Recent-onset Atrial Fibrillation Research Articles

Efficacy of smart device heart rhythm monitoring to detect spontaneous conversion to sinus rhythm in patients scheduled for electric cardioversion of atrial fibrillation. Kardiover Study

Abstract Introduction the management of patients with recent-onset atrial fibrillation (AF) is to achieve sinus rhythm (SR) by electrical or pharmacological cardioversion (CV). However, frequently SR is spontaneously restored, making scheduled admission and/or transesophageal echocardiogram (TEE) unnecessary and therefore causing misutilization of healthcare resources. Emerging medical technology has allowed for monitoring of heart rhythm abnormalities. Objective A prospective multicenter study was designed to evaluate the diagnostic ability of a smart device ECG monitor to detect spontaneous conversion to SR in AF patients, preventing unnecessary admission and providing an earlier management. Methods A prospective multicenter study was designed including patients with first diagnosed, paroxysmal or persistent AF scheduled for ambulatory electrical cardioversion in cardiology departments of 7 hospitals of Spain. Patients were asked to submit ECG recordings to a central Corelab daily, twice a day and whenever they present symptoms, until cardioversion (spontaneous or scheduled) and a week afterwards. Whenever a spontaneous conversion to SR was detected, investigators were contacted to confirm SR and abort admission, likewise when AF recurrence after cardioversion was detected. Patients’ satisfaction was evaluated using a test for perceived utility and value, convenience, and accessibility. Results A total of 62 patients were enrolled (age 62±10 years). Baseline characteristics of the study population are described in the Table. Fifteen patients (24%) did not undergo CV as they showed spontaneous conversion to SR. Among 47 patients admitted for CV, it was successful in 41 (87%). One patient aborted CV because of atrial thrombus on TEE. During follow up after conversion to SR (spontaneous or electrical), recurrences of AF occurred in 20 of 56 patients (36%) correctly detected by the devices. At the end of the follow-up 41 of 56 patients (73%) remained in SR. Due to the early detection of spontaneous conversion to SR, a total of 15 admissions and 9 TEE were prevented and these resources used for other patients. Adherence was high with a rate of ECG transmission over 80% in 56 patients (90%). Perceived satisfaction was also high with an overall punctuation of 9 over 10 in the patient’s feedback test. Conclusion Digital devices for heart rhythm monitoring can optimize the management of AF patients scheduled for CV, avoiding unnecessary admissions and providing a more rational use of healthcare resources.Table

CLASS 1C AGENTS ARE EFFECTIVE AND SAFE IN TERMINATING RECENT–ONSET ATRIAL FIBRILLATION IN ELDER PATIENTS TOO

Abstract Background Amiodarone is still widely used in recent–onset atrial fibrillation (AF), mainly in elder people, for its presumed safety. Nevertheless the growing experience with class 1c agents could encourage their use in order to improve the management of AF in elderly too. Aim: To assess whether class 1c agents could be considered effective and safe in elder people, as well in younger, in terminating recent–onset AF. Methods We retrospectively evaluated a three–years experience in over 75 patients treated in the Emergency Department of University Hospital of Verona for recent–onset AF (< 48 h). We excluded patients submitted to electrical cardioversion and those in whom the choice of treatment was forced by clinical conditions or coronary and structural heart disease. Then we compared the results in terms of effectiveness and safety between the two groups of treatment, class 1c agents vs amiodarone. Statistical analysis was performed using Chi–square test, with significance level set at p<0.05. Results We attempted at restoration of sinus rhythm in 264 patients older than 75 years observed for recent–onset AF from January 2018 to December 2020. According to exclusion criteria, the study population was restricted to 147 patients (53 males, 94 females; mean age 80 years, range 75–95) where the treatment depended on the physician‘s choice only. Most of these patients (61.2%) was treated with amiodarone, while in 38.8% class 1c agents were administered. Mean age was not significantly different between the groups (81 vs 78.5). After treatment, stable restoration of sinus rhythm was reported in 43 patients (47.7%) in amiodarone and in 47 (82.4%) in class 1c group (p<0.01). Median time of conversion was 240 minutes (range 30–680) in amiodarone while 60 (range 15–530) in class 1c group (p<0.01), as shown in fig. 1. Surprisingly, even the narrow sample did not allow any significance, the incidence of adverse events was notably superior in amiodarone patients, both in number (5 cases) and seriousness (2 cases). Whereas in class 1c group we reported only one mild adverse event. At the end of observation, 43 patients (75.4%) in class 1c but only 38 (42.2%) in amiodarone group were discharged with stable sinus rhythm (p<0.02). Conclusions Class 1c agents appear to be more effective and as safe as amiodarone in terminating recent–onset AF even in selected elder people. However these preliminary results need to be confirmed in a larger and prospective study.

Orally Inhaled Flecainide for Conversion of Atrial Fibrillation to Sinus Rhythm: INSTANT Phase 2 Trial.

