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Biomedical subjects

H Garan

Publications and source records attributed to H Garan.

At least 91 records · Page 5Linked to original sources

Electrophysiologic effects of beta blockers in ventricular arrhythmias.

Beta-adrenergic receptor blocking agents are effective antiarrhythmic drugs in patients with ventricular arrhythmias. However, these agents exert little or no measurable electrophysiologic effect on normal Purkinje and ventricular muscle fibers when administered acutely. They prevent catecholamine-induced increases in Purkinje fiber automaticity and may interfere with catecholamine-dependent slow responses. beta-adrenergic blocking drugs also prevent the decrease in ventricular fibrillation threshold induced by catecholamines. In the acutely ischemic ventricle, some beta blockers selectively depress conduction within the ischemic zone. The long-term administration of some beta blockers has, in contrast to their short-term effects, been shown to prolong action potential duration and effective refractory period in the ventricle. Which of these observed electrophysiologic effects, either alone or in combination, contributes to the ventricular antiarrhythmic effects of beta-blocking drugs in man is at present unknown.

Adrenergic beta-Antagonists↗

Electrophysiologic effects of d-sotalol in humans.

Sotalol is a beta-adrenergic blocking agent that prolongs the duration of the cardiac action potential in humans, without affecting the upstroke velocity of depolarization. The dextrorotatory isomer, d-sotalol, retains these class III effects, but has little beta-blocking activity in vitro. d-Sotalol has not been studied extensively in humans. The electrocardiographic (ECG) and electrophysiologic effects of d- and d,l-sotalol were therefore assessed in a prospective randomized study of 20 patients. Each patient received either d-sotalol (1, 1.5 or 2 mg/kg body weight) or d,l-sotalol (1 mg/kg) by intravenous infusion. The QT and QTc intervals were prolonged and refractoriness increased in the atrium, atrioventricular (AV) node, His-Purkinje system and right ventricle after both d- and d,l-sotalol. After d-sotalol, the increases in both QT and QTc intervals and in atrial and ventricular effective refractory periods were dose dependent. Highly significant linear correlation was demonstrated between the plasma sotalol level and the change in QT (r = 0.86, p = 0.001) and QTc intervals (r = 0.79, p = 0.002), and between the plasma sotalol level and the effective refractory period of the right atrium (r = 0.75, p = 0.005) and ventricle (r = 0.70, p = 0.025). This study confirms that d-sotalol has effects consistent with class III properties. It demonstrates these effects in humans, and suggests that d-sotalol may prove to be a useful antiarrhythmic agent.

Adolescent↗

Incidence and determinants of multiple morphologically distinct sustained ventricular tachycardias.

The incidence and determinants of multiple morphologically distinct ventricular tachycardias were examined prospectively in 71 consecutive patients with at least one documented spontaneous episode of sustained monomorphic ventricular tachycardia. Mean frontal and horizontal QRS axes were determined from the 12 lead electrocardiograms (ECGs) of 190 spontaneous and 352 induced tachycardias. Two or more morphologically distinct spontaneous tachycardias were observed in 19 (43%) of 44 patients who had at least two documented spontaneous episodes. In 43 (61%) of the 71 patients, multiple morphologically distinct tachycardias were induced by programmed ventricular stimulation. Overall, 57 (80%) of the 71 patients had at least two morphologically distinct tachycardias. Predictors of multiple tachycardia configurations were selected by multivariate analysis from clinical and angiographic variables and were similar for both spontaneous and induced ventricular tachycardia: presence of multiple previous myocardial infarctions (p = 0.032 spontaneous, p = 0.005 induced) and number of different antiarrhythmic drug treatments during which ventricular tachycardia was documented (p = 0.0089 spontaneous, p less than 0.0001 induced). These data demonstrate that a large majority of patients with sustained monomorphic ventricular tachycardia exhibit more than one distinct QRS configuration when adequate ECG documentation of multiple episodes is obtained during different antiarrhythmic drug treatments. In individual patients, caution should be used in attributing clinical significance to a single unique QRS configuration.

Anti-Arrhythmia Agents↗

Endocardial, intramural, and epicardial activation patterns during sustained monomorphic ventricular tachycardia in late canine myocardial infarction.

