Search PubMed⌕ Search

Biomedical subjects

G Sanz

Publications and source records attributed to G Sanz.

At least 37 records · Page 2Linked to original sources
PubMed2001

Aortocardiac fistulas complicating infective endocarditis.

This study sought to determine the clinical and echocardiographic features, surgical approach, and outcome of patients with infective endocarditis complicated with aortocardiac fistulas among a series of 346 consecutive cases between 1988 and 1998. Nine patients (2%) were found to have aortocardiac fistulas complicating infective endocarditis caused by highly pyogenic pathogens (4 patients had ruptured abscesses of the right sinus of Valsalva, 3 had fistulous communications from the left coronary sinus, and 1 had a fistulized abscess in the noncoronary sinus). Mortality in these patients was very high (55%), even when surgery was attempted early in the course of the disease and reconstructive procedures were implemented.

Adult↗
PubMed2001

Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro.

R115777 [(B)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)-methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone] is a potent and selective inhibitor of farnesyl protein transferase with significant antitumor effects in vivo subsequent to oral administration in mice. In vitro, using isolated human farnesyl protein transferase, R115777 competitively inhibited the farnesylation of lamin B and K-RasB peptide substrates, with IC50s of 0.86 nM and 7.9 nM, respectively. In a panel of 53 human tumor cell lines tested for growth inhibition, approximately 75% were found to be sensitive to R115777. The majority of sensitive cell lines had a wild-type ras gene. Tumor cell lines bearing H-ras or N-ras mutations were among the most sensitive of the cell lines tested, with responses observed at nanomolar concentrations of R115777. Tumor cell lines bearing mutant K-ras genes required higher concentrations for inhibition of cell growth, with 50% of the cell lines resistant to R115777 up to concentrations of 500 nM. Inhibition of H-Ras, N-Ras, and lamin B protein processing was observed at concentrations of R115777 that inhibited cell proliferation. However, inhibition of K-RasB protein-processing could not be detected. Oral administration b.i.d. of R115777 to nude mice bearing s.c. tumors at doses ranging from 6.25-100 mg/kg inhibited the growth of tumors bearing mutant H-ras, mutant K-ras, and wild-type ras genes. Histological evaluations revealed heterogeneity in tumor responses to R115777. In LoVo human colon tumors, treatment with R115777 produced a prominent antiangiogenic response. In CAPAN-2 human pancreatic tumors, an antiproilferative response predominated, whereas in C32 human melanoma, marked induction of apoptosis was observed. The heterogeneity of histological changes associated with antitumor effects suggested that R115777, and possibly farnesyl protein transferase inhibitors as a class, alter processes of transformation related to tumor-host interactions in addition to inhibiting tumor-cell proliferation.

3T3 Cells↗
PubMed2001

Recent improvements in outcome for elderly patients with de novo acute myeloblastic leukemia.

A retrospective analysis was performed on 263 consecutive patients aged over 60 with de novo acute myeloid leukemia (AML) diagnosed in a single institution between 1979 and 1998. Eighty-nine patients (33%) received only palliative treatment, while 174 patients (67%) were treated with different intensive chemotherapy regimens. The 5- and 10-year overall survival (OS) for the whole series was 7.7+/-1.2 and 4.3+/-1.6%, respectively. For patients receiving chemotherapy, OS was 10.5+/-2.5 and 7+/-2.6%, while for those patients receiving supportive treatment it was 1.1+/-1.1 and 0%, respectively (P=0.002). Within the group of patients receiving chemotherapy, the complete remission (CR) rate was 46%; treatment failure rate was 54% (36% due to treatment-related mortality and 18% due to resistant disease). Variables influencing CR rate were FAB subtype, CD7 positivity, chemotherapy regimen, creatinine level, hepatomegaly, and period of diagnosis. Median disease-free survival (DFS) duration was 8.4 months with a probability of being disease-free at 10 years of 10+/-5%. There were no significant differences in DFS according to age. According to the period of diagnosis (1979-1986 vs. 1987-1998), improvements in the CR rate (27 vs. 56%, P=0.0002), and OS (10.9 vs. 15.7 months, P=0.0007) were observed. This large single-center study of unselected de novo AML elderly patients substantiates the progressive improvement achieved in the management of elderly patients with AML, probably due to an improvement in supportive care and the administration of conventional induction chemotherapy.

Aged↗
PubMed2001

[Estradiol enhances endothelium-dependent vasodilation via a nitric oxide pathway].

