Treatment Of Paroxysmal Atrial Fibrillation Research Articles

Comparing pulsed field ablation and thermal energy catheter ablation for paroxysmal atrial fibrillation: A cost-effectiveness analysis of the ADVENT trial

Background Pulsed field ablation (PFA) has emerged as an effective technology in the treatment of paroxysmal atrial fibrillation (AF). Objective To evaluate the cost-effectiveness of PFA vs. thermal ablation from a US healthcare payer perspective using data from a randomized trial. Methods A hybrid decision tree and Markov model was developed comparing patients receiving PFA to thermal ablation (either radiofrequency or cryoballoon ablation) from a US healthcare payer perspective at 5-, 10-, 20-, and 40-year time horizons. Direct medical costs (in 2024 US Dollars), quality-adjusted life years (QALYs), and the net monetary benefit were evaluated at a willingness-to-pay (WTP) threshold of $100,000/QALY. Univariate and probabilistic sensitivity analyses were performed to test model uncertainty. The budget impact for a standard US healthcare payer with 1 million beneficiaries was also assessed. Results Over a 40-year time horizon, PFA resulted in an additional 0.044 QALYs at a lower cost of $2,871 compared to thermal ablation. PFA was cost-effective in 54.9% of simulations. Anticoagulation and ablation procedure costs had the largest impact on model uncertainty. The expected cost savings per member per month for a US healthcare payer adopting PFA were $0.00015, $0.0059, and $0.02343 in years 1, 4, and 6, respectively. Conclusions PFA was at least as cost-effective as conventional thermal ablation modalities for treatment of paroxysmal AF and potentially reduces US healthcare payer costs. Providers and payers should consider designating PFA among the preferred first-line therapies for eligible patients.

Anatomical-guided third-generation laser balloon ablation for the treatment of paroxysmal atrial fibrillation assessed by continuous rhythm monitoring: results from a multicentre prospective study.

The third-generation laser balloon (LB3) is an established ablation device for pulmonary vein isolation (PVI) that allows direct visualization of the anatomical target. Equipped with an automatic circumferential laser delivery modality, it aims at continuous circumferential PVI, improving both acute and clinical outcomes. We sought to evaluate the clinical efficacy of LB3 ablation using an anatomical-based approach without verifying electrical isolation. Among 257 paroxysmal AF patients undergoing LB3 ablation across four Italian centres, 204 (72% male, mean age 60.4 ± 11.1 years) were included. The primary endpoint was freedom from any atrial tachyarrhythmia (ATa) recurrence after the blanking period (BP), assessed with implantable cardiac monitors (ICMs). All pulmonary veins (PVs) were targeted using the LB3, with the RAPID mode used on an average of 96 ± 8, 86 ± 19, 98 ± 11, and 84 ± 15% for the left superior, left inferior, right superior, right inferior PV, and left common ostium, respectively. Freedom from arrhythmia recurrences was 84.8% at 1, 80.4% at 2, and 76.0% at 3 years. An ATa burden ≥ 5% was documented in 2.5, 4.4, and 5.4% at 1, 2, and 3 years, respectively. Relapses during the BP [hazard ratio (HR) = 2.182, P = 0.032] and left atrial dilation (HR = 1.964, P = 0.048) were independent predictors of recurrences. Anatomical-guided LB3 ablation for paroxysmal AF is a safe and effective approach, providing excellent clinical outcomes as assessed by ICM over nearly 3 years of follow-up.

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.

