Pharmacogenomics of Low Dose Empagliflozin and its Association with Treatment Outcomes inPatients with Heart failure

Heart failure (HF) is a complex clinical syndrome resulting from structural or functional cardiac disorders that impair the ventricle's ability to fill or eject blood, affecting 1-2% of the global population. Apoptosis, myocyte death, and disruptions in calcium homeostasis are all part of the pathophysiology of HF, with ATP2A2 (SERCA2a) failure being a major contributing factor. Furthermore, neurotrophins, such as Brain-DerivedNeurotrophic Factor (BDNF), have been linked to the development of cardiovascular disorders, underscoring their potential as therapeutic targets and biomarkers. The purpose of this study is to examine the clinical effectiveness of low-dose empagliflozin in patients with heart failure, with particular emphasis on the part played by genetic variations in the ATP2A2 (rs1860561) and BDNF (rs6265) genes. 112 Patients ranged in age from 18 to 75 years having a confirmed diagnosis of heart failure, a stabletreatment regimen for at least three months, and a left ventricular ejection fraction (LVEF) between 25% and 45% or preserved (≥45%) were included in the study. Exclusion criteria were pregnancy, recent hospitalization, severe renal impairment, and major comorbidities that affected BNP levels. The patients with heart failure who were enrolled provided DNA samples for genetic analysis. BNP and EF changes were measured before and after patients received low-dose empagliflozin therapy. Sanger sequencing was used to genotype the BDNF gene for rs6265 and the ATP2A2 gene for rs1860561. Analysis was done on genotype distributions and how they relate to therapy response. The mean BNP levels in all patients dropped from 1073.75 pg/mL prior to therapy to 608.78 pg/mL following treatment (p = 0.0094). The group as a whole showed no discernible change in EF (mean rise from 36.7 to 38.25, p = 0.2623). In responder groups, EF increased from 35.16 to 39.75 (p = 0.00187), while BNP levels dramatically dropped from 1161.88 pg/mL to 511.97 pg/mL (p = 0.0056). A positive response to therapy was linked to the BDNF rs6265 polymorphism, with the CC genotype exhibiting the greatest gains in BNP reduction and enhancement in EF. The BNP decrease response rate was 90.91% for patients with the CC genotype and lower for those with the T allele (p = 0.612). 76.92% of respondents with the CC genotype had EF, while the CT genotype had a significantly lower response rate (16.67%, p =0.013). For ATP2A2 rs1860561, the GA genotype was linked to a higher proportion of x responders (88.89%) compared to the GG genotype (71.43%), indicating a more favorable response in GA carriers.