Sci Trans Med: 预测心力衰竭预后的新方法

临床医师

心力衰竭（Heart Failure, HF）的发病率和死亡率都很高，当前用于预测HF发展的危险分层方法（Risk stratification approaches）还不完善。美国乔治华盛顿大学医学与健康科学学院（SMHS）和约翰霍普金斯大学医学院的研究人员，开发了一种新方法来确定是否患者的心脏会衰竭，有望在未来帮助内科医生更好地治疗患者和为患者“量身定制”治疗干预措施。他们的新方法，可有助于预测哪位心力衰竭患者将会良好康复，哪位患者则不能。根据美国疾病控制和预防中心（CDCP）的资料显示，在美国，每年有500万人患心力衰竭，估计成本为320亿美元。

该研究成果以“Metabolic Rates of ATP Transfer Through Creatine Kinase (CK Flux) Predict Clinical Heart Failure Events and Death”为题发表在12月11日的Science Translational Medicine杂志上。

该论文的共同第一作者、SMHS心力衰竭和机械支撑项目主任、医学助理教授Gurusher Panjrath博士说：“虽然目前有各种各样的预测方法，但这些方法中没有一种能够反映心脏衰竭的根本机制。此外，一些措施与其预测能力不太一致。非常有必要发展一种更具体和可重复的新方法。通过靶定受损的能量代谢，未来可能开发和量身定制针对这个新靶点的疗法。”

Panjrath和他的同事们，利用磁共振波谱分析（MRS），测量了58位患有非缺血性心肌病，或非动脉阻塞性心力衰竭的心衰患者的能量代谢。然后，他们对这些患者进行了平均4.7年的随访，记录他们的任何住院治疗、心脏移植、心室辅助装置放置和各种原因的死亡。他们着眼于研究，三磷酸腺苷（ATP）——心肌细胞的能量来源和称为肌酸激酶（CK）的能量储备——和能与ATP相互作用来保持能量不断供给跳动心脏的一种酶。研究人员利用MRS，测量了通过CK的ATP合成率（称为CK通量）。研究者发现，在病情恶化的心力衰竭患者中，CK通量的测量值明显更低。

这种检测心脏能量代谢的新方法，被证明是临床预后的一个重要预测器，它不依赖患者的症状、种族或心力。然而，研究人员强调，还需要规模更大的研究来验证这些结果，代谢成像方法与其它临床参数结合，能够被用于设计一种更完整的预测心力衰竭事件和死亡的方法，帮助医生更好地为他们的患者计划疗程。

该研究的另一位共同第一作者是约翰霍普金斯大学磁共振研究部主任及教授Paul Bottomley博士。资深作者是约翰霍普金斯大学医学院的医学教授Robert Weiss博士。

原文链接：

---

Metabolic Rates of ATP Transfer Through Creatine Kinase (CK Flux) Predict Clinical Heart Failure Events and Death

Abstract：Morbidity and mortality from heart failure (HF) are high, and current risk stratification approaches for predicting HF progression are imperfect. Adenosine triphosphate (ATP) is required for normal cardiac contraction, and abnormalities in creatine kinase (CK) energy metabolism, the primary myocardial energy reserve reaction, have been observed in experimental and clinical HF. However, the prognostic value of abnormalities in ATP production rates through CK in human HF has not been investigated. Fifty-eight HF patients with nonischemic cardiomyopathy underwent 31P magnetic resonance spectroscopy (MRS) to quantify cardiac high-energy phosphates and the rate of ATP synthesis through CK (CK flux) and were prospectively followed for a median of 4.7 years. Multiple-event analysis (MEA) was performed for HF-related events including all-cause and cardiac death, HF hospitalization, cardiac transplantation, and ventricular-assist device placement. Among baseline demographic, clinical, and metabolic parameters, MEA identified four independent predictors of HF events: New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), African-American race, and CK flux. Reduced myocardial CK flux was a significant predictor of HF outcomes, even after correction for NYHA class, LVEF, and race. For each increase in CK flux of 1 μmol g−1 s−1, risk of HF-related composite outcomes decreased by 32 to 39%. These findings suggest that reduced CK flux may be a potential HF treatment target. Newer imaging strategies, including noninvasive 31P MRS that detect altered ATP kinetics, could thus complement risk stratification in HF and add value in conditions involving other tissues with high energy demands, including skeletal muscle and brain.