Pulmonary Vein Isolation Followed by Biatrial Ablation of Rotational Activity in Patients with Persistent Atrial Fibrillation: Results of the Cryo-Vest Study.

Background and Aims: Noninvasive mapping allows the identification of patient-specific atrial rotational activity (RA) that might play a key role in the perpetuation of persistent atrial fibrillation (PsAF). So far, the impact of pulmonary vein isolation by cryoballoon (Cryo-PVI) on RA is unclear. Moreover, the long-term effect of periprocedural termination of AF during the ablation procedure is controversial. Methods: Noninvasive electrocardiographic mapping with a 252-electrode vest was performed in 42 patients with PsAF. After the first analysis, Cryo-PVI was performed. The RA was analyzed again and then targeted by radiofrequency catheter ablation. The primary clinical endpoint was periprocedural termination of AF. The secondary endpoint was freedom from any atrial arrhythmia >30 s during a 12-month follow-up. Results: In 33 patients (79%), right atrial RA was identified leading to biatrial ablation, and nine patients (21%) had left atrial RA only. Twelve patients (28.6%) converted from AF to sinus rhythm (SR) (Group A). Thirteen patients (30.9%) converted to atrial tachycardia (AT) (Group B). In 17 patients (40.5%), AF was not terminated by ablation (Group C). After a mean follow-up time of 13.8 months, 26 patients were free from AF and AT (61.9%). In terms of rhythm, control Group A (75%) and B (83.3%) showed higher success rates than Group C (33.3%) (p < 0.01). Cryo-PVI had no substantial impact on RA. Conclusions: The RA-based ablation approach showed acceptable success rates. Periprocedural termination of AF had a positive predictive impact on the outcome. No difference was observed between conversion to SR or to AT. Cryo-PVI had no impact on RA.

Economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from an English National Health Service perspective.

INTRODUCTION: Three recent randomised controlled trials have demonstrated that pulmonary vein isolation as an initial rhythm control strategy with cryoablation reduces atrial arrhythmia recurrence in patients with symptomatic paroxysmal atrial fibrillation (PAF) compared with antiarrhythmic drug (AAD) therapy. The aim of this study was to evaluate the cost-effectiveness of first-line cryoablation compared with first-line AADs for treating symptomatic PAF in an English National Health Service (NHS) setting. METHODS: Individual patient-level data from 703 participants with PAF enrolled into Cryo-FIRST (Catheter Cryoablation Versus Antiarrhythmic Drug as First-Line Therapy of Paroxysmal Atrial Fibrillation), STOP AF First (Cryoballoon Catheter Ablation in an Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation) and EARLY-AF (Early Aggressive Invasive Intervention for Atrial Fibrillation) were used to derive the parameters applied in the cost-effectiveness model (CEM). The CEM comprised a hybrid decision tree and Markov structure. The decision tree had a 1-year time horizon and was used to inform the initial health state allocation in the first cycle of the Markov model (40-year time horizon; 3-month cycle length). Health benefits were expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3.5% per year. Model outcomes were generated using probabilistic sensitivity analysis. RESULTS: The results estimated that cryoablation would yield more QALYs (+0.17) and higher costs (+£641) per patient over a lifetime than AADs. This produced an incremental cost-effectiveness ratio of £3783 per QALY gained. Independent of initial treatment, individuals were expected to receive ~1.2 ablations over a lifetime. There was a 45% relative reduction in time spent in AF health states for those initially treated with cryoablation. DISCUSSION: AF rhythm control with first-line cryoablation is cost effective compared with first-line AADs in an English NHS setting.

