Atrial Fibrillation In Congestive Heart Failure Research Articles

Autonomic Remodeling in the Left Atrium and Pulmonary Veins in Heart Failure

Background— Atrial fibrillation (AF) is commonly associated with congestive heart failure (CHF). The autonomic nervous system is involved in the pathogenesis of both AF and CHF. We examined the role of autonomic remodeling in contributing to AF substrate in CHF. Methods and Results— Electrophysiological mapping was performed in the pulmonary veins and left atrium in 38 rapid ventricular–paced dogs (CHF group) and 39 control dogs under the following conditions: vagal stimulation, isoproterenol infusion, β-adrenergic blockade, acetylcholinesterase (AChE) inhibition (physostigmine), parasympathetic blockade, and double autonomic blockade. Explanted atria were examined for nerve density/distribution, muscarinic receptor and β-adrenergic receptor densities, and AChE activity. In CHF dogs, there was an increase in nerve bundle size, parasympathetic fibers/bundle, and density of sympathetic fibrils and cardiac ganglia, all preferentially in the posterior left atrium/pulmonary veins. Sympathetic hyperinnervation was accompanied by increases in β 1 -adrenergic receptor R density and in sympathetic effect on effective refractory periods and activation direction. β-Adrenergic blockade slowed AF dominant frequency. Parasympathetic remodeling was more complex, resulting in increased AChE activity, unchanged muscarinic receptor density, unchanged parasympathetic effect on activation direction and decreased effect of vagal stimulation on effective refractory period (restored by AChE inhibition). Parasympathetic blockade markedly decreased AF duration. Conclusions— In this heart failure model, autonomic and electrophysiological remodeling occurs, involving the posterior left atrium and pulmonary veins. Despite synaptic compensation, parasympathetic hyperinnervation contributes significantly to AF maintenance. Parasympathetic and/or sympathetic signaling may be possible therapeutic targets for AF in CHF.

Dronedarone in patients with congestive heart failure: insights from ATHENA

AimsDronedarone is a new multichannel blocking antiarrhythmic drug for treatment of atrial fibrillation (AF). In patients with recently decompensated congestive heart failure (CHF) and depressed LV function, the drug was associated with excess mortality compared with a placebo group. The present study aimed to analyse in detail the effects of dronedarone on mortality and morbidity in AF patients CHF.Methods and resultsWe performed a post hoc analysis of ATHENA, a large placebo-controlled outcome trial in 4628 patients with paroxysmal or persistent AF, to evaluate the relationship between clinical outcomes and dronedarone therapy in patients with stable CHF. The primary outcome was time to first cardiovascular (CV) hospitalization or death. There were 209 patients with NYHA class II/III CHF and a left ventricular ejection fraction ≤0.40 at baseline (114 placebo, 95 dronedarone patients). A primary outcome event occurred in 59/114 placebo patients compared with 42/95 dronedarone patients [hazard ratio (HR) 0.78, 95% CI = 0.52–1.16]. Twenty of 114 placebo patients and 12/95 dronedarone patients died during the study (HR 0.71, 95% CI = 0.34–1.44). Fifty-four placebo and 42 dronedarone patients were hospitalized for an intermittent episode of NYHA class IV CHF (HR = 0.78, 95% CI = 0.52–1.17).ConclusionIn this post-hoc analysis of ATHENA patients with AF and stable CHF, dronedarone did not increase mortality and showed a reduction of CV hospitalization or death similar to the overall population. However, in the light of the ANtiarrhythmic trial with DROnedarone in Moderate to severe CHF Evaluating morbidity DecreAse study, dronedarone should be contraindicated in patients with NYHA class IV or unstable NYHA classes II and III CHF.

