Influence of Cheyne-Stokes respiration on ventricular response to atrial fibrillation in heart failure.

In subjects with sinus rhythm, respiration has a profound effect on heart rate variability (HRV) at high frequencies (HF). Because this HF respiratory arrhythmia is lost in atrial fibrillation (AF), it has been assumed that respiration does not influence the ventricular response. However, previous investigations have not considered the possibility that respiration might influence HRV at lower frequencies. We hypothesized that Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) would entrain HRV at very low frequency (VLF) in AF by modulating atrioventricular (AV) nodal refractory period and concealed conduction. Power spectral analysis of R-wave-to-R-wave (R-R) intervals and respiration during sleep were performed in 13 subjects with AF and CSR-CSA. As anticipated, no modulation of HRV was detected at HF during regular breathing. In contrast, VLF HRV was entrained by CSR-CSA [coherence between respiration and HRV of 0.69 (SD 0.22) at VLF during CSR-CSA vs. 0.20 (SD 0.19) at HF during regular breathing, P < 0.001]. Comparison of R-R intervals during CSR-CSA demonstrated a shorter AV node refractory period during hyperpnea than apnea [minimum R-R of 684 (SD 126) vs. 735 ms (SD 147), P < 0.001] and a lesser degree of concealed conduction [scatter of 178 (SD 56) vs. 246 ms (SD 72), P = 0.001]. We conclude that CSR-CSA entrains the ventricular response to AF, even in the absence of HF respiratory arrhythmia, by inducing rhythmic oscillations in AV node refractoriness and the degree of concealed conduction that may be a function of autonomic modulation of the AV node.     

Optimal ventricular rate slowing during atrial fibrillation by feedback AV nodal-selective vagal stimulation

Although the beneficial effects of ventricular rate (VR) slowing during atrial fibrillation (AF) are axiomatic, the precise relationship between VR and hemodynamics has not been determined. We hypothesized that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) by varying the nerve stimulation intensity could achieve precise graded slowing and permit evaluation of an optimal VR during AF. The aims of the present study were the following: 1) to develop a method for computerized vagally controlled VR slowing during AF, 2) to determine the hemodynamic changes at each level of VR slowing, and 3) to establish the optimal anterograde VR during AF. AVN-VS was delivered to the epicardial fat pad that projects parasympathetic nerve fibers to the AVN in 14 dogs. Four target average VR levels, corresponding to 75%, 100%, 125%, and 150% of the sinus cycle length (SCL), were achieved by computer feedback algorithm. VR slowing resulted in improved hemodynamics and polynomial fit analysis found an optimum for the cardiac output at VR slowing of 87% SCL. We conclude that this novel method can be used to maintain slow anterograde conduction with best hemodynamics during AF.     

Selective AV nodal vagal stimulation improves hemodynamics during acute atrial fibrillation in dogs

Although the atrioventricular node (AVN) plays a vital role in blocking many of the atrial impulses from reaching the ventricles during atrial fibrillation (AF), a rapid irregular ventricular rate nevertheless persists. The goals of the present study were to explore the feasibility of novel epicardial selective vagal nerve stimulation for slowing of the ventricular rate during AF and to characterize the hemodynamic benefits in vivo. Electrophysiological-echocardiographic experiments were performed on 11 anesthetized open-chest dogs. Hemodynamic measurements were performed during three distinct periods: 1) sinus rate, 2) AF, and 3) AF with vagal nerve stimulation. AF was associated with significant deterioration of all measured parameters (P < 0.025). The vagal nerve stimulation produced slowing of the ventricular rate, significant reversal of the pressure and contractile indexes (P < 0.025), and a sharp reduction in one-half of the abortive ventricular contractions. The present study provides comprehensive evidence that slowing of the ventricular rate during AF by selective ganglionic stimulation of the vagal nerves that innervate the AVN successfully improved the hemodynamic responses.     

Mathematical modeling of ventricular disturbances following atrial fibrillation

The present study presents the results of mathematical and computer modeling of atrial fibrillation and ventricular disturbances following atrial fibrillation. The model is based on the assumption, that electric impulsation arriving on the atrioventricular node during atrial fibrillation is sum N of independent pulse streams with various amplitude-frequency and phase characteristics. With this model it becomes possible to investigate the dependence of nonlinear dynamics of PP and RR intervals on amplitude-frequency and phase characteristics pulse streams. Results of computer experiments are compared with real physiological experiments on rabbits. Identification of model was carried out by means of least-squares procedure.     

Mathematical modeling of ventricular disturbances following atrial fibrillation

The present study presents the results of mathematical and computer modeling of atrial fibrillation and ventricular disturbances following atrial fibrillation. The model is based on the assumption that electric impulsation arriving on the atrioventricular node during atrial fibrillation is sum of N independent pulse streams with various amplitude-frequency and phase characteristics. With this model it becomes possible to investigate the dependence of nonlinear dynamics of PP and RR intervals on amplitude-frequency and phase characteristics pulse streams. Results of computer experiments are compared with real physiological experiments on rabbits. Identification of model was carried out by means of least-squares procedure.     

ABC of atrial fibrillation. Antithrombotic treatment for atrial fibrillation.

