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Wolfram Doehner

Publications and source records attributed to Wolfram Doehner.

30 records · Page 2Linked to original sources
PubMed2003

Uric acid and survival in chronic heart failure: validation and application in metabolic, functional, and hemodynamic staging.

BACKGROUND: Serum uric acid (UA) could be a valid prognostic marker and useful for metabolic, hemodynamic, and functional (MFH) staging in chronic heart failure (CHF). METHODS AND RESULTS: For the derivation study, 112 patients with CHF (age 59+/-12 years, peak oxygen consumption [Vo2] 17+/-7 mL/kg per minute) were recruited. In separate studies, we validated the prognostic value of UA (n=182) and investigated the relationship between MFH score and the decision to list patients for heart transplantation (n=120). In the derivation study, the best mortality predicting UA cutoff (at 12 months) was 565 micromol/L (9.50 mg/dL) (independently of age, peak Vo2, left ventricular ejection fraction, diuretic dose, sodium, creatinine, and urea; P<0.0001). In the validation study, UA >or=565 micromol/L predicted mortality (hazard ratio, 7.14; P<0.0001). In 16 patients (from both studies) with UA >or=565 micromol/L, left ventricular ejection fraction <or=25% and peak Vo2 <or=14 mL/kg per min (MFH score 3), 12-month survival was lowest (31%) compared with patients with 2 (64%), 1 (77%), or no (98%, P<0.0001) risk factor. In an independent study, 51% of patients with MFH score 2 and 81% of patients with MFH score 3 were listed for transplantation. The positive predictive value of not being listed for heart transplantation with an MFH score of 0 or 1 was 100%. CONCLUSIONS: High serum UA levels are a strong, independent marker of impaired prognosis in patients with moderate to severe CHF. The relationship between serum UA and survival in CHF is graded. MFH staging of patients with CHF is feasible.

Biomarkers↗
PubMed2003

The relationship between age and production of tumour necrosis factor-alpha in healthy volunteers and patients with chronic heart failure.

BACKGROUND: Ageing is associated with an altered immune response. Elevated plasma levels of tumour necrosis factor-alpha (TNF-alpha) are present in patients with advanced chronic heart failure (CHF). However, the relationship between age and the immune response in CHF is unknown. METHODS: We investigated the relationship between age and the TNF-alpha generating capacity of lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) in nine healthy control subjects (mean age 51.6+/-3.6 years, age range 39-75 years) and 22 stable patients with CHF (mean age 68.3+/-1.5 years, age range 52-78 years, NYHA class 3.0+/-0.2). We also tested the TNF-alpha generating capacity of all control subjects and 18 CHF patients in whole blood cultures. RESULTS: Subjects were subgrouped according to baseline TNF-alpha secretion in PBMC cultures into low- and high-responders, with the latter producing TNF-alpha even without LPS stimulation. High-responders produced more TNF-alpha than low-responders at all LPS doses (0.001-10 ng/ml, P<0.0001, repeated measures ANOVA), and high-responders were significantly older than low-responders (controls: 65.8+/-9.2 vs. 47.5+/-2.5 years; patients: 71.9+/-1.9 vs. 65.9+/-1.9 years, both P<0.05). Age correlated with TNF-alpha production in both patients and controls. This effect was independent of NYHA class. CONCLUSIONS: LPS-responsiveness appears to relate to age in both healthy controls and CHF patients. When assessing the immune status of CHF patients, age should therefore be considered an important confounding factor. In whole blood these findings could only be confirmed at the highest LPS concentration used, thus suggesting that certain factors in the blood may be able to abolish LPS activity at lower concentrations.

Adult↗
PubMed2003

Body mass and survival in patients with chronic heart failure without cachexia: the importance of obesity.

