Non-permanent Atrial Fibrillation Research Articles

Spontaneous fluctuation in atrial fibrillation burden and duration in patients with implantable loop monitors.

Most studies of device-detected atrial fibrillation (AF) have recommended indefinite anticoagulation once a patient crosses a particular threshold for AF duration or burden. However, durations and burdens are known to fluctuate over time, but little is known about the magnitude of spontaneous fluctuations and the potential impact on anticoagulation decisions. To quantify spontaneous fluctuations in AF duration and burden in patients with implantable loop recorders (ILRs) METHODS: We reviewed all ILR interrogations for patients with non-permanent AF at our institution from 2018 to 2023. We excluded patients treated with rhythm control. The duration of longest AF episode at each interrogation was classified as<6, 6-24, and>24h, and the AF burden reported at each interrogation was classified as<2%, 2%-11.4%, and>11.4%. Out of 156 patients, the mean age at ILR implant was 70.9±12.5 years, CHA2DS2-VASc score was 4.2±1.8, duration of ILR follow-up was 23.4±11.2 months, and number of ILR interrogations per patient was 18.0±8.9. The duration of longest AF episode at any point during follow-up was<6, 6-24, and>24h in 110, 30, and 16 patients, respectively. Among the 30 patients with a longest AF episode of 6-24h at some point during follow-up, out of 594 total ILR interrogations, only 75 (12%) showed a longest episode of 6-24h. In the remaining 519 interrogations, the longest episode was<6h. In patients with a longest episode of>24h at any point during follow-up (n=16), only 47 out of 320 total ILR interrogations (15%) showed an episode of>24h. When evaluating AF burden, 96, 38, and 22 patients had maximum reported AF burdens of<2%, 2%-11.4%, and>11.4% at any point during ILR follow-up. Among those with a maximum burden of 2%-11.4% at some point during follow-up (n=38), out of 707 ILR interrogations, only 76 (11%) showed a burden of 2%-11.4%. In the remaining 631 interrogations, the burden was<2%. In the 22 patients with a burden>11.4% at some point during follow-up, only 80 out of 480 interrogations (17%) showed a burden of>11.4%. In 65% of interrogations, the burden was<2%. Significant, spontaneous fluctuations in AF burden and duration are common in patients with ILRs. Even in patients with AF episodes of 6-24h or>24h at some point during follow-up, the vast majority of interrogations show episodes of<6h. Similarly, in patients with burdens of 2%-11.4% or>11.4% at some point during follow-up, the vast majority of interrogations show burdens of<2%. More data are needed to determine whether crossing an AF burden or duration threshold once is sufficient to merit lifelong anticoagulation or whether spontaneous fluctuations in AF burden and duration should impact anticoagulation decisions.

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.

Snoring and lack of REM sleep is associated with same-day atrial arrhythmias in a cohort of patients with atrial fibrillation: initial results of TriggersAF

Abstract Introduction Sleep-disordered breathing (SDB) is a known risk factor for the development of atrial fibrillation (AF). Few studies analyse the temporal relation between snoring, sleep phases and atrial arrhythmia episodes. Purpose The TriggersAF trial (NCT05526170) investigates the temporal relation between atrial arrhythmias and potential triggers. In this preliminary analysis, the authors hypothesised that snoring and disturbance of sleep phases may be associated with same-day atrial arrhythmias. Methods In a single-centre prospective cohort study patients with previously diagnosed AF were recruited for home monitoring of 7 days. A single-lead continuous electrocardiogram (ECG) of the reference Holter monitor (Bittium, Kuopio, Finland) documented the cardiac rhythm. The recordings were manually annotated as: 1) AF, 2) atrial tachycardia or flutter (AT), 3) frequent premature atrial contractions (PAC), defined as bigeminy, trigeminy, quadrigeminy or couplets, and 4) no arrhythmia. Sleep disorders were evaluated using a validated sleep tracking mat (Withings Sleep Analyzer, Issy-les-Moulineaux, France) and described by the number of snoring episodes, durations of snoring, light, deep, and rapid-eye-movement (REM) phases. Heart echocardiography with strain imaging of left atrium (LA) was performed to further characterize the subjects. Results The study consisted of 49 patients, aged 55.8±11.7 years, 67.3% male. All patients were with previously diagnosed non-permanent AF and sinus rhythm at the moment of inclusion. The monitoring duration yielded a total of 300 days. The occurrence of AF, AT and PAC was detected in 32/300, 108/300 and 85/300 of days, respectively. As revealed by the sleep analysis a greater number of snoring episodes was associated with the same-day episodes of AF when compared to patients with no AF (5.0 (2-10.2) vs. 2.0 (0-7), P=0.029, respectively). A longer snoring duration was associated with the same-day episodes of AF (36 (6-80) min vs. 12 (0-52) min, P=0.057). A shorter duration of the REM phase was associated with AT (63 (28-93) min vs. 79 (42-105) min, P=0.032) and PAC (60 (32-91) min vs. 79 (37-102) min, P= 0.058). No significant relations were observed between the durations of light or deep phases and any type of arrhythmias. A smaller mean conduit strain of LA was highly associated with AF (-7,5 (-12,5, -7,5)) compared to patients with no AF (-11,0 (-14,8, -8,5), P= 0.002). In the Fast-and-Frugal Decision Tree for the prediction of same-day AF, a model combining the mean conduit strain of less than -9, a body mass index of more than 27.8, and a snoring duration of more than 29 minutes yielded a sensitivity of 97%, a specificity of 59% and a balanced accuracy of 78%. Conclusions The higher frequency and duration of snoring, as well as reduced REM phase of sleep are linked to same-day atrial arrhythmias. Long-term SDB monitoring and LA strain imaging predict the episodes of AF with high accuracy.Number of snoring episodes vs. AFAF by LA strain, BMI and snoring