The Cost-Effectiveness of First-Line Cryoablation vs First-Line Antiarrhythmic Drugs in Canadian Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: The EARLY-AF (NCT02825979), STOP AF First (NCT03118518), and Cryo-FIRST (NCT01803438) randomised controlled trials (RCTs) demonstrated that cryoballoon pulmonary vein isolation reduces atrial fibrillation (AF) recurrence compared with antiarrhythmic drugs (AADs) in patients with symptomatic paroxysmal atrial fibrillation (PAF). The present study developed a cost-effectiveness model (CEM) of first-line cryoablation compared with first-line AADs for PAF, from the Canadian health care payer's perspective. METHODS: Data from the 3 RCTs were analysed to estimate key CEM parameters. The model structure used a decision tree for the first 12 months and a Markov model with a 3-month cycle length for the remaining lifetime time horizon. Costs were set at 2023 Canadian dollars, health benefits were expressed as quality-adjusted life years (QALYs), and both were discounted 3% annually. Probabilistic sensitivity analysis (PSA) considered parameter uncertainty. RESULTS: The statistical analysis estimated that first-line cryoablation generates a 47% reduction (P < 0.001) in the rate of AF recurrence, a 73% reduction in the rate of subsequent ablation (P < 0.001), and a 4.3% (P = 0.025) increase in health-related quality of life, compared with first-line AADs. The PSA indicates that an individual treated with first-line cryoablation accrues less costs (-$3,862) and more QALYs (0.19) compared with first-line AADs. Cryoablation is cost-saving in 98.4% of PSA iterations and has a 99.9% probability of being cost-effective at a cost-effectiveness threshold of $50,000 per QALY gained. Cost-effectiveness results were robust to changes in key model parameters. CONCLUSIONS: First-line cryoballoon ablation is cost-effective when compared with AADs for patients with symptomatic PAF.

An economic evaluation of first-line cryoballoon ablation vs antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from a U.S. Medicare perspective.

Background: Three recent randomized controlled trials have demonstrated that, as an initial rhythm control strategy, first-line cryoballoon ablation (cryoablation) reduces atrial arrhythmia recurrence compared with antiarrhythmic drugs (AADs) in patients with symptomatic paroxysmal atrial fibrillation (PAF). Objective: The study sought to evaluate the cost-effectiveness of first-line cryoablation compared with first-line AADs for treating symptomatic PAF from a U.S. Medicare payer perspective. Methods: Individual patient-level data from 703 participants with PAF enrolled into the Cryo-FIRST (NCT01803438), STOP AF First (NCT03118518), and EARLY-AF (NCT02825979) trials were used to derive parameters for the cost-effectiveness model. The cost-effectiveness model used a hybrid decision tree and Markov structure. The decision tree had a 1-year time horizon and was used to inform the initial health state allocation in the first cycle of the Markov model. The Markov model used a 40-year time horizon (3-month cycle length). Health benefits were expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3% per year. Results: Cryoablation was estimated to yield higher QALYs (+0.17) and higher costs (+$4274) per patient over a 40-year time horizon than AADs. Ultimately, this produced an average incremental cost-effectiveness ratio of $24,637 per QALY gained. Independent of initial treatment, individuals were expected to receive ∼1.2 ablations over a lifetime. There was a 45% relative reduction in time spent in atrial fibrillation health states for those initially treated with cryoablation compared with AADs. Conclusion: Initial rhythm control with first-line cryoballoon ablation is highly cost-effective compared with first-line AADs from a U.S. Medicare payer perspective.

Impact of intracardiac echocardiography usage on the safety of cryoballoon atrial fibrillation ablation: Subanalysis of the prospective FREEZE cluster cohort study.

