Permanent Atrial Fibrillation Patients Research Articles

Stroke risk assessment in different atrial fibrillation subtypes: CHA2DS2-VASc score and beyond

Abstract Background Patients with atrial fibrillation (AF) have been known to have an inhomogeneous risk of stroke, with several well-documented risk factors including hypertension, history of stroke, and diabetes mellitus that have been incorporated into the CHA2DS2–VASc score to stratify risk levels. Accumulating evidence has suggested that AF subtype, namely persistent AF and paroxysmal AF, also have an impact on stroke development. Purpose This study focused on the impact of AF subtype on stroke risk in a large, long-term follow-up cohort as to provide insight of the impact on ischemic stroke risks. Such findings may play a role in future ischemic stroke risk stratification in selected patients. Methods A total of 7346 AF patients were followed up for 10 years from January 2010 to December 2020 (mean follow-up time 2.74 years). Among these patients, 2460 (33.5%) had persistent or permanent AF (PerAF) and 4886 (66.5%) had paroxysmal AF (PAF). The study evaluated the risk of ischemic stroke between the two groups using Cox models adjusting for all components of the CHA2DS2–VASc score. Analyses were further stratified into the usage of oral anticoagulation (OAC) or no OAC. Results Comparing AF patients based on subtype, it was found that PerAF patients were older, had a higher prevalence of previous stroke, congestive heart failure, PAD, DM, and were more often prescribed anticoagulants. Univariate analysis found patients with PerAF at a higher risk for ischemic stroke (HR 1.262, p<0.001). The results remained significant after multivariate analysis with factors of the CHA2DS2–VASc score (HR 1.234, p<0.001). After stratifying patients according to anticoagulation prescription, PerAF and PAF patients were found to have similar rates of developing ischemic stroke in patients under DOAC. Conclusions Patients with PerAF have a higher risk of stroke during follow-up independent of components of the CHA2DS2VASc score. In patients with OAC use, there was no difference in stroke risk between AF subtypes.Stroke Risk in OAC-naive patientsStroke Risk in OAC-experienced patients

Novel Entropy-Based Metrics for Long-Term Atrial Fibrillation Recurrence Prediction Following Surgical Ablation: Insights from Preoperative Electrocardiographic Analysis.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia often treated concomitantly with other cardiac interventions through the Cox-Maze procedure. This highly invasive intervention is still linked to a long-term recurrence rate of approximately 35% in permanent AF patients. The aim of this study is to preoperatively predict long-term AF recurrence post-surgery through the analysis of atrial activity (AA) organization from non-invasive electrocardiographic (ECG) recordings. A dataset comprising ECGs from 53 patients with permanent AF who had undergone Cox-Maze concomitant surgery was analyzed. The AA was extracted from the lead V1 of these recordings and then characterized using novel predictors, such as the mean and standard deviation of the relative wavelet energy (RWEm and RWEs) across different scales, and an entropy-based metric that computes the stationary wavelet entropy variability (SWEnV). The individual predictors exhibited limited predictive capabilities to anticipate the outcome of the procedure, with the SWEnV yielding a classification accuracy (Acc) of 68.07%. However, the assessment of the RWEs for the seventh scale (RWEs7), which encompassed frequencies associated with the AA, stood out as the most promising individual predictor, with sensitivity (Se) and specificity (Sp) values of 80.83% and 67.09%, respectively, and an Acc of almost 75%. Diverse multivariate decision tree-based models were constructed for prediction, giving priority to simplicity in the interpretation of the forecasting methodology. In fact, the combination of the SWEnV and RWEs7 consistently outperformed the individual predictors and excelled in predicting post-surgery outcomes one year after the Cox-Maze procedure, with Se, Sp, and Acc values of approximately 80%, thus surpassing the results of previous studies based on anatomical predictors associated with atrial function or clinical data. These findings emphasize the crucial role of preoperative patient-specific ECG signal analysis in tailoring post-surgical care, enhancing clinical decision making, and improving long-term clinical outcomes.

Prevalence of Cardio-Embolic Brain Complications in Permanent and Paroxysmal Atrial Fibrillation Patients.