Thirteen dogs in whom at least one morphologically distinct sustained ventricular tachycardia (VT) could be reproducibly initiated by programmed cardiac stimulation 18 +/- 3 days following experimental myocardial infarction were placed on total cardiopulmonary bypass for detailed study of the endocardial and epicardial activation during VT under hemodynamically stable conditions. Thirteen morphologically distinct monomorphic VTs were investigated by simultaneous epicardial, endocardial, and intramural bipolar recordings. Local electrograms were used to generate computer-assisted isochronous-activation sequence maps. A complete reentry circuit could be mapped on the epicardial surface in 4 animals and on the endocardial surface in one other animal. In the remaining 8 animals, there was a gap period lasting 43-62 msec in the cardiac cycle during which no endocardial or epicardial activity was observed. In 6 of the 8 animals, bipolar intramural recordings from sites closely associated with regions of endocardial and epicardial conduction block showed intramural activity progressing slowly during the gap period. In these 6 animals, a reentry circuit could be completed by incorporating the local electrograms recorded from the intramural sites. VT could be reproducibly terminated by selectively rendering only these intramural sites refractory by critically timed extrastimuli that failed to result in global ventricular capture. VT could be terminated by epicardial cooling in 2 of the 4 animals with epicardial reentry. By contrast, epicardial cryoablation did not effect intramural reentry and failed to interrupt VT. In this study, intramural pathways constituted an integral part of the reentry circuit in a large proportion of the VTs.

Animals↗

Management of refractory supraventricular tachyarrhythmias using low-energy transcatheter shocks.

Alteration of atrioventricular (AV) conduction was attempted in 7 consecutive patients with severely symptomatic, drug-refractory supraventricular tachyarrhythmias using low-energy, direct-current transcatheter shocks of between 20 and 50 J. A single shock of 50 J or less delivered at the AV junction resulted immediately in complete AV block in 6 of the patients. Complete AV block has persisted in 3 patients, and in another who received a second shock 24 hours after the first. AV conduction was altered in the 3 patients in whom conduction either persisted or returned in such a way that supraventricular arrhythmias no longer occurred or were associated with a much slower ventricular response. After a follow-up of 20 to 37 months (mean 27 +/- 8), all 7 patients have improved symptomatically and 6 are taking no antiarrhythmic drugs. Thus, single low-energy transcatheter shocks can be used to ablate AV conduction. Such shocks may also modify AV conduction without production of complete AV block, but with changes in anterograde or retrograde conduction that may favorably influence recurrent symptomatic supraventricular tachyarrhythmias.

Aged↗

Reproducibility of ventricular tachycardia suppression by antiarrhythmic drug therapy during serial electrophysiologic testing in coronary artery disease.

The short-term reproducibility of pharmacologic suppression of ventricular tachycardia (VT) induced by programmed cardiac stimulation was tested in patients with coronary artery disease presenting with documented recurrent VT or ventricular fibrillation. Sixty-three consecutive patients in whom sustained VT (30 patients) or nonsustained VT (33 patients) was induced by programmed cardiac stimulation without antiarrhythmic drug treatment, and in whom at least 1 oral antiarrhythmic drug regimen suppressed the induced VT during serial electrophysiologic testing, were entered into the study. Programmed cardiac stimulation was repeated after a mean of 37 +/- 14 hours during the same antiarrhythmic drug regimen. No VT was induced in 59 of the 63 patients during the second study, resulting in a rate of 94% for short-term reproducibility of pharmacologic suppression of induced VT. Of the remaining 4 patients, programmed cardiac stimulation during the second drug study induced sustained VT in 1 patient and nonsustained VT in 3 patients. There was no significant difference in mean right ventricular effective refractory period and QT interval between the first and second drug study. Thus, in this selected population of patients, pharmacologic suppression of electrically induced VT is a reproducible phenomenon.

Aged↗

Influence of drive cycle length during programmed stimulation on induction of ventricular arrhythmias: analysis of 403 patients.

The drive cycle length at which programmed ventricular stimulation is performed is a fundamental variable in all stimulation protocols, but the influence of this variable on the ability to induce ventricular arrhythmias has not been systematically analyzed. This study, which included 403 patients with prior ventricular tachycardia (VT) or ventricular fibrillation undergoing programmed ventricular stimulation with a uniform protocol that incorporated 3 basic drive cycle lengths from the right ventricular apex, was performed to examine the influence of drive cycle length on the induction of ventricular arrhythmias. The sensitivity of the protocol was 62% for nonsustained VT, 73% for ventricular fibrillation and 89% for sustained VT. Fifty-four percent (217 patients) had an arrhythmia induced with programmed ventricular stimulation during ventricular pacing. No arrhythmia was induced in 96 patients (24%), whereas induction was accomplished during sinus rhythm in 61 patients (15%) and rapid ventricular pacing in 29 patients (7%). With this protocol, the sensitivity for single and double extrastimuli during ventricular pacing increases using decremental drive cycle lengths. Although only 2 patients had induction of a ventricular arrhythmia at a drive cycle length of 700 to 650 ms using a single extrastimulus, 14, 8 and 3 patients had ventricular arrhythmias induced by single extrastimuli at drive cycle lengths of 600 to 550, 500 to 450 and 400 ms, respectively. Of 163 patients with arrhythmias induced with double extrastimuli, only 6 had an arrhythmia induced at drive cycle lengths of 700 to 650 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Perioperative and long-term results after electrophysiologically directed ventricular surgery for recurrent ventricular tachycardia.

