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Biomedical subjects

P Dorian

Publications and source records attributed to P Dorian.

At least 91 records · Page 5Linked to original sources
PubMed1994

Sotalol in patients with implanted automatic defibrillators: effects on defibrillation and comparison with amiodarone.

OBJECTIVES: Although many patients receiving implanted cardioverter defibrillators receive concomitant antiarrhythmic therapy, the risks and benefits of different agents for such patients are not well understood. It was hypothesized that sotalol, a drug with beta-blocking and class II antiarrhythmic properties would be useful in these patients. DESIGN: Nonrandomized prospective cohort study of the effects of sotalol versus other antiarrhythmic therapy on defibrillation energy requirements. SETTING: Tertiary care referral centre. PATIENTS: Patients referred for management of life threatening ventricular arrhythmia in whom an implanted cardioverter defibrillator was indicated on standard clinical grounds. INTERVENTIONS: Intraoperative testing of defibrillation energy requirements, exercise testing, electrophysiological testing. MAIN RESULTS: Fifteen patients were treated with oral sotalol (173.3 +/- 59.8 mg/day). Sotalol blunted maximal heart rate during treadmill exercise (120.9 +/- 29.9 beats/min). Mean right ventricular effective refractory period increased from 251.7 +/- 21.7 to 276.7 +/- 25.7 ms (P = 0.05). All patients received one large (28 cm2) and one small (14 cm2) epicardial electrode patch. The lowest energy to defibrillate successfully from induced ventricular fibrillation (VF) was 5.9 +/- 3.7 J (median 4.1 J), with all patients defibrillated at 15 J or less. In a concurrent comparison group of 16 similar patients not treated with sotalol (13 on amiodarone and three on beta-blockers), with identical or larger patch size, and identical placement, the lowest successful energy to defibrillate from induced VF was significantly higher (16 +/- 8.8 J) (P < 0.05). Mean cycle length of VF from intracardiac recordings was 232 +/- 37 ms, and was significantly inversely correlated with lowest successful energy (r = 0.61, P < 0.05). CONCLUSIONS: Oral sotalol may be useful in conjunction with an automatic defibrillator; it is associated with low defibrillation energy requirements in humans, and may alter VF.

Administration, Oral↗
PubMed1993

Canadian Implantable Defibrillator Study (CIDS): study design and organization. CIDS Co-Investigators.

The Canadian Implantable Defibrillator Study (CIDS) is an on-going randomized multicenter clinical trial that compares implantable cardioverter-defibrillator (ICD) therapy against amiodarone in patients with prior cardiac arrest or hemodynamically unstable ventricular tachycardia. Eligible patients are equally randomized to receive or not receive an ICD as initial management. Those not receiving an ICD receive amiodarone. All patients are seen in follow-up every 6 months. The primary outcome event cluster is arrhythmic death or any other death occurring within 30 days of therapy initiation. Secondary outcomes are all-cause mortality and nonfatal occurrences of ventricular tachycardia or fibrillation. The goal of the study is to recruit 400 patients over 4 years. All patients will be followed to the end of the year. This will result in an 80% chance of detecting a reduction in arrhythmic death of 58% by ICD if such a difference in truth exists. Recruitment began in October 1990 and 184 patients have been enrolled to date.

Amiodarone↗
PubMed1993

Effect of sotalol on ventricular fibrillation and defibrillation in humans.

Antiarrhythmic drugs are frequently administered to patients receiving implanted cardioverter defibrillators. Some of these drugs may decrease the efficacy of defibrillation shocks from the defibrillator. Sotalol, a drug with beta-blocking and class III antiarrhythmic properties, lowers defibrillation energy requirements in experimental animals and may do so in humans. Oral sotalol 171 +/- 58 mg was administered before and after device implantation in 25 patients receiving implanted defibrillators. During sotalol therapy, the lowest energy required for successful defibrillation was 5.9 +/- 3.4 J (range 2-15J). In a concurrent nonrandomized comparison group of 23 patients, including 18 treated with amiodarone, the lowest successful energy was 16 +/- 10 J (p < 0.01). In 5 sotalol patients, ventricular fibrillation (VF) could not be induced at all (1 patient) or more than 2 or 3 times (4 patients) despite repeated 60 Hz stimulation. The induced VF had a pronounced tendency to terminate spontaneously, with the termination occurring at up to 23 seconds after the offset of 60 Hz stimulation. The cycle length of the VF was 236 +/- 34 msec, significantly greater than in patients not given drug therapy (191 +/- 21 msec, p < 0.01). In 10 patients, but none of the controls, intracardiac electrograms during surface electrocardiographic VF were regular, monoform, and without low-amplitude diastolic activity. In addition, monophasic action potentials during apparent VF showed maintenance of distinct and normal morphology. The ventricular effective refractory period increased after sotalol (249.4 +/- 19 to 278.4 +/- 24 msec; p < 0.03) and the maximum heart rate response to exercise was limited to 120 +/- 28 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