Utility of Brain Natriuretic Peptide as a Predictor of Atrial Fibrillation After Cardiac Operations

Atrial fibrillation (AF) occurs frequently after coronary bypass grafting and valve operations. Brain natriuretic peptide (BNP) has been shown to predict recurrence of AF in congestive heart failure. It is a potential biomarker for preoperative risk stratification for development of AF in at-risk patients. A total of 398 consecutive patients were prospectively evaluated for new-onset AF after heart operations. Patients with a history of AF and presence of permanent pacemaker were excluded. BNP levels were measured before and immediately after the operation. AF occurred in 20%. AF was more likely to develop in patients who were older, who underwent valve operations, had a lower ejection fraction, and a larger left atrial size. Preoperative exposure to statins (62% vs 43%, p < 0.01) and angiotensin inhibitors (60% vs 45%, p = 0.02) was more common in patients without AF. BNP values were insignificantly higher preoperatively (361 vs 302 mg/dL, p = 0.3) and postoperatively (312 vs. 229 mg/dL, p = 0.15) in patients with AF. Multivariate logistic analysis showed that older age (odds ratio [OR], 3.1, 95% confidence interval [CI], 1.7 to 5.6), lower ejection fraction (OR, 2.0; 95% CI, 1.2 to 3.3), larger left atrial size (OR, 3.1; 95% CI, 1.9 to 4.9), and nonuse of angiotensin inhibitors (OR, 2.3; 95% CI, 1.1 to 4.8) were independently associated with AF. This study does not support use of BNP for prediction of AF. Age, low ejection fraction, large left atrial size, and nonuse of angiotensin blocking agents were found to be significant predictors of AF development.

Abstract 4863: Rhythm Versus Rate Control Strategies In Heart Failure Patients With Atrial Fibrillation: Impact On Lv Function And Functional Status: Echocardiographic Insights From Af-chf

Background: In heart failure patients, the recently published AF-CHF (Atrial Fibrillation in Congestive Heart Failure) trial did not demonstrate the superiority of a rhythm control (RhyC) over a rate control (RaC) strategy in terms of cardiovascular mortality. Nevertheless, the deleterious hemodynamic effects of AF can lead to further decrease in LV function and symptoms progression. This AF-CHF echocardiographic sub-study was designed to compare the effects of the two treatment strategies (RhyC and RaC) on LV ejection fraction (LVEF), chamber dimensions and volumes, valvular regurgitation, functional status and exercise tolerance. Methods: 59 patients (29 RhyC:30 RaC) enrolled in AF-CHF were prospectively followed in this echocardiography study, with a standardized exam at baseline and 12 months. The primary endpoint was the change in LVEF. Results: (Table 1 ) Mean LVEF at baseline was severely depressed (RhyC:27.0±4.9% and RaC:27.6±7.4%, p=0.73), with significant improvement at follow-up for both groups. Other echocardiographic parameters were unchanged at follow-up, including changes in LV and LA volumes and valvular regurgitation. Clinically, mean six-minute walked distance increased significantly in both groups as did NYHA class without any additional benefit for the rhythm control strategy (both p=NS). Conclusion: In patients with HF and AF, improvements in LVEF and functional status are observed at 12 months without any additional benefit of rhythm control over a rate control strategy.

Left atrial dyssynchrony assessed by strain imaging in predicting future development of atrial fibrillation in patients with heart failure

Background The clinical and echocardiographic parameters associated with the risk of developing new onset atrial fibrillation (AF) in congestive heart failure (CHF) have not been studied comprehensively. We determined if dyssynchronous left atrial (LA) lengthening and contraction predicted future development of new onset AF in patients with CHF. Methods One hundred fifty-eight patients who were admitted for CHF without past or current AF were evaluated. We measured the time to peak velocity and time to peak strain with reference to the QRS complex during ventricular systole (reservoir) and late diastole (atrial contraction) in mid-portion of 4 LA walls. Dyssynchronous atrial lengthening and contraction (atrial dyssynchrony) was defined as the standard deviation of each parameter. Results New onset AF developed in 21 patients (13.3%) after a mean follow-up of 43 ± 15 months. Based on univariate Cox analysis, older age, larger LA dimension and volume index, lower LA fractional shortening, and the presence of atrial dyssynchrony were associated with new onset AF. In multivariate Cox analysis, atrial dyssynchrony based on strain (> 39 ms, HR 10.0, p = 0.003) and LA size (≥ 45 mm, HR 4.3, p = 0.016) were independent predictors of new onset AF in CHF. Conclusions We demonstrated that atrial dyssynchrony based on strain is the strongest univariate and multivariate predictor for new onset AF in hospitalized patients with CHF.