INSTANT (INhalation of flecainide to convert recent-onset SympTomatic Atrial fibrillatioN to sinus rhyThm) was a multicenter, open-label, single-arm study of flecainide acetate oral inhalation solution (FlecIH) for acute conversion of recent-onset (≤48 hours) symptomatic atrial fibrillation (AF) to sinus rhythm. This study investigated the efficacy and safety in 98 patients receiving a single dose of FlecIH delivered via oral inhalation. Patients self-administered FlecIH over 8minutes in a supervised medical setting using a breath-actuated nebulizer and were continuously monitored for 90minutes using a 12-lead Holter. Mean age was 60.5 years, mean body mass index was 27.0kg/m2, and 34.7% of the patients were women. All patients had≥1 AF-related symptoms at baseline, and 87.8% had AF symptoms for≤24 hours. The conversion rate was 42.6% (95%CI: 33.0%-52.6%) with a median time to conversion of 14.6minutes. The conversion rate was 46.9% (95%CI: 36.4%-57.7%) in a subpopulation that excluded predose flecainide exposure for the current AF episode. Median time to discharge among patients who converted was 2.5 hours, and only 2 patients had experienced AF recurrence by day 5. In the conversion-no group, 44 (81.5%) patients underwent electrical cardioversion by day 5. The most common adverse events were related to oral inhalation of flecainide (eg, cough, oropharyngeal irritation/pain), which were mostly of mild intensity and limited duration. The risk-benefit of orally inhaled FlecIH for acute cardioversion of recent-onset AF appears favorable. FlecIH could provide a safe, effective, and convenient first-line therapeutic option. (INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm [INSTANT]; NCT03539302).

Efficacy and Safety of Intravenous Vernakalant in Rapid Cardioversion of Recent Onset Atrial Fibrillation: A Retrospective Single-Centre Study.

We use vernakalant, an intravenous anti-arrhythmic, to cardiovert paroxysmal atrial fibrillation (AF) into sinus rhythm. It is a relatively atrium-selective, early-activating potassium and frequency-dependent sodium channel blocker with a half-life of 2 to 3 hours. Due to concerns regarding its safety profile, it is not Food and Drug Administration (FDA)-approved. This study aims to assess the efficacy of intravenous vernakalant in cardioversion of paroxysmal AF and the safety of its use. Patients with paroxysmal AF who presented to the American University of Beirut Medical Center (AUBMC) between 2015 and 2020 and received vernakalant for cardioversion were included. Patients did not receive vernakalant if they had any of the following: QTc > 440 ms, heart rate < 50 bpm, acute coronary syndrome within the last 30 days, second- and third-degree atrioventricular (AV) block in the absence of a pacemaker, severe aortic stenosis (AS), use of intravenous antiarrhythmics (class I and class III) within four hours of vernakalant infusion, systolic blood pressure <100 mmHg, and heart failure (New York Heart Association (NYHA) III or NYHA IV class). The primary endpoint is conversion to sinus rhythm for at least one minute within 90 minutes of the start of the vernakalant infusion. The secondary endpoint included the presence of these side effects: bradycardia, QTc prolongation, AV block, ventricular arrhythmias, hypotension, taste alteration/dysgeusia, sneezing, nausea, vomiting, paresthesia, cardiogenic shock, or death. The study included 23 patients with paroxysmal AF (15 men, mean age 54 ± 14 years). Fourteen patients (61%) cardioverted to sinus rhythm within 90 minutes of the start of the Vernakalant infusion. Seven patients (30%) reverted to sinus rhythm within 15 minutes after the first infusion. After treatment with vernakalant, four patients (17%) developed sinus bradycardia, and four patients (17%) developed first-degree AV block. No patient had a QTc greater than 460 ms. None of the patients experienced sinus pauses, high-grade AV block, ventricular arrhythmias, hypotension, dysgeusia, sneezing, nausea, vomiting, paresthesia, cardiogenic shock, or death. Vernakalant had 61% efficacy in the rapid cardioversion of paroxysmal AF to sinus rhythm, was well tolerated, and had a low rate of adverse events in our study population.

Safety and Effectiveness of Antidysrhythmic Drugs for Pharmacologic Cardioversion of Recent-Onset Atrial Fibrillation: a Systematic Review and Bayesian Network Meta-analysis.

