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Biomedical subjects

K A Ellenbogen

Publications and source records attributed to K A Ellenbogen.

At least 55 records · Page 3Linked to original sources
PubMed1997

Acute hemodynamic effects of intravenous ibutilide in patients with or without reduced left ventricular function.

Many antiarrhythmic agents have adverse hemodynamic effects which limit their use in patients with impaired ventricular function or during tachyarrhythmias. Ibutilide is an intravenous, selective class III antiarrhythmic agent that is effective for conversion of atrial fibrillation or flutter. This multicenter, randomized, placebo-controlled, dose-ranging study evaluated the effects of intravenous ibutilide on hemodynamic parameters during invasive monitoring in 47 patients with or without reduced left ventricular ejection fraction (LVEF) > 35% or < or = 35%. Patients received either placebo or ibutilide as a 10-minute loading and a 30-minute maintenance infusion using 1 of the following dosing regimens: placebo then placebo (n = 12); 0.01 then 0.002 mg/kg (n = 12); 0.02 then 0.004 mg/kg (n = 12); or 0.03 then 0.006 mg/kg (n = 11). Ibutilide significantly increased QT and QTc intervals in a dose-related manner with mean increases ranging from 51 to 99 ms, but did not alter the PR interval or QRS duration. During ibutilide infusion, a few small but statistically significant changes from baseline in several hemodynamic variables were present. However, the changes in cardiac output, pulmonary artery or capillary wedge pressures, blood pressure, or heart rate in patients receiving ibutilide were not significantly different from the changes in patients receiving placebo. Thus, ibutilide did not cause clinically important adverse hemodynamic effects, even in patients with depressed ventricular function. One patient developed 2 episodes of nonsustained torsades de pointes during ibutilide. These results demonstrate that with careful monitoring for proarrhythmia, ibutilide can be used safely from a hemodynamic standpoint in the acute treatment of arrhythmias, even in patients with reduced ventricular function.

Adult↗
PubMed1997

The pacemaker syndrome -- a matter of definition.

Pacemaker syndrome is an iatrogenic disease that is often underdiagnosed. We propose that pacemaker syndrome represents the clinical consequences of suboptimal atrioventricular (AV) synchrony or AV dyssynchrony, regardless of the pacing mode. Clinicians implanting and programming pacemakers should attempt to optimize AV synchrony to prevent the occurrence of pacemaker syndrome.

Cardiac Output, Low↗
PubMed1997

Tachycardia-induced cardiomyopathy: a review of animal models and clinical studies.

The increasing prevalence of congestive heart failure has focused importance on the search for potentially reversible etiologies of cardiomyopathy. The concept that incessant or chronic tachycardias can lead to ventricular dysfunction that is reversible is supported by both animal models of chronic rapid pacing as well as human studies documenting improvement in ventricular function with tachycardia rate or rhythm control. Sustained rapid pacing in experimental animal models can produce severe biventricular systolic dysfunction. Hemodynamic changes occur as soon as 24 h after rapid pacing, with continued deterioration in ventricular function for up to 3 to 5 weeks, resulting in end-stage heart failure. The recovery from pacing-induced cardiomyopathy demonstrates that the myopathic process associated with rapid heart rates is largely reversible. Within 48 h after termination of pacing, hemodynamic variables approach control levels, and left ventricular ejection fraction shows significant recovery with subsequent normalization after 1 to 2 weeks. In humans, descriptions of reversal of cardiomyopathy with rate or rhythm control of incessant or chronic tachycardias have been reported with atrial tachycardias, accessory pathway reciprocating tachycardias, atrioventricular (AV) node reentry and atrial fibrillation (AF) with rapid ventricular responses. Control of AF rapid ventricular responses has been demonstrated to improve ventricular dysfunction with cardioversion to sinus rhythm, pharmacologic ventricular rate control and AV junction ablation and permanent ventricular pacing. The investigation of potential tachycardia-induced cardiomyopathy in patients with heart failure requires further prospective confirmation in larger numbers of patients, with study of mechanisms, patient groups affected and optimal therapies.

Animals↗
PubMed1997

Factors associated with elevated impedance with a nonthoracotomy defibrillation lead system.

