Real-world utilization of the pill-in-the-pocket method for terminating episodes of atrial fibrillation: data from the multinational Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey.

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Episodes may stop spontaneously (paroxysmal AF); may terminate only via intervention (persistent AF); or may persist indefinitely (permanent AF) (see European and American guidelines, referenced below, for more precise definitions). Recently, there has been renewed interest in an approach to terminate AF acutely referred to as 'pill-in-the-pocket' (PITP). The PITP is recognized in both the US and European guidelines as an effective option using an oral antiarrhythmic drug for acute conversion of acute/recent-onset AF. However, how PITP is currently used has not been systematically evaluated. METHODS AND RESULTS: The recently published Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey included questions regarding current PITP usage, stratified by US vs. European countries surveyed, by representative countries within Europe, and by cardiologists vs. electrophysiologists. This manuscript presents the data from this planned sub-study. Our survey revealed that clinicians in both the USA and Europe consider PITP in about a quarter of their patients, mostly for recent-onset AF with minimal or no structural heart disease (guideline appropriate). However, significant deviations exist. See the Graphical abstract for a summary of the data. CONCLUSION: Our findings highlight the frequent use of PITP and the need for further physician education about appropriate and optimal use of this strategy.

Atrial Fibrillation can adversely impact Heart Failure with Preserved Ejection Fraction by its association with Heart Failure Progression and Mortality: A Post-Hoc Propensity Score-Matched Analysis of the TOPCAT Americas Trial.

AIMS: Prevalent atrial fibrillation (AF) is associated with excess cardiovascular (CV) death (D) and hospitalizations (H) in heart failure (HF) with preserved ejection fraction (pEF). We evaluated if it had an independent role in excess CVD in HFpEF and studied its impact on cause-specific mortality and HF morbidity. METHODS AND RESULTS: We used propensity score-matched (PSM) cohorts from the TOPCAT Americas trial to account for confounding by other co-morbidities. Two prevalent AF presentations at study entry were compared: (i) subjects with Any AF event by history or on electrocardiogram (ECG) with PSM subjects without an AF event and (ii) subjects in AF on ECG with PSM subjects in sinus rhythm. We analyzed cause-specific modes of death and HF morbidity during a mean follow-up period of 2.9 years. A total of 584 subjects with Any AF event and 418 subjects in AF on ECG were matched. Any AF was associated with increased CVH [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.11-1.61, P = 0.003], HFH (HR 1.44, 95% CI 1.12-1.86, P = 0.004), pump failure death (PFD) (HR 1.95, 95% CI 1.05-3.62, P = 0.035), and HF progression from New York Heart Association (NYHA) classes I/II to III/IV (HR 1.30, 95% CI 1.04-1.62, P = 0.02). Atrial fibrillation on ECG was associated with increased risk of CVD (HR 1.46, 95% CI 1.02-2.09, P = 0.039), PFD (HR 2.21, 95% CI 1.11-4.40, P = 0.024), and CVH and HFH (HR 1.37, 95% CI 1.09-1.72, P = 0.006 and HR 1.65, 95% CI 1.22-2.23, P = 0.001, respectively). Atrial fibrillation was not associated with risk of sudden death. Both Any AF and AF on ECG cohorts were associated with PFD in NYHA class III/IV HF. CONCLUSION: Prevalent AF can be an independent risk factor for adverse CV outcomes by its selective association with worsening HF, HFH, and PFD in HFpEF. Prevalent AF was not associated with excess sudden death risk in HFpEF. Atrial fibrillation was also associated with HF progression in early symptomatic HFpEF and PFD in advanced HFpEF. TRIAL REGISTRATION: TOPCAT trial is registered at www.clinicaltrials.gov:identifier NCT00094302.

