercise (TMR during recovery, TMRrec). The primary end point was cardiovascular events; secondary end points were all-cause mortality, ventricular arrhythmias, and atrial fibrillation with median follow-up of 7 years. Genome-wide association studies for TMRex and TMRrec were performed, and genetic risk scores were derived and tested for association in independent samples from the full UKB cohort (N=360 631).\u0000\u0000\u0000RESULTS\u0000A total of 1743 (3.2%) individuals in UKB who underwent the exercise stress test had a cardiovascular event, and TMRrec was significantly associated with cardiovascular events (hazard ratio, 1.11; P=5×10-7), independent of clinical variables and other ECG markers. TMRrec was also associated with all-cause mortality (hazard ratio, 1.10) and ventricular arrhythmias (hazard ratio, 1.16). We identified 12 genetic loci in total for TMRex and TMRrec, of which 9 are associated with another ECG marker. Individuals in the top 20% of the TMRrec genetic risk score were significantly more likely to have a cardiovascular event in the full UKB cohort (18 997, 5.3%) than individuals in the bottom 20% (hazard ratio, 1.07; P=6×10-3).\u0000\u0000\u0000CONCLUSIONS\u0000TMR and TMR genetic risk scores are significantly associated with cardiovascular risk in a UK middle-aged population, supporting the hypothesis that increased spatio-temporal heterogeneity of ventricular repolarization is a substrate for cardiovascular risk and the validity of TMR as a cardiovascular risk predictor.","PeriodicalId":10167,"journal":{"name":"Circulation: Arrhythmia and Electrophysiology","volume":"46 1","pages":"e007549"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86524428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter by Sepehri Shamloo et al Regarding Article, \"Atrial Fibrillation Catheter Ablation Improves 1-Year Follow-Up Cognitive Function, Especially in Patients with Impaired Cognitive Function\".","authors":"Alireza Sepehri Shamloo, N. Dagres, G. Hindricks","doi":"10.1161/CIRCEP.119.007822","DOIUrl":"https://doi.org/10.1161/CIRCEP.119.007822","url":null,"abstract":"October 2019 1 Alireza Sepehri Shamloo, MD Nikolaos Dagres, MD Gerhard Hindricks, MD To the Editor: The term cognitive function in the context of cardiac arrhythmias was first introduced 30 years ago when evidence of cognitive impairment was reported in patients with chronic atrial fibrillation (AF). During the last decades, the topic of cognitive function assessment in AF patients has emerged as a hot topic in the field of electrophysiology; >50 studies have investigated the relationship between these 2 significant public health concerns so far.1 The recently published study conducted by Jin et al2 is groundbreaking and not only confirms findings previously reported by Bunch et al3 about the positive impact of AF ablation on cognitive function but also emphasizes the importance of considering patient-centered outcomes as end points in clinical trials. During the last few decades, hundreds of studies in the field of cardiac arrhythmias have investigated the impact of different therapeutic strategies on major clinical variables including bleeding, stroke, arrhythmia recurrence, and mortality; and a number of them have covered the psychocognitive status as main outcomes. We think that the findings of this current study call to attention the importance of including patient-centered outcomes and also patient-reported outcomes as end points in clinical trials. Currently, management of cognitive dysfunction and controlling the global burden of dementia is one of the top public health priorities designated by the World Health Organization. Moreover, we should not forget that the adherence of treatment and medication intake might be adversely affected by cognitive dysfunction, thereby negatively influencing outcomes and therapy efficiency in the patients suffering from arrhythmias. Although more investigations are required to better define the impact of AF ablation on cognitive status, the recent findings of Jin et al, in conjunction with other studies might be an indication that