Treatment Of Paroxysmal Atrial Fibrillation Research Articles

LINAC-Based STereotactic Arrhythmia Radioablation (STAR) for paroxysmal atrial fibrillation in elderly: a prospective phase II trial

Abstract Background and aims Stereotactic arrhythmia radioablation (STAR) is a novel therapeutic approach for cardiac arrhythmias. The aim of this trial is to investigate the feasibility of STAR for the treatment of paroxysmal atrial fibrillation (AF) in elderly patients. Method inclusion criteria were: age > 70 years, symptomatic AF, antiarrhythmic drugs failure or intolerance. All patients underwent to 4D cardiac Computed Tomography simulation. The clinical target volume was identified in the area around pulmonary veins (PV). STAR was performed with a total dose of 25 Gy (single fraction) delivered in 3 minutes. Results Twenty patients were enrolled and 18 underwent STAR. One patient withdrew informed consent before treatment and 1 patient was excluded due to unfavorable esophagus position. With a median follow-up (FU) of 16 months (range 12-23), no acute toxicity more than grade 3 was reported. Five patients had a grade 1 esophagitis 24 hours after STAR; eight patients had an asymptomatic grade 1 pericardial effusion, one patient had a torsade de pointes treated effectively by electrical cardioversion and subsequent cardiac ICD implantation. Most patients had a significant reduction in AF episodes. Five patients, due to arrhythmias recurrences after STAR, performed electrophysiological study documenting successful PV isolation. Finally, a significant improvement of quality of life was documented (48 ± 15 at enrollment vs 75 ± 15 at 12 months FU; p < 0.001). Conclusion The present phase II trial demonstrated the feasibility of STAR in paroxysmal AF elderly patients and its potential role in increasing the quality of life. Surely, more robust data are needed about safety and efficacy.

Charge-density mapping to evaluate non-pulmonary vein substrate in patients with paroxysmal atrial fibrillation: the ACUPRED study

Abstract Background/introduction Pulmonary veins (PV) electrical isolation (PVI) is the main ablation strategy for the treatment of paroxysmal atrial fibrillation (AF), since the description of PV triggers. However, non-PV substrate and triggers in AF are not a negligible clinical issue. Indeed, in up to 22% of patients with AF recurrence after PVI, all PV are found isolated. Non-PV triggers can be demonstrated in up to 10-15% of non-selected patients at first AF ablation and non-PV substrate has been related to functional slow conduction and fibrosis also in paroxysmal AF. Purpose The aim of this study is to evaluate non-PV substrate (slow conduction) and triggers with charge-density (CD) mapping in patients with paroxysmal AF. Methods All patients, were prospectively enrolled in 2023. Inclusion criteria for the study were: 1) paroxysmal AF patients undergoing PVI procedure with a single-shot device and 2) CD mapping pre- and post- PVI. CD mapping was performed during CS proximal pacing at cycle length (CL) 600 ms and CS proximal pacing at CL 300 ms, pre- and post- PVI. Conduction velocity (CV) magnitude (in cm/s) and vector (direction and sense) were calculated offline for each CD map for all anatomical vertices. Reduction map was defined as the map of CV magnitude difference between CL 600 ms and CL 300 ms, Figure 1. Refraction map was defined as the map of CV direction difference between CL 600 ms and CL 300 ms, Figure 1. Non-PV substrate was defined at pre-PVI maps as: 1) slow conduction (<30 cm/s) at CL 600 ms or CL 300 ms, or 2) difference in CV magnitude (>25 cm/s) at reduction map, a marker of functional slow conduction (induced by fast pacing), or 3) difference in CV direction more than 90° between two neighboring vertices at refraction map, a marker of anisotropy, Figure 1. Non-PV triggers were defined as non-PV premature atrial contractions >10/min or inducing AF. Results A total of 43 patients (60.6 ± 11.2 years, 74.4% males) with paroxysmal AF undergoing first procedure PVI were analyzed. Non-PV substrate was found in 13 patients (30.2%). Non-PV triggers were found in 3 patients (6.9%), including one patient on the posterior wall near right PV antra and two patients on the posterior wall near the left PV antra. At a mean follow-up of 5.6 months, a total of 5 patients (11.6%) experienced a recurrence. Patients experiencing a recurrence had more frequently non-PV substrate (80.0% vs 23.7%, p=0.024) and lower CV magnitude at CL 600 ms pre-PVI (72.3 cm/s vs 83.1 cm/s, p=0.04). At survival analysis for 34 patients (79.1%) out of the 2 months blanking period, patients with non-PV substrate had lower freedom from AF recurrence (56% vs 90%, p=0.0028), Figure 2. Conclusion In patients with paroxysmal AF undergoing index PVI, non-PV substrate or triggers can be found in up to 37.1% of cases. Non-PV substrate is associated with worse arrhythmic prognosis.Figure 1Figure 2

An economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from a Danish healthcare perspective

Abstract Background As demonstrated in three randomized clinical trials (RCTs), initial rhythm control with first-line pulmonary vein isolation (PVI) using cryoballoon ablation decreases atrial arrhythmia recurrence compared to antiarrhythmic drug (AAD) therapy in patients with symptomatic paroxysmal atrial fibrillation (PAF). Purpose To assess the cost-effectiveness of first-line cryoablation versus first-line AADs in a Danish healthcare setting. Methods Data from 703 participants with symptomatic PAF enrolled into Cryo-FIRST, STOP AF First and EARLY-AF RCTs were used to estimate risk equations (rate of ablation, AF recurrence and resolution, AF-related hospital attendance in addition to health-related quality-of-life (HRQoL) utilities). These were then incorporated into a cost-effectiveness model (CEM) . The Danish cost data was derived from published Danish literature, DRG tariffs and pharmaceutical list prices in Denmark. Where parameters could not be derived, inputs were sourced from published literature or expert opinion. The CEM consisted of a decision tree (one-year time horizon) and a Markov model (three-month cycle length) hybrid, with a lifetime (40 years) time horizon. The CEM is from the perspective of the Danish healthcare system. Health benefits were expressed in quality-adjusted life-years (QALYs), and all costs and benefits were discounted at 3%. As there is no official cost-effectiveness threshold in Denmark, the UK threshold of £20,000 (~€23,200) was assumed. Input uncertainty within the CEM was explored using probabilistic sensitivity analysis. The results presented include data from the initial 12-week blanking period for all studies. Results The three-monthly rate of AF symptom recurrence had a reduction, on average, of 46.7% (p<0.001) in those treated with cryoablation. In addition, the cryoablation arm had a 72.8% (p<0.001) reduction in the monthly rate of receiving an ablation following initial treatment. The average cryoablation patient was also associated with a 4.3% (p=0.025) increase in their HRQoL. Finally, there was no difference in the rate of AF symptom resolution in those who failed initial treatment. Base case results per patient are presented in Table 1. Cryoablation was shown to be dominant when compared to AADs (0.159 more QALYs and €2,519 less costly), with a 99.96% probability of being cost-effective at a willingness-to-pay threshold of ~€23,200 per QALY gained. Individuals in both arms of the model were also expected to receive ~1.2 ablations over a lifetime horizon. Nonetheless, there was a 45% relative reduction in time spent in symptomatic AF states for individuals who were initially treated with cryoablation. Scenario analysis results are presented in Table 2. Cryoablation remained cost-effective over AADs in all scenarios conducted. Conclusions Initial rhythm control with cryoballoon ablation is cost-effective (dominant) when compared to AADs in the Danish healthcare system.Table 1:Key results (per patient)Table 2.Deterministic scenario analysis

Role of high-density voltage map guiding parosysmal atrial fibrillation ablation

Abstract Background High-density mapping of the pulmonary vein antra has been demonstrated to improve the detection of conduction gaps in wide antral catheter ablation (WACA) approach for the treatment of paroxysmal atrial fibrillation (AF). Purpose We aimed to compare the AF recurrencies in patients treated with WACA for pulmonary veins isolation (PVI) guided by high-density bipolar voltage map (BVM) vs WACA guided by a standard 20-pole circumferential mapping catheter (CMC-20). Methods This prospective study included patients scheduled for AF ablation in a single center. In group A (85 patients) PVI was achieved with a conventional approach using CMC-20; in group B (96 patients) high density BVM was acquired by sequential multielectrode mapping through Pentaray Catheter (Biosense Webster). More than 1000 voltage points per map were acquired. Acute PVI was defined as an entrance and exit block after ≥ 20 min waiting period. In both groups WACA was perfomed using a contact force sensing catheter targeting an interlesion distance ≤6 mm and ablation index ≥400 at posterior wall and ≥550 at anterior wall. The primary endpoint was the AF recurrencies in the two groups. Results A total of 181 patients were included (mean age 64.9±10.6 years, 33.1% female): in 85 patients AF ablation was guided by CMC-20, in 96 patients AF ablation was guided by BVM; WACA PVI was achieved in all patients. There were no significant differences in the clinical characteristics of the two groups (table 1). At 12-month follow-up, AF recurrencies were significantly lower in the BVM group compared with CMC-20 group [11/96 (11.4%) vs 19/85 (22.3%) respectively, p=0.01]. Conclusions High-density BVM might increase success rate of AF ablation compared with a conventional 20-pole circumferential mapping approach.

