Mild hypoxia disrupts recollection, not familiarity.

Yonelinas et al. (2002) found that hypoxic patients exhibited deficits in recollection that left familiarity relatively unaffected. In contrast, Manns, Hopkins, Reed, Kitchener, and Squire (2003) studied a group of hypoxic patients who suffered severe and equivalent deficits in recollection and familiarity. We reexamine those studies and argue that the discrepancy in results is likely due to differences in the hypoxic groups that were tested (i.e., differences in amnestic severity, subject sampling methods, and patient etiology). Yonelinas et al. examined memory in 56 cardiac arrest patients who suffered a brief hypoxic event, whereas Manns et al. examined a group of severely amnesic patients that consisted of 2 cardiac arrest patients, 2 heroin overdose patients, 1 carbon monoxide poisoning patient, and 2 patients with unknown etiologies. We also consider an alternative explanation proposed by Wixted and Squire (2004), who argued that the two patient groups suffered similar deficits, but that statistical or methodological artifacts distorted the results of each of Yonelinas et al.'s experiments. A consideration of those results, however, indicates that such an explanation does not account for the existing data. All of the existing evidence indicates that recollection, but not familiarity, is disrupted in mild hypoxic patients. In more severe cases of hypoxia, or those with more complex etiologies such as heroin overdose, more profound deficits may be observed.

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).

Factors associated with cognitive recovery after cardiopulmonary resuscitation.

BACKGROUND: A range of neuro-cognitive sequelae, from mild intellectual impairments to brain death, have been reported in survivors of aborted sudden cardiac death. PURPOSE: To determine to what extent, if any, factors associated with cardiopulmonary resuscitation, left ventricular function, and mood state are related to outcomes in five cognitive areas, namely orientation, attention, memory, reasoning, and motor performance. METHODS: Repeated measures were used to assess cognitive outcomes in 45 sudden cardiac arrest survivors over the 6 months following cardiopulmonary resuscitation. A battery of neuro-psychological tests was used to assess cognitive outcomes and psychological status over time. The relationship of the cardiopulmonary resuscitation, left ventricular function, and psychological variables to cognitive outcomes were assessed at each data point. The independent variables included time to cardiopulmonary resuscitation, time to defibrillation, duration of cardiopulmonary resuscitation, time to awakening, ejection fraction, New York Heart Association Class I to IV, tension, anger, and depression. RESULTS: During hospitalization 38 of the 45 survivors (84%) had mild to severe deficits in one or more cognitive areas; 19 of 38 survivors (50%) continued to be impaired in one or more cognitive areas at 6 months. Of these, all had mild to severe deficits in at least one aspect of memory, with delayed recall the most frequent impairment. Time to awakening accounted for a unique portion of the variance in orientation and memory outcomes over time. The left ventricular function variables accounted for a significant portion of the variance in motor speed. CONCLUSIONS: Our results suggest that half of the long-term survivors of aborted sudden cardiac death are cognitively intact 6 months after resuscitation but that 25% have moderate to severe impairment in memory, which could hamper and/or preclude the resumption of prearrest roles.

Impact of aborted sudden cardiac death on survivors and their spouses: the phenomenon of different reference points.

BACKGROUND: Although anecdotal data suggest that spouses of aborted sudden cardiac death survivors become enmeshed in the physical and emotional recovery of their mates, few longitudinal studies address the personal struggle of aborted sudden cardiac death survivors and their spouses during recovery. OBJECTIVE: To identify and explore phenomena experienced by aborted sudden cardiac death survivors and their spouses, and to determine implications for care. METHODS: This was a phenomenological study; qualitative interviews were conducted within 3 weeks of aborted sudden cardiac death and continued through 24 weeks after arrest at 6- to 8-week intervals. A total of 180 interviews were conducted with 40 survivors and 30 spouses. Interviews were tape-recorded, transcribed, and analyzed for recurrent themes. RESULTS: For the spouses the point of focus, or reference point, for future decision making was the arrest; for the survivors the reference point was prearrest life. These different reference points led to different concerns between spouses and survivors, from which spousal protectiveness and entrapment emerged. CONCLUSIONS: Acknowledgment of different reference points is essential in planning interventions for aborted sudden cardiac death survivors and their spouses. This population must be encouraged to express their questions, concerns, and fears early. Differences in perspectives should be identified to avoid troubled communication and conflicts.

