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Aims: Ischaemic cardiomyopathy (ICM) leads to impaired contraction andventricular dysfunction causing high rates of morbidity and mortality.Epigenomics allows the identification of epigenetic signatures in humandiseases. We analyse the differential epigenetic patterns of ASB gene family inICM patients and relate these alterations to their haemodynamic and functionalstatus. Methods and Results: Epigenomic analysis was carried out using 16 leftventricular (LV) tissue samples, 8 from ICM patients undergoing hearttransplantation and 8 from control (CNT) subjects without cardiac disease. Weincreased the sample size up to 13 ICM and 10 CNT for RNA-sequencing and to 14ICM for pyrosequencing analyses. We found a hypermethylated profile(cg11189868) in the ASB1 gene that showed a differential methylation of 0.26beta difference, P < 0.05. This result was validated by pyrosequencingtechnique (0.23 beta difference, P < 0.05). Notably, the methylation patternwas strongly related to LV ejection fraction (r = -0.849, P = 0.008) strokevolume (r = -0.929, P = 0.001) and end-systolic and diastolic LV diameters (r =-0.743, P = 0.035 for both). ASB1 showed a down regulation in mRNA levels (-1.2fold, P < 0.05). Conclusion: Our findings link a specific ASB1 methylationpattern to LV structure and performance in end-stage ICM, opening newtherapeutic opportunities and providing new insights regarding which is thefunctionally relevant genome in the ischemic failing myocardium. Keywords:ischaemic cardiomyopathy; epigenomics; heart failure; left ventriculardysfunction; stroke volume; ASB1.

ASB1 differential methylation in ischaemic cardiomyopathy. Relationship with left ventricular performance in end stage heart failure patients