Biomedical subjects
Publications and source records attributed to P Dorian.
Cardioverter-defibrillators were implanted in children aged 4 to 16 years over a 5-year period with no mortality and eventual clinically appropriate shocks in 6 of 11 patients. Both transvenous and epicardial implantable cardioverter-defibrillators were safe and effective in children resuscitated from sudden death or at high risk for sudden death.
In order to compare the efficacy and long-term tolerability of flecainide acetate versus quinidine, 239 patients with paroxysmal atrial fibrillation were prospectively treated with flecainide (n = 122) or quinidine (n = 117) in an open-label, randomized trial. All patients were followed for 1 year after initiation of therapy unless their antiarrhythmic drug was discontinued due to an inadequate therapeutic response or intolerable side effects. Although both drugs were equally effective in adequately controlling recurrences of atrial fibrillation (difference, p = 0.282; not significant), fewer flecainide patients had to have their therapy discontinued due to adverse experiences (p = 0.012). Based on both endpoints (efficacy and tolerability), an estimated 70.5% of flecainide versus 55.4% of quinidine patients would remain effectively treated at the end of 1 year on therapy (p < or = 0.007). The findings of this prospective study suggest that in the treatment of paroxysmal atrial fibrillation (1) flecainide and quinidine are equally effective in the acceptable suppression of symptomatic paroxysmal atrial fibrillation; (2) flecainide is better tolerated than quinidine and is less likely to be discontinued due to adverse effects; and (3) given the overall endpoint of efficacy and tolerability, more patients are likely to continue long-term therapy with flecainide than with quinidine.
Reentrant paroxysmal supraventricular tachycardia (PSVT) are frequently encountered in clinical practice. Verapamil and flecainide have both been successfully used as chronic oral therapy to prevent PSVT recurrences. This open-label, randomized, multicenter study was designed to compare the efficacy and adverse effects of verapamil (median dose, 240 mg/day) versus flecainide (median dose, 200 mg/day) in patients with frequent and symptomatic attacks of PSVT (other than atrial fibrillation or flutter). A total of 121 patients receiving flecainide (n = 63) or verapamil (n = 58) were followed for 8.1 +/- 5.1 and 7.5 +/- 5.4 months, respectively. Response was judged clinically as effective or not by the treating physician. By life table analysis, 11% discontinued flecainide and 19% discontinued verapamil for inefficacy at 1 year (difference not significant). Both groups showed a marked reduction in the frequency of attacks of PSVT. Before therapy, 71% of flecainide patients and 73% of verapamil patients had > or = 2 attacks per month. During therapy, 86% of all flecainide patient-months and 73% of all verapamil patient-months occurred with 0 or 1 attack; 19 (30%) patients on flecainide completed the trial ( > 270 days) without symptomatic attacks versus 7 (13%) of the patients on verapamil (p = 0.026). Both drugs were well tolerated; 19% of the flecainide group discontinued primarily because of adverse effects, compared with 24% discontinuing verapamil for this reason (difference not significant). Both flecainide and verapamil are effective and well tolerated for the prevention of recurrences of PSVT. For patients in whom radiofrequency ablation procedures cannot be performed or are not indicated, either therapy is a reasonable choice for long-term prophylaxis.
