Joerg Neuzner

An Entirely Subcutaneous Implantable Cardioverter–Defibrillator

BACKGROUND Implantable cardioverter-defibrillators (ICDs) prevent sudden death from cardiac causes in selected patients but require the use of transvenous lead systems. To eliminate the need for venous access, we designed and tested an entirely subcutaneous ICD system. METHODS First, we conducted two short-term clinical trials to identify a suitable device configuration and assess energy requirements. We evaluated four subcutaneous ICD configurations in 78 patients who were candidates for ICD implantation and subsequently tested the best configuration in 49 additional patients to determine the subcutaneous defibrillation threshold in comparison with that of the standard transvenous ICD. Then we evaluated the long-term use of subcutaneous ICDs in a pilot study, involving 6 patients, which was followed by a trial involving 55 patients. RESULTS The best device configuration consisted of a parasternal electrode and a left lateral thoracic pulse generator. This configuration was as effective as a transvenous ICD for terminating induced ventricular fibrillation, albeit with a significantly higher mean (+/-SD) energy requirement (36.6+/-19.8 J vs. 11.1+/-8.5 J). Among patients who received a permanent subcutaneous ICD, ventricular fibrillation was successfully detected in 100% of 137 induced episodes. Induced ventricular fibrillation was converted twice in 58 of 59 patients (98%) with the delivery of 65-J shocks in two consecutive tests. Clinically significant adverse events included two pocket infections and four lead revisions. After a mean of 10+/-1 months, the device had successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. CONCLUSIONS In small, nonrandomized studies, an entirely subcutaneous ICD consistently detected and converted ventricular fibrillation induced during electrophysiological testing. The device also successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. (ClinicalTrials.gov numbers, NCT00399217 and NCT00853645.)

Effect of Biphasic Waveform Pulse on Endocardial Defibrillation Efficacy in Humans

Several clinical studies have proved increased defibrillation efficacy for implantable cardioverter defibrillators with biphasic pulse waveforms compared to monophasic pulse waveforms. This difference in defibrillation efficacy depends on the type of defibrillation lead system used. The influence of biphasic defibrillation pulse waveforms on the defibrillation efficacy of purely endocardial defibrillation lead systems has not yet been sufficiently examined, we, therefore studied 30 consecutive patients with drug refractory ventricular tachyarrhythmias during the implantation of a cardioverter defibrillator. After implanting an endocardial “integrated” sensing/defibrillation lead we performed a prospective randomized comparison of the defibrillation efficacy of monophasic and biphasic defibrillation waveform pulses. For endocardial defibrillation with the biphasic waveform the mean defibrillation threshold was 12.5 ± 4.9 joules and for the monophasic waveform 22.2 ± 5.6 joules (P < 0.0001). There was a decrease in the required defibrillation energy of biphasic defibrillation in 29/30 patients. Thus considering purely endocardial defibrillation a statistically significant and clinically relevant increase in defibrillation efficacy can be demonstrated for biphasic defibrillation waveform pulses.

Safety and efficacy of implantable defibrillator therapy with programmed shock energy at twice the augmented step-down defibrillation threshold: results of the prospective, randomized, multicenter low-energy endotak trial ☆

Whether the safety and efficacy of implantable cardioverter defibrillator (ICD) therapy can be assured with lower output devices is an important question. The purpose of this study was to evaluate whether programming the device output at twice the augmented defibrillation threshold was as safe and effective as using the maximum energy. Patients indicated for ICD therapy, but without slow monomorphic ventricular tachycardia (MVT), who achieved an augmented defibrillation threshold (DFT plus) < or = 15 joules (J) with a single endocardial lead system and a biphasic defibrillator were included in the study. Prior to ICD implantation, patients were randomized into 2 groups. The shock energies in test group patient were set as follows: first shock at twice DFT plus, the second to fifth shocks at maximum output (34 J). In control group patients, all shocks were programmed at 34 J. The study population consisted of 166 consecutive patients (mean age 57.4 +/- 12.1 years, mean left ventricular ejection fraction 36.8 +/- 13.8%). Mean DFT plus was 9.6 +/- 3.2 J in test group patients and 10.1 +/- 3.5 J in control group patients (p = 0.36). During a mean follow-up of 24.2 +/- 9.6 months, 736 arrhythmia episodes were analyzed. The first shock efficacy was 98.3% in the test group patients versus 97.4% in the control group (p = 0.45). Total mortality was 6%, equally distributed in both study groups. The results of this study prove that the method of doubling the defibrillation energy at the DFT plus level provides an adequate safety margin in defibrillator therapy.