Introduction to atrial fibrillation and heart failure: a mutually noxious association.

The complex interactions between atrial fibrillation (AF) and congestive heart failure (CHF) have been long and vigorously debated, with few firm conclusions reached. Several unresolved issues persist, beginning with epidemiology. The only reliable data pertain to permanent or chronic AF, which, within equivalent age groups, is markedly more prevalent among patients with CHF than in the general population [1]. This prevalence increases in parallel with the New York Heart Association (NYHA) CHF functional class and disease progression, from 10–26% among patients suffering from mild to moderate CHF (NYHA functional class II and III), to 30–50% among patients in NYHA class IV [2]. In contrast, no reliable data are available regarding the prevalence and incidence of paroxysmal AF, which should be one of the first questions addressed with the support of new implantable devices with powerful diagnostic functions. These devices, whether pacemakers or cardioverter defibrillators (ICD), are implanted at rapidly increasing rates in patients suffering from CHF without indications for treatment of bradycardia. Observational studies should be conducted with the assistance of these invaluable diagnostic tools, not only to measure the prevalence of paroxysmal AF at various stages of CHF, but also to define better its characteristics, including frequency of episodes, triggering mechanisms, circumstances surrounding its development, and spontaneous evolution. Numerous experimental and clinical observations suggest that both the triggers and electrophysiological substrates of AF in patients with CHF are different from those present in patients without structural heart disease [3]. The diagnostic functions of implanted devices offer a unique opportunity to confirm these observations, and to sharpen the focus on effective preventive therapies. Besides its epidemiology, the prognostic significance of AF in CHF remains poorly understood. Subgroup analyses of large clinical trials, such as SOLVD [4] or VAL-HeFT [5], and the recent report …

AFFIRM and RACE trials: implications for the management of atrial fibrillation.

The Atrial Fibrillation (AF) Follow-up Investigation of Rhythm Management (AFFIRM) and Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Study (RACE) Trials evaluated strategies of rate control or rhythm control in atrial fibrillation. AFFIRM enrolled patients with recent onset AF, and at entry over half of all patients were in sinus rhythm. At any point in the trial, the achieved difference in cardiac rhythm was likely only about 30%. In RACE all patients were entered in AF, and at the end of the study, sinus rhythm was present in 10% vs 39%. The strategy of rate control was non-inferior to the rhythm control strategy in both trials, and permits consideration of rate control as primary therapy. However, the actual differences in rhythm were relatively small, and do not allow the conclusion that maintenance of sinus rhythm is inferior to non-maintenance. Current guidelines recommend that patients with paroxysmal AF receive warfarin if they have risk factors for stroke. This is supported by data from AFFIRM. Most strokes in AFFIRM occurred either during subtherapeutic INR, or after cessation of warfarin. Since more patients in the rhythm control arm of AFFIRM discontinued warfarin, it is possible that asymptomatic recurrences of paroxysmal AF fostered clot development and embolization. We cannot answer from the data available whether or not it is safe to discontinue anticoagulation if all episodes of AF are suppressed. Among the reasons that AF is associated with increased mortality may be that it encourages development of congestive heart failure or progressive left ventricular dysfunction. Congestive heart failure occurrence was monitored in both trials, and occurred at a rate of 2-5% without significant differences between rate and rhythm arms. In patients with heart failure at entry, a mortality trend in AFFIRM favored the rhythm control arm. The issue of survivorship and rhythm control in AF in congestive heart failure is undergoing further testing.

