27 results on '"Mitchell LB"'
Search Results
2. Impact of implantable cardioverter-defibrillator, amiodarone, and placebo on the mode of death in stable patients with heart failure: analysis from the sudden cardiac death in heart failure trial.
- Author
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Packer DL, Prutkin JM, Hellkamp AS, Mitchell LB, Bernstein RC, Wood F, Boehmer JP, Carlson MD, Frantz RP, McNulty SE, Rogers JG, Anderson J, Johnson GW, Walsh MN, Poole JE, Mark DB, Lee KL, and Bardy GH
- Subjects
- Cause of Death, Combined Modality Therapy, Death, Sudden, Cardiac epidemiology, Follow-Up Studies, Heart Failure mortality, Humans, Kaplan-Meier Estimate, Placebos, Proportional Hazards Models, Risk Factors, Tachycardia mortality, Amiodarone therapeutic use, Anti-Arrhythmia Agents therapeutic use, Death, Sudden, Cardiac prevention & control, Defibrillators, Implantable, Heart Failure drug therapy, Tachycardia drug therapy
- Abstract
Background: The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter-defibrillator (ICD) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction < or =35% on optimal medical therapy. Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown., Methods and Results: SCD-HeFT randomized 2521 subjects to placebo, amiodarone, or shock-only, single-lead ICD therapy. Over a median follow-up of 45.5 months, a total of 666 deaths occurred, which were reviewed by an Events Committee and initially categorized as cardiac or noncardiac. Cardiac deaths were further adjudicated as resulting from sudden death presumed to be ventricular tachyarrhythmic, bradyarrhythmia, heart failure, or other cardiac causes. ICD therapy significantly reduced cardiac mortality compared with placebo (adjusted hazard ratio, 0.76; 95% confidence interval, 0.60 to 0.95) and tachyarrhythmia mortality (adjusted hazard ratio, 0.40; 95% confidence interval, 0.27 to 0.59) and had no impact on mortality resulting from heart failure or noncardiac causes. The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure. The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease. Compared with placebo, amiodarone had no significant effect on any mode of death., Conclusions: ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality. Amiodarone had no effect on all-cause mortality or its cause-specific components, except an increase in non-cardiac mortality in class III patients. [corrected], Clinical Trial Registration Information: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000609.
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- 2009
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3. Overdrive ventricular pacing to clarify the diagnosis of a left bundle branch block morphology tachycardia.
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Quinn FR, Mitchell LB, Mardell A, and Veenhuyzen GD
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- Adult, Cardiac Electrophysiology, Electrocardiography, Female, Humans, Recurrence, Bundle-Branch Block diagnosis, Cardiac Pacing, Artificial, Tachycardia diagnosis
- Published
- 2008
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4. Atrial fibrillation following cardiac surgery.
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Mitchell LB, Crystal E, Heilbron B, and Pagé P
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- Heart Atria, Humans, Practice Guidelines as Topic, Atrial Fibrillation etiology, Atrial Fibrillation prevention & control, Cardiac Surgical Procedures adverse effects, Tachycardia etiology, Tachycardia prevention & control
- Abstract
Atrial tachyarrhythmias, usually atrial fibrillation or atrial flutter, are the most common complications of cardiac surgery. Atrial tachyarrhythmias are associated with patient discomfort/anxiety, hemodynamic deterioration, cognitive impairment, thromboembolic events (including stroke), exposure to the risks of antiarrhythmic treatments, longer hospital stays and increased costs. Many approaches to the prevention of postoperative atrial tachyarrhythmias have been studied. Of these, studies using perioperative beta-blocking agents or amiodarone provide level A evidence of efficacy and, in properly selected patients, have shown a high degree of safety. Less convincing, level B evidence exists for the use of postoperative temporary atrial pacing and for perioperative intravenous magnesium treatment. The treatment of postoperative atrial tachyarrhythmias is similar to those occurring in other settings and includes excluding other potential causes of atrial tachyarrhythmias, antithrombotic or anticoagulation therapy, control of the ventricular response rate and consideration of restoring/maintaining sinus rhythm. The selection of therapies to achieve these goals should consider the sympathetic nervous system discharge state of the postoperative environment and the natural history of postoperative atrial fibrillation, which includes spontaneous resolution of the arrhythmogenic tendency after approximately six weeks. The Canadian Cardiovascular Society Consensus Conference recommendations for the prevention of atrial tachyarrhythmias after cardiac surgery and for the treatment of atrial tachyarrhythmias that occur after cardiac surgery are presented along with evidence that supports these recommendations.
- Published
- 2005
5. Myocardial uptake and pharmacodynamics of procainamide in patients with coronary heart disease and sustained ventricular tachyarrhythmias.
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Gillis AM, Duff HJ, Mitchell LB, and Wyse DG
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- Aged, Coronary Circulation, Dose-Response Relationship, Drug, Electrocardiography, Female, Humans, Male, Middle Aged, Procainamide pharmacology, Procainamide therapeutic use, Coronary Disease metabolism, Myocardium metabolism, Procainamide metabolism, Tachycardia metabolism
- Abstract
Little information is available currently regarding the time course of myocardial accumulation and the onset of the electrophysiologic effects of antiarrhythmic drugs in humans. The myocardial uptake and pharmacodynamics of the antiarrhythmic drug, procainamide, were studied during i.v. infusion in nine patients with ventricular tachycardia undergoing electrophysiologic study. Myocardial procainamide uptake was determined by serial measurements of arterial-coronary sinus drug concentration differences and measurement of coronary sinus blood flow during a 50-min procainamide infusion. The myocardial uptake of procainamide was 10 +/- 4% (mean +/- S.D.) of the total dose at 50 min. Coronary sinus procainamide concentrations equilibrated with arterial concentrations within 30 min of the start of the infusion. However, peripheral venous procainamide concentrations did not reach equilibrium with the arterial compartment during the 50-min drug infusion. Changes in the QRS duration, ventricular conduction time, QTc and ventricular refractory periods correlated in a linear fashion with changes in the plasma procainamide concentrations. The slopes of the arterial and coronary sinus concentration-effect relationships were similar and significantly greater than the slopes of the peripheral venous concentration-effect relationships (P < .05). Thus, procainamide equilibrates rapidly, but not instantaneously, in the myocardium. Short-term electrophysiologic effects correlate best with the arterial and coronary sinus drug concentrations. During this period, venous procainamide concentrations do not accurately reflect the myocardial concentration, effects or the eventual steady-state relationships.
- Published
- 1993
6. Use-dependent electrophysiologic effects of amiodarone in coronary artery disease and inducible ventricular tachycardia.
