Atrial Fibrillation In Association Research Articles

Molecular mechanisms of postoperative atrial fibrillation in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) promotes atrial remodeling and fibrosis, providing a substrate for atrial fibrillation (AF). Herein, we investigate the pathophysiological mechanisms of AF in association with OSA in a cohort of cardiac surgery patients. A prospective study including patients undergoing cardiac surgery. Biomarkers reflective of AF pathophysiology (interleukin [IL-6], C-reactive protein [CRP], von Willebrand factor [vWF], N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity Troponin T [hs-TnT], and Galectin-3 [Gal-3]) was assessed by functional or immunological assays. miRNAs involved in AF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Using atrial tissue samples, fibrosis was assessed by Masson's trichrome. Connexin 40 and 43 (Cx40; Cx43) were evaluated by immunolabeling. Fifty-six patients (15 with OSA and 41 non-OSA) were included in this hypothesis-generating pilot study. OSA group had a higher incidence of postoperative AF (POAF) (46.7% vs. 19.5%; p = .042), presented an increased risk of POAF (OR 3.61, 95% CI 1.01-12.92), and had significantly higher baseline levels of NT-proBNP (p = .044), vWF (p = .049), Gal-3 (p = .009), IL-6 (p = .002), and CRP (p = .003). This group presented lower levels of miR-21 and miR-208 (both p < .05). Also, lower Cx40 levels in POAF and/or OSA patients (50.0% vs. 81.8%, p = .033) were found. The presence of interstitial fibrosis (according to myocardial collagen by Masson's trichrome) was raised in OSA patients (86.7% vs. 53.7%, p = .024). Several biomarkers and miRNAs involved in inflammation and fibrosis were dysregulated in OSA patients, which together with a higher degree of interstitial fibrosis, altered miRNA, and Cxs expression predisposes to the development of a substrate that increases the AF risk.

Glucagon-Like Peptide-1 Protects Against Atrial Fibrillation and Atrial Remodeling in Type 2 Diabetic Mice

Atrial fibrillation (AF) is highly prevalent in type 2 diabetes where it increases morbidity and mortality. Glucagon-like peptide (GLP)-1 receptor agonists are used in the treatment of type 2 diabetes (T2DM), but their effects on AF in T2DM are poorly understood. The present study demonstrates type 2 diabetic db/db mice are highly susceptible to AF in association with atrial electrical and structural remodeling. GLP-1, as well as the long-acting GLP-1 analogue liraglutide, reduced AF and prevented atrial remodeling in db/db mice. These data suggest that GLP-1 and related analogues could protect against AF in patients with T2DM.

Atrial fibrillation: focus on monitoring strategies after cryptogenic stroke.

Atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes, with stroke potentially being the first manifestation of a previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic events, searching for unknown AF after stroke requires a comprehensive diagnostic workup. Prospective data have demonstrated the benefits of long-term cardiac monitoring to identify AF in association with cryptogenic stroke, as most strokes are presumed to result from AF. However, strategies of empirical anticoagulation using oral anticoagulants following cryptogenic stroke failed to improve outcomes. We herein summarize contemporary evidence and knowledge gaps on searching for AF after a stroke and the potential secondary prevention strategies to prevent further recurrences.

Long-Term Exposures to Air Pollution and the Risk of Atrial Fibrillation in the Women's Health Initiative Cohort.