The available evidence to determine which antidysrhythmic drug is superior for pharmacologic cardioversion of recent-onset (onset within 48h) atrial fibrillation (AF) is uncertain. We aimed to identify the safest and most effective agent for pharmacologic cardioversion of recent-onset AF in the emergency department. We searched MEDLINE, Embase, and Web of Science from inception to February 21, 2023 (PROSPERO: CRD42018083781). Eligible studies were randomized controlled trials that enrolled adult participants with AF ≤ 48h, compared a guideline-recommended antidysrhythmic drug with another antidysrhythmic drug or a different formulation of the same drug or placebo and reported specific adverse events. The primary outcome was immediate, serious adverse event - cardiac arrest, sustained ventricular tachydysrhythmia, atrial flutter 1:1 atrioventricular conduction, hypotension, and bradycardia. Additional analyses included the outcomes of conversion to sinus rhythm within 4h and 24h. We extracted data according to PRISMA-NMA and appraised trials using Cochrane RoB 2. We performed Bayesian network meta-analysis (NMA) using a Markov Chain Monte Carlo method with random-effect model and vague prior distribution to calculate odds ratios with 95% credible intervals. We assessed confidence using CINeMA. We used surface under the cumulative ranking curve (SUCRA) to rank agent(s). The systematic review initially identified 5545 studies. Twenty-five studies met eligibility criteria, and 22 studies (n = 3082) provided data for NMA, which demonstrated that vernakalant (SUCRA = 70.9%) is most likely to be safest. Additional effectiveness NMA demonstrated that flecainide (SUCRA = 89.0%) is most likely to be superior for conversion within 4h (27 studies; n = 2681), and ranolazine-amiodarone IV (SUCRA 93.7%) is most likely to be superior for conversion within 24h (24 studies; n = 3213). Confidence in the NMA estimates is variable and limited mostly by within-study bias and imprecision. Among guideline-recommended antidysrhythmic drugs, the combination of digoxin IV and amiodarone IV is definitely among the least safe for cardioversion of recent onset AF; flecainide, vernakalant, ibutilide, propafenone, and amiodarone IV are definitely among the most effective for cardioversion within 4h; flecainide is definitely among the most effective for cardioversion within 24h. Further, randomized controlled trials with predetermined and strictly defined, hemodynamic adverse event outcomes are recommended.

Inhibition of the KCa2 potassium channel in atrial fibrillation: a randomized phase 2 trial

Existing antiarrhythmic drugs to treat atrial fibrillation (AF) have incomplete efficacy, contraindications and adverse effects, including proarrhythmia. AP30663, an inhibitor of the KCa2 channel, has demonstrated AF efficacy in animals; however, its efficacy in humans with AF is unknown. Here we conducted a phase 2 trial in which patients with a current episode of AF lasting for 7 days or less were randomized to receive an intravenous infusion of 3 or 5 mg kg−1 AP30663 or placebo. The trial was prematurely discontinued because of slow enrollment during the coronavirus disease 2019 pandemic. The primary endpoint of the trial was cardioversion from AF to sinus rhythm within 90 min from the start of the infusion, analyzed with Bayesian statistics. Among 59 patients randomized and included in the efficacy analyses, the primary endpoint occurred in 42% (5 of 12), 55% (12 of 22) and 0% (0 of 25) of patients treated with 3 mg kg−1 AP30663, 5 mg kg−1 AP30663 or placebo, respectively. Both doses demonstrated more than 99.9% probability of superiority over placebo, surpassing the prespecified 95% threshold. The mean time to cardioversion, a secondary endpoint, was 47 (s.d. = 23) and 41 (s.d. = 24) minutes for 3 mg kg−1 and 5 mg kg−1 AP30663, respectively. AP30663 caused a transient increase in the QTcF interval, with a maximum mean effect of 37.7 ms for the 5 mg kg−1 dose. For both dose groups, no ventricular arrhythmias occurred and adverse event rates were comparable to the placebo group. AP30663 demonstrated AF cardioversion efficacy in patients with recent-onset AF episodes. KCa2 channel inhibition may be an attractive mechanism for rhythm control of AF that should be studied further in randomized trials. ClinicalTrials.gov registration: NCT04571385.

Rhythm versus rate control in patients with newly diagnosed atrial fibrillation – Observations from the GARFIELD-AF registry

BackgroundInvestigate real-world outcomes of early rhythm versus rate control in patients with recent onset atrial fibrillation. MethodsThe Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF) is an international multi-centre, non-interventional prospective registry of newly diagnosed (≤6 weeks’ duration) atrial fibrillation patients at risk for stroke. Patients were stratified according to treatment initiated at baseline (≤48 days post enrolment), and outcome risks evaluated by overlap propensity weighted Cox proportional-hazards models. ResultsOf 45,382 non-permanent atrial fibrillation patients, 23,858 (52.6 %) received rhythm control and 21,524 (47.4 %) rate control. Rhythm-controlled patients had lower median age (68.0 [Q1;Q3: 60.0;76.0] versus 73.0 [65.0;79.0]), fewer histories of stroke/transient ischemic attack/systemic embolism (9.4 % versus 13.0 %), and lower expected probabilities of death (median GARFIELD-AF death score 4.0 [2.3;7.5] versus 5.1 [2.8;9.2]). The two groups had the same median CHA2DS2-VASc scores (3.0 [2.0;4.0]) and similar proportions of anticoagulated patients (rhythm control: 66.0 %, rate control: 65.5 %). The propensity-score-weighted hazard ratios of rhythm vs rate control (reference) were 0.85 (95 % CI: 0.79–0.92, p-value < 0.0001) for all-cause mortality, 0.84 (0.72–0.97, p-value 0.020) for non-haemorrhagic stroke/systemic embolism and 0.90 (0.78–1.04, p-value 0.164) for major bleeding. ConclusionRhythm control strategy was initiated in about half of the patients with newly diagnosed non-valvular non-permanent atrial fibrillation. After balancing confounders, significantly lower risks of all-cause mortality and non-haemorrhagic stroke were observed in patients who received early rhythm control.

