Search PubMed⌕ Search

Biomedical subjects

B B Lerman

Publications and source records attributed to B B Lerman.

At least 37 records · Page 2Linked to original sources
PubMed1999

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.

Aged↗
PubMed1998

Right ventricular outflow tract tachycardia due to a somatic cell mutation in G protein subunitalphai2.

Idiopathic ventricular tachycardia is a generic term that describes the various forms of ventricular arrhythmias that occur in patients without structural heart disease and in the absence of the long QT syndrome. Many of these tachycardias are focal in origin, localize to the right ventricular outflow tract (RVOT), terminate in response to beta blockers, verapamil, vagal maneuvers, and adenosine, and are thought to result from cAMP-mediated triggered activity. DNA was prepared from biopsy samples obtained from myocardial tissue from a patient with adenosine-insensitive idiopathic ventricular tachycardia arising from the RVOT. Genomic sequences of the inhibitory G protein Galphai2 were determined after amplification by PCR and subcloning. A point mutation (F200L) in the GTP binding domain of the inhibitory G protein Galphai2 was identified in a biopsy sample from the arrhythmogenic focus. This mutation was shown to increase intracellular cAMP concentration and inhibit suppression of cAMP by adenosine. No mutations were detected in Galphai2 sequences from myocardial tissue sampled from regions remote from the origin of tachycardia, or from peripheral lymphocytes. These findings suggest that somatic cell mutations in the cAMP-dependent signal transduction pathway occurring during myocardial development may be responsible for some forms of idiopathic ventricular tachycardia.

Amino Acid Sequence↗
PubMed1998

Heart rate changes preceding ventricular ectopy in patients with ventricular tachycardia caused by reentry, triggered activity, and automaticity.

OBJECTIVES: Although enhanced sympathetic tone is thought to be proarrhythmic and beta-blockade reduces the risk of sudden cardiac death in survivors of myocardial infarction, the role of the autonomic nervous system in triggering spontaneous ventricular ectopy and ventricular tachycardia (VT) has not been fully elucidated. The purpose of this study was to compare and contrast autonomic tone preceding spontaneous ventricular arrhythmias in patients with reentrant, triggered, and automatic forms of VT. BACKGROUND: The prevailing model of reentrant VT is based on a triggering beat interacting with a fixed substrate. Within this model, cyclic fluctuations in autonomic tone comprise a "third factor" that may initiate the triggering extrasystoles as well as alter the substrate, facilitating perpetuation of tachycardia. Consistent with this model, adrenergic stimulation can facilitate the induction of reentrant arrhythmias as well as arrhythmias resulting from enhanced automaticity and those caused by triggered activity resulting from cyclic adenosine monophosphate-dependent delayed afterdepolarizations. METHODS AND RESULTS: On the basis of the results at electrophysiologic study, 26 patients with coronary artery disease were identified as having reentrant VT, 11 were identified as having idiopathic VT caused by triggered activity, and 4 were identified as having idiopathic VT caused by enhanced automaticity. Each patient underwent 24-hour electrocardiographic monitoring, and the mean sinus R-R intervals immediately preceding each sinus beat as well as the 15 beats preceding sinus beats, premature ventricular contractions (VPCs), and complex ventricular ectopy (couplet/non-sustained VT) were computed. In addition, high-frequency heart rate variability was determined. Heart rate accelerated before spontaneous ventricular ectopy for all three arrhythmia mechanisms. R-R intervals preceding episodes of complex ventricular ectopy were significantly shorter than the corresponding intervals preceding single VPCs in patients with 'riggered VT [p=0.006 and 0.01, R-R(-1) and R-R(-15), respectively] and in those with reentrant VT (p=0.007 and p=0.05). There were no corresponding differences in high-frequency heart rate variability. R-R intervals preceding single VPCs were significantly shorter than the corresponding intervals preceding sinus beats in patients with automatic VT (p=0.0004 and 0.0001, respectively), which was accompanied by a small reduction in high-frequency heart rate variability (p=0.04). CONCLUSIONS: Heart rate accelerates before spontaneous ventricular ectopy in patients with VT. The acceleration is disproportionate to parasympathetic withdrawal, implicating increased endogenous sympathetic tone in the genesis of spontaneous ventricular arrhythmias caused by all three electrophysiologic mechanisms: reentry, triggered activity, and automaticity.

Adolescent↗
PubMed1997

Adenosine-sensitive ventricular tachycardia: right ventricular abnormalities delineated by magnetic resonance imaging.