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Chiamvimonvat N, Mitchell LB, Gillis AM, Wyse DG, Sheldon RS, and Duff HJ
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- Amiodarone administration & dosage, Cardiac Pacing, Artificial, Electrocardiography, Female, Heart Conduction System physiopathology, Humans, Male, Middle Aged, Regression Analysis, Tachycardia diagnosis, Time Factors, Amiodarone therapeutic use, Coronary Disease drug therapy, Heart Conduction System drug effects, Sodium Channels drug effects, Tachycardia drug therapy
- Abstract
Amiodarone produces use-dependent block of cardiac sodium channels in vitro. This study assessed whether similar use-dependent block occurred in 19 patients with coronary artery disease and inducible, sustained, monomorphic ventricular tachycardia treated with amiodarone. Beat-to-beat measurements of ventricular paced QRS durations during 12-beat trains at cycle lengths of 700, 600, 400 and 300 ms were analyzed at a baseline antiarrhythmic drug-free study and after 2 and 10 weeks of amiodarone therapy. At the drug-free study, there were no significant changes in paced QRS durations within the 12-beat trains at any pacing cycle lengths. After 2 and 10 weeks of amiodarone therapy, progressive prolongation of paced QRS durations occurred over the 12-beat trains at pacing cycle lengths of 600, 400 and 300 ms (p less than 0.05). Significant changes in QRS duration were not observed at a pacing cycle length of 700 ms. This progressive prolongation in QRS duration can be fitted as a function of beat number to a monoexponential equation and occurred with an onset time constant of 1.02 +/- 0.41 beats (306 +/- 122 ms) at a pacing cycle length of 300 ms. The magnitude of QRS prolongation increased as the pacing cycle length was shortened. The magnitudes of QRS prolongation were similar after 2 and 10 weeks of amiodarone therapy. In conclusion, use-dependent prolongation in QRS duration occurs at rapid pacing cycle lengths in humans receiving amiodarone.
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- 1992
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7. Electrocardiographic body surface mapping in patients with ventricular tachycardia. Assessment of utility in the identification of effective pharmacological therapy.
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Mitchell LB, Hubley-Kozey CL, Smith ER, Wyse DG, Duff HJ, Gillis AM, and Horacek BM
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- Cardiac Pacing, Artificial, Female, Heart Conduction System physiopathology, Humans, Male, Middle Aged, Predictive Value of Tests, Tachycardia drug therapy, Tachycardia physiopathology, Anti-Arrhythmia Agents therapeutic use, Electrocardiography methods, Quinidine therapeutic use, Signal Processing, Computer-Assisted, Tachycardia diagnosis
- Abstract
Background: Body surface maps of net QRST deflection areas (isointegrals) reflect regional ventricular repolarization properties. Vulnerability to ventricular tachyarrhythmias is associated with maps that feature multiple islands (extrema) of positive and negative values; such maps reflect regional disparity of ventricular recovery properties. The value of body surface mapping in prediction of the efficacy of antiarrhythmic therapy for ventricular tachyarrhythmias has not been determined., Methods and Results: Isointegral ECG body surface mapping was performed in 51 patients with inducible ventricular tachycardia having programmed stimulation studies at baseline and after oral quinidine therapy. The degree of nondipolarity of QRST isointegral distribution was expressed by the number of extrema and by the percentage contribution of nondipolar eigenvectors after Karhunen-Loeve transformation. QRST isointegral nondipolarity was greater in ventricular tachycardia patients than in 51 age- and sex-matched normal subjects expressed as mean number of extrema (4.1 +/- 2.8 versus 2.0 +/- 0.2, respectively), mean eigenvector-determined nondipolar content percentages (12.4 +/- 10.1% versus 4.5 +/- 4.9%), prevalence of abnormal numbers of extrema (63% versus 4%), or prevalence of abnormal nondipolar content percentages (33% versus 4%) (each p less than 0.01). Quinidine prevented ventricular tachycardia induction in 14 patients. Patients for whom quinidine was or was not effective had similar nondipolarity indexes at baseline. However, maps on quinidine differed as a function of antiarrhythmic efficacy. Although effective therapy produced no significant mean changes in nondipolarity, ineffective therapy increased the number of extrema compared with baseline (5.4 +/- 3.4 versus 3.8 +/- 2.5, respectively) (p = 0.002). Individually, 43% of patients on effective therapy had drug-induced decreases in numbers of extrema compared with 14% of those on ineffective therapy (p = 0.02). Furthermore, 29% of patients on effective therapy showed drug-induced increases in numbers of extrema compared with 62% of those on ineffective therapy (p = 0.03)., Conclusions: QRST isointegral body surface mapping shows promise as a noninvasive measure of drug efficacy in patients with ventricular tachycardia.
- Published
- 1992
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8. Drug therapy of ventricular tachycardia: a cost comparison of randomized noninvasive and invasive approaches.
- Author
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Mitchell LB, Duff HJ, Miller CE, Eliasoph HP, and Wyse DG
- Subjects
- Anti-Arrhythmia Agents economics, Canada, Drug Costs, Electrocardiography, Exercise Test, Follow-Up Studies, Heart Ventricles, Humans, Tachycardia economics, Anti-Arrhythmia Agents therapeutic use, Hospitalization economics, Tachycardia drug therapy, Ventricular Fibrillation drug therapy
- Abstract
Objective: Economic evaluation of noninvasive (suppression of ventricular arrhythmias detected by ambulatory monitoring) and invasive (suppression of arrhythmias induced by programmed stimulation) approaches to antiarrhythmic drug selection for ventricular tachyarrhythmias., Design/setting: Randomized clinical trial/tertiary-care hospital., Patients: Of 124 consecutive patients referred for treatment of symptomatic ventricular tachyarrhythmias, 57 consenting patients were eligible to have drug therapy selected by either noninvasive or invasive approaches., Measurements: Costs of initial and follow-up (26 +/- 15 months) admissions for the two groups were compared. This economic evaluation also considered relative efficacies of the approaches using the primary outcome variable of symptomatic, sustained ventricular tachyarrhythmia recurrence (including sudden death)., Results: Initial hospitalization for therapy selection was less costly by the noninvasive approach ($6,869 +/- 4,019) than by the invasive approach ($13,164 +/- 6,740) (P less than 0.001). However, the noninvasive approach generated higher follow-up hospital costs ($9,204 +/- 9,217) than the invasive approach ($3,784 +/- 4,944) (P = 0.01). Thus, total hospital costs of the noninvasive ($16,073 +/- 9,423) and invasive approaches ($16,949 +/- 7,174) were equivalent. The two-year actuarial probability of a recurrent, sustained, symptomatic ventricular tachyarrhythmia was greater in noninvasive (0.50 +/- 0.10) than in invasive (0.20 +/- 0.08) approach patients (P = 0.02)., Conclusions: The lower initial hospital costs of the noninvasive approach are offset by greater follow-up costs. Within two years the costs of the two approaches are equivalent. Thus, greater antiarrhythmic efficacy can be achieved by the invasive approach to drug selection without increasing total hospital costs.