First-time catheter ablation outcomes for atrial fibrillation are dependent on low-voltage areas rather than paroxysmal vs. persistent classifications: a REAL-AF study

Abstract Background Left atrial low-voltage areas (LA LVA) measured at time of catheter ablation for atrial fibrillation (AF) have been increasingly recognized as an indicator of atrial fibrosis [1]. However, little is known whether first-time catheter ablation outcomes differ between paroxysmal AF (PAF) and persistent AF (PerAF) in patients with higher LA LVA, which may indicate a more advanced substrate independent of clinical subtype. Purpose To evaluate whether outcomes of first-time catheter ablation for AF are dependent on LA LVA rather than PAF vs. PerAF types in a multicenter registry of patients. Methods The Real-world Experience of Catheter Ablation for the Treatment of Symptomatic PAF and PerAF Using Novel Contact Force Technologies registry (REAL-AF) is a prospective, observational multicenter registry of patients undergoing catheter ablation. We evaluated 4181 patients undergoing first-time catheter ablation for both PAF and PerAF to determine AF recurrence within 12 months. Contact maps were created using a 5-spline high-density catheter. LA LVA was calculated using these contact maps based on a bipolar voltage of <0.50 mV. LA LVA was categorized into low (<5%) vs. high (≥5%) based on preliminary data. Risk of recurrence was analyzed using Cox proportional hazard models. Results Patients with LA LVA ≥5% who underwent first-time catheter ablation for AF (both PAF and PerAF) experienced a higher risk of AF recurrence within 12 months (Hazard ratio (HR): 1.95, p<0.001), see Figure 1. Overall, 82.0% of patients were free of AF in the LA LVA <5% group compared to 69.1% in the LA LVA ≥5% group. This association remained significant in a subpopulation of patients presenting in normal sinus rhythm (N = 2463) at time of ablation (HR: 1.90, p<0.001). 12-month ablation outcomes between PAF and PerAF in patients with LA LVA ≥5% (N = 1590) were not statistically significant (71.0% vs 67.3% respectively, HR: 1.15, p=0.30), see Figure 2. Finally, in the LA LVA <5% group (N = 2591), patients with PerAF had a 1.42 times higher risk for AF recurrence within 12 months after catheter ablation (p=0.04). Conclusion This is the largest real-world registry to date demonstrating that LA LVA ≥5% is associated with a higher risk of AF recurrence within 12 months in patients undergoing first-time catheter ablation for AF. Among patients with LA LVA ≥5%, AF recurrence was not associated with AF type. These findings motivate further studies into using LA LVA as a prognostic tool for patients undergoing first-time catheter ablation for AF and using non-invasive methods to assess this in order to stratify patients further.

LINAC–BASED STEREOTACTIC ARRHYTHMIA RADIOABLATION (STAR) FOR PAROXYSMAL ATRIAL FIBRILLATION IN ELDERLY: A PROSPECTIVE PHASE II TRIAL

Abstract Background and Aims The aim of this trial is to investigate the feasibility of radiotherapy for the treatment of paroxysmal atrial fibrillation (AF) in elderly patients. Method inclusion criteria were: age > 70 years, symptomatic AF, antiarrhythmic drugs failure or intolerance. All patients underwent to 4D cardiac Computed Tomography simulation. The clinical target volume was identified in the area around pulmonary veins (PV). STAR was performed with a total dose of 25 Gy (single fraction) delivered in 3 minutes. Results Twenty patients were enrolled and 18 underwent STAR. One patient withdrew informed consent before treatment and 1 patient was excluded due to unfavorable esophagus position. With a median follow–up (FU) of 16 months (range 12–23), no acute toxicity more than grade 3 was reported. Five patients had a grade 1 esophagitis 24 hours after STAR; eight patients had an asymptomatic grade 1 pericardial effusion, one patient had a torsade de pointes treated effectively by electrical cardioversion and subsequent cardiac ICD implantation. Most patients had a significant reduction in AF episodes. Five patients, due to arrhythmias recurrences after STAR, performed electrophysiological study documenting successful PV isolation. Finally, a significant improvement of quality of life was documented (48 ± 15 at enrollment vs 75 ± 15 at 12 months FU; p < 0.001). Conclusion The present phase II trial demonstrated the feasibility of STAR in paroxysmal AF elderly patients and its potential role in increasing the quality of life. Surely, more robust data are needed about safety and efficacy.

Dual energy for pulmonary vein isolation using dual-energy focal ablation technology integrated with a three-dimensional mapping system: SmartfIRE 3-month results.

