Advanced TecHnologies For SuccEssful AblatioN of AF in Clinical Practice

Official title

Advanced TecHnologies For SuccEssful AblatioN of AF in Clinical Practice: ATHENA Study

Overview

ATHENA is a prospective, multicenter, non-randomized post-market study. All patients will be treated according to the standard care followed by each center. The protocol requires enrollment of consecutive patients from each center, according to eligibility criteria. During the 12 months follow-up period, clinical atrial fibrillation recurrence, occurrence of all kind of atrial arrhythmias and of all Adverse Events in the study population will be collected. The purpose of this study is to prospectively evaluate during time a large population of patients with an indication for ablation of AF, collecting data on procedural success in the acute and medium- to long-term follow-up. The primary objective of the study is the determination of up to 20 clinical and procedural parameters predicting the recurrence-free at the medium-long term follow-up in consecutive patients undergoing atrial fibrillation ablation through a standard of care pathway. The success of the ablation is defined in terms of percentage of patients free from any clinical atrial arrhythmia at a 12-month follow-up from the procedure.

Detailed description

Worldwide, atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting about 3% of the adult population and a 2.3-fold rise is expected, owing to extended longevity in the general population and intensifying search for undiagnosed AF. Despite therapeutic advancements, AF remains one of the major causes of stroke, heart failure and sudden death and constitutes a significant burden for the health system.

AF catheter ablation is a well-established treatment for the prevention of AF recurrences. While several ablation strategies have been claimed to be effective, the standard approach to the treatment of paroxysmal AF (PAF) and non-longstanding persistent AF is pulmonary vein isolation (PVI).

Worldwide catheter ablation is increasingly being performed in AF patients. The clinical approach to catheter ablation today reflects a range in operator training and workflow preferences for different types of AF ablation procedures. More structured characterization and treatment have been proposed in order to better individualize AF treatments to reflect the highly individualized AF disease state. In important ways, however, the procedure remains relatively unchanged and is constrained by a somewhat limited set of diagnostic and therapeutic modalities. These constraints are further compounded by incoherence in an understanding of clinically meaningful endpoints for intervention and particularly catheter ablation. New technologies present EPs with greater choice and the potential for greater understanding, and it is of paramount importance to identify which patient will benefit most from a specific ablation technology and approach.

To date, several predictors of recurrence have been identified in various studies. Increasing age is a prominent AF risk factor, but increasing burden of other comorbidities including hypertension, diabetes mellitus, heart failure (HF), coronary artery disease (CAD), chronic kidney disease (CKD), obesity, and obstructive sleep apnoea (OSA) have been demonstrated to be also important; modifiable risk factors are potent contributors to AF development and progression. However, not one of these clinical parameters is able to predict arrhythmia recurrences at a high level of evidence and the only clinical parameter that demonstrated a potential link to AF recurrence was AF type. A possible explanation of these results is that the studies on AF ablation are extremely heterogeneous regarding patient selection, patient characteristics, follow-up, variation in most of the clinical variables and procedural features. This variability claims for a structured data collection that possibly overcomes intrinsic limitation of a conventional, retrospective data collection in a multicenter, standard of care fashion. Identifying upfront individuals at higher risk of developing AF in the community could facilitate targeting of preventive interventions and screening programs for early AF detection, for example in high-risk subgroups such as post-stroke patients.

In addition, although ablative treatment has been extensively evaluated in specific patient subgroups and in controlled clinical trials, information derived from clinical practice, and in particular regarding long-term outcome, is generally few and fragmented, also lacking a large cohort of prospective and multicenter study that can confirm the results of scientific research in the "real world". To date, in fact, in clinical practice registries, a limited amount of information is available about indications, acute and long-term results and complications. It is therefore of the utmost importance to evaluate the actual management of patients undergoing ablation, so as to be able to assess the trends in the therapeutic approach and potentially identify critical issues that may be subject to improvement.

The primary objective of the study is the determination of a series of clinical and procedural parameters predicting the recurrence-free at the medium-long term follow-up in consecutive patients undergoing atrial fibrillation ablation through a standard of care pathway. The success of the ablation is defined in terms of percentage of patients free from any clinical atrial arrhythmia at a 12-month follow-up from the procedure.

Secondary objectives of the study are: percentage of patients free from any clinical atrial arrhythmias, evaluation of acute procedural success, correlation between acute success and medium- long-term success, evaluation of the proportion of patients who will be asymptomatic during follow-up, patient reported outcomes, rate of clinical atrial fibrillation recurrence during follow up, rate of occurrence of other arrhythmias during follow-up, association between occurrence of atrial arrhythmias and therapy adoption and patient' selection, association between ECG characteristics before / after ablation and its variations and patients' outcome, estimation of costs associated with the use of health care resources, rate of the adverse events associated with the primary ablation procedure and overall procedure time.

Interventions

• Procedure AF ablation
  Patients with standard indications to AF ablation

Primary outcome measures

• Baseline patient's characteristic (clinical history and drug therapy) and procedural measures for subjects undergoing catheter ablation [Time frame: 12 months]

Secondary outcome measures (11)

• Acute procedural success of AF ablation [Time frame: within 30 minutes after ablation procedure]
• Number and percentage of patients with clinical atrial arrhythmia recurrences in the mid-term [Time frame: 12 months]
• Number and percentage of patients with clinical atrial arrhythmia recurrences in the long- and very long- term [Time frame: 60 months]
• Procedural ablation parameters [Time frame: Intraoperative]
• Patient management parameters [Time frame: 7 days after the procedure]
• Rate of adverse events and complications during procedure and follow up [Time frame: 12 months for adverse events during follow up and intraoperative for acute adverse events]
• Estimate costs related to the use of health care resources [Time frame: 12 months]
• Patient reported outcomes: EQ-5D-5L [Time frame: 12 months]
• Patient reported outcomes: EHRA Score of AF-related Symptoms [Time frame: 12 months]
• ECG characteristics before ablation [Time frame: 12 months]
• ECG characteristics after ablation [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Patients with an indication to an ablation procedure of Atrial Fibrillation according to current international and local guidelines (and future revisions), existing IFU and per physician discretion
• Patients who are willing and capable of providing informed consent, participating in all testing at an approved clinical investigational center.
• Patients whose age is 18 years or above, and of legal age to give informed consent specific to state and national law.

