Interleukin-1 receptor antagonist levels predict favorable outcome after bermekimab, a first-in-class true human interleukin-1α antibody, in a phase III randomized study of advanced colorectal cancer.

Bermekimab is a true human monoclonal antibody that targets interleukin-1alpa (IL-1α), an inflammation-mediating alarmin. IL-1 receptor antagonist (IL-1Ra) is a natural molecule that blocks IL-1α activity by occupying the IL-1 receptor. The effect of endogenous IL-1Ra levels on the effectiveness of bermekimab is unknown. We investigated whether pre-treatment levels of circulating IL-1Ra, assessed by an enzyme-linked immunoassay, correlated with achievement of the primary outcome endpoint (effect on lean body mass and symptoms at week 8) in a Phase III study (2:1 randomization) of bermekimab versus placebo (each with best supportive care) in advanced colorectal cancer. Patients who responded to bermekimab in terms of achieving the primary endpoint had lower levels of IL-1Ra than non-responders (N = 204 patients; median = 843 vs. 1035 pg/ml, p=0.0092); no such relationship was observed in the placebo arm (N = 100 patients; 901 vs. 984 pg/ml, p = 0.55). Multivariate analysis corroborated that, in the bermekimab group, patients with lower baseline IL-1Ra levels were more likely to achieve the primary endpoint (odds ratio (OR) 1.7 (95% confidence interval (CI), 1.1 to 2.6), p = 0.017); in contrast, in the placebo arm, pre-treatment plasma IL-1Ra levels were not associated with outcome (OR 1.2 (95% CI 0.6 to 2.5), p = 0.57). The current findings demonstrate that, in a randomized phase III trial, patients with advanced colorectal cancer and lower levels of circulating IL-1Ra are more responsive to treatment with the IL-1α-targeting antibody bermekimab and these observations define a potential biomarker for anti-IL-1α therapy.

MABp1 as a novel antibody treatment for advanced colorectal cancer: a randomised, double-blind, placebo-controlled, phase 3 study.

BACKGROUND: MABp1, an antibody that targets interleukin 1α, has been associated with antitumour activity and relief of debilitating symptoms in patients with advanced colorectal cancer. We sought to establish the effect of MABp1 with a new primary endpoint in patients with advanced colorectal cancer. METHODS: Eligible patients for the double-blind phase of this ongoing, placebo-controlled, randomised, phase 3 trial, had metastatic or unresectable disease, Eastern Cooperative Oncology Group performance status score 1 or 2, systemic inflammation, weight loss, and other disease-related morbidities associated with poor prognosis, and were refractory to oxaliplatin and irinotecan. Patients were randomly assigned 2:1 to receive either MABp1 or placebo. Randomisation codes were obtained from a centrally held list via an interactive web response system. Patients received an intravenous infusion of 7·5 mg/kg MABp1 or placebo given every 2 weeks for 8 weeks. The primary endpoint was assessed in patients who received at least one dose of MABp1 or placebo (modified intention-to-treat population), and was a composite of stable or increased lean body mass and stability or improvement in two of three symptoms (pain, fatigue, or anorexia) at week 8 compared with baseline measurements. This study is registered with ClinicalTrials.gov, number NCT02138422. FINDINGS: Patients were enrolled between May 20, 2014, and Sept 2, 2015. The double-blind phase of the study was completed on Nov 3, 2015. Of 333 patients randomly assigned treatment, 207 received at least one dose of MABp1 and 102 at least one dose of placebo. 68 (33%) and 19 (19%) patients, respectively, achieved the primary endpoint (relative risk 1·76, 95% CI 1·12-2·77, p=0·0045). The most common grade 3-4 adverse events in the MABp1 group compared with in the placebo group were anaemia (eight [4%] of 207 vs five [5%] of 102 patients), increased concentration of alkaline phosphatase (nine [4%] vs two [2%]), fatigue (six [3%] vs seven [7%]), and increased concentration of aspartate aminotransferase (six [3%] vs two [2%]). After 8 weeks, 17 (8%) patients in the MABp1 group and 11 (11%) in the placebo group had died, but no death was judged to be related to treatment. The incidence of serious adverse events was not significantly different in the MABp1 group and placebo groups (47 [23%] vs 33 [32%], p=0·07). INTERPRETATION: The primary endpoint was a useful means of measuring clinical performance in patients. MABp1 might represent a new standard in the management of advanced colorectal cancer. FUNDING: XBiotech.

