Response In Atrial Fibrillation Research Articles

Circulating microRNAs and DNA Methylation as Regulators of Direct Oral Anticoagulant Response in Atrial Fibrillation and Key Elements for the Identification of the Mechanism of Action (miR-CRAFT): Study Design and Patient Enrolment.

Direct oral anticoagulants (DOACs) are the standard treatment for thromboembolic protection in atrial fibrillation (AF) patients. Epigenetic modifications, such as DNA methylation and microRNAs, have emerged as potential biomarkers of AF. The epigenetics of DOACs is still an understudied field. It is largely unknown whether epigenetic modifications interfere with DOAC response or whether DOAC treatment induces epigenetic modifications. To fill this gap, we started the miR-CRAFT (Circulating microRNAs and DNA methylation as regulators of Direct Oral Anticoagulant Response in Atrial Fibrillation) research study. In miR-CRAFT, we follow, over time, changes in DNA methylation and microRNAs expression in naïve AF patients starting DOAC treatment. The ultimate goal of miR-CRAFT is to identify the molecular pathways epigenetically affected by DOACs, beyond the coagulation cascade, that are potentially mediating DOAC pleiotropic actions and to propose specific microRNAs as novel circulating biomarkers for DOAC therapy monitoring. We herein describe the study design and briefly present the progress in participant enrolment.

The Role of Hypomagnesemia in Cardiac Arrhythmias: A Clinical Perspective.

The importance of magnesium (Mg2+), a micronutrient implicated in maintaining and establishing a normal heart rhythm, is still controversial. It is known that magnesium is the cofactor of 600 and the activator of another 200 enzymatic reactions in the human organism. Hypomagnesemia can be linked to many factors, causing disturbances in energy metabolism, ion channel exchanges, action potential alteration and myocardial cell instability, all mostly leading to ventricular arrhythmia. This review article focuses on identifying evidence-based implications of Mg2+ in cardiac arrhythmias. The main identified benefits of magnesemia correction are linked to controlling ventricular response in atrial fibrillation, decreasing the recurrence of ventricular ectopies and stopping episodes of the particular form of ventricular arrhythmia called torsade de pointes. Magnesium has also been described to have beneficial effects on the incidence of polymorphic ventricular tachycardia and supraventricular tachycardia. The implication of hypomagnesemia in the genesis of atrial fibrillation is well established; however, even if magnesium supplementation for rhythm control, cardioversion facility or cardioversion success/recurrence of AF after cardiac surgery and rate control during AF showed some benefit, it remains controversial. Although small randomised clinical trials showed a reduction in mortality when magnesium was administered to patients with acute myocardial infarction, the large randomised clinical trials failed to show any benefit of the administration of intravenous magnesium over placebo.

Acute Lower Extremity Embolism Resulting in Rheumatic Mitral Stenosis: A Case Report

A 52-year-old woman was admitted with sudden onset of acute arterial occlusion in the right lower limb. We found 3-4/6 diastolic murmur and, in the ECG, rapid ventricular response in atrial fibrillation. The patient underwent an emergency operation. We applied transthoracic and transesophageal echocardiography to investigate the etiology of thromboembolism and diagnosed the patient with mitral stenosis. The patient was recommended for a mitral valve surgery. Preoperative coronary angiography revealed a normal picture. The mitral valve was resected in the operation. We also performed carbon-coated bileaflet prosthetic valve replacement. The left atrial appendix was ligated. The patient did not have any postoperative clinical problems. Having recommended appropriate medical treatment, the patient was discharged. In conclusion, thromboembolism and atrial fibrillation in patients with rheumatic heart diseases should be kept in mind throughout the diagnosis process. Keywords: Thromboembolism; Mitral Stenosis; Atrial Fibrillation.

