Does the progression of myocardial fibrosis lead to atrial fibrillation in patients with hypertrophic cardiomyopathy?

The majority of left ventricular (LV) inflow volumes in hypertrophic cardiomyopathy (HCM) depend on atrial contraction because of impaired LV relaxation. If HCM is complicated by atrial fibrillation (AF), heart failure can develop because of the loss of atrial contraction. The purpose of this study was to determine the relationship between the development of AF and myocardial fibrosis or intramyocardial small artery (IMSA) stenosis in autopsied hearts with HCM. Studies were performed in five HCM hearts with AF (AF group) and five HCM hearts without AF (non-AF group). LV specimens were divided into the inner (IT), middle (MT), and outer (OT) thirds. We selected at random 120 fields and 20 IMSAs from each layer and assessed them quantitatively using an image analyzer. We determined the extent of fibrosis (%F) and the degree of stenosis of each IMSA (%L). The %F in the AF group was greater than in the non-AF group (P<.01). In the AF group, the %F of the IT was greater than in the MT and the OT (P<.01). In the non-AF group, the %F of the IT was greater than in the MT (P<.05), and the %F of the MT was greater than in the OT (P<.01). The %L was similar in the AF and non-AF groups. In both groups, the %L of the IT was lower than in the MT (P<.01), which was lower than that of the OT (P<.05). LV fibrosis is more severe in patients with HCM and AF than in those without AF. Therefore, myocardial fibrosis might impair LV relaxation, resulting in hemodynamic intolerance to AF.     

Inflammation and atrial fibrillation: Is Chlamydia pneumoniae a candidate pathogen of atrial fibrillation?

Atrial fibrillation is the most common arrhythmia, however, the mechanism of atrial fibrillation is not well explained. It has been considered that inflammation plays a role in atrial fibrillation, recently. Patients undergoing coronary artery bypass graft are at high risk for developing postoperative atrial fibrillation. The peak levels of C-reactive protein (CRP) were paralleled to the incidence of postoperative atrial fibrillation. In general population, CRP was also higher in patients with atrial fibrillation than in control people. Persistent atrial fibrillation patients had a higher CRP level than paroxysmal atrial fibrillation patients. CRP was not only associated with the presence of atrial fibrillation but may also predict patients at increased risk for future development of atrial fibrillation. Why inflammation markers in atrial fibrillation are high is a puzzling problem. We hypothesized that Chlamydia pneumoniae infection is a possible cause of atrial fibrillation by initiating inflammation response. It was demonstrated that infection of endothelial cells with C. pneumoniae elicited the production of Monocyte Chemoattractant Protein-1, interleukin-1, interleukin-8, interleukin-18, tumor necrosis factor, interferon and soluble intercellular adhesion molecule. Most of these cytokines play a crucial role in inflammation response that associate with the initiating and maintenance of atrial fibrillation. There are so many pathogens that can trigger inflammation. Some evidences showed that C. pneumoniae was the most likely pathogen of atrial fibrillation. In epidemic study, the incidence of atrial fibrillation increased from younger to elder and atrial fibrillation was more common in men than in women. C. pneumoniae has the same epidemic trend as the incidence of atrial fibrillation. Hypertension, myocardial infarction and reduced lung function are predictors of atrial fibrillation. C. pneumoniae infection is high in the patients with the above diseases. C. pneumoniae was found in endomyocardial biopsy samples, which supported C. pneumoniae was the candidate pathogen, too. Chlamydia infection can cause myocardial interstitial fibrosis and inflammation cells infiltration. The pathology characters of C. pneumoniae infection are similar to that found in atrial fibrillation. Seroepidemic study should be carried out to evaluate if there is relationship between C. pneumoniae and atrial fibrillation. If the hypothesis is confirmed, macrocyclic lactone antibiotics may be used to eliminate the pathogen. It will be a new target point to treat atrial fibrillation.     

Expression of angiogenesis-related genes in right atrial appendages from patients with advanced myocardial ischemia – preliminary results

Introduction

The most frequent cause of myocardial ischemia is atherosclerotic lesions which narrow coronary vessels leading to impaired blood flow or their total occlusion.

Material and methods

Using HG-U133A oligonucleotide microarrays (Affymetrix) we studied the expression levels of angiogenesis-related genes in patients with different types of heart failure. We analyzed the RNA from right atrial appendages from patients: 1) with advanced coronary disease and myocardial infarction history, 2) with advanced stable coronary disease and no infarction history, and 3) after surgery due to mitral stenosis, but with no coronary vessel lesions.