- Published
- 1992
9. Reduction in defibrillator shocks with an implantable device combining antitachycardia pacing and shock therapy.
- Author
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Leitch JW, Gillis AM, Wyse DG, Yee R, Klein GJ, Guiraudon G, Sheldon RS, Duff HJ, Kieser TM, and Mitchell LB
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- Anti-Arrhythmia Agents therapeutic use, Cardiac Pacing, Artificial methods, Electrocardiography, Ambulatory, Equipment Design, Evaluation Studies as Topic, Female, Humans, Male, Middle Aged, Tachycardia mortality, Electric Countershock instrumentation, Pacemaker, Artificial, Prostheses and Implants, Tachycardia therapy
- Abstract
Implantable defibrillators reduce the risk of sudden death in patients with malignant ventricular arrhythmias, but significant restriction in quality of life can occur as a result of frequent device activation. To determine if a device that provides both antitachycardia pacing and shock therapy can safely reduce the frequency of shocks after implantation, 46 consecutive patients undergoing initial implantation of a defibrillator were studied. In all patients, the implanted device provided antitachycardia pacing and shock therapy. Detected tachycardia characteristics and the results of therapy were stored in the device's memory. There were 42 men and 4 women, aged 26 to 71 years (mean 58.7 +/- 13.5). Left ventricular ejection fraction ranged from 13% to 67% (mean 32.2 +/- 13.4%) and 31 patients had experienced one or more episodes of cardiac arrest. Induced arrhythmias included sustained monomorphic ventricular tachycardia in 38 patients, nonsustained polymorphic ventricular tachycardia in 2 and ventricular fibrillation in 4. Over a total follow-up period of 255 patient-months (range 1 to 13, mean 6.1), 25 patients experienced spontaneous arrhythmic events. In 22 patients, 909 episodes of tachycardia were treated by antitachycardia pacing, which was successful on 840 occasions (92.4%). Acceleration of ventricular tachycardia by pacing therapy was estimated to have occurred 39 times. Syncope occurred once during pacing-induced acceleration of ventricular tachycardia. Forty-four episodes of tachycardia in seven patients were treated directly by shocks because of short tachycardia cycle length; 88% of all detected tachycardias were treated without the need for shocks. Four patients died from cardiorespiratory failure and one patient died suddenly without any detected tachyarrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1991
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10. Drug response at electropharmacologic study in patients with ventricular tachyarrhythmias: the importance of ventricular refractoriness.
- Author
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Gillis AM, Wyse DG, Duff HJ, and Mitchell LB
- Subjects
- Coronary Disease physiopathology, Electrocardiography, Electrophysiology, Evaluation Studies as Topic, Female, Heart Conduction System physiopathology, Humans, Male, Middle Aged, Refractory Period, Electrophysiological drug effects, Regression Analysis, Tachycardia diagnosis, Anti-Arrhythmia Agents therapeutic use, Cardiac Pacing, Artificial, Heart Conduction System drug effects, Tachycardia drug therapy
- Abstract
The clinical and electrophysiologic predictors of successful antiarrhythmic drug therapy for patients with inducible ventricular tachycardia were evaluated in 59 consecutive patients undergoing serial electropharmacologic trials. Structural heart disease was less frequently present in patients for whom effective therapy was found (p less than 0.05). The presence of coronary artery disease and a history of prior myocardial infarction were significantly more frequently present in patients for whom antiarrhythmic drug therapy could not be found (p less than 0.05). The corrected QT interval and ventricular effective refractory period measured at a pacing cycle length of 400 ms were significantly shorter in responders compared with nonresponders (QT interval 428 +/- 52 versus 460 +/- 59 ms; ventricular effective refractory period 237 +/- 28 versus 254 +/- 24 ms; (p less than 0.05). In addition, the interelectrogram coupling interval of the ventricular extrastimulus initiating ventricular tachycardia was significantly shorter in responders compared with nonresponders (223 +/- 37 versus 251 +/- 33 ms; p = 0.003). Logistic regression analysis identified a short ventricular interelectrogram coupling interval (p less than 0.01) and absence of prior myocardial infarction (p less than 0.05) as the only independent predictors of antiarrhythmic drug suppression of the induction of ventricular tachycardia. Greater drug-induced increments in the ventricular effective and functional refractory periods were observed in responders than in nonresponders as was the shortest ventricular interelectrogram coupling interval. Thus, baseline electrophysiologic measurements identify patients with inducible ventricular tachycardia who are likely to respond to antiarrhythmic drug therapy. Furthermore, these patients demonstrate greater drug-induced electrophysiologic changes.
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- 1991
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11. Drug therapy for ventricular tachyarrhythmias: how many electropharmacologic trials are appropriate?
- Author
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Kavanagh KM, Wyse DG, Duff HJ, Gillis AM, Sheldon RS, and Mitchell LB
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- Actuarial Analysis, Electrophysiology, Female, Humans, Male, Middle Aged, Probability, Tachycardia diagnosis, Time Factors, Ventricular Fibrillation diagnosis, Anti-Arrhythmia Agents therapeutic use, Cardiac Pacing, Artificial, Tachycardia drug therapy, Ventricular Fibrillation drug therapy
- Abstract
To determine how many electropharmacologic drug trials should be performed to select therapy for patients with ventricular tachyarrhythmias, the outcome of 150 consecutive patients with inducible ventricular tachyarrhythmias undergoing serial electropharmacologic testing was examined. The probability of identifying predicted effective therapy (inductive of fewer than five ventricular responses with three ventricular extrastimuli at three pacing cycle lengths) and the probability of that therapy preventing sustained ventricular tachyarrhythmia recurrences were determined as a function of the number of preceding trials. The probability ( +/- SE) of identifying predicted effective therapy by the first trial (0.23 +/- 0.03) was significantly higher than that of the second (0.09 +/- 0.04), third (0.08 +/- 0.04) and fourth (0.05 +/- 0.04) trials (p = 0.001). No patient had predicted effective therapy identified by subsequent trials. The 2 year actuarial probability of freedom from sustained ventricular tachyarrhythmias on predicted effective therapy was higher for the first (0.79 +/- 0.08), second (0.73 +/- 0.13) and third (0.86 +/- 0.13) trials than for the fourth (0.33 +/- 0.27) trial (p = 0.02). Thus, the probability of selecting therapy with long-term efficacy was highest for the first trial (0.18), intermediate for the second (0.07) and third (0.07) trials and lowest for the fourth (0.02) and subsequent (0.00) trials. Accordingly, the electropharmacologic approach to therapy selection should be abandoned after three unsuccessful trials.
