Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel and University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
GREAT Network, Rome, Italy.
Clin Res Cardiol. 2022 Jun;111(6):627-637. doi: 10.1007/s00392-021-01909-9. Epub 2021 Jul 23.
Quantifying the activity of the adrenomedullin system might help to monitor and guide treatment in acute heart failure (AHF) patients. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity.
This was a prospective multicentre study. AHF diagnosis and phenotype were centrally adjudicated by two independent cardiologists among patients presenting to the emergency department with acute dyspnoea. Adrenomedullin system activity was quantified using the biologically active component, bioactive adrenomedullin (bio-ADM), and a prohormone fragment, midregional proadrenomedullin (MR-proADM). Bio-ADM and MR-proADM concentrations were measured in a blinded fashion at presentation and at discharge. Interaction with specific treatments at discharge and the utility of these biomarkers on predicting outcomes during 365-day follow-up were assessed.
Among 1886 patients with adjudicated AHF, 514 patients (27.3%) died during 365-day follow-up. After adjusting for age, creatinine, and treatment at discharge, patients with bio-ADM plasma concentrations above the median (> 44.6 pg/mL) derived disproportional benefit if treated with diuretics (interaction p values < 0.001). These findings were confirmed when quantifying adrenomedullin system activity using MR-proADM (n = 764) (interaction p values < 0.001). Patients with bio-ADM plasma concentrations above the median were at increased risk of death (hazard ratio 1.87, 95% CI 1.57-2.24; p < 0.001). For predicting 365-day all-cause mortality, both biomarkers performed well, with MR-proADM presenting an even higher predictive accuracy compared to bio-ADM (p < 0.001).
Quantifying the adrenomedullin's system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF.
定量检测肾上腺髓质素系统的活性，可能有助于监测和指导急性心力衰竭（AHF）患者的治疗。本研究的目的是：（1）确定在出院时接受特定治疗的 AHF 患者中具有明显获益或不良预后的患者；（2）通过定量检测肾上腺髓质素系统的活性来预测死亡率。
这是一项前瞻性多中心研究。AHF 的诊断和表型由两位独立的心脏病专家在急诊科以急性呼吸困难就诊的患者中进行中心评估。使用生物活性成分生物活性肾上腺髓质素（bio-ADM）和前激素片段中区域 proadrenomedullin（MR-proADM）来定量检测肾上腺髓质素系统的活性。在就诊时和出院时以盲法测量 bio-ADM 和 MR-proADM 浓度。评估了在出院时与特定治疗的相互作用以及这些生物标志物在预测 365 天随访期间结局的效用。
在 1886 名经裁决的 AHF 患者中，514 名（27.3%）在 365 天随访期间死亡。在校正年龄、肌酐和出院时的治疗后，与 bio-ADM 血浆浓度中位数（>44.6pg/ml）以下的患者相比，如果接受利尿剂治疗，获益不成比例（交互 p 值<0.001）。当使用 MR-proADM （n=764）定量检测肾上腺髓质素系统活性时，也证实了这一发现（交互 p 值<0.001）。与 bio-ADM 血浆浓度中位数以下的患者相比，血浆浓度中位数以上的患者死亡风险增加（危险比 1.87，95%CI 1.57-2.24；p<0.001）。对于预测 365 天全因死亡率，这两种生物标志物均具有良好的性能，与 bio-ADM 相比，MR-proADM 具有更高的预测准确性（p<0.001）。
定量检测肾上腺髓质素系统的活性可能有助于个性化出院后利尿剂治疗，并使 AHF 患者能够进行准确的风险预测。
