Cohort Of Atrial Fibrillation Patients Research Articles

The impact of peri-procedural imaging on safety and efficacy of atrial fibrillation ablation: insights from the Israeli AF Catheter Ablation Registry (ICAR).

Pulmonary vein isolation (PVI) is the most effective therapy to achieve rhythm control in atrial fibrillation (AF). Peri-procedural imaging is used in many but not all centers. However, the impact of imaging on safety and efficacy of PVI is not clear. The Israeli Catheter Ablation Registry (ICAR) is a great opportunity to explore this issue in real-world practice. To describe the real-world utilization of peri-procedural imaging technologies in a large cohort of patients undergoing ablation for AF. A prospective-multicenter cohort of AF patients who underwent PVI during the years 2019-2021. Peri-procedural imaging (CT, ICE, TEE) was utilized based on the center and operator discretion. The study endpoints were peri-procedural complications and AF recurrence at 12months follow-up among patients with and without peri-procedural imaging. Between January 2019 and December 2021, a total of 921 patients underwent PVI. Peri-procedural imaging (at least 1 modality of CT, TEE, and or ICE) was utilized in 753 (81.8%) and no imaging among 168 (18.2%) patients. Cryoablation was the dominant energy used for PVI in both groups (92.3% of the non-imaging group, and 95.3% among imaging group), while RF was used in the rest of the patients. Fluoroscopy time was not different between the 2 groups; however, procedure duration was longer among the imaging group (90min) compared to the non-imaging group (74.5min, p = 0.006). By 12months, the incidence of AF recurrence and repeated ablation were not different between the groups. Complications and re-hospitalization for cardiocerebrovascular reasons were not different among the 2 groups. Cox regression model demonstrated no association between preprocedural imaging and the risk of AF recurrence after ablation. This real-world multicenter prospective registry study demonstrated that the rate of complications and the rate of recurrence of AF during 1year follow-up were not different among patients who had PVI either with or without peri-procedural imaging.

Early rhythm control in patients with recently diagnosed atrial fibrillation: findings from the GLORIA-AF Registry Phase III

Abstract Background Early rhythm control (ERC) can improve outcomes in select patients with atrial fibrillation (AF) but real-world data are lacking. Purpose To evaluate the effectiveness of ERC in a real-world cohort of AF patients. Methods From the global, prospective GLORIA-AF Phase III Registry, adult patients with recent diagnosis (< 3 months and < 4.5 months in Latin America) of AF and CHA2DS2-VASc score ≥1 were included. ERC was defined as treatment with an antiarrhythmic drug, catheter ablation, or cardioversion at the baseline. Multivariable logistic regression analysis determined the odds of receiving ERC and an oral anticoagulant [OAC] with results reported as adjusted Odds Ratio (aOR) and 95% Confidence Intervals (95%CI). Risk of major outcomes was determined using multiple Cox regression analyses. The primary outcome was a composite of all-cause death and major adverse cardiovascular events (MACE). Secondary outcomes included all-cause death, thromboembolism and major bleeding. Results were reported as adjusted Hazard Ratio (aHR) and 95%CI. Results 21,051 AF patients (age: 70.2±10.3, 45% female) were included. Of these, 6,932 (32.9%) received ERC, while 14,119 (67.1%) did not. Patients receiving ERC were younger with a higher prevalence of paroxysmal AF (62.8% vs. 53.2%) and heart failure (23.1% vs. 21.4%). They were less likely to have prior stroke/transient ischemic attack (TIA), chronic obstructive pulmonary disease (COPD), and they had a lower mean CHA2DS2-VASc score (3.0±1.5 vs. 3.3±1.5). Age ≥75 [aOR: 0.53; 95%CI (0.0.49-0.57)] and age 65-75 [aOR: 0.76; 95%CI (0.70-0.82)] were associated with lower odds of receiving ERC. Those with prior stroke/TIA [aOR: 0.55; 95%CI (0.50-0.61)] and COPD [aOR: 0.82; 95%CI (0.71-0.94)], as well as patients with more sustained form of AF and patients recruited in North America were less likely to receive ERC. Conversely, female sex, higher symptom burden, hypertension and coronary artery disease were associated with higher odds of receiving ERC (Figure 1). Patients who received ERC were more likely to receive OACs [aOR: 1.36; 95%CI (1.25-1.48)]. Survival curve for the primary outcome according to ERC are shown in Figure 2. During a median follow-up of 3.0 [IQR: 2.9-3.1] years, ERC was associated with lower risk of the primary composite outcome (aHR: 0.88, 95% CI:0.80-0.96, p=0.006); Similar results were observed for the secondary outcomes. Conclusions In a real-world population with recently diagnosed AF, clinical risk factors and characteristics were associated with ERC. Patients who received ERC had a reduced risk of major outcomes. These findings suggest that in real-world patients with AF, ERC may provide beneficial effects on long-term outcome.Odds Ratios to be treated with ERC.Survival curve.

