key: cord-0934383-j3h88kox
authors: Camm, A. John; Blomström‐Lundqvist, Carina; Boriani, Giuseppe; Goette, Andreas; Kowey, Peter R.; Merino, Jose L.; Piccini, Jonathan P.; Saksena, Sanjeev; Reiffel, James A.
title: AIM‐AF: A Physician Survey in the United States and Europe
date: 2022-03-04
journal: J Am Heart Assoc
DOI: 10.1161/jaha.121.023838
sha: 602203b694329651d8966ebc45cb96a497692f92
doc_id: 934383
cord_uid: j3h88kox

BACKGROUND: Guideline recommendations are the accepted reference for selection of therapies for rhythm control of atrial fibrillation (AF). This study was designed to understand physicians’ treatment practices and adherence to guidelines. METHODS AND RESULTS: The AIM‐AF (Antiarrhythmic Medication for Atrial Fibrillation) study was an online survey of clinical cardiologists and electrophysiologists that was conducted in the United States and Europe (N=629). Respondents actively treated ≥30 patients with AF who received drug therapy, and had received or were referred for ablation every 3 months. The survey comprised 96 questions on physician demographics, AF types, and treatment practices. Overall, 54% of respondents considered guidelines to be the most important nonpatient factor influencing treatment choice. Across most queried comorbidities, amiodarone was selected by 60% to 80% of respondents. Other nonadherent usage included sotalol by 21% in patients with renal impairment; dofetilide initiation (16%, United States only) outside of hospital; class Ic agents by 6% in coronary artery disease; and dronedarone by 8% in patients with heart failure with reduced ejection fraction. Additionally, rhythm control strategies were frequently chosen in asymptomatic AF (antiarrhythmic drugs [AADs], 35%; ablation, 8%) and subclinical AF (AADs, 38%; ablation, 13%). Despite guideline algorithms emphasizing safety first, efficacy (48%) was selected as the most important consideration for AAD choice, followed by safety (34%). CONCLUSIONS: Despite surveyed clinicians recognizing the importance of guidelines, nonadherence was frequently observed. While deviation may be reasonable in selected patients, in general, nonadherence has the potential to compromise patient safety. These findings highlight an underappreciation of the safe use of AADs, emphasizing the need for interventions to support optimal AAD selection.

A trial fibrillation (AF) is the most common sustained tachyarrhythmia and is associated with a 5-fold increased relative risk of stroke, 1 a 3-fold increased relative risk of heart failure (HF), 2 and a doubled relative risk of mortality. 3 The prevalence of AF is increasing worldwide, predicted to affect 6 to 12 million people in the United States by 2050 and 18 million people in Europe by 2060. 4 For the past 2 decades, the European Society of Cardiology (ESC) 5 and the American Heart Association/ American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) 6, 7 have provided physicians with guidelines to direct the management of patients with AF. Both recommend the use of antiarrhythmic drugs (AADs) for rhythm control in patients with symptomatic AF only. [5] [6] [7] Additionally, both guidelines indicate that selection of antiarrhythmic therapies should consider arrhythmia burden, presence of underlying heart disease, severity of symptoms, and risk of side effects. [5] [6] [7] Since the publication of the Etude en Activité Libérale de la Fibrillation Auriculaire study over 2 decades ago, 8 the clinical landscape of AF treatment has evolved considerably, as have the guidelines. Two new AADs, dofetilide and dronedarone, are now available (although dofetilide is available in the United States only 9 ), and the use of ablation therapy has become increasingly widespread.

Real-world data from the United States indicated that between 1990 and 2005, there was a 13-fold increase in the proportion of patients with AF who received ablation (P < 0.001) 10 ; a 12.5% annual rate of increase worldwide is predicted from 2019 to 2025. 11 However, in the current clinical landscape, prescribing practices of physicians and their attitudes toward the management of patients with AF are poorly understood. Accordingly, the AIM-AF (Antiarrhythmic Interventions for Managing Atrial Fibrillation) study was designed to explore cardiologist and electrophysiologist antiarrhythmic treatment practices in patients with AF. The results of the study are reported in the context of the 2020 ESC guidelines, 5 and the 2014 and 2019 AHA/ACC/HRS guidelines. 6, 7 METHODS Qualified researchers may request access to data including the study summary, study questionnaire with any amendments, and data set specifications for validation purposes. Only fully anonymized data will be provided.