BACKGROUND AND AIM: The mechanisms by which estradiol dilates arterial vessels are still unclear. Our aim was to study if estradiol enhances endothelium-dependent vasodilation in an experimental model of human arteries in vitro, and if this effect is nitric oxide mediated. METHODS: Using organ bath chambers, we studied 18 arterial rings obtained from left internal mammary arteries during coronary artery bypass grafting surgery. Response to acetylcholine was evaluated at baseline and after the addition of estradiol 10-6 mol/l to the medium, both in the presence or absence of a nitric oxide synthase inhibitor (L-NNA 10-4 mol/l). RESULTS: Estradiol significantly enhanced the relaxation of the arterial rings in response to acetylcholine (52 +/- 20% after estradiol versus 42 +/- 22% at baseline; n = 10; p = 0.02). However, endothelium-dependent vasodilation relaxation after estradiol addition was not enhanced in the presence of L-NNA (47 +/- 25% after estradiol versus 38 +/- 22% at baseline; n = 8; p = NS). CONCLUSIONS: Estradiol in vitro enhances endothelium-dependent vasodilation of internal human mammary artery rings; this effect is blunted after the addition to the medium of a nitric oxide inhibitor. Therefore, the vasodilator properties of estradiol at the studied dosage depend on the nitric oxide pathway.

Aged↗
PubMed2001

[Intracardial thrombosis and primary antiphospholipid syndrome. A familial case report].

The main clinical manifestation of antiphospholipid syndrome is repeated thrombotic events in young patients without cardiovascular risk factors. There are several clinical features but the most frequent ones are repeated fetal losses and acute cerebral ischemic events. Cardiac involvement is less frequent. We present a family case with intracardiac thrombosis and secondary cerebral embolism.

Adult↗
PubMed2001

Coronary artery revascularization in patients with sustained ventricular arrhythmias in the chronic phase of a myocardial infarction: effects on the electrophysiologic substrate and outcome.

OBJECTIVES: The objective of this study was to analyze the influence of coronary artery revascularization in patients with ventricular arrhythmias. BACKGROUND: Coronary artery revascularization is an effective treatment for myocardial ischemia; however, its effect on ventricular arrhythmias not related to an acute ischemic event has not been carefully studied. METHODS: Sixty-four patients (58 men, mean age 65 +/- 8 years old) with prior myocardial infarction, spontaneous ventricular arrhythmias not related to an acute ischemic event (55 ventricular tachycardia, 9 ventricular fibrillation) and coronary lesions requiring revascularization were studied prospectively. Electrophysiological study was performed before and after revascularization, and events during follow-up were analyzed. RESULTS: At initial study 61 patients were inducible into sustained ventricular arrhythmias. After revascularization, in 62 survivors, 52 out of 59 patients previously inducible were still inducible (group A), and 10 patients were noninducible (group B). No differences were found in clinical, hemodynamic, therapeutic and electrophysiological characteristics between both groups. During 32 +/- 26 months follow-up, 28/52 patients in group A (54%) and 4/10 patients in group B (40%) had arrhythmic events (p = 0.46). An ejection fraction <30% predicted recurrent arrhythmic events (p = 0.02), but not the presence of demonstrable ischemia before revascularization (p = 0.42), amiodarone (p = 0.69) or beta-adrenergic blocking agent therapy (p = 0.53). Total mortality was 10% in both groups. CONCLUSIONS: In patients with ventricular arrhythmias in the chronic phase of myocardial infarction, probability of recurrence is high despite coronary artery revascularization, but mortality is low if combined with appropriate antiarrhythmic therapy. Recurrences are related to the presence of a low ejection fraction but not to demonstrable ischemia before revascularization, amiodarone or beta-blocker therapy nor are they the results of electrophysiological testing after revascularization.

Aged↗
PubMed2001

Disparity for the minor histocompatibility antigen HA-1 is associated with an increased risk of acute graft-versus-host disease (GvHD) but it does not affect chronic GvHD incidence, disease-free survival or overall survival after allogeneic human leucocyte antigen-identical sibling donor transplantation.