THE IMPACT OF PACING ALGORITHMS ON DELIVERY OF BIVENTRICULAR PACING: ANALYSIS OF DEVICE DATA FROM 76,955 CRT PATIENTS

Lower percentage of bi-ventricularly paced beats (%VP) is associated with a higher mortality in Cardiac Resynchronization Therapy (CRT) patients. Modern CRT devices provide algorithms to increase %VP, such as Ventricular Sense Response (VSR), Conducted Atrial Fibrillation Response (CAFR) and Atrial

Low-dose diltiazem in atrial fibrillation with rapid ventricular response

Objectives Diltiazem is one of the most commonly used medications to control the rapid ventricular response in atrial fibrillation (AF). The recommended starting dose is an intravenous bolus of 0.25 mg/kg over 2 minutes. To avoid hypotension, we have empirically used a lower dose of diltiazem. We compared the efficacy and safety of different doses of diltiazem in rapid AF. Methods A retrospective chart review was undertaken in patients who presented to the emergency department with rapid AF. Patients were divided into 3 groups according to diltiazem dosage: low dose (≤0.2 mg/kg), standard dose (>0.2 and ≤0.3 mg/kg), and high dose (>0.3 mg/kg). We compared the rates of therapeutic response (adequate rate control) and complications (such as hypotension). Multivariate regression analysis was used to determine the effect of diltiazem dose on the occurrence of complications. Results A total of 180 patients were included in the analysis. There were no significant differences in the rates of therapeutic response for the low-, standard-, and high-dose groups (70.5%, 77.1%, and 77.8%; P = .605). The rates of hypotension in the low-, standard-, and high-dose groups were 18%, 34.9%, and 41.7%, respectively. After adjusting confounding variables, the rate of hypotension was significantly lower in the low-dose group in comparison with the standard-dose group (adjusted odds ratio, 0.39; 95% confidence interval, 0.16-0.94). Conclusions Low-dose diltiazem might be as effective as the standard dose in controlling rapid AF and reduce the risk of hypotension.

Use of intravenous magnesium to treat acute onset atrial fibrillation: a meta-analysis

Objectives:To assess the effects of intravenous magnesium on converting acute onset atrial fibrillation to sinus rhythm, reducing ventricular response and risk of bradycardia.Design and data sources:Randomised controlled trials evaluating intravenous...

Response of Atrial Fibrillation to Pulmonary Vein Antrum Isolation Is Directly Related to Resumption and Delay of Pulmonary Vein Conduction

Response of Atrial Fibrillation to Pulmonary Vein Antrum Isolation Is Directly Related to Resumption and Delay of Pulmonary Vein Conduction

Response of Atrial Fibrillation to Pulmonary Vein Antrum Isolation Is Directly Related to Resumption and Delay of Pulmonary Vein Conduction

Response of Atrial Fibrillation to Pulmonary Vein Antrum Isolation Is Directly Related to Resumption and Delay of Pulmonary Vein Conduction

Response of Atrial Fibrillation (AF) to Pulmonary Vein Antrum Isolation (PVAI) is directly related to resumption and delay of Pulmonary Vein (PV) conduction

Response of Atrial Fibrillation (AF) to Pulmonary Vein Antrum Isolation (PVAI) is directly related to resumption and delay of Pulmonary Vein (PV) conduction

Carvedilol's antiarrhythmic properties: Therapeutic implications in patients with left ventricular dysfunction

Carvedilol is a beta- and alpha-adrenergic-blocking drug with clinically important antiarrhythmic properties. It possesses anti-ischemic and antioxidant activity and inhibits a number of cationic channels in the cardiomyocyte, including the HERG-associated potassium channel, the L-type calcium channel, and the rapid-depolarizing sodium channel. The electrophysiologic properties of carvedilol include moderate prolongation of action potential duration and effective refractory period; slowing of atrioventricular conduction; and reducing the dispersion of refractoriness. Experimentally, carvedilol reduces complex and repetitive ventricular ectopy induced by ischemia and reperfusion. In patients, carvedilol is effective in controlling the ventricular rate response in atrial fibrillation (AF), with and without digitalis, and is useful in maintaining sinus rhythm after cardioversion, with and without amiodarone. In patients with AF and heart failure (HF), carvedilol reduces mortality risk and improves left ventricular (LV) function. Large-scale clinical trials have demonstrated that combined carvedilol and angiotensin-converting enzyme inhibitor therapy significantly reduces sudden cardiac death, mortality, and ventricular arrhythmia in patients with LV dysfunction (LVD) due to chronic HF or following myocardial infarction (MI). Despite intensive neurohormonal blockade, mortality rates remain relatively high in patients with post-MI and nonischemic LVD. Recent trials of implantable cardioverter-defibrillators added to pharmacologic therapy, especially beta blockers, have shown a further reduction in arrhythmic deaths in these patients.

