Implantable defibrillators impedance measurement using pacing pulses versus shock delivery with intact and modified high voltage lead system.

At present the only method for measuring the high voltage system lead impedance in patients with an ICD is to deliver a low energy test shock. This is painful, requires sedation, and carries a risk of ventricular fibrillation induction. We sought to assess the shock lead and electrode function by calculating IMP using low voltage pacing pulses, and compared it to the measured impedance of a shock through the same lead. This was performed in both an intact and a modified lead system in order to mimic common clinical scenarios that alter lead system IMP (e.g., lead fracture). In an anesthesized canine model (n = 12) a standard (S) transvenous defibrillation lead (TDL), a modified (M) TDL (two-thirds of coil covered with heat-shrunk tubing), an active can (AC), and a M epicardial patch (EP) (two of four coils were disconnected) were used. Three configurations (C) were tested: C1:S/TDL-->AC, C2:M/TDL-->AC, and C3:M/TDL-->MEP. A measured IMP was obtained by an ICD using a 5-J shock as control. IMP was calculated using a 5-J shock, pacing pulses of 10-, 5-, 2-, and 1-V amplitude, as well as from a square wave drive train of low amplitude/high frequency signals (1 and 0.2 V, at 10 kHz) in all Cs. Ohm's law (V = IR) was utilized for measuring calculated IMP. As the surface area of the high voltage lead system decreased, the mean measured IMP (control) increased from C 1 to 3 (63 +/- 10, 95 +/- 4, and 127 +/- 20 omega, respectively). The correlation of calculated IMP from all Cs to measured impedance (control) remained high throughout the IMP range (range of correlation coefficient (r): 0.921-0.981). Calculated IMP using delivery of pacing pulses is highly correlated to IMP measured during shock delivery. This correlation remains high over a clinically significant range of high voltage lead system IMP changes. This study suggests that pacing pulses can be used to predict the IMP changes in the high voltage lead system which may occur clinically, reducing the need to deliver a shock for IMP measurement.

Improved clinical efficacy of external cardioversion by fluoroscopic electrode positioning and comparison to internal cardioversion in patients with atrial fibrillation.

BACKGROUND: Despite using different electrode positions, "conventional" external DC cardioversion in patients with atrial fibrillation is ineffective in 6%-50% of cases. An alternative when DC cardioversion is not successful is low energy internal cardioversion, which is performed at increased risk. We tested the hypothesis that optimization of electrode pad position under fluoroscopy to encompass as much atrial muscle as possible might improve the success rate of external cardioversion and thus minimize the need for internal cardioversion. METHODS: Fifteen (9 males, 6 females) patients (age: 54 +/- 15 years, weight: 124 +/- 35 kg) with chronic atrial fibrillation (> 8 weeks) who had undergone unsuccessful conventional external cardioversion entered the study. Repeat conventional external cardioversion with electrodes in standard (right anterior and left posterior) positions was followed by "optimized" external cardioversion by positioning electrodes under fluoroscopy (using metallic markers). In case of failure, internal cardioversion was performed. RESULTS: All 15 patients had undergone unsuccessful conventional external cardioversion with 360-J shocks. Eight patients (group A) reverted to sinus rhythm with one or two 360-J shocks using fluoroscopy-guided pad placement (53%). Six of the remaining 7 (86%) patients (group B) had successful internal cardioversion with biphasic shocks (12 +/- 3 J). The body weight and body mass index were statistically lower in group A vs group B (106 +/- 27 vs 145 +/- 33 kg, p = 0.03 and 35 +/- 8 vs 45 +/- 8 kg/m2, P = 0.48, respectively). There was no statistically significant in age, height, body surface area, duration of atrial fibrillation, amiodarone therapy, ejection fraction, or underlying heart disease. CONCLUSION: Unsuccessful external DC cardioversion, in some patients, is in part due to suboptimal conventional positioning of electrode pads that can be improved under fluoroscopic guidance by achieving the best possible vector encompassing the right and left atria. The optimized external cardioversion technique may minimize the need for internal cardioversion, which remains an effective approach when external cardioversion fails.

