Electrophysiologic characteristics of accessory atrioventricular connections in an inherited form of Wolff-Parkinson-White syndrome.

INTRODUCTION: A familial form of Wolff-Parkinson-White syndrome (WPW) occurs in association with hypertrophic cardiomyopathy and intraventricular conduction abnormalities. This syndrome, demonstrating autosomal dominant inheritance and segregating with a high degree of penetrance but variable expressivity, has been genetically linked to chromosome 7q3. The purpose of this study is to detail the electrophysiologic characteristics of accessory atrioventricular connections (AC) in four members of a kindred with this syndrome. METHODS AND RESULTS: We clinically evaluated 32 members of a single kindred and identified 20 individuals with ventricular preexcitation, abnormal intraventricular conduction including complete AV block and/or ventricular hypertrophy. Genetic linkage analysis mapped the disease gene in this kindred to the chromosome 7q3 locus (maximum logarithm of the odds score = 6.88, theta = 0); recombination events in affected individuals reduced the genetic interval from 7 centimorgans (cM) to 5 cM. Electrophysiologic study of four individuals with preexcitation, identified seven AC (1 right sided, 3 septal, and 3 left sided). All four individuals had inducible orthodromic tachycardia; while three had multiple AC. Bidirectional conduction was demonstrated in 6 of 7 AC. Successful ablation was accomplished in 5 of 7 AC. CONCLUSION: The electrophysiologic characteristics and location of AC in family members having this complex cardiac phenotype are similar to those seen in individuals with isolated WPW. Identification of WPW in more than one family member should prompt clinical evaluation of relatives for additional findings of ventricular hypertrophy or conduction abnormalities.

Evaluation of the safety and efficacy of deep sedation for electrophysiology procedures administered in the absence of an anesthetist.

UNLABELLED: Several procedures performed in the electrophysiology laboratory (EP lab) require surgical manipulation and are lengthy. Patients undergoing such procedures usually receive general anesthesia or deep sedation administered by an anesthesiologist. In 536 consecutive procedures performed in the EP lab, we assessed the safety and efficacy of deep sedation administered under the direction of an electrophysiologist and in the absence of an anesthetist. Patients were monitored with pulse oximetry, noninvasive blood pressure recordings, and continuous ECGs. The level of consciousness and vital signs were evaluated at 5-minute intervals. Deep sedation was induced in 260 patients using midazolam, phenergan, and meperidine, then maintained with intermittent dosing of meperidine at the following mean doses: midazolam 0.031 +/- 0.024 mg/kg; phenergan 0.314 +/- 0.179 mg/kg; and meperidine 0.391 +/- 0.167 mg/kg per hour. In the remaining 276 patients, deep sedation was induced with midazolam and fentanyl and maintained with a continuous infusion of fentanyl at a mean dose of 2.054 +/- 1.43 micrograms/kg per hour. Fourteen patients experienced a transient reduction in oxygen saturation that was readily reversed following administration of naloxone. An additional 11 patients desaturated secondary to partial airway obstruction, which resolved after repositioning the head and neck. Fourteen patients experienced hypotension with fentanyl. All but one returned to baseline blood pressures following an infusion of normal saline. No patient required intubation and no death occurred. Only three patients had recollection of periprocedure events. No patient remembered experiencing pain with the procedure. Hospital stays were not prolonged as a result of the sedation used. IN CONCLUSION: (1) deep sedation during EP procedures can be administered safely under the guidance of the electrophysiologist without an anesthetist present; (2) the drugs used should be readily reversible in case of respiratory depression; and (3) this approach may reduce the overall cost of the procedures in the EP lab, maintaining adequate patient comfort.

Safety of nurse-administered deep sedation for defibrillator implantation in the electrophysiology laboratory.

UNLABELLED: Implantation of implantable cardioverter defibrillators (ICDs) in the electrophysiology (EP) laboratory has been shown to be safe. However, general endotracheal anesthesia and/or administration of sedatives is mostly performed by anesthesiologists. In 53 patients undergoing ICD implantation in the EP laboratory, we prospectively assessed whether deep sedation without endotracheal intubation can be administered by nursing personnel under medical supervision. The mean patient age was 67 +/- 7 years, and the mean ejection fraction was 32 +/- 8%. All ICDs were placed in the abdomen requiring lead tunneling. Patients were monitored with pulse oximetry and noninvasive blood pressure recordings. The level of consciousness and vital signs were evaluated at 5-minute intervals. Deep sedation was induced with phenergan and midazolam and maintained with either meperidine or fentanyl. The mean doses given were as follows: phenergan 0.33 +/- 0.15 mg/kg, midazolam 0.05 +/- 0.03 mg/kg, meperidine 0.46 +/- 0.10 mg/kg per hour, and fentanyl 1.94 +/- 0.71 micrograms/kg per hour. None of the patients required intubation during or after the procedure. No death occurred and no patient had any recollection of the procedure. In three patients, O2 desaturation was easily managed by transient reversion of the effects of meperidine or fentanyl with naloxone. No patient experienced prolonged hospitalization after the implant (mean 2.4 +/- 0.5 days). IN CONCLUSION: (1) adequate sedation for ICD implantation and testing can be administered safely by nursing staff in the EP lab; (2) optimum sedation protocols should include drugs easy to reverse in case of excessive respiratory depression; and (3) this may represent a more cost-effective approach to ICD implantation.

