Permanent Atrial Fibrillation Patients Research Articles

Increased level of resistin predicts development of atrial fibrillation

BackgroundResistin is a peptide hormone that is secreted from lipid cells and is linked to type-2 diabetes, obesity, and inflammation. Being an important adipocytokine, resistin was proven to play an important role in cardiovascular disease. We compared resistin levels in patients with and without atrial fibrillation (AF) to demonstrate the relationship between plasma resistin levels and AF. MethodOne hundred patients with AF and 58 control patients who were matched in terms of age, gender, and risk factors were included in the trial. Their clinical risk factors, biometric measurements, echocardiographic work up, biochemical parameters including resistin and high-sensitivity C-reactive protein (hs-CRP) levels were compared. ResultsIn patients with AF, plasma resistin levels (7.34±1.63ng/mL vs 6.67±1.14ng/mL; p=0.003) and hs-CRP levels (3.01±1.54mg/L vs 2.16±1.28mg/L; p=0.001) were higher than control group. In subgroup analysis, resistin levels were significantly higher in patients with paroxysmal (7.59±1.57ng/mL; p=0.032) and persistent AF (7.73±1.60ng/mL; p=0.006), but not in patients with permanent AF subgroups (6.86±1.61ng/mL; p=0.92) compared to controls. However, hs-CRP levels were significantly higher only in permanent AF patients compared to control group (3.26±1.46mg/L vs 2.16±1.28mg/L; p=0.02). In multivariate regression analysis using model adjusted for age, gender, body mas index, hypertension, diabetes mellitus, and creatinine levels, plasma resistin levels [odds ratio (OR): 1.30; 95% confidence interval (CI): 1.01–1.70; p=0.04] and hs-CRP levels (OR: 1.44; 95% CI: 1.12–1.86; p=0.004) were the only independent predictors of AF. ConclusionThe elevated levels of plasma resistin were related to paroxysmal AF group and persistent AF group, but not to permanent AF group.

Association of CA-125 Levels with Presence of Permanent Atrial Fibrillation in Patients with Systolic Heart Failure

Association of CA-125 Levels with Presence of Permanent Atrial Fibrillation in Patients with Systolic Heart Failure

Surgical treatment of atrial fibrillation by ultrasounds with epicor system

Objectives: The efficacy of surgical treatment of atrial fibrillation (AF) by ultrasounds, with the EPICOR system (St Jude), has been proven on selected patients. The UltraCinch allows pulmonary vein exclusion; his size is chosen according to the left atrium diameter. Another device (UltraWand) allows mitral line ablation. We evaluated the efficacy of this technique on a series of non-selected patients. Methods: Between March 2006 and March 2012, 148 patients underwent surgical treatment of AF with EPICOR system. One hundred forty-six (99%) underwent a concomitant surgical procedure; 63 patients (43%) underwent mitral surgery; two patients (1%) underwent isolated AF treatment. Eighty-seven (59%) patients were on permanent AF before the operation. According to the logistic EuroSCORE value, expected mortality was 6±6 (1-56), mean CHADSVasc Score was 2.76±1.70. Results: Mortality was 6% (9 patients). Mean size of the Ultracinch was 10±2 (8-13). Ultrawand was used in 53 patients (36%), 20 patients (14%) underwent left appendage resection. Mean CPB and aortic cross-clamp times were 83±32 and 67±28 minutes. Two patients (1%) underwent postoperative surgical revision for bleeding. A follow-up after the third postoperative month was available for 100 patients with a mean of 10±10 months. Seventy patients (70%) were free from AF, 34 on 62 (55%) among permanent AF patients, 36 on 38 (95%) among paroxysmal/persistent AF patients. Eighty-three patients (83%) were on oral anticoagulant therapy, 44 patients (44%) were on anti-arrhythmic therapy. Predictive factors of AF recurrence were age, preoperative permanent AF, and mean CHADSVasc score; concomitant mitral valve surgery and adherence to the clinical follow-up were protective against AF recurrence. Neither device size nor mitral line ablation was predictive factors of arrhythmia recurrence. Conclusion: EPICOR system allows surgical treatment of AF even in non-selected patients without increasing operative mortality and operative times. Strict adherence to the clinical follow-up is mandatory to improve outcomes. Weaning form oral anti-coagulant therapy should not be an indication for surgical ablation of AF.