Management of atrial fibrillation: two decades of progress - a scientific statement from the European Cardiac Arrhythmia Society.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. The aim of this review was to evaluate the progress made in the management of AF over the two last decades. RESULTS: Clinical classification of AF is usually based on the presence of symptoms, the duration of AF episodes and their possible recurrence over time, although incidental diagnosis is not uncommon. The majority of patients with AF have associated cardiovascular diseases and more recently the recognition of modifiable risk factors both cardiovascular and non-cardiovascular which should be considered in its management. Among AF-related complications, stroke and transient ischaemic accidents (TIAs) carry considerable morbidity and mortality risk. The use of implantable devices such as pacemakers and defibrillators, wearable garments and subcutaneous cardiac monitors with recording capabilities has enabled to access the burden of "subclinical AF". The recent introduction of non-vitamin K antagonists has led to improve the prevention of stroke and peripheral embolism. Agents capable of reversing non-vitamin K antagonists have also become available in case of clinically relevant major bleeding. Transcatheter closure of left atrial appendage represents an option for patients unable to take oral anticoagulation. When treating patients with AF, clinicians need to select the most suitable strategy, i.e. control of heart rate and/or restoration and maintenance of sinus rhythm. The studies comparing these two strategies have not shown differences in terms of mortality. If an AF episode is poorly tolerated from a haemodynamic standpoint, electrical cardioversion is indicated. Otherwise, restoration of sinus rhythm can be obtained using intravenous pharmacological cardioversion and oral class I or class III antiarrhythmic is used to prevent recurrences. During the last two decades after its introduction in daily practice, catheter ablation has gained considerable escalation in popularity. Progress has also been made in AF associated with heart failure with reduced or preserved ejection fraction. CONCLUSIONS: Significant progress has been made within the past 2 decades both in the pharmacological and non-pharmacological managements of this cardiac arrhythmia.

AIM-AF: A Physician Survey in the United States and Europe.

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.

Clinical classification and the subclinical atrial fibrillation challenge: a position paper of the European Cardiac Arrhythmia Society.

Symptomatic atrial fibrillation (AF) or clinical AF is associated with impaired quality of life, higher risk of stroke, heart failure, and increased mortality. Current clinical classification of AF is based on the duration of AF episodes and the recurrence over time. Appropriate management strategy should follow guidelines of Scientific Societies. The last decades have been marked by the advances in mechanism comprehension, better management of symptomatic AF, particularly regarding stroke prevention with the use of direct oral anticoagulants and a wider use of AF catheter or surgical ablations. The advent of new tools for detection of asymptomatic AF including continuous monitoring with implanted electronic devices and the use of implantable cardiac monitors and recently wearable devices or garments have identified what is called "subclinical AF" encompassing atrial high-rate episodes (AHREs). New concepts such as "AF burden" have resulted in new management challenges. Oral anticoagulation has proven to reduce substantially stroke risk in patients with symptomatic clinical AF but carries the risk of bleeding. Management of detected asymptomatic atrial arrhythmias and their relation to clinical AF and stroke risk is currently under evaluation. Based on a review of recent literature, the validity of current clinical classification has been reassessed and appropriate updates are proposed. Current evidence supporting the inclusion of subclinical AF within current clinical classification is discussed as well as the need for controlled trials which may provide responses to current therapeutic challenges particularly regarding the subsets of asymptomatic AF patients that might benefit from oral anticoagulation.

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

BACKGROUND: Heart failure (HF) emergence in atrial fibrillation (AF) patients undergoing different treatment strategies has not been studied. METHODS: AFFIRM trial subjects with no history of HF, without clinical HF and normal left ventricular ejection fraction at enrollment were identified. The principal outcome was time to development of a composite of New York Heart Association class ≥II HF and/or cardiovascular (CV) death. It was compared for rate and rhythm strategies and correlated with electrocardiographic parameters on follow-up (FU). RESULTS: A total of 1,771 patients (880 rate, 891 rhythm) were evaluated. The principal outcome occurred in 21.4% of rate and 16.8% of rhythm subjects at 5 years (hazard ratio [HR] 1.32, 95% CI 1.04-1.69, P = .024). HF increment by 2 classes increased total mortality (HR 2.83, 95% CI 1.91-4.18, P < .0001), cardiac mortality, (HR 4.27, 95% CI 2.03-9.04, P = .0001), and CV hospitalizations (HR 3.04, 95% CI 2.15-4.29, P < .0001). HF emergence during FU was associated with AF (P = .0004), ventricular rate >80 beats/min (P = .0106), and higher frequency of recorded AF in the rhythm arm (25%-75% vs <25%, HR 1.69, 95% CI 1.09-2.64, P = .020; >75% vs <25%, HR 3.15, 95% CI 1.87-5.34, P =< .001). CONCLUSIONS: (1) In AF patients without HF, symptomatic HF emergence was more frequent with rate control than with rhythm control. (2) HF appearance presages increased mortality risk. (3) Delaying HF emergence is associated with effective rhythm control with documented sinus rhythm during >75% of FU visits as well as ventricular rate control.

