Patterns of cognitive recovery in sudden cardiac arrest survivors: the pilot study.

OBJECTIVE: To determine the prevalence, type, severity, and natural evolution of cognitive impairments in survivors of sudden cardiac arrest over time and to assess the relation of selected clinical and psychologic variables to those outcomes. DESIGN: Longitudinal with repeated measures. Twenty-five consecutive patients underwent extensive neuropsychologic testing during hospitalization within 3 weeks of their initial cardiac arrest. Of these, 17 completed additional testing at 6 to 9 weeks, 12 to 15 weeks, and 22 to 25 weeks after the event. SETTING: Cardiac electrophysiologic services at a university teaching hospital, a community hospital, and home. OUTCOME VARIABLES: Orientation, attention, concentration, immediate recall, early retention, delayed recall, reasoning, motor speed, and motor regularity were measured. RESULTS: During hospitalization, 72% of the patients had mild to severe impairments in one or more cognitive areas. Memory, particularly delayed recall, was the most common deficit. At 6 months after the arrest event, 29% (5 of 17) of the patients continued to be impaired, and all had deficits in delayed recall. Depression was significantly related to deficits in attention and delayed recall at 6 months only. Time to postarrest awakening was the most reliable predictor of long-term cognitive functioning in this patient sample. CONCLUSION: A significant minority of sudden death survivors incur long-term cognitive impairments, particularly in delayed recall or short-term memory. The occurrence of long-term cognitive deficits in these patients can be estimated from the duration of unconsciousness after resuscitation (time-to-awakening).

Intravenous amiodarone for recurrent sustained hypotensive ventricular tachyarrhythmias. Intravenous Amiodarone Multicenter Trial Group.

OBJECTIVES: We sought to determine the response rate and safety of intravenous amiodarone in patients with ventricular tachyarrhythmias refractory to standard therapies. BACKGROUND: Numerous small retrospective reports suggest a response of refractory ventricular tachyarrhythmias to intravenous amiodarone, yet no controlled prospective trials exist. METHODS: Two hundred seventy-three patients with recurrent hypotensive ventricular tachyarrhythmias refractory to lidocaine, procainamide and bretylium were randomized to receive one of three doses of intravenous amiodarone: 525, 1,050 or 2,100 mg/24 h (mean [+/- SE] dose 743.7 +/- 418.7, 1,175.2 +/- 483.7, 1,921.2 +/- 688.8 mg, respectively) by continuous infusion over 24 h. RESULTS: Of the 273 patients, 110 (40.3% response rate) survived 24 h without another hypotensive ventricular tachyarrhythmic event while being treated with intravenous amiodarone as a single agent (primary end point). A significant difference in the time to first recurrence of ventricular tachyarrhythmia (post hoc analysis) over the first 12 h was observed when the combined 1,050- and 2,100-mg dose groups were compared with the 525-mg dose group (p = 0.046). The number of supplemental (150 mg) infusions of intravenous amiodarone (given for breakthrough destabilizing tachyarrhythmias) during hours 0 to 6 (prespecified secondary end point) was significantly greater in the 525-mg dose group than in the 2,100-mg dose group (1.09 +/- 1.57 vs. 0.51 +/- 0.97, p = 0.0043). However, there was no clear dose-response relation observed in this trial with respect to success rates (primary end point), time to first recurrence of tachyarrhythmia (post hoc analysis) or mortality (secondary end point) over 24 h. CONCLUSIONS: Intravenous amiodarone is a relatively safe therapy for ventricular tachyarrhythmias refractory to other medications.

Implantable cardioverter defibrillator: Ventritex Cadence.

The Ventritex Cadence Model V-100 Tiered Therapy Defibrillator is a third generation antitachyarrhythmia device currently completing clinical trials in the United States. The implantable pulse generator is capable of high energy defibrillation, low energy cardioversion, as well as antitachycardia and bradycardia pacing. In addition, this microprocessor controlled device can deliver monophasic or biphasic defibrillation/cardioversion shocks, is noncommitted to deliver shock therapy after initiating charging for defibrillation or cardioversion therapy, and can store electrograms of spontaneous tachyarrhythmia episodes. These expanded device capabilities should improve therapy efficacy and patient management, and represent a major advance in the treatment of patients with ventricular tachyarrhythmias.

Automatic implantable cardioverter defibrillator: surgical approaches for implantation.

