Conventional programmed electrical stimulation (PES) of the ventricle isuseful for establishing inducibility or noninducibility of clinicalventricular arrhythmias (VA) but is complex and time consuming. The presentstudy was designed to compare a standard PES protocol with an alternativemethod using ultrarapid train stimulation in patients with VA and coronaryartery disease (CAD). A prospective, randomized, crossover design was used.During each session in the electrophysiology laboratory, patients werestudied using both the trains and PES protocols in randomized order. In 82matched pairs of comparisons in 50 patients, results were concordant in85% (p < 0.0001). There were no differences related to type ofclinical arrhythmia or to the presence of antiarrhythmic drugs. There wereno significant differences in the induction of nonclinical arrhythmias withthe two methods (p < 0.0001 for concordance). There were no significantdifferences related to the cycle length of the trains (10, 20, or 30 ms,equivalent to 100, 50, or 33 Hz). The number of drive-extrastimuli sequencesand the time required to complete the trains protocol was significantlyshorter (p < 0.0001) using trains versus PES. Ultrarapid train stimulationprovides results in CAD patients that are comparable with those ofconventional PES protocols. There is a significant savings in time, addingpractical value to intrinsic electrophysiologic interest. Trains may beuseful when multiple inductions are desirable, for example, in the settingof antitachycardia pacing parameters in an implantable defibrillator (ICD),during ICD implantation, or in other circumstances where the main questionis inducibility of ventricular arrhythmias.

We have developed a cell culture system to study molecular mechanisms important in myocardial hypertrophy. α1-Adrenergic receptor stimulation produces hypertrophy of neonatal rat cardiac myocytes. Myocyte hyperplasia is not induced by α1 stimulation, although α1-adrenergic receptor-mediated DNA synthesis and cell division have been observed in other types of cells. The myocyte hypertrophic response does not require contractile activity. Activation of the α1 receptor also produces highly specific alterations in gene expression, as measured at the mRNA and protein levels. In particular, there is selective up-regulation of two contractile protein isogenes that are expressed in vivo during early development and in pressure-load hypertrophy, skeletal α-actin and β-myosin heavy chain. Studies with an in vitro transcription assay indicate that stimulation of the α1-adrenergic receptor leads to a distinctive temporal sequence of transcriptional activation. Transcription of the skeletal α-actin isogene is induced preferentially to that of cardiac α-actin. Thus, early developmental isogene induction in α1-stimulated hypertrophy reflects a fundamental change in the transcriptional program of the cardiac myocyte nucleus. The goal now is to define an intracellular pathway connecting the α1-adrenergic receptor in the plasma membrane to activation of RNA polymerase II on the skeletal α-actin gene in the cardiac myocyte nucleus. There is evidence that protein kinase C may be one component of this pathway. A model for α1-mediated transcription is presented.

The values of two Holter ambulatory electrocardiographic monitoring criteria and one programmed stimulation efficacy criterion reported to be predictive of the efficacy of amiodarone were compared in 70 patients taking amiodarone for sustained ventricular tachyarrhythmias. At baseline, all patients had ventricular tachycardia inducible by programmed stimulation. After amiodarone loading (935 ± 271 mg for 16 ± 7 days), efficacy was determined by a programmed stimulation criterion (ventricular tachycardia no longer inducible or ≤15 beats) and two Holter monitoring criteria (Holter I = ≥85% reduction of ventricular premature complexes and abolition of couplets and triplets in 64 patients who had ≥ 10 ventricular premature complexes/h or couplets or triplets or both before therapy; Holter II = abolition of triplets in 41 patients who had triplets before therapy). Amiodarone was effective in 12 of 70 patients by the programmed stimulation criterion, in 49 of 64 patients by Holter criterion I and in 37 of 41 patients by Holter criterion II. In assessing efficacy of amiodarone, programmed stimulation and Holter criteria were discordant in 69% of patients or more (p < 0.001). There were 16 recurrences or sudden deaths during the entire follow-up period (19 ± 19 months). Arrhythmia-free survival rates at 24 months of patients with efficacy and inefficacy by each criterion, respectively, were 90 and 78% by programmed stimulation, 84 and 62% by Holter criterion I (p < 0.05) and 73 and 50% by Holter criterion II (p < 0.05). At 24 months, sensitivities of programmed stimulation and Holter I and II criteria were 92, 42 and 18%, respectively; specificities were 17, 86 and 94%, respectively, and predictive accuracies were 43, 71 and 63%, respectively. In patients with discordance between Holter monitoring and programmed stimulation findings, the specificity of programmed stimulation was less than 10% and the sensitivity of Holter monitoring was less than 20% at 12 months. Conclusions: 1) Treatment with amiodarone in a significant number of patients cannot be managed by Holter monitoring. 2) Inefficacy by Holter criteria predicts poor outcome but efficacy does not preclude poor outcome (insensitive). 3) Inefficacy by programmed stimulation does not preclude good outcome (nonspecific). 4) Many patients have inefficacy by programmed stimulation despite efficacy by Holter criteria; this is due to both insensitivity of Holter monitoring and nonspecificity of programmed stimulation. 5) Further studies should be conducted to identify predictors of efficacy of amiodarone in patients with discordant results.

