Biomedical subjects

A Bojic

Publications and source records attributed to A Bojic.

9 recordsLinked to original sources

PubMed2005

Neurohormonal risk stratification for sudden death and death owing to progressive heart failure in chronic heart failure.

BACKGROUND: This study tested various neurohormones for prediction of heart failure death (death owing to progressive deterioration of ventricular function; HFD). Moreover, B-type natriuretic peptide (BNP) as a predictor of sudden death (SD; as reported previously) and the best predictor of HFD were combined for a simple risk stratification model. DESIGN: BNP, the N-terminal fragment of BNP (N-BNP), and of the atrial natriuretic peptide (N-ANP) and big endothelin levels were obtained from 452 patients with a left ventricular ejection fraction </= 35%. Outcome was documented during an observation period up to 3 years. RESULTS: Two hundred and ninety-eight patients survived without heart transplantation, 65 patients underwent heart transplantation and 89 patients died (SD 44 patients, HFD 31 patients, other causes 14 patients). The only independent predictor of SD was BNP (as reported), and the best independent predictor of HFD was N-ANP (P = 0.0001). Analyzing 293 survivors and 44 patients with SD, fewer patients with BNP < 130 pg mL(-1) (Group A, n = 110) died [1%] as compared with patients with BNP > 130 pg mL(-1) and N-ANP < 6300 fmol mL(-1) (Group B, n = 177; 18%; P = 0.0001) and patients with BNP > 130 pg mL(-1) and N-ANP > 6300 fmol mL(-1) (Group C, n = 50; 19%; P = 0.0001). Analyzing 293 survivors and 31 patients with HFD, fewer patients died in Group A (n = 109; 0%; P = 0.0001) and Group B (n = 153; 6%; P = 0.0001) as compared with patients of Group C (n = 62; 34%). CONCLUSION: Prognostic power of neurohormones depends on the mode of death. The combined determination of BNP and N-ANP identifies patients with minimal risk of death, elevated SD but low HFD risk as well as elevated SD and HFD risk.

Aged↗

PubMed2002

Prediction of outcome by neurohumoral activation, the six-minute walk test and the Minnesota Living with Heart Failure Questionnaire in an outpatient cohort with congestive heart failure.

AIMS: To compare the precursor of atrial and brain natriuretic peptide (N-ANP, N-BNP), brain natriuretic peptide (BNP), big endothelin-1, the 6-min walk test and the Minnesota Living with Heart Failure Questionnaire (LHFQ) with regard to short-term outcome in an ambulatory heart failure population. METHODS AND RESULTS: Ninety-six individuals (left ventricular ejection fraction of 26+/-10%) were included in the study. Within 1 day blood samples of N-ANP, N-BNP, BNP and big endothelin-1 were obtained, and the 6-min walk test and LHFQ were measured. The predictive power of these variables - including renin-angiotensin system antagonist therapy - in respect of 1-year event-free survival were calculated with a Cox regression analysis. All investigated variables had the power to predict outcome in a univariate analysis. Multivariate analysis revealed that N-ANP (chi-square=58 P<0.0001), BNP (chi-square=8 P<0.01), the LHFQ (chi-square=6 P<0.02) and the renin-angiotensin system antagonist (chi-square=4 P<0.05), are independent predictors. CONCLUSION: We conclude that, in an open clinical cohort of patients with large differences in the progression of the disease, N-ANP, BNP and LHFQ are the most reliable predictors of worsening heart failure in the short term. However, the dosage of the ACE inhibitor influenced short-term survival in this population.

Activities of Daily Living↗

PubMed2001

Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction.