A randomized phase II study of Xilonix, a targeted therapy against interleukin 1α, for the prevention of superficial femoral artery restenosis after percutaneous revascularization.

OBJECTIVE: The purpose of this study was to evaluate an anti-interleukin 1α antibody for its ability to reduce acute postprocedural inflammation, thereby reducing neointimal hyperplasia and restenosis after superficial femoral artery (SFA) angioplasty. Restenosis of the SFA after endovascular intervention is a common problem leading to 1-year primary patency as low as 40%. These failures are primarily due to the development of neointimal hyperplasia, resulting from arterial wall inflammation. METHODS: This was a randomized, phase II trial examining SFA restenosis in patients after percutaneous revascularization. Randomization occurred after successful revascularization, and patients were assigned to either the standard of care arm or the Xilonix (XBiotech USA, Inc, Austin, Tex) plus standard of care arm (N = 43). Xilonix was administered immediately after revascularization, every 2 weeks intravenously for four doses, and monthly subcutaneously until month 12. The major efficacy end points were target vessel event-free survival and incidence of major adverse cardiovascular events (MACEs). RESULTS: At 12 months of follow-up, MACE (43% vs 36%; P = .76) and target vessel restenosis (24% vs 27%; log-rank, P = .79) rates were not significantly different between the groups. At 3-month follow-up, which covers the intravenous dosing period, a trend toward lower incidence of restenosis (0 of 22 [0%] vs 2 of 21 [10%]; P = .14) and MACE (2 of 22 [9%] vs 5 of 21 [24%]; P = .22) was observed in the Xilonix cohort. Adverse events were equally distributed in both arms. CONCLUSIONS: Xilonix was well tolerated. Observed tendency to improved vessel patency with intravenous dosing suggests Xilonix could potentially represent a safe and effective therapeutic approach to preserving vessel patency.

Xilonix, a novel true human antibody targeting the inflammatory cytokine interleukin-1 alpha, in non-small cell lung cancer.

BACKGROUND: Advanced non-small cell lung cancer (NSCLC) patients were treated as part of a Phase I dose escalation and expansion study evaluating a true human monoclonal antibody targeting IL-1α (Xilonix), which is intended to modulate the malignant phenotype-inhibiting tumor growth, spread and offering relief of symptoms. METHODS: Sixteen NSCLC patients were included. Patients failed a median of 4 chemotherapy regimens, including 10/16 failing anti-EGFR therapy. Disease progression was evaluated using a multi-modal approach: tumor response, patient reported outcomes (EORTC-QLQC30), and lean body mass (LBM). Patients received infusions every 2 or 3 weeks until progression, and were followed 24 months to assess survival. RESULTS: There were no infusion reactions, dose-limiting toxicities, or deaths due to therapy. Albeit not statistically significant, there was a trend in IL-6 (-2.6 ± 18.5 (0.1 [-2.8-2.4]), platelet counts (-11 ± 54 (-4[-36.0-1.0]), CRP (-3.3 ± 30.2 (0.4 [-10.7-1.8]) and LBM (1.0 ± 2.5 (0.4 [-0.5-2.6]). Self-reported outcomes revealed reductions in pain, fatigue and improvement in appetite. Median survival was 7.6 (IQR 4.4-11.5) months, stratification based on prior anti-EGFR therapy revealed a median survival of 9.4 months (IQR 7.6-12.5) for those pretreated (N = 10) versus a survival of 4.8 months (IQR 4.3-5.7) for those without (N = 6, logrank p = 0.187). CONCLUSION: Xilonix was well tolerated, with gains in LBM and improvement in symptoms suggesting a clinically important response. Although not statistically significant, the survival outcomes observed for patients with and without prior anti-EGFR therapy raises intriguing questions about the potential synergy of IL-1α blockade and anti-EGFR therapy. Further study for this agent in NSCLC is warranted.