This double-blind, randomized, placebo crossover study was used to evaluate the effects of a cholinesterase inhibitor--slow-release pyridostigmine (180 mg orally every 12 hours)--on the anticholinergic and antiarrhythmic properties of disopyramide. Quantitative side effects questionnaire scores were used to guide disopyramide administration in 20 men with ventricular tachycardia. Disopyramide was given to each patient both with placebo and with active pyridostigmine. The maximal administered dose for each regimen was used in conjunction with corresponding questionnaire scores to calculate an index or estimate of the maximal tolerable dose of disopyramide. Additional evaluations performed at baseline and at each maximal administered dose regimen included tear and saliva quantitation, 24 hour electrocardiogram (ECG), exercise testing and programmed ventricular stimulation. Results showed that the maximal administered dose of disopyramide was greater with active pyridostigmine than with placebo: 295 +/- 75 versus 245 +/- 100 mg every 6 hours (p less than 0.05). The calculated maximal tolerable dose was substantially greater in the presence of pyridostigmine: 355 +/- 90 versus 260 +/- 115 mg every 6 hours (p less than 0.001). Maximal side effects questionnaire scores also reflected decreased anticholinergic activity in the presence of pyridostigmine compared with placebo: 101.9 +/- 2.2 versus 104.6 +/- 2.8, respectively (p less than 0.005). Baseline tear and saliva production was significantly reduced during disopyramide therapy, but was restored toward normal by the addition of pyridostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

B rodman R, et al : Surgical techniques for implantation of the automatic implantable cardioverter defibrillator . The technological differences between the two automatic implantable cardioverter defibrillator units currently available for implantation, the AICD‐B and the AICD‐BR, are outlined. A comprehensive overview of implantation techniques for the lead‐electrode System and pulse generator is presented, and includes techniques for implantation, electrophysiology, surgical complications, and problems related to interaction with implanted pacemakers .

UNLABELLED:Programmed electrical stimulation (PES) and 24-hour Holter monitoring were compared in 30 patients with ventricular tachycardia (VT) or ventricular fibrillation (VF) before and during treatment with mexiletine. Before treatment, all patients had greater than or equal to 30 ventricular premature complexes (VPCs)/hr and 22 patients had nonsustained VT on Holter. All had inducible sustained VT by PES (one to three extrastimuli). Mexiletine was effective in only 23% by PES criteria (VT no longer inducible or less than or equal to 15 beats in duration and effective in 57%, 57%, and 73% by Holter criteria I, II, and III, respectively (Holter I greater than or equal to 50% reduction of VPCs, greater than or equal to 90% reduction of couplets and abolition of nonsustained VT; Holter II greater than or equal to 83% reduction of VPCs and abolition of VT; Holter III abolition of VT in patients who had VT during baseline Holter). Results of PES and Holter were discordant in 67%, 60%, and 55% (PES vs Holter I, II, and III, respectively). The majority (greater than or equal to 75%) of the discordance occurred due to mexiletine appearing effective by Holter criteria but ineffective by PES criteria (suggesting insensitivity of efficacy by Holter criteria and/or nonspecificity of induced VT during treatment with mexiletine). CONCLUSIONS:PES and Holter are discordant in assessing efficacy of mexiletine (p less than 0.05). Efficacy of mexiletine by Holter criteria is easier to achieve than efficacy by PES. The discordance between the two methods, both with very good reported predictive values, calls for randomized clinical follow-up studies to determine sensitivity and specificity of each method in assessing efficacy of mexiletine.

The value of programmed elecfrical stimulation (PES) and Holter monitoring in the assessment of amiodarone efficacy was reviewed. Many physicians have been disturbed by the persistent inducibility of arrhythmias in patients treated with amiodarone, who nevertheless do very well during the follow‐up period. Noninducibility was associated with a favorable prognosis among 366 VT patients. Eighty‐eight (24%)were noninducible on amiodarone, and 10% of these had recurrences, vs 39% in patients who remained inducible. Further, increased difficulty of induction with PES or induction of a slower or better tolerated VT may indicate a favorable outlook, and add to the value of PES. Few papers rigorously employed Holter monitoring in the assessment of amiodarone. In general, suppression of previously frequent arrhythmias implies excellent protection for patients with benign arrhythmias and moderate protection with malignant arrhythmias. By Holter assessment in 186 VT patients, arrhythmias were suppressed in 114 (61%), and 18% of these had recurrences vs 50% in patients whose arrhythmias were not suppressed. Studies attempting to correlate the results of PES and Holter monitoring in the same patients are lacking and may prove useful.