Background:Atrial fibrillation (AF) is associated with substantial morbidity and mortality. Short-term exposures to air pollution have been associated with AF triggering; less is known regarding associations between long-term air pollution exposures and AF incidence.Objectives:Our objective was to assess the association between long-term exposures to air pollution and distance to road on incidence of AF in a cohort of U.S. women.Methods:We assessed the association of high resolution spatiotemporal model predictions of long-term exposures to particulate matter ( and ), sulfur dioxide (), nitrogen dioxide (), and distance to major roads with incidence of AF diagnosis, identified through Medicare linkage, among 83,117 women in the prospective Women’s Health Initiative cohort, followed from enrollment in Medicare through December 2012, incidence of AF, or death. Using time-varying Cox proportional hazards models adjusted for age, race/ethnicity, study component, body mass index, physical activity, menopausal hormone therapy, smoking, diet quality, alcohol consumption, educational attainment, and neighborhood socioeconomic status, we estimated the relative risk of incident AF in association with each pollutant.Results:A total of 16,348 incident AF cases were observed over 660,236 person-years of follow-up. Most exposure–response associations were nonlinear. was associated with risk of AF in multivariable adjusted models [; 95% confidence interval (CI): 1.13, 1.24, comparing the top to bottom quartile, ]. Women living closer to roadways were at higher risk of AF (e.g., ; 95% CI: 1.01, 1.13 for living within of A3 roads, compared with , ), but we did not observe adverse associations with exposures to , , or . There were adverse associations with (top quartile ; 95% CI: 1.05, 1.16, ) and (top quartile ; 95% CI: 1.03, 1.14, ) in sensitivity models adjusting for census region.Discussion:In this study of postmenopausal women, and distance to road were consistently associated with higher risk of AF. https://doi.org/10.1289/EHP7683

Preoperative atrial fibrillation in association with reduced haemoglobin predicts increased 30-d mortality after cardiac surgery

Objectives Atrial fibrillation is the most common arrhythmia occurring after cardiac surgery. Less attention has been focused on preoperative atrial fibrillation and anaemia as risk factors for mortality after cardiac surgery. The aim of this study was to determine preoperative risk factors for 30-d mortality after open-heart surgery. Design. The study population consisted of 2015 patients (73.4% men; mean age 68 years) undergoing coronary artery bypass grafting (CABG) (52.0%), aortic valve replacement (AVR) (18.6%), AVR and CABG (10.0%), mitral valve plasty or replacement (14.0%), and AVR and aortic root reconstruction (ARR) (5.5%) in Kuopio University Hospital from January 2013 to December 2016. Univariate and multivariate Cox proportional hazards models were used for statistical analyses. Kaplan–Meier survival curves were generated. Results. Total 30-d mortality was 1.8%. By Cox regression analysis, predictors of 30-d mortality (hazard ratio [HR] [95% confidence interval [CI]]) included female gender (1.95 [1.00–3.77]), preoperative atrial fibrillation, (2.38 [1.12–5.03]) reduced haemoglobin level (3.40 [1.47–7.90]), and pulmonary congestion (3.16 [1.52–6.55]). The combination of preoperative reduced haemoglobin and preoperative atrial fibrillation was a strong predictor (12.37 [4.40–34.77], p < .001). Estimated glomerular filtration rate (eGFR) predicted 30-d mortality in univariate models but was not an independent predictor in multivariate models. Conclusions. According to the main findings of our study, the combination of preoperative atrial fibrillation and reduced haemoglobin level substantially increase the risk of 30-d mortality after cardiac surgery. Identification of high-risk patients pre-operatively could help to make optimal clinical decisions for timing of operation and perioperative treatment.

Ibrutinib and Novel Oral Anticoagulants: Three Case Reports from a Single Center Real Life Experience