OBJECTIVES: The study assessed the relative predictive potency of neurohumoral factors in patients with advanced left ventricular (LV) dysfunction during neurohumoral blocking therapy. BACKGROUND: The course of heart failure is characterized by progressive LV deterioration associated with an increase in cardiac (natriuretic peptides) and predominantly extracardiac (norepinephrine, big endothelin [big ET]) hormone plasma levels. METHODS: Plasma hormones were measured at baseline and months 3, 6, 12 and 24 in 91 patients with heart failure (left ventricular ejection fraction [LVEF] <25%) receiving 40 mg enalapril/day and double-blind atenolol (50 to 100 mg/day) or placebo. After the double-blind study phase, patients were followed up to four years. Stepwise multivariate regression analyses were performed with 10 variables (age, etiology, LVEF, symptom class, atenolol/placebo, norepinephrine, big ET, log aminoterminal atrial natriuretic peptide, log aminoterminal B-type natriuretic peptide [N-BNP] and log B-type natriuretic peptide [BNP]). During the study, the last values prior to patient death were used, and in survivors the last hormone level, New York Heart Association class and LVEF at month 24 were used. RESULTS: Thirty-one patients died from a cardiovascular cause during follow-up. At baseline, log BNP plasma level (x2 = 13.9, p = 0.0002), treatment allocation (x2 = 9.5, p = 0.002) and LVEF (x2 = 5.6, p = 0.017) were independently related to mortality. During the study, log BNP plasma level (x2 = 21.3, p = 0.0001) remained the strongest predictive marker, with LVEF (x2 = 11.2, p = 0.0008) log N-BNP plasma level (x2 = 8.9, p = 0.0027) and treatment allocation (x2 = 6.4, p = 0.0109) providing additional independent information. CONCLUSIONS: In patients with advanced LV dysfunction receiving high-dose angiotensin-converting enzyme inhibitors and beta-blocker therapy BNP and N-BNP plasma levels are both independently related to mortality. This observation highlights the importance of these hormones and implies that they will likely emerge as a very useful blood test for detection of the progression of heart failure, even in the face of neurohumoral blocking therapy.

Adrenergic beta-Antagonists↗

PubMed2001

Long-term effect of atenolol on ejection fraction, symptoms, and exercise variables in patients with advanced left ventricular dysfunction.

AIMS: We recently reported a beneficial clinical effect of atenolol, a beta(1) selective adrenergic antagonist, in 100 ambulatory heart failure patients with low left ventricular ejection fraction (LVEF, <or=25%) who were receiving background therapy with 40 mg/day enalapril. In this sub-study, we investigated the effects of atenolol vs placebo on LVEF, New York Heart Association (NYHA) class, workload, and peak oxygen consumption (Vo(2)). METHODS AND RESULTS: We included 43 patients (23 receiving atenolol, 20 receiving placebo) who had similar entry characteristics. We evaluated LVEF once a year and evaluated workload, pVO(2), and NYHA class before and after 6, 12, and 24 months. Repeated measures of analysis of variance were used for comparison of serial measurements. After 2 years, both atenolol (18% +/- 5% vs 36% +/- 18%, p < 0.05) and placebo (18% +/- 5% vs 23% +/- 5%, p < 0.05) increased LVEF, with a more pronounced effect of atenolol (p = 0.02), which also changed NYHA class distribution more favorably over time (p < 0.05). Workload and peak Vo(2) increased after atenolol (110 +/- 47 vs 140 +/- 48 watts, p < 0.05, and 18 +/- 5 vs 21 +/- 5 ml/kg/min, p < 0.05) but not after placebo (100 +/- 35 vs 110 +/- 38 watts, p < 0.05, between groups and 17 +/- 4 vs 19 +/- 7 ml/kg/min, not significant, between groups). CONCLUSIONS: In patients with advanced heart failure who tolerate long-term atenolol vs placebo treatment added to high-dose enalapril for 2 years without cardiac events, systolic left ventricular function is markedly improved. These patients experience greater relief of symptoms and increased exercise tolerance.

Adrenergic beta-Antagonists↗

PubMed2001

Oxidative modification of rat liver 5'-nucleotidase: the mechanisms for protection and re-activation.

The effect of oxidative stress catalysed by transition metals appears to have a critical relevance for the structure and function not only of membrane lipids but also of integral membrane proteins in a complex lipid-protein assembling, and membrane-dependent function. The integral membrane enzyme 5'-nucleotidase is susceptible to Fe((2+))-ion catalysed oxidative modification, and the extent of enzyme inhibition is in inverse relationship (r = -0.820) with lipid peroxidation (MDA) level. This work is also a comparative study about possible effectiveness of different Fe-ion chelators (deferoxamine, Na-citrate, Na-salicylate, ammonium oxalate and EDTA), antioxidants (GSH, GSH/GSH-Px system, Cu, Zn-SOD and mannitol) and metal cations (Mg(2+) and Mn(2+)) to protect or restore Fe(2+)-ion induced 5'-nucleotidase inhibition and to suppress Fe(2+)-ion enhanced lipid peroxidation. Among the examined chelators it was only deferoxamine and Na-citrate that exerted a fully protective and reactivating ability; among the antioxidants it was only GSH; among the metal cations it was only Mn(2+). The ability to protect or restore 5'-nucleotidase activity and to diminish chain-induced lipid peroxidation is explicable in terms of: metal-binding ability, capacity of taking iron away from a biological molecule, or ability of transferring the damage to itself. After a short incubation period, the iron associated with enzyme or lipid hydroperoxides could be in a labile coordinative linkage, still able to interact with possible ligands or metal cations.