Peak current flow across the heart determines the success of defibrillation and is inversely dependent on impedance between defibrillation electrodes. Factors associated with elevated impedance in patients with implantable defibrillators using nonthoracotomy lead systems have not been well described. Clinical and echocardiographically derived variables were analyzed in 41 patients in whom implantation of a nonthoracotomy lead system was attempted. Lead impedance was measured at end-expiration with 5-J monophasic shocks. Successful defibrillation with or without addition of a subcutaneous patch with < or = 20 J with a monophasic waveform was required for nonthoracotomy lead placement. Patients were divided into 2 groups based on impedance: low (< or = 47 ohms, n = 30) and high (>47 ohms, n = 11). Twenty-four patients had successful defibrillator implantation using a transvenous lead alone, 13 required placement of a subcutaneous patch, and 4 required epicardial patch placement. The mean left ventricular end-diastolic and end-systolic volumes were significantly smaller (p = 0.01 for both) in patients in the low- versus high-impedance groups and were significantly correlated with impedance (r = 0.44, p <0.005 for both). Impedance was not significantly different between patients with successful defibrillation using a transvenous lead alone compared with those who required either subcutaneous or epicardial patches. Thus, impedance using a nonthoracotomy lead system with monophasic shocks is significantly correlated with both end-systolic and end-diastolic volumes, but elevated impedance does not predict increased defibrillation energy requirements.

Defibrillators, Implantable↗
PubMed1997

Pathophysiologic basis for vasodepressor syncope.

The current knowledge regarding the pathophysiologic basis of the vasodepressor response was reviewed. The balance of evidence indicates that the mechanoreceptor hypothesis seems unlikely to be the sole afferent alteration that leads to the vasodepressor response. Alternative afferent mechanisms should include neurohumoral mediated sympathoinhibition triggered by opioid mechanisms as well as impaired endothelial and NO responses to orthostatic stress in susceptible individuals. It is possible that impaired cardiovagal and sympathetic outflow control of arterial baroreceptors is enhanced by the aforementioned mechanisms. The role of central sympathoinhibition and vagal excitation triggered directly from pathways within the temporal lobe or triggered by alterations in regional cerebral blood flow should be considered as potential alternative mechanisms. Efferent autonomic outflow during vasodepressor syncope include sympathetic neural outflow withdrawal in addition to activation of parasympathetic outflow to the heart and abdominal viscera. Further human research is needed to understand the underlying mechanisms that result in the described neural and vascular responses.

Blood Flow Velocity↗
PubMed1997

Neural monitoring of vasovagal syncope.

Head-up tilt testing has become a valuable and widely accepted diagnostic tool for evaluation of patients with vasovagal syncope. This test has afforded clinical researchers the opportunity to focus on the hemodynamic, humoral, and neural changes that accompany syncope. We review the animal and clinical studies that provide insight into the possible pathophysiological mechanisms involved in vasovagal syncope. Hemodynamic measurements in patients with vasovagal syncope suggest that a relative decrease in ventricular size and increase in cardiac contractility may be seen in many patients with vasovagal syncope. Patients with vasovagal syncope have also demonstrated numerous "exaggerated" neurohumoral responses to syncope. Differential changes in plasma levels of epinephrine, renin, endothelin, vasopressin, cortisol, prolactin, beta endorphins, and substance P have been reported by some investigators either prior to or during a syncopal episode in patients with vasovagal syncope. The precise pathophysiological significance of these measurements is unknown at the present time. Measurements of autonomic tone may be accomplished indirectly with analysis of heart rate variability or baroreflex slope, or directly by sympathetic neural recordings of the peroneal nerve. We have demonstrated decreased baroreflex slopes in patients with vasovagal syncope. Using microneurography, we and others have demonstrated decreased sympathetic nerve activity occurring 11 +/- 3 seconds prior to syncope during head-up tilt table testing. A variety of other abnormal reflexes, including blunted forearm blood flow responses during exercise, have been demonstrated by others. These observations suggest that pacing instituted after the event may not be as helpful as the use of a hemodynamic sensor that will result in the initiation of pacing prior to sympathetic withdrawal or modify the decrease in sympathetic tone that occurs prior to syncope.

Adrenergic Agonists↗
PubMed1997

Failure of automatic mode switching: recognition and management.

