Slowing of the Ventricular Rate During Atrial Fibrillation by Ablation of the Slow Pathway of AV Nodal Reentrant Tachycardia

Influence of Slow Pathway Ablation on Atrial Fibrillation. Introduction : The mechanisms whereby radiofrequency catheter modification of AV nodal conduction slows the ventricular response are not well defined. Whether a successful modification procedure can be achieved by ablating posterior inputs to the AV node or by partial ablation of the compact AV node is unclear. We hypothesized that ablation of the well-defined slow pathway in patients with AV nodal reentrant tachycardia would slow the ventricular response during atrial fibrillation.
Methods and Results : In 34 patients with dual AV physiology and inducible AV nodal reentrant tachycardia, atrial fibrillation was induced at baseline and immediately after successful slow pathway ablation and at 1-week follow-up. The minimal, maximal, and mean RR intervals during atrial fibrillation increased from 353 ± 76,500 ± 121, and 405 ± 91 msec to 429 ± 84 (P < 0.01), 673 ± 161 (P < 0.01), and 535 ± 98 msec (P < 0.01), respectively. These effects remained stable during follow-up at 1 week. The AV block cycle length increased from 343 ± 68 msec to 375 ± 60 msec (P < 0.05) immediately and to 400 ± 56 msec (P < 0.01) at 1-week follow-up. The effective refractory period of the AV node prolonged from 282 ± 83 msec to 312 ± 89 msec and to 318 ± 81 msec after 1 week (P < 0.05), respectively.
Conclusion : This study shows a decrease in ventricular response to pacing-induced atrial fibrillation after ablation of the slow pathway in patients with AV nodal reentrant tachycardia. Since the AV nodal conduction properties could be defined, this study supports the hypothesis that the main mechanism of AV nodal modification in chronic atrial fibrillation is caused by ablation of posterior inputs to the AV node.     

Incidence of ICD Lead Related Complications During Long-Term Follow-Up: Comparison of Epicardial and Endocardial Electrode Systems

The aim of this study was to evaluate the longterm stability of epicardial and endocardial lead systems for third-generation cardioverter defibrillators (ICDs) and to assess the usefulness of diagnostic tools. One hundred forty patients with 61 epicardial (43.6%) and 79 nonthoracotomy systems (56.4%) were followed for 2 5 ± 19 months. A total of 18 (12.9%) lead related complications were documented. Complications of epicardial systems were detected in 10 patients (16.4%) during a follow-up time of 36 ± 8 months: crinkling of patch electrodes in 6 patients (9.8%), insulation breakage of sensing electrodes in 2 patients (3.3%), and adapter defect in 2 patients (3.3%). Eight of the patients (10.1%) with transvenous-subcutaneous systems had lead related complications during a 13 ± 6 months follow-up: fracture of the subcutaneous patch lead in 2 patients (2.5%), dislodgment of the right ventricular lead in 2 patients (2.5%), dislodgment of the superior vena cava lead in 2 patients (2.5%), insulation breakage of sensing electrodes in 1 patient (1.3%), and connector defect in 1 patient (1.3%). There was no significant difference in the incidence of lead related complications between epicardial and endocardial systems (P > 0.05). Fractures, dislodgments, and crinklings were documented within the first 8 ± 5 months by regular chest X ray. Defects of insulation, adapter, or connector were detected 22 ± 10 months after implantation and were associated with delivery of multiple inappropriate ICD therapies. An operative lead revision was indicated for 4 epicardial (6.6%) and 6 endocardial (7.6%) lead systems. Conclusions: Endocardial lead systems offer a similar long-term stability as compared to epicardial had systems. Chest X ray is the most useful tool to detect lead fracture, dislodgment. and patch crinkling. Marker recordings or real-time electrograms have not been helpful in this series to identify patients with suspected lead defects prior to the experience of inappropriate ICD discharges.     

The Effects of Potassium Chromate and Citrinin on Rat Renal Membrane Transport

The Effects of Potassium Chromate and Citrinin on Rat RenalMembrane Transport. Ansari, R. A., Thakran, R. S., and Berndt,W. O. (1991). Fundam. Appl Toxicol 16, 701–709. Both chromateand citrinin have been shown to produce acute renal damage.Although both substrates act on the proximal tubule in the rat,they affect different parts of that nephron segment. As withmost nephrotoxicants, the mechanism(s) or subcellular target(s)for citrinin or chromate is unknown. The availability of methodologyfor isolation of functional membrane vesicles has afforded theopportunity to study the plasma membrane as a target for theeffects of citrinin and chromate. Whether studied solely within vitro conditions or after administration to the rat, chromateexhibited its primary action on the basolateral (BL) membranevesicles. This was exhibited by a reduction in the p-aminohippurate(PAH) overshoot. At both 3 and 16 hr after treatment (40 mg/kg,sc) there was a significant, but relatively modest, effect onglucose transport by brush border (BB) vesicles. Citrinin, whenstudied in vitro, inhibited PAH transport (BL vesicles), buthad only equivocal effects on BB glucose transport. However,after pretreatment of the rats with citrinin (60 mg/kg, ip),both BL and BB membrane vesicle function was reduced markedlyat 3 hr. By 16 hr, an overshoot had returned for both transportsubstrates, although the glucose overshoot was still significantlybelow control. These data demonstrate that both citrinin andchromate alter proximal tubular cell membrane function and doso relatively early after administration to the rat. This effectsuggests that alteration of membrane function by these nephrotoxicantsis an early, if not initiating, event in the production of acutetubular necrosis.     

