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CLINICAL RESEARCH: HEART FAILURE

Altered Intestinal Function in Patients With Chronic Heart Failure

Anja Sandek, MD, Juergen Bauditz, MD, Alexander Swidsinski, MD, Sabine Buhner, PhD, Jutta Weber-Eibel, MD, Stephan von Haehling, MD, Wieland Schroedl, Tim Karhausen^_*, Wolfram Doehner, MD, PhD^_*, Mathias Rauchhaus, MD, PhD^_*, Philip Poole-Wilson, MD, FMedSci, Hans-Dieter Volk, MD, PhD^||, Herbert Lochs, MD, PhD and Stefan D. Anker, MD, PhD^_*,,_*

^_* Division of Applied Cachexia Research, Department of Cardiology, Charite, Campus Virchow-Klinikum, Berlin, Germany
Department of Gastroenterology, Charite, Campus Mitte, Berlin, Germany
Department of Clinical Cardiology, National Heart & Lung Institute, Imperial College London, London, United Kingdom
Institute of Bacteriology and Mycology, Veterinary Faculty, Leipzig, Germany
^|| Department of Medical Immunology, Charite, Campus Mitte, Berlin, Germany.

Manuscript received October 23, 2006; revised manuscript received June 26, 2007, accepted July 17, 2007.

^_* Reprint requests and correspondence: Prof. Stefan D. Anker, Division of Applied Cachexia Research, Department of Cardiology, Charité, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany. (Email: s.anker{at}cachexia.de).

Objectives: We evaluated morphology and function of the gut in patients with chronic heart failure (CHF).

Background: Intestinal translocation of bacterial endotoxin may contribute to the inflammatory state observed in patients with CHF. The morphology and function of the gut may be abnormal.

Methods: We studied 22 patients with CHF (age 67 ± 2 years, left ventricular ejection fraction [LVEF] 31 ± 1%, New York Heart Association functional class 2.3 ± 0.1, peak VO ₂ 15.0 ± 1.0 ml/kg/min) and 22 control subjects (62 ± 1 years, LVEF 68 ± 2%, peak VO ₂ 24.7 ± 1.3 ml/kg/min). Bowel wall thickness was assessed by transcutaneous sonography, small intestinal permeability by the lactulose-mannitol test, passive carrier-mediated transport by D-xylose test, large intestinal permeability by sucralose test (5- and 26-h urine collection, high-performance liquid chromatography), and mucosal bacterial biofilm by fluorescence in situ hybridization in biopsies taken during sigmoidoscopy.

Results: Chronic heart failure patients, compared with control patients, showed increased bowel wall thickness in the terminal ileum (1.48 ± 0.16 mm vs. 1.04 ± 0.08 mm), ascending colon (2.32 ± 0.18 mm vs. 1.31 ± 0.14 mm), transverse colon (2.19 ± 0.20 vs. 1.27 ± 0.08 mm), descending colon (2.59 ± 0.18 mm vs. 1.43 ± 0.13 mm), and sigmoid (2.97 ± 0.27 mm vs. 1.64 ± 0.14 mm) (all p < 0.01). Chronic heart failure patients had a 35% increase of small intestinal permeability (lactulose/mannitol ratio: 0.023 ± 0.001 vs. 0.017 ± 0.001, p = 0.006), a 210% increase of large intestinal permeability (sucralose excretion: 0.62 ± 0.17% vs. 0.20 ± 0.06%, p = 0.03), and a 29% decrease of D-xylose absorption, indicating bowel ischemia (26.7 ± 3.0% vs. 37.4 ± 1.4%, p = 0.003). Higher concentrations of adherent bacteria were found within mucus of CHF patients compared with control subjects (p = 0.007).

Conclusions: Chronic heart failure is a multisystem disorder in which intestinal morphology, permeability, and absorption are modified. Increased intestinal permeability and an augmented bacterial biofilm may contribute to the origin of both chronic inflammation and malnutrition.

Abbreviations and Acronyms   CHF = chronic heart failure   ELISA = enzyme-linked immunosorbent assay   FISH = fluorescence in situ hybridization   hs CrP = high-sensitivity C-reactive protein   IL = interleukin   LPS = lipopolysaccharide   LVEF = left ventricular ejection fraction   NYHA = New York Heart Association   PI = permeability index   TNF = tumor necrosis factor   Vo2 = oxygen consumption