Clinical Evaluation of Automatic Tachycardia Diagnosis by an Implanted Device

Reliable discrimination between sinus tachycardia (ST) and pathologic tachycardia has been a major problem for automatic implantable antitachycardia devices. In patients whose sinus response to activity is as rapid or faster than their pathologic tachycardia (rate crossover), these unsophisticated devices deliver the programmed tachycardia response to either the pathologic or sinus tachycardia. Over a one-year period, 50 Intermedics Intertach Model 262–12 antitachycardia pulse generators were implanted to evaluate the specificity of a new group of tachycardia recognition algorithms. Patients were subjected to exercise testing and noninvasive programmed stimulation to demonstrate the efficacy of this new approach. The five recognition algorithms tested were various combinations of the following criteria: high rate HR), sudden onset (SO), rate stability (RS), and sustained high rate (SHR). False positive rates (tachycardia response inappropriately triggered by ST) were as follows: HR (93%); HR + SO (3%); HR + RS (63%); HR + (RS or SHR) (87%); HR + HS + SO (8%). Pair-wise significance testing between HR only and HR + SO (p < 0.001), HR + RS (p = 0.01) and HR + SO + RS (p < 0.001), demonstrated a significant reduction in the rate of false positives through the use of the sudden onset and rate stability criteria in concert with the standard high rate criterion.     

Chronic Morpholine Exposure of Rats

Chronic Morpholine Exposure of Rats. HARBISON, R. D., MARINO,D. J., CONAWAY, C. C., RUBIN, L. F., AND GANDY, J. (1989). FundamAppl. Toxicol. 12,491–507. The chronic toxicity and carcinogenicpotential of morpholine were evaluated in 60 Sprague-Dawleyrats/sex/group receiving morpholine at mean inhalation exposureconcentrations of 0, 10, 50 and 150 ppm for 6 hr/day, 5 days/week,for 104 weeks. Survival, body weight gains, organ weights, hematology,and clinical chemistries were normal in exposed groups and comparableto those of the control animals. The incidences of palpabletissue masses and of histologically confirmed neoplasia werecomparable among all groups, including the control groups, andwere typical of the strain and age of the rats tested. In-lifeclinical examinations revealed increased incidences of irritationaround the eyes and nares, chromadacryorrhea, and urine stainson the fur, predominately in high-dose animals. Morpholine exposurewas associated with corneal irritation seen by ophthalmoscopicexamination and confirmed microscopically as keratitis limitedto the highest exposure group. Irritation of the maxillary andnasoturbinates as indicated by infiltration of neutrophils,focal squamous metaplasia of the turbinate epithelium, and necrosisof the turbinate bone was observed in high-dose animals. Therefore,chronic exposure of rats to morpholine for 2 years at concentrationsof 150 ppm or less revealed no carcinogenic potential or chronicsystemic toxicity. Consistent with its known irritating properties,morpholine produced only local irritation, which was limitedalmost exclusively to high-dose animals.     

Mouse Liver Carcinogenesis: Mechanisms and Relevance

Symposium Overview: Mouse Liver Carcinogenesis: Mechanisms andRelevance. GOODMAN, J. I., WARD, J. M., POPP, J. A., KALUNIG,J. E., AND FOX, T. R. (1991). Fundam. Appl. Toxicol. 17, 651–665.     

THE CHILD SUICIDE RISK ASSESSMENT: A SCREENING MEASURE OF SUICIDE RISK IN PRE-ADOLESCENTS

This study documents the initial reliability and validity of the Child Suicide Risk Assessment (CSRA) for children under the age of 13. The revised CSRA retained 18 of 20 original items based on item-specific psychometric data from 140 pre-adolescents in out-of-home treatment programs. The CSRA demonstrated adequate internal consistency (α = .69) for a multi-dimensional scale (3 factors: Worsening Depression, Lack of Support, and Death as Escape). CSRA scores correlated significantly with criterion measures of prior suicide attempts and ideations. A receiver operating characteristic (ROC) curve discriminated significantly between prior attempters and non-attempters and was used to select preliminary CSRA cut-off scores for identifying substantial suicide risk. The CSRA is the first screening measure of suicide risk in pre-adolescents validated by associations with suicide attempts as well as ideations.     

