AF Progression Research Articles

Association of kidney function and atrial fibrillation progression to clinical outcomes in patients with cardiac implantable electronic devices

Kidney function may promote progression of AF. We evaluated the association of kidney function to AF progression and resultant clinical outcomes in patients with cardiac implantable electronic devices (CIED). We performed a retrospective cohort study using national clinical data from the Veterans Health Administration linked to CIED data from the Carelink® remote monitoring data warehouse (Medtronic Inc, Mounds View, MN). All devices had atrial leads and at least 75% of remote monitoring transmission coverage. Patients were included at the date of the first AF episode lasting ≥6 minutes, and followed until the occurrence of persistent AF in the first year, defined as ≥7 consecutive days with continuous AF. We used Cox regression analyses with persistent AF as a time-varying covariate to examine the association to stroke, myocardial infarction, heart failure and death. Of, 10,323 eligible patients, 1,771 had a first CIED-detected AF (mean age 69 ± 10 years, 1.2% female). In the first year 355 (20%) developed persistent AF. Kidney function was not associated with persistent AF after multivariable adjustment including CHA2DS2-VASc variables and prior medications. Only higher age increased the risk (HR: 1.37 per 10 years; 95% CI:1.22-1.54). Persistent AF was associated to higher risk of heart failure (HR: 2.27; 95% CI: 1.88-2.74) and death (HR: 1.60; 95% CI: 1.30-1.96), but not stroke (HR: 1.28; 95% CI: 0.62-2.62) or myocardial infarction (HR: 1.43; 95% CI: 0.91-2.25). Kidney function was not associated to AF progression, whereas higher age was. Preventing AF progression could reduce the risk of heart failure and death.

Profiling of miR-205/P4HA3 Following Angiotensin II-Induced Atrial Fibrosis: Implications for Atrial Fibrillation.

Objective: Atrial fibroblasts are the main component of atrial fibrosis. Data in previous studies proved the implication of miRNAs in AF progression and the association of miR-205 with cancer associated-fibroblasts, while no evidence supported the implication of miR-205 in atrial fibrosis. Therefore, this study aims to explore the effect and mechanism of miR-205/P4HA3 axis on atrial fibrosis.Methods: Angiotensin II (Ang II) was used to induce atrial fibrosis model in rats, which was verified by H&E staining and Masson staining. qRT-PCR and Western blot were applied to measure the expressions of miR-205, P4HA3, collagen I, and α-SMA. The rat atrial fibroblasts were isolated and then subjected to Ang II treatment or cell transfection for determination of cell biological functions using CCK-8, BrdU assay, TUNEL staining, and cell scratch assay. qRT-PCR and Western blot was applied to analyze the expressions of miR-205, P4HA3, collagen I, α-SMA, JNK, and p-JNK in atrial fibroblasts. Dual-luciferase reporter gene assay and RNA immune-precipitation experiment was employed to verify the binding relationship between miR-205 and P4HA3.Results: Ang II induced rats had disordered arrangement of atrial muscles with uneven nuclear sizes and necrotic atrial myocytes, and increased collagen deposition, in which elevated expressions of P4HA3, collagen I, and α-SMA as well as suppressed expression level of miR-205 were found. In vitro, Ang II treatment in atrial fibroblasts with overexpression of P4HA3 facilitated cellular migration and proliferation, with the induction of JNK signaling pathway. However, these trends were reversed after transfection with miR-205 mimic. P4HA3 is a target gene of miR-205.Conclusion: The miR-205/P4HA3 axis is implicated in atrial fibrosis by inhibition of rat fibroblast proliferation and migration and the inactivation of JNK signaling pathway.

AF Begets Autonomic Nervous System Dysfunction: A Possible Contributor to “AF begets AF”

Although chronic low-level vagal nerve stimulation (LLTS) reduces AF burden, efferent autonomic tone does not influence AF progression. The role of cardiac afferents in AF progression is not defined. We evaluated whether AF disturbs cardiac afferent (volume-sensitive) reflexes.

