Impaired cardiovascular function in primary biliary cirrhosis

Abstract

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.

Large‐scale characterization study of patients with antimitochondrial antibodies but nonestablished primary biliary cholangitis

“…This hypothesis is indeed supported by the increase in non-liver-related mortality reported in some population-based studies (26,28) and the growing evidence that patients with PBC may suffer from significant systemic dysfunctions. (29,30) The limitations of our study are inherent to its large-scale design mainly based on the goodwill of voluntary physicians and their declarative data. These include low rate of participation, incomplete exhaustiveness, frequent missing data, and residual uncertainties from unaudited data.…”

Impact of primary biliary cirrhosis on perceived quality of life: The UK-PBC national study

“…In the central model brain injury, perhaps arising as a consequence of inflammatory processes occurring as a result of cholestasis inflammation (a model supported by animal modeling data for cholestasis 25 ), would affect autonomic regulating areas of the brain, leading to secondary peripheral autonomic effects. In the peripheral model vasomotor changes associated with liver disease and/or specific cardiac dysfunction associated with cardiac muscle abnormality in PBC 26,27 would give rise to processes mimicking central autonomic dysfunction peripherally. These models are, of course, Fig.…”

Hepato-cardiac disorders

“…The effects of autonomic dysfunction may alter the perfusion patterns in tissues, potentially reducing muscle perfusion and contributing to peripheral mechanisms of fatigue. A generic tendency towards altered myocardial function was shown in PBC and did not typically appear to be symptomatic in terms of "classical" myocardial dysfunction symptoms [44] .…”