Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
Norwich Medical School, University of East Anglia, Norwich, UK.
Pharmacol Ther. 2018 Feb;182:95-114. doi: 10.1016/j.pharmthera.2017.08.001. Epub 2017 Aug 15.
Both heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF) are associated with high morbidity and mortality. Although many established pharmacological interventions exist for HFrEF, hospitalization and death rates remain high, and for those with HFpEF (approximately half of all heart failure patients), there are no effective therapies. Recently, the role of impaired cardiac energetic status in heart failure has gained increasing recognition with the identification of reduced capacity for both fatty acid and carbohydrate oxidation, impaired function of the electron transport chain, reduced capacity to transfer ATP to the cytosol, and inefficient utilization of the energy produced. These nodes in the genesis of cardiac energetic impairment provide potential therapeutic targets, and there is promising data from recent experimental and early-phase clinical studies evaluating modulators such as carnitine palmitoyltransferase 1 inhibitors, partial fatty acid oxidation inhibitors and mitochondrial-targeted antioxidants. Metabolic modulation may provide significant symptomatic and prognostic benefit for patients suffering from heart failure above and beyond guideline-directed therapy, but further clinical trials are needed.
射血分数降低的心力衰竭（HFrEF）和射血分数保留的心力衰竭（HFpEF）均与高发病率和死亡率相关。尽管存在许多针对 HFrEF 的既定药物干预措施，但住院率和死亡率仍然很高，而对于 HFpEF 患者（约占所有心力衰竭患者的一半），目前尚无有效的治疗方法。最近，随着确定脂肪酸和碳水化合物氧化能力降低、电子传递链功能受损、向细胞质转移 ATP 的能力降低以及产生的能量利用效率降低，心脏能量状态受损在心力衰竭中的作用得到了越来越多的认识。这些心脏能量损伤发生的节点为潜在的治疗靶点提供了依据，最近的实验和早期临床研究提供了有前景的数据，评估了肉毒碱棕榈酰基转移酶 1 抑制剂、部分脂肪酸氧化抑制剂和线粒体靶向抗氧化剂等调节剂。代谢调节可能为心力衰竭患者提供显著的症状和预后益处，超过了指南指导的治疗，但仍需要进一步的临床试验。