5'-Nucleotidase↗

PubMed2000

Prognostic value of hemodynamic vs big endothelin measurements during long-term IV therapy in advanced heart failure patients.

STUDY OBJECTIVE: To compare hemodynamics and plasma big endothelin levels in patients awaiting heart transplantation who are receiving continuous IV therapy, and to establish their respective potency for predicting future cardiac events. DESIGN: A randomized, prospective trial of ambulatory continuous treatment with IV prostaglandin E(1) (PGE(1)) vs dobutamine. A subanalysis was conducted of all patients who completed 4 weeks of follow-up in regard to treatment effects on hemodynamics and big endothelin plasma levels. PATIENTS: Thirty-two listed heart transplant candidates who were refractory to oral treatment, 21 patients who were receiving PGE(1), and 11 patients receiving dobutamine. MEASUREMENTS AND RESULTS: Hemodynamics and plasma big endothelin levels were measured at baseline and after 4 weeks. The cardiac index increased significantly (PGE(1) group, 1.7 +/- 0.4 vs 2.5 +/- 0.6 L/min/m(2); dobutamine group, 1.8 +/- 0.3 vs 2.3 +/- 0.6 L/min/m(2); p < 0.05), whereas the systemic vascular resistance index (SVRI) decreased significantly only in the PGE(1) group (3,352 +/- 954 vs 2,178 +/- 519 dyne. s. cm(-5)/m(2); p < 0. 05). The plasma big endothelin level decreased significantly (PGE(1) group, 7.6 +/- 3.1 vs 4.7 +/- 2.6 fmol/mL; dobutamine group, 6.5 +/- 3.7 vs 5.0 +/- 2.6 fmol/mL; p < 0.01 for the time effect). Plasma big endothelin (beta = 0.393; chi(2) = 10.8; p = 0.001) and SVRI (beta = 0.003; chi(2) = 6.9; p < 0.01), both measured after 4 weeks of continuous treatment, were the only independent predictors of future outcome. CONCLUSION: Continuous treatment over 4 weeks with either PGE(1) or dobutamine in patients awaiting heart transplantation yields an improved hemodynamic state accompanied by a reduction of increased big endothelin levels. Plasma big endothelin measured after 4 weeks of continuous therapy provides prognostic information about future outcome.

Adult↗

PubMed1999

Bridging to heart transplantation: prostaglandin E1 versus prostacyclin versus dobutamine.

BACKGROUND: Prostaglandin E1 (PGE1) and prostacyclin have potent pulmonary and systemic vasodilating properties. This prospective, randomized trial compared PGE1 vs prostacyclin vs. low-dose dobutamine in patients with low-output heart failure awaiting heart transplantation (HTx) who were refractory to oral treatment. METHODS: Patients in advanced heart failure in New York Heart Association (NYHA) Class IV, with a cardiac index < or = 2.5 L/minute/m2 and a pulmonary capillary wedge pressure > or = 20 mmHg, who were listed for HTx were studied. In an inpatient study phase of 12 hours duration, therapy was aimed to increase cardiac output by 20% or more, when compared to baseline values, and to achieve a reduction of pulmonary vascular resistance below 550 dyn.s/cm-5m-2. During a long-term outpatient phase, the drugs were continuously infused to bridge these patients to HTx using three combined negative endpoints (worsening heart failure, serious adverse events, death) for analysis. RESULTS: Sixty-eight patients were enrolled, 30 patients on PGE1, 8 patients on prostacyclin, and 30 patients on dobutamine. During the inpatient study phase, maximum doses were 22 +/- 1.8 ng/kg/minute for PGE1, 7 +/- 1 ng/kg/minute for prostacyclin and 5 +/- 0.4 micrograms/kg/minute for dobutamine. During the inpatient study phase 21 patients failed, 4/30 (13%) patients on PGE1, 4/8 patients on prostacyclin (50%), and 13/30 (43%) on dobutamine (p < 0.05). Long-term continuous intravenous drug infusion in outpatients was begun in 26 patients on PGE1, in 4 patients on prostacyclin, and in 17 patients on dobutamine. Infusion therapy lasted for 88 +/- 14 days in the PGE1 group with 31 +/- 22 days in the prostacyclin group, and 30 +/- 8 days in the dobutamine group (NS). During the outpatient phase 23 patients reached a negative endpoint with 16 patients developing worsening heart failure, 5 severe adverse events and 2 deaths. Seven out of 26 (27%) failed on PGE1, 4/4 (100%) failed on prostacyclin, and 12/17 (71%) failed on dobutamine (p < 0.05, log rank test). Because prostacyclin treatment was ineffective in the first 8 patients, this trial arm was stopped prematurely. CONCLUSIONS: The findings from this prospective open pilot trial suggest that continuous PGE1 infusions at individualized dosages can be useful in certain patients as a pharmacologic bridging procedure with reduced risk to develop worsening heart failure before HTx compared to prostacyclin and dobutamine. Further comparative studies are warranted to investigate the effects of PGE1 among other bridging agents.

