Efficacy of Antitachycardia Pacing in Patients Presenting with Cardiac Arrest

The efficacy of antitachycardia pacing (ATP) incorporated into implantable cardioverter defibrillators (ICDs) was assessed in 29 consecutive survivors of cardiac arrest, not attributable to acute myocardial infarction, ischemia, or drug and electrolyte effects. The cohort included 25 men and 4 women with a mean age of 65 years and a mean left ventricular ejection fraction of 29%. Seventeen patients had coronary artery disease, 11 had nonischemic dilated cardiomyopathy, and 1 had long QT syndrome. Programmed stimulation yielded monomorphic ventricular tachycardia (VT) in 17 patients, polymorphic VT in 6, and no inducible VT in 6. During a mean follow-up of 22 months, a total of 91 episodes of monomorphic VT occurred, 73 of which were successfully pace terminated (83%). Monomorphic VT amenable to pace termination recurred only in the group that had this arrhythmia inducible. The recurrent arrhythmias in the 12 patients having either no inducible VT or polymorphic VT were all rapid VTs, having a cycle length < 220 ms; and therefore, not amenable to pace termination. These results suggest that ATP incorporated into ICDs is useful in survivors of cardiac arrest and may significantly reduce the number of shocks that these patients would otherwise receive. Programmed stimulation may also help to define those patients who would receive the maximum benefit from ATP.     

Interaction of troponin-H and glutathione S-transferase-2 in the indirect flight muscles of Drosophila melanogaster

Summary Drosophila indirect flight muscles (IFMs) contain a 35 kDa protein which cross-reacts with antibodies to the IFM specific protein troponin-H isoform 34 (TnH-34). Peptide fingerprinting and peptide sequencing showed that this 35 kDa protein is glutathione S-transferase-2 (GST-2). GST-2 is present in the asynchronous indirect flight muscles but not in the synchronous tergal depressor of the trochanter (jump muscle). Genetic dissection of the sarcomere showed that GST-2 is stably associated with the thin filaments but the presence of myosin is required to achieve the correct stoichiometry, suggesting that there is also an interaction with the thick filament. The two Drosophila TnHs (isoforms 33 and 34) are naturally occurring fusion proteins in which a proline-rich extension of ~250 amino acids replaces the 27 C-terminal residues of the muscle-specific tropomyosin II isoform. The proteolytic enzyme, Igase, cleaves the hydrophobic C-terminal sequence of TnH-34 at three sites and TnH-33 at one site. This results in the release of GST-2 from the myofibril. The amount of GST-2 stably bound to the myofibril is directly proportional to the total amount of undigested TnH. It is concluded that GST-2 in the thin filament is stabilized there by interaction with TnH. We speculate that the hydrophobic N-terminal region of GST-2 interacts with the hydrophobic C-terminal extension of TnH, and that both are close to a myosin cross-bridge. This revised version was published online in August 2006 with corrections to the Cover Date.     

Acute and Chronic Cycle Length Dependent Increase in Ventricular Pacing Threshold

Several factors have been shown to influence ventricuJar pacing threshold in humans, including pacing lead location (endocardial vs epicardial), lead maturation, and antiarrhythmic agents. To determine whether ventricuJar pacing rate has a significant influence on acute and chronic pacing thresholds, we measured pacing thresholds in 16 patients receiving an implantafaleantitachycardia pacemaker cardioverter defibrillator (Cadence?). Ventricular pacing thresholds were determined using the device programmer at cycle lengths of GOO, 400, and 300 msec at the time of implantation; prior to hospital discharge at 3-14 days; and during follow-up outpatient visits at 6-8 weeks, 3 months, and 6 months to 1 year. Eleven patients had an epicardial lead system and five an endocardial lead system. Eleven patients were being treated with antiarrhythmic drug therapy. Device output ranged from 1-10 V and was adjustable in 1-V increments (pulse width was held constant at 1 msec). A cycle length dependent increase in pacing threshold (defined as a ≤ 1-V increase in threshold at 400 or 300 msec relative to 600 msecj was observed in 10/16 patients during 12/72 pacing trials at 400 msec, and in 15/16 patients during 31/67 trials at 300 msec. In trials in which an increase in pacing threshold occurred, the magnitude of the increase at 400 msec relative to 600 msec was only 1 V in all 12 trials, but at 300 msec the increase ranged from 4–9 V in 7/31 (23%) trials. There was an equal percentage (67%) of patients demonstrating a cycle length dependent increase in threshold with measurements made at the time of device implantation and at the 6 month to 1 year follow-up period. Two-way analysis of variance showed a significant effect of cycle length and time from implantation on mean pacing thresholds at the three cycle lengths. In conclusion, a cycle length dependent increase in pacing threshold occurred in virtually all patients during follow-up of up to 12 months and, thus, its presence was independent of lead location, presence of antiarrhythmic agents, and the state of lead maturation. These findings suggest that pacing thresholds measured at rates just above the sinus rate may not always apply to the faster rates utilized for antitachycardia pacing and indicates the need for threshold measurement at the designed pacing rate.     

