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Biomedical subjects

R Pacher

Publications and source records attributed to R Pacher.

At least 19 recordsLinked to original sources
PubMed2006

Copeptin, a fragment of the vasopressin precursor, as a novel predictor of outcome in heart failure.

BACKGROUND: Natriuretic peptides, particularly brain natriuretic peptide (BNP), are elevated in heart failure and therefore considered to be excellent predictors of outcome. Vasopressin is also known to be related to the severity of heart disease. Copeptin--an inactive fragment of the vasopressin precursor--has not been previously investigated in the context of heart failure. MATERIALS AND METHODS: We prospectively studied 268 patients with advanced heart failure after they had been discharged from the hospital. We investigated the ability of BNP and copeptin to predict death, re-hospitalization due to heart failure, and a combination of the two endpoints. RESULTS: Over a mean follow-up period of 15.8 months (up to 24 months), 83 patients died, 122 patients experienced worsening of heart failure, and 145 patients achieved the combined endpoint. Univariate predictors of death were copeptin, BNP, age and impaired kidney function. In multivariate analysis, copeptin (chi(2) = 16, P < 0.0001) and age (chi(2) = 4, P < 0.05) were independent predictors. Univariate predictors of re-hospitalization due to heart failure were copeptin, BNP, age and impaired kidney function. Furthermore, in multivariate analysis BNP (chi(2) = 18, P < 0.0001), age (chi(2) = 11.8, P < 0.001) and copeptin (chi(2) = 4.2, P < 0.05) were found to be independent predictors. CONCLUSION: Our study is the first to show that copeptin is an excellent predictor of outcome in advanced heart failure patients. Its value is superior to that of BNP in predicting death and a combined endpoint, although BNP is still suitable for predicting chronic heart failure (CHF) re-hospitalization. Our data imply that vasopressin antagonism might be a new target to improve outcome in this population.

Aged↗
PubMed2005

Non-invasive beat-to-beat cardiac output monitoring by an improved method of transthoracic bioimpedance measurement.

The report describes a method of impedance cardiography using an improved estimate of thoracic volume. The formulas and their implementation in hardware and software are explained and new shortband electrodes are described which generate a good homogeneous thoracic field. Examples of stroke volume and cardiac output curves underline the capabilities of the monitoring system "Task Force Monitor". In several experiments, results are compared to thermodilution as well as to BioZ measurements: the new method excels in comparison with thermodilution and is comparable to the BioZ device. Compared to traditional electrodes, the new shortband electrodes are shown to provide better reproducibility.

Cardiac Output↗
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↗
PubMed2004

Natriuretic peptides and the prevalence of congestive heart failure in patients with pacemakers.

AIM: The aim of the study was to investigate the diagnostic potential of natriuretic cardiac peptide measurement in the context of left ventricular dysfunction and comorbidities in a pacemaker population. MATERIAL AND METHODS: Ninety-five consecutive patients with pacemakers were included in the study. All patients underwent echocardiography and were asked to complete the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Brain natriuretic peptide (BNP), N-terminal proatrial natriuretic peptide (N-ANP) and atrial natriuretic peptide levels in plasma were measured. RESULTS: Twenty-six percent of patients had reduced systolic left ventricular function; only 16 patients had a history of congestive heart failure. BNP was abnormally elevated in 64%, N-BNP in 72% and N-ANP in 96% of patients. Both BNP (r = 0.30; P < 0.01) and N-ANP (r = 0.39; P < 0.0005) correlated with MLHFQ. The strongest correlation was found between N-ANP and the ejection fraction (r = 0.6; P < 0.0001). Patients were stratified in a high-risk group and a low risk-group according to their N-ANP (N-ANP > 5000 fmol L(-1); n = 63 and N-ANP < 5000 fmol L(-1), n = 32) and BNP levels (BNP > 400 pg mL(-1); n = 17 and BNP < 400 pg mL(-1), n = 78). N-ANP was correlated with hypertension (P < 0.003) and atrial fibrillation (P < 0.03), and BNP with mitral insufficiency (P < 0.002). CONCLUSIONS: Cardiac natriuretic peptides are markedly elevated in the majority of patients with pacemakers. The prognostic significance of BNP and N-ANP in left ventricular dysfunction warrants close follow-up schedules.

