Multicenter Cooperative Study Research Articles

Outcome of Patients with West Syndrome: A Multicenter Cooperative Study.

Outcome of Patients with West Syndrome: A Multicenter Cooperative Study.

Relation of a postmortem renal index of hypertension to atherosclerosis in youth. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group.

In a cooperative multicenter study, Pathobiological Determinants of Atherosclerosis in Youth, of 1164 young men 15 through 34 years of age who died of external causes and were autopsied in forensic laboratories, we measured atherosclerosis of the aorta and the right coronary artery. Using the ratio of intimal thickness to outer diameter of the small renal arteries to predict mean arterial pressure (MAP) during life, we classified the cases as either normotensive (MAP < 110 mm Hg) or hypertensive (MAP > or = 110 mm Hg). By this criterion, the prevalence of hypertension in blacks was 16%; in whites, 12%. Hypertension was associated directly with blood level of glycohemoglobin (an indicator of blood glucose concentration) and with body mass index (BMI) but inversely with thickness of the panniculus adiposus. Among hypertensive compared with normotensive cases, the extent of raised lesions (mainly fibrous plaques) was greater in the aortas of 30- to 34-year-old men and in the right coronary arteries of 25- to 34-year-old men. The prevalence of raised lesions involving 5% or more of the intimal surface was twofold greater in the aortas and right coronary arteries of hypertensive men throughout the 15-to-34-year age span of the study cases. The association of hypertension with raised lesions was not accounted for by adjusting for glycohemoglobin level, BMI, or thickness of the panniculus adiposus. Hypertension is associated with accelerated atherosclerosis in youth.

Multinational clinical and pathologic registry of retinoblastoma. Retinoblastoma International Collaborative Study report 2.

The Retinoblastoma International Collaborative Study is a multinational prospective clinical and pathologic registry designed to collect baseline clinical information, data on methods of treatment, and information on the subsequent clinical course of children with retinoblastoma. 206 children with newly diagnosed retinoblastoma were evaluated in the participating clinical centers between 1 July 1987 and 31 December 1989. All of the children underwent comprehensive baseline assessment of multiple clinical variables prospectively according to a standard protocol. The recorded values were tabulated and analyzed. The 206 children with retinoblastoma included 99 boys (48.1%) and 107 girls (51.9%). The mean age at diagnosis was 21.2 mo in the total study group. One hundred twenty-seven of the 206 children (61.7%) had unilateral disease, while 79 (38.3%) had bilateral involvement. The mean age at diagnosis in the bilateral cases (14.6 mo) was substantially less than in the unilateral ones (23.5 mo). The great majority of patients (approximately 75%) had advanced disease (group V in both Reese-Ellsworth and Essen prognosis classifications) in the affected eye (unilateral cases) or the more severely affected eye (bilateral cases). This study shows that there is a dedicated group of international ophthalmologists and other physicians who are willing to participate in multicenter cooperative clinical studies of retinoblastoma and that a relatively large group of children with this ocular malignancy can be enrolled within this framework during a reasonably short time for the purposes of future studies.

Relation of glycohemoglobin and adiposity to atherosclerosis in youth. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group.

In a cooperative multicenter study (Pathobiological Determinants of Atherosclerosis in Youth, PDAY) of 1532 young persons 15 through 34 years of age who died of external causes and were autopsied in medical examiners' laboratories, we quantified atherosclerosis of the aorta and the right coronary artery. We analyzed postmortem blood cells for glycohemoglobin and postmortem serum for lipoprotein cholesterol and thiocyanate (as an indicator for smoking). We measured the thickness of the panniculus adiposus and the body mass index (weight per height squared) as indicators of adiposity. Glycohemoglobin levels exceeding 8% were associated with substantially more extensive fatty streaks and raised lesions in the right coronary artery in persons more than 25 years of age and with more extensive raised lesions in the aorta in persons more than 30 years of age. Both thickness of the panniculus adiposus and body mass index were associated with more extensive fatty streaks and raised lesions in the right coronary artery. The associations of atherosclerotic lesions with glycohemoglobin and adiposity were not explained by a less favorable lipoprotein profile or smoking. The results show that atherosclerosis in young adults is associated with the prediabetic or early diabetic state, as indicated by elevated glycohemoglobin levels, and with obesity.

