Lejonberg Carl, Czuba Tomasz, Egerstedt Anna, Ghosh Nilanjana, Celik Selvi, Ljungman Charlotta, Lundgren Jakob, Rådegran Göran, Gidlöf Olof, Smith J Gustav
Department of Cardiology, Clinical Sciences Lund University Lund Sweden.
Wallenberg Center for Molecular Medicine and Lund University Diabetes Center Lund University Lund Sweden.
J Am Heart Assoc. 2025 Jul 15;14(14):e039248. doi: 10.1161/JAHA.124.039248. Epub 2025 Jul 14.
Heart failure (HF) is characterized by hemodynamic derangements that are likely to mediate systemic metabolic perturbations but limited data are available. Plasma metabolite profiling provides opportunities for comprehensive investigation of such perturbations. Here, we aimed to characterize plasma profiles that associate with HF and their relationship with central hemodynamics, symptom burden, and response to restoration of cardiac function by heart transplantation.
Untargeted metabolite profiling was conducted with mass spectrometry in 2 independent case-control samples.
In total, 89 of 797 studied metabolites were significantly associated with HF in both cohorts with concordant directionality. Amino acid, carbohydrate, and nucleotide metabolites were enriched for association with HF and were consistently increased in HF cases. A subset of patients with advanced HF subsequently underwent heart transplantation, after which 17 of the 89 metabolites returned significantly toward healthy control levels. These 17 metabolites represent increased catecholamine and heme metabolism, conjugated bile acids, kynurenine pathway mediators, spermidine metabolism, and allantoin, as well as tricarboxylic acid cycle and glycolysis intermediates. Most of these metabolites associated with symptom burden and at least 1 of 12 central hemodynamic parameters, primarily relating to either increased systemic or pulmonary venous congestion, lower cardiac output, or lower left ventricular stroke work.
We comprehensively identified metabolite profiles associated with HF and central hemodynamics that reverse by cardiac transplantation. Increased levels of most metabolites also associated with higher symptom burden. Our findings provide perspectives on the metabolic consequences of HF with potential implications for noninvasive monitoring and tailored therapy.
心力衰竭（HF）的特征是血流动力学紊乱，这可能介导全身代谢紊乱，但相关数据有限。血浆代谢物谱分析为全面研究此类紊乱提供了机会。在此，我们旨在表征与HF相关的血浆谱及其与中心血流动力学、症状负担以及心脏移植恢复心功能反应的关系。
在2个独立的病例对照样本中采用质谱法进行非靶向代谢物谱分析。
在两个队列中，797种研究代谢物中的89种与HF显著相关，且方向性一致。氨基酸、碳水化合物和核苷酸代谢物与HF的关联更为丰富，在HF病例中持续增加。一部分晚期HF患者随后接受了心脏移植，之后89种代谢物中的17种显著恢复至健康对照水平。这17种代谢物代表儿茶酚胺和血红素代谢增加、结合胆汁酸、犬尿氨酸途径介质、亚精胺代谢和尿囊素，以及三羧酸循环和糖酵解中间体。这些代谢物大多与症状负担以及12个中心血流动力学参数中的至少1个相关，主要与全身或肺静脉淤血增加、心输出量降低或左心室每搏功降低有关。
我们全面鉴定了与HF和中心血流动力学相关的代谢物谱，这些谱可通过心脏移植逆转。大多数代谢物水平升高也与更高的症状负担相关。我们的研究结果为HF的代谢后果提供了见解，对无创监测和个体化治疗具有潜在意义。
