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Biomedical subjects

H F Pitschner

Publications and source records attributed to H F Pitschner.

At least 37 records · Page 2Linked to original sources

Detection of ventricular fibrillation in implantable defibrillators with automatic gain control amplifiers: effects of programming sensitivity.

AIMS: In newer implantable cardioverter-defibrillators with automatic gain control amplifiers the maximum possible sensitivity is programmed with the aim of securing optimal detection of ventricular fibrillation. This study was designed to prove that a reduction in maximum sensitivity is safe with respect to appropriate sensing of ventricular fibrillation, while avoiding sensing of extracardiac signals. METHODS AND RESULTS: Forty-two consecutive patients, undergoing defibrillator implantation/replacement with programmable maximum auto-gain sensing sensitivity (Ventak Mini III, Ventak AV , Guidant, St. Paul, MN, U.S.A.), were prospectively investigated. Thirty-four patients were implanted with a dual-coil lead system, providing integrated bipolar sensing (Endotak, Guidant, St. Paul, MN, U.S.A.), eight patients received a single-coil lead system with true bipolar sensing (Sprint, Medtronic, Minneapolis, MN, U.S.A.). During device implantation and pre-discharge testing, arrhythmia detection times of induced ventricular fibrillation were compared at programmed maximum (0.18 mV) and minimum (0.43 mV) sensitivity in a randomized manner. Seventy-six induced episodes of ventricular fibrillation were analysed. The mean arrhythmia detection times did not differ between the programmed sensing levels (maximum sensitivity: 1612 +/- 307 ms, vs minimal sensitivity: 1,602 +/- 330 ms; P = ns). The results were not affected by the type of implanted lead system (integrated bipolar versus true bipolar sensing). CONCLUSION: In the implantable defibrillator devices, reduction in maximum sensitivity did not impair the detection of induced episodes of ventricular fibrillation.

Amplifiers, Electronic↗

Comparison of pulsed versus continuous radiofrequency energy delivery: diameter of lesions induced with multipolar ablation catheter.

The aim of this study was to compare the efficacy of pulsed versus continuous RF energy delivery via multipolar ablation catheters. In vitro tests were performed in endomyocardial preparations of fresh bovine hearts in a both of physiological saline solution (37 degrees C) at constant flow conditions (1.5 L/min). The catheters were applied to the endocardium at a constant pressure. Energy was delivered pulsed (to 4 electrodes simultaneously, 5-ms duty cycle) or continuously (to each electrode separately). In vivo experiments were performed under fluoroscopy in eight anesthetized pigs, guided by endocardial electrograms to place the catheters in 22 different intraatrial positions. Lesion volume was calculated from measurements of the lesion diameter with a microcaliper. The homogeneity of the lesions was classified from 1 (highest) to 4 (least). More homogeneous linear lesions were produced in significantly less time with pulsed than with continuous energy delivery. There were no differences in electrode temperature or impedance values in vitro and in vivo. The results in the in vitro experiments were reproducible in the intact animal experiments. Significantly larger and more homogeneous linear lesions were created more rapidly with pulsed than with continuous energy delivery.

Animals↗

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.

Adult↗

Midterm results after the Mini-Maze procedure.

OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia. However, its precise electrophysiologic mechanism is still not well understood. Chronic symptomatic AF resistant to medical therapy, can successfully be treated by the Maze III procedure (M III). However, there are several publications dealing with alternative surgical techniques. This study describes technique and midterm results of a Mini-variant of the M III procedure. METHODS: During a 38-month period we performed either an M III (seven patients) (group I) or a MINI-operation (45 patients) (group II) with chronic symptomatic AF and additional cardiac pathology. Patients were controlled 3.6 +/- 0.9 and 14.9 +/- 2.2 months after operation by means of thorough electrophysiological assessment, right heart catheterization, magnetic resonance imaging (MRI), echocardiography, stress-EGG and 24-h-ECG. RESULTS: There was no significant differences between the two groups with regard to sex, age and duration of AF. Echocardiographic left atrial diameter (LAD) was 75 +/- 11 mm in group I and 67 +/- 8 mm in group II (P = 0.01). Whereas right atrial diameter was 62 +/- 8 mm in group I and 56 +/- 7 mm in group II (NS). Perioperative data (n = 52): aortic cross clamp time was 127 +/- 40 mm in group I and 87 +/- 21 mm in group II, (P = 0.0002). Cardiopulmonary bypass time was 185 +/- 71 mm in group I and 137 +/- 46 mm in group II, (P = 0.02). Postoperative data: there was no difference between the two groups with regard to sinus rhythm, prolonged sinus node recovery time, pacemaker (PM) in AAI-mode, inducible atrial fibrillation, reduction of left and right atrial size after a follow-up interval of 3.6 months and 1 year, respectively. CONCLUSION: Midterm results are identical after M III and MINI. MINI is less complex compared to the M III procedure and there is a significant reduction of crossclamp- and ECC-time. We recommend the MINI especially for polymorbid patients, and for those with poor left ventricular function.