Antithrombotic prophylaxis with long term warfarin or aspirin reduces thromboembolic risk in atrial fibrillation. Identification, risk assessment, and regular review of all patients with atrial fibrillation should be routine in general and hospital practice. Risk stratification is easily performed on clinical grounds--echocardiography may refine it.     

Nonlinear synchronization assessment between atrial and ventricular activations series from the surface ECG in atrial fibrillation

Atrial fibrillation (AF) is the most common form of arrhythmia encountered in clinical practice. Its presence causes a rapid and irregular ventricular response, being the topic of intensive research in rate control therapies of AF. To this respect, recent studies suggest that ventricular response is notably influenced by atrial activity (AA) temporal organization. However, the interdependency between atrial and ventricular activations has not been adequately explored to date in real-life AF patients. The present work introduces a novel methodology to quantitatively assess synchronization and coupling between real atrial and ventricular activation series. Furthermore, the method operates on surface ECG recordings, thus providing an easy and cost-effective way to be applied. The method is based on a nonlinear index, such as cross-sample entropy (CSE), which estimates the conditional probability to find similar patterns within both activation series. The study has been carried out on patients with paroxysmal and persistent AF in order to be applied over atrial activation series with different properties in their organization. Results showed a statistically significant positive correlation between AA organization and the synchronization between atrial and ventricular activations (R = 0.53, p < 0.01). Furthermore, higher CSE values were observed for persistent (0.759 ± 0.053) than for paroxysmal AF episodes (0.662 ± 0.091), thus suggesting more synchronization between atrial and ventricular activations in paroxysmal AF. As a consequence, CSE provided findings consistent with previous works and could be used to reveal clinically useful information in the improvement of current rate control therapies, which are mainly focused on controlling ventricular rate without paying much attention to the atrial fibrillatory process.     

Acceleration of ventricular rate by amiodarone in atrial fibrillation associated with the Wolff-Parkinson-White syndrome

Amiodarone has proved to be a valuable drug in atrial fibrillation associated with the Wolff-Parkinson-White syndrome. When it was administered to a patient with this syndrome in atrial fibrillation, who had previously suffered an inferior myocardial infarction, the ventricular rate accelerated from 170 to 230 beats/minute.This unusual case emphasises the need for full electrophysiological assessment of patients with the Wolff-Parkinson-White syndrome for whom amiodarone treatment is being considered.     

Treatment of nonvalvular atrial fibrillation.

Nonvalvular atrial fibrillation is an increasingly common condition. It may cause disabling symptoms and is an important risk factor for stroke. The goals of treatment include the relief and prevention of rate- and rhythm-related symptoms and the prevention of stroke and systemic emboli. Three principal treatments should be considered: pharmacologic rate control, cardioversion and antiarrhythmic therapy to restore and maintain sinus rhythm, and prophylactic anticoagulation or antiplatelet therapy to reduce the risk of stroke. The risks and benefits of each of these therapies have been reviewed. Symptoms, if present, can often be managed safely with rate-directed therapy alone. Until issues regarding safety and long-term efficacy are resolved, cardioversion and antiarrhythmic therapy should be limited to those patients whose symptoms cannot otherwise be controlled. The benefits of warfarin anticoagulation for the primary and secondary prevention of stroke in nonvalvular atrial fibrillation have been demonstrated convincingly by several randomized clinical trials. These benefits must be weighed against the real risk of major hemorrhage. For patients at low risk of stroke, the use of aspirin may be an acceptable alternative to warfarin sodium therapy.     

Neurochemical approaches to the prevention of ventricular fibrillation

Current evidence indicates that susceptibility to ventricular fibrillation (VF) can be reduced by decreasing cardiac sympathetic activity and by increasing vagal tone. Pharmacological agents that favor such a pattern of autonomic outflow protect the heart against fibrillation. These include morphine sulfate, clonidine, digitalis drugs, and bromocriptine. An intriguing new approach involves changing the serum concentration of amino acid precursors of the central neurotransmitters that modulate autonomic traffic. Considerable evidence indicates that accumulation of serotonin in the brain reduces sympathetic neural activity. When L-tryptophan or 5-hydroxytryptophan is administered with phenelzine (a monoamine oxidase inhibitor) and carbidopa (a selective peripheral L-amino acid decarboxylase inhibitor) to raise brain serotonin, a significant increase in myocardial electrical stability is observed. This effect results from a decrease in cardiac sympathetic tone as indicated by selective denervation and nerve recording studies. Enhancing serotoninergic neurotransmission can also significantly reduce vulnerability to VF during acute coronary artery occlusion. The effect of augmenting serotoninergic activity without the use of enzyme inhibitors has been investigated by administering agents such as melatonin, 5-methoxytryptophol, and 6-chloro-2-(1-piperazinyl) pyrazine (MK-212). Each of these substances increases cardiac electrical stability. The protective influence is unaffected by bilateral vagotomy but is blocked by the specific serotonin antagonist methergoline. Diminution of cardiac sympathetic drive appears to be the main mechanism of action. Thus, neurochemical interventions can exert a profound effect on cardiac electrical stability. Recent advances in neurochemistry and psychopharmacology promise new insights into the problem of sudden death and suggest a fresh approach for the management of life-threatening arrhythmias.