Background: Atrial fibrillation (AF) is the most frequent of all cardiac arrhythmias, with an increasing prevalence in the last 20 years. Cardio-embolic brain complications (CEBC) related to AF often occur or recur, even following appropriate treatment. Method: We conducted a retrospective study and analyzed the presence of stroke, dementia, and Parkinson’s disease (PD) in both paroxysmal and permanent AF patients. The records of 1111 consecutive admitted patients with primary diagnosis of AF at the Municipal Emergency University Hospital, Timisoara, between 2015 and 2016 were examined. Statistical analysis was performed on the patients included in the study based on the inclusion and exclusion criteria. Results: A significant statistical difference was noted among the permanent AF group for stroke (48.75% vs. 26.74%, p < 0.001) and dementia (10.25% vs. 3.86%, p < 0.001) compared to paroxysmal AF patients. Permanent AF patients presented a higher risk of developing stroke, dementia, and PD compared to patients with paroxysmal AF. Meanwhile, male gender and an increase in age showed an increase in the odds of having cardio-embolic brain complications in patients with paroxysmal AF. Conclusion: Based on the results obtained, it can be concluded that the risk of cardio-cerebral embolic complications is greater in permanent AF patients compared to paroxysmal AF cases. Ischemic stroke and dementia are more frequent in the permanent AF group, but analyzing the data regarding the age of onset paroxysmal AF is critical due to the fact that it involves a younger population. Prompt diagnosis and treatment can help significantly in saving stroke patients.

Major Interleukins: Role in the Pathogenesis of Atrial Fibrillation

Interleukins (IL) are a group of cytokines with complex immunomodulatory functions, whereas atrial fibrillation (AF) is the most common cardiac arrhythmia. This review article highlights the role of major IL in the pathogenesis of AF. IL-1 had elevated levels in permanent and persistent AF patients as compared to paroxysmal AF. A study had shown a straightforward connection between the development of postoperative atrial fibrillation and IL-2 sera levels shortly after cardiopulmonary bypass graft for the first time. IL-4 has been involved in anti-inflammatory response and played no role in the contribution of AF. The elevated level of IL-6 rapidly induces atrial electrical remodeling by downregulating cardiac connexins. This change could be significantly increased the risk of AF and related complications during active inflammatory processes. Moreover, a study has shown higher IL-8 levels in permanent AF patients as compared with paroxysmal AF patients. An association was found between IL-10 gene -592A/C polymorphism and AF in Han Chinese. Recombinant human IL-11 therapy shortened atrial refractoriness and also created favorable conditions for AF by an indirect mechanism involving volume expression, stretching of atrial myocardial tissue and sodium retention. An elevated IL-12 expression was observed in the left atrial tissues of AF patients. IL-17 signaling pathway has played a significant role, and some genes could be used as potential therapeutic targets for AF. An association between the risk of AF with single nucleotide polymorphism of IL-18 and also resulted in the increased left atrial diameter and decreased left ventricular ejection fraction in AF subjects as compared to control. IL-27 genetic variants had increased the occurrence of AF. AF patients had elevated levels of IL-37 that were closely linked with AF subgroups.

Pulse deficit in atrial fibrillation — a different perspective on rhythm or rate control strategy

Pulse deficit (PD) is a frequently unused but crucial clinical finding in atrial fibrillation (AF) diagnosis. We aimed to investigate the relationship between PD and exercise intolerance in AF patients to remodel the treatment in case of a favorable outcome. This prospective study was conducted with 273 permanent AF patients between September 2019 and October 2020. An exercise stress test stratified by age and sex-matched was performed to determine exercise intolerance, and the patients were divided into 2 groups based on physical capacity: low (<75 percentile as Group 1) (n = 160; 58.6%) and adequate (≥75 percentile as Group2) (n = 113; 41.4%). The mean (standard deviation [SD]) PD of exercise intolerance patients was significantly higher than patients with adequate exercise capacity (17 [4] vs. 12 [2]; P <0.001). Moreover, PD was independently associated with exercise intolerance after adjusting for potential covariates (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.51-0.69; P <0.001). In both univariate and multivariable analyses, higher heart rates had a stronger relationship with exercise intolerance (mean [SD], 107 [11] vs. 99 [10]; P <0.001; OR, 0.92; 95% CI, 0.89-0.96; P <0.001). Also, there was a positive correlation between heart rate and PD (r = 0.431; P <0.001). Increased PD was associated with decreased exercise capacity in persistent AF patients. Rhythm control strategy should be considered to increase left ventricular filling pressures in AF patients with high PD and exercise intolerance.

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.