Disparity for the minor histocompatibility antigen HA-1 between patient and donor has been associated with an increased risk of acute graft-versus-host disease (GvHD) after allogeneic human leucocyte antigen (HLA)-identical sibling donor stem cell transplantation (SCT). However, no data concerning the impact of such disparity on chronic GvHD, relapse or overall survival are available. A retrospective multicentre study was performed on 215 HLA-A2-positive patients who received an HLA-identical sibling SCT, in order to determine the differences in acute and chronic GvHD incidence on the basis of the presence or absence of the HA-1 antigen mismatch. Disease-free survival and overall survival were also analysed. We detected 34 patient-donor pairs mismatched for HA-1 antigen (15.8%). Grades II-IV acute GvHD occurred in 51.6% of the HA-1-mismatched pairs compared with 37.1% of the non-mismatched. The multivariate logistic regression model showed statistical significance (P: 0.035, OR: 2.96, 95% CI: 1.07-8.14). No differences were observed between the two groups for grades III-IV acute GvHD, chronic GvHD, disease-free survival or overall survival. These results confirmed the association between HA-1 mismatch and risk of mild acute GvHD, but HA-1 mismatch was not associated with an increased incidence of chronic GvHD and did not affect relapse or overall survival.

Acute Disease↗
PubMed2001

Development of non-ABO RBC alloantibodies in patients undergoing allogeneic HPC transplantation. Is ABO incompatibility a predisposing factor?

BACKGROUND: Data from the appearance of RBC antibodies other than ABO in patients undergoing HPC transplantation are limited. STUDY DESIGN AND METHODS: The incidence and specificity of non-ABO RBC alloantibodies are described in a series of 217 patients undergoing allogeneic HPC transplantation because of various hematologic malignancies. RESULTS: Eight patients (3.7%) developed 10 antibodies after transplant. None of these patients had previously been immunized. Seven patients had one RBC antibody and one patient had three RBC antibodies. Antibody specificity were anti-Jk(b) (2 patients), -Kell (2), -M (2), -Le(b) (1), and -D (1). Finally, two patients had a panagglutinin. The mean time between transplant and antibody detection was 23 days (range, 16-672). The source of the HPCs, the conditioning regimen administered, and the type of GVHD prophylaxis administered did not influence the rate of antibody formation. On multivariate analysis, ABO blood group incompatibility (p = 0.005) and patient's age (p = 0.02) were the only two variables significantly associated with the development of RBC alloantibodies. CONCLUSION: Patients undergoing allogeneic HPC transplantation are at risk of developing RBC-specific antibodies despite the immunosuppressive therapy administered. Antibody formation was more frequently observed in ABO-mismatched cases, which suggests a potential role of this incompatibility in facilitating antibody production.

ABO Blood-Group System↗
PubMed2001

Acute and mid-term combined hormone replacement therapy improves endothelial function in post-menopausal women with angina and angiographically normal coronary arteries.

AIMS AND BACKGROUND: Coronary endothelial dysfunction improves after acute oestradiol treatment in women with angina and normal coronary angiograms. We sought to analyse whether this effect is also seen in the peripheral circulation and whether it is sustained after a mid-term period of treatment. METHODS: We studied 20 women with angina, signs suggestive of myocardial ischaemia and normal coronary angiograms. In five of them, coronary and peripheral endothelial functions were studied at baseline. Brachial artery flow-mediated dilation was reanalysed after 24 h of transdermal oestradiol treatment. In the other 15 women, brachial artery vasoreactivity was studied at baseline and after a 6-week period of treatment with transdermal oestradiol and medroxyprogesterone (HRT) or placebo in a double-blinded crossover fashion. RESULTS: An abnormal coronary artery response to acetylcholine was observed in all women as well as impaired brachial flow-mediated dilation. Brachial flow-mediated dilation significantly increased after 24 h of oestradiol treatment (4.8+/-0.8% vs 0.06+/-0.6%, P<0.001). Peripheral flow-mediated dilation also increased after a 6-week period of HRT compared with baseline (4.1+/-3% vs 0.4+/-1%, P<0.01) and placebo treatment (4.1+/-3% vs 0.6+/-1.7%, P<0.01). CONCLUSION: Impaired endothelium-dependent vasodilation exists both at the coronary and peripheral circulation in post-menopausal women with angina and normal coronary angiograms. Flow-mediated dilation improves in these women after short and mid-term therapy with transdermal oestradiol irrespective of concomitant progesterone use.

Aged↗
PubMed2001

The use of neural networks and logistic regression analysis for predicting pathological stage in men undergoing radical prostatectomy: a population based study.