Impact of treatment strategies for AF on the progression and regression of AF type in the CABANA trial

Abstract Background The CABANA trial compared drug vs ablation therapy yet did not identify a difference in the primary endpoint of death, stroke, severe bleeding, or cardiac arrest or the secondary endpoint of all-cause mortality by intention to treat (ITT) analysis. Nevertheless, there was evidence of improved outcomes and survival in the as-treated and per-protocol analyses. Objectives To determine how the treatment strategies of drug therapy vs ablation impact the atrial fibrillation progression and regression. Methods CABANA randomized 2204 pts with AF ≥65 yrs old or <65 with ≥1 risk factor for stroke at 126 sites worldwide to ablation with pulmonary vein isolation vs drug including rate/rhythm control medication. AF type was recorded at the time of enrollment in the CABANA Trial. Following treatment with drug therapy or ablation, the AF type was assessed as recorded at the patient's last follow-up. Comparisons between baseline AF type and last AF type were performed according to ITT. Results Following treatment with ablation, 64% maintained sinus rhythm with elimination of AF, 11% experienced AF regression, and only 7% had progression of AF. In contrast, in those randomized to drug therapy, only 48% experienced maintenance of sinus rhythm, 10% experienced AF regression, and 13% had progression of AF. Moreover, in the drug arm there was a 32% increase in long-standing persistent compared with a 49% reduction in the ablation arm. Conclusion Catheter ablation significantly alters the natural history of atrial fibrillation. Intention to treat analysis reveals that catheter ablation provides superior elimination of AF, protection against AF progression, and dramatically lower risks of long-standing persistent AF. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health

The 4S-AF Scheme (Stroke Risk; Symptoms; Severity of Burden; Substrate): A Novel Approach to In-Depth Characterization (Rather than Classification) of Atrial Fibrillation.

Atrial fibrillation (AF) is a complex condition requiring holistic management with multiple treatment decisions about optimal thromboprophylaxis, symptom control (and prevention of AF progression), and identification and management of concomitant cardiovascular risk factors and comorbidity. Sometimes the information needed for treatment decisions is incomplete, as available classifications of AF mostly address a single domain of AF (or patient)-related characteristics. The most widely used classification of AF based on AF episode duration and temporal patterns (that is, the classification to first-diagnosed, paroxysmal, persistent/long-standing persistent, and permanent AF) has contributed to a better understanding of AF prevention and treatment but its limitations and the need for a multidimensional AF classification have been recognized as more complex treatment options became available. We propose a paradigm shift from classification toward a structured characterization of AF, addressing specific domains having treatment and prognostic implications to become a standard in clinical practice, thus aiming to streamline the assessment of AF patients at all health care levels facilitating communication among physicians, treatment decision-making, and optimal risk evaluation and management of AF patients. Specifically, we propose the 4S-AF structured pathophysiology-based characterization (rather than classification) scheme that includes four AF- and patient-related domains-Stroke risk, Symptoms, Severity of AF burden, and Substrate severity-and provide a hypothetical model for the use of 4S-AF characterization scheme to aid treatment decision making concerning the management of patients with AF in clinical practice.

Assessment of progression of atrial fibrillation in middle-aged individuals with hypertension in combination with comorbid extracardial diseases