Alprostadil↗

PubMed1998

Relationship between kidney function, hemodynamic variables and circulating big endothelin levels in patients with severe refractory heart failure.

UNLABELLED: Fluid retention is a major characteristic of symptomatic, progressive heart failure when a main factor implicated in the pathogenesis of renal dysfunction is renal hypoperfusion. This may be a consequence of forward cardiac failure, resulting in a low cardiac output integrating poor left ventricular function secondary to myocardial impairment and increased resistance in the regional renal vasculature secondary to locally released vasoconstrictors, e.g. endothelin. So far, the role of the pulmonary circulation in perpetuating renal dysfunction in heart failure is unclear. METHODS: We investigated the relationship of hemodynamic variables obtained during right heart catheterization and plasma big endothelin levels to renal function variables in 18 male patients aged 52 +/- 3 years, with heart failure in the NYHA function class III-IV, based on idiopathic causes in 8 and ischemic causes in 10 patients. Renal plasma flow (RPF) was established by paraaminohippurate (PAH) clearance and the glomerular filtration rate (GFR) was measured by iothalamate clearance. RESULTS: Plasma big endothelin (ET) levels were increased above the upper normal range (1.8 fmol/ml) in 16 out of 18 patients, averaging 5.0 +/- 0.8 fmol/ml (1.7-11.9 fmol/ml). Positive correlations to big ET plasma levels were detected with mean pulmonary pressure (r = 0.73, p < 0.001) pulmonary capillary wedge pressure (r = 0.56, p < 0.05) and pulmonary vascular resistance index (r = 0.69, p < 0.01). Glomerular filtration rate (70 +/- 7 ml/min) and renal plasma flow (358 +/- 36 ml/min) were considerably reduced and exhibited a tendency to correlate inversely with big ET levels (r = -0.46, p = 0.056 and r = -0.44, p = 0.069, respectively). Contrary to expectations, RPF did not correlate significantly with cardiac index, systemic vascular resistance index or arterial blood pressure. In contrast, significant correlations were detected of RPF with pulmonary capillary wedge pressure (r = -0.69, p < 0.01), mean pulmonary artery pressure (r = -0.65, p < 0.01), right atrial pressure (r = -0.47, p < 0.05) and right ventricular ejection fraction (r = 0.49, p < 0.05). CONCLUSION: The findings suggest a role for endothelin in renal vasoconstriction and accord well with the concept that in severe heart failure renal hypoperfusion--by volume retention--as well as increased endothelin synthesis--by pulmonary vasoconstriction--play a part in the increased pulmonary filling pressures.

Endothelin-1↗

PubMed1997

Prostaglandin E1 infusion compared with prostacyclin infusion in patients with refractory heart failure: effects on hemodynamics and neurohumoral variables.

Prostaglandin E1 or prostacyclin were randomly infused in 18 patients with severe chronic heart failure who did not respond to oral treatment. Maximally tolerated dosages of both agents increased cardiac index; however, only prostacyclin decreased mean arterial pressure and increased plasma norepinephrine significantly. Twelve hours after 50% peak dose reduction, atrial natriuretic peptide levels, right atrial pressure, mean pulmonary artery pressure, and mean arterial pressure continued to decrease with prostaglandin E1, whereas the increase in cardiac index was sustained; in contrast, at 50% prostacyclin dose reduction, cardiac index decreased toward baseline, suggesting that, with reduced dosages for chronic infusions, desired hemodynamic changes seem to be sustained with prostaglandin E1 only.

Alprostadil↗