Rate control in atrial fibrillation, calcium channel blockers versus beta-blockers

ObjectiveTo investigate heart rate differences between non-dihydropyridine calcium channel blockers and beta-blockers in patients with non-permanent atrial fibrillation (AF).MethodsUsing data from ‘A Comparison of Rate Control and Rhythm Control in...

Cardiorespiratory fitness in individuals with and without atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Liaison Committee for Education, Research and Innovation in Central Norway (Samarbeidsorganet). Background Cardiorespiratory fitness is an important marker of cardiopulmonary health. The majority of published data is however based on healthy individuals. To improve clinical decisions and tailor exercise as treatment for patients with atrial fibrillation (AF), knowledge on impact of AF with and without other cardiovascular diseases (CVD) is essential. Purpose To explore impact of age, sex, presenting rhythm during cardiopulmonary exercise testing (CPET) and presence of other CVDs on directly measured peak oxygen uptake (VO2peak) in participants from a general health-survey with and without AF. Methods We used cross-sectional data from the HUNT4 Fitness Study, a subsample of the Trøndelag Health Study (HUNT, 2017-2019). All participants (n = 2548, 49 % women) completed a standardized CPET with ECG monitoring. We stratified participants into categories of validated AF diagnosis (yes/no) and whether the CPET was performed in sinus or AF rhythm among those with AF. As we did not have precise data for subtype of AF, cardiac rhythm under testing was used as a proxy for permanent/persistent AF or non-permanent AF. Other CVD (yes/no) was defined as stroke, coronary heart diseases, or heart failure, using validated diagnoses from hospital registries for those with AF and self-reported diagnoses for non-AF participants. We used a general linear model to investigate the differences in predicted means for VO2peak per category of AF, other CVD, age, and sex testing for interaction between covariates. Results In total, 355 participants had valid AF, and among them 139 performed CPET with AF rhythm (Table 1). Mean VO2peak was 26 and 35 mL/kg/min for women and men, respectively, with non-permanent AF (sinus) and 22 and 26 mL/kg/min for women and men with permanent AF. Results from the general linear model are shown as predicted means with 95% confidence and prediction intervals in Figure 1. VO2peak decreased with higher age for both women and men, with and without other CVD, and were generally lower for women than for men. For both sexes and categories of CVD, participants with permanent/persistent AF, and hence AF during CPET, had lower VO2peak than those with non-permanent AF tested in sinus rhythm, and those without AF. The difference was more prominent in the younger age groups. There were, however, only small differences between participants with non-permanent AF and those without AF. Predicted means for VO2peak were lower for women and men with other CVD than without other CVD. Conclusion VO2peak was similar in participants with AF performing CPET in sinus rhythm to those without AF when no other CVD was present. Permanent/persistent AF and presence of other CVDs were the two factors with the most negative impact on VO2peak for both men and women across age groups.

