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Biomedical subjects

B F Uretsky

Publications and source records attributed to B F Uretsky.

At least 37 records · Page 2Linked to original sources
PubMed1998

Superiority of "triple" drug therapy in heart failure: insights from the PROVED and RADIANCE trials. Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin. Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme.

OBJECTIVES: We sought to study the efficacy of "triple" therapy with digoxin, diuretic and angiotensin-converting enzyme inhibitor (ACEI) compared to other combinations of these drugs in patients with symptomatic left ventricular systolic dysfunction. BACKGROUND: Controversy continues concerning the role of combining digoxin with diuretic and ACEI in the initial management of patients with heart failure. METHODS: The study utilized data from two studies of digoxin efficacy: Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin (PROVED) and Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE). Worsening heart failure defined as augmentation of heart failure therapy or an emergency room visit or hospitalization for increased heart failure was the main outcome measure. RESULTS: A total of 266 patients comprising the four treatment groups of the combined PROVED (diuretic alone or digoxin and diuretic) and RADIANCE (ACEI and diuretic, or digoxin, diuretic and ACEI) trials were analyzed. Worsening heart failure occurred in only 4 of the 85 patients who continued digoxin, diuretic and ACEI therapy (4.7%) compared to 18 of the 42 patients (19%) on digoxin and diuretic therapy (p=0.009), to 23 of the 93 patients (25%) on ACEI and diuretic therapy (p=0.001) and to 18 of the 46 patients (39%) on diuretic alone (p < 0.001). Life table and multivariate analysis also demonstrated that worsening heart failure was least likely in patients treated with triple therapy (p < 0.01 vs. all other groups). CONCLUSION: Pending definitive, prospective clinical trials, our results argue for triple therapy as the initial management of patients with symptomatic heart failure due to systolic dysfunction.

Adult↗
PubMed1997

Relation of unstable angina and myocardial infarction to progression of coronary narrowing in patients undergoing coronary artery bypass grafting (utilizing an internal mammary artery).

We examined the relation of an ischemic syndrome with the progression of coronary disease early (<3 years) after multiple bypass grafting utilizing an internal mammary artery and saphenous vein grafts. Data indicate that an ischemic syndrome is associated with progression of native coronary disease distal to the graft or total occlusion of the saphenous vein graft in most cases.

Aged↗
PubMed1997

Effects of long-term infusion of prostacyclin (epoprostenol) on echocardiographic measures of right ventricular structure and function in primary pulmonary hypertension. Primary Pulmonary Hypertension Study Group.

BACKGROUND: Right heart failure is an important cause of morbidity and mortality in primary pulmonary hypertension. In a recent prospective, randomized study of severely symptomatic patients, treatment with prostacyclin (epoprostenol) produced improvements in hemodynamics, quality of life, and survival. This article describes the echocardiographic characteristics of participants in this trial; the relationship of echocardiographic variables to hemodynamic parameters, exercise capacity, and quality of life; and the echocardiographic changes associated with prostacyclin therapy. METHODS AND RESULTS: The 81 patients enrolled in this multicenter trial were randomized to treatment with a long-term infusion of prostacyclin in addition to conventional therapy (n = 41) or conventional therapy alone (n = 40) for 12 weeks. Echocardiograms and assessments of hemodynamics, exercise capacity, and quality of life were performed before and after the treatment phase. On baseline evaluation, patients had marked right ventricular dilatation and dysfunction, abnormal septal curvature, and significant tricuspid regurgitation with a high regurgitant velocity. Pericardial effusions were common. More pronounced abnormalities in right heart structure and function were associated with higher pulmonary arterial and mean right atrial pressures, lower cardiac index, and impaired exercise capacity but had no predictable relationship to quality-of-life indicators. The 12-week infusion of prostacyclin had beneficial effects on right ventricular size, curvature of the interventricular septum, and maximal tricuspid regurgitant jet velocity. CONCLUSIONS: The echocardiographic manifestations of severe primary pulmonary hypertension reflect abnormalities in hemodynamics and exercise capacity. Prostacyclin has beneficial effects on right heart structure and function that may contribute to the clinical improvement and prolonged survival observed with this drug.