Long-term physical functioning and psychosocial adjustment in survivors of sudden cardiac death.

OBJECTIVE: To identify and describe a range of functional health outcomes in a sample of sudden cardiac death survivors. DESIGN: Cross-sectional survey. SETTING: Northern California tertiary medical center. SUBJECTS: Sixty-one sudden cardiac death survivors at least 6 months but not more than 4 years after cardiac arrest. Subjects were excluded if they had uncontrolled congestive heart failure, unstable angina, other debilitating cardiac or concomitant illness, or evident cognitive deficits. METHODS: Chart reviews, patient interviews, and a standardized questionnaire. RESULTS: Survivors reported significantly poorer physical functioning than normal subjects (p < 0.001), although none were limited in self-care. Mental Health Index Scores and subscale scores for psychologic well-being were within established norms. However, mean scores for the psychologic distress subscale were elevated (p < 0.001). Initial work return was 72%. Of the 37 (61%) survivors who were sexually active before their arrests, 78% resumed coitus. Twenty-five survivors reported mild to moderately severe impairments in memory or other cognitive skills. Poor physical functioning was associated with illness severity, change in work status, and increased anxiety. Psychologic distress was associated with change in work status and poor physical functioning, but not illness severity. CONCLUSIONS: Despite significant decreases in physical functioning and reports of mild to moderately severe cognitive impairments, only a minority of sudden cardiac death survivors are severely psychologically distressed. Illness severity is a strong predictor of physical functioning, but its contribution to psychologic distress is indirect, acting largely through the aegis of poor physical functioning and loss of prearrest work status.

Survival after implantation of the cardioverter defibrillator.

The actuarial survival of 60 consecutive recipients of the implanted cardioverter defibrillator (ICD) were compared with 120 matched concurrent medically treated patients using a case-control design. All ICD patients and controls presented with either sustained ventricular tachycardia or ventricular fibrillation. Controls were matched to ICD recipients according to 5 variables: age, left ventricular ejection fraction, arrhythmia at presentation, underlying heart disease and drug therapy status. Mean ages were 58 and 59 years in ICD patients and controls, and the average ejection fractions were 36 and 35%. Coronary artery disease was present in 75 and 79% of ICD patients and controls, respectively. During follow-up, sudden deaths were fewer in ICD recipients than in controls (5 vs 10%, p less than 0.01). At 1 and 3 years, actuarial survival was 0.89 vs 0.72 and 0.65 vs 0.49 for ICD recipients and controls. The 5-year actuarial survival curves were significantly different by the Cox proportional hazards model (p less than 0.05). It is concluded that in this retrospective case-control study, the use of the ICD in the management of patients at risk for sudden death results in improved probability of survival.

Long-term results of amiodarone therapy in patients with recurrent sustained ventricular tachycardia or ventricular fibrillation.

Four hundred sixty-two patients, all with either documented spontaneous sustained ventricular tachycardia or cardiac arrest unresponsive to other antiarrhythmic drugs (2.6/patient), were treated with amiodarone. Thirty-five patients (7.6%) failed to respond or died during the initial oral or intravenous loading phase. The remaining 427 patients were discharged on treatment with oral amiodarone and followed up for up to 98 months. Recurrence of ventricular tachycardia or sudden cardiac death at 1, 3 and 5 years by life-table analysis was 19%, 33% and 43%, respectively, for patients discharged on amiodarone therapy. The sudden cardiac death rate was 9%, 15% and 21%, respectively, at 1, 3 and 5 years. Side effects were reported by 45% of patients after 1 year, by 61% after 2 years and by 86% after 5 years. Amiodarone was discontinued because of side effects in 14%, 26% and 37% of patients after 1, 3 and 5 years, respectively. Incidence rates of recurrence of arrhythmia, sudden cardiac death and side effects were highest in the early months and then decreased. By multivariate analysis, advanced age, low ejection fraction and a history of cardiac arrest were independent risk factors for sudden cardiac death during amiodarone therapy.

