Igor Singer

Placebo-controlled, randomized clinical trial of azimilide for prevention of ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator.

Background—Although implanted cardioverter defibrillators (ICDs) effectively treat sustained ventricular tachyarrhythmias, up to 50% of ICD recipients eventually require concomitant antiarrhythmic drug therapy to prevent symptomatic arrhythmia recurrences and hence reduce the number of device therapies. Methods and Results—A total of 633 ICD recipients were enrolled in a randomized, double-blind, placebo-controlled study to evaluate the effect of daily doses of 75 or 125 mg of azimilide on recurrent symptomatic ventricular tachyarrhythmias and ICD therapies. Total all-cause shocks plus symptomatic ventricular tachycardia (VT) terminated by antitachycardia pacing (ATP) were significantly reduced by azimilide, with relative risk reductions of 57% (hazard ratio [HR]=0.43, 95% CI 0.26 to 0.69, P=0.0006) and 47% (HR=0.53, 95% CI 0.34 to 0.83, P=0.0053) at 75- and 125-mg doses, respectively. The reductions in all-cause shocks with both doses of azimilide did not achieve statistical significance. The incidence of all appropriate ICD therapies (shocks or ATP-terminated VT) was reduced significantly among patients taking 75 mg of azimilide (HR=0.52, 95% CI 0.30 to 0.89, P=0.017) and those taking 125 mg of azimilide (HR=0.38, 95% CI 0.22 to 0.65, P=0.0004). Five patients in the azimilide groups and 1 patient in the placebo group had torsade de pointes; all were successfully treated by the device. One patient taking 75 mg of azimilide had severe but reversible neutropenia. Conclusions—Azimilide significantly reduced the recurrence of VT or ventricular fibrillation terminated by shocks or ATP in ICD patients, thereby reducing the burden of symptomatic ventricular tachyarrhythmia.

Report of the NASPE Policy Conference on Antibradycardia Pacemaker Follow‐Up: Effectiveness, Needs, and Resources

On May 4–5, 1993, a policy conference was held in San Diego, California, under the sponsorship of the North American Society of Pacing and Electrophysiology (NASPE) to identify the fundamental goals of antibradycardia pacemaker follow‐up, evaluate the effectiveness with which it achieves those goals, and formulate specific recommendations as to how it can be made more effective. The conference addressed clinical, administrative, and educational objectives, focusing on existing and potential resources for follow‐up testing and the appropriate frequency of their application. The training of physicians and associated professionals engaged in follow‐up also was addressed, as were regulatory and reimbursement issues. This report summarizes the conclusions and recommendations arrived at during the conference and subsequently approved by the NASPE Board of Trustees.

Pathologic findings related to the lead system and repeated defibrillations in patients with the automatic implantable cardioverter-defibrillator

The purpose of the present study was to examine at autopsy the effect of multiple defibrillations on the myocardium and the pathologic consequences of short- and long-term placement of the intravascular and interpericardial leads of the automatic implantable cardioverter-defibrillator. Twenty-five patients were examined at autopsy; 8 of them underwent lead implantation only and 17 received both leads and the automatic implantable cardioverter-defibrillator. Twelve patients (48%) died of ventricular tachycardia or ventricular fibrillation; seven (28%) died of other causes. Acute pericarditis occurred in all patients, resulting in a localized, progressive fibrosis around the apical patch lead without giving rise to pericardial restriction. Thrombus formation was associated with the superior vena cava spring electrode in four patients (17%) and the right ventricular rate-sensing electrode in one patient (4%). Asymptomatic pulmonary emboli occurred in two patients (8%). In one patient who underwent defibrillation 59 times, superior vena cava changes consisted of vein wall destruction, fibrosis and thrombus formation. Pathologic changes under the apical patch related to defibrillation were observed in seven patients; two of these had fewer than 5 defibrillations, one had 8 defibrillations and four had 21 to 74 defibrillations. These changes consisted of contraction band necrosis in four patients, vacuolar cytoplasmic clearing and loss of myocytes confined to the myocardium under the patch electrode in five patients who had multiple defibrillations. The observed pathologic changes were estimated to affect less than 2% of the total myocardial mass. Thus, the automatic implantable cardioverter-defibrillator lead system and multiple defibrillations result in localized myocardial injury confined to the tissue under the patch electrode.(ABSTRACT TRUNCATED AT 250 WORDS)