Adult↗
PubMed1997

A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST).

This trial evaluated the effects of epoprostenol on patients with severe left ventricular failure. Patients with class IIIB/IV congestive heart failure and decreased left ventricular ejection fraction were eligible for enrollment if angiography documented severely compromised hemodynamics while the patient was receiving a regimen of digoxin, diuretics, and an angiotensin-converting enzyme inhibitor. We randomly assigned 471 patients to epoprostenol infusion or standard care. The primary end point was survival; secondary end points were clinical events, congestive heart failure symptoms, distance walked in 6 minutes, and quality-of-life measures. The median dose of epoprostenol was 4.0 ng/kg/min, resulting in a significant increase in cardiac index (1.81 to 2.61 L/min/m2), a decrease in pulmonary capillary wedge pressure (24.5 to 20.0 mm Hg), and a decrease in systemic vascular resistance (20.76 to 12.33 units). The trial was terminated early because of a strong trend toward decreased survival in the patients treated with epoprostenol. Chronic intravenous epoprostenol therapy is not associated with improvement in distance walked, quality of life, or morbid events and is associated with an increased risk of death.

Aged↗
PubMed1997

Patients with mild heart failure worsen during withdrawal from digoxin therapy.

OBJECTIVES: We investigated whether patients with mild heart failure due to left ventricular systolic dysfunction were at risk of worsening during digoxin withdrawal. BACKGROUND: Deterioration during digoxin withdrawal is often believed to be restricted to patients with moderate to severe clinical evidence of heart failure. To test this hypothesis, we studied the outcome of patients categorized by treatment assignment and a clinical signs and symptoms heart failure score in two rigorously designed clinical heart failure trials: the Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin (PROVED) and the Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE) trial. METHODS: Potential differences in treatment failure, left ventricular ejection fraction and exercise capacity were evaluated in three groups of patients: those with mild heart failure (score < or = 2) who were withdrawn from digoxin (Dig WD Mild); those with moderate heart failure (score > 2) who were withdrawn from digoxin (Dig WD Moderate); and patients who continued receiving digoxin regardless of heart failure score (Dig Cont). RESULTS: Heart failure score at randomization did not predict outcome during follow-up in Dig Cont-group patients. Dig WD Mild-group patients were at increased risk of treatment failure and had deterioration of exercise capacity and left ventricular ejection fraction compared with that in Dig Cont-group patients (all p < 0.01). Patients in the Dig WD Moderate group were significantly more likely to experience treatment failure than patients in either the Dig WD Mild or Dig Cont group (both p < 0.05). CONCLUSIONS: Patients with systolic left ventricular dysfunction were at risk of clinical deterioration after digoxin withdrawal despite mild clinical evidence of congestive heart failure.

Aged↗
PubMed1997

Hemodynamic changes of aortic regurgitation.

Hemodynamic changes associated with acute AR include a rapid increase in LV pressures during diastole, markedly elevated pressures at end diastole, and premature closure of the mitral valve. Systemic diastolic pressures may be low, but there is a minimal increase in pulse pressure. In very severe cases of acute AR, cardiac output may decrease, leading to hypotension. In chronic AR, the LV remodels to accommodate the regurgitant volume flow, and stroke volume increases to maintain effective forward blood flow. These adaptations lead to a dilated LV, a widened pulse pressure, and a low diastolic blood pressure, which are the classic findings of chronic AR.

Aortic Valve Insufficiency↗
PubMed1996

Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. US Carvedilol Heart Failure Study Group.