Long-term outcome of catheter ablation in atrial fibrillation patients with coexistent metabolic syndrome and obstructive sleep apnea: impact of repeat procedures versus lifestyle changes.

INTRODUCTION: Metabolic syndrome (MS) and obstructive sleep apnea (OSA) are well-known independent risk factors for atrial fibrillation (AF) recurrence. This study evaluated ablation outcome in AF patients with coexistent MS and OSA and influence of lifestyle modifications (LSM) on arrhythmia recurrence. METHODS AND RESULTS: We included 1,257 AF patients undergoing first catheter ablation (30% paroxysmal AF). Patients having MS + OSA were classified into Group 1 (n = 126; 64 ± 8 years; 76% male). Group 2 (n = 1,131; 62 ± 11 years; 72% male) included those with either MS (n = 431) or OSA (n = 112; no CPAP users) or neither of these comorbidities (n = 588). Patients experiencing recurrence after first procedure were divided into 2 subgroups; those having sporadic events (frequency < 2 months) remained on previously ineffective antiarrhythmic drugs (AAD) and aggressive LSM, while those with persistent arrhythmia (incessant or ≥2 months) underwent repeat ablation. After 34 ± 8 months of first procedure, 66 (52%) in Group 1 and 386 (34%) in Group 2 had recurrence (P < 0.001). Recurrence rate in only-MS, only-OSA, and without MS/OSA groups were 40%, 38%, and 29%, respectively. Patients with MS + OSA experienced substantially higher recurrence compared to those with lone MS or OSA (52% vs. 40% vs. 38%; P = 0.036). Of the 452 patients having recurrence, 250 underwent redo-ablation and 194 remained on AAD and LSM. At 20 ± 6 months, 76% of the redo group remained arrhythmia-free off AAD whereas 74% of the LSM group were free from recurrence (P = 0.71), 33% of which were off AAD. CONCLUSIONS: MS and OSA have additive negative effect on arrhythmia recurrence following single procedure. Repeat ablation or compliant LSM increase freedom from recurrent AF.

MABp1, a first-in-class true human antibody targeting interleukin-1α in refractory cancers: an open-label, phase 1 dose-escalation and expansion study.

BACKGROUND: Inflammation is an important feature of the malignant phenotype and promotes angiogenesis, tumour invasiveness, metastases, and cachexia. We used a first-in-class, monoclonal antibody (MABp1) cloned from a human being to target interleukin-1α, a mediator of chronic inflammation. We aimed to assess the safety and tolerability of MABp1 for interleukin-1α blockade in a refractory cancer population. METHODS: We did an open-label, dose-escalation, and phase 1 study of MABp1 in adults with metastatic cancer at the MD Anderson Clinical Center for Targeted Therapy (Houston, TX, USA). We used a standard 3+3 design to identify the maximum tolerated dose. Patients received MABp1 intravenously once every 3 weeks through four dose levels: 0.25 mg/kg, 0.75 mg/kg, 1.25 mg/kg, and 3.75 mg/kg. After the dose-escalation phase, a second dosing arm was started with dosing every 2 weeks at the maximum tolerated dose. The primary objectives were safety, tolerability, characterisation of the pharmacokinetic profile, and identification of the recommended phase 2 dose. Secondary endpoints included pharmacodynamic effects and antitumour activity. All patients who received at least one dose of MABp1 were included in the safety analyses. This trial is registered with ClinicalTrials.gov, NCT01021072. FINDINGS: Between March 15, 2010, and July 30, 2012, 52 patients with metastatic cancer (18 tumour types) received anti-interleukin-1α monotherapy in dose-escalation and expansion groups. MABp1 was well tolerated, with no dose-limiting toxicities or immunogenicity. Thus, the recommended phase 2 dose was concluded to be 3.75 mg/kg every 2 weeks. Pharmacokinetic data were consistent at all dose levels and showed no evidence of accumulation or increased clearance of MABp1 at increasing doses. For 42 assessable patients, median plasma interleukin-6 concentrations had decreased from baseline to week 8 by a median of 2.7 pg/mL (IQR -12.6 to 3.0; p=0.08). Of the 34 patients restaged, one patient had a partial response and ten had stable disease. 30 patients were assessable for change in lean body mass, which increased by a mean of 1.02 kg (SD 2.24; p=0.02) between baseline and week 8. The most common adverse events possibly related to the study drug were proteinuria (n=11; 21%), nausea (7; 13%), and fatigue (7; 13%). The most frequent grade 3-4 adverse events (regardless of relation to treatment) were fatigue (3; 6%), dyspnoea (2; 4%), and headache (2; 4%). Two patients (4%) had grade 5 events (death due to disease progression), which were unrelated to treatment. INTERPRETATION: MABp1 was well tolerated, no dose-limiting toxicities were experienced in this study, and disease control was observed. Further study of MABp1 anti-interleukin-1α antibody therapy for advanced stage cancer is warranted.