The effects of high-intensity interval training and moderate-to-vigorous intensity on cardiorespiratory fitness in patients with permanent or persistent atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): the Innovations Fund of the Alternate Funding Plan for the Academic Health Sciences Centre of the Ministry of Ontario. Background Lower cardiorespiratory fitness (CRF) in atrial fibrillation (AF) is associated with higher risk of mortality. Moderate-to-vigorous intensity continuous training (MICT) increases CRF; however, growing evidence indicates that high-intensity interval training (HIIT) elicits similar or greater improvements in CRF in people with cardiovascular disease. Purposes The purposes of this study were to: (1) compare the effects of HIIT and MICT on CRF in patients with persistent and permanent AF; and, (2) assess the proportion of participants who achieved a clinically meaningful increase in CRF (i.e., 3.5 mL/kg/min, associated with significant reduction in mortality in AF). Methods This was a subanalysis of an RCT to examine the effects of HIIT and MICT on functional capacity. Participants completed cardiopulmonary exercise test (CPET) and were randomly assigned to 12-week, twice weekly supervised HIIT or MICT. Each HIIT session was 23 min in duration, completed on a stationary bike, and consisted of: (1) a 2-min warm up; (2) two blocks of 8 x 30-sec high-intensity work periods at 80-100% peak power output interspersed with 30-sec active recovery periods, with 4 min active recovery between the blocks; and, a 1-min cooldown. Each MICT session consisted of (1) a 15-min warm up; (2) 30-min of continuous aerobic exercise; and, (3) a 15-min cooldown. A subset of willing participants completed follow-up CPET. Repeated measures ANOVA was used to compare the changes in CRF between HIIT and MICT. Descriptive statistics was used to assess the proportion of patients meeting the clinically meaningful increase in CRF. Results Of 94 patients consented, 13 in HIIT (67±4 years old, 26% females) and 10 in MICT (71±9 years old, 40% females) completed pre and post CPET. Exercise adherence (i.e., % of sessions attended) was 91% for HIIT and 85% for MICT, respectively, and did not differ between the groups. At week 12, 76% of participants in HIIT and 80% in MICT achieved the prescribed exercise intensity targets. Our per-protocol analysis showed no overall change in CRF (pre: 19.0±5.1 vs. post: 19.4±4.6 mL/kg/min, p=0.461). No significant differences in changes in CRF were observed between HIIT (pre: 20.1±5.3 vs. post: 20.3±4.5 mL/kg/min) and MICT (pre: 17.6±4.8 vs. post: 18.4±4.7 mL/kg/min, interaction effect p=0.681). Two participants in HIIT (15.4%) and two in MICT (20.0%) achieved clinically meaningful increases. Conclusions Twice weekly HIIT or MICT for 12 weeks did not improve CRF in patients with persistent and permanent AF who completed CPET. Further, a small proportion of these patients (≤ 20%) achieved clinically meaningful increase in CRF. Considering a greater increase in CRF (3.2±2.5 mL/kg/min) in patients with non-permanent AF following high-volume HIIT (a total of 16 min at high intensity per session, three times per week) in a previous RCT, a larger exercise volume may be required to improve the CRF of patients with persistent and permanent AF.

Left atrial appendage thrombus formation, potential of resolution and association with prognosis in a large real-world cohort

Comprehensive data on factors influencing left atrial appendage (LAA) thrombus formation, resolution and impact on survival are limited. In this single-center, retrospective study 7759 (2010–2015) patients with symptomatic ongoing atrial fibrillation (AF) on admission were screened for LAA thrombi. 450 patients had LAA thrombi. 481 patients without LAA thrombi were randomly selected as controls. We assessed clinical, echocardiographic, laboratory parameters and long-term survival of both groups. Patients with LAA thrombi compared to controls were older, had more strokes, higher CHA2DS2 -VASc scores, worse renal function, less controlled diabetes, advanced heart failure, lower LAA emptying velocities, higher levels of cardiac and inflammatory markers (all p < 0.001). 56.3% of followed-up patients (304) dissolved their LAA thrombi. Chances of thrombus resolution increased with rising LAA flow velocities (OR 1.061, p = 0.022), whereas advanced age (OR 0.950, p < 0.001) and presence of permanent AF (OR 0.354, p < 0.001) decreased chances of thrombus resolution. Presence of LAA thrombi was associated with a markedly reduced 10-year survival probability (31% versus 69%). LAA thrombus formation is promoted by advanced structural heart disease, inflammation, diabetes and impaired renal function. Younger age, non-permanent AF and higher LAA flow velocities were predictors of thrombus resolution. Thrombus formation was associated with poor prognosis.

Exercise Improves Health Related Quality of Life in Patients with Non-Permanent Atrial Fibrillation; a Randomized Trial

Exercise Improves Health Related Quality of Life in Patients with Non-Permanent Atrial Fibrillation; a Randomized Trial

Association of Intravenous Potassium and Magnesium Administration With Spontaneous Conversion of Atrial Fibrillation and Atrial Flutter in the Emergency Department

Whether the simultaneous intravenous administration of potassium and magnesium is associated with the probability of spontaneous conversion to sinus rhythm (SCV) in the acute treatment of atrial fibrillation (AF) and atrial flutter (AFL) is unknown. To assess potassium and magnesium administration and SCV probability in AF and AFL in the emergency department. A registry-based cohort study was conducted in the Department of Emergency Medicine of the Medical University of Vienna, Austria. All consecutive patients with AF or AFL were screened between February 6, 2009, and February 16, 2020. Intravenous administration of potassium, 24 mEq, and magnesium, 145.8 mg. The primary outcome was the probability of SCV during the patient's stay in the emergency department. Multivariable cluster-adjusted logistic regression was used to estimate the association between potassium and magnesium administration and the probability of SCV. A total of 2546 episodes of nonpermanent AF (median patient age, 68 [IQR, 58-75] years, 1411 [55.4%] men) and 573 episodes of nonpermanent AFL (median patient age, 68 [IQR, 58-75] years; 332 [57.9%] men) were observed. In AF episodes, intravenous potassium and magnesium administration vs no administration was associated with increased odds of SCV (19.2% vs 10.4%; odds ratio [OR], 1.98; 95% CI, 1.53-2.57). In AFL episodes, in contrast, no association was noted for the probability of SCV with potassium and magnesium vs no administration (13.0% vs 12.5%; OR, 1.05; 95% CI, 0.65-1.69). The findings of this registry-based cohort study on intravenous administration of potassium and magnesium suggest an increased probability of SCV in nonpermanent AF, but not AFL, during a patients' stay in the emergency department.

