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Biomedical subjects

M E Josephson

Publications and source records attributed to M E Josephson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Hybrid pharmacologic and ablative therapy: a novel and effective approach for the management of atrial fibrillation.

INTRODUCTION: Maintenance of sinus rhythm in patients with recurrent atrial fibrillation is often difficult to achieve with pharmacologic therapy. Complex catheter ablative procedures are being developed, but efficacy and safety issues remain to be clarified. We hypothesized that combined pharmacologic and simple ablative therapies in a targeted subset of patients will improve success in the treatment of atrial fibrillation. METHODS AND RESULTS: We identified 13 patients (mean age 61.5 +/- 16.2 years) with atrial fibrillation who converted to electrocardiographic atrial flutter during antiarrhythmic drug treatment. Surface ECG suggested "typical" atrial flutter in 11 patients and "atypical" atrial flutter in 2. Intracardiac mapping and entrainment studies revealed 9 patients had counterclockwise isthmus-dependent atrial flutter, and the remaining 4 had complex activation patterns, suggesting the presence of multiple wavefronts. All 9 patients with typical atrial flutter underwent successful ablation. None of the 4 patients with complex activation patterns had successful ablation. Patients were followed for recurrences of atrial arrhythmias via clinic visits, record review, and interviews. In patients who underwent successful ablation and continued on antiarrhythmic drugs, 88.9% remain in sinus rhythm after a mean follow-up of 14.3 +/- 6.9 months (range 1 to 28). CONCLUSION: In patients who experience conversion of atrial fibrillation to atrial flutter during antiarrhythmic drug treatment, ablation and continuation of pharmacologic therapy is a safe and effective means of achieving and maintaining sinus rhythm.

Adult↗
PubMed1998

Mapping techniques and catheter ablation of ventricular tachycardia due to coronary artery disease.

In contrast to the high success rates for catheter ablation of focal ventricular tachycardia, radiofrequency ablation for ventricular tachycardia due to coronary artery disease has met with limited to variable success. In performing catheter ablation for ventricular tachycardia due to coronary disease, mapping techniques used to locate the isthmus of the reentrant circuit are crucial. Appropriate use of mapping techniques determines the success rate of the procedure. We classify different methods of mapping into indirect and direct. The indirect methods include analysis of the 12-lead electrocardiogram, endocardial pace-mapping, and analysis of electrograms recorded from different parts of the heart during sinus rhythm. The direct methods include activation sequence mapping and entrainment mapping. The direct methods are more important in evaluating ventricular tachycardia due to coronary disease. While using the technique of entrainment mapping, three criteria are important: a) entrainment with concealed fusion; b) post pacing interval within or less than 10 ms of tachycardia cycle length; c) stimulus-to-QRS interval should equal electrogram-to-QRS interval. A high success rate in terminating the tachycardia is seen if these criteria are met.

Catheter Ablation↗
PubMed1997

Coronary sinus pacing prevents induction of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is due to reentry, and its incidence has been shown to decrease after dual-site atrial or biatrial pacing. We investigated whether a simpler pacing approach via the distal coronary sinus (CSd) could eliminate AF inducibility by high right atrial (HRA) extrastimuli (APDs). We based our hypothesis on our previous observation that AF inducibility by HRA APDs was associated with conduction delays to the posterior triangle of Koch, whereas AF was never induced with CSd APDs, which were associated with minimal intra-atrial conduction delays. METHODS AND RESULTS: Programmed electrical stimulation was performed from the high right atrium and CSd, and bipolar recordings were obtained from the high right atrium, His bundle, posterior triangle of Koch, and coronary sinus. In 13 patients (age, 44+/-18 years), AF was reproducibly induced with a critically timed HRA APD (220+/-22 ms) delivered during HRA pacing. AF was not induced in any of the patients when HRA APDs were delivered during CSd pacing at the same critical coupling intervals. Coronary sinus APDs delivered during HRA pacing also were not associated with AF induction. The APD coupling interval measured at the posterior triangle of Koch during CSd pacing was significantly prolonged compared with the one measured during HRA pacing and AF induction (381+/-58 versus 263+/-37 ms; P<.0001). CONCLUSIONS: We propose that CSd pacing suppresses the propensity of HRA APDs to induce AF by limiting their prematurity at the posterior triangle of Koch and not allowing local conduction delay and local reentry to occur.