BACKGROUND: We tested the hypothesis that carvedilol inhibits clinical progression in patients with mildly symptomatic heart failure due to left ventricular (LV) systolic dysfunction. METHODS AND RESULTS: Patients (n = 366) who had mildly symptomatic heart failure with an LV ejection fraction (LVEF) < or = 0.35, had minimal functional impairment (defined as the ability to walk 450 to 550 m on a 6-minute walk test), and were receiving optimal standard therapy, including ACE inhibitors, were randomized double-blind to carvedilol (n = 232) or placebo (n = 134) and followed up for 12 months. The primary end point was clinical progression, defined as death due to heart failure, hospitalization for heart failure, or a sustained increase in heart failure medications. Clinical progression of heart failure occurred in 21% of placebo patients and 11% of carvedilol patients, reflecting a 48% (P = .008) reduction in the primary end point of heart failure progression (relative risk, 0.52; CI, 0.32 to 0.85). This effect of carvedilol was not influenced by sex, age, race, cause of heart failure, or baseline LVEF. Carvedilol also significantly improved several secondary end points, including LVEF, heart failure score, NYHA functional class, and the physician and patient global assessments. Carvedilol reduced all-cause mortality but had no effects on the Minnesota Living With Heart Failure scale, the distance walked in 9 minutes on a self-powered treadmill, or cardiothoracic index. The drug was well tolerated. CONCLUSIONS: Carvedilol, when added to standard therapy, including an ACE inhibitor, reduces clinical progression in patients who are only mildly symptomatic with well-compensated heart failure.

Adolescent↗
PubMed1996

Comparison of metabolic, ventilatory, and neurohumoral responses during light forearm isometric exercise and isotonic exercise in congestive heart failure.

Maximal treadmill exercise responses were compared with light forearm isometric exercise responses in patients with chronic, stable heart failure (n = 14), and normal sedentary controls (n = 11). Isometric exercise was performed to exhaustion with 25% of maximal voluntary contraction. Gas-exchange analysis was used to determine oxygen consumption (VO2), carbon dioxide production (VCO2), and minute ventilation (VE) during exercise. Significant correlations were observed in normal controls, but not in patients with heart failure, between peak isotonic exercise and peak isometric exercise for VO2 (r = 0.75, p = 0.001) and VCO2 (r = 0.67, p <0.03), and between submaximal isotonic exercise (50% of peak) and peak isometric exercise for VO2 (r = 0.75, p = 0.007), VCO2 (r = 0.67, p = 0.02), and VE (r = 0.71, p = 0.01). At 90 seconds after isometric exercise in both groups, significant correlations (p <0.05) were observed with peak isotonic exercise for VE (r = 0.62 normals, and r = 0.63 heart failure). Plasma norepinephrine increased significantly (p <0.01) after both isotonic and isometric exercise in patients with heart failure, although peak values were greater with isotonic than with isometric exercise (p = 0.01). Plasma atrial natriuretic peptide and renin activity did not change with either isotonic or isometric exercise. In conclusion, maximal isotonic exercise responses are not predictive of peak isometric VO2 or VCO2 in patients with heart failure. However, VE during maximal isotonic exercise predicts postisometric exercise ventilation in both normals and patients with heart failure; this may determine the extent of dyspnea that patients with heart failure experience with isometric activities of daily living.

Adult↗
PubMed1996

A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension.

BACKGROUND: Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospective, randomized trial to improve survival. METHODS: We conducted a 12-week prospective, randomized, multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol (formerly called prostacyclin) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension (New York Heart Association functional class III or IV). RESULTS: Exercise capacity was improved in the 41 patients treated with epoprostenol (median distance walked in six minutes, 362 m at 12 weeks vs. 315 m at base line), but it decreased in the 40 patients treated with conventional therapy alone (204 m at 12 weeks vs. 270 m at base line; P < 0.002 for the comparison of the treatment groups). Indexes of the quality of life were improved only in the epoprostenol group (P < 0.01). Hemodynamics improved at 12 weeks in the epoprostenol-treated patients. The changes in mean pulmonary-artery pressure for the epoprostenol and control groups were -8 percent and +3 percent, respectively (difference in mean change, -6.7 mm Hg; 95 percent confidence interval, -10.7 to -2.6 mm Hg; P < 0.002), and the mean changes in pulmonary vascular resistance for the epoprostenol and control groups were -21 percent and +9 percent, respectively (difference in mean change, -4.9 mm Hg/liter/min; 95 percent confidence interval, -7.6 to -2.3 mm Hg/liter/min; P < 0.001). Eight patients died during the study, all of whom had been randomly assigned to conventional therapy (P = 0.003). Serious complications included four episodes of catheter-related sepsis and one thrombotic event. CONCLUSIONS: As compared with conventional therapy, the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement, as well as improved survival in patients with severe primary pulmonary hypertension.