Dual chamber pacing is desirable to optimize AV synchrony and to potentially decrease the incidence of supraventricular tachyarrhythmias. Patients with alternating periods of both supraventricular tachyarrhythmias and bradycardia pose a difficult challenge when standard dual chamber pacemakers are implanted. The automatic mode switching mode algorithm was introduced to prevent tracking of paroxysmal supraventricular tachyarrhythmias and avoid the adverse hemodynamic and symptomatic consequences of a rapid ventricular response. In some cases, failure to mode switch may take place when the atrial signal during tachycardia is of insufficient amplitude to be sensed. Failure to mode switch may also occur when the atrial signal periodically occurs in the atrial blanking period(s). In this article, we describe failure to mode switch in seven patients with paroxysmal supraventricular tachyarrhythmias after a Telectronics Meta DDDR 1254 device was implanted. Each patient had paroxysmal atrial flutter and/or atrial fibrillation and presented with either repetitive episodes of oscillation between atrial tracking and mode switching to a nonatrial tracking pacing mode or complete failure to mode switch. Six of seven patients were taking antiarrhythmic drugs that resulted in slowing of the atrial cycle length. Pacemaker reprogramming was required in each case to restore reliable mode switching during subsequent recurrences of the atrial tachyarrhythmias. We conclude that careful pacemaker programming of patients with paroxysmal atrial flutter and the Telectronics Meta DDDR 1254 is necessary when patients are taking an antiarrhythmic drug that slows atrial cycle length.

Aged↗
PubMed1996

Selective slow pathway ablation does not alter enhancement of vagal tone on sinus and atrioventricular nodal function.

We studied the effects of edrophonium on sinus cycle length, atrioventricular (AV) nodal fast pathway refractoriness, and AV nodal Wenckebach cycle length in 21 patients with AV nodal reentrant tachycardia (AVNRT) who received edrophonium, and 8 patients who received phenylephrine before and after selective slow pathway ablation. Changes in sinus cycle length, fast pathway conduction, and refractoriness were not altered by radiofrequency ablation of the slow pathway, suggesting that parasympathetic denervation does not occur after slow pathway ablation of AVNRT.

Adult↗
PubMed1996

Elucidating the mechanisms of atrial flutter cycle length variability using power spectral analysis techniques.

BACKGROUND: The mechanism of the small beat-to-beat variations in cycle length of atrial flutter in humans has not been fully explained. We investigated the beat-to-beat control of atrial flutter cycle length using time and frequency analysis techniques. METHODS AND RESULTS: Mean, SD, and power spectra of atrial cycle lengths were calculated from atrial recordings in 28 patients with type I atrial flutter. In control patients, mean and SD values of atrial cycle length were 265 +/- 37 and 4.9 +/- 1.7 ms. Power spectra contained two or three major peaks with 10.6 +/- 9.2% in band 1 (0.0 to 0.18 Hz), 26.7 +/- 15.9% in band 2 (0.18 to 0.6 Hz), and 63.1 +/- 17.7% in band 3 (0.6 to 2.2 Hz). Isoproterenol infusion (n = 8) increased percentage of total power in band 1 (7.1 +/- 5.6% to 25.7 +/- 18.9%, P < .001). Percentage of total power in band 1 was less in patients receiving (n = 5) versus not receiving (n = 18) oral beta-blockers (2.2 +/- 1.9% versus 10.6 +/- 9.2%, P = .003). Standard deviation (2.5 +/- 1.3 versus 4.9 +/- 1.7 ms, P = .009) and total power (2025 +/- 1350 versus 9768 +/- 8874 ms2, P = .005) were less in heart transplant recipients (n = 5) than control patients. Increases in respiratory rate (n = 6) shifted band 2 frequency peak to higher frequencies (0.26 +/- 0.13 to 0.38 +/- 0.18 Hz, P < .05). Atrial cycle length was longer and monophasic action potential duration was shorter during inspiration than during expiration. Band 3 frequency peak was correlated with heart rate (r = .797, P < .0001). CONCLUSIONS: Atrial flutter cycle length variability has an underlying periodic pattern that is detected by spectral analysis. Atrial flutter is modulated on a beat-to-beat basis by an interplay between the autonomic nervous and respiratory systems and the ventricular rate.