Adolescent↗
PubMed1997

Origin of junctional rhythm during radiofrequency ablation of atrioventricular nodal reentrant tachycardia in patients without structural heart disease.

Junctional rhythm is commonly observed during radiofrequency catheter ablation of the fast or slow pathways of atrioventricular nodal reentrant tachycardia (AVNRT). However, the origin of these beats remains unclear. We analyzed the retrograde atrial activation sequence of 16 patients (mean +/- SD: 41.2 +/- 18.9 years old) undergoing catheter ablation for typical AVNRT with detailed catheter mapping of the triangle of Koch. The earliest atrial activations were concordant during tachycardia and junctional rhythm in only 5 of 16 patients. The findings suggest that junctional rhythm is unlikely to represent direct stimulation of the atrioventricular (AV) node via a discrete slow pathway but rather results from enhanced automaticity from > or =1 sites in the AV nodal transitional zone. The ensuing atrial activation pattern results from anisotropic spread from these sites. In addition, these data imply that the original concept of the AV node comprising 2 anatomically defined pathways may not be valid, and that a functionally defined pathway model may be a more accurate representation.

Adolescent↗
PubMed1997

The AVID trial: evidence based or randomized control trials--is the AVID study too late? Antiarrhythmics Versus Implantable Defibrillators.

A great body of clinical evidence has been accumulated--before and without the AVID trial--showing that implantable defibrillators prolong life better than currently available antiarrhythmic drugs. With this evidence already available, we question the validity of a trial that attempted, in effect, to place a price tag on life and quality of life.

Anti-Arrhythmia Agents↗
PubMed1997

Procainamide induced change of the width of the zone of entrainment and its relation to the inducibility of reentrant ventricular tachycardia.

Procainamide depresses conduction velocity and prolongs refractoriness in myocardium responsible for reentrant VT, but the mechanism by which the induction of VT is suppressed after procainamide administration remains to be determined. In the present study, the relationship between electrophysiological parameters and the noninducibility of VT was assessed during procainamide therapy with a special reference to the change of an excitable gap. Clinically documented monomorphic sustained VT was induced in 30 patients and, utilizing the phenomenon of transient entrainment, the zone of entrainment was measured as the difference between the cycle length of VT and the longest paced cycle length interrupting VT (block cycle length) which was determined as the paced cycle length decreased in steps of 10 ms, and used as an index of the excitable gap. The effective refractory period was measured at the pacing site and the paced QRS duration was used as an index of the global conduction time in the ventricle. The cycle length of VT, the block cycle length, and the width of the zone of entrainment were determined and compared between the responders and nonresponders. In 15 patients, these parameters were determined at the intermediate dose and related to subsequent noninducibility at the final dose. At the final doses of procainamide, VT was suppressed in 8 (26.7%) of 30 patients. However, the cycle length of VT, the block cycle length, and the width of the zone of entrainment were unable to predict the drug efficacy, i.e., noninducibility. The change in the effective refractory period at the pacing site or the width of the paced QRS duration was not different between the responders and nonresponders. Among the variables, only the width of the zone of entrainment showed a significant narrowing in the responders at the intermediate dose of procainamide, and it was smaller than that of the nonresponders. The significant narrowing of the width of the zone of entrainment was associated with the subsequent noninducibility of VT at the final dose. The present study showed that the baseline cycle length of VT, the block cycle length, the drug induced change of the effective refractory period, or the paced QRS duration was not a predictor of the noninducibility after procainamide administration. However, a significant narrowing of the width of the zone of entrainment at the intermediate dose was associated with the noninducibility of VT at the final dose.

Adolescent↗
PubMed1997

Therapy of "idiopathic" ventricular tachycardia.