Abstract 11662: Efficacy And Safety Outcome Of Intravenous Vernakalant For Recent-onset Atrial Fibrillation: A Systematic Review And Meta-analysis

Introduction: Vernakalant hydrochloride is a relatively new atrial-selective antiarrhythmic approved in &gt;40 countries to pharmacologically cardiovert patients with recent-onset atrial fibrillation (ROAF). Due to safety concerns, it is yet to be approved in the USA. Objectives: To determine the effectiveness and safety of vernakalant in patients with ROAF. Methods: We systematically searched PubMed, EMBASE, Ovid MEDLINE, and CENTRAL from inception to December 2022 for studies that compared intravenous vernakalant to another drug(s) or placebo in patients with ROAF (onset ≤7 days). The pre-specified efficacy endpoint was conversion to sinus rhythm within 90minutes of administering interventions. Safety outcome of interest was mortality rate. Random-effects model meta-analysis was performed on extracted quantitative data. Results: 886 patients got vernakalant, 353 received placebo, and 401 got an antiarrhythmic agent. Vernakalant was significantly superior to placebo (conversion rate: 49.5% vs 6.2%, OR: 14.94, 95% CI: 7.18-31.07, P&lt;0.001, I 2 : 49%), Flecainide (72.3% vs 53.8%, OR: 2.44, 95% CI: 1.46-4.06, p&lt;0.001, I 2 : 0%), Amiodarone (55.7% vs 8.5%, OR: 17.42, 95% CI: 7.75-39.13, p&lt;0.001, I 2 : 0%), but not Ibutilide (62.4% vs 47.3%, OR: 1.77, 95% CI: 0.61-5.08, p=0.29, I 2 : 67%) in efficacy endpoint. In the vernakalant group, there was significantly lower incidence of ventricular arrhythmia (OR:0.65, 95% CI: 0.45-0.95, p=0.027) but higher incidence of bradycardia (OR:8.58, 95% CI: 4.69-15.67, p&lt;0.0001) and dysgeusia (OR:14.51, 95% CI: 7.03-29.95, p&lt;0.0001). No significant difference in mortality rate between vernakalant and other groups combined (OR: 2.51, 95% CI: 0.26-24.21, p=0.427). Conclusions: This hypothesis-generating study showed that intravenous vernakalant, though associated with a higher incidence of bradycardia and dysgeusia, is superior to placebo, Flecainide, and Amiodarone not Ibutilide in converting ROAF to sinus rhythm.

Cardioversion strategy impacts rate control during recurrences in patients with paroxysmal atrial fibrillation: A subanalysis of the RACE 7 ACWAS trial.

In the Rate Control versus Electrical Cardioversion Trial 7-Acute Cardioversion versus Wait and See, patients with recent-onset atrial fibrillation (AF) were randomized to either early or delayed cardioversion. This prespecified sub-analysis aimed to evaluate heart rate during AF recurrences after an emergency department (ED) visit identified by an electrocardiogram (ECG)-based handheld device. After the ED visit, included patients (n = 437) were asked to use an ECG-based handheld device to monitor for recurrences during the 4-week follow-up period. 335 patients used the handheld device and were included in this analysis. Recordings from the device were collected and assessed for heart rhythm and rate. Optimal rate control was defined as a target resting heart rate of <110 beats per minute (bpm). In 99 patients (29.6%, mean age 67 ± 10 years, 39.4% female, median 6 [3-12] AF recordings) a total of 314 AF recurrences (median 2 [1-3] per patient) were identified during follow-up. The average median resting heart rate at recurrence was 100 ± 21 bpm in the delayed vs 112 ± 25 bpm in the early cardioversion group (p = .011). Optimal rate control was seen in 68.4% [21.3%-100%] and 33.3% [0%-77.5%] of recordings (p = .01), respectively. Randomization group [coefficient -12.09 (-20.55 to -3.63, p = .006) for delayed vs. early cardioversion] and heart rate on index ECG [coefficient 0.46 (0.29-0.63, p < .001) per bpm increase] were identified on multivariable analysis as factors associated with lower median heart rate during AF recurrences. A delayed cardioversion strategy translated into a favorable heart rate profile during AF recurrences.

Pharmacological cardioversion of atrial fibrillation: practical considerations.