BACKGROUND: Adenosine-sensitive ventricular tachycardia (VT) is thought to be due to cAMP-mediated triggered activity. It typically originates from the RVOT and occurs in patients with apparently normal hearts. Using magnetic resonance imaging (MRI), we tested the hypothesis that adenosine-sensitive VT occurs in patients without structural heart disease. METHODS AND RESULTS: Fourteen patients (9 women; age, 47+/-19 years) presented with sustained VT (n=3), repetitive monomorphic VT (n=7), or both (n=4). VT terminated with adenosine in each patient and was sensitive to vagal maneuvers in 9 of 11 and verapamil in 10 of 12. VT originated from the right ventricular outflow tract in 10 patients, the right ventricular apex in 1, and the left ventricular septum in 3. Conventional studies included normal signal-averaged ECGs in 9 of 9, normal right ventricular echocardiography in 10 of 10, and normal left ventriculography and coronary angiography in 6 of 7. In contrast, MRI scans were abnormal in 10 of 14 patients. These abnormalities included focal thinning (6), fatty infiltration (4), and wall motion abnormalities (4) of the right ventricle. The most common site of MRI abnormalities was the right ventricular free wall, but there was a poor correlation between the site of MRI abnormalities and the origin of VT. Among 18 control patients without clinical heart disease, thinning of the right ventricular wall was noted in only 1 patient (patients versus control subjects, P=.0001). CONCLUSIONS: Patients with idiopathic adenosine-sensitive VT comprise a heterogeneous group as assessed by MRI, with 70% demonstrating mild structural abnormalities. However, it is unlikely that these findings are causally related to tachycardia, and the functional significance of these anatomic abnormalities is uncertain.

Adenosine↗
PubMed1997

Precordial QT dispersion and inducible ventricular tachycardia.

We compared the performance of precordial QT dispersion, late potentials on the signal-averaged electrocardiogram (ECG), and reduced left ventricular ejection fraction for identification of inducible ventricular tachycardia (VT) in 162 patients undergoing electrophysiologic study (EPS). QT(apex) dispersion in 56 patients with inducible VT (72 +/- 55 msec) was greater than that in 106 patients without inducible VT (55 +/- 36 msec, p < 0.01); dispersion was greater in both groups than in 144 normal subjects (33 +/- 19 msec). A QT(apex) dispersion partition of more than 68 msec, the upper ninety-fifth percentile in normal subjects, identified inducible VT with a specificity of 75% and a sensitivity of 45%. Although the performances of late potentials (specificity 82%, sensitivity 59%) and reduced ejection fraction (specificity 86%, sensitivity 54%) were each stronger than QT dispersion alone for identification of inducible VT, abnormal QT(apex) dispersion remained a significant additional predictor of inducible VT in a logistic regression model that included the three variables (specificity 78%, sensitivity 75%).

Adult↗
PubMed1997

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.

Adrenergic beta-Antagonists↗
PubMed1997

Vasodepressor syncope due to subclinical myocardial ischemia.

INTRODUCTION: Vasodepressor syncope is a common cause of syncope, but the initiating event that triggers the vasodepressor response remains incompletely understood. Although ischemia due to acute right coronary occlusion may precipitate hypotension and bradycardia through the Bezold-Jarisch reflex, an ischemic precipitant for the common vasodepressor faint has not been previously identified. In the present study, we present evidence for a causal relationship between myocardial ischemia and vasodepressor syncope. METHODS AND RESULTS: Two patients referred for evaluation of syncope underwent upright tilt table testing with either ST segment monitoring, sestamibi scintigraphy and echocardiography during the tilt test, or coronary angiography. Both patients had positive tilt table tests during the control study. Patient 1 was documented to have reproducible ischemic ECG changes during atypical chest pressure induced by upright tilt, despite a normal coronary angiogram with ergonovine provocation. Subsequent tilt testing with simultaneous sestamibi perfusion imaging and echocardiography revealed reversible anterolateral hypoperfusion corresponding with anterolateral hypokinesis during upright tilt that preceded syncope. Ischemic ECG changes during incremental rapid atrial pacing further suggested ischemia on the basis of microvascular disease. Follow-up tilt testing on verapamil was negative. Patient 2 developed ischemic ECG changes during the recovery phase of an exercise stress test, which was followed by a vasodepressor response and frank syncope. Coronary angiography revealed a 90% distal right coronary artery stenosis that was successfully dilated, after which follow-up tilt table testing off all other medication was negative. CONCLUSIONS: These two cases illustrate a previously unrecognized causality between myocardial ischemia and clinical vasodepressor syncope, and demonstrate that subtle manifestations of myocardial ischemia, associated with either atypical angina or silent ischemia, can provoke syncope.