Background: Chronic Lymphocytic Leukemia (CLL) represents 7% of Non Hodgkin Lymphoma being the most common leukemia. Efficacy and safety data on Ibrutinib used as a single agent for treatment of previously treated CLL comes from RESONATE trial, which showed 6% of Overall incidence of grade 3 atrial fibrillation (AF).Another side effect of Ibrutinib is increased rate of bleeding. The 2019 long term follow-up of RESONATE 2 trial of Ibrutinib in previously untreated CLL reported major hemorrhage and grade 3 AF in 11% and 5% of patients on Ibrutinib arm, respectively; notably, 67% of patients who experienced Grade 3 Major hemorrhage were taking concomitant anticoagulation therapy. The use of Ibrutinib in patients with AF requiring anticoagulation therapy could be challenging, given that both the optimal starting dose of Novel Anti Coagulants (NOACs) and the specific NOAC to be used in patients taking ibrutinib have not been established yet. Here we describe the clinical history of three CLL patients affected by AF treated with ibrutinib associated with NOACs. Cases : 1. The first patient was a 72-year-old male affected by IGHV unmutaded CLL with no TP53 disruption relapsed five years after the achievement of first complete remission through 6 courses R-Bendamustine. He started full dose Ibrutinib on august 2019. When he started ibrutinib there were no bulky lesions, the biggest node diameter was 2.7 cm, spleen longest diameter was 18 cm, Hb was 9.3 g/dL, platelets were 166,000/µL, neutrophils 4,000/µL and ALC 129,000/ µL, b symptoms were absent. Since 2018 he suffered from chronic AF treated with Apixaban at the dose of 5 mg BID. He achieved partial response with no evidence of lymphadenopathy and lymphocytosis after 6 months of treatment with no occurrence of major bleeding. On April 2020 he came to our attention with minor bleeding consisting of small petechial macules. Neither epistaxis nor bruising were reported. Petechiae resolved on May 2020, at last follow-up clinical visit (July 2020) Ibrutinib and Apixaban are still well tolerated and signs and symptoms of both CLL and bleeding are absent. 2. The second patient was a 65-year-old male affected by IGHV unmutated CLL with no TP53 disruption, relapsed three years after a complete response achieved with first line treatment with 6 courses of R-Bendamustine. When he started full dose Ibrutinib (420 mg OD), Hb was 11.8 g/dL, neutrophils 5,100/ µL, lymphocyte 145,000/ µL and platelets 51,000/ µL. He achieved partial remission on May 2020. On April 2020, high rate AF was diagnosed, heart rate was 162 beats per min, systolic and diastolic blood pressure were 125 and 80 mmHg, respectively. The cardiologist prescribed bisoprolole 1.25 mg OD and after 24h heart rate became normal (60 beats per min). An Echocardiography was performed showing ejection fraction of 60% with all other parameters being normal. CHADS-VASc score was 3 and HAS-BLED score was 2, so he started Edoxaban at the dose of 30 mg OD, while Ibrutinib was never stopped. The patient now has neither signs and symptoms of CLL, nor those of AF and bleeding. 3. The last patient was a 81-year-old male affected by previously untreated IGHV mutated CLL with TP53 mutation and absence of del 17p. High rate AF was diagnosed on may 2020 and edoxaban 30 mg OD was started. He started reduced dose Ibrutinib (280 mg OD) on the first days of July 2020 due to risk of bleeding. Hb, neutrophils, lymphocyte and platelets were 10.8 g/dL, neutrophils 2,730/ µL, lymphocyte 195,000/µL and platelets were 116,000/µL. RAI and Binet where 3 and B, respectively. CLL-IPI was 8 (very high risk), neither bulky nodes nor B symptoms were present. After 1 month-follow-up there is no evidence of bleeding and AF is still asymptomatic. Conclusions: In our limited experience and according with literature, Ibrutinib could be safely used in patients with pre-existing or de novo AF in association with NOACs with no or minimal bleeding signs. Therefore, patients affected by AF might completely benefit from this highly effective therapy for CLL. Disclosures No relevant conflicts of interest to declare.

Electrical and structural remodeling contribute to atrial fibrillation in type 2 diabetic db/db mice

Atrial fibrillation (AF) is highly prevalent in diabetes mellitus (DM), yet the basis for this finding is poorly understood. Type 2 DM may be associated with unique patterns of atrial electrical and structural remodeling; however, this has not been investigated in detail. The purpose of this study was to investigate AF susceptibility and atrial electrical and structural remodeling in type 2 diabetic db/db mice. AF susceptibility and atrial function were assessed in male and female db/db mice and age-matched wildtype littermates. Electrophysiological studies were conducted invivo using intracardiac electrophysiology and programmed stimulation. Atrial electrophysiology was also investigated in isolated atrial preparations using high-resolution optical mapping and in isolated atrial myocytes using patch-clamping. Molecular biology studies were performed using quantitative polymerase chain reaction and western blotting. Atrial fibrosis was assessed using histology. db/db mice were highly susceptible to AF in association with reduced atrial conduction velocity, action potential duration prolongation, and increased heterogeneity in repolarization in left and right atria. In db/db mice, atrial K+ currents, including the transient outward current (Ito) and the ultrarapid delayed rectifier current (IKur), were reduced. The reduction in Ito occurred in association with reductions in Kcnd2 mRNA expression and KV4.2 protein levels. The reduction in IKur was not related to gene or protein expression changes. Interstitial atrial fibrosis was increased in db/db mice. Our study demonstrates that increased susceptibility to AF in db/db mice occurs in association with impaired electrical conduction as well as electrical and structural remodeling of the atria.