Results

Analysis of the data from oligonucleotide microarrays allowed identification of 2 genes (ENG and NPPB) differentiating the examination grups.

Conclusions

Analysis of the expression profile of genes involved in angiogenesis, carried out using data obtained from examined individuals’ samples, suggests that necrosis accompanying myocardial infarction is a significant factor leading to elevated expression levels of genes involved in neoangiogenesis.     

Is there a role for long-chain ω3 or oil-rich fish in the treatment of atrial fibrillation?

Atrial fibrillation is the most common cardiac arrhythmia in Europe and north America, and recently it was described as an epidemic. Treatment and management of this arrhythmia consists of using drugs, external electrical cardioversion and in extreme cases, internal electrical pacing. Despite treatment, this arrhythmia continues to impact on morbidity and mortality. The possible benefit from dietary interventions in relation to the primary and secondary prevention of atrial fibrillation have largely been overlooked. Our hypothesis is that increasing the intake of long-chain polyunsaturated omega3 fatty acids (LCn3) from eating a diet containing moderate amounts of oil-rich fish, will benefit people with persistent atrial fibrillation. A number of possible anti-arrhythmic actions from LCn3 have been found from animal and laboratory studies, mainly on ventricular arrhythmias. These include reducing pro-arrhythmic eicosanoids and inhibiting sodium and calcium currents. If found to be beneficial to these patients, dietary advice to eat more oil-rich fish, or take LCn3 supplements, could be part of a package of care for people with this arrhythmia. We have currently started a randomised controlled trial to test our hypothesis.     

Prediction of atrial fibrillation recurrence after cardioversion—Interaction analysis of cardiac autonomic regulation

Today atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice accounting for approximately one third of hospitalizations and accompanied with a 5 fold increased risk for ischemic stroke and a 1.5 fold increased mortality risk. The role of the cardiac regulation system in AF recurrence after electrical cardioversion (CV) is still unclear.The aim of this study was to investigate the autonomic regulation by analyzing the interaction between heart rate and blood pressure using novel methods of nonlinear interaction dynamics, namely joint symbolic dynamics (JSD) and segmented Poincaré plot analysis (SPPA). For the first time, we applied SPPA to analyze the interaction between two time series. Introducing a parameter set of two indices, one derived from JSD and one from SPPA, the linear discriminant function analysis revealed an overall accuracy of 89% (sensitivity 91.7%, specificity 86.7%) for the classification between patients with stable sinus rhythm (group SR, n = 15) and with AF recurrence (group REZ, n = 12). This study proves that the assessment of the autonomic regulation by analyzing the coupling of heart rate and systolic blood pressure provides a potential tool for the prediction of AF recurrence after CV and could aid in the adjustment of therapeutic options for patients with AF.     

Autoantibodies in atrial fibrillation: actor, biomaker or bystander?

Atrial fibrillation (AF) is one of the most common arrhythmias in patients with congestive heart failure, although the underlying mechanism has still to be determined. There is increasing evidence to suggest that autoimmunity may play an important role in the pathogenesis of AF. To date, at least three types of autoantibody have been found in AF: the anti-myosin heavy chain autoantibody, the anti-M2 muscarinic receptor autoantibody and the anti-heat shock protein autoantibody. The question is: are these autoantibodies actors, biomakers or merely bystanders? How much knowledge do we have?     

Emergency department protocolised management of acute atrial fibrillation: how many patients in a tertiary hospital are eligible?

An emergency observation department unit (EDOU) treatment protocol for the management of acute atrial fibrillation (AAF) has been demonstrated to be feasible in the United States of America. The aim of this study was to quantify the number of patients presenting with AAF eligible for EDOU protocolized management in an Irish hospital. A retrospective observational study was performed by identifying a sample of patients admitted to hospital with acute atrial fibrillation between January and December 2002. Medical records of one hundred and eleven patients presenting with AAF were identified. Nine patients were eligible for EDOU management. Fourteen patients (12.6%) reverted spontaneously to sinus rhythm in the ED without medical intervention. Eight percent of patients presenting with AAF in an Irish hospital are eligible for protocolized EDOU management.     