The implantable defibrillator and antiarrhythmic drugs--competitive and complementary treatment for severe ventricular arrhythmia.

Most patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) are at high risk of recurrence. Implanted defibrillators (ICDs) are highly effective in sensing and converting VT or VF to a perfusing rhythm. "Conventional" antiarrhythmic agents, which primarily block cardiac sodium channels, are relatively ineffective in preventing arrhythmia recurrence; amiodarone and sotalol appear to be effective in reducing recurrence and mortality rates, although the extent of benefit is not well understood. Despite the apparent advantage of ICDs, they have short- and long-term complications, are costly, and their benefit in prolonging the quantity or quality of life remains unproven. Randomized clinical trials which compare the effect of ICDs with that of antiarrhythmic drugs on mortality, cost, and quality of life will be necessary to understand how patients with malignant arrhythmias ought to be treated. If an ICD is implanted, adjunctive therapies need to be considered to treat the underlying heart disease and to derive optimum benefit from the device. Drugs may have beneficial or adverse interactions with devices, and the full understanding of these interactions requires further study.

Amiodarone↗
PubMed1993

Randomized controlled comparison of antitachycardia pacing algorithms for termination of ventricular tachycardia.

OBJECTIVES: This study compared the efficacy and safety of two antitachycardia pacing algorithms in the treatment of ventricular tachycardia. BACKGROUND: There is agreement that antitachycardia pacing should be adapted to tachycardia rate and be delivered in a burst, but the ideal pacing pattern is not well understood. Effective antitachycardia pacing burst patterns include those with a between-burst decrement (SCAN) with or without an additional within-burst decrement (RAMP). METHODS: Prospective randomized crossover comparison of two antitachycardia pacing algorithms (RAMP vs. SCAN) on identical induced sustained ventricular tachycardias was performed. RESULTS: Sixty-five ventricular tachycardias (mean cycle length 364 +/- 74 ms) from 37 invasive studies performed in 29 patients were studied; 86% of patients had coronary artery disease and 72% were receiving antiarrhythmic therapy at the time of study. Of the 65 tachycardias, 40 were identical pairs and 25 were unpaired (including 8 with a > 30-ms difference in cycle length of induced ventricular tachycardia pairs). In the paired pacing trials, conversion to sinus rhythm occurred, respectively, in 85% of SCAN versus 90% of RAMP protocols (p = 0.63, power = 93%) and within 1.4 +/- 0.7 versus 1.7 +/- 1.1 attempts (p = 0.41). Discordance for pacing success was seen in three pairs. In unpaired trials, conversion to sinus rhythm occurred in 73% and 57%, respectively (p = 0.68, power = 88%). Tachycardia acceleration during pacing occurred in 7 (11%) of 65 attempts (5 SCAN, 2 RAMP). Acceleration in unpaired ventricular tachycardia trials was correlated with tachycardia cycle length. Failure to convert ventricular tachycardia was associated with a shorter tachycardia cycle length (p < 0.05). CONCLUSIONS: In the patients studied, adaptive antitachycardia pacing was safe and effective and, when successful, occurred within three attempts of an 8-beat adaptive burst algorithm. Changes in burst pattern did not affect pacing safety or efficacy. Antitachycardia pacing success was dependent on induced ventricular tachycardia cycle length.

Aged↗
PubMed1993

Sotalol and type IA drugs in combination prevent recurrence of sustained ventricular tachycardia.

