Larry Gorkin

Biobehavioral variables and mortality or cardiac arrest in the Cardiac Arrhythmia Pilot Study (CAPS)

The frequency of ventricular premature complexes and the degree of impairment of left ventricular ejection fraction are major predictors of cardiac mortality and sudden death in the year after acute myocardial infarction. Recent studies have implicated psychosocial factors, including depression, the interaction of social isolation and life stress, and type A-B behavior pattern, as predictors of cardiac events, controlling for known parameters of disease severity. However, results tend not to be consistent and are sometimes contradictory. The present investigation was designed to test the predictive association between biobehavioral factors and clinical cardiac events. This evaluation occurred in the context of a prospective clinical trial, the Cardiac Arrhythmia Pilot Study (CAPS). Five-hundred two patients were recruited with greater than or equal to 10 ventricular premature complexes/hour or greater than or equal to 5 episodes of nonsustained ventricular tachycardia, recorded 6 to 60 days after a myocardial infarction. Baseline behavioral studies, conducted in approximately 66% of patients, included psychosocial questionnaires of anxiety, depression, social desirability and support, and type A-B behavior pattern. In addition, blood pressure and pulse rate reactivity to a portable videogame was assessed. The primary outcome was scored on the basis of mortality or cardiac arrest. Results indicated that the type B behavior pattern, higher levels of depression and lower pulse rate reactivity to challenge were significant risk factors for death or cardiac arrest, after adjusting statistically for a set of known clinical predictors of disease severity. The implication of these results for future research relating behavioral factors to cardiac endpoints is discussed.

Baseline Quality of Life as a Predictor of Mortality and Hospitalization in 5,025 Patients With Congestive Heart Failure

This study examined the independent relation of health-related quality of life (HRQL) to mortality and congestive heart failure (CHF)-related hospitalizations in patients with an ejection fraction of < 0.35 followed for a mean of 36.5 months. A brief HRQL questionnaire was administered at baseline to patients randomized to placebo or enalapril in the Studies of Left Ventricular Dysfunction (SOLVD) trial. Participants had an ejection fraction of < 0.35 and either symptomatic CHF (treatment trial, n = 2,465) or asymptomatic CHF (prevention trial, n = 2,560). Baseline assessment of HRQL predicted mortality and CHF-related hospitalizations in symptomatic and asymptomatic patients randomized to enalapril and placebo treatment. Domains that were the stronger univariate predictors of mortality and CHF-related hospitalizations were activities of daily living (relative risk [RR] for mortality: 1.163, p < 0.000; for hospitalization: 1.215, p < 0.000), general health (RR for mortality: 1.205, p < 0.000; for hospitalization: 1.188, p < 0.000), and social functioning (RR for mortality 1.098, p < 0.000; for hospitalization: RR 1.156, p < 0.000). In the multivariate model, activities of daily living (RR for mortality 1.41, p < 0.000; for hospitalization: RR 1.43, p < 0.002), general health (RR for mortality 1.21, p < 0.000; for hospitalization RR 1.16, p < 0.013) and heart failure symptoms (RR for mortality 1.02, p < 0.025; for hospitalization RR 1.03, p < 0.004) were found to be independent risk factors. HRQL independently predicted mortality and CHF-related hospitalizations after adjustment for ejection fraction, age, treatment, and New York Heart Association classification in patients with an ejection fraction of < 0.35, randomized to enalapril and placebo treatment. HRQL provides additional clinical information regarding disease course and outcome that is not captured by traditional indexes of clinical status.

Assessment of quality of life as observed from the baseline data of the Studies of Left Ventricular Dysfunction (SOLVD) trial quality-of-life substudy

The improvement of aspects of a patients quality of life may be as important as prolonging survival in evaluating clinical trials of heart failure. The purpose of this study was to analyze the psychometric properties of the baseline measures from the quality-of-life substudy from the Studies of Left Ventricular Dysfunction (SOLVD) trial. The measures included the 6-Minute Walk Test, Dyspnea Scale, Living with Heart Failure, Physical Limitations, Psychologic Distress and Health Perceptions, as reported by both patients and staff. Cognitive functioning, such as Vocabulary, Digit Span and Trails Making, was also assessed. Patients were classified as New York Heart Association class I (n = 158) versus II or III (n = 150). The internal consistencies (i.e., reliabilities) of the self-report measures were high, except for the Health Perceptions of Class II or III patients. Reliability of the SOLVD quality-of-life battery was confirmed by significantly better life quality among New York Heart Association class I patients versus class II or III patients combined on the Walk Test, Physical Limitations, Dyspnea, Living with Heart Failure, Psychologic Distress and staff perceptions of patient health. In accordance with prior studies, the measures were uncorrelated with left ventricular ejection fraction. By demonstrating strong internal consistencies, reliability based on physician reports, and independence of ejection fraction levels, use of this quality-of-life assessment battery in this and other clinical trials of compromised ventricular functioning is supported.