Left atrial appendage clipping during hybrid atrial fibrillation ablation: a very long-term, single-center experience

Abstract Background/introduction Epicardial left atrial appendage (LAA) clipping is an effective strategy for stroke prophylaxis in high thromboembolic (TE) and bleeding risk patients with atrial fibrillation (AF). In addition to LAA exclusion from systemic circulation, clipping promotes concomitant appendage isolation, which might have positive impacts on arrhythmia control. Purpose The aim of this study was to report safety, success rate, and the long-term clinical outcomes of LAA clipping in a large cohort of AF patients undergoing concomitant hybrid ablation. Methods Consecutive patients undergoing hybrid AF ablation between 2013 and 2023 were enrolled. Hybrid ablation was performed in a one-step procedure consisting of thoracoscopic epicardial radiofrequency (RF) ablation followed by endocardial mapping and ablation, if needed. Ablation lesion set included pulmonary vein (PV) and posterior wall (PW) isolation, as well as RF applications to the LAA/posterolateral ridge. LAA clipping was performed via Atriclip exclusion system (Atricure, Inc., The Nederlands) after epicardial ablation. Additional endocardial lesions were performed in case of incomplete epicardial ablation or at physician’s discretion. Results A total of 130 patients were included (mean age: 65±9.4; 72.3% males); among them, 19.2% and 55.4% had persistent or long-standing persistent AF, respectively. Mean CHA2DS2-VASC and HAS-BLED were 3.1±1.1 and 2.3+-0.5. Five patients (3.8 %) had absolute contraindication to long-term oral anticoagulation, 3 (2.3%) had previous life-threatening bleeding events, 17 (13.1%) had a previous TE event. The final clip size was 35mm in 90.7% cases. Acute success was achieved in 97.7%; failure was due to LAA size (n=1), proximity to phrenic nerve (n=1), or bypass graft (n=1). One patient had incomplete occlusion due to a large secondary lobe, which required a second clip. No periprocedural complications related to clipping were documented. At a mean follow-up of 51±35 months, one (0.8%) patient had a stroke and 3 (2.3%) a transient ischemic attack (4 events per 552 patient/years; 0.7%). One patient had a microreentrant tachycardia mapped from the area near the LAA clipping. Conclusion In a large cohort undergoing hybrid AF ablation, epicardial LAA clipping was safe and highly successful. Acute failure was rare and due to LAA morphology or proximity to phrenic nerve and bypass graft. Thromboembolic event rate was very low.

Effect of early cryoballoon ablation on atrial fibrillation recurrence-A Danish nationwide register study.

Cryoballoon ablation is a safe and efficient rhythm control strategy in atrial fibrillation (AF) patients. The impact of time from diagnosis to ablation is unclear. The aim of this study was to examine the impact of timing of first-time cryoballoon ablation on AF recurrence in a nationwide cohort of AF patients. From nationwide registers, all AF patients ≥18 years of age who underwent first-time AF cryoballoon ablation in Denmark from 2012 to 2018 were included. The AF patients were stratified by ablation timing: Early group (≤1 year after AF diagnosis), intermediate group (1-3 years after AF diagnosis), and late group (≥3 years after AF diagnosis). By adjusted Cox regression models, the effect of timing on AF recurrence was examined. This study included 1064 AF patients with a median age of 63 years. Most patients were male (66%) and had paroxysmal AF (67%). The 1-year risk of AF recurrence increased from 31% in the early group to 41% and 44% in the intermediate and late group. The hazard ratios (95% confidence intervals) were 1.28 (0.95, 1.74) in the intermediate group and 1.42 (1.09, 1.86) in the late group when compared to the early group. Continuous diagnosis-to-ablation time seemed to have the greatest impact on AF recurrence within the first 2 years. In AF patients undergoing cryoballoon ablation, late timing of ablation was associated with a significantly higher AF recurrence rate when compared to early timing of ablation. These findings support early cryoballoon ablation to improve the outcomes after ablation.

Targeting subclinical ventricular dysfunction in atrial fibrillation: What can myocardial work add?

Atrial fibrillation (AF) could impact on left ventricular function leading to a sublinical myocardial dysfunction, as identified by myocardial work parameters in a population-based cohort of AF patients compared with healthy individuals; factors associated with these parameters are also shown. SBP: systolic blood pressure; LAVI: left atrial volume index.

