Recent-onset Atrial Fibrillation Research Articles

INSTRUCTIONS: Implementation of a Procainamide-Based Cardioversion Strategy for the Management of Recent-Onset Atrial Fibrillation.

INSTRUCTIONS: Implementation of a Procainamide-Based Cardioversion Strategy for the Management of Recent-Onset Atrial Fibrillation.

Implementation of a Procainamide-Based Cardioversion Strategy for the Management of Recent-Onset Atrial Fibrillation.

Atrial fibrillation/flutter (AF) remains the most common rhythm disturbance in adult patients presenting to emergency departments (EDs). Although pharmacologic cardioversion has been established as safe and effective in recent-onset AF, its use in U.S. EDs is uncommon. The purpose of this study was to assess the safety and efficacy of intravenous (IV) procainamide for pharmacologic cardioversion in patients presenting to the ED with AF of <48-hr duration. Patients presenting to the ED with recent-onset AF (<48 hr) undergoing a cardioversion strategy with IV procainamide from 2017 to 2019 were reviewed. Clinical outcomes assessed included rates of cardioversion, hospital admission, stroke, and return ED visits for arrhythmia or serious adverse events. A total of 64 patients received procainamide therapy-60.9% achieved cardioversion and 35.9% were admitted to the hospital. The mean dose was 1062.4 mg (12.1 mg/kg). No patients returned to the ED secondary to stroke and 9.4% experienced complications attributed to procainamide, the most common being hypotension. Within 30 days of therapy, 20.3% of patients returned to the ED secondary to arrhythmia recurrence. Patients experiencing cardioversion with procainamide were less likely to be admitted to the hospital (25.6% vs. 52.0%; p = 0.04) or receive a rate control agent (17.9% vs. 64.0%; p = 0.001). There was no significant difference in the rate of 30-day return between those who experienced pharmacologic cardioversion and those who did not (p = 0.220). The implementation of a procainamide-based acute cardioversion strategy for patients presenting to the ED with recent-onset AF resulted in a 60% cardioversion rate, which was associated with a significantly higher rate of discharge from the ED. Transient hypotension was the most common adverse event. Further investigation into ED-based protocols for management of recent-onset AF is necessary to better understand their safety and efficacy.

Efficacy and Safety of Ibutilide for the Cardioversion of Atrial Fibrillation: A Systematic Review and Meta-Analysis

Background: Ibutilide has been approved for cardioversion of Atrial Fibrillation (AF), but its side-effects include a high risk of torsade de pointes, besides, one recent meta-analysis showed ibutilide was inferior to vernakalant for conversion (AF&lt;7 days). Hence, the aim of this study is to evaluate the efficacy and safety of ibutilide for the cardioversion of AF within 90 days. Methods: The Embase, PubMed, Web of Science, Cochrane Central databases and clinical trials.gov were comprehensively searched for relevant studies from January 1991 to May 2020 using the keywords “ibutilide” and “atrial fibrillation”. Only Randomized Controlled Trials (RCTs) comparing ibutilide with placebo or other Anti-Arrhythmic Drugs (AADs) for the termination of AF (duration of AF ≤90 days) were included. The primary outcome was successful cardioversion in response to ibutilide versus placebo or other AADs within 4h. Related adverse events were defined as secondary outcomes. Results: A total of 1712 patients in 13 RCTs met the eligibility criteria. Four trials compared ibutilide to placebo; nine trials compared ibutilide to other active drugs. The results revealed that ibutilide had a higher success rate for the termination of recent-onset atrial fibrillation compared to placebo within 4h [Risk Ratio (RR), 4.64; 95% Confidence Interval (CI), 1.30-16.56, P=0.006]; and ibutilide also showed superiority to DL-sotalol, Propafenone, Procainamide for successful termination of recent-onset AF within 4h. As compared to other active drugs, Ibutilide was associated with a lower risk of hypotension (RR 0.23, 95% CI 0.09-0.57, P=0.002); but significantly increased the incidence of Polymorphic ventricular tachycardia (RR 3.78, 95% CI 1.08-13.23, P=0.04). Conclusion: Intravenous ibutilide could be an accessible choice for the cardioversion of recent-onset AF patients without contraindications, but under strict monitored condition is needed for at least 6 hours.

