Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study.

Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for ~1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.

Safety and Effectiveness of Pulsed Field Ablation for Atrial Fibrillation in Patients with Heart Failure: A MANIFEST-PF Sub-analysis.

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) coexist, increasing morbidity and mortality. Studies have demonstrated improved outcomes following AF ablation in HF patients with reduced ejection fraction (EF). OBJECTIVE: To assess the outcomes of pulsed-field ablation (PFA) in HF. METHODS: MANIFEST-PF is a multicenter patient-level registry of consecutive patients undergoing PFA for paroxysmal (PAF) or persistent AF (PerAF). In this sub-study, patients were stratified as: no history of HF (no-HF), HF with preserved EF (HFPEF; LVEF≥50%) or HF with reduced/mildly-reduced EF (HFMR/REF; LVEF<50%). The primary effectiveness and safety endpoints were freedom from documented atrial arrhythmias lasting ≥30s and major adverse events (MAEs), respectively. RESULTS: Of the 1,381 patients, 85% (n=1,174) were no-HF, 6.2% (n=87) were HFPEF, and 8.6% (n=120) were HFMR/REF. No-HF patients had less PerAF than patients with HF (p<0.001), with no difference between HF subtypes (p=1.00). The 1-year freedom from atrial arrhythmia was significantly higher in no-HF than with HFPEF or HFMR/REF (79.9%, 71.3%, 67.5%, p<0.001), but similar between HFMR/REF and HFPEF (p=0.26). However, there was no significant difference in freedom from atrial arrhythmia among patients with no-HF vs HFPEF vs HFMR/REF for those with PAF (82.8%/82.4%/71.7%, p=0.09) and PerAF (73.3%, 64.2%, and 64.9%, p=0.14.MAE rates were similar between the no-HF, HFPEF and HFMR/REF groups (1.9%, 0%, and 2.5%, respectively). CONCLUSION: PFA appears to be potentially safe and effective in AF patients with HF. Freedom from atrial arrhythmia post-PFA was higher in patients without a history of HF, with no significant difference between HF subtypes.

State-of-the-art pulsed field ablation for cardiac arrhythmias: ongoing evolution and future perspective.

Pulsed field ablation (PFA) is an innovative approach in the field of cardiac electrophysiology aimed at treating cardiac arrhythmias. Unlike traditional catheter ablation energies, which use radiofrequency or cryothermal energy to create lesions in the heart, PFA utilizes pulsed electric fields to induce irreversible electroporation, leading to targeted tissue destruction. This state-of-the-art review summarizes biophysical principles and clinical applications of PFA, highlighting its potential advantages over conventional ablation methods. Clinical data of contemporary PFA devices are discussed, which combine predictable procedural outcomes and a reduced risk of thermal collateral damage. Overall, these technological developments have propelled the rapid evolution of contemporary PFA catheters, with future advancements potentially impacting patient care.

Safety and Effectiveness of Pulsed Field Ablation for Atrial Fibrillation in Patients With Heart Failure.

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) coexist, increasing morbidity and mortality. Studies have demonstrated improved outcomes following AF ablation in HF patients with reduced ejection fraction (EF). OBJECTIVE: This study sought to assess the outcomes of pulsed field ablation (PFA) in HF. METHODS: MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-Approval Clinical Use of Pulsed Field Ablation) is a multicenter, patient-level registry of consecutive patients undergoing PFA for paroxysmal AF or persistent AF (PerAF). In this substudy, patients were stratified as no history of HF (no-HF), HF with preserved EF (HFpEF) (left ventricular EF of ≥50%) or HF with reduced/mildly reduced EF (HFmr/rEF) (left ventricular EF of <50%). The primary effectiveness and safety endpoints were freedom from documented atrial arrhythmias lasting ≥30 seconds and major adverse events, respectively. RESULTS: Of the 1,381 patients, 85% (n = 1,174) were no-HF, 6.2% (n = 87) were HFpEF, and 8.6% (n = 120) were HFmr/rEF. No-HF patients had less PerAF than patients with HF (P < 0.001), with no difference between HF subtypes (P = >0.99). The 1-year freedom from atrial arrhythmia was significantly higher in no-HF patients than in those with HFpEF or HFmr/rEF (79.9%, 71.3%, and 67.5%, respectively; P < 0.001) but similar between patients with HFmr/rEF and HFpEF (P = 0.26). However, there was no significant difference in freedom from atrial arrhythmia among patients with no-HF vs HFpEF vs HFmr/rEF for those with paroxysmal AF (82.8%, 82.4%, and 71.7%, respectively; P = 0.09) and PerAF (73.3%, 64.2%, and 64.9%, respectively; P = 0.14). Major adverse event rates were similar between the no-HF, HFpEF, and HFmr/rEF groups (1.9%, 0%, and 2.5%, respectively). CONCLUSIONS: PFA appears to be potentially safe and effective in AF patients with HF. Freedom from atrial arrhythmia post-PFA was higher in patients without a history of HF, with no significant difference between HF subtypes.