The AIM-AF study was an exploratory, online physician survey, designed by a steering committee of 9 global experts in AF. Practicing physicians from the M3 Global International Market Research Panel were invited to complete the survey, with a geographical spread across the United States and European countries involved, to avoid potential selection bias. Ethics approval was obtained from the Western Institutional Review Board committee (Ref: 1-1337237-1) , and from the local ethics committee in Uppsala, Sweden; participants provided informed consent in accordance with institutional guidelines.

The survey aimed to recruit 600 clinical cardiologists, including clinical electrophysiologists and interventional electrophysiologists from the United States, Germany, Italy, Sweden, and the United Kingdom. These countries were selected to ensure that physicians from Central, Northern, Southern, and Western Europe were represented. Inclusion criteria were as follows: qualification in their specialty for >3 years and <40 years; >40% of their time spent actively treating patients; ≥30 new or existing patients with AF seen within a 3-month period (before the COVID-19 pandemic); and management of patients with AF who have received ablation or have been referred for ablation.

The survey was conducted between October 2, 2020, and February 12, 2021, and was intended to take 60 minutes to complete. Respondents were asked to complete 96 questions (Table S1) , including a set of screening questions to ascertain demographics and eligibility. Questions were grouped on the basis of topics such as physician setting and patient caseload; treatment journey, with a focus on oral AADs; prescribing/ treatment practices; and use/referral of ablation. Since no formal hypothesis was tested, data analyses are descriptive in nature. Univariate tests were conducted for comparisons between the 2 groups (United States versus Europe) and the Z test was applied to determine statistical significance (P value boundary of <0.05); however, P values should be considered notional since no adjustment was made for multiple testing.

To distinguish the degree of nonadherence between survey responses and recommendations from the 2020 ESC 5 and 2014/2019 AHA/ACC/HRS guidelines, 6,7 we established 4 definitions to describe adherence: compliance with guidelines (AAD use aligns with guideline recommendations); noncompliance with guidelines (AAD use contradicts guideline recommendations); deviation from guidelines (guidelines recommend use of an alternative therapy or alternative practice in this setting); and potential noncompliance with guidelines (use in this setting could contradict guideline recommendations, but clinical thresholds differed between the survey questions and the guidelines, preventing absolute certainty). Estimated percentage of nonadherence was calculated for each AAD, which described the proportion of physicians who selected an AAD in at least 1 clinical circumstance that fell into any of the "noncompliance with guidelines," "deviation from guidelines," or "potential noncompliance with guidelines" definitions.

The survey completion rate (all questions answered) was 7% in the United States and 16% in Europe (Table 1) . A total of 629 physicians completed the survey, of 6428 approached, with similar characteristics between the global population, the United States, and Europe (Table 2) . Overall, the proportion of cardiologists (57%) was higher than that of electrophysiologists (43%), with 80% reporting a specialization in AF. At the time of the survey, respondents had been qualified in their specialty for an average of 14.5 years. The most common clinical practice setting was a university hospital/clinic (40% global; 31% United States, 49% Europe) or a general community hospital/clinic (37% global; 33% United States, 40% Europe). Over a typical 3-month period (before the COVID-19 pandemic), the average total cardiology patient caseload, including all diagnoses and conditions, was 549; the average caseload of follow-up patients was greater than the average caseload of new patients with AF (158 versus 94, respectively). Most respondents referred patients for ablation, rather than performing ablations themselves (55% versus 45%, respectively).

Overall, 97% of respondents stated that they follow guidelines for their treatment decisions. Approximately half (49%) of the respondents primarily referred to the AHA/ACC/HRS guidelines 6,7 for their decision making, with 43% referring to the ESC guidelines. 5 Overwhelmingly, US respondents chose the AHA/ ACC/HRS guidelines 6,7 as their primary reference (96%), although 20% also referred to the ESC guidelines. 5 European respondents generally chose the ESC guidelines 5 as their primary reference (82%), with 32% also referring to the AHA/ACC/HRS guidelines. 6, 7 Guidelines were chosen as the first and second most important nonpatient factor that influenced treatment strategy by 54% and 28% of respondents, respectively; other scientific literature was chosen by 23% and 41%, respectively. Most respondents (65%), including 58% of European respondents, were unsure whether the 2020 ESC guideline 5 update had influenced their survey responses.