Quality indicators of the atrial fibrillation management from the European (EORP) and Asia-Pacific (APHRS) registries

Abstract Background The 2020 ESC guideline for atrial fibrillation (AF) recommends universal quality indicators to identify areas for improvement in clinical practice. It also recommends using clinical registries to monitor clinical practice and identify areas for improvement. We have analysed two large comprehensive prospective clinical registries of patients with AF, the EURObservational Research Programme (EORP) and the Asia Pacific Heart Rhythm Society (APHRS), to compare the achievement of the ESC quality indicators in two major world populations. Methods The EORP and APHRS registries used the same electronic case report forms to collect data. T-test and Chi-squared test were used to compare registries. Logistic regression was used to identify pharmacological rate control therapy predictors in permanent AF. The model was adjusted for age, oral anticoagulation (OAC), EHRA and CHA2DS2-VASc scores, heart rate on the latest ECG and the region of recruitment (Europe or Asia) (STATA Corp, version 13). Results All 11096 EORP patients (59.3% males, age 69±11 years) and 5460 APHRS patients (66.3% males, age 68±12 years) had CHA2DS2-VASc and HAS-BLED scores documented at enrolment. The EORP register included a higher proportion of patients with CHA2DS2VASc ≥2 (81% vs 70%, p&amp;lt;0.001). These patients had similar OAC use (87%) in both registries, but NOAC use was higher in the APHRS (67% vs 34%, p&amp;lt;0.001), while dual antithrombotic use was more common in the EORP (14% vs 8%, p&amp;lt;0.001). The Table lists paraments that may impact OAC prescription. In patients with permanent AF, heart rate (82±20 vs 78±20, p&amp;lt;0.001) and antiarrhythmic pharmacotherapy (9% vs 5%) was higher in the EORP registry. On logistic regression, independent predictors of rate control with antiarrhythmic pharmacotherapy were higher EHRA 3 score (adjusted odds ratio (aOR) 1.8; 95% confidence interval (CI) 1.3–2.5, p&amp;lt;0.001); faster heart rate (aOR 1.01; 95% CI 1.00–1.02, p&amp;lt;0.001); younger age (aOR 0.97; 95% CI 0.96–0.98, p&amp;lt;0.001) and being recruited to the APHRS (aOR 0.56; 95% CI 0.40–0.79, p=0.001). APHRS vs EORP patients with non-permanent AF were less symptomatic (EHRA score I in 56% vs 38%) with less frequent use of antiarrhythmics (25% vs 37%), rhythm-management interventions (32% vs 46%), but higher use of catheter ablation (p&amp;lt;0.001 for all). Conclusion There are significant regional variations in achievement of the ESC quality indicator for AF. The variations may be due to differences in healthcare systems, but they may also reflect the population characteristics. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Since the start of EORP, the following companies have supported theprogramme: Abbott Vascular Int. (2011-2014), Amgen Cardiovascular(2009-2018), AstraZeneca (2014-2017), Bayer AG (2009-2018),Boehringer Ingelheim (2009-2019), Boston Scientific (2009-2012), TheBristol Myers Squibb and Pfizer Alliance (2011-2016), The Alliance DaiichiSankyo Europe GmbH and Eli Lilly and Company (2011-2017), Edwards(2016-2019), Gedeon Richter Plc. (2014-2017), Menarini Int. Op. (2009-2012), MSD-Merck &amp; Co. (2011-2014), Novartis Pharma AG (2014-2017), ResMed (2014-2016), Sanofi (2009-2011), and SERVIER (2009-2018).The Atrial Fibrillation NETwork (AFNET), conducting the registryin Germany, received support from The Bristol Myers Squibb/PfizerAlliance (2014-2018) and the German Centre for CardiovascularResearch (DZHK).