INTRODUCTION: Cryoballoon ablation (CBA) aiming at pulmonary vein isolation (PVI) became a standardized atrial fibrillation (AF) ablation procedure. Life-threatening complications like cardiac tamponade exist. Intracardiac echocardiography (ICE) usage is associated with superior safety in radiofrequency ablation. It is unclear if ICE has an impact on safety of CBA. METHODS: The FREEZE Cohort (NCT01360008) subanalysis included patients undergoing "PVI only" CBA. Patients with intraprocedural transesophageal echocardiography were excluded. Group A comprises conventional, group B ICE-guided CBA. Periprocedural results were compared. RESULTS: From 2011 to 2016, a total of 4189 patients were enrolled, and 1906 (45.5%) were included in this subanalysis, split up in two groups (A: 1066 [55.9%], B: 840 [44.1%]). Group A was younger (60.6 ± 10.8 vs. 62.4 ± 10.5 years, p < .001), with smaller left atria (41 vs. 43 mm, p < .001), and less persistent AF (23.1 vs. 38.1%, p < .001). Procedure, left atrial, and fluoroscopy times were shorter in group A as compared to group B. Dose area product was significantly higher in group A (2911 vs. 2072 cGyxcm2 , p < .001). In-hospital major adverse cerebrovascular and cardiac event rates including two deaths in group A were not different between groups (0.5% vs. 0.1%, p = .18). The rate of total procedural (10.4% vs. 5.1%, p < .001) and major complications (3.2% vs. 1.3%, p < .001) was significantly higher in group A. Cardiac tamponade occurred significantly more frequently in group A (8 [0.8%] vs. 1 [0.1%], p = .046). Independent predictors for major complications were female sex (odds ratio [OR] 2.03, p = .03) and non-ICE usage (OR 2.38, p = .02). No differences were observed for persistent phrenic nerve palsy, nor for groin complications. CONCLUSION: CBA was significantly safer and required less radiation if ICE was used, although the procedures were more complex. The risk of groin complications was not increased with ICE usage. Non-ICE usage was the only modifiable independent predictor of major complications.

A worldwide survey on incidence, management, and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: the POTTER-AF study.

AIMS: Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management, and outcome are sparse. METHODS AND RESULTS: This international multicentre registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553 729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed, at 214 centres in 35 countries. In 78 centres 138 patients [0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (P < 0.0001)] were diagnosed with an oesophageal fistula. Peri-procedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8% and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) [odds ratio 7.463 (2.414, 23.072) P < 0.001]. CONCLUSION: Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high.

A rare case of right heart failure with the necessity for veno-arterial extracorporeal membrane oxygenation following pulmonary vein stenosis after radiofrequency ablation for atrial fibrillation.

Pulmonary vein stenosis (PVS) after radiofrequency energy-mediated percutaneous pulmonary vein isolation as a treatment option for atrial fibrillation is a serious complication and the prevalence in historical reports varies between 0% and 42%. Symptoms of PVS are nonspecific and can include general symptoms such as dyspnea, cough, recurrent pneumonia, and chest pain. Pathophysiologically it increases the postcapillary pressure in the pulmonary circuit and may result in pulmonary hypertension (PH). Misdiagnosis and delayed treatment are common. We here report a case of a 59-year-old female with a history of pulmonary vein ablation followed by progressive dyspnea (New York Heart Association IV), right heart failure, CPR, and the need for extracorporeal membrane oxygenation (ECMO). Further treatment strategy includes pulmonary vein dilatation and stenting of both the left superior pulmonary vein and left inferior pulmonary vein, as well as balloon dilatation of RIPV under temporary ECMO support. Symptomatic, severe PVS is a rare complication after catheter ablation of atrial fibrillation. PVS can result in life-threatening complications such as PH with acute right heart failure. Early diagnosis is crucial but challenging. Mechanical cardiopulmonary support by veno-arterial ECMO for bridging to angioplasty could be a lifesaving option.

Electrophysiology lab efficiency comparison between cryoballoon and point-by-point radiofrequency ablation: a German sub-analysis of the FREEZE Cohort study.