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- 1991
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12. Arrhythmogenic right ventricular dysplasia: a generalized cardiomyopathy?
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Manyari DE, Klein GJ, Gulamhusein S, Boughner D, Guiraudon GM, Wyse G, Mitchell LB, and Kostuk WJ
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- Adult, Cardiomyopathies complications, Cardiomyopathies pathology, Echocardiography, Electrocardiography, Exercise Test, Female, Heart Ventricles pathology, Heart Ventricles physiopathology, Humans, Male, Middle Aged, Stroke Volume, Technetium, Wolff-Parkinson-White Syndrome physiopathology, Cardiomyopathies physiopathology, Tachycardia etiology
- Published
- 1983
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13. Mexiletine-quinidine combination: electrophysiologic correlates of a favorable antiarrhythmic interaction in humans.
- Author
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Duff HJ, Mitchell LB, Manyari D, and Wyse DG
- Subjects
- Adult, Aged, Drug Synergism, Drug Therapy, Combination, Electrocardiography, Female, Follow-Up Studies, Heart Ventricles, Humans, Male, Middle Aged, Tachycardia physiopathology, Mexiletine therapeutic use, Quinidine therapeutic use, Tachycardia drug therapy
- Abstract
Combination therapy with mexiletine and quinidine has been shown to be more effective than either agent alone. The ability of mexiletine monotherapy, quinidine monotherapy and mexiletine-quinidine combination therapy to suppress inducible sustained ventricular tachycardia was related to drug-induced changes in ventricular refractoriness, conduction times and monophasic action potential duration recorded from both ventricles. Ventricular tachycardia could no longer be induced in 7 (35%) of the 20 patients studied with combination therapy. This was a significantly higher proportion of patients than that of the groups responding to either monotherapy (quinidine, 10%; mexiletine, 5%). Ventricular effective and functional refractory periods were measured when applying single (S2), double (S3) and triple (S4) extrastimuli. Quinidine monotherapy increased functional and effective refractory periods of both single and multiple extrastimuli. However, when comparing measurements made during mexiletine treatment with those at baseline, mexiletine monotherapy increased only the refractory periods of S4. The effective refractory period of S4 during mexiletine monotherapy (200 +/- 20 ms) was significantly longer than at baseline (160 +/- 21 ms). Similarly, when comparing measurements made during combination therapy with those during quinidine monotherapy, combination therapy significantly increased the refractory periods only of multiple extrastimuli. The effective refractory period of S4 during combination therapy (253 +/- 26 ms) was significantly longer than that of quinidine monotherapy (223 +/- 27 ms).(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1987
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14. Programmed electrical stimulation studies for ventricular tachycardia induction in humans. I. The role of ventricular functional refractoriness in tachycardia induction.
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Mitchell LB, Wyse DG, and Duff HJ
- Subjects
- Adult, Aged, Electric Stimulation, Heart Ventricles, Humans, Middle Aged, Tachycardia etiology, Time Factors, Heart physiology, Neural Conduction, Refractory Period, Electrophysiological, Tachycardia physiopathology
- Abstract
Closely coupled extrastimuli are frequently necessary to induce ventricular tachycardia at electrophysiologic study. Although induction usually requires propagated extrastimuli, systematic evaluations of minimal coupling intervals have focused on nonpropagated measures (effective refractory periods) rather than on propagated measures (functional refractory periods). The effects of procedural factors on ventricular functional refractory periods were examined in 10 patients. Like the effective refractory period, the functional refractory period shortens with rapid pacing cycle lengths (281 +/- 12 ms at a cycle length of 600 ms; 260 +/- 15 ms at a cycle length of 400 ms) and with multiple extrastimuli (279 +/- 16 ms with one extrastimulus; 214 +/- 16 ms with two extrastimuli). The effects of multiple extrastimuli exceed those of shortening pacing cycle length. Unlike the effective refractory period, the functional refractory period is affected by recording site (increasing as the distance from the pacing site increases) but is not affected by increasing the stimulus intensity above twice diastolic threshold (282 +/- 14 ms at 2 times threshold; 282 +/- 13 ms at 16 times threshold) or by increasing the pulse width above 2 ms (282 +/- 13 ms at a pulse width of 2 ms; 282 +/- 14 ms at a pulse width of 5 ms). The effect of varying stimulus intensity on ventricular tachycardia induction was examined in a second group of 11 patients with documented, spontaneous ventricular tachycardia. No change in ventricular tachycardia inducibility accompanied changes in stimulus intensity from 2 to 10 times threshold.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1986
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15. Concentration-response relationships of disopyramide in patients with ventricular tachycardia.
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Duff HJ, Mitchell LB, Nath CF, Manyari DE, Baynton R, and Wyse DG
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- Disopyramide blood, Disopyramide therapeutic use, Dose-Response Relationship, Drug, Electric Stimulation, Electrocardiography, Female, Heart Ventricles drug effects, Heart Ventricles physiopathology, Humans, Infusions, Intravenous, Male, Stroke Volume drug effects, Tachycardia etiology, Disopyramide administration & dosage, Tachycardia drug therapy
- Abstract
The protein binding of disopyramide is altered when concentration is increased within the therapeutic range. A wide range of free concentrations may be produced at a given total concentration. The present study assessed whether intracardiac electrophysiologic responses to disopyramide related better to free or to total concentration. Intravenous infusions of disopyramide were evaluated in 17 patients with inducible sustained ventricular tachycardia. The first maintenance infusion produced total serum concentrations of 11.7 +/- 2 mumols/L, and no significant increase occurred at higher-dose infusions. However, free concentrations during the first and second maintenance infusions were significantly different at 5.3 +/- 1 mumols/L and 6.8 +/- 1 mumols/L, respectively. Free fraction also increased significantly, from 45% +/- 8% to 50% +/- 7%. Overall change in QTc interval and ventricular tachycardia cycle length correlated with free concentration but not with total concentration. This study showed that some intracardiac measurements correlate with free concentration but that none correlate with total concentration.
- Published
- 1989
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16. Amiloride. Antiarrhythmic and electrophysiologic actions in patients with inducible sustained ventricular tachycardia.