Sex differences in cognitive impairment and association with all-cause mortality: a report from a contemporary cohort of patients with atrial fibrillation

Abstract Background Cognitive impairment (Cogn-Imp) in patients with atrial fibrillation (AF) has been associated with adverse outcomes. The impact of sex on the association between AF and Cogn-Imp is complex and there are limited data on specific sex-differences in AF patients with Cogn-Imp and association with outcomes. Purpose To investigate the impact of sex on Cogn-Imp, as well as the association of Cogn-Imp with adverse outcomes at follow-up in a contemporary cohort of patients with AF. Methods We analyzed patients enrolled in prospective observational study of AF patients. Cognitive status was evaluated by the Mini-Mental State Examination (MMSE). Patients were stratified according to MMSE scores obtained at baseline. A MMSE score <24 was considered suggestive of Cogn-Imp. All-cause mortality was the primary outcome. Results A total of 931 AF patients were included (median age 75 [IQR 66-82], CHA2DS2VASc score median 4 [2-5], HASBLED median 1 [1-2]). Almost ninenty percent (830/910, 89.2%) of the patients were treated with oral anticoagulants (OACs). Overall, 159/931 (17.1%) of the patients had a MMSE score <24 at baseline, indicative of Cogn-Imp. Female patients had a significant higher prevalence of Cogn-Imp compared to males (22.2% vs 14.0%, p=0.001). At the multivariable logistic regression analysis (adjusted for age, hypertension, previous stroke, coronary artery disease, diabetes, CKD, PAD, heart failure, AF type and use of OACs) female sex was independently associated with Cogn-Imp (adjusted OR 1.70, 95% CI 1.13-2.57). After a median follow-up of 633 [IQR 199-1503] days, all-cause mortality was 15.6% with a significant higher prevalence in patients with Cogn-Imp vs. No-Cogn-Imp, both for males (33.3% vs 15.8%, p<0.001) and females (29.6% vs 10.5%, p<0.001). Kaplan-Meier analysis showed a lower cumulative survival of patients with Cogn-Imp vs. No-Cogn-Imp (Log Rank p=0.01, Figure). At the adjusted Cox regression analysis, Cogn-Imp was associated with an independent higher risk of all-cause mortality both in males (adjusted HR 1.99, 95% CI 1.17-3.39) and females (adjusted HR 2.03, 95% CI 1.05-3.93). Stratifying the population by age, some differences in terms of association between Cogn-Imp and all-cause mortality were evident (Table). Cognitive impairment was associated with a higher risk of all-cause mortality in female patients aged 75-84 and ≥85 years old, but among males only in patients aged 75-84. Conclusions In a prospective observational real-world cohort of AF patients, female sex was independently associated with a higher occurrence of Cogn-Imp compared to male sex. Cognitive impairment was independently associated with a higher risk of all-cause mortality in both sexes with some differences across age categories suggesting peculiar pathophysiological interactions which warrant further investigations.

Impact of chronic obstructive pulmonary disease on the natural history of atrial fibrillation: a report from the GLORIA-AF registry phase II & III

Abstract Background The relationship between chronic obstructive pulmonary disease (COPD) and atrial fibrillation (AF) remains unclear. COPD may influence the management and prognosis of AF and may affect treatments, including beta-blockers prescription. Purpose To investigate the association between COPD and AF, and assess the impact of COPD on treatment patterns and major adverse outcomes in a large contemporary global cohort of AF patients. Methods The GLORIA-AF Registry enrolled newly diagnosed AF patients with at least 1 stroke risk factor. Diagnosis of COPD and treatments (including oral anticoagulant [OAC]) prescribed were recorded by investigators at baseline. We evaluated clinical characteristics associated with the diagnosis of COPD at baseline, OAC and other treatment prescription, and risk of OAC discontinuation. Adjusted Cox-regression models were utilized to analyse the relationship of COPD with major outcomes including a primary composite outcome of all-cause death and major adverse cardiovascular events (MACE). Results 36,263 patients (mean age 70.1±10.5 years, 45.3% females) were included in this analysis. Patients with COPD (n=2,261, 6.2%) were older, and had higher thromboembolic risk. Increasing age, smoking status, BMI and cardiovascular comorbidities were associated with higher odds of COPD diagnosis at baseline. COPD was associated with higher odds of receiving OACs (Odds Ratio [OR] and 95% Confidence Interval [CI]: 1.31, 1.15-1.49), and with a higher risk of discontinuing OACs during follow-up (hazard ratio (HR): 1.14, 95%CI: 1.03-1.27). COPD patients were more likely prescribed with digoxin and verapamil or diltiazem, with lower prescription of beta-blockers (OR [95%CI]: 0.79, 0.72-0.87; Figure 1) and amiodarone (OR [95%CI]: 0.83, 0.73-0.96). Patients with COPD were at higher risk of the primary outcome of all-cause death and MACE (Hazard Ratio [95%CI]: 1.78, 1.58-2.01; Figure 2), and were also found at higher risk of all-cause mortality, cardiovascular death, MACE and major bleeding, while no statistically significant differences were observed for thromboembolism. There was no statistically significant interaction between beta-blocker use and risk of the primary composite outcome in COPD patients. Conclusions COPD is associated with different treatment patterns in AF patients, higher risk of OAC discontinuation, and ultimately a poorer clinical prognosis, with an increased risk of all-cause death, MACE and major bleeding. Beta-blocker use appeared safe in COPD patients.Figure 1Figure 2

Patterns of comorbidities and influence on the natural history of patients with atrial fibrillation: a latent class analysis from a prospective observational european AF registry