Association Between Permanent Non-Valvular Atrial Fibrillation with Microalbuminuria and C-Reactive Protein

Background: An understanding of atrial fibrillation (AF) mechanisms, as the most common cardiac arrhythmia, is essential for primary and secondary prevention. Some studies indicated an association between microalbuminuria and C-reactive protein (CRP) protein, with the incidence and prevalence of AF. This study aimed to investigate the relationship between permanent non-valvular AF with microalbuminuria and reactive protein C. Materials and Methods: In this case-control study, 40 permanent non-valvular AF patients and 40 non-AF patients (control group) were studied. Demographic data and measurements of albumin, urine creatinine, CRP, and microalbuminuria were recorded and compared between the two groups. Results: In patients with permanent non-valvular atrial fibrillation, CRP level (P&lt;0.001) and microalbuminuria (P=0.012) were significantly higher than the control group. Also, in patients with permanent non-valvular AF, the CRP positive (P = 0.014) and microalbuminuria (P = 0.003) were significantly higher than controls. The results showed that elevated chance of permanent non-valvular AF with abnormal CRP was 4.25 (odds ratio [OR]= 4.25, 95% confidence interval [CI]: 1.18-1.28; P= 0.026), and with microalbuminuria was 6.54 (OR= 6.54, 95% CI: 1.65-25.89; P=0.007). Conclusion: An elevated CRP level and microalbuminuria were significantly associated with permanent non-valvular atrial fibrillation. A longitudinal study is necessary. [GMJ.2021;10:e2106]

Association Between Permanent Non-Valvular Atrial Fibrillation with Microalbuminuria and C-Reactive Protein

Background: An understanding of atrial fibrillation (AF) mechanisms, as the most common cardiac arrhythmia, is essential for primary and secondary prevention. Some studies indicated an association between microalbuminuria and C-reactive protein (CRP) protein, with the incidence and prevalence of AF. This study aimed to investigate the relationship between permanent non-valvular AF with microalbuminuria and reactive protein C. Materials and Methods: In this case-control study, 40 permanent non-valvular AF patients and 40 non-AF patients (control group) were studied. Demographic data and measurements of albumin, urine creatinine, CRP, and microalbuminuria were recorded and compared between the two groups. Results: In patients with permanent non-valvular atrial fibrillation, CRP level (P&lt;0.001) and microalbuminuria (P=0.012) were significantly higher than the control group. Also, in patients with permanent non-valvular AF, the CRP positive (P = 0.014) and microalbuminuria (P = 0.003) were significantly higher than controls. The results showed that elevated chance of permanent non-valvular AF with abnormal CRP was 4.25 (odds ratio [OR]= 4.25, 95% confidence interval [CI]: 1.18-1.28; P= 0.026), and with microalbuminuria was 6.54 (OR= 6.54, 95% CI: 1.65-25.89; P=0.007). Conclusion: An elevated CRP level and microalbuminuria were significantly associated with permanent non-valvular atrial fibrillation. A longitudinal study is necessary. [GMJ.2021;10:e2106]

The Benefit of Atrioventricular Junction Ablation for Permanent Atrial Fibrillation and Heart Failure Patients Receiving Cardiac Resynchronization Therapy: An Updated Systematic Review and Meta-analysis

BackgroundAtrial fibrillation (AF) is correlated with a poor biventricular pacing and inadequate response to cardiac resynchronization therapy (CRT). Biventricular pacing improvement can be achieved by conducting the atrioventricular junction ablation (AVJA). We aimed to investigate the benefit of AVJA for permanent AF and heart failure with reduced ejection fraction (HFrEF) patients receiving CRT.MethodsIn August 2020, a systematic review and meta-analysis study comparing CRT plus AVJA versus CRT for permanent AF and HFrEF patients was conducted. Relevant articles were identified through the electronic scientific database such as ClinicalTrials.gov, ProQuest, ScienceDirect, PubMed, and Cochrane. The pooled risk ratio (RR) and pooled mean difference (MD) were estimated.ResultsA total of 3199 patients from 14 cohort studies were involved in this study. Additional AVJA reduced cardiovascular mortality (RR = 0.75, 95% confidence interval [CI] = 0.61 to 0.93, P < 0.01) in permanent AF and HFrEF patients receiving CRT. Biventricular pacing rate was higher in CRT plus AVJA group (MD = 8.65%, 95% CI = 5.62 to 11.67, P < 0.01) than in CRT alone group. The reverse remodeling characterized by the reduction of left ventricular end-diastolic diameter (LVEDD) was greater in the CRT plus AVJA group (MD = −2.11 mm, 95% CI = −3.79 to −0.42, P = 0.01).ConclusionIn permanent AF and HFrEF patients receiving CRT, AVJA effectively increased the biventricular pacing rate. Adequate biventricular pacing rate provided a better response to the CRT marked by the greater ventricular reverse remodeling and survival from cardiovascular mortality.