Is defibrillation testing safe

Determination of defibrillation thresholds (DFTs) and implantable cardioverter defibrillalur (ICD) testing requires repeated inductions of ventricular fibrillation (VF) and defibrillation attempts using known energy outputs. Little is known about the individual and cumulative effects of repetitive brief episodes of VF and hypoperfusion on cerebral function. The potential clinical utility of quantitative electroencephalographic (QEEG) monitoring during intraoperative ICD testing, by using processed 19‐channel EEG (0.5–35 Hz bandwidth), was examined in ten anesthetized patients, five males and five females (mean age 62 ± 10 years), who underwent ICD implantation and testing. Ischemic QEEG patterns were defined as those with a 3 standard deviation increase (P < 0.01) in absolute delta (1.5–3.5 Hz) power persisting for ≥ 2.5 minutes. The majority (80%) of the VF episodes (70) were accompanied by QEEG “slowing” (doubling of the pre‐VF low frequency delta waves amplitude). All the patients (5/5) experiencing > 6 VF episodes showed a statistically significant increase in the low frequency amplitude. In contrast, this EEG abnormality was apparent in only one of five patients experiencing < 6 VF episodes. These results suggest a cumulative QEEG depression associated with ICD testing. QEEG may provide an objective means for establishing an individualized upper safe limit of DFT testing and the total number of induced VF episodes.

Hemodynamic and surface electrocardiographic effects of a new aqueous formulation of intravenous amiodarone

Intravenous amiodarone is an effective antiarrhythmic agent. However, the standard formulation (Cordarone IV) frequently causes hypotension. Hemodynamic studies have attributed this adverse effect to the solvents employed. A newly developed aqueous formulation (Amio-Aqueous) lacks solvents and thus may not causes hypotension. This study evaluated the hemodynamic effects in a cardiac catheterization laboratory. Two boluses of 150-mg aqueous amiodarone were administered via a peripheral vein to 32 hemodynamically stable patients who underwent cardiac catheterization. Boluses were administered initially over 2 to 5 minutes and in the last 9 patients over 2 minutes. Hemodynamic evaluation was performed and 12-lead electrocardiograms were obtained at baseline, immediately after each bolus, and following 30 minutes of observation. No patient developed hypotension. There were no significant changes in systolic and diastolic blood pressure (BP) following the boluses. Compared with baseline, heart rate (HR) significantly decreased 5 minutes after the second bolus (73 +/- 12 vs 67 +/- 11 beats/min, p <0.05). Mean arterial BP increased (90 +/- 14 vs 100 +/- 16 mm Hg, p <0.05) and dp/dt decreased (1,599 +/- 645 vs 1,294 +/- 531 mm Hg/s p <0.05), whereas the PR, QT, and JT intervals increased (174 +/- 30 vs 182 +/- 33; 402 +/- 32 vs 424 +/- 35; 317 +/- 37 vs 336 +/- 32 ms, p <0.05, respectively) by the end of the 30-minute observation period. Amio-Aqueous possesses pharmacodynamic effects that have been attributed to amiodarone, whereas it lacks the hypotensive effect of the standard intravenous amiodarone formulation. Amio-Aqueous appears to be a safer alternative to Cordarone IV when rapid administration is indicated.