ablation can improve depression and cognitive function.3–5 This, if supported by further studies, might ultimately lead to the question whether it is time to consider psychocognitive impairments as new indications for AF catheter ablation. Although the current study by Jin et al helps us complete the puzzle of the association between AF, the most common cardiac arrhythmia, and cognitive function, the question which arrhythmia is associated with a greater impairment of cognitive function is still unanswered. Moreover, there is a still a lack of evidence about the impact of different arrhythmia-related procedures, including medical treatment, cardiac device implantation, ablation, or others on patients’ cognitive function. So, when we face this question: Do we need further studies in this field?; the answer is definitely yes. More specifically, the 2 main topics that in our opinion need to be addressed more intensively are (1) the epidemiological understanding of the association b","PeriodicalId":10167,"journal":{"name":"Circulation: Arrhythmia and Electrophysiology","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73241187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contemporary Management of Antiplatelet and Anticoagulation for Cardiac Implantable Device Procedures.","authors":"C. DeSimone, D. DeSimone, Y. Cha","doi":"10.1161/CIRCEP.119.007863","DOIUrl":"https://doi.org/10.1161/CIRCEP.119.007863","url":null,"abstract":"The use of oral anticoagulation and antiplatelet therapy is common among patients undergoing placement of pacemakers or defibrillators. This comes as no surprise as patients requiring cardiac implantable electronic devices (CIEDs) are older and more often have comorbidities such as atrial fibrillation, ischemic cardiomyopathy, or both. Continuation of anticoagulation confers stroke prophylaxis, whereas antiplatelet continuation is necessary in those with recent stent placement. In patients with high stroke risk, heparin bridging can be used in the perioperative setting. The concern that comes to fruition at the time of CIED implantation is the risk of not achieving adequate hemostasis intraprocedurally, as well as the risk of postimplant device pocket hematoma (DPH). DPH is fraught with several issues including patient comorbidities such as pain/discomfort, need for pocket reintervention for hematoma evacuation, increased infection risk, and significant costs associated with length of hospitalization and additional procedures.1–3","PeriodicalId":10167,"journal":{"name":"Circulation: Arrhythmia and Electrophysiology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72645750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms by Which Ranolazine Terminates Paroxysmal but Not Persistent Atrial Fibrillation.","authors":"R. Ramirez, Y. Takemoto, R. Martins, D. Filgueiras-Rama, S. Ennis, S. Mironov, Sandesh Bhushal, M. Deo, S. Rajamani, O. Berenfeld, L. Belardinelli, J. Jalife, S. Pandit","doi":"10.1161/CIRCEP.117.005557","DOIUrl":"https://doi.org/10.1161/CIRCEP.117.005557","url":null,"abstract":"BACKGROUND\u0000Ranolazine inhibits Na+ current (INa), but whether it can convert atrial fibrillation (AF) to sinus rhythm remains unclear. We investigated antiarrhythmic mechanisms of ranolazine in sheep models of paroxysmal (PxAF) and persistent AF (PsAF).\u0000\u0000\u0000METHODS\u0000PxAF was maintained during acute stretch (N=8), and PsAF was induced by long-term atrial tachypacing (N=9). Isolated, Langendorff-perfused sheep hearts were optically mapped.\u0000\u0000\u0000RESULTS\u0000In PxAF ranolazine (10 μmol/L) reduced dominant frequency from 8.3±0.4 to 6.2±0.5 Hz (P<0.01) before converting to sinus rhythm, decreased singularity point density from 0.070±0.007 to 0.039±0.005 cm-2 s-1 (P<0.001) in left atrial epicardium (LAepi), and prolonged AF cycle length (AFCL); rotor duration, tip trajectory, and variance of AFCL were unaltered. In PsAF, ranolazine reduced dominant frequency (8.3±0.5 to 6.5±0.4 Hz; P<0.01), prolonged AFCL, increased the variance of AFCL, had no effect on singularity point density (0.048±0.011 to 0.042±0.016 cm-2 s-1; P=ns) and failed to convert AF to sinus rhythm. Doubling the ranolazine concentration (20 μmol/L) or supplementing with dofetilide (1 μmol/L) failed to convert PsAF to sinus rhythm. In computer simulations of rotors, reducing INa decreased dominant frequency, increased tip meandering and produced vortex shedding on wave interaction with unexcitable regions.