Impact of Angiotensin Receptor- Neprilysin inhibition combined with enteral nutritional therapy on cardiac performance and inflammatory burden in hemodialysis-Associated heart failure: Clinical and experimental evidence

Abstract

Background: Cardiovascular complications remain the leading cause of mortality in patients undergoing maintenance hemodialysis (MHD), with heart failure (HF) representing a major clinical challenge. Beyond neurohormonal dysregulation, malnutrition and chronic
microinflammation contribute significantly to disease progression. This study investigated whether angiotensin receptor–neprilysin
inhibition combined with enteral nutritional support could provide additive benefits in this high-risk population.
Methods: A randomized controlled clinical study was conducted involving 60 MHD patients with HF, allocated to standard therapy or
combined intervention groups. The intervention consisted of sacubitril/valsartan administration together with structured enteral
nutrition support. Cardiac structure and function, inflammatory markers, nutritional indices, immune parameters, and quality-of-life
scores were evaluated over 6 months. In parallel, a rat model of post-infarction HF was established to validate mechanistic and
physiological changes, including echocardiographic measurements and serum biomarker assessment.
Results:  Patients receiving the combined regimen demonstrated superior improvement in left ventricular systolic performance, with greater reductions in LV dimensions and circulating BNP levels compared with conventional treatment. Inflammatory mediators including
IL-1β, IL-6, and CRP were significantly attenuated, while serum albumin, total protein, hemoglobin, and immunoglobulin levels 
increased more prominently. Quality-of-life scores improved without excess adverse events. Experimental findings mirrored clinical
observations: treated rats exhibited improved LVEF, reduced ventricular remodeling indices, and decreased BNP and pro-inflammatory cytokines relative to untreated HF controls.
Conclusion: The integration of sacubitril/valsartan therapy with enteral nutritional supplementation exerts synergistic effects on cardiac
remodeling, inflammatory modulation, and metabolic recovery in MHD-associated HF. These findings support a multidimensional
therapeutic strategy targeting both neurohormonal activation and nutritional-inflammatory imbalance.