Monitoring the complexity of ventricular response in atrial fibrillation

Atrial fibrillation does not present a uniform extent of variability of the ventricular response exemplifying periodicities and more complex fluctuations, due to varying number and shape of atrial wavelets and aberrant conduction in the AV‐junction. It was sought to categorise different degrees of complexity introducing an uncomplicated monitoring method for that objective.The fluctuation of RR‐intervals was investigated in 66 patients presenting with atrial fibrillation at different times of the day using conventional statistical methods as well as methods derived from non‐linear dynamics. Specifically Poincaré‐plots were employed to analyse the data. One hundred and seventy data sets consisting of 5000–8000 intervals each were considered.Statistical methods were shown to describe the observed dynamics not adequately due to background noise in the acquired data as well as owing to intrinsic qualities of the data sets. Namely non‐uniformly distributed data and trends within the data sets constituted limitations of statistical methods.Poincaré‐plots were proven to be an inexpensive and effective method to categorise the complexity of the ventricular response in atrial fibrillation. Periodical variation of interval lengths could be clearly differentiated from continuous variation in the considered data sets. The latter could be shown to exemplify either stochastic fluctuation or complex non‐linear dynamics of RR‐interval variation. Thus, different degrees of complexity could be clearly distinguished.It could be shown exemplary that the observed dynamics remained nearly constant within the observation period.Poincaré‐plots, thus, provide a means to appreciate the fluctuation of RR‐intervals semiquantitatively and to distinguish different patterns of fluctuation dynamics of the ventricular response in atrial fibrillation without being affected by contaminated or inconsistent data.For a complete visualisation of the concerned dynamics relatively small data sets suffice. Thus, it is possible to observe the pattern of fluctuation essentially in real time which makes them ideally suited for future investigation.

Respiratory systolic pressure variability during atrial fibrillation and sinus rhythm.

Previous studies have found that respiratory variations of ventricular response in atrial fibrillation are infrequent and inconsistent. This asynchrony between heart rate and respiration may characterize the physiological mechanisms coupling heart rate and systolic blood pressure oscillations in the respiratory band. The aim of this study was to evaluate whether synchronous variations in systolic blood pressure and respiration depend on a simultaneous change in heart rate. Univariate and bivariate spectral analyses were made of the R-R interval, systolic blood pressure, and respiratory signals during controlled respiration (16 breaths/min) in 24 patients with atrial fibrillation before and after efficacious electrical cardioversion and in 24 age- and sex-matched control subjects. During atrial fibrillation, the spectral coherence between respiration and heart rate was low (0.18+/-0.03), but there was a high level of coherence between respiration and systolic blood pressure (0.67+/-0.05). After cardioversion, the coherence between respiration and heart rate increased to 0.86+/-0.04, whereas the geometric mean values of the concomitant respiratory systolic blood pressure oscillations decreased by 72% (from 21.1 to 5.9 mm Hg(2), P<0.001), which was similar to that observed in the control group (5. 7 mm Hg(2)). These results confirm the inconsistent effect of respiration on heart rate response during atrial fibrillation and demonstrate that respiratory sinus arrhythmia is not a prerequisite for systolic blood pressure oscillations but may play an antioscillatory role in respiratory systolic blood pressure variability, which is probably mediated by arterial baroreflex mechanisms.

Ventricular response in atrial fibrillation: random or deterministic?

The ventricular response in atrial fibrillation is often described as "chaotic," but this has not been demonstrated in the strict mathematical sense. A defining feature of chaotic systems is sensitive dependence on initial conditions: similar sequences evolve similarly in the short term but then diverge exponentially. We developed a nonlinear predictive forecasting algorithm to search for predictability and sensitive dependence on initial conditions in the ventricular response during atrial fibrillation. The algorithm was tested for simulated R-R intervals from a linear oscillator with and without superimposed white noise, a chaotic signal (the logistic map) with and without superimposed white noise, and a pseudorandom signal and was then applied to R-R intervals from 16 chronic atrial fibrillation patients. Short-term predictability was demonstrated for the linear oscillators, without loss of predictive ability farther into the future. The chaotic system demonstrated high short-term predictability that declined rapidly further into the future. The pseudorandom signal was unpredictable. The ventricular response in atrial fibrillation was weakly predictable (statistically significant predictability in 8 of 16 patients), without sensitive dependence on initial conditions. Although the R-R interval sequence is not completely unpredictable, a low-dimensional chaotic attractor does not govern the irregular ventricular response during atrial fibrillation.