Purpose. To assess the progression of atrial fibrillation in middle-aged people with hypertension in combination with comorbid extracardiac diseases.Materials and methods. In an observational cohort study, 308 patients aged 45–65 years with atrial fibrillation (paroxysmal and persistent forms) with hypertension in combination with extracardiac pathology were observed: diabetes mellitus (n = 40), thyrotoxicosis (n = 42), hypothyroidism (n = 59), abdominal obesity (n = 64) and chronic obstructive pulmonary disease (n = 47). The control group consisted of 56 patients with hypertension + AF without concomitant extracardiac disease. The level of MMP-9 was determined using the Human MMP-9 (total) Immunoassay test-system (USA); NT-proBNP — using the NTproBNP-IFA-Best reagent kit; galectin-3 — with ELISA — Bender MedSystems (Austria). Echocardiography was performed using an Acuson Aspen apparatus (USA), 24-hour ECG monitoring with Schiller Medilog Holter system. All statistical calculations were carried out in the program Rstudio 0.99.879 (RStudio, USA).Results. In patients with hypertension and atrial fibrillation, the combination of diabetes mellitus (p = 0.041) and abdominal obesity (p = 0.004) is the most prognostic factor for AF progression. In groups of patients with diabetes mellitus, hypothyroidism and abdominal obesity, the most pronounced indicators of diastolic dysfunction of the left ventricle were: E/A, LVMI (men); the size of the left atrium and the end-diastolic size of the left ventricle are increased in all clinical groups. The prognostic value of biomarkers of fibrosis and remodeling of galectin-3 and MMP-9, and NT-proBNP in the progression of atrial fibrillation in patients with hypertension in combination with extracardial diseases is shown.Conclusion. There is no doubt that in case of hypertension, the decompensation of long-term hypertrophic myocardium is based on a violation of the balanced growth of its various structures and the formation of fibrosis and myocardial dystrophy, which was confirmed in the present study. The detected elevated levels of MMP-9, galectin-3 and NT-proBNP, as well as ultrasonic signs of myocardial remodeling, confirmed that they statistically significantly affect the progression of atrial fibrillation. In this regard, a personalized approach to a patient with atrial fibrillation in combination with comorbid pathology is required, especially in middle-aged people at the stage of comorbidity formation, under the conditions of received diagnostic information on the electrical function of the heart and assessment of the functional capabilities of CVS during its transition to various levels of functioning.

Remodeling of myocardial energy and metabolic homeostasis in a sheep model of persistent atrial fibrillation

BackgroundAtrial fibrillation (AF) is the most common progressive cardiac arrhythmia and is often associated with rapid contraction in both atria and ventricles. The role of atrial energy and metabolic homeostasis in AF progression is under-investigated. ObjectivesTo determine the remodeling of energy metabolism during persistent AF and the effect of eplerenone (EPL), an aldosterone inhibitor, on metabolic homeostasis. MethodsA nonsustained atrial pacing sheep model was developed to simulate the progression of AF from paroxysmal to persistent. Metabolomic and proteomic analyses at termination of the experiment were used to analyze atrial tissues obtained from sheep in sham, sugar pill (SP) and EPL-treated groups. ResultsProteomic analysis indicated that compared to the sham group, in SP group, fatty acid (FA) synthesis, FA oxidation, tricarboxylic acid (TCA) cycle processes and amino acids (AAs) transport and metabolism were reduced, while glycolytic processes were increased. In metabolomic analysis, the levels of intermediate metabolites of the glycolytic pathways, including 2-phosphoglyceric acid (2 PG), 1,3-bisphosphoglyceric acid (1,3 PG), and pyruvate, HBP (uridine diphosphate-N-acetylglucosamine, UDP-GlcNAc), TCA (citrate) and AAs were greater while the levels of the majority of lipid classes, including phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylglycerol (PG), glycerophosphoglycerophosphates (PGP), glycerophosphoinositols (PI) and glycerophosphoserines (PS), were decreased in the atria of SP group than in those of sham group. EPL-pretreatment decreased the expression of glut4 and increased the content of acylcarnitines and lipids, such as lyso phospholipids, phospholipids and neutral lipids. ConclusionIn the metabolic remodeling during AF, glucose and lipid metabolism were up- and down-regulated, respectively, to sustain TCA cycle anaplerosis. EPL partialy reversed the metabolic shifting.

Heat shock protein inducer GGA*-59 reverses contractile and structural remodeling via restoration of the microtubule network in experimental Atrial Fibrillation