Loss of insulin signaling may contribute to atrial fibrillation and atrial electrical remodeling in type 1 diabetes

Atrial fibrillation (AF) is prevalent in diabetes mellitus (DM); however, the basis for this is unknown. This study investigated AF susceptibility and atrial electrophysiology in type 1 diabetic Akita mice using in vivo intracardiac electrophysiology, high-resolution optical mapping in atrial preparations, and patch clamping in isolated atrial myocytes. qPCR and western blotting were used to assess ion channel expression. Akita mice were highly susceptible to AF in association with increased P-wave duration and slowed atrial conduction velocity. In a second model of type 1 DM, mice treated with streptozotocin (STZ) showed a similar increase in susceptibility to AF. Chronic insulin treatment reduced susceptibility and duration of AF and shortened P-wave duration in Akita mice. Atrial action potential (AP) morphology was altered in Akita mice due to a reduction in upstroke velocity and increases in AP duration. In Akita mice, atrial Na+ current (INa) and repolarizing K+ current (IK) carried by voltage gated K+ (Kv1.5) channels were reduced. The reduction in INa occurred in association with reduced expression of SCN5a and voltage gated Na+ (NaV1.5) channels as well as a shift in INa activation kinetics. Insulin potently and selectively increased INa in Akita mice without affecting IK Chronic insulin treatment increased INa in association with increased expression of NaV1.5. Acute insulin also increased INa, although to a smaller extent, due to enhanced insulin signaling via phosphatidylinositol 3,4,5-triphosphate (PIP3). Our study reveals a critical, selective role for insulin in regulating atrial INa, which impacts susceptibility to AF in type 1 DM.

NPR-C (Natriuretic Peptide Receptor-C) Modulates the Progression of Angiotensin II-Mediated Atrial Fibrillation and Atrial Remodeling in Mice.

Atrial fibrillation (AF) commonly occurs in hypertension and in association with elevated Ang II (angiotensin II) levels. The specific mechanisms underlying Ang II-mediated AF are unclear, and interventions to prevent the effects of Ang II are lacking. NPs (natriuretic peptides), which elicit their effects through specific NP receptors, including NPR-C (natriuretic peptide receptor-C), are cardioprotective hormones that affect cardiac structure and function. This study used wild-type and NPR-C knockout (NPR-C-/-) mice to investigate the effects of Ang II (3 mg/kg per day for 3 weeks) on AF susceptibility and atrial function using in vivo electrophysiology, high-resolution optical mapping, patch clamping, and molecular biology. In some experiments, wild-type mice were cotreated with Ang II and the NPR-C agonist cANF (0.07-0.14 mg/kg per day) for 3 weeks. In wild-type mice, Ang II increased susceptibility to AF in association with a prolongation of P-wave duration, increased atrial refractory period, and slowed atrial conduction. These effects were exacerbated in Ang II-treated NPR-C-/- mice. Ang II prolonged action potential duration and reduced action potential upstroke velocity (Vmax). These effects were greater in left atrial myocytes from Ang II-treated NPR-C-/- mice. Ang II also increased fibrosis in both atria in wild-type mice, whereas Ang II-treated NPR-C-/- mice exhibited substantially higher fibrosis throughout the atria. Fibrotic responses were associated with changes in expression of profibrotic genes, including TGFβ and TIMP1. Cotreating wild-type mice with Ang II and the NPR-C agonist cANF dose dependently reduced AF inducibility by preventing some of the Ang II-induced changes in atrial myocyte electrophysiology and preventing fibrosis throughout the atria. NPR-C may represent a new target for the prevention of Ang II-induced AF via protective effects on atrial electrical and structural remodeling.