Clinical characteristics and management practice among patients diagnosed with atrial ibrillation in Benghazi Libya, A cross sectional study

Introduction: There are no data so far regarding the frequency and outcome of the different types of atrial fibrillation (AF) in the clinical setting for Libyan patients. Furthermore, it is unknown whether the actual clinical management and therapy of AF in Libya conform to the international guidelines. The aim of this study was to determine the frequency, demographic, and clinical characteristics of AF patients. Patients and Methods: Three hundred patients attending the outpatient clinic and cardiology department at Benghazi Medical Center and National Cardiac Center between May 2020 and October 2020 were included. Patients' data were obtained through medical records using the chart review. Patients were categorized into a clinical type of AF, based on the physician's perception of the AF at the time of presentation. Results: Three hundred patients with an established diagnosis of AF were enrolled, including 210 (70%) females and 90 (30%) males. The mean age at the time of diagnosis was 49.5 ± 21.5 years, with an age range of 29–79 years. Of them 139 (46.3%) were diagnosed as permanent AF, 132 (44%) paroxysmal AF, while new-onset AF was diagnosed in 29 (9.7%). The three clinical categories of AF were enrolled under the care of both cardiologists and internal medicine physicians, but permanent AF patients were more often enrolled under the care of a cardiologist. Patients with permanent AF were older compared with those with paroxysmal subtype (61.8 ± 9 and 50.1 ± 12, respectively), with significant female predominance (P = 0.03), and more often had coronary artery disease (CAD), valvular heart disease, and a previous stroke/TIA (P = 0.01, P = 0.124, and P = 0.002, respectively). Diabetes was the most prevalent associated medical condition, followed by hypertension and hyperlipidemia. CAD was diagnosed among 122 patients. Of permanent AF patients, 28 patients (20.1%) previously suffered from a stroke, mostly TIA, in contrast to 14 patients (10.6%) of the other AF patients. Conclusion: Our AF patients were characterized by an unfavorable cardiovascular risk profile. We recognize a lower rate of oral anticoagulation prescription, which needs further evaluation.

Analysis of Atrial Fibrillation Treatment Regimes in a Multicenter Cohort of Transcatheter Edge-to-Edge Mitral Valve Repair Patients.

Background Atrial fibrillation (AF) is a highly prevalent comorbidity in patients with severe mitral valve regurgitation (MR). Recent studies show a deleterious outcome of patients with concomitant AF after transcatheter mitral valve repair (TMVR). This underlines the essential need for additional strategies that ameliorate the prognosis of these patients. Fundamental data on AF characteristics and treatment regimes in this special cohort of patients are lacking. Methods We retrospectively analyzed the data of 542 consecutive patients with severe MR undergoing TMVR in three tertiary heart centers with special focus on AF type and underlying treatment strategies. Results The prevalence of concomitant AF was 73.3%, and AF did not affect the procedural success or the incidence of major adverse cardiac and cerebrovascular events. The patients with AF were more frequently >75 years, had more tricuspid regurgitation, and less coronary artery disease than non-AF patients. The distribution of AF types was 32% paroxysmal AF, 27% persistent AF, and 41% permanent AF. Except for a higher degree in severe tricuspid regurgitation and a higher likelihood of male sex, no substantial differences were observed while comparing permanent and nonpermanent AF patients. The predominant treatment regime was rate control (57%), with only beta blockers (BB) in the majority of persistent and permanent AF patients, while additional digitalis or a pacemaker was used infrequently. Rhythm control was mainly achieved with BB alone in paroxysmal AF patients and with additional antiarrhythmic drugs in the majority of persistent AF patients. Interventional rhythm control therapy was performed in 2.5% and 30.9% of paroxysmal and persistent AF patients, respectively. The guideline-adherent use of oral anticoagulants was comparable and high in both groups (91.9% in nonpermanent vs. 90.1% in permanent AF). Conclusion This is the first study to provide necessary information for the understanding of the current clinical practice in dealing with TMVR patients. Since evidence suggests that AF is not a benign concomitant disease, further investigations are needed to assess the prognostic impact of these different AF treatment strategies.

