Abstract Body (Do not enter title and authors here): Background:
Changes in metabolic pathways have been described in patients with heart failure (HF) and reduced ejection fraction. Selected patients with end-stage HF are candidates for left ventricular assist devices (LVAD) implantation to improve survival and quality of life. Myocardial tissue obtained at the time of LVAD implantation offers the possibility to study the metabolic pathways at end-stage HF. The effects of HF etiology and sex on the metabolomic profile of end-stage HF have not been described. Our objective was to compare the sex-specific metabolomic signatures in end-stage HF of ischemic (ICMP) and non-ischemic (NICMP) cardiomyopathy patients.

Methods:
Blood and myocardial tissue were collected at the time of left ventricular assist device (LVAD) implantation in end-stage HF patients. A total of 119 patients were included in the study. Of these 35 (29.4%) were female. Fifty-four (45.4%) patients had ICMP. The mean age of our cohort was 57.8 ± 12.9 years, and 105 (88.2%) were white. A total of 96 blood samples and 119 myocardial tissue samples were analyzed. Metabolomic profiles for blood and myocardial tissue were obtained utilizing proton nuclear magnetic resonance (¹H-NMR) and liquid chromatography coupled with mass spectrometry (LC-MS). Patients were classified according to sex and etiology of HF (NICMP and ICMP). Concentrations of metabolites were compared between groups. Those metabolites with a p-value <0.05 were considered significantly different.

Results:
Substantial differences were observed in the metabolome when samples were analyzed according to sex and etiology of HF (graphic representation in Figure 1). In serum, a total of 673 metabolites were accurately quantified. In males, 4 metabolites were increased in ischemic cardiomyopathy (1A), whereas 50 metabolites were different in female patients (1B). In myocardial tissue, a total of 576 metabolites were quantified. In males, 200 metabolites differed between ischemic and non-ischemic cardiomyopathy (1C), whereas female patients had differential concentration of 100 different metabolites (1D).

Conclusion:
The metabolome of blood and myocardial tissue in patients with end-stage HF differs between ischemic and non-ischemic cardiomyopathy, the differences are accentuated in a sex specific manner. Further studies are required to determine the implications of these differences in the progression and recovery of HF.