Adult↗

Bipolar atrial sensing thresholds in sinus rhythm and atrial tachyarrhythmias. A comparative analysis in patients with DDDR pacemakers.

UNLABELLED: Automatic mode switching (AMS) function in dual chamber pacemakers depends on adequate detection of atrial tachyarrhythmias. There are few data on showing how intra-operative atrial signal amplititude during sinus rhythm can predict atrial tachyarrhythmias after pacemaker implantation. In 43 patients undergoing DDDR pacemaker implantation and atrioventricular nodal ablation for the treatment of drug-refractory paroxysmal atrial fibrillation, atrial sensing thresholds during sinus rhythm and during induced atrial tachyarrhythmias (24-48 h after device implantation) were analysed. Five different DDDR pacemaker systems were implanted (Chorus 7034, Ela Medical n = 13; Meta DDDR 1254, Telectronics Pacing Systems n = 12; Vigor DR 1230, Guidant n = 6; Trilogy DR 2364, Pacesetter, n = 2; Kappa DR 401, Medtronic USA n = 10). Every patient received a steroid-eluting, screwing, bipolar atrial lead (Medtronic, Capsure-Fix 4068). The mean P wave amplitude during implantation was 3.91 +/- 1.14 mV. The mean atrial sensing threshold during sinus rhythm and during all modes of induced atrial tachyarrhythmias was 3.35 +/- 1.0 mV, and 1.52 +/- 0.92 mV, respectively (P < 0.001). Atrial fibrillation was induced in 36 patients. The mean sensing threshold during sinus rhythm in this patient group was 3.39 +/- 1.01 mV, the mean sensing threshold during atrial fibrillation was 1.27 +/- 0.56 mV, reflecting a 63% reduction of sensing threshold compared with sinus rhythm (P < 0.001). Atrial flutter was induced in seven patients. The mean sensing threshold during sinus rhythm was 2.92 +/- 1.19 mV, the mean sensing threshold during atrial flutter was 2.79 +/- 1.26 mV, reflecting a reduction of 5% (ns) compared with sinus rhythm. Atrial sensing thresholds during sinus rhythm were significantly correlated with sensing thresholds during atrial tachyarrhythmias (r = 0.44; P < 0.002), but there were significant variations in intra-individual results. The reduction of atrial sensing thresholds between sinus rhythm and induced atrial tachyarrhythmias ranged from 30% to 82%. CONCLUSION: Bipolar atrial sensing thresholds during sinus rhythm are correlated with sensing thresholds during atrial tachyarrhythmias, but there is a large degree of variance in individual patients. A 4:1 to 5:1 atrial sensing safety margin based on sensing threshold during sinus rhythm is a predictor for adequate postoperative detection of atrial tachyarrhythmias and the function of AMS devices.

Arrhythmia, Sinus↗

[Therapy with implanted cardioverter-defibrillator: Is a replacement of the impulse generator due to battery depletion also necessary without the occurrence of a tachyarrhythmia episode?].