BACKGROUND: Pulmonary vein isolation (PVI) is recommended to treat paroxysmal and persistent atrial fibrillation (AF). This analysis aimed to assess the hospital efficiency of single-shot cryoballoon ablation (CBA) and point-by-point radiofrequency ablation (RFA). METHODS: The discrete event simulation used PVI procedure times from the FREEZE Cohort study to establish the electrophysiology (EP) lab occupancy time. 1000 EP lab days were simulated according to an illustrative German hospital, including 3 PVI cases per day using CBA at one site and RFA at the other. RESULTS: The analysis included 1560 CBA patients and 1344 RFA patients from the FREEZE Cohort. Some baseline patients' characteristics were different between groups (age, AF type, and some concomitant diseases), without being statistically associated to ablation procedure time. Mean procedure time was 122.2 ± 39.4 min for CBA and 160.3 ± 53.5 min for RFA (p < 0.0001). RFA was associated with a more than five-fold increase of cumulative overtime compared to CBA over the simulated period (1285 h with RFA and 253 h with CBA). 70.7% of RFA lab days included overtime versus 25.7% for CBA. CBA was associated with more days with an additional hour at the end of the EP lab shift compared to RFA (47.8% vs 11.5% days with one hour left, respectively). CONCLUSION: CBA is faster and more predictable than point-by-point RFA, and enables improvements in EP lab efficiency, including: fewer cumulative overtime hours, more days where overtime is avoided and more days with remaining time for the staff or for any EP lab usage. Clinical trial registration NCT01360008 (first registration 25/05/2011).

Impact of cryoballoon application abortion due to phrenic nerve injury on reconnection rates: a YETI subgroup analysis.

AIMS: Cryoballoon (CB)-based pulmonary vein isolation (PVI) is an effective treatment for atrial fibrillation (AF). The most frequent complication during CB-based PVI is right-sided phrenic nerve injury (PNI) which is leading to premature abortion of the freeze cycle. Here, we analysed reconnection rates after CB-based PVI and PNI in a large-scale population during repeat procedures. METHODS AND RESULTS: In the YETI registry, a total of 17 356 patients underwent CB-based PVI in 33 centres, and 731 (4.2%) patients experienced PNI. A total of 111/731 (15.2%) patients received a repeat procedure for treatment of recurrent AF. In 94/111 (84.7%) patients data on repeat procedures were available. A total of 89/94 (94.7%) index pulmonary veins (PVs) have been isolated during the initial PVI. During repeat procedures, 22 (24.7%) of initially isolated index PVs showed reconnection. The use of a double stop technique did non influence the PV reconnection rate (P = 0.464). The time to PNI was 140.5 ± 45.1 s in patients with persistent PVI and 133.5 ± 53.8 s in patients with reconnection (P = 0.559). No differences were noted between the two populations in terms of CB temperature at the time of PNI (P = 0.362). The only parameter associated with isolation durability was CB temperature after 30 s of freezing. The PV reconnection did not influence the time to AF recurrence. CONCLUSION: In patients with cryoballon application abortion due to PNI, a high rate of persistent PVI rate was found at repeat procedures. Our data may help to identify the optimal dosing protocol in CB-based PVI procedures. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03645577?term=YETI&cntry=DE&draw=2&rank=1 ClinicalTrials.gov Identifier: NCT03645577.

Guideline Directed Medical Therapy at Discharge and Further Uptitration Leading to Reduction in Indication for Prophylactic ICD Implantation during Protected Waiting Period.

