Intestinal blood flow in patients with chronic heart failure: a link with bacterial growth, gastrointestinal symptoms, and cachexia.

BACKGROUND: Blood flow in the intestinal arteries is reduced in patients with stable heart failure (HF) and relates to gastrointestinal (GI) symptoms and cardiac cachexia. OBJECTIVES: The aims of this study were to measure arterial intestinal blood flow and assess its role in juxtamucosal bacterial growth, GI symptoms, and cachexia in patients with HF. METHODS: A total of 65 patients and 25 controls were investigated. Twelve patients were cachectic. Intestinal blood flow and bowel wall thickness were measured using ultrasound. GI symptoms were documented. Bacteria in stool and juxtamucosal bacteria on biopsies taken during sigmoidoscopy were studied in a subgroup by fluorescence in situ hybridization. Serum lipopolysaccharide antibodies were measured. RESULTS: Patients showed 30% to 43% reduced mean systolic blood flow in the superior and inferior mesenteric arteries and celiac trunk (CT) compared with controls (p < 0.007 for all). Cachectic patients had the lowest blood flow (p < 0.002). Lower blood flow in the superior mesenteric artery and CT was correlated with HF severity (p < 0.04 for all). Patients had more feelings of repletion, flatulence, intestinal murmurs, and burping (p < 0.04). Burping and nausea or vomiting were most severe in patients with cachexia (p < 0.05). Patients with lower CT blood flow had more abdominal discomfort and immunoglobulin A-antilipopolysaccharide (r = 0.76, p < 0.02). Antilipopolysaccharide response was correlated with increased growth of juxtamucosal but not stool bacteria. Patients with intestinal murmurs had greater bowel wall thickness of the sigmoid and descending colon, suggestive of edema contributing to GI symptoms (p < 0.05). In multivariate regression analysis, lower blood flow in the superior mesenteric artery, CT (p < 0.04), and inferior mesenteric artery (p = 0.056) was correlated with the presence of cardiac cachexia. CONCLUSIONS: Intestinal blood flow is reduced in patients with HF. This may contribute to juxtamucosal bacterial growth and GI symptoms in patients with advanced HF complicated by cachexia.

Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure.

BACKGROUND: Small intestinal function may be altered in decompensated chronic heart failure (CHF) and translocating LPS may contribute to systemic inflammation observed in CHF. METHODS: We measured intestinal permeability (melibiose and rhamnose), active (3-O-methyl-d-glucose (3-OMG)) and passive (d-xylose) carrier-mediated absorption in 20 CHF patients (12 edematous and 8 non-edematous) and 8 controls by saccharide absorption technique assessing urinary recovery of orally administered sugars. We additionally measured LPS concentrations in 42 patients with decompensated heart failure and after recompensation. RESULTS: CHF patients had a 54% reduction of active carrier-mediated intestinal transport compared to controls (p<0.0001). This reduction was strongest in edematous compared to non-edematous patients and controls (recovery in urine: 13.2±2.0% vs. 20.8±2.4% vs. 36.0 ± 3.7%, all p ≤ 0.05). Patients showed a 34% reduction of passive carrier-mediated transport, strongest in edematous patients (p=0.006). A greater impairment of active carrier-mediated transport remained significant after adjustment for non-mucosal factors in CHF (p=0.0004). Non carrier-mediated intestinal permeability was not altered. Data from 42 decompensated patients showed a decrease in LPS after recompensation (p=0.004). Edematous patients had highest blood concentrations of LPS, TNF and sTNF-R1 (p<0.04). CHF patients with abnormal LPS concentrations >0.50EU/mL (n=7) had the highest concentrations of TNF (7.0 ± 1.6 vs. 3.1 ± 0.3pg/mL, p<0.02), and sTNF-R1 (3499 ± 52 vs. 1599±219 pg/mL, p=0.02). CONCLUSION: Active carrier-mediated intestinal transport is reduced in decompensated CHF indicating epithelial dysfunction possibly as a consequence of intestinal ischemia. Higher LPS concentrations in edematous CHF relate to inflammation. LPS decreased after recompensation. This suggests a cause/effect relationship between edematous gut wall, epithelial dysfunction and translocating LPS.

Risk stratification in patients with chronic heart failure based on metabolic-immunological, functional and haemodynamic parameters.

BACKGROUND: A vast array of parameters has been proposed to predict mortality in chronic heart failure (CHF). Their applicability into clinical practice remains challenging due to economical and availability considerations. METHODS AND RESULTS: We studied serum uric acid, total cholesterol, and soluble tumour necrosis factor receptor 1 (sTNF-R1) in 114 CHF patients (63.0 ± 1.0 years, NYHA functional class I/II/III/IV: 11/34/54/15) recruited prospectively into a metabolic study program. All patients underwent assessment of left ventricular ejection fraction and measurement of peak oxygen consumption (pVO(2)). Patients were followed for 24 months or until death. A total of 31 patients died; cumulative survival was 78% (95% confidence interval [CI] 70-86%) and 73% (65-81%) at 12 and 24 months, respectively. In single predictor Cox proportional hazard analysis, uric acid, pVO2, sTNFR-1, LVEF (all p<0.0001) and cholesterol (p<0.02) all predicted survival. All parameters remained significant predictors of death after multivariable adjustment (all p<0.02). Receiver-operator characteristic (ROC) curve analyses showed that uric acid and sTNF-R1 are equally strong with regards to their prognostic performance in CHF like pVO(2,) but even better than LVEF. The combination of pVO(2), LVEF, uric acid, and sTNF-R1 in ROC statistics turned out as the best model with the highest prognostic value in CHF (AUC: 0.91, sensitivity: 90.4, specificity: 74.2, p=0.0001). CONCLUSION: Including metabolic-immunological parameters into risk assessment might result in a better risk stratification than modeling based on clinical parameters alone, probably due to a better reflection of CHF as multisystem disease. We suggest metabolic-immunological parameters to be tested in larger populations.

Enzymatic diagnostic test for Muscle-Eye-Brain type congenital muscular dystrophy using commercially available reagents.

OBJECTIVES: Mutations disrupting the interaction of extra-cellular ligands and alpha-dystroglycan are responsible for an etiologically heterogeneous group of autosomal recessive congenital muscular dystrophies (CMD) that can have associated brain and eye abnormalities. The objective is to develop a diagnostic test for one of these CMDs, Muscle-Eye-Brain disease (MEB), due to mutations in the gene encoding Protein O-Mannosyl beta-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1). DESIGN AND METHODS: POMGnT1 enzyme activity was determined in extracts of muscle biopsies from four MEB patients and various controls using commercially available reagents. RESULTS: All four MEB muscle samples showed a highly significant decrease in POMGnT1 activity relative to controls. CONCLUSIONS: The assay of POMGnT1 activity in MEB muscle provides a rapid and relatively simple diagnostic test for this disease. CMDs associated with brain malformations such as MEB, WWS and FCMD are heterogenous in clinical presentation and on radiologic examination, suggesting that POMGnT1 assays of muscle biopsies should be used as a screening procedure for MEB in all CMD patients associated with brain malformations.