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With greater understanding of the impact of neuroendocrine stimulation on the adverse outcomes of heart failure, especially lethal arrhythmias and sudden cardiac death, focus has returned to the potential benefits of β-adrenergic blockade. In patients with myocardial infarction and left ventricular (LV) dysfunction, particularly those prone to life-threatening arrhythmias, β-blocker therapy has been associated with a lower incidence of arrhythmias and improved survival. Even in the absence of angiotensin-converting enzyme (ACE) inhibition, β blockade has improved cardiac function and LV contractility in nonischemic heart failure, leading to a decrease in LV end-diastolic pressure and improved clinical status. Both the Metoprolol in Dilated Cardiomyopathy (MDC) trial and the Cardiac Insufficiency Bisoprolol Study (CIBIS) found β blockade to be associated with decreased mortality rates in patients with nonischemic heart failure. Of the 3 large randomized mortality trials now under way, the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF) is specifically designed to investigate the effects of β blockade on total mortality when used as an adjunct to ACE inhibition in patients with ischemic or nonischemic heart failure. Unresolved issues to be addressed include whether: (1) β-blocker therapy in heart failure can improve survival and/or reduce the incidence of sudden cardiac death; (2) β blockade is equally effective in ischemic and nonischemic heart failure; (3) any specific β blocker may be better tolerated initially and cause fewer adverse effects; and (4) all β blockers result in improved exercise tolerance and quality of life.

The relation between the circadian occurrence of ventricular premature depolarizations (VPD) and sudden arrhythmic death was examined in a subset of patients entered into the Cardiac Arrhythmia Suppression Trial (CAST). Ambulatory electrocardiographic recordings with hourly measurement of VPD frequency were available in 357 patients. Forty percent of the patients (142 of 357) demonstrated circadian variation in VPD frequency between 6:00 a.m. and 9:59 a.m. that was significantly higher (p (Am J Cardiol 1996;78:881–885)

This report focuses on the subset of 235 patients from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study receiving randomly assigned medical therapy to treat angina and suppress ischemia detected on ambulatory electrocardiography: 121 patients received the sequence of atenolol and nifedipine, and 114 diltiazem and isosorbide dinitrate. After 12 weeks of therapy, the primary end point (absence of ambulatory electrocardiographic (ECG) ischemia and no clinical events) was reached in 47% of atenolol/nifedipine- versus 31% of diltiazem/isosorbide dinitrate-treated patients (adjusted p = 0.03). A trend to increased exercise time to ST depression was seen in the atenolol and nifedipine versus diltiazem and isosorbide dinitrate regimens (median treadmill duration 5.8 vs 4.8 minutes; p = 0.04). However, when adjusted for baseline imbalances in ambulatory ECG ischemia, the 2 medical combinations were similar in suppression of ambulatory ECG ischemia. In both medication regimens, an association between mean heart rate and ischemia on ambulatory electrocardiography after 12 weeks of treatment was observed so that patients on either regimen with a mean heart rate80 beats/min had ischemia detectable almost twice as often as those with a mean heart rate70 beats/min (p0.001).

A subgroup analysis was performed in black patients who participated in the Metoprolol CR/XL Randomized Intervention trial in Congestive Heart Failure trial. Results suggest a beneficial effect of beta blockade and support the use of beta blockers in black patients with clinically stable heart failure and left ventricular dysfunction.

The Cardiac Arrhythmia Suppression Trial (CAST) showed antiarrhythmic drug suppression of asymptomatic or mildly symptomatic ventricular arrhythmias in survivors of myocardial infarction to be harmful. This study retrospectively searched the CAST results for evidence of mortality and morbidity reduction in patients receiving optional β-blocker therapy. All enrolled (n = 2,611) and suppressed main study (n = 1,735) CAST patients with an ejection fraction of ≤40% were examined using univariate analysis, Kaplan-Meier curves, and a Cox proportional-hazards multivariate analysis with respect to optional β-blocker therapy prescribed at baseline. CAST patients receiving β-blocker therapy had significantly enhanced survival at 30 days, and at 1 and 2 years of follow-up against all-cause and arrhythmic death or nonfatal cardiac arrest. Multivariate analysis showed β-blocker therapy to be independently associated with a one-third reduction in arrhythmic death or cardiac arrest (p = 0.036). In CAST patients with a history of congestive heart failure, β-blocker therapy was independently associated with longer time to occurrence of new or worsened congestive heart failure (p = 0.015). This study supports the secondary preventive benefit of β-blocker therapy in high-risk post-myocardial infarction patients, and calls attention to the possible preventive benefit of β-blocker therapy against proarrhythmic events experienced in the CAST.