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Duff HJ, Mitchell LB, Kavanagh KM, Manyari DE, Gillis AM, and Wyse DG
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- Adult, Aged, Amiloride pharmacology, Electrophysiology, Female, Heart Conduction System physiopathology, Humans, Male, Middle Aged, Stroke Volume, Tachycardia diagnosis, Amiloride therapeutic use, Anti-Arrhythmia Agents, Cardiac Pacing, Artificial, Heart Conduction System drug effects, Tachycardia drug therapy
- Abstract
This study assessed the antiarrhythmic activity of amiloride in 35 patients with inducible sustained ventricular tachycardia. Patients had failed to respond to 3.6 +/- 1.0 antiarrhythmic drugs. Ventricular tachycardia was reproducibly induced by programmed electrical stimulation in all patients at the baseline study. Amiloride was given at 10 and 20 mg/day p.o. on a twice-daily schedule that achieved serum concentrations of 21 +/- 17 and 36 +/- 18 ng/ml, respectively. The mean left ventricular ejection fraction was unchanged from 36 +/- 14% at baseline to 37 +/- 17% during amiloride treatment. Amiloride significantly increased serum potassium from 4.6 +/- 0.4 to 5.1 +/- 0.4 mM. Four patients failed amiloride therapy with spontaneous nonsustained ventricular tachycardia. The remaining 31 patients were assessed by repeat programmed stimulation. Six patients had complete antiarrhythmic response, and an additional six patients had less than 15 beats of ventricular tachycardia induced. Therefore, amiloride was an efficacious antiarrhythmic treatment in 12 of 35 (34%) patients. Amiloride concentrations were significantly higher (52 +/- 20 ng/ml) in patients that responded than in patients that did not respond (30 +/- 15 ng/ml). The only electrophysiologic measurement that changed significantly was the ventricular functional refractory period (from 269 +/- 24 to 283 +/- 25 msec, p less than 0.05). Amiloride also suppressed frequent, spontaneous ventricular premature beats in eight of 15 patients (53%). No somatic side effects occurred. Two of the five patients discharged on amiloride therapy developed asymptomatic nonsustained ventricular tachycardia, and this prompted a change in antiarrhythmic therapy. Both died suddenly of arrhythmia during substitute empiric antiarrhythmic drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1989
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17. A randomized clinical trial of the noninvasive and invasive approaches to drug therapy of ventricular tachycardia.
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Mitchell LB, Duff HJ, Manyari DE, and Wyse DG
- Subjects
- Anti-Arrhythmia Agents therapeutic use, Clinical Trials as Topic, Electrocardiography, Exercise Test, Female, Follow-Up Studies, Humans, Male, Middle Aged, Monitoring, Physiologic, Random Allocation, Recurrence, Tachycardia physiopathology, Tachycardia prevention & control, Ventricular Fibrillation drug therapy, Tachycardia drug therapy
- Abstract
There is controversy over whether therapy to prevent ventricular tachyarrhythmias should be selected noninvasively (by trying drugs and monitoring the patient electrocardiographically) or invasively (by selecting a drug that prevents induction of the arrhythmia by programmed stimulation). We randomly assigned 57 patients with symptomatic and demonstrable ventricular tachyarrhythmias to therapy selected either noninvasively or invasively. The tachyarrhythmias involved were sustained ventricular tachycardia (35 patients), nonsustained ventricular tachycardia with hypotension (15 patients), and ventricular fibrillation (7 patients). The noninvasive approach sought reduction of ventricular premature beats by more than 80 percent and of couplets by more than 90 percent, with elimination of three or more successive ventricular beats on ambulatory monitoring and exercise testing. The invasive approach sought to prevent the induction of five or more repetitive beats by programmed stimulation. The noninvasive approach required fewer drug trials (3.2 +/- 1.8 [mean +/- SD] vs. 5.5 +/- 2.8, P less than 0.001) and fewer hospital days (20 +/- 15 vs. 33 +/- 24, P = 0.01) and identified a therapy predicted to be effective for more patients than did the invasive approach (29 of 29 vs. 15 of 28, P less than 0.001). When a predicted effective therapy was not found, amiodarone was prescribed despite persisting inducibility of ventricular tachycardia. Patients randomly assigned to the noninvasive approach had more symptomatic recurrences of tachyarrhythmia than those treated by the invasive approach (two-year actuarial probabilities of 0.50 +/- 0.10 vs. 0.20 +/- 0.08, P = 0.02). Similar differences were observed when amiodarone recipients were excluded. There were only three deaths from recurrent ventricular tachyarrhythmias--two in the group whose treatment was selected noninvasively and one in the group whose treatment was selected invasively (not significant). We conclude that therapy selected by the invasive approach prevents recurrences of ventricular tachyarrhythmias better than that selected by the noninvasive approach.
- Published
- 1987
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18. Antiarrhythmic efficacy of propranolol: comparison of low and high serum concentrations.
- Author
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Duff HJ, Mitchell LB, and Wyse DG
- Subjects
- Adult, Aged, Electrophysiology, Female, Heart Rate drug effects, Humans, Male, Middle Aged, Propranolol blood, Receptors, Adrenergic, beta drug effects, Tachycardia physiopathology, Cardiac Pacing, Artificial, Propranolol therapeutic use, Tachycardia drug therapy
- Abstract
Propranolol has been effective in suppressing ventricular arrhythmias in up to 70% of patients in some series; however, a wide range of concentrations was required to produce this degree of efficacy. In one series, 40% of responders required high serum concentrations (greater than 500 ng/ml) in excess of those required for physiologic beta-receptor blockade (25 to 150 ng/ml). To assess the relative contribution of high concentration electrophysiologic effects to antiarrhythmic efficacy the results of programmed electrical stimulation were compared at high and low (beta-blocking) concentrations in 28 patients with inducible sustained ventricular tachycardia. Propranolol was given as a series of loading and maintenance infusions producing first a mean concentration of 130 +/- 72 ng/ml (beta-blocking) and then a mean concentration of 743 +/- 523 ng/ml (high). Beta-blockade was assessed by the percent reduction in exercise-induced tachycardia. Near maximal beta-blockade was achieved by a concentration of 150 ng/ml. At a low concentration, 6 of 28 patients had a response to propranolol (complete in 5 and partial in 1). At a high concentration, one additional patient had a complete response while three had a partial antiarrhythmic response. At high concentrations of propranolol there was a significant shortening of the QTc interval relative to that seen during the low dose infusion. No other significant electrophysiologic changes occurred at high versus low concentration. In summary, an antiarrhythmic response to propranolol occurs most frequently at a beta-blocking concentration. High concentration electrophysiologic effects occur and these appear to contribute to antiarrhythmic efficacy in some patients.