OBJECTIVES: This study assessed the efficacy of the combination of sotalol and either quinidine or procainamide in preventing sustained ventricular tachycardia inducibility and recurrence and prospectively evaluated the ability of the drug combination to prevent ventricular tachycardia recurrence when the arrhythmia remained inducible but was modified. BACKGROUND: Individual antiarrhythmic drugs are often ineffective in preventing the induction and recurrence of sustained ventricular tachycardia. Beta-adrenergic blockade and prolongation of refractoriness may be important components of successful antiarrhythmic therapy in patients with ventricular tachycardia. We reasoned that the combination of sotalol, which has beta-adrenergic blocking properties and prolonged ventricular refractoriness, and quinidine or procainamide, two agents that slow conduction and prolong refractory periods, would be effective therapy in such patients. METHODS: We administered low dose sotalol (205 +/- 84 mg/day) plus quinidine sulfate (1,278 +/- 479 mg/day) or procainamide (2,393 +/- 1,423 mg/day) to 50 patients with spontaneous sustained ventricular tachycardia or fibrillation and inducible ventricular tachycardia. RESULTS: In 21 (46%) of 46 patients, ventricular tachycardia was rendered noninducible at electrophysiologic study (group I), and in 17 patients (37%), inducible tachycardia was modified according to prospectively identified criteria (group II), for a combined 83% response rate. Ventricular refractory periods increased from 252 +/- 24 to 316 +/- 28 ms and from 265 +/- 33 to 316 +/- 24 ms in groups I and II, respectively (p < 0.001), but from 234 +/- 19 to only 286 +/- 13 ms in the group of patients with unmodified ventricular tachycardia inducibility (n = 8, group III, p < 0.001). Cycle length of induced ventricular tachycardia slowed from 324 +/- 62 to 432 +/- 70 ms in group II patients (p < 0.001), whereas it slowed less in group III patients (279 +/- 73 to 314 +/- 63 ms, p = NS). Forty-two of the 50 patients (including all patients in groups I and II) were discharged on treatment with the drug combination. After 25 +/- 19 months of follow-up, the actuarial recurrence rate of ventricular tachycardia was 6%, 6% and 11% at 1, 2 and 3 years, respectively. Among patients in whom this drug combination was unsuccessful at electrophysiologic study (group III) and in those who received alternative therapy after combination therapy was discontinued because of side effects, actuarial recurrence rates were 9%, 14% and 32% at 1, 2 and 3 years, respectively. CONCLUSIONS: The combination of sotalol plus quinidine or procainamide markedly prolongs ventricular refractoriness and slows induced ventricular tachycardia in a high proportion of patients. Patients with modified or noninducible tachycardia have a low rate of arrhythmia recurrence in follow-up. This drug combination deserves further evaluation.

Aged↗
PubMed1993

Cellular mechanism underlying the efficacy of the sotalol-quinidine combination.

The combination of quinidine and sotalol is very effective in prevention of recurrent sustained ventricular tachycardia (SVT). The cellular mechanisms underlying this efficacy were examined in guinea pig papillary muscle, using standard microelectrode techniques and stimulation frequencies of 1, 2, and 3 Hz. Action potential duration (APD) and effective refractory period (ERP) were measured under control conditions, after 30-min perfusion with quinidine (5 microM) or sotalol (6 microM), and after an additional 30 min of quinidine + sotalol (5 and 6 microM, respectively). Quinidine, sotalol, and quinidine + sotalol all prolonged APD at 90% repolarization (APD90) by 9 +/- 1, 13 +/- 1, and 15 +/- 2%, respectively (at 3 Hz; p = NS, comparison of the three drugs; p < 0.05 for each drug as compared with control). Quinidine + sotalol prolonged ERP (at 3 Hz) by 27 +/- 2% as compared with 11 +/- 2% after sotalol and 18 +/- 2% after quinidine alone (p < 0.05). As a result, the ERP/APD ratio was increased by the combination to 0.87 +/- 0.2 (p < 0.05) as compared with 0.78 +/- 0.2 for control 0.79 +/- 0.1 for sotalol, and 82 +/- 0.1 for quinidine (at 3 Hz). Although sotalol alone decreased the maximum rate of depolarization of phase 0 of the AP (Vmax) by only 3 +/- 2% (p = NS), sotalol attenuated Vmax decrease of quinidine (at 3 Hz) from 40 +/- 4 to 16 +/- 3% (p < 0.05). Effects at 1 and 2 Hz were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1993

Psychiatric assessment of patients with life-threatening cardiac arrhythmias.