Adult↗
PubMed1996

Coronary artery fistula after heart transplantation: a disappearing entity?

A high incidence of coronary artery fistulas has been observed angiographically after heart transplantation. To determine the present incidence of this finding and the natural history of fistulas in this setting, we reviewed coronary angiograms and clinical course on all patients (n = 480) transplanted from 1980 to 1990 who survived until the first annual coronary angiogram and compared the incidence of coronary artery fistulas in the early (patients #1-160), middle (patients #161-320), and late transplant (patients #321-480) groups. The 3-yr coronary artery fistula incidence for the early group was 3.5%, 6.9% for the middle group, and 2.9% in the late group (P < 0.05, early vs late). Patients who developed fistulas were followed longitudinally. Angiographic follow-up data (median duration: 6 yr) were available in 14 patients having 17 fistulas. No fistula increased in size, and in 10 of 14 patients (71%), fistulas became angiographically undetectable. No patient had any clinical complication related to the fistula. In summary, the incidence of coronary artery fistulas is presently lower than previously reported, which may in turn be related to refinements in heart biopsy technique. The lack of long-term clinical sequelae and the relatively high rate of disappearance favor a conservative approach of "watchful waiting."

Coronary Angiography↗
PubMed1996

Prediction of mortality in patients awaiting cardiac transplantation: increased risk of sudden death in ischemic compared to idiopathic dilated cardiomyopathy.

A major problem in cardiac transplantation is the death of candidates due to the increasing shortage of donors and the consequent longer waiting periods. To determine whether clinical markers for death could be identified in these patients, 168 adult candidates with heart failure (NYHA class III and IV) listed between August 1987 and December 1989 were analyzed. There were 104 patients with ischemic cardiomyopathy (ISCM) and 64 with idiopathic dilated cardiomyopathy (IDCM). Transplantation was performed in 93 patients (55%). Actuarial 1 year survival was 61% in the ISCM group and 78% in the IDCM group (P = NS). Freedom from sudden death at one year was significantly lower in the ISCM group (73%) than in the IDCM group (96%) (P < 0.01). The rate of patients who did not die from terminal myocardial failure was 83% in the ISCM group and 81% in the IDCM group (P = NS). There were no significant differences between the two groups in right atrial, pulmonary artery, and pulmonary wedge pressures, transpulmonic pressure gradient, pulmonary vascular resistance, cardiac index, and ejection fraction. We conclude that candidates for cardiac transplantation with ISCM are at higher risk for sudden death during the first year on the waiting list than patients with IDCM. These results warrant consideration of aggressive arrhythmia control measures, including an automatic implantable defibrillator, to "bridge" these high risk patients to transplantation.

Actuarial Analysis↗
PubMed1995

Predisposing risk factors and natural history of acute neurologic complications of left-sided cardiac catheterization.

The reported incidence of acute neurologic complications of left heart catheterization varies from 0.03% to 0.3%. The predisposing risk factors, clinical features, and natural history have not been well characterized. We retrospectively reviewed all cases of acute neurologic complications developing during or within 36 hours of diagnostic catheterization or angioplasty to determine the incidence, clinical features, and natural history, and (using a case-control methodology) the clinical variables associated with their development. During the 37-month study, 6,465 patients underwent diagnostic left-sided cardiac catheterization and balloon angioplasty or valvuloplasty, and 27 patients developed an acute neurologic complication (0.4%). The most common symptoms were visual disturbances (26%), hemiparesis (26%), and facial droop (26%). Deficits were localizable to the anterior or posterior circulation in 22 patients: posterior in 8 (36%), and anterior in 14 (64%). Long-term follow-up was available in all patients, with 17 of 27 (63%) having complete resolution with no residuum. With use of a case-control methodology and multiple logistic regression analysis, female gender, the presence of left ventricular hypertrophy, depressed ejection fraction, and the presence of > or = 2 coronary arteries with > 50% narrowing were independent predictors of a neurologic event.