Predictors of spontaneous echo contrast and left atrial appendage thrombosis in nonvalvular atrial fibrillation

Aim. To identify predictors of spontaneous echo contrast (SEC) and/or left atrial appendage (LAA) thrombosis in patients with nonvalvular atrial fibrillation (AF) who are referred for elective cardioversion or catheter ablation (CA).Material and methods. A retrospective analysis of data from 638 patients with nonvalvular AF who were hospitalized from 2014 to 2017 for cardioversion or CA was performed. All patients underwent diagnostic tests, including transthoracic and transesophageal echocardiography (TEE).Results. According to the TEE results, two groups of patients were formed: group 1 — 95 patients (14,9%) with signs of SEC and/or thrombosis in LAA; group 2 — 543 patients (85,1%) without SEC or thrombosis in LAA. Patients with the phenomenon of SEC and/or LAA thrombosis were older, had a higher risk on the CHA2DS2-VASc score. These patients were more likely to have coronary heart disease (CAD), hypertension, stage IIA chronic heart failure, obese class &gt;II, persistent or permanent AF Patients in both groups did not differ in anticoagulant therapy. Patients in group 1 had a larger size of the left and right atria, right ventricle, left ventricular (LV) end-systolic and end-diastolic diameters, higher LV mass index, lower values of LV ejection fraction and blood flow velocity in LAA. Logistic regression revealed following independent predictors of SEC and/or LAA thrombosis: CAD (odds ratio (OR) 2,289; 95% confidence interval (CI) 1,313-3,990; p=0,003), persistent or permanent AF (OR 2,071; 95% CI 1,222-3,510; p=0,007), LA diameter &gt;43 mm (OR 3,569; 95% CI 2,0822-6,117; p&lt;0,001), concentric or eccentric LV hypertrophy (OR 2,230; 95% CI 1,302-3,819; p=0,003).Conclusion. As the result, all patients referring for CA or cardioversion, regardless of the CHA2DS2-VASc score, should underwent LAA. According to this study, the presence of CAD, persistent or permanent AF, LA diameter &gt;43 mm, concentric or eccentric LV hypertrophy are independent predictors of SEC and/or LAA thrombosis.

A greater burden of atrial fibrillation is associated with worse endothelial dysfunction in hypertension.

Atrial fibrillation (AF) and hypertension often co-exist and both are associated with endothelial dysfunction. We hypothesised that AF would further worsen endothelium-dependent flow-mediated dilatation (FMD) in hypertension patients compared to those without AF. In a cross-sectional comparison, we measured brachial artery diameter at rest and during reactive hyperaemia following 5 min of arterial occlusion in two patient groups: AF (and hypertension) (n = 61) and hypertension control groups (n = 33). The AF (and hypertension) subgroups: permanent AF (n = 30) and paroxysmal AF (n = 31) were also assessed. The permanent AF patients received heart rate and blood pressure (BP) control optimisation and were then followed up after eight weeks for repeat FMD testing. There was no significant difference in FMD between AF (and hypertension) group and hypertension control group (4.6%, 95% CI [2.6-5.9%] vs 2.6%, 95% CI [1.9-5.3%]; p = 0.25). There was a significant difference in FMD between permanent AF and paroxysmal AF groups (3.1%, 95% CI [2.3-4.8%] vs 5.9%, 95% CI [4.0-8.1%]; p = 0.02). Endothelium-dependent FMD response showed a non-significant improvement trend following eight weeks of heart rate and BP optimisation (3.1%, 95% CI [2.3-4.8%] (baseline) vs 5.2%, 95% CI [3.9-6.5%] (follow up), p = 0.09). Presence of AF generally does not incrementally worsen endothelial dysfunction in hypertension patients, although the duration and frequency of AF (paroxysmal AF to permanent AF) does lead to worsening endothelial function. Eight weeks of BP optimisation did not significantly improve endothelial dysfunction as measured by FMD.

