A.David Goldberg

Five-year follow-up for adverse outcomes in males with at least minimally positive angiograms: Importance of "denial" in assessing psychosocial risk factors.

The purpose of this study was to test the role of denial (spouse/friend minus self-ratings on parallel versions of the same questionnaire) in diluting the predictive value of emotional distress for cardiac events (deaths, new MIs, and/or revascularizations). One hundred forty-four men with no history of prior revascularization who had at least minimally positive diagnostic coronary angiograms, and someone they selected as someone who knows you well, completed parallel versions of the Ketterer Stress Symptom Frequency Checklist (KSSFC). They were followed up by phone an average of 59.7 months after recruitment. Length of follow-up, baseline cardiac risk factors, and a number of baseline-obtained psychosocial risk factors were tested as prospective predictors of combined events (death by any cause, new MIs, and/or revascularizations) and current anginal frequency. Only spouse/friend observed anxiety on the KSSFC predicted current anginal frequency (p = 0.001). On the self-report version of the KSSFC, patients with one or more events reported less anger (p = 0.031), depression (p = 0.008), and anxiety (p = 0.003). These results may be attributable to denial because there were no differences in spouse/friend ratings, and difference scores (spouse/friend minus patient) on the KSSFC scales, particularly anger, were also related to events: AIAI (p = 0.002); depression (p = 0.063); and anxiety (p = 0.010). Denial may be a major limiting factor in accurately assessing emotional distress in cardiac populations, and may help account for a number of the previous findings.

Reinnervation of the transplanted human heart as evidenced from heart rate variability studies

This study evaluated heart rate variability (HRV) after cardiac transplantation in humans in an attempt to test the hypothesis that cardiac reinnervation occurs in the post-transplant period. HRV was measured using 24-hour Holter recordings performed on 37 ambulant patients 1 to 122 months after cardiac transplantation. All patients were free of histologic rejection and were taking no medication likely to influence HRV. Time and frequency domain were analyzed and circadian rhythm of hourly average heart rate was calculated. HRV increased with time after the transplant. Compared with patients in the early post-transplant period, patients > 36 months after transplant had lower 24-hour heart rates (86 vs 93 beats/min), an increased average of all 5-minute SDs of NN intervals (17.6 vs 11.3), and higher low-and high-frequency power. Ten of the 27 patients > 3 years after transplantation had evidence of functional cardiac reinnervation. Compared with patients who had no reinnervation, these patients had increased circadian variability with lower nocturnal heart rates (76 vs 91 beats/min) and greater sympathetic activity during daytime (natural logarithm sympathetic power -0.36 vs -1.45) and nighttime (natural logarithm sympathetic power -0.43 vs -1.98). Despite lower nocturnal heart rates, there was no HRV evidence for an increase in parasympathetic activity. Thus, patients late after cardiac transplantation have HRV evidence for an increase in sympathetic control of the heart.

Psychosocial factors related to unrecognized acute myocardial infarction

Acute myocardial infarction (AMI) often is unrecognized (i.e., a patient fails to notice or report the event to the physician, or the physician fails to diagnose it). Psychosocial differences between patients with recognized and unrecognized AMI have not been examined. We compared 40 patients who sought treatment for a documented AMI with 30 patients who were found on routine electrocardiogram to have had an AMI for which they did not seek medical care. Patients with unrecognized AMI showed greater alexithymia, or deficient psychologic awareness (p = 0.04; Alexithymia Provoked Response Interview), and a greater belief that chance factors determine their health (p = 0.004; Multidimensional Health Locus of Control Scale). Patients with unrecognized AMI were less likely to have angina, yet did not differ from those with recognized AMI with regard to demographics, smoking, systemic hypertension, diabetes mellitus, AMI location, depression, or hypochondriasis. We hypothesize that deficient psychologic awareness may impede AMI symptom perception or recognition, and that the belief in chance or fate as determining health may inhibit treatment-seeking.

Psychological factors affecting a medical condition: ischemic coronary heart disease

The criteria for scientific validation of the entities currently subsumed under the DSM-IV category of Psychological Factors Affecting a Medical Condition have never been clearly enumerated. Historically, its precursor category (Psychophysiological Disorder) was rarely used, and predicated upon clinical observation of personality styles among patients with specific physical illnesses, or clinical observations relating psychosocial events and symptom exacerbation. Because of logical flaws with either of these methods, clarification of the most rigorous criteria for demonstrating a cause-effect relationship is necessary. With the increase in well-designed and carefully executed epidemiological and treatment studies, this diagnostic category has evolved into an arena where cutting-edge insights and therapies are becoming available for a growing variety of medical conditions, especially ischemic coronary heart disease. The present article reviews the nature of the scientific evidence necessary to accept an etiological or aggravating role for psychological events.

Effectiveness of imazodan for treatment of chronic congestive heart failure

A 12-week, multicenter, double-blind, randomized, placebo-controlled trial of imazodan, a type III phosphodiesterase inhibitor, was conducted in 147 patients with congestive heart failure to determine clinical efficacy and safety. Patients were randomized to placebo or 2, 5 or 10 mg of imazodan administered twice daily. Patients were maintained on their standard therapy including diuretics, digoxin and an angiotensin-converting enzyme inhibitor. The mean ejection fraction was 23 +/- 10%. Exercise time increased from baseline in all 4 groups. There was no significant difference observed between the placebo group and any of the treated groups with regard to exercise time, ejection fraction, frequency of ventricular premature complexes or ventricular tachycardia. When analyzed by intent to treat, the placebo mortality was 7% (3 of 44) and the imazodan mortality was 8% (8 of 103) (p = not significant). This study failed to demonstrate that imazodan provided any benefit in exercise performance when compared with placebo.

