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Biomedical subjects

M E Josephson

Publications and source records attributed to M E Josephson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Non-pharmacological treatment of supraventricular arrhythmias.

In recent years the recognition of toxicity and relative ineffectiveness of antiarrhythmic drugs in the management of arrhythmias has led to the development of non-pharmacological approaches. In the setting of supraventricular arrhythmias, such non-pharmacological approaches include preventative pacing, atrial defibrillation, surgery and radiofrequency catheter ablation. Success rates for catheter ablation exceeding 90% are expected in A-V nodal reentrant tachycardia. A-V reentry due to concealed or manifest bypass tracts, and incessant atrial tachycardias. Success rates in the management of atrial flutter are rapidly approaching this. Atrial fibrillation remains the main problem for which pharmacological therapy may still be useful. New preventative pacing modes, automatic atrial defibrillation, and perhaps surgical or radiofrequency procedures to limit the ability to sustain atrial fibrillation are on the horizon.

Cardiac Pacing, Artificial↗
PubMed1996

Nonuniform anisotropy is responsible for age-related slowing of atrioventricular nodal reentrant tachycardia.

INTRODUCTION: AV nodal reentrant tachycardia cycle length has been shown to be longer in the elderly population. Microfibrosis associated with aging producing nonuniform anisotropic conduction or changes in membrane ionic properties could explain this finding. METHODS AND RESULTS: Forty-five patients (33 women and 12 men) with typical AV nodal reentrant tachycardia were studied to analyze the effects of age on electrophysiologic characteristics of the tachycardia using high-density catheter mapping of the triangle of Koch. We classified patients into group A (age < or = 45 years, mean [+/-SD] 32.7 +/- 8.8, n = 27) and group B (age > 45 years, mean [+/-SD] 61.1 +/- 10.2, n = 18). Retrograde atrial activation was recorded during tachycardia by means of a 2-mm decapolar catheter at the His bundle, a quadripolar catheter at the high right atrium, a multipolar catheter (6 to 10 poles) in the coronary sinus, and a deflectable quadripolar catheter at the posterior triangle of Koch. The AH interval at the AV junction as well as HA intervals at several atrial sites were measured during tachycardia. HA intervals at all atrial recording sites except in the posterior triangle of Koch were significantly longer in group B, as well as the tachycardia cycle length (362 vs 329 msec, P = 0.01). The mean AH interval was prolonged by 24 msec in group B, but this difference did not reach statistical significance. A sequential pattern of retrograde atrial activation during tachycardia was more frequently recorded in group B. CONCLUSIONS: Since the delayed activation to the atrium was heterogeneous, transverse nonuniform anisotropic conduction is a likely explanation of these age-related modifications of AV nodal reentrant tachycardia characteristics.

Adolescent↗
PubMed1996

Pathophysiologic substrate for ventricular tachycardia in coronary artery disease and non-ischemic heart disease.

Sustained uniform monomorphic ventricular tachycardia is usually due to abnormalities of conduction, including coronary artery disease and right ventricular dysplasia. These conduction abnormalities are due to non-uniform anisotropy which is characterized by fragmented electrograms. Less is known about the pathophysiologic substrate of sustained ventricular tachycardia in the absence of coronary artery disease or cardiomyopathy.

Coronary Disease↗
PubMed1995

Systematic characterization of the reentrant circuit during atrioventricular nodal reentrant tachycardia.

This study was conducted to systematically characterize the excitable gap and conduction properties of the reentrant circuit during atrioventricular nodal reentrant tachycardia (AVNRT). Previous studies have attempted to analyze these properties by introducing single ventricular extrastimuli during tachycardia. These studies have been limited, however, by the inability of single extrastimuli to engage the circuit in the majority of patients studied. Thus, in most cases, the nature of the excitable gap and the conduction properties of the anterograde and retrograde limbs of the circuit during tachycardia remain undefined. In this series, 11 patients with typical AVNRT were studied. During tachycardia, both single and double ventricular extrastimuli (the first extrastimulus acting as a conditioning stimulus) were used to scan diastole. The resetting response of the reentrant circuit, as well as the conduction properties of the retrograde fast and anterograde slow pathways, was recorded and analyzed. Whereas atrial preexcitation and resetting of the reentrant circuit could be demonstrated in only 1 patient with single ventricular extrastimuli, resetting was achieved in all 11 patients with closely coupled double ventricular extrastimuli. Over the full range of coupling intervals used, no retrograde delay in fast pathway conduction could be demonstrated before tachycardia termination or ventricular refractoriness. Penetration of the reentrant circuit resulted in a progressive increasing delay in the anterograde portion of the subsequent return cycle and an increasing resetting response pattern in all cases. Thus, the reentrant circuit during AVNRT demonstrates heterogeneous excitability. While the fast pathway remains fully excitable during tachycardia, the slow pathway uniformly demonstrates decremental conduction, resulting in an increasing resetting response pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effect of subendocardial resection on sinus rhythm endocardial electrogram abnormalities.

