1026-85 Enhanced Defibrillation Efficacy with an Active Pectoral Pulse Generator

An active pectoral pulse generator can be incorporated in a single coil defibrillation lead system to achieve low defibrillation thresholds (DFT). However, the incremental benefit of an active pulse generator with an integrated lead system has not been evaluated. Accordingly, we performed a prospective trial of a 65 cc pulse generator shell with an Endotak lead in 22 consecutive pts undergoing defibrillator implantation. Energy (E) and leading edge voltage (V) at DFT was measured using a step down protocol to first failure with biphasic waveforms (60:40 tilt). Either lead alone (proximal coil = anode) or lead + shell (proximal coil and shell = anode) were tested with paired testing in random order.E(joules)V(volts)R(ohms)Lead alone13.1±6.7395±10549±5Lead + Shell8.5±3.1*319±61*42±4**p<0.001A DFT of≤10J was found in 50% (11/22) of patients with lead alone and 86% (19/22) of patients with lead + shell (p<0.02).In conclusion, adding an active pulse generator to an integrated transvenous lead significantly reduced DFTs and system impedance (R). The consistently low defibrillation energy requirements with the use of an active small pectoral shell, makes the development of a defibrillator with reduced size and lower maximal output feasible

Atrial defibrillation with a transvenous lead A randomized comparison of active can shocking pathways

AbstractOBJECTIVESThe purpose of this study was to compare transvenous atrial defibrillation thresholds with lead configurations consisting of an active left pectoral electrode and either single or dual transvenous coils.BACKGROUNDLow atrial defibrillation thresholds are achieved using complex lead systems including coils in the coronary sinus. However, the efficacy of more simple ventricular defibrillation leads with active pectoral pulse generators to defibrillate atrial fibrillation (AF) is unknown.METHODSThis study was a prospective, randomized assessment of shock configuration on atrial defibrillation thresholds in 32 patients. The lead system was a dual coil Endotak DSP lead with a left pectoral pulse generator emulator. Shocks were delivered either between the right ventricular coil and an active can in common with the proximal atrial coil (triad) or between the atrial coil and active can (transatrial).RESULTSDelivered energy at defibrillation threshold was 7.1 ± 6.0 J in the transatrial configuration and 4.0 ± 4.2 J in the triad configuration (p < 0.005). Moreover, a low threshold (≤3 J) was observed in 69% of subjects in the triad configuration but only 47% in the transatrial configuration. Peak voltage and shock impedance were also lowered significantly in the triad configuration. Left atrial size was the only clinical predictor of the defibrillation theshold (r = 0.57, p < 0.002).CONCLUSIONSThese results indicate that low atrial defibrillation thresholds can be achieved using a single-pass transvenous ventricular defibrillation lead with a conventional ventricular defibrillation pathway. These data support the development of the combined atrial and ventricular defibrillator system

Kinematic/Dynamic Characteristics for Visual and Kinesthetic Virtual Environments

Work was carried out on two topics of principal importance to current progress in virtual environment research at NASA Ames and elsewhere. The first topic was directed at maximizing the temporal dynamic response of visually presented Virtual Environments (VEs) through reorganization and optimization of system hardware and software. The final results of this portion of the work was a VE system in the Advanced Display and Spatial Perception Laboratory at NASA Ames capable of updating at 60 Hz (the maximum hardware refresh rate) with latencies approaching 30 msec. In the course of achieving this system performance, specialized hardware and software tools for measurement of VE latency and analytic models correlating update rate and latency for different system configurations were developed. The second area of activity was the preliminary development and analysis of a novel kinematic architecture for three Degree Of Freedom (DOF) haptic interfaces--devices that provide force feedback for manipulative interaction with virtual and remote environments. An invention disclosure was filed on this work and a patent application is being pursued by NASA Ames. Activities in these two areas are expanded upon below

The strong enhancer element in the immediate early region of the human cytomegalovirus genome

The human cytomegalovirus (HCMV), a member of the herpesvirus group, was found to possess a strong transcription enhancer in the immediate early gene region. Co-transfection of enhancerless SV40 DNA with randomly fragmented HCMV DNA yielded two SV40-like recombinant viruses , each containing HCMV DNA fragments that were substituting for the missing SV40 enhancer. The two inserts , 341 and 262 bp in length , are overlapping segments of genuine viral DNA representing part of the 5'flanking region of the major immedistte early gene i n HCMV. Studies with deletion mutants showed that different nonoverlapping subsets of the HCMV enhancer region can substitute for the 72 bp repeats of SV40. Transient expression assays indicated that the HCMV enhancer is significantly stronger than the SV40 element, activating cis-linked heterologous promoters in a wide spectrum of cultured cells. It appears that the HCMV enhancer is positively regulated by viral immediate early genes