Surgical approaches for implantation of the automatic cardioverter defibrillator are sternotomy, left thoracotomy, subxiphoid, and subcostal. Although any one of these may be combined with insertion of one or more of the electrodes transvenously, surgical entry into the chest is required for every noninvestigational defibrillator implantation operation. The approaches differ in exposure provided for selecting electrode sites and for handling untoward events, in amount and location of tissue that must be divided or dissected, and in average time required. The operation is an electrical one. Its purpose is to obtain reliable rhythm sensing so that defibrillation or cardioversion shocks will occur only when necessary, and to obtain low enough defibrillation thresholds for shocks of 30 joules or less to have a 10-joule defibrillation safety margin. Many of the patients have had previous cardiac operations. They usually have low or very low ejection fractions. Intraoperative electrophysiological testing with often multiple defibrillation episodes is required. The choice of approach varies with the state of the patient, the institutional experience, and the surgeon. This article describes technique, and the advantages and disadvantages of the four approaches as used by four surgeons in four different institutions.

Clinical pharmacology of intravenous enoximone: pharmacodynamics and pharmacokinetics in patients with heart failure.

Twenty-one patients with heart failure (New York Heart Association [NYHA] class II to IV) received a 24-hour infusion of enoximone followed by a 12-hour washout period. Patients were randomly assigned to one of four treatment groups. Groups I to III received an 0.5 mg/kg bolus, followed by a maintenance infusion of 2.5, 5.0, or 10.0 micrograms/kg/min. Group IV patients received a maintenance infusion of 5.0 micrograms/kg/min without a loading dose. Serial assessment of hemodynamics, plasma levels of enoximone and enoximone sulfoxide, and ventricular ectopy were performed. Enoximone produced a clinically significant increase in cardiac index, and a decrease in mean pulmonary artery wedge pressure and systemic vascular resistance in all groups. Enoximone mildly increased heart rate, and had a minimal effect on mean arterial pressure. There was no statistically significant change in ventricular ectopy during the infusion. Significant hemodynamic improvement was noted at even the lowest infusion rate, and did not increase in linear fashion at higher infusion rates. In patients who did not receive an initial loading bolus of 0.5 mg/kg, the increase in cardiac index was delayed by approximately 1 hour. Plasma concentrations of both enoximone and its major metabolite continued to rise throughout the 24-hour infusion in group III (10.0 micrograms/kg/min), rather than reaching steady state as predicted by the terminal exponential half-lives of these compounds. This is suggestive of nonlinear pharmacokinetics and indicates a potential for excessive accumulation of enoximone and its metabolite during prolonged infusion. These findings may have important implications in guiding the intravenous administration of enoximone.(ABSTRACT TRUNCATED AT 250 WORDS)

Disposition kinetics of orally administered enoximone in patients with moderate to severe heart failure.

Enoximone is a phosphodiesterase inhibitor, which has been studied extensively for use in the management of patients with moderate-to-severe heart failure. The authors have studied the absorption and disposition kinetics of enoximone and its primary metabolite, enoximone sulfoxide, after both single oral doses of enoximone and at steady-state after short-term chronic oral therapy. A total of ten patients (two female, eight male) with moderate-to-severe heart failure (NYHA class II-IV) were enrolled into the study after giving written informed consent. The plasma levels of enoximone sulfoxide were greater than those of enoximone at all sampling times. The peak enoximone sulfoxide plasma concentrations ranged from 3.5 to 17.3 times the peak enoximone plasma levels for individual patients. The average steady-state plasma concentrations for enoximone were 115 +/- 40 ng/mL and 190 +/- 78 ng/mL for 50 mg every 8 hours and 100 mg every 8 hours dosage regimens, respectively. The absorption and disposition kinetics of enoximone were found to be significantly variable between patients. The authors also evaluated the relationship between dose administered and steady-state plasma levels as well as the relationship between the observed and predicted steady-state plasma levels. The authors found a linear relationship between the dose that was administered and the accrued plasma levels, as well as a good correlation between the predicted and observed steady-state levels. Although these data confirm previous reports that the sulfide metabolite of enoximone accumulates extensively in the plasma during oral therapy, reaching levels much higher than those of enoximone, these data do not support previous suggestions that the disposition of enoximone is nonlinear.

Comparison of pre- and postoperative conduction patterns in patients surgically cured of atrioventricular node reentrant tachycardia.