The aim of this retrospective study was to evaluate the necessity of the replacement of an implantable cardioverter/defibrillator (ICD) in patients with pulse generator battery depletion without an adequate, spontaneous arrhythmia episode during the life-time of the first implanted device. In this study 213 patients with implanted ICDs were enrolled. In 62 patients an elective generator replacement due to battery depletion was performed. Both patient groups (Group A: patients with generator replacement n = 62 and Group B: patients without replacement n = 151) were not different with regard to main clinical characteristics, such as underlying heart disease and left ventricular function. In both groups there was a predominance of male patients (Group A: 89%; Group B: 83%). The mean age was 58 +/- 11 years and 59 +/- 11 years in Group A and Group B, respectively. Coronary artery disease was present in 66% and 68% of the patients. There was a comparable left ventricular ejection fraction: Group A: 30.5 +/- 9% vs Group B: 31.9 +/- 9%. The follow-up time was much longer in Group A patients compared to Group B patients (50.5 +/- 14 vs. 16.5 +/- 11 months). For the total patient group there was a 5 year event-free probability of 23%, no differences were found between both groups. The subanalysis in Group A patients revealed no difference in the probability of ICD-shock occurrence prior to or after the replacement of the pulse generator. In 48/62 (77%) of Group A patients adequate ICD discharges were documented. In 15/62 (24%) patients shock occurred before and after generator replacement. In 6/62 (10%) of Group A patients, the first adequate ICD-therapy was documented after generator replacement. The results of this study indicate the necessity of an ICD-pulse generator replacement even in patients without an adequate device discharge during the life-time of the first implanted device.

Aged↗

[Dysfunctions of transvenous cardioverter/defibrillator electrode systems: clinical significance of system integrated diagnosis and measurement function--possibilities of partially automated system control].

UNLABELLED: The aim of this study is the analysis of electrical failures in transvenous cardioverter/defibrillator (ICD) lead systems with regard to the importance of device implemented diagnostic and measurement functions and the potential role of an automated device-control in the detection of lead failures. METHODS: All consecutive ICD patients at our institution were enrolled in this retrospective investigation. The routine follow-up controls consisted in a complete evaluation of all diagnostic and measurement ICD features and additional controls in case of spontaneous arrhythmia episodes. RESULTS: Two hundred thirty patients, 193 male and 37 female, were enrolled in this study (mean age: 61.5 +/- 10.2 years; mean LVEF 32 +/- 9%). During a mean follow-up period of 29.5 +/- 18.4 (6-76) months, lead failure occurred in 19 patients (8%), 16 patients were implanted with an ICD, capable of diagnostic and measurement functions. All nonadequate device discharges could be classified as sensing-failure by stored electrograms. Device implemented measurement features revealed clinical important information in 13/16 patients (81%). In 14/16 patients, the lead defect could not be detected during routine follow-up. At the time of documented lead failure the safety of the implanted devices was already lost in 6/16 patients (38%). CONCLUSIONS: Device implemented diagnostic and measurement options are of great importance in the early detection of ICD lead failures. The implementation of automated measurements of lead related parameters in connection with a patient alert function may contribute to a further increase in the safety of ICD therapy.

Adult↗

Interrelation of tissue temperature versus flow velocity in two different kinds of temperature controlled catheter radiofrequency energy applications.