Administration of isoproterenol and adenosine to guide supplemental ablation after pulmonary vein antrum isolation.

BACKGROUND: Pulmonary vein antrum isolation (PVAI) remains associated with atrial fibrillation (AF) recurrence. We administered adenosine and isoproterenol (ISP) after PVAI to uncover non-PV atrial triggers and PV reconnection, potentially increasing ablation success rate. METHODS: One hundred and ninety-two consecutive patients with symptomatic AF presenting for PVAI were prospectively studied (group 1). Following PVAI, adenosine (18-24 mg) and ISP (20-30 mcg/min) were administered intravenously. Supplemental ablation was performed in patients with non-PV triggers that induced AF (group 1A). Other subgroups included patients with (group 1B) or without (group 1C) consistent non-PV atrial foci that did not induce AF. A cohort of 196 matched control patients undergoing PVAI without drug challenge was used for comparison (group 2). RESULTS: A total of 132 atrial non-PV foci were revealed (31 inducing AF). The majority of atrial foci were observed with ISP (113/132, 86%). Less than 5% of patients had persistent PV recovery during the drug challenge. During a mean follow-up of 22 ± 8 months, PVAI was successful in 110/192 (57%, group 1) versus 100/196 (52%, group 2), P = 0.038. Furthermore, the success rate was statistically different between group 1A (25/32, 78%), group 1B (28/83, 34%), and group 1C (57/74, 74%), P < 0.001. CONCLUSION: After PVAI, ablation guided by the administration of adenosine and ISP to target non-PV triggers inducing AF increased AF ablation outcomes. Patients with non-PV foci that did not induce AF had no further ablation, with the lowest ablation success rate. This group may likely benefit from further ablation after PVAI.

Safety and effectiveness of transvenous lead extraction in octogenarians.

INTRODUCTION: As the population ages, the number of elderly patients with implantable cardiac devices referred for transvenous lead extraction will dramatically increase in Western countries. The safety and effectiveness of lead extraction in elderly patients has not been well evaluated. We report the safety and effectiveness of transvenous lead extraction in octogenarians. METHODS AND RESULTS: From January 2005 to January 2011, we reviewed data from consecutive patients ≥ 80 years referred to our institutions for transvenous lead extraction because of cardiac device infection or lead malfunction. Clinical characteristics, procedural features, and periprocedural major and minor complications were compared between octogenarians and younger patients. Out of 849 patients undergoing lead extraction in the participating institutions during the study period, 150 (18%) patients were octogenarians (mean age 84 years; range 80-96; 64% males). A significantly higher percentage of octogenarians presented with chronic renal failure (55% vs 26%; P < 0.001), history of malignancy (22% vs 6%; P < 0.001), and chronic obstructive pulmonary disease (46% vs 19%; P < 0.001). Complete lead extraction rates were similar in the 2 age groups (97% in octogenarians vs 96% in patients <80 years; P = 0.39). Periprocedural death occurred in 2 (1.3%) patients ≥80 years and in 5 (0.72%) patients <80 years (P = 0.45 for comparison). No differences in terms of other periprocedural major and minor complications were found between the 2 age groups. CONCLUSION: Despite presenting with a significantly higher rate of comorbidities, transvenous lead extraction can be performed safely and successfully in octogenarians.

Dilator method and needle method for atrial transseptal puncture: a retrospective study from a cohort of 4443 patients.