PURPOSE: Clinical under staging occurs in 40% to 60% of patients who undergo radical prostatectomy for prostate cancer. To decrease under staging several methods of predicting pathological stage preoperatively have been developed based on statistical logistic regression analysis and neural networks. To our knowledge none has been validated in our homogeneous regional patient population to date. We created logistic regression and neural network models, and implemented and adapted them into our practice. We also compared the 2 methods to determine their value and practicality in daily clinical practice. We present the results of our novel approach for predicting pathological staging of prostate adenocarcinoma. MATERIALS AND METHODS: Between 1986 and 1999, 600 white men from the Aragon region of Spain underwent surgery for prostate cancer; of whom 468 were selected for study. Predictive study variables included patient age, clinical stage, biopsy Gleason score and preoperative prostate specific antigen (PSA). The predicted result included in analysis was organ confined or nonorgan confined disease. Data were analyzed by multivariate logistic regression and a supervised neural network (multilayer perceptron and radial basis function). Results were compared by comparing the areas under the receiver operating characteristics curves. RESULTS: We generated 5 logistic regression models. The model created with clinical staging, Gleason biopsy score and PSA distributed in 5 categories (p <0.001) with an area under the receiver operating characteristics curve of 0.840 proved to be most predictive of pathological stage. Similarly of the 6 neural network models evaluated the radial basis function model, which included age, clinical stage, Gleason biopsy score and preoperative PSA distributed in 5 categories with an area under the curve of 0.882, proved the most predictive but not superior to the logistic regression model. The difference in the area under the curves in the 2 chosen models was 0.042 (p = 0.1). CONCLUSIONS: It is possible to generate useful predictive models of organ confined disease using logistic regression or neural networks with high indexes of clinical and statistical validity. However, using these variables neural networks did not prove to be better than logistic regression analysis. Therefore, better predictive variables must be identified, preferably nonlinear characteristics with respect to the probability of organ confined tumor, to generate better predictive models using neural networks.

Aged↗
PubMed2000

[Effect of cyclooxygenase inhibition on the adaptation of coronary blood flow to tachycardia].

BACKGROUND: The role of different endothelium-derived vasoactive substances in the regulation of coronary circulation during tachycardia is not well defined. In order to elucidate the contribution of prostacyclin to the adaptation of coronary blood flow to tachycardia, the effect of meclofenamate, a cyclooxygenase inhibitor on the coronary blood flow response to rapid atrial pacing was analyzed in a porcine model. METHODS: A group of seventeen pigs were instrumented for coronary blood flow, aortic pressure and atrial pacing. Heart rate was increased by 20 beats every 5 minutes. Coronary blood flow and aortic pressure were measured, and coronary resistance calculated, basally and at each pacing interval, before and after saline serum (n = 6), meclofenamate 5 mg/kg, i.v. (n = 7) or meclofenamate 35 mg/kg, i.v. (n = 4). RESULTS: Neither saline nor meclofenamate modified the normal increase of coronary blood flow provoked by rapid atrial pacing (163 +/- 28% increase before versus 172 +/- 29% after saline; 159 +/- 21% increase before versus 161 +/- 22% after meclofenamate low doses and 201 +/- 39% before vs 172 +/- 36 after meclofenamate high doses). There were no differences in the response of coronary vascular resistance to tachycardia before and after meclofenamate (44% reduction vs 40% respectively). CONCLUSION: Cyclooxygenase blockade does not modify the response of coronary circulation to rapid atrial pacing, suggesting that prostacyclin does not play a limiting role in the regulation of coronary blood flow during tachycardia in this model.

Animals↗
PubMed2000

[The efficacy of platelet IIb/IIIa receptor blockers in acute coronary syndromes].

The knowledge of the central role of platelets in the pathogenesis of acute coronary syndromes, on the one hand, and the fact that aspirin is a weak antiplatelet agent on the other, have led to an intensive investigational activity in antiplatelet drugs in the last years. Actually, the literature in the last two years is inundated with studies on the use of platelet IIb/IIIa receptor blockers in different clinical settings. Agents that block the IIb/IIIa platelet receptor have shown to be useful in improving prognosis of patients with acute coronary syndromes, especially in those undergoing percutaneous coronary revascularization procedures. However, their potential risk of bleeding and their high cost have prevented them from being applied universally and routinely. Furthermore there are still some unclear issues regarding the use of these drugs such as their correct dosage, the optimal duration of treatment and the direct comparison of the efficacy of different types of IIb/IIIa blockers available. On the other hand, oral IIb/IIIa antagonists have not improved the efficacy of aspirin to date and, moreover, they have been proven to be unsafe. Finally, it is necessary to identify those patients who will obtain the greatest benefit from the treatment in order to avoid the unnecessary risks and costs that would be derived from their universal use.

