https://orcid.org/0000-0003-0535-2120
Abstract
Atrial arrhythmia is the most common complication of patent foramen ovale (PFO) closure. The real incidence of post-PFO closure atrial arrhytmia and whether this complication can be prevented is unknown.
The Assessment of Flecainide to Lower the PFO closure risk of Atrial fibrillation or Tachycardia (AFLOAT) trial is a prospective, national, multicentre, randomized, open-label, superiority trial with a blind evaluation of all the endpoints (PROBE design). A total of 186 patients are randomized in a 1:1:1 ratio immediately after PFO closure to receive Flecainide (150 mg per day in a single sustained-release (SR) dose) for 6 months (Group 1), Flecainide (150 mg per day in a single SR dose) for 3 months (Group 2), or no additional treatment (standard of care) for 6 months (Group 3). The primary endpoint is the percentage of patients with at least one episode of symptomatic or asymptomatic atrial arrhythmia episode (≥30 s) recorded within 3 months after PFO closure on long-term monitoring with an insertable cardiac monitor. Whether 3 months of treatment is sufficient compared to 6 months will be analysed as a secondary objective of the study.
AFLOAT is the first trial to test the hypothesis that a short treatment with oral Flecainide can prevent the new-onset of atrial arrhythmia after PFO closure.
NCT05213104 (clinicaltrials.gov).
Design of the AFLOAT trial; AA: atrial arrhythmia; ICM = insertable cardiac monitor; od = once a day; PFO = patent foramen ovale; SR = sustained-release.
Abbreviations
- AA
atrial arrhythmia
- AFLOAT
Assessment of Flecainide to Lower the patent foramen ovale closure risk of Atrial fibrillation or Tachycardia
- ECG
electrocardiogram
- ICM
insertable cardiac monitor
Introduction
Several randomized studies and subsequent meta-analyses have shown a significant reduction in recurrent neurological events after patent formaen ovale (PFO) percutaneous closure as compared with medical therapy alone.1–9 At the same time, a higher rate of newly-detected atrial arrhythmias (AA) was recorded after PFO closure as compared with controls. Randomized studies reported low rates of atrial fibrillation after PFO closure (∼6%) but have relied on patient-reported symptomatic episodes only.10–13 In a recent prospective paper using a loop recorder monitoring for at least one month after PFO closure, AA was diagnosed in 20.9% of patients.14 New-onset AA is the most frequent complication of PFO closure15 and most AA cases occur within 6 weeks after the procedure, with a median delay of 2 weeks,14,16 a finding that suggests that the procedure itself induces AA. Several causes of early AA events after PFO closure have been suggested: AA events may possibly be triggered by the procedure itself or local inflammation1,17,18; the interatrial conduction, via Bachmann's bundle lying in the roof of the atrium at the superior margin of the fossa ovalis, may be compromised by the device,19 which may act as a mechanical barrier, creating a macroreentrant circuit20; left atrium dysfunction related to PFO and atrial septum aneurism may be responsible for AA independently of closure but triggered by the device implantation.21 These AA episodes are unforeseeable, can be poorly tolerated, and bare the risk of a new stroke in these patients with a significant CHA2DS2VASc score.9 When AA occurs, antiarrhythmic treatment and anticoagulation (all these patients have by a CHA2DS2VASc score of 2 or more) are urgently required, with sometimes hospitalization in case of poor rhythm or hemodynamic tolerance. In addition, more aggressive therapy may be required such as electrical or chemical cardioversion and/or an ablation procedure.14 Atrial arrhythmias being the most frequent, unforeseeable, and certainly not a trivial complication of PFO closure, it deserves more attention.