The Impact of Antitachycardia Pacing with Defibrillation

Chronic recurrent ventricular tachycardia (VT) can be reproducibly terminated by programmed endocardiaJ right ventricular stimulation. However, antitachycardia pacing can be associated with possible acceleration of VT, while frequent episodes of VT and patient discomfort can limit treatment by an implantable cardioverter defibrillator (ICD). The combined use of antitachycardia pacing and the AICD (automatic implantable cardioverier defibrillator) was evaluated in 6 out of 51 patients (age 57 ± 11 years) in whom the AICD had been implanted because of recurrent VT. In each instance VT could be terminated by temporary overdrive pacing. The interactive mode of VT termination by a pacemaker (Tachylog) as well as by the AICD was assessed after implantation. In the automatic mode, the Tachylog functioned as a bipolar, ventricular inhibited (VVI) device with antitachycardia burst stimulation capability, allowing two to five stimuli at intervals of 260–300 ms and one or two interventions. During follow-up of 47 ± 24 months, the Tachylog terminated VT reliably 50–505 times per patient. When burst stimulation accelerated VT, termination was achieved by AICD discharge. Thus, drug resistant VT can be terminated by antitachycardia pacing to avoid patient discomfort. In the event of tachycardia acceleration, VT was terminated by the AICD. A universal pacemaker-defibrillafor should combine antibradycardia and antitachycardia pacing with back-up cardioversion defibrillation.     

Verification of Linear Lesions Using a Noncontact Multielectrode Array Catheter versus Conventional Contact Mapping Techniques

INTRODUCTION: Creation of linear lesions is an established ablation goal. Verification of complete conduction block at the ablation line is required to determine ablation success. Conventional mapping techniques are sequential endocardial activation mapping and documentation of double potentials. Recently, a noncontact multielectrode array catheter was developed that allows instantaneous three-dimensional mapping by simultaneous reconstruction of > 3,000 electrograms. In this study, we prospectively compared the accuracy of noncontact mapping to identify discontinuities in linear lesions and to verify a conduction block with that of conventional mapping techniques. METHODS AND RESULTS: In 12 patients with atrial flutter, radiofrequency pulses were applied between the tricuspid annulus and either the inferior vena cava or the eustachian ridge. Following each application, pulse propagation at the ablation line was determined during pacing by conventional mapping techniques. The findings were compared to high-density isopotential mapping using the noncontact multielectrode array catheter. It was found that noncontact mapping reliably distinguished conduction delays from a conduction block as defined by contact mapping. In addition, noncontact mapping instantaneously identified the area where a discontinuity in the line of block was present. In these patients, complete conduction block was achieved by radiofrequency pulses guided by the noncontact mapping system. CONCLUSION: Noncontact mapping is highly accurate in distinguishing conduction delays from a complete conduction block. By providing an instantaneous high-density propagation vector at all sites along the ablation line, three-dimensional isopotential mapping is helpful in localizing discontinuities of linear lesions and, thus, may facilitate the creation of a complete conduction block.     

Dual antiplatelet therapy unmasks distinct platelet reactivity in patients with coronary artery disease

Summary. Background: Platelet‐induced thrombosis is a major risk factor for recurrent ischemic events, although platelet function in patients with cardiovascular disease taking aspirin and clopidogrel is very poorly characterized. The aim of this study was to assess platelet reactivity in patients with cardiovascular disease taking aspirin and clopidogrel. Methods: We developed a rapid assay to measure platelet aggregation in response to arachidonic acid, collagen, adenosine diphosphate (ADP), epinephrine and thrombin receptor activating peptide (TRAP) in 80 healthy volunteers. We then recruited 200 consecutive patients from outpatient clinics and the cardiac catheterization laboratory and tested platelet function. Platelet aggregation induced by epinephrine is a marker of global platelet reactivity. We tested platelet function in 146 patients compliant with antiplatelet therapy. Platelet aggregation to epinephrine was divided into quartiles. The platelet response to the other agonists was analysed based on the response to epinephrine. Results: Platelet reactivity increased significantly across the quartiles in response to epinephrine in healthy volunteers and patients (P < 0.0001). A significant increase in response across quartiles was seen with all agonists in healthy volunteers (P < 0.001). In contrast, a significant increase in response across quartiles was only seen with ADP in patients (P < 0.0001). Hypertension, smoking and diabetes were significantly associated with increasing platelet reactivity to epinephrine (P < 0.05). Conclusion: This study shows that platelet response differs between healthy volunteers and patients on dual antiplatelet therapy. In patients with cardiovascular disease, dual antiplatelet therapy unmasks a distinct type of platelet reactivity in response to epinephrine and ADP but not other agonists.     