P1087Prevalence and significance of mitral regurgitation in atrial fibrillation coexisting with HFpEF and HFmEF

Abstract Background Recent data has acknowledged atrial induced functional mitral valve regurgitation (MR) in the setting of atrial fibrillation (AF) and/or heart failure with preserved ejection fraction (HFpEF) as a distinct type of secondary MR, holding prognostic significance. However, evidence on its prevalence is still scarce, especially in the phenotype of mid-range ejection fraction heart failure (HFmEF). Purpose The aim of this study is to evaluate the occurrence of left atrial (LA) enlargement and MR in AF patients with or without heart failure with preserved or mid-range ejection fraction. Methods This retrospective study included 750 consecutive patients with AF admitted to a tertiary hospital from January 2018 to June 2019. We excluded patients with primary valvular disease and HF with reduced EF. MR presence and severity were assessed by evaluating the valve morphology, colour flow imaging and, when feasible, vena contracta and PISA methods. We measured LA anteroposterior diameter and used LA dilatation as a surrogate marker for mitral annulus dilatation. Results We evaluated 584 AF patients: mean age 72.22 ± 10.10 years; 58,73% females; 79.75% had HF: 73.13% of them had HFpEF and 26.87% had HFmEF. Compared to those without HF, patients with HF had a relative risk (RR) of associating LA enlargement of 5.37 (95%CI = 3.05-9.48, p &amp;lt; 0.001) and a RR of associating MR of 1.47 (95%CI 1.08-2.00, p = 0.01). Mean LA diameter was higher in the HF group, compared to non-HF (47.06 ± 7.26 mm vs 40.91 ± 7.10 mm, p &amp;lt; 0.001). MR severity was more likely associated with HF (RR = 1.68, 95%CI = 1.46-1.94, p &amp;lt; 0.001). When comparing results between the two HF subgroups, patients with HFmEF had a higher mean LA diameter than those with HFpEF (48.52 ± 5.68 mm vs 46.36 ± 7.57 mm, p = 0.011), without associating a significant difference in the MR prevalence (72.97% vs 73.98%, p = 0.94). The presence of a dilated LA was directly correlated with MR in the HF group (RR = 1.94, 95%CI = 1.18-3.20, p = 0.023), but not in those without HF (RR = 1.04, 95%CI = 0.57-1.90, p = 0.89). In HF patients, permanent AF associated the highest prevalence of LA dilatation (96.67%) and MR (81.73%) in contrast to paroxysmal AF (81.10%, p &amp;lt; 0.01, respectively 63.43%, p = 0.0002). Conclusions LA dilatation, the presence and severity of MR correlated with AF and HF, especially in permanent AF patients. In patients without HF, LA dilatation did not correlate with the presence of MR. MR prevalence was similar in patients with HFmEF and HFpEF, irrespective of a higher degree of LA dilatation in HFmEF. Our results suggest that the pathophysiological mechanisms involved in LA enlargement and MR are different for different phenotypes of AF in patients with or without HF.

Inflammatory Cytokines During Cardiac Rehabilitation After Heart Surgery and Their Association to Postoperative Atrial Fibrillation

Inflammation is associated with atrial fibrillation (AF), but little is known about the association of AF with the inflammatory serum cytokines after the acute postoperative phase. Thus, we aimed to explore how plasma cytokines concentrations modify during a 3-week cardiac rehabilitation after heart surgery, comparing patients who developed postoperative AF (POAF) and those with permanent AF with patients free from AF (NoAF group). We enrolled 100 consecutive patients and 40 healthy volunteers as a control group. At the beginning of cardiac rehabilitation, 11 days after surgery, serum levels of MPO, PTX3, ADAM17, sST2, IL-25, and IL-33 were dramatically higher, whereas TNFα and IL-37 levels were much lower in NoAF, POAF, and permanent AF patients than in the healthy volunteers. After rehabilitation, most of the cytokines changed tending towards normalization. POAF patients (35% of the total) had higher body mass index and abdominal adiposity than NoAF patients, but similar general characteristics and risk factors for POAF. However, ADAM-17 and IL-25 were always lower in POAF than in NoAF patients, suggesting a protective role of IL-25 and ADAM 17 against POAF occurrence. This finding could impact on therapeutic strategies focusing on the postoperative prophylactic antiarrhythmic interventions.

Interleukin-22 is elevated in the atrium and plasma of patients with atrial fibrillation and increases collagen synthesis in transforming growth factor-β1-treated cardiac fibroblasts via the JNK pathway.