Cardiac Pacing, Artificial↗
PubMed1997

Mechanisms of idiopathic left ventricular tachycardia.

Idiopathic left ventricular tachycardia (ILVT) differs from idiopathic right ventricular outflow tract (RVOT) tachycardia with respect to mechanism and pharmacologic sensitivity. ILVT can be categorized into three subgroups. The most prevalent form, verapamil-sensitive intrafascicular tachycardia, originates in the region of left posterior fascicle of the left bundle. This tachycardia is adenosine insensitive, demonstrates entrainment, and is thought to be due to reentry. The tachycardia is most often ablated in the region of the posteroinferior interventricular septum. A second type of ILVT is a form analogous to adenosine-sensitive RVOT tachycardia. This tachycardia appears to originate from deep within the interventricular septum and exits from the left side of the septum. This form of VT also responds to verapamil and is thought to be due to cAMP-mediated triggered activity. A third form of ILVT is propranolol sensitive. It is neither or initiated or terminated by programmed stimulation, does not terminate with verapamil, and is transiently suppressed by adenosine, responses consistent with an automatic mechanism. Recognition of the heterogeneity of ILVT and its unique characteristics should facilitate appropriate diagnosis and therapy in this group of patients.

Humans↗
PubMed1996

Mechanism of ventricular rate control after radiofrequency modification of atrioventricular conduction in patients with atrial fibrillation.

BACKGROUND: Modification of atrioventricular (AV) conduction during atrial fibrillation (AF) may be achieved by radiofrequency ablation in the posteroseptal region of the tricuspid annulus. We tested the hypothesis that elimination of the posterior atrionodal input rather than direct damage to the compact AV node accounts for the decrease in ventricular rate after AV nodal modification. METHODS AND RESULTS: Twenty-four patients with the typical form of AV nodal reentrant tachycardia (AVNRT) underwent selective radiofrequency ablation of the slow AV nodal pathway in the posteroseptal tricuspid annulus. AF was induced before ablation (phase 1), 30 minutes after ablation (phase 2), and during follow-up 24 hours after ablation (phase 3), both with and without concurrent infusion of isoproterenol (4 micrograms/min). Successful elimination of AVNRT was achieved in all patients. During phase 3, 11 patients (46%) had residual dual pathway physiology. AV nodal Wenckebach cycle length (AVNW-CL) increased progressively during each phase of the protocol (356 +/- 72 versus 371 +/- 78 ms versus 432 +/- 104 ms, P < .0001), as did the effective refractory period of the AV node (279 +/- 60 versus 304 +/- 67 ms versus 372 +/- 56 ms, P < .0001). Minimal, mean, and maximal RR intervals during AF progressively increased immediately after ablation and 24 hours later (485 +/- 88 versus 533 +/- 116 ms versus 637 +/- 142 ms for mean RR, P < .0001). The changes in AVNW-CL, AV nodal effective refractory period, and ventricular response during AF were independent of residual dual pathway physiology after ablation. Similar observations were observed during isoproterenol infusion. CONCLUSIONS: Modification of AV nodal conduction during AF by radiofrequency ablation in the posteroseptal tricuspid annulus is independent of the presence or absence of a residual slow AV nodal pathway. On the basis of these observations, the mechanism of AV nodal modification is consistent with elimination of the posterior atrionodal input.

Adult↗
PubMed1996

Posterior fast atrioventricular node pathways: implications for radiofrequency catheter ablation of atrioventricular node reentrant tachycardia.

OBJECTIVES: This study sought to present evidence that fast atrioventricular (AV) node pathways with posterior exit sites may participate in typical AV node reentry. BACKGROUND: Catheter ablation of the slow AV node pathway in the posteroseptal right atrium is the preferred therapeutic approach in patients with AV node reentrant tachycardia. Despite the success achieved with this approach, electrophysiologic changes consistent with fast pathway ablation are occasionally observed. One potential explanation is the presence of an aberrant posterior fast pathway. METHODS: The location of fast and slow AV node pathways was determined by atrial activation mapping along the tricuspid valve annulus during tachycardia and was further confirmed by the effect of radiofrequency catheter ablation. RESULTS: Seven patients with AV node reentrant tachycardia had evidence of a posterior fast pathway near the coronary sinus os. Abolition of anterograde and retrograde fast pathway conduction followed radiofrequency ablation in the posteroseptal region in six patients. Consistent with fast pathway ablation, the AH interval increased from 70 +/- 24 to 195 +/- 35 ms (mean +/- SD), and tachycardia was no longer inducible. Selective slow pathway ablation was performed in one other patient with a posterior fast pathway. CONCLUSIONS: Functionally fast AV node pathways may be located in the posteroseptal right atrium, where slow pathway modification is performed. These data delineate the limitation of an anatomically guided slow pathway ablative approach and emphasize the importance of detailed mapping and localization of the retrograde fast pathway exit site before ablation. Failure to recognize the presence of posterior fast AV node pathways may account for sporadic examples of AV block, complicating posteroseptal ablation in patients with AV node reentry.

