Whilst metabolic inflexibility and substrate constraint have been observed in heart failure for many years, their exact causal role remains controversial. In parallel, many of our fundamental assumptions about cardiac fuel use are now being challenged like never before. For example, the emergence of sodium glucose cotransporter 2 inhibitor (SGLT2i) therapy as one of the four “pillars” of heart failure therapy is causing a revisit of metabolism as a key mechanism and therapeutic target in heart failure. Improvements in the field of cardiac metabolomics will lead to a far more granular understanding of the mechanisms underpinning normal and abnormal human cardiac fuel use, an appreciation of drug action, and novel therapeutic strategies. Technological advances and expanding biorepositories offer exciting opportunities to elucidate the novel aspects of these metabolic mechanisms. Methodologic advances include comprehensive and accurate substrate quantitation such as metabolomics and stable-isotope fluxomics, improved access to arterio-venous blood samples across the heart to determine fuel consumption and energy conversion, high quality cardiac tissue biopsies, biochemical analytics, and informatics. Pairing these technologies with recent discoveries in epigenetic regulation, mitochondrial dynamics, and organ-microbiome metabolic crosstalk will garner critical mechanistic insights in heart failure. In this state-of-the-art review, we focus on new metabolic insights, with an eye on emerging metabolic strategies for heart failure. Our synthesis of the field will be valuable for a diverse audience with an interest in cardiac metabolism.

中文翻译：

---

利用新陈代谢改善心力衰竭的结局


虽然多年来一直在心力衰竭中观察到代谢不灵活和底物限制，但它们的确切因果作用仍然存在争议。与此同时，我们关于心脏燃料使用的许多基本假设现在正受到前所未有的挑战。例如，钠葡萄糖协同转运蛋白 2 抑制剂 （SGLT2i） 疗法作为心力衰竭治疗的四大“支柱”之一的出现，正在促使人们重新审视代谢作为心力衰竭的关键机制和治疗靶点。心脏代谢组学领域的改进将导致对支持正常和异常人类心脏燃料使用的机制、对药物作用和新治疗策略的理解得到更精细的理解。技术进步和不断扩大的生物储存库为阐明这些代谢机制的新方面提供了令人兴奋的机会。方法学的进步包括全面和准确的底物定量，如代谢组学和稳定同位素通量组学，改善了对心脏动静脉血样的获取，以确定燃料消耗和能量转换，高质量的心脏组织活检，生化分析和信息学。将这些技术与表观遗传调控、线粒体动力学和器官-微生物组代谢串扰的最新发现相结合，将获得对心力衰竭的关键机制见解。在这篇最先进的综述中，我们专注于新的代谢见解，并着眼于心力衰竭的新兴代谢策略。我们对该领域的综合对于对心脏代谢感兴趣的不同受众来说将是有价值的。