UNLABELLED: The influence of blood flow cooling down the energy delivering electrode during temperature controlled radiofrequency energy application is an important factor for ablation success. In this experimental in-vitro study, using tempered saline as blood equivalent, we observed a highly significant increase in tissue temperature, lesion depth and required energy amount with increasing flow velocity. Second, we found significant deeper lesions with use of pulsed radiofrequency energy application compared to continuous application. We conclude that, even with lower electrode temperatures, success can be achieved dependent on the local blood flow velocity, and deeper lesions can be created with the use of pulsed radiofrequency energy application. BACKGROUND: Success in temperature-controlled radiofrequency (RF) catheter ablation of arrhythmogenic areas in human hearts depend largely (among others) on the size of the electrode, developed pressure of electrode against tissue, as well as on the localization of the thermistor sensor within the electrode. In addition, the blood flow velocity at various sites of ablation is an important factor for the calculation of heat transport from the electrode, which obviously has not been given much consideration of in the past. The aim of the present in-vitro study, therefore, was to evaluate this important factor's influence on the temperature developed at the electrode and within the myocardial tissue. METHODS AND RESULTS: All experiments were carried out in a bath containing NaCl solution at 37 degrees C. Four different flow velocities were applied (0, 110, 180, 320 ml/cm2 *min). During and after temperature-controlled unipolar radiofrequency energy delivery (60 degrees C, 40 sec) the electrode temperature, the tissue temperature 5 mm in depth, and the total energy delivered were measured, as well as the actual depth of the lesion. The amount of energy applied to the electrode was regulated by the thermosensor in the electrode to obtain a maximum temperature of 60 degrees C. Two different kinds of radiofrequency energy delivery have been used: (1) continuous radiofrequency energy delivery as usual regarding clinical use, (2) pulsed radiofrequency energy delivery with a duty cycle length of 10 ms and a pause of at least the same duration during two consecutive duty cycles. At pulsed radiofrequency energy application, the energy for each duty cycle was held constant during delivery. The amount of pulses delivered to the electrode was regulated by the electrode's thermosensor. With both modes of radiofrequency energy delivery a uniform observation could be made. The more the flow velocity applied accelerated, the more the tissue temperature rose (R = 0.85; p < 0.00000001), and the lesion depth increased in spite of electrode temperature being held constant. The amount of the total energy delivered rose in proportion to the cooling down of the electrode dependent on the flow velocity (R = 0.69, p < 0.0000004). Steady-state temperatures had not been accomplished after 40 sec time. When energy was delivered at the pulsed mode, intramyocardial temperatures proved higher compared to the continuous mode with significant differences (p < 0.05) at comparable flow velocities applied between 180 and 320 ml/cm2*min and at same electrode temperatures. This resulted in significantly (p < 0.05) larger lesion depths in pulsed radiofrequency energy delivery. We suppose that this significant difference can be explained by a higher amount of total energy delivered at comparable electrode temperature in the pulsed mode as compared to the continuous mode.

Acceleration↗

Multielectrode basket catheter mapping for human atrial fibrillation.

In 9 patients with a history of paroxysmal atrial fibrillation (AF), basket catheters with 64 electrodes were used to determine electrophysiologic aspects of onset and early minutes of AF in the right atrium. Mapping was performed using 32 bipolar recordings after induction of AF by programmed atrial stimulation. In 7 patients, registrations were obtained that allowed the onset of AF to be analyzed after the induction. The most common mode of induction was a conduction block and local fragmentation of electrical activation in the area anterior to the tricuspid valve; this was observed in 5 patients. Local cycle lengths (5 min) and correlation dimension of repolarization Dpw_De (2 min) was calculated in 7 patients. The recording sites of the basket catheter were fluoroscopically projected to the anatomic sites of the right atrium. The highest Dpw_Re dimensions as an expression of pronounced chaotic activity were found in the area anterior to the tricuspid valve.

Algorithms↗

Clinical predictors of defibrillation energy requirements.

In implantable cardioverter-defibrillator therapy with endocardial lead systems, certain clinical variables are associated with defibrillation energy requirements. Because of the weak correlation coefficients, these variables cannot predict defibrillation thresholds in individual patients.

Age Factors↗

Implantable cardioverter-defibrillator therapy: influence of left ventricular function on long-term results.