The choice between rhythm and rate control strategy represents one of the most intriguing dilemmas in the management of atrial fibrillation (AF). Although the advantage of rhythm over rate control in terms of outcome has not been equivocally proven, the initial management of patients with symptomatic episodes of AF frequently involves an attempt of early cardioversion. As electrical cardioversion (EC) is challenging in terms of fasting status and involvement of anesthesiology team, pharmacological cardioversion (PC) is usually selected as the first step towards rhythm conversion. Proper qualification for PC or EC is similar and should comprise assessment of hemodynamic status, estimation of duration of arrhythmic episode, evaluation of anticoagulation regimen, exclusion of other supraventricular arrhythmias and assessment of the chance of rhythm conversion and persistence of sinus rhythm. Finally, the choice of adequate antiarrhythmic drug (AAD) depends on the presence of structural heart disease and local experience. In patients without structural heart disease, complications occur rarely, hence traditional (propafenone, flecainide) or nonclassical Vaughan-Williams class I (antazoline) or class III (vernakalant, ibutilide or dofetilide) drugs are preferred. The presence of structural heart disease consistent with any left ventricular hypertrophy, heart failure, myocardial ischemia or valvular heart disease confines the choice of AAD to amiodarone. Given the risk of ventricular proarrhythmia of AAD, safety should always prevail over the enticing possibility of rhythm conversion. The present review aims to provide a comprehensible summary of proper qualification for PC, selection of suitable AAD and state-of-the-art periprocedural management of patients with recent-onset AF.

Atrial fibrillation and stroke prevention: 25 years of research at EP Europace journal.

Stroke prevention in patients with atrial fibrillation (AF) is one pillar of the management of this common arrhythmia. Substantial advances in the epidemiology and associated pathophysiology underlying AF-related stroke and thrombo-embolism are evident. Furthermore, the introduction of the non-vitamin K antagonist oral anticoagulants (also called direct oral anticoagulants) has clearly changed our approach to stroke prevention in AF, such that the default should be to offer oral anticoagulation for stroke prevention, unless the patient is at low risk. A strategy of early rhythm control is also beneficial in reducing strokes in selected patients with recent onset AF, when compared to rate control. Cardiovascular risk factor management, with optimization of comorbidities and attention to lifestyle factors, and the patient's psychological morbidity are also essential. Finally, in selected patients with absolute contraindications to long-term oral anticoagulation, left atrial appendage occlusion or exclusion may be considered. The aim of this state-of-the-art review article is to provide an overview of the current status of AF-related stroke and prevention strategies. A holistic or integrated care approach to AF management is recommended to minimize the risk of stroke in patients with AF, based on the evidence-based Atrial fibrillation Better Care (ABC) pathway, as follows: A: Avoid stroke with Anticoagulation; B: Better patient-centred, symptom-directed decisions on rate or rhythm control; C: Cardiovascular risk factor and comorbidity optimization, including lifestyle changes.

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.

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. 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. Our findings highlight the frequent use of PITP and the need for further physician education about appropriate and optimal use of this strategy.

Cardioversion strategy impacts quality of rate control during recurrences of atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Netherlands Organization for Health Research and Development Introduction In the Rate Control versus Electrical Cardioversion Trial 7–Acute Cardioversion versus Wait and See, patients with recent-onset atrial fibrillation (AF) were randomised to either early or delayed cardioversion. Purpose This pre-specified sub-analysis aimed to evaluate heart rate during AF recurrences after an emergency department (ED) visit identified by an electrocardiogram (ECG)-based handheld device. Methods After the ED visit, included patients (n=437) were asked to use an ECG-based handheld device to monitor for recurrences during the four-week follow-up period. 335 patients used the handheld device and were included in this analysis. Recordings from the device were collected and assessed for heart rhythm and rate. Optimal rate control was defined as a target resting heart rate of &amp;lt;110 bpm. Results In 99 patients (29.6%, mean age 67±10 years, 39.4% female, median 6 [3-12] AF recordings) a total of 314 AF recurrences (median 2 [1-3] per patient) were identified during the follow-up. The average median resting heart rate at recurrence was 100±21 bpm in the delayed vs 112±25 bpm in the early cardioversion group (p=0.011). Additionally, the maximum heart rate was also significantly lower in the delayed cardioversion group (115 [94-131] vs 136 [118-147], p=0.001). Optimal rate control was seen in 68.4% [21.3-100%] of the performed recordings per patient in the delayed, and 33.3% [0-77.5%] of the performed recordings per patient in the early cardioversion group (p=0.01). Randomisation group (coefficient -12.09 (-20.55 - -3.63, p=0.006) for delayed versus early cardioversion) and heart rate on index ECG (coefficient 0.46 (0.29-0.63, p&amp;lt;0.001) per bpm increase) were identified as multivariable adjusted factors associated with lower median heart rate during AF recurrences. Conclusion A delayed cardioversion strategy translated into lower median heart rates as well as lower peak heart rates during AF recurrences. Apart from the randomized treatment, heart rate at recurrence was influenced by the intrinsic heart rate on presentation.