Contact force (CF)-sensing radiofrequency (RF) catheters with an ablation index have shown reproducible outcomes for the treatment of atrial fibrillation (AF) in large multicentre studies. A dual-energy (DE) focal CF catheter to deliver RF and unipolar/biphasic pulsed field ablation (PFA), integrated with a three-dimensional (3D) mapping system, can provide operators with additional flexibility. The SmartfIRE study assessed the safety and efficacy of this novel technology for the treatment of drug-refractory, symptomatic paroxysmal AF. Results at 3 months post-ablation are presented here. Pulmonary vein isolation (PVI) was performed using a DE focal, irrigated CF-sensing catheter with the recommendation of PFA at posterior/inferior and RF ablation at the anterior/ridge/carina segments. Irrespective of energy, a tag size of 3 mm; an inter-tag distance ≤6 mm; a target index of 550 for anterior, roof, ridge, and carina; and a target index of 400 for posterior and inferior were recommended. Cavotricuspid isthmus ablation was permitted in patients with documented typical atrial flutter. The primary effectiveness endpoint was acute procedural success. The primary safety endpoint was the rate of primary adverse events (PAEs) within 7 days of the procedure. A prespecified patient subset underwent oesophageal endoscopy (EE; 72 h post-procedure), neurological assessment (NA; pre-procedure and discharge), and cardiac computed tomography (CT)/magnetic resonance angiogram (MRA) imaging (pre-procedure and 3 months post-procedure) for additional safety evaluation, and a mandatory remapping procedure (Day 75 ± 15) for PVI durability assessment. Of 149 patients enrolled between February and June 2023, 140 had the study catheter inserted (safety analysis set) and 137 had ablation energy delivered (per-protocol analysis set). The median (Q1/Q3) total procedure and fluoroscopy times were 108.0 (91.0/126.0) and 4.2 (2.3/7.7) min (n = 137). The acute procedural success rate was 100%. First-pass isolation was achieved in 89.1% of patients and 96.8% of veins. Cavotricuspid isthmus ablations were successfully performed in 12 patients [pulsed field (PF) only: 6, RF only: 5, and RF/PF: 1]. The PAE rate was 4.4% [6/137 patients; 2 pulmonary vein (PV) stenoses, 2 cardiac tamponades/perforations, 1 stroke, and 1 pericarditis]. No coronary artery spasm was reported. No oesophageal lesion was seen in the EE subset (0/31, 0%). In the NA subset (n = 30), microemboli lesions were identified in 2 patients (2/30, 6.7%), both of which were resolved at follow-up; only 1 was symptomatic (silent cerebral lesion, 3.3%). In the CT/MRA subset (n = 30), severe PV narrowing (of >70%) was detected in 2 patients (2/30, 6.7%; vein level 2/128, 1.6%), of whom 1 underwent dilatation and stenting and 1 was asymptomatic; both were associated with high index values and a small inter-tag distance. In the PV durability subset (n = 30), 100/115 treated PVs (87%) were durably isolated and 18/30 patients (60.0%) had all PVs durably isolated. A DE focal CF catheter with 3D mapping integration showed a 100% acute success rate with an acceptable safety profile in the treatment of paroxysmal AF. Prespecified 3-month remapping showed notable PVI durability. ClinicalTrials.gov Identifier: NCT05752487.

Pulsed field ablation with the pentaspline catheter compared with cryoablation for the treatment of paroxysmal atrial fibrillation in the UK NHS: a cost-comparison analysis

ObjectivesPulsed field ablation (PFA) is a promising new ablation modality for the treatment of atrial fibrillation (AF) that has recently become available in the UK National Health Service (NHS). We...

Comparing pulsed field electroporation and radiofrequency ablation for the treatment of paroxysmal atrial fibrillation: design and rationale of the BEAT PAROX-AF randomized clinical trial.

Using thermal-based energy sources [radiofrequency (RF) energy/cryo energy] for catheter ablation is considered effective and safe when performing pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (AF). However, treatment success remains limited and complications can occur due to the propagation of thermal energy into non-target tissues. We aim to compare pulsed field ablation (PFA) with RF ablation in terms of efficacy and safety for patients with drug-resistant paroxysmal AF. The BEAT PAROX-AF trial is a European multicentre, superiority, open-label randomized clinical trial in two parallel groups. A total of 292 participants were recruited in 9 high-volume European clinical centres in 5 countries. Patients with paroxysmal AF were randomized to PFA (FARAPULSE Endocardial Ablation System©, Boston Scientific) or RF using the CLOSE protocol with contact force sensing catheter (SmartTouch© catheter and CARTO© Biosense Webster). The primary endpoint will be the 1-year recurrence of atrial arrhythmia, and the major secondary safety endpoint will be the occurrence of acute (<7 days) procedure-related serious adverse events, or pulmonary vein stenosis, or atrio-oesophageal fistula up to 12 months. Additionally, five sub-studies investigate the effect of PFA on oesophageal safety, cerebral lesions, cardiac autonomic nervous system, durability of PVI as assessed during redo ablation procedures, and atrial and ventricular function. The study began on 27 December 2021 and concluded recruitment on 17 January 2024. Results will be available in mid-2025. The BEAT PAROX-AF trial aims to provide critical insights into the optimal treatment approach for patients with paroxysmal AF.