QRS duration widening: reduced synchronization of endocardial activation or transseptal conduction time?

Antegrade activation of the His-Purkinje system (HPS) results in synchronized activation of the right ventricular (RV) and left ventricular (LV) endocardia forming normal, narrow QRS duration (QRSD). An alteration in septal activation and transseptal conduction time have been reported to be the causes for QRSD widening seen with bundle branch block. However, reduced synchronization of activation of RV and LV endocardia as another potential mechanism for QRSD widening has not been systematically studied. Fifteen consecutive patients underwent radiofrequency ablation (RFA) for treatment of supraventricular tachycardia. After RFA, mean QRSD in normal sinus rhythm was 86 +/- 8 ms with mean HV interval of 40 +/- 5 ms. Right atrial (RA), coronary sinus (CS), simultaneous (S) RA-CS, RV apex (RVA), LV apex (LVA), and SRVA-LVA pacing were performed. Mean QRSD with RA, CS, SRA-CS pacing was similar to normal sinus rhythm (87 +/- 7, 87 +/- 8 and 88 +/- 8 ms respectively). Mean QRSD was significantly longer with SRVA-LVA and either RVA or LVA pacing alone compared to normal sinus rhythm (106 +/- 8, 146 +/- 12 and 157 +/- 13 ms, respectively). However, QRSD was significantly shorter with SRVA-LVA pacing compared to either RVA or LVA pacing alone (P < 0.0001). We conclude that shorter QRSD with SRVA-LVA pacing compared to either RVA or LVA pacing alone is due to elimination of transseptal conduction delay; longer QRSD with SRVA-LVA pacing compared to sinus or atrial paced rhythm is due to reduced synchronization of endocardial activation secondary to ectopic entry of impulses into the HPS network and inability to take advantage of the branching structure of the HPS. Therefore, in addition to transseptal conduction delay, reduced synchronization of endocardial activation is another potential mechanism for QRSD widening.

Clinical significance of an equivocal signal-averaged electrocardiogram.

Patients with an equivocal signal averaged electrocardiogram (SAECG) had less heart disease and better prognosis than patients with overtly abnormal SAECGs. An equivocal SAECG should not prompt further invasive diagnostic testing for ventricular tachycardia unless other clinical risk factors are present.

Evaluation of an open-loop, computer-based infusion system designed to achieve a series of constant, targeted plasma procainamide concentrations in patients undergoing electrophysiologic testing.

STUDY OBJECTIVE: To evaluate the performance of a computer-based procainamide infusion system in patients undergoing electrophysiologic testing. DESIGN: Prospective case series. SETTING: Electrophysiology laboratory in a university hospital. PATIENTS: Thirty-four patients with inducible sustained ventricular tachycardia. INTERVENTIONS: Intravenous infusion of procainamide to achieve and maintain targeted plasma concentrations. MEASUREMENTS AND MAIN RESULTS: System performance was assessed by comparing targeted and observed plasma concentrations. The population median absolute performance error (size of typical miss) was 12.6% (95% CI 11.2-14.1%). The population median performance error (system bias) was not significantly different from zero. A small but statistically significant improvement in performance over time was observed (population absolute performance error divergence -0.125%/min). Population wobble (overall system stability) was 7.6% (95% CI 6.8-8.3%). Population-based estimates of central compartment volume and volume of distribution at steady state were significantly higher and lower, respectively, than estimates used by the infusion system. CONCLUSION: The computer-based infusion system is capable of achieving and maintaining a series of targeted procainamide concentrations in patients undergoing electrophysiologic testing.

Electrophysiologic interactions of procainamide and N-acetylprocainamide in isolated canine cardiac Purkinje fibers.