The present randomized study hypothesized that prevention may be possible with a short antiarrhythmic treatment started at the time of PFO closure. Drugs that are used to convert AA of recent onset to sinus rhythm are class IA, IC, and III antiarrhythmic agents. The class IC agent Flecainide, whose primary electrophysiologic effect is a slowing of conduction in a wide range of cardiac tissues, has the advantage of acting rapidly with a great efficacy.22 Placebo-controlled studies have shown success rates ranging from 58 to 95%.23,24 Few adverse effects have been reported and the drug is globally well tolerated in patients without underlying heart disease.25
The hypothesis of the AFLOAT study is that a temporary treatment with Flecainide could safely prevent the occurrence of any AA episode in these young patients without underlying heart disease. As there is uncertainty on the period to cover for AA prevention with Flecainide, two arms with two different durations of treatment were considered (3 and 6 months), based on the expected device endothelialization duration26 and the AA risk period after PFO closure.14,16
Methods/Design
Study design
AFLOAT is a prospective, national, multicenter, randomized, and open-label superiority trial with a blind evaluation of all endpoints (PROBE study design).
Patients with a PFO closure indication (cryptogenic stroke, peripheral paradoxical embolism, platypnoae-orthodeoxia, diving decompression sickness) are screened, and the indication for PFO closure is retained by an ad hoc multidisciplinary committee. The patient signs an informed consent form. After PFO device implantation and during the same setting, a small insertable cardiac monitor (ICM) (CONFIRM RX, Abbott®), providing a long-term cardiac monitoring, is implanted under the skin to detect AA.27–30
Immediately after successful implantation of both the PFO closure device and the ICM, the ICM is activated in the catheterization laboratory, and the patient randomly assigned in a 1:1:1 ratio, to Flecainide (150 mg per day in a single sustained-release (SR) dose) for 6 months (Group 1), Flecainide (150 mg per day in a single SR dose) for 3 months (Group 2), or no additional treatment (standard of care) for 6 months (Group 3). Randomization is performed using an electronic Case Report Form (eCRF) and is stratified by participating centres.
Clinical follow-up is conducted during hospitalization, 3 months and 6 months (M6) after hospital discharge. A contrast echocardiography is recommended at M6. Telemonitoring using a mobile app (myMerlin™) provides daily notifications in case of an arrhythmic event occurring over the 6-month follow-up period allowing immediate action from the physician according to current guidelines on atrial fibrillation management31,32 (see Graphical Abstract).
An observational period will follow the 6-month interventional phase in patients who keep the ICM beyond the 6-month follow-up period of the randomized study. Atrial arrhythmias detection will be continued.
A blind reading of all ICM recordings and a blind adjudication of clinical events by an independent clinical event committee will be performed.
Participants need to be more than 18-year-old and affiliated to the Social Security system and to provide a signed written consent form. The exclusion criteria are the presence or any prior history of AA (paroxysmal, persistent, or permanent), an electrocardiographic diagnosis of ventricular pre-excitation or bundle-branch block (QRS > 120 ms), an ischaemic heart disease, a dilated or hypertrophic cardiomyopathy, a history of heart failure, hemodynamic valvular heart disease, or left ventricular dysfunction (ejection fraction < 50%), a long QT interval or Brugada syndrome, the bradycardia—tachycardia syndrome (resting heart rate, ≤50 bpm, or repetitive sinoatrial blocks during waking hours), documentation of previous episodes of second or third-degree atrioventricular block, high heart rate at baseline >100 bpm, renal insufficiency (Glomerular filtration rate estimated by the Cockcroft and Gault formula < 30 ml/min/m²), previous hypokalemia (potassium level <3 mmol/L), suspected or known pregnancy, a known intolerance to Flecainide, contemporaneous enrolment in a different clinical trial.
Drug tested
Flecainide is a well-tolerated drug with rare side effects. The most frequently reported side effects (usually at the start of treatment) are minor effects that rarely require interruption of treatment: nausea, asthenia, vertigo, dyspnea, diarrhoea, headache, angina symptoms, and allergy. Transient atrial flutter with a rapid ventricular rate owing to an atrioventricular conduction ratio of 1:1 has been exceptionally reported (< 0.2% of patients).25 Specific risk factors for ventricular proarrhythmic associated to class IC antiarrhythmic drugs (such as Flecainide) are well documented but do not apply to our population of patients without any underlying heart disease. These risk factors have been, however, mentioned as exclusion criteria in the AFLOAT study.
Study objectives
The primary objective of the AFLOAT study is to assess if Flecainide SR 150 mg od can prevent AA episodes as compared with the standard of care without antiarrhythmic treatment (control group) at 3 months after PFO closure. The main secondary objective is to assess whether 6 months of Flecainide is more effective than 3 months of Flecainide to prevent AA episodes at 6-month follow-up. The safety of Flecainide will be carefully analysed.