On-Demand Mobile Health Infrastructure for Remote Rhythm Monitoring within a Wait-and-See Strategy for Recent-Onset Atrial Fibrillation: TeleWAS-AF

Recently, we introduced the TeleCheck-AF approach, an on-demand mobile health (mHealth) infrastructure using app-based heart rate and rhythm monitoring for 7 days, to support long-term atrial fibrillation (AF) management through teleconsultation. Herein, we extend the mHealth approach to patients with recent-onset AF at the emergency department (ED). In the proposed TeleWAS-AF approach, on-demand heart rate and rhythm monitoring are used to support a wait-and-see strategy at the ED. All stable patients who present to the ED with recent-onset symptomatic AF and who are able to use mHealth solutions for heart rate and rhythm monitoring are eligible for this approach. Patients will receive both education on AF and instructions on the use of the mHealth technology before discharge from the ED. A case coordinator will subsequently check whether patients are able to activate the mHealth solution and to perform heart rate and rhythm measurements. Forty hours after AF onset, the first assessment teleconsultation with the physician will take place, determining the need for delayed cardioversion. After maximal 7 days of remote monitoring, a second assessment teleconsultation may occur, in which the rhythm can be reassessed and further treatment strategy can be discussed with the patients. This on-demand mHealth prescription increases patient involvement in the care process and treatment decision-making by encouraging self-management, while avoiding excess data-load requiring work-intensive and expensive data management. Implementation of the TeleWAS-AF approach may facilitate the management of AF in the ED and reduce the burden on the ED system, which enhances the capacity for health care utilization.

Single-dose oral anti-arrhythmic drugs for cardioversion of recent-onset atrial fibrillation: a systematic review and network meta-analysis of randomized controlled trials.

Single oral dose anti-arrhythmic drugs (AADs) are used to cardiovert recent-onset atrial fibrillation (AF); however, the optimal agent is uncertain. We performed a systematic review and network meta-analysis of randomized trials testing single oral dose AADs vs. any comparator to cardiovert AF <7 days duration. We searched MEDLINE, Embase, and CENTRAL to April 2020. The primary outcome was successful cardioversion at timepoint nearest 8 h after administration. From 12 712 citations, 22 trials (2320 patients) were included. Thirteen trials included patients with some degree of heart failure; 19 included patients with some degree of ischaemic heart disease vs. placebo or rate-control (32% success) at 8 h, flecainide [73%, network odds ratio (OR) 7.6, 95% credible interval (CrI) 4.4-14.0], propafenone (70%, OR 4.6, CrI 2.9-7.3), and pilsicainide (59%, OR 10.0, CrI 1.8-69.0), but not amiodarone (28%, OR 1.0, CrI 0.4-2.8) were superior. Flecainide (OR 7.5, CrI 2.6-24.0) and propafenone (OR 4.5, CrI 1.6-13.0) were superior to amiodarone; propafenone vs. flecainide did not statistically differ (OR 0.6, CrI 0.3-1.1). At longest follow-up, amiodarone was superior to placebo (OR 11.0, CrI 3.2-41.0), flecainide vs. amiodarone (OR 0.79, CrI 0.19-3.1), and propafenone vs. amiodarone (OR 0.36, CrI 0.092-1.4) were not statistically different, and flecainide was superior to propafenone (OR 2.2, CrI 1.1-4.8). Atrial and ventricular tachyarrhythmias, bradyarrhythmias, and hypotension were rare with PO AADs. Single oral dose Class 1C AADs are effective and safe for cardioversion of recent-onset AF. Flecainide may be superior to propafenone. Amiodarone is a slower acting alternative.

Adverse Events Among Emergency Department Patients With Cardiovascular Conditions: A Multicenter Study