INTRODUCTION: We assessed the effect of d-sotalol on defibrillation voltage and energy requirements in patients undergoing automatic defibrillator implantation. Drugs that primarily prolong cardiac refractoriness generally decrease the energy requirements for defibrillation in animal models. Despite the widespread use of antiarrhythmic drugs in patients with implanted cardioverter defibrillators, the effect of such drugs on defibrillation energy requirements in humans has not been well studied. Sotalol (in the d,l racemic form) is an antiarrhythmic with beta-blocking and cardiac refractoriness prolonging effects. The d-isomer of sotalol is largely devoid of beta-blocking effects; both forms decrease defibrillation energy requirements in animals. We hypothesized that d-sotalol would decrease defibrillation voltage and energy requirements in humans. METHODS AND RESULTS: Fifteen patients undergoing implanted cardioverter defibrillator implantation were studied before and 20 minutes after d-sotalol infusion (2 mg/kg IV in 15 min, followed by 1 mg/kg per hour). The estimated energy (E50) and voltage (V50) for 50% success in defibrillation (estimated from two successive defibrillation "threshold" measurements), ventricular effective refractory period, monophasic action potential duration, and mean cycle length of ventricular fibrillation were measured, along with heart rate, blood pressure, and plasma concentration of d-sotalol. There was a significant decrease in defibrillation energy (E50 = 12.4 +/- 5.0 J before and 8.4 +/- 4.0 J after d-sotalol, P < 0.003) and voltage (V50 = 440 +/- 77 V before and 354 +/- 93 V after d-sotalol, P < 0.001). Consistent with the Class III effect of d-sotalol, ventricular effective refractory period increased from 284 +/- 21 to 330 +/- 24 msec (P < 0.001), and action potential duration was prolonged from 296 +/- 28 to 340 +/- 22 msec (P < 0.001). Following d-sotalol, there was a tendency for induced tachyarrhythmia to self-terminate (23/102 episodes before vs 74/150 after sotalol, P < 0.001), and ventricular fibrillation cycle length was increased from 216 +/- 20 msec before to 274 +/- 23 msec (P < 0.001) after d-sotalol, despite the persistence of a rapid, disorganized rhythm of the surface ECG. No patient suffered adverse effects. CONCLUSIONS: d-Sotalol lowers defibrillation energy by a mean 32% +/- 27% at concentrations producing a 16% +/- 7% increase in ventricular effective refractory period. Along with its other antiarrhythmic effects, d-sotalol may increase the safety margin for defibrillation or allow lower programmed energies in patients with implanted defibrillators.
Explore the source record for details and available documents.
BACKGROUND: Drugs that prolong cardiac refractoriness can decrease defibrillation energy requirements. In particular, barium, a relatively selective blocker of cardiac Ik1 channels, produces marked decreases in defibrillation energy. The mechanism of this effect is unknown, and may relate to modulation of the effect of defibrillatory shocks, or an alteration of the pattern of ventricular fibrillation (VF) by the drug. METHODS AND RESULTS: Accordingly, the effect of barium chloride was examined, 1.1 mg/kg followed by 0.1 mg/kg/min intravenously, or saline control, on the pattern of unipolar electrograms using a 120 electrode array, during 73 episodes of VF (37 after saline, 36 after barium ). For each episode of VF, peak-dV/dt associated with local activations and mean activation-activation (ACT-ACT) intervals for the last 2 s of a 10 s episode of VF were measured for each electrode. 'Organization' in VF was measured by the variability in ACT-ACT intervals, their visually assessed pattern, and the relation between local activations on adjacent electrodes. Voltage gradients were measured at each of 40 epicardial sites for each defibrillation shock, delivered at voltages ranging from to 20% to 100% successful in defibrillation. At identical voltage shocks (400 V), mean voltage gradients before and after barium were similar: 18+/-9 and 19+/-1.2 V/cm, respectively. Mean peak -dV/dt for all activations was -8.7+/-0.5 V/s before and -7.7+/-2.8 V/s after barium, suggesting no apparent change in local conduction velocity. When the lowest voltage gradient at any site was less than 3.5 V/cm, defibrillation was successful 14% of the time (two of 14 ) during control, but 88% of the time (14 to 16) after barium infusion (P<0.01). Mean ACT-ACT intervals after barium for all episodes over all electrodes was 107.5+/-14.1 ms, significantly longer than 89.7 +/-3.9 ms after saline, indicating a 20% increase in the cycle length of fibrillation. During saline control, local epicardial electrogram patterns showed irregular, variable morphology electrograms and a mean lowest SD of ACT-ACT intervals over any electrode of 5.1+/-1.5 ms, compared with 1.2+/-0.7 ms after barium (P < 0.0001). Following barium, most unipolar epicardial electrograms showed regular, phasic activations that appear to reflect an organized, uniformly repetitive local activation pattern, suggesting spatially homogeneous and temporally regular activation wavefronts. CONCLUSIONS: During VF after barium, despite an apparently disorganized surface electrocardiographic pattern, epicardial electrogram patterns are altered and reflect a more ¿ordered', homogeneous and regular local activation. This increased order may be in part responsible for the decreased defibrillation energy requirements observed after barium.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