Acute Disease↗
PubMed1995

Safety and efficacy of epoprostenol in patients with severe congestive heart failure. Epoprostenol Multicenter Research Group.

Patients with advanced heart failure often remain severely symptomatic and have a high mortality rate despite currently available therapy. We studied the safety and efficacy of a new approach to the patient with refractory heart failure: continuous intravenous treatment via a portable infusion pump with epoprostenol (prostacyclin), a potent pulmonary and systemic vasodilator. A group of 33 patients with severe heart failure (64% New York Heart Association class IV and 36% class III) and profound ventricular dysfunction (median left ventricular ejection fraction, 0.15)--despite prior treatment with diuretics (100%), digitalis (91%), angiotensin-converting enzyme inhibitors (85%), and dobutamine (30%)--underwent a baseline 6-minute walk test prior to dose titration with epoprostenol during invasive hemodynamic monitoring. Subjects responding during the dose titration were randomized, on an open basis, to receive either continuous epoprostenol infusion via an indwelling central venous catheter plus conventional therapy or conventional therapy alone for 12 weeks. The initial dose-ranging study with epoprostenol produced a significant decline in systemic and pulmonary vascular resistance and a substantial increase in cardiac index despite a fall in pulmonary capillary wedge pressure. Symptoms related to vasodilation were noted within the first week after randomization to epoprostenol in 9 of 16 patients but resolved with adjustment of the infusion and concomitant medications in all but one subject. Dose adjustments during the chronic epoprostenol infusion were infrequent after the first week and complications related to the drug delivery system were rare. The change in distance walked from baseline to the last available 6-minute walk test was significantly greater in patients who received epoprostenol compared with patients assigned to standard therapy (72 +/- 40 vs -39 +/- 32 m, mean +/- SEM; p = 0.033). Our study suggests that long-term intravenous infusion of epoprostenol is feasible in patients with severe heart failure and our hemodynamic and functional results suggest clinical benefit as well. However, until recent results indicating an adverse effect of epoprostenol on survival are fully evaluated, the role of this drug in the treatment of advanced heart failure will remain uncertain.

Aged↗
PubMed1995

Neurohormonal activation and exercise function in patients with severe heart failure and patients with left ventricular assist system. A comparative study.

OBJECTIVES: The aim of this study was to evaluate the effects of implantation of a left ventricular assist system (LVAS) on the neurohormonal status, exercise capacity and symptomatic state in patients with severe congestive heart failure (CHF). BACKGROUND: Severe CHF is characterized by decreased exercise tolerance and activation of several neurohormonal systems. METHODS: Parameters of neurohormonal activation and exercise capacity in patients with LVAS (n = 7) were compared with those in groups of New York Heart Association (NYHA) class 3 (n = 121) and class 4 (n = 81) patients. Plasma levels of norepinephrine (NE), plasma renin activity (PRA), and atrial natriuretic peptide (ANP) and maximal and submaximal exercise capacities were measured monthly in LVAS patients and compared with results in CHF patients. RESULTS: Plasma NE and PRA levels were significantly lower in LVAS patients than in NYHA class 4 patients, and plasma ANP levels in LVAS patients were significantly lower than those in NYHA class 3 and 4 patients. The distance walked during submaximal exercise testing and peak oxygen consumption during maximal exercise testing were similar for the LVAS and NYHA class 3 patients. The class 4 patients were unable to exercise. CONCLUSIONS: We conclude that the LVAS lessens the neurohormonal activation and exercise intolerance characteristic of the CHF state and that the exercise capacity early after LVAS (< 4 months) is similar to that observed in NYHA class 3 patients.

Adolescent↗