Adrenergic beta-Antagonists↗
PubMed1996

Efficacy of ibutilide for termination of atrial fibrillation and flutter.

The clinical utility of ibutilide fumarate (Corvert) for the acute conversion of atrial tachyarrhythmias to normal sinus rhythm has been demonstrated in several randomized, placebo-controlled clinical trials. The efficacy of intravenous ibutilide for rapid conversion of atrial flutter is in the range of 50-70%, whereas its efficacy for conversion of atrial fibrillation is 30-50%. Approximately 80% of atrial tachyarrhythmias that terminate do so within 30 minutes from the initiation of the intravenous infusion. Ibutilide is more effective than either intravenous procainamide or intravenous sotalol for conversion of atrial fibrillation and atrial flutter to sinus rhythm. Age, presence of structural heart disease, gender and concomitant medication do not appear to influence the efficacy of ibutilide; however, shorter duration of atrial fibrillation is a strong predictor of successful termination. Plasma concentration of ibutilide and QTc interval prolongation are not directly correlated with the success rate for conversion of atrial tachyarrhythmias. Ibutilide's greater efficacy compared with other antiarrhythmic drugs may be related to its ability to cause greater prolongation of atrial monophasic action potential duration relative to atrial cycle length. Termination of atrial flutter with ibutilide was preceded by increased atrial cycle length variability. Ibutilide rapidly and effectively converts atrial fibrillation and atrial flutter to sinus rhythm when administered as a 1-mg total dose followed by a second 1-mg dose. It should be used in conjunction with continuous electrocardiographic monitoring for at least 4 hours after the termination of the infusion, or until the QTc interval returns to baseline. Hypokalemia and hypomagnesemia should be corrected before the start of the infusion. An external cardiac defibrillator, intravenous magnesium, and an external transcutaneous cardiac pacemaker should be readily available for immediate use in the event that palymorphic ventricular tachyarrhythmias occur. Ibutilide is a new intravenous agent that safely and rapidly converts atrial fibrillation and atrial flutter to sinus rhythm.

Anti-Arrhythmia Agents↗
PubMed1996

Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators.

BACKGROUND: Currently available antiarrhythmic drugs have limited efficacy for acute termination of atrial fibrillation and flutter, especially if the arrhythmia is not of recent onset. The purpose of this multicenter study was to determine the efficacy and safety of repeated doses of intravenous ibutilide, a class III antiarrhythmic drug, in terminating atrial fibrillation or flutter. METHODS AND RESULTS: Two hundred sixty-six patients with sustained atrial fibrillation (n = 133) or flutter (n = 133), with an arrhythmia duration of 3 hours to 45 days, were randomized to receive up to two 10-minute infusions, separated by 10 minutes, of ibutilide (1.0 and 0.5 mg or 1.0 and 1.0 mg) or placebo. The conversion rate was 47% after ibutilide and 2% after placebo (P < .0001). The two ibutilide dosing regimens did not differ in conversion efficacy (44% versus 49%). Efficacy was higher in atrial flutter than fibrillation (63% versus 31%, P < .0001). In atrial fibrillation but not flutter, conversion rates were higher in patients with a shorter arrhythmia duration or a normal left atrial size. Arrhythmia termination occurred a mean of 27 minutes after start of the infusion. Of 180 ibutilide-treated patients, 15 (8.3%) developed polymorphic ventricular tachycardia during or soon after the infusion. The arrhythmia required cardioversion in 3 patients (1.7%) and was nonsustained in 12 patients (6.7%). CONCLUSIONS: Intravenous ibutilide given in repeated doses is effective in rapidly terminating atrial fibrillation and flutter and under monitored conditions is an alternative to current cardioversion options.

Aged↗
PubMed1996

Sensing lead-related complications in patients with transvenous implantable cardioverter-defibrillators.