An elevated late INa increases the diastolic SR-Ca-leak in atrial cardiomyocytes via a CaMKII-dependent mechanism

The late Na current (late INa) is elevated in heart failure (HF) and atrial fibrillation (AF) and may induce cardiac arrhythmias. Similarly, SR-Ca-leak is increased in both pathologies. The aim of the study was to determine a crosstalk between late INa, Ca/calmodulin-dependent kinase II (CaMKII) and the SR-Ca-leak in atrial myocytes. We hypothesized that an increased late INa leads to diastolic Ca-overload (via Na/Ca-exchanger, NCX), which activates CaMKII in AF and triggers CaMKII-dependent phosophorylation of ryanodine-receptor type 2 (RyR2). Furthermore, CaMKII was found to phosphorylate cardiac Na-channles thereby elevating late INa. Thus, a vitious circle could take place maintaining arrhythmogenity in AF. We isolated atrial cardiomyocytes (CM) from mice, paced them at 3 Hz for 20 beats and scanned for diastolic Ca-sparks (confocal microscopy). The low basal Ca-spark-frequency (CaSpF) of atrial CM (22±8/s/10-4 m) could be increased by the late INa enhancer ATX-II (0.5 nM) to 169±28/s/10-4m (by 668±155%, n=43 vs. 43, P<0.001). Simultaneous CaMKII-inhibition by AIP (1 μM) completely prevented the ATX-II-induced 11-fold increase of the total calculated SR-Ca-leak (n=48 vs. 43, p<0.001) suggesting a CaMKII-dependent mechanism. Late INa inhibition using ranolazine (Ran 10 μM, n=32 vs. 43) as well as the specific Na+-channel blocker tetrodotoxin (TTX, n=28 vs. 26) also normalized the total SR-Ca-leak in ATX-II-treated atrial cardiomyocytes (P=0.001). The ATX-II mediated induction of the SR-Ca2+-leak could further neither be detected when the Na+-Ca2+-exchanger (NCX) was inhibited with KBr (n=35 vs. 20) nor in CaMKIIδc-knockout mice (n=34 vs. 27). To validate these data for human AF we freshly isolated human atrial CM from patients in sinus rhythm (SR) and permanent AF. There was a strong tendency towards a higher calculated SR-Ca-leak in AF compared to SR (338.4±88.9 vs. 148.6±31.5, n =31 vs. 38, p=0.07). Indeed, superfusion of atrial CM from AF patients with Ran (10 μM) could significantly reduce the diastolic SR-Ca-leak compared to untreated control (by 78±9%, n=27 vs. 30, p<0.05). Additionally, treatment with AIP (1 μM) significantly reduced Ca-spark-frequency by 63±12% (p<0.05, n =28 vs. 41). These data suggest that an increased late INa induces diastolic SR-Ca-leak in murine and human atrial CM via CaMKII-dependent ryanodine receptor regulation. This mechanism might constitute a trigger for the induction and perpetuation of atrial arrhythmias. Ran seems to exert antiarrhythmic effects by reducing the SR-Ca-leak and is currently evaluated for antiarrhythmic therapy in patients with AF.

MIR146A polymorphisms predict cardiovascular risk in atrial fibrillation patients

