Characterization of the anatomy and conduction velocities of the human right atrial flutter circuit determined by noncontact mapping.

OBJECTIVES: This study was done to characterize human right atrial (RA) flutter (AFL) using noncontact mapping. BACKGROUND: Atrial flutter has been mapped using sequential techniques, but complex anatomy makes simultaneous global RA mapping difficult. METHODS: Noncontact mapping was used to map the RA of 13 patients with AFL (5 with previous attempts), 11 with counterclockwise and 2 with clockwise AFL. "Reconstructed" electrograms were validated against contact electrograms using cross-correlation. The Cartesian coordinates of points on a virtual endocardium were used to calculate the length and thus the conduction velocity (CV) of the AFL wave front within the tricuspid annulus-inferior vena cave isthmus (IS) and either side of the crista terminalis (CT). RESULTS: When clearly seen, the AFL wave front split (n = 3) or turned in the region of the coronary sinus os (n = 6). Activation progressed toward the tricuspid annulus (TA) from the surrounding RA in 10 patients, suggesting that the leading edge of the reentry wave front is not always at the TA. The IS length and CV was 47.73 +/- 24.40 mm (mean +/- SD) and 0.74 +/- 0.36 m/s. The CV was similar for the smooth and trabeculated RA (1.16 +/- 0.48 m/s and 1.22 +/- 0.65 m/s, respectively [p = 0.67]) and faster than the IS (p = 0.03 and p = 0.05 for smooth and trabeculated, respectively). CONCLUSIONS: Noncontact mapping of AFL has been validated and has demonstrated that IS CV is significantly slower than either side of the CT.

Relationship of heart rate variability to parasympathetic effect.

BACKGROUND: Baroreflex-mediated parasympathetic stimulation has variable effects on heart rate variability (HRV). We postulated that a quadratic function would describe the relationship between HRV and parasympathetic effect better than a linear function. METHODS AND RESULTS: Twenty-nine normal volunteers (15 women; mean age 39+/-12 years) were studied after beta-adrenergic blockade with intravenous propranolol. Five-minute ECG recordings were made during graded infusions of phenylephrine and nitroprusside to achieve baroreflex-mediated increases and decreases in parasympathetic effect, respectively. Time- and frequency-domain measures of HRV were calculated from the R-R interval tachograms. The R-R interval and the vagal-sympathetic effect (VSE=R-R interval/intrinsic R-R interval) were used as indices of parasympathetic effect. The data were fit to both quadratic and linear models. In each case, the quadratic model (with a negative coefficient for the squared term) was superior to the linear model. There was some evidence that age influenced the responsiveness of the HRV parameters with changing parasympathetic effect, although the regression analysis was significant only in the models for MSSD (P<0.03) and pNN50 (P<0.001). CONCLUSIONS: The relationship between HRV and parasympathetic effect is best described by a function in which there is an ascending limb where HRV increases as parasympathetic effect increases until it reaches a plateau level; HRV then decreases as parasympathetic effect increases. Because there is marked interindividual variation in this relationship, differences in HRV between individuals may reflect differences in this relationship and/or differences in autonomic effects.

Effects of age and gender on the QT response to exercise.

Although gender differences in resting corrected QT intervals have been well documented, the effects of age and exercise on gender differences in QT have not been well characterized. Data were analyzed from 91 healthy volunteers (47 women). Forty-five young subjects (aged 20 to 39 years) and 46 older subjects (61 to 84 years) were recruited. All underwent Bruce protocol stress testing. QT offset and QT peak were measured at exercise stages and during recovery. In a heart rate (HR)-independent analysis, data were divided into HR bins of 10 beats/min. In a HR-dependent analysis, 6 models were used to approximate the QT-RR relation; the best were used to analyze age and gender effects. Women had longer QT intervals than men at a HR < 100 beats/min for QT offset and < 110 beats/min for QT peak. At faster HRs, no significant differences were found. Older subjects had slightly longer QT intervals than the younger group, with a mean difference of 2 ms for QT offset and 9 ms for QT peak. Women had increased constant and slope coefficients. The QT increase in the elderly was relatively small. Gender differences in QT disappear at faster HRs, whereas age differences are smaller but are present throughout exercise, with no significant age-gender interaction. A natural logarithmic model provides the best approximation of the QT-RR relation with exercise, is simple to implement, and should become the preferred method of QT correction.