Abstract Background Patients with Atrial Fibrillation (AF) usually present with multiple comorbidities at diagnosis, and their combinations heterogeneously influence management and outcomes. While the effect of multimorbidity on the natural history of AF is well-known, the influence of patterns of multimorbidity is far less understood. Purpose To identify and analyse subgroups of AF patients according to their comorbidities, through a latent class analysis of a contemporary cohort of AF patients. Methods We used data from a European-wide prospective observational AF registry, and performed a latent class analysis, according to the presence of chronic diseases (including cardiovascular, respiratory, metabolic and other conditions); class membership was assigned according to the modal posterior probability. Multivariable logistic regression models were used to analyse odds of receiving oral anticoagulant (OAC) prescription and type of OAC received; the risk of the primary outcome of all-cause death and MACE was assessed using multivariable Cox-regression model. Results 9,613 AF patients were included in this analysis (mean age 68.9 ± 11.4 years, 40.2% females), and were grouped in 5 classes, which were different according to the burden of comorbidities: low morbidity pattern (46.1%), cardiovascular pattern (25.0%), metabolic pattern (11.3%), heart failure pattern (9.7%) and multisystemic pattern (8.0%) (Figure 1). Patients in the multisystemic pattern were older and more frequently frail and with polypharmacy compared to other classes. Compared to the low morbidity pattern, odds of receiving OAC was lower in those with cardiovascular pattern (OR [95%CI]: 0.73 [0.62-0.86]), heart failure pattern (OR [95%CI]: 0.60 [0.48-0.75] and multisystemic pattern (OR [95%CI]: 0.28 [0.22-0.36]), while those with metabolic pattern were more likely prescribed OAC (OR [95%CI]: 1.55 [1.20-2.00]). All patterns were less likely treated with NOAC compared to VKA (Figure 2). When analysing the risk of the primary composite outcome, all patterns except for the metabolic pattern were associated with higher hazard of events, with highest magnitude observed for the heart failure pattern (HR 2.68 [95%CI: 2.22-3.25]) and the multisystemic pattern (HR 2.67 [2.13-3.35]) (Figure 2). Conclusions Comorbidities are heterogeneously distributed in the AF population, and different phenotypes of AF patients may be identified according to the combination of other chronic diseases, with different OAC use for stroke prevention and an unequal impact on long-term prognosis. These findings reinforce the need for tailored preventive strategies to improve outcomes in AF patients, especially those with multimorbidity.Figure 1Figure 2

Combined Radiofrequency Ablation and Left Atrial Appendage Closure in Atrial Fibrillation and Systolic Heart Failure.

Managing patients with atrial fibrillation (AF) and comorbid heart failure (HF) with reduced (HFrEF) or mildly reduced ejection fraction (HFmrEF) is of clinical importance but a great challenge. This study aimed to evaluate the clinical benefit of the combined radiofrequency catheter ablation (RFCA) and left atrial appendage closure (LAAC) procedure in AF patients complicated with systolic HF. AF patients with HFrEF or HFmrEF who underwent the combined RFCA and LAAC procedure were prospectively enrolled in the LAACablation registry. The procedural complications and long-term outcomes were evaluated. Another cohort of AF patients with systolic HF who did not undergo either RFCA or LAAC were used for prognosis comparison. Among 802 AF patients who underwent the combined procedure, 65 patients were comorbid with systolic HF (25 with HFrEF and 40 with HFmrEF). The overall procedural complication rate was 9.2%, which was mainly attributed to acute decompensated HF (6.2%). Accompanied with markedly reduced AF burden (from median [25th, 75th percentile]: 100 [100, 100] to 0 [0, 1.2]%, p < 0.001), upward trajectories of cardiac function were observed in 51 (78.4%) patients, showing improvement in New York Heart Classification (p < 0.01), natriuretic peptide levels (from 1492 [809, 3259] to 413 [163, 880] pg/mL, p < 0.001) and left ventricular EF (from 42.6 ± 5.3 to 53.8 ± 8.2%, p < 0.001). During the 27-month follow-up period, death, thromboembolism, major bleeding, and HF rehospitalization were observed in three, one, one, and four patients, respectively. The observed event rates showed a significant reduction compared with the non-procedure AF-HF cohort (n = 138; for composite endpoint: hazard ratio: 2.509, 95% confidence interval: 1.415-4.449, p = 0.002) and with the respective rates predicted by risk scores. Combining RFCA and LAAC achieves acceptable safety and credible long-term efficacy in AF patients with systolic HF. Further randomized studies are warranted in a larger patient cohort.