Familial combined hyperlipidemia in children: Clinical expression, metabolic defects, and management

The first evidence that elevation of plasma levels of cholesterol is a risk factor for the development of atherosclerosis in children came from the Bogalusa Heart Study in 1986, which reported an association between aortic fatty streaks in 3- to 26-year-old subjects and increased plasma levels of low-density lipoprotein cholesterol (LDL-C). The most compelling evidence of a cause-and-effect relationship has come from the multicenter cooperative study called the Pathobiological Determinants of Atherosclerosis in Youth. When the investigators examined the abdominal aorta and the right coronary artery of adolescents and young adults who had died of trauma, they found a significant relationship between the sum of the very low density lipoprotein (VLDL) plus LDL-C level and both fatty streaks and raised atherosclerotic lesions. They also found an inverse relationship between those lesions and increased high-density lipoprotein cholesterol (HDL-C) levels. In addition, their studies showed that smoking (as assessed by the serum thiocyanate level) promotes atherogenesis in children as young as age 15 years. Thus many pediatricians have now accepted the importance of identifying children with significant hypercholesterolemia so that appropriate dietary and life-style modifications can be recommended. This is especially important because there is often a major genetic component to the hyperlipidemia seen in children.

Do Intensive Hospital Antibiotic Control Programs Prevent the Spread of Antibiotic Resistance?

The relation between antibiotic control and resistance was assessed by review of selected journal articles from 1988 through 1994. Most studies of control or monitoring do not report susceptibility pattern as an outcome measure. Several aspects of bias and confounding prevent more than analysis of temporal association between antibiotic use restriction and resistance pattern. However, in a few institutions there has been an increase in susceptibility to antimicrobials following intensive control or monitoring. Moreover, in a few hospitals, intensive antibiotic control for selected drug-organism pairs was associated with a high prevalence of susceptibility, and the proportion susceptible fell abruptly when control or monitoring was relaxed or removed. These examples, coupled with the recent emergence of new resistant organisms, justify attempts to determine the value of intensive antibiotic control as a preventive practice. Because these studies were performed in single institutions, their power to distinguish associations was poor. Cooperative multicenter studies are needed in which selection and classification biases are addressed prospectively, and in which confounding factors are controlled.

Long-term outcome of myocardial revascularization in patients with Kawasaki coronary artery disease: A multicenter cooperative study

The long-term outcome of myocardial revascularization by coronary artery bypass grafting in patients with severe coronary obstruction caused by Kawasaki disease is largely unknown. A multicenter follow-up study was performed in 1991. A total of 168 patients with Kawasaki disease (127 male [75.6%] and 41 female patients [24.4%]) who had undergone coronary bypass grafting were enrolled. Obstructive coronary artery disease affected the left main trunk in 11.8%, the right coronary artery in 77.6%, the left anterior descending in 87.6%, and the left circumflex in 25.9%. Old myocardial infarction was noted in 46.0% of the patients. Fifty-four patients (32%, 12.4 ± 9.8 years) underwent bypass grafting with saphenous vein grafts alone. The remaining 114 patients (68%, 9.8 ± 7.1 years) received at least one internal thoracic artery graft to the left anterior descending coronary artery. Gastroepiploic artery grafts were used in 12 patients. There were no significant differences between the saphenous vein and internal thoracic artery groups in the mean age at operation (12.4 versus 9.8 years), female ratio (22% versus 25%), the number of patients over 20 years of age (9.3% versus 9.6%), previous history of infarction (51.9% versus 41.2%), impaired left ventricular function (ejection fraction < 0.5) (13.0 versus 11.4%), left main trunk disease (11.1% versus 10.5%), the number of vessels involved (2.2 ± 0.8 versus 2.0 ± 0.6 per patient), or the mean number of grafts used (1.7 ± 0.7 versus 1.7 ± 0.7 per patient). The operative death rate was also the same in the two groups (1.9% versus 0%), but the late cardiac death rate was significantly higher in the saphenous vein graft group (13.0%) than in the internal thoracic artery group (0.9%) (p < 0.003). Actuarial analysis showed a significantly higher survival in the internal thoracic artery group (98.7% ± 1.2% versus 81.6% ± 7.0%, p < 0.05) at 90 months after the operation. Late death was strongly related to the absence of an internal thoracic artery graft (p < 0.003) and to the age at the time of operation (p < 0.05). The actuarial patency rate was significantly higher for arterial grafts (77.1% ± 1.1%, n = 151) than for vein grafts (46.2% ± 6.3%, n = 126) 85 months after the operation (p < 0.003). Arterial grafts were used for the non–left anterior descending coronary arteries in only 41 of 155 grafts (26.5%); in contrast, vein grafts were used in 85 of 133 grafts (63.9%) (p < 0.005 to 0.001). However, the actuarial patency rate was significantly higher for arterial grafts (81.4% ± 8.2%, n = 39) than for vein grafts (37.5% ± 8.0%, n = 81) to the left circumflex and right coronary arteries. The difference in patency was even greater in children younger than 7 years old at operation (p < 0.005). In conclusion, internal thoracic artery grafts showed significantly better long-term patency than saphenous vein grafts in patients with Kawasaki disease, and the use of internal thoracic artery grafts reduced the likelihood of late cardiac death. (J THORAC CARDIOVASC SURG 1994;107:663-74)

