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.

Recurrent polymorphic ventricular tachycardia complicating radiofrequency catheter ablation of the atrioventricular junction.

Recurrent ventricular tachycardia and ventricular fibrillation were observed immediately after RF ablation of the AV junction in a 64-year-old man. This arrhythmia was preceded by ventricular bigeminy and a long-short sequence. It was not associated with prolongation of the QT interval compared to baseline, and recurred 3 months later despite ventricular pacing at 90 beats/min. This is the first reported case of sustained ventricular arrhythmia complicating RF AV junction ablation despite rapid ventricular pacing, and recurring 3 months after discharge. It may explain the rare cases of sudden death complicating this procedure.

De novo monomorphic and polymorphic ventricular tachycardia following coronary artery bypass grafting.

We compared de novo monomorphic and polymorphic ventricular tachycardia (VT) occurring after coronary artery bypass graft surgery in 21 patients. Our findings support an underlying arrhythmogenic substrate for de novo monomorphic VT, whereas polymorphic VT is more likely related to transient perioperative abnormalities.

Response of neurocardiac syncope to beta-blocker therapy: interaction between age and parasympathetic tone.

Beta-blockers are a first line therapy for neurocardiac syncope, but are not always effective. The purpose of this study was to determine whether differential autonomic responses to orthostasis predict the response of patients with neurocardiac syncope to beta-adrenergic blockade. We computed the RMS successive difference of the RR intervals (RMSSD: a measure of cardiac parasympathetic tone) during supine and upright phases of the initial tilt test in 28 patients with syncope and positive tilt tests who were treated with atenolol. Follow-up tilt testing was performed to assess the efficacy of the drug in preventing tilt induced neurocardiac syncope. RMSSD did not differ at baseline (supine) between those who did (n = 20) and did not (n = 8) respond to beta-blockade. However, withdrawal of parasympathetic tone in response to tilt varied inversely with age (r = -0.69; P < 0.01). Reduced age adjusted parasympathetic withdrawal during orthostasis was associated with a 47% versus 8% risk of beta-blockade failure (odds ratio = 11; P = 0.01). Patients with diminished age adjusted parasympathetic withdrawal during orthostatic stress are less likely to respond to beta-blocker therapy of neurocardiac syncope than their counterparts. This may reflect a correspondingly greater sympathetic response to orthostasis in these patients, but the mechanism for this interaction is undetermined.

Mechanism of repetitive monomorphic ventricular tachycardia.

BACKGROUND: The most common form of idiopathic ventricular tachycardia (VT) is repetitive monomorphic VT (RMVT), which is characterized by frequent ventricular ectopy and salvos of nonsustained VT with intervening sinus rhythm. Unlike most other forms of idiopathic VT, this tachycardia typically occurs at rest and is nonsustained. The mechanism of RMVT is undefined. Because of a common site of origin, the right ventricular outflow tract (RVOT), we hypothesized that RMVT is mechanistically related to paroxysmal sustained, exercise-induced VT, which has been shown to be consistent with cAMP-mediated triggered activity. Therefore, in this study, we sought to identify (1) the mechanism of RMVT at the cellular level by using electropharmacological probes known to activate either stimulatory or inhibitory G proteins and thereby modify intracellular cAMP levels, (2) potential autonomic triggers of RMVT through analysis of heart rate variability, and (3) whether well-characterized somatic activating mutations in the stimulatory G protein, G alpha s, underlie RMVT. METHODS AND RESULTS: Twelve patients with RMVT underwent electrophysiological study. Sustained monomorphic VT was reproducibly initiated and terminated with programmed stimulation and/or isoproterenol infusion in 11 of the 12 patients (the other patient had incessant RMVT). Induction of VT demonstrated cycle length dependence and was facilitated by rapid atrial or ventricular pacing. Termination of VT occurred in response to interventions that either lowered stimulated levels of intracellular cAMP (and thus decreased intracellular Ca2+)--ie, adenosine (12 of 12), vagal maneuvers or edrophonium (8 of 9), and beta-blockade (3 of 5)--or directly decreased the slow-inward calcium current--ie, verapamil (10 of 12). Analysis of heart rate variability during 24-hour ambulatory monitoring in 7 patients showed that the sinus heart rate is increased and accelerates before nonsustained VT (P < .05), whereas high-frequency heart rate variability is unchanged. These findings are consistent with transient increases in sympathetic tone preceding nonsustained VT. Finally, myocardial biopsy samples were obtained from the site of origin of the VT (typically the RVOT) and from the right ventricular apex from 9 patients. Genomic DNA was extracted from each biopsy sample, and three exons of G alpha s in which activating mutations have previously been described were amplified by polymerase chain reaction. All sequences from these regions were found to be identical to that of control. CONCLUSIONS: Although the arrhythmia occurs at rest, the constellation of findings in idiopathic VT that is characterized by RMVT is consistent with the mechanism of cAMP-mediated triggered activity. Therefore, the spectrum of VT resulting from this mechanism includes not only paroxysmal exercise-induced VT but also RMVT.