Study endpoints
To assess the efficacy of Flecainide, the primary endpoint is the percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥30 s) recorded on long-term monitoring with ICM during the 3-month period following PFO closure. Atrial arrhythmias are defined as any episode of atrial fibrillation, atrial flutter, or atrial tachycardia that lasts 30 s or more, in accordance with the 2012 consensus statement from the Heart Rhythm Society and others.33 The safety endpoints are the rate of Flecainide-related adverse events (Table 1). The secondary efficacy endpoints are presented in Table 1.
Primary, secondary, and safety endpoints of the AFLOAT trial
| Primary endpoint | Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥30 s) recorded on long-term monitoring with ICM during the 3 month period following PFO closure |
| Secondary endpoints | Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥30 s) recorded on long-term monitoring with ICM between 3 and 6 months after PFO closure |
| Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥6 min) recorded on long-term monitoring with ICM device during the 3 months after PFO closure | |
| AA burden and its evolution over time | |
| Time to first recurrence of AA between 3 and 6 months after PFO closure | |
| Percentage of patients with at least one episode of symptomatic palpitations during the 3- and 6-month periods after PFO closure | |
| Percentage of patients with at least one episode of fatal or non-fatal stroke or transient ischaemic attack during the 3- and 6-month periods after PFO closure | |
| Percentage of patients with at least one episode of non-scheduled practitioner-consultation or hospitalization for any cardiovascular reason during the 3- and 6-month periods after PFO closure | |
| All-cause mortality during the 3- and 6-month period after PFO closure | |
| Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥6 min) recorded on long-term monitoring with ICM device during the whole follow-up period | |
| Safety endpoints | Nausea |
| Digestive disorder | |
| Dizziness | |
| Tremors | |
| Blurred vision | |
| Tiredness | |
| Headache | |
| Allergy | |
| Worsening of pre-existing heart failure | |
| Worsening of arrhythmia or appearance of new heart rhythm disorders | |
| Cardiac conduction disorders | |
| Pulmonary fibrosis or interstitial lung disease |
| Primary endpoint | Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥30 s) recorded on long-term monitoring with ICM during the 3 month period following PFO closure |
| Secondary endpoints | Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥30 s) recorded on long-term monitoring with ICM between 3 and 6 months after PFO closure |
| Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥6 min) recorded on long-term monitoring with ICM device during the 3 months after PFO closure | |
| AA burden and its evolution over time | |
| Time to first recurrence of AA between 3 and 6 months after PFO closure | |
| Percentage of patients with at least one episode of symptomatic palpitations during the 3- and 6-month periods after PFO closure | |
| Percentage of patients with at least one episode of fatal or non-fatal stroke or transient ischaemic attack during the 3- and 6-month periods after PFO closure | |
| Percentage of patients with at least one episode of non-scheduled practitioner-consultation or hospitalization for any cardiovascular reason during the 3- and 6-month periods after PFO closure | |
| All-cause mortality during the 3- and 6-month period after PFO closure | |
| Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥6 min) recorded on long-term monitoring with ICM device during the whole follow-up period | |
| Safety endpoints | Nausea |
| Digestive disorder | |
| Dizziness | |
| Tremors | |
| Blurred vision | |
| Tiredness | |
| Headache | |
| Allergy | |
| Worsening of pre-existing heart failure | |
| Worsening of arrhythmia or appearance of new heart rhythm disorders | |
| Cardiac conduction disorders | |
| Pulmonary fibrosis or interstitial lung disease |
AA = atrial arrhythmia; ICM = insertable cardiac monitor; PFO = patent foramen ovale.