\u0000\u0000\u0000CONCLUSIONS\u0000PxAF and PsAF respond differently to ranolazine. Cardioversion in the former can be attributed partly to decreased dominant frequency and singularity point density, and prolongation of AFCL. In the latter, increased dispersion of AFCL and likely vortex shedding contributes to rotor formation, compensating for any rotor loss, and may underlie the inefficacy of ranolazine to terminate PsAF.","PeriodicalId":10167,"journal":{"name":"Circulation: Arrhythmia and Electrophysiology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87007134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response by Jin et al to Letter Regarding Article, \"Atrial Fibrillation Catheter Ablation Improves 1-Year Follow-Up Cognitive Function, Especially in Patients With Impaired Cognitive Function\".","authors":"M. Jin, Tae‐Hoon Kim, Ki-Woon Kang, H. Yu, J. Uhm, B. Joung, Moon‐Hyoung Lee, Eosu Kim, H. Pak","doi":"10.1161/CIRCEP.119.007880","DOIUrl":"https://doi.org/10.1161/CIRCEP.119.007880","url":null,"abstract":"","PeriodicalId":10167,"journal":{"name":"Circulation: Arrhythmia and Electrophysiology","volume":"228 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83674885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of Atrial Fibrillation Ablation in Morbidly Obese Patients Following Bariatric Surgery Compared With a Nonobese Cohort.","authors":"E. Donnellan, O. Wazni, M. Kanj, A. Hussein, B. Baranowski, B. Lindsay, A. Aminian, W. Jaber, P. Schauer, W. Saliba","doi":"10.1161/CIRCEP.119.007598","DOIUrl":"https://doi.org/10.1161/CIRCEP.119.007598","url":null,"abstract":"BACKGROUND\u0000Morbid obesity is associated with unacceptable high recurrence rates following atrial fibrillation ablation. The role of risk-factor modification including weight loss and improved glycemic control in reducing arrhythmia recurrence following ablation has been highlighted in recent years. In this study, we compared arrhythmia recurrence rates in morbidly obese patients who underwent prior bariatric surgery (BS) with those of nonobese patients following atrial fibrillation ablation in addition to morbidly obese patients who did not undergo BS.\u0000\u0000\u0000METHODS\u0000This was a single-center observational cohort study. We matched 51 morbidly obese patients [body mass index ≥40 kg/m2] who had undergone prior BS in a 2:1 manner with 102 nonobese patients and 102 morbidly obese patients without prior BS on the basis of age, sex, and timing of atrial fibrillation ablation. Our primary outcome of interest was arrhythmia recurrence.\u0000\u0000\u0000RESULTS\u0000From the time of BS to ablation, BS was associated with a significant reduction in body mass index (47.6±9.3 to 36.7±7; P<0.0001), glycated hemoglobin (6.7±1.5 to 5.8±0.6; P<0.0001), and systolic blood pressure (145±13 to 118±11; P<0.0001). During a mean follow-up of 29±13 months following ablation, recurrent arrhythmia occurred in 10/51 (20%) patients in the BS group compared with 25/102 (24.5%) patients in the nonobese group and 56 (55%) patients in the non-BS morbidly obese group (P<0.0001). No procedural complications were observed in the BS group.