Idiopathic ventricular tachycardias occur in "normal" hearts and are generally benign arrhythmias. They can arise from either the left or right ventricle, and the origin is usually predictable from the surface ECG. These arrhythmias are produced by diverse mechanisms. When treatment is indicated, empiric pharmacotherapy can be successful. However, if drugs are not tolerated or fail, radiofrequency (RF) ablation may be indicated. During electrophysiologic study, arrhythmia mechanism can be determined, and pace and activation mapping can be used to localize the site of ventricular tachycardia origin to direct application of RF lesions. RF ablative therapy has been associated with high success rates.

Electrophysiology↗
PubMed1997

Modulation of procainamide's effect on conduction by cellular uncoupling in perfused rabbit hearts.

INTRODUCTION: How cell-to-cell electrical coupling influences an antiarrhythmic agent's effect on conduction is largely unknown. To investigate this, we evaluated the effects of procainamide on myocardial conduction at decreasing degrees of cell-to-cell electrical coupling induced by graded doses of heptanol. METHODS AND RESULTS: Electrograms were recorded from 50 ventricular epicardial sites in a 1 cm x 0.5 cm area during pacing to produce conduction longitudinal or transverse to myocardial fiber orientation in Langendorff-perfused rabbit hearts. The effects of procainamide (15 mg/L) on conduction velocity were determined in the presence of increasing doses of heptanol (0.2, 0.5, and 1.0 mM). In addition, using standard microelectrode techniques in isolated superfused rabbit myocardium, intracellular potentials were recorded in the presence of 15 mg/L procainamide and heptanol (1.0 mM). In the absence of heptanol, procainamide slowed conduction velocity. In the presence of increasing doses of heptanol, procainamide's contribution to the depressant effect on conduction velocity was attenuated and reversed at the highest dose. The latter effect was preferentially seen for conduction longitudinal to myocardial fiber orientation. Heptanol had no effect on action potential amplitude or maximum rate of depolarization in the presence of procainamide. CONCLUSIONS: Procainamide's effect on conduction velocity is influenced by the underlying degree of cell-to-cell electrical coupling. The present model should be useful in evaluating the relative ability of other pharmacologic agents to modulate conduction under conditions of changing cell coupling.

Action Potentials↗
PubMed1997

Pathophysiologic substrate for sustained ventricular tachycardia in coronary artery disease.

Sustained ventricular tachycardia (VT) in the presence of coronary artery disease (CAD) is almost always associated with prior infarction. Its mechanism is reentrant excitation and it can be initiated > 95% of the time. Disrupted and delayed endocardial activation and prolonged, fragmented electrograms recorded during sinus rhythm distinguish patients with VT from those with normal ventricles and those of prior infarction without VT. The extent of abnormalities of activation and number of abnormal, fragmented and late electrograms are greatest in patients with sustained VT. These abnormalities are associated with scar tissue separating the viable myocytes. Fragmented electrograms are due to discontinuous activation due to nonuniform anisotropy caused by the scar tissue. Patients with CAD demonstrate depressed excitability and prolonged relative refractory periods (ie, an upward shift in the strength-interval curve) at sites of infarction but effective refractory periods measured at 10 mA comparable to normals and dispersion of refractory periods. However the associated abnormalities of conduction and activation produce an abnormal dispersion of recovery. Intraoperative mapping of patients with CAD has shown that most of the abnormalities of endocardial activation and conduction are in the subendocardial layers and subendocardial resection of these areas cures VT and abolishes delayed, fragmented electrograms and split potentials and normalizes the electrograms recorded from the subjacent tissue. This supports the hypothesis that abnormalities of conduction are the critical pathophysiologic substrate of VT in CAD.

Arrhythmias, Cardiac↗
PubMed1997

Electrophysiology of atrial fibrillation and its prevention by coronary sinus pacing.

