John W. Lehmann

Cryoballoon Ablation of Pulmonary Veins for Paroxysmal Atrial Fibrillation: First Results of the North American Arctic Front (STOP AF) Pivotal Trial

OBJECTIVES This study sought to assess the safety and effectiveness of a novel cryoballoon ablation technology designed to achieve single-delivery pulmonary vein (PV) isolation. BACKGROUND Standard radiofrequency ablation is effective in eliminating atrial fibrillation (AF) but requires multiple lesion delivery at the risk of significant complications. METHODS Patients with documented symptomatic paroxysmal AF and previously failed therapy with ≥ 1 membrane active antiarrhythmic drug underwent 2:1 randomization to either cryoballoon ablation (n = 163) or drug therapy (n = 82). A 90-day blanking period allowed for optimization of antiarrhythmic drug therapy and reablation if necessary. Effectiveness of the cryoablation procedure versus drug therapy was determined at 12 months. RESULTS Patients had highly symptomatic AF (78% paroxysmal, 22% early persistent) and experienced failure of at least one antiarrhythmic drug. Cryoablation produced acute isolation of three or more PVs in 98.2% and all four PVs in 97.6% of patients. PVs isolation was achieved with the balloon catheter alone in 83%. At 12 months, treatment success was 69.9% (114 of 163) of cryoblation patients compared with 7.3% of antiarrhythmic drug patients (absolute difference, 62.6% [p < 0.001]). Sixty-five (79%) drug-treated patients crossed over to cryoablation during 12 months of study follow-up due to recurrent, symptomatic AF, constituting drug treatment failure. There were 7 of the resulting 228 cryoablated patients (3.1%) with a >75% reduction in PV area during 12 months of follow-up. Twenty-nine of 259 procedures (11.2%) were associated with phrenic nerve palsy as determined by radiographic screening; 25 of these had resolved by 12 months. Cryoablation patients had significantly improved symptoms at 12 months. CONCLUSIONS The STOP AF trial demonstrated that cryoballoon ablation is a safe and effective alternative to antiarrhythmic medication for the treatment of patients with symptomatic paroxysmal AF, for whom at least one antiarrhythmic drug has failed, with risks within accepted standards for ablation therapy. (A Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation [Stop AF]; NCT00523978).

Lower Incidence of Thrombus Formation With Cryoenergy Versus Radiofrequency Catheter Ablation

Background—Radiofrequency (RF) catheter ablation is limited by thromboembolic complications. The objective of this study was to compare the incidence and characteristics of thrombi complicating RF and cryoenergy ablation, a novel technology for the catheter-based treatment of arrhythmias. Methods and Results—Ablation lesions (n=197) were performed in 22 mongrel dogs at right atrial, right ventricular, and left ventricular sites preselected by a randomized factorial design devised to compare RF ablation with cryocatheter configurations of varying sizes (7F and 9F), cooling rates (−1°C/s, −5°C/s, and −20°C/s) and target temperatures (−55°C and −75°C). Animals were pretreated with acetylsalicylic acid and received intraprocedural intravenous unfractionated heparin. Seven days after ablation, the incidence of thrombus formation was significantly higher with RF than with cryoablation (75.8% versus 30.1%, P =0.0005). In a multiple regression model, RF energy remained an independent predictor of thrombus formation compared with cryoenergy (OR, 5.6; 95% CI, 1.7, 18.1;P =0.0042). Thrombus volume was also significantly greater with RF than with cryoablation (median, 2.8 versus 0.0 mm3;P <0.0001). More voluminous thrombi were associated with larger RF lesions, but cryolesion dimensions were not predictive of thrombus size. Conclusions—RF energy is significantly more thrombogenic than cryoenergy, with a higher incidence of thrombus formation and larger thrombus volumes. The extent of hyperthermic tissue injury is positively correlated with thrombus bulk, whereas cryoenergy lesion size does not predict thrombus volume, most likely reflecting intact tissue ultrastructure with endothelial cell preservation.