Simultaneous occurrence of atrial fibrillation and atrial flutter.

INTRODUCTION: Early reports suggested that some patients with "atrial fibrillation/flutter" might have atrial fibrillation in one atrium and atrial flutter in the other. However, more recent conceptions of atrial fibrillation/flutter postulate that the pattern is due to a relatively organized (type I) form of atrial fibrillation. We report the occurrence and ECG manifestations of simultaneous atrial fibrillation and flutter in patients undergoing attempted catheter ablation of atrial flutter. METHODS AND RESULTS: In patients undergoing radiofrequency ablation for atrial flutter, an attempt was made to entrain atrial flutter by pacing in the right atrium. The arrhythmias observed occurred following attempts at entrainment, or spontaneously in one case. Twelve transient episodes of simultaneous atrial fibrillation and flutter were observed in five patients. The atrial fibrillation was localized to all or a portion of one atrium, during which the other atrium maintained atrial flutter. In each case, the surface 12-lead ECG reflected the right atrial activation pattern. No patients had interatrial or intra-atrial conduction block during sinus rhythm, suggesting functional intra-atrial block as a mechanism for simultaneous atrial fibrillation/flutter. CONCLUSION: In certain patients, the occurrence of transient, simultaneous atrial fibrillation and flutter is possible. In contrast to prior studies in which it was suggested that left atrial or septal activation determines P wave morphology, the results of the present study show that P wave morphology is determined by right atrial activation. Functional interatrial block appears to be a likely mechanism for this phenomenon.

Proper use of antiarrhythmic therapy for reduction of mortality after myocardial infarction.

In this review, we summarise Vaughan Williams' classification of antiarrhythmic agents and the trials that have explored their efficacy in reducing mortality after myocardial infarction (MI). After analysing the data, it is clear that there is no role for class I antiarrhythmic agents as prophylaxis after MI since their use has been associated with increased mortality. Class II agents, i.e. beta-blockers, have demonstrated a reduction in mortality in combined and individual trials which extended for up to 6 years after the initial event. The class III drug, d,l-sotalol has been shown to have possible benefit, whereas its isomer without any beta-blocking properties, dexsotalol, has been shown to increase the incidence of arrhythmias. Amiodarone appears to reduce the incidence of deaths due to arrhythmia and sudden deaths without changing overall mortality. As a group, the calcium antagonists, class IV agents, have not been shown to reduce mortality and, in the case of nifedipine, may even increase it. Verapamil has been shown to be beneficial in one large study and may have a role in those patients in whom the use of beta-blockers is contraindicated. At this time, we recommend early implementation of beta-blockers for all patients without contraindications after MI. Further studies evaluating implantable defibrillators as primary and secondary prevention have provided significant risk reductions in certain high risk patient subsets. Future efforts will need to focus on more accurate risk stratification of post-MI patients and the role of both defibrillators and, possibly, amiodarone in improving survival.

Electrophysiological and anatomic heterogeneity in evolving canine myocardial infarction.

Although the heterogeneity of electrophysiological properties is increased after myocardial infarction, the degree of this heterogeneity has not been well quantitated and its relationship to the histological changes that occur after infarction has not been carefully examined. The purpose of the present study was to test the hypothesis that alterations in electrophysiological properties in healing canine infarction are related to particular histological changes. Experimental infarction was produced by left anterior descending coronary ligation. Six dogs were used as controls, six were studied 5 days following, and six were studied 8 weeks following infarction. Pacing thresholds, effective refractory periods, and activation-recovery times were determined at 112 sites on the anterior left ventricle using a multiple electrode plaque. Conduction velocity, conduction-heterogeneity index--a measure of conduction disturbance--and histology of the epimyocardium underlying the plaque were assessed. The effective refractory periods and activation-recovery times were greater in both infarction groups, most prominently in the subacute group. In subacute infarction, significant postrepolarization refractoriness was present. In healed infarction, conduction velocity was decreased and the conduction-heterogeneity index was increased compared to controls and subacute infarction. Dispersion of excitability and repolarization was associated with more extensive local scarring. Dispersion of myocardial fiber angles was associated with the conduction-heterogeneity index. Some but not all of the electrophysiological changes noted in the animals with infarction were also seen in sham operated animals. Thus, heterogeneity in repolarization and refractoriness is greatest in the subacute phase of myocardial infarction and is associated with the extent of local cell death. In contrast, disturbances in conduction are greatest in healed infarction and associated with disarray of myocardial fibers.