Biomarkers of Atrial Fibrillation Recurrence in Patients with Paroxysmal or Persistent Atrial Fibrillation Following External Direct Current Electrical Cardioversion.

Atrial fibrillation (AF) is associated with atrial remodeling, cardiac dysfunction, and poor clinical outcomes. External direct current electrical cardioversion is a well-developed urgent treatment strategy for patients presenting with recent-onset AF. However, there is a lack of accurate predictive serum biomarkers to identify the risks of AF relapse after electrical cardioversion. We reviewed the currently available data and interpreted the findings of several studies revealing biomarkers for crucial elements in the pathogenesis of AF and affecting cardiac remodeling, fibrosis, inflammation, endothelial dysfunction, oxidative stress, adipose tissue dysfunction, myopathy, and mitochondrial dysfunction. Although there is ample strong evidence that elevated levels of numerous biomarkers (such as natriuretic peptides, C-reactive protein, galectin-3, soluble suppressor tumorigenicity-2, fibroblast growth factor-23, turn-over collagen biomarkers, growth differential factor-15) are associated with AF occurrence, the data obtained in clinical studies seem to be controversial in terms of their predictive ability for post-cardioversion outcomes. Novel circulating biomarkers are needed to elucidate the modality of this approach compared with conventional predictive tools. Conclusions: Biomarker-based strategies for predicting events after AF treatment require extensive investigation in the future, especially in the presence of different gender and variable comorbidity profiles. Perhaps, a multiple biomarker approach exerts more utilization for patients with different forms of AF than single biomarker use.

Factors predictive of spontaneous reversion to sinus rhythm: Findings from an integrated acute atrial fibrillation pathway

Recent evidence suggests that delayed cardioversion of uncomplicated acute AF is non-inferior to early cardioversion in the Emergency Department (ED), 1 Pluymaekers N.A.H.A. Dudink E.A.M.P. Luermans J.G.L.M. et al. Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation. N Engl J Med. 2019; 380: 1499-1508 Crossref PubMed Scopus (95) Google Scholar and most patients will revert spontaneously to sinus rhythm (SR) by a rate control strategy. 2 Abadie B.Q. Hansen B. Walker J. et al. Likelihood of Spontaneous Cardioversion of Atrial Fibrillation Using a Conservative Management Strategy Among Patients Presenting to the Emergency Department. Am J Cardiol. 2019; 124: 1534-1539 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar We adopted a new inter-departmental acute AF clinical pathway 3 Al-Busaidi I.S. Clare G.C. Joyce L.R. et al. Presentation, Treatment and Long-Term Outcomes of a Multidisciplinary Acute Atrial Fibrillation Pathway: A 12-Month Follow-Up Study. Heart Lung Circ. 2022; 31: 216-223 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar in 2015 which involves a ‘rate-and-wait’ strategy where patients are managed with rate control agents followed by a review in a ward-based clinic within 24-72 hours (97% attend within this time frame). Over two-thirds (71%) of pathway patients spontaneously reverted to SR by clinic review. 3 Al-Busaidi I.S. Clare G.C. Joyce L.R. et al. Presentation, Treatment and Long-Term Outcomes of a Multidisciplinary Acute Atrial Fibrillation Pathway: A 12-Month Follow-Up Study. Heart Lung Circ. 2022; 31: 216-223 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar We examined predictors of spontaneous reversion to SR at AF clinic follow-up.

Vernakalant for Cardioversion of Recent-Onset Atrial Fibrillation in the Emergency Department: The SPECTRUM Study

Introduction: Intravenous vernakalant is a therapeutic option for symptomatic, recent-onset atrial fibrillation (AF). This secondary analysis from the large SPECTRUM study assessed the safety and effectiveness of vernakalant when used in the emergency department setting (ED group) or in an inpatient hospital setting (non-ED group). Methods: This post hoc analysis of the international, observational, post-authorization SPECTRUM study included 1,289 and 720 recent-onset AF episodes in adults in the ED and non-ED groups, respectively. Safety endpoints included the evaluation of pre-defined health outcomes of interest (HOIs) and other serious adverse events (SAEs) during vernakalant treatment and during the first 24 h after the last infusion. Effectiveness endpoints comprised the rate of successful vernakalant cardioversion, the time from the start of the vernakalant infusion to cardioversion, and the length of hospital stay. Data were analysed using descriptive statistics. Results: The safety profile of vernakalant was similar in the ED and non-ED groups. In the ED group, 12 pre-defined HOIs were reported in 11 patients (0.9%); all but one occurred within 2 h after start of the first infusion. These events comprised nine significant bradycardia cases, of which one was associated with transient hypotension and three with sinus arrest, and 2 cases of atrial flutter with 1:1 conduction. Five other SAEs were reported. All patients with vernakalant-related events recovered without sequelae. No Torsade de Pointes, ventricular fibrillation, or deaths occurred. Successful cardioversion was reported in 67.8% (95% confidence interval: 65.2–70.4) and 66.4% (62.5–70.1) of episodes, with a median time to conversion of 11.0 and 10.0 min in the ED and non-ED groups, respectively. Patients had a median length of hospital stay of 7.4 h and 17.1 h in the ED and non-ED groups, respectively. Conclusion: Intravenous vernakalant was well tolerated with similar cardioversion rates in patients treated in the ED or non-ED setting and does not require admission to a coronary care unit or intensive care unit. First-line treatment with vernakalant could allow an early discharge in patients with recent-onset AF treated in the ED.

