SmartDelay Determined AV Optimization: A Comparison of AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV): Rationale and Design

Background: The clinical benefit of cardiac resynchronization therapy (CRT) for patients with moderate-to-severely symptomatic heart failure, left ventricular systolic dysfunction, and ventricular conduction delay is established. However, some patients do not demonstrate clinical improvement following CRT. It is unclear whether systematic optimization of the programmed atrioventricular (AV) delay improves the rate of clinical response.
Methods: SMART-AV is a randomized, multicenter, double-blinded, three-armed trial that will investigate the effects of optimizing AV delay timing in heart failure patients receiving CRT + defibrillator (CRT-D) therapy. A minimum of 950 patients will be randomized in a 1:1:1 ratio using randomly permuted blocks within each center programmed to either DDD or DDDR with a lower rate of 60. The study will include echocardiographic measurements of volumes and function [e.g., left ventricular end-systolic volume (LVESV)], biochemical measurements of plasma biomarker profiles, and functional measurements (e.g., 6-minute hall walk) in CRT-D patients who are enrolled and randomized to fixed AV delay (i.e., 120 ms), AV delay determined by electrogram-based SmartDelay, or an AV delay determined by echocardiography (i.e., mitral inflow). Patients will be evaluated prior to initiation of CRT, 3 and 6 months post-implant. The primary endpoint is the relative change in LVESV at 6 months between the groups. Patient enrollment commenced in May 2008 and the study is registered at clinicaltrials.gov.
Conclusion: SMART-AV is a randomized, clinical trial designed to evaluate three different methods of AV delay optimization to determine whether systematic AV optimization is beneficial for patients receiving CRT for 6 months post-implant. (PACE 2010; 54–63)     

Preparation for action: An ERP study about two tasks provoking variability in response speed

This study focused on the covariation of response speed and event-related potentials during response preparation and on whether these variations can be brought under experimental control. Two S1-S2 choice response tasks with temporal uncertainty were conducted. In Experiment I, S1 was 100% informative. Fast subjects showed larger P3s with S1 than slow subjects. The terminal CNV (tCNV) increased intraindividually with response speed. In Experiment 2.50% of S1s were uninformative and the visual display was designed to attract more attention. Effects of information were found on P3 amplitude, on the topography of tCNV, and on the temporal distribution of response times. Interindividual differences disappeared in Experiment 2. The results suggest that group differences in Experiment 1 were due to different strategies of allocating visual attention. Interindividual variations of strategy showed a pattern of effects different from intraindividual variations of efficiency.     

Adrenoceptor of the alpha2-subtype mediating inhibition of the human fat cell adenylate cyclase

Abstract. In an attempt to characterize the adenylate cyclase-coupled alpha-adrenoceptors of human fat cells the effects of various alpha-adrenergic agonists and antagonists were examined in the presence of 0.05 mmol/1 of propranolol.
The order of agonist potencies with respect to alpha-adrenergic inhibition was (—)-adrenaline > alpha-methyl-(-)-noradrenaline >> (—)-phenylephrine with half-maximal inhibition occurring at 2 μmol/1 of (-)-adrenaline and 7 μmol/l of alpha-methyl-(-)-noradrenaline respectively.
The inhibition of adenylate cyclase induced by 005 mmol/1 of (—)-adrenaline was reversed by the alpha-blocking agents yohimbine and prazosin, with the alphai-site-directed antagonist yohimbine being more than 100-times more potent than prazosin which is more active at alphai-sites.
The results show that the cyclase-coupled alpha-adrenoceptors of human fat cells, which probably represent the physiologically relevant target of antili-polytic catecholamine effects, display characteristic features of the alpha₂-adrenoceptor subtype.     

HLA B27 and defects in the T-cell system in Whipple''s disease

The cellular immune system was tested in nine patients with Whipples' disease. Three patients had active disease, and six had been in remission for up to 10 years. Intradermal delayed hypersensitivity reactions to candidin, trichophytin, tuberculin and varidase, T-cell counts as determined by E-rosettes, allogeneic stimulation of lymphocytes in the mixed lymphocyte culture, and mitogenic activation of lymphocytes by concanavalin A, phytohaemagglutinin and by pokeweed mitogen, were tested in the patients and compared with control subjects. HLA typing was performed in all patients. The reaction to tuberculin and varidase, the T-cell counts and the activation of lymphocytes by concanavalin A were significantly reduced in patients with active disease and in patients during remission. The reaction to candidin and trichophytin was poor even in the controls. The mean results of the mixed lymphocyte culture, phytohaemagglutinin, and pokeweed mitogen activation tests were not significantly different from the controls. In patients with active disease the mixed lymphocyte culture reaction and the T-cell counts were less than in patients in remission. The results suggest a persistent defect of T-cells in patients with Whipple's disease, a defect that is more severe in patients with active disease. The finding of HLA B27 in four of thenine patients supports the hypothesis of primary rather than secondary impairment of the cellular immune system in Whipple's disease.     