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

Survival benefit of the implantable cardioverter-defibrillator in patients on the waiting list for cardiac transplantation.

BACKGROUND: The implantable cardioverter-defibrillator (ICD) effectively reduces sudden cardiac death in patients with severe LV dysfunction. Effect of ICD therapy on total mortality in patients on the waiting list for cardiac transplantation is still uncertain. METHODS AND RESULTS: We retrospectively analyzed 854 unselected consecutive patients (ICD therapy, n=102; 11.9%) on the waiting list for cardiac transplantation between January 1992 and March 2000. Actuarial 12-month total mortality rate on the waiting list was 24.2%; sudden cardiac death was the predominant mode of death (66.7% of total deaths). Kaplan-Meier analysis revealed improved survival for ICD (total mortality, 13.2%) compared with non-ICD (total mortality, 25.8%) patients (log rank, P=0.03). No event of sudden death occurred in ICD patients, whereas in non-ICD patients, 12-month sudden death rate was 20.1% (P=0.0001). Nonsudden death rates did not differ between ICD and non-ICD patients (P=0.16). A Cox proportional hazards model demonstrated that absence of an ICD was a powerful independent predictor of total mortality (P=0.02; relative risk, 2.22; 95% confidence interval, 1.16 to 4.17) and sudden cardiac death (P<0.0001; infinite relative risk) on the waiting list. CONCLUSIONS: ICD therapy, because it prevents sudden cardiac death, significantly improves survival on the waiting list for cardiac transplantation. The present study supports the use of ICDs as a bridge to transplantation in patients who are at risk of sudden cardiac death. Prospective randomized trials are needed to evaluate the potential benefit of prophylactic ICD therapy as a bridge to transplantation in all patients on cardiac transplant waiting lists.

Comorbidity↗
PubMed2001

Effects of endothelin a receptor blockade on endothelial function in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is associated with impaired endothelium-dependent vasodilation and increased basal vascular tone due, in part, to elevated endothelin-1 plasma levels. In the present study, we investigated whether a reduction of vascular tone using an endothelin A receptor blocker attenuates the impairment of endothelium-dependent, flow-mediated vasodilation (FMD). METHODS AND RESULTS: Twenty-one patients with CHF randomly received either the endothelin A receptor blocker LU 135252 (30 mg/d, n=7; 300 mg/d, n=7) or a placebo (n=7). Using high-resolution ultrasound, FMD and endothelium-independent, nitroglycerin-induced dilation of the brachial artery were assessed at baseline in the 21 patients with CHF and in 11 controls and after 3 weeks treatment in the 21 patients with CHF. FMD at baseline was impaired in all 21 patients with CHF (3.2+/-2%) when compared with the 11 controls (9.7+/-4.9%; P=0.0005). In comparison with baseline, FMD significantly improved after 3 weeks of treatment with LU 135252 in all 14 patients receiving it (from 3.0+/-2.0% to 4.9+/-2.9%; P=0.04), but FMD remained unchanged with placebo. Subgroup analysis, according to different dosages, revealed a significant increase of FMD compared with baseline (from 2.4+/-1.5% to 5.5+/-2.4%; P=0.03) in the patients treated with the low-dose (30 mg/d), whereas a high dose of 300 mg/d failed to increase FMD significantly. Improvement in the high-dose group, however, may have been masked by reduced vasodilator capacity due to a significant increase in vessel size (from 4.8+/-0.4 to 5.1+/-0.7 mm; P=0.03). CONCLUSIONS: These results suggest that endothelin A receptor blockade improves FMD in CHF patients.

