Arnold Pinter

The effect of vernakalant (RSD1235), an investigational antiarrhythmic agent, on atrial electrophysiology in humans.

Objectives: To determine the acute effects of vernakalant (RSD1235) on electrophysiologic (EP) properties in humans. Background: Vernakalant is an investigational mixed ion channel blocker that can terminate acute atrial fibrillation (AF) in humans at 2 to 5 mg/kg and may be more “atrial-selective” than available agents. Methods: Patients (N = 19; 53% male; age, 48 ± 11 years) underwent EP study before and after 25 minutes of intravenous vernakalant administration: 2 mg/kg over 10 min + 0.5 mg/kg/hr for 35 min or 4 mg/kg over 10 min + 1 mg/kg/hr for 35 min. EP measurements, including atrial refractory period (AERP) and ventricular refractory period (VERP), were obtained. Results: The lower dose prolonged AERP at 600, but not at 400 or 300 msec paced cycle length. The higher dose significantly prolonged AERP from 203 ± 31 msec to 228 ± 24 msec at 600 msec, 182 ± 30 msec to 207 ± 27 msec at 400 msec, and 172 msec ± 24 to 193 ± 21 msec at 300 msec. There was no significant prolongation of VERP at either dose or at any cycle length. There was a small but significant prolongation of AV nodal refractoriness; Wenckebach cycle length prolonged by 18 ± 12 msec (from baseline 343 ± 54 msec) at the higher dose (P < 0.05). Sinus node recovery time also increased by 123 ± 158 msec (from baseline 928 ± 237 msec) at the higher dose (P < 0.05). There was a slight prolongation of QRS duration at the higher dose, during ventricular pacing at CL = 400 msec (15 ± 15 msec, P = 0.0547). QT and HV intervals were unchanged. Conclusions: At doses similar to those tested clinically, vernakalant dose-dependently prolonged atrial refractoriness, prolonged AV nodal conduction and refractoriness, and slightly prolonged QRS duration, but it had no effect on ventricular refractoriness.

Sex differences in implantable cardioverter-defibrillator outcomes: findings from a prospective defibrillator database.

BACKGROUND Sex differences in the use and outcomes of implantable cardioverter-defibrillators (ICDs) have not been fully studied. OBJECTIVE To examine potential sex differences in ICD implantation and device outcomes. DESIGN Health payer-mandated, prospective study of patients referred for ICD implantation, with comprehensive, longitudinal follow-up for complications, deaths, and device outcomes. SETTING 18 ICD implantation and follow-up centers in Ontario, Canada. PATIENTS 6021 patients (4733 men) referred for ICD implantation from February 2007 to July 2010. MEASUREMENTS Multivariate-adjusted ICD implantation rate, complications up to day 45, multivariate-adjusted complications, device outcomes (including appropriate shocks and therapies), and deaths occurring during 1-year follow-up. RESULTS Rates of ICD implantation were similar in men and women (relative risk, 0.99 [95% CI, 0.97 to 1.02]; P = 0.60). However, women were significantly more likely to experience major complications by 45 days (odds ratio, 1.78 [CI, 1.24 to 2.58]; P = 0.002) and 1 year (hazard ratio [HR], 1.91 [CI, 1.48 to 2.47]; P < 0.001) after implantation. Occurrence of any major or minor complication was also increased in women at both 45-day follow-up (odds ratio, 1.50 [CI, 1.12 to 2.00]; P = 0.006) and 1-year follow-up (HR, 1.55 [CI, 1.25 to 1.93]; P < 0.001). After implantation, women were less likely than men to receive appropriate ICD shock (HR, 0.69 [CI, 0.51 to 0.93]; P = 0.015) or appropriate therapy via shock or antitachycardia pacing (HR, 0.73 [CI, 0.59 to 0.90]; P = 0.003). Total mortality among defibrillator recipients did not differ between men and women (HR, 1.00 [CI, 0.64 to 1.55]; P = 0.99). LIMITATION The differential effects of sex on prereferral events were not examined. CONCLUSION Although ICD implantation rates were similar after referral to an electrophysiologist, women who underwent ICD implantation had greater risks for complications and were less likely to experience appropriate ICD-delivered therapies than men. PRIMARY FUNDING SOURCE Canadian Institutes of Health Research and Ontario Ministry of Health and Long-Term Care.