Wideband black-blood late gadolinium enhancement imaging for improved myocardial scar assessment in patients with cardiac implantable electronic devices.

PURPOSE: Wideband phase-sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) enables myocardial scar imaging in implantable cardioverter defibrillators (ICD) patients, mitigating hyperintensity artifacts. To address subendocardial scar visibility challenges, a 2D breath-hold single-shot electrocardiography-triggered black-blood (BB) LGE sequence was integrated with wideband imaging, enhancing scar-blood contrast. METHODS: Wideband BB, with increased bandwidth in the inversion pulse (0.8-3.8 kHz) and T2 preparation refocusing pulses (1.6-5.0 kHz), was compared with conventional and wideband PSIR, and conventional BB, in a phantom and sheep with and without ICD, and in six patients with cardiac devices and known myocardial injury. ICD artifact extent was quantified in the phantom and specific absorption rate (SAR) was reported for each sequence. Image contrast ratios were analyzed in both phantom and animal experiments. Expert radiologists assessed image quality, artifact severity, and scar segments in patients and sheep. Additionally, histology was performed on the sheep's heart. RESULTS: In the phantom, wideband BB reduced ICD artifacts by 62% compared to conventional BB while substantially improving scar-blood contrast, but with a SAR more than 24 times that of wideband PSIR. Similarly, the animal study demonstrated a considerable increase in scar-blood contrast with wideband BB, with superior scar detection compared with wideband PSIR, the latter confirmed by histology. In alignment with the animal study, wideband BB successfully eliminated severe ICD hyperintensity artifacts in all patients, surpassing wideband PSIR in image quality and scar detection. CONCLUSION: Wideband BB may play a crucial role in imaging ICD patients, offering images with reduced ICD artifacts and enhanced scar detection.

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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%. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04524364.

Analysis of the effectiveness of the latest 4th-generation cryoballoon catheters in pulmonary vein isolation using high-resolution mapping.

BACKGROUND: Long-term data showed that up to 27% of pulmonary veins are reconnected using cryoballoon ablation. This study aimed to evaluate the efficacy of the latest 4th-generation cryoballoon catheters using ultra high-resolution mapping. METHODS: In patients with atrial fibrillation, a standard pulmonary vein isolation (PVI) with the latest 4th-generation cryoballoon catheter (Arctic Front Advance PRO, Medtronic Minneapolis, USA) and the spiral mapping catheter (Achieve Advance, Medtronic, Minneapolis, MN, USA) was performed. Subsequently, high-resolution mapping was achieved using the novel multipolar grid mapping catheter (Advisor HD Grid SE, Abbott Laboratories, USA). Follow-up was obtained after 6 months by means of a 7-day Holter electrocardiogram. RESULTS: In our study, acute PVI was successfully achieved in all 31 patients. The latest 4th-generation cryoballoon catheter is safe in the acute phase of PVI. Additional high-resolution mapping (mean points per map 21,001 ± 4911) using the multipolar grid mapping catheter enabled us to identify residual gaps only in the carina pulmonary vein region; therefore, no additional ablation was performed. Three of 31 patients (10%) presented with atrial arrhythmia recurrence always related with pulmonary vein reconnection; using high-resolution mapping had no additional benefit in identifying pulmonary veins in which reconnection will occur. CONCLUSION: The utility of additional high-density mapping, facilitated by the HD Grid catheter after PVI with the 4th-generation cryoballoon catheter do not substantiate a discernible advantage over conventional mapping methodologies, particularly, the spiral mapping catheter. Residual carinal conduction was observed in a substantial cohort of patients (48%), highlighting a persistent challenge in achieving complete electrical isolation.

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.

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: The BEAT PAROX-AF trial aims to provide critical insights into the optimal treatment approach for patients with paroxysmal AF.

Impact of Left Atrial Posterior Wall Ablation During Pulsed-Field Ablation for Persistent Atrial Fibrillation.