The widespread use of the redesigned Endotak lead (CPI, St. Paul, Minnesota), which combines transvenous pacing, sensing, and defibrillation on a single transvenous lead in patients receiving transvenous implantable cardioverter-defibrillators (ICDs), has reduced morbidity and shortened length of hospital stay after ICD implantation. We describe the incidence and management of Endotak sensing lead-related failures in a series of 348 consecutive patients from 4 institutions who underwent implantation between 1990 and 1995. We retrospectively reviewed the databases for patients receiving an ICD with an Endotak lead for the incidence of lead-related sensing abnormalities. Ten patients (2.8%) with lead-related sensing abnormalities were detected at a mean of 15 +/- 11 months after ICD implantation. Sensing abnormalities were detected in 6 patients after they received inappropriate shocks. Noise or oversensing was noted in 7 patients from interrogation of the devices' data logs. Eight patients had a new transvenous sensing lead placed, 1 patient had a new Endotak lead placed, and 1 had a chronic pacemaker sensing lead converted to function as a sensing lead. No further sensing problems were noted in 8 of 10 patients during a mean follow-up of 14 +/- 8 months. The site of the sensing lead failure was localized to the subrectus pocket in 5 patients and to the clavicle-first rib area in 3 patients; it was undetermined and presumed to be in the clavicle-first rib area in the other 2 patients. One patient had late failure of the defibrillation lead. We conclude that Endotak sensing lead failure does not require insertion of a new Endotak lead, but can be managed with close follow-up and insertion of a new transvenous sensing lead. Endotak lead fractures are frequently localized to the ICD pocket.

Aged↗
PubMed1996

Modulation of atrial repolarization by site of pacing in the isolated rabbit heart.

BACKGROUND: Single-site or multisite atrial pacing may reduce the incidence of atrial fibrillation in humans. The therapeutic mechanisms may include synchronization of atrial repolarization (repolarization "memory") and/or decreased dispersion of atrial repolarization. These responses have not been well documented in intact atria. METHODS AND RESULTS: Monophasic action potential recordings were made from six atrial epicardial sites in 39 isolated perfused rabbit heart preparations during 3 hours of continuous right atrial, left atrial, or biatrial pacing. Action potential recordings obtained at times 0, 45, 90, 135, and 180 minutes were computer analyzed for activation time (AT) and 90% action potential duration (APD) at each site. No consistent relationship could be demonstrated between APD and AT at any time during atrial pacing (all P > .05). On average, left atrial APDs were longer than right atrial APDs by up to 6.3 ms at all times, regardless of the site of pacing (P < or = .05). At all times, dispersion of atrial repolarization was minimized by left atrial pacing compared with right atrial pacing (21.6 +/- 9.1 versus 32.4 +/- 15.1 ms, respectively, at time 0; P < .05). Biatrial pacing provided no further reduction in dispersion of repolarization compared with left atrial pacing (all P > .05). CONCLUSIONS: No relationship can be demonstrated between atrial AT and APD in the isolated rabbit heart preparation. This differs from ventricular repolarization "memory," which is demonstrable under the same conditions. Left atrial APD is, on average, longer than right atrial APD, suggesting spatial heterogeneity in repolarization. Dispersion of atrial repolarization is minimized by left atrial pacing in this preparation with no further advantage to biatrial pacing.

Action Potentials↗
PubMed1996

Comparative efficacy of intravenous ibutilide versus procainamide for enhancing termination of atrial flutter by atrial overdrive pacing.

This study compares the influence of intravenous ibutilide, a class III antiarrhythmic agent, with procainamide, a class IA antiarrhythmic agent, and with placebo on its ability to terminate atrial flutter using rapid atrial pacing. Fifty-nine episodes of atrial flutter in 54 patients who failed to terminate with an intravenous infusion of ibutilide, procainamide, or placebo alone underwent attempts at pacing termination using a standard protocol of burst atrial overdrive pacing. Atrial flutter cycle length and atrial monophasic action potential duration recorded from the right atrium during atrial flutter were measured at baseline and following infusion of ibutilide, procainamide, or placebo. Both ibutilide and procainamide significantly enhanced (p <0.001) pacing-induced termination of atrial flutter compared with placebo. Pacing converted 2 of 11 patients (18%) who received placebo, 13 of 15 patients (87%) who received ibutilide, and 29 of 33 patients (88%) who received procainamide to sinus rhythm. Ibutilide and procainamide compared with placebo markedly reduced (p <0.001) the incidence of pacing-induced atrial fibrillation. The atrial flutter cycle length was prolonged significantly less (p <0.001), and the atrial monophasic action potential duration was increased significantly more (p <0.001) by ibutilide than by procainamide. Although the electrophysiologic changes induced by these antiarrhythmic agents contributed to facilitating pacing-induced termination, neither tachycardia cycle length nor action potential duration were useful predictors of the ability of pacing to terminate atrial flutter. In conclusion, despite differing electrophysiologic effects, the use of intravenous ibutilide or procainamide enhances the termination of atrial flutter by atrial overdrive pacing.