BackgroundAtrial Fibrillation (AF) is the most common progressive tachyarrhythmia. AF progression is driven by abnormalities in electrical impulse formation and contractile function due to structural remodeling of cardiac tissue. Previous reports indicate that structural remodeling is rooted in derailment of protein homeostasis (proteostasis). Heat shock proteins (HSPs) play a critical role in facilitating proteostasis. Hence, the HSP-inducing compound geranylgeranylacetone (GGA) and its derivatives protect against proteostasis derailment in experimental models for AF. Whether these compounds also accelerate reversibility from structural remodeling in tachypaced cardiomyocytes is unknown. ObjectiveTo investigate whether the potent HSP inducer GGA*-59 restores structural remodeling and contractile dysfunction in tachypaced cardiomyocytes and explore the underlying mechanisms. Materials and resultsHL-1 cardiomyocytes post-treated with GGA*-59 or recombinant HSPB1 (rcHSPB1) revealed increased levels of HSPB1 expression and accelerated recovery from tachypacing (TP)-induced calcium transient (CaT) loss compared to non-treated cardiomyocytes. In addition, protein levels of the microtubule protein (acetylated) α-tubulin, and contractile proteins cardiac troponin I (cTnI) and troponin T (cTnT) were reduced after TP and significantly recovered by GGA*-59 or rcHSPB1 post-treatment. The mRNA levels of α-tubulin encoding genes, but not cardiac troponin genes, were reduced upon TP and during recovery, but significantly enhanced by GGA*-59 and rcHSPB1 post-treatment. In addition, TP increased calpain activity, which remained increased during recovery and GGA*-59 post-treatment. However, HDAC6 activity, which deacetylates α-tubulin resulting in microtubule disruption, was significantly increased after TP and during recovery, but normalized to control levels by GGA*-59 or rcHSPB1 post-treatment in HL-1 cardiomyocytes. ConclusionsOur results imply that the HSP inducer GGA*-59 and recombinant HSPB1 accelerate recovery from TP-induced structural remodeling and contractile dysfunction in HL-1 cardiomyocytes. GGA*-59 increases HSPB1 levels, represses HDAC6 activity and restores contractile protein and microtubule levels after TP, indicating that HSP-induction is an interesting target to accelerate recovery from AF-induced remodeling.

Association between AF progression phenotypes with LAA strain, cardiac NT-proANP and VCAM1 levels in atrial fibrillation

Atrial natriuretic peptide (ANP) is specifically secreted from the atria in response to tension stress and together with vascular cell adhesion protein-1 (VCAM-1) is associated with AF progression and recurrences. Recently we demonstrated an association between NT-proANP and VCAM1 levels with AF progression phenotypes based on persistent AF and low voltage areas (LVA): paroxysmal AF with/without LVA (PAF−/PAF + ), persistent AF with/without LVA (PersAF ± ). The aim of the current analysis was to investigate NT-proANP and VCAM1 levels in peripheral and cardiac circulation and to analyze potential association with LAA strain. The study included 116 patients undergoing first AF catheter ablation. Left atrial appendage (LAA) was analyzed before ablation with mid-esophageal echocardiographic in 2D-speckle tracking imaging. LAA total longitudinal strain (LAA-TLS) was assessed as the absolute difference of the maximal systo-diastolic values in extracted strain-curves. Blood plasma samples from femoral vein and LA were collected before catheter ablation. NT-proANP and VCAM1 were analyzed using commercially available assays. There were significant differences between the groups with LAA-TLS ( P < 0.001), cardiac NT-proANP ( P = 0.009), and VCAM1 ( P = 0.048). On univariable analysis, age, gender, PersAF, LAA-TLS, renal function, and cardiac NT-proANP and VCAM1 significantly predicted LVA. However, on multivariable analysis, age (OR 1.097, 95%CI 1.009–1.192, P = 0.029), PersAF (OR 4.713, 95%CI 1.131–19.649, P = 0.033), LAA-TLS (OR 0.945, 95%CI 0.898–0.995, P = 0.032) and VCAM1 (OR 1.002, 95%CI 1.000–1.004, P = 0.034) remained significant predictors for LVA. Beside age and AF type, LAA-TLS and VCAM1 were significant predictors for LVA. Larger studies analyzing non-invasive predictors for electro-anatomical remodeling in AF patients are needed to prove our results.

CircRNA-miRNA cross-talk in the transition from paroxysmal to permanent atrial fibrillation

BackgroundAtrial fibrillation (AF) is the most prevalent cardiac arrhythmia in western countries. The factors governing the progression of AF to a permanent chronic condition are still not well characterized. Among epigenetic factors, non-coding RNAs (ncRNAs) such as miRNAs and lncRNAs have been recently described as important players involved in the AF progression. We hypothesize about the existence of additional regulatory layers in AF involving an intricate cross-talk between different ncRNA species, namely miRNAs and circRNAs for the establishment of a chronic AF condition. Methods and resultsWe have performed an unbiased study analyzing the expression profile for miRNAs and circRNAs in left-atrial biopsies from patients with paroxysmal and permanent AF by RNA-seq. The transition from paroxysmal to permanent AF is characterized by a pattern of down-regulated miRNAs, concomitant to the appearance of specific circRNA species. The analysis of the sponging activities of the circRNAs exclusively expressed in permanent AF samples, allowed us to determine that they could be responsible for the downregulation of specific miRNAs in establishment of a permanent AF condition. ConclusionSponging activity of circRNAs sequestering specific miRNAs is an important factor to be considered for the determination of the molecular mechanisms involved in AF progression.