The study objective was to characterize the electrophysiologic interactions of procainamide (PA) and its metabolite, N-acetylprocainamide (NAPA), in canine Purkinje fibers. Cell (N = 43) action potentials were measured in Tyrode's solution (K+ = 4.0 mM, 36 degrees C) at a basic cycle length of 1,000 ms using standard microelectrode techniques. Six PA concentrations (0.020-0.32 mM) and six NAPA concentrations (0.010-0.24 mM) were studied alone and in combination. PA caused concentration-dependent decreases in Vmax and APD50 but did not alter APD90, ERP, or RMP. NAPA caused a small but not significant concentration-dependent decrease in Vmax, no change in RMP, and significant concentration-dependent increases in APD50, APD90, and ERP. Low NAPA concentrations increased, intermediate concentrations did not affect, and high NAPA concentrations again increased PA's effect on Vmax. PA-NAPA combinations resulted in concentration-dependent changes in APD50 that were intermediate between the effects of PA or NAPA alone. PA did not significantly alter NAPA's effects on APD90 at NAPA concentrations less than or equal to 0.040 mM, while it antagonized NAPA's effect at higher concentrations. The effects of PA-NAPA combinations on ERP were generally similar to their effects on APD90. The electrophysiologic effects of PA-NAPA combinations in normal canine Purkinje fibers are complex functions of the relative and absolute concentrations of the two compounds.

Syncope.

Syncope is a clinical entity of diverse cause. The historical features surrounding the syncopal event and the presence or absence of heart disease are the most important features in establishing the cause for syncope. Passive head-up tilt study provides a means of identifying many patients with vasodepressor syncope. Electrophysiologic study is important in the elucidation of syncope in patients who have syncope undefined after noninvasive evaluation. With proper use of the modalities available, few patients will have an undefined cause for syncope.

Pharmacologic suppression of atrial flutter induced by atrial stimulation.

To examine the electrophysiologic properties of human atrial flutter and its response to various classes of antiarrhythmic drugs, 39 patients were identified as having inducible sustained atrial flutter with atrial extra-stimulation techniques. Measurement of intra-atrial, interatrial, atrioventricular node and His-Purkinje-conduction intervals, atrial refractory periods, and atrial flutter-cycle length were made before and after intravenous administration of verapamil, ouabain, or cedilanid, propranolol, and procainamide in these 39 patients, as well as in seven control patients. Verapamil significantly shortened flutter-cycle length but suppressed atrial-flutter induction in only one of seven patients. Two of nine patients who received propranolol proved resistant to flutter provocation; the seven patients who remained nonsuppressible exhibited greater prolongation of interatrial-conduction time. Ouabain and cedilanid suppressed flutter inducibility in four of seven patients, and flutter-cycle length increased in those patients remaining inducible. Procainamide suppressed flutter induction in nine of 11 patients. These results suggest that procainamide is the most effective agent of those agents tested in suppressing atrial flutter induced by atrial extra-stimulation. Verapamil and propranolol proved quite ineffective in suppressing inducible atrial flutter.

The autonomic and hemodynamic effects of oral theophylline in patients with vasodepressor syncope.

Adenosine appears to be an important mediator of hypotension and bradycardia in certain subsets of patients with vasodepressor syncope. Adenosine receptor blockage with methylxanthines may hypothetically prevent the vasodepressor spell. We studied the chronotropic, hemodynamic, and cardiac autonomic responses to head-up tilt in patients (mean age 40.7 +/- 18.1 years) with vasodepressor syncope before and after treatment with oral theophylline. At baseline, hypotension and syncope or near syncope were induced at 11.7 +/- 2.3 minutes of 60 degrees head-up tilt in all patients. Cardiac vagal and sympathetic tone showed biphasic and directionally opposite changes during tilt. Repeat tilt during oral theophylline therapy (6-12 mg/kg/day for 14 +/- 6 days) did not provoke symptomatic hypotension in 82% of patients. During 10.7 +/- 6.1 months of follow-up, seven patients had no recurrence of vasodepressor syncope and seven patients discontinued theophylline because of adverse reactions. Low-dose theophylline prevents tilt-induced vasodepressor syncope and may prevent spontaneous vasodepressor syncope in selected patients who can tolerate theophylline.

Clinical significance of terminal QRS abnormalities in the setting of inferior myocardial infarction.