Psychosocial predictors of mortality in the Cardiac Arrhythmia Suppression Trial-1 (CAST-1).

Psychosocial variables predict the recurrence of clinical events in symptomatic patients, controlling for measures of disease severity. The Cardiac Arrhythmia Suppression Trial-1, a pharmacologic test of the arrhythmia suppression and mortality hypothesis among postmyocardial infarction patients, allowed a prospective test of the relationship of distress, perceived support, social interaction, life stress, and other variables, to mortality, adjusting statistically for ejection fraction, arrhythmia rates, and other known risk factors for coronary heart disease. Results indicated that the treatment medications, encainide and flecainide, were powerful predictors of mortality. Although the psychosocial variables were significant as univariate predictors, these variables were not significant as predictors in a multivariate model that included drug treatment. When the data analysis was restricted to patients randomized to placebo, thereby eliminating the antiarrhythmic drug effect, the level of perceived social support was a significant multivariate predictor of mortality, adjusting for measures of disease severity. The adjusted hazards ratio for a 1-point decrease in the perceived support score is equal to 1.46, based on the multivariate model.

Psychological distress as a predictor of ventricular arrhythmias in a post-myocardial infarction population

A prospective study examining the relationship between psychological distress and ventricular ectopy was conducted with 125 post-myocardial infarction patients equipped with a transtelephonic ECG monitor. Subjects were subsequently grouped according to the occurrence (n = 59) or nonoccurrence (n = 65) of ventricular arrhythmias over a 1-year period. Results indicated a direct relationship between self-reported distress levels and occurrence of ectopic beats. This relationship was unaltered by adjusting simultaneously for known predictors of arrhythmias, including cardiac risk, age, and the prescription of beta-blocker agents. Thus this study represents an initial demonstration in a post-myocardial infarction population that psychosocial factors have prognostic significance for arrhythmias and, presumably, sudden death.

Clinical trial enrollers vs. nonenrollers: the Cardiac Arrhythmia Suppression Trial (CAST) Recruitment and Enrollment Assessment in Clinical Trials (REACT) project.

The Recruitment and Enrollment Assessment in Clinical Trials (REACT) was a National Heart, Lung, and Blood Institute (NHLBI)-sponsored substudy to the Cardiac Arrhythmia Suppression Trial (CAST). Two-hundred-sixty (260) patients who enrolled in CAST and 140 partially or fully eligible patients who did not enroll were compared across several parameters, including demographic variables, disease severity, psychosocial functioning, health beliefs, recruitment experience, and understanding of informed consent procedures used in CAST. Significant predictors of enrollment included several demographic variables (e.g., being male, not having medical insurance), episodes of ventricular tachycardia, and health beliefs (e.g., extra beats are harmful, a higher degree of general health concern). Enrollment was higher for those who read and understood the informed consent and those who were initially recruited after hospital discharge, particularly nondepressed patients. In the multivariate model, the key variables that emerged were the patients reading of the informed consent form and the patients lack of medical insurance. These results suggest that (1) the clinical trial staffs interaction with the patient and the time when recruitment is initiated contribute significantly to the decision to enroll; and (2) it may be a greater challenge to motivate patients to enroll in future clinical trials if health care reform improves access to medical insurance coverage. Some of the significant variables are modifiable, suggesting interventions that may increase enrollment rates in future trials.

Relation of psychosocial and stress reactivity variables to ventricular arrhythmias in the Cardiac Arrhythmia Pilot Study (CAPS)