Blood Flow Velocity↗
PubMed2001

Lessons learned from the first clinical implants of the DeBakey ventricular assist device axial pump: a single center report.

BACKGROUND: The bridge to transplantation with pulsatile mechanical assist devices became a standard procedure for patients deteriorating on the waiting list. Recently, continuous flow axial impeller pumps were introduced to clinical application offering new advantages. METHODS: From November 1998 till September 2000, 6 male patients (mean age 53 plus or minus 11 years) with end-stage left heart failure were implanted with a DeBakey ventricular assist device (VAD) axial-flow pump for bridge to transplantation. RESULTS: Three patients were successfully transplanted after 74, 115, and 117 days, respectively. Two other patients died after 25 and 133 days. One patient is still on the device after 108 days. Because of modification of the implantation technique after the first 2 patients, mean pump-flow within the first 3 weeks was increased from 4.3 +/- 0.6 L/min to 6.7 +/- 0.3 L/min. Patients were put on regular bicycle-ergometer training and improved their exercise capacities up to a mean maximum oxygen consumption of 20.2 mL/kg/min. CONCLUSIONS: Initial implants of the DeBakey VAD demonstrated support properties comparable to pulsatile pumps but without significant restrictions for extended use.

Equipment Design↗
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

Angiogenesis stimulation in explanted hearts from patients pre-treated with intravenous prostaglandin E(1).

BACKGROUND: Prostaglandin E(1) (PGE(1)) is a potent vasodilator and induces angiogenesis in animal tissues. Previous clinical studies demonstrated that PGE(1) improves hemodynamic parameters in patients with heart failure listed for heart transplantation (HTX). Therefore, we designed a retrospective immunohistochemistry study to investigate various markers of angiogenesis using hearts explanted from PGE(1)-treated patients with idiopathic dilated cardiomyopathy (IDCM). METHODS AND RESULTS: We investigated neovascularization in 18 hearts explanted from patients with IDCM: 9 patients received treatment with chronic infusions of PGE(1) for end-stage heart failure before HTX, whereas the remaining patients with IDCM did not receive PGE(1) and served as controls. We used immunoreactivity against CD34, von Willebrand factor (vWf), vascular endothelial growth factor (VEGF), and MIB-1 (Ki-67) to quantify angiogenesis, and used sirius red staining to determine the degree of fibrosis. Compared with the control group, PGE(1)-treated patients had significantly more CD34-, vWf- and MIB-1-positive cells in the sub-endocardium, myocardium and sub-epicardium (p < 0.01). The degree of fibrosis in the hearts of PGE(1)-treated patients was significantly lower than in control patients (p < 0.05), but we did not see any difference in the percentage of muscle mass. Finally, throughout the ventricles, we found significantly more VEGF-positive capillaries in the PGE(1) group (p < 0.0001). CONCLUSIONS: The data suggest that PGE(1) could be a potent inducer of angiogenesis and the angiogenic factor VEGF, and could cause reduced fibrosis in the failing human heart.

Alprostadil↗
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

Pathogenesis of heart failure.

Heart failure is a complex clinical syndrome, and only part of this syndrome is based on the mechanical failure of the heart muscle itself to provide sufficient systemic perfusion. Heart failure is accompanied by the activation of various immunologic and neurohumoral mechanisms. These may be intended by nature to be physiologically beneficial, but eventually become deleterious as they provoke ischemic, proarrhythmic, vascular, and structural changes in the myocardium that contribute to the versatile symptoms of the heart failure syndrome. Today's concept of the pathogenesis of heart failure regards heart failure as a dynamic state influenced by at least 2 major mechanisms, namely "neurohumoral" activation and ventricular remodeling. Progressive chronic heart failure can be viewed as a result of the prolonged impact of both pathogenetic mechanisms. This article will describe briefly the features of the neurohumoral forces on the pathogenesis of heart failure, including immunologic forces, which also influence the remodeling process.

Animals↗
PubMed2001

Isokinetic strength testing in patients with chronic heart failure--a reliability study.