Activation of α1-adrenoceptors modulates the inwardly rectifying potassium currents of mammalian atrial myocytes

The selective ₁-adrenergic agonist methoxamine (10^–4–10^–3M), in the presence of propranolol (10^–6M), can reduce both the inwardly rectifying K⁺ background current (I _K1) and the muscarinic cholinergic receptor-activated K⁺ current (I _{K, ACh}) in rabbit atrial myocytes resulting in action potential prolongation during the final phase of repolarization and a depolarization of the resting membrane potential. The reduction of these K⁺ current(s) by ₁-adrenoceptor stimulation was insensitive to pre-treatment of artial myocytes with pertussis toxin (0.15–0.5 g/ml) and was irreversible following intracellular dialysis with the non-hydrolysable guanosine triphosphate (GTP) analogue, Gpp(NH)p (1–5×10^–3M). Neither the protein kinase C (PKC) inhibitors, 1-(5-isoquinolinesulphonyl)-2-methylpiperoxine (H-7) (5×10^–5M) and staurosporine (1×10^–7M), nor downregulation of PKC by prolonged phorbol ester exposure (5×10^–7M, for 7–8 h) had an effect on the ₁-adrenergic modulation of this K⁺ current. Under cellattached patch-clamp conditions, bath application of methoxamine reversibly decreased acetylcholine-induced single-channel activity, thus confirming the observed reduction of the ACh-induced current under whole-cell voltage clamp. These results demonstrate that the ₁adrenoceptor, once activated, can reduce current through two different inwardly rectifying K⁺ channels in rabbit atrial myocytes. These current changes are mediated via a pertussis toxin-insensitive GTP-binding protein, and do not appear to involve the activation of PKC.     

Can atrial vagal denervation influence ventricular function in a failing heart?

Atrial fibrillation (AF) and congestive heart failure (CHF) often coexist (AF-CHF), and each adversely affects the other with respect to management and prognosis. Therapy with antiarrhythmic drugs to maintain sinus rhythm was disappointing. Ablation is more successful than antiarrhythmic drug therapy for the prevention of AF with few complications, although in patients with AF-CHF it is noted. Ablating autonomic nerves and ganglia on the large vessels and the heart can result in AF suppression with little damage to healthy myocardium. Our study in patients with AF-CHF found that cardiac function aggravation was more frequent in patients with AF recurrence than that of those who successfully maintain sinus rhythm. The autonomic nervous system is a fine network spreading throughout the myocytes; hence the elimination of atrial vagal with radiofrequency catheter ablation can influence the innervation in sinus and AV nodes even in the ventricular region. Thus we propose that atrial vagal denervation may result in paratherapeutic sympathovagal imbalance in the ventricular region, which has a negative effect in a failing heart, although it is neutralized by the benefit accrued from sinus rhythm after successful ablation.     

Predictors of incident atrial fibrillation and influence of medications: a retrospective case�Ccontrol study

Background

Atrial fibrillation (AF) is a common condition, associated with raisedmortality and risk of majormorbidity, and is predicted to increase due to an aging population.

Aim

To update earlier research of AF predictors using UK data.

Design and setting

Case–control analysis of adults aged 18 years and older with a diagnosis of AF in practices registered with the General Practice Research Database (GPRD) in the UK.

Method

Using the GPRD, a case.control analysis was performed using logistic regression to compare 55 412 incident AF cases to 216 400 controls, for medical history and prior use of drugs. The association between time since start of diagnosis or drug use and AF risk was summarised using Spline regression.

Results

The following were confirmed as risk factors for AF: heart failure (risk ratio [RR] 2.91 [95% CI = 2.59 to 3.27]); ischaemic heart disease (IHD) (RR 2.00 [95% CI = 1.78 to 2.24]); hypertension (RR 2.60 [95% CI = 2.32 to 2.92]); hyperthyroidism (RR 1.56 [95% CI = 1.39 to 1.75]); being a heavy drinker (RR 1.43 [95% CI = 1.27 to 1.60]); cerebrovascular accident (RR 1.48 [95% CI = 1.32 to 1.66]); and obesity (bodymass index ≥30 kg/m² RR 1.29 [95% CI = 1.15 to 1.45]). Current use of oral glucocorticoids (RR 1.62 [95% CI = 1.44 to 1.82]) and of beta-2 agonists (RR 1.30 [95% CI = 1.16 to 1.46]) were identified as significant risk factors, and statins (RR 0.82 [95% CI = 0.73 to 0.92]) as a significant protective factor. No effect was found for current use of bisphosphonates (RR 0.95 [95% CI = 0.85 to 1.07]), renin.angiotensin.aldosterone system (RAAS) agents (RR 1.04 [95% CI = 0.93 to 1.17]), or xanthine derivatives (RR 1.09 [95% CI = 0.97 to 1.22]). Spline regression analysis found the effect of heart failure, IHD, use of oral glucocorticoids, and use of statins on the likelihood of developing AF was sustained over a number of years.