Peri-procedural use of direct anticoagulation agents during cardiac device implantation: vitamin K antagonists vs direct oral anticoagulants.

BACKGROUND: Warfarin is deemed safe compared to bridging with heparin in the peri-procedure setting while implanting cardiac devices. The timing of discontinuation and re-initiation of direct anticoagulant agents (DOACs) such as dabigatran, apixaban, and rivaroxaban in the peri-procedural setting in comparison to warfarin is not well studied. OBJECTIVE: We wanted to compare three DOAC agents with warfarin during cardiac device implantation. METHODS: Consecutive patients on treatment with dabigatran, rivaroxaban, or apixaban (group A) undergoing a cardiac device generator change, upgrade, or new implantation procedure were compared to those on warfarin (group B). Incidence of hematoma, infection, effusion, stroke, and other complications were noted at 1 day, 1 week, and 3 months. RESULTS: A total of 311 patients in group A underwent the above procedures with 73 patients on dabigatran, 153 on rivaroxaban, and 85 on apixaban. There were 467 patients on warfarin in group B. Mean age of the total population was 68 ± 12 years with 67% males and > 80% Caucasians. The last dose of the DOAC was the night prior to the procedure and resumed the night of the procedure (single dose interruption for apixaban and dabigatran and no un-interruption for rivaroxaban). There was no difference noted in the incidence of minor or major hematoma (9% vs 8.5%, p = 0.7). No stroke occurred in either group. CONCLUSION: Use of DOAC agents with transient interruption of one dose is as safe as warfarin in the peri-procedural setting during implantation of cardiac devices.

Heart failure progression and mortality in atrial fibrillation patients with preserved or reduced left ventricular ejection fraction.

BACKGROUND: Atrial fibrillation (AF) worsens cardiovascular (CV) outcomes of heart failure (HF) and vice versa. The impact of rate or rhythm control strategies on HF progression and survival remains unclear. METHODS: We examined the risk of HF progression in AF patients (pts) with a prior HF event and minimal or no HF burden (NYHA class 0 or 1). They were stratified into HF with a preserved left ventricular ejection fraction (≥ 40%, pEF) or reduced EF (< 40%, rEF). HF subgroups from the Rate and Rhythm arm were compared for the primary outcome of worsening HF or death (WHFD), total mortality, cardiovascular mortality, and cardiovascular hospitalizations. RESULTS: Four hundred ninety-two AF pts (HFpEF = 349, HFrEF = 143) were analyzed. Baseline characteristics were generally comparable in the Rate and Rhythm arms of the two subgroups. Over a median follow-up of 4 years, HF recurred and worsened in 66.6% and 41.2% of pts by ≥ 1 and ≥ 2 NYHA classes, respectively. HF progression by even 1 NYHA class increased the mortality risk in HFpEF (hazard ratio (HR) 2.06; 95% confidence intervals (CI) 1.25-3.4; p = 0.004) and HFrEF (HR 1.9; 95% CI 0.99-3.66; p = 0.054). Cardiovascular hospitalization (CVH) increased in HFpEF (HR 3.67; 95% CI 2.56, 5.25; p < 0.0001) and HFrEF (HR 2.8; 95% CI 1.53-5.14; p = 0.0009). HF progression by 2 or more NYHA classes or death was significantly worse in pts with HFrEF with the Rate control strategy compared with the Rhythm control (HR 1.62; 95% CI 1.03-2.53; p = 0.036) but similar in pts with HFpEF (HR 0.88; 95% CI 0.64-1.21; p = 0.440).The time to first AF recurrence was longer in the Rhythm arms of both HF subgroups as compared with Rate (Figure, p < 0.05). CONCLUSIONS: (1) HF progression in AF pts with a prior HF event confers significant mortality and CVH risk in both HFrEF and HFpEF populations. (2) HF progression is more pronounced with a Rate control strategy in AF pts with HFrEF, but is comparable to Rhythm control in AF pts with HFpEF. (3) A Rhythm control strategy may be desirable to reduce HF progression in pts with HFrEF and AF. Prospective clinical trials appear warranted to examine HF progression by treatment strategy in HFpEF and HFrEF populations with AF.