There is a strong link between atherothrombosis and atrial fibrillation (AF). MicroRNAs (miRNAs) have emerged as critical players in cardiovascular biology. In particular, miR-146a-3p is recognized as an important inflammation down-regulator. To date, neither the role of miR-146a-3p nor their functional polymorphisms (miRSNPs) rs2431697 and rs2910164, both affecting miR-146a-3p levels in monocytes, have been related with cardiovascular disease. We evaluate their prognostic role a large cohort of anticoagulated permanent AF patients. Methods: We studied 904 patients (50% male; median age 76) with permanent AF stabilized for 6 months (INR=2-3). Patients were followed-up for 2 years and adverse cardiovascular events were recorded. MiRSNPs were genotyped by Taqman® analysis. In vitro studies were performed in immunoselected monocytes from healthy controls homozygous for the two genotypes of rs2431697 (n=9 of each genotype). Monocytes were activated with10 ng/mL LPS. MiR-146a-3p and IL6-mRNA levels were measured by qRT-PCR. Plasma IL6 levels were analyzed at entry and the better cut-offs were calculated by ROC curves. Results: The genetic frequencies in AF patients were similar to those reported in Caucasians. After adjusting by CHADS2DS2-VASc score and high plasma IL6 levels we found that rs2431697 TT genotype was independently associated with adverse cardiovascular events (HR, 95% CI: 1.67,1.11-2.51; p=0.002). MiRSNP rs2910164 showed no association. We studied the effect of rs2431697 in monocyte miR-146a-3p levels. After 24h activation, LPS induced an increase of miR-146a-3p levels. Monocytes from CC individuals had a 65% increase of miR-146a-3p levels while TT individuals only increased by 28%. These data suggest that TT individuals may be prone to a highest pro-inflammatory state after an inflammatory stress, due in part to lower levels of miR-146a-3p. Indeed, IL6-mRNA levels, previously shown to be influenced by miR-146a-3p, were inversely correlated with those of miR-146a-3p. Thus, after 24h of LPS activation, TT monocytes showed a higher increase of IL6 expression than CC (52% vs. 26%). Conclusions: We showed that MIR146A rs2431697 might have a prognostic role in AF patients. Accordingly, AF patients carrying the rs2431697 TT genotype would have a minor response to pro-inflammatory signals than CC, resulting in reduced levels of miR-146a-3p and a final increased production of pro-inflammatory targets such as IL-6, which might contribute to the higher risk of adverse cardiovascular events of these patients. Financial support: ISCIII and FEDER (PI11/00566, P11/1256, and Red RECAVA RD12/0042/0050)

Left ventricular diastolic dysfunction and N-terminal probrain sodium-uretic peptid level in patients with atrial fibrillation

In our study 100 consecutive non-valvular permanent atrial fibrillation patients with NYHA I – III heart failure, 43 - 86 years old (65 men and 35 women) were examined. Control group consisted of 30 patients with arterial hypertension and coronary artery disease matched by age, sex with basic group. Relationship of NT-proBNP with echocardiographic parameters of left heart were studied. Transthoracic echocardiography with tissue doppler measurements were performed on echocardiograph “SONOS7500”. For left ventricular filling pressure assessment ratio Em/Ea was used due to its diagnostic value in atrial fibrillation (regardless of left ventricular ejection fraction). Mean left ventricular filling pressure was increased in patients with heart failure: in atrial fibrillation group and controls as well. In comparison with controls atrial fibrillation group was more likely to have higher both systolic and diastolic left atrial square and volume. According to Em/Ea in 95% of patients with non-valvular atrial fibrillation high left ventricular filling pressure was observed, this testifies to diastolic dysfunction. This parameter correlated well with left atrial square and volume during systole and diastole. Correlation between NT pro-BNP level and NYHA class of heart failure, left ventricular filling pressure was determined in patients with atrial fibrillation. Tissue doppler echocardiography makes it possible to diagnose left ventricular diastolic dysfunction in atrial fibrillation patients.

Atrial selectivity of antiarrhythmic drugs

New antiarrhythmic drugs for treatment of atrial fibrillation should ideally be atrial selective in order to avoid pro-arrhythmic effects in the ventricles. Currently recognized atrial selective targets include atrial Nav1.5 channels, Kv1.5 channels and constitutively active Kir3.1/3.4 channels, each of which confers atrial selectivity by different mechanisms. Na(+) channel blockers with potential- and frequency-dependent action preferentially suppress atrial fibrillation because of the high excitation rate and less negative atrial resting potential, which promote drug binding in atria. Kv1.5 channels are truly atrial selective because they do not conduct repolarizing current IKur in ventricles. Constitutively active IK,ACh is predominantly observed in remodelled atria from patients in permanent atrial fibrillation (AF). A lot of effort has been invested to detect compounds which will selectively block Kir3.1/Kir3.4 in their remodelled constitutively active form. Novel drugs which have been and are being developed aim at atrial-selective targets. Vernakalant and ranolazine which mainly block atrial Na(+) channels are clinically effective. Newly designed selective IKur blockers and IK,ACh blockers are effective in animal models; however, clinical benefit in converting AF into sinus rhythm (SR) or reducing AF burden remains to be demonstrated. In conclusion, atrial-selective antiarrhythmic agents have a lot of potential, but a long way to go.