Relative efficacy of different tilts with biphasic defibrillation in humans.

OBJECTIVE: The goal of this study was to assess if tilt bears any impact on defibrillation efficacy of biphasic shocks. BACKGROUND: Although it has been shown that biphasic waveform may increase the defibrillation efficacy, this pulsing method has not been as extensively studied in patients, and information regarding the effect of different tilts is lacking. METHODS: This study consisted of two similar but distinct protocols including 33 patients undergoing transvenous defibrillator implant. In 17 patients (Part I) defibrillation threshold was obtained delivering biphasic waveforms with 50%, 65%, and 80% tilt in random fashion. Similarly, in 16 patients (Part II) testing of biphasic waveform with 40%, 50%, and 65% tilt was performed in random order. The electrode system used consisted of two transvenous leads and a subcutaneous patch in all 33 patients. RESULTS: In Part I, tilt of 50% demonstrated a defibrillation threshold significantly lower than 65% tilt (7.5 +/- 4.3 J vs 9.7 +/- 5.0 J; P = 0.04) and 80% tilt (7.5 +/- 4.3 J vs 11.7 +/- 5.9 J; P < 0.01). Similarly, 65% tilt provided a lower defibrillation threshold than 80% tilt (9.7 +/- 5.0 J vs 11.7 +/- 5.9 J; P = 0.02). In Part II, no significant difference was observed in terms of defibrillation threshold between 40% tilt and the two tilts of 50% and 65%. However, as in Part I, 50% tilt provided a significant reduction of the energy to defibrillate as compared to 65% tilt (6.3 +/- 3.6 J vs 9.0 +/- 4.8 J; P < 0.01). The 50% tilt resulted in better defibrillation efficacy than 65% tilt independent of the lead system used for testing (Medtronic Transvene and CPI Endotak-C). CONCLUSIONS: Biphasic shocks with 50% tilt required less energy for defibrillation than 40%, 65%, and 80% tilts. However, in the clinical setting a programmable tilt may be preferable to account for some patient-to-patient variability.

Sensing failure in a tiered therapy implantable cardioverter defibrillator: role of auto adjustable gain.

Implantable cardioverter defibrillators have an established role in the management of life-threatening tachyarrhythmias. These devices use sophisticated sensing circuitry to detect and promptly treat a vast majority of these arrhythmias. However, they are not foolproof. We report one case where the device failed to sense every other QRS complex during induced ventricular fibrillation due to marked electrical alterans. Thus, undersensing can be a potentially fatal problem despite the use of auto adjustable gain.

Efficacy of different treatment strategies for neurocardiogenic syncope.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of different therapeutic approaches for patients with a history of syncope and positive head-up tilt testing. BACKGROUND: Head-up tilt testing has gained broad acceptance as a reliable diagnostic method for the assessment of patients with recurrent unexplained syncope. However, once the diagnosis is established, there is no consensus on the most appropriate treatment. In this respect, efficacy of drug therapy in preventing recurrence of symptoms in such patients is not entirely clear, and controversies exist regarding the need to confirm the effects of pharmacological interventions. METHODS: Clinical follow-up was obtained in 303 patients with a history of syncope and positive head-up tilt testing. After the diagnostic head-up tilt, patients were assigned to different therapeutic approaches according to their preference or logistic impediments. Of 303 patients, 44 received empiric therapy, 210 were treated with medications proven effective during repeated head-up tilt testing, and 49 refused or discontinued medical therapy. The three groups were similar with regard to age, sex, and clinical presentation. The mean follow-up was 2.8 +/- 1.8 years. Among the patients treated according to head-up tilt guided therapy, 130 were on beta blockers, 35 on theophylline, 10 on ephedrine, 31 on disopyramide, and 4 on miscellaneous regimens. Empiric treatment consisted of beta blockers in 37 of 44 patients and other drugs in the remaining patients. RESULTS: During the follow-up, recurrence of symptoms was experienced in 12 (6%) of the 210 patients receiving the head-up tilt guided therapy, 16 (36%) of 44 in the empiric therapy group, and 33 (67%) of 49 in the no therapy group. Recurrence of symptoms in patients on empiric or no therapy was significantly more frequent as compared to the head-up tilt guided therapy group (P < 0.01). CONCLUSIONS: In patients with unexplained syncope and positive upright tilt testing, therapeutic strategies identified on the basis of response during head-up tilt have a more positive impact on the recurrence of symptoms during follow-up.

Preliminary experience with a hybrid nonthoracotomy defibrillating system that includes a biphasic device: comparison with a standard monophasic device using the same lead system.