Heart failure with reduced ejection fraction (LV-EF < 35%) is diagnosed in app. 11,000,000 patients worldwide. For the treatment of these patients, guideline directed medical therapy has proven to reduce mortality and rehospitalization regardless of the disease's etiology. It is implemented to treat clinical symptoms by improving the left ventricular ejection fraction. Patients with a transient risk of ventricular tachycardia and sudden cardiac death can be protected by a defibrillator vest. The defibrillator vest is capable to detect and terminate ventricular arrhythmias during Guideline Directed Medical Therapy (GDMT). It is based on the recommendations of the European society of cardiology for 3 months. Afterwards, the WCD wear time could be prolonged, or, in case of persistent low ejection fraction (LV-EF ≤ 35%), an implantable cardioverter defibrillator (ICD) should be implanted, as shown in the WEARIT-II-registry. Our goal was to evaluate the effects of GDMT on LV-recovery and reduction of ICD implantations under protection with a defibrillator vest­depending on the uptitration of GDMT. Methods: 339 consecutive patients between August 2017 and September 2020 with newly diagnosed cardiomyopathy and an EF ≤ 35% were analyzed retrospectively by chart review. All patients were protected by a wearable cardioverter defibrillator (WCD). GDMT as recommended by the ESC started at discharge from hospital. The left ventricular ejection fraction (LV-EF) was determined by transthoracic echocardiography at week 4, 8 and at week 12 (in case of prolonged WCD wear time). Uptitration was performed after 4 and 8 weeks during patient visits. We focused on baseline medication as per GDMT and the dosage increase at week 4, 8 and 12. The aim was the uptitration to the maximum dosage tolerated by the patient. We also compared the LV-EF improvement in the group with and without uptitration of medication dosage. Results: The patient age was, on average, 63.2 years (SD ± 11.9 years). A total of 129 pts (38%) had ICM, 196 (58%) had NICM (incl 66 pts (19%) with DCM and 51 pts (15%) with Myocarditis, 79 pts (24%) with unknown origin) and 14 pts (4%) had other entities (e.g., Tachycardiomyopathy). In total, 21 pts (6%) had an LV-EF of less than 16%, 130 pts (38%) between 16−25% and 183 pts (54%) between 26−35%. GDMT started at discharge from the hospital included treatment with beta blocker for 327 pts (96.5%), ACE-inhibitors/Angiotensin/ARNI for 283 pts (83.5%) and Mineralcorticoid receptor antagonists (MRA) for 334 pts (88.4%). Uptitration was performed in all groups at a rate of 82.3%, 91.1% and 81.0% after 4 weeks and 64.7%, 50.3% and 66.3% after 8 weeks, respectively. After 4 weeks, 25 pts (7.4%) and, after 8 weeks, 171 pts (50.4%) had an EF increase of 5% or more (mean 14.2%). After 4 weeks, 81 patients had an LV-EF more than 35%. A total of 169 pts had a wear time of 12 weeks and an improvement of LVEF of more than 35%. Interestingly, in our study we did not find a significant difference in LV-EF improvement between the group with no uptitration and the group with uptitration. Conclusions: Guideline-directed medical therapy under protection with a WCD from ventricular arrhythmia can reduce the need for implantation of an ICD and can lead to an improvement of ejection fraction. Interestingly, the LV-EF improvement depends on the GDMT at discharge. Current guidelines recommend an initiation of all therapy columns of GDMT (sacubitril/valsartan, ACE-inhibitor/AT1-blocker, mineralcorticoidreceptorblocker, beta blocker) at once and further uptitration to the maximal dosage (ESC Guidelines 2021). A further uptitration of all drugs of GDMT should lead to improvement of LV-EF and consequently to a reduction in ICD implantations.

New evidence: Cryoballoon ablation vs. antiarrhythmic drugs for first-line therapy of atrial fibrillation.

Atrial fibrillation (AF) is a commonly encountered chronic and progressive heart rhythm disorder, characterized by exacerbations and remissions. Contemporary clinical practice guidelines recommend a trial of antiarrhythmic drugs (AADs) as the initial therapy for sinus rhythm maintenance; however, these medications have modest efficacy and are associated with significant adverse effects. Recently, several trials have demonstrated that an initial treatment strategy of cryoballoon catheter ablation significantly improves arrhythmia outcomes (e.g. freedom atrial tachyarrhythmia and reduction in arrhythmia burden), produces clinically meaningful improvements in patient-reported outcomes (e.g. symptoms and quality of life), and significantly reduces subsequent healthcare resource utilization (e.g. hospitalization), without increasing the risk of serious or any adverse events. These findings are relevant to patients, providers, and healthcare systems, helping inform the decision regarding the initial choice of rhythm-control therapy in patients with treatment-naïve AF.

High Resting Heart Rates Are Associated with Early Posthospitalization Mortality in Low Ejection Fraction Patients.