Usefulness of sotalol for drug-refractory malignant ventricular arrhythmias.

Fifty patients with recurrent sustained symptomatic ventricular tachycardia (43 patients) or ventricular fibrillation (7 patients) resistant to a mean of 2.8 + 1.4 antiarrhythmic drugs were treated with sotalol, a beta-adrenergic receptor antagonist, and 45 underwent invasive electrophysiologic testing before and after sotalol therapy. The arrhythmia became noninducible in 10, was slower and hemodynamically well tolerated in 12 and was poorly tolerated in 23. Four patients were empirically treated with long-term administration of oral sotalol as were 21 patients who either had noninducible arrhythmia (10 patients) or had hemodynamically stable ventricular tachycardia (11 patients). In these 25 patients treated with long-term administration of sotalol, there was no recurrence of ventricular tachycardia in the group with noninducible arrhythmia, whereas 37% of patients with inducible ventricular tachycardia had new ventricular tachycardia or sudden death. Programmed ventricular stimulation with up to three extrastimuli proved to be an excellent predictor of drug efficacy and a good predictor of inefficacy. A positive prior response to amiodarone was not a reliable indicator of a positive response to sotalol. Side effects included those attributed to both beta-adrenergic blockade as well as proarrhythmic effects. The latter were observed in two of four patients with a QT interval greater than 600 ms. Sotalol was found to be effective therapy for a subset of patients with ventricular tachycardia unresponsive to type IA drugs.

Use of intravenous amiodarone for emergency treatment of life-threatening ventricular arrhythmias.

Efficacy, side effects and predictors of response for intravenous amiodarone were evaluated in 46 patients with recurrent drug-refractory sustained ventricular tachycardia or ventricular fibrillation, or both, who were treated with intravenous amiodarone. Of the 46 patients, 27 (58.5%) responded early to intravenous amiodarone and 6 (13%) showed a late response to amiodarone. The majority of patients who responded to intravenous amiodarone did so within the first 2 h of therapy, and all responded within 84 h. Patients with an ejection fraction greater than 25% were more likely to respond (p less than 0.05). Major side effects occurred in 13% of patients. The cumulative 2 year mortality rate due to arrhythmia recurrence or sudden death for responders discharged from the hospital was 23% and the cumulative overall 2 year mortality rate was 46%. In conclusion, intravenous amiodarone is rapidly effective in the majority of patients with recurrent ventricular tachycardia or ventricular fibrillation refractory to other drugs. The poor long-term outcome of patients who require this therapy, respond to it and are discharged on long-term oral amiodarone therapy warrants consideration of other long-term treatment of these patients. Use of intravenous amiodarone is an important new modality in the treatment of drug-refractory malignant ventricular arrhythmias.

Electrophysiologic testing and follow-up of patients with aborted sudden death.