Diastolic wall strain predicts progression from paroxysmal to persistent or permanent atrial fibrillation in structurally normal hearts

BackgroundAtrial fibrillation (AF) is characterized by a progression from paroxysmal to persistent or permanent AF. Recent studies have shown that AF progression is related to a worse morbidity and mortality, and poorer outcomes of radiofrequency catheter ablation (RFCA). We previously showed that left ventricular (LV) compliance assessed by diastolic wall strain (DWS) was a strong determinant of prevalent AF. Methods and resultsWe studied 306 paroxysmal AF patients with structurally normal hearts. The DWS was non-invasively measured with echocardiography. During a follow-up of 35±19 months, AF progression occurred in 60 of 172 (35%) patients treated with medications only (medication group), and 3 of 134 (2%) who underwent RFCA (RFCA group) (p<0.001). In the medication group, patients with a DWS <0.38 had a higher incidence of AF progression than those without (log-rank p<0.001), while the AF progression rate was low irrespective of the DWS in the RFCA group. In a multivariate analysis, the DWS and left atrium volume index (LAVI) were independent predictors of AF progression in the medication group (hazard ratio, 1.13 per 0.01 decrease; 95% CI: 1.08–1.18; p<0.001, and 1.04 per 1mm increase; 95% CI: 1.01–1.08; p=0.012, respectively). In the medication group, AF progression occurred in only 5 of 61 (8%) patients with a DWS ≥0.38, whereas 27 of 40 (68%) with a DWS <0.38 and LAVI >34mL/m2 progressed to persistent or permanent AF. ConclusionsThe LV compliance estimated by the DWS was independently associated with AF progression. The DWS would be useful to stratify patients at risk of AF progression who could benefit from an earlier RFCA intervention.

P374AF type and low voltage areas: biomarkers distinguish AF progression phenotypes

P374AF type and low voltage areas: biomarkers distinguish AF progression phenotypes

Progression of late postoperative atrial fibrillation in patients with tetralogy of Fallot.

ToF patients are at risk for ventricular deterioration at a relatively young age, which can be aggravated by AF development. Therefore, knowledge on AF development and its timespan of progression is essential to guide treatment strategies for AF. We examined late postoperative AF onset and progression in ToF patients during long-term follow-up after ToF correction. In addition, coexistence of AF with regular supraventricular tachyarrhythmias (SVT) and ventricular tachyarrhythmias (VTA) was analyzed. ToF patients (N=29) with AF after ToF correction referred to the electrophysiology department between 2000 and 2015 were included. All available rhythm registrations were reviewed for AF, regular SVT, and VTA. AF progression was defined as transition from paroxysmal AF to (longstanding) persistent/permanent AF or from (longstanding) persistent AF to permanent AF. At the age of 44 ± 12 years, ToF patients presented with paroxysmal (N=14, 48%), persistent (N=13, 45%) or permanent AF (N=2, 7%). Age of AF development was similar among patients who either underwent initial shunt creation (N=15, 45 ± 11 [25-57] years) or primary total ToF correction (N=14, 43 ± 13 [26-66] years) (P=0.785). AF coexisted with regular SVT (N=18, 62%) and VTA (N=13, 45%). Progression of AF occurred in 11 patients (38%) within 5 ± 5 years after AF onset despite antiarrhythmic drug class II (AAD, P=0.052) or III (P=0.587) usage. AF in our ToF population developed at a young age and showed rapid progression. Rhythm control by pharmacological therapy was ineffective in preventing AF progression.