Thirty-six patients underwent ventricular aneurysmectomy and electrophysiologically directed endocardial resection for treatment of recurrent ventricular tachycardia refractory to antiarrhythmic drug therapy. The surgical mortality rate was 17% and all 30 patients discharged from the hospital were alive at the end of the follow-up period (range 6 to 54 months), yielding a cumulative projected survival rate of 83% by actuarial analysis. Poor systolic function of the nonaneurysmal ventricular segments was the strongest and the only independent predictor of operative mortality among the clinical, hemodynamic, angiographic and electrophysiologic variables analyzed by stepwise logistic regression. Ventricular tachycardia recurred early in four of the six patients in whom the endocardial resection was limited to a small area for technical reasons. Twelve patients, including 10 with sustained ventricular tachycardia still inducible by postsurgical programmed electrical stimulation, were discharged receiving antiarrhythmic drugs that had been tried unsuccessfully before surgery. During a mean follow-up period of 25 +/- 15 months, nonfatal sustained ventricular tachycardia recurred in two patients after discharge. Inadequate endocardial resection was a significant predictor of arrhythmia recurrence.

Actuarial Analysis↗

Ventricular tachycardia: historical perspective.

Ventricular tachycardia is now diagnosed frequently in patients with organic heart disease. Although ventricular tachycardia was first demonstrated electrocardiographically 75 years ago, the natural history, fundamental mechanisms, and optimal management have remained elusive. Early observers commented on the rarity of occurrence and poor prognosis associated with this arrhythmia, yet with time, some patients with ventricular tachycardia were reported to survive for prolonged periods. Because of the sporadic nature of the arrhythmia and its variable prognosis, assessment of the efficacy of therapies has been difficult. A wide variety of treatments has been advocated with enthusiasm, but only a few have been consistently reported to be effective. Citation of historical data to claim benefit from new treatments should be viewed with caution.

Cardiac Pacing, Artificial↗

Precipitation of cardiac arrest by verapamil in patients with Wolff-Parkinson-White syndrome.

After the administration of verapamil for rapid tachycardias, five patients developed ventricular fibrillation or required urgent cardioversion. All episodes occurred in hospital emergency rooms, and each patient was resuscitated. Examination of electrocardiograms confirmed the presence of the Wolff-Parkinson-White syndrome. In four patients, the presenting tachyarrhythmia was atrial fibrillation with preexcited ventricular complexes, and in one patient a narrow QRS complex tachycardia was initially recorded. Acceleration of atrioventricular conduction occurred within 10 minutes of administration of verapamil, 5 to 10 mg intravenously. Subsequently, intracardiac electrophysiologic studies confirmed the presence of accessory atrioventricular pathways capable of rapid antegrade conduction in each patient. Because of this potentially fatal adverse response, verapamil should not be used in patients with atrial fibrillation and preexcited ventricular complexes.

Adolescent↗

Flecainide: electrophysiologic and antiarrhythmic properties in refractory ventricular tachycardia.