OBJECTIVES: This study analyzed the advantage of combining a biphasic device with a transvenous system and compared the results with those obtained with a standard monophasic device. BACKGROUND: Available lead systems use monophasic pulses and may require lengthy intraoperative testing to achieve adequate defibrillation threshold in a conspicuous number of patients. The option of biphasic waveform may provide further benefits. However, clinical experience with a permanent implant is lacking. METHODS: Fifty-five patients underwent testing and received a permanent implant using the Endotak lead system associated with a CPI monophasic device. The remaining 36 patients received a permanent implant with the Endotak lead system connected to a biphasic device. In both groups a subcutaneous patch was combined when needed to obtain acceptable defibrillation thresholds. RESULTS: Biphasic pulses resulted in lower mean (+/- SD) defibrillation thresholds (monophasic 15 +/- 4.7 J vs. biphasic 12 +/- 5 J, p = 0.03) and a better implantation rate (100% biphasic vs. 89% monophasic, p = 0.07). Biphasic pulses allowed implantation with less ventricular fibrillation induction (7.4 +/- 3.2 vs. 3.5 +/- 1.8, p < 0.01) and a mean shorter procedure time (168 +/- 39 vs. 111 +/- 30 min, p < 0.01). With the biphasic waveform a greater proportion of patients met the implantation criteria with the lead system alone (83% vs. 45%, p < 0.01). When needed, the left prepectoral location of the patch electrode was always sufficient in left subscapular position was required in 15 patients in the monophasic group. Implantation of the biphasic device was associated with a shorter mean hospital stay (3.8 +/- 0.8 vs. 5.4 +/- 2.2 days, p < 0.01). CONCLUSIONS: Incorporation of a biphasic device in a transvenous implantable cardioverter-defibrillator uniformly increases the efficacy of the system and the ease of implantation.

Indomethacin and aspirin: effect of nonsteroidal anti-inflammatory agents on the rate of fracture repair in the rat.

A total of 210 male Charles River CD rats, 45 days old, were subjected to a fracturing of the right radius and ulna by digital pressure while under ether anesthesia. These animals were then assigned randomly to dose groups (1, 2 or 4 mg/kg/day of indomethacin and 100, 200, or 300 mg/kg/day of aspirin) and were dosed for 21 days. Dose levels were chosen to provide approximately equipotent levels of the test compounds with the highest dose approaching toxicity. Radiographs were taken of control-rat fractures on days 8, 14, and 21. Three rats at 4 mg/kg/day of indomethacin died of interstinal perforation prior to scheduled sacrifice. On day 22, all remaining rats were sacrificed by exsanguination under anesthesia. Histologic secretions of the radius and ulna were examined in random sequence without knowledge of the treatment regimen. A histologic grade based on the morphologic stage of fracture healing was given. There was a drug- and dose-related retardation of fracture healing, which was statistically significant at all dose levels of indomethacin and the highest level of aspirin, as compared to controls. Decreased mean grades in the groups given 100 and 200 mg/kg/day of aspirin, though not statistically significant, suggest a retarding effect on fracture healing at these levels also. No statistically significant changes in numbers of pseudoarthroses were found.

Application of a new surface labeling reagent, EDTA derivative, on erythrocytes and platelets.

The modes of binding of a new class of impermeant metal-chelating probe, the complex of 111In3+ to 1-(p-benzenediazonium) ethylenediamine tetraacetic acid (azo-phenyl-EDTA), to human and rabbit erythrocyte membranes and the effect of binding on the function of rabbit platelets have been studied. The metal chelate, azo-phenyl-EDTA.[111In3+] bound covalently to membrane proteins following reaction with intact erythrocytes. The amount and the pattern of labeling was assessed by sodium dodecyl sulfate (SDS)-polyacrylamide disc and slab gels for radioactivity. The pattern of labeling of intact human erythrocytes by azo-phenyl-EDTA.[111In3+], by pyridoxal phosphate-NaB3H7 and by galactose oxidase-NaB3H4 was also compared. The following results were obtained: (a) The pattern of labeling of intact human erythrocyte by azo-phenyl-EDTA.[111In3+] differed from other commonly used probes for labeling external membrane surfaces. Five polypeptides were labeled by the metal chelates. In addition to the known major proteins (protein band III, PAS-1, PAS-2 and PAS-3 of Fairbanks et al. (1972) Biochemistry 10, 2606--2617) a protein (radioactive band 4) which migrated slightly slower than PAS-3 in SDS gel was labeled heavily by the metal chelate. This protein has an apparent molecular weight of 37,500 in 8.4% acrylamide-SDS gel. About 40% of bound radioactivity was found in this protein. The diazo linkage of the metal chelate to this protein was found to be especially unstable to heat. (b) In rabbit erythrocyte membranes, the metal chelate bound to three polypeptides with apparent molecular weights of 96,000, 43,000 and 33,000 in 8.4% acrylamide gel. They are probably glycoproteins in nature. (c) The binding of the probe to platelets did not affect the platelet aggregability induced by adenosine diphoshpate. In vivo studies indicated that the labeled platelets accumulated at the plague of atherosclerotic rabbits. (d) The bifunctional analog of EDTA may permit new applications of metals with useful physical properties for studies of cell membranes.