The Atrial Electrogram During Clinical Electrophysiologic Studies: Onset versus the Local/Intrinsic Deflection

The Local Atrial Deflection. Introduction : As a wave front passes unfiltered bipolar recording electrodes, the point of local depolarization is marked by a maximal change in voltage, i.e., the intrinsic deflection. However, during electrophysiologic studies, the depolarization (A) on the lead recording the His-bundle potential traditionally has been measured at the first rapid reproducible deflection on a filtered electrogram. This methodology permits considerable latitude for subjective interpretation. The purpose of this study was to assess the timing of the atrial electrogram using the intrinsic deflection of relatively unfiltered electrograms (0.1-4.0 to 1,250 Hz) or the equivalent on filtered recordings. Methods and Results : To do this we studied 70 patients without evidence of atrial or atrioventricular (AV) nodal disease, documenting the difference in timing between the A wave as traditionally measured and as measured at its peak local deflection (A_L) determined from simultaneously recorded filtered and relatively unfiltered electrograms. New ranges based on the A_L were established for timing of intra-atrial and AV nodal conduction intervals. The P-A (41 ± 11 msec) was significantly shorter than the P-A_L (55 ± 12) and the A-H (80 ± 20) was longer than the A_L-H (66 ± 21 msec), both P <0.001. Interobserver differences in measurements were smaller when using the local (A_L) rather than traditional criteria. Conclusions : Conventional measurement of the A deflection provides only a rough estimate of local depolarization of the atrium near the AV node. The criteria proposed in the present article may (1) provide a better estimate of the timing of local depolarization; (2) have application in computerized timing of intervals; and (3) decrease technical problems and subjective error.     

Sudden Death Mortality in Implantable Cardioverter Defibrillator Patients

Implanfable Cardioverter defibrillator (ICD) prevention of sudden cardiac death (SCD) is not absolute and our experience was reviewed to determine the frequency and nature of SCO in this population. The incidence and cause of mortality in 56 consecutive patients, who underwent ICD implantation beginning May 1982 with follow-up through May 19, 1990 were analyzed. Twenty-one patients died, 33% of the mortality was due to SCD, and 52% of deaths may be considered arrhythmic. The cumulative 1, 3, and 5 year SCD survivals were 93%, 89%, and 75%. All seven patients dying of SCD presented initially with SCD, all received previous shocks prior to SCD, and two of the seven patients had devices that were probably inactive at the time of death. We conclude that ICDs reduce but by no means eliminate arrhythmic death, particularly in those at highest risk for SCD. Arrhythmic death remained the most common cause of death in this population.     

The Psychological Impact of Implantable Cardioverter-Defibrillator Recalls and the Durable Positive Effects of Counseling

Background: It is known that patients with lifesaving devices such as implantable cardioverter-defibrillators (ICDs) may be alarmed and worried by recalls or alerts related to their ICDs.
Objectives: This study aimed to determine whether counseling has any short- or long-term benefits, and to look for characteristics that identify those most worried and those most in need of counseling.
Methods: Among 100 patients with recall or alert ICDs, 14 were pacer dependent; 50 had ICDs for 1° prevention and 22 were women. Patients completed a survey indicating how worried they were on learning of the recall or alert (0–10 scale). After counseling and advice in accordance with manufacturer guidelines, patients were asked to indicate their level of worry, and were again asked after 6 months.
Results: For all patients, the "worry level" at the initial interview was 5.0 ± 3.7, falling to 2.2 ± 3.0 after counseling (P < 0.001) and 1.4 ± 2.3 after 6 months (P < 0.001 vs both earlier levels). There were no significant differences between those implanted for 1° versus 2° prevention or for pacer dependency. Women were initially more worried than men, but not for the long term. The 49 patients whose ICDs could be managed by reprogramming or software fix had significant reduction in worry after counseling and at 6 months compared to others. The 18 patients recommended for operative intervention remained more concerned after counseling (3.5 ± 3.3 vs 1.9 ± 2.9, P = 0.043).
Conclusions: Patients' concerns resulting from ICD recalls or alerts can be reduced by appropriate counseling. Those patients whose ICDs could be reprogrammed to safer parameters had the most reduction in worry levels.     