AADs were chosen as a typical treatment choice across multiple patient comorbidity categories, with extensive use of amiodarone (selected by 60% to 80% of respondents across most queried comorbidities), despite guidelines recommending alternative first-line agents in most settings. Sotalol use ranged from 18% to 46% between comorbidity categories, and dronedarone was used by 8% to 27% of respondents, while use of class Ic drugs was generally low. Estimated percentage of nonadherence for each agent was 93% for amiodarone, 61% for flecainide, 60% for sotalol, 48% for propafenone, 40% for dronedarone, and 25% for dofetilide.

In patients with no or minimal structural heart disease (SHD), 25% of respondents selected amiodarone as a typical treatment option ( Figure 1A ). Despite guidelines recommending that alternative agents should be considered first, class Ic agents were selected by the highest number of respondents (54%) in this patient group.

Sotalol and class Ic agents were selected as a typical treatment choice in left ventricular hypertrophy (LVH) by 33% and 12%, respectively ( Figure 1B ). This could indicate potential noncompliance, as these agents are not recommended in patients with severe LVH (ESC guidelines 5 ) or significant LVH (wall thickness >1.5 cm; AHA/ACC/HRS guidelines 6,7 ). In patients with HF with preserved ejection fraction, guidelines do not recommend use of class Ic agents, yet they were selected by 18% of respondents, indicating noncompliance ( Figure 2 ).

The guideline-preferred AADs for use in patients with coronary artery disease (CAD) are dronedarone (IA) and sotalol (IIbA in ESC guidelines), 5 plus dofetilide in the United States. However, class Ic agents were selected as a typical treatment choice in CAD (average across myocardial infarction presentations and revascularized CAD; Figure 1C ) by 6% of respondents (numbers reported are the average use of flecainide and propafenone; Figure 2 ), indicating noncompliance with guidelines.

Amiodarone is recommended for use in patients with HF with reduced ejection fraction (HFrEF) by both sets of guidelines and AHA/ACC/HRS recommendations 6,7 also include dofetilide in this setting. Dronedarone may be used in patients with mildly impaired but stable left ventricular function according to the ESC guidelines 5 and was used by 9% of respondents. Notably, sotalol was selected by 18% of respondents, despite ESC guidelines 5 not recommending it and AHA/ACC/HRS guidelines 6,7 advising to exclude or use with caution in this setting. Class Ic agents were used by 6% for patients with HFrEF ( Figure 1D ), which directly contradicts guidelines, indicating noncompliance ( Figure 2 ).

Class Ic drugs (43%) and sotalol (29%) were selected as typical choices in chronic lung disease ( Figure 1A ), which could indicate potential noncompliance, as guidelines recommend avoiding use in patients with asthma. In patients with renal impairment (estimated glomerular filtration rate <60 mL/min per 1.73 m 2 ), sotalol was selected by 21% of respondents, which contradicts AHA/ACC/HRS guidelines 6,7 and may indicate 5 which state that sotalol should not be used if creatinine clearance is <30 mL/min. Responses also suggested potential noncompliant use of class Ic drugs in chronic liver disease (25%) and renal impairment (24%) (Figure 2 ).

A notable number of respondents indicated they initiated sotalol therapy outside a hospital setting (53%). While this does not directly contradict recommendations, the 2014 AHA/ACC/HRS guidelines 6 state that hospital initiation of sotalol should be considered. As such, these responses suggest deviation from guidelines. A number of respondents (United States only) initiated dofetilide outside a hospital setting (16%). This does not follow the 2014 AHA/ACC/HRS guidelines 6 or the US Food and Drug Administration labeling for this agent, 9 which recommend inpatient initiation of dofetilide because of QT prolongation and risk of torsades de pointes.

Guidelines recommend close monitoring of proarrhythmic risk factors in individuals using AADs. In general, respondents requested routine investigations (at least annually) most often with amiodarone ( Figure 3 ). ECGs were routinely requested by 80% of respondents with amiodarone, sotalol, and class Ic drugs. Routine requests for electrolyte monitoring was similar between all AADs, but notably low for sotalol (52%) and class Ic drugs (50%). Renal function monitoring was also notably low with sotalol (57%) and dofetilide (US respondents only; 62%), despite both guidelines recommending electrolyte and renal function monitoring for all patients receiving sotalol. Respiratory function monitoring was requested by 64% of respondents with amiodarone and 14% with dronedarone. Monitoring of hepatic function with amiodarone, dronedarone, and class Ic drugs was requested by 84%, 57%, and 27% of respondents, respectively.