Predictors of short-term clinical response to cardiac resynchronization therapy

Aims: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with symptomatic heart failure and QRS prolongation but there is uncertainty about which patient characteristics predict short-term clinical response. Methods and results: In an individual patient meta-analysis of three double-blind, randomized trials, clinical composite score (CCS) at 6 months was compared in patients assigned to CRT programmed on or off. Treatment–covariate interactions were assessed to measure likelihood of improved CCS at 6 months. MIRACLE, MIRACLE ICD, and REVERSE trials contributed data for this analysis (n = 1591). Multivariable modelling identified QRS duration and left ventricular ejection fraction (LVEF) as predictors of CRT clinical response (P &lt; 0.05). The odds ratio for a better CCS at 6 months increased by 3.7% for every 1% decrease in LVEF for patients assigned to CRT-on compared to CRT-off, and was greatest when QRS duration was between 160 and 180 ms. Conclusions: In symptomatic chronic heart failure patients (NYHA class II–IV), longer QRS duration and lower LVEF independently predict early clinical response to CRT

Temporal decline in defibrillation thresholds with an active pectoral lead system

AbstractOBJECTIVESThe objective of this study was to characterize temporal changes in defibrillation thresholds (DFTs) after implantation with an active pectoral, dual-coil transvenous lead system.BACKGROUNDVentricular DFTs rise over time when monophasic waveforms are used with non-thoracotomy lead systems. This effect is attenuated when biphasic waveforms are used with transvenous lead systems; however, significant increases in DFT still occur in a minority of patients. The long-term stability of DFTs with contemporary active pectoral lead systems is unknown.METHODSThis study was a prospective assessment of temporal changes in DFT using a uniform testing algorithm, shock polarity and dual-coil active pectoral lead system. Thresholds were measured at implantation, before discharge and at long-term follow-up (70 ± 40 weeks) in 50 patients.RESULTSThe DFTs were 9.2 ± 5.4 J at implantation, 8.3 ± 5.8 J before discharge and 6.9 ± 3.6 J at long-term follow-up (p < 0.01 by analysis of variance; p < 0.05 for long-term follow-up vs. at implantation or before discharge). The effect was most marked in a prespecified subgroup with high implant DFTs (≥15 J). No patient developed an inadequate safety margin (<9 J) during follow-up.CONCLUSIONSThe DFTs declined significantly after implantation with an active pectoral, dual-coil transvenous lead system, and no clinically significant increases in DFT were observed. Therefore, routine defibrillation testing may not be required during the first two years after implantation with this lead system, in the absence of a change in the cardiac substrate or treatment with antiarrhythmic drugs

The Subcutaneous ICD: A Review of the UNTOUCHED and PRAETORIAN Trials

The ICD is an important part of the treatment and prevention of sudden cardiac death in many high-risk populations. Traditional transvenous ICDs (TV-ICDs) are associated with certain short- and long- term risks. The subcutaneous ICD (S-ICD) was developed in order to avoid these risks and complications. However, this system is associated with its own set of limitations and complications. First, patient selection is important, as S-ICDs do not provide pacing therapy currently. Second, pre-procedural screening is important to minimise T wave and myopotential oversensing. Finally, until recently, the S-ICD was primarily used in younger patients with fewer co-morbidities and less structural heart disease, limiting the general applicability of the device. S-ICDs achieve excellent rates of arrhythmia conversion and have demonstrated noninferiority to TV-ICDs in terms of complication rates in real-world studies. The objective of this review is to discuss the latest literature, including the UNTOUCHED and PRAETORIAN trials, and to address the risk of inappropriate shocks

Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of tau protein aggregates in the basal ganglia, brainstem and cerebral cortex leading to rapid disease progression and death. The neurofibrillary tangles that define the neuropathology of PSP are comprised of aggregated 4R tau and show a well-defined distribution. Classically, PSP is diagnosed by symptoms that include progressive gait disturbance, early falls, vertical ophthalmoparesis, akinetic-rigid features, prominent bulbar dysfunction and fronto-subcortical dementia. There are currently no effective therapies for the treatment of this rapidly degenerating and debilitating disease. Davunetide is a novel neuroprotective peptide that is thought to impact neuronal integrity and cell survival through the stabilization of microtubules. Preclinical activity in models of tauopathy has been translated to clinical studies, demonstrating pharmacologic activity that has supported further development. Davunetide’s efficacy and tolerability are being tested in a placebo-controlled study in PSP patients, making it the most advanced drug candidate in this indication. This review examines the disease characteristics of PSP, the rationale for treating PSP with davunetide and assesses some of the challenges of clinical trials in this patient population