BACKGROUND: Cachexia in chronic heart failure carries a poor prognosis, but little is known about the influence of body mass on the prognosis of noncachectic heart failure patients. METHODS: We studied 589 consecutive chronic heart failure patients followed for at least a year, in whom there were accurate baseline data for body mass. RESULTS: Average age was 64.5 +/- 12.4 years, left ventricular ejection fraction (LVEF) 30.9 +/- 0.73%. Cachexia was present in 64. Noncachectic patients were divided into quintiles of body mass index (BMI), Q1 (BMI 22.2 +/- 1.5) to Q5 (BMI 34.1 +/- 2.8). There was no difference among the 5 groups in age, exercise capacity or LVEF. Survival was greatest in Q4 (1-year survival [95% confidence interval (CI)]) 0.91 (0.85-0.96) and 3-year survival 0.81 (0.73-0.89). Relative risks compared with Q4 were Q1: 2.3 (1.4-3.8); Q2: 1.7 (1.1-2.9); Q3: 1.8 (1.1-3.0); and Q5: 1.5 (0.9-2.5). In multivariate analysis of 1 year follow-up, peak oxygen consumption (hazard ratio with 95% CI) (0.89 [0.82-0.97]; P =.006), LVEF (0.94 [0.91-0.97]; P =.0002) and BMI (0.90 [0.82-0.98]; P =.02) independently predicted 1-year survival with a combined Chi;(2) value of 42.4. Age (1.01 [0.98-1.05] and diagnosis (1.56 [0.78-3.11]) was not a predictor of survival. CONCLUSION: In patients with chronic heart failure, increasing BMI is not an adverse prognostic feature. Thinner patients appear to have a poorer prognosis.

Adrenergic beta-Agonists↗
PubMed2002

Effect of interleukin-10 on the production of tumor necrosis factor-alpha by peripheral blood mononuclear cells from patients with chronic heart failure.

Chronic heart failure (HF) is a state of inflammatory immune activation characterized by elevated circulating levels of tumor necrosis factor-alpha (TNF-alpha). Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that inhibits TNF-alpha production and lessens endotoxin bioactivity. It is not known whether IL-10 reduces lipopolysaccharide (LPS) stimulated TNF-alpha production of peripheral blood mononuclear cells (PBMCs) from patients with chronic HF. PBMCs were isolated from 15 patients with chronic HF (New York Heart Association functional class 3.0 +/- 0.2, left ventricular ejection fraction 30 +/- 2%, peak oxygen consumption 18.1 +/- 0.8 ml/kg/min) and 15 healthy control subjects and stimulated with 1 and 10 ng/ml LPS for 24 hours with or without prior addition of IL-10 (10 ng/ml). TNF-alpha was quantified in cell-free supernatants by an enzyme-linked immunosorbent assay. TNF-alpha, soluble TNF receptors, IL-10, and LPS were quantified in plasma. LPS stimulated TNF-alpha production was highest in those patients in New York Heart Association class II (p <0.01 vs New York Heart Association class III and IV, p <0.001 vs control subjects). IL-10 reduced PBMC TNF-alpha production in all stimulated samples at 1 and 10 ng/ml LPS (mean reduction 43% at 1 ng/ml, p <0.01 and 55% at 10 ng/ml, p <0.0001). The percentage reduction in TNF-alpha release did not differ significantly between patients and control subjects or with respect to severity of chronic HF or baseline immune parameters. Independently of clinical severity, IL-10 profoundly inhibits TNF-alpha release from PBMCs isolated from patients with chronic HF. IL-10 is, therefore, a potential therapy for use in chronic HF associated with inflammatory immune activation.

Aged↗
PubMed2002

Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patients with chronic heart failure: results from 2 placebo-controlled studies.