OBJECTIVES: We hypothesized that QT dispersion would be increased in patients with diabetes mellitus and autonomic dysfunction and that QT dispersion would be related to abnormal iodine-123 (I-123) metaiodobenzylguanidine (MIBG) uptake. BACKGROUND: Patients with diabetes mellitus and autonomic dysfunction have an increased incidence of sudden death. This event may be due to a sympathetic imbalance causing disturbances of repolarization. QT dispersion has recently been demonstrated to reflect dispersion of ventricular refractoriness and is a marker of arrhythmogenic potential. Uptake of I-123 MIBG is a reliable measure of whether the tissue examined receives sympathetic neuronal innervation. METHODS: Fifty-one diabetic patients and 11 normal subjects were studied. All patients had clinical evaluation for autonomic dysfunction (defined as at least two abnormal heart rate and blood pressure responses to five validated tests). Rest 12-lead electrocardiograms were recorded for measurement of QT dispersion, defined as the longest QT interval minus the shortest QT interval, and corrected for heart rate using Bazett's formula. Visual and quantitative measurements of I-123 MIBG uptake were performed using I-123 MIBG, and technetium-99m sestamibi uptake was used to assess perfusion. RESULTS: Thirty-five diabetic patients had autonomic dysfunction. Corrected QT dispersion was significantly greater in the patients than in the normal subjects (p = 0.02). The I-123 MIBG scores were also significantly greater in patients with than without autonomic dysfunction (p = 0.0004) and in normal subjects (p = 0.008). There was no correlation between QT dispersion and I-123 MIBG uptake score (r = 0.006, p = 0.97). CONCLUSIONS: Diabetic patients with autonomic dysfunction have increased QT dispersion and larger I-123 MIBG uptake defects. This finding suggests that such patients have a greater inhomogeneity of repolarization. The lack of correlation between QT dispersion and I-123 MIBG uptake suggests that these abnormalities are mediated by different mechanisms.
Ventricular premature complexes (VPCs) after acute myocardial infarction (AMI) remain important determinants of survival in the post-thrombolytic era. The role of thrombolysis, left ventricular function, and Holter ST-segment depression in modulating VPC frequency is unclear. In a placebo-controlled, randomized study of tissue-type plasminogen activator (t-PA) in 103 patients with AMI (Tissue Plasminogen Activator: Toronto study), VPC frequency and ST depression on Holter monitoring (day 7), ejection fraction by radionuclide scan (day 9), and infarct artery patency and cross-sectional area on day 1 (n = 42) were assessed. After administering t-PA, VPC frequency was 10 +/- 58/hour (mean +/- SD), similar to that after placebo (23.5 +/- 91.7, p = NS). However, patients with ST depression had greater VPC frequency (56 +/- 140/hour) than those without it (1.3 +/- 2.6/hour, p = 0.05). Ejection fraction was negatively correlated with VPC frequency (r = -0.33, p < 0.001). By multivariate analysis, ejection fraction (F = 7.0, p < 0.01) and ST depression (F = 5.8, p < 0.02) were the only independent predictors of VPC frequency. In this placebo-controlled study, VPC frequency after AMI was not related to thrombolytic administration but was associated with ST depression and ejection fraction. This suggests that the underlying extent of both infarcted and ischemic myocardium is important in modulating ventricular arrhythmias after AMI.
Implanted cardioverter defibrillators (ICDs) are very effective in the treatment of life-threatening ventricular arrhythmias. Among patients with severe left ventricular (LV) dysfunction, ICDs can defibrillate at energies similar to those in patients with well-preserved LV function; the perioperative mortality rate with transvenous systems is low, even in patients with a low ejection fraction (EF). In patients whose EF is < 30%, sudden death and total mortality rates are relatively low. However, at most only 50% of deaths in patients with low EFs are sudden, and life in these patients may be only slightly prolonged by successful defibrillator shocks. The true value of ICDs in these patients can be determined only by comparison with optimal medical therapy in randomized controlled studies. The Canadian Implantable Defibrillator Study randomly assigns patients with ventricular fibrillation or ventricular tachycardia to ICD or amiodarone. Current patient profiles show that most of these patients have poor LV function (mean EF, 33.6%), and most receive optimal medical therapy. Results of this and other studies will clarify the benefits from ICDs in these patients with severe heart disease.