30Optimising the predictive capability of a mathematical model of AF progression using cardiac device data

30Optimising the predictive capability of a mathematical model of AF progression using cardiac device data

The Year in Cardiology 2016: arrhythmias and cardiac implantable electronic devices.

The year 2016 was characterized by numerous relevant contributions in cardiac arrhythmias. A selected group of articles providing information with potential impact in daily practice has been identified by the authors and is reported in the present article. ### Supraventricular tachycardia: diagnosis and treatment Supraventricular tachycardia (SVT) continues to be a frequent cause of emergency hospital admission. The REVERT study evaluated the best and most efficient acute treatment strategy for SVT and compared postural modification (leg elevation and supine positioning applied for 15 sec at the end of 15 sec) with standardized strain Valsalva manoeuvre (i.e. pressure of 40 mm Hg sustained for 15 s by forced expiration measured by aneroid manometer with the target pressure visible to the treating team).1 The modified treatment was found to terminate SVTs in a significantly larger proportion of patients (43% of 214) than using conventional manoeuvres (17% of 214; P < 0.0001). As a consequence, significantly less patients in the study arm required adenosine (50% vs. 69%) or emergency anti-arrhythmic treatment (57% vs. 80%) to terminate the incident arrhythmia1 and no differences in time to discharge from hospital. This finding may considerably affect daily practice and reduce drug-related patient discomfort at time of emergency treatment in patients with SVT. The full scope of up-to-date diagnosis and treatment of SVTs can be reviewed best in 2016 EHRA/ESC consensus document on SVT management (Katritsis et al. , EHJ 2016 in press) ### Atrial fibrillation: pathophysiology, risks, treatment opportunities, and the new ESC AF guidelines The intense scientific discussion about the pathophysiology of atrial fibrillation and particularly the drivers for AF progression was enriched and stimulated by a very interesting experimental and clinical study on atrial remodeling.2 It was shown that atrial adipose tissue, which has been previously identified as a strong risk factor for AF development, is progressively replaced by fibrotic tissue that serves as the substrate for AF progression.2 These data may further explain …

Anxiety and atrial fibrillation: an interesting bidirectional association.

Atrial fibrillation stands as one of the most common supraventricular arrhythmias. Its incidence in general population has escalated significantly over the last few decades. The health-related quality of life (HRQoL) of patients with atrial fibrillation is currently a vital concern in cardiovascular health management. Accordingly, key elements of meager HRQoL of AF patients demand better clarification. Nowadays, several reports have tested the mutual relation between anxiety and AF initiation and progression. Significantly, anxiety affects how the patients approach their disease and, additionally, anxiety may affect the efficiency of various AF therapies. The goal of this research is to explore an area that considered by patients to be challenging before the therapeutic work-up. Study concluded that there is a multifaceted relationship between AF and anxiety. AF can ground anxiety among patients and equally, anxiety can pave a background that is favorable for the initiation and Progression of AF.

Cardioversion and subsequent quality of life and natural history of atrial fibrillation

Using the nationwide prospective ORBIT-AF registry, cardioversion patients were propensity matched 3:1 to noncardioverted patients and Cox proportional hazards modeling evaluated hospitalization at 1 year in those with and without cardioversion. Cardiovascular outcomes, AF progression, and quality of life were evaluated for the matched cohorts with and without cardioversion. Among 9,642 patients, 817 patients (8%) underwent 906 cardioversions during a median follow-up of 12 (interquartile range 6-18) months. Among matched cardioverted and noncardioverted patients, 1-year cardiovascular hospitalization rates were 43% vs 21% (adjusted hazard ratio 2.2, 95% CI 1.8-2.8, P<.001), and sinus rhythm at both first and second follow-ups was 36% vs 27% (P=.042), respectively. Findings were similar among first-time cardioversion patients. Matched cardioversion patients did not exhibit greater symptom improvement (34% vs 42%) or less symptomatic progression (15% vs 4%) by European Heart Rhythm Association scores. Cardioversion was associated with AF progression with an odds ratio of 1.6 (95% CI 1.2-2.2, P=.001) after cardioversion and 2.7 (P<.001) after first cardioversion vs matched noncardioversion patients. After cardioversion, only 18% of patients not previously on an antiarrhythmic started one, less than 5% underwent ablation, and 22% stopped their antiarrhythmic. Cardioversion was not associated with improved AF-related quality of life or less progression. Many patients who undergo cardioversion do not receive adjunctive rhythm control therapies. These findings may help to better inform therapeutic decision making.