Spontaneous Echo Contrast and Atrial Fibrillation Response

Spontaneous Echo Contrast and Atrial Fibrillation Response

Effective use of a novel rate-smoothing algorithm in atrial fibrillation by ventricular pacing.

It is still unknown whether a fast heart rate or an irregular ventricular response in atrial fibrillation causes tachycardiomyopathy. Reduction in the variability of RR intervals without an increase in heart rate might be an alternative treatment when antiarrhythmic drugs fail to control the irregularity accompanying atrial fibrillation. Eight patients underwent temporary right ventricular pacing, using a novel rate-smoothing algorithm prior to DC cardioversion or His bundle ablation. A rate-smoothing algorithm was utilized by right ventricular apical stimulation. Spontaneous and paced RR intervals during atrial fibrillation were quantified and processed for statistical analysis. The rate-smoothing algorithm resulted in a substantial reduction in the variance of the RR intervals (slow mode 73.1%, fast mode 40.0%) and RR range (slow mode 49.3%, fast mode 34.3%). In contrast to previous algorithms, the mean heart rate during pacing intervention in atrial fibrillation did not change significantly to the heart rate directly preceding the pacemaker intervention (+2%). This initial study of the novel rate-smoothing algorithm shows that pacing intervention is a relatively safe, rapid and reliable alternative therapy for controlling irregular ventricular rhythms due to atrial fibrillation. Incorporation of the algorithm in implantable pacemakers appears justified, but demands further prospective studies in patients to evaluate relief of symptoms and reduction of tachycardiomyopathy due to atrial fibrillation.

Importance of assessing changes in ventricular response to atrial fibrillation during evaluation of new heart failure therapies: Experience from trials of flosequinan

This study evaluated the effects of flosequinan on ventricular rate in patients with congestive heart failure and atrial fibrillation to determine whether this agent has a facilitatory effect on atrioventricular conduction and whether such an effect may be deleterious. Flosequinan is known to have a dose-dependent positive chronotropic effect on the sinus node, but its effect on atrioventricular conduction has not been evaluated. An excessive increase in ventricular rate during the treatment of heart failure could raise a safety concern and counterbalance beneficial responses. Data were analyzed from 338 patients participating in three similarly designed placebo-controlled exercise trials with flosequinan who also underwent ambulatory electrocardiographic monitoring. The effects of two doses of flosequinan on supine, standing, ambulatory, and exercise heart rates and on exercise capacity in patients in sinus rhythm and atrial fibrillation were compared. Flosequinan increased heart rate in a dose-dependent manner, in patients both with sinus rhythm and atrial fibrillation. A 100 mg once daily dose produced significant increases, in both rhythms, ranging from 6 to 11 beats/min, in supine and standing heart rate, ambulatory heart rate, and exercise heart rate. With a dose of 75 mg twice daily, heart rates under these conditions increased by >20 beats/min in flosequinan-treated patients in atrial fibrillation, a change significantly greater than that observed with placebo or flosequinan, 100 mg once daily and also more than in patients in sinus rhythm treated with the same dose. These results indicate that flosequinan facilitates atrioventricular nodal conduction, increasing the ventricular response in atrial fibrillation, especially at higher dosages. This finding could result from a direct drug action, such as phosphodiesterase inhibition, or reflex sympathetic activation. This response is of sufficient magnitude potentially to impair left ventricular function and interfere with clinical benefit. The effect of heart-failure drugs on ventricular responses in atrial fibrillation should be examined to provide insight into potential mechanisms of both action and safety in this common patient group.

