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Abstract：
Background: Heart failure (HF) remains a leading cause of morbidity and mortality globally, necessitating the identification of reliable prognostic biomarkers to guide therapeutic interventions. Recent clinical observations have underscored phenylalanine (PHE) as a prognostic marker in HF, although the mechanisms involving inter-organ crosstalk remain understood. Methods: This study adopted a dull approach, with a retrospective analysis of 550 HF patients to establish the prognostic value of pre-discharge PHE levels and a study on the inter-organ crosstalk of PHE among 24 patients. We analyzed the correlations between PHE concentrations and clinical outcomes, alongside a comprehensive examination of PHE metabolism across the skeletal muscle, liver, heart, kidney, and lung. Results: In the clinical prognostic analysis of 550 patients hospitalized for acute decompensated HF, elevated PHE levels (≥65.6 μM) were significantly and independently associated with increased all-cause mortality during a median follow-up of 4.5 years (log rank = 36.7, p < 0.001), underscoring its value as a prognostic marker in HF. The inter-organic crosstalk study elucidated the mechanism associated with PHE elevation in patients with HF, characterized by an increase in PHE output in skeletal muscle and a decrease in hepatic and cardiac PHE uptakes. Notably, PHE concentration gradients across these organs were correlated with HF severity, such as the NYHA functional class, B-type natriuretic peptide levels, and the presence of acute HF. Conclusions: Our findings confirm the prognostic significance of PHE in patients with HF and unveil the complex metabolic interplay among key organs that contribute to PHE dysregulation. These insights not only reinforce the importance of metabolic monitoring in HF management but also open avenues for therapeutic targets.
摘要：
背景：心力衰竭（HF）仍然是全球发病率和死亡率的主要原因，需要鉴定可靠的预后生物标志物以指导治疗干预。最近的临床观察强调苯丙氨酸（PHE）作为HF的预后标志物，尽管涉及器官间串扰的机制仍被理解。方法:本研究采用沉闷的方法,对550例HF患者进行回顾性分析，以确定出院前PHE水平的预后价值，并对24例患者中PHE的器官间串扰进行研究。我们分析了PHE浓度与临床结果之间的相关性，除了全面检查骨骼肌中的PHE代谢，肝脏,心,肾,还有肺.结果:550例急性失代偿性心力衰竭住院患者的临床预后分析,PHE水平升高（≥65.6μM）在4.5年的中位随访期间与全因死亡率增加显著且独立相关（logrank=36.7，p<0.001），强调其作为HF预后标志物的价值。器官间串扰研究阐明了HF患者与PHE升高相关的机制，其特征是骨骼肌中PHE输出增加，肝脏和心脏PHE摄取减少。值得注意的是,这些器官的PHE浓度梯度与HF严重程度相关，例如NYHA功能类，B型利钠肽水平，和急性HF的存在。结论：我们的发现证实了PHE在HF患者中的预后意义，并揭示了导致PHE失调的关键器官之间复杂的代谢相互作用。这些见解不仅加强了代谢监测在HF管理中的重要性，而且还为治疗目标开辟了途径。