- Published
- 1986
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19. Procainamide, disopyramide and quinidine: discordant antiarrhythmic effects during crossover comparison in patients with inducible ventricular tachycardia.
- Author
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Wyse DG, Mitchell LB, and Duff HJ
- Subjects
- Adult, Aged, Disopyramide blood, Dose-Response Relationship, Drug, Electrocardiography, Female, Humans, Male, Middle Aged, Procainamide blood, Quinidine blood, Ventricular Fibrillation drug therapy, Disopyramide therapeutic use, Procainamide therapeutic use, Quinidine therapeutic use, Tachycardia drug therapy
- Abstract
A crossover comparison of intravenous procainamide, disopyramide and quinidine was made in 32 patients. All three drugs had dosage-related effects on electrocardiographic intervals, refractory periods and cycle length of ventricular tachycardia. Significant linear relations between serum drug levels and changes in refractory periods and ventricular tachycardia cycle length were also observed. Ventricular tachycardia was no longer inducible on at least one drug in 11 patients but concordance of this effect on both of the others was 36% and on either of the others it was 45%. Ventricular tachycardia remained inducible on at least one drug in 28 patients and concordance of this effect on both of the others was 75% and on either of the others was 79%. Continued inducibility on quinidine, the drug producing the greatest electrophysiologic effects, was the best individual predictor of continued inducibility on the others. Subdivision of continued inducibility into easier to induce, inducibility unchanged, or harder to induce dramatically decreased concordance of this effect. Thus the antiarrhythmic effects of these drugs are discordant in individual patients despite electrophysiologic similarities. Nevertheless, continued inducibility after high dosages of any one of these drugs is clinically useful for screening for continued inducibility on the others and this is dose-related rather than drug specific.
- Published
- 1987
- Full Text
- View/download PDF
20. Efficacy of verapamil in chronic, recurrent ventricular tachycardia.
- Author
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Mason JW, Swerdlow CD, and Mitchell LB
- Subjects
- Adult, Age Factors, Chronic Disease, Drug Evaluation, Electrocardiography, Female, Heart Ventricles, Humans, Male, Middle Aged, Tachycardia physiopathology, Tachycardia drug therapy, Verapamil administration & dosage
- Abstract
Verapamil, 0.25 mg/kg, was given to 24 patients with chronic, recurrent ventricular tachycardia (VT) whose clinical tachyarrhythmias were reproduced at electrophysiologic study. Seven patients (29%) responded acutely to verapamil: VT was not inducible in 5 and spontaneously terminated within 5 seconds of induction in 2 patients in whom it was previously sustained. Four of the 7 responders had no identifiable structural heart disease, and 3 had coronary artery disease. Responders were younger and had better left ventricular function than did nonresponders. Long-term therapy with verapamil, attempted in 5 of the 7 responders, was effective in 3, ineffective in 1, and of uncertain efficacy in 1. Verapamil therapy was discontinued because of worsened congestive heart failure in 2 patients. The short-term efficacy of verapamil in these patients compares favorably with the efficacy of other antiarrhythmic agents against VT induction in patients with long-term, recurrent, drug-refractory VT. The short-term efficacy of verapamil correlated with its long-term efficacy. These observations provide preliminary evidence that verapamil may be useful in the treatment of some patients with recurrent VT. When standard drugs are not effective, verapamil should be given a trial, especially in young patients with good left ventricular function.
- Published
- 1983
- Full Text
- View/download PDF
21. Programmed electrical stimulation studies for ventricular tachycardia induction in humans. II. Comparison of indwelling electrode catheter and daily catheter replacement.
- Author
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Duff HJ, Mitchell LB, and Wyse DG
- Subjects
- Adult, Aged, Anti-Arrhythmia Agents therapeutic use, Electric Stimulation methods, Electrodes, Female, Humans, Male, Middle Aged, Tachycardia drug therapy, Tachycardia etiology, Time Factors, Cardiac Catheterization, Catheters, Indwelling adverse effects, Tachycardia physiopathology
- Abstract
Suppression of the ability to induce ventricular tachycardia by programmed electrical stimulation during serial drug testing has been used as a therapeutic end point to identify long-term prophylactic antiarrhythmic therapy. However, ventricular tachycardia induction, particularly with an indwelling electrode catheter, has not been systematically assessed over the time period required for serial drug testing. In this study, the results of programmed electrical stimulation were evaluated daily during serial drug-free conditions before testing various antiarrhythmic drugs. Twenty-four patients were randomly allocated to be studied with the electrode catheter left in place or replaced daily. All patients had inducible sustained ventricular tachycardia during the first study. Loss of the ability to induce ventricular tachycardia occurred in 8 of 13 patients whose catheter was left in place whereas this did not occur in patients whose catheter was replaced daily (p less than 0.01). In addition, use of an in situ catheter was accompanied by significant (p less than 0.05) changes in other electrophysiologic measurements, including number of extrastimuli required to induce ventricular tachycardia and length of ventricular functional and effective refractory periods. The serial changes seen with indwelling catheters in the drug-free state may mimic effective antiarrhythmic drug action.
- Published
- 1986
- Full Text
- View/download PDF
22. Comparison of the electrophysiologic effects of intravenous and oral lorcainide in patients with recurrent ventricular tachycardia.
- Author
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Echt DS, Mitchell LB, Kates RE, and Winkle RA
- Subjects
- Administration, Oral, Aged, Anti-Arrhythmia Agents blood, Electrocardiography, Heart Ventricles, Humans, Infusions, Parenteral, Injections, Intravenous, Middle Aged, Piperidines blood, Recurrence, Anti-Arrhythmia Agents administration & dosage, Benzeneacetamides, Piperidines administration & dosage, Tachycardia drug therapy
- Abstract
The electrophysiologic effects of intravenous lorcainide (2.2 mg/kg) in 10 patients were compared with the electrophysiologic effects of oral lorcainide (mean dose 400 mg/day for 8 days) in 11 patients, all with recurrent ventricular tachycardia that could be induced with programmed stimulation. Intravenous and oral lorcainide resulted in similar prolongation of the QRS, QT, and HV intervals, but only oral lorcainide resulted in prolongation of the AH interval and atrial and ventricular effective refractory periods. After both oral and intravenous lorcainide, ventricular tachycardia could still be induced, but the arrhythmia was slower and better tolerated hemodynamically. The mean plasma lorcainide level during a maintenance intravenous infusion was 1254 +/- 662 ng/ml compared with a lorcainide level of 562 +/- 41 ng/ml and a norlorcainide level of 1212 +/- 653 ng/ml after oral dosing. No norlorcainide was detected in plasma after intravenous lorcainide. These data suggest that the short-term electrophysiologic effects of intravenous lorcainide may be different from those of short-term therapy with the oral drug. These differences should be considered during short-term studies of lorcainide.