Mapping the coronary sinus and great cardiac vein

GIUDICI, M., et al.: Mapping the Coronary Sinus and Great Cardiac Vein. The purpose of this study was to develop a better understanding of the pacing and sensing characteristics of electrodes placed in the proximal cardiac veins. A detailed mapping of the coronary sinus (CS) and great cardiac vein (GCV) was done on 25 patients with normal sinus rhythm using a deflectable electrophysiological catheter. Intrinsic bipolar electrograms and atrial and ventricular pacing voltage thresholds were measured. For measurement purposes, the GCV and the CS were each subdivided into distal (D), middle (M), and proximal (P) regions, for a total of six test locations. Within the CS and GCV, the average atrial pacing threshold was always lower (P < 0.05) than the ventricle with an average ventricular to atrial ratio > 5, except for the GCV‐D. The average atrial threshold in the CS and GCV ranged from 0.2– to 1.0‐V higher than in the atrial appendage. Diaphragmatic pacing was observed in three patients. Atrial signal amplitude was greatest in the CS‐M, CS‐D, and GCV‐P and smaller in the CS‐P, GCV‐M, and GCV‐D. Electrode spacing did not significantly affect P wave amplitude, while narrower electrode spacing attenuated R wave amplitude. The average P:R ratio was highest with 5‐mm‐spaced electrodes compared to wider spaced pairs. The P:R ratio in the CS was higher (P < 0.05) than in all positions of the GVC. It is possible to pace the atrium independent of the ventricle at reasonably low thresholds and to detect atrial depolarization without undue cross‐talk or noise using closely spaced bipolar electrode pairs. The areas of the proximal, middle, and distal CS produced the best combination of pacing and sensing parameters.

Electrode Surface Area Is An Important Variable for Defibrillation

Previous studies have established efficacy of transseptal defibrillation. The purpose of the present study was to evaluate the role of transvenous electrode surface area for defibrillation. Sixteen dogs were randomized to 8 French and 5 French EnGuard™ electrodes; 8 dogs in each group. The length of the defibrillation coils was identical for both, but the surface area was different due to differences in the electrode diameters. Defibrillation threshold (DFT) testing was performed using a biphasic shock waveform, 6 msec+/2 msec‐. Logistic regression analysis was used to determine if the probability of defibrillation adjusted for voltage, current, and energy was different for 8 French electrodes. Logistic regression analysis found significant differences between 8 French and 5 French electrodes, with less voltage (P < 0.005), current (P < 0.03), and energy (P < 0.001) required at any level of probability to defibrillate for 8 French electrodes. These results support the conclusion that the surface area for endocardial electrodes is a significant factor for defibrillation. Therefore, when designing endocardial electrodes a desirable objective of reducing the electrode size should be weighed against the need to minimize DFTs.

Potential Hazards of Fixed Gain Sensing and Arrhythmia Reconfirmation for Implantable Cardioverter Defibrillators

Appropriate sensing of ventricular tachycardia (VT) and ventricular fibrillation (VF)is of paramount importance for safety of patients with implanted cardioverter defibrillators (ICDs). Recently, the GuardianR ATP 4210, a new third generation ICD that uses programmable but fixed sensing during sinus rhythm and doubles its sensitivity settings when VF is detected, to a maximum programmable sensitivity of 1 mV, has been tested in phase I and II clinical trials. A reconfirmation algorithm of this ICD confirms the presence of VT or VF prior to therapy. This case report describes undersensing of VF in a patient with the GuardianR ATP 4210 at the maximum programmed sensitivity of 1 mV. Inappropriate episodes of asystole and prolonged bradycardias were also observed in this patient due to shortcomings in the reconfirmation algorithm design. Reoperation was required, with positioning of a new endocardial sensing lead to correct the undersensing of VF. This, however, did not correct asystolic pauses following antitachycardia pacing or spontaneous tachycardio termination prior to therapy. This case report highlights the hazards of fixed gain sensing for implantable ICDs and a potential limitation of a specific tachyarrhythmia reconfirmation algorithm used in this device.

Transseptal defibrillation is superior for transvenous defibrillation.