Our previous studies demonstrated that interleukin (IL)-22 is involved in cardiovascular diseases such as hypertension, cardiac fibrosis and aortic dissection. The purpose of the present study was to detect IL-22 expression in patients with atrial fibrillation (AF). Atrial tissue was collected from donors with sinus rhythm and patients with permanent AF, and the expression level of IL-22 and its receptors (IL-22R1 and IL-10R2) in both the left atrium (LA) and right atrium (RA) of each sample was detected. Blood samples were also obtained from donors with paroxysmal, persistent and permanent AF and from donors without AF history, and IL-22 levels were measured. In addition, the effects of IL-22 on collagen synthesis in TGF-β1-treated cardiac fibroblasts were investigated. IL-22R1, IL-10R2 and IL-22 expression was elevated in both the LA and RA in permanent AF patients. Elevated IL-22 expression positively correlated with the collagen areas and fibrosis marker levels in the atria of these patients. Plasma IL-22 levels were higher in AF patients compared with healthy donors and increased with increasing AF duration (from paroxysmal to persistent to permanent AF). A positive correlation was observed between IL-22 levels and TGF-β1 levels in AF patients. In vitro, recombinant mouse IL-22 treatment upregulated α-SMA, collagen I and collagen III expression in TGF-β1-treated cardiac fibroblasts. These effects were reversed by SP600125, an inhibitor of the JNK pathway. To conclude, IL-22 levels are elevated in patients with AF and may exacerbate collagen synthesis in TGF-β1-induced cardiac fibroblasts. IL-22 may also influence AF by activating the JNK pathway.

Inflammatory activation and endothelial dysfunction markers in patients with permanent atrial fibrillation: a cross-sectional study.

In recent years a growing body of evidence supported the role of inflammation in the initiation, maintenance and outcome of atrial fibrillation (AF). Nevertheless, despite a large amount of information, whether AF or the underlying structural heart disease (SHD) is the cause of the inflammatory process is still under debate. We, therefore, sought to determine if the inflammatory process reflect an underlying disease or the arrhythmia ‘per se’. We evaluated plasma levels of soluble Interleukin 2 Receptor Alpha (sIL-2Rα), TNF-α and IL-18 in 100 consecutive patients with permanent AF, (43 with a SHD and 57 without a SHD) compared to 121 age and sex-matched controls which had normal sinus rhythm. We also evaluated the endothelial function in both groups of patients using reactive hyperemia index (RHI) values measured by Endo-PAT2000. Compared to controls, AF patients showed higher circulating levels of inflammatory markers and a lower mean value of RHI. At multiple logistic regression analysis, the inflammatory markers and RHI were significantly associated with AF presence, whereas ROC curve analysis had good sensitivity and specificity in inflammatory variables and RHI for AF presence. No significant association was observed in the group of permanent AF patients, between inflammatory markers and the presence of an underlying SHD. These findings could help to clarify the role of inflammation in subjects with AF and suggest that the markers of systemic inflammation are not associated with the underlying cardiovascular disease, rather with the atrial fibrillation ‘per se’.

Patient and provider-level factors associated with changes in utilization of treatments in response to evidence on ineffectiveness or harm

High-quality health care not only includes timely access to effective new therapies but timely abandonment of therapies when they are found to be ineffective or unsafe. Little is known about changes in use of medications after they are shown to be ineffective or unsafe. In this study, we examine changes in use of two medications: fenofibrate, which was found to be ineffective when used with statins among patients with Type 2 diabetes (ACCORD lipid trial); and dronedarone, which was found to be unsafe in patients with permanent atrial fibrillation (PALLAS trial). We examine the patient and provider characteristics associated with a decline in use of these medications. Using Medicare fee-for-service claims from 2008 to 2013, we identified two cohorts: patients with Type 2 diabetes using statins (7 million patient-quarters), and patients with permanent atrial fibrillation (83 thousand patient-quarters). We used interrupted time-series regression models to identify the patient- and provider-level characteristics associated with changes in medication use after new evidence emerged for each case. After new evidence of ineffectiveness emerged, fenofibrate use declined by 0.01 percentage points per quarter (95% CI - 0.02 to - 0.01) from a baseline of 6.9 percent of all diabetes patients receiving fenofibrate; dronedarone use declined by 0.13 percentage points per quarter (95% CI - 0.15 to - 0.10) from a baseline of 3.8 percent of permanent atrial fibrillation patients receiving dronedarone. For dronedarone, use declined more quickly among patients dually-enrolled in Medicare and Medicaid compared to Medicare-only patients (P < 0.001), among patients seen by male providers compared to female providers (P = 0.01), and among patients seen by cardiologists compared to primary care providers (P < 0.001).