Outcome of advisory implantable cardioverter-defibrillator replacement: one-year follow-up.

BACKGROUND Implantable cardioverter defibrillator (ICD) generator advisories present management dilemmas for physicians regarding competing risks of ICD failure and replacement-related complications. There is currently a paucity of long-term data concerning the complications associated with advisory ICD replacement. OBJECTIVE In a large multicenter advisory ICD generator replacement cohort followed for 12 months, we aimed to assess replacement-related complications by performing a case-control determination of complication risk factors to identify characteristics that could assist with advisory ICD replacement decision making. METHODS Twelve large ICD implanting centers reviewed the 1-year follow-up outcome of advisory ICDs replaced between October 2004 and October 2005. The complication cohort was characterized and compared in a nested case-control analysis with age- and gender-matched controls without complications from the same replacement population. RESULTS At the 12 participating institutions, 451 of 2635 advisory ICD devices were replaced (17.1%). Over 355 +/- 204 days of follow-up, there were 41 (9.1%) complications; 27 (5.9%) required reoperation and included two deaths. There were 14 minor complications (3.1%). Multivariate analysis demonstrated that the number of previous pocket procedures was associated with an increase in complications and that combined consultant and fellow operators was associated with a decrease in complications compared with a single operator alone. CONCLUSIONS Complications from advisory ICD generator replacement are frequent and include infection and, rarely, death. The risk of replacement is increased in patients with multiple previous pocket procedures.

Complications due to abandoned noninfected pacemaker leads.

BÖHM, Á., et al.: Complications Due to Abandoned Noninfected Pacemaker Leads. Noninfected unwanted pacemaker leads are usually abandoned since the reported complication rate related to them is low. We followed 60 patients with noninfected retained leads, and complication was observed in 12 (20%) of them. Lead migration occurred in 5 patients, skin erosion in 3 patients, venous thrombosis in 2 patients, and muscle stimulation in 2 patients. Management of the complications was a surgical procedure in seven patients, including two cases of open heart surgery, while chronic medical treatment was necessary in the other five patients. The results of this study suggest that complications due to noninfected abandoned leads may not be as rare as it was previously thought and may present a significant morbidity and cost burden. With the lead extraction technique available, the issue of the removal of all unwanted pacemaker leads should be addressed.

New Body Surface Isopotential Map Evaluation Method to Detect Minor Potential Losses in Non–Q-Wave Myocardial Infarction

BACKGROUND Potential losses caused by stable non-Q-wave myocardial infarction (MI) are too small to diagnose with the use of standard ECG. The aim of the present study was to obtain accurate diagnostic criteria for this prognostically important disease with the help of body surface mapping. METHODS AND RESULTS Body surface potentials were recorded with the use of 63 unipolar leads in 45 patients with a non-Q-wave MI (41 to 75 years old); 24 healthy adults, 42 patients with unstable angina, and 70 patients with Q-wave MI served as reference groups. Qualitative pathological features of the isopotential maps, such as onset time and site and magnitude of the first right-anterior/anterior minimum, as well as pathological negativities at that time, were defined in non-Q-wave MI cases. These features, which account for the activation sequence and the body surface projections of specific cardiac regions (Selvester classification), showed a 91% sensitivity and an 88% specificity for the detection of non-Q-wave MI. In comparison, the different departure maps (first third QRS, QRS, and QRST isoarea) resulted in less favorable specificities (50% to 58%). Concordance between the isopotential maps and the acute-phase ECG (90%), hypokinesis (64%), fixed perfusion defects (59%), and significant stenosis of the infarct-related coronary artery (87%) supported the concept that these isopotential map changes correspond to the supposed sites of MI. There were pathological features in 69% of patients with unstable angina, with similar concordances as in non-Q-wave MI. CONCLUSIONS Isopotential maps revealed characteristic features that were suitable for the detection and localization of non-Q-wave MI in the clinical setting of unstable coronary artery disease.

Role of antiarrhythmic drugs in patients with implantable cardioverter defibrillators

The transvenous implantable cardioverter defibrillator (ICD) has emerged as the primary therapy for patients at high risk of life-threatening ventricular arrhythmias. A high number of ICD recipients will require subsequent adjunctive treatment with antiarrhythmic drugs (AADs). This review provides an overview of potential reasons for AAD initiation, candidates for treatment, current medical options, and possible drug-device interactions.