Survey responses indicated notable variation in control strategy, dependent on AF subtype ( Figure 4 ). Use of rate control agents was most frequent for asymptomatic and subclinical AF (57% and 56%, respectively). However, rhythm control strategies were also reported in these 2 AF groups, using AADs (35% and 38%, respectively) and performing ablation (8% and 13%, respectively). Ablation was the most common treatment strategy for recurrent episodes of symptomatic AF (61%), and its use increased with the prior failure of single (62%) or multiple AADs (74%) in preventing AF recurrence, as well as with prior failure of AAD combinations (71%) (Figure 4 ). On average, AADs were primarily used more often as a first-line strategy than rate control agents in paroxysmal AF (in 60% versus 32% of patients, respectively). For the management of persistent AF, rate control agents were primarily used over AADs (in 51% versus 42% of patients, respectively).

Beta blockers (90%) were the most frequently used rate control agent in combination with an AAD for rhythm control, followed by calcium channel blockers (32%), and digitalis (19%). Drug combinations were most frequently used for the treatment of persistent AF (in 36% of patients), mixed persistent/paroxysmal AF (in 34% of patients) and paroxysmal AF (in 32% of patients).

Amiodarone was the AAD most frequently selected in combination with a rate control agent, used by 66% of John Camm et al A Physician Survey of Antiarrhythmic Drug Use respondents in combination with digitalis, 44% with a beta blocker, and 42% with a calcium channel blocker ( Figure 5 ). The ESC guidelines 5 recommend avoiding combinations of >1 AAD to minimize proarrhythmic risk. However, 10% reported that this was the most common type of combination regimen used for rhythm control. On average, respondents would try combinations of AADs (add-on) in 20% of patients if they experienced a recurrence while receiving an AAD.

Despite guideline algorithms emphasizing safety first, efficacy was felt to be the most important nonpatient factor for selection of rhythm control therapy (48% ranked it first from a list of 9 general considerations; data not shown), while safety was considered the second most important factor (34%). Symptomatic status was ranked by 38% as the most important patient factor in guiding the choice of rhythm control therapy (data not shown). Overall, the combination of both antiarrhythmic properties and rate control properties in a single drug with multichannel effects, such as amiodarone, dronedarone, or sotalol, influenced 68% of respondents regarding their choice of AAD; 23% felt that their AAD choice was not influenced, and 9% were unsure.

The largest difference in treatment practice overall between US and European respondents was the use of dofetilide in the United States (selected across patient subgroups, by 7% to 38% of respondents), whereas this agent is not marketed for use in Europe and was not selected by European respondents. This is likely to have led to regional disparities in the selection of other agents, most notably amiodarone, which was selected by significantly more European respondents (P < 0.05) across all SHD subgroups apart from in patients with LVH. However, sotalol was used more frequently by US respondents across most comorbidity categories, including LVH and HFrEF. Across all AADs used in both regions, routine investigations were generally requested by fewer US respondents than European respondents. Regional differences were also seen in the degree of adherence to specific guideline recommendations (Table 3) . Considering AAD usage clearly noncompliant with guidelines, class Ic agents were selected in HFrEF, and propafenone was selected in LVH by significantly more US than European respondents (P < 0.05). Additionally, significantly more European than US respondents selected flecainide in LVH (19% versus 11%, P < 0.05). Renal function monitoring with sotalol, which is recommended by guidelines, was performed by statistically significantly more US respondents than European respondents (64% versus 50%, respectively; P < 0.05), against the general trend for US practitioners to request fewer routine follow-up investigations. Use of AADs for rhythm control was statistically significantly lower in US respondents than European respondents for asymptomatic AF (31% versus 39%, respectively; P < 0.05) and subclinical AF (33% versus 43%, respectively; P < 0.05), both deviating from guideline recommendations.