Atrial fibrillation (AF) is a re-entrant rhythm, and patients with AF have intra-atrial conduction abnormalities as evidenced by prolonged P-wave duration, abnormal SAECG of P wave, fragmented atrial electrograms and greater intra-atrial conduction delays in response to APDs. Our previous work has proposed that intra-atrial conduction delays and dispersion of refractoriness during extrastimulus testing are site dependent; high right atrial (HRA) stimulation results in marked prolongation of intra-atrial conduction times and AF, whereas distal coronary sinus (CS) stimulation is associated with minimal conduction delays and absence of AF inducibility. Patients with AF induction during HRA stimulation also manifest non-uniform anisotropic conduction in the region of the posterior triangle of Koch. We postulated that if the posterior triangle of Koch is a critical area for re-entry that initiates AF, then prevention of early activation of the posterior triangle may prohibit AF induction by HRA APDs. Distal CS pacing pre-excites the posterior triangle in relation to HRA activation, therefore a subsequent HRA APD will activate the posterior triangle with a longer coupling interval. AF induction by HRA APDs following HRA pacing is prevented when same HRA APDs follow distal CS pacing. We propose that distal CS pacing eliminates the propensity of HRA extrasystoles to induce AF. This observation may have further clinical applicability in AF prevention.

Atrial Fibrillation↗
PubMed1996

Site-dependent intra-atrial conduction delay. Relationship to initiation of atrial fibrillation.

BACKGROUND: Atrial dysrhythmia patients have exaggerated intra-atrial conduction delays and prolonged relative refractoriness in response to atrial premature depolarizations (APDs). Furthermore, atrial fibrillation (AF) is more readily inducible by APDs from the high right atrium (HRA) than the coronary sinus (CS). In this study, we postulated that site-specific intra-atrial conduction delays can explain why AF is initiated more from the HRA than from the CS. METHODS AND RESULTS: We examined 17 patients (age, 49 +/- 22 years) without a history of atrial flutter, AF, or structural heart disease. Programmed stimulation was carried out from the HRA and distal CS, and bipolar recordings were made at the HRA, His bundle, posterior triangle of Koch, and CS. More prolongations in conduction and relative refractoriness in all intra-atrial sites were observed during HRA than CS APDs. AF was induced in 8 patients after HRA and not CS stimulation. During HRA stimulation, patients with AF inducibility exhibited significant prolongation of conduction to the posterior triangle of Koch and marked broadening of the posterior triangle of Koch electrogram compared with CS stimulation. In patients without AF inducibility, the posterior triangle of Koch electrogram width was the same during HRA and CS stimulation. CONCLUSIONS: The existence of site-dependent intra-atrial conduction delays and site-dependent dispersion of refractoriness appears to be a common property of the atrial myocardium and does not necessarily forecast AF inducibility. However, the presence of nonuniform anisotropic characteristics of the posterior triangle of Koch may be critical for AF induction.

Adult↗
PubMed1996

Nonsustained ventricular tachycardia in coronary artery disease: relation to inducible sustained ventricular tachycardia. MUSTT Investigators.

BACKGROUND: Many physicians believe that electrocardiographic characteristics of nonsustained ventricular tachycardia correlate with the risk for sudden death in survivors of myocardial infarction. Sustained ventricular tachycardia induced by programmed electrical stimulation has also been shown to predict sudden death. OBJECTIVE: To determine whether electrocardiographic characteristics of spontaneous nonsustained ventricular tachycardia can predict the inducibility of sustained ventricular tachycardia by programmed electrical stimulation in patients with coronary artery disease having abnormal ventricular function. DESIGN: Observational cohort study. SETTING: 70 clinical electrophysiology laboratories in the United States and Canada. PATIENTS: 1480 consecutive patients with coronary artery disease, left ventricular ejection fraction of 0.40 or less, and asymptomatic nonsustained ventricular tachycardia. INTERVENTION: Electrophysiologic study attempting to induce sustained monomorphic ventricular tachycardia. MEASUREMENTS: Daily frequency, duration, and cycle length of spontaneous episodes of nonsustained ventricular tachycardia, measured by standard electrocardiographic recordings. RESULTS: No statistically significant difference in the frequency or duration of spontaneous nonsustained ventricular tachycardia was seen between patients with and those without inducible sustained ventricular tachycardia. Rates of spontaneous tachycardia were slightly slower in patients with inducible ventricular tachycardia than in patients without inducible ventricular tachycardia (P = 0.047), but the difference was not clinically significant. CONCLUSION: Electrocardiographic characteristics of spontaneous nonsustained ventricular tachycardia do not predict which patients with coronary artery disease will have inducible sustained ventricular tachycardia.