Atrial fibrillation and cryptogenic stroke. What is the current evidence? Role of electrocardiographic monitoring.

The diagnosis of cryptogenic stroke is made by exclusion. However, current evidence supports the role of atrial fibrillation episodes as a cause of this condition. Prospective data have demonstrated the benefits of long‐term electrocardiographic monitoring to identify atrial fibrillation in association with cryptogenic stroke. This aim of this article was to analyze the contemporary evidence for the possible relationship between atrial fibrillation and cryptogenic stroke and the role of continuous electrocardiographic monitoring to clarify this hypothesis.

Antithrombotic therapy in atrial fibrillation associated with valvular heart disease: a joint consensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology Working Group on Thrombosis, endorsed by the ESC Working Group on Valvular Heart Disease, Cardiac Arrhythmia Society of Southern Africa (CASSA), Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), South African Heart

Atrial fibrillation (AF) is a major worldwide public health problem, and AF in association with valvular heart disease (VHD) is also common. However, management strategies for this group of patients have been less informed by randomized trials, which have largely focused on 'non-valvular AF' patients. Thrombo-embolic risk also varies according to valve lesion and may also be associated with CHA2DS2VASc score risk factor components, rather than only the valve disease being causal. Given marked heterogeneity in the definition of valvular and non-valvular AF and variable management strategies, including non-vitamin K antagonist oral anticoagulants (NOACs) in patients with VHD other than prosthetic heart valves or haemodynamically significant mitral valve disease, there is a need to provide expert recommendations for professionals participating in the care of patients presenting with AF and associated VHD. To address this topic, a Task Force was convened by the European Heart Rhythm Association (EHRA) and European Society of Cardiology (ESC) Working Group on Thrombosis, with representation from the ESC Working Group on Valvular Heart Disease, Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart) Association and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE) with the remit to comprehensively review the published evidence, and to publish a joint consensus document on the management of patients with AF and associated VHD, with up-to-date consensus recommendations for clinical practice for different forms of VHD. This consensus document proposes that the term 'valvular AF' is outdated and given that any definition ultimately relates to the evaluated practical use of oral anticoagulation (OAC) type, we propose a functional Evaluated Heartvalves, Rheumatic or Artificial (EHRA) categorization in relation to the type of OAC use in patients with AF, as follows: (i) EHRA Type 1 VHD, which refers to AF patients with 'VHD needing therapy with a Vitamin K antagonist (VKA); and (ii) EHRA Type 2 VHD, which refers to AF patients with 'VHD needing therapy with a VKA or a Non-VKA oral anticoagulant (NOAC)', also taking into consideration CHA2DS2VASc score risk factor components. This consensus document also summarizes current developments in the field, and provides general recommendations for the management of these patients based on the principles of evidence-based medicine.

Atrial Fibrillation in Hypertensive Heart Disease is Associated with Distinct Patterns of Electrical Remodeling in the Left and Right Atria

Atrial fibrillation (AF) is a major complication in hypertensive heart disease and has been linked to alterations in angiotensin II (AngII) signaling; however, the mechanisms underlying the increase in susceptibility to AF in the presence of AngII are poorly understood. The goal of this study was to characterize changes in atrial electrophysiology in mice treated chronically with AngII. AngII treated mice developed elevated blood pressure and cardiac hypertrophy in comparison to saline treated controls. In intracardiac programmed stimulation studies, 50% of AngII treated mice (n=10) were induced into AF vs. 0% of saline treated mice (P<0.05; n=9). P wave duration, a measure of atrial conduction, was prolonged in AngII treated mice (P<0.001; n=12 mice). Electrical remodeling following AngII treatment was investigated by patch-clamping atrial myocytes. In right atrial myocytes, AngII prolonged action potential (AP) duration compared to saline (P<0.05; n=9-11 myocytes) without changes in AP upstroke velocity (Vmax; P=0.66) or overshoot (OS; P=0.53). Strikingly, in left atrial myocytes AngII treatment resulted in greater AP prolongation (P<0.001; n=12-14 myocytes) and reductions (P<0.05) in AP Vmax and AP overshoot vs. saline controls. Voltage clamp studies demonstrate that in right atrial myocytes (n=21-26) the transient outward potassium current (Ito) was reduced (P<0.05) following AngII treatment. Similarly, 4-aminopyradine (4-AP; 100 µM) reduced right atrial K+ currents (P<0.05) indicating a reduction in the ultra-rapid delayed rectifier K+ current (IKur) after AngII treatment. In left atrial myocytes, (n=11-13) Ito and 4-AP sensitivity were both reduced (P<0.05) following AngII treatment. The reduction in Ito was larger (P<0.05) in left vs. right atrial myocytes. Our study demonstrates that chronic AngII treatment creates a substrate for AF in association with distinct electrophysiological alterations in right and left atrial myocytes.

Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study

SummaryBisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year.IntroductionBisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure.MethodsWe performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95 % confidence intervals (CI). The BP exposure was classified into current (<90 days prior to ID), recent (91–180), past (181–364), and distant past (≥365) use, with the latter category being used as a reference point. A subgroup analysis by individual BP was then carried out.ResultsIn comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95 % CI = 1.46–2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95 % CI, 1.59–2.43).ConclusionIn our nested case-control study, current users of BP are associated with a higher risk of atrial fibrillation as compared with those who had stopped BP treatment for more than 1 year.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-014-3020-y) contains supplementary material, which is available to authorized users.

Increased atrial arrhythmia susceptibility induced by intense endurance exercise in mice requires TNFα

Atrial fibrillation (AF) is the most common supraventricular arrhythmia that, for unknown reasons, is linked to intense endurance exercise. Our studies reveal that 6 weeks of swimming or treadmill exercise improves heart pump function and reduces heart-rates. Exercise also increases vulnerability to AF in association with inflammation, fibrosis, increased vagal tone, slowed conduction velocity, prolonged cardiomyocyte action potentials and RyR2 phosphorylation (CamKII-dependent S2814) in the atria, without corresponding alterations in the ventricles. Microarray results suggest the involvement of the inflammatory cytokine, TNFα, in exercised-induced atrial remodelling. Accordingly, exercise induces TNFα-dependent activation of both NFκB and p38MAPK, while TNFα inhibition (with etanercept), TNFα gene ablation, or p38 inhibition, prevents atrial structural remodelling and AF vulnerability in response to exercise, without affecting the beneficial physiological changes. Our results identify TNFα as a key factor in the pathology of intense exercise-induced AF.

Is catheter ablation the best way to restore endothelial function?: Reply

We would like to thank Dr. Guo and his colleagues for their kind interest in our manuscript [1,2]. Several mechanisms may be responsible for impaired endothelial function in the context of atrial fibrillation (AF). Noris et al. [3] reported that the magnitude and dynamic nature of fluid shear stress have a major influence on endothelial cell nitric oxide (NO) synthesis. Laminar shear stress associated with sinus rhythm dose-dependently upregulates NO synthesis by cultured endothelial cells, whereas turbulent shear stress characteristic of AF has no effect on NO synthetic pathways. Minamino et al. [4] demonstrated that plasma levels of nitrite/nitrate and platelet cyclic guanosine monophosphate (cGMP) levels were decreased in patients with AF in association with the presence of abnormalities in hemostatic conditions. Furthermore, endothelial function improved after restoration of sinus rhythm from AF. Takahashi et al. [5] confirmed that endothelium-dependent vasodilation in response to acetylcholine was impaired in patients with AF and that this deficit was ameliorated after restoration of sinus rhythm via electrical cardioversion. Shin et al. [6] confirmed that AF patients have impaired brachial artery flow mediated dilatation (FMD), which can be reversed through induction and maintenance of sinus rhythm via catheter ablation. We did not explore whether antiarrhythmic drugs can restore endothelial function in our study as Dr. Guo and his colleagues stated in their letter [1]. However, endothelial function appears to improve after restoration of sinus rhythm irrespective of the strategy used to achieve conversion to sinus rhythm. Of note, previous studies examining the strategy of rhythm control versus rate control in the management of AF have not yet proven the benefit of a return to sinus rhythm [7]. Therefore, we agree with the suggestions by Guo and colleagues that our study would have benefited from inclusion of a rhythm control vs. rate control analysis to investigate whether antiarrhythmic drugs can restore endothelial function. We conclude that assessment of endothelial function may offer important information for AF patients who are scheduled to undergo conversion to sinus rhythm.