Asymptomatic vs. symptomatic atrial fibrillation: Clinical outcomes in heart failure patients

BackgroundThe outcome implications of asymptomatic vs. symptomatic atrial fibrillation (AF) in specific groups of patients according to clinical heart failure (HF) and left ventricular ejection fraction (LVEF) need to be clarified. MethodsIn a prospective observational study, patients were categorized according to overt HF with LVEF≤40 %, or with LVEF>40 %, or without overt HF with LVEF40 %≤ or > 40 %, as well as according to the presence of asymptomatic or symptomatic AF. ResultsA total of 8096 patients, divided into 8 groups according to HF and LVEF, were included with similar proportions of asymptomatic AF (ranging from 43 to 48 %).After a median follow-up of 730 [699 -748] days, the composite outcome (all-cause death and MACE) was significantly worse for patients with asymptomatic AF associated with HF and reduced LVEF vs. symptomatic AF patients of the same group (p = 0.004). On adjusted Cox regression analysis, asymptomatic AF patients with HF and reduced LVEF were independently associated with a higher risk for the composite outcome (aHR 1.32, 95 % CI 1.04-1.69) and all-cause death (aHR 1.33, 95 % CI 1.02-1.73) compared to symptomatic AF patients with HF and reduced LVEF. Kaplan-Meier curves showed that HF-LVEF≤40 % asymptomatic patients had the highest cumulative incidence of all-cause death and MACE (p < 0.001 for both). ConclusionsIn a large European cohort of AF patients, the risk of the composite outcome at 2 years was not different between asymptomatic and symptomatic AF in the whole cohort but adverse implications for poor outcomes were found for asymptomatic AF in HF with LVEF≤40 %.

Less major bleeding and higher hemoglobin after left atrial appendage closure in high-risk patients: Data from a long-term, longitudinal, two-center observational study.

Left atrial appendage closure (LAAC) is a mechanical alternative for stroke prevention in patients at risk who cannot tolerate oral anticoagulation (OAC). Our hypothesis was that the reduction of anticoagulation following LAAC results in a decrease of bleeding events and a rise in serum hemoglobin in a high-risk collective of patients with atrial fibrillation (AF). Bleeding events, use of erythrocyte concentrates, anticoagulation, embolic events, and serum hemoglobin levels before and following LAAC were compared over more than 4 years. Seventy-five patients (CHA₂DS₂-VASc score 4.4 ± 1.7, HAS-BLED score 4.6 ± 1.1) were analyzed. Before LAAC (observation period 1.8 ± 1.8 years), 67 patients experienced 1.8 ± 1.4 bleeding events (0.9 ± 1.3 major) per year resulting in 0.7 ± 1.3 transfusions per year. After LAAC (2.6 ± 2.0 years), 26 patients (p < .0001 vs. before) had 0.6 ± 2.1 bleeding events (p < .0001), 0.2 ± 0.6 major bleedings (p < .0001) and received 0.6 ± 1.9 transfusions per year (p = .671). Fourteen patients had stroke before and 3 after LAAC (p = .008). Serum hemoglobin increased from initially 9.9 ± 3.0to 11.9 ± 2.3 g/dL until the end of follow-up (p = .0005). Adverse embolic events did not differ before and after LAAC in our collective. In this clinical relevant cohort of AF patients with high risk for stroke and intolerance to OAC, we show that LAAC was able to reduce the rate of stroke and bleeding events, which translated into a rising serum hemoglobin concentration.

Genetic Basis of Early Onset Atrial Fibrillation in Patients without Risk Factors.

Atrial fibrillation (AF) is the most common arrhythmia and typically occurs in elderly patients with other cardiovascular and extracardiac diseases. However, up to 15% of AF develops without any related risk factors. Recently, the role of genetic factors has been highlighted in this particular form of AF. The aims of this study were to determine the prevalence of pathogenic variants in early-onset AF in patients without known disease-related risk factors and to identify any structural cardiac abnormalities in these patients. We conducted exome sequencing and interpretation in 54 risk factor-free early-onset AF patients and further validated our findings in a similar AF patient cohort from the UK Biobank. Pathogenic/likely pathogenic variants were found in 13/54 (24%) patients. The variants were identified in cardiomyopathy-related and not arrhythmia-related genes. The majority of the identified variants were TTN gene truncating variants (TTNtvs) (9/13 (69%) patients). We also observed two TTNtvs founder variants in the analysed population-c.13696C>T p.(Gln4566Ter) and c.82240C>T p.(Arg27414Ter). Pathogenic/likely pathogenic variants were found in 9/107 (8%) individuals from an independent similar AF patient cohort from the UK Biobank. In correspondence with our Latvian patients, only variants in cardiomyopathy-associated genes were identified. In five (38%) of the thirteen Latvian patients with pathogenic/likely pathogenic variants, dilation of one or both ventricles was identified on a follow-up cardiac magnetic resonance scan. We observed a high prevalence of pathogenic/likely pathogenic variants in cardiomyopathy-associated genes in patients with risk factor-free early-onset AF. Moreover, our follow-up imaging data indicate that these types of patients are at risk of developing ventricular dilation. Furthermore, we identified two TTNtvs founder variants in our Latvian study population.

MicroRNA-21 mediated cross-talk between cardiomyocytes and fibroblasts in patients with atrial fibrillation.