AIMS: To compare the safety and efficacy of a new dilator method vs the traditional needle method for transseptal puncture (TSP) in a large cohort study. METHODS AND RESULTS: From February 1995 to December 2010, 4443 consecutive patients undergoing TSP done either by a needle method or by a new dilator method were reviewed retrospectively. Data as procedure-related time and complications were evaluated. For the standard needle method, TSP was performed by extending out the needle. In comparison, for the new dilator technique, TSP was performed without an outer sheath and with the needle kept within the dilator; the blunt tip of the dilator was used to help locating the position of the fossa ovalis on purpose. Transseptal puncture was performed by the new dilator method in 2151 patients (48.4%) and by the traditional needle method in 2292 patients (51.6%). The average TSP time needed by the dilator method was longer than that needed by the needle method (5.6 ± 3.9 vs. 3.8 ± 2.9 min, P< 0.05). Additional left atrial angiography was required in seven (0.33%) patients for the dilator and in 39 patients (1.70%) for the needle method (P< 0.05). The total rate of severe complications and obvious TSP-related complications was significantly lower in patients who underwent the dilator method than in those who underwent the needle method (0.33 vs. 1.18%, and 0.20 vs. 1.00%, respectively, P < 0.05). CONCLUSION: Our data suggest that the new dilator technique is much safer than that of the standard needle method. It needs relatively longer procedure time but results in significantly fewer episodes of severe complications. Particularly, the blunt tip of the dilator can be used to help locate the fossa ovalis. Therefore, the new dilator technique might be a better choice for relatively less-experienced operators.

Worldwide experience with the robotic navigation system in catheter ablation of atrial fibrillation: methodology, efficacy and safety.

INTRODUCTION: The Hansen Robotic system has been utilized in ablation procedures for atrial fibrillation (AF). However, because of the lack of tactile feedback and the rigidity of the robotic sheath, this approach could result in higher risk of complications. This worldwide survey reports a multicenter experience on the methodology, efficacy, and safety of the Hansen system in AF ablations. METHODS AND RESULTS: A questionnaire addressing questions on patient's demographics, procedural parameters, ablation success rate and safety information was sent to all centers where more than 50 robotic AF ablation cases have been performed. From June 2007 to December 2009, 1,728 procedures were performed at 12 centers utilizing the Hansen robotic navigation technology. The overall complication rate was 4.7% and the success rate was 67.1% after 18 ± 4 months of follow-up. In 5 low volume centers there appeared to be a learning curve of about 50 cases (complication rate 11.2% for the first 50 cases vs 3.7% for the 51-100 cases; P = 0.044) and a trend showing a decrease of complication rate with increasing case volume. However, in the remaining 7 centers no learning curve was present and the complication rate was stable over time (3.7% for the first 50 cases vs 3.6% for the 51st case thereafter; P = 0.942). CONCLUSION: The Hansen robotic system can be used for AF ablation safely. In low volume centers, there appeared to be a learning curve of the first 50 cases after which the complication rate decreased. With a higher case volume, the success rate increased.

Ablation of ventricular arrhythmias in arrhythmogenic right ventricular dysplasia/cardiomyopathy: arrhythmia-free survival after endo-epicardial substrate based mapping and ablation.

BACKGROUND: In patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy, freedom from ventricular arrhythmias (VAs) after endocardial ablation is limited. We compared the long-term freedom from recurrent VAs by using endocardial-alone ablation versus endo-epicardial substrate-based ablation. METHODS AND RESULTS: Forty-nine patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy undergoing ablation of ventricular tachycardia (VT) were divided into 2 groups: endocardial-alone ablation (group 1, n = 23) and endo-epicardial ablation (group 2, n = 26). All patients had an implantable cardioverter-defibrillator (ICD). Conventional and 3D mappings were used to determine the mechanism of induced VTs and to identify area of "scar" or "abnormal" myocardium. All critical sites responsible for VTs and points with "abnormal" potential were targeted for ablation from endocardium (group 1) or from both endocardium and epicardium (group 2). The procedural end point was noninducibility of sustained, monomorphic VT with isoproterenol. The presence of frequent premature ventricular contractions at the end of ablation was recorded. Patients were followed up by ECG, Holter, and ICD interrogation. After a follow-up of at least 3 years, freedom from VAs or ICD therapy was 52.2% (12/23) in group 1 and 84.6% (22/26) in group 2 (P = 0.029), with 21.7% (5/23) and 69.2% (18/26) patients off antiarrhythmic drugs (P < 0.001), respectively. Compared with patients with no premature ventricular contractions after ablation, patients with frequent premature ventricular contractions after ablation were more likely to have VA recurrence/ICD therapy [3/33 (9%) versus 12/16 (75%); log-rank P<0.001]. CONCLUSIONS: An endo-epicardial-based ablation strategy achieves higher long-term freedom from recurrent VAs off antiarrhythmic therapy in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy when compared with endocardial-alone ablation. The presence of ≥ 10 premature ventricular contractions per minute after ablation is associated with more VA recurrence.