High resolution mapping of the pulmonary vein and the vein of marshall during induced atrial fibrillation and atrial tachycardia in a canine model of pacing-induced congestive heart failure

ObjectivesThe study examined the activations in the pulmonary veins (PVs) and the vein of Marshall (VOM) during atrial fibrillation (AF) in dogs with congestive heart failure (CHF). BackgroundThe patterns of activation within the PVs and the VOM during AF in CHF are unclear. MethodsWe induced CHF in nine dogs by rapid ventricular pacing. The patterns of activation during induced AF were studied one week after ceasing ventricular pacing. ResultsThe duration of induced AF averaged 80.7 ± 177.3 s. The termination of low-amplitude fractionated activity in the PVs preceded the termination of AF in 25 of 29 episodes. High-density mapping (1-mm resolution) showed that the PV was activated by a focal wave front independent of left atrial (LA) activation in 22 AF episodes. Frequent intra-PV conduction blocks and multiple wave fronts in the PVs were recorded during 10 AF episodes. Focal activations were observed within the VOM in 4 of 12 episodes of AF. Three atrial tachycardia (AT) episodes originated from a focus within a PV. Histological studies showed extensive fibrosis in the PVs and in the atria. The PVs in five normal dogs did not have focal or fractionated activity during induced AF. ConclusionsAtrial fibrillation in canine CHF is associated with independent focal activations in the PVs and the VOM, and with complex wave fronts within the PVs. The PVs may also serve as the origin of AT. These findings suggest that electrical and anatomical remodeling of the PVs and the VOM are important in the maintenance of AF and AT in dogs with CHF.

Failing atrial myocardium: energetic deficits accompany structural remodeling and electrical instability.

The failing ventricular myocardium is characterized by reduction of high-energy phosphates and reduced activity of the phosphotransfer enzymes creatine kinase (CK) and adenylate kinase (AK), which are responsible for transfer of high-energy phosphoryls from sites of production to sites of utilization, thereby compromising excitation-contraction coupling. In humans with chronic atrial fibrillation (AF) unassociated with congestive heart failure (CHF), impairment of atrial myofibrillar energetics linked to oxidative modification of myofibrillar CK has been observed. However, the bioenergetic status of the failing atrial myocardium and its potential contribution to atrial electrical instability in CHF have not been determined. Dogs with (n = 6) and without (n = 6) rapid pacing-induced CHF underwent echocardiography (conscious) and electrophysiological (under anesthesia) studies. CHF dogs had more pronounced mitral regurgitation, higher atrial pressure, larger atrial area, and increased atrial fibrosis. An enhanced propensity to sustain AF was observed in CHF, despite significant increases in atrial effective refractory period and wavelength. Profound deficits in atrial bioenergetics were present with reduced activities of the phosphotransfer enzymes CK and AK, depletion of high-energy phosphates (ATP and creatine phosphate), and reduction of cellular energetic potential (ATP-to-ADP and creatine phosphate-to-Cr ratios). AF duration correlated with left atrial area (r = 0.73, P = 0.01) and inversely with atrial ATP concentration (r = -0.75, P = 0.005), CK activity (r = -0.57, P = 0.054), and AK activity (r = -0.64, P = 0.02). Atrial levels of malondialdehyde, a marker of oxidative stress, were significantly increased in CHF. Myocardial bioenergetic deficits are a conserved feature of dysfunctional atrial and ventricular myocardium in CHF and may constitute a component of the substrate for AF in CHF.

Atrial fibrillation and congestive heart failure: specific considerations at the intersection of two common and important cardiac disease sets.

Atrial fibrillation (AF) and congestive heart failure (CHF) are two increasingly common cardiac disorders with a growing prevalence in the overall population. Improved treatment of acute medical conditions has increased the incidence of these cardiac disorders. AF and CHF have similar epidemiologic characteristics and adversely affect quality of life and life expectancy of affected patients. CHF predisposes to AF, and AF may worsen the prognosis of CHF. The relevant literature was intensively reviewed with emphasis on aspects at the intersection of both disease sets. Recent advances in basic research have provided a more in-depth view of changes promoting the occurrence of AF in CHF. Data from clinical trials have provided means to improve medical treatment of AF. Precautions must be taken for specific CHF-related side effects, such as torsades de pointes tachycardia, when treating AF. The specific electrophysiologic basis of AF associated with CHF may provide targets for improved treatment modalities. New treatment approaches, both pharmacologic and nonpharmacologic, as well as the results of ongoing controlled clinical studies are likely to greatly alter AF therapy over the next 5 to 10 years in patients with CHF.