Twenty-two patients with coronary artery disease and spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) underwent intracardiac electrophysiologic evaluation and, when possible, ambulatory monitoring before and after therapy with flecainide (mean dose 418 +/- 87 mg [mean +/- standard deviation]). An average of 4 antiarrhythmic agents were used and were unsuccessful before therapy with flecainide was begun. During 64 +/- 16 hours of control Holter monitoring in 16 patients, all had 1 or more salvos of VT, as well as ventricular premature complexes (VPCs). Programmed stimulation during the control period induced VT in 17 of 22 patients. After flecainide therapy, Holter monitoring showed elimination of all forms of VT in all but 1 patient, as well as significant reduction of paired VPCs by 95% (p less than 0.03) and single VPCs by 70% (p less than 0.005). Electrophysiologic study during flecainide therapy showed significant increases in AH, HV, PR, QRS and QTc intervals, and the ventricular effective refractory period. Programmed stimulation in 17 patients taking flecainide, with a mean plasma level of 1,075 +/- 521 ng/ml, showed ablation of inducible VT in only 2 patients, a worsening in 5 and continued VT inducibility in 10. Adverse effects that required drug withdrawal were infrequent and encountered in patients who received higher drug levels: 1 patient with congestive heart failure and 1 with severe sinus bradycardia. Thus, although flecainide suppresses complex ventricular arrhythmias on Holter recordings, it rarely alters the response to programmed stimulation. Caution is recommended in its use for recurrent sustained VT or VF and in the interpretation of electrophysiologic studies until the predictive value of programmed stimulation with flecainide therapy is established.

Adult↗

Aggravation of electrically provoked ventricular tachycardia during treatment with propafenone.

Propafenone is a new class Ic antiarrhythmic agent currently being investigated in the United States. It is generally well tolerated. We administered propafenone to 16 patients with ventricular tachycardia (VT) that had been refractory to conventional antiarrhythmic drug therapy. Three of these 16 patients developed electrically provoked incessant VT during treatment with propafenone without other evidence of toxicity. These arrhythmias subsided after lidocaine was administered. Propafenone therapy was discontinued in each case. Incessant VT did not develop in any of these patients in the absence of antiarrhythmic drugs or on antiarrhythmic drugs other than propafenone. Alternative effective treatment was identified for each patient. Although VT was initially provoked by pacing in each of these patients, these observations suggest that propafenone, like some other class Ic drugs, may favor the development of incessant VT in occasional patients. This appears most likely to occur in patients with ventricular dysfunction and prior sustained VT or ventricular fibrillation.

Aged↗

Serial analysis of electrically induced ventricular arrhythmias in a canine model of myocardial infarction.

To determine the rate of induction, specificity and evolution of electrically induced postmyocardial infarction ventricular arrhythmias, 10 dogs that underwent a sham operation and 20 dogs with experimental transmural apical myocardial infarction underwent serial closed chest electrophysiologic studies with programmed ventricular stimulation under light anesthesia 1, 2, 4 and 6 weeks after the operation. The reproducibility of the electrically induced ventricular arrhythmias was at a maximum when three extrastimuli were used during ventricular pacing for induction. The reproducibility of the arrhythmias was also a function of the age of the infarct. Electrically induced sustained monomorphic ventricular tachycardia, observed in 45 to 50% of the animals, was a highly specific postinfarction finding (0% specificity in control animals, regardless of the mode or timing of programmed cardiac stimulation), whereas nonsustained polymorphic ventricular tachycardia was not. The specificity of induced ventricular fibrillation was a function of the mode and timing of programmed stimulation. The rate of induction of the electrically induced ventricular arrhythmias did not change significantly during the 6 week period after myocardial infarction. A large infarct size (determined by postmortem examination) and a low left ventricular ejection fraction (determined during premortem cardiac catheterization) were the only variables identified that predisposed the animals to electrically induced sustained monomorphic ventricular tachycardia. These factors, however, did not correlate with the presence of electrically induced ventricular fibrillation or nonsustained ventricular tachycardia.

Animals↗

Determinants of the outcome of electrophysiologic study in patients with ventricular tachyarrhythmias.

To determine those factors predictive of the ability to both initiate and suppress ventricular tachyarrhythmias during electrophysiologic study, the results of programmed cardiac stimulation were evaluated in 261 patients: 66 presenting with nonsustained ventricular tachycardia, 91 with sustained ventricular tachycardia and 104 with ventricular fibrillation. Multivariate logistic regression analysis revealed that the presenting arrhythmia was a potent and independent predictor of the ability to provoke ventricular arrhythmias at electrophysiologic study; a history of myocardial infarction and male sex were also significant independent predictors. Of patients presenting with sustained ventricular tachycardia, 89% (81 of 91) had inducible ventricular arrhythmias compared with 61 (40 of 66) and 66% (69 of 104) of patients with nonsustained ventricular tachycardia and ventricular fibrillation, respectively. Complete suppression of inducible arrhythmias could be achieved in only 52% (34 of 66) of patients with sustained ventricular tachycardia, compared with 73 (24 of 33) and 75% (46 of 61) of patients presenting with nonsustained ventricular tachycardia and ventricular fibrillation, respectively. Multivariate analysis showed that the major independent determinants of the ability to suppress inducible arrhythmias were the number of drug trials performed before electrophysiologic study (inversely correlated) and the nature of the induced arrhythmia. The nature of the presenting clinical arrhythmia is, therefore, a highly significant and independent predictor of the ability to induce ventricular arrhythmias during electrophysiologic testing and an important determinant of the ability to suppress induced arrhythmias in patients with spontaneous ventricular tachyarrhythmias.