Atrial fibrosis represents a major hallmark in disease progression of atrial fibrillation (AF). We have previously shown that circulating microRNA-21 (miR-21) correlates with the extent of left atrial fibrosis in patients undergoing catheter ablation for AF and can serve as a biomarker to predict ablation success. In this study, we aimed to validate the role of miR-21-5p as a biomarker in a large cohort of AF patients and to investigate its pathophysiological role in atrial remodeling. For the validation cohort, we included 175 patients undergoing catheter ablation for AF. Bipolar voltage maps were obtained, circulating miR-21-5p was measured, and patients were followed-up for 12 months including ECG holter monitoring. AF was simulated by tachyarrhythmic pacing of cultured cardiomyocytes, the culture medium was transferred to fibroblast, and fibrosis pathways were analysed. 73.3% of patients with no/minor LVAs, 51.4% of patients with moderate LVAs and only 18.2% of patients with extensive LVAs were in stable sinus rhythm (SR) 12 months after ablation (p < 0.01). Circulating miR-21-5p levels significantly correlated with the extent of LVAs and event-free survival. In-vitro tachyarrhythmic pacing of HL-1 cardiomyocytes resulted in an increased miR-21-5p expression. Transfer of the culture medium to fibroblasts induced fibrosis pathways and collagen production. The HDAC1 inhibitor mocetinostat was found to inhibit atrial fibrosis development. We validated miR-21-5p as a biomarker that reflects the extent of left atrial fibrosis in AF patients. Furthermore, we found that miR-21-5p is released in-vitro from cardiomyocytes under tachyarrhythmic conditions and stimulates fibroblasts in a paracrine mode to induce collagen production.

Factors Associated with Progression of Atrial Fibrillation and Impact on All-Cause Mortality in a Cohort of European Patients.

Paroxysmal atrial fibrillation (AF) may often progress towards more sustained forms of the arrhythmia, but further research is needed on the factors associated with this clinical course. We analyzed patients enrolled in a prospective cohort study of AF patients. Patients with paroxysmal AF at baseline or first-detected AF (with successful cardioversion) were included. According to rhythm status at 1 year, patients were stratified into: (i) No AF progression and (ii) AF progression. All-cause death was the primary outcome. A total of 2688 patients were included (median age 67 years, interquartile range 60-75, females 44.7%). At 1-year of follow-up, 2094 (77.9%) patients showed no AF progression, while 594 (22.1%) developed persistent or permanent AF. On multivariable logistic regression analysis, no physical activity (odds ratio [OR] 1.35, 95% CI 1.02-1.78), valvular heart disease (OR 1.63, 95% CI 1.23-2.15), left atrial diameter (OR 1.03, 95% CI 1.01-1.05), or left ventricular ejection fraction (OR 0.98, 95% CI 0.97-1.00) were independently associated with AF progression at 1 year. After the assessment at 1 year, the patients were followed for an extended follow-up of 371 days, and those with AF progression were independently associated with a higher risk for all-cause death (adjusted hazard ratio 1.77, 95% CI 1.09-2.89) compared to no-AF-progression patients. In a contemporary cohort of AF patients, a substantial proportion of patients presenting with paroxysmal or first-detected AF showed progression of the AF pattern within 1 year, and clinical factors related to cardiac remodeling were associated with progression. AF progression was associated with an increased risk of all-cause mortality.

328 IMPACT OF INTEGRATED CARE WITH ABC PATHWAY IN PATIENTS WITH ATRIAL FIBRILLATION AND HEART FAILURE: DATA FROM MORE THAN 11000 PATIENTS ENROLLED IN A EUROPEAN REGISTRY

Abstract Background and aim Heart failure (HF) is closely associated with atrial fibrillation (AF). The Atrial fibrillation Better Care (ABC) pathway is recommended in guidelines as a holistic or integrated care approach to AF management. However, few data are specifically available on ABC pathway adherence in AF patients with HF, especially according to HF phenotypes. Therefore, we aimed to retrospectively investigate the effect of ABC management in a large contemporary cohort of AF patients with HF and the impact on the clinical outcomes. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. According to the availability of HF status and ejection fraction (EF) values, patients were categorized as follows: i) non-HF; ii) HF EF&amp;gt;40% iii) HF EF≤40%. The primary outcome was a composite outcome of all-cause death and major adverse cardiac events. Results Among the original 11 096 AF patients enrolled, 9175 (82.7%) were included in this analysis (median age 71 years, interquartile range [IQR 63-77], 40.1% were female, with median EF 55% [IQR 45-61%] and median CHA2DS2-VASc 3 [2-4]). In this cohort, 5935 (64.7%) were non-HF patients, and 3240 (35.3%) had HF patients. According to the EF values, 2005 (65%) were categorized as HF EF&amp;gt;40%, and 1235 (35%) were HF EF≤40%. Overall, ABC pathway adherence in HF patients was 23.3% [95% CI: 21.6-25.2], being higher in HF EF≤40% patients (28.0%) and lower in HF EF&amp;gt;40% ones (21.9%). After a median follow-up of 731[IQR 690-748] days, ABC adherence was associated with a lower risk for the composite outcome compared to non-ABC adherent patients in each HF group (HF EF&amp;gt;40%: ABC 15.4% vs no ABC 20.9%; HF EF≤40%: ABC 20.3% vs no ABC 33.9%; both p&amp;lt;0.001). Cox regression analysis showed that ABC adherence was associated with a lower risk of composite outcome in each HF category (HF EF&amp;gt;40%: HR 0.66 [95% CI: 0.46-0.96], p=0.030; HF EF≤40%: HR 0.60 [95% CI: 0.40-0.90], p=0.013). ABC adherence was associated with a consistent risk reduction for the composite outcome across the entire EF spectrum [Figure]. Conclusions In this large contemporary cohort of AF-HF patients, adherence to the ABC pathway was associated with a lower occurrence of the primary outcome, irrespective of baseline EF. ABC pathway is consistently associated with a lower risk for adverse outcomes across the entire spectrum of EF.