Dronedarone versus sotalol in patients with atrial fibrillation: a systematic literature review and network meta-analysis

Abstract Background There are limited comparative data on safety and efficacy within Vaughn Williams class III anti-arrhythmic drugs (AADs) for maintenance of sinus rhythm in adults with atrial fibrillation (AF). Purpose We sought to compare the safety and efficacy of dronedarone and sotalol, two commonly prescribed Vaughn Williams class III AADs with class II rate-controlling properties in patients with non-permanent AF. Methods A systematic literature review was conducted by searching MEDLINE®, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) up to June 15, 2021. Clinical trials and observational studies that evaluated safety and efficacy of dronedarone or sotalol in adults with AF were included. Where feasible, Bayesian random-effects network meta-analysis (NMA) was conducted to estimate comparative safety and efficacy. Where possible, sensitivity analyses were conducted by including only randomized controlled trials (RCTs). Results Of 3,581 records identified through database searches, 37 unique studies (23 RCTs, 13 observational studies, and 1 non-randomized trial) were included in the NMA. Dronedarone was associated with a statistically significantly lower risk of all-cause death versus sotalol in the all-studies NMA (hazard ratio [HR]: 0.38; 95% credible interval [CrI]: 0.19, 0.74; 22 studies); sensitivity analysis followed the same trend numerically (HR: 0.46; 95% CrI: 0.21, 1.02; 16 RCTs). Risk ratios of AF recurrence were not significantly different between dronedarone and sotalol in both all-studies and sensitivity analyses. Conclusion Dronedarone, compared with sotalol, was associated with significantly lowered risk of all-cause death in the analysis combining RCTs and observational studies, with no differences in AF recurrence observed between the two therapies. This meta-analysis provides a comprehensive assessment of safety and efficacy evidence useful in evaluating treatment options in AF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sanofi

Effect of an Exercise and Nutrition Program on Quality of Life in Patients With Atrial Fibrillation: The Atrial Fibrillation Lifestyle Project (ALP)

BackgroundStudies of separate exercise and weight loss interventions have reported improvements in quality of life (QoL) or reduction in atrial fibrillation (AF) burden. We investigated the impact of a structured exercise, nutrition, and risk-factor-modification program on QoL and AF burden. MethodsIn this trial, 81 successive patients with body mass index > 27 kg/m2 and nonpermanent AF were randomized to an intervention (n = 41) or control group (n = 40). The intervention consisted of cardiovascular risk management and a 6-month nutrition and exercise program, followed by a 6-month maintenance program. All participants received usual AF care. The primary end-point was QoL at 6 and 12 months. ResultsAt 6 months, we observed improved QoL among patients in the intervention group, relative to that among control-group patients (intervention (I) n = 34, control (C) n = 38) in the 36-item Short Form Survey Instrument scores on the subscales of vitality (I: 13.2 ± 20.4; C: 1.0 ± 14.9, P < 0.001), social functioning (I: 14.7 ± 24.1; C: 2.4 ± 21.2, P = 0.018), emotional well-being (I: 5.5 ± 14.1 ; C: –1.0 ± 13.3, P = 0.017), and general health perceptions (I: 8.1 ± 12.3; C: 2.7 ± 13.3, P = 0.009). At the 6-month follow-up, improvement in the scores on the subscales of vitality (P = 0.021) and emotional well-being (P = 0.036) remained significant. The burden of AF as measured by Holter monitor and Toronto AF symptom score was not significantly changed. ConclusionsA structured exercise and nutrition program resulted in significant sustained improvements in QoL, without reduction in AF burden. This type of program may provide an additional treatment for people with impaired QoL due to AF.

Rhythm control without catheter ablation may have benefits beyond stroke prevention in rivaroxaban-treated non-permanent atrial fibrillation

The current treatment paradigm for atrial fibrillation (AF) prioritizes rate control over rhythm control; however, rhythm control has shown benefits over other AF strategies. This study compares the outcomes of rivaroxaban with and without concomitant antiarrhythmic drugs (AADs), using propensity score matching to correct for statistical effects of baseline discrepancies. This multi-center retrospective study included 1,477 patients with non-permanent AF who took rivaroxaban for at least one month between 2011 and 2016 and had not received catheter ablation. Concomitant AAD use was compared against clinical outcome endpoints for effectiveness, safety, and major adverse cardiac events (MACE). Associations with concomitant AAD use were evaluated using multivariate Cox proportional hazard analyses. Patients were divided into two matched groups: rivaroxaban alone (n = 739) and with concomitant AADs (n = 738). The cumulative incidences of safety (p = 0.308), effectiveness (p = 0.583), and MACE (p = 0.754) were similar between the two groups, and multivariate analysis showed no significant differences. The new thromboembolism and all-cause death rates were higher in rivaroxaban alone (2.7% vs 0.8%, p = 0.005; and 10% vs. 6.9%, p = 0.032, respectively). The heart failure readmission rate was higher in the concomitant-AAD group (8.4% vs. 13.3%, p = 0.003). The concomitant use of rivaroxaban with AADs appears to be well-tolerated, with lower rates of thromboembolism and all-cause death, but is associated with more occurrences of congestive heart failure.

Clinical Outcome of Hospitalized COVID-19 Patients with History of Atrial Fibrillation.