Cryoablation versus hybrid radiofrequency with high- and very-high-power short-duration catheter ablation for the treatment of paroxysmal atrial fibrillation

BackgroundHigh-power short-duration (HPSD) and very-high-power short-duration (vHPSD-90 W/4 s) radiofrequency (RF) technology has reduced the procedure time of pulmonary vein isolation (PVI) using RF without compromising the efficacy of the technique. The current study compares the novel technology of HPSD/vHPSD with cryoablation (CRYO) in terms of efficacy, safety, and procedure time in a cohort of symptomatic patients with paroxysmal atrial fibrillation (pAF). MethodsThis is a prospective, non-randomized trial. Patients with pAF received either CRYO or HPSD/vHPSD RF PVI. The primary endpoint of the study was arrhythmia recurrence in a 12 month follow-up period. Secondary endpoints included procedure time, fluoroscopy time, and safety. Results104 patients were included (45 in HPSD/vHPSD and 59 in CRYO), with comparable characteristics between groups. The follow-up was 12.4 ± 0.5 months. There was no significant difference regarding arrhythmia recurrences during the early post-procedural period of the first 3 months (8.9% recurrences in HPSD/vHPSD versus 5.1% in CRYO-p 0.463) and in the mid-term follow-up of 12 months (17.8% recurrences in HPSD/vHPSD versus 10.2% in CRYO-p 0.385). Safety was excellent for both procedures. CRYO was a procedure of significantly shorter duration (64.64 ± 8.94 min versus 75.29 ± 18.30 min, p = 0.0001) at the expense of longer fluoroscopy time (HPSD/vHPSD 5.34 ± 1.83 versus 7.89 ± 3.70 min CRYO, p 0.001). ConclusionsHPSD/vHPSD and CRYO in pAF were comparable regarding the arrhythmia recurrence rates in a 12-month follow-up with excellent safety. The hybrid approach of HPSD/vHPSD has accelerated RF-PVI compared to conventional RF, but CRYO remains a procedure of significantly shorter duration at the expense of longer fluoroscopy time.

Cryoballoon ablation without use of contrast for the treatment of paroxysmal atrial fibrillation.

Cryoballoon ablation (CBA) for atrial fibrillation (AF) is usually preceded by demonstrating pulmonary vein (PV) occlusion using contrast. The aim of the study was to determine efficacy and safety of a simplified protocol for CBA performed without demonstrating PV occlusion and compare achieved results with conventional CBA. Paroxysmal AF patients undergoing a first-time CBA were prospectively included. In the non-contrast (NC) group CBA was performed using standardized protocol without demonstrating PV occlusion. In the conventional contrast (CC) group ablations were performed after confirmation of PV occlusion. The NC and CC groups comprised 51 and 22 patients, respectively. PVI according to the group assignment was achieved in 34 (67%) and 21 (95.5%) patients from the NC and CC groups, respectively (p < 0.001). In the NC group, 184 (90%) out of 204 veins were isolated without venography. There were no differences between the NC and CC groups in terms of procedure duration (89.7 ± 22.6 vs. 90.0 ± 20.6 min; p = 0.7) and fluoroscopy time (15.3 ± 6.3 vs. 15 ± 4.5 min; p = 0.8). In the NC group, the use of contrast was significantly lower compared to the CC group (4.9 ± 10.1 vs. 19.4 ± 8.6 mL, p < 0.001). There were no serious adverse events in both groups. A 1-year freedom from AF was achieved in 73.5% and 71.5% of patients from the NC and CC groups, respectively (p = 1). Cryoballoon ablation without demonstrating vein occlusion with contrast is safe and feasible. Proposed simplified approach enables isolation of the vast majority of pulmonary veins with a significant reduction in the amount of contrast used.

Comparative Safety of Pulsed Field Ablation and Cryoballoon Ablation Technologies for Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation: A Critical Literature Review and Indirect Treatment Comparison.