Performance of the signal-averaged electrocardiogram: relation to baseline QRS duration.

Analysis of the duration and terminal components of the filtered QRS complex on the signal-averaged electrocardiogram (ECG) has been widely used for the detection of late potentials. Although filtered QRS duration is strongly related to 12-lead QRS duration, the relation of performance of the signal-averaged ECG to baseline QRS duration has not been critically examined. To examine the relation of test performance of the signal-averaged ECG to 12-lead QRS duration and to test the hypothesis that the difference between filtered and baseline 12-lead QRS duration would reflect more accurately the presence of late potentials than would analysis of the filtered QRS alone, we evaluated signal-averaged and 12-lead ECGs in 144 normal subjects and in 132 patients who were examined by electrophysiologic study and of whom 45 had inducible sustained monomorphic ventricular tachycardia. The signal-averaged ECG was considered positive by standard late potential criteria when the filtered vector QRS duration was > 114 msec and either the root-mean-square voltage of the terminal 40 msec of the filtered QRS was < 20 microV or the low-amplitude signal of the terminal filtered QRS was > 38 msec. A new signal-averaged ECG criterion for the presence of late potentials was developed in the 144 normal subjects on the basis of the difference between the longest filtered QRS duration in any of the orthogonal leads and QRS duration on the baseline 12-lead ECG ("the QRS difference"), which was adjusted by regression analysis for the decreasing QRS difference found with increasing baseline QRS duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure to decrease parasympathetic tone during upright tilt predicts a positive tilt-table test.

The most frequently proposed mechanism for vasodepressor syncope is based on cardiac mechanoreceptor activation by augmented sympathetic tone. Because of the central role of the autonomic nervous system in this response, we hypothesized that the responses of the sympathetic and parasympathetic nervous systems (as assessed by analysis of heart rate variability) to orthostatic stress would differentiate patients with a positive from those with a negative tilt-table response. We therefore evaluated 28 patients undergoing tilt-table testing for presumed vasodepressor syncope. Based on 5-minute electrocardiographic samples obtained during the supine and upright phases (without isoproterenol infusion), we computed the mean RR interval, reflecting integrated cardiac sympathetic and parasympathetic tone, as well as the root-mean-square of successive differences of the RR intervals (RMSSD), a measure of high-frequency heart rate variability that is correlated with parasympathetic tone. Eleven patients had a negative and 17 a positive tilt response. There were no differences between the groups at baseline. In response to upright tilt, the mean RR decreased by a similar magnitude in both groups. In contrast, RMSSD decreased by 36% (p = 0.05) in response to upright tilt in patients with a negative response, but did not change significantly in patients with a positive tilt response. Absence of a decrease in RMSSD in response to orthostatic stress had 100% specificity and 41% sensitivity for predicting a positive test result. Thus, failure of withdrawal of parasympathetic tone (as assessed by RMSSD) during upright tilt predicts a positive tilt response.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonlinear forecasting and the dynamics of cardiac rhythm.

Since the initial development of the electrocardiogram, cardiologists have made dramatic advances in the description and understanding of cardiac arrhythmias. Despite these successes, the analysis of cardiac rhythm has remained largely descriptive. Recently, the principles of nonlinear dynamics, or chaos theory, have been applied to the quantitative analysis of cardiac rhythm in a variety of diverse situations. In chaos theory, three types of signals can be defined: periodic signals, which repeat themselves over some finite time interval, chaotic signals, which, while deterministic, demonstrate complex behavior and do not repeat themselves, and random signals, which are unpredictable and nondeterministic. The technique of nonlinear forecasting defines trajectories in a suitably defined phase space and uses the future evolution of trajectories that are close to each other over short distances to make predictions for times further into the future. The ability to reliably predict the future evolution of the trajectories derived from any signal is an important characteristic of the underlying dynamics of the signal and can therefore used to determine those dynamics. The foundation of nonlinear forecasting is reviewed, and an algorithm is described that can be used to determine the underlying dynamics of a signal and has been applied to the analysis of R-R interval data.

Differential therapeutic responses of patients with isoproterenol-dependent and isoproterenol-independent vasodepressor syncope.