Is the Atrial High Rate Episode Diagnostic Feature Reliahle in Detecting Paroxysmal Episodes of Atrial Tachyarrhythmias?

The atrial high rate episode diagnostic in The Thera® pacemaker reports frequency, duration, and date/time of atrial tachyarrbytbmias according to programmed criteria. The aim of The study was to validate The atrial high rate episode diagnostic feature. Episodes of atrial fibrillation recorded by Holter monitoring were compared to episodes detected by the pacemaker. Eorty five ambulatory (Holter) recordings were used for evaluation. Thirty of 45 ambulatory (Holter) recordings showed sinus rhythm. On 4 of these 30 ambulatory (Holter) recordings, The Thera® detected 12 episodes of atrial tachyarrbythmias as false-positives (sinus rhythm was detected as atrial tacbyarrbytbmia). The main reason was far-field R and T wave oversensing. On 15 of 45 ambulatory (Holter) recordings, 125 episodes of atrial tachyarrhytbmias were recorded. Ninety-three of these events also were detected by the pacemaker, while for 32 events the Thera® reported sinus rhythm. The main reason was that the episodes were of too short duration. Therefore, the Thera® (programmed with detection rate 160 beats/min, detection beats 40, termination beats 10) was unable to detect atrial tachycardias. Software simulation of The diagnostic algorithm under several programming settings using the digitized Holter files demonstrated highly reliable detection of atrial tachyarrhythmias (sensitivity 98%, specificity 100%) when programmed as follows: detection rate 220 beats/min, detection beats 10, termination beats 20. It can be concluded that Thera®'s high rate episode monitor is a reliable tool for detection of a trial tachyarrhythmias, if programmed as recommended.     

Avoid Delivering Therapies for Nonsustained Fast Ventricular Tachyarrhythmia in Patients with Implantable Cardioverter/Defibrillator: The ADVANCE III Trial

Introduction: The purpose of this investigation is to evaluate whether a prolonged detection interval for life threatening ventricular tachyarrhythmia (VT) is able to reduce therapies (Rx) delivered by an implantable cardioverter/defibrillator (ICD). Until now, only the PREPARE trial demonstrated a reduction of ICD Rx in a cohort of primary prevention patients.
Methods and Results: The ADVANCE III study is a prospective, randomized, parallel trial with 2 arms evaluating different intervals to detect (NID), i.e., 18/24 (as currently used) versus 30/40. The primary endpoint is to demonstrate a 20% reduction of ICD Rx (antitachycardia pacing or shocks) delivered to terminate spontaneous VT with a cycle length ≤320 ms in patients with Class I-IIA indication for ICD therapy, regardless of cardiac resynchronization capabilities. The worldwide investigation started in spring 2008 and is expected to be finished in 2011.
Conclusions: The ADVANCE III trial is the first randomized investigation evaluating the reduction of ICD Rx for fast VT due to a prolongation of NID in a general ICD patient cohort.     

How Reliable is Atrial Sensing in Single-Lead VDD Pacing: Comparison of Three Systems

This study evaluated the reliability of atrial sensing, expressed as AV synchronous stimulation, in three VDD systems with the atrial sensitivity (AS) programmed to a conventional value with a 2:1 safety margin compared to most-sensitive values. We studied 34 sex- and age-matched patients with 3 VDD systems: 14 with Unity 292–07, 10 with Saphir 600, and 10 with Thera VDD (5 model 8948 and 5 model 8968i). Two 24-hour Hollers were performed on consecutive days. The AS was programmed in a randomized order to its most-sensitive value or to a 2:1 safety margin. All other parameters were programmed identically. The patients underwent a myopotential oversensing test and a daily life activity protocol. A beat-to-beat analysis of the Holters was performed to determine AV synchrony. For the entire group AV synchrony with conventional AS was 98.63%± 2.57%, compared to 99.80%± 0.43% with most-sensitive values (p = 0.002). There was no difference between the three systems with conventional AS. With the most-sensitive AS, AV synchrony was: Unity 99.99%± 0.03%, Saphir 99.42%± 0.60% (P = 0.002), Thera 99.81 %± 0.35% (ns). In the Saphir system with an atrial blanking period of 150 ms, ventricular far-field sensing could be demonstrated in 5 of 10 patients. This reduced the percentage of AV synchrony due to an unwanted mode-switch to a nontracking mode. Myopotential oversensing was not detected in any patient. Conclusion: The VDD systems tested under identical conditions showed reliable P wave sensing at the most-sensitive atrial sensing setting without myopotential oversensing. Ventricular far-field sensing reduced AV synchrony and must be avoided by appropriate refractory periods.