Guideline-directed medical therapy (GDMT) is crucial in reducing mortality in patients with heart failure with heart rate lowering by a beta blocker (BB) being an important therapeutic concept. We aimed to assess the usefulness of a wearable cardioverter/defibrillator (WCD) to provide detailed information about heart rate for managing patients with reduced left ventricular ejection fraction (LVEF) and symptoms of heart failure and to correlate mortality with the mean heart rate. A total of 4509 consecutive patients (mean age: 59 + 13 years, 88% male) were analyzed retrospectively. All patients had reduced LVEF and were prescribed a WCD for protection from sudden cardiac death (SCD) during GDMT uptitration awaiting LVEF recovery. The device continuously measured nighttime and daytime HR at the beginning and end of WCD use. Patients who died during wear time had significantly higher HRs compared with survivors: daytime beginning of use (BOU), 80 ± 15 bpm vs. 76 ± 13, p < 0.01; nighttime BOU, 76 ± 14 vs. 69 ± 13, p < 0.0001; daytime end of use (EOU), 84 ± 20 vs. 73 ± 13, p < 0.0001; nighttime EOU, 80 ± 20 vs. 65 ± 12, p < 0.0001). In conclusion, HR monitoring with a WCD yields important prognostic information and may assist in optimal usage of BB in patients with low LVEF.

Phrenic Nerve Injury During Cryoballoon-Based Pulmonary Vein Isolation: Results of the Worldwide YETI Registry.

BACKGROUND: Cryoballoon-based pulmonary vein isolation (PVI) has emerged as an effective treatment for atrial fibrillation. The most frequent complication during cryoballoon-based PVI is phrenic nerve injury (PNI). However, data on PNI are scarce. METHODS: The YETI registry is a retrospective, multicenter, and multinational registry evaluating the incidence, characteristics, prognostic factors for PNI recovery and follow-up data of patients with PNI during cryoballoon-based PVI. Experienced electrophysiological centers were invited to participate. All patients with PNI during CB2 or third (CB3) and fourth-generation cryoballoon (CB4)-based PVI were eligible. RESULTS: A total of 17 356 patients underwent cryoballoon-based PVI in 33 centers from 10 countries. A total of 731 (4.2%) patients experienced PNI. The mean time to PNI was 127.7±50.4 seconds, and the mean temperature at the time of PNI was -49±8°C. At the end of the procedure, PNI recovered in 394/731 patients (53.9%). Recovery of PNI at 12 months of follow-up was found in 97.0% of patients (682/703, with 28 patients lost to follow-up). A total of 16/703 (2.3%) reported symptomatic PNI. Only 0.06% of the overall population showed symptomatic and permanent PNI. Prognostic factors improving PNI recovery are immediate stop at PNI by double-stop technique and utilization of a bonus-freeze protocol. Age, cryoballoon temperature at PNI, and compound motor action potential amplitude loss >30% were identified as factors decreasing PNI recovery. Based on these parameters, a score was calculated. The YETI score has a numerical value that will directly represent the probability of a specific patient of recovering from PNI within 12 months. CONCLUSIONS: The incidence of PNI during cryoballoon-based PVI was 4.2%. Overall 97% of PNI recovered within 12 months. Symptomatic and permanent PNI is exceedingly rare in patients after cryoballoon-based PVI. The YETI score estimates the prognosis after iatrogenic cryoballoon-derived PNI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03645577. Graphic Abstract: A graphic abstract is available for this article.

Initial rhythm control with cryoballoon ablation vs drug therapy: Impact on quality of life and symptoms.

BACKGROUND: Cryoballoon ablation (CBA) as a first-line rhythm control strategy is superior to antiarrhythmic drugs (AADs) for preventing atrial fibrillation (AF) recurrence; the impact of first-line CBA on quality of life (QoL) and symptoms has not been well characterized. METHODS: Patients aged 18 to 75 with symptomatic paroxysmal AF naïve to rhythm control therapy were randomized (1:1) to CBA (Arctic Front Advance, Medtronic) or AAD (Class I or III). Symptoms and QoL were assessed at baseline, 1, 3, 6, 9, and 12 months using the EHRA classification and Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and SF-36v2 questionnaires. Symptomatic palpitations were evaluated via patient diary. RESULTS: Overall, 107 patients were randomized to CBA and 111 to AAD; crossovers occurred in 9%. Larger improvements in the AFEQT summary, subscale and treatment satisfaction scores were observed at 12 months with CBA vs AAD (all P <0.05). At 12 months, the mean adjusted difference in the AFEQT summary score was 9.9 points higher in the CBA group (95% CI: 5.5 -14.2, P <0.001). Clinically important improvements in the SF-36 physical and mental component scores were observed at 12 months in both groups, with no significant between group differences at this timepoint. In the CBA vs AAD group, larger improvements in EHRA class were observed at 6, 9 and 12 months (P <0.05) and the incidence rate of symptomatic palpitations was lower (4.6 vs 15.2 days/year post-blanking; IRR: 0.30, P <0.001). CONCLUSIONS: In patients with symptomatic AF, first-line CBA was superior to AAD for improving AF-specific QoL and symptoms. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01803438.