We aim to determine incidence and type of adverse events (adverse outcomes related to emergency care) among emergency department (ED) patients discharged with recent-onset atrial fibrillation, acute heart failure, and syncope. This 5-year prospective cohort study included high-acuity adult patients discharged with the 3 sentinel diagnoses from 6 tertiary care Canadian EDs. We screened all ED visits for eligibility and performed telephone interviews 14 days postdischarge to identify flagged outcomes: death, hospital admission, return ED visit, health care provider visit, and new or worsening symptoms. We created case summaries describing index ED visit and flagged outcomes, and trained emergency physicians reviewed case summaries to identify adverse events. We reported adverse event incidence and rates with 95% confidence intervals and contributing factor themes. Among 4,741 subjects (mean age 70.2 years; 51.2% men), we observed 170 adverse events (3.6 per 100 patients; 95% confidence interval 3.1 to 4.2). Patients discharged with acute heart failure were most likely to experience adverse events (5.3%), followed by those with atrial fibrillation (2.0%) and syncope (0.8%). We noted variation in absolute adverse event rates across sites from 0.7 to 6.0 per 100 patients. The most common adverse event types were management issues, diagnostic issues, and unsafe disposition decisions. Frequent contributing factor themes included failure to recognize underlying causes and inappropriate management of dual diagnoses. Among adverse events after ED discharge for patients with these 3 sentinel cardiovascular diagnoses, we identified quality improvement opportunities such as strengthening dual diagnosis detection and evidence-based clinical practice guideline adherence.

Efficacy and Safety of flecainide p.os. in cardioversion of recent-onset atrial fibrillation

Aim: The aim of the study was to identify the level of safety and the efficacy of flecainide per o.s. in patients with recent-onset (<48 hours) AF. The management of patients with recent-onset Atrial Fibrillation (AF) presenting at emergency departments varies widely.Materials and Methods: Eighty-one eligible, consecutive patients with AF were enrolled in a prospective, randomized study. Patients were randomly allocated in two groups: patients in Group A (41 patients, 28 Men – 13 Women, mean age 64.7+ 15.67 years), received flecainide 200mg and in case of no conversion an addition of 100 mg after one hour was given. In Group B (40 patients, 26 Men – 14 Women, mean age 67.5+18.74 χρόνων) a rate control strategy was adopted. The efficacy and safety of flecainide in 45 min, 60 min, 3-6 hours, 6-12 hours, 12-24 hours and 24-36 hours were studied. The primary endpoint for efficacy was time to cardioversion. The safety of flecainide was described by registration and monitoring of side effects.Results: Successful cardioversion was achieved in 37 patients (90.24%) from Group A versus 5 patients (12.5%) from Group B (p<0.0005). Cardioversion rate was 72.97% the first three hours in patients given flecainide and most of them were discharged from the hospital. Flecainide administration (OR=2.47 – p<0.0001) and patients’ heart rate on admission (OR=1.15 – p=0.04) were associated with the success of pharmacological cardioversion in 24 hours while negative prognostic factors were patients’ age (OR=1.08 – p=0.04), duration of AF (OR=0.94 – p=0.01) and left atrium size (OR=0.87 – p=0.04). There were no reported side effects. Conclusion: In carefully selected patients presenting with recent-onset AF and without structural heart disease the use of flecainide per os has shown a significant efficacy for cardioversion and has a low incidence of adverse effects.

The role of timing in treatment of atrial fibrillation: An AFFIRM substudy

In contrast to historical trials, the Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4) suggests the superiority of early rhythm control over rate control in patients with recent-onset atrial fibrillation (AF). The relative contribution of timing vs improvement in AF therapeutics over time is unclear. This study aimed to isolate the assessment of early intervention for AF from temporal changes in AF treatments through a secondary analysis of subjects from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. We compared rate and rhythm control treatments in AFFIRM subjects stratified by time from their diagnosis of AF. Time-to-event analysis was performed to compare all-cause mortality, cardiovascular hospitalizations, stroke, and number of hospitalization days. Of the 4060 AFFIRM subjects, 2526 subjects (62.2%) had their first episode of AF within 6 months of study enrollment. Participants with "new" AF had a decreased risk of all-cause mortality (P = .001) than did those with prior AF diagnoses. Individuals previously diagnosed with AF were similar in age and demographic characteristics, but had more medical comorbidities, including myocardial infarction (P = .006), diabetes mellitus (P = .002), smoking (P = .003), and hepatic or renal comorbidities (P = .008). There were no differences in mortality, cardiovascular hospitalizations, or stroke between rate and rhythm control strategies in either AF subgroup. AFFIRM subjects diagnosed with AF within 6 months of study enrollment showed no difference in survival, cardiovascular hospitalization, or ischemic stroke between rate and rhythm control strategies. Superiority of rhythm control strategies reported by newer AF trials may be more attributable to the refinement of AF therapies and less related to the timing of intervention.