The degree of left ventricular impairment in an acknowledged important prognostic marker of long-term outcome for patients being evaluated for implantation of cardioverter-defibrillators. Just how left ventricular function impacts freedom from all-cause mortality, as well as from sudden death and cardiac death, is a subject of current major debate, and is analyzed hereunder from a large, recent multicenter ICD patient cohort. The multicenter database consists of data from 361 patients receiving implantable cardioverter-defibrillators for standard indications, that is, documented episodes of ventricular fibrillation or sustained ventricular tachycardias with poor hemodynamic toleration. Data were collected from 1988 to 1995 at three centers in Germany. Two-hundred and three patients (56%) had a left ventricular ejection fraction (LVEF) > 0.30 (group I), and 158 patients (44%) had a LVEF < or = 0.30 respectively (group II). The mean follow-up was 23.9 months (range 3-98 months). Overall survival at 5 years for group II patients was lower, as expected, at 74.1% versus 94.2%, respectively (P < 0.0001). Mortality was higher for each different cause of death in group II patients than in Group I: sudden arrhythmic deaths, 5 versus 1 (P < 0.048); nonsudden cardiac deaths, 16 versus 5 (P < 0.002); noncardiac deaths, 7 versus 2 (P < 0.03). Group II patients received a higher rate of at least one presumably appropriate shock at 86 (54.4%) versus 89 (43.8%) in group I (P < 0.05). However (and somewhat surprisingly), neither the time from ICD implantation to death, comparing only the patients who died, nor the event-free probability of appropriate shocks due to very rapid, sustained ventricular arrhythmias (> 230 beats/min), including a presumed risk of sudden arrhythmogenic death, differed between groups I and II. Sudden cardiac death was only marginally affected by LVEF (group I, 1.5% actuarial, 5-year survival 99.5%; group II, 3.1% and 95.8%, respectively). Therefore, the lower overall survival in ICD patients with LVEF < or = 0.30 resulted mainly from causes of death that cannot be directly influenced by cardioverter-defibrillator therapy. However, because group II patients had a far higher incidence of at least one ventricular tachyarrhythmia terminated by ICD shocks than group I patients, they also probably derived benefit from ICD therapy.

Cohort Studies↗

[Catheter ablation in supraventricular tachycardia].

The first report about successful radio frequency ablation of a right-posterior-septal accessory pathway appeared in 1986. Since then, the technology of both guidable ablation catheters and radio frequency generators has been considerably improved in an initially clinical-experimental phase. At the same time, electrophysiologists were equally able to enlarge their knowledge in the field of signal characteristics of arrhythmogenic substrates. This included the discovery of action potentials of accessory pathways (preexcitation syndromes), the location of fast and slow AV node conduction (AV nodal reentrant tachycardia, AVNRT), the functional importance of the anatomical isthmus between the os of the coronary sinus, the tricuspid valve and the inferior caval vein (atrial flutter). Mapping techniques such as transient and concealed entrainment became, among others, significant tools in finding the best localization for radio frequency catheter ablation. Thus, technical development and the increased knowledge of clinical electrophysiologists resulted in firmly establishing the procedure of catheter ablation as the method of first choice in the curative treatment of supraventricular tachycardias in a potential collective of about 5 per mill of the normal population (without atrial fibrillation). Supraventricular tachycardias with a reentry mechanism in the broadest sense (> 95% of all pts. with SVT) and those with focal automaticity (< 5%) occur as atrial fibrillation or atrial flutter in about 60% of all pts. (4-6 per mill of the normal population). Manifestation of the remaining reentrant tachycardias is mainly in the form of AVNRT (retrograde conduction via the fast pathway > 90% versus uncommon type < 10%). AV reentry via accessory pathways is found in about 15%, with orthodromic conduction via the AV node (> 90%). Atrial reentrant tachycardias are rather rare (with the exception of atrial fibrillation/flutter). The literature suggests medical therapy to be successful in about 60% of these patients. Those patients who are presently proposed to receive radio frequency catheter ablation usually continue to be symptomatic despite pharmacological therapy and/or have a potential risk for sudden cardiac death due to atrial fibrillation in WPW syndrome, or rate-dependent hemodynamic compromise secondary to cardiac disease. Since 1989-1995, our laboratory had a > 93% success rate in treating 466 patients with AV reentrant tachycardia via accessory AV pathways, and in treating 398 patients with AV nodal reentrant tachycardias. Forty patients with atrial flutter and 16 patients with different atrial tachycardias (14 with focal origin, 2 reentries) were free from tachycardia in 80% after ablation. This corresponds to the literature published by other centers. Some abstracts and articles suggest that ablation of atrial fibrillation may be possible. However, there is still a lack of basic experience with view to mapping procedures and, thus, insufficient knowledge of the electrophysiological pathophysiology with regard to different cardiac diseases. As a consequence, this procedure, despite first documentation of both successful treatment and severe complications occurring in catheter ablation of atrial fibrillation, as based on the experience of the MAZE procedure, is applied in humans, at the time being, in a purely experimental setting. The only exception relates to the ablation of the AV node at accurate diagnosis for pacemaker implantation (VVIR; DDDR switch mode) which has become part of routine therapy, although, of course, atrial fibrillation itself or necessary anticoagulation cannot be abolished. Thus, our center shows a success rate of 98% in treating 117 patients by this method. First promising reports are available describing the attempt of AV node modification in the posterior nodal part with the goal of reducing the ventricular rate in atrial fibrillation.