Patients with atrioventricular (AV) node reentrant tachycardia characteristically have short and constant retrograde His-atrium conduction times (H2A2 intervals) during the introduction of ventricular extrastimuli. It has therefore been suggested that the tachycardia circuit involves retrograde conduction up an accessory pathway located in perinodal tissue. If the mechanism of surgical cure of AV node reentrant tachycardia is interruption of this accessory pathway, postoperative changes in retrograde conduction would be expected. Thirteen patients with drug-refractory AV node reentrant tachycardia underwent surgery. Preoperatively, H2A2 intervals were short and constant. During AV node reentrant tachycardia, earliest atrial activation was seen near the His bundle and was 0 to 25 ms before ventricular activation in all patients except one. Surgery consisted of dissection of right atrial septal and anterior inputs to the AV node and central fibrous body. Postoperatively, the H2A2 interval remained short and constant compared with preoperative values although it was slightly prolonged (74 +/- 18 versus 61 +/- 21 ms, p less than 0.005). Twelve of the 13 patients are free of tachycardia after 28 +/- 13 months and no patient has had evidence of AV node block. Thus, surgical cure of AV node reentrant tachycardia is highly successful; however, there is no reason to postulate an accessory pathway or use of perinodal tissue as part of the tachycardia circuit and the mechanism of surgical success remains obscure.

Pharmacodynamics of enoximone during intravenous infusion.

Twenty-one patients with heart failure (NYHA class II-IV) received a 24-hour infusion of enoximone, followed by a 12-hour washout period. Patients were randomly assigned to one of four treatment groups. Groups I-III received a 0.5 mg/kg bolus, followed by a maintenance infusion of 2.5, 5.0 or 10.0 micrograms/kg/minute. Group IV patients received a maintenance infusion of 5.0 micrograms/kg/minute without the bolus. Serial assessments of haemodynamics, plasma levels of enoximone and enoximone sulphoxide, and ventricular ectopy were performed. Enoximone produced a significant increase in cardiac index (28.1-46.7%) and a decrease in mean pulmonary artery wedge pressure (6.4-35.7%) and systemic vascular resistance (34.7-78.9%). Enoximone had minimal effect on heart rate and blood pressure. In patients who did not receive an initial bolus of 0.5 mg/kg, haemodynamic changes were delayed by approximately 1 hour. Significant haemodynamic improvement was noted at even the lowest infusion rate and did not increase in linear fashion at higher infusion rates. During infusion of enoximone at 10.0 micrograms/kg/minute, both enoximone and its sulphoxide accumulated non-linearly and did not achieve a steady state. No significant adverse effects were noted in these patients. Enoximone infusion at rates greater than 5.0 micrograms/kg/minute may confer minimal additional haemodynamic benefit, while resulting in significant accumulation of enoximone and enoximone sulphoxide. Ventricular ectopy did not increase significantly in most patients.

Effect of duration of ventricular fibrillation on defibrillation efficacy in humans.

The currently available automatic implantable cardioverter-defibrillator has proven highly successful for termination of ventricular tachycardia and fibrillation. Newer devices, however, permit lower energy shocks to be delivered initially and longer episodes of arrhythmia to occur before shocks are delivered. These changes may result in longer durations of arrhythmia before successful termination. Little is known about the effects of the duration of ventricular fibrillation on the efficacy of defibrillating shocks. In this study, we examined the efficacy of defibrillating shocks in 22 patients undergoing automatic implantable cardioverter-defibrillator implantation or generator change. Defibrillating shocks ranging from 300 to 600 V (5.9-24.2 J) were delivered in matched pairs after 5 and 15 seconds of ventricular fibrillation. For the 300-V shocks (5.9 J), defibrillation was accomplished in 82% of patients when the shocks were given after 5 seconds of ventricular fibrillation and in only 45% of patients when the shocks were delivered after 15 seconds (p less than 0.01). At higher energies, there was no difference in the efficacy of defibrillation shocks delivered after 5 compared with 15 seconds of ventricular fibrillation. The postshock aortic, systolic, and diastolic blood pressures were significantly lower when the shocks were given after 15 seconds of ventricular fibrillation than after only 5 seconds. We conclude that the duration of ventricular fibrillation affects defibrillation efficacy especially at energies that are relatively low compared with maximal device outputs and that longer episodes of ventricular fibrillation cause more postshock hemodynamic depression. These observations have implications for defibrillation threshold testing at the time of device implantation and for the design and programming of future automatic implantable antitachycardia devices.

The diurnal variability of ventricular premature depolarizations: influence of heart rate, sleep, and wakefulness.