Frontal plane QRS-T angle in the monitoring of intravenous amiodarone infusion for pharmacological cardioversion of acute atrial fibrillation.

Intravenous amiodarone infusion is effective and widely used treatment for pharmacological cardioversion of recent-onset atrial fibrillation (Af). Although amiodarone may trigger various alterations in cardiac electrophysiology and electrocardiography (ECG), the impact of amiodarone treatment on frontal plane QRS-T angle remains unclear. Frontal plane QRS-T angle is the angle between the depolarization and repolarization axes and indicates instability in the cardiac cellular electrophysiology. Therefore, the present study aimed to investigate whether intravenous amiodarone infusion has effect on frontal plane QRS-T angle in patients with acute Af. A total of 179 patients with acute-onset Af who underwent pharmacological cardioversion with intravenous amiodarone infusion were included into the study. Patients with successful and failed pharmacological cardioversion were compared regarding pre- and post-treatment frontal plane QRS-T angle. At the end of the amiodarone infusion, sinus rhythm was restored in 112 (62.6%) patients, whereas Af was persisted in 67 (37.4%) patients. Despite the similar frontal plane QRS-T angle at baseline (59.6°±21.73°vs.60.4°±25.67°, p=0.822), patients with failed pharmacological cardioversion had significantly higher post-treatment frontal plane QRS-T angle compared to patients with successful pharmacological cardioversion (68.8°±21.71°vs.58.6°±25.15° p<0.001). Furthermore, multivariate analysis demonstrated that post-treatment increased frontal plane QRS-T angle was found to be an independent predictor of failure of pharmacological cardioversion with amiodarone infusion (OR:1.233, 95% CI:1.147-1.919, p=0.024). Amiodarone may significantly affect the frontal plane QRS-T angle. As a parameter that can be easily calculated from automated ECG recordings, frontal plane QRS-T angle may be useful in the monitoring of intravenous amiodarone treatment.

Frequency and Determinants of Spontaneous Conversion to Sinus Rhythm in Patients Presenting to the Emergency Department with Recent-onset Atrial Fibrillation: A Systematic Review.

The exact frequency and clinical determinants of spontaneous conversion (SCV) in patients with symptomatic recent-onset AF are unclear. The aim of this systematic review is to provide an overview of the frequency and determinants of SCV of AF in patients presenting at the emergency department. A comprehensive literature search for studies about SCV in patients presenting to the emergency department with AF resulted in 25 articles – 12 randomised controlled trials and 13 observational studies. SCV rates range between 9–83% and determinants of SCV also varied between studies. The most important determinants of SCV included short duration of AF (<24 or <48 hours), low number of episodes, normal atrial dimensions and absence of previous heart disease. The large variation in SCV rate and determinants of SCV was related to differences in duration of the observation period, inclusion and exclusion criteria and in variables used in the prediction models.

Cardioversion of recent-onset atrial fibrillation: current evidence, practical considerations, and controversies in a complex clinical scenario.

Atrial fibrillation (AF) represents the most common arrhythmia and is associated with increased morbidity and mortality generating high social costs. Due to its high prevalence, AF is usually managed not only by cardiologists but also by general practitioners or clinicians in emergency departments. The conventional classification of AF includes "recent‑onset AF" defined as an arrhythmia episode shorter than 48 hours. In patients with a definite duration of AF of less than 24 hours and a very low-risk profile (CHA2DS2VASc of 0 in men and 1 in women), the thromboembolic risk seems to be low, and the standard 4‑week anticoagulation therapy is now regarded as optional treatment. Cardioversion (electrical or pharmacological) in recent‑onset AF represents a valid rhythm control strategy. Electrical cardioversion is usually reserved for hemodynamically unstable patients and performed with biphasic waveform shocks. On the other hand, pharmacological cardioversion is preferred in hemodynamically stable patients. Several antiarrhythmic drugs have been studied so far, but some questions still remain unresolved mainly due to lack of randomized clinical trials and prospective studies. The current guidelines do not uniformly agree on which drug to use for pharmacological cardioversion, and drug preference varies widely in clinical practice. The aim of this narrative review is to sum up and critically evaluate novel evidence regarding recent‑onset AF as well as to provide some practical considerations particularly focused on rhythm control with pharmacological cardioversion.