Primary, secondary, and safety endpoints of the AFLOAT trial
| Primary endpoint | Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥30 s) recorded on long-term monitoring with ICM during the 3 month period following PFO closure |
| Secondary endpoints | Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥30 s) recorded on long-term monitoring with ICM between 3 and 6 months after PFO closure |
| Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥6 min) recorded on long-term monitoring with ICM device during the 3 months after PFO closure | |
| AA burden and its evolution over time | |
| Time to first recurrence of AA between 3 and 6 months after PFO closure | |
| Percentage of patients with at least one episode of symptomatic palpitations during the 3- and 6-month periods after PFO closure | |
| Percentage of patients with at least one episode of fatal or non-fatal stroke or transient ischaemic attack during the 3- and 6-month periods after PFO closure | |
| Percentage of patients with at least one episode of non-scheduled practitioner-consultation or hospitalization for any cardiovascular reason during the 3- and 6-month periods after PFO closure | |
| All-cause mortality during the 3- and 6-month period after PFO closure | |
| Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥6 min) recorded on long-term monitoring with ICM device during the whole follow-up period | |
| Safety endpoints | Nausea |
| Digestive disorder | |
| Dizziness | |
| Tremors | |
| Blurred vision | |
| Tiredness | |
| Headache | |
| Allergy | |
| Worsening of pre-existing heart failure | |
| Worsening of arrhythmia or appearance of new heart rhythm disorders | |
| Cardiac conduction disorders | |
| Pulmonary fibrosis or interstitial lung disease |
| Primary endpoint | Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥30 s) recorded on long-term monitoring with ICM during the 3 month period following PFO closure |
| Secondary endpoints | Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥30 s) recorded on long-term monitoring with ICM between 3 and 6 months after PFO closure |
| Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥6 min) recorded on long-term monitoring with ICM device during the 3 months after PFO closure | |
| AA burden and its evolution over time | |
| Time to first recurrence of AA between 3 and 6 months after PFO closure | |
| Percentage of patients with at least one episode of symptomatic palpitations during the 3- and 6-month periods after PFO closure | |
| Percentage of patients with at least one episode of fatal or non-fatal stroke or transient ischaemic attack during the 3- and 6-month periods after PFO closure | |
| Percentage of patients with at least one episode of non-scheduled practitioner-consultation or hospitalization for any cardiovascular reason during the 3- and 6-month periods after PFO closure | |
| All-cause mortality during the 3- and 6-month period after PFO closure | |
| Percentage of patients with at least one episode of symptomatic or asymptomatic AA episode (≥6 min) recorded on long-term monitoring with ICM device during the whole follow-up period | |
| Safety endpoints | Nausea |
| Digestive disorder | |
| Dizziness | |
| Tremors | |
| Blurred vision | |
| Tiredness | |
| Headache | |
| Allergy | |
| Worsening of pre-existing heart failure | |
| Worsening of arrhythmia or appearance of new heart rhythm disorders | |
| Cardiac conduction disorders | |
| Pulmonary fibrosis or interstitial lung disease |
AA = atrial arrhythmia; ICM = insertable cardiac monitor; PFO = patent foramen ovale.
Statistical analysis
The primary analysis will be based on the intention-to-treat population. Considering the design of the trial, groups 1 and 2 (both treated with Flecainide within 3 months post-PFO closure) will be pooled and compared to group 3 (control group) for the primary endpoint, as well as for secondary endpoints regarding events that occurred within 3 months after PFO closure. For secondary endpoints regarding the 6-month period post-PFO closure, the 3 groups will be compared using two-by-two comparisons. All tests regarding the 3-month post-PFO period will be two-sided at a 5% significance level. Regarding tests comparing the 6-month post-PFO period, the adjustment for multiplicity proposed by Hayter will be used to avoid inflation of alpha risk under both null or alternative hypotheses.34
Sample size calculation
Based on literature,3–5,14,15 we considered that the average spontaneous risk of AA after PFO closure at 3 months is 5% (vs. 1% in patients without PFO closure) and that systematic CONFIRM RX recording will increase the AA rate by a factor 5. Thus, the average rate of AA after PFO closure measured by systematic CONFIRM RX recording will be close to 25% (note that it would be 5% if no closure occurred). We hypothesized that Flecainide will reduce this rate to 8.5% at 3 months (still higher than the expected rate of 5% in patients without PFO closure). Considering the design, the ratio of Flecainide vs. standard of care (control group) treated patients will be 2:1 before 3 months thus a 56 patients/group will allow a 80% power to detect the anticipated difference at 3 months using a chi-square test at a two-sided alpha level of 5%. Considering a 10% attrition rate, 186 patients will be included.