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.

Although the beneficial effects of long-term therapy with β-adrenergic blocking agents in patients recovering from acute myocardial infarction (AMI) are established, the effect of this therapy on the cardiac event rate in patients recovering from a non-Q-wave AMI is unknown. This post hoc analysis of the Beta Blocker Heart Attack Trial (BHAT) evaluates the effects of daily administration of propranolol 180 or 240 mg/day after non-Q-wave AMI. The study population consisted of 601 patients with enzymatically proven non-Q-wave AMI, which represented 17% of the BHAT patients. Of these, 310 patients were randomized to receive propranolol and 291 patients to placebo. There were no significant baseline differences between groups. The median follow-up was 24.6 months. Mortality was 7.8% (sudden death 4.8%) in the propranolol group and 7.9% (sudden death 4.8%) in the placebo group (p >0.99, log rank test). Reinfarction rate was 7.4% in the propranolol group and 6.5% in the placebo group (p >0.63, log rank test). The need for coronary bypass surgery was similar in the 2 groups. However, more patients randomized to placebo developed angina. In this post hoc group analysis of the BHAT, propranolol was not shown to be beneficial in reducing the cardiac event rate in patients recovering from a non-Q-wave AMI.

We prospectively studied 490 patients who had a first myocardial infarction and performed a complete 2-dimensional echocardiographic studyor=48 hours of admission. In addition to left ventricular ejection fraction, multiple echocardiographic parameters of left ventricular systolic and diastolic performances were found to be independent predictors of 2-year mortality rate and congestive heart failure.

Clinical observations suggest that β-adrenergic blocking agents can modify the circadian occurrence of a variety of ischemic events. Morning awakening is associated with a rapid increase in blood pressure and pulse, serum catecholamine content and platelet activation, at a time of decreased blood thrombolytic activity. Beta-adrenergic blocking agents have the potential to modify many of these events. Current data indicate that these agents modify blood pressure and pulse, but do not prevent their early morning increase. In addition, β-adrenergic blocking agents decrease ventricular ectopy and its circadian variation. Recent studies in humans indicate, however, that metoprolol does not affect the circadian increase in platelet activity or serum catecholamines. The specific mechanism by which β blockers affect the circadian occurrence of ischemic events remains uncertain.

Transthoracic echocardiography and color flow Doppler have been shown to be of value in evaluating regurgitant St. Jude Medical (SJM) prostheses in the aortic valve position. 1 These studies have emphasized the limitations of this technique in diagnosing SJM mitral regurgitation because of flow masking and signal attenuation produced by the echo-reflective metallic valves. 2 Transesophageal echocardiography and color flow Doppler overcome these problems and show promise in evaluating normal functioning and regurgitant SJM mitral valves. 3,4 This report describes our transesophageal ultrasound experience with 28 normal functioning and 8 regurgitant SJM prostheses in the mitral valve position.

In conclusion, the results of this study indicate that severity of functional MR in patients with low ejection fraction appears to be dictated primarily by increased sphericity of the left ventricle rather than by mitral annular dilatation or LV chamber enlargement.

Systemic embolism is a frequent complication in mitral stenosis (MS). 1 Its incidence increases with age and the presence of atrial fibrillation. 2,3 Although patients with MS and sinus rhythm can also develop systemic emboli, the frequency of this event is lower in these patients than in those with atrial fibrillation. 1 Patients with MS and atrial fibrillation are considered at high risk of systemic embolism and require anticoagulant therapy. 4 Because patients with MS and sinus rhythm are considered at low risk for systemic embolism, anticoagulant therapy is not routinely recommended. 4 It is desirable to identify patients with MS in sinus rhythm who are at high risk for systemic embolism. There are no reliable clinical or laboratory parameters available to stratify this risk. Recently developed assays are capable of detecting peptides released during activation of the coagulation cascade and thrombogenesis. 5,6 Measurement of these markers may be used to identify patients at risk for thromboembolism. This study was performed to test the hypothesis that there is activation of coagulation in patients with MS and sinus rhythm. Fibrinolytic activity was assayed by measuring D-dimers that are generated from plasmic degradation of cross-linked fibrin. 5 Thrombin activation was assayed by measuring thrombinantithrombin III complexes. 6