Aged↗
PubMed1996

Pharmacologic alterations in human type I atrial flutter cycle length and monophasic action potential duration. Evidence of a fully excitable gap in the reentrant circuit.

OBJECTIVES: This study compared the effect of changes in action potential duration versus conduction velocity on atrial flutter cycle length to determine whether there is a fully or partially excitable gap in atrial flutter. BACKGROUND: In an excitable gap reentrant circuit, cycle length is proportional to conduction velocity. Action potential duration is not a direct determinant of cycle length when the gap is fully excitable. METHODS: Right atrial monophasic action potentials were recorded from 41 patients during type I atrial flutter before and during pharmacologic interventions. RESULTS: Adenosine (17 +/- 3 mg [mean +/- SD]) shortened (p < 0.001) action potential duration but did not change cycle length. Edrophonium (10 mg) had no significant effect on action potential duration or cycle length. Isoproterenol (0.03 microgram/kg body weight per min) shortened (p < 0.05) and procainamide (15 mg/kg, then 2 mg/min) prolonged (p < 0.001) action potential duration and cycle length. Alterations in cycle length were not correlated with changes in action potential duration. Procainamide's prolongation of action potential duration was reversed by adenosine without affecting cycle length. Procainamide's prolongation of action potential duration and cycle length was partially reversed by isoproterenol. Adenosine's and isoproterenol's shortening of action potential duration and isoproterenol's shortening of cycle length were enhanced by procainamide. CONCLUSIONS: Atrial flutter cycle length is determined primarily by conduction velocity and does not depend directly on action potential duration. Atrial flutter has a fully excitable gap, and procainamide does not convert the gap from full to partial excitability. Adenosine and isoproterenol interact with procainamide such that their effects are enhanced and procainamide's effects are diminished.

Action Potentials↗
PubMed1996

Conversion of atrial flutter by ibutilide is associated with increased atrial cycle length variability.

OBJECTIVES: This study was designed to test the hypothesis that conversion of atrial flutter in humans by ibutilide, a new class III antiarrhythmic agent, is characterized by an increase in atrial cycle length variability. BACKGROUND: Conversion of tachyarrhythmias has been associated with increased oscillations of cycle length. METHODS: Electrograms and monophasic action potentials from the right atrium in 35 patients with spontaneous, sustained atrial flutter were recorded before, during and after intravenous ibutilide (0.005 to 0.025 mg/kg body weight, n = 25) or placebo (n = 10). Atrial cycle length, cycle length variability (coefficient of variation), diastolic interval and diastolic interval variability were measured from 10 consecutive cycles at baseline and 3 min before, 1 min before, 30 s before and immediately before conversion. Similar measurements were made in patients who received ibutilide or placebo but did not convert. RESULTS: Ibutilide converted atrial flutter in 14 of 25 patients 25 +/- 16 min (mean +/- SD) after initiation of the infusion, whereas placebo converted no patients. Atrial cycle length was prolonged to the same extent in ibutilide converters and nonconverters (36 +/- 19 vs. 38 +/- 21 ms, p = NS) and was not affected by placebo. Beat-to-beat variability in atrial cycle length (baseline 1.2 +/- 0.7 vs. preconversion 7.3 +/- 4.9, p < 0.01) and diastolic interval (baseline 11 +/- 8 vs. preconversion 33 +/- 23, p < 0.05) increased significantly just before atrial flutter conversion and remained unchanged in ibutilide nonconverters and placebo group patients. CONCLUSIONS: Ibutilide prolongs atrial cycle length, but conversion of atrial flutter by ibutilide is characterized by increased variability in atrial cycle length and diastolic interval.

Aged↗