BACKGROUND: Patients with sustained ventricular tachycardia after acute myocardial infarction frequently have characteristic abnormalities of left ventricular endocardial electrical activity, including fractionated (prolonged, multicomponent, low-amplitude), split (having discrete widely separated deflections), and late (extending after the end of the QRS complex) electrograms. The exact cause and source of these electrograms are not clear. METHODS AND RESULTS: In this study, endocardial electrograms from 18 patients were recorded with a 20-electrode array from the same area immediately before and immediately after resection of subendocardial tissue at the time of surgery for ventricular tachycardia. Electrograms could be compared before and after resection from 298 of 360 (83%) of the electrodes. Before resection, split electrograms were present in 130 (44%) and late components in 81 (27%) of the recordings. Recordings made after resection showed fewer abnormalities, including complete absence of split electrograms as well as all previously recorded late components (P < .02). Mean electrogram amplitude increased from 0.5 +/- 0.8 to 1.0 +/- 1.6 mV (P < .0001) because of removal of the attenuating effect of endocardial scar; mean duration decreased from 112 +/- 38 to 65 +/- 27 ms (P < .0001) mainly because of loss of late and split components. Overall electrogram contour was very similar aside from these changes. CONCLUSIONS: These data show that (1) some of the signal recorded on the endocardial surface is derived from deeper tissue layers and (2) split and late electrogram components appear to be generated by cells in the superficial endocardial layers, since they are eradicated by removal of this tissue. These findings correspond well with previous histological studies of resection specimens that show bundles of surviving muscle cells separated by layers of dense scar that act as an insulator.

Adult↗
PubMed1995

Characterization of return cycle responses predictive of successful pacing-mediated termination of ventricular tachycardia.

OBJECTIVES: The purpose of this study was to characterize response patterns during overdrive pacing that predict successful termination of ventricular tachycardia. BACKGROUND: Overdrive pacing during ventricular tachycardia typically results in entrainment at slow pacing rates and in termination or acceleration at faster rates. The factors that determine the critical paced cycle length that results in tachycardia termination have not been extensively studied. METHODS: Ventricular tachycardias in 14 patients with coronary artery disease were studied with overdrive pacing at several cycle lengths. Return cycles were measured after each additional paced beat at each paced cycle length. The return cycle responses during pacing trials that resulted in tachycardia termination and those that resulted in entrainment were compared. RESULTS: Three return cycle responses were identified: flat, plateau and increasing. Twenty trials of overdrive pacing resulted in tachycardia termination; all were characterized by an increase in the return cycle with the delivery of each successive beat in the pacing drive until the tachycardia terminated (increasing response). Thirty-four pacing trials resulted in entrainment and not termination; these were characterized either by a constant return cycle (flat response) or an initial increase in return cycle followed by a longer, constant return cycle (plateau response) with the delivery of additional paced beats. The longest paced cycle length that resulted in tachycardia termination correlated with the relative refractory period of the circuit, defined as the tachycardia cycle length minus the fully excitable gap (r2 = 0.764, p = 0.0001). Tachycardia termination was not observed unless the paced cycle length was shorter than the relative refractory period of the circuit. CONCLUSIONS: The critical paced cycle length that causes termination of ventricular tachycardia depends on the relative refractory period of the circuit because this factor determines whether the nth + 1 beat of the pacing drive will encounter partially recovered tissue. These data provide insights into the mechanism of pacing-mediated tachycardia termination and entrainment and are applicable to the development of improved antitachycardia pacing algorithms.

Aged↗
PubMed1995

Efficacy of antitachycardia pacing in patients presenting with cardiac arrest.