Circadian variation in hemostatic factors may contribute to a higher frequency of cardiac events observed in the morning and with activity. Diurnal changes in these factors were investigated by measuring in vitro platelet aggregability in response to epinephrine and adenosine diphosphate together with beta-thromboglobulin and platelet factor 4 as indexes of in vivo platelet activation. Activation of coagulation was measured by thrombin-antithrombin III complexes and D-Dimers. Tests were performed in 9 normal healthy subjects. Circadian changes occurred in beta-thromboglobulin (p less than 0.05) and platelet factor 4 (p less than 0.06). Plasma levels of beta-thromboglobulin and platelet factor 4 were lowest with patients supine and resting at 7 and 8 A.M., and increased with activity, with peak levels achieved at 3 P.M. (p less than 0.01). Thrombin-antithrombin III complexes (p = 0.44), D-Dimer (p = 0.36) and in vitro platelet aggregability to adenosine diphosphate (p = 0.20) did not show diurnal variation. There was a trend toward circadian variation in vitro platelet aggregability to epinephrine, but these changes did not achieve statistical significance (p = 0.16). Circadian changes of in vivo release of beta-thromboglobulin and platelet factor 4 correlated to patient activity and not to the morning peaks in ischemic events. These data indicate that changes in platelet function and not in coagulation have a diurnal occurrence.

The effect of empiric antiarrhythmic therapy with quinidine and procainamide on long-term mortality was examined in 209 patients with coronary artery disease resuscitated after out-of-hospital cardiac arrest. The antiarrhythmic agent used was determined by the patient's private physician without knowledge of the study ambulatory electrocardiogram. Of the 209 patients, procainamide was prescribed in 45 (22%), quinidine in 48 (23%) and no antiarrhythmic therapy in 116 (55%). Digoxin therapy was initiated in 101 patients. The 2-year total survival rate for the quinidine, procainamide and nontreated patients was 61, 57 and 71% (p less than 0.05), and for sudden death was 69, 69 and 89% (p less than 0.01), respectively. These observations suggest that empiric antiarrhythmic therapy in survivors of out-of-hospital cardiac arrest did not affect total mortality and was associated with an increased frequency of sudden death.

The effect of propranolol on mortality and reinfarction after acute myocardial infarction (AMI) in cigarette smokers and nonsmokers was studied in the Beta Blocker Heart Attack Trial. Cigarette smokers (n = 2,332) were 5 years younger than nonsmokers and had a lower incidence of diabetes mellitus, systemic hypertension, previous AMI and cardiomegaly. Among cigarette smokers, the placebo group had a higher total mortality rate than the propranolol group (11.0 vs 7.4%, p less than 0.0008) and more sudden cardiac deaths (7.1 vs 4.6%, p less than 0.009). In nonsmokers the placebo group had a mortality (7.9 vs 7.1%, p greater than 0.64) similar to the propranolol group. After baseline adjustment, cigarette smokers were estimated to have 1.6 times the risk of dying as compared to nonsmokers (p less than 0.0007). Adjusting for baseline differences, both treatment with propranolol and nonsmoking were predictors of survival. No detectable nonsmoking/propranolol interaction could be identified. In survivors of AMI a beneficial effect of propranolol is observed for cigarette smokers. Nevertheless, cigarette smoking continues to be a risk factor for mortality after AMI even for those receiving propranolol.

For transplant wait-list patients with end-stage congestive heart failure, reversibility of pulmonary hypertension tested with acute administration of vasodilators is a prerequisite to listing for transplantation. We have shown that the magnitude of the initial pulmonary vasodilatory response to nitroprusside predicts neither the extent of the long-term hemodynamic response nor the subsequent need for transplantation versus clinical improvement and removal from transplant consideration.