Cryoballoon ablation (CBA) is a standard catheter ablation technology with demonstrated clinical effectiveness for the treatment of paroxysmal atrial fibrillation (PAF); however, it can be associated with major adverse events, including phrenic nerve paralysis. Pulsed field ablation (PFA) is a novel, minimally thermal technology with comparable effectiveness and low safety risk. This study aimed to compare the safety profiles of PFA and CBA through critical analyses of the literature and indirect treatment comparisons. Studies were identified by searching the MEDLINE database and the Clinicaltrials.gov registry. Registered clinical trials and/or Food and Drug Administration Investigation Device Exemption (FDA IDE) studies evaluating PFA or CBA in adult patients with drug-refractory PAF between January 2008 and March 2023 were selected. Comparative safety between PFA and CBA was assessed for major and prespecified adverse events. Indirect comparisons were conducted using the proportion of patients experiencing adverse events and confirmed with single-arm meta-analyses and sensitivity analyses. Data were extracted from three PFA publications including a total of 497 patients and six CBA studies including a total of 1113 patients. The analysis revealed that PFA was associated with significantly lower risk of major adverse events {risk difference-4.3% [95% confidence interval (CI)-5.8,-2.8]; risk ratio 0.16 [95% CI 0.07, 0.45]} and prespecified adverse events [risk difference -2.5% (95% CI-4.4,-0.5); risk ratio 0.53 (95% CI 0.31, 0.96)]. Meta-analyses confirmed the lower rate of major adverse events for PFA [0.4% (95% CI 0.0, 1.3)] vs. CBA [5.6% (95% CI 2.6, 8.6)] and prespecified adverse events for PFA [2.7% (95% CI 1.2, 4.1)] vs. CBA [5.8% (95% CI 2.7, 9.0)]. Sensitivity analyses exploring heterogeneity across studies confirmed robustness of the main analyses. The findings of this study show that PFA has a more favorable safety profile than CBA, with significantly lower risks of major and prespecified adverse events. These indirect comparisons help contextualize the safety of PFA compared to CBA for the treatment of drug-refractory PAF in the absence of head-to-head studies.

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

IntroductionThree 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...

Temperature to time Catch-Up: a novel procedural endpoint to predict durable pulmonary vein isolation after cryoballoon ablation of paroxysmal atrial fibrillation.

Cryoballoon ablation is a widely used single-shot technique for pulmonary vein isolation (PVI) in the treatment of paroxysmal atrial fibrillation (AF). Procedural endpoints ensuring maximal PVI durability are important. To assess the performance of cryoablation procedural markers to predict long-term PVI. In a single center, consecutive patients who underwent redo ablation with high-density mapping for symptomatic AF recurrence after cryoballoon ablation were included and cryoballoon procedural data were collected, including temperature values at 30 and 60s, time to isolation, nadir temperature and the velocity of temperature decline estimated with the temperature/time catch-up point (T2T-Catch-Up) defined as positive when the freeze temperature in minus degree equals the time in seconds after cryoablation initiation (e.g. -15°C in the first 15s of the ablation impulse). 47 patients (62% male; 58.3 ± 11.2years) were included. Overall, 38 (80.9%) patients had ≥ 1 reconnected PV. Among 186 PVs, 56 (30.1%; 1.2 per patient on average) were reconnected. Univariate analysis revealed T2T-Catch-Up in 103 (56%) and more frequent in durably isolated than in reconnected PVs (93 [72%] vs 10 [19%], p < 0.0001). Among binary endpoints, T2T-Catch-Up had the highest specificity (82%) and predictive value for durable PVI at redo ablation (90%). In multivariable analyses, absence of T2T-Catch-Up (Odds-ratio 0.12, 95% CI [0.05-0.31], p < 0.0001) and right superior PV (Odds-ratio 3.14, 95% CI [1.27-7.74], p = 0.01) were the only variables independently associated with PV reconnection. T2T-Catch-Up, a new and simple cryoballoon procedural endpoint demonstrated excellent predictive value and strong statistical association with durable PVI.

Long-term success rates of a stable, low pressure cryo balloon for the treatment of paroxysmal atrial fibrillation - results of the prospective, international, multicenter POLAR-ICE study

Abstract Background/Introduction Pulmonary vein isolation (PVI) using a cryo balloon is well-established for the treatment of paroxysmal atrial fibrillation (PAF). Compared to other available technologies, the usage of a stable, low pressure cryo balloon (POLARx, Boston Scientific) has demonstrated lower nadir temperatures and longer thawing times. However, long term efficacy and safety still needs to be proven. Purpose The aim of the POLAR-ICE Study was to evaluate long-term efficacy and safety outcome of cryo balloon ablation in patients with paroxysmal atrial fibrillation. Methods POLAR ICE, a prospective, non-randomized, international, multicenter study, enrolled 399 patients across 19 centers, between Aug 2020 and May 2021. Patients with paroxysmal atrial fibrillation undergoing de novo PVI were included into the study. During the index procedure, procedural characteristics, such as time to isolation (TTI), cryoablations per pulmonary vein, balloon nadir temperature, and occlusion grade were recorded. Procedural success was defined as successful isolation of each vein proven by entrance block. Follow up visits were at 3, 6, and 12 months. Recurrence is defined as any documented (ECG/Holter) episode of atrial fibrillation / atrial tachycardia longer than 30sec. after a blanking period of 3 months. Results 399 patients (mean age 61 years, 36% female) were included into the study. After 12 months, freedom from any arrhythmia was 83.5% and freedom from atrial fibrillation 88.1% (Figure 1). Procedure/ablation related Serious adverse events occurred in 8.7% of patients, and included access complications (2.6%), cardiac tamponade (0.5%), air embolism (0.3%), AV block (0.3%), effusion (0.3%) phrenic nerve palsy (0.3%), stroke (0.3%), transient ischemic attack (0.3%). Redo procedures have been conducted in 19 patients. In 14/19 pts reconnection of at least one PV could be identified (RSPV n=8, RIPV n=12, LSPV n=9, LIPV n=11). Freedom from any arrhythmia was associated with lower nadir temperature (p=0.008) and longer time to thaw (p=0.05) during the index procedure. Conclusions In this prospective, non-randomized, international, multicenter study, isolation of the pulmonary veins using a stable, low pressure cryo balloon was highly effective and safe in patients treated for paroxysmal atrial fibrillation. Lower nadir temperatures and a longer thawing time were predictors of clinical success.

An economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from a German healthcare service payer perspective

Abstract Background Three recent randomized controlled trials demonstrated that, in patients with symptomatic paroxysmal atrial fibrillation (PAF), first-line pulmonary vein isolation (PVI) with cryoballoon ablation reduces atrial arrhythmia recurrence when compared to initial antiarrhythmic drug (AAD) therapy. Purpose To evaluate the cost-effectiveness of initial rhythm control therapy from a German healthcare service payer perspective. Methods The cost-effectiveness model (CEM) structure consisted of a hybrid decision tree and Markov model, where the decision tree informed the initial health state allocation in the first cycle of the Markov model and had a one-year time horizon. The Markov model had a 40-year time horizon using a three-month cycle length. Health benefits were expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3.5% p.a. Individual patient-level data from 703 participants with untreated PAF enrolled into Cryo-FIRST (NCT01803438), STOP AF First (NCT03118518) and EARLY-AF (NCT02825979) were used to estimate efficacy, resource use and health-related quality of life parameters. Cost inputs were sourced from diagnosis-related groups and the Institute for the Hospital Remuneration System (InEK). Where parameters could not be derived, inputs were sourced from available published literature or determined through clinical expert opinion. Probabilistic sensitivity analyses were conducted to explore the impact of any assumptions on model outputs. Results In those treated with cryoablation, the three-month rate of AF recurrence was reduced by 46.7% (p&amp;lt;0.001) on average. Similarly, the average monthly rate of receiving an ablation following initial treatment was reduced by 72.8% (p&amp;lt;0.001). Cryoablation was also associated with a 4.3% (p=0.025) increase in health-related quality of life at 12 months, assessed through the standard EQ-5D-3L instrument. There was no difference in the rate of AF resolution in those who failed initial treatment. CEM results are shown in Table 1. Analysis shows that cryoablation is cost-effective, incurring a cost of ∼€1,000 per patient over a lifetime compared to AADs, while offering an increase in QALYs. Cryoablation attains an average ICER of ∼€5,500, with a 94.1% probability of being cost-effective at a willingness-to-pay threshold of €35,000 per QALY gained. Through 5,000 iterations, the probabilistic sensitivity analysis indicates that cryoablation has ∼20% probability of being cost-saving. Individuals are expected to receive a total of ∼1.2 ablations over a lifetime, regardless of initial treatment. Although, those initially treated with cryoablation as opposed to AADs experience a 45% reduction in time spent in AF health states. Conclusion Initial rhythm control with cryoballoon ablation in PAF is a cost-effective treatment option in a German healthcare setting.Table 1:Key results (per patient)

Abstract 13916: Patient Outcomes 6 Months Following Pulmonary Vein Isolation for Atrial Fibrillation With a Novel RF Catheter: Initial Data From NEwTON AF

Introduction: The combination of local impedance (LI), a direct measure of electrical resistance at the catheter tip, and contact force (CF) may facilitate treatment of atrial fibrillation (AF). This trial is designed to examine the safety and effectiveness of a novel RF catheter that allows measurement of both LI and CF. Hypothesis: Demonstrate the safety and effectiveness of a novel radiofrequency catheter with LI and CF for treatment of drug refractory, recurrent, symptomatic Paroxysmal AF (PAF). Methods: NEwTON AF is a multi-center, global, prospective, single arm study. Patients received index treatment for PAF with the study catheter. The present 6-month endpoint analysis was prospectively planned. Results: The study treated 299 patients at 45 sites in North America, Europe, and Asia. Patients were 39.5% female with a mean age of 62yrs (±12), and had a mean LVEF of 59% and an LA diameter of 3.9cm. Procedure time, LA dwell, and fluoroscopy times were 166, 136, and 15 minutes, respectively. High-power short-duration (HSPD, 45-50W) was exclusively used in 210 cases, which had notably shorter procedure times than the 82 cases that used conventional power, 148 vs 208 min, respectively. Acute procedural success was observed in 98.3% of cases. As of 6 months, freedom from documented recurrence of any atrial arrhythmia was 79.9% (Figure). Recurrence in relation to LI shows that pts with a 20Ω LI drop (in at least 60% of lesions) had better 6m outcomes (84.2% vs 73.3, p=0.04). The freedom from safety event rate at 30d was 96.0%; events included pericarditis (6), access complications (2), pulmonary edema (2), embolism (2), cerebrovascular accident (1), tamponade (1). Pericarditis was higher in pts with a history of COVID at enrollment, 16.3% vs 5.9%, p=0.025. Conclusions: This data suggests that patient outcomes and safety for this novel catheter are promising. Further data from this study, including 12m outcomes, and detailed analysis of local impedance data are forthcoming.