Background and objectives: Pre-existing atrial fibrillation (AF) is a frequent comorbidity in hospitalized patients with COVID-19; however, little is still known about its prognostic role in infected patients. The aim of our study was to evaluate whether the pre-existing AF as comorbidity would contribute to increase the risk for severe forms of COVID-19, worse prognosis, or even higher mortality. Materials and Methods: We retrospectively evaluated all consecutive COVID-19 patients admitted to the emergency department of nine Italian Hospitals from 1 March to 30 April 2020.The prevalence and the type of pre-existing AF have been collected. The correlation between the history and type of AF and the development of severe ARDS and in-hospital mortality has been evaluated. Results: In total, 467 patients (66.88 ± 14.55 years; 63% males) with COVID-19 were included in the present study. The history of AF was noticed in 122 cases (26.1%), of which 12 (2.6%) with paroxysmal, 57 (12.2%) with persistent and 53 (11.3%) with permanent AF. Among our study population, COVID-19 patients with AF history were older compared to those without AF history (71.25 ± 12.39 vs. 65.34 ± 14.95 years; p < 0.001); however, they did not show a statistically significant difference in cardiovascular comorbidities or treatments. Pre-existing AF resulted in being independently associated with an increased risk of developing severe ARDS during the hospitalization; in contrast, it did not increase the risk of in-hospital mortality. Among patients with AF history, no significant differences were detected in severe ARDS and in-hospital mortality between patients with permanent and non-permanent AF history. Conclusions: Pre-existing AF is a frequent among COVID-19 patients admitted to hospital, accounting up to 25% of cases. It is independently associated with an increased risk of severe ARDS in hospitalized COVID-19 patients; in contrast, it did not affect the risk of death. The type of pre-existing AF (permanent or non-permanent) did not impact the clinical outcome.

Autonomic Afferent Dysregulation in Atrial Fibrillation.

This study sought to evaluate the role of cardiac afferent reflexes in atrial fibrillation (AF). Efferent autonomic tone is not associated with atrial remodeling and AF persistence. However, the role of cardiac afferents is unknown. Individuals with nonpermanent AF (n=48) were prospectively studied (23 in the in-AF group and 25 in sinus rhythm [SR]) with 12 matched control subjects. We performed: 1) low-level lower body negative pressure (LBNP), which decreases cardiac volume, offloading predominantly cardiac afferent (volume-sensitive) low-pressure baroreceptors; 2) Valsalva reflex (predominantly arterial high-pressure baroreceptors); and 3) isometric handgrip reflex (both baroreceptors). We measured beat-to-beat mean arterial pressure (MAP) and heart rate (HR). LBNP elicits reflex vasoconstriction, estimated using venous occlusion plethysmography-derived forearm blood flow (∝1/vascular resistance), maintaining MAP. To assess reversibility, we repeated LBNP (same day) after 1-hour low-level tragus stimulation (in n=5 in the in-AF group and n=10 in the in-SR group) and >6weeks post-cardioversion (n=7). The 3 groups were well matched for age (59 ± 12 years, 83% male), body mass index, and risk factors (P=NS). The in-AF group had higher left atrial volume (P< 0.001) and resting HR (P = 0.01) but similar MAP (P = 0.7). The normal LBNP vasoconstriction (-49 ± 5%) maintaining MAP (control subjects) was attenuated in the in-SR group (-12 ± 9%; P = 0.005) and dysfunctional in the in-AF group (+11 ± 6%; P< 0.001), in which MAP decreased and HR was unchanged. Valsalva was normal throughout. Handgrip MAP response was lowest in the in-AF group (P = 0.01). Interestingly, low-level tragus stimulation and cardioversion improved LBNP vasoconstriction (-48 ± 15%; P = 0.04; and -32 ± 9%; P = 0.02, respectively). Cardiac afferent (volume-sensitive) reflexes are abnormal in AF patients during SR and dysfunctional during AF. This could contribute to AF progression, thus explaining "AF begets AF." (Characterisation of Autonomic function in Atrial Fibrillation [AF-AF Study]; ACTRN12619000186156).

Polygraphy as a new screening method for obstructive sleep apnea in patients with atrial fibrillation?