Acute Disease↗
PubMed2000

[In-hospital evolution and current prognosis of unstable angina].

INTRODUCTION AND PROGNOSIS: The prognosis of patients with unstable angina has improved in recent years resulting in a progressive reduction in hospital stay and treatment. The aim of this study was to know the current prognosis of patients with unstable angina in a non-selected population followed for up to 3 months. PATIENTS AND METHODS: 478 consecutive patients with unstable angina were studied. They were treated following a strict protocol and a management policy guided by symptoms and the results of an exercise test or a pharmacological stress test performed before hospital discharge. RESULTS: The mean age was 66 +/- 11 years with 30% being females. Thirty-five percent had a prior history of myocardial infarction, 61% presented ischemic changes on the admission ECG, and 16% had elevation of the CK-MB plasma levels. An echocardiogram was performed in 80% of the patients, a stress test in 62%, coronary angiography in 51%, and a revascularization procedure in 27% of the patients. During hospitalization, the incidence of mortality or myocardial infarction, refractory angina or ischemic complications was of 3.6%, 11% and 13%, respectively. After hospital discharge and during a 3-month follow-up, the incidence of these complications was of 3.3%, 9% and 10% (NS compared to the in-hospital period). Overall, from the time of hospital admission to the 3-month follow-up, 4.2% of the patients died, 7% died or had an infarction, 20% had refractory angina, and 26% had some ischemic complication. CONCLUSION: The in-hospital prognosis of unstable angina is currently good. However, patients discharged from hospital after stabilization, present an important number of ischemic complications during the following 3 months, similar to that presented by all patients during the acute phase.

Aged↗
PubMed2000

Prognostic value of serum cytokines in patients with congestive heart failure.

BACKGROUND: Increased levels of circulating cytokines have been previously reported in patients with congestive heart failure; however, whether they have prognostic implications is still unknown. The aim of this study was to assess the prognostic implications of elevated serum cytokines in patients with heart failure and to identify the predictors of cytokine activation. METHODS AND RESULTS: We assessed neurohormonal determinations, circulating cytokines, ejection fraction (EF) and end-diastolic and end-systolic left ventricular lengths in 87 patients (aged 57 +/- 9 years) with left ventricular dysfunction (EF 24% +/- 6%). In 48 patients, we also assessed cytokine receptors. During follow-up (mean, 14 +/- 9 months), 8 patients died and 12 had new heart failure episodes that required hospital admission, 5 of whom underwent heart transplantation. The univariate predictors of these events were serum interleukin-6 (IL-6) (p = 0.00001), New York Heart Association (NYHA) functional class (p = 0.0004), tumor necrosis factor-soluble receptor I (p = 0. 001), atrial natriuretic peptide (p = 0.002), tumor necrosis factor-soluble receptor II (p = 0.004), angiotensin II (p = 0.006), serum interleukin-1 beta (p = 0.01), and plasma renin activity (p = 0.02). Increased serum interleukin-6 (>10 pg/ml) was a significant predictor of death or new heart failure episodes according to the Kaplan-Meier survival method by log-rank test (p = 0.004). By Cox regression analysis, serum IL-6 (p = 0.0005) and the NYHA functional class (p = 0.005) were identified as independent predictors of prognosis. CONCLUSIONS: In patients with congestive heart failure, increased serum IL-6 was identified as a powerful independent predictor of the combined end point: death, new heart failure episodes, and need for heart transplantation.

Adult↗
PubMed2000

Nitric oxide synthase II mRNA expression in cardiac tissue of patients with heart failure undergoing cardiac transplantation.

OBJECTIVES: To examine whether inducible nitric oxide synthase is expressed in myocardial tissue of patients with heart failure. BACKGROUND: There is increasing evidence that alterations in nitric oxide synthesis are of pathophysiologic importance in heart failure. Nitric oxide (NO) can exert negative inotropic and cytotoxic effects on cardiomyocytes. A number of studies have shown altered nitric oxide production by the endothelial constitutive isoform of nitric oxide synthase (NOS III), but there is little information on the role of NOS II. Expression of NOS II could lead to excessive production of NO in the myocardium and affect cardiac contractility. METHODS: NOS II mRNA expression in myocardial tissue of 18 patients with idiopathic dilated cardiomyopathy (DCM), 7 patients with ischemic cardiopathy and severe ventricular dysfunction (ISCH), 4 patients with acute myocardial infarction (AMI) and 11 controls. Serum concentration of NO2-/NO3- (NOx) was also measured. RESULTS: NOS II gene expression occurred in all the patients with DCM, in 1 out of the 7 ISCH patients, in 2 out of the 4 patients with AMI and in none of the controls. Moreover, DCM patients showed a significant 6-fold increase in NOx concentration (253+/-47 nm/ml) as compared to controls (40+/-2 nm/ml) P < 0.001, a phenomenon not observed in ISCH patients (56+/-3 nm/ml). CONCLUSIONS: NOS II expression occurs in failing human cardiac myocytes and can play an specific role in the pathogenesis of DCM.