The study started in March 2022. On September 2023, all patients were enrolled in the AFLOAT Trial (see Figure 1).
Randomization curve of the AFLOAT trial (03/2022–09/2023).
Patients >50 y/o, women, diabetic patients, active smoking patients, patients with BMI > 30 kg/m², prior history of hypertension, prior history of migraine, pulmonary disease (including COPD and sleep apnea syndrome) patients with atrial septum aneurysm (septum excursion >10 mm), Eustachian valve or Chiari network, left atrium size, type, and size of PFO closure device are predefined subgroups of interest.
The study is performed according to the ethical principles of the Declaration of Helsinki, the International Conference on Harmonization/Good Clinical Practice, and applicable regulatory requirements.
Discussion
This study is the first study evaluating a short-term treatment to prevent the most frequent complication of PFO closure i.e. flecainide to prevent AA. It evaluates also the optimal duration of Flecainide (3 months vs. 6 months). This study will bring also solid information on the real incidence of AA after a transcatheter PFO closure by a systematic long-term ICM starting exactly at the time of PFO closure.
In the past 6 years, the percutaneous procedures of PFO closure have increased rapidly reaching high volumes in many centers. This is the consequence of the publication of major randomized studies2–5 and of the development of Neurovascular Units for the management of acute stroke with thrombolysis and thrombectomy. The systematic etiological investigation after an ischaemic stroke, especially in young patients, has led to the frequent diagnosis of PFO with an indication for closure. Patent foramen ovale closure is a safe procedure but it is critical to monitor PFO closure-related adverse events, the most frequent being AA occurring in general in the following weeks after the procedure. The most recent studies suggest that this complication has been underestimated and that the real prevalence of AA after PFO closure is much higher than what was reported in the initial randomized trials, which did not focus their follow-up on this complication.14 Thus, AFLOAT will provide contemporary information on the prevalence of AA in the ‘standard of care’ group, with a minimum of 6-month follow-up.
Atrial arrhythmias after PFO closure is not a trivial side effect of the procedure, as AA bares its own risk of stroke, whereas the procedure is performed to reduce the risk of stroke related to PFO.9 Atrial arrhythmias usually needs replacement of antiplatelet by anticoagulant therapy in patients who all have a CHA2DS2VASc score requiring anticoagulation, and specific antiarrhythmic treatments may also be required, including antiarrhythmic drugs, cardioversion, or ablation. AFLOAT will provide a precise description of atrial and ventricular arrhythmia episodes occurring after PFO closure, their duration, recurrence, or persistence, and importantly will answer the question of an effective prevention of such episodes using systematically Flecainide during the period at risk. Furthermore, AFLOAT design has two experimental groups with 2 different treatment durations (3 vs. 6 months). If Flecainide works, this design will allow us to conclude on the optimal treatment duration to prevent AA after PFO closure. Although the literature indicates that AA complicating PFO closure occurs within the first 2 months after the procedure, it is not known if this type of procedure-related AA is predictive of AA at longer term. The prolongation of ICM monitoring beyond 6 months will allow to know if recurrent episodes of AA occur in the 2 years after the end of the study drug intervention of the randomized part of the trial.
The characteristics of participants to AFLOAT may differ from the population profiles of prior randomized trials. Indeed, we enrol all comers presenting for PFO closure. As there is no age limit in our trial, we may have patients older than 60 years. We do not limit inclusion to stroke patients but other indications may lead to PFO closure in our trial (e.g. peripheral emboli, platypnea-orthodeoxia syndrome, etc). We do not impose PFO closure with one type of device but all devices available on the market may be used. We will perform also an analysis of factors that may predict AA in our population of PFO closure.
Conclusion
AFOAT is a national multicenter, prospective, and randomized study with three parallel arms to test the hypothesis that Flecainide after PFO closure can prevent post-procedural AA.
Acknowledgement
We thank all the investigators (listed in the Appendix) and the study nurses/study coordinators involved in the AFLOAT study. We thank Martine Tanke from URC Lariboisière and Laura Blanchet from the DRCI, APHP, for their support.
