Activity of the adrenomedullin system to personalise post-discharge diuretic treatment in acute heart failure,Clinical Research in Cardiology

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Activity of the adrenomedullin system to personalise post-discharge diuretic treatment in acute heart failure
Clinical Research in Cardiology ( IF 5 ) Pub Date : 2021-07-23 , DOI: 10.1007/s00392-021-01909-9
Nikola Kozhuharov _{1,

2,

3} , Leong Ng _{4,

5} , Desiree Wussler _{1,

2,

6} , Ivo Strebel _{1,

2} , Zaid Sabti _{1,

2} , Oliver Hartmann ₇ , Mohamed Eltayeb _{4,

5} , Iain Squire _{4,

5} , Albina Nowak _{1,

2,

8} , Max Rieger _{1,

2} , Jasmin Martin _{1,

2,

6} , Eleni Michou _{1,

2} , Sabrina Stefanelli _{1,

2} , Christian Puelacher _{1,

2,

6} , Samyut Shrestha _{1,

2} , Maria Belkin _{1,

2} , Tobias Zimmermann _{1,

2,

6} , Pedro Lopez-Ayala _{1,

2} , Joachim Struck ₇ , Andreas Bergmann ₇ , Alexandre Mebazaa ₉ , Alice Blet ₉ , Danielle Menosi Gualandro _{1,

2} , Tobias Breidthardt _{1,

2,

6} , Christian Mueller _{1,

2}

Affiliation

Background

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.

Methods

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.

Results

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).

Conclusions

Quantifying the adrenomedullin’s system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF.

中文翻译：

肾上腺髓质素系统对急性心力衰竭患者出院后利尿剂治疗的个性化作用

背景

量化肾上腺髓质素系统的活动可能有助于监测和指导急性心力衰竭 (AHF) 患者的治疗。目的是 (1) 识别出院时从特定治疗中显着受益或伤害的 AHF 患者，以及 (2) 通过量化肾上腺髓质素系统活动来预测死亡率。

方法

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就诊的急性呼吸困难患者中集中判定。使用生物活性成分、生物活性肾上腺髓质素 (bio-ADM) 和激素原片段中区肾上腺髓质素原 (MR-proADM) 对肾上腺髓质素系统活性进行量化。Bio-ADM 和 MR-proADM 浓度在就诊时和出院时以盲法测量。评估了出院时与特定治疗的相互作用以及这些生物标志物在 365 天随访期间预测结果的效用。

结果

在 1886 名确诊为 AHF 的患者中，514 名患者（27.3%）在 365 天的随访期间死亡。在调整年龄、肌酐和出院治疗后，如果使用利尿剂治疗，血浆 bio-ADM 浓度高于中位数 (> 44.6 pg/mL) 的患者会获得不成比例的益处（相互作用p值 < 0.001）。当使用 MR-proADM ( n = 764) (交互p值 < 0.001)量化肾上腺髓质素系统活动时，这些发现得到了证实。bio-ADM 血浆浓度高于中位数的患者死亡风险增加（风险比 1.87，95% CI 1.57–2.24；p < 0.001)。对于预测 365 天全因死亡率，两种生物标志物都表现良好，与 bio-ADM 相比，MR-proADM 具有更高的预测准确度 ( p < 0.001)。