Heat Shock Protein 70 Is Associated With Cardioversion Outcome and Recurrence of Symptomatic Recent Onset Atrial Fibrillation in Hypertensive Patients.

Accumulating evidence indicates that heat shock proteins (HSPs) may represent a suitable biomarker to predict atrial fibrillation (AF). We investigated the relation of circulating serum HSP70 (sHSP70) with inflammatory cytokines and recurrence of symptomatic recent onset AF (ROAF). We enrolled 90 patients with ROAF (the duration from onset of symptoms ≤24 hours) and 30 controls. Patients received amiodarone for cardioversion and rhythm control. The association of serum HSP70, serum interleukin-2 (sIL-2), and serum interleukin-4 (sIL-4) with the presence of cardioversion and AF recurrence within a year was investigated. Toll-like receptor 4 (TLR4) signaling dependence for IL-2 and IL-4 induction in response to stimulation with HSP70 was tested in rat aortic vascular smooth muscle cell cultures. Patients had higher sHSP70 and sIL-2 and lower sIL-4 compared with controls. Serum HSP70 was independently associated with ROAF (P = 0.005) and correlated with sIL-2 (r = 0.494, P < 0.001) and sIL-4 (r = -0.550, P < 0.001). By 48 hours, 71 of the 90 patients were cardioverted, with noncardioverted patients having higher sHSP70 and sIL-2 and lower sIL-4, which were the only independent factors associated with cardioversion. AF recurred in 38 of the 71 cardioverted patients in 1 year. A cutoff value of sHSP70 ≥0.65 ng/mL and sIL-2 ≥0.21 pg/mL was the only independent factor associated with AF recurrence (hazard ratio: 3.311, 95% confidence interval: 1.503-7.293, P = 0.003 and hazard ratio: 3.144, 95% confidence interval: 1.341-7.374, P = 0.008, respectively). The exposure of smooth muscle cell to HSP70 in vitro increased the expression of IL-2 (5×) and IL-4 (1.5×) through TLR4-dependent and receptor-independent mechanisms. In conclusion, sHSP70 and sIL-2 might constitute a prognostic tool for determining the cardioversion and recurrence likelihood in ROAF.

Vernakalant for Rapid Cardioversion of Recent-Onset Atrial Fibrillation: Results from the SPECTRUM Study

AimsRapid restoration of sinus rhythm using pharmacological cardioversion is commonly indicated in patients with symptomatic recent-onset atrial fibrillation (AF). The objectives of this large, international, multicenter observational study were to determine the safety and effectiveness of intravenous (IV) vernakalant for conversion of AF to sinus rhythm in daily practice.Methods and ResultsConsenting patients with symptomatic recent-onset AF (< 7 days) treated with IV vernakalant were enrolled and followed up to 24 h after the last infusion or until discharge, in order to determine the incidence of predefined serious adverse events (SAEs) and other observed SAEs and evaluate the conversion rate within the first 90 min. Overall, 2009 treatment episodes in 1778 patients were analyzed. The age of patients was 62.3 ± 13.0 years (mean ± standard deviation). Median AF duration before treatment was 11.1 h (IQR 5.4–27.0 h). A total of 28 SAEs occurred in 26 patients including 19 predefined SAEs, i.e., sinus arrest (n = 4, 0.2%), significant bradycardia (n = 11, 0.5%), significant hypotension (n = 2, 0.1%), and atrial flutter with 1:1 conduction (n = 2, 0.1%). There were no cases of sustained ventricular arrhythmias or deaths. All patients who experienced SAEs recovered fully (n = 25) or with sequelae (n = 1). Conversion rate to sinus rhythm was 70.2%, within a median of 12 min (IQR 8.0–28.0 min).ConclusionsThis large multicenter, international observational study confirms the good safety profile and the high effectiveness of vernakalant for the rapid cardioversion of recent-onset AF in daily hospital practice.