Childhood immunization: Meeting targets yet respecting consent

In England and Wales, general practitioners receive extra paymentswhen they meet the set targets that certain percentages of theiryoungest patients are immunized. Fifty-eight primary healthcare practitioners were interviewed about their views on childhoodimmunization and how targets with financial incentives mightaffect parents' choice about Immunization. They were asked about2 responsibilities which can potentially be in conflict: toincrease rates of childhood immunization, yet also to respectparents' voluntary choice about whether their child is to beimmunized. Professionals' reported uncertainties and disagreementsare described and the view that these can be resolved throughtraining in communication skills is discussed.     

Comparison of Simultaneous Versus Sequential Defibrillation Pulsing Techniques Using a Nonthoracotomy System

The defibrillation threshold (DFT) using simultaneous (SIML) versus sequential (SEQ) pathways for shock delivery was compared in 16 patients with an implanted cardioverter defibrillator. All patients had three-lead nonthoracotomy systems (NTL) using a left chest subcutaneous patch, a right ventricular endocardial lead, and a lead in the coronary sinus (n = 5) or superior vena cava (n = 11). The DFT were determined 2–44 days (17 ± 17 days) after implantation. The DFT was defined as the lowest energy shock that resulted in successful defibrillation. The first pathway tested was SIML in 12 and SEQ in 4 patients with output beginning at or above the intraoperative DFT, routinely 18 J. The second pathway was tested beginning 2–4 J above the DFT of the first tested pathway. All shocks were delivered in 2–4 J decrement or increment steps. The SEQ pathway shocks resulted in a significantly lower DFT than SIML pathway shocks (14 ± 6 vs 18 ± 6 J; I < 0.01). There was no difference in the time delay after ventricular fibrillation initiation before shock delivery for the successful defibrillation between SIML versus SEQ pathways (7 ± 2 secs for both pathways). In 7 of 16 patients, defibrillation using SEQ pathway resulted in a > 5 J lowering of DFT, while only one patient had > 5 J lowering of DFT using SIML shocks (P <0.05). These results have important implications for selecting the optimal pathway for implantable cardioverter defibrillator therapy with a multilead NTL system.     

Early Postoperative Increase in Defibrillation Threshold with Nonthoracotomy System in Humans

The stability of the defibrillation threshold (DFT) early after implantation of an implantable cardioverter defibrillator was evaluated in 15 patients. All but one patient had a three lead nonthoracotomy system using a subcutaneous patch, a right ventricular endocardial lead, and a lead in coronary sinus (n = 5) or superior vena cava (n = 9). Shocks were delivered using simultaneous in nine, sequential in three, and single pathway (coronary sinus not used) in one patient. DFTs were measured at implant (n = 15), 2–8 days postoperation (postop, n = 15), and 4–6 weeks later (n = 8). The DFT was defined as the lowest energy shock that resulted in successful defibrillation. The DFT was assessed with output beginning at 18 joules or 2–4 joules above the implant DFT. All shocks were delivered in 2- to 4-joule increments or decrements. DFTs were significantly higher postoperatively than DFTs at implant (22.7 ± 7.0 J vs 16.9 ± 3.9 J; P < 0.05), Eight of 15 patients had DFT determined at all three study periods. In these patients, DFT increased at postop (22.8 ± 8.3 J vs 16.4 ± 3.9 J at implant: P < 0.05) and returned to baseline at 4–6 weeks (16 ± 7.1) vs 16.4 ± 3.9 J at implant; P = N.S.). Thus, in patients with a multilead nonthoracotomy system, a DFT rise was observed early after implant. The DFT appears to return to baseline in 4–6 weeks. These results have important implications for programming energy output after implantable cardioverter defibrillator implantation.