Abstract 12420: Orally Inhaled Flecainide for the Conversion of Recent-Onset, Symptomatic Atrial Fibrillation to Sinus Rhythm: Final Results From the Phase 2 Instant Trial

Introduction: The INSTANT trial was a multicenter, open-label, single-arm study of flecainide acetate oral inhalation solution (FlecIH) for acute conversion of recent-onset, symptomatic atrial fibrillation (AF) to sinus rhythm (SR). The initial dose-ranging stage of the trial established safety and feasibility, while showing a dose- and concentration-dependent increase in efficacy (dose range: 30-120 mg); the highest dose was selected for this evaluation. Methods: Patients with symptomatic paroxysmal AF (≤ 48 hours) self-administered 120 mg FlecIH over 8 minutes in a monitored setting using a breath-actuated nebulizer and were continuously monitored for 90 minutes using a 12-lead Holter. Symptoms, vital signs and adverse events were recorded. Safety analyses included all patients who received 120 mg FlecIH (N=98). Efficacy analyses were performed on a modified intention to treat population (N=81) that excluded patients with systemic flecainide present prior to dosing with study drug. Results: The population had a mean age of 60.5 years, a mean BMI of 27.0 kg/m2 and 34.7% were female. All patients reported ≥1 AF-related symptoms at baseline and 87.8% presented with AF symptoms ≤ 24 hours in duration. The conversion rate was 46.9% (95% CI: 36.4%, 57.7%), with a median time of 13.7 minutes from the start of the inhalation. A greater proportion of patients were asymptomatic or had improved symptoms following conversion of AF to SR with inhaled flecainide compared to patients whose AF did not convert (92.1% and 45.4%, respectively, p &lt; 0.001). Two patients had CV events that were considered serious (bradycardia and atrial flutter with 1:1 AV conduction). Both CV events were transient (12 and 6 minutes, respectively), required no treatment and resolved without sequelae. Median time to discharge was 2.5 hours for patients whose AF converted to SR with inhaled flecainide and by Day 5 none had experienced AF recurrence. In contrast, 35 (81.4%) patients in the no conversion group had undergone ECV by Day 5. Conclusions: The risk-benefit of orally inhaled flecainide acetate inhalation solution for acute cardioversion of recent onset AF appears favorable and may provide a safe, effective, and convenient first-line therapeutic option for AF conversion.

Incidence and Determinants of Spontaneous Cardioversion of Early Onset Symptomatic Atrial Fibrillation

Atrial fibrillation (AF) is the most frequent chronic arrhythmia worldwide, and it is associated with significant morbidity and mortality, making it a considerable burden both to patients and the healthcare system. Nowadays, an early attempt to restore sinus rhythm in acute symptomatic AF through electrical or pharmacological cardioversion is the most common approach in the Emergency Department (ED). However, considering the high percentage of spontaneous cardioversion of paroxysmal AF reported by many studies, this approach may not be the ideal choice for all patients. In this manuscript we performed a review of the most relevant studies found in literature with the aim of identifying the main determinants of spontaneous cardioversion, focusing on those easy to detect in the ED. We have found that the most relevant predictors of spontaneous cardioversion are the absence of Heart Failure (HF), a small atrial size, recent-onset AF, rapid Atrial Fibrillatory Rate and the relationship between a previous AF episode and Heart Rate/Blood Pressure. A number of those are utilized, along with other easily determined parameters, in the recently developed "ReSinus" score which predicts the likelihood of AF spontaneous cardioversion. Such identification may help the physician decide whether immediate cardioversion is necessary, or whether to adopt a "watch-and-wait" strategy in the presence of spontaneous cardioversion determinants.