Application of noninvasive and invasive tests for risk assessment in patients with ventricular arrhythmias.

Sudden cardiac death remains a major public health problem in western society. Because most patients who experience cardiac arrest are not successfully resuscitated, primary prevention of sudden death remains an important challenge. A number of noninvasive risk stratification techniques have been suggested as providing useful information in patients with underlying structural heart defects. Unfortunately, the positive predictive value of most of these techniques has been limited. Left ventricular ejection fraction, the presence of nonsustained ventricular tachycardia on Holter monitoring, and inducible sustained ventricular tachycardia at electrophysiologic testing in patients with coronary artery disease remain the best established prognostic test. However, with the exception of two ICD studies using the combination of these markers, prospective studies have not yet completely validated the use of these and other prognostic markers. Further understanding of the pathophysiology of ventricular fibrillation and other risk stratification techniques will be necessary before a clear algorithm can be developed for application to patients at risk for sudden death.

Uncertainty principle of signal-averaged electrocardiography.

BACKGROUND: Signal-averaged ECG (SAECG) reproducibility is reported to have a component that is independent of residual noise. Methods and Results-In group 1, multiple paired SAECGs were obtained to noise levels of 0.3+/-0.1 and 0.5+/-0.2 microV. For the 0.5- and 0. 3-microV noise recordings, QRS duration (QRSd) was 101.2+/-11.3 and 104.6+/-9.6 ms, respectively (P<0.0001), and the differences in paired QRSd (DeltaQRSd) were normally distributed, with variances of 11.4 and 26.2 ms(2) (P<0.0001). Paired SAECGs were obtained in group 2 patients without and with late potentials; DeltaQRSd variance was 3.3 and 217.9 ms(2) (P<0.0001). In group 3, >/=10 SAECGs were acquired at noise levels of 0.2 to 0.8 microV, in 0.1-microV increments. QRSd increased as noise level decreased. The variance was greater in low-noise (0.2 to 0.4 microV) versus higher-noise (0. 5 to 0.8 microV) recordings. In group 4, SAECGs were analyzed with bidirectional and Bispec filters, with no difference in QRSd between the 2 filters and a normally distributed DeltaQRSd. A computer simulation demonstrated that alterations in the phase relationship of noise to signal results in a normal distribution of signal end points. CONCLUSIONS: Within the acceptable noise range for SAECG, lower noise results in longer QRSd and larger variance, suggesting that more accurate recordings may have less reproducibility. The random timing of noise relative to signal results in the distribution/variance of repeated measurements. Statistical strategies may be used to reduce some of this variance and may enhance the diagnostic utility of SAECG.

Endocardial mapping of atrial fibrillation in the human right atrium using a non-contact catheter.

BACKGROUND: Endocardial mapping of atrial fibrillation in humans is limited by its low resolution and by complexities in the arrhythmia and atrial anatomy. METHODS AND RESULTS: A catheter mounted non-contact multielectrode was deployed in the right atrium of 11 patients with atrial fibrillation and used to reconstruct 3360 electrograms, superimposed onto a computer-simulated model of the endocardium, using inverse solution mathematics. This allows construction of isopotential maps of the right atrium. Patients had either sustained atrial fibrillation (n=3) for >6 months or developed atrial fibrillation during the study (n=8). Spontaneous initiation of atrial fibrillation was recorded in one patient and was demonstrated by the non-contact system to arise from two successive atrial ectopic beats from the site of a roving contact catheter. Reconstruction of electrograms recorded during atrial fibrillation was validated by comparison with contact electrograms with cross-correlation. During established atrial fibrillation, four patients predominantly had a single right atrial wave front, two had two wave fronts and five patients had three to five wave fronts for most of the time. Periods of electrical silence were seen in the right atrium in eight patients, after which, activity emerged from consistent septal sites alone, suggesting a left atrial origin. During intravenous administration of flecainide, atrial fibrillation in two patients terminated spontaneously or following pacing manoeuvres, while in the remaining patient sinus rhythm was restored via atrial tachycardia. CONCLUSION: Non-contact mapping of the right atrium has demonstrated modes of initiation and termination of atrial fibrillation, characterized different patterns of right atrial activation in atrial fibrillation and suggests that the left atrium may sustain atrial fibrillation in some patients. Simultaneous mapping of the right and left atrium is required to further elucidate the mechanisms of human atrial fibrillation.