Non-alcoholic fatty liver disease is associated with an increased prevalence of atrial fibrillation in hospitalized patients with Type 2 diabetes

NAFLD (non-alcoholic fatty liver disease) and AF (atrial fibrillation) are two pathological conditions that are highly prevalent in developed countries and share multiple risk factors. The relationship between NAFLD and AF in Type 2 diabetes is currently unknown. We studied a hospital-based sample of 702 patients with Type 2 diabetes discharged from our Division of Endocrinology during 2007-2011. The diagnosis of AF was confirmed in affected participants on the basis of ECGs and medical history by experienced cardiologists. NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other liver diseases. Of the 702 hospitalized patients included in the study, 514 (73.2%) of them had NAFLD and 85 (12.1%) had persistent or permanent AF. NAFLD was associated with an increased risk of prevalent AF {OR (odds ratio), 3.04 [95% CI (confidence interval), 1.54-6.02]; P<0.001}. Adjustments for age, sex, systolic BP (blood pressure), HbA1c, (glycated haemoglobin), estimated GFR (glomerular filtration rate), total cholesterol, electrocardiographic LVH (left ventricular hypertrophy), COPD (chronic obstructive pulmonary disease), and prior history of HF (heart failure), VHD (valvular heart disease) or hyperthyroidism did not attenuate the association between NAFLD and AF [adjusted OR, 5.88 (95% CI, 2.72-12.7); P<0.001]. In conclusion, our results show that ultrasound-diagnosed NAFLD is strongly associated with an increased prevalence of persistent or permanent AF in patients with Type 2 diabetes, independently of several clinical risk factors for AF. The potential impact of NAFLD on AF deserves particular attention, especially with respect to the implications for screening and surveillance strategies in the growing number of patients with NAFLD.

OPG/RANK/RANKL Axis in Stabilization of Spontaneously Restored Sinus Rhythm in Permanent Atrial Fibrillation Patients after Mitral Valve Surgery

Objective: To investigate the expression of the osteoprotegerin (OPG)/receptor activator of nuclear factor-ĸB (RANK)/RANK ligand (RANKL) axis in the stabilization of spontaneously restored sinus rhythm (SR) in permanent atrial fibrillation (AF) patients after mitral valve (MV) surgery and study its clinical significance. Methods: Clinical data, biopsies of right atrial appendages were collected from 135 permanent AF patients who spontaneously restored SR after conventional isolated MV replacement. A comparison was made between patients who had recurrence of AF within 7 days and patients with persistent SR for more than 7 days. Results: AF patients had an increased expression of RANK, RANKL, and the RANKL/OPG ratio compared to SR patients, and the degree of fibrosis was lower in SR compared to AF in the atria. Moreover, the expressions of RANK, RANKL, and the RANKL/OPG ratio were positively correlated with the degree of fibrosis. Conclusion: These findings suggest that the OPG/RANK/RANKL axis plays important roles in the stabilization of restored SR after MV surgery by stimulating AF-related atrial remodeling in AF patients.

STUDY ON RELATIONSHIP BETWEEN VENTRICULAR RATE CONTROL AND CARDIOPULMONARY EXERCISE FUNCTION & QUALITY OF LIFE AMONG PERMANENT ATRIAL FIBRILLATION PATIENTS

ObjectivesIt is controversial regarding the goal for controlling ventricular rate among permanent atrial fibrillation (AF) patients. RACE II tests showed that both the level 1 composite end point and the...

Distribution and Risk Profile of Paroxysmal, Persistent, and Permanent Atrial Fibrillation in Routine Clinical Practice

Background— There is a paucity of international data on the various types of atrial fibrillation (AF) outside the highly selected populations from randomized trials. This study aimed to describe patient characteristics, risk factors, comorbidities, symptoms, management strategy, and control of different types of AF in real-life practice. Methods and Results— Real-life global survey evaluating patients with atrial fibrillation (RealiseAF) was a contemporary, large-scale, cross-sectional international survey of patients with AF who had ≥1 episode in the past 12 months. Investigators were randomly selected to avoid bias. Among 9816 eligible patients from 831 sites in 26 countries, 2606 (26.5%) had paroxysmal, 2341 (23.8%) had persistent, and 4869 (49.6%) had permanent AF. As AF progressed from paroxysmal to persistent and permanent forms, the prevalence of comorbidities, such as heart failure (32.9%, 44.3%, and 55.6%), coronary artery disease (30.0%, 32.9%, and 34.3%), cerebrovascular disease (11.7%, 10.8%, and 17.6%), and valvular disease (16.7%, 21.2%, and 35.8%), increased, and the prevalence of lone AF decreased. Similarly, there was an increase in mean CHADS 2 [cardiac failure, hypertension, age, diabetes, stroke (doubled)] score (1.7, 1.8, and 2.2), and more than half of patients (51.0%, 56.7%, and 67.3%) qualified for oral anticoagulants. Almost 90% of patients received ≥1 antiarrhythmic drug, but &gt;60% had European Heart Rhythm Association symptom scores from II to IV. Furthermore, 40.7% of persistent and 49.8% of permanent AF patients were still in AF with a heart rate &gt;80 beats per minute. Conclusions— This survey disclosed high cardiovascular risks and an unmet need in daily practice for patients with any type of AF, especially those with the permanent form.