- Published
- 1983
- Full Text
- View/download PDF
23. Clinical efficacy and electrophysiology of imipramine for ventricular tachycardia.
- Author
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Connolly SJ, Mitchell LB, Swerdlow CD, Mason JW, and Winkle RA
- Subjects
- Adult, Aged, Cardiac Pacing, Artificial, Desipramine blood, Electrocardiography, Electrophysiology, Female, Follow-Up Studies, Heart Conduction System drug effects, Heart Ventricles, Humans, Imipramine adverse effects, Imipramine blood, Male, Middle Aged, Imipramine therapeutic use, Tachycardia drug therapy
- Abstract
Invasive electrophysiologic studies were performed before and during treatment with imipramine in 18 patients with inducible ventricular tachycardia (VT). All received imipramine, 50 mg twice daily for 3 days, and then 100 mg twice daily for 3 days. Imipramine increased the infranodal conduction times (HV) (from 58 +/- 7.8 to 65 +/- 10 ms) and QRS duration (from 133 +/- 21 to 153 +/- 39 ms) and significantly decreased sinus cycle length (from 875 +/- 145 to 711 +/- 116 ms) and maximal corrected sinus nodal recovery time (from 457 +/- 656 to 380 +/- 603 ms). The Wenckebach cycle length tended to decrease and the QT interval to increase, but these changes were not statistically significant. Atrial and ventricular refractory periods, atrioventricular nodal conduction times and induced VT cycle length did not change significantly. Imipramine prevented induction of VT in 2 patients, and VT was more difficult to induce in 1 patient. These 3 patients received chronic imipramine therapy. The 2 patients in whom no VT could be induced while taking imipramine have had no recurrence of arrhythmia at 6 and 12 months of follow-up. The third patient died suddenly 4 months after discharge from the hospital. One patient had worsening of arrhythmias while taking imipramine and 61% had minor adverse effects. The mean combined plasma imipramine and desmethylimipramine concentration at the time of the repeat electrophysiologic study was 227 +/- 114 ng/ml. Imipramine is effective against VT in some patients; however, like other type I antiarrhythmic drugs, the rate of efficacy is low.
- Published
- 1984
- Full Text
- View/download PDF
24. Right and left ventricular function during chronic amiodarone therapy.
- Author
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Sheldon RS, Mitchell LB, Duff HJ, Wyse DG, and Manyari DE
- Subjects
- Aged, Amiodarone analogs & derivatives, Amiodarone blood, Electrocardiography, Electrophysiology, Exercise Test, Female, Humans, Male, Middle Aged, Prospective Studies, Tachycardia blood, Tachycardia drug therapy, Amiodarone therapeutic use, Myocardial Contraction drug effects, Stroke Volume drug effects, Tachycardia physiopathology
- Abstract
Although chronic therapy with amiodarone is an effective means of suppressing ventricular tachycardia, its long-term effects on ventricular function have not been evaluated. Therefore, left ventricular (LV) and right ventricular (RV) ejection fraction (EF) as well as wall motion score were assessed in 21 patients with ventricular tachycardia before therapy and after 2, 6, 10 and 20 weeks of amiodarone therapy. Serum amiodarone levels after 2, 6, 10 and 20 weeks were 1.9 +/- 0.7, 1.7 +/- 0.6, 1.5 +/- 0.6 and 1.5 +/- 0.7 micrograms/ml, respectively. Drug therapy did not significantly affect the mean LVEF (0 weeks 38 +/- 17, 2 weeks 40 +/- 17, 6 weeks 40 +/- 17, 10 weeks 41 +/- 18 and 20 weeks 40 +/- 18%) or the mean RVEF. Neither LV wall motion score nor RV wall motion score were changed significantly during amiodarone therapy. Fourteen patients had a drug-free LVEF less than 40% (mean 28 +/- 7%). Ventricular function in this subgroup was not impaired after 20 weeks of amiodarone therapy (drug-free LVEF 28 +/- 7%, 20 weeks LVEF 29 +/- 9%; drug-free RVEF 42 +/- 13%, 20 weeks RVEF 41 +/- 12%). Ten patients who were evaluated 34 +/- 6 months after initiation of amiodarone therapy had no significant change in LVEF (drug-free 37 +/- 20%, 34 months 43 +/- 20%). Ventricular functional reserve was assessed after 20 weeks of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1988