Orthostatic stress during tilt table testing (TTT) is used to examine patients who may have vasodepressor syncope. This response is thought to be mediated by activation of left ventricular mechanoreceptors. Isoproterenol, by increasing the rate of discharge of these mechanoreceptors, has been proposed to increase the sensitivity of TTT without decreasing its specificity. This mechanism is not, however, totally consistent with recent observations of vasodepressor responses after cardiac transplantation in patients with denervated hearts. These reports and data showing that not all sympathomimetic agents increase the sensitivity of TTT suggest that more than one mechanism may be responsible for a positive TTT result. Therefore we hypothesized that patients with positive TTT results tests not requiring isoproterenol (iso-independent) would have a different clinical and therapeutic response than patients who required isoproterenol (iso-dependent). One hundred sixty-one consecutive patients who underwent TTT for the evaluation of unexplained syncope were included in the study. TTT was performed without and during isoproterenol infusion. A positive TTT result was defined as syncope or presyncope with a sudden decrease in systolic blood pressure and reproduction of the patient's clinical symptoms. Patients with a positive TTT result underwent a second test after 1 to 2 weeks of therapy with an oral beta-blocking agent; if the result remained positive, TTT was performed again with other agents until a satisfactory therapeutic response was obtained. Sixty-six (41%) of 161 patients had a positive result; 18 (27%) were iso-independent, and 48 (73%) were iso-dependent. There were no significant differences in age, gender, or presence of underlying heart disease between these two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiologic role of atrio-Hisian and nodo-Hisian bypass tracts in supraventricular tachycardia.

Atrio-Hisian bypass tracts are considered to be rare electrophysiologic curiosities. The prevalence and functional significance of these tracts are unknown. We examined the incidence of atrio-Hisian and nodo-Hisian bypass tracts, their electrophysiologic manifestations, and their physiologic role in supraventricular tachycardia in 200 consecutive patients referred for evaluation of supraventricular tachycardia. In one patient it was demonstrated for the first time that a concealed (retrograde only) nodo-Hisian bypass tract functioned as the retrograde limb of orthodromic reciprocating tachycardia. The VA interval was negative during tachycardia, similar to that sometimes observed in atrioventricular nodal reentry. In a second patient an anterograde and retrograde conducting pathway resulted in a pseudo Wolff-Parkinson-White electrocardiographic pattern and served as an "innocent bystander," permitting a rapid ventricular response during atrial flutter. In conclusion, although atrio-Hisian and nodo-Hisian bypass tracts are rare, they are sufficiently prevalent to make them observable in a larger referral series. Most importantly, they may participate as bystanders during supraventricular tachycardia or as either the anterograde or retrograde limbs of reciprocating tachycardia. They may possess features that mimic Wolff-Parkinson-White syndrome and/or AV nodal reentry.

Comparison of methods for removal of ectopy in measurement of heart rate variability.

Heart rate variability (HRV) analysis uses variations in heart rate to assess activity of the autonomic nervous system. Ectopic beats can affect HRV by introducing mathematical artifact into the computations of time- and frequency-domain measures. Exclusion of ectopy-containing segments of data from analysis has been used to correct for ectopy, but this technique eliminates data and may bias HRV measurements if ectopic beats are causally associated with changes in autonomic tone. We have assessed algorithms for correcting for ectopy: deletion, in which ectopic beats are removed from the R-R sequence; linear and cubic spline interpolation; and nonlinear predictive interpolation, in which ectopy-free R-R sequences are used as templates for replacing ectopic beats. The null method (no ectopy correction) was evaluated to determine the importance of ectopy correction. These methods were applied to computer-generated sequences created by adding simulated ventricular premature depolarizations to 5-min ectopy-free R-R sequences. The null method resulted in significant alterations in HRV. Deletion and nonlinear predictive interpolation performed superiorly to linear or cubic spline interpolation, which overestimated low-frequency power and underestimated high-frequency power. Thus ectopy correction is necessary for HRV analysis; deletion of ectopic beats performs as well as or better than more complicated methods for these relatively short data samples.

Mechanism-specific effects of adenosine on atrial tachycardia.

BACKGROUND: Recent reports suggest that adenosine, in addition to terminating supraventricular tachycardia involving the atrioventricular (AV) node, may have antiarrhythmic effects on atrial tachycardia. The electrophysiological effects of adenosine on supraventricular tissue include shortening of action potential duration in atrial myocytes mediated by the potassium current, IKACh,Ado; shortening of action potential duration and hyperpolarization in sinus node cells; and anti-adrenergic electrophysiological effects resulting from inhibition of adenylyl cyclase. We therefore hypothesized that the response of atrial tachycardia to adenosine would be mechanism specific, with termination of atrial tachycardia due to sinus node reentry or cAMP-mediated triggered activity, transient suppression of automatic atrial tachycardia, and an absence of antiarrhythmic effect on tachycardia due to intraatrial reentry. METHODS AND RESULTS: Adenosine (mean +/- SD, 143 +/- 54 micrograms/kg IV) was administered to 27 patients (55 +/- 19 years) in atrial tachycardia whose mechanism was confirmed by electrophysiological study. Adenosine terminated sinus node reentrant tachycardia in 6 of 6 patients and terminated atrial tachycardia due to triggered activity in the 1 patient in whom it was identified. Adenosine transiently suppressed automatic atrial tachycardia in 7 of 7 patients and had no effect in 13 patients with intra-atrial reentrant tachycardia, including 8 patients with atrial flutter. CONCLUSIONS: These findings demonstrate that adenosine's effects on atrial tachycardia are mechanism specific and can be used to differentiate between reentrant tachycardia confined to the region of the sinus node or atria and between nonreentrant atrial tachycardia due to either triggered activity or automaticity.

