Introduction: Heart failure with reduced ejection fraction (HFrEF) is a severe clinical condition associated with high mortality and morbidity rates. The –786T/C (rs2070744) polymorphism in the NOS3 gene may influence nitric oxide production and alter cardiovascular outcomes in HFrEF patients. Methods: A cross-sectional descriptive study was conducted at Bac Lieu General Hospital, Vietnam from April 2023 to June 2024. Ninety patients with HFrEF (LVEF <40%) underwent genotyping for NOS3 rs2070744 polymorphism using RFLP-PCR. Patients were followed up at 3 and 6 months for heart failure-related readmission and mortality outcomes. Results: Of the 90 patients (mean age 64.5 ± 13.3 years; 53.3% male), genotype frequencies were TT (61.1%), CT (32.2%), and CC (6.7%). At 3 months, 32.2% were readmitted for heart failure and 10.0% died; at 6 months, readmission and mortality rates were 25.9% and 8.6%, respectively. The CC genotype was associated with significantly higher readmission and mortality rates at 3 months (p<0.05). Multivariate Cox regression identified CC/CT genotype (HR=4.24; 95% CI=1.03–17.39; p<0.05) and dyslipidemia (HR=8.63; 95% CI=2.12–41.03; p<0.05) as independent predictors of mortality. Discussion: The presence of the C allele may influence adverse cardiovascular outcomes in HFrEF patients, potentially via modulation of nitric oxide production, endothelial dysfunction, and autonomic dysregulation. Conclusion: The rs2070744 polymorphism in the NOS3 gene may serve as a prognostic biomarker for poor outcomes in HFrEF. Patients with CC/CT genotypes and dyslipidemia have higher risks of readmission and mortality.
