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Impaired cardiovascular function in primary biliary cirrhosis

Lookup NU author(s): Professor David Jones, Dr Kieren Hollingsworth, Dr Gulnar Fattakhova, Dr Guy MacGowanORCiD, Professor Roy Taylor, Professor Andrew BlamireORCiD, Emerita Professor Julia Newton

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Abstract

Jones DE, Hollingsworth K, Fattakhova G, MacGowan G, Taylor R, Blamire A, Newton JL. Impaired cardiovascular function in primary biliary cirrhosis. Am J Physiol Gastrointest Liver Physiol 298: G764-G773, 2010. First published February 4, 2010; doi:10.1152/ajpgi.00501.2009.-Cardiovascular system dysregulation in the form of autonomic dysfunction is common at all stages of the disease process in the autoimmune liver disease primary biliary cirrhosis (PBC) and associates with the symptom of fatigue. The mechanisms underpinning autonomic dysfunction in PBC are, however, at present unclear. In this study we set out to explore, for the first time, cardiac structure and function in PBC using impedance cardiography (ICG) and magnetic resonance methodologies. ICG was assessed beat to beat in response to orthostasis (by head-up tilt) in age and sex case-matched high-fatigue and low-fatigue PBC groups (assessed by Fatigue Impact Scale), normal control subjects (n = 15 each group) and a liver disease control cohort (primary sclerosing cholangitis). Cardiac structure and bioenergetics were examined in 15 of the PBC subjects and 8 of the normal control subjects by magnetic resonance spectroscopy and cine imaging. Capacity of the left ventricle to respond to orthostasis [left ventricular ejection time (LVET)] was impaired in PBC compared with matched normal control subjects (P = 0.05). This was a PBC-specific phenomenon unrelated to fatigue status. PBC patients exhibited significantly lower cardiac muscle phosphocreatine-to-ATP ratio (PCr/ATP ratio; measure of cardiac bioenergetic integrity) compared with control subjects (P < 0.01). PCr/ATP <1.6 (indicative of increased risk of death in cardiomyopathy) was present in 6/15 (40%) PBC patients (0/8 control subjects; P < 0.05). Cardiac structure and function were similar in all measures of left ventricular morphology between control subjects and PBC. The close relationship between PCr/ATP and LVET seen in normal subjects (r(2) = 0.6; P < 0.05) was lost in PBC patients, a finding compatible with myocardial dysfunction. Significant correlation was seen between fatigue severity in PBC and fall in cardiac output on orthostasis (r(2) = 0.25; P = 0.005). Our findings suggest the presence of altered myocardial function in PBC. Autonomic "dysfunction" may, rather than being an abnormal process, represent a compensatory mechanism to increase cardiac return to mitigate these effects.

Publication metadata

Author(s): Jones DEJ, Hollingsworth K, Fattakhova G, MacGowan G, Taylor R, Blamire A, Newton JL

Publication type: Article

Publication status: Published

Journal: American Journal of Physiology: Gastrointestinal and Liver Physiology

Year: 2010

Volume: 298

Issue: 5

Pages: G764-G773

Print publication date: 04/02/2010

ISSN (print): 0193-1857

ISSN (electronic): 1522-1547

Publisher: American Physiological Society

URL: http://dx.doi.org/10.1152/ajpgi.00501.2009

DOI: 10.1152/ajpgi.00501.2009

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