A cost-consequence analysis comparing three distinct cardiac ablation strategies for the treatment of paroxysmal atrial fibrillation

Abstract Background Cardiac ablation is a well-established treatment option for preventing atrial fibrillation (AF). While radiofrequency, cryo-energy, and laser energies are commonly employed in catheter ablation, they present the risk of potential damage to adjacent organs such as the oesophagus and phrenic nerve. To address these concerns, new technologies are being explored including pulsed field ablation (PFA), a non-thermal energy approach that employs high-voltage, short-duration pulses to selectively destroy target cells. Purpose The present analysis aims at: i) quantifying the short-term costs related to three ablation strategies for paroxysmal AF (PFA, radiofrequency ablation -RFA-, and cryo-balloon ablation -CRYO-), identify the cost drivers, and assess potential variations in resource consumption for each treatment alternative; ii) comparing the medium-term (1-year) economic implications of adopting the three alternatives, in terms of redo procedures (effectiveness) and complications (safety). Methods A cost-consequence model was developed to compare economic outcomes of the three ablation strategies for paroxysmal AF in the short- (during procedure) and medium-term (1-year). Resource consumption data during the procedure were collected by two European medical centres specialized in cardiac ablation (N=61 patients). For the medium-term analysis, costs were correlated to the effectiveness and safety of the procedures. The clinical data (i.e., redo and complication rates) considered in the model were retrieved from published literature. Costs and tariffs were collected from economic formularies of the respective hospitals. A scenario analysis was conducted to evaluate economic outcomes under various hypothetical difference in the prices of treatment kits. Results A significant difference was registered in terms of pre-procedural (mean±SD: 13.9±4.4 min for PFA, 20.1±7.6 min for CRYO and 20.5±7.7 min for RFA; ANOVA test p=0.003) and procedural time (skin-to-skin), favouring PFA over RFA and CRYO (53.6±26.8 min for PFA, 72.4±28.1 min for CRYO and 149.9±99.9 min for RFA; p&amp;lt;0.0001; Table 1). PFA was associated with lower procedural costs vs CRYO (-€400) and RFA (-€827). A similar economic advantage was observed in the medium-term (Table 2). The scenario analysis showed that PFA would be cost-saving vs CRYO (Δtotal costs ≤ 0) up to a price difference of +€881 (i.e., PFA kit is more expensive than CRYO kit), and similarly, up to a price difference of +€1,306 vs RFA. Above these thresholds, PFA would be considered cost-effective vs CRYO or RFA, due to its efficacy despite being more expensive. Conclusion In summary, PFA emerges as cost-effective or even cost-saving over CRYO and RFA, thanks to its faster execution, lower redo, and complications rate. Moreover, PFA time predictability would facilitate hospital planning. For a complete analysis, these benefits should be evaluated against the difference in acquisition costs among treatments.Procedural time by phase and techniqueCumulative savings per technique

The long-term outcome of pulmonary vein isolation in paroxysmal atrial fibrillation is significantly influenced by diabetes mellitus in general as well as by an antidiabetic therapy

Abstract Introduction Over the last decades pulmonary vein isolation became a cornerstone in the interventional treatment of paroxysmal atrial fibrillation. Postprocedural recurrences of atrial fibrillation are present in patients with and without concomitant cardiovascular diseases. Purpose The aim of this study was to assess the influence of diabetes mellitus and an antidiabetic therapy on the long-term outcome, defined as freedom of atrial fibrillation, of pulmonary vein isolation in patients with paroxysmal atrial fibrillation Methods All patients underwent pulmonary vein isolation using the combination of a radiofrequency ablation catheter, a pulmonary mapping catheter and a 3D electroanatomic mapping system. Every procedure was carried out according to current clinical and scientific standards. Procedural, clinical and follow-up data were stored for later statistical analysis. All patients received 4 follow-ups in total. In the first 12 postprocedural months patients were followed up after 3, 6 and 12 months. Furthermore, there was one long-term follow-up up to 6 years after the procedure. Results A total of n=1282 patients were included in the study. 39.2% of the patients were female and 60,8% were male. At the timepoint of the procedure the mean age was 63.7 years. The mean follow-up time was 2.2 years. For n=1144 of the included patients the presence respectively the absence of diabetes mellitus was documented. 8.0% (n=92) of these patients had the diagnosis of diabetes mellitus, from which 73.9% (n=68) were and 26.1% (n=24) were not under an antidiabetic therapy. Regarding the long-term outcome, patients without diabetes mellitus had significantly better results (log rank p=0.039). The according Kaplan-Meier-Analysis is shown in figure 1. Patients with diabetes mellitus were significantly older (69.5 years) when compared to patients without diabetes mellitus (63.1 years). However, when data was adjusted for age and gender, diabetes mellitus was still an independent, significant predictor of the recurrence of atrial fibrillation after pulmonary vein isolation. In addition, diabetics under an antidiabetic therapy had a significantly better long-term outcome than the untreated ones (log rank p=0.011). Figure 2 shows the according Kaplan-Meier-Analysis. Conclusion Diabetes mellitus has a significant influence on the long-term outcome of pulmonary vein isolation in patients with atrial fibrillation (log rank p=0.039). Patients without diabetes mellitus showed significantly better outcomes when compared to patients with diabetes mellitus also when adjusting the data for age and gender. Furthermore, the presence of an antidiabetic therapy in diabetics influences the long-term outcomes significantly (log rank p=0.011).