Abstract Background Obstructive sleep apnea (OSA) is a modifiable risk factor of atrial fibrillation (AF) but is underdiagnosed in these patients. According to the 2020 European Society of Cardiology guidelines for the diagnosis and management of AF, it seems reasonable to test for OSA in symptomatic AF patients before initiation of rhythm control therapy. A good OSA screening pathway is lacking in the guidelines and in daily clinical practice in most centers today. Polysomnography (PSG) is the gold standard for diagnosing OSA but it is not an ideal screening method, due to its expensiveness, labour-intensiveness and limited availability. Purpose The aim of this study was to validate and examine the performance of different (cardiorespiratory) polygraphy (PG) devices, used with their automated algorithm to detect OSA in an AF cohort, compared with PSG as gold standard. Methods Prospective study with three PGs (ApneaLink Air (ALA), SOMNOtouch RESP (STR) and SpiderSAS (SpS) combined with ResMed Airview-, SomnoMedics DOMINO- and Microport SYNESCOPE software respectively) in consecutive AF patients who were referred for a PSG evaluation. Patients received the three devices with instructions for use after their PSG and were requested to use each one during three consecutive nights at home. Severity of OSA was classified according to the Apnea-Hypopnea Index (AHI) with &amp;lt;5 events/hour= no OSA, 5–14= mild-, 15–30= moderate-, &amp;gt;30= severe OSA. Results A total of 100 AF patients presenting for PSG were included (64.0±8.6 years, 73% male, 87% non-permanent AF, mean Body Mass Index 30.6±5.9 kg/m2, mean CHA2DS2-VASc score 2.4±1.7, mEHRA≥2 in 64%; mean AF history 5.4±5.6 years). PSG diagnosed ≥mild OSA in 90% of patients, ≥moderate in 69%, and severe OSA in 33%. Successful PG execution to determine the AHI, i.e. ≥4 hours of data on automated analysis, was obtained in 72.0%, 73.0% and 79.0% of patients with the ALA, STR and SpS respectively. In screening for clinically relevant OSA (i.e. at least moderate OSA), the PGs had an area under the curve of 0.802, 0.761 and 0.803 for the ALA, STR and SpS respectively (Figure 1). Conclusions This first analysis shows that PGs combined with an automated algorithm for AHI determination, can be used as OSA screening tools in AF patients before referral for PSG. Further optimisation is likely by choosing an appropriate AHI cut-off value for each PG. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This study is supported by the Antwerp University Cardiology Research Fund, and is part of Limburg Clinical Research Center, supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish government, Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. Figure 1

Efficacy and safety of dronedarone across age and sex subgroups: a post hoc analysis of the ATHENA study among patients with non-permanent atrial fibrillation/flutter.

Age and sex may impact the efficacy of antiarrhythmic drugs on cardiovascular outcomes and arrhythmia recurrences in patients with atrial fibrillation (AF). We report on a post hoc analysis of the ATHENA study (NCT00174785), which examined cardiovascular outcomes in patients with non-permanent AF treated with dronedarone vs. placebo. Efficacy and safety of dronedarone were assessed in patients according to age and sex. Baseline characteristics were comparable across subgroups, except for cardiovascular comorbidities, which were more frequent with increasing age. Dronedarone significantly reduced the risk of cardiovascular hospitalization or death due to any cause among patients 65-74 [n = 1830; hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.60-0.83; P < 0.0001] and ≥75 (n = 1925; HR 0.75, 95% CI 0.65-0.88; P = 0.0002) years old and among males (n = 2459; HR 0.74, 95% CI 0.64-0.84; P < 0.00001) and females (n = 2169; HR 0.77, 95% CI 0.67-0.89; P = 0.0002); outcomes were similar for time to AF/AFL recurrence. Among patients aged <65 years (n = 873), cardiovascular hospitalization or death due to any cause with dronedarone vs. placebo was associated with an HR of 0.89 (95% CI 0.71-1.11; P = 0.3). The incidence of all treatment-emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation was comparable among males and females, and increased with increasing age. These results support the use of dronedarone for the improvement of clinical outcomes among patients aged ≥65 years and regardless of sex.

Stroke Prevention by Anticoagulants in Daily Practice Depending on Atrial Fibrillation Pattern and Clinical Risk Factors.

The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns. A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors. In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.50–0.98) for dabigatran, 0.68 (95% CI, 0.53–0.86) for rivaroxaban, and 0.73 (95% CI, 0.52–1.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.14–0.68), 0.64 (95% CI, 0.39–1.06), and 0.70 (95% CI, 0.33–1.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients. Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.

Non-valvular atrial fibrillation recurrence after sinus rhythm restoring at different follow-up periods: phenotype-genotype high-risk groups, considering rs10465885 polymorphism in connexin-40 gene