The cardiac neuronal hierarchy and susceptibility to arrhythmias

The cardiac neuronal hierarchy and susceptibility to arrhythmias

Mortality in patients with atrial fibrillation: improving or not?

This editorial refers to ‘Mortality in patients with atrial fibrillation has significantly decreased during the last three decades: 35 years of follow-up in 1627 pacemaker patients’ † by S. Asbach et al. on page 391 Atrial fibrillation (AF) is the commonest sustained arrhythmia, with an increasing incidence. 1 With the increasing elderly population, the prevalence of AF is estimated to rise, conferring a significant mortality and morbidity. In the Framingham study, the presence of AF independently increased mortality in men by 1.5-fold and in women by 1.9-fold. 2 Given that the average lifetime risk of developing AF is 25% 3 and the high economic cost associated with AF, 4 it is clear that we are dealing with a condition with major public health implications. The mortality and morbidity associated with AF are probably not homogeneous when taking into consideration related co-morbidities, complications, and treatment strategies. The lowest risk group is probably that with the so-called ‘lone AF’, which is essentially a diagnosis of exclusion, where AF is associated with no obvious pre-disposing factor on thorough clinical history and examination, with a structurally normal heart on echocardiography, normal ECG (except for AF), normal blood tests, and normal chest X-ray. 5 As we recently highlighted, some series even report an increased mortality with lone AF patients. 6 This may reflect how hard we look for associated co-morbidities, and furthermore, as patients get older, new co-morbidities will intervene. 5 At the other extreme, the presence of AF in patients with acute coronary syndromes, 7 congestive cardiac failure, and in the post-operative setting conditions associated with greater risk of adverse events. For example, an analysis from the TRAndolapril Cardiac Evaluation (TRACE) 7 study reported AF to increase total mortality by 33%, with a risk ratio for sudden cardiac death (SCD) of 1.31 (95% CI: 1.07– 1.60; P , 0.009). Furthermore, the adjusted risk ratio of AF for non-SCD was 1.43 (95% CI: 1.21–1.70; P , 0.0001). Similarly, data from the Framingham Heart Study 8 reported that AF associated with the subsequent development of heart failure resulted in an increased mortality [men: hazard ratio (HR) 2.7, 95% CI: 1.9–3.7 and women: HR 3.1, 95% CI: 2.2–4.2]. Clearly, AF in association with heart disease is not a good combination. Perhaps what has attracted much interest in AF is the morbidity and mortality associated with stroke and thrombo-embolism. 9 Overall, AF increases the risk of stroke by up to 5-fold, but this risk is not homogeneous. 9,10 Stroke risk in AF is increased with the presence of associated stroke risk factors such as previous stroke, increasing age, hypertension, diabetes mellitus, and so on—with the risk being cumulative with increasing co-morbidities. 11,12 For example, this risk increases with age, with stroke occurring in 1.5% of the under 60 year olds and rising to 23.5% in the over 80s 11 and is further increased (for example) by concomitant hypertension. Given the improvements in the recognition and management of the co-morbid conditions associated with AF— especially hypertension, heart failure, and coronary artery disease—one would expect an improvement in the clinical outcome and prognosis of this arrhythmia. Is this really the case?