Safety and effectiveness of the first contact force ablation catheter with a flexible tip

Catheter ablation is an established therapy for paroxysmal atrial fibrillation (PAF). The TactiFlex Ablation Catheter, Sensor Enabled (TactiFlex SE) is a next-generation radiofrequency ablation catheter incorporating fiber optics-based contact force-sensing technology with a flexible, laser-cut tip. The study sought to evaluate the safety and effectiveness of the TactiFlex SE ablation catheter for treatment of drug-refractory PAF. The TactiFlex AF investigational device exemption was a prospective, nonrandomized, multicenter clinical study. Enrollment began on June 26, 2020 and completed June 18, 2021. Subjects with PAF underwent de novo pulmonary vein isolation and, if indicated, ablation for typical atrial flutter. Subjects were followed for 12 months. Of the 355 subjects enrolled at 37 sites worldwide, 334 underwent ablation with the TactiFlex SE catheter. The Kaplan-Meier estimate of 12-month freedom from AF/atrial flutter (AFL)/atrial tachycardia recurrence was 72.9% (95% confidence interval [CI] 95% CI 67.2%-77.8%) and clinical success was 83.6% (95% CI 95% CI 78.1%-87.2%). As-treated analyses compared subjects treated at high power (left atrium time-averaged power setting 40-50 W; n = 222) vs low power (<40 W; n = 97). The Kaplan-Meier estimate of 12-month freedom from AF/AFL/atrial tachycardia recurrence was 76.4% (95% CI 69.3%-82.0%) and clinical success was 83.9% (95% CI 77.5%-88.6%) in the high-power group compared with 66.8% (95% CI 56.1%-75.5%) and 80.7% (95% CI 70.8%- 87.5%), respectively, in the low-power group. The primary safety event rate in all treated subjects was 4.3%; 4.1% in the HP group and 5.2% in the LP group (P = .7671). TactiFlex SE is safe and effective for treatment of drug-refractory PAF and concomitant AFL and enables more efficient procedures than previous generation catheters.

Liquid Nitrogen Cryoballoon Ablation System for Paroxysmal Atrial Fibrillation: A Multicenter, Prospective, Single-Arm Clinical Trial

BackgroundCryoballoon ablation (CBA) has emerged as an effective treatment for atrial fibrillation (AF). ObjectivesThis study sought to assess the performance of a novel liquid nitrogen–driven CBA system and evaluate its safety and efficacy in the treatment of drug-resistant paroxysmal atrial fibrillation (PAF). MethodsThis was a prospective multicenter single-arm clinical trial with 10 participating tertiary hospitals enrolling 176 patients with PAF. All participants received liquid nitrogen–driven CBA developed by the Cryofocus Medtech Company. Scheduled follow-up was performed before discharge and 3 months, 6 months, and 12 months after CBA. The primary endpoints were defined as 1) treatment success (freedom from antiarrhythmic drugs and atrial tachycardia at 12 months after CBA); and 2) immediate success rate of pulmonary vein isolation. The safety endpoint was the incidence of device- and procedure-related adverse events (AEs) and all-cause mortality. ResultsA total of 172 participants were included, with an average age of 59.22 ± 9.25 years and 99 (57.56%) of them men. Immediate success rate was 97.67% (95% CI: 94.15%-99.36%) and 12-month treatment success rate was 82.56% (95% CI: 76.89%-88.23%), including a late recurrence rate of 13.61%. Incidences of device- and procedure-related AEs were 2.27% and 25.00%, respectively. Phrenic nerve palsy (PNP) occurred in 6 patients, of which 5 recovered during follow-up. Although the incidence of total severe AEs was 17.05%, including an all-cause mortality of 0.57%, only 1 case of permanent PNP was related to the CBA procedure. ConclusionsThis premarketing prospective multicenter single-arm clinical trial demonstrated that the liquid nitrogen cryoablation system is safe and effective in the treatment of 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.

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). 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. 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 cycleof 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. 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. Initial rhythm control with first-line cryoballoon ablation is highly cost-effective compared with first-line AADs from a U.S. Medicare payer perspective.