Impact of cardiac resynchronization therapy on the severity of mitral regurgitation.

AIMS: Functional mitral regurgitation (MR) could be managed by both cardiac resynchronization therapy (CRT) and mitral-valve surgery. Clinical decision making regarding the appropriateness of mitral-valve surgery vs. CRT is a challenging task. This study assessed the prevalence and prognosis of various degrees of functional MR in CRT candidates. Additionally, we sought to identify functional MR patients who either can be adequately managed by CRT only or will need surgery. METHODS AND RESULTS: Cardiac resynchronization therapy recipients (n= 794) were followed-up for 26 ± 18 months. Mitral regurgitation severity was quantified on scale 0-4. Cardiac resynchronization therapy responders were identified based on improvement in the New York Heart Association class and left-ventricular ejection fraction. Severity of MR and LV reverse remodelling were assessed at 3 and 12 months. Predictors of long-term MR change and CRT response were explored with multivariable models. Mitral regurgitation was present in 86%, with 35% prevalence of advanced MR (grade 3-4). Improvement of MR ≥ 1° after 12 months occurred in 46% of patients. It was relatively more frequent in patients with advanced MR at baseline (63%, P< 0.01). Baseline MR severity and change in MR at 3-month follow-up predicted response to CRT. Patients with ≥ 1° MR improvement at 12 months had more reverse remodelling compared with those with no change or worsening of MR. CONCLUSIONS: Mitral regurgitation improvement at 3 months predicts CRT response and MR improvement at 12-month follow-up. This finding could have implications for subsequent MR surgical therapies.

Stiff left atrial syndrome after catheter ablation for atrial fibrillation: clinical characterization, prevalence, and predictors.

BACKGROUND: There have been no studies of atrial diastolic function after catheter ablation of atrial fibrillation (AF). We encountered a few patients with symptomatic left atrial (LA) diastolic dysfunction and associated pulmonary hypertension (PH) that developed after catheter ablation for atrial fibrillation. Similar findings were described in patients after cardiac surgery and were referred to as the "stiff left atrial syndrome." OBJECTIVE: The purpose of this study was to prospectively quantify the incidence of patients developing PH associated with diastolic hemodynamic abnormalities of the LA after radiofrequency ablation of AF and to identify the possible predictors. METHODS: Between January 2009 and July 2010, data on 1,380 consecutive patients were prospectively collected. Before ablation and at follow-up, all patients had an echocardiogram to assess for the presence of PH. Patients with no echocardiographic evidence of PH but complaining of unexplained dyspnea with LA diastolic abnormalities were evaluated with right heart catheterization (RHC). Patients were included in the analysis if they developed new or worsening PH postablation with evidence of LA diastolic dysfunction by RHC or direct LA pressure measurement. All patients were evaluated for pulmonary vein stenosis and excluded if this condition was identified. RESULTS: The mean age was 62 ± 11 (75% male), and nonparoxysmal AF was the predominant arrhythmia (71%). New or worsening PH with associated LA diastolic abnormalities was detected in 19 (1.4%) patients after ablation. The prevalence of PH did not differ between AF types (P = .612). Compared with patients who did not develop PH, LA scarring (P <.001), diabetes (P = .026), and obstructive sleep apnea (OSA; P = .006) were more frequently observed among those who developed PH. In a multivariable logistic model, preprocedure LA size ≤45 mm (odds ratio [OR] = 6.13; P = .033), mean LA pressure (OR 1.14; P = .025), severe LA scarring (OR = 4.4; P = .046), diabetes mellitus (OR = 9.5; P = .004), and OSA (OR = 6.2; P = .009) were independently associated with the development of PH postablation. CONCLUSIONS: After radiofrequency catheter ablation of atrial fibrillation (RFCAF), PH with LA diastolic dysfunction or the so-called stiff LA syndrome is a rare but potentially significant complication of AF ablation. Severe LA scarring, LA ≤45 mm, diabetes mellitus, OSA, and high LA pressure are clinical variables that predict the development of this syndrome. The main clinical findings include dyspnea, congestive heart failure, PH, and large V waves on pulmonary capillary wedge pressure (PCWP) or LA pressure tracings in the absence of mitral regurgitation.