The efficacy of antitachycardia pacing (ATP) incorporated into implantable cardioverter defibrillators (ICDs) was assessed in 29 consecutive survivors of cardiac arrest, not attributable to acute myocardial infarction, ischemia, or drug and electrolyte effects. The cohort included 25 men and 4 women with a mean age of 65 years and a mean left ventricular ejection fraction of 29%. Seventeen patients had coronary artery disease, 11 had nonischemic dilated cardiomyopathy, and 1 had long QT syndrome. Programmed stimulation yielded monomorphic ventricular tachycardia (VT) in 17 patients, polymorphic VT in 6, and no inducible VT in 6. During a mean follow-up of 22 months, a total of 91 episodes of monomorphic VT occurred, 73 of which were successfully pace terminated (83%). Monomorphic VT amenable to pace termination recurred only in the group that had this arrhythmia inducible. The recurrent arrhythmias in the 12 patients having either no inducible VT or polymorphic VT were all rapid VTs, having a cycle length < 220 ms; and therefore, not amenable to pace termination. These results suggest that ATP incorporated into ICDs is useful in survivors of cardiac arrest and may significantly reduce the number of shocks that these patients would otherwise receive. Programmed stimulation may also help to define those patients who would receive the maximum benefit from ATP.

Adult↗
PubMed1994

Successful and unsuccessful sites of radiofrequency catheter ablation of accessory atrioventricular connections.

Local electrograms from 47 consecutive patients who underwent successful radiofrequency catheter ablation of 49 accessory atrioventricular (AV) connections were analyzed. One hundred twenty-two local electrograms were recorded at 27 successful and 95 unsuccessful sites immediately before radiofrequency catheter ablation of 27 manifest accessory AV connections during preexcited sinus rhythm or atrial pacing. Continuous electric activity was found in 96% of successful sites versus 71% of unsuccessful sites (p < 0.01). Possible accessory pathway (AP) potentials were present only in 15% of successful and 2% of unsuccessful sites, respectively (p < 0.05). All measured time intervals were significantly shorter for successful sites as compared to unsuccessful sites of ablation of manifest accessory AV connections. Unipolar electrograms from the tip of the ablation catheter of each successful and unsuccessful ablation site were available for the last 16 patients with manifest accessory AV connections. A PQS pattern of the unipolar electrogram was associated with a higher success rate, whereas a PrS pattern never resulted in successful ablation of an accessory AV connection. Multivariate logistic regression analysis of the local electrogram characteristics of rapidly conducting, concealed accessory AV connections revealed the interval between the onset of the local ventricular and atrial electrogram (VoAo interval) as the only independent variable associated with successful sites for radiofrequency catheter ablation. The only study patient with a slowly conducting, concealed accessory AV connection underwent successful ablation with the first lesion of radiofrequency energy at the site with the shortest VoAo interval. We conclude that (1) the shortest local AV intervals and local ventricular electrograms preceding the earliest onset of the delta wave in any surface lead are predictive of successful ablation of manifest accessory AV connections; (2) the shortest local VA intervals during orthodromic AV reentry tachycardia or right ventricular pacing are predictive of successful ablation of concealed accessory AV connections; and (3) unipolar recordings from the tip of the ablation catheter should be recorded routinely during mapping of manifest accessory AV connections to identify appropriate target sites for radiofrequency energy applications.

Action Potentials↗
PubMed1994

Ischemia-induced changes in human endocardial electrograms during percutaneous transluminal coronary angioplasty.