Clinical Experience with a New Cardioverter Defibrillator Capable of Biphasic Waveform Pulse and Enhanced Data Storage: Results of a Prospective Multicenter Study

A recently introduced cardioverter defibrillator was implanted in 162 patients with refractory ventricular tachyarrhythmias and/or aborted sudden cardiac death. The new device is capable of delivering monophasic and biphasic defibrillation waveform pulses, arrhythmia detection, and therapy in two independently programmable zones, antibradycardia and postshock pacing. Additionally, the device provides enhanced data logs by storing intracardiac “far‐field” electrograms of spontaneous arrhythmic episodes. One hundred sixty‐two patients (mean age 55.5 years; mean left ventricular ejection fraction 36%) were enrolled in this multicenter investigation; coronary artery disease was the primary cardiac disease in 63.6% of the patients, idiopathic cardiomyopathy in 23.8%. Ventricular fibrillation was present in 49.7% of the patients; 29.3% of the patients experienced ventricular fibrillation and ventricular tachycardia; monomorphic ventricuiar tachycardia alone was present in 19.1% of the patients. In 26 patients the device was implanted with standard epicardial defibrillation leads (mean defibrillation threshold 11.5±3.7J). One hundred thirty‐nine patients underwent testing for implantation of a nonthoracotomy system and in 136 (98%), a nonthoracotomy system could be implanted. Defibrillation thresholds with a biphasic waveform (mean 10.2 ± 4.3 J) were lower than with a monophasic waveform (mean 17.4 ± 5.7 J). Two patients (1.2%) died perioperatively (< 30 days). During study time period follow‐up, there were 338 device discharges in 49 patients. Analysis of stored electrograms classified 25% of discharges as inappropriate and due to supraventricular tachyarrhythmias. At a mean follow‐up of 10.8 months, cumulative survival from sudden cardiac death was 98.8%, and survival from all‐cause mortality was 96.3%. This study demonstates the effectiveness of a new implantable cardioverter defibrillator in preventing arrhythmic death and the superior defibrillation efficacy of biphasic waveform pulses, which results in a higher implantation rate of nonthoracotomy systems, as well as the accurate arrhythmia classification made possible by the stored electrograms.

The rationale and design of the Shockless IMPLant Evaluation (SIMPLE) trial: A randomized, controlled trial of defibrillation testing at the time of defibrillator implantation

Defibrillation testing (DT) has been an integral part of defibrillator (implantable cardioverter defibrillator [ICD]) implantation; however, there is little evidence that it improves outcomes. Surveys show a trend toward ICD implantation without DT, which now exceeds 30% to 60% in some regions. Because there is no evidence to support dramatic shift in practice, a randomized trial is urgently needed. The SIMPLE trial will determine if ICD implantation without any DT is noninferior to implantation with DT. Patients will be eligible if they are receiving their first ICD using a Boston Scientific device (Boston Scientific, Natick, MA). Patients will be randomized to DT or no DT at the time of ICD implantation. In the DT arm, physicians will make all reasonable efforts to ensure 1 successful intraoperative defibrillation at 17 J or 2 at 21 J. The first clinical shock in all tachycardia zones will be set to 31 J for all patients. The primary outcome of SIMPLE will be the composite of ineffective appropriate shock or arrhythmic death. The safety outcome of SIMPLE will include a composite of potentially DT-related procedural complications within 30 days of ICD implantation. Several secondary outcomes will be evaluated, including all-cause mortality and heart failure hospitalization. Enrollment of 2,500 patients with 3.5-year mean follow-up will provide sufficient statistical power to demonstrate noninferiority. The study is being performed at approximately 90 centers in Canada, Europe, Israel, and Asia Pacific with final results expected in 2013.

Myocardial injury during radiofrequency catheter ablation: comparison of focal and linear lesions.

CARLSSON, J., et al.: Myocardial Injury During Radiofrequency Catheter Ablation: Comparison of Focal and Linear Lesions. The aim of study was to investigate the extent of myocardial injury incurred by creation of continuous RF current induced linear ablation lesions (LL; ablation of atrial fibrillation, right atrial procedure) in comparison to focal RF lesions (FL; AV node reentry tachycardia, WPW tachycardia). In 23 patients with LL (age 51.3 ± 11.2 years, 18 men, 5 women) and in 16 patients with FL (age 53.9 ± 5.1 years, 8 men and 8 women), levels of creatine kinase (CK), myoglobin (MG), CKMB mass (CKMB M), CKMB activity (CKMB A), and cardiac troponin T (cTnT) were determined before and 2, 4, 8, 24, and 48 hours after ablation. CKMB A was normal in 87% in LL and 100% in FL (< 6% of CK) with median maximum CK values of 214 (45–1583) U/L in LL and 36 (29–212) U/L in FL. Peak values of all parameters were significantly higher in LL than in FL. The sensitivity of cTnT was 50% in FL and 100% in LL. In FL MG, total CK, and CKMB M were abnormal in only 12.5% of cases while in LL MG and CKMB M were pathological in 100% and total CK was abnormal in 91.3% of patients. The amount of energy and number of RF applications correlated with cTnT, MG, and CKMB M (P = 0.01). In conclusion, (1) long linear RF current lesions for ablation of atrial fibrillation are associated with significantly greater myocardial injury than focal ablations. (2) In focal lesions only cTnT provided a sensitivity of 50% in the detection of myocardial injury while in linear lesions cTnT, CKMBM, and CKMB M seemed suitable for detection of RF current induced myocardial damage with 100% sensitivity. All biochemical parameters do not differentiate patients with coronary ischemia up to 48 hours after an ablation. (3) Further investigations are necessary to determine if RF current linear lesions lead to impaired atrial contractility in cases of extensive tissue damage.