The AIM-AF physician survey extensively explored cardiologist and electrophysiologist treatment decisions regarding antiarrhythmic treatment for AF in 629 respondents. The response rate seen was in line with those previously reported from online physician surveys. [12] [13] [14] The major finding from this study is that there is a high level of deviation, of varying degrees, from the 2020 ESC 5 and 2014/2019 AHA/ACC/HRS guidelines 6, 7 ; a particularly surprising result, since 97% of respondents stated that they follow guidelines and 54% felt that guidelines were the most important nonpatient factor influencing their treatment decisions. It is not possible to determine from these data whether this degree of deviation results from an unexpectedly high level of adaptation of treatment to suit individual patients or reflects a serious knowledge gap among treating physicians. However, the survey questions were worded to ascertain general treatment practices, so respondents would not be expected to select answers based on individual patient circumstances. While deviations from guidelines may be reasonable in select clinical circumstances, a high degree of nonadherence raises concerns regarding patient safety. 15, 16 Despite the growing use of ablation, appropriate AAD use is an increasingly important issue in clinical practice, as one study found that antiarrhythmic prescriptions nearly tripled between 2004 and 2016 in the United States, with the most substantial increases observed for amiodarone, sotalol, flecainide, The choice between rate control and rhythm control in the treatment of patients with AF was widely debated until the publication of the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) study, which found no clear survival advantage when using a rhythm control strategy compared with rate control. 18 However, more recent data have shown greater improvement in quality of life, 19 functional status, [19] [20] [21] [22] exercise tolerance, 23 and also reductions in both symptoms 24 and symptomatic HF incidence 25 with restoration of sinus rhythm (using ablation or AADs) compared with rate-controlled AF. Moreover, The Early Treatment of Atrial Fibrillation for Stroke Prevention Trial found that early comprehensive rhythm control reduced the risk of adverse cardiovascular outcomes (a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of HF or acute coronary syndrome) versus usual care, demonstrating that AADs remain an important treatment option for many patients with AF. 26 A key finding in this survey was the factors that drive contemporary AAD selection. Both the ESC 5 and AHA/ ACC/HRS guidelines 6,7 advocate a safety-based algorithm for AAD selection; however, almost half (48%) of respondents in our survey considered efficacy to be the most important consideration for selection of rhythm control. This finding has implications for patient management and likely explains the high use of amiodarone regardless of the clinical scenario.

Despite the well-known organ toxicity and complex drug interaction profile associated with its use, amiodarone was frequently chosen as a typical treatment across multiple patient comorbidity categories, although both guidelines recommend consideration of other AADs first. However, routine monitoring via all queried parameters was considerably higher with amiodarone than other AADs, suggesting that respondents were aware of the increased safety considerations related to amiodarone. While class Ic drugs were mainly used in patients with minimal or no SHD, a notable proportion were also used in patients with CAD, HFrEF/HF with preserved ejection fraction, or LVH, which is contrary to guidelines and increases the risk of potentially life-threatening proarrhythmia. In the ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation), 44% of investigators used a class Ic agent in patients with CAD, representing documented noncompliance with guidelines. Additionally, 35% used amiodarone as a first-line therapy in patients without HF or LVH, representing the second most common instance of noncompliance in the ORBIT-AF registry. 27 In our study, the extent to which sotalol was selected as a typical treatment in patients with LVH (33%), renal impairment (21%), and HFrEF (18%) was of concern. Similar results were seen in the GWTG-AFib (Get With The Guidelines-Atrial Fibrillation) study, where 20% and 17% of patients, respectively, received sotalol in the presence of HF and LVH. 28 In the 2020 update to the ESC guidelines, 5 sotalol was downgraded from a class I to a class IIb recommendation on the basis of evidence of increased mortality compared with placebo 29 and other AADs. 30, 31 There was no downgrading of sotalol in the 2019 update to the AHA/ACC/HRS guidelines, 7 perhaps a contributing factor to greater overall use of sotalol in the United States than in Europe, but close monitoring in line with the ESC guidelines is advised. 5 The 2020 update to the ESC guidelines include no specific recommendations with regard to sotalol initiation in hospital 5 ; however, according to the AHA/ACC/HRS guidelines, hospital initiation of sotalol should be considered, although it is acknowledged that there is considerable experience of sotalol initiation in patients with a low risk of torsades de pointes outside of a hospital. 6, 7 It is perhaps unsurprising, therefore, that our study found that statistically significantly fewer US respondents initiated sotalol outside of a hospital compared with European respondents (39% versus 66%; P < 0.05). With dofetilide, however, despite the clear guideline recommendation for hospital initiation, 16% of US respondents still initiated dofetilide outside of hospital. Although a recent study found that safe outpatient initiation of dofetilide was possible with intensive monitoring, 32 this involved a very small patient cohort and should not yet inform clinical practice.