Cardiomyopathy, Dilated↗
PubMed2000

Nitric oxide inhibition intensifies the depressant effect of cocaine on the left ventricular function in anaesthetized pigs.

Myocardial ischaemia and left ventricular dysfunction have been described in cocaine users. Whether nitric oxide (NO) inhibition may potentiate the effects of cocaine on coronary circulation and ventricular function is still unknown. In order to test this hypothesis, 38 pentobarbital-anaesthetized pigs were instrumented for systolic blood pressure, coronary blood flow, left ventricular dp/dt, cardiac output, left ventricular end-diastolic and end-systolic lengths and shortening fraction. The pigs were randomized into three groups: control group: i.v. saline (n = 5); group 1: i.v. cocaine, 10 mg kg-1 over 20 min (n = 17); group 2: the same doses of cocaine 30 min after i.c. L-NAME 20 microg/kg min-1 infusion (n = 16). In order to know whether the observed effects were specific of NO inhibition, in five pigs i.c. L-arginine was simultaneously infused with L-NAME, in five pigs i.c. NTG, an endothelial-independent vasodilator, was simultaneously infused with L-NAME before cocaine was administered, and in nine additional pigs the proximal left anterior descending (LAD) flow was reduced to around 20% of the basal value by means of a mechanical occluder before cocaine was administered. Cocaine i.v did not change the coronary blood flow, while it induced a significant reduction in cardiac output, left ventricular dp/dt and shortening fraction (15 +/- 4-8 +/- 4%, P < 0.05). When cocaine was administered after L-NAME infused i.c. during 30 min, a significantly more severe reduction of the shortening fraction (12 +/- 3-4 +/- 2%, P < 0.0001) was induced; this effect was abolished by simultaneous perfusion of L-arginine i.c. NTG. The results when cocaine was administered after the 20% LAD flow reduction by mechanical occluder did not differ from those of cocaine alone. NO inhibition intensifies the cocaine-induced left ventricular dysfunction.

Anesthesia↗
PubMed2000

Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure.

AIMS: The aim of the study was to assess the incidence and clinical implications of increased plasma angiotensin II despite chronic ACE inhibitor therapy in patients with heart failure. METHODS AND RESULTS: The studied population consisted of 70 patients (mean age 59+/-9 years). Plasma renin activity and plasma concentration of aldosterone, norepinephrine, atrial natriuretic peptide, angiotensin II, tumour necrosis factor, interleukin-6 and interleukin-1B were assessed at 6 months of ACE inhibitor therapy. Mean left ventricular ejection fraction was 24+/-5% and the end-systolic and end-diastolic diameters were 59+/-9 and 71+/-8 mm, respectively. Despite chronic enalapril or captopril therapy, 35 patients (50%) had increased plasma angiotensin II (median 33 pg. ml(-1), range 17-84), while it was in the normal range in the remaining 35 patients (median 10 pg. ml(-1), range 5-15). Plasma renin activity (P=0.005), interleukin-6 (P=0.004), New York Heart Association functional class III-IV (P=0. 006), furosemide dose (P=0.01), lack of beta-blocker therapy (P=0. 04) and norepinephrine (P=0.04) were univariately associated with increased angiotensin II. Multivariate regression analysis identified the plasma renin activity (0.0004), norepinephrine (0.02) and interleukin-6 (0.03) as independent predictors of plasma angiotensin II. During follow-up (35+/-29 months), nine (12.8%) patients died and 13 had new heart failure episodes. Increased plasma angiotensin II, despite ACE inhibitor therapy, was a significant predictor of death or heart failure according to the Kaplan-Meier survival method by log rank test (P=0.002). CONCLUSION: Fifty per cent of patients with heart failure, ha increased plasma angiotension II despite chronic ACE inhibitor therapy. These patients had higher neurohormonal activation and poor prognosis.

Angiotensin II↗