Hemodynamic response after intravenous and oral administration of a new phosphodiesterase inhibitor, CI-914, was studied in 13 patients with severe congestive heart failure. Comparable significant increases in cardiac index of 26% (p less than 0.01) and 19% (p less than 0.02) after intravenous and oral administration were observed. Systemic vascular resistance, right atrial and pulmonary artery wedge pressure decreased significantly after intravenous drug administration. Although similar changes occurred after oral administration, they were not statistically significant. Peak CI-914 plasma concentration occurred 2.3 +/- 2.2 hours after oral drug administration and exhibited measurable hemodynamic effects for up to 10 to 12 hours. Seven of the 13 patients received long-term oral CI-914 for as long as 12 weeks and exhibited an improvement in New York Heart Association functional class and exercise capacity. Five patients died with progressive heart failure, 1 patient died suddenly and 1 died of sepsis. The drug was well tolerated and appears to have potential as a cardiotonic agent.

To determine the clinical value of echocardiographic evaluation of porcine bioprosthetic valves, the findings in all patients who had porcine bioprosthetic valve replacement and adequate quality echocardiographic studies from 1978 to 1982 were analyzed. The study includes 309 normal and 59 dysfunctioning valves. Valve dysfunction resulted from spontaneous cusp degeneration in 39 (34 valve regurgitations, 5 stenoses), infective endocarditis in 12, paravalvular regurgitation in 5, regurgitation of redundant cusps, mitral valve thrombi, and aortic stent stenosis in 3 others. Echocardiographic findings were correlated with gross surgical pathologic or autopsy findings in 45 of the 59 dysfunctioning valves. Echocardiographic abnormalities were demonstrated in 41 of 59 (69%) dysfunctioning valves. A systolic mitral or diastolic aortic valve flutter was diagnostic of a regurgitant valve caused by a torn or unsupported cusp margin and was observed in 28 of 34 (82%) regurgitant valves with no false-positive studies. Echocardiographic cusp thickness of greater than or equal to 3 mm correctly identified all regurgitant and stenotic valves with gross anatomic evidence of localized or generalized cusp thickening or calcific deposits. Echocardiographic valve abnormalities were observed in only 4 of 12 patients with infective endocarditis and in 1 of 5 with paravalvular regurgitation. Thus, echocardiography provides important information regarding the function of porcine bioprosthetic valves and is of value in the decision to replace these valves, especially when dysfunction is due to spontaneous cuspal degeneration. Echocardiography is neither sensitive nor specific in patients with infective endocarditis and paravalvular regurgitation.

The frequency spectrum of the aortic component of the second sound (A2) was measured noninvasively in 77 patients. Fourteen had a normal aortic valve, 14 had calcific aortic stenosis and 49 had an aortic porcine xenograft. Phonocardiograms were recorded on magnetic tape on line with a Spectral Dynamics signal processor with which the frequency spectrum and dominant frequency of A2 were determined. In 14 patients with a normal aortic valve, the dominant frequency of A2 was 53 ± 3 hertz (mean ± standard error of the mean); in 14 patients with aortic stenosis A2 frequency was higher, 87 ± 5 hertz (p < 0.001). In 15 patients with a porcine aortic valve heterograft implanted for 18 months or less, A2 frequency was 48 ± 5 hertz, which did not differ significantly from that of patients with a normal natural aortic valve. However, in 19 patients with an aortic porcine heterograft that was in place 5 to 7.5 years, the dominant frequency of A2 was higher, 81 ± 4 hertz (p < 0.001), and within the range of that observed in patients with aortic stenosis. Among these 19 patients, 2 required replacement of the prosthetic aortic valve because of valve degeneration. The association of a higher than normal frequency of A2 with a stiffened valve, such as occurs in aortic stenosis, is predictable on the basis of factors that affect the frequency of valve vibration and pressure fluctuations productive of sound. The data suggest that the frequency of A2 may be of value in detecting degenerative changes of porcine aortic xenografts.