Measurement of skeletal muscle strength gains increasing importance as outcome parameter in patients with chronic heart failure. This study aimed at establishing short-term reliability of isokinetic strength measurements of knee extensor and flexor muscles in 38 patients with chronic heart failure. Strength tests were performed on the Cybex 6000 dynamometer. Trunk fixation was restricted to pelvic fixation. Two bouts of strength testing were performed on day 1 and one on day 5. Each isokinetic bout consisted of 3 reciprocal knee extension and flexion movements with an angular speed of 60 degrees per second. Isometric strength was measured at 30 degree knee angulation. Intraclass correlations ranged between 0.96 and 0.99 for isokinetic and isometric peak torque of knee extensor muscles and 0.82-0.96 for flexor muscles. Analysis of repeated measurements showed significant differences among the values of flexor peak torque in the isokinetic mode and between all measurements in the isometric mode (p < 0.05). Pearson's correlation coefficients for isokinetic and isometric extensor peak torques ranged between 0.95 and 0.99, for flexor peak torques between 0.81 and 0.85 (all p < 0.0001). Measurement of isokinetic knee extensor and flexor peak torque is a reliable method to assess muscle strength in patients with chronic heart failure even with altered trunk fixation.

Adult↗
PubMed2001

Cross-cultural adaptation of the Minnesota Living with Heart Failure Questionnaire for German-speaking patients.

We performed a cross-cultural adaptation of the "Minnesota Living with Heart Failure Questionnaire" (LHFQ) for use in German-speaking chronic heart failure patients. The instrument was translated and back translated, pre-tested and reviewed by a committee. The German version was tested in 114 patients with chronic heart failure. Reliability was assessed by a test-retest procedure and Cronbach's coefficient alpha of internal consistency (0.94). To assess concurrent validity, we compared the LHFQ sum scores with the New York Heart Association classification rating (r = 0.53; p < 0.0001), the 6-minute walk (r = -0.39; p < 0.0001), the left ventricular ejection fraction (r = -0.24; p = 0.011) and big-endothelin (r = 0.27; p = 0.004). Construct validity on the LHFQ scores in comparison with the Medical Outcomes Study SF-36 Health Survey (MOS SF-36) was significant (-0.41 to -0.74; all p < 0.0001). The reliability and validity of the German version of the LHFQ was proved; the questionnaire can be recommended for use in future clinical trials.

Aged↗
PubMed2001

Improvement of thigh muscles by neuromuscular electrical stimulation in patients with refractory heart failure: a single-blind, randomized, controlled trial.

OBJECTIVE: To determine the impact of an 8-wk neuromuscular stimulation program of thigh muscles on strength and cross-sectional area in patients with refractory heart failure listed for transplantation. DESIGN: Forty-two patients with a stable disease course were assigned randomly to a stimulation group (SG) or a control group (CG). The stimulation protocol consisted of biphasic symmetric impulses with a frequency of 50 Hz and an on/off regime of 2/6 sec. RESULTS: Primary outcome measures were isometric and isokinetic thigh muscle strength and muscle cross-sectional area. Our results showed an increase of muscle strength by mean 22.7 for knee extensor and by 35.4 for knee flexor muscles. The CG remained unchanged or decreased by -8.4 in extensor strength. Cross-sectional area increased in the SG by 15.5 and in the CG by 1.7. CONCLUSIONS: Activities of daily living as well as quality of life increased in the SG but not in the CG. Subscales of the SF-36 increased significantly in the SG, especially concerning physical functioning by +7.5 (1.3-30.0), emotional role by +33.3 (0-66.6), and social functioning by +18.8 (0-46.9), all P < 0.05. Neither a change nor a decrease was observed in the CG. Neuromuscular electrical stimulation of thigh muscles in patients with refractory heart failure is effective in increasing muscle strength and bulk and positively affects the perception of quality of life and activities of daily living.

Activities of Daily Living↗