\u0000\u0000\u0000CONCLUSIONS\u0000Bariatric surgery is associated with a reduction in arrhythmia recurrence following atrial fibrillation ablation in morbidly obese patients to those of nonobese patients. Morbidly obese patients should be considered for BS before atrial fibrillation ablation.","PeriodicalId":10167,"journal":{"name":"Circulation: Arrhythmia and Electrophysiology","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83184112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Bypassing Traditional Weight-Loss the Answer for Atrial Fibrillation?","authors":"M. Middeldorp, D. Lau, P. Sanders","doi":"10.1161/CIRCEP.119.007864","DOIUrl":"https://doi.org/10.1161/CIRCEP.119.007864","url":null,"abstract":"Cardiovascular risk factors have been recognized to contribute to abnormal atrial remodeling leading to increased incident atrial fibrillation (AF) as well as AF progression and poorer outcomes with rhythm control strategies.1 There has been an increasing focus on obesity as a modifiable risk factor contributing to the AF substrate because of its rising prevalence.2 In an individual with metabolic syndrome, a stepwise increase in the AF risk has been described with increasing number of risk components including impaired fasting glucose, elevated blood pressure, increased waist circumference, and dyslipidemia.3 Fortunately, the abnormal AF substrate has been shown to be partially reversible when the underlying risk factors are aggressively targeted.4–8 The risk factor management clinic targeted weight-loss of at least 10% with dietary control, frequent moderate-intensity exercise up to 250 min/wk, blood pressure <130/80 mm Hg, glycaemic control with HbA1c ≤6.5%, active screening for obstructive sleep apnea with continuous positive airway pressure therapy to achieve apnea-hypopnea index <5/h, complete smoking cessation, alcohol consumption to <30 g/wk and lipid management.9 These strategies have resulted in reducing AF burden and symptoms, improving catheter ablation outcomes, and reversal of AF accompanied by beneficial reverse cardiac remodeling.4–8 Notably, the subjects included in these studies have mean body mass index (BMI) in the range of 30 to 34 kg/m2. Data remain lacking in those who are morbidly obese (BMI ≥40 kg/m2) and with regards to alternate weightloss strategy. A single-center observational study in obese individuals with a BMI of 38±4 kg/m2 and long-standing persistent AF failed to observe improvement in AF symptoms or burden despite significant weight-loss and raised the possibility of a point of no return in terms of the impact of weight-loss.10 It is in this context that the series of articles presented by Donnellan et al11,12 on the role of bariatric surgery (BS) on the outcomes of AF ablation in morbidly obese individuals further advances our knowledge on the importance of risk factor management in the spectrum of obese individuals undergoing ablation. In their first report, they present data on 239 patients who were morbidly obese and underwent AF ablation (defined as BMI ≥40 or ≥35 kg/m2 with obesity-related complications).11 Of these 51 had undergone BS before ablation. At a mean follow-up of 36 months after ablation, 20% who had undergone BS compared to 61% without BS had recurrent arrhythmia (P<0.0001).11 These results are further expanded using the same cohort in a study published in the Journal.12 In this article, the authors compared in a 2:1 manner the 51 morbidly obese patients who underwent BS with ageand gender-matched 102 nonobese and 102 morbidly obese patients without prior BS who underwent catheter ablation around the same time period. The BMI between the 3 groups was significantly different: 25.6±3 kg/m2 in t","PeriodicalId":10167,"journal":{"name":"Circulation: Arrhythmia and Electrophysiology","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74430465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote Magnetic Versus Manual Catheter Navigation for Atrial Fibrillation Ablation: A Meta-Analysis.","authors":"S. Virk, Saurabh Kumar","doi":"10.1161/CIRCEP.119.007517","DOIUrl":"https://doi.org/10.1161/CIRCEP.119.007517","url":null,"abstract":"October 2019 1 Catheter ablation of atrial fibrillation (AF) is a technically challenging procedure with suboptimal long-term success rates, non-negligible risk of major complications, and significant radiation exposure. In recent years, remote magnetic navigation (RMN) systems have emerged that offer increased precision and greater stability of catheter-tissue contact. Despite considerable enthusiasm surrounding the potential benefits of RMN systems, a rigorous analysis of their impact on the clinical outcomes and procedural efficiency of AF