The conventional electrode configuration of current internal defibrillation systems most commonly use superior vena caval (SVC) or combined SVC and subcutaneous (SC) electrodes as anode, and right ventricular apex (HVA) electrode as cathode. We have demonstrated earlier that the septal mass is important for defibrillation. The purpose of the present study was to compare a transseptal to a conventional electrode arrangement in the canine model. Three endocardial electrodes, 5 French EnGuard™ were positioned in RVA, SVC, and the right ventricular outflow (RVO) in eight dogs. A 5 French SC electrode was positioned in the fifth left intercostal space. RVA‐RVO‐/SC+ (configuration 2) was compared to SVC‐SC+/RVA‐(configuration 1). Defibrillation threshold testing was performed using asymmetrical biphasic shock, 6 msec+/2 msec‐. Probit fit was used to compare the results at 40%, 50%, 60%, and 90% probabilities, and the logistic regression analysis to estimate the impact of variables. Electrode configuration had the strongest predictive value. Configuration 2 was superior to configuration 1 (P = 0.0016). At any voltage settings the probability of success for configuration 2 was greater, and current less (P < 0.00005). The energy requirements were reduced by approximately 33% for configuration 2. There were no significant differences in impedance between the two configurations. We conclude that transseptal defibrillation is more effective because of the improved lead geometry and voltage gradient.

False-Positive Troponin I in a Patient with Acute Cholecystitis and Positive Rheumatoid Factor Assay

Accessible online at: www.karger.com/journals/crd Dear Sir, Here we describe a unique case of falsely elevated cardiac troponin I (cTnI) in a patient presenting with acute cholecystitis and positive rheumatoid factor (RF) without any clinical or laboratory evidence of myocardial damage. Several studies have shown improved specificity of cTnI over creatinine kinase (CK-MB) for acute myocardial damage [1, 2]. It is extensively used as an indicator of myocardial damage to identify acute myocardial infarction. Because of its high specificity, a false-positive result is very rare with the second-generation assays. A 52-year-old Afro-American female presented with a 3 days’ history of right upper quadrant abdominal pain radiating to the right intracapsular area which was associated with anorexia, nausea and low grade fever. She denied any vomiting, diarrhea, chest discomfort or dyspnea. Her previous medical history included asthma, obstructive sleep apnea, hypertension, nephrolithiasis and hysterectomy. The patient did not give any history of immunization or exposure to animals. Physical examination was remarkable for tenderness and guarding in the right upper abdominal quadrant. Laboratory abnormalities included a white cell count of 23.1 ! 103/Ìl with normal serum transaminases, amylase, lipase and renal function. A 12-lead electrocardiogram did not show any evidence of myocardial infarction. Echocardiography showed left ventricular ejection fraction 60% with no evidence of segmental wall motion abnormalities. Cardiac catheterization showed normal coronary arteries and normal left ventriculography. CT scan of the abdomen showed diffused inflammation of the gallbladder with cholelithasis. Cardiac enzymes are shown in table 1. In our laboratory cTnI is measured by using Abbot Laboratories AXSYM systems (AXSYM). It is a dual-site assay, which uses mouse monoclonal antibody. The patient was initially treated with intravenous antibiotic and fluids, which resolved the acute cholecystitis. Subsequently, she underwent elective cholecystectomy, which confirmed cholelithiasis and acute cholecystitis. At 1-month follow-up, serum cTnI was repeated and noted to be 14.7 ng/ml. At this time, the cTnI assay was repeated from the same sample using a different method, Stratus Cardiac Troponin-I Immunoassay from Dade Behring Laboratories (Stratus), which is also a dual-site assay, but uses different antibodies. Troponin I was reported to be within the normal range (0.1 ng/ml). When the same sample was treated with heterophilic antibody adsorption reagent, cTnI was measured to be 2.3 ng/ml, which was mildly elevated. Since it was previously reported that RF present in serum of some patients may interfere with measurements of some biochemical assays using a similar type of dual-site immunoassays as the AXSYM system [3], an RF assay was done to exclude this