The REDUCE pivotal trial: a prospective, randomized controlled pivotal trial of a dual intragastric balloon for the treatment of obesity

BACKGROUND Saline-filled intragastric balloon devices are reversible endoscopic devices designed to occupy stomach volume and reduce food intake. OBJECTIVE To evaluate the safety and effectiveness of a dual balloon system plus diet and exercise in the treatment of obesity compared to diet and exercise alone. SETTING Academic and community practice, United States. METHODS Participants (n = 326) with body mass index (BMI) 30-40 kg/m(2) were randomized to endoscopic DBS treatment plus diet and exercise (DUO, n = 187) or sham endoscopy plus diet and exercise alone (DIET, n = 139). Co-primary endpoints were a between-group comparison of percent excess weight loss (%EWL) and DUO subject responder rate, both at 24 weeks. Thereafter DUO patients had the DBS retrieved followed by 24 additional weeks of counseling; DIET patients were offered DBS treatment. RESULTS Mean BMI was 35.4. Both primary endpoints were met. DUO weight loss was over twice that of DIET. DUO patients had significantly greater %EWL at 24 weeks (25.1% intent-to-treat (ITT), 27.9% completed cases (CC, n = 167) compared with DIET patients (11.3% ITT, P = .004, 12.3% CC, n = 126). DUO patients significantly exceeded a 35% response rate (49.1% ITT, P<.001, 54.5% CC) for weight loss dichotomized at 25%EWL. Accommodative symptoms abated rapidly with support and medication. Balloon deflation occurred in 6% without migrations. Early retrieval for nonulcer intolerance occurred in 9%. Gastric ulcers were observed; a minor device change led to significantly reduced ulcer size and frequency (10%). CONCLUSION The DBS was significantly more effective than diet and exercise in causing weight loss with a low adverse event profile.

Incidence and Significance of Early Recurrences of Atrial Fibrillation After Cryoballoon Ablation Insights From the Multicenter Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) Trial

Background—Early recurrence of atrial fibrillation (ERAF) is common after radiofrequency catheter ablation for AF. We sought to determine the incidence and prognostic significance of ERAF after cryoballoon ablation. Moreover, the benefit of early reablation for ERAF after cryoballoon ablation is undetermined. Methods and Results—The Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) trial randomized 245 patients with paroxysmal AF to medical therapy versus cryoballoon-based pulmonary vein ablation. Patients were followed for 12 months. ERAF was defined as any recurrence of AF >30 seconds during the first 3 months of follow-up. Late recurrence (LR) was defined as any recurrence of AF >30 seconds between 3 and 12 months. Of the 163 patients randomized to cryoablation, 84 patients experienced ERAF (51.5%). The only significant factor associated with ERAF was male sex (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.03–4.61; P=0.041). LR was observed in 41 patients (25.1%), and was significantly related to ERAF (55.6% LR with ERAF versus 12.7% without ERAF; P<0.001). Among patients with ERAF, only current tobacco use (HR, 3.84; 95% CI, 1.82–8.11; P<0.001) was associated with LR. Conversely, early reablation was associated with greater freedom from LR (3.3% LR with early reablation versus 55.6% without; HR, 0.04; 95% CI, 0.01–0.32; P=0.002). Conclusions—ERAF after cryoballoon ablation occurs in ≈50% of patients and is strongly associated with LR. Early reablation for ERAF is associated with excellent long-term freedom from recurrent AF.

Incidence and Significance of Early Recurrences of Atrial Fibrillation after Cryoballoon Ablation: Insights from The Multicenter STOP AF Trial

Background—Early recurrence of atrial fibrillation (ERAF) is common after radiofrequency catheter ablation for AF. We sought to determine the incidence and prognostic significance of ERAF after cryoballoon ablation. Moreover, the benefit of early reablation for ERAF after cryoballoon ablation is undetermined. Methods and Results—The Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) trial randomized 245 patients with paroxysmal AF to medical therapy versus cryoballoon-based pulmonary vein ablation. Patients were followed for 12 months. ERAF was defined as any recurrence of AF >30 seconds during the first 3 months of follow-up. Late recurrence (LR) was defined as any recurrence of AF >30 seconds between 3 and 12 months. Of the 163 patients randomized to cryoablation, 84 patients experienced ERAF (51.5%). The only significant factor associated with ERAF was male sex (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.03–4.61; P=0.041). LR was observed in 41 patients (25.1%), and was significantly related to ERAF (55.6% LR with ERAF versus 12.7% without ERAF; P<0.001). Among patients with ERAF, only current tobacco use (HR, 3.84; 95% CI, 1.82–8.11; P<0.001) was associated with LR. Conversely, early reablation was associated with greater freedom from LR (3.3% LR with early reablation versus 55.6% without; HR, 0.04; 95% CI, 0.01–0.32; P=0.002). Conclusions—ERAF after cryoballoon ablation occurs in ≈50% of patients and is strongly associated with LR. Early reablation for ERAF is associated with excellent long-term freedom from recurrent AF.