Cryoballoon Ablation as Initial Treatment for Atrial Fibrillation: JACC State-of-the-Art Review.

Atrial fibrillation (AF), the most common sustained arrhythmia observed in clinical practice, is a chronic and progressive disorder characterized by exacerbations and remissions. Guidelines recommend antiarrhythmic drugs as the initial therapy for the maintenance of sinus rhythm; however, antiarrhythmic drugs have modest efficacy to maintain sinus rhythm and can be associated with significant adverse effects. An initial treatment strategy of cryoballoon catheter ablation in patients with treatment-naïve AF has been shown to significantly improve arrhythmia outcomes (freedom from any, or symptomatic atrial tachyarrhythmia), produce clinically meaningful improvements in patient-reported outcomes (symptoms and quality of life), and significantly reduce subsequent health care resource use (hospitalization), and it does not increase the risk of serious or any adverse events compared with initial antiarrhythmic drug therapy. These findings are relevant to inform patients, providers, and health care systems regarding the initial choice of rhythm-control therapy in patients with treatment-naïve AF.

Segmental nonocclusive cryoballoon ablation of pulmonary veins and extrapulmonary vein structures: Best practices III.

Although cryoballoon ablation of atrial fibrillation (AF) traditionally has been guided by pulmonary vein (PV) occlusion, there is evidence and growing interest in performing segmental, nonocclusive cryoballoon ablation to target not only large/common PVs but extra-PV structures such as the left atrial (LA) roof and posterior wall in conjunction with PV isolation. A number of studies have demonstrated improved clinical efficacy associated with nonocclusive cryoballoon ablation of the LA roof and posterior wall in addition to PV isolation, particularly in patients with persistent AF. Not only can the cryoballoon be used for targeting extra-PV structures through segmental, nonocclusive ablation, but the large size and durability of cryolesions coupled with the enhanced stability afforded through cryoadhesion render the cryoballoon an effective tool for such an approach. This article reviews the rationale and practical approach to segmental, nonocclusive cryoballoon ablation of large/common PV antra and the LA roof and posterior wall.

Cryoballoon ablation vs. antiarrhythmic drugs: first-line therapy for patients with paroxysmal atrial fibrillation.

AIMS: Treatment guidelines for patients with atrial fibrillation (AF) suggest that patients should be managed with an antiarrhythmic drug (AAD) before undergoing catheter ablation (CA). This study evaluated whether pulmonary vein isolation employing cryoballoon CA is superior to AAD therapy for the prevention of atrial arrhythmia (AA) recurrence in rhythm control naive patients with paroxysmal AF (PAF). METHODS AND RESULTS: A total of 218 treatment naive patients with symptomatic PAF were randomized (1 : 1) to cryoballoon CA (Arctic Front Advance, Medtronic) or AAD (Class I or III) and followed for 12 months. The primary endpoint was ≥1 episode of recurrent AA (AF, atrial flutter, or atrial tachycardia) >30 s after a prespecified 90-day blanking period. Secondary endpoints included the rate of serious adverse events (SAEs) and recurrence of symptomatic palpitations (evaluated via patient diaries). Freedom from AA was achieved in 82.2% of subjects in the cryoballoon arm and 67.6% of subjects in the AAD arm (HR = 0.48, P = 0.01). There were no group differences in the time-to-first (HR = 0.76, P = 0.28) or overall incidence [incidence rate ratio (IRR)=0.79, P = 0.28] of SAEs. The incidence rate of symptomatic palpitations was lower in the cryoballoon (7.61 days/year) compared with the AAD arm (18.96 days/year; IRR = 0.40, P < 0.001). CONCLUSIONS: Cryoballoon CA was superior to AAD therapy, significantly reducing AA recurrence in treatment naive patients with PAF. Additionally, cryoballoon CA was associated with lower symptom recurrence and a similar rate of SAEs compared with AAD therapy.

