Ahmad Tariq, Fiuzat Mona, Neely Benjamin, Neely Megan L, Pencina Michael J, Kraus William E, Zannad Faiez, Whellan David J, Donahue Mark P, Piña Ileana L, Adams Kirkwood F, Kitzman Dalane W, O'Connor Christopher M, Felker G Michael
Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina.
Duke Clinical Research Institute, Durham, North Carolina.
JACC Heart Fail. 2014 Jun;2(3):260-8. doi: 10.1016/j.jchf.2013.12.004.
The aim of this study was to determine whether biomarkers of myocardial stress and fibrosis improve prediction of the mode of death in patients with chronic heart failure.
The 2 most common modes of death in patients with chronic heart failure are pump failure and sudden cardiac death. Prediction of the mode of death may facilitate treatment decisions. The relationship between amino-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3, and ST2, biomarkers that reflect different pathogenic pathways in heart failure (myocardial stress and fibrosis), and mode of death is unknown.
HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤35%). An independent clinical events committee prospectively adjudicated mode of death. NT-proBNP, galectin-3, and ST2 levels were assessed at baseline in 813 subjects. Associations between biomarkers and mode of death were assessed using cause-specific Cox proportional hazards modeling, and interaction testing was used to measure differential associations between biomarkers and pump failure versus sudden cardiac death. Discrimination and risk reclassification metrics were used to assess the added value of galectin-3 and ST2 in predicting mode of death risk beyond a clinical model that included NT-proBNP.
After a median follow-up period of 2.5 years, there were 155 deaths: 49 from pump failure, 42 from sudden cardiac death, and 64 from other causes. Elevations in all biomarkers were associated with increased risk for both pump failure and sudden cardiac death in both adjusted and unadjusted analyses. In each case, increases in the biomarker had a stronger association with pump failure than sudden cardiac death, but this relationship was attenuated after adjustment for clinical risk factors. Clinical variables along with NT-proBNP levels were stronger predictors of pump failure (C statistic: 0.87) than sudden cardiac death (C statistic: 0.73). Addition of ST2 and galectin-3 led to improved net risk classification of 11% for sudden cardiac death, but not pump failure.
Clinical predictors along with NT-proBNP levels were strong predictors of pump failure risk, with insignificant incremental contributions of ST2 and galectin-3. Predictability of sudden cardiac death risk was less robust and enhanced by information provided by novel biomarkers.
本研究旨在确定心肌应激和纤维化的生物标志物是否能改善对慢性心力衰竭患者死亡方式的预测。
慢性心力衰竭患者最常见的两种死亡方式是泵衰竭和心源性猝死。预测死亡方式可能有助于治疗决策。氨基末端脑钠肽前体(NT-proBNP)、半乳糖凝集素-3和ST2是反映心力衰竭不同致病途径(心肌应激和纤维化)的生物标志物,它们与死亡方式之间的关系尚不清楚。
HF-ACTION(心力衰竭:运动训练结局的对照试验)是一项针对因左心室收缩功能障碍(左心室射血分数≤35%)导致的慢性心力衰竭患者进行运动训练与常规治疗对比的随机对照试验。一个独立的临床事件委员会前瞻性地判定死亡方式。在813名受试者的基线时评估NT-proBNP、半乳糖凝集素-3和ST2水平。使用特定病因的Cox比例风险模型评估生物标志物与死亡方式之间的关联,并使用交互检验来衡量生物标志物与泵衰竭和心源性猝死之间的差异关联。使用辨别和风险重新分类指标来评估半乳糖凝集素-3和ST2在预测死亡风险方式方面超出包含NT-proBNP的临床模型的附加价值。
在中位随访期2.5年后,有155例死亡:49例死于泵衰竭,42例死于心源性猝死,64例死于其他原因。在调整和未调整分析中,所有生物标志物升高均与泵衰竭和心源性猝死风险增加相关。在每种情况下,生物标志物升高与泵衰竭的关联比与心源性猝死的关联更强,但在调整临床风险因素后这种关系减弱。临床变量与NT-proBNP水平相比,对泵衰竭(C统计量:0.87)的预测能力比对心源性猝死(C统计量:0.73)更强。加入ST2和半乳糖凝集素-3可使心源性猝死的净风险分类提高11%,但对泵衰竭无此效果。
临床预测指标与NT-proBNP水平是泵衰竭风险的强预测指标,ST2和半乳糖凝集素-3的增量贡献不显著。心源性猝死风险的可预测性较弱,新型生物标志物提供的信息可增强其可预测性。