Long-term patient clinical benefits and healthcare utilization after pulsed field ablation in paroxysmal atrial fibrillation: sub-analyses from the multicenter inspIRE trial

Abstract Background/Introduction The treatment of atrial fibrillation (AF) with pulsed field ablation (PFA) aims to prevent AF recurrence while reducing complications from the ablation modality. Similar to thermal ablation, PFA has proven to be safe and effective for treatment of paroxysmal AF (PAF); however, there is scarce evidence on patient-related clinical benefits, including healthcare utilization, using this new energy modality. Purpose The objective of this study is to assess long-term clinical improvements in patient care, symptoms, and quality-of-life (QOL) after PFA ablation in PAF. Methods InspIRE was a multicentre study evaluating the safety and efficacy of variable loop PFA catheters integrated with a 3D mapping system for treatment of symptomatic PAF. Patients were followed for up to 12 months for the following QOL and healthcare utilization endpoints: Atrial Fibrillation Effect on Quality-of-Life (AFEQT) score, Class I/III AAD utilization, repeat ablation, incidence of direct current cardioversion (DCCV), and cardiovascular (CV) hospitalization. Post-hoc Kaplan-Meier estimates for clinical benefit success at 12 months were provided. Success was defined as composite freedom from occurrence of the following events post-blanking: repeat ablation, CV hospitalization, AAD utilization, and DCCV post-blanking. Predictors of clinical benefit success were explored via multivariate logistic regression analysis. Results A total of 186 enrolled patients (59±10 years; 70.0% male; CHA2DS2-VASC score 1.3±1.2) underwent PVI. Compared to baseline: 1) improvements in the AFEQT composite score were seen at 12 months (P&amp;lt;0.001); 2) Class I/III AAD use was reduced from 81.7% to 20.1% at 6-12 months (P&amp;lt;0.05); and 3) the proportion of subjects with DCCV decreased from 13.7% up to 12 months before the index procedure to 3.3% up to 12 months after the index procedure (P&amp;lt;0.001, Figure 1). Minimal clinically important difference in QoL (≥5 points improvement in AFEQT) was achieved in 85.2% of patients. Patients free from 12-month AF/AT/AFL recurrence (asymptomatic and symptomatic) had significantly greater improvements in AFEQT scores from baseline to 12 months versus those with recurrence (P=0.01). The clinical benefit success rate at 12 months was 87.5% (Figure 2). Patients who failed the clinical benefit endpoint were counted, including those with repeat ablation (7.5%), those on new or higher dose of AAD (6.5%), those hospitalized for CV (4.8%), and those who had DCCV post-blanking (1.6%). Multivariate logistic regression analysis showed that left ventricle ejection fraction &amp;lt;60% (OR: 0.22; 95% CI: 0.08-0.62; P&amp;lt;0.05) and incidence of diabetes (OR: 7.25; 95% CI: 2.00, 26.3; p&amp;lt;0.05) were associated with a higher risk of clinical benefit failure. Conclusions PFA ablation of PAF patients led to a clinical benefit success rate of 87.5%, with clinically meaningful improvement in QOL, as well as a reductions in AAD use, cardioversion, and hospitalization.Figure 1.Improvements in QoL and HealthFigure 2.Kaplan-Meier Analysis of Time