Limitations of adenosine in assessing the efficacy of radiofrequency catheter ablation of accessory pathways.

Adenosine has been shown to reliably confirm the success of accessory pathway catheter ablation by producing transient atrioventricular (AV) block during atrial and ventricular pacing. This is due to the insensitivity of accessory pathway conduction to adenosine (with the rare exception of accessory pathways with decremental conduction properties). However, 4 of 204 consecutive patients who underwent successful accessory pathway ablation (as shown by adenosine-induced transient AV block) had recurrent AV reciprocating tachycardia involving a second, previously nonmanifest accessory pathway. In each case, the second accessory pathway was localized to a site disparate from the original pathway. No pathway showed decremental anterograde or retrograde conduction properties. In 2 patients, adenosine initially did not show the presence of the second concealed accessory pathway, because the refractory period of the accessory pathway was longer than the pacing cycle length used to assess ventriculoatrial conduction. Only when the refractory period of this second accessory pathway was shortened by infusion of isoproterenol did adenosine reveal the presence of the pathway during follow-up electrophysiologic study. In another patient, a non-decremental accessory pathway was shown to be sensitive to adenosine. In the remaining patient, the second accessory pathway may have been transiently injured during the initial study, thereby simulating adenosine sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonlinear predictive interpolation. A new method for the correction of ectopic beats for heart rate variability analysis.

Heart rate variability (HRV) analysis is a technique that uses the beat-to-beat variations in RR intervals as a measure of the level of activity of the autonomic nervous system. However, the presence of ectopic beats can alter measures of HRV by introducing mathematical artifact and thus, prevent accurate determinations of HRV. Simple exclusion of those portions of data that contain ectopy from analysis inappropriate because (1) it can lead to a substantial reduction in the amount of data available for analysis and (2) if the presence (and frequency) of ectopic beats is correlated with specific alterations in autonomic tone, then the utilization of only ectopy-free data for analysis will lead to bias in the measures. For this reason, methods for the correction of ectopic beats have been devised and applied in the determination of HRV. The authors therefore propose a new method for the correction of ectopic beats: nonlinear predictive interpolation. Using the fact that beat-to-beat changes in heart rate occur in a deterministic fashion as the only assumption, the authors apply the methods of chaos theory in order to locate ectopy-free portions of the RR interval sequence that describe trajectories in phase space that are locally similar to that of the ectopy-containing segments. The authors then determine which of these trajectories most closely approximates that of a particular ectopy-containing segment, and use it to determine replacement RR intervals for the ectopic beats.

Antimicrobial properties of VLC liners.

The antimicrobial activity of several visible light cured glass ionomer and liner materials against three bacteria commonly found in the oral cavity is discussed. Vitrabond light cure glass ionomer produced zones of inhibition against all the bacteria tested in this study. It appeared to resemble a true glass ionomer cement in regard to its antimicrobial properties whereas the other materials used in this study appeared to possess no antimicrobial activity.

Microleakage of three glass ionomer cement bases.

This study compared the marginal leakage in Class V restorations using three different GIC bases and a composite resin sandwich. The specimens were randomly divided into three equal groups, and the following GIC materials were used as bases: Group I: Ketac-Bond Aplicap; Group II: GC Dentin Cement; Group III: Shofu GlasIonomer Base. The results indicated less microleakage in restorations with a Shofu GlasIonomer Base while no statistical differences were noted between Ketac-Bond Aplicap and GC Dentin Cement.

Antimicrobial properties of glass-ionomer cements and other restorative materials.

The antimicrobial properties of 14 different restorative materials, nine of which were glass-ionomer cements, were compared and observed in this study. The materials were mixed according to manufacturers' specifications and exposed to four types of bacteria commonly found in caries and plaque. Zones of bacterial inhibition were measured for all materials in millimeters. Glass-ionomer cement materials, materials containing zinc oxide, and amalgam produced measureable zones of inhibition.