BACKGROUND: Pulmonary vein isolation (PVI) alone is insufficient to treat many patients with persistent atrial fibrillation (PersAF). Adjunctive left atrial posterior wall (LAPW) ablation with thermal technologies has revealed lack of efficacy, perhaps limited by the difficulty in achieving lesion durability amid concerns of esophageal injury. OBJECTIVES: This study aims to compare the safety and effectiveness of PVI + LAPW ablation vs PVI in patients with PersAF using pulsed-field ablation (PFA). METHODS: In a retrospective analysis of the MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-approval Clinical Use of Pulsed Field Ablation) registry, we studied consecutive PersAF patients undergoing post-approval treatment with a pentaspline PFA catheter. The primary effectiveness outcome was freedom from any atrial arrhythmia of ≥30 seconds. Safety outcomes included the composite of acute and chronic major adverse events. RESULTS: Of the 547 patients with PersAF who underwent PFA, 131 (24%) received adjunctive LAPW ablation. Compared to PVI-alone, patients receiving adjunctive LAPW ablation were younger (65 vs 67 years of age, P = 0.08), had a lower CHA2DS2-VASc score (2.3 ± 1.6 vs 2.6 ± 1.6, P = 0.08), and were more likely to receive electroanatomical mapping (48.1% vs 39.0%, P = 0.07) and intracardiac echocardiography imaging (46.1% vs 17.1%, P < 0.001). The 1-year Kaplan-Meier estimate for freedom from atrial arrhythmias was not statistically different between groups in the full (PVI + LAPW: 66.4%; 95% CI: 57.6%-74.4% vs PVI: 73.1%; 95% CI: 68.5%-77.2%; P = 0.68) and propensity-matched cohorts (PVI + LAPW: 71.7% vs PVI: 68.5%; P = 0.34). There was also no significant difference in major adverse events between the groups (2.2% vs 1.4%, respectively, P = 0.51). CONCLUSIONS: In patients with PersAF undergoing PFA, as compared to PVI-alone, adjunctive LAPW ablation did not improve freedom from atrial arrhythmia at 12 months.

Local VA index for the differential diagnosis of supraventricular tachycardia.

BACKGROUND: Differentiating between atypical atrioventricular nodal reentrant tachycardia (AVNRT) and orthodromic reciprocating tachycardia utilizing a septal accessory pathway is a complex challenge. OBJECTIVE: The purpose of this study was to describe the "local VA index," a straightforward method based on signals from the coronary sinus catheter, to distinguish between these arrhythmias during tachycardia and entrainment. The ventriculoatrial (VA) interval on the coronary sinus catheter is measured during tachycardia and entrainment, at the site of earliest atrial activity. The difference between these 2 situations defines the "local VA index." We also propose a mechanism to clarify the limitations of historical pacing maneuvers, such as postpacing interval minus tachycardia cycle length (PPI-TCL) and stimulus-atrial interval minus ventriculoatrial interval (SA-VA), by examining nodal decrement and intraventricular conduction delay. METHODS: In a retrospective study of 75 patients referred for supraventricular tachycardia evaluation, 37 were diagnosed with atrioventricular reentrant tachycardia (AVRT) with orthodromic reciprocating tachycardia, and 38 with AVNRT (27 typical, 11 atypical). RESULTS: In comparison to AVRT patients, AVNRT patients exhibited longer PPI-TCL (176 ± 47 ms vs 113 ± 42 ms; P <.01) and SA-VA (138 ± 47 ms vs 64 ± 28 ms; P <.01). The AVRT group had mean local VA index of -1 ± 13 ms, whereas the AVNRT group had a significantly longer index of 91 ± 46 ms (P <.01). An optimal threshold for differentiation was a local VA index of 40 ms. Importantly, there was no significant correlation between pacing cycle length and nodal decrement as well as intraventricular delay related to pathway location. This interindividual variability might explain misleading interpretations of PPI-TCL and SA-VA. CONCLUSION: This novel approach is advantageous because of its simplicity and effectiveness, requiring only 2 diagnostic catheters. A local VA interval difference <40 ms provides a clear distinction for AVRT.

Assessment of myocardial injuries in ischaemic and non-ischaemic cardiomyopathies using magnetic resonance T1-rho mapping.

AIMS: To identify clinical correlates of myocardial T1ρ and to examine how myocardial T1ρ values change under various clinical scenarios. METHODS AND RESULTS: A total of 66 patients (26% female, median age 57 years [Q1-Q3, 44-65 years]) with known structural heart disease and 44 controls (50% female, median age 47 years [28-57 years]) underwent cardiac magnetic resonance imaging at 1.5 T, including T1ρ mapping, T2 mapping, native T1 mapping, late gadolinium enhancement, and extracellular volume (ECV) imaging. In controls, T1ρ positively related with T2 (P = 0.038) and increased from basal to apical levels (P < 0.001). As compared with controls and remote myocardium, T1ρ significantly increased in all patients' sub-groups and all types of myocardial injuries: acute and chronic injuries, focal and diffuse tissue abnormalities, as well as ischaemic and non-ischaemic aetiologies (P < 0.05). T1ρ was independently associated with T2 in patients with acute injuries (P = 0.004) and with native T1 and ECV in patients with chronic injuries (P < 0.05). Myocardial T1ρ mapping demonstrated good intra- and inter-observer reproducibility (intraclass correlation coefficient = 0.86 and 0.83, respectively). CONCLUSION: Myocardial T1ρ mapping appears to be reproducible and equally sensitive to acute and chronic myocardial injuries, whether of ischaemic or non-ischaemic origins. It may thus be a contrast-agent-free biomarker for gaining new and quantitative insight into myocardial structural disorders. These findings highlight the need for further studies through prospective and randomized trials.