OBJECTIVE: This article describes the development of a protocol specifically designed for the psychiatric assessment of patients with life-threatening ventricular arrhythmias. METHOD: Psychiatric assessment occurs in the context of a team approach in which the cardiologist has a pivotal role. Initial findings and one-year follow-up data on the first twenty-five patients evaluated psychiatrically are presented. RESULTS: Findings tend to confirm that psychiatric complaints are common on initial assessment and suggest that patients with life-threatening ventricular arrhythmias who do not use the psychological mechanism of denial and volunteer psychological complaints may constitute a subgroup of patients who would be more amenable to psychiatric intervention compared to those denying psychological complaints at initial psychiatric interview. CONCLUSION: Psychiatrists and associated professionals should become more involved with patients with life-threatening cardiac arrhythmias.

Adaptation, Psychological↗
PubMed1992

Pathophysiology and prognostic significance of Holter-detected ST segment depression after myocardial infarction. The Tissue Plasminogen Activator: Toronto (TPAT) Study Group.

OBJECTIVES: We performed Holter monitoring on days 4 and 7 after acute myocardial infarction in 109 patients to assess whether ST segment shift would identify those with more severe coronary artery disease, left ventricular dysfunction and unfavorable prognosis. BACKGROUND: Silent myocardial ischemia is a frequent and prognostically significant event after acute myocardial infarction. However, the specific pathophysiologic mechanisms and the impact of thrombolytic therapy are uncertain. METHODS: In addition to Holter monitoring, patients underwent exercise testing, radionuclide angiography on days 1 and 9 and quantitative coronary angiography on day 9. RESULTS: Thirty-five patients (32%) had ST segment depression and had similar recombinant tissue-type plasminogen activator (rt-PA) treatment assignment and a reduced cross-sectional area of the infarct-related artery (0.59 +/- 0.57 vs. 1.04 +/- 1.26 mm2, p < 0.05). Global left ventricular function improved from day 1 to day 9 in patients without (4% +/- 11%, p < 0.001) but not in those with (0% +/- 7%) ST segment depression. In-hospital event rates were similar; however, follow-up 18 +/- 11 months after hospital discharge revealed a greater frequency of death and recurrent myocardial infarction in patients with compared with those without ST segment depression (27% vs. 6%, p = 0.03). CONCLUSIONS: After acute myocardial infarction, approximately one third of patients have ST segment depression on Holter monitoring, independent of the use of thrombolytic therapy. The unfavorable prognosis observed in these patients may be related to greater lumen obstruction in the infarct-related artery and lack of improvement in left ventricular function.

Cardiac Catheterization↗
PubMed1992

Use of telemetry functions in the assessment of implanted antitachycardia device efficacy.

Twenty patients (aged 50 +/- 21 years and mean left ventricular ejection fraction 37 +/- 17%) with recurrent ventricular arrhythmias were treated with an investigational, implantable combined antitachycardia-pacing cardioverter defibrillator. The device's telemetry capabilities include both stored (1-second snapshots) and real-time display of endocardial and device-circuit signals. The device can store these before, during and after up to 50 tachycardia and antitachycardia pacing episodes. All stored events are indexed to a 24-hour internal clock. During 10.1 +/- 5.1 months of follow-up, the device was used in 11 of 20 patients. In the entire group, antitachycardia pacing was activated on 44 +/- 14 occasions per patient (total 874) and shock delivery occurred on 8 +/- 14 occasions per patient (total 156). Reconstruction by stored telemetry of all device-therapy episodes was possible. Twenty-six percent of all shocks delivered were not appropriate and were due to atrial arrhythmias in 2 patients and dysfunction of the sensing lead in 3. The absence of a relation between symptoms and appropriate shock delivery was documented in 1 patient. Antitachycardia pace acceleration occurred in 5.3% of cases; 7% of attempts at pacing were unsuccessful and needed shock therapy. It is concluded that the enhanced telemetry available in newer antitachycardia devices enables more accurate assessment of device use and enhances diagnosis of inappropriate therapy delivery.

Electric Countershock↗
PubMed1992

The effects of cardiac transplantation and cyclosporine therapy on digoxin pharmacokinetics.