Polypharmacy and adverse events in atrial fibrillation: Main cause or reflection of multimorbidity?

BackgroundPrevious evidence indicated that atrial fibrillation (AF) patients with polypharmacy presented increased probability of adverse events. We investigated the prevalence of polypharmacy, risk factors for polypharmacy, and the impact of polypharmacy in clinical outcomes in a ‘real-world’ cohort of AF patients starting vitamin K antagonists (VKAs). MethodsProspective study including AF outpatients starting VKA therapy from July, 2016 to June, 2018. At inclusion, all concomitant drugs were carefully collected and recorded. Polypharmacy was defined as the intake of ≥ 5 concomitant drugs. During 2-years of follow-up, ischemic strokes/transient ischemic attacks (TIAs), fatal/nonfatal myocardial infarctions (MIs), bleeding events, venous thromboembolisms, and all-cause deaths were recorded. Results1050 patients (51.5 % females, median age 77 [69–83] years) were included, and the prevalence of polypharmacy was 32.9 % (345). Female sex (OR 1.5; 95 % CI 1.11–2.03), hypertension (OR 2.53; 95 % CI 1.51–4.22), diabetes (OR 3.11; 95 % CI 2.31–4.17), vascular disease (OR 3.08; 95 % CI 2.19–4.33), heart failure (OR 1.86; 95 % CI 1.35–2.58) and dyslipidemia (OR 2.61; 95 % CI 1.9–3.58) were independently associated to the polypharmacy. Patients with polypharmacy showed significantly higher incidence of major bleeding, net clinical outcomes (composite of major bleeding, ischemic stroke/TIA, and mortality), MACE (composite of ischemic stroke/TIA, MI, and cardiovascular death), and composite thrombotic/thromboembolic events; being an independent risk factor for major bleeding (HR 1.77, 95 % CI 1.07–2.92), and composite thrombotic/thromboembolic events (HR 1.55, 95 % CI 1.05–2.31). ConclusionIn this “real world” AF cohort, polypharmacy was highly prevalent and conditioned worse prognosis due to its association with bleeding and thromboembolic events.

Identifying unmet antithrombotic therapeutic need, and implications for stroke and systemic embolism in atrial fibrillation patients: a population-scale longitudinal study.

Guidelines recommend anticoagulation (AC) in atrial fibrillation (AF) to reduce stroke and systemic embolism (SSE) risk; however, implementation has been slow across many populations. This study aimed to quantify the potential impact of changing prevalence of AF, associated risk, and AC prescribing on SSE hospitalizations and death. We evaluated temporal trends of AF, CHA2DS2-VASc, antithrombotic prescriptions, SSE hospitalizations, death, and their associations between 2012 and 2018 in a longitudinal cohort of AF patients in Wales UK. Multi-state Markov models were used to estimate expected SSE rates given the AC coverage, adjusting for CHA2DS2-VASc scores. SSE rates were modelled for various past and future AC scenarios. A total of 107 137 AF patients were evaluated (mean age = 74 years, 45% female). AF prevalence increased from 1.75 to 2.22% (P-value <0.001). SSE hospitalizations decreased by 18% (2.34-1.92%, P-value <0.001). Increased AC coverage from 50 to 70% was associated with a 37% lower SSE rate, after adjustment for individual time-dependent CHA2DS2VASc scores. The observed AC increase accounted for approximately 80 fewer SSE hospitalizations per 100 000/year. If 90% AC coverage had been achieved since 2012, an estimated 279 SSE per 100 000/year may have been prevented. Our model also predicts that improving AC coverage to 90% over the next 9 years could reduce annual SSE rates by 9%. We quantified the relationship between observed AC coverage, estimating the potential impact of variation in the timing of large-scale implementation. These data emphasize the importance of timely implementation and the considerable opportunity to improve clinical outcomes in the Wales-AF population.