Value of Pre-Hospital Discharge Defibrillation Testing in Recipients of Implanted Cardioverter Defibrillators

Opinions vary regarding the need to perform defibrillation testing prior to hospital discharge in recipients of state-of-the-art cardioverter defibrillators (ICDs). Our protocol is to perform predischarge ICD testing 1 day after implant. This report includes 682 consecutive implants. Adverse observations at testing were grouped into (1) risk of defibrillation failure, (2) surgical complications, (3) sensing/pacing issues or narrow defibrillation margin warranting closer follow-up, or (4) findings correctable by device reprogramming. Among the 682 patients, 63% had single-chamber and 37% dual-chamber or biventricular ICDs. In 48 patients (7%) there were 69 concerns and/or interventions, with overlaps among the four categories, including one failure to defibrillate (0.15%), and six other patients at risk. Surgical complications included 11 hematomas (1.6%), and six lead dysfunctions. Closer follow-up was indicated in 19 patients (2.7%), for high pacing thresholds in seven, sensing issues in seven, and <10 J defibrillation margin in five. Device reprogramming was needed in 31 patients (4.5%), for tachycardia detection and therapy settings in 12, and for pacing/sensing functions in 22 patients. In eight patients ventricular fibrillation could not be induced. There was no morbidity or mortality due to testing. The state-of-the-art ICDs delivering biphasic shocks are remarkably reliable. The routine pre-hospital discharge defibrillation testing of such ICDs may be optional and left to the physicians' discretion.     

Design and Objectives of the Evaluation of Oral Xemilofiban in Controlling Thrombotic Events (EXCITE) Study

Clinical trials have demonstrated the efficacy of glycoprotein (GP) IIb/IIIa antagonists in preventing the thrombotic end points of death, myocardial infarction, and urgent revascularization when they are administered at the time of percutaneous coronary revascularization (PTCR). It has been postulated that prolongation of receptor blockade beyond acute intervention would extend the clinical benefit of these agents. The Evaluation of Oral Xemilofiban in Controlling Thrombotic Events (EXCITE) study was a multicenter, international, randomized placebo-controlled trial of the oral GP IIb/IIIa antagonist Xemilofiban administered prior to and after PTCR. The study was designed to assess the efficacy and safety of continuing oral xemilofiban for 6 months to prevent these primary thrombotic end points. More than 7,200 patients were randomized in 29 countries to receive placebo or one of two doses of xemilofiban. Stenting was performed at the discretion of the operator. All patients received aspirin and periprocedural heparin; all stented patients received continuous xemilofiban, or ticlopidine for 2–4 weeks followed by xemilofiban-placebo. Most patients were also evaluated 1 month after conclusion of the study drug treatment. Clinical data from up to 6 months of drug treatment and 1 month posttreatment were used to evaluate the acute and long-term efficacy and safety of xemilofiban. Secondary end points included the need for any revascularization, repeat hospitalization for unstable angina, and nonhemorrhagic stroke. The cumulative incidence of bleeding events and effects of xemilofiban in stented and nonstented patients were evaluated. The efficacy of continuing xemilofiban and aspirin therapy as the sole antithrombotic medications following stent deployment was assessed against a ticlopidine and aspirin control group. The incremental clinical benefit of long-term receptor blockade over acute receptor antagonism was evaluated.