This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: j.jacc.2007.07.016v1 50/16/1561    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sandek, A. Articles by Anker, S. D. Search for Related Content PubMed PubMed Citation Articles by Sandek, A. Articles by Anker, S. D.

CLINICAL RESEARCH

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

This article has been cited by other articles:

				S. von Haehling, J. C. Schefold, E. A. Jankowska, J. Springer, A. Vazir, P. R. Kalra, A. Sandek, G. Fauler, T. Stojakovic, M. Trauner, et al. Ursodeoxycholic Acid in Patients With Chronic Heart Failure: A Double-Blind, Randomized, Placebo-Controlled, Crossover Trial J. Am. Coll. Cardiol., February 7, 2012; 59(6): 585 - 592. [Abstract] [Full Text] [PDF]

				N. Pathan, M. Burmester, T. Adamovic, M. Berk, K. W. Ng, H. Betts, D. Macrae, S. Waddell, M. Paul-Clark, R. Nuamah, et al. Intestinal Injury and Endotoxemia in Children Undergoing Surgery for Congenital Heart Disease Am. J. Respir. Crit. Care Med., December 1, 2011; 184(11): 1261 - 1269. [Abstract] [Full Text] [PDF]

				B. J. Wrigley, G. Y. H. Lip, and E. Shantsila The role of monocytes and inflammation in the pathophysiology of heart failure Eur J Heart Fail, November 1, 2011; 13(11): 1161 - 1171. [Abstract] [Full Text] [PDF]

				S. G. John, P. J. Owen, L. E. A. Harrison, C.-C. Szeto, K.-B. Lai, P. K. T. Li, and C. W. McIntyre The Impact of Antihypertensive Drug Therapy on Endotoxemia in Elderly Patients with Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., October 1, 2011; 6(10): 2389 - 2394. [Abstract] [Full Text] [PDF]

				A. L. Clark 2 Heart failure syndromes Oxford Textbook of Heart Failure, January 1, 2011; 1(1): med-9780199577729-chapter - med-9780199577729-chapter. [Abstract] [Full Text]

				M. Vistnes, A. Waehre, S. Nygard, I. Sjaastad, K. B. Andersson, C. Husberg, and G. Christensen Circulating cytokine levels in mice with heart failure are etiology dependent J Appl Physiol, May 1, 2010; 108(5): 1357 - 1364. [Abstract] [Full Text] [PDF]

				C.-C. Szeto, B. C.-H. Kwan, K.-M. Chow, K.-B. Lai, W.-F. Pang, K.-Y. Chung, C.-B. Leung, and P. K.-T. Li ENDOTOXEMIA IS ASSOCIATED WITH BETTER CLINICAL OUTCOME IN INCIDENT CHINESE PERITONEAL DIALYSIS PATIENTS: A PROSPECTIVE COHORT STUDY Perit. Dial. Int., March 1, 2010; 30(2): 178 - 186. [Abstract] [Full Text] [PDF]

				S. P. Dunn, B. Bleske, M. Dorsch, T. Macaulay, B. Van Tassell, and O. Vardeny Nutrition and Heart Failure: Impact of Drug Therapies and Management Strategies Nutr Clin Pract, February 1, 2009; 24(1): 60 - 75. [Abstract] [Full Text] [PDF]

				K. A. Tappenden Inflammation and Intestinal Function: Where Does It Start and What Does It Mean? JPEN J Parenter Enteral Nutr, November 1, 2008; 32(6): 648 - 650. [Abstract] [Full Text] [PDF]