Adverse effects of aspirin in the treatment of asymptomatic carotid artery stenosis

We prospectively analyzed adverse effects of aspirin in a multicentered cooperative study undertaken to determine the role of endarterectomy in the treatment of asymptomatic carotid artery stenosis. Persons with active peptic ulcer disease or known intolerance to aspirin were excluded from the study. Patients initially received 650 mg aspirin twice daily. After a 54-month recruitment period, 444 patients in 11 centers were followed up for as many as 8 years (mean 47.9 ± 27.9 months). Patients intolerant to 650 mg aspirin twice daily could be switched to enteric-coated aspirin or “low-dose” aspirin (80 to 325 mg daily). At the conclusion of the study, we performed a cross-sectional analysis of aspirin usage and complications. Overall, there were 757 episodes reported wherein adjustments in study medications were made, including cessation and change in formulation or dosage. At the conclusion of the study, at the time of death, or at occurrence of a neurologic end point, 16% of patients were off medication entirely, 51% had been converted to enteric-coated aspirin, and only 33% were taking regular aspirin with 27% of those having been placed on a reduced dosage. Adverse reactions were ascertained from 4954 patient visit records. In all there were a total of 837 adverse reactions reported, or one in every 5.9 visits. The most frequently reported reaction was heartburn or stomach pain for which 372 episodes were reported in 184 (42%) patients. Nausea or vomiting occurred on 79 occasions in 58 patients, and bloody stools were reported 52 times in 41 patients. We conclude that high-dose aspirin therapy for asymptomatic carotid artery stenosis is poorly tolerated and that adverse reactions even to low-dose enteric-coated aspirin are common even in patients screened for aspirin intolerance.

Effects of danazol at the immunologic level in patients with adenomyosis, with special reference to autoantibodies: A multi-center cooperative study

We attempted to evaluate the effects of danazol on autoantibodies, in particular, to phospholipids, and on the immune system in patients with adenomyosis. Forty-two patients with adenomyosis who had high titers of autoantibodies were randomly chosen, and they received 400 mg/day of danazol for 4 months (n = 22) or underwent hysterectomy (n = 20). Among the six autoantibodies we investigated, the incidence of antiphosphatidylinositol immunoglobulin G was the highest (42.9%), followed by antiphosphatidylglycerol immunoglobulin G (38.1%). The autoantibody titers decreased with time and were comparable to the control values 16 weeks after treatment in both groups. Total serum levels of immunoglobulin G and M were high before treatment, but immunoglobulin M levels decreased significantly in week 8 during treatment with danazol, whereas C4 levels increased and C3 levels decreased with danazol. Danazol has an inhibitory effect on the autoimmunologic response associated with adenomyosis.

Initiales Ansprechen auf die Therapie als wichtigster prognostischer Faktor bei der akuten lymphoblastischen Leukämie im Kindesalter