Comparison of embolism and bleeding risk profile in patients with atrial fibrillation and chronic kidney disease

Abstract Introduction Clinical decision-making on anticoagulation in chronic kidney disease (CKD) patients with atrial fibrillation (AF) is challenging. Current strategies are based on small observational studies with conflicting results. A better comprehension of patients' risk profiles is therefore needed. Purpose The present study explores the impact of glomerular filtration rate (GFR) in the embolic–haemorrhagic balance among a large cohort of AF patients. Methods The study cohort included all patients from the health area of Vigo (Galicia, Spain) diagnosed with AF between January 2014 and April 2020. Subjects without data regarding to glomerular filtration rate were excluded. The final population of the study consisted of 15,457 patients. The risk of ischaemic stroke and major bleeding was determined by competing risk regression using the Fine and Gray model, considering death as a competing risk. Results During a mean follow-up of 4.29±1.82 years, 3,678 patients died (23.80%), 850 had an ischaemic stroke (5.50%) and 961 had a major bleeding (6.22%). The incidence of stroke and bleeding increased as baseline GFR declined. GFR &amp;lt;30 mL/min/1.73 m2 was associated with increased stroke and major bleeding (Figure 1). Interestingly, below GFR &amp;lt;30 mL/min/1.73 m2, bleeding risk was clearly higher than the embolic risk (Figure 2). As glomerular filtration rate decreased, anticoagulation was associated with an increased bleeding risk (sHR 1.72, 95% CI 1.15–2.56; P=0.01 for patients with GFR 30–59 mL/min/1.73 m2 and 2.05, 95% CI 0.80–5.28; P=0.13 for subjects with &amp;lt;30 mL/min/1.73 m2 in comparison with those with GFR &amp;gt;60 mL/min/1.73 m2, respectively), but it was not associated with a reduction in embolic risk in patients with GFR &amp;lt;30 mL/min/1.73 m2 (sHR 1.91, 95% CI 0.73–5.04; P=0.19) Conclusions In advanced chronic kidney disease (GFR &amp;lt;30 mL/min/1.73 m2), the increase of major bleeding risk was higher than the increase of ischaemic stroke risk, with a negative anticoagulation balance (greater increase in bleeding than reduction in embolism). In this setting, left atrial appendage occlusion appears to be an alternative to consider. Funding Acknowledgement Type of funding sources: None.

Epidemiology and impact of frailty in patients with atrial fibrillation in Europe.

Frailty is a medical syndrome characterised by reduced physiological reserve and increased vulnerability to stressors. Data regarding the relationship between frailty and atrial fibrillation (AF) are still inconsistent. We aim to perform a comprehensive evaluation of frailty in a large European cohort of AF patients. A 40-item frailty index (FI) was built according to the accumulation of deficits model in the AF patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. Association of baseline characteristics, clinical management, quality of life, healthcare resources use and risk of outcomes with frailty was examined. Among 10,177 patients [mean age (standard deviation) 69.0 (11.4) years, 4,103 (40.3%) females], 6,066 (59.6%) were pre-frail and 2,172 (21.3%) were frail, whereas only 1,939 (19.1%) were considered robust. Baseline thromboembolic and bleeding risks were independently associated with increasing FI. Frail patients with AF were less likely to be treated with oral anticoagulants (OACs) (odds ratio 0.70, 95% confidence interval 0.55-0.89), especially with non-vitamin K antagonist OACs and managed with a rhythm control strategy, compared with robust patients. Increasing frailty was associated with a higher risk for all outcomes examined, with a non-linear exponential relationship. The use of OAC was associated with a lower risk of outcomes, except in patients with very/extremely high frailty. In this large cohort of AF patients, there was a high burden of frailty, influencing clinical management and risk of adverse outcomes. The clinical benefit of OAC is maintained in patients with high frailty, but not in very high/extremely frail ones.

Gender difference in association between diabetes mellitus and all-cause mortality in atrial fibrillation patients

ObjectiveThere may be gender difference in correlation of diabetes mellitus (DM) and cardiovascular events. We attempt to investigate whether there is gender-heterogeneity in one-year outcomes of atrial fibrillation (AF) patients with DM or not. MethodsPatients who were diagnosed with AF admitted to the emergency departments in the Chinese AF Multicenter Registry study were enrolled. Basic demographics information, initial Blood Pressure and heart rate, medical histories, and treatments of each patient were collected. Follow-up was carried out with a mean duration of one year. The primary endpoint was all-cause mortality and systemic embolism. ResultsA total of 2016 patients were selected from September 2008 and April 2011. All-cause mortality was significantly higher in male AF patients with DM than those without (21.8 % & 13.6 %, P = 0.014). Cox regression analysis showed that there was an interaction between gender and DM for one-year all-cause mortality (P = 0.049). DM was significantly associated with one-year all-cause mortality regardless of univariate analysis (HR = 1.436, 95%CI:1.079–1.911, P = 0.013) or multivariate analysis (HR = 1.418, 95%CI: 1.059–1.899, P = 0.019). For male patients with AF, DM was significantly associated with one-year all-cause mortality (P = 0.048), but not for female patients with AF (P = 0.362). ConclusionDM was independently associated with one-year all-cause mortality in the entire cohort of AF patients. This association was found mainly in male patients with AF, but not in female patients. DM management programs may need to reflect gender difference.