Conclusion

These findings update the risk factors that are associated with AF, and confirmthe protective properties of statins and the risks of beta-2 agonists in developing AF, but not the supposed protective qualities of glucocorticoids and RAAS agents.     

Automatic detection of atrial fibrillation using the coefficient of variation and density histograms of RR and ΔRR intervals

The paper describes a method for the automatic detection of atrial fibrillation, an abnormal heart rhythm, based on the sequence of intervals between heartbeats. The RR interval is the interbeat interval, and ΔRR is the difference between two successive RR intervals. Standard density histograms of the RR and ΔRR intervals were prepared as templates for atrial fibrillation detection. As the coefficients of variation of the RR and ΔRR intervals were approximately constant during atrial fibrillation, the coefficients of variation in the test data could be compared with the standard coefficients of variation (CV test). Further, the similarities between the density histograms of the test data and the standard density histograms were estimated using the Kolmogorov-Smirnov test. The CV test based on the RR intervals showed a sensitivity of 86.6% and a specificity of 84.3%. The CV test based on the ΔRR intervals showed that the sensitivity and the specificity are both approximately 84%. The Kolmogorov-Smirnov test based on the RR intervals did not improve on the result of the CV test. In contrast, the Kolmogorov-Smirnov test based on the ΔRR intervals showed a sensitivity of 94.4% and a specificity of 97.2%.     

Oral anticoagulant treatment in management of elderly patients with atrial fibrillation [corrected]: is it beneficial or detrimental?

Atrial fibrillation (AF) is supraventricular tachyarrhythmia characterized by uncontrolled atrial activation, and deteriorates atrial function. In AF patients, increasing of age is related with enlarge left atrium (LA), diminished flow velocity of left atrial appendage (LAA), and spontaneously contrast echo, with other factors which are predisposition for LA thrombus. In AF patients, thromboemboli after cardioversion without anticoagulant administration is 1.5-3.0%. Elderly patient is not contraindication for anticoagulant, although higher risk for bleeding. For stroke prevention in >65 years of age whilst the patient is candidate for oral anticoagulant warfarin, it should be prescribed to reach INR 2.0-3.0. Some reports on anticoagulant evaluation (INR) and bleeding as complication of warfarin prescribed for AF treatment are not significantly different in elderly and younger patients.     

Differential lusitropic responsiveness to β-adrenergic stimulation in rat atrial and ventricular cardiac myocytes

Cardiac myocyte relaxation is brought about mainly through Ca2+ uptake into the sarcoplasmic reticulum (SR) by a Ca2+-ATPase isoform, SERCA2a. Its activity is modulated by another protein, phospholamban (PLB). The levels of both proteins differ in some mammals between atrial and ventricular myocardium and this may lead to differences in relaxation, especially under stimulatory conditions. At a concentration of 100 nM, the beta-adrenergic agonist isoprenaline (ISO) accelerates the relaxation of rat papillary muscle more than that of the left atria (16.4 versus 4.0% hastening of time to 50% relaxation, respectively). Ventricular myocytes were 24.7% quicker in reaching 50% of their diastolic length after contraction when treated with ISO compared to atrial myocytes, which were only 3.6% faster. Ca2+ fluorescence transients were also abbreviated in ventricular compared to atrial myocytes exposed to ISO (41.9 versus 25.2% hastening of time to 50% peak Ca2+ respectively). Ca2+ uptake into ventricular SR vesicles was increased by 13% in the presence of protein kinase A while that into atrial SR vesicles remained unaffected. Western blotting analysis revealed 23% less SERCA2a protein, but 76% more PLB in ventricular compared to atrial tissue. We conclude that the distinct levels of SERCA2a and PLB in ventricular and atrial myocardium are responsible for the differential modulation of the relaxation process arising from beta-adrenergic stimulation in single rat atrial and ventricular myocytes.