- Full Text
- View/download PDF
25. Effect of oral combination therapy with mexiletine and quinidine on left and right ventricular function.
- Author
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Sheldon RS, Duff HJ, Mitchell LB, Wyse DG, and Manyari DE
- Subjects
- Cardiac Pacing, Artificial, Clinical Trials as Topic, Drug Therapy, Combination, Electrophysiology, Exercise Test, Female, Humans, Male, Mexiletine administration & dosage, Middle Aged, Quinidine administration & dosage, Mexiletine therapeutic use, Myocardial Contraction drug effects, Quinidine therapeutic use, Stroke Volume drug effects, Tachycardia drug therapy
- Abstract
Combination therapy with mexiletine (MEX) and quinidine (Q) may be more efficacious than monotherapy with either drug in suppressing ventricular arrhythmias, but its effects on ventricular performance are not known. Thus, right ventricular ejection fraction (RVEF) and left ventricular ejection fraction (LVEF) and wall motion score (WMS) were assessed in 14 patients with ventricular tachycardia before antiarrhythmic therapy, during MEX and Q monotherapies, and during combination therapy. During monotherapy, the daily doses and serum drug levels were: MEX, 621 mg/day and 3.4 microM/L; Q, 1573 mg/day and 8.3 microM/L, respectively. With combination therapy, the daily doses and serum drug levels were: MEX, 636 mg/day and 3.3 microM/L; Q, 1643 mg/day and 9.5 microM/L, respectively. Drug therapy did not affect group LVEF (drug free = 36 +/- 19%, MEX = 34 +/- 18%, Q = 36 +/- 19%, and combination MEX-Q = 35 +/- 19%), RVEF (drug free = 34 +/- 11%, MEX = 35 +/- 11%, Q = 36 +/- 13%, and combination MEX-Q = 36 +/- 12%), or WMS. Ventricular function reserve was assessed in five patients. Drug therapy did not affect group exercise LVEF (drug free = 44 +/- 14%, MEX = 42 +/- 12%, Q = 43 +/- 13%, and MEX-Q = 45 +/- 12%), RVEF (drug free = 38 +/- 10%, MEX = 40 +/- 11%, Q = 39 +/- 12%, and MEX-Q = 40 +/- 12%), WMS, or exercise duration. Combination MEX-Q therapy did not have a significant effect on exercise performance or ventricular function in seven additional patients in whom no exercise studies were done during monotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1988
- Full Text
- View/download PDF
26. Long-term Reproducibility of Ventricular Tachycardia Induction in Patients With Implantable Cardioverter/Defibrillators
- Author
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George J. Klein, Raymond Yee, Robert S. Sheldon, A M Gillis, Mitchell Lb, Wyse Dg, James W. Leitch, and Duff Hj
- Subjects
Male ,Tachycardia ,medicine.medical_specialty ,Time Factors ,Heart disease ,Defibrillation ,medicine.medical_treatment ,Ventricular tachycardia ,Physiology (medical) ,Internal medicine ,medicine ,Hospital discharge ,Humans ,In patient ,Aged ,Reproducibility ,business.industry ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Defibrillators, Implantable ,Electrophysiology ,Heart Function Tests ,Ventricular fibrillation ,Tachycardia, Ventricular ,Cardiology ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Noninvasive electrophysiological studies (EPSs) can be performed in current implantable antitachycardia pacemaker/cardioverter/defibrillators (ICDs). Thus, these devices may be used as tools to study changes in the electrophysiological substrate and ventricular tachycardia characteristics over time. Methods and Results Fifty-five patients receiving an ICD for treatment of sustained ventricular tachyarrhythmias underwent serial EPSs after implantation of the ICD. Studies were performed before hospital discharge and 1, 3, 5, 9, 12, 18, 24, and 36 months after ICD implantation. Sustained monomorphic ventricular tachycardia (VT) was induced in 37 patients (group 1) at the predischarge EPS, whereas no sustained arrhythmia could be induced in 18 patients (group 2) at baseline. Group 1 patients underwent 165 noninvasive EPSs after discharge. Sustained monomorphic VT was induced during 72% of the follow-up EPSs, ventricular fibrillation (VF) was induced during 11% of follow-up EPSs, and no sustained VT or VF was induced during 17% of follow-up visits. Sustained VT was induced at every follow-up EPS in 23 patients (62%), whereas no sustained VT/VF could be induced at least once during follow-up in 14 patients (38%). Clinical or electrophysiological variables did not predict noninducibility during follow-up. However, the probability that a patient would experience spontaneous VT decreased significantly over time in patients in whom VT was not inducible during at least 1 follow-up EPS ( P =.05). Group 2 patients underwent 86 noninvasive EPSs after discharge. Sustained monomorphic VT was induced during 22% of follow-up EPSs, VF was induced during 19% of follow-up EPSs, and no sustained VT/VF could be induced during 68% of follow-up EPSs. No sustained VT/VF could be induced during every follow-up EPS in 9 patients (50%), whereas sustained monomorphic VT was induced at least once during follow-up in 7 patients (34%). Persistent noninducibility of VT during follow-up was associated with low probability of occurrence of spontaneous VT (11%), whereas inducibility of VT at least once during follow-up was associated with the occurrence of spontaneous VT (89%, P =.003). Conclusions Considerable variability of VT induction is observed over a lengthy period in patients presenting with sustained VT/VF. Persistent noninducibility of VT is associated with a reduced probability of spontaneous VT. These observations suggest that the substrates for inducible and spontaneous VT change in parallel over time.
- Published
- 1995
27. A Randomized Clinical Trial of the Noninvasive and Invasive Approaches to Drug Therapy of Ventricular Tachycardia
- Author
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Henry J. Duff, Wyse Dg, Dante E. Manyari, and Mitchell Lb
- Subjects
Male ,Programmed stimulation ,medicine.medical_specialty ,medicine.medical_treatment ,Ventricular tachycardia ,law.invention ,Electrocardiography ,Random Allocation ,Pharmacotherapy ,Randomized controlled trial ,Recurrence ,law ,Tachycardia ,Internal medicine ,Humans ,Medicine ,cardiovascular diseases ,Monitoring, Physiologic ,Clinical Trials as Topic ,Chemotherapy ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Signal-averaged electrocardiogram ,Anesthesia ,Ventricular Fibrillation ,Ventricular fibrillation ,Ambulatory ,Exercise Test ,cardiovascular system ,Cardiology ,Female ,business ,Anti-Arrhythmia Agents ,Follow-Up Studies - Abstract
There is controversy over whether therapy to prevent ventricular tachyarrhythmias should be selected noninvasively (by trying drugs and monitoring the patient electrocardiographically) or invasively (by selecting a drug that prevents induction of the arrhythmia by programmed stimulation). We randomly assigned 57 patients with symptomatic and demonstrable ventricular tachyarrhythmias to therapy selected either noninvasively or invasively. The tachyarrhythmias involved were sustained ventricular tachycardia (35 patients), nonsustained ventricular tachycardia with hypotension (15 patients), and ventricular fibrillation (7 patients). The noninvasive approach sought reduction of ventricular premature beats by more than 80 percent and of couplets by more than 90 percent, with elimination of three or more successive ventricular beats on ambulatory monitoring and exercise testing. The invasive approach sought to prevent the induction of five or more repetitive beats by programmed stimulation. The noninvasive approach required fewer drug trials (3.2 +/- 1.8 [mean +/- SD] vs. 5.5 +/- 2.8, P less than 0.001) and fewer hospital days (20 +/- 15 vs. 33 +/- 24, P = 0.01) and identified a therapy predicted to be effective for more patients than did the invasive approach (29 of 29 vs. 15 of 28, P less than 0.001). When a predicted effective therapy was not found, amiodarone was prescribed despite persisting inducibility of ventricular tachycardia. Patients randomly assigned to the noninvasive approach had more symptomatic recurrences of tachyarrhythmia than those treated by the invasive approach (two-year actuarial probabilities of 0.50 +/- 0.10 vs. 0.20 +/- 0.08, P = 0.02). Similar differences were observed when amiodarone recipients were excluded. There were only three deaths from recurrent ventricular tachyarrhythmias--two in the group whose treatment was selected noninvasively and one in the group whose treatment was selected invasively (not significant). We conclude that therapy selected by the invasive approach prevents recurrences of ventricular tachyarrhythmias better than that selected by the noninvasive approach.
- Published
- 1987
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