Safety and efficacy of esmolol (ASL-8052: an ultrashort-acting beta-adrenergic blocking agent) for control of ventricular rate in supraventricular tachycardias.

Esmolol (ASL-8052) is a new intravenous beta-adrenergic blocking agent that has exhibited both cardiac selectivity and an extremely short half-life in animal studies. To assess its clinical efficacy, 16 patients were studied with a rapid ventricular rate associated with atrial flutter (n = 2), atrial fibrillation (n = 10), atrial tachycardia (n = 2) and multifocal atrial tachycardia (n = 2). During a 30 minute control period of observation, the ventricular rate ranged from 121 to 150 beats/min (mean 133.2 +/- 10.6). Using a double blind crossover method, esmolol was infused intravenously for a maximum of 60 minutes. Infusions of 50, 100, 150, 200, 250 and 300 micrograms/kg per min were given in consecutive 5 minute periods (during the first minute of each period, a loading dose of 500 micrograms/kg was given). Not all patients received the maximal dose. A response was defined as conversion to sinus rhythm or a 20% reduction in ventricular rate. One patient with atrial fibrillation associated with the Wolff-Parkinson-White syndrome did not respond. In the remaining 15 patients, their highest esmolol infusion rate was maintained for an additional 30 minutes. This resulted in a reduction in ventricular rate to a mean of 97.8 +/- 12.9 beats/min (range 72 to 119) (p less than 0.001). Conversion from flutter/fibrillation to sinus rhythm occurred in two patients. During the infusion, six had transient asymptomatic hypotension that was mild and manageable. After infusion, ventricular rate and blood pressure returned rapidly toward control values within 25 minutes in patients without conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Ejection fraction response to supine exercise in asymptomatic aortic regurgitation: relation to simultaneous hemodynamic measurements.

The change in ejection fraction during exercise is frequently employed as a measure of left ventricular functional reserve in patients with aortic regurgitation. However, little information is available about its relation to invasive measurements of cardiac performance. Therefore, simultaneous hemodynamic measurements and supine exercise blood pool scintigraphy were performed in 14 patients with severe, asymptomatic or minimally symptomatic aortic regurgitation associated with cardiomegaly but preserved left ventricular function at rest. Their hemodynamic measurements at rest were normal and their exercise capacity was excellent. When the patients were categorized into those patients whose ejection fraction increased or did not decrease by more than 0.05 (Group 1) and those whose ejection fraction decreased by more than 0.05 (Group 2), important differences were apparent. Echocardiographic, radionuclide and hemodynamic measurements at rest in the two patient groups were similar, but Group 1 exhibited a greater increase in cardiac index during supine exercise (2.8 +/- 0.4 to 10.0 +/- 1.8 versus 2.7 +/- 0.5 to 6.9 +/- 1.0 liters/min per m2; p less than 0.005) and a lesser increase in pulmonary capillary wedge pressure (13 +/- 4 to 19 +/- 7 versus 12 +/- 4 to 31 +/- 8 mm Hg; p less than 0.01). The severity of regurgitation decreased during exercise in all patients, but end-diastolic volume decreased and end-systolic volume decreased or was unchanged in Group 1, whereas end-diastolic volume was unchanged and end-systolic volume increased in Group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of esmolol on airway function in patients with asthma.

In a double-blind, randomized, crossover study in ten patients with asthma, the effects on specific airway resistance of esmolol, a new ultra-short-acting beta 1-selective adrenoceptor blocker, were compared with those of placebo. Specific airway resistance was measured during increasing doses of esmolol infusion, during dry air provocation tests, and following isoproterenol inhalation. These same studies were later carried out on six of ten patients following intravenous propranolol infusion. All patients were able to tolerate the maximum dose of esmolol (300 micrograms/kg/min); treatment differences between esmolol and placebo were not found. In contrast, intravenous propranolol produced marked symptomatic bronchoconstriction after the lowest dose (1 mg) in two of six patients. Esmolol produced slight but statistically significant enhancement of patients' sensitivity to dry air provocation. Similarly, a slight but significant inhibition of bronchomotor sensitivity to isoproterenol was noted during esmolol infusion. After infusion of 5 mg of intravenous propranolol, one of four patients had a clinically significant increase in sensitivity to dry air. It is concluded that esmolol, because of its short duration of action and relative lack of effect on airway resistance, may be preferred over propranolol in patients with asthma who require treatment with an intravenous beta-blocking agent.