Exclusion criteria

• Patients who are currently enrolled in another investigational study or registry that would directly interfere with the current study, except when the subject is participating in a mandatory governmental registry, or a purely observational registry with no associated treatments
• Patients who are unwilling or unable to sign an authorization to use and disclose health information or an Informed Consent.
• Patients unavailable or not willing to complete follow up visits and examination for the duration of the study at the center.
• Life expectancy ≤ 12 months per physician judgment.
• Unrecovered/unresolved Adverse Events from any previous invasive procedure;
• Women of childbearing potential who are, or plan to become, pregnant during the time of the study (method of assessment upon physician's discretion)
• Left atrial thrombus in pre-procedure imaging within 4 weeks of the ablation procedure.
• AF secondary to electrolyte imbalance, thyroid disease or reversible non- cardiac cause

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Italy · 1 center

• Azienda Ospedaliero Universitaria Pisana — Pisa

Publications

• Anselmino M, Bianchi S, De Lucia R, Tondo C, Iacopino S, Solimene F, Rossillo A, Bertini M, Themistoclakis S, Meynet I, Russo M, Dello Russo A, Zingarini G, Bandino S, Volpicelli M, Rossi P, Bianchini L, Schillaci V, De Simone A, Scaglione M, Rovaris G, De Ferrari GM, Malacrida M, Saglietto A, Zucchelli G. Machine learning prediction of outcome following pulsed-field atrial fibrillation ablation: PMID 42134812
• Schiavone M, Solimene F, Dello Russo A, Bianchi S, Iacopino S, Malacrida M, Rossillo A, Themistoclakis S, Bertini M, Meynet I, Moltrasio M, Schillaci V, Casella M, Bisignani A, Colella J, Russo M, Volpicelli M, Bandino S, Zingarini G, Mitacchione G, Casula M, Fassini G, Rordorf R, De Sanctis V, De Simone A, Rovaris G, Zucchelli G, Tondo C. Pulsed field ablation for atrial fibrillation in patients PMID 41910215
• Ribatti V, Dello Russo A, Riva S, Malacrida M, Bianchi S, Solimene F, Iacopino S, De Simone A, Rossillo A, Pelargonio G, Zucchelli G, Maggio R, Russo M, Pecora D, Bertini M, Bandino S, Volpicelli M, Compagnucci P, De Sanctis V, Anselmino M, Rordorf R, Zingarini G, Rovaris G, Agus E, Themistoclakis S, Mitacchione G, Mea R, Valeri Y, Tondo C, Casella M. De Novo Pulmonary Vein Isolation by Means of P PMID 41676924
• Moltrasio M, Iacopino S, Solimene F, Bianchi S, Schiavone M, Themistoclakis S, Rossillo A, Bertini M, Zirolia D, Volpicelli M, Zingarini G, Dello Russo A, Malacrida M, Zucchelli G, Tondo C. Termination of atrial arrhythmia and restoration of sinus rhythm during pulsed field ablation with a pentaspline catheter in patients with persistent atrial fibrillation. Europace. 2025 Jul 1;27(7):euaf144. doi PMID 40624924
• Dello Russo A, Tondo C, Bianchi S, Schillaci V, Iacopino S, Casella M, Rossillo A, Maggio R, Themistoclakis S, Bertini M, Russo M, Volpicelli M, Viola G, Rordorf R, Schiavone M, Valeri Y, Colella J, Rossi P, Tundo F, Zingarini G, De Simone A, Bianchini L, Di Vilio A, Compagnucci P, Malacrida M, Zucchelli G, Solimene F. Does Age Impact Safety and Efficacy During Pulse-Field Ablation for Atrial Fibr PMID 40265595
• Bisignani A, Solimene F, Iacopino S, Polselli M, Dello Russo A, Tondo C, Rossillo A, Themistoclakis S, Maggio R, Russo M, Volpicelli M, Schillaci V, Schiavone M, Colella J, Casella M, Malacrida M, Zucchelli G, Bianchi S. Insight Into Early Recurrences After Pulsed-Field Ablation for Atrial Fibrillation: Results From a Multicenter Experience. J Cardiovasc Electrophysiol. 2025 Jun;36(6):1323-1332. d PMID 40190033
• Bisignani A, Schiavone M, Solimene F, Dello Russo A, Filannino P, Magnocavallo M, Tondo C, Schillaci V, Casella M, Petretta A, Rossi P, Fassini G, Rossillo A, Maggio R, Themistoclakis S, Pandozi C, Polselli M, Tundo F, Arestia A, Compagnucci P, Valente Perrone A, Malacrida M, Iacopino S, Bianchi S. National workflow experience with pulsed field ablation for atrial fibrillation: learning curve, eff PMID 38814525
• Iacopino S, Colella J, Dini D, Mantovani L, Sorrenti PF, Malacrida M, Filannino P. Sedation strategies for pulsed-field ablation of atrial fibrillation: focus on deep sedation with intravenous ketamine in spontaneous respiration. Europace. 2023 Aug 2;25(9):euad230. doi: 10.1093/europace/euad230. PMID 37494101

Identifiers

NCT: NCT05617456 · 20977

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