Our survey results revealed that a rhythm control strategy is being frequently used to treat asymptomatic and subclinical AF, with only 38% of respondents ranking symptomatic status as the top factor for influencing selection of rhythm control rather than rate control. While the use of early rhythm control is gaining more interest and supporting evidence, 26 the ESC and AHA/ ACC/HRS guidelines recommend that rhythm control should be confined only to otherwise symptomatic patients. [5] [6] [7] Of note, the Euro Heart Survey also found that rhythm control strategies were used in 44% to 46% of asymptomatic patients. 33 This study extensively explored physicians' attitudes toward antiarrhythmic therapies and their treatment practices in patients with AF. Strengths of the AIM-AF study include the fact that responses were gathered from cardiology physicians across several countries, the majority of whom considered AF to be their subspecialty. Additionally, the survey explored physicians' attitudes to therapy selection, which provided a better understanding of physicians' decisionmaking processes.

A key limitation of the study is that data were dependent on the accurate reporting of information by the respondents, which may have been subject to recall bias. Additionally, the survey sample was taken from physicians who were part of the M3 Global International Market Research Panel, and only from 4 European countries. The survey completion rate was rather low (7% in the United States and 16% in Europe), as is often the case with wide-reaching surveys such as the one used in this study; as such, the respondents may not be wholly representative of the general population of John Camm et al A Physician Survey of Antiarrhythmic Drug Use physicians treating AF. However, it is likely that physicians who did respond to the survey were more representative of high-quality standards of care, which is particularly noteworthy in this context, given that adherence to guidelines was unsatisfactory. Another study limitation lies in the fact that this survey did not consider AAD dosing, which can condition both safety and efficacy of therapy and, as such, could have influenced physician responses. Furthermore, the threshold values assigned for certain questions were different than thresholds cited in the guidelines; for instance, guidelines recommend against using sotalol in patients with creatinine clearance <30 mL/min, while the survey classified renal impairment as estimated glomerular filtration rate <60 mL/min per 1.73 m 2 . Results were not stratified by degree of renal impairment; therefore, it remains difficult to accurately estimate the number of respondents who are noncompliant in this regard. Both the lack of information on dosing and the inclusion of data on potential noncompliant prescribing could have had the effect of overinflating the nonadherence rates calculated for each agent, as each could result in compliant practice being scored as nonadherent. Furthermore, these rates do not include any weighting for the degree of deviation from the guidelines or the potential outcomes of nonadherence; for example, the use of a contraindicated agent in a patient with HF, which could severely compromise patient safety, has the same weight as a guideline-compliant dose reduction in a patient with renal impairment.

Across the United States and Europe, many physicians considered guidelines to be the most important nonpatient factor influencing treatment decisions with regard to AAD use. However, nonadherence with guideline recommendations was common, and responses indicated notable noncompliance and potential noncompliance, which may compromise patient safety. Further research to better understand physicians' reasons for nonadherence and interventional opportunities to improve adherence to guidelines is warranted. 

Medical writing and editorial support for the development of this manuscript was provided by Mariya Jamali, MPharm, and Rosalind Perrett, BA, respectively, of Ashfield MedComms, an Ashfield Health company. Support with survey design, fieldwork, and data analysis was provided by the Research & Insights team of Ashfield MedComms, an Ashfield Health Company. The AIM-AF study investigators thank all the clinicians who participated in this survey.

The AIM-AF study and medical writing and editorial support for the development of this manuscript was funded by Sanofi. The funder had no role in either the study design, data collection, data analysis, data interpretation, or the decision to publish the study. Adverse event reporting This study is funded by a pharmaceutical company and for this reason we are required to pass on any possible Adverse Events, Product Complaints and Special Reporting Situations. The details of these will be reported anonymously unless you agree to disclose your personal details, only and exclusively for the purpose of follow-up by the client's drug safety team. Please select one of the options below: Please select one 1. I would like to proceed and agree to be contacted by the drug safety team for follow-up 2. I would like to proceed but do not wish to be contacted by the drug safety team for follow-up 3. I do not wish to proceed S11

Please select which region/area you work in.

Options were provided in an appendix Section A: Setting and caseload A1 A1a Which health care settings do you spend your time at?