MHealth-based assessment of rate control during recurrent paroxysms after an emergency department visit for recent-onset atrial fibrillation: a subanalysis of the RACE 7 ACWAS trial

Abstract Introduction Achieving adequate rate control is a mainstay in the treatment of atrial fibrillation (AF). In the Rate Control versus Electrical Cardioversion Trial 7 – Acute Cardioversion versus Wait and See (RACE 7 ACWAS) trial, an early cardioversion approach was compared to a delayed cardioversion approach for patients with recent-onset symptomatic AF, followed by a four-week monitoring period using mobile health (mHealth). Purpose To assess the adequacy of rate control during recurrences of AF in the four weeks after an emergency department visit for recent-onset AF using mHealth. Methods After restoration of sinus rhythm (spontaneous or through cardioversion), patients (n=335) were asked to record one minute heart rate and rhythm recordings three times daily and in case of symptoms by using an electrocardiographic-based handheld device to monitor for recurrences for four weeks after the index visit. Recordings from the handheld device were collected at the end of the follow-up period. For this subanalysis, a cut-off for lenient rate control during AF recurrences was used and this was defined as a heart rate of &amp;lt;110 beats per minute. A p-value of &amp;lt;0.05 was considered statistically significant. Results mHealth-based monitoring identified 99 patients with a total of 314 recurrences (29.6% of the included patients; median age 67 [interquartile range (IQR) 13] years, 60.6% male, 49.5% delayed cardioversion group, median number of recurrences 2 [IQR 2]). Two recurrences in one patient were excluded from analysis because heart rate could not be adequately assessed due to too much interference. Rate control was always adequate during 126 recurrences (40.4%), always inadequate during 111 recurrences (35.6%) and varying between adequate and inadequate in the remaining 75 recurrences (24.0%). On a patient level, rate control was always adequate in 26 patients (26.5%), always inadequate in 20 patients (20.4%) and varying between or within recurrences in the remaining 52 patients (53.1%) (Figure 1). Although there were no differences in clinical characteristics of the patients based on their adequacy of rate control, there is a trend towards significance regarding randomisation group (p=0.051), with patients with adequate rate control being more often in the delayed cardioversion group compared to those with varying and inadequate rate control (18 (69.2%) vs 24 (46.2%) vs 7 (35.0%), respectively). Conclusion It is feasible to assess heart rate and the adequacy of rate control during recurrences of recent-onset AF using mHealth. Whether real time mHealth-based rate and rhythm monitoring can be integrated in a remote management pathway to adapt rate control in AF patients warrants further studies. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Netherlands Organization for Health Research and Development–Health Care Efficiency Research Program

Rhythm versus rate control in patients with newly diagnosed atrial fibrillation: observations from the GARFIELD-AF registry

Abstract Background Atrial fibrillation is associated with considerable morbidity and mortality. Real-world reports on the effect of early rhythm control on patient outcomes in patient with recent onset atrial fibrillation are limited. Purpose To assess the effect of early rhythm versus rate control on clinical outcomes in patients with newly diagnosed non-valvular atrial fibrillation. Method The Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF) is a non-interventional registry of adult (≥18 years) patients with newly diagnosed atrial fibrillation (≤ six weeks' duration) and at least one investigator determined risk factor for stroke. Patients were enrolled in 1317 participating sites in 35 countries between March 2010 and August 2016. Patients with permanent atrial fibrillation were excluded. Stratification to rhythm or rate control was based on treatment strategy initiated at baseline (≤48 days post enrolment). Rhythm control was defined as investigator reported initiation of rhythm control (antiarrhythmic drug(s), cardioversion, or ablation – alone or in combination with rate modifiers). Rate control was defined as investigator reported initiation of rate control and absence of rhythm control therapy. Overlap propensity weighting and Cox proportional-hazards models were used to evaluate effect on outcomes. Results Of 45,382 included patients, 23,858 (52.6%) received rhythm control and 21,524 (47.4%) rate control. Rates of rhythm control were similar throughout the study time period (52.7% in 2010/2011, 54.2% in 2015/2016). Patients in the rhythm control group were younger (median age (Q1; Q3) 68.0 (60.0; 76.0) versus 73.0 (65.0; 79.0)), had lower rates of prior stroke/transitory ischemic attack/systemic embolism (9.4% vs 13.0%), and a lower median GARFIELD death score (4.0 (2.3; 7.5) versus 5.1 (2.8; 9.2)). Median CHA2DS2-VASc Scores were 3.0 (2.0; 4.0) in both groups. Rate of anticoagulation treatment was similar in the rhythm and rate control group (66.0% versus 65.5%). After propensity score overlap weighting, patients of the two groups were well balanced on all observed characteristics. Event rates per 100 person-years (95% confidence interval [CI]) over two years follow-up in the rhythm and rate control group were 2.94 (2.78–3.10) versus 4.43 (4.22–4.64) for mortality, 0.84 (0.75–0.92) versus 1.16 (1.05–1.27) for non-haemorrhagic stroke/systemic embolism and 0.84 (0.76–0.93) versus 1.16 (1.06–1.27) for major bleeding. Adjusted hazard ratios (95% CI) for the same time period were 0.85 (0.79–0.92), 0.84 (0.72–0.97) and 0.9 (0.78–1.04). Conclusion In this large, internation registry, a rhythm control strategy was initiated at baseline in about half of the patients with newly diagnosed non-valvular atrial fibrillation. After adjustment for confounding factors, a significantly lower risk of all-cause mortality and non-haemorrhagic stroke/systemic embolism were observed for patients that received an early rhythm control strategy. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by the Thrombosis Research Institute (London, UK).