Polymorphic ventricular tachycardia in association with prolongation of the QT interval on the surface electrocardiogram (ECG) has long been recognized as an important cause of life threatening arrhythmias that can occur with congenital or acquired abnormalities of cardiac repolarization. One hypothesis of the origin of these arrhythmias states that overactivity of the left-sided sympathetic or under activity of the right-sided sympathetic neural input to the heart leads to prolonged repolarization and ventricular arrhythmias. This hypothesis has led to the application of left cervicothoracic sympathetectomy for control of arrhythmias in congenital long QT syndromes. Although animal models have shown QT prolongation following right stellate ganglionic section or left stellate stimulation, spontaneous ventricular arrhythmias following stellate stimulation or block in man have not been demonstrated. We report the case of a patient with life threatening ventricular arrhythmias following surgical damage to the right cardiothoracic sympathetic nerves.
Explore the source record for details and available documents.
Certain antiarrhythmic drugs that inhibit myocardial repolarizing currents decrease defibrillation energy, but the effect of blocking particular currents on defibrillation is not well understood. We therefore investigated the effect of barium, a relatively selective blocker of inwardly rectifying potassium current (Ik1) on voltage and energy requirements for defibrillation in an open-chest dog model. Defibrillation energy and voltage requirements were assessed by delivering monophasic shocks through epicardial electrode patches at varying voltages to construct a dose-dependent curve of energy and voltage versus success in defibrillation. The energy and voltage for 50% success in defibrillation (E50 and V50, respectively) were determined by logistic regression. Monophasic action potential duration at 90% repolarization (MAPD90) was measured with a contact electrode, and ventricular refractory period (VERP) was measured. After baseline measurements were obtained of E50, V50, MAPD90, and VERP, saline (control) (n = 6) or barium (1.1 mg/kg/min for 5 min followed by 0.25 mg/kg/min) (n = 11) was administered. Defibrillation voltage and energy requirements and electrophysiologic measures were repeated after 30 and 120 min of barium or saline infusion. In control animals, there was no significant change with time in V50 (2.0 +/- 12.4 and -0.2 +/- 16.0% at 30 and 120 min, respectively), VERP (+3 +/- 5 and -2 +/- 3% at 30 and 120 min, respectively) or MAPD90 (+1 +/- 4 and -2 +/- 6, at 30 and 120 min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
The successful implantation of an ICD system with hardware from three different manufacturers is described. This case exemplifies the need for compatibility of components among different manufacturers. This is most relevant at a time when rapidly changing technology and hardware availability may require a mixing, by informed practitioners, of ICD system components. The parallel to the development of the uniform IS-1 standard for bradycardia devices is made.
Explore the source record for details and available documents.
BACKGROUND: Thrombolytic therapy reduces mortality after acute myocardial infarction, even when treatment is initiated relatively late after onset of symptoms. The mechanism underlying this survival benefit is incompletely understood. METHODS AND RESULTS: In a prospectively designed ancillary study of a randomized, placebo-controlled trial of late thrombolytic therapy (LATE), the signal-averaged (SA) ECG was recorded before hospital discharge in an effort to assess the effect of thrombolytic therapy on arrhythmia substrate. Three hundred ten patients were enrolled at 23 participating sites; 160 patients received placebo, and 150 patients received recombinant tissue-type plasminogen activator (rTPA) therapy 6 to 24 hours after onset of symptoms. Compared with placebo, rTPA tended to reduce the frequency of SAECG abnormality (filtered QRS duration > 120 milliseconds) by 37% (95% CI, -64%, +6%; P = .087) and the filtered QRS duration (105.7 +/- 13.8 versus 108.8 +/- 14.6 milliseconds, P = .05). In the prespecified subgroup of 185 patients with ST elevation on the qualifying ECG, rTPA resulted in a 52% reduction (95% CI, 4% to 77%, P = .011) of SAECG abnormality and a shorter filtered QRS duration (105.7 +/- 10.9 versus 110.7 +/- 15.9 milliseconds, P = .01). No benefit was seen in patients without ST elevation on ECG. CONCLUSIONS: Late thrombolytic therapy produced a more stable electrical substrate, which probably represents an important mechanism of mortality benefit.