General anesthesia reduces the prevalence of pulmonary vein reconnection during repeat ablation when compared with conscious sedation: results from a randomized study.

BACKGROUND: Radiofrequency catheter ablation of atrial fibrillation can be performed under general anesthesia or conscious sedation at the physician's preference. OBJECTIVE: We randomized a series of consecutive patients with paroxysmal atrial fibrillation (AF) undergoing radiofrequency catheter ablation to either general anesthesia or conscious sedation to assess differences in pulmonary vein (PV) reconnection during redo procedures and impact on success rate. METHODS: A total of 257 consecutive patients with paroxysmal AF undergoing AF ablation were enrolled and randomized to either conscious sedation with fentanyl or midazolam (128 patients, group 1) and general anesthesia (129 patients, group 2). In all patients, a high dosage of isoproterenol up to 30 µg/min was used to disclose PV reconnection or extra PV firings. RESULTS: Baseline clinical characteristics were not significantly different between the 2 groups. At 17 ± 8 month follow-up after the first ablation, 88 (69%) patients in group 1 were free of atrial arrhythmias off all antiarrhythmic drugs (AAD), as compared with 114 (88%) in group 2 (log-rank P <.001). All patients with recurrence had a second procedure. At the repeat procedure, 42% (66 of 158) of PVs in group 1 had recovered PV conduction, compared with 19% (11 of 57) in group 2 (P = .003). Compared with group 1, group 2 had a significantly shorter fluoroscopy time (53 ± 9 min vs. 84 ± 21 min, P <.001) and procedure time (2.4 ± 1.4 h vs. 3.6 ± 1.1 h, P <.001). CONCLUSION: The use of general anesthesia is associated with higher cure rate with a single procedure, and it seems to reduce the prevalence of PV reconnection observed at the time of repeat ablation.

Ablation of atrial fibrillation utilizing robotic catheter navigation in comparison to manual navigation and ablation: single-center experience.

BACKGROUND: Robotic catheter navigation and ablation either with magnetic catheter driving or with electromechanical guidance have emerged in the recent years for the treatment of atrial fibrillation. OBJECTIVE: The aim of this study was to compare our center's experience of atrial fibrillation ablation using the Hansen Robotic Medical System with our current manual ablation technique in terms of acute and chronic success, as well as procedure time and radiation exposure to both the patient and the operator. METHODS: A total of 390 consecutive patients with symptomatic and drug-resistant atrial fibrillation (289 males, 62 +/- 11 years) were prospectively enrolled in the study. All patients underwent the procedure either with conventional manual ablation (group 1, n = 197) or with the robotic navigation system (RNS) (group 2, n = 193). RESULTS: The success rate for RNS was 85% (164 patients), while for manual ablation it was 81% (159 patients) (p = 0.264) at 14.1 +/- 1.3 months with AADs previously ineffective. Fluoroscopy time was significantly lower for RNS (48.9 +/- 24.6 minutes for RNS vs. 58.4 +/- 20.1 minutes for manual ablation, P < 0.001). Mean fluoroscopy time was statistically reduced after 50 procedures (61.8 +/- 23.2 minutes for first 50 cases vs. 44.5 +/- 23.6 minutes for subsequent procedures, P < 0.0001). CONCLUSION: Robotic navigation and ablation of atrial fibrillation is safe and effective. Fluoroscopy time decreases with experience.