To ascertain the clinical relevance of terminal electrocardiographic (ECG) QRS prolongation in the setting of inferior myocardial infarction, 32 patients were studied by radionuclide ventriculography to evaluate regional left ventricular contractility. Of the 32 patients, 16 had evidence of terminal QRS prolongation and notching associated with inferior myocardial infarction, and 16 had isolated ECG evidence of inferior myocardial infarction without terminal QRS prolongation. The regional ejection fraction in the posterolateral and inferoapical regions of patients with terminal conduction delay was lower than those without this conduction delay. This group also demonstrated a lower global ejection fraction than those patients with ECG evidence of inferior myocardial infarction without terminal QRS changes. Terminal QRS abnormalities are important qualitative predictors of left ventricular dysfunction in the setting of inferior myocardial infarction.

Mitral valve prolapse: cardiac arrest with long-term survival.

Cardiac arrest has been reported in patients with mitral valve prolapse; however, clinical characteristics and survival information are limited since most of the cases reported include autopsy data. Nine patients (2 male, 7 female) with mitral valve prolapse were identified who had cardiac arrest; ventricular fibrillation was documented in 8 patients; resuscitation was unsuccessful in 2. Eight had a history of palpitations (months to 15 years duration) and ventricular arrhythmias, 3 had a history (5-15 years) of recurrent syncope, and 1 was totally asymptomatic. Cardiac catheterization-angiographic studies in 8 patients demonstrated normal coronary artery anatomy and mitral valve prolapse. All 9 patients had auscultatory and echocardiographic evidence of mitral valve prolapse. Seven survivors (6 still alive) were followed from 3 to 14 years after cardiac arrest. A subset of patients with mitral valve prolapse and cardiac arrest is described in whom past medical history is compatible with cardiac arrhythmias or syncope, and whose long-term prognosis appears better than patients with other causes of cardiac arrest.

Antiarrhythmic activity and unbound concentrations of disopyramide enantiomers in patients.

Six patients with reproducible inducible atrial flutter randomly received, in double-blinded fashion, 77 mg of S(+)-disopyramide and R(-)-disopyramide over 20 min by intravenous infusion on two occasions separated by at least 24 h. The S(+) enantiomer prevented the inducibility of atrial flutter in five of the six patients; atrial flutter was inducible following R(-) enantiomer administration in all six patients (p less than 0.05). The mean (+/- SD) antiarrhythmic unbound serum concentration range of S(+)-disopyramide was 0.55 +/- 0.31-0.90 +/- 0.81 mg/L. The binding of disopyramide was stereoselective: the mean unbound fractions of S(+)- and R(-)-disopyramide were 0.207 +/- 0.119 and 0.338 +/- 0.214 (p less than 0.05). Binding of the individual enantiomers in some patients was markedly concentration dependent. The data suggest that the antiarrhythmic activity associated with racemic disopyramide resides in the S(+) enantiomer.

Hemodynamic and electrophysiologic effects of disopyramide enantiomers in a canine blood superfusion model.

The use of disopyramide is often limited because of adverse hemodynamic or electrophysiologic side effects. We compared the S(+) and R(-) enantiomers of disopyramide to the clinically used racemic mixture in a canine blood superfusion model. Eighteen support animals (group I) provided extracorporeal blood superfusion of isolated canine cardiac Purkinje fibers. Following administration of 2 mg/kg disopyramide intravenously (i.v.) [S(+), R(-), or racemic] hemodynamic and electrocardiographic parameters were temporally assessed in the support animals while simultaneous cellular electrophysiologic effects were recorded from the blood-superfused Purkinje fibers. An additional 13 animals (group II) underwent extended hemodynamic and pharmacokinetic analysis without the external atrioventricular (AV) shunt required for blood superfusion. Mean peak serum concentrations of racemic disopyramide and its enantiomers were similar (2.7 to 3.1 mg/L), but clearance was stereo-specific [half-life (t1/2) of 1.99 h for S(+) vs. 2.79 h for R(-) disopyramide]. Left ventricular (LV) function was impaired following drug administration, irrespective of optical rotation (cardiac output decreased by 20.8%, LV dP/dtmax decreased by 22.4%). Depression of phase 0 Vmax of the Purkinje fiber action potential was also nonstereo-dependent. S(+) disopyramide prolonged the QTC interval by 11.5% and increased terminal action potential duration (APD75) and effective refractory period (ERP) by 21.2 and 19.0%, respectively. R(-) disopyramide slightly increased the QTC interval (+2.3%) but decreased APD75 and ERP by 8.9 and 6.8%, respectively. The effect of racemic disopyramide on repolarization indexes was intermediate to that of its enantiomers. These data support nonstereodependent depression of both myocardial contractility and sodium channel conductance by disopyramide. Changes in APD and refractoriness were dependent on stereochemical configuration.