Feasibility of Automated Detection of Advanced Sleep Disordered Breathing Utilizing an Implantable Pacemaker Ventilation Sensor

Objectives: This study tested the feasibility of automatically detecting advanced sleep disordered breathing (SDB) from a pacemaker trans‐thoracic impedance sensor.

Possible Role of Epicardial Left Ventricular Programmed Stimulation in Brugada Syndrome

CARLSSON, J., et al.: Possible Role of Epicardial Left Ventricular Programmed Stimulation in Brugada Syndrome. A patient with recurrent syncope due to polymorphic ventricular tachcardia was diagnosed with Brugada syndrome. Programmed right ventricular stimulation could not induce arrhythmia. Epicardial stimulation from a left ventricular site through the coronary sinus led to polymorhic VT. The stimulation protocol for risk stratification in Brugada syndrome is discussed.

Electrophysiological Heterogeneity of Atrial Fibrillation and Local Effect of Propafenone in the Human Right Atrium: Analysis Based on Symbolic Dynamics

A recently developed algorithm that is based on symbolic dynamics and computation of the normalized algorithmic complexity (Cα) was applied to basket-catheter mapping of the atrial fibrillation (AF). The aim of our study was to analyze the spatial distribution of the Cα during AF and effects of propafenone on this distribution. During right atrial mapping in 25 patients with AF 31 intra-atrial and 1 surface bipolar channels were acquired. The anatomical location of the intra-atrial electrodes was defined fluoroscopically. Cα was calculated for a moving window (size: 2000 points; step 500 points). Generated Cα was analyzed within 10 minutes before and after administration of propafenone. The inter-regional Cα distribution was analyzed using the Friedman-test (intra-individually) and Kruskall-Wallis-H-test (inter- individually). A value of p=0.05 was set for an error probability. Inter-regional Cα differences were found in all patients (p<0.001). The right atrium could be divided in high- and low complexity areas according to individual patterns. A significant Cα increase in cranio-caudal direction (with the exception of septum) was confirmed inter-individually (p<0.01). The administration of propafenone enlarged the areas of low complexity.Conclusions: This new method utilizing the combination of symbolic dynamics and adaptive power estimation can provide complex evaluation of the dynamics of AF in man. High-density mapping will be required for further evaluation of results.

Homogeneity and Diameter of Linear Lesions Induced With Multipolar Ablation Catheters: In Vitro and In Vivo Comparison of Pulsed Versus Continuous Radiofrequency Energy Delivery

AbstractBackground: For invasive treatment of atrial fibrillation, linear lesions induced with multipolar ablation catheters (MAC) are needed to prevent recurrence. The aim of the study was to compare the efficacy of pulsed versus continuous radiofrequency (RF)-energy delivery using MAC. Methods: In vitro tests were performed using endomyocardial preparations of fresh pig hearts in a 10-liter-bath of physiologic saline solution (37°C) at constant flow conditions (1.5[emsp4 ]l/min). The MAC were placed with a constant pressure of 20 ponds onto the endocardium. The energy (generator: Osypka HAT 200 S) was delivered either pulsed (4 electrodes simultaneously, 5[emsp4 ]ms duty-cycle) or continuously (each electrode separately). In vivo experiments were performed in 6 anesthetized pigs using fluoroscopic positioning of MAC at 40 different intracardial positions and with similar conditions as in vitro experiments. Lesion volume (LV) was calculated after measuring lesion diameter with a microcaliper. The homogeneity of the lesions (LH) was classified from 1–4; with 1 as highest homogeneity. Results: Pulsed energy delivery produced more homogeneous linear lesions in significantly less time. There was no difference in electrode temperature values (50.2±0.8 and 51.3±1.4°C) in vitro and in vivo. In the in vivo experiments, lesion depth and calculated lesion volume were less in both modes of energy delivery but pulsed energy delivery was superior regarding lesion depth and homogeneity. Conclusion: With pulsed energy delivery it is possible to create linear lesions of significantly greater homogeneity. Moreover, larger lesions are induced in less time by pulsed energy delivery in vitro and in vivo.