Interatrial septal pacing to suppress atrial fibrillation in patients with dual chamber pacemakers: A meta-analysis of randomized, controlled trials

BackgroundAtrial fibrillation (AF) is of frequent occurrence in a population with bradycardia indicated for permanent dual chamber pacing. Whether selective site pacing at interatrial septum (IAS) could better prevent AF as compared with standard atrial pacing (AP) from right atrial appendage or high right atrium in these conditions remains in question. Its safety profile has yet to be elucidated. MethodsMajor web databases were searched up to February 2015 for controlled, randomized clinical trials on IAS versus conventional pacing. The primary end point was freedom from persistent/permanent AF. Secondary outcomes included device-recorded AF burden and frequency of AF episodes, lead-related complications, and major adverse events (MAEs). ResultsWe identified 10 eligible studies incorporating a total of 1245 patients. Compared to conventional AP, IAS pacing conferred no additional benefit on the persistent/permanent AF free survival (hazard ratio 0.76, 95% confidence interval [CI] 0.48 to 1.22); it was associated with notably reduced device-detected AF burden (standard mean difference [SMD] −0.32, 95% CI −0.55 to −0.09) and AF frequency (SMD −0.54, 95% CI −0.83 to −0.24). The odds of lead-related complications (odds ratio [OR] 1.64, 95% CI 0.87 to 3.08) and combined rate of MAEs (OR 1.05, 95% CI 0.60 to 1.82) were similar between two groups. ConclusionsIAS pacing has no influence on the persistent/permanent AF progression and MAEs, although it appears to lower device-detected AF burden and AF frequency, and may carry similar risks of lead-related complications as compared to standard AP.

Heart rate is associated with progression of atrial fibrillation, independent of rhythm

ObjectiveAtrial fibrillation (AF) often progresses from paroxysmal or persistent to more sustained forms, but the rate and predictors of AF progression in clinical practice are not well described.MethodsUsing the Outcomes...

Atrial fibrillation compendium: historical context and detailed translational perspective on an important clinical problem.

### Circulation Research Compendium on Atrial Fibrillation: Atrial Fibrillation Compendium: Historical Context and Detailed Translational Perspective on an Important Clinical Problem The Clinical Profile and Pathophysiology of Atrial Fibrillation: Relationships Among Clinical Features, Epidemiology, and Mechanisms Emerging Directions in the Genetics of Atrial Fibrillation Cellular and Molecular Electrophysiology of Atrial Fibrillation Initiation, Maintenance and Progression Role of the Autonomic Nervous System in Atrial Fibrillation: Pathophysiology and Therapy Mathematical Approaches to Understanding and Imaging Atrial Fibrillation: Significance for Mechanisms and Management Atrial Fibrillation Therapy Now and in the Future: Drugs, Biologicals, and Ablation Guest Editor: Stanley Nattel Atrial fibrillation (AF), the most common sustained tachyarrhythmia, currently affects 1% to 2% of the general population.1 Age is arguably the strongest determinant of AF occurrence, and the prevalence of AF is increasing as the population ages, projected to increase from ≈7 million today to ≈12 to 16 million predicted for the United States in 2050 (including estimates for paroxysmal and silent AF).1 There has been a marked progress in our understanding of the basic mechanisms underlying AF for the past 20 years.2–5 The management of AF continues to face huge challenges, but advancing knowledge and new technologies have also created unprecedented opportunities, which will undoubtedly revolutionize AF management over the next 20 years.6 Recognizing the importance of this area and the rapid pace of knowledge development, the Editorial Board of Circulation Research decided to develop a Compendium on Atrial Fibrillation. The compendium includes 6 state-of-the-art review articles on themes of clinical features and pathophysiology of AF,1 molecular electrophysiology of AF initiation, maintenance, and progression,7 autonomic nervous system control of AF,8 genetic factors determining AF occurrence and risk,9 the use of mathematical modeling to understand and manage AF better,10 and the mechanisms governing present and future therapy of the arrhythmia. …