Clinical, electrophysiologic and follow-up data were analyzed for 108 patients with aborted sudden death. The mean follow-up interval was 2 years. All patients underwent baseline drug-free invasive electrophysiologic studies. Seventy-five patients (group I) had inducible ventricular arrhythmias (including nonsustained and sustained ventricular tachycardia and ventricular fibrillation) and 33 patients (group II) had no inducible arrhythmias. Noninducibility was not predictive of a favorable outcome, because the incidence of both sudden death and recurrent ventricular tachycardia was similar in the two groups. Treatment guided by electrophysiologic testing was used in 17 patients; in 13 (17%) in group I arrhythmias became noninducible, and in 4 (5%) sustained ventricular arrhythmias became nonsustained after administration of conventional drugs. There was a significantly higher incidence of sudden death and recurrent ventricular tachycardia in the 4 patients with inducible arrhythmias (n = 3, 75%) compared with the 13 patients whose arrhythmias were noninducible (n = 2, 15%) (p less than 0.05). For the group as a whole, 11% died suddenly and 15% had recurrence of ventricular tachycardia. Sixty-four patients were treated with amiodarone and, of these, four (6%) died suddenly during the follow-up period and nine (14%) had recurrent ventricular tachycardia. Ventricular arrhythmias could be induced in 69% of patients with aborted sudden death but inducibility could be suppressed in only 20% of them. The role of therapy guided by electrophysiologic testing could therefore not be fully assessed. The findings reveal a significant recurrence rate of symptomatic, potentially life-threatening ventricular arrhythmias in medically treated patients with aborted sudden death.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term results of amiodarone therapy.

In order to assess the long-term efficacy of amiodarone, we followed 187 survivors of cardiac arrest and 316 patients with nonsustained or sustained ventricular tachycardia and compared the results of amiodarone therapy with the results of conventional therapy. All patients treated with amiodarone had failed to respond to one or more conventional agents. For survivors of cardiac arrest, survival of patients treated with amiodarone was equal to survival of patients treated with conventional agents. For patients with ventricular tachycardia, two-year survival was 91% in the conventional therapy group and 68% in the amiodarone group but incidence of sudden death was similar, probably reflecting increased non-sudden death due to advanced age and left ventricular dysfunction in the amiodarone-treated group. Side effects led to the discontinuation of amiodarone in approximately 25% of patients over a mean follow-up of 28 months. In a subgroup of patients who had demonstrated a proarrhythmic effect to Class I antiarrhythmic agents, amiodarone proved safe and effective. Amiodarone was well tolerated and effective therapy for atrial fibrillation in 59% of patients who had failed to respond to conventional agents. Thus, amiodarone is a useful option for patients with arrhythmias unresponsive to standard antiarrhythmic agents.

Cardiac arrest and sudden death in patients treated with amiodarone for sustained ventricular tachycardia or ventricular fibrillation: risk stratification based on clinical variables.

Multivariate analysis of 11 clinical variables was performed in 104 patients with sustained, symptomatic ventricular tachycardia (VT) or ventricular fibrillation treated with amiodarone to determine variables predictive of subsequent cardiac arrest or sudden death. Twenty-five patients (24%) had fatal or nonfatal cardiac arrest after 7.3 +/- 6.2 months (mean +/- standard deviation) of therapy. Multivariate analysis identified an ejection fraction of less than 0.40, syncope or cardiac arrest before amiodarone therapy, and VT (3 or more consecutive ventricular premature complexes) during predischarge ambulatory electrocardiographic monitoring as variables associated with a high risk of subsequent fatal or nonfatal cardiac arrest (p less than 0.03). Patients who had these 3 clinical variables had a much higher predicted incidence of cardiac arrest at 6 months (62%) and 12 months (76%) than did patients with an ejection fraction greater than 0.40, without syncope or cardiac arrest before amiodarone therapy, and without VT during predischarge ambulatory electrocardiographic monitoring (2% and 5%, respectively) (p less than 0.02). Risk stratification using clinical variables can predict which patients are at high risk of recurrent cardiac arrest or sudden death during amiodarone therapy.

Electrophysiologic testing in bundle branch block and unexplained syncope.