Both animal and human data implicate psychosocial distress and cardiovascular reactivity in response to challenge in the etiology of sudden cardiac death. In this study, the relation of these biobehaviorial factors to frequency of ventricular premature complexes, a predictor of sudden death was investigated. The study population was made up of patients enrolled in the National Heart, Lung, and Blood Institutes Cardiac Arrhythmia Pilot Study (CAPS). Ventricular premature complexes (VPCs) were assessed by multiple, 24-hour ambulatory electrocardiographic recordings. Patients completed trait psychosocial measures assessed at baseline and state psychosocial measures assessed periodically during a 1-year follow-up period. Psychosocial measures included self-reports of depression, anxiety, anger and type A behavior pattern. A competitive challenge using a video game was used as a stressor to elicit cardiovascular reactivity and was administered at baseline and during follow-up sessions. Cardiovascular reactivity was defined as peak level during stressor exposure minus the mean of resting levels for systolic and diastolic blood pressure and pulse rate. Results indicated that biobehavioral factors were not associated with diurnal VPC rates. Furthermore, biobehavioral factors did not predict response to antiarrhythmic therapy. Based upon the results of this study, it is speculated that the established relation between behavioral factors and sudden death may not be mediated by VPC rates.

Determinants of Perceived Health in Patients With Left Ventricular Dysfunction: A Structural Modeling Analysis

Objective Few studies have evaluated the determinants of perceived health in patients with chronic illness. The present study was designed to evaluate the role of biomedical, demographic, and psychosocial influences on global subjective health by means of a structural Equation modelingapproach. Method A conceptual model of perceived health was tested in a subsample of patients (N = 146) from the multicenter Studies of Left Ventricular Dysfunction (SOLVD) trial. Domain-specific quality of life constructs (emotional status, social support, and physical functioning), were assessed by means of multiple indicators. These latent (mediating) variables, along with six single-indicator biomedical and background variables, were modeled as predictors of a composite index of perceived health. Results A satisfactory fit was obtained for the proposed model, with practical fit indices ranging from.89 to.95. High levels of perceived health were associated with low levels of emotional distress and high levels of physical functioning. Social support was positively correlated with physical functioning and negatively associated with emotional distress. Among the background variables, no direct associations were observed between any of the single-indicator variables and perceived health. Several background variables (eg, age, income, walk-test scores) had indirect effects via associations with the latent variables of physical functioning and emotional distress. Conclusions These findings support the use of a structural modeling approach in assessing determinants of perceived health in patients with congestive heart failure. Further research is needed to evaluate the utility of the model in other patient populations.

The effects of a transtelephonic surveillance and prehospital emergency intervention system on the 1-year course following acute myocardial infarction☆

We evaluated the effect on morbidity and mortality of a post-myocardial infarction management and intervention system. One thousand four patients were prospectively randomized to an intervention group that included routine and emergency transtelephonic follow-up and ECG monitoring or to control; all subjects were followed for 1 year. For symptoms suggestive of myocardial ischemia, intervention patients telephoned the project emergency office, were instructed by a project nurse to self-administer intramuscular lidocaine with an auto-injector, and were then transported to the nearest emergency facility. Cardiac death or arrest was decreased 29% in intervention patients (p = 0.066), while all-cause mortality was decreased by 24% (p less than 0.11). Routine transtelephonic ECG monitoring detected ventricular ectopy in 48% of intervention patients, with almost 50% of these findings classified as complex forms. Ventricular ectopy detected during routine calls within 60 days of the acute myocardial infarction conferred a threefold increase in mortality (p = 0.001). In addition, control patients were 2.4 times more likely to be clinically depressed (p less than 0.03) and returned to work less quickly (p less than 0.03) when compared to intervention patients. Lidocaine injections were associated with an absence of ventricular ectopy on arrival at the Emergency Room in 64% and with a low incidence of lidocaine-associated side effects. There was only one case of unauthorized use of the self-injector. These findings demonstrate that an outpatient post-myocardial infarction transtelephonic surveillance program can be safely and effectively conducted, can detect complex ventricular arrhythmias of prognostic significance, can improve the quality of life, and may reduce 1-year cardiac mortality.

Moricizine and quality of life in the Cardiac Arrhythmia Suppression Trial II (CAST II).

The Cardiac Arrhythmia Suppression Trial II (CAST II) was a double-masked placebo-controlled randomized trial that compared the survival effects of moricizine to placebo in postmyocardial infarction arrhythmia patients. The quality-of-life outcome measures were designed prospectively for CAST and were previously shown to have high reliability and clinical discriminative validity. The CAST quality-of-life instrument detected significant differences between moricizine and placebo. In particular, moricizine was most strongly associated with inferior social activity and satisfaction scores (p = .014) and lower scores for overall contentment with life (p = .007). Moreover, the quality-of-life measures improved significantly for both the moricizine and placebo treatment groups after entry into the clinical trial. These results indicate that the CAST quality-of-life instrument is sensitive for assessing pharmacological therapies in the treatment of heart disease.