The relationships between ventricular premature depolarizations (VPDs) and heart rate (HR) were determined in 14 patients with ventricular arrhythmias and the influence of these relationships on the diurnal variability of ventricular arrhythmias was evaluated. The influence of sleep state, wakefulness, and level of activity on the frequency of VPDs was also studied. Subjects completed 48-72 h of ambulatory electrocardiographic monitoring and nocturnal sleep recordings. Plots of VPD frequency vs. HR were examined and subjects were categorized as HR-dependent if they manifested log-linear increase in VPDs with increasing HR and as HR-independent if no relation between VPD frequency and HR was detected. Sleep suppression of VPDs was observed in the HR-dependent group (p less than 0.05). The reduction in VPD frequency correlated with the reduction in HR and was independent of sleep state or wakefulness. No change in VPD frequency was observed during wakefulness, rapid eye movement sleep, or non-rapid-eye-movement sleep in the HR-independent group. The influence of level of activity on ventricular arrhythmia frequency was also assessed in seven subjects. Any decreases in VPD frequency observed during inactivity were associated with a decrease in HR. These observations suggest that HR is a major determinant of the diurnal variation of VPD frequency in a subset of patients with frequent VPDs.

Long-term outcome with the automatic implantable cardioverter-defibrillator.

The automatic implantable cardioverter-defibrillator was implanted in 270 patients because of life-threatening arrhythmias over a 7 year period. There was a history of sustained ventricular tachycardia or fibrillation, or both, in 96% of these patients, 80% had one or more prior cardiac arrests and 78% had coronary artery disease as their underlying diagnosis. The average ejection fraction was 34%, and 96% of these patients had had an average of 3.4 antiarrhythmic drug failures per patient before defibrillator implantation. There were four perioperative deaths and eight patients had generator infection or generator erosion, or both, during the perioperative period or during long-term follow-up. Concomitant antiarrhythmic drug therapy was given to 69% of patients. Shocks from the device were given to 58% of patients. and 20% received "problematic" shocks. The device was removed from 16 patients during long-term follow-up for a variety of reasons. There were 7 sudden cardiac deaths and 30 nonsudden cardiac deaths, 18 of which were secondary to congestive heart failure. The actuarial incidence of sudden death, total cardiac death and total mortality from all causes was 1%, 7% and 8%, respectively, at 1 year, and 4%, 24% and 26% at 5 years. The automatic implantable cardioverter-defibrillator nearly eliminates sudden death over a long-term follow-up period in a high risk group of patients. It has an acceptable rate of complications or problems, or both, and most late deaths in these patients are nonsudden and of cardiovascular origin.

Improved low energy defibrillation efficacy in man with the use of a biphasic truncated exponential waveform.

The standard implantable defibrillator waveform is a truncated exponential of approximately 6 msec duration. This study compares the defibrillation efficacy of a standard monophasic truncated exponential to a biphasic 12 msec truncated exponential waveform in 21 patients undergoing automatic implantable cardioverter defibrillator (AICD) surgery. For the biphasic waveform, the polarity was reversed and remaining capacitor voltage was attenuated by 75% after 6 msec. Two hundred thirty episodes of VF were induced with 115 "matched pairs" of monophasic and biphasic waveforms of identical initial capacitor voltages given over a range from 70 to 600 V (0.35 to 25.7 joules). The biphasic waveform was superior to the monophasic waveform (p less than 0.006), especially for "low energy" defibrillation. For initial voltages less than 200 V, the percent successful defibrillation was 28% for the monophasic waveform versus 64% for the biphasic waveform and from 200 to 290 V (energies less than 6.4 joules) it was 45% versus 69%. There was no difference in the two waveforms in time to the first QRS complex or in the blood pressure following defibrillation. This study shows that a 12 msec biphasic truncated exponential is superior to a 6 msec monophasic waveform for defibrillation in man, especially at energies less than 6.4 joules. The waveform can be achieved in an implanted device without any increase in capacitor size or in battery energy consumption.

Clinical experience with sotalol in patients with drug-refractory ventricular arrhythmias.

Sixty-five patients with symptomatic, drug-refractory, sustained ventricular tachycardia or fibrillation were treated with oral sotalol (80 to 480 mg twice daily). Sotalol was withdrawn in 11 patients because of continued inducibility of ventricular tachycardia at the time of follow-up electrophysiologic study. Therefore, the clinical effectiveness of sotalol could be evaluated in 54 patients followed up for 11.5 +/- 6 months (range 0.2 to 25). The actuarial incidence of successful sotalol therapy was 54 +/- 13% at 6 months and 47 +/- 13% at 12 months. In 39 patients who underwent electrophysiologic testing while receiving oral sotalol, the drug prevented the reinduction of ventricular tachycardia/fibrillation in 8 (20%). During follow-up study, arrhythmia recurred in 1 (17%) of 6 patients whose ventricular tachycardia was noninducible with oral sotalol and in 8 (44%) of 18 with inducible tachycardia but who were continued on oral sotalol therapy. Adverse effects were noted in 28 patients (42%), requiring drug withdrawal in 13 (22%) and dose reduction after hospital discharge in 10 (15%). Exacerbation of ventricular arrhythmia occurred in six patients (9%), one of whom had associated hypokalemia. Sotalol is frequently useful in the control of intractable, life-threatening ventricular arrhythmias, and its efficacy appears to be predicted by programmed stimulation. However, there is a high rate of limiting side effects, which precludes its use in a large number of patients, and a substantial risk of arrhythmia exacerbation.

