Current guidelines recommend pulmonary-vein isolation by means of catheter ablation as treatment for drug-refractory paroxysmal atrial fibrillation. Radiofrequency ablation is the most common method, ...and cryoballoon ablation is the second most frequently used technology.
We conducted a multicenter, randomized trial to determine whether cryoballoon ablation was noninferior to radiofrequency ablation in symptomatic patients with drug-refractory paroxysmal atrial fibrillation. The primary efficacy end point in a time-to-event analysis was the first documented clinical failure (recurrence of atrial fibrillation, occurrence of atrial flutter or atrial tachycardia, use of antiarrhythmic drugs, or repeat ablation) following a 90-day period after the index ablation. The noninferiority margin was prespecified as a hazard ratio of 1.43. The primary safety end point was a composite of death, cerebrovascular events, or serious treatment-related adverse events.
A total of 762 patients underwent randomization (378 assigned to cryoballoon ablation and 384 assigned to radiofrequency ablation). The mean duration of follow-up was 1.5 years. The primary efficacy end point occurred in 138 patients in the cryoballoon group and in 143 in the radiofrequency group (1-year Kaplan-Meier event rate estimates, 34.6% and 35.9%, respectively; hazard ratio, 0.96; 95% confidence interval CI, 0.76 to 1.22; P<0.001 for noninferiority). The primary safety end point occurred in 40 patients in the cryoballoon group and in 51 patients in the radiofrequency group (1-year Kaplan-Meier event rate estimates, 10.2% and 12.8%, respectively; hazard ratio, 0.78; 95% CI, 0.52 to 1.18; P=0.24).
In this randomized trial, cryoballoon ablation was noninferior to radiofrequency ablation with respect to efficacy for the treatment of patients with drug-refractory paroxysmal atrial fibrillation, and there was no significant difference between the two methods with regard to overall safety. (Funded by Medtronic; FIRE AND ICE ClinicalTrials.gov number, NCT01490814.).
Efficacy of the Novel Cryoballoon
Introduction
The cryoballoon technology has the potential to isolate a pulmonary vein (PV) with a single energy application. However, using the first‐generation ...cryoballoon (CB‐1G) repeated freezing or additional focal ablation is often necessary. The novel second‐generation cryoballoon (CB‐2G) features a widened zone of optimal cooling comprising the whole frontal hemisphere. The aim of this study was to investigate the impact of the novel design on procedural efficacy of cryoballoon PV isolation (CB‐PVI).
Methods and Results
Single transseptal CB‐PVI using an endoluminal spiral mapping catheter was performed in 60 consecutive patients (CB‐1G, 28 mm, 300 seconds application time: 30 patients; CB‐2G, 28 mm, 240 seconds application time: 30 patients). When compared to the CB‐1G, using the CB‐2G increased single‐shot PVI rate from 51% to 84% (P < 0.001) and decreased procedure duration (128 ± 27 vs 98 ± 30 minutes; P < 0.001), and fluoroscopy exposure time (19.5 ± 7.4 vs 13.4 ± 5.3 min; P = 0.001). Effective CB‐2G PVI could be performed with increased real‐time PVI visualization rate (49% vs 76%; P < 0.001). Time to PVI (TPVI) was shorter in the CB‐2G group (79 ± 60 vs. 52 ± 36 seconds; P = 0.049). Procedure‐related complications occurred in 2 patients in the CB‐1G group and 1 patient in the CB‐2G group.
Conclusions
The CB‐2G significantly improved procedural efficacy compared to the CB‐1G and provided reliable TPVI measurement. TPVI may be used to adjust application time and number individually in future studies. Final conclusions regarding the safety profile of the CB‐2G requires additional research.
The primary safety and efficacy endpoints of the randomized FIRE AND ICE trial have recently demonstrated non-inferiority of cryoballoon vs. radiofrequency current (RFC) catheter ablation in patients ...with drug-refractory symptomatic paroxysmal atrial fibrillation (AF). The aim of the current study was to assess outcome parameters that are important for the daily clinical management of patients using key secondary analyses. Specifically, reinterventions, rehospitalizations, and quality-of-life were examined in this randomized trial of cryoballoon vs. RFC catheter ablation.
Patients (374 subjects in the cryoballoon group and 376 subjects in the RFC group) were evaluated in the modified intention-to-treat cohort. After the index ablation, log-rank testing over 1000 days of follow-up demonstrated that there were statistically significant differences in favour of cryoballoon ablation with respect to repeat ablations (11.8% cryoballoon vs. 17.6% RFC; P = 0.03), direct-current cardioversions (3.2% cryoballoon vs. 6.4% RFC; P = 0.04), all-cause rehospitalizations (32.6% cryoballoon vs. 41.5% RFC; P = 0.01), and cardiovascular rehospitalizations (23.8% cryoballoon vs. 35.9% RFC; P < 0.01). There were no statistical differences between groups in the quality-of-life surveys (both mental and physical) as measured by the Short Form-12 health survey and the EuroQol five-dimension questionnaire. There was an improvement in both mental and physical quality-of-life in all patients that began at 6 months after the index ablation and was maintained throughout the 30 months of follow-up.