BACKGROUND: In patients with chronic heart failure (CHF), hyperuricemia is a common finding and is associated with reduced vasodilator capacity and impaired peripheral blood flow. It has been suggested that the causal link of this association is increased xanthine oxidase (XO)-derived oxygen free radical production and endothelial dysfunction. We therefore studied the effects of XO inhibition with allopurinol on endothelial function and peripheral blood flow in CHF patients after intra-arterial infusion and after oral administration in 2 independent placebo-controlled studies. METHODS AND RESULTS: In 10 CHF patients with normal serum uric acid (UA) levels (315+/-42 micromol/L) and 9 patients with elevated UA (535+/-54 micromol/L), endothelium-dependent (acetylcholine infusion) and endothelium-independent (nitroglycerin infusion) vasodilation of the radial artery was determined. Coinfusion of allopurinol (600 microg/min) improved endothelium-dependent but not endothelium-independent vasodilation in hyperuricemic patients (P<0.05). In a double-blind, crossover design, hyperuricemic CHF patients were randomly allocated to allopurinol 300 mg/d or placebo for 1 week. In 14 patients (UA 558+/-21 micromol/L, range 455 to 743 micromol/L), treatment reduced UA by >120 micromol/L in all patients (mean reduction 217+/-15 micromol/L, P<0.0001). Compared with placebo, allopurinol improved peak blood flow (venous occlusion plethysmography) in arms (+24%, P=0.027) and legs (+23%, P=0.029). Flow-dependent flow improved by 58% in arms (P=0.011). Allantoin, a marker of oxygen free radical generation, decreased by 20% after allopurinol treatment (P<0.001). There was a direct relation between change of UA and improvement of flow-dependent flow after allopurinol treatment (r=0.63, P<0.05). CONCLUSIONS: In hyperuricemic CHF patients, XO inhibition with allopurinol improves peripheral vasodilator capacity and blood flow both locally and systemically.

Administration, Oral↗
PubMed2002

Insulin resistance in moderate chronic heart failure is related to hyperleptinaemia, but not to norepinephrine or TNF-alpha.

OBJECTIVES: Chronic heart failure (CHF) has emerged as an insulin-resistant state, independently of ischaemic aetiology. The underlying mechanisms of this finding are not known. Catecholamines, tumor necrosis factor alpha (TNFalpha) and leptin, the adipocyte specific hormone, have all been implicated as mediators of impaired insulin sensitivity. The purpose of this study was to examine in patients with CHF and in comparison to healthy controls subjects whether norepinephrine, TNFalpha or leptin relate to insulin sensitivity. DESIGN: 41 patients with CHF (age 60+/-2 years, NYHA I/II/III/IV 4/12/22/3, peak oxygen consumption 17.6+/-1.0 ml/kg per min) and 21 healthy controls of similar age and total and regional fat distribution were studied in a cross-sectional study. Insulin sensitivity was assessed by intravenous glucose tolerance testing using the minimal model approach; catecholamines, TNFalpha and soluble TNF receptors 1 and 2 were also measured. Total and regional body fat mass was assessed by dual energy X-ray absorptiometry. RESULTS: Insulin sensitivity was reduced in CHF patients compared to controls by 31% (P<0.01) and fasting insulin was higher in patients than in controls (79.1+/-9.7 vs. 41.4+/-6.0 pmol/l, P<0.01). Patients had, compared to healthy controls, elevated serum leptin levels (8.28+/-0.84 vs. 4.83+/-0.68 ng/ml), norepinephrine (3.45+/-0.34 vs. 1.87+/-0.16 nmol/l, both P<0.01) and soluble TNF-receptors 1 (1280+/-141 vs. 639+/-52 pg/ml) and 2 (2605+/-184 vs. 1758+/-221 pg/ml, both P<0.01). Leptin levels corrected for total body fat mass were higher in CHF patients than in controls (41.3+/-3 vs. 24.3+/-2 pg/ml per 100 g, P<0.001). TNFalpha was not significantly different between the groups. In both groups there was an inverse correlation between insulin sensitivity and serum leptin (r=-0.65, P<0.0001 for pooled subjects); in contrast, no significant relation was found between insulin sensitivity and norepinephrine or TNFalpha. In multivariate regression analysis, leptin emerged as the only significant predictor of insulin sensitivity (standardised coefficient=-0.59, P<0.001), independent of body fat mass, age and peak VO2. CONCLUSION: In moderate CHF, elevated leptin levels directly and independently predict insulin resistance. Elevated serum leptin levels could play a role in the impaired regulation of energy metabolism in CHF. In contrast to observations in other conditions, TNFalpha and norepinephrine are not related to insulin resistance in moderate CHF.

Adipose Tissue↗
PubMed2002

Cardiac cachexia in early literature: a review of research prior to Medline.