ablation is lacking. We thus conducted a meta-analysis to assess the relative safety and efficacy of RMN versus manual catheter navigation (MCN) for AF ablation. We searched Medline, EMBASE, and CENTRAL (Cochrane Central Register of Controlled Trials) databases for controlled studies comparing outcomes of AF ablation performed with RMN versus MCN. The primary efficacy end point was freedom from AF at ≥1-year follow-up. The primary safety end point was major periprocedural complications. Secondary end points included fluoroscopy and procedure durations. Meta-analyses were performed using random-effects models. Fifteen observational studies met criteria for inclusion, involving a total of 3246 patients (RMN=1475; MCN=1771; Table).1–15 Compared with MCN, RMN was associated with reduced major periprocedural complications (relative risk, 0.51; 95% CI, 0.29–0.91; I2=0%; P=0.02). In the 12 studies with ≥1-year median followup, late recurrence of AF was not significantly reduced (relative risk, 0.97; 95% CI, 0.89–1.05; I2=0%; P=0.43). Fluoroscopy times were significantly shorter with RMN (mean difference, 13.3 minutes; 95% CI, 6.9–19.7; I2=99%; P<0.001) but total procedure (mean difference, 51.3 minutes; 95% CI, 32.0–70.6; I2=94%; P<0.001) and radiofrequency ablation (mean difference, 15.7 minutes; 95% CI, 8.2–23.2; I2=94%; P<0.001) durations were significantly longer. In our meta-analysis, RMN was associated with almost 50% lower risk of major procedural complications compared with MCN. The enhanced safety of RMN may be because of lower contact force exerted by magnetic-tipped catheters and their increased flexibility. Although prior studies have largely failed to demonstrate a significant risk reduction, they were likely underpowered because of their small sample sizes and low event rates.1,3,5,9,12,13 Of note, the population in this metaanalysis represents a relatively low-risk AF cohort with preserved left ventricular function in the majority of patients and few comorbidities. Further studies are thus required to assess whether the safety benefits of RMN translate to higher-risk AF ablation cohorts. Long-term freedom from AF following catheter ablation is dependent on the formation of durable transmural lesions that maintain bidirectional conduction block between ablated sites and surrounding cardiac tissue. Stability of cathetertissue contact is a key determinant of lesion size and transmurality. It has thus be","PeriodicalId":10167,"journal":{"name":"Circulation: Arrhythmia and Electrophysiology","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75296224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remotely Navigated Ablations in Ventricle Myocardium Result in Acute Lesion Size Comparable to Force-Sensing Manual Navigation.","authors":"J. Jež, G. Caluori, T. Jadczyk, F. Lehár, M. Pešl, Tomas Kulik, S. Belaskova, Václav Kubeš, Z. Stárek","doi":"10.1161/CIRCEP.119.007644","DOIUrl":"https://doi.org/10.1161/CIRCEP.119.007644","url":null,"abstract":"October 2019 1 Ventricular arrhythmias are one of the most life-threatening conditions. Radiofrequency ablation (RFA) is one of the most important treatment options for ventricular tachycardia. The therapy is constantly advancing with modern technology implementation.1 RFA invasive treatment is commonly performed via catheter with the support of 3-dimensional electroanatomic mapping systems,2 with either manual navigation (MAN) or robotic remote magnetic-navigated (RMN) catheters3 (Figure [A]). A comparative and contact force-stratified biophysical evidence of the RMN ablation features is still missing and might impair further spreading of the technique and its benefits. The data that support the findings of this study are available from the corresponding author upon reasonable request. The protocol used in this study was approved by the Ethical Commission of Veterinary and Pharmaceutical University in Brno. The study was performed on ten 6-month-old female large white swine (weight 50–60 kg). The animals were prepared and monitored as previously reported.4 The animals were divided into 5 groups of 2 