The electrophysiologic sequelae of acute reversible transmural myocardial ischemia in humans are poorly understood. Experimental models have demonstrated slowing of conduction in ischemic myocardium, but similar evidence in humans is lacking. We used percutaneous transluminal coronary angioplasty as a model for reversible ischemia to (1) analyze the regional endocardial electrogram response to ischemia and (2) determine whether an initial episode of ischemia may mitigate the effects of a subsequent bout of ischemia (preconditioning). We recorded bipolar left ventricular endocardial electrograms during elective angioplasty in 11 patients and examined changes in amplitude and duration on the electrogram. Each of the 11 patients underwent two to seven balloon inflations. The electrogram amplitude at 90 seconds of balloon occlusion fell to 86% +/- 17% of the control value, and the electrogram duration increased to 109% +/- 12% of the control value. These variables returned to baseline values by 30 and 120 seconds, respectively, after balloon deflation. Among the six patients in the preconditioning protocol, the electrogram duration at 90 seconds was less with the second inflation (106% +/- 7%) than with the first (115% +/- 17%, p < 0.05). The difference in electrogram amplitude between the first and the second inflation was not significant (88% +/- 17% vs 85% +/- 13%, p = NS). At 60 seconds of ischemia there was no difference between normal sinus rhythm and paced complexes in the magnitude of change in electrogram amplitude or duration. We conclude that acute transmural myocardial ischemia in humans is associated with a decrease in local bipolar endocardial electrogram amplitude and an increase in electrogram duration. These findings are consistent with slowed conduction in the ischemic zone and are in agreement with experimental findings in animals. Furthermore, a preconditioning effect on electrogram duration suggests a possible protective effect for repeated bouts of ischemia.

Acute Disease↗
PubMed1994

Initiating reentry: the role of nonuniform anisotropy in small circuits.

Until recently only two types of media have been considered to provide the nonuniformities necessary to initiate cardiac reentry: (1) continuous isotropic media with intrinsic repolarization inhomogeneities; and (2) continuous isotropic media free of inhomogeneities in which repolarization nonuniformities are introduced transiently. The purpose of this article is to establish cellular coupling as a basis for arrhythmias by placing a new type of inhomogeneity, nonuniform anisotropy due to sparse side-to-side coupling between cells, in an overall perspective with the other nonuniformities that lead to reentry. Review of experimental and theoretical models of reentry leads to the following picture: with slowed conduction, reentrant circuits diminish in size and the nonuniformities necessary for reentry are provided by nonuniform anisotropy. Repolarization nonuniformities create functionally different pathways for reentrant circuits of relatively large size (> 30-50 mm2). Nonuniform anisotropic cellular coupling, which is associated with underlying microfibrosis, makes it possible for reentry to occur in small areas (< 10-15 mm2). A general property found in nonuniform anisotropic bundles is the presence of functionally different pathways in the absence of intrinsic repolarization inhomogeneities--one of fast longitudinal conduction with a longer refractory period, and another of "very slow" transverse conduction with a shorter refractory period. Since it is not known if nonuniform anisotropy exists in the AV node, the best known structure with small reentrant circuits, we performed microscopic extracellular measurements in the AV node of the rabbit. The transitional zone of the AV node was found to have markedly nonuniform anisotropic conduction properties. The analysis provides the view that functionally different pathways of small reentrant circuits, including those of the AV node, need to be reevaluated in terms of the role of nonuniform anisotropic cellular coupling.

Animals↗
PubMed1993

Endocardial mapping during sinus rhythm in patients with coronary artery disease and nonsustained ventricular tachycardia.

Programmed stimulation in patients with nonsustained ventricular tachycardia (VT) and coronary artery disease (CAD) induces sustained VT in 30 to 50% of patients. The presence of inducible, sustained VT identifies patients at high risk for sudden death. This study sought to determine whether patients with nonsustained VT who have inducible, sustained VT would have differences of left ventricular endocardial activation and conduction compared with those of patients without inducible, sustained VT. Thirty-six patients with CAD referred for evaluation of nonsustained VT underwent programmed ventricular stimulation and catheter mapping of left ventricular endocardial activation. Using previously validated methods, electrograms were classified as normal, abnormal or fractionated based on measurement of local electrogram duration and amplitude. Programmed stimulation induced sustained, uniform VT in 16 of 36 patients (44%). Patients with inducible, sustained, uniform VT had significantly more sites with abnormal (48%) and fractionated (5.5%) electrograms than did those without inducible VT (35% abnormal and 0.4% fractionated; p = 0.05 and 0.01, respectively). Patients with inducible VT had a mean of 15% of mapped sites displaying late electrograms versus only 3% in those without inducible VT (p < 0.01). The duration of the longest local electrogram in patients with inducible, sustained, uniform VT was 128 ms compared with 100 ms in those without inducible VT (p < 0.001). Thus, patients with CAD presenting with nonsustained VT who have inducible, sustained, uniform VT have significantly greater degrees of local conduction slowing and delayed activation than do those without inducible, sustained, uniform VT. These observations support reentry as the mechanism of the induced arrhythmias in these patients.

Cardiac Pacing, Artificial↗