Funding
This study was fully funded by a research grant (PHRA) from the ACTION Group (www.action-coeur.org) and Confirm Rx devices were provided free of charge by Abbott Medical France SAS.
Conflict of interest: Dr. Guedeney has received transportation assistance from Sanofi. Dr. Laredo has received consultancy fees from Abbott and Biotronik. Prof. Montalescot has received research grants to the institution or consulting and lecture fees from Abbott, Amgen, AstraZeneca, Ascendia, Bayer, BMS, Boehringer-Ingelheim, Boston-Scientific, Celecor, CSL Behring, Idorsia, Lilly, Novartis, Novo, Opalia, Pfizer, Quantum Genomics, Sanofi, and Terumo. Prof. Silvain has received consulting fees or transportation assistance from AstraZeneca, Abbott Medical France, Bayer HealthCare, Abbott Medical France SAS, Biotronik, Boehringer Ingelheim France, CSL Behring SA, Gilead Science, Sanofi France, Terumo France, and Zoll; and is a stockholder in 4P-Pharma. Prof. Hammoudi has received consulting and lecture fees from Abbott, Boehringer Ingelheim, Bayer, and Novartis. Prof Vicaut has received consulting fees from Abbott, Amgen, Bristol–Myers Squibb, Celgene, LFB, Pfizer, Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Prof. Cayla received consulting fees from Edwards, Medtronic, Microport CRM, payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol–Myers Squibb, Edwards, Microport, Medtronic, Pfizer, and Sanofi-Aventis.
Appendix
Members of the steering committee
Dr. Gilles Montalescot (Chairman)
Dr. Marie Hauguel-Moreau (principal investigator)
Dr. Guillaume Duthoit
Dr. Eric Vicaut
Members of the Clinical Event Committee (CEC)
Dr. Mikael Laredo (Chairman)
Dr. Thomas Rolland
Dr. Yassine Temmar
Members of the Data Safety and Monitoring Board (DSMB)
Dr. Nicolas Lellouche (Chairman)
Dr. Gilles Chatellier
Dr. Stéphane Edhery
List of investigators
Gilles Montalescot, Sorbonne Université, ACTION Study Group, INSERM UMRS1166, ICAN - Institute of CardioMetabolism and Nutrition Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
Claire Dauphin, Hôpital Gabriel Montpied, CHU Clermont-Ferrand, Clermont-Ferrand, France
Vincent Auffret, University Hospital Pontchaillou, Cardiology and Vascular Disease Department, CIC-IT 804, Rennes 1 University, France
Eloi Marijon, Cardiology Department, European Georges Pompidou Hospital, Paris, France
Farzin Beygui, CHU de la Côte de Nacre, Département de Cardiologie, Caen, France
Philippe Aldebert, Cardiology Division, Hôpital La Timone, Marseille, France
Jean-Michel Clerc, Cardiology Department, Centre Hospitalier Universitaire de Tours, Tours, France.
Meyer Elbaz, Department of Cardiology, Institute CARDIOMET, CHU-Toulouse, Toulouse, France.
Jean-Christophe Macia, Montpellier University Hospital, UFR de Médecine, Université Montpellier 1, Department of Cardiology, Montpellier, France.
Antoine Da Costa, Service de cardiologie, hôpital Nord, université Jean-Monnet, CHU de Saint-Étienne, 42055 Saint-Étienne cedex 2, France.
Wissam Abi Khalil, Institut Mitovasc, University of Angers, UMR CNRS 6015-INSERMU1083, Angers, France.
Simon Elhadad, Service de Cardiologie, Centre hospitalier de Marne-la-Vallée, Jossigny, France.
Guillaume Cayla, Service de Cardiologie, Centre Hospitalier Universitaire de Nîmes, Nîmes, France.
Xavier Iriart, Department of Pediatric and Adult Congenital Cardiology, Hôpital Cardiologique du Haut-Lévêque, CHU de Bordeaux, Bordeaux-Pessac, France.
Notes
AFLOAT: Assessment of Flecainide to Lower the patent foramen Ovale closure risk of Atrial fibrillation or Tachycardia trial (NCT05213104).