Prognostic factors to estimate the risk of relapse are crucial for risk-adapted therapy in acute lymphoblastic leukemia (ALL). In a cooperative multicenter treatment study for childhood ALL (COALL-03-85) the prognostic relevance of the bone marrow (BM) blast count at day 28 was evaluated. Treatment was adjusted to the initial risk factors; patients with high risk (white blood count (WBC) greater than or equal to 25/nl, age greater than or equal to 10 years, T- or NULL-ALL) received intensified therapy consisting of rotation of 6 non cross-resistant drug combinations with 12 different agents. After 4 weeks 289/305 (94.8%) children were in complete remission (CR); one child died of infection, and 15 (14 high-risk patients) still had more than 5% blasts in the BM. Twelve of these 15 patients were in remission after 2 to 4 weeks additional treatment. Poor responders often had a high initial WBC, age above 10 years of T- or NULL-ALL. In spite of continuation of intensive therapy all children with more than 10% blasts in the BM on day 28 suffered an early relapse except 2 who were transplanted in first remission. Event-free survival for the poor responders is 0.15 compared to 0.71 (p = 0.0001) for the good responders (median observation time 48 months). In multivariate analysis remission status on day 28 was the only significant prognostic factor in high-risk patients above one year of age; traditional risk factors as initial WBC, age above 10 years, hepatosplenomegaly, and immunological subtype were of no prognostic significance in this study. (ABSTRACT TRUNCATED AT 250 WORDS)

Clinical application of FR-860 to hemodialysis: Multicenter cooperative study in Japan.

A multicenter cooperative study was designed to evaluate the efficacy and safety of FR-860 as an anticoagulant in hemodialysis. Sixty-five stable maintenance hemodialysis patients were enrolled into the study from fourteen institutions in Japan. 4 cases were excluded from the efficacy analysis because of protocol deviation (a violation of the concomitant drugs). The period of the study was fixed at two weeks. Dosage requirements were 15.0-20.0 anti-Xa units/kg as a bolus and 7.5-10.0 anti-Xa units/kg/hr for continuous hourly administration. Total dosage of FR-860 (F) was 2, 505±127 anti-Xa units compared to that of a conventional heparin (CH) dose of 6, 124 ±190 units. No difference in the residual blood in the extracorporeal circuit was observed between the F and CH groups. The hemostatic time at the puncture site after the completion of dialysis was significantly shortened in the F group (7.9±0.7 min) in comparison with the CH group (11.4±1.1 min; p<0.01). The plasma anti-Xa levels were 0.24±0.03 and 0.36±0.04 units/ml 1 hr after the initiation and at the completion of dialysis, respectively. ACT, measured by the Hemochron method, was not prolonged during dialysis. APTT varied from 34.3±1.2 before dialysis to 41.0±1.9 (p<0.01) 1 hr after the start of dialysis and 39.9±1.6 sec (p<0.01) at the end of dialysis. Plasma AT III activity increased from 96.8±2.5 before dialysis to 113.0±3.2% (p<0.01) at the end of dialysis. No significant changes were observed in either ADP-or collagen-induced platelet aggregation during dialysis. Dialysis efficiency in the F group was similar to that in the CH group. Slight itching developed in one of the 65 cases. No abnormal laboratory data were observed during the study.In conclusion, FR-860 was demonstrated to be a convenient alternative to conventional heparin as an anticoagulant in hemodialysis treatment.

Is the progress in cancer treatment results adequate or are we confronted with a more or less worldwide stagnation?

Recent results of ongoing multicenter cooperative studies on patients treated with multimodality therapies of small-cell bronchial carcinoma are used as an example to demonstrate the definite progress of treatment results. This was possible only after a gradual development of aggressive intermittent long-term chemotherapy by different combinations of cytostatic drugs combined with various other kinds of therapy during the last three decades. The evaluation of results was only feasible after a step-by-step development of the international uniform pTNM staging system. This example is also useful to demonstrate the possible increased impact of these results, in spite of a very selected small number of patients, on the overall statistical survival with the assumption that the evaluable methods will be applied by a greater number of cooperative groups and in general practice. The life-table curves of pTNM-I-staged patients show a plateau of over 60% for the 4-year-survival rate, demonstrating much better results by comparison with non-surgical combined modality (radio- and chemotherapy) treatments. They are also much better than generally expected, which in turn demonstrates the great discrepancy in importance between the results from a scientific theoretical and a practical point of view. Only since the TNM staging system was developed has it been possible to distinguish the stages based on clinical diagnostic procedures, with a lower grade of certainty, from those with the precise pTNM staging based on the pathohistological findings.