Proximal atrioventricular bundle, atrioventricular node, and distal atrioventricular bundle are distinct anatomic structures with unique histological characteristics and innervation.

BACKGROUND: Direct 3D analysis (ie, stereotaxic analysis of 3 planes) has shown that the atrioventricular (AV) node (AVN) is continuous with only specialized myocardium of the proximal AV bundle (PAVB) and distal AV bundle (DAVB) or His bundle. The purpose of the present study was to determine whether the PAVB, AVN, and DAVB possess histological features distinct from each other and from the ordinary myocardium. METHODS AND RESULTS: A protocol that preserves the cytoplasmic and interstitial integrity of the tissue and permits serial sections of the AV junction region to be made in 3 orthogonal planes showed that the PAVB, AVN, and DAVB are characterized by myocardium aggregated into fascicles containing approximately 8 myofibers. Myofibers within the fascicles are coiled or spiraled about each other; and spiraling is most compact in the PAVB. Collagen encases individual fascicles and segregates primary fascicles into secondary fascicles. Fascicles, and not myofibers, are in parallel array in the PAVB, interwoven in the AVN, and parallel in the DAVB. Narrow junctions of parallel fascicles separate the AVN from the PAVB and DAVB. Myocytes, which are largest in DAVB, possess clear perinuclear regions; thin finger-like end processes, which are most numerous in the AVN; uniform, delicate cross-striations; and intercalated disks, which are broader in the PAVB and form short stacks in the AVN. Sheaves of nerve terminals are found, including boutons as in skeletal muscle [corrected]. CONCLUSIONS: The PAVB, AVN, and DAVB have distinct histological features. Collagen septation of primary and secondary fascicles presents natural barriers within the tissues and to surrounding myocardium and structures. These findings confirm that the AV junction region contains a specialized conduction system that is anatomically isolated from ordinary myocardium.

Differential effects of parasympathetic blockade and parasympathetic withdrawal on heart rate variability.

INTRODUCTION: Low heart rate variability (HRV) has been shown to have important prognostic significance in multiple settings. Although this is believed to reflect reduced parasympathetic tone, the physiology of reduced parasympathetic tone has not been elucidated. METHODS AND RESULTS: To evaluate whether parasympathetic withdrawal and partial parasympathetic blockade result in similar changes in HRV, 27 normal volunteers underwent complete beta-adrenergic blockade and then were given (1) graded doses of nitroprusside to achieve baroreflex-mediated parasympathetic withdrawal and (2) low-dose atropine (0.01 mg/kg) to achieve partial parasympathetic blockade. Five-minute ECG recordings were obtained for HRV analysis. In 19 subjects, paired 5-minute recordings from each condition were available with mean RR intervals that differed by < 50 msec (low-dose atropine: 869 +/- 96 msec and nitroprusside 875 +/- 99 msec). The root mean square of the successive RR interval differences was lower following low-dose atropine than following parasympathetic withdrawal with nitroprusside (16 +/- 11 msec vs 22 +/- 15 msec; P < 0.02). During parasympathetic withdrawal, the low-frequency (LF) power was 0.917 +/- 0.602 bpm2 and the high-frequency (HF) power was 0.501 +/- 0.521 bpm2. During partial parasympathetic blockade, the LF and HF powers were significantly lower (0.443 +/- 0.474 bpm2, P < 0.005; and 0.198 +/- 0.207 bpm2, P < 0.02). CONCLUSION: These data confirm that HRV reflects the character of parasympathetic modulation of the heart rate rather than parasympathetic tone per se. Furthermore, this study identifies two distinct physiologic explanations for the finding of low HRV, namely, diminished vagal discharge and resistance of cardiac muscarinic receptors to vagal discharge. Further delineation of the relationships between parasympathetic tone and HRV will allow for better understanding of the pathophysiologic derangements associated with low HRV.

New technique for vagal nerve stimulation.