Cryoballoon catheter ablation versus antiarrhythmic drugs as a first-line therapy for patients with paroxysmal atrial fibrillation: Rationale and design of the international Cryo-FIRST study.

BACKGROUND: Radiofrequency current (RFC) catheter ablation for patients with paroxysmal atrial fibrillation (AF) has been shown to be safe and effective in first-line therapy. Recent data demonstrates that RFC ablation provides better clinical outcomes compared to antiarrhythmic drug (AAD) in the treatment of early AF disease. Furthermore, studies comparing RFC and cryoballoon have established comparable efficacy and safety of pulmonary vein isolation (PVI) for patients with symptomatic paroxysmal AF. OBJECTIVES: The Cryo-FIRST trial was designed to compare AAD treatment against cryoballoon PVI as a first-line therapy in treatment naïve patients with AF. Efficacy and safety will be compared between the two cohorts and amongst subgroups. METHODS: The primary hypothesis is that cryoablation is superior to AAD therapy. To test this hypothesis, patients will be randomized in a 1:1 design. Using a 90-day blanking period, primary efficacy endpoint failure is defined as (at least) one episode of atrial arrhythmia with a duration >30 sec (documented by 7-day Holter or 12-lead ECG). Secondary endpoints (Quality-of-Life, rehospitalization, arrhythmia recurrence rate, healthcare utilization, and left atrial function) and adverse events will also be evaluated. Study enrollment will include 218 patients in up to 16 centers. CONCLUSIONS: This study will be a multi-national randomized controlled trial comparing cryoablation against AAD as a first-line treatment in patients with paroxysmal AF. The results may help guide the selection of patients for early AF disease therapy via cryoballoon ablation.

Left atrial roof ablation in patients with persistent atrial fibrillation using the second-generation cryoballoon: benefit or wasted time?

INTRODUCTION: It is unknown whether left atrial (LA) roof ablation combined with pulmonary vein isolation (PVI) using a second-generation cryoballoon provides additional benefit beyond that of PVI alone in patients with persistent atrial fibrillation (AF). The aim of this study was to compare arrhythmia recurrence rates after PVI alone versus PVI plus LA roof ablation. METHODS AND RESULTS: In this observational study, we analyzed 399 symptomatic patients with persistent AF treated with cryoballoon ablation. After univariate and multivariate analyses of the entire cohort, propensity score matching resulted in two groups of 86 patients each: (1) PVI plus LA roof ablation (PVI-plus group) and (2) PVI alone (PVI-only group). The primary endpoint was the first documented > 30-s arrhythmia recurrence after a 3-month blanking period. PVI was successful in all patients. A bidirectional conduction block across the LA roof was verified in 91.9% of patients in the PVI-plus group. During a median mid-term follow-up of 33 months, 21 patients (24.4%) in the PVI-plus group and 37 patients (43.0%) in the PVI-only group (P = 0.01) reached the primary endpoint. Multivariate analysis revealed AF history > 2 years (hazard ratio [HR] = 2.04, P < 0.01), LA area > 21 cm2 (HR = 2.36, P < 0.01), female sex (HR = 1.92, P = 0.02), and LA roof ablation (HR = 0.47, P < 0.01) as significant predictors of outcome. CONCLUSIONS: We observed a significant difference in arrhythmia recurrence rates between the two groups. LA roof ablation is an effective adjuvant treatment option that shows improved outcome compared with PVI alone.