ST2 and B-type natriuretic peptide kinetics during exercise in severe heart failure

In chronic heart failure (HF), risk stratification is one of the most challenging issues, with a plethora of biomarkers available for this purpose. The key role is played by B-type natriuretic peptide (BNP) and/or its amino-terminal fragment NT-proBNP. Accordingly, all new biomarkers must be compared with BNP and/or must be characterized by prognostic capability in selected HF populations. Soluble ST2 has been recently introduced among the new biomarkers. The presence of high levels of ST2 is related to the severity of HF and to an increased risk of complications, such as arrhythmias, acute decompensation, and death, independently of natriuretic peptide. Indeed, a prognostic role of ST2 has been suggested in low-risk populations, in patients with chronic , advanced, and acute heart failure. Regardless, at present, the most defined role of ST2 is to provide a prognostic value additive to that of NT-proBNP within a multiparametric prognostic approach. The changes in ST2 in response to an acute hemodynamic event are presently unknown, and specifically it is unknown whether an ST2 response to an acute hemodynamic event has the same magnitude and time frame of that reported for BNP. Indeed, in patients with severe HF, BNP increases even during a 10-minute maximal exercise, probably mirroring acute pulmonary hemodynamic worsening. We studied 30 (67±10 years, 28M) consecutive patients with chronic severe HF. Patients underwent a 10-minute cycle-ergometer ramp cardiopulmonary exercise test (CPET) protocol. Immediately before exercise and at peak exercise, venous blood was sampled for BNP and ST2 determination. At the same time, lung diffusion (DLCO) and its two components membrane diffusion (DM) and capillary volume (Vcap) were measured. DLCO was measured by the single-breath constant expiratory flow technique. We showed, using a simple but intriguing physiological research model, that exercise-induced hemodynamic impairment is associated with a major increase of BNP but not of ST2, confirming that the causes and/or the time frame of their responses to acute and short-lasting pulmonary pressure increase are different.慢性心力衰竭（chronic heart failure, HF）的风险分层是临床实践中极具挑战性的议题之一，目前已有大量生物标志物可用于该方向的评估。其中，B型利钠肽（B-type natriuretic peptide, BNP）及其氨基末端片段NT-proBNP发挥着核心作用。因此，所有新型生物标志物均需与BNP进行对比验证，或需在特定HF人群中证实其预后评估能力。 可溶性ST2（soluble ST2）作为新型生物标志物之一，近年来被纳入研究范畴。高水平ST2的表达与HF的严重程度及心律失常、急性失代偿、死亡等并发症风险升高显著相关，且该相关性独立于利钠肽系统。事实上，已有研究提示ST2在低危人群、慢性、晚期及急性HF患者中均具备预后评估价值。但截至目前，ST2最明确的作用是在多参数预后评估体系中，为NT-proBNP的预后价值提供增量补充。目前，关于ST2对急性血流动力学事件的应答变化仍不明确，尤其是ST2在急性血流动力学事件中的应答幅度与时间窗是否与BNP的已报道结果一致，尚有待验证。事实上，在重度HF患者中，即使仅进行10分钟极量运动，BNP水平也会升高，这或许反映了急性肺血流动力学状态的恶化。 本研究纳入30例连续就诊的慢性重度HF患者，患者平均年龄为67±10岁，其中男性28例。所有患者均接受了10分钟自行车测力计递增式心肺运动试验（cycle-ergometer ramp cardiopulmonary exercise test, CPET）方案。在运动前即刻及运动峰值时刻，采集静脉血样以检测BNP与ST2水平；与此同时，还检测了肺弥散功能（DLCO）及其两个组分：膜弥散功能（membrane diffusion, DM）与毛细血管容积（capillary volume, Vcap）。肺弥散功能采用单次呼吸恒定呼气流速法进行检测。 本研究通过一个简洁但颇具启发性的生理学研究模型证实：运动诱导的血流动力学损伤与BNP水平的显著升高相关，但与ST2水平无显著关联，这证实了二者对急性、短暂性肺压力升高的应答机制和/或时间窗存在差异。