pigs, according to target force (MAN-5G, -10G, -15G, and -20G to compare with RMN). Carto 3 (Biosense Webster Inc) was used to support navigation and ablation. Each animal underwent 8 endocardial RFA applications in selected areas of the left ventricle (Figure [B]) Orientation of the catheter tip to the wall of the heart was as perpendicular as possible. The same generator settings were used in all study groups (40 W with limited power if the temperature exceeded 50°C, maximum duration of 60 seconds, irrigation rate of 20 mL/min). Whole hearts were fixed in 10% PFA and scanned in transversal view by 9.4T MRI (Soucek et al, under review). Selected lesions were then cut on the transversal plane and prepared for histopathologic examination via hematoxylin/ eosin staining. If not otherwise stated, continuous data are presented as raw means±SDs. For groups comparisons, the significance levels were calculated using the F test with Kenward-Roger adjustment. An ablation composite index (ACI) was implemented in this study, to integrate all the procedural parameters and findings, defined as Equation 1:","PeriodicalId":10167,"journal":{"name":"Circulation: Arrhythmia and Electrophysiology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75968666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Ablation of TASK-1 (Tandem of P Domains in a Weak Inward Rectifying K+ Channel-Related Acid-Sensitive K+ Channel-1) (K2P3.1) K+ Channels Suppresses Atrial Fibrillation and Prevents Electrical Remodeling.","authors":"C. Schmidt, F. Wiedmann, C. Beyersdorf, Zhihan Zhao, I. El-Battrawy, H. Lan, G. Szabó, Xin Li, S. Lang, S. Korkmaz‐Icöz, K. Rapti, A. Jungmann, Antonius Ratte, O. Müller, M. Karck, G. Seemann, I. Akin, M. Borggrefe, Xiaobo Zhou, H. Katus, Dierk Thomas","doi":"10.1161/CIRCEP.119.007465","DOIUrl":"https://doi.org/10.1161/CIRCEP.119.007465","url":null,"abstract":"BACKGROUND\u0000Despite an increasing understanding of atrial fibrillation (AF) pathophysiology, translation into mechanism-based treatment options is lacking. In atrial cardiomyocytes of patients with chronic AF, expression, and function of tandem of P domains in a weak inward rectifying TASK-1 (K+ channel-related acid-sensitive K+ channel-1) (K2P3.1) atrial-specific 2-pore domain potassium channels is enhanced, resulting in action potential duration shortening. TASK-1 channel inhibition prevents action potential duration shortening to maintain values observed among sinus rhythm subjects. The present preclinical study used a porcine AF model to evaluate the antiarrhythmic efficacy of TASK-1 inhibition by adeno-associated viral anti-TASK-1-siRNA (small interfering RNA) gene transfer.\u0000\u0000\u0000METHODS\u0000AF was induced in domestic pigs by atrial burst stimulation via implanted pacemakers. Adeno-associated viral vectors carrying anti-TASK-1-siRNA were injected into both atria to suppress TASK-1 channel expression. After the 14-day follow-up period, porcine cardiomyocytes were isolated from right and left atrium, followed by electrophysiological and molecular characterization.\u0000\u0000\u0000RESULTS\u0000AF was associated with increased TASK-1 transcript, protein and ion current levels leading to shortened action potential duration in atrial cardiomyocytes compared to sinus rhythm controls, similar to previous findings in humans. Anti-TASK-1 adeno-associated viral application significantly reduced AF burden in comparison to untreated AF pigs. Antiarrhythmic effects of anti-TASK-1-siRNA were associated with reduction of TASK-1 currents and prolongation of action potential durations in atrial cardiomyocytes to sinus rhythm values. Conclusions Adeno-associated viral-based anti-TASK-1 gene therapy suppressed AF and corrected cellular electrophysiological remodeling in a porcine model of AF. Suppression of AF through selective reduction of TASK-1 currents represents a new option for antiarrhythmic therapy.","PeriodicalId":10167,"journal":{"name":"Circulation: Arrhythmia and Electrophysiology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89602438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}