Efficacy and safety of dofetilide in the treatment of frequent ventricular tachyarrhythmias after amiodarone intolerance or failure.

To the Editor: Many patients with an implantable cardioverter-defibrillator (ICD) require concomitant antiarrhythmic drug (AAD) therapy at some point. Sotalol and especially amiodarone have been shown to reduce the number of ventricular tachycardia (VT)/ventricular fibrillation (VF) episodes and

Intravenous antiarrhythmic agents.

Intravenous antiarrhythmic drugs can be used as diagnostic tools; for example, adenosine can be used to reveal the underlying rhythm in narrow QRS tachycardia. Newer class III antiarrhythmic agents, like ibutilide and dofetilide, are effective at the conversion of acute atrial fibrillation; however, electrical cardioversion is still the most effective method for restoration of sinus rhythm in persistent atrial fibrillation. Lidocaine and bretylium in the treatment and prevention of ventricular tachyarrhythmia are de-emphasized because of inefficacy, safety concerns (lidocaine), or shortage of drug (bretylium). Procainamide is effective for stable ventricular tachycardia, and amiodarone is effective in the treatment of shock-refractory ventricular fibrillation. Adrenergic blockade is likely important in the management of tachyarrhythmias, particularly in electrical storm, but more data will be necessary to establish its role.

The Burden of Atrial Fibrillation: Should We Abandon Antiarrhythmic Drug Therapy?

Atrial fibrillation (AF) is the most common sustained arrhythmia, exacting a substantial toll in cardiovascular morbidity and mortality. Until recently, the prevailing philosophy has been that restoration and maintenance of normal sinus rhythm, as opposed to control of ventricular response rate, was the optimal approach to treatment of AF. A series of landmark trials (AFFIRM, RACE, STAF, and PIAF) have called this strategy into question, suggesting outcomes are equivalent with both approaches. These data do not mean that rhythm control is not beneficial, but highlight the limitations of current therapies to achieve and maintain sinus rhythm. Limitations of the rhythm-control strategy may be related to our difficulty in accurately documenting symptomatic benefit from this approach, the lack of efficacy and excessive adverse-effect burden associated with currently available antiarrhythmic agents, and selection biases in the enrollment of patients in clinical trials of rhythm control versus rate control, making the trials incompletely representative of the population eligible for therapy. New pharmacologic agents under development feature increased atrial selectivity or multi-channel-blocking properties (or both). As a result, these compounds may be more effective in prolonging atrial refractoriness and may also have reduced proarrhythmic potential. It is premature to abandon the concept of rhythm control in AF until we have trials designed to include younger and highly symptomatic patients, more sensitive tools to measure symptomatic improvement, and safer, more effective antiarrhythmic agents.

Three-dimensional localization versus fluoroscopically only guided ablations: a meta-analysis.

Abstract Objectives. Data regarding efficacy and safety of three-dimensional localization systems (3D) are limited. We performed a meta-analysis of randomized trials comparing combined fluoroscopy- and 3D guided to fluoroscopically-only guided procedures. Design. A systematic search was performed using multiple databases between 1990 and 2010. Outcomes were acute and long-term success, ablation, procedure and fluoroscopic times, radiation dose (RD), and complications. Results. Thirteen studies involving 1292 patients were identified. 3D were tested against fluoroscopic guidance in 666 patients for supraventricular tachycardia (SVT), atrial flutter (AFL), atrial fibrillation (AF), and ventricular tachycardia (VT). Acute and long-term freedom from arrhythmia was not significantly different between 3D and control for AFL (acute success, 97% vs. 93%, p = 0.57; chronic success, 93% vs. 96%, p = 0.90) or for SVT (acute success, 94% vs. 100%, p = 0.36; chronic success, 88% vs. 88%, p = 0.80). A shorter fluoroscopic time was achieved with 3D in AFL (p < 0.001) and in SVT (p = 0.002). RD was significantly less for both AFL (p = 0.002) and SVT (p = 0.01). Ablation and procedure time and complications were not statistically different. Conclusions. Success, procedure time, and complications were similar between fluoroscopy- and 3D-guided ablations. Fluoroscopic time and RD were significantly reduced for ablation of AFL and SVT with 3D.