Clinical effect of low molecular weight heparin (Fragmin) on DIC : A multicenter cooperative study in Japan

A multicenter cooperative study was carried out involving 47 nationwide institutes in Japan to assess the efficacy and safety of low molecular weight heparin (Fragmin) on DIC. Fifty-six DIC cases were challenged by Fragmin injection principally for 5 days with the doses of 75 U/kg/day in the I group (n=27) and 150 U/kg/day in the II group (n=29). Scoring points were defined based on the severity of bleeding symptoms, organ failures and abnormal coagulation-fibrinolytic examinations, and therapeutic effect of Fragmin was evaluated objectively according to the improvement degrees of these scores. Six cases (10.7%) died of the underlying diseases or complications other than DIC and hemorrhagic side effects occurred in 3.7 and 10.3% cases of the I and II groups, respectively. However, in bleeding symptoms, 45.5 and 31.6% cases of the I and II groups improved excellently or moderately. In organ failures and coagulation-fibrinolytic examinations, remarkable improvement was observed in 31.6 and 66.7% cases of the I group, while they remained 14.3 and 51.7% in the II group, respectively. The overall utility of Fragmin was 66.7% in the I group and 58.6% in the II group. These results demonstrate that Fragmin is effective on DIC with a dose of 75 U/kg/day.

An electrophysiological approach to pathogenesis in entrapment neuropathy

Ictal piloerection is an infrequent seizure semiology that is commonly overlooked as an ictal epileptic manifestation. Piloerection is considered to be principally caused by temporal lobe activity although frontal and hypothalamic seizure origins have been reported. The described etiology has shown a wide variety of structural causes such as mesial temporal sclerosis, tumors, posttraumatic, cavernomas and cryptogenic epilepsies.We retrospectively reviewed the incidence of ictal piloerection in the clinical records of patients who underwent video-EEG monitoring (VEEGM) between 2007 and 2013 in a multicenter cooperative study. All patients presented refractory epilepsies and were evaluated with a protocol that included brain MRI, neuropsychology and VEEGM.A total of 766 patients were evaluated in four tertiary centers in Spain. Five patients showed piloerection as principal seizure semiology (prevalence 0.65%). The mean age at seizure onset was 39.6 years and the average epilepsy duration was 5.2 years (range 2–14) before diagnosis. Four patients were additionally examined with FDG-PET and/or SPECT-SISCOM. All presented temporal lobe epilepsy (TLE), three right-sided and two left-sided. A typical unilateral hippocampal sclerosis was described in 3 cases. The etiology detected in all cases was limbic encephalitis. Three had LGI1, one anti-Hu, and another Ma2 antibodies.Our series describes a so far not well-recognized autoimmune association of pilomotor seizures to limbic encephalitis. This etiology should be ruled out through a comprehensive diagnostic work-up even in cases of long-lasting TLE with typical hippocampal atrophy on MRI.

The Natural History of Factor VIII:C Inhibitors in Patients With Hemophilia A: A National Cooperative Study. II. Observations on the Initial Development of Factor VIII:C Inhibitors

AbstractDuring a 4-year multicenter cooperative study of acquired factor VIII inhibitors in persons with hemophilia A, new inhibitors were detected in 31 of 1,306 patients who entered the study without an inhibitor or the history of an inhibitor. The incidence of new inhibitors was eight per 1,000 patient-years of observation. The factor VIII:C level before inhibitor development was ≤0.03 U/mL in 29 individuals and 0.06 U/mL and 0.07 U/mL in the remaining two. Factor VIII:Ag levels were measured in 27 individuals and were < 0.03 U/mL in 23 and 0.05 to 0.11 U/mL in the remaining four. Maximum inhibitor levels ranged from 1.0 to 9,044 Bethesda U/mL. In seven patients under the age of 20, relatively weak inhibitors (none higher than 4.3 Bethesda U/mL) were detected on only a single occasion despite continued factor VIII challenge. In the other 24 patients with inhibitors detected on multiple occasions, 50% had appeared by age 20 and 71 % by age 30. Seventeen of the 31 inhibitors, including 12 of 15 with maximum values >10 Bethesda U/mL, developed within 75 exposure days to factor VIII.1988 by Grune & Stratton, Inc.0006-4971/88/7102-0005$3.00/0

The natural history of factor VIII:C inhibitors in patients with hemophilia A: a national cooperative study. II. Observations on the initial development of factor VIII:C inhibitors