This report describes a fibrosarcoma of the right ventricle in a 19 year old girl who had rapid onset of severe right heart failure with clinical signs of pulmonic stenosis and tricuspid insufficiency. Electrocardiographic changes were consistent with right ventricular hypertrophy and right bundle branch block. Cardiac catheterization demonstrated findings consistent with pulmonary valvular and infundibular stenosis. Right ventricular angiocardiography demonstrated a filling defect caused by the tumor. Surgical removal of the tumor was followed by dramatic improvement. Four months after the operation she had recurrence of symptoms due to recurrence of the tumor. Radiation therapy produced only transient beneficial effects.

A 30 year old woman complained of progressive fatigue and was noted to have systolic and diastolic murmurs. At cardiac catheterization, pressure gradients were found across the tricuspid and pulmonary valves. Selective angiocardiography demonstrated a large, mobile right ventricular intracavitary filling defect. Three months after surgical removal of a right ventricular myxoma, no evidence of residual valve obstruction was noted on pressure pullback recordings or cineangiocardiograms, and the cardiac output had doubled. Clinical improvement was good.

Sudden cardiac death (SCD) is a major problem confronting cardiology. We need to know more about the mechanisms responsible for its occurrence so that preventive measures may be designed. Recent evidence shows a morning increase in SCD,1,2 similar to the morning increase in myocardial infarction3,4 and transient myocardial ischemia.5 This suggests that increased sympathetic activity associated with assumption of the upright posture may be involved. Beta blockers have been shown to eliminate the morning increase in myocardial ischemia and infarction.3–5 Accordingly, we examined the timing of out-of-hospital SCD in the Beta Blocker Heart Attack Trial (BHAT) population to determine (1) if this morning increase was present in the placebo group and (2) whether it was eliminated by the use of β blockers.

To correlate cardiac event rate with infarct location on the electrocardiogram in patients recovering from a non-Q-wave acute myocardial infarction (AMI), 135 consecutive patients with enzymatically proven non-Q-wave AMI were followed prospectively for a median of 9.9 months. Of these, 65 patients were classified as having had an anterior non-Q-wave AMI, defined as new ST- or T-wave changes, or both, in leads V1 through V4 (group 1). The remaining 70 patients were classified as having had inferior or lateral non-Q-wave AMI, or both, defined as ST- or T-wave changes in 2 consecutive leads (II, II aVF; II and aVL or V5 and V6) (group 2). At baseline group I was older and had a higher incidence of previous AMI than group 2. After adjusting for baseline variables, the patients in group I had a 29% reinfarction and 32% mortality rate, which was significantly higher (p less than 0.002 for both) when compared to group 2, which had a reinfarction and mortality rate of 8 and 9%, respectively. Patients with anterior non-Q-wave AMI are at very high risk for developing a major cardiac event very soon after the index AMI. This high risk is probably related to a larger area of residual ischemic but viable myocardium in the infarct-related artery when compared to inferolateral non-Q-wave AMI.

The echocardiographic features are presented of degeneration of nine glutaraldehyde-fixed porcine xenograft valves implanted in eight patients. These features occurred 11 to 68 months after implantation and were correlated with surgical and necropsy findings. Acute bacterial endocarditis was present in two patients, and had been successfully treated medically in three other patients 47 to 52 months before valve degeneration was recognized. The valve was severely thickened in four patients and in two of the four the thickening was associated with a significant hemodynamic transvalve gradient. M mode echocardiography demonstrated increased thickness and loss of the cusp detail. In five patients severe regurgitation due to a tear in one or more cusps developed in the the valve in the mitral position. M mode echocardiography in all five patients revealed on the valve systolic or diastolic fluttering echoes, or both. The two dimensional echocardiogram demonstrated thickened cusps with systolic protrusion of the leaflets into the left atrium. Both modes of echocardiography were of valve in identifying degeneration of the porcine xenograft valve.