Cyclic Adenosine Monophosphate Phosphodiesterase Type 4 Protects Against Atrial Arrhythmias

This study was designed to examine whether a cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE), PDE4, is expressed in human atrium and contributes to the control of electrical stability. Atrial fibrillation is accompanied by a profound remodeling of membrane receptors and alterations in cAMP-dependent regulation of Ca(2+) handling. Being responsible for cAMP hydrolysis, PDEs are likely to play a role in this setting. In the rodent heart, PDE4 contributes up to 60% of total cAMP-hydrolytic activity. However, its role in the human heart remains controversial. L-type Ca(2+) current and spontaneous Ca(2+) release were recorded in isolated human atrial myocytes. Intracellular cAMP was measured by live cell imaging using a fluorescence resonance energy transfer-based sensor. Contractile force and arrhythmias were recorded in human atrial trabeculae. PDE activity was measured in human atrial tissue from patients in sinus rhythm and permanent atrial fibrillation. PDE4 is expressed in human atrial myocytes and accounts for approximately 15% of total PDE activity. PDE4D represents the major PDE4 subtype. PDE4 inhibition increased intracellular cAMP and L-type Ca(2+) current and dramatically delayed their decay after a brief β-adrenergic stimulation. PDE4 inhibition also increased the frequency of spontaneous Ca(2+) release at baseline, as well as the contractile response and the incidence of arrhythmias in human atrial strips during β-adrenergic stimulation. Total PDE activity decreased with age, and the relative PDE4 activity was lower in patients with permanent atrial fibrillation than in age-matched sinus rhythm controls. PDE4 is critical in controlling cAMP levels and thereby Ca(2+) influx and release in human atrial muscle, hence limiting the susceptibility to arrhythmias.

Continuous versus Intermittent Monitoring of Ventricular Rate in Patients with Permanent Atrial Fibrillation

Ventricular rate control (VRC) is an important treatment strategy for patients with permanent atrial fibrillation (AF). We assessed the prevalence of poor VRC and the adequacy of various intermittent monitoring regimens to accurately characterize VRC during permanent AF. We retrospectively analyzed data from dual chamber implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D) patients in the Medtronic Discovery™ Link having permanent AF (AF burden >23 hours/day) and ≥ 365 consecutive days of device data. Poor VRC was defined as a day with the mean ventricular rate during AF >100 beats/minute (bpm) for ICD patients and >90 bpm for CRT-D patients. Intermittent monitoring regimens were simulated from continuous device data by randomly selecting subsets of days in which data were available for analysis. Assessments of poor VRC were computed after replicating 1,000 simulations. ICD (n = 1,902, age = 71 ± 10) and CRT-D (n = 3,397, age = 72 ± 9) patients were included and followed for 365 days. The prevalence of poor VRC was 24.8% among ICD patients and 28.6% among CRT-D patients. Significantly more patients were identified as having poor VRC with continuous monitoring compared to all intermittent monitoring regimens (sensitivity range = 8%-31%). Furthermore, 11.6% of ICD patients and 17.9% of CRT-D patients experienced ≥ 7 days with poor VRC, to which the sensitivities of annual 7- and 21-day recordings were <7% and <20%, respectively. A significant proportion of permanent AF patients experience poor VRC that would be missed with random intermittent monitoring. Whether improved knowledge of VRC with continuous monitoring will lead to improved outcomes compared to intermittent monitoring requires further study.

