Cardiac torsion-strain relationships in fatigued Primary Biliary Cirrhosis

243/250 words) 39 The autoimmune liver disease Primary Biliary Cirrhosis (PBC) is associated with life-altering 40 fatigue in approximately 50% of patients. Previous work suggests that fatigued PBC subjects 41 have evidence of autonomic dysfunction and may be at a higher risk of sudden cardiac 42 death. The manifestation of this risk is not clear. This pilot study investigated whether 43 alterations in cardiac torsion and strain could be detected in fatigued or non-fatigued early44 stage PBC patients. We performed cardiac tissue tagging and anatomical cine-imaging in 13 45 early stage PBC patients (including 7 with significant fatigue) and 10 control subjects to 46 calculate cardiac torsion and strain throughout systole and diastole. From the cardiac 47 tagging, we calculated the torsion-to-shortening ratio (TSR), a measure of subepicardial 48 torsion exerting mechanical advantage over subendocardial shortening. Autonomic function 49 testing was performed to evaluate baroreceptor effective index on standing. TSR was 50 markedly increased in the fatigued PBC patients (0.70 ± 0.13) compared to both controls 51 (0.46 ± 0.11, p=0.002) and non-fatigued PBC patients (0.44 ± 0.12, p=0.003). Decreased 52 baroreceptor effective index on standing strongly correlated with increased TSR within the 53 whole PBC group (r=-0.71, p=0.007). Fatigued PBC patients demonstrate a redistribution of 54 myocardial strain characteristic of a reduced relative contribution to contraction from the 55 subendocardium. This is analogous to the changes found in healthy ageing for subjects 56 approximately 16 years older than the fatigued PBC patients. Hence the hearts of fatigued 57 PBC patients may be subject to processes of accelerated ageing. 58