Atrial Fibrillation↗

[The new potassium channel blocker tedisamil and its hemodynamic, anti-ischemic and neurohumoral effect in patients with coronary heart disease].

Thirty-two patients with angiographically proven coronary artery disease and reproducible ST-segment depression in the exercise ECG took part in this open dose-finding study on the hemodynamic and anti-ischemic effects of tedisamil, using right heart catheterization and bicycle exercise testing. Tedisamil--a bispidine derivative--is a new potassium channel blocking agent with negative chronotropic (i.e., direct effects on sinus node automaticity) and class III antiarrhythmic properties. Four groups of 8 patients each received rising doses of 0.1, 0.2, 0.3, and 0.4 mg/kg BW tedisamil intravenously. Being well tolerated, tedisamil was found to be dose-linear with the dose of 0.3 mg/kg BW having the most favorable anti-ischemic effects accompanied by a significant decrease in heart rate at rest (-13%, p < 0.001) and maximum exercise (-9%, p < 0.05). There was a consecutive fall of CO (by 10%, p < 0.05), while stroke volume remained unaltered. Despite singular significant changes, PCWPm and RV-EF, as indirect parameters of ventricular function, showed different responses without a clear tendency. PAPm increased slightly in accordance with peripheral and pulmonary vascular resistance, being significant at 3.3 mm Hg (p < 0.05) only at the dose of 0.4 mg/kg BW. Mean arterial pressure demonstrated a slight increase at rest (9% at 0.4 mg/kg BW; p < 0.05). Plasma catecholamine levels fell in a dose-dependent way by a maximum of 115-150 pg/ml (p < 0.01) on treatment with 0.4 mg/kg BW. QTc was found significantly prolonged by 16% (p < 0.001) on 0.4 mg/kg BW. During treatment with 0.3 mg/kg BW, tedisamil produced a dose-dependent reduction of ST segment depression at a maximum of 42% (p < 0.001) as well as a decrease in myocardial oxygen consumption, pressure rate product, and plasma lactate concentrations. In conclusion, tedisamil lowered heart rate and showed favorable hemodynamic, anti-ischemic, and neurohumoral effects in patients with coronary artery disease.

Aged↗

Anti-beta 1-adrenoceptor autoantibodies with chronotropic activity from the serum of patients with dilated cardiomyopathy: mapping of epitopes in the first and second extracellular loops.

In a preceding communication (Wallukat et al., 1992, Z Kardiol 81 [Suppl. 4]: 79-83), it was reported that synthetic peptides, corresponding in amino acid sequence to either the first or the second extracellular loop of the human beta 1-adrenoceptor, selectively suppressed the metoprolol- and bisoprolol-sensitive positive chronotropic action exerted in cultures of beating neonatal rat cardiomyocytes by the serum immunoglobulin fraction of patients with myocarditis and idiopathic dilated cardiomyopathy (DCM) and by affinity-purified autoantibodies from that fraction. These observations added to existing evidence that these antibodies were directed against the beta 1-adrenoceptor and might thus contribute to the harmful chronic cardiac adrenergic drive to which patients with DCM are believed to be exposed. Specifically, they pointed to the putative first and second extracellular loops of this receptor (these loops are each identical in man and the rat) as the sites of epitopes recognized by the chronotropically active, beta 1-agonistic autoantibodies. Now we report on the mapping of these epitopes with the help of two series of short synthetic overlap peptides, one series forming part of the first and the other of the second extracellular loop of the beta 1-adrenoceptor. Inhibition of the positive chronotropic response of cultured rat cardiomyocytes to the anti-beta 1-receptor autoantibodies (EC50 = 0.14 +/- 0.01 nM) from the serum immunoglobulin fraction of patients with DCM was taken as reflecting the neutralization of these antibodies by a particular overlap peptide. In this way the sequences S-F-F-C-E-L (residues 129-134) and A-R-R-C-Y-N-D (residues 206-212) emerged as the dominant epitopes in the first and second extracellular loops, respectively, followed with respect to neutralizing ability by the first loop sequence E-Y-G-S-F-F (residues 126-131) and the second loop sequences H-W-W-R-A-E (residues 197-202) and P-K-C-C-D-F (residues 213-218). Synthetic peptides corresponding to the sequences of the third extracellular loop of the beta 1-receptor (residues 346-356) and of the second extracellular loop of the human beta 2-receptor (residues 172-197) failed to neutralize the beta 1-agonistic autoantibodies. Using dithiothreitol as a reducing agent a disulfide bridge between cysteine 132 in the first and cysteine 209 in the second extracellular loop was considered to be essential for the chronotropic action of these autoantibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Safety of antitachycardia pacing in patients with implantable cardioverter defibrillators and severely depressed left ventricular function.