Effect of physical exercise training on muscle strength and body composition, and their association with functional capacity and quality of life in patients with atrial fibrillation: A randomized controlled trial

Atrial fibrillation diminishes cardiac function, exercise tolerance and quality of life. The objective of this study was to determine whether exercise training in atrial fibrillation affects muscle strength, body composition, maximal exercise capacity and walking capacity positively, thus improving quality of life. Randomized clinical trial. Twelve weeks of physical exercise training or control. Forty-nine patients in permanent atrial fibrillation were randomized to training or control. Intervention consisted of aerobic training for 1 h 3 times per week at 70% of maximal exercise capacity vs control. Muscle strength, exercise capacity, 6-minute walk test, lean body mass, fat percentage, and quality of life were assessed. Muscle strength increased in the training group (p = 0.01), but no change was observed in controls. Lean body mass was unchanged in both groups. Fat percentage decreased in both groups, but there was no significant difference between the groups. Exercise capacity improved in the training group (p < 0.001), with no change in the control group. There was a significant difference after the training period between the training and control groups in terms of exercise capacity. (p = 0.001). Six-min walk test improved in the training group compared with controls (p < 0.01). Overall quality of life score, as measured by the Minnesota Living with Heart Failure Questionnaire, improved in the training group (p = 0.03). Quality of life, measured by Short Form-36, improved in the training group in 3 out of 8 subscales: physical functioning (p = 0.02), general health perceptions (p = 0.001) and vitality (p = 0.02). Muscle strength, exercise capacity and quality of life increased with exercise training in subjects with atrial fibrillation. Lean body mass was unchanged.

Relation of hs-CRP and BNP levels with the atrial spontaneous echo contrast and thrombi in permanent atrial fibrillation patients with different etiologies

SummaryBackgroundThromboembolic risk in permanent atrial fibrillation (AF) is strongly associated with the underlying etiology, and inflammatory parameters may contribute. The present study aimed to investigate the relationship of hs-CRP and BNP levels with left and right atrial appendage (LAA and RAA) function, presence of spontaneous echo contrast (SEC) and thrombus.Material/MethodsEighty-four permanent AF patients with different etiologies (20 mitral stenosis, 44 hypertension and 20 hyperthyroidism) and 23 patients with sinus rhythm were included. LAA and RAA flow velocities were measured by pulsed-wave Doppler and wall motion velocities with tissue Doppler imaging (TDI) in transesophageal echocardiography.ResultsHs-CRP and BNP levels significantly differed among the 3 AF groups: levels were highest in mitral stenosis patients (8.6±5.3 mg/L and 98.0±125.7 pg/mL, respectively), the lowest hs-CRP was in hyperthyroidism patients (4.3±3.8 mg/L), and the lowest BNP was in hypertensive patients (64.8±44.3 pg/mL). There were also significant differences between the AF group and controls regarding hs-CRP and BNP levels. In the correlation analysis, BNP level was not significantly correlated with LAA and RAA functions, whereas hs-CRP level was significantly correlated with some LAA and RAA functions. On the other hand, hs-CRP level was significantly related to the presence of mild-moderate SEC and thrombi, mainly in mitral stenosis patients. Moreover, hs-CRP was the most important determinant of RAA thrombus formation, followed by RAA ejection fraction. In contrast, no positive or negative correlation was found between BNP levels and RAA and LAA thrombi.ConclusionsHigher hs-CRP levels in AF patients may be a predictor for the presence of SEC and thrombi in the atria.

Efficacy of Low Interatrial Septum and Right Atrial Appendage Pacing for Prevention of Permanent Atrial Fibrillation in Patients With Sinus Node Disease

Background— The role of pacing sites and atrial electrophysiology on the progression of atrial fibrillation (AF) to the permanent form in patients with sinus node dysfunction (SND) has never been investigated. The aim of the study was to investigate the relationship between atrial electrophysiology and the efficacy of atrial pacing at the low interatrial septum (IAS) or at the right atrial appendage (RAA) to prevent persistent/permanent AF in patients with SND. Methods and Results— The Electrophysiology-Guided Pacing Site Selection (EPASS) Study was a prospective, controlled, randomized study. Atrial refractoriness, basal and incremental conduction times from the RAA to the coronary sinus ostium were measured before implantation, and the difference (ΔCTos) was calculated. Patients with ΔCTos ≥50 ms (study group) and those with ΔCTos &lt;50 ms (control group) were randomly assigned to RAA or IAS with algorithms for continuous atrial stimulation “on.” The primary end point was time to development of permanent or persistent AF within a 2-year follow-up in the study group, IAS versus RAA. Data were analyzed by intention to treat. One hundred two patients (77±7 years, 44 mol/L) were enrolled, 69 (68%) in the study group and 33 (32%) in the control group. Of these, 97 ended the study, respectively, randomly assigned: 29 IAS versus 36 RAA and 18 IAS versus 14 RAA. After a mean follow-up of 15±7 (median, 17) months, 11 (16.6%) patients in the study group met the primary end point: 2 IAS versus 9 RAA (log rank=3.93, P =0.047). Conclusions— In patients with SND and intra-atrial conduction delay, low IAS pacing was superior to RAA pacing in preventing progression to persistent or permanent AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00239226.