Thirty-two patients with bundle branch block and unexplained syncope underwent electrophysiologic testing, including programmed ventricular stimulation with up to triple extrastimuli. The infranodal conduction time (HV) was 70 ms or greater in 12 patients. Pathologic infranodal block during atrial pacing occurred in 2 patients. Unimorphic ventricular tachycardia (VT) was induced in 9 patients (28%) and polymorphic VT in 5 (16%). A permanent pacemaker was implanted in patients with infranodal block during atrial pacing and, generally, in patients with an HV of 70 ms or more. Patients with inducible unimorphic or sustained polymorphic VT were treated with an antiarrhythmic drug. The mean follow-up period was 19 +/- 14 months (+/- standard deviation). Three patients died suddenly: a noncompliant patient with inducible sustained VT; a patient with a normal electrophysiologic study treated empirically with quinidine for premature ventricular complexes; and a patient with an HV of 70 ms and no inducible VT treated with a permanent pacemaker. The actuarial incidence of sudden death was 10% at 45 months of follow-up. Only 2 patients had recurrent syncope; both had a normal electrophysiologic study. Approximately 50% of patients with bundle branch block and unexplained syncope who undergo electrophysiologic testing are found to have a clinically significant abnormality (HV of 70 ms or more, infranodal block during atrial pacing and inducible unimorphic VT), and some patients have more than 1 abnormality. Long-term management guided by the results of electrophysiologic testing generally is successful in preventing recurrent syncope.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term efficacy and toxicity of high-dose amiodarone therapy for ventricular tachycardia or ventricular fibrillation.

Amiodarone was administered to 154 patients who had sustained, symptomatic ventricular tachycardia (VT) (n = 118) or a cardiac arrest (n = 36) and who were refractory to conventional antiarrhythmic drugs. The loading dose was 800 mg/day for 6 weeks and the maintenance dose was 600 mg/day. Sixty-nine percent of patients continued treatment with amiodarone and had no recurrence of symptomatic VT or ventricular fibrillation (VF) over a follow-up of 6 to 52 months (mean +/- standard deviation 14.2 +/- 8.2). Six percent of the patients had a nonfatal recurrence of VT and were successfully managed by continuing amiodarone at a higher dose or by the addition of a conventional antiarrhythmic drug. One or more adverse drug reactions occurred in 51% of patients. Adverse effects forced a reduction in the dose of amiodarone in 41% and discontinuation of amiodarone in 10% of patients. The most common symptomatic adverse reactions were tremor or ataxia (35%), nausea and anorexia (8%), visual halos or blurring (6%), thyroid function abnormalities (6%) and pulmonary interstitial infiltrates (5%). Although large-dose amiodarone is highly effective in the long-term treatment of VT or VF refractory to conventional antiarrhythmic drugs, it causes significant toxicity in approximately 50% of patients. However, when the dose is adjusted based on clinical response or the development of adverse effects, 75% of patients with VT or VF can be successfully managed with amiodarone.

Electrophysiologic studies in patients with bundle branch block.

A total of 401 patients with chronic bundle branch block underwent electrophysiologic studies and were followed for a mean of approximately 30 months. Patients with an infranodal conduction time (H-Q) greater than or equal to 70 ms had a significantly higher incidence of progression to spontaneous second-degree or third-degree atrioventricular (AV) block (12%) compared with those with H-Q less than 70 ms (3.5%). The incidence of AV block was 25% for those with H-Q greater than or equal to 100 ms. Although the incidences of all deaths and cardiac deaths were higher for the H-Q greater than or equal to 70 ms group, there was no statistically significant difference in the incidence of sudden deaths in the two groups. A subgroup of 77 patients underwent prophylactic pacemaker insertion based on the presence of transient neurologic symptoms and/or a prolonged H-Q interval. We found no significant difference in the incidence of relief of symptoms or incidence of cardiac or sudden deaths between paced and unpaced groups. A subgroup of 25 patients with syncope underwent ventricular stimulation studies and ventricular tachycardia was induced in 14. We conclude that a markedly prolonged H-Q interval (greater than or equal to 100 ms) may be of value in detection of spontaneous AV block. Prophylactic pacing is of no value in either relief of symptoms or prolongation of life. Complete electrophysiologic studies, including ventricular stimulation studies, are indicated for patients with bundle branch block and syncope.