Adult↗
PubMed1996

Idiopathic right ventricular outflow tract tachycardia: a clinical approach.

Right ventricular outflow tract (RVOT) tachycardia is the most common form of idiopathic ventricular tachycardia (VT). Phenotypically, RVOT tachycardia segregates into two predominant forms, one characterized by repetitive monomorphic nonsustained VT and the other by paroxysmal exercise induced sustained VT. There is an increasing body of evidence to support the concept that both forms of tachycardia reflect disparate clinical manifestations of an identical cellular mechanism (i.e., cAMP-mediated triggered activity), which is identified clinically by the tachycardia's sensitivity to adenosine. The clinical characteristics, natural history, and approaches to therapy of RVOT tachycardia are delineated herein.

Adenosine↗
PubMed1996

Adenosine-sensitive ventricular tachycardia: a conceptual approach.

Idiopathic ventricular tachycardia (VT) is a term that refers to tachycardia that arises from ventricles devoid of apparent structural abnormalities. This form of VT is now recognized to be related to several distinct entities and includes a reentrant form typically located in the region of the left posterior fascicle, an automatic form that may originate from either ventricle, and a form that originates from the right ventricular outflow tract. This last type can account for up to 80% of cases of idiopathic VT and with few exceptions can be further subdivided into repetitive monomorphic VT and paroxysmal stress-induced VT. Evidence has accumulated suggesting that both forms of VT are related to cAMP-mediated triggered activity. The experimental underpinnings of this conclusion as well as the clinical characteristics of this form of idiopathic VT are elucidated in this review.

Adenosine↗
PubMed1995

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.

Adenosine↗
PubMed1995

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)

Adult↗
PubMed1995

Fractal clustering of ventricular ectopy correlates with sympathetic tone preceding ectopic beats.

BACKGROUND: Fractal geometric analysis of ventricular ectopy yields a fractal dimension, which can range from zero to one and is inversely related to clustering of ventricular premature contractions (VPCs). Low values of this fractal dimension, which reflect significantly nonuniform distributions of ventricular ectopy, are found in patients with life-threatening ventricular arrhythmias and predict adverse outcomes in selected patients with congestive heart failure and with mitral regurgitation. However, the physiological mechanism and correlates of the fractal dimension are unknown. METHODS AND RESULTS: To explore the physiological correlates of clustered ventricular ectopy, we studied 30 patients with a history of sustained ventricular tachycardia or ventricular fibrillation who had inducible sustained monomorphic ventricular tachycardia during electrophysiological study and also underwent drug-free 24-hour ambulatory ECG. In addition to fractal dimension (determined by use of our previously described algorithm), we measured the mean RR interval (+/- SD) for all sinus beats preceding a sinus beat and for all sinus beats preceding a single VPC and the mean root-mean-square difference (RMSSD) of all windows of 15 successive RR intervals (excluding ectopic beats) preceding a sinus beat and preceding a single VPC. Based on the directional changes of mean RR (a measure of both sympathetic and parasympathetic tone) and of RMSSD (a measure of parasympathetic tone), each patient's inferred relative sympathetic tone preceding ventricular ectopy was classified as increased, unchanged, or decreased. If these values changed concordantly, relative sympathetic tone was indeterminate. Fractal dimension did not correlate with the mean RR interval, SD of the RR interval, or RMSSD preceding sinus beats or preceding VPCs (all P > .10). In 20 patients, fractal dimension was significantly lower among those with increased relative sympathetic tone (n = 14) than those with unchanged or decreased sympathetic tone (n = 6, P = .008). Ten patients had indeterminate relative sympathetic tone. CONCLUSIONS: Clustering of ventricular ectopy, as measured by the fractal dimension, is observed in patients at increased risk of sudden cardiac death. A low fractal dimension (clustered ventricular ectopy) is related to changes in heart rate and heart rate variability that are consistent with transient increases in cardiac sympathetic tone.

Aged↗