Atrial fibrillation as an independent risk factor for stroke: the Framingham study

A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study

Epidemiologic features of chronic atrial fibrillation-the Framingham study

Atrial fibrillation: the current epidemic

2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS)

AHA/ ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society

AHA/ John Camm et al A Physician Survey of Antiarrhythmic Drug Use

AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons

Characterization of different subsets of atrial fibrillation in general practice in France: the ALFA study. The College of French Cardiologists

Food and Drug Administration (FDA)

Trends in catheter ablation for atrial fibrillation in the United States

Cardiac Ablation Market: Global Industry Analysis, Trends, Market Size, and Forecasts up to 2025

A randomized trial and economic evaluation of the effect of response mode on response rate, response bias, and item non-response in a survey of doctors

Incentive and reminder strategies to improve response rate for internetbased physician surveys: a randomized experiment

Surveying clinicians by web: current issues in design and administration

Adherence to oral anticoagulants among patients with atrial fibrillation: a systematic review and meta-analysis of observational studies

Adherence to antithrombotic therapy guidelines improves mortality among elderly patients with atrial fibrillation: insights from the REPOSI study

Trends in antiarrhythmic drug use among patients in the United States between

The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation

A randomized, controlled study of rate versus rhythm control in patients with chronic atrial fibrillation and heart failure: (CAFÉ-II Study)

Functional status in rate-versus rhythm-control strategies for atrial fibrillation: Results of the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Functional Status Substudy

For the Investigators of the Hot Cafe Polish Study. Functional status with rhythm-versus rate-control strategy for persistent atrial fibrillation

A randomized controlled trial of catheter ablation versus medical treatment of atrial fibrillation in heart failure (the CAMTAF trial)

Successful catheter ablation improves exercise tolerance in persistent atrial fibrillation patients, especially those with reduced ventricular contraction, preserved atrial function, or a high CHADS2 score

Health-related quality of life in patients with atrial fibrillation treated with rhythm control versus rate control: insights from a prospective international registry

Impact of initial heart failure emergence on clinical outcomes of atrial fibrillation patients in the AFFIRM trial

Breithardt G for the EAST-AFNET 4 Trial Investigators. Early rhythm-control therapy in patients with atrial fibrillation

Treatment of atrial fibrillation and concordance with the American Heart Association/American College of Cardiology/Heart Rhythm Society Guidelines: Findings from ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation)

Guideline-concordant antiarrhythmic drug use in the Get with the Guidelines Atrial Fibrillation Registry

Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation

Ventricular arrhythmia and death among atrial fibrillation patients using anti-arrhythmic drugs

Safety of dronedarone in routine clinical care

Outpatient initiation of dofetilide: insights from the complexities of atrial fibrillation management during the COVID-19 lockdown

Atrial fibrillation management: a prospective survey in ESC Member Countries: The Euro Heart Survey on Atrial Fibrillation

A1b Please indicate your main practice setting. Thinking about the patients you would see in a typical three-month period (i.e. prior to the COVID-19 pandemic):What is your typical total cardiology patient caseload?

What is your typical caseload of new patients with AF?And what is your typical caseload of follow-up patients with AF?

In a typical three-month period… ____ total cardiology patient caseload ____ new patients with AF ____follow-up patients with AF

Thinking about your AF patient caseload ([pipe number from A3b&c "AF patients"] patients), what percentage fall into each of the following subgroups?Please type % for each row 1. First onset AF: AF presenting for the first time and not yet classified as paroxysmal, persistent, or permanent 2. Paroxysmal AF: Self-terminating, in most cases within 48 hours. Some AF paroxysms may continue for up to 7 days. AF episodes that are cardioverted within 7 days should be considered paroxysmal 3. Persistent AF: AF that lasts longer than 7 days, including episodes that are terminated by cardioversion, either with drugs or by direct current cardioversion, after 7 days or more 4. Mixed paroxysmal and persistent 5. Long-standing persistent AF: Where the patient has had continuous AF for a year or longer, but rhythm control will be tried 6. Permanent AF: Where AF is present continuously for more than one year but no rhythm control will be attempted A5Thinking In what % of your patients in the following groups do you use an AAD after the ablation procedure:Type in % per row 1. Directly after the ablation procedure in all patients irrespective of symptoms/recurrences until first post-ablation visit after 3-6 months ___% 2. Directly after ablation procedure in all patients irrespective of symptoms/recurrences for 1-2 months post-ablation ___% 3. Any time post-ablation if symptomatic AF recurrences ___% 4. Short term if AF recurrence and a re-ablation is planned ___% 5. Long term if AF recurrence and a re-ablation is not planned ___% D6ai You stated the uptake of ablation will decrease in the next 3-5 years. Please tell us the approximate decrease.Please select one