Abstract 15742: An Open-label, Multicenter Study of Flecainide Acetate Oral Inhalation Solution Shows Acute Conversion of Recent-onset, Symptomatic Atrial Fibrillation to Sinus Rhythm in a Dose- and Concentration-dependent Manner

Introduction: Oral and intravenous (IV) flecainide are recommended as first line therapy for pharmacological cardioversion of recent-onset atrial fibrillation (AF) in patients without known relevant structural heart disease. In the present open-label, dose-escalation study, the feasibility of using flecainide acetate inhalation solution (FlecIH) for acute conversion of recent-onset AF to sinus rhythm (SR) was evaluated. Hypothesis: We hypothesized that FlecIH quickly gives rise to plasma concentrations sufficient to rapidly restore SR in patients with recent-onset AF. Methods: Patients (n=95) with symptomatic AF (for ≤ 48 hours) were enrolled and self-administered FlecIH using a breath-actuated nebulizer (30 mg [n=10], 60 mg [n=20], 90 mg [n=21], 120 mg [n=17], and 120 mg in a formulation containing saccharin [n=27]). Blood samples were collected for flecainide plasma concentrations, electrocardiograms were obtained, cardiac rhythm with a 4-hour Holter and vital signs were monitored, and adverse events (AEs) were recorded. Patients who did not convert to SR were offered alternative treatment per the investigator’s discretion. Results: Conversion rates increased with dose and maximum plasma concentrations (C max ) of flecainide. At the highest dose, 45% of patients converted to normal SR. Patients with C max &gt; 300 ng/mL had a conversion rate of 53% whereas those with C max &lt; 200 ng/mL had a conversion rate of 33%. The median time to conversion was 3.5 min after FlecIH administration. AEs were typically mild and transient. Commonly reported AEs associated with inhalation of flecainide included: cough, throat pain, and throat irritation; at the highest dose with the formulation containing saccharin, these AEs were reported for 37%, 11%, and 4% of patients, respectively. Cardiac AEs consistent with those observed with oral and IV flecainide and considered serious were uncommon and included 2 post-conversion pauses and 1 bradycardia, and 1 atrial flutter with 1:1 atrioventricular conduction; none required treatment and all resolved without sequelae. Conclusions: FlecIH was well tolerated. Inhalation of FlecIH at the 120 mg dose yielded therapeutic plasma levels and conversion rates within the range reported for oral and IV administration.

Timing of cardioversion in atrial fibrillation: the sooner the better?

Management of recent-onset (<36 h) atrial fibrillation (AF) in the emergency room is highly variable, particularly concerning the type and timing of cardioversion, and the logistics of the treatment pathway. In clinical practice, it is fairly common for patients with recent-onset AF an attempt at re-establishing sinus rhythm, either with electric or pharmacologic cardioversion, as soon as feasible. Nonetheless, a ‘wait-and-see’ approach, and potentially delayed cardioversion, could represent a valid alternative to early cardioversion, considering that, often, in recent-onset AF, sinus rhythm is re-established spontaneously, thus repealing the need for active cardioversion, hence avoiding the possible risks of treatment. These concepts form the rationale for a recent multicentric randomized trial, Rate Control vs. Electrical Cardioversion Trial 7 – Acute Cardioversion vs. Wait and See (RACE 7 ACWAS), comparing the efficacy of delayed cardioversion, within 48 h from symptoms onset, in case of lack of spontaneous conversion, with early cardioversion in symptomatic patients with recent-onset AF. In patients presenting to the emergency department with recent-onset, symptomatic AF, a wait-and-see approach was non-inferior to early cardioversion in maintaining the sinus rhythm at 4 weeks. Nonetheless a system employing a delayed cardioversion strategy increases the costs of treatment, complicates the treatment pathway, and could represent a psychological burden for the patients. Accordingly, delayed cardioversion could not represent a practical choice for many hospitals with limited resources and without an adequate outpatient organization.

Timing and degree of left atrial stunning and reverse functional remodeling following electrical cardioversion in patients with recent onset atrial fibrillation