Myocardial injury and inflammation following pulsed-field ablation and very high-power short-duration ablation for atrial fibrillation.

INTRODUCTION: Pulmonary vein isolation (PVI) using radiofrequency ablation (RFA) is an established treatment strategy for atrial fibrillation (AF). To improve PVI efficacy and safety, high-power short-duration (HPSD) ablation and pulsed-field ablation (PFA) were recently introduced into clinical practice. This study aimed to determine the extent of myocardial injury and systemic inflammation following PFA, HPSD, and standard RFA using established biomarkers. METHODS: We included 179 patients with paroxysmal AF receiving first-time PVI with different ablation technologies: standard RFA (30-40 W/20-30 s, n = 52), power-controlled HPSD (70 W/5-7 s, n = 60), temperature-controlled HPSD (90 W/4 s, n = 32), and PFA (biphasic, bipolar waveform, n = 35). High-sensitivity cardiac troponin T (hs-cTnT), creatine kinase (CK), CK MB isoform (CK-MB), and white blood cell (WBC) count were determined before and after ablation. RESULTS: Baseline characteristics were well-balanced between groups (age 63.1 ± 10.3 years, 61.5% male). Postablation hs-cTnT release was significantly higher with PFA (1469.3 ± 495.0 ng/L), HPSD-70W (1322.3 ± 510.6 ng/L), and HPSD-90W (1441.2 ± 409.9 ng/L) than with standard RFA (1045.9 ± 369.7 ng/L; p < .001). CK and CK-MB release was increased with PFA by 3.4-fold and 5.8-fold, respectively, as compared to standard RFA (p < .001). PFA was associated with the lowest elevation in WBC (Δ1.5 ± 1.5 × 109 /L), as compared to standard RFA (Δ3.8 ± 2.5 × 109 /L, p < .001), HPSD-70W (Δ2.7 ± 1.7 × 109 /L, p = .037), and HPSD-90W (Δ3.6 ± 2.5 × 109 /L, p < .001). CONCLUSION: Among the four investigated ablation technologies, PFA was associated with the highest myocardial injury and the lowest inflammatory reaction.

Cardiac structure discontinuities revealed by ex-vivo microstructural characterization. A focus on the basal inferoseptal left ventricle region.

BACKGROUND: While the microstructure of the left ventricle (LV) has been largely described, only a few studies investigated the right ventricular insertion point (RVIP). It was accepted that the aggregate cardiomyocytes organization was much more complex due to the intersection of the ventricular cavities but a precise structural characterization in the human heart was lacking even if clinical phenotypes related to right ventricular wall stress or arrhythmia were observed in this region. METHODS: MRI-derived anatomical imaging (150 µm3) and diffusion tensor imaging (600 µm3) were performed in large mammalian whole hearts (human: N = 5, sheep: N = 5). Fractional anisotropy, aggregate cardiomyocytes orientations and tractography were compared within both species. Aggregate cardiomyocytes orientation on one ex-vivo sheep whole heart was then computed using structure tensor imaging (STI) from 21 µm isotropic acquisition acquired with micro computed tomography (MicroCT) imaging. Macroscopic and histological examination were performed. Lastly, experimental cardiomyocytes orientation distribution was then compared to the usual rule-based model using electrophysiological (EP) modeling. Electrical activity was modeled with the monodomain formulation. RESULTS: The RVIP at the level of the inferior ventricular septum presented a unique arrangement of aggregate cardiomyocytes. An abrupt, mid-myocardial change in cardiomyocytes orientation was observed, delimiting a triangle-shaped region, present in both sheep and human hearts. FA's histogram distribution (mean ± std: 0.29 ± 0.06) of the identified region as well as the main dimension (22.2 mm ± 5.6 mm) was found homogeneous across samples and species. Averaged volume is 0.34 cm3 ± 0.15 cm3. Both local activation time (LAT) and morphology of pseudo-ECGs were strongly impacted with delayed LAT and change in peak-to-peak amplitude in the simulated wedge model. CONCLUSION: The study was the first to describe the 3D cardiomyocytes architecture of the basal inferoseptal left ventricle region in human hearts and identify the presence of a well-organized aggregate cardiomyocytes arrangement and cardiac structural discontinuities. The results might offer a better appreciation of clinical phenotypes like RVIP-late gadolinium enhancement or uncommon idiopathic ventricular arrhythmias (VA) originating from this region.