Efficacy and safety of anticoagulant treatment for non-valvular atrial fibrillation in multimorbid patients

Assessment of the safety and efficacy of anticoagulant treatment in patients with nonvalvular atrial fibrillation (AF) in a multimorbidity setting. The cross-sectional study included 104 patients diagnosed with nonvalvular AF and followed in the medical facilities of Yekaterinburg. The subjects were interviewed, anthropometric measurements were made, and the risk of thromboembolic complications was evaluated using the CHA2DS2-VASc score. The Charlson multimorbidity index was calculated, and patients were divided into two groups: Group 1 with a low level of multimorbidity (not more than 5 points) and Group 2 with a high level of multimorbidity (6 points or more). The data are presented as a median and interquartile range (25%; 75%). The study population included 40 males and 64 females. The median age was 71 (62.5; 80) years. The level of multimorbidity was estimated as 5 (3; 6) points. Group 1 included 64 patients, and Group 2 included 40 patients. Thirty-nine percent of the sample patients had a paroxysmal form of AF, 10% had a persistent form, and 51% had permanent AF. The group of patients with a high level of multimorbidity included more patients with permanent AF and fewer patients with paroxysmal AF as compared with a moderate level of multimorbidity (p&lt;0.01). Anticoagulant treatment was indicated for 92 (88.5%) patients. It was administered to 70.7% of patients; 29.3% did not receive it. Among patients receiving anticoagulants, warfarin was administered to 18.5%, and new oral anticoagulants (NOACs) were administered to 81.5%. Complications were reported in 15.2% of anticoagulant treatment cases. Bleeding was reported in 21.7% of cases of warfarin administration and 12.5% of cases of NOAC treatment (p=0.32). The median number of risk factors for bleeding per patient was 5 (4; 5.5). The Charlson index and the total number of risk factors are significantly correlated (R=0.37, p&lt;0.05). In real-world clinical practice in Ekaterinburg, Russia, 7 of 10 patients with AF for whom anticoagulant treatment was indicated actually received it; NOACs are prescribed four times more often than warfarin. With a higher level of multimorbidity, the risk of bleeding under the pressure of anticoagulant treatment increases; thus, NOACs should be preferred over warfarin for treatment of multimorbid patients.

P6557Permanent atrial fibrillation development in patients with DDD pacemaker -Rrisk factors and association with mortality in long-term

Abstract Background In patients undergoing permanent DDD cardiac pacing, the maintenance of atrial contractility is important to ensure adequate ventricular filling and to guarantee an optimal ventricular ejection capacity. Atrial fibrillation (AF) is a major risk factor for thromboembolic events and is associated with increased cardiovascular and all-cause mortality. Purpose To analyse the risk factors for development of permanent AF in patients with DDD pacemaker and determine its association with all-cause mortality in long-term follow-up. Methods Retrospectively collected records comprised all consecutive patients who underwent primary DDD pacemaker implantation at single-centre between 1984–2014. Patients who were lost to follow-up after hospital discharge were excluded from analysis. Follow-up was completed on 31st August 2016. Definition of permanent AF was the occurence of AF which persisted until the end of follow-up. Data on patients' survival status and deceased patients' dates of death were collected from the national death registration system. Information of death date was available as of 31st August 2016. The endpoint was all-cause mortality. Results We included a total of 3771 patients and 24,432 patient-years of follow-up and exluded 157 (4%) patients who were lost to follow-up after hospital discharge. Mean follow-up was 78±62 months (max. 370 months), 1761 (47%) were female. Paroxysmal AF prior to DDD pacemaker implantation was detected in 1276 patients (34%). During entire follow-up 717 (19%) patients developed permanent AF in a mean period of 55±50 months. Analysis of risk factors for development of permanent AF is presented in Figure. Cox proportional hazards model with time-dependent covariate showed that development of permanent AF significantly increased mortality during follow-up (HR = 1.885, 95% CI, 1.654–2.148, P&lt;0.001; with adjustment for age at implantation and sex: HR = 1.475, 95% CI, 1.294–1.682, P&lt;0.001). Permanent AF risk factors Conclusions Female sex protected against permanent AF development, whereas age at implantation, history of paroxysmal AF and apical position of RV lead increased the risk. Permanent AF was significantly increasing the all-cause mortality, even after adjustment for age at implant and gender. Acknowledgement/Funding None