Automatic Implantable Cardioverter/ Defibrillator (AICD) and Antitachycardia Pacemaker (Tachylog): Combined use in Ventricular Tachyarrhythmias

Antitachycardia pacing in ventricular tachyarrhythmias (VT) is associated with potential acceleration of VT: frequency of VT and discomfort of the patient (pt) can limit treatment with the AICD. We therefore evaluated the combined use of antitachycardia pacing and AICD in 6 of 14 patients (age 50–70. mean 60 years) with AICD implantation because of VT, which could he terminated by temporary overdrive pacing. With the interactive mode of the Tachylog, termination of VT by the pacemaker as well as by the AICD was assessed after implantation. In the automatic mode, the Tachylog functioned as a bipolar VVI device with antitachycardia burst stimulation: 2–5 stimuli, interval 260–300 ms. 1–2 interventions. During follow-up of 12±5 months, the Tachylog terminated VT reliably 20 to 327 times per patient. In three patients, burst stimulation accelerated VT, which was terminated then by the AICD discharge. Conclusion: Drug resistant ventricular tachyarrhythmias can be terminated by the Tachylog pacemaker avoiding patients' discomfort. In case of acceleration. ventricular tachyarrhythmias can be controlled by the automatic implantable cardioverter/defibrillator. A universal pacemaker should combine antitachycardia pacing with back-up defibrillation mode.     

Multilineage mobilization of peripheral blood progenitor cells in humans following administration of PEG-rHuMGDF

The most important physiological regulator of megakaryocytopoiesis is the ligand for the c-mpl receptor (thrombopoietin/megakaryocyte growth and development factor, MGDF). We examined the effect of pegylated-recombinant human MGDF (PEG-rHuMGDF): patients received PEG-rHuMGDF at doses of 0.03, 0.1, 0.3 or 1.0 μg/kg/d or placebo for 10 d maximum in a double-blinded randomized study. There was a dose-dependent elevation in circulating platelet counts but no alteration in erythrocyte or total leucocyte counts. The number of bone marrow megakaryocytes was increased approximately 2-fold. The frequency of bone marrow progenitor cells was not altered. In contrast, both to the bone marrow results and to published pre-clinical data, there was a dose-dependent mobilization into the blood of progenitor cells of multiple cell lineages. Increased levels of Meg-CFC (maximum increase 30-fold), day 7 and day 14 GM-CFC and BFU-E were demonstrated at doses of 0.3 and 1.0 μg/kg/d PEG-rHuMGDF. At 0.1 μg/kg/d, mobilization of Meg-CFC alone occurred in two-thirds of patients. Maximum blood levels of progenitor cells occurred at day 12. Thus, administration of PEG-rHuMGDF to humans resulted in mobilization of progenitor cells of multiple lineages despite its 'lineage-specific' activity on mature cell development.     

MORPHOLOGICAL AND BIOCHEMICAL CONFIRMATION OF GRAY PLATELET SYNDROME IN TWO SIBLINGS

A case report is presented of Gray Platelet syndrome in siblings. The absence of platelet α-granules in these patients was confirmed by electron microscopy and by analysis of the platelet protein profile using SDS-polyacrylamide gel electrophoresis. This was further confirmed by quantitation of individual α-granule protein constituents. The results in these two patients are compared with those of the four reported patients with this syndrome.     

Comparison of Two Antitachycardia Pacing Modes in Supraventricular Tachycardia

The comparative efficacy of two different antitachycardia pacing techniques was evaluated in 22 consecutive patients who received the pacemaker Intertach® with an atrial electrode for drug refractory, recurrent Supraventricular tachycardia (SVT). The Intertach® has two consecutive programmable primary and secondary termination modes. The termination programs investigated were adaptive autodecremental burst pacing and adaptive decremental scanning. Atrioventricular nodal reentrant tachycardia was present in 15 patients and atrioventricular reentrant tachycardia due to Wolff-Parkinson-White syndrome in seven patients. The prospective comparison was arranged in a randomized, cross-over study over a period of 12 months. To assess long-term efficacy, diagnostic data of the pacemakers were obtained in intervals of 3 months. In addition, noninvasive programmed stimulation was performed to compare the incidence of pacing-induced atrial fibrillation with both termination programs. During a follow-up of 12 months the overall success rate of autodecremental burst pacing and decremental scanning was 80% and 95%, respectively. Decremental scanning was more effective in 12 patients and less successful in two patients than autodecremental burst pacing. During noninvasive electrophysiological studies, pacing induced atrial fibrillation could be documented in three often patients (30%) using autodecremental burst pacing, compared to one often patients (10%) using decremental scanning. These data suggest that decremental scanning proved to be more successful in the long-term management of patients with recurrent S VT than autodecremental burst pacing. Furthermore, the occurrence of pacing-induced atrial fibrillation could be documented more frequently with autodecremental burst pacing compared to decremental scanning.