Patients treated with cryoballoon as opposed to RFC ablation had significantly fewer repeat ablations, direct-current cardioversions, all-cause rehospitalizations, and cardiovascular rehospitalizations during follow-up. Both patient groups improved in quality-of-life scores after AF ablation.
ClinicalTrials.gov identifier: NCT01490814.
Improved Efficacy of Second‐Generation Cryoballoon
Background
The second‐generation cryoballoon (CB2) has recently been introduced featuring improved surface cooling. Increased procedural efficacy of ...pulmonary vein isolation (PVI) when compared to the first‐generation balloon (CB1) has been reported. The aim of the study was to investigate the clinical outcome of cryoballoon PVI after 1 year using the CB2 as compared to the CB1.
Methods and Results
A total of 105 consecutive patients with paroxysmal atrial fibrillation (AF) were studied. Cryoballoon PVI (28 mm) was performed in 50 patients using the CB1, and in 55 patients using the CB2. Patients were scheduled for 72‐hour Holter ECG recording at 3, 6, 9, and 12 months and every 6 months thereafter. The study endpoint was defined as recurrent AF or atrial tachycardia >30 seconds documented after a blanking period of 90 days after the procedure. Complete PVI was achieved in 49/50 (98%) and 55/55 (100%) patients in the CB1 and CB2 group, respectively. After a mean follow‐up of 416 ± 75 days, 21 (CB1 group) and 10 (CB2 group) patients reached the study endpoint. Kaplan–Meier estimates of arrhythmia‐free survival after a single procedure without AAD therapy after 1 year were 63.9% versus 83.6% (P = 0.008) in the CB1 and CB2 group, respectively. Persistent phrenic nerve palsy with delayed healing occurred in 2 (CB1 group) and 3 (CB2 group) patients.
Conclusion
Clinical outcome of PVI using the CB2 was significantly improved when compared to the CB1.
Introduction
Pulsed field ablation (PFA) is a new ablation technology for atrial fibrillation (AF). Data regarding early recurrences of atrial tachyarrhythmia (ERAT) after PFA‐pulmonary vein ...isolation (PVI) are sparse.
Methods
Consecutive patients with symptomatic AF were enrolled to undergo PFA‐PVI. A dedicated catheter delivering bipolar energy (1.9–2.0 kV) was used. Late recurrence (LR) was defined as documented AF/atrial tachycardia (AT) lasting more than 30 s after a 90‐day blanking period.
Results
Two hundred and thirty‐one patients (42% female, age 69 ± 12, 55% paroxysmal AF PAF) were included in this analysis. Median follow‐up time was 367 days (interquartile range: 253–400). Forty‐six patients (21%) experienced ERAT after a median of 23 days (46% in PAF and 54% in persistent AF persAF). Kaplan–Meier estimated freedom of AF/AT was 74.2% at 1 year, 81.8% for PAF, and 64.8% for persAF (p = .0079). Of patients experiencing ERAT, an LR was observed in 54%. There was no significant difference of LR between those who presented with very early ERAT (0–45 days) and those with ERAT (46–90 days) (p = .57). In multivariate analysis, ERAT (hazard ratio HR: 3.370; 95% confidence interval 95% CI: 1.851–6.136; p < .001) and female sex (HR: 2.048; 95% CI: 1.114–3.768; p = .021) were the only independent predictors for LR.
Conclusions
ERAT could be recorded in 21% of patients after PFA‐PVI and was an independent predictor for LR. We found no difference in the rate of LRs among patients experiencing ERAT before or after 45 days.
ERAT could be recorded in 21% of patients after PFA‐PVI and was an independent predictor for LR. We found no difference in the rate of LRs among patients experiencing ERAT before or after 45 days.