Most patients needing cardiac transplantation are treated with digoxin for heart failure. Because of its narrow therapeutic range, even recommended doses of digoxin may cause severe toxicity. Several drugs, including quinidine, amiodarone, verapamil, and propafenone can interact with digoxin, leading to toxic accumulation of the glycoside. The authors have recently reported two cases of severe digitalis toxicity after the initiation of cyclosporine treatment in patients awaiting cardiac transplantation. A preliminary study on two additional patients suggested that cyclosporine reduced the plasma clearance and volume of distribution of digoxin. To assess the mechanism of this interaction, the authors studied digoxin pharmacokinetics in patients awaiting cardiac transplantation and again after the surgery, during chronic cyclosporine therapy. To separate the effects of transplantation and cyclosporine on digoxin pharmacokinetics, pharmacokinetic studies were subsequently performed in dogs to allow controlled experimental conditions for evaluation of the digoxin-cyclosporine interaction.

Administration, Oral↗
PubMed1992

Isoproterenol increases defibrillation energy requirements in dogs.

The effect of intravenous isoproterenol on the energy requirements for successful defibrillation (DF) was examined in anesthetized dogs following cholinergic blockade with atropine (n = 5) and following treatment with d- and d,l-sotalol (n = 16). Defibrillation shocks were administered through left and right ventricular epicardial patch electrodes and the energy requirements for DF were studied using two different methods. Multiple shocks of varying energies were delivered and the energies required for 50% success (E50) and 80% success (E80) in DF were estimated using logistic regression. Atropine (0.04 mg/kg) increased E50 by 32 +/- 30% (p = 0.046) and E80 by 39 +/- 38% (p = ns). Subsequent administration of isoproterenol (10 micrograms/ml), increasing the heart rate by 52 +/- 35% (p = 0.025), resulted in a further 108 +/- 21% (p = 0.015) and 88 +/- 55% (p = 0.02) rise in E50 and E80 values, respectively. In a second set of experiments, d- (n = 9) and d,l-sotalol (n = 7) (4 mg/kg bolus followed by 0.025 mg/kg/min maintenance infusion) were administered and baseline curves relating delivered energy to % success in DF were calculated. Isoproterenol (10 +/- 4 micrograms/min) was given to increase the heart rate by 54 +/- 32% (p less than 0.025), and resulted in decreases in % success at each of two energy levels, falling in the midrange of the dose-response curve. Following d,l-sotalol, % successful shocks fell from 60 +/- 15 to 42 +/- 28% (p less than 0.05); following d-sotalol, the % success fell from 66 +/- 13 to 38 +/- 36% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Psychiatric treatment strategies for patients at risk of dying suddenly.

This paper outlines the development of psychiatric treatment approaches to certain patients with life-threatening ventricular arrhythmias which may affect outcome, both psychological and, at times, medical. Three cases sketches which illustrate psychiatric management strategies are presented. One case history indicates how lack of adherence to such treatment contributed to a negative outcome. Emphasis is placed on an integrated approach to psychiatric treatment which is individualized for each patient. The importance of close liaison with cardiologist, selective psychotherapy, stress management skills and family involvement is highlighted.

Adaptation, Psychological↗
PubMed1991

Oral clofilium produces sustained lowering of defibrillation energy requirements in a canine model.

The effect of long-term oral administration of antiarrhythmic drugs on defibrillation energy requirements is not well understood. We examined the effect of clofilium, a drug that prolongs cardiac action potential duration without slowing cardiac conduction, on defibrillation energy requirements and ventricular effective refractory periods in a canine model during a 3-week period. Epicardial patch electrodes were implanted in 12 dogs, and baseline testing was conducted under fentanyl anesthesia on day 7. An oral clofilium (100 mg/day) regimen was started on day 8. Six clofilium-treated and six control dogs underwent repeated testing on days 14, 21, and 28 after surgery. Truncated trapezoidal shocks were given repeatedly at various stored energies in random order; delivered current and impedance were measured; and delivered energy was calculated. The energy and current for 50% success in defibrillation (E50 and I50, respectively) were determined. For control animals, E50 increased by a mean 34 +/- 78%, 60 +/- 83%, and 69 +/- 122% compared with baseline (day 7) on days 14, 21, and 28, respectively. In contrast, E50 in clofilium-treated dogs decreased by 39 +/- 62%, 24 +/- 33%, and 32 +/- 15% on days 14, 21, and 28, respectively. Mean current requirements (I50) remained relatively stable compared with baseline in control animals (-7 +/- 39%, +25 +/- 36%, +40 +/- 75% on days 14, 21, and 28, respectively). After clofilium administration I50 decreased by 36 +/- 22%, 32 +/- 17%, and 33 +/- 17% on days 14, 21, and 28, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