See Article by Daubert et al

It has long been recognized that key components of the cardiac energetic system are downregulated in the failing heart. Under normoxic conditions, mitochondrial oxidative phosphorylation generates ≈95% of the ATP content in the heart,¹ which is essential for the process of excitation contraction, as well as maintenance of membrane transport systems. Studies in patients with end-stage cardiomyopathy have shown that the total adenine nucleotide pool (ATP, ADP, and AMP), creatine kinase activity (required for ATP synthesis), creatine phosphate concentration, and the Cr/ATP ratio (a marker of impaired energy metabolism) are all decreased in the failing heart, which has given rise to the notion that the failing heart is an engine out of fuel.^1,2 Although multiple mechanisms have been proposed to explain the profoundly abnormal energetics in the failing heart, recent advances in our understanding of mitochondrial biology³ have raised the intriguing possibility that mitochondria-targeted therapeutics may lead to improved energy production in the heart.⁴ Accordingly, a study in this issue of the Circulation: Heart Failure by Daubert et al,⁵ which evaluates the safety of elamipretide, a novel mitochondria-targeted peptide, in heart failure patients with a reduced ejection fraction (HFrEF) is of considerable interest.⁵

Daubert et al⁵ conducted a double-blind placebo-controlled ascending-dose trial with elamipretide in patients with HFrEF (<35%) who were receiving evidence-based medical therapies for heart failure. Patients were randomized to a single 4-hour intravenous infusion of …

参见Daubert等的文章

早已认识到，心脏衰竭系统中心脏能量系统的关键组件被下调。在常氧条件下，线粒体的氧化磷酸化作用会产生心脏中ATP含量的约95％¹，这对于激发收缩以及维持膜运输系统至关重要。对终末期心肌病患者的研究表明，总腺嘌呤核苷酸库（ATP，ADP和AMP），肌酸激酶活性（ATP合成所需），磷酸肌酸浓度和Cr / ATP比（受损的标志物）能量代谢）在衰竭的心脏中都减少了，这引起了这样的观念，即衰竭的心脏是燃料的动力。^1，2尽管已经提出了多种机制来解释心脏衰竭中极度异常的能量学现象，但我们对线粒体生物学的理解^3的最新进展提出了以线粒体为靶点的治疗药物可能会改善心脏能量产生的引人入胜的可能性。⁴因此，Daubert等人在本期《循环：心力衰竭》中的一项研究⁵评估了射血分数降低（HFrEF）的心力衰竭患者中Elamipretide（一种新型的线粒体靶向肽）的安全性。⁵

Daubert等[ ^5]对正在接受循证医学治疗心力衰竭的HFrEF（<35％）的患者进行了Elamipretide的双盲安慰剂对照升剂量试验。患者被随机分配到…的单次4小时静脉输注。