Epicardial Pulsed Field Ablation for the Treatment of Paroxysmal Atrial Fibrillation During Cardiac Surgery

Epicardial Pulsed Field Ablation for the Treatment of Paroxysmal Atrial Fibrillation During Cardiac Surgery

A danish healthcare-focused economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation

IntroductionThree randomised controlled trials (RCTs) have demonstrated that first-line cryoballoon pulmonary vein isolation decreases atrial tachycardia in patients with symptomatic paroxysmal atrial fibrillation (PAF) compared with antiarrhythmic drugs (AADs). The aim of this study was to develop a cost-effectiveness model (CEM) for first-line cryoablation compared with first-line AADs for the treatment of PAF. The model used a Danish healthcare perspective.MethodsIndividual patient-level data from the Cryo-FIRST, STOP AF and EARLY-AF RCTs were used to parameterise the CEM. The model structure consisted of a hybrid decision tree (one-year time horizon) and a Markov model (40-year time horizon, with a three-month cycle length). Health-related quality of life was expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3% per year. Model outcomes were produced using probabilistic sensitivity analysis.ResultsFirst-line cryoablation is dominant, meaning it results in lower costs (-€2,663) and more QALYs (0.18) when compared to first-line AADs. First-line cryoablation also has a 99.96% probability of being cost-effective, at a cost-effectiveness threshold of €23,200 per QALY gained. Regardless of initial treatment, patients were expected to receive ∼ 1.2 ablation procedures over a lifetime horizon.ConclusionFirst-line cryoablation is both more effective and less costly (i.e. dominant), when compared with AADs for patients with symptomatic PAF in a Danish healthcare system.

A cost-consequence analysis comparing three cardiac ablation strategies for the treatment of paroxysmal atrial fibrillation

Background and aims Cardiac ablation is a well-established method for treating atrial fibrillation (AF). Pulsed field ablation (PFA) is a non-thermal therapeutic alternative to radiofrequency ablation (RFA) and cryoballoon ablation (CRYO). PFA uses high-voltage electric pulses to target cells. The present analysis aims to quantify the costs, outcomes, and resources associated with these three ablation strategies for paroxysmal AF. Methods Real-world clinical data were prospectively collected during index hospitalization by three European medical centers (Belgium, Germany, the Netherlands) specialized in cardiac ablation. These data included procedure times (pre-procedural, skin-to-skin and post-procedural), resource use, and staff burden. Data regarding complications associated with each of the three treatment options and redo procedures were extracted from the literature. Costs were collected from hospital economic formularies and published cost databases. A cost-consequence model from the hospital perspective was built to estimate the impact of the three treatment options in terms of effectiveness and costs. Results Across the three centers, N = 91 patients were included over a period of 12 months. A significant difference was seen in pre-procedural time (mean ± SD, PFA: 13.6 ± 3.7 min, CRYO: 18.8 ± 6.6 min, RFA: 20.4 ± 6.4 min; p < .001). Procedural time (skin-to-skin) was also different across alternatives (PFA: 50.9 ± 22.4 min, CRYO: 74.5 ± 24.5 min, RFA: 140.2 ± 82.4 min; p < .0001). The model reported an overall cost of €216,535 per 100 patients treated with PFA, €301,510 per 100 patients treated with CRYO and €346,594 per 100 patients treated with RFA. Overall, the cumulative savings associated with PFA (excluding kit costs) were €850 and €1,301 per patient compared to CRYO and RFA, respectively. Conclusion PFA demonstrated shorter procedure time compared to CRYO and RFA. Model estimates indicate that these time savings result in cost savings for hospitals and reduce outlay on redo procedures. Clinical practice in individual hospitals varies and may impact the ability to transfer the results of this analysis to other settings.

New Perspectives in The Management of Paroxysmal Atrial Fibrillation: Dual AntiArrhythmic Medications.

Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice projected to affect 12.1 million individuals by the year 2030. Patients who are diagnosed with AF have an increased risk of morbidity and mortality. Although catheter ablation is a class I treatment recommendation in patients with symptomatic paroxysmal AF, antiarrhythmic medications (AAM) continue to be the mainstay of treatment in limited resource settings not offering ablation procedures. Currently, the most used AAMs are those which block either the sodium or potassium channels. We hypothesized that the use of selective dual AAM (sodium and potassium channel blockers) (DAAM) improves the chance of maintaining sinus rhythm and decreases the need for catheter ablation when compared with single AAM (SAAM). This retrospective observational study was conducted in 150 patients with paroxysmal AF over 5 years at Richmond University Medical Center in Staten Island, New York. The following data were collected: age, sex, comorbidities, electrocardiogram findings, ejection fraction by echocardiography, classes of AAM, duration, and response to treatments. The primary endpoint included the absence of symptoms and maintenance of sinus rhythm. The secondary endpoint included the requirement of electrical cardioversion or catheter ablation. A total of 86 patients met the inclusion criteria in our analysis. The average age of the patients was 71.06 years (SD = 7.66). About 45 patients were given DAAM of either amiodarone + flecainide or dronedarone + flecainide and were treated for an average of 15.4 months, followed by catheter ablation, if needed. Also, 41 patients received a SAAM followed by catheter ablation, if needed. A Mann-Whitney test indicated that electrical cardioversion and catheter ablation were greater for the SAAM group (Md = 1) than for the DAAM group (Md = 0) (U = 294.00, P value <0.001; U = 507.00, P value <0.001, respectively). No pro-arrhythmic side effects or death were encountered in either group. Treatment of paroxysmal AF with DAAM is effective compared with SAAM and is less likely to need catheter ablation or electrical cardioversion. Well-designed prospective studies are needed to further explore the use of DAAM in the management of paroxysmal AF and its clinical impact in limited resource settings.

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 &amp;gt; 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 &amp;lt; 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 (&amp;lt;30 cm/s) at CL 600 ms or CL 300 ms, or 2) difference in CV magnitude (&amp;gt;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 &amp;gt;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&amp;lt;0.001) in those treated with cryoablation. In addition, the cryoablation arm had a 72.8% (p&amp;lt;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 &amp;lt;0.50 mV. LA LVA was categorized into low (&amp;lt;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&amp;lt;0.001), see Figure 1. Overall, 82.0% of patients were free of AF in the LA LVA &amp;lt;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&amp;lt;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 &amp;lt;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.

Associations between stroke risk factors and left atrial low-voltage areas in patients with atrial fibrillation undergoing catheter ablation from the REAL-AF registry