Cachexia has been known to physicians since ancient Greek times as a 'signum mali ominis' in various diseases indicating end stage disease and poor quality of life. Cardiac cachexia is recently receiving growing attention as modern treatment options prevent early death from cardiac events and more patients live with chronic compensated heart failure. Nevertheless, observation and clinical documentation of this condition go back as long as medical science itself. Pioneering studies on the reasons and mechanisms of cachexia were performed several decades ago. These studies provide fundamental insights and guidance towards a better understanding of cachexia. This review presents an overview of early thoughts and milestone studies on metabolic abnormalities and cachexia in chronic heart failure.

Cachexia↗
PubMed2002

Clinical characteristics and survival of patients with chronic heart failure and prolonged QRS duration.

BACKGROUND: Abnormal prolongation of QRS duration is a common finding in patients with chronic heart failure, and is associated with an impaired prognosis. The optimum QRS duration for separating chronic heart failure patients with respect to prognosis has not been determined. Whilst resynchronisation of ventricular conduction may benefit patients with QRS>150 ms, this has yet to be determined for patients with moderate QRS prolongation. METHODS: We evaluated 155 patients with chronic heart failure (New York Heart Association class 2.6+/-0.8, mean+/-S.D.). The mean follow-up period was 838+/-748 days. Patients were sub-grouped according to QRS duration: <120 ms (normal QRS, n=82), 120-150 ms (moderate prolongation, n=44) and >150 ms (severe prolongation, n=29). RESULTS: The optimal QRS duration for stratifying patients for 2-year event free survival was 120 ms (receiver operating characteristic analysis: area under curve 0.73; 95% CI 0.64-0.81). Moderate prolongation of QRS duration was associated with a worse New York Heart Association class, peak oxygen consumption and left ventricular ejection fraction when compared to patients with normal QRS duration (all P<0.05). Patients with moderate prolongation of QRS duration had similar impairment of New York Heart Association class and peak oxygen consumption as compared with patients with QRS duration >150 ms (all P>0.05). CONCLUSIONS: The optimum QRS duration for stratifying patients for medium to long-term event-free survival was 120 ms. Heart failure patients with moderate QRS prolongation share similar impairment of exercise capacity and functional class to those with severe prolongation.

Aged↗
PubMed2002

The cardiac component of cardiac cachexia.

BACKGROUND: Recent evidence suggests the importance of noncardiac mechanisms in the genesis of the syndrome of cardiac cachexia. This raises the question of the relative role of the heart itself in this syndrome. This study sought to assess the cardiac dimensions, mass, and function and changes in these parameters over time in patients with chronic heart failure with and without cachexia. METHODS: Doppler echocardiography was performed in 28 patients with nonedematous weight loss (>7.5% over a period of >6 months) compared with 56 matched patients without weight loss in a ratio of 1:2 (age 71 +/- 13 vs 67 +/- 8 years, P =.07; New York Heart Association class 2.9 +/- 0.7 vs 2.6 +/- 0.6, P =.08). In 18 cachectic and 35 noncachectic patients with previous echocardiographic recordings, we analyzed the changes in left ventricular (LV) dimensions and mass over time. RESULTS: Cardiac dimensions including LV diastolic (69 +/- 9 mm vs 67 +/- 13 mm) and systolic cavity diameter (58 +/- 11 mm vs 55 +/- 15 mm), LV mass (480 +/- 180 g vs 495 +/- 190 g), and LV systolic and diastolic function including fractional shortening (16% +/- 10% vs 18% +/- 10%), isovolumic relaxation time (29 +/- 22 ms vs 36 +/- 27 ms), and E/A ratio (2.7 +/- 1.6 vs 3.3 +/- 2.9) did not differ between cachectic and noncachectic patients (all P >.1). By analyzing changes in LV mass over time, we found an increase (>20%) in 2 (11%) cachectic and 14 (40%) noncachectic patients and a decrease in LV mass (>20%) in 9 (50%) cachectic and 8 (23%) noncachectic patients (chi2 test, P <.05). CONCLUSIONS: Although no specific cardiac abnormality could be detected echocardiographically in cachectic patients compared with patients with noncachectic chronic heart failure in a cross-sectional study, over time a significant loss of LV mass (>20%) occurs more frequently in patients with cardiac cachexia.

Cachexia↗