Anticoagulant and Antiplatelet Therapy Use in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: The Need for Consensus and a Management Guideline

There is a lack of published evidence on what is the optimal management strategy in anticoagulated patients with nonvalvular atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI) and, hence, need antiplatelet therapy. Review of cases of patients with nonvalvular AF undergoing PCI in our hospital, either as an elective case or following acute coronary syndrome (ACS). By means of our local West Midlands Regional Health Authority computerized Hospital Activity Analysis register, we obtained a list of all patients seen at our hospital with a diagnosis of AF in association with ACS or PCI between 2000 and 2005. Patient clinical details and antithrombotic therapy management during PCI were recorded. Of the drugs prescribed on discharge, aspirin and clopidogrel were prescribed to 25 patients (71.4%), while 6 patients (17.1%) were discharged receiving triple therapy, 2 patients (5.7%) receiving clopidogrel alone, and 2 patients (5.7%) receiving warfarin plus one antiplatelet drug (either aspirin or clopidogrel). There was wide variability in the antithrombotic regime and duration of treatment used by the four interventionists in our unit. This case series reveals the lack of any coordinated strategy in the prevention of thrombotic or thromboembolic events in patients with AF and a recent PCI. Further large studies are required to assess the bleeding and thrombotic risk with various post-PCI strategies in order to facilitate the development of guidelines. Suggested management guidelines are made in this article.

Drug-Induced Changes in Fibrillation Cycle Length and Organization Index Can Predict Chemical Cardioversion of Long-Lasting Atrial Fibrillation With Bepridil Alone or in Combination With Aprindine

The aim of this study was to investigate whether drug-induced changes in fibrillation wave characteristics can predict pharmacological conversion of long lasting persistent atrial fibrillation (AF). The study group comprised 23 consecutive patients with AF lasting > or =1 month. Patients first received bepridil (200 mg/day) for 2-4 weeks. When sinus rhythm was not restored with bepridil, oral aprindine (40 or 60 mg/day) was added to bepridil. Fast Fourier transform analysis of fibrillation waves using lead V1 was performed to calculate the fibrillation cycle length (FCL). The spectral areas were measured and the maximum area divided by the total area was termed the fibrillation organization index (FOI). Sinus rhythm was restored in 16 of 23 patients (70%); 8 of these 16 patients received only bepridil (Group I) and the other 8 responders received bepridil and aprindine (Group II). In Group I bepridil increased both FCL (p<0.001) and FOI (p<0.01) and terminated AF after 20+/-12 days. In Group II bepridil increased FCL (p<0.001), but did not change FOI. The addition of aprindine terminated AF in association with an increase in both FCL (p<0.005) and FOI (p<0.005) within 19+/-8 days. In the remaining 7 patients who did not have restoration of sinus rhythm, bepridil increased both FCL and FOI significantly, but less than in Group I, and the addition of aprindine did not further increase either of them. Chemical cardioversion of AF occurred in all patients with FCL > or =190 ms and FOI > or =45% after drug administration. Bepridil alone or in combination with aprindine converted long lasting persistent AF in association with an increase in both FCL and FOI. The combination of FCL and FOI after drug administration is helpful in predicting chemical cardioversion of persistent AF.

Atrial fibrillation in patients with heart failure: pharmacologic options.

Atrial fibrillation is a common arrhythmia in patients with heart failure. The presence of atrial fibrillation deteriorates cardiac function and increases the risk of thromboembolic events. The management of patients with atrial fibrillation in association with heart failure should consist of ventricular rate control, prevention of thromboembolic events, and conversion to normal sinus rhythm. Traditionally, digoxin has been widely used in patients with heart failure and atrial fibrillation; however, it does very little to restore sinus rhythm and requires the addition of another rate-limiting agent to control ventricular rate. The likelihood of successful cardioversion is dependent on the duration of heart failure and the degree of neurohormonal activation. The initiation of antiarrhythmic drug therapy in patients with heart failure should be guided by safety issues as well as consideration of potential benefits vs. risks associated with therapy. Amiodarone has been evaluated in numerous clinical trials and appears to be safe and effective when used in low dosage. Treatment with dofetilide is another option. Comparative studies with oral dofetilide vs. amiodarone are needed to evaluate their efficacy in restoration and maintenance of sinus rhythm in patients with heart failure. Such trials will clearly define the role of dofetilide in the treatment of atrial fibrillation. Routine prophylactic use of antiarrhythmic drug therapy for chronic atrial fibrillation in the setting of heart failure is not recommended due to a low efficacy rate and high proarrhythmic risk. Anticoagulation with warfarin and rate control remain the standard therapy. (c)2001 by CHF, Inc.