During a 4-year multicenter cooperative study of acquired factor VIII inhibitors in persons with hemophilia A, new inhibitors were detected in 31 of 1,306 patients who entered the study without an inhibitor or the history of an inhibitor. The incidence of new inhibitors was eight per 1,000 patient-years of observation. The factor VIII:C level before inhibitor development was less than or equal to 0.03 U/mL in 29 individuals and 0.06 U/mL and 0.07 U/mL in the remaining two. Factor VIII:Ag levels were measured in 27 individuals and were less than 0.03 U/mL in 23 and 0.05 to 0.11 U/mL in the remaining four. Maximum inhibitor levels ranged from 1.0 to 9,044 Bethesda U/mL. In seven patients under the age of 20, relatively weak inhibitors (none higher than 4.3 Bethesda U/mL) were detected on only a single occasion despite continued factor VIII challenge. In the other 24 patients with inhibitors detected on multiple occasions, 50% had appeared by age 20 and 71% by age 30. Seventeen of the 31 inhibitors, including 12 of 15 with maximum values greater than 10 Bethesda U/mL, developed within 75 exposure days to factor VIII.

The Multicenter Co-Operative Study on Clinical Evaluation of Platelet Concentrates Stored for 72 Hours

The Multicenter Co-Operative Study on Clinical Evaluation of Platelet Concentrates Stored for 72 Hours

A cooperative multicenter study of captopril in congestive heart failure: hemodynamic effects and long-term response

A cooperative multicenter study of captopril in congestive heart failure: hemodynamic effects and long-term response

VA Cooperative Study on Alcoholic Hepatitis. IV. The significance of clinically mild alcoholic hepatitis--describing the population with minimal hyperbilirubinemia.

As part of a large multicenter Veterans Administration Cooperative Study of Alcoholic Hepatitis, 89 patients with clinically mild biopsy-proven disease were followed for at least 30 months. Although clinical and laboratory abnormalities were minimal, cirrhosis was present in 38%, and mortality was 22% at 30 months. Clinical features suggesting more advanced disease (i.e., ascites and encephalopathy) and laboratory parameters for the diagnosis of alcoholic hepatitis and/or cirrhosis were imprecise and frequently misleading. The histologic diagnosis of cirrhosis correlated best with changes in immunoglobulin A, prothrombin time, and SGOT/SGPT. However, by using logistic discriminant analysis on 26 commonly available laboratory tests to diagnose cirrhosis, only a 72% sensitivity and 88% specificity could be obtained. Mortality in the patients with cirrhosis (10/34) was significantly higher at 1 and 2 yr compared with patients without cirrhosis (10/55, p less than 0.01). The high mortality in noncirrhotics may have resulted from progression to cirrhosis subsequent to the initial evaluation. Thus, liver biopsy in this population with minimal disease seems necessary to establish both an accurate diagnosis and the reversibility of the disease.

A cooperative multicenter study of captopril in congestive heart failure: Hemodynamic effects and long-term response

The acute hemodynamic effects, long-term clinical efficacy, and safety of the oral angiotensin-converting enzyme inhibitor, captopril, were assessed in a multicenter cooperative study of 124 patients with heart failure resistant to digitalis and diuretics. The cardiac status of most patients was deteriorating prior to the study. Favorable acute hemodynamic effects consistently occurred with captopril. Maximal mean percentage increases in cardiac index, stroke index, and stroke work index were, respectively, 35%, 44%, and 34%. Systemic and pulmonary vascular resistances were each decreased by approximately 40%, as were the filling pressures of the right and left heart. Infusion of nitroprusside in some of the same patients to an end point of a pulmonary capillary wedge pressure of 12 to 18 mm Hg (equivalent to that after captopril) revealed no significant difference in the effect of either drug on the other hemodynamic parameters. Recatheterization after 8 weeks of captopril therapy revealed sustained hemodynamic changes. Significant and sustained improvements in clinical status were observed in most patients as measured by changes in New York Heart Association (NYHA) functional classification and exercise tolerance times. Seventy-nine percent of patients for whom there were adequate NYHA class data improved. Twenty percent remained unchanged and 1% deteriorated. Those patients who had both pretreatment and post-treatment exercise stress testing exhibited a highly significant mean increase in exercise tolerance times of 34% (317 ± 32 seconds pretreatment to 425 ± 34 seconds, final measurement). There was no evidence of tachyphylaxis over an 18-month period. Survival rates at 6, 12, 18, and 24 months were 79%, 63%, and 58%, respectively. Cardiothoracic ratios showed a significant decrease from a mean of 0.60 to 0.57 at 2 months. All patients with hypokalemia at entry and all but one with hyponatremia normalized rapidly on captopril therapy. Captopril was generally well tolerated, although hypotension caused withdrawal of the drug in 6% of patients. The results suggest a useful role for captopril in heart failure.