Positive therapeutic effects of intercessory prayer in a coronary care unit population.

The therapeutic effects of intercessory prayer (IP) to the Judeo-Christian God, one of the oldest forms of therapy, has had little attention in the medical literature. To evaluate the effects of IP in a coronary care unit (CCU) population, a prospective randomized double-blind protocol was followed. Over ten months, 393 patients admitted to the CCU were randomized, after signing informed consent, to an intercessory prayer group (192 patients) or to a control group (201 patients). While hospitalized, the first group received IP by participating Christians praying outside the hospital; the control group did not. At entry, chi-square and stepwise logistic analysis revealed no statistical difference between the groups. After entry, all patients had follow-up for the remainder of the admission. The IP group subsequently had a significantly lower severity score based on the hospital course after entry (P less than .01). Multivariant analysis separated the groups on the basis of the outcome variables (P less than .0001). The control patients required ventilatory assistance, antibiotics, and diuretics more frequently than patients in the IP group. These data suggest that intercessory prayer to the Judeo-Christian God has a beneficial therapeutic effect in patients admitted to a CCU.

Leaving a cardiology service against medical advice.

In an exploratory retrospective study of 64 hospitalized patients, we examined the demographic, medical, and psychologic correlates in patients who left our Cardiology Service against medical advice (AMA). Based on a medical chart review, the AMA and control groups were found to be significantly different regarding prior cardiac disability level, physical signs of chronic alcohol abuse on admission, cardiac complications, and requirement of antihypertensive/diuretic medications while hospitalized. The two groups were also significantly different with regard to somatic complaints, apparent anxiety and use of psychotropic medication on the day before leaving against medical advice. This study indicates that a multifactorial assessment of patients hospitalized on a cardiology service can enhance identification of those at risk to leave the hospital against medical advice.

Long-term digitalis therapy improves left ventricular function in heart failure.

To clarify the controversy regarding the benefits of long-term oral digoxin in the treatment of heart failure, we evaluated hemodynamics at rest and during exercise in nine patients in sinus rhythm with symptomatic heart failure. Patients were studied during long-term digoxin therapy, after withdrawal of the drug, and six hours after readministration. Upon withdrawal of digoxin, pulmonary capillary-wedge pressure increased from 21 +/- 8 to 29 +/- 10 mm Hg, and cardiac index decreased from 2.4 +/- 0.7 to 2.1 +/- 0.6 liters per minute per square meter of body-surface area, suggesting a deterioration in left ventricular function. In addition, heart rate tended to increase and stroke-work index, stroke-volume index, and radioangiographic ejection fraction decreased. Acute readministration restored the hemodynamic values to those observed during long-term digoxin therapy. The improvement in hemodynamics during long-term digoxin administration was also observed during exercise. This improvement demonstrated the value of long-term oral digoxin therapy in congestive heart failure.

Comparison of the efficacy and safety of esmolol, a short-acting beta blocker, with placebo in the treatment of supraventricular tachyarrhythmias. The Esmolol vs Placebo Multicenter Study Group.

The efficacy and safety of esmolol, a short-acting intravenous beta-adrenergic-blocking agent, and placebo were compared in patients with supraventricular tachyarrhythmias (heart rate greater than 120 bpm) in a multicenter, double-blind, partial-crossover study. Seventy-one patients were randomized to receive either esmolol (n = 36) or placebo (n = 35) as initial treatment. Therapeutic failures were crossed over to the other study medication. Therapeutic response was defined as greater than or equal to 20% reduction in heart rate, heart rate less than 100 bpm, or conversion to normal sinus rhythm. The therapeutic response to esmolol during the initial treatment period (72%) was similar to that obtained when esmolol was given as a second agent. The average esmolol dosage producing a therapeutic response was 97.5 micrograms/kg/min. Four patients (6%) converted to normal sinus rhythm during esmolol infusion. In the majority of patients (80%), therapeutic response was lost within 30 minutes following discontinuation of esmolol infusion, a finding indicative of rapid reversal of beta-adrenoceptor blockade. The most prevalent adverse effect during esmolol infusion was hypotension which occurred in eight patients (12%). Hypotension and associated symptoms resolved within 30 minutes after discontinuation of esmolol infusion, which is consistent with the short duration of action of esmolol (elimination half-life of 9.2 minutes).