Acute and chronic hemodynamic effects of nicardipine hydrochloride in patients with heart failure

Acute and chronic hemodynamic effects at rest and during exercise of a new dihydropyridine calcium antagonist, nicardipine hydrochloride, were studied in 10 patients with chronic heart failure. Acute intravenous administration of nicardipine resulted in a significant decrease in arterial blood pressure, systemic vascular resistance, and pulmonary capillary wedge pressure. There was a significant increase in cardiac index, stroke volume index, and the left ventricular stroke work index. Cardiac index measured at peak exercise increased significantly when compared with the cardiac index obtained at peak exercise before the infusion. After 9 days of continuous therapy with nicardipine, 30 mg three times a day, a significant decrease in arterial blood pressure and systemic vascular resistance and a significant increase in the cardiac index, stroke volume index, and left ventricular stroke work index at rest were observed in response to a single oral dose of 30 mg nicardipine. Data at peak exercise were also obtained before and 2 hours after the oral administration of nicardipine. With this comparison there was a significant increase in cardiac index, stroke work index, and exercise duration. It is concluded that in this group of patients with severe chronic heart failure, nicardipine enhanced myocardial performance during rest and exercise and this enhancement is sustained after 9 days of oral therapy.

Long-term assessment of heart rate variability in cardiac transplant recipients

Sympathetic and parasympathetic reinnervation of the transplanted heart were evaluated by assessing time and frequency domain measurements of heart rate variability at 5 and 8 years. Continuous 24-hour ECG measurements were performed in 13 patients (57 +/- 6 months and 90 +/- 7 months) after orthotopic cardiac transplantation and in 22 healthy age and gender-matched controls, and were analyzed for heart rate variability in the time and frequency domains. Heart rate variability measures reflective of sympathetic reinnervation were sub-normal at 5 years and unchanged at 8 years: those reflective of parasympathetic reinnervation were absent.

Impact of Medical Therapy on Pulmonary Hypertension in Patients With Congestive Heart Failure Awaiting Cardiac Transplantation

Pulmonary artery (PA) hypertension in transplant recipients increases mortality from right heart failure following heart transplantation. We examined the impact of long-term medical therapy on the severity of PA hypertension in patients with end-stage congestive heart failure on a transplant waiting list. The initial and final, quarterly right heart catheterization data on 60 patients (50 men, aged 50 +/- 9 years, New York Heart Association class III to IV) awaiting heart transplantation were analyzed and the patients divided into 2 groups: group A, those with persistent elevated systolic PA pressures throughout the 10-month follow-up (n = 31 of 60), and group B, those who had any decrease in systolic PA pressure during that period (n = 29 of 60). Group A had no change in hemodynamics. Group B had a significant decrease( +/- SD) in right atrial (11 +/- 7 to 5 +/- 4 mm Hg), PA (57 +/- 11 to 37 +/- 11 mm Hg), and PA wedge (25 +/- 9 to 14 +/- 7 mm Hg) pressures, with increases in cardiac output (3.8 +/- 0.9 to 4.7 +/- 1.1 L/min) and ejection fraction (18 +/- 6% to 27 +/- 11%) (p < 0.05). The combined end point of transplant or death occurred in 28 of 31 patients (90%) in group A versus 14 of 29 (50%) in group B (p = 0.0004). Ischemic etiology was present in 71 % of patients in group A versus 68% with idiopathic dilated cardiomyopathy in group B (p = 0.003). The reversibility of PA hypertension rather than its initial severity is predictive of patient clinical outcome. Idiopathic, as opposed to ischemic, cardiomyopathy responds better to medical therapy.

Chest pain and the treatment of psychosocial/emotional distress in CAD patients.

Treatment of psychosocial/emotional distress as a strategy for diminishing chest pain in such patients remains entirely unutilized in standard care. Sixty-three patients with known or suspected CAD were entered in an aggressive lifestyle modification program. Patients completed the Symptom Checklist 90—Revised (SCL90R) at the diagnostic interview session, at 3 and at 12 months. Statistically significant drops were observed on multiple scales of the SCL90R at both 3 and 12 months. An item from the SCL90R was used as a proxy for angina. Multiple measures of emotional distress at baseline were found to correlate with chest pain at baseline, but not a number of traditional cardiovascular risk factors. The chest pain item displayed improvement at both 3 and 12 months. Improvement on all scales of the SCL90R correlated with improvement in chest pain. It may be possible to control chest pain in some CAD patients with psychosocial interventions.

Increasing daytime vascular resistance with progressive hypertension in ambulant patients

Twenty-four-hour recordings of intra-arterial blood pressure, heart rate, and calculation of the index of peripheral vascular resistance were obtained in 20 untreated ambulant hypertensive patients during their routine activities outside the hospital. Blood pressures and heart rates were higher during the day, with a mean night-to-day increase of 22%, 34%, and 26%, for systolic, diastolic, and mean pressures, respectively. The average increase in the heart rate was 32%. Overall, the index of resistance was lower (12%) during the day. However, eight patients (40%) demonstrated no change or an increase in the peripheral vascular resistance. Six of these eight patients had an average daytime mean pressure above 120 mm Hg. There was a significant decrease in the index of resistance during exercise in all but one of the 16 subjects. Hemodynamic parameters of 1 hour before and 1 hour after awakening were similar to the values obtained during the entire night and the rest of the day, respectively. Our data suggest that in patients with progressive hypertension, the ability to decrease vascular resistance from night to day is compromised.