Abstract Background Prior research indicates that increased left atrial low-voltage areas (LA LVA) are linked to comorbidities and CHA2DS2-VASc score in patients with persistent atrial fibrillation (PerAF) undergoing catheter ablation. However, given the heterogeneity of AF where patients may transition between paroxysmal AF (PAF) and PerAF types, it is biologically plausible that these associations span all forms of AF. Purpose To investigate the relationship of stroke demographics and comorbidities to LA LVA and AF type in a multicenter registry of patients undergoing catheter ablation. 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 6053 patients undergoing first-time catheter ablation for both PAF and PerAF to identify associations between stroke risk factors and LA LVA. LA LVA was determined in contact maps as bipolar voltage &amp;lt;0.50 mV. Mapping was completed using 5-spline high-density catheters before ablation. LA LVA was categorized into low (&amp;lt;5%) vs. high (≥5%) based on preliminary data. Analyses were conducted using independent samples t-test and Chi-square test. Results LA LVA was associated with greater CHA2DS2-VASc score (3.2 vs. 2.5, p &amp;lt;0.001). Age 75+ (Odds ratio (OR): 2.22, p&amp;lt;0.001), congestive heart failure (CHF) (OR: 2.01, p&amp;lt;0.001), female sex (OR): 1.51, p&amp;lt;0.001), vascular disease (OR: 1.50, p&amp;lt;0.001), age 65-74 (OR: 1.20, p=0.001), hypertension (OR: 1.38, p&amp;lt;0.001), history of stroke (OR: 1.29, p=0.004) and diabetes (OR: 1.25, p=0.001) were also associated with LA LVA (Table 1). These associations remained significant among a subgroup of those presenting in normal sinus rhythm (N = 3546). Patients with CHF (OR: 2.09, p&amp;lt;0.001), hypertension (OR: 1.89, p&amp;lt;0.001) and male sex (OR: 0.60, p&amp;lt;0.001) were more likely to have PerAF in the LVA ≥5% subgroup (n=1594) (Table 2). All other components of the CHA2DS2-VASc score were not significantly associated with AF type in this subgroup. While there was a significant association between AF type and CHA2DS2-VASc score (PAF: 3.15, PerAF: 3.42, p&amp;lt;0.001) in the LA LVA ≥5% subgroup, the effect size was small (Cohen’s d = -0.179). Conclusion LA LVA ≥5% was associated with all separate components and overall CHA2DS2-VASc score. In patients with LA LVA ≥5%, there were only associations between PerAF and CHF, hypertension, and male sex, implying a special role in substrate progression. Our findings suggest that LA LVA may represent a more sensitive clinical phenotyping tool of AF rather than current duration-based ones. This is the largest study to our knowledge in elucidating the relationship between increased LA LVA and stroke risk factors in the AF population.

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 &amp;gt; 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 &amp;lt; 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...

Predictors of Success for Pulmonary Vein Isolation With Pulsed-field Ablation Using a Variable-loop Catheter With 3D Mapping Integration: Complete 12-month Outcomes From inspIRE.

We previously presented the safety and early efficacy of the inspIRE study (Study for Treatment of Paroxysmal Atrial Fibrillation [PAF] by Pulsed-field Ablation [PFA] System With Irreversible Electroporation [IRE]). With the study's conclusion, we report the outcomes of the full pivotal study cohort, with an additional analysis of predictors of success. InspIRE was a prospective, multicenter, single-arm clinical trial of drug-refractory paroxysmal atrial fibrillation. Pulmonary vein isolation was performed with a variable-loop circular catheter integrated with a 3-dimensional mapping system. Follow-up with 24-hour Holter was at 3, 6, and 12 months, as well as remote rhythm monitoring: weekly from 3 to 5 months, monthly from 6 to 12 months, and for symptoms. The primary effectiveness end point (PEE) was acute pulmonary vein isolation plus freedom from any atrial arrhythmia at 12 months. Additional subanalyses report predictors of PEE success. The patient cohort included 186 patients: aged 59±10 years, female 30%, and CHA2DS2-VASc 1.3±1.2. The previously reported primary adverse event rate was 0%. One serious procedure-related adverse event, urinary retention, was reported. The PEE was achieved in 75.6% (95% CI, 69.5%-81.8%). The clinical success of freedom from symptomatic recurrence was 81.7% (95% CI, 76.1%-87.2%). Simulating a monitoring method used in standard real-world practice (without protocol-driven remote rhythm monitoring), this translates to a freedom from all and symptomatic recurrence of 85.8% (95% CI, 80.8%-90.9%) or 94.0% (95% CI, 90.6%-97.5%), respectively. Multivariate analyses revealed that left ventricular ejection fraction ≥60% (adjusted odds ratio, 0.30) and patients receiving ≥48 PFA applications (adjusted odds ratio, 0.28) were independent predictors of PEE success. Moreover, PEE success was 79.2% in patients who received ≥12 PFA applications per vein compared with 57.1% in patients receiving fewer PFA applications. The inspIRE study confirms the safety and effectiveness of pulmonary vein isolation using the novel 3-dimensional mapping integrated circular loop catheter. An optimal number of PFA applications (≥48 total or ≥12 per vein) resulted in an improved 1-year success rate of ≈80%. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04524364.