Metastases remain the major cause of death from cancer. Recent molecular advances have highlighted the importance of metabolic alterations in cancer cells, including the Warburg effect that describes ...an increased glycolysis in cancer cells. However, how this altered metabolism contributes to tumour metastasis remains elusive. Here, we report that phosphorylation-induced activation of lactate dehydrogenase A (LDHA), an enzyme that catalyses the interconversion of pyruvate and lactate, promotes cancer cell invasion, anoikis resistance and tumour metastasis. We demonstrate that LDHA is phosphorylated at tyrosine 10 by upstream kinases, HER2 and Src. Targeting HER2 or Src attenuated LDH activity as well as invasive potential in head and neck cancer and breast cancer cells. Inhibition of LDH activity by small hairpin ribonucleic acid or expression of phospho-deficient LDHA Y10F sensitized the cancer cells to anoikis induction and resulted in attenuated cell invasion and elevated reactive oxygen species, whereas such phenotypes were reversed by its product lactate or antioxidant N-acetylcysteine, suggesting that Y10 phosphorylation-mediated LDHA activity promotes cancer cell invasion and anoikis resistance through redox homeostasis. In addition, LDHA knockdown or LDHA Y10F rescue expression in human cancer cells resulted in decreased tumour metastasis in xenograft mice. Furthermore, LDHA phosphorylation at Y10 positively correlated with progression of metastatic breast cancer in clinical patient tumour samples. Our findings demonstrate that LDHA phosphorylation and activation provide pro-invasive, anti-anoikis and pro-metastatic advantages to cancer cells, suggesting that Y10 phosphorylation of LDHA may represent a promising therapeutic target and a prognostic marker for metastatic human cancers.
Background
Radiofrequency high‐power ablation appears to be a novel concept for atrial fibrillation (AF). The ablation index (AI) value has been associated with durability of pulmonary vein isolation ...(PVI).
Objectives
This study aimed to report the procedural data and initial results of a combined ablation technique using AI‐guided high‐power (AI‐HP; 50 W) ablation for PVI.
Methods
Symptomatic AF patients were consecutively enrolled and underwent wide‐area contiguous circumferential PVI. Contact‐force catheters were used, ablation power was set to 50 W targeting AI values (550 anterior and 400 posterior). Esophageal temperature was monitored during procedure, all patients underwent postablation esophageal endoscopy.
Results
PVI was achieved in all (n = 50, mean age: 68 ± 9 years, female: 60%) patients, rate of first‐round PVI was 92%. A total of N = 2105 AI‐guided ablation lesions were analyzed. Comparing left anterior wall vs left posterior wall and right anterior wall vs right posterior wall, mean ablation time (s) per lesion was 20.5 ± 8 vs 8.6 ± 3 and 12.2 ± 4 vs 9.3 ± 3; mean contact force (g): 17.1 ± 12 vs 25.4 ± 14 and 33.7 ± 13 vs 21.0 ± 11; mean AI: 547 ± 48 vs 445 ± 55 and 555 ± 56 vs 440 ± 47 (all P < .0001). Procedure and fluoroscopy time (minute) were 55.6 ± 6.6 and 6 ± 1.7, respectively. Only one (2%) patient had a minimal esophageal lesion. During In‐hospital and 1‐month follow‐up no major complications such as death, stroke, tamponade, or atriaesophageal fistula (AE) occurred. Preliminary 6‐month follow‐up showed 48 of 50 (96%) patients were free from clinical AF/atrial tachycardia recurrence.
Conclusion
AI‐HP (50 W) ablation appears to be a feasible, safe, fast, and effective ablation technique for PVI.
Introduction
The ablation strategy for atrial fibrillation (AF) despite pulmonary vein isolation (PVI) is controversial. Left atrial appendage isolation (LAAI) may contribute to improve outcome. We ...describe an ablation approach (“Maze‐like”‐LAAI) that (1) modifies the underlying LA substrate by linear ablation (2) eliminates the LAA as a putative AF trigger site and (3) incorporates an unambiguous procedural endpoint. The role of LAA closure (LAAC) after LAAI was investigated.
Methods
Patients with atrial tachyarrhythmias nonresponsive to PVI underwent a LAAI ablation procedure. LAAI was achieved by combining (a) an anterior line, (b) a LA roof line and (c) a mitral isthmus line. Patients continued oral anticoagulation (OAC) therapy or underwent LAAC ≥6 weeks after LAAI.
Results
Maze‐like LAAI was attempted in our center in 107 of 3,611 AF ablation procedures (2.9%) and achieved in 88 of 107 patients (82%). In 8 of 107 (7%) patients cardiac tamponade occurred, all managed conservatively. During follow‐up sinus rhythm was established in 65% at 1 year. After LAAI, 45 patients remained on OAC and 40 underwent LAAC. In both groups 1 patient experienced a bleeding complication. Thromboembolism exclusively occurred in the OAC group in 3 (7%) patients.
Conclusion
LAA isolation by Maze‐like substrate modification may be considered a viable option for PVI non‐responders. It offers a reproducible approach with an unambiguous procedural endpoint and leads to a favorable clinical outcome. However, extensive LA ablation increased the risk of tamponade. Consecutive LAA occlusion may offer a nonpharmacologic strategy to overcome the high thromboembolic risk associated with absent mechanical LAA contraction.
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