The purpose of this study was to investigate the efficacy and safety of antitachycardia pacing (ATP) in third-generation implantable cardioverter defibrillators (ICDs) for terminating spontaneously occurring ventricular tachycardias (VTs) in patients with severely depressed left ventricular (LV) function. Ninety-one patients with active ATP were followed for 16 +/- 13 months. During this period, 775 VT episodes occurring in 36 patients were treated by ATP. The patients were divided into two groups according to their LV ejection fraction (LVEF): group A with LVEF < or = 30% (n = 20), and group B with LVEF > 30% (n = 16). There were no differences between both groups in age, gender, underlying heart disease, indication for ICD therapy, or drug therapy. The VT rates were comparable (group A: 183 +/- 16 beats/min; group B: 180 +/- 21 beats/min; P = NS). Eighty-three percent of all episodes (n = 332) in group A and 93% of the VTs (n = 443) in group B were ATP terminated (P < 0.01). Ten percent of VTs in group A were accelerated by ATP into the ventricular fibrillation zone versus 2% in group B (P < 0.01). The individual termination rate and acceleration rate per patient were comparable in both groups. All VT episodes unresponsive to ATP were converted by backup shocks. The efficacy of first-shock therapy was similar in both groups (group A: 89%; group B: 97%; P = NS). The proportion of patients who needed at least one backup shock for unsuccessful ATP was comparable in both groups (group A: 65%; group B: 56%; P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Defibrillators, Implantable↗

Programmable VT detection enhancements in implantable cardioverter defibrillator therapy.

This report describes the distribution of automatically measured values of enhanced arrhythmia detection parameters such as "rate stability" and "rate onset" in various forms of spontaneous arrhythmia episodes in patients treated with a new, third-generation, tiered therapy implantable cardioverter defibrillator (ICD). The study population consisted of 27 patients who received the Ventak PRxII cardioverter defibrillator, which provides extensive diagnostic options such as electrogram storage capabilities, and the ability to store measured values of additional arrhythmia detection parameters such as rate stability and rate onset during spontaneous arrhythmia episodes. During a follow-up period of 11.1 +/- 5.2 months, this device detected 264 arrhythmia episodes. The analysis of stored electrograms revealed 13 episodes of sinus tachycardia, 52 episodes of atrial tachyarrhythmias, and 201 episodes of monomorphic ventricular tachycardias (VTs). The mean measured values of rate stability and rate onset were: 2.2 +/- 0.9 msec, 0% in sinus tachycardias; 41.0 +/- 24.1 msec, 8.5% +/- 9.5% in atrial tachyarrhythmias; and 7.8 +/- 6.0 msec, 30.6% +/- 12.1% in monomorphic VTs. There was a wide zone of overlapping measured values for rate stability and rate onset in ventricular and nonventricular rhythms. No episode of VT showed a measured rate stability criterion > 35 msec. The subanalysis of arrhythmia episodes presenting with a heart rate < 160 beats/min revealed no episode of VT with a rate stability value > 24 msec. The calculated, rate dependent specificities for these programmed rate stability parameters in detecting VTs were 46.2% and 81.8%, respectively. The analysis of the rate onset algorithm revealed no comparable relationship between sensitivity and specificity in the detection of VTs.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