INTRODUCTION: The vagus nerve travels in a neurovascular bundle with the carotid artery and internal jugular vein. The present study was designed to assess whether transvascular stimulation through the carotid artery of the dog can be used to directly stimulate the vagus nerve and increase parasympathetic tone. METHODS: In five anesthetized dogs, a steerable electrode catheter was positioned under fluoroscopic guidance in the right carotid artery in the mid neck via the femoral artery. Multipolar catheters were positioned transvenously through the femoral vein in the right atrium, across the tricuspid valve to record a His-bundle electrogram, and in the right ventricle. RESULTS: In all five animals, vagal nerve stimulation was successfully achieved with outputs ranging between 10 and 30 mA. Sinus cycle length increased from 473 +/- 113 ms at baseline to 894 +/- 315 ms (P < 0.025) during stimulation from the right carotid artery. There was an increase in the AH interval from 55 +/- 14 to 77 +/- 23 ms (P < 0.03), a shortening of the atrial effective refractory period from 136 +/- 8 to 126 +/- 6 ms (P < 0.01), and a fall in the systolic blood pressure from 135 +/- 20 to 117 +/- 20 mmHg (P < 0.005) with stimulation from the right carotid artery. A prolongation of the AV and VA block cycle lengths and the AV nodal effective refractory period was also noted with stimulation from the right carotid artery. Atrial fibrillation was not induced at baseline in any animal. During stimulation from the right carotid artery, atrial fibrillation was induced in three of five animals and persisted for the duration of stimulation from the right carotid artery. CONCLUSION: Cardiac parasympathetic stimulation can be achieved by positioning a catheter in the neurovascular bundle in the neck adjacent to the vagus nerve with resultant effects on cardiac electrophysiology.

Inappropriate implantable cardioverter-defibrillator therapy due to the detection of premature ventricular complexes.

Inappropriate shocks delivered by implantable cardioverter-defibrillators may occur in 15%-40% of patients treated with these devices. This article describes a rare cause for inappropriate shocks. Two patients received inappropriate shocks due to the presence of premature ventricular complexes during attempted reconfirmation of ventricular fibrillation. Knowledge of device algorithms for detection and reconfirmation of ventricular fibrillation, designed to have a high degree of sensitivity and therefore lower specificity, allows for reprogramming to avoid further inappropriate shocks.

Nonsustained ventricular tachycardia in the setting of acute myocardial infarction: tachycardia characteristics and their prognostic implications.

BACKGROUND: Nonsustained ventricular tachycardia (NSVT) has significant prognostic implications in the setting of healing and healed myocardial infarction (MI), but only limited information is available on its importance in the setting of acute MI. We evaluated the prognostic significance of NSVT characteristics in the setting of acute MI. METHODS AND RESULTS: A prospective database was used to identify 112 patients with NSVT within 72 hours of acute MI. A control group was identified matched for age, sex, type of MI, and thrombolytic treatment. Mean age was 64 to 65 years in the 2 groups with 71% to 72% men. Q-wave MI was noted in 52% to 53%, and thrombolytic therapy was administered to 31% to 32% of patients in each group. In-hospital ventricular fibrillation occurred more frequently in the NSVT group (9% versus 0% in the control group; P<0. 001), but total in-hospital (10% versus 4%) and follow-up mortality (10% versus 17%) did not differ between the 2 groups. With a Cox regression model, specific NSVT characteristics were predictive of mortality. The strongest predictor was time from presentation to occurrence of NSVT. Shortest RR interval during NSVT was also a univariate predictor of mortality. Multivariate analysis identified time from presentation to occurrence of NSVT as the strongest predictor of mortality (P<0.0001). The increased relative risk of NSVT was first significant when it occurred 13 hours from presentation and continued to increase as the time from presentation to occurrence of NSVT increased, plateauing at approximately 24 hours with a relative risk of 7.5. CONCLUSIONS: Contrary to prevailing clinical opinion, NSVT that occurs in the setting of acute MI does have important prognostic significance. Specifically, the currently accepted notion that NSVT that occurs within 48 hours of acute MI has no prognostic significance needs to be adjusted. Although NSVT that occurs within the first several hours of presentation does not have an associated adverse prognosis, NSVT that occurs beyond the first several hours after presentation is associated with significant increases in relative risk.