Radiofrequency Catheter Ablation Versus Modification of the AV Node for Control of Rapid Ventricular Response in Atrial Fibrillation

Atrial fibrillation is a common arrhythmia, which is frequently difficult to control. Symptoms and ventricular dysfunction may be caused by a rapid ventricular response to atrial fibrillation. Radiofrequency catheter ablation techniques for ventricular rate control have been developed, including AV node modification and AV node ablation with pacemaker implantation. For both AV node modification and ablation, radiofrequency energy is applied via a 4-mm tipped electrode catheter. For AV node ablation radiofrequency energy is applied near the compact AV node or His bundle via the right atrium, or occasionally at the His bundle via the left ventricle. For AV node modification radiofrequency energy is applied in the low middle or posterior septal right atrium near the tricuspid valve annulus. Both techniques can effectively control ventricular response to atrial fibrillation and the associated symptoms, although AV node modification is effective in only about 70% of patients compared to AV node ablation, which is effective in nearly 100%. In patients responding to AV node modification, maximal and mean ventricular response to atrial fibrillation is reduced by 25% to 35% chronically. Inadvertent AV block may occur during attempted AV node modification. It seems appropriate to attempt AV node modification prior to AV node ablation in patients with refractory atrial fibrillation and rapid ventricular response, in order to avoid the need for permanent pacemaker implantation. Although unproven, studies suggest that the mechanism by which AV node modification achieves ventricular rate control may be slow-pathway ablation in the low posterior septal right atrium.

993-44 The Ventricular Response in Atrial Fibrillation is Not Chaotic

In nonlinear dynamics, chaos refers to a system that is aperiodic but deterministic (nonrandom). Although the ventricular response during atrial fibrillation (AF) is commonly described as chaotic, it has yet to be demonstrated that this represents chaos in the mathematical sense. A defining characteristic of chaotic systems is sensitive dependence on initial conditions; i.e. similar sequences evolve similarly in the near future, but then diverge exponentially. We developed a nonlinear predictive forecasting algorithm to search for evidence of short-term predictability and sensitive dependence on initial conditions in recordings of 2000 ectopy-and artifact-free RR intervals obtained during routine activity in 5 pts with AF. The algorithm: 1) uses the technique of lags to reconstruct phase spaces with embedding dimensions from 3 to 10,2) the 3 nearest neighbors of a given trajectory are used to predict the evolution of the trajectory from 1 to 10 intervals into the future and 3) the correlation coefficient between predicted and actual evolution is computed for all RR intervals in the time series. The results were compared to test sequences from linear oscillators with high and low signal-noise ratios and a system with chaotic dynamics (the logistic map). Distinct from each of the test sets, the ventricular response in AF was only weakly predictable at all time scales, and did not exhibit sensitive dependence on initial conditions. The irregular ventricular response during AF is not governed by a low-dimensional chaotic attractor.

Ventricular response in atrial fibrillation is not chaotic

Ventricular response in atrial fibrillation is not chaotic

Variability of the ventricular response in atrial fibrillation and prognosis in chronic nonischemic mitral reurgitation

Although reduced heart rate (HR) variability during sinus rhythm is associated with an adverse prognosis in a variety of clinical settings, the significance of measures of variability of the ventricular response in atrial fibrillation (AF) requires clarification. AF is common among patients with chronic severe mitral regurgitation (MR) and potentially limits the application of HR variability techniques in this population. Therefore, this study examined the physiologic correlates and prognostic significance of measures of HR variability in 21 patients with nonischemic causes of chronic severe MR who had chronic AF and underwent 24-hour ambulatory electrocardiography as part of a prospective study of the natural history of regurgitant valvular heart disease. Patients were followed for up to 9.1 years and end points of mortality and progression to mitral valve surgery were tabulated. Time- and frequency-domain measurements of high-, low-, and ultralow-frequency HR variability were computed and compared with resting ventricular function by radionuclide cineangiography and outcome. All measures of HR variability were covariate (pair-wise r values between 0.48 and 0.99, all p values < 0.03), and none of the variables was significantly related to age, ventricular premature complex (VPC) density, or right or left ventricular ejection fraction. Reductions in time-domain measurements of ultra-low- and high-frequency HR variability were significant predictors of the combined risk of mortality or requirement for mitral valve surgery (p = 0.02 and p = 0.05, respectively). Thus, although measures of HR variability in AF with MR are not associated with age, VPC density, or ventricular performance, variability of the ventricular response in chronic AF is inversely related to risk in patients with chronic severe MR.