Adolescent↗

Long-term reproducibility of responses to programmed cardiac stimulation in spontaneous ventricular tachyarrhythmias.

Programmed electrical stimulation (PES) of the heart has been used to initiate and terminate ventricular tachyarrhythmias under controlled conditions in patients in whom these arrhythmias have occurred spontaneously. The long-term reproducibility of the response to programmed cardiac stimulation in patients with ventricular arrhythmias is unknown. Seventeen patients with previously documented spontaneously occurring ventricular tachyarrhythmias were evaluated: 5 with nonsustained ventricular tachycardia (VT), 10 with sustained VT and 2 with ventricular fibrillation. The underlying cardiac diagnosis was atherosclerotic coronary heart disease (CAD) in 11 patients, dilated cardiomyopathy in 2 patients, congenital heart disease in 1 patient and no structural heart disease in 3. All patients underwent PES in the absence of antiarrhythmic drug treatment, and patients with inducible VT underwent serial electrophysiologic-pharmacologic testing in an attempt to suppress the arrhythmia. All 17 patients were reexamined with PES at a mean of 18 months (range 2 to 42) after their initial electrophysiologic study, during which time none had a myocardial infarction or intervening cardiac surgery. Repeat electrophysiologic studies, performed in the absence of antiarrhythmic agents, were undertaken because of drug intolerance, availability of new drugs, recurrent arrhythmia or preoperative reevaluation. All 11 patients with CAD had inducible VT on both the first and second electrophysiologic evaluation. Of the 6 patients with no CAD, only 1 had inducible VT on both occasions. Thus, long-term reproducibility of PES-induced VT in patients with stable CAD appears to be high.

Adolescent↗

Long-term clinical outcome of ventricular tachycardia or fibrillation treated with amiodarone.

The determinants of long-term clinical outcome were studied in 42 patients with recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) who were treated with amiodarone as the sole antiarrhythmic agent. Of the 42 patients, 11 (26%) either died suddenly or had recurrent, symptomatic, sustained VT during a mean follow-up period of 10 months (range 0.3 to 45). Of the 19 patients without inducible VT/VF during electrophysiologic study while receiving amiodarone, 1 patient died suddenly but no patient had recurrent VT/VF. Ten of the 23 patients (43%) with persistently inducible arrhythmia have died suddenly or have had recurrent VT/VF. Using survival and stepwise logistic regression analyses, 2 significant independent predictors of recurrent arrhythmia were identified; persistently inducible VT during electrophysiologic testing in patients receiving amiodarone therapy (p less than 0.002) and the left ventricular ejection fraction at rest (p less than 0.05). The predictive accuracy of the response to serial electrophysiologic testing during amiodarone therapy was 67%, the sensitivity was 58% and the specificity was 91%. Thus, serial electrophysiologic testing is useful for determining the prognosis in patients with inducible VT/VF treated with amiodarone.

Aged↗

Electrophysiologic properties of flecainide acetate.

Preliminary clinical experience indicates that flecainide is a useful antiarrhythmic agent for the suppression of spontaneous ventricular arrhythmias. The drug also exerts marked effects on accessory atrioventricular (AV) pathway and retrograde fast AV nodal pathway refractoriness, and therefore may be effective in treatment and prevention of reentrant supraventricular tachycardias. Electrophysiologic studies indicate that flecainide slows atrial, AV nodal, His-Purkinje and intraventricular conduction and, to a far lesser degree, prolongs refractory periods in these tissues. The effect of the drug in slowing conduction within the His-Purkinje system is particularly marked and is commonly associated with prolongation of the HV interval beyond the normal range. Flecainide causes a small but significant increase in the QT interval duration, which results largely from prolongation of the QRS interval. Significant prolongation of the sinus node recovery time has been observed in patients with preexisting sinus node dysfunction. Available electrophysiologic data suggest that flecainide should not be administered to patients with advanced disease of the His-Purkinje system or sinus node. The safety of the drug in patients with mild to moderate abnormalities of His-Purkinje conduction or sinus node function awaits further study.

Anti-Arrhythmia Agents↗