Effect of cimetidine on quinidine bioavailability.

Elevations in quinidine steady-state serum concentrations have been reported in patients who received cimetidine concurrently. Studies in normal volunteers have shown that areas under the serum concentration-time curve of orally administered quinidine are higher when quinidine is given during chronic cimetidine therapy as compared to under control conditions. The mechanism for this interaction is generally ascribed to decreased hepatic clearance as a consequence of enzyme inhibition. In this study, we show that cimetidine also decreases the bioavailable fraction of quinidine.

Stereospecific effects of disopyramide enantiomers following pretreatment of canine cardiac Purkinje fibers with verapamil and nisoldipine.

The effect of racemic disopyramide and its enantiomers on the action potential was studied in Tyrodes (4.0 mM KCL)-superfused canine cardiac Purkinje fibers. Nonstereodependent depression of action potential amplitude and phase 0 Vmax was observed in control fibers and following pretreatment with either nisoldipine or verapamil. Stereospecific effects of the enantiomers were prominent during repolarization phases of the action potential and could be modified by pretreatment with the calcium channel blocking agents. R(-) disopyramide decreased action potential duration at 90% repolarization and shortened the effective refractory period. S(+) disopyramide increased action potential duration at 90% repolarization and prolonged refractoriness. This disparate effect of the enantiomers was eliminated following pretreatment with verapamil. Stereospecific effects on repolarization persisted when fibers were pretreated with nisoldipine, a more selective calcium channel blocking agent that lacks effects on outward plateau current. The data suggest that the increase in action potential duration and refractoriness produced by disopyramide is mediated by a stereospecific inhibition of outward repolarizing current by the S(+) enantiomer.

Localization of the site of ventricular premature complexes by radionuclide angiographic phase imaging.

To investigate whether gated radionuclide angiographic phase imaging is useful for visually displaying the origin of ventricular premature complexes (VPCs), 82 patients were studied by gating only VPCs. The VPC "origin" by the scintigraphic method was defined as the area of earliest phase and was compared with that predicted by 12-lead electrocardiographic criteria in all patients and to invasive electrophysiologic mapping in 10. Separating the right ventricle into 3 and the left ventricle into 4 segments, the phase imaging method and the electrocardiographic criteria agreed as to ventricle of VPC origin in 69 patients (84%) and segment of origin within each ventricle in 46 (56%). When baseline ventricular wall motion was analyzed, the 2 methods agreed to the ventricle of VPC origin in 31 of 33 patients (94%) with normal wall motion, 20 of 23 (87%) with segmental wall motion abnormalities and 19 of 26 (73%) with diffuse wall motion abnormalities. Agreement between the 2 methods as to specific segmental localization of the arrhythmia focus was noted in 21 of 33 patients (64%) with normal wall motion, 11 of 23 (48%) with segmental wall motion abnormalities and 12 of 26 (46%) with diffuse hypocontractility. In the 10 patients with endocardial mapping studies, the phase imaging technique confirmed the segment of VPC origin in all 10; the electrocardiographic method was accurate in 8. Thus, gated radionuclide angiographic phase imaging methods may be of value in noninvasively defining the origin of spontaneous VPCs. The visual format allows ready interpretation of the arrhythmia origin, and there may be an advantage to this approach over electrocardiographic morphometric criteria.