POSTER PRESENTATIONS

POSTER PRESENTATIONS

Getting to the heart of cardiac remodeling; how collagen subtypes may contribute to phenotype

The objective of this study was to investigate the nature and biomechanical properties of collagen fibers within the human myocardium. Targeting cardiac interstitial abnormalities will likely become a major focus of future preventative strategies with regard to the management of cardiac dysfunction. Current knowledge regarding the component structures of myocardial collagen networks is limited, further delineation of which will require application of more innovative technologies. We applied a novel methodology involving combined confocal laser scanning and atomic force microscopy to investigate myocardial collagen within ex-vivo right atrial tissue from 10 patients undergoing elective coronary bypass surgery. Immuno-fluorescent co-staining revealed discrete collagen I and III fibers. During single fiber deformation, overall median values of stiffness recorded in collagen III were 37±16% lower than in collagen I [p<0.001]. On fiber retraction, collagen I exhibited greater degrees of elastic recoil [p<0.001; relative percentage increase in elastic recoil 7±3%] and less energy dissipation than collagen III [p<0.001; relative percentage increase in work recovered 7±2%]. In atrial biopsies taken from patients in permanent atrial fibrillation (n=5) versus sinus rhythm (n=5), stiffness of both collagen fiber subtypes was augmented (p<0.008). Myocardial fibrillar collagen fibers organize in a discrete manner and possess distinct biomechanical differences; specifically, collagen I fibers exhibit relatively higher stiffness, contrasting with higher susceptibility to plastic deformation and less energy efficiency on deformation with collagen III fibers. Augmented stiffness of both collagen fiber subtypes in tissue samples from patients with atrial fibrillation compared to those in sinus rhythm are consistent with recent published findings of increased collagen cross-linking in this setting.

Prevention of all-cause and sudden cardiac death in atrial fibrillation patients with long RR interval by pacemaker implantation and evaluation of quality of life

ObjectiveTo investigate the occurrence of all-cause and sudden cardiac death, and cardiovascular events in atrial fibrillation (AF) patients with long RR interval and to evaluate their quality of life after...

Role of oral amiodarone in patients with atrial fibrillation and congestive heart failure

Amiodarone is recognized as the most effective therapy for maintaining sinus rhythm (SR) post cardioversion in patients with atrial fibrillation (AF). It is also recommended for controlling AF in patients with congestive heart failure (CHF). We retrospectively examined the efficacy and safety of oral amiodarone in patients with AF and CHF. Forty-eight consecutive AF patients whose left ventricular ejection fraction (LVEF) was less than 50% and B-type natriuretic peptide (BNP) was higher than 100 pg/ml were investigated retrospectively, and divided into 3 groups: paroxysmal AF, 16 patients; persistent AF, 9 patients; and permanent AF, 23 patients. The permanent AF group had a longer history of AF, larger left ventricular end-diastolic diameter (LVDd) and left atrial diameter (LAD) than paroxysmal and persistent AF groups (p<0.05). After median follow-up of 265 days, amiodarone suppressed paroxysms in 88% of paroxysmal AF patients, while SR was maintained in all persistent AF patients, and 35% of permanent AF patients. Of the 32 persistent and permanent AF patients, 12 (71%) out of 17 maintained SR after successful electrical cardioversion, and conversion to SR occurred spontaneously in 5 (33%) out of 15. The effective group had significantly smaller LVDd and LAD than the ineffective group. In the effective group, BNP decreased significantly from 723±566 pg/ml to 248±252 pg/ml, (p<0.0005) and LVEF increased significantly from 33±7% to 50±13% (p<0.0005) during follow up, while no changes were observed in the ineffective group. The patients with low LVEF (≤30%) benefited comparably from amiodarone to the patients with LVEF >30%. Complications occurred in 24 (50%) patients leading to discontinuation of amiodarone in 11 (23%). Oral amiodarone helped restore SR in paroxysmal and persistent AF patients with CHF. The successful rhythm control by amiodarone resulted in the improvement of LV function and the decrease of BNP levels.