Transvenous catheter ablation of extranodal accessory pathways.

Twelve patients with an accessory pathway and recurrent symptomatic reciprocating tachycardia or atrial fibrillation, or both, underwent attempted transvenous catheter ablation of the accessory pathway. In one patient with a small right coronary artery, the pathway was along the right free wall. In 11 patients, the pathway was located at or within 15 mm of the coronary sinus os. For these patients, a quadripolar electrode catheter was placed in the coronary sinus and positioned, if possible, so that the proximal pair of electrodes straddled the pathway. For those patients with a pathway greater than 5 mm within the coronary sinus, the most proximal electrode was placed at the os. This proximal pair of electrodes was connected to the cathodal output of a defibrillator with an anterior chest wall patch serving as the current sink. Two shocks were then delivered for a cumulative energy of 500 to 600 J (stored energy). Among the eight patients with a pathway at or within 5 mm of the coronary sinus os, conduction over the pathway was abolished in five and modified in one. Among the four patients with a pathway farther from the os (10 to 15 mm) and along the right free wall, pathway conduction was modified only in two. Rupture of the coronary sinus did not occur in any patient. There were no serious complications. Minor damage surrounding the area of ablation was seen at the time of surgical division of the accessory pathway in two of five patients with unsuccessful ablation who subsequently underwent surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Worsening of ventricular tachycardia by amiodarone.

The details of worsening of ventricular tachycardia in 8 (4.1%) of 194 patients receiving treatment with amiodarone are reported. Two forms of amiodarone-induced tachycardia were recognized: first, the development of new tachycardias (three patients) and second, a change in the pattern of recurrence of clinical tachycardia (five patients). In retrospect, the time from the initiation of amiodarone to the initial documentation of worsening ranged from 1 to 23 days (mean +/- SD, 9.4 +/- 8.2 days) and the time from the initiation of therapy to the recognition of worsening ranged from 6 to 26 days (14.6 +/- 10.1 days). Seven patients survived the worsening of tachycardia and one died. The total dose of amiodarone received and the duration of administration did not correlate with time to manifestation or time to resolution of worsening. This report emphasizes that worsening of ventricular tachycardia as a result of amiodarone is often difficult to differentiate from inadequate drug loading or early recurrence of 2 patient's clinical tachycardia. Further, because of the pharmacokinetics of the drug, the manifestations of worsening may be prolonged. In the cases reported, it ranged from 2 to 26 days (7.9 +/- 8.3 days), which is longer than previously reported. Because of the potential for amiodarone to cause life-threatening worsening of ventricular tachycardia and in accordance with current results, a period of in-hospital monitoring of at least 10 days at the start of therapy with amiodarone is recommended.

Comparison of defibrillation efficacy in humans using a new catheter and superior vena cava spring-left ventricular patch electrodes.

The automatic implantable cardioverter-defibrillator currently utilizes an electrode system that requires a major operation for implantation. Effective defibrillation using an implantable cardioverter-defibrillator catheter positioned transvenously would eliminate the morbidity associated with such surgery. Fifteen patients undergoing defibrillator implantation were studied to compare the efficacy of the catheter with that of the superior vena cava spring (6.7 cm2, anode)-left ventricular patch (13.5 cm2, cathode) electrode system using truncated exponential waveforms with 60% tilt. The catheter is 11F in diameter and tripolar. A distal platinum-iridium tip used for pacing was separated by 4 mm from a middle 4.3 cm2 platinum electrode; these were positioned at the right ventricular apex. The proximal 8.5 cm2 platinum electrode was situated at the superior vena cava-right atrial junction. Defibrillation was performed using the middle (cathode) and proximal (anode) electrodes. Ventricular fibrillation was induced by alternating current six times, and defibrillation shocks of 1, 5, 10, 15, 20 or 25 J were given in random order, first using the catheter and then the spring-patch system. Rescue shocks of higher energy were given if there was failure. Although very low energy levels appeared to be slightly more efficacious when using the spring-patch system, there was no statistically significant difference between the electrode systems for any of the energies tested. Permanent implantation of the catheter would have been suitable in 45% of the patients, as compared with 54% of patients with the spring-patch system (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)