Abstract Background Atrial fibrillation (AF) results in left atrial electrical, structural and functional remodeling. Restoration of sinus rhythm hallmarks the beginning of reverse remodeling, the extent of which may depend on the type of AF. Purpose The aim of the study was to assess resumption of left atrial function after electric cardioversion in patients with recent onset AF and to explore the association between reverse remodeling and the type of atrial fibrillation. Methods Patients with AF duration &amp;lt;48 hours were prospectively included. Trans-thoracic echocardiography was performed prior, immediately after (2–4 hours) and 7–10 days following CV. Left atrial volume index (LAVI), left atrial global longitudinal strain during reservoir (LAGLS-res), conduit (LAGLS-cond) and contractile (LAGLS-contr) phases, left atrial ejection fraction (LAEF) and left ventricular ejection fraction (LVEF) were measured. Results Forty-three patients (84% males) aged 55±9.6 years, (mean±SD), with median CHA2DS2-VASc score 1 (interquartile range 0–1) were included. Repeated measure analysis of variance revealed a statistically significant overall change for LAGLS-res F(2,78)=55.4, p&amp;lt;0,001, LAGLS-cond F(2,78)=23.3, p&amp;lt;0,001, LAGLS-contr F(2,78)=39.7, p&amp;lt;0,001, LAEF F(2,80)=28.5, p&amp;lt;0.001 and LVEF F(2,80)=8.4, p&amp;lt;0.001. At 7–10 days, LAGLS-contr 12±4%, LAEF 53±9% and LVEF 60±6 (mean±SD) return within normal reference intervals. Notably left atrial recovery seems to precede left ventricular recovery. No statistical significant interaction with the type of atrial fibrillation could be shown. Conclusion Left atrial functional reverse remodeling occurs within ten days after successful electric cardioversion of patients with recent onset atrial fibrillation. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swedish Heart-Lung Foundation, Correvio International Sárl (Geneva Switzerland), Selanders Stiftelse

Activation of inflammatory/coagulation system following electrical cardioversion of patient with recent onset atrial fibrillation: an explorative study of the relation to white matter hyperintensities

Abstract Background White matter hyperintensities (WMH), assessed using Fazekas scale, are more prevalent in patients with atrial fibrillation (AF), although its pathophysiologic mechanism(s) is unclear. Purpose The study objective was to explore the association between cardiac, inflammatory and coagulation biomarkers and white matter hyperintensities in anticoagulant-naïve patients following electrical cardioversion (CV) of recent onset AF. Methods Patients with AF duration &amp;lt;48 hours were prospectively included. Brain magnetic resonance imaging (MRI), C-reactive protein (CRP), high-sensitivity troponin T (hs-TNT), NT-proBNP, Interleukin 6, P-selectin, D-dimer, prothrombin fragment 1+2, von Willebrand factor Ag, coagulation factor VIII C and fibrinogen, were obtained sequentially prior, after (2–4 hours) and 7–10 days following CV. Repeated measure analysis of variance was performed. Results Forty-three patients (84% males), aged 55±9.6 years, (mean±SD) with median CHA2DS2-VASc score 1 (interquartile range 0–1) were included. Sequential MRI showed no new brain lesions after CV, while WMH were present at baseline in 21/43 (49%) patients. Repeated measure analysis of variance revealed a statistically significant overall change for hs-TNT: F(2,84)=6.056, p=0.03, NT-proBNP: F(2,84)=106.02, p&amp;lt;0.001, P-selectin: F(2,84)=8.69, p&amp;lt;0.001 and vWF:Ag: F(2,84)=4.078, p=0.02. CRP, IL-6, coagulation factor VIII-C and fibrinogen showed the same pattern, however none reached statistical significance. Patients with WMH had persistent higher values for CRP, hs-TNT, D-dimer, prothrombin fragment 1+2 and fibrinogen prior and after CV, as values at 7–10 days coincided; however, statistical interaction was not significant. Conclusion Transient activation of inflammatory and coagulation systems during atrial fibrillation subsides within 7–10 days after electric cardioversion of recent onset atrial fibrillation. A tendency of higher degree of activation during atrial fibrillation was observed in patients with white matter hyperintensities. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swedish Heart-Lung Foundation, Swedish Research Council, Correvio International Sárl (Geneva Switzerland), Selanders Stiftelse

Serial Magnetic Resonance Imaging after Electrical Cardioversion of Recent Onset Atrial Fibrillation in Anticoagulant-Naïve Patients - A Prospective Study Exploring Clinically Silent Cerebral Lesions.