Coronary Disease↗
PubMed1996

Heterogeneity of retrograde fast-pathway conduction pattern in patients with atrioventricular nodal reentry tachycardia: observations by simultaneous multisite catheter mapping of Koch's triangle.

BACKGROUND: Selective ablation of either the fast of the slow pathway resulting in cure of AV nodal reentry tachycardia (AVNRT) has led to the concept that these pathways are discrete, anatomically defined structures. We hypothesized that if a discrete retrograde fast pathway exists, it should be possible to record a single focus of early atrial activation near the apex of Koch's triangle, with sequential spread of depolarization to the rest of the atria. METHODS AND RESULTS: We evaluated 46 patients (33 women, 13 men; mean age, 45 +/- 17 years) undergoing electrophysiology study and catheter ablation for typical AVNRT. Retrograde atrial activation during AVNRT (337 +/- 43 ms) and ventricular pacing at a similar cycle length (352 +/- 51 ms) was recorded in the region of Koch's triangle with a decapolar catheter in the His bundle position, a multipolar catheter in the coronary sinus, and a deflectable quadripolar catheter along the tricuspid annulus anterior to the coronary sinus ostium. Earliest atrial activation was recorded at the apex of the triangle of Koch in 38 patients during ventricular pacing and in 43 patients during AVNRT. A broad wave front of atrial activation was recorded in 17 patients during ventricular pacing and in 26 patients during AVNRT. During AVNRT, only 2 patients had a single early site with focal and sequential activation along the tendon of Todaro. There was concordance in the pattern of atrial activation between ventricular pacing and AVNRT in only 21 of 46 patients. CONCLUSIONS: Retrograde atrial activation over the fast pathway is heterogeneous within Koch's triangle and the coronary sinus, both for the entire population and for individual patients during different modes of activation. These data do not support the concept of an anatomically discrete retrograde fast pathway.

Adult↗
PubMed1996

The variable contribution of functional and anatomic barriers in human ventricular tachycardia: an analysis with resetting from two sites.

OBJECTIVES: This study sought to investigate the influence of stimulation site on the properties of the circuit in ventricular tachycardia. BACKGROUND: A fully excitable gap can be demonstrated in most human ventricular tachycardias. This requires the presence of an arc of block so that the entire circuit can recover from refractoriness within the period of the cycle length. Resetting characterizes the conduction properties of the tissue within the ventricular tachycardia circuit. Previous studies have not investigated the possibility of site-dependent differences in the resetting response. METHODS: Resetting was performed from the right ventricular apex and outflow tract in 23 patients. Two characteristics of the resetting response were analyzed: 1) the total duration of the flat portion, and 2) the slope of the increasing portion. RESULTS: A flat portion of the resetting response was observed in 18 tachycardias; in 8 of the 18, there was a significant site-dependent difference (> or = 40 ms) in the duration of the flat portion. A significant site-dependent difference in the slope of the increasing portion of the resetting curve was seen in 6 of 22 tachycardias. In all, a stimulation site-dependent change in at least one characteristic of the resetting response was seen in 12 (52%) of the 23 tachycardias. CONCLUSIONS: A stimulation site-dependent change in the flat portion of the resetting response is compatible with an arc of block that is at least partially functional in nature. A change in the slope of the increasing portion is compatible with either partially functional circuit barriers or variation in properties of conduction and refractoriness at different locations within the circuit, or both. These observations suggest that a spectrum of circuit properties may exist in humans, with a variable contribution of anatomic and functional characteristics.

Adult↗