This study examines the relation between the change in clinical status and the change in plasma norepinephrine concentration in patients with congestive heart failure (CHF) receiving standard medical therapy. Hemodynamic measurements in 11 patients with CHF (ejection fraction 19 +/- 4%) were obtained before and immediately after the administration of digoxin and angiotensin-converting enzyme inhibitors. Patients were then followed for 1 year. Clinical status was determined using the Boston Clinical Heart Failure scoring system. Of the 11 patients, 6 demonstrated significant clinical improvement after therapy, based on the Boston score, over a 1-year period. Five patients did not respond to therapy: 4 died and the remaining patient had worsening CHF. There was no difference between responders and nonresponders in either baseline hemodynamics or acute response to the administration of digoxin and an angiotensin-converting enzyme inhibitor. In the patients who improved, plasma norepinephrine decreased from 706 +/- 235 to 545 +/- 223 pg/ml (p = 0.08) after 1 year of medical therapy. In patients whose CHF worsened or who died, plasma norepinephrine increased from 715 +/- 275 at baseline to 1,237 +/- 671 pg/ml at their last measurement (p = 0.06). Although at baseline the plasma norepinephrine levels were similar in both groups of patients, a significant difference between responders and nonresponders was observed at final follow-up (p less than 0.002). Change in plasma norepinephrine correlated with change in CHF score (r = 0.79, p less than 0.004). Thus, in patients with CHF, serial measurements of plasma norepinephrine correlate with changes in clinical status.

Prodromal symptoms and cardiac history were examined in 227 patients with coronary artery disease who were successfully resuscitated after out-of-hospital cardiac arrest. Cardiac arrest was sudden—with either no symptoms or symptoms for less than 1 hour—in 71% of the patients. Nonsudden death—death occurring after more than 1 hour of symptoms—occurred in 29% of the patients. A history of cardiovascular disease was present in 85% of patients with sudden cardiac arrest and in 83% with nonsudden arrest. Cardiac arrest occurred without symptoms in 38% of the patients with sudden cardiac arrest and was the first expression of coronary artery disease in 4% of the entire study group. This study indicates that cardiac arrest usually occurs with symptoms and almost always in the setting of a history of cardiovascular disease.

Balloon occlusion of a stenotic coronary artery during percutaneous coronary artery angioplasty provides a unique opportunity to study the effect of acute myocardial ischemia on left ventricular (LV) function. Simultaneous M-mode and 2-dimensional (2-D) echocardiograms and a 6-lead electrocardiogram were recorded during 20 episodes of coronary artery occlusion and release in 12 patients. No patient had previous myocardial infarction and all had normal LV function by angiography. All patients had isolated single coronary artery disease, with left anterior descending stenosis in 8 and right coronary stenosis in 4. In 18 of 20 episodes (90%), M-mode echocardiography during balloon occlusion revealed a significant (p less than 0.001) decrease in LV systolic, diastolic and percent systolic wall thickness; systolic excursion; systolic and diastolic endocardial velocities; and fractional shortening. These changes were observed in the area of the ventricular septum in patients with left anterior descending occlusion and posteroinferior wall in those with right coronary artery occlusion. Two-dimensional echocardiography revealed varying degrees of hypokinesia, akinesia and dyskinesia during balloon occlusion in 18 instances. The echocardiographic changes were observed within 15 to 20 seconds of balloon occlusion and resolved 10 to 20 seconds after balloon deflation. All patients who had echocardiographic changes during balloon occlusion also had concomitant electrocardiographic (ECG) ST-segment elevation, whereas 2 patients with normal LV function had no ECG changes. Both of these patients had profuse collateral blood supply to the stenotic coronary artery. The echocardiographic and ECG abnormalities increased proportionately to the length of balloon occlusion. This study confirms previous animal and recent human studies of transient LV dysfunction during coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

CI-930, a new type III phosphodiesterase inhibitor, was evaluated for treatment of refractory congestive heart failure. The hemodynamic, pharmacokinetic and clinical response to the drug was determined in 10 patients. At the peak plasma concentration after intravenous CI-930, cardiac index increased from 2.0 to 2.7 liters/min/m2 (p less than 0.002), pulmonary artery wedge pressure decreased from 26 to 17 mm Hg (p less than 0.001) and systemic vascular resistance decreased from 1,999 to 1,471 dynes cm-5 (p less than 0.05). Heart rate and blood pressure did not change significantly. Similar changes were observed with oral CI-930. Peak CI-930 plasma concentration occurred 1.2 +/- 0.8 hours after oral administration. Beneficial hemodynamic effects were sustained 12 to 18 hours after the oral dose. The sustained hemodynamic effects observed after oral administration appear to be related to an active metabolite of CI-930 that has prolonged duration of action and slow washout. The drug was well tolerated and has potential for treatment of congestive heart failure.