Abstract Funding Acknowledgements Type of funding sources: None. Purpose to provide risk stratification of non-valvular atrial fibrillation (AF) recurrence after sinus rhythm restoring (SRR) in patients (pts) with AF at different follow-up periods (3 months (AFr3m), 12 months (AFr12m) and 18 months [AFr18m]), based on phenotype-genotype high-risk groups, considering rs10465885 polymorphism in connexin-40 gene (SNP-Cx40). Methods. We enrolled 186 pts (mean age (55 ± 10) years; males 123 [66,1%]) with AF (paroxysmal – 86, persistent – 72, stable – 28 pts; first onset (FO) AF – 48 pts). Clinical, laboratory and echocardiographic data were analyzed. SNP-Cx40 was genotyped by real time PCR (T – reference, C – minor allele) in 112 pts. The genotypes were distributed as follows: TT – 25,9% (n = 29); CT – 49,1% (n = 55); CC – 25,0% (n = 28). SRR was performed in 112 cases (102 pts) with non-permanent AF: 30 – pharmacological cardioversion (PCV), 62 – direct-current cardioversion (DCV), 20 cases – radiofrequency ablation (RFA). AFr3m occurred in 53 (43,4%) of 122 available cases; AFr12m – 65,5% (76/116); AFr18m – 75,2% (79/105). The Artificial Neural networks (ANNs) analysis was performed to select the AF recurrence predictors. We considered the ANN activation function value (Y) and its relation to Y cut-off value (Ycrit). In case of Y &amp;gt; Ycrit, the AF recurrence risk was considered as «high». Results. We built three nonlinear ANN models (multilayer perceptrons) for AFr3m (Ycrit = 0,496), AFr12m (Ycrit = 0,503) and AFr18m (Ycrit = 0,720) risk prediction. In case of SNP-Cx40 CC genotype carriage, we determined the additional increase of AFr3m risk after PCV in pts with CHA2DS2-VASc score «0» and normal (Y = 0,629) or mildly decreased (Y = 0,616) left ventricular mid-wall fractional shortening, and in the case of its moderate decrease – both after PCV (Y = 0,585) and DCV (Y = 0,627). The CC genotype was associated with AFr12m high risk in pts without heart failure (HF) and mildly increased left atrial dimension (LAD) – both after PCV (FO AF with known precise event duration (PED); Y = 0,906) or DCV (FO AF with unknown PED; Y = 0,911). Additionally, CC genotype was associated with AFr12m high risk after RFA in pts without HF and normal or mildly increased LAD (Y = 0,912), and in pts with HF B or C1 stage (according to modified AHA/ACC classification) with moderately increased LAD (Y = 0,912). The high-risk groups of AFr18m in pts with CC genotype were as follows (Y = 0,913): after RFA in pts with recurrent AF and presence of episodes lasting ≥7 days; after PCA in case of FO AF with unknown PED and index episode lasting ≥1 month; after DCV in case of FO AF with unknown PED and index episode lasting ≥12 months. Conclusion. AFr3m, AFr12m and AFr18m, besides SNP-Cx40, were non-linearly associated with SRR type, and certain clinical and echocardiographic phenotypic parameters, which could be used for AF recurrence risk stratification, with the selection of phenotype-genotype high-risk groups, considering SNP-Cx40.

Usefulness of different screening questionnaires and scoring systems for obstructive sleep apnea in patients with atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): This study is part of Limburg Clinical Research Center, supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish government, Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. OnBehalf Research Group Cardiovascular Diseases, University of Antwerp Background Obstructive sleep apnea (OSA) influences the progression of atrial fibrillation (AF) but is underdiagnosed in this population. Studies have shown that its treatment can help to reduce AF recurrences and improve symptoms. Polysomnography (PSG) is currently the gold standard for diagnosing OSA but being expensive and requiring overnight examination it is therefore not the ideal screening method. Different OSA screening tools such as questionnaires and scoring systems already exist but their value in AF patients remains unclear. Purpose The aim of this study was to examine the performance of different screening questionnaires and scoring systems for diagnosing OSA in an AF cohort, compared with PSG as gold standard. Methods Prospective study of the predictive performance of seven screening questionnaires and scoring systems (the Epworth Sleepiness Scale (ESS), the Berlin Questionnaire (BQ), Sleep Apnea Clinical Score (SACS), OSA50, STOP-BANG, NoSAS, MOODS) in consecutive AF patients referred to two sleep clinics. Results A total of 100 AF patients presenting for PSG were included (64.0 ± 8.6 years, 73% male, 87% non-permanent AF, mean Body Mass Index 30.6 ± 5.9 kg/m2, mean CHA2DS2-VASc score 2.4 ± 1.7, mEHRA≥2 in 64%; mean AF history 5.4 ± 5.6 years). Forty-two percent of patients were referred to the sleep clinic by cardiologists. PSG diagnosed ≥mild OSA in 90% of patients, ≥moderate in 69%, and severe OSA in 33%. In screening for mild OSA, NoSAS, STOP-BANG and MOODS screening questionnaires had a fair area under the curve (AUC) of 0.773, 0.710 and 0.709 respectively. For at least moderate OSA, only the SACS and the NoSAS questionnaires had an AUC of 0.704 and 0.712 respectively (Figure 1). None of the seven screening questionnaires/scoring systems were performant enough (i.e. a fair AUC &amp;gt; 0.7) to detect severe OSA. Conclusions Our analysis shows that screening questionnaires and scoring systems such as ESS, BQ, SACS, NoSAS, OSA50, STOP-BANG and MOODS are not very useful to predict clinically relevant OSA (i.e. at least moderate OSA) in AF patients. Therefore, other screening modalities for OSA in AF patients should be investigated and validated. Abstract Figure 1