Patients with atrial fibrillation (AF) have a high incidence of cognitive impairment, which may be related to clinically silent microembolism causing cerebral infarctions. To explore the occurrence and timing of silent brain lesions following electrical cardioversion (CV) of recent onset AF in anticoagulant-naïve patients and to study related effects on cognitive function and biomarkers of cerebral damage, S100b. Patients with AF duration > 48 hours were prospectively included. Brain magnetic resonance imaging (MRI) and S100b, were obtained prior, after and 7-10 days following CV. Trail making tests (TMT-A and TMT-B) and their difference, ΔΤΜΤ, were assessed prior to CV, 7-10 days and 30 days after CV. Forty-three patients (84% males) with median CHA2DS2-VASc score 1 (interquartile range 0-1) were included. Sequential MRI, including diffusion weighted scans, showed no new brain lesions after CV. Chronic white matter hyperintensities were present at baseline in 21/43 (49%) patients. The S100b (µg/l) levels increased significantly from baseline, (mean ±SD) 0.0472±0.0182 to 0.0551±0.0185 after CV, p=0.001 and then decreased 7-10 days after CV to 0.0450±0.0186, p <.;0.001. Consecutive TMT scores improved successively after CV, being statistically and clinically significant for TMT-B (p<0.01) and ΔΤΜΤ (p=0.005) between 7-10 days and 30 days after CV (Reliable Change Index >1.96). New brain lesions could not be detected on MRI after CV, but the high incidence of white matter hyperintensities and the transient increase in S100b may indicate transient or minor brain damage undetectable by MRI thus heightening the need to reevaluate thromboembolic risk prior to CV even in low risk patients.

Ranolazine depresses conduction of rapid atrial depolarizations in a beating rabbit heart model.

Previous clinical studies have shown that ranolazine (RAN) added to amiodarone (AMIO) might accelerate the termination of recent-onset atrial fibrillation. This study was undertaken to delineate possible mechanisms that contribute to the enhancement of the antiarrhythmic efficacy of RAN-AMIO coadministration. Ten rabbits were anesthetized and two monophasic action potential (MAP) catheters were sequentially inserted into the right atrium. One MAP electrode was used to pace and record; the other electrode was used only for recording MAP from an adjacent atrial region. Intraatrial conduction time (IACT), 2:1 intraatrial conduction block (IACB), and atrial post-repolarization refractoriness (aPRR) were consecutively determined by high-rate atrial burst pacing and programmed stimulation, respectively. All parameters were evaluated during baseline and following AMIO (3 mg/kg iv) or AMIO+RAN (2.4 mg/kg iv bolus +0.134 mg/kg/min maintenance infusion). The IACT remained unchanged post AMIO compared with baseline (37.6 ± 3.8 vs 36.4 ± 2.4 ms), whereas the addition of RAN to AMIO significantly prolonged IACT (50.4 ± 3.6 ms, p < .001). The pacing cycle length producing 2:1 IACB was 101.2 ± 21.7 ms at baseline , 117.5 ± 15 ms after AMIO (p = 0.265), and 150 ± 14 ms after AMIO+RAN (p < .001). Baseline aPRR was longer following AMIO treatment (35 ± 5 vs 50 ± 9 ms, p < .01) but remarkably prolonged with RAN supplementation (105 ± 11 ms, p < .001). RAN significantly prolonged the propagation time of rapid atrial depolarizations and potentiated the AMIO-induced moderate increases in aPRR. These mechanisms possibly contribute to the earlier termination of atrial fibrillation when RAN is co-administered with AMIO.

Paradigm shifts in pathophysiology and management of atrial fibrillation-atale of the RACE trials in the Netherlands.

In the past 20 years the Netherlands-based RACE trials have investigated important concepts in clinical atrial fibrillation (AF). Their scope ranged from rhythm versus rate control to early or delayed cardioversion and also included early comprehensive management of AF in two trials, one focusing on early ‘upstream therapy’ and risk factor management and the other on integrated chronic nurse-led care. Studies were mostly triggered by simple clinical observations including futility of electrical cardioversion in persistent AF; many patients with permanent AF tolerating day-after-day ‘uncontrolled’ resting heart rates of up till 110 beats/min; patients being threatened more by vascular risks than AF itself; and insufficient guideline-based treatments for AF. Also the observation that recent-onset atrial fibrillation generally converts spontaneously, obviating cardioversion, triggered one of the studies. The RACE trials shifted a number of paradigms and by that could change the AF guidelines. The initial ‘shock-and-forget’ attitude made place for increased attention for anticoagulation, and in turn, broader vascular risks were recognised. In a nutshell, the adage eventually became: ‘look beyond the ECG, treat the patient’.Electronic supplementary materialThe online version of this article (10.1007/s12471-020-01476-0) contains supplementary material, which is available to authorized users.