Adrenomedullin: a marker of impaired hemodynamics, organ dysfunction, and poor prognosis in cardiogenic shock

Tolppanen, Heli; Rivas‐Lasarte, Mercedes; Lassus, Johan; Sans‐Roselló, Jordi; Hartmann, Oliver; Lindholm, Matias Greve; Arrigo, Mattia; Tarvasmäki, Tuukka; Køber, Lars; Thiele, Holger; Pulkki, Kari; Špinar, Jindřich; Parissis, John; Banaszewski, Marek; Silva-Cardoso, José; Carubelli, Valentina; Sionís, Alessandro; Harjola, Veli‐Pekka; Mebazaa, Alexandre

doi:10.1186/s13613-016-0229-2

Cited by 58 publications

(49 citation statements)

References 38 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the present study, we found that higher bio‐ADM levels were independently associated with poorer clinical outcome in patients with new‐onset and worsening HF. This finding confirms previous studies that reported added prognostic value of bio‐ADM for shorter‐term outcomes . We also found that higher levels of bio‐ADM were independently associated with an increased risk of the combined endpoint, which includes both all‐cause mortality and HF hospitalization.…”

Section: Discussionsupporting

confidence: 91%

Bio‐adrenomedullin as a marker of congestion in patients with new‐onset and worsening heart failure

Maaten¹,

Kremer²,

Demissei

et al. 2019

European J of Heart Fail

View full text Add to dashboard Cite

Background Secretion of adrenomedullin (ADM) is stimulated by volume overload to maintain endothelial barrier function, and higher levels of biologically active (bio‐) ADM in heart failure (HF) are a counteracting response to vascular leakage and tissue oedema. This study aimed to establish the value of plasma bio‐ADM as a marker of congestion in patients with worsening HF. Methods and results The association of plasma bio‐ADM with clinical markers of congestion, as well as its prognostic value was studied in 2179 patients with new‐onset or worsening HF enrolled in BIOSTAT‐CHF. Data were validated in a separate cohort of 1703 patients. Patients with higher plasma bio‐ADM levels were older, had more severe HF and more signs and symptoms of congestion (all P < 0.001). Amongst 20 biomarkers, bio‐ADM was the strongest predictor of a clinical congestion score (r2 = 0.198). In multivariable regression analysis, higher bio‐ADM was associated with higher body mass index, more oedema, and higher fibroblast growth factor 23. In hierarchical cluster analysis, bio‐ADM clustered with oedema, orthopnoea, rales, hepatomegaly and jugular venous pressure. Higher bio‐ADM was independently associated with impaired up‐titration of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers after 3 months, but not of beta‐blockers. Higher bio‐ADM levels were independently associated with an increased risk of all‐cause mortality and HF hospitalization (hazard ratio 1.16, 95% confidence interval 1.06–1.27, P = 0.002, per log increase). Analyses in the validation cohort yielded comparable findings. Conclusions Plasma bio‐ADM in patients with new‐onset and worsening HF is associated with more severe HF and more oedema, orthopnoea, hepatomegaly and jugular venous pressure. We therefore postulate bio‐ADM as a congestion marker, which might become useful to guide decongestive therapy.

show abstract

Section: Discussionsupporting

confidence: 91%

Bio‐adrenomedullin as a marker of congestion in patients with new‐onset and worsening heart failure

Maaten¹,

Kremer²,

Demissei

et al. 2019

European J of Heart Fail

View full text Add to dashboard Cite

show abstract

“…Bio-ADM is known as a vasodilation factor,18 and the prognostic value of bio-ADM has been shown in several different critical conditions 8 19 20. Moreover, its predictive role was recently extended to the AHF setting.…”

Section: Discussionmentioning

confidence: 99%

Bioactive adrenomedullin, proenkephalin A and clinical outcomes in an acute heart failure setting

et al. 2019

Self Cite

View full text Add to dashboard Cite

ObjectivesIn an acute heart failure (AHF) setting, proenkephalin A 119–159 (penKid) has emerged as a promising prognostic marker for predicting worsening renal function (WRF), while bioactive adrenomedullin (bio-ADM) has been proposed as a potential marker for congestion. We examined the diagnostic value of bio-ADM in congestion and penKid in WRF and investigated the prognostic value of bio-ADM and penKid regarding mortality, rehospitalisation and length of hospital stay in two separate European AHF cohorts.MethodsBio-ADM and penKid were measured in 530 subjects hospitalised for AHF in two cohorts: Swedish HeArt and bRain failure inVESTigation trial (HARVEST-Malmö) (n=322, 30.1% female; mean age 75.1+11.1 years; 12 months follow-up) and Italian GREAT Network Rome study (n=208, 54.8% female; mean age 78.5+9.9 years; no follow-up available).ResultsPenKid was associated with WRF (area under the curve (AUC) 0.65, p<0.001). In multivariable logistic regression analysis of the pooled cohort, penKid showed an independent association with WRF (adjusted OR (aOR) 1.74, p=0.004). Bio-ADM was associated with peripheral oedema (AUC 0.71, p<0.001), which proved to be independent after adjustment (aOR 2.30, p<0.001). PenKid was predictive of in-hospital mortality (OR 2.24, p<0.001). In HARVEST-Malmö, both penKid and bio-ADM were predictive of 1-year mortality (aOR 1.34, p=0.038 and aOR 1.39, p=0.030). Furthermore, bio-ADM was associated with rehospitalisation (aOR 1.25, p=0.007) and length of hospital stay (β=0.702, p=0.005).ConclusionIn two different European AHF cohorts, bio-ADM and penKid perform as suitable biomarkers for early detection of congestion severity and WRF occurrence, respectively, and are associated with pertinent clinical outcomes.

show abstract

“…After adjusting for the other biomarkers, plasma bio‐ADM remained a strong predictor of a cardiovascular event . Another study showed that bio‐ADM was a marker of impaired haemodynamics, organ dysfunction, and poor prognosis in patients with cardiogenic shock . We recently studied the clinical correlation and prognostic value of serial measurements of plasma bio‐ADM levels in 1562 patients admitted for acute decompensated heart failure .…”

Section: Adrenomedullin Is Elevated In Heart Failure and Related To Cmentioning

confidence: 99%

“…54 Another study showed that bio-ADM was a marker of impaired haemodynamics, organ dysfunction, and poor prognosis in patients with cardiogenic shock. 55 We recently studied the clinical correlation and prognostic value of serial measurements of plasma bio-ADM levels in 1562 patients admitted for acute decompensated heart failure. 56 We showed that plasma bio-ADM had the strongest association with clinically assessed congestion during hospital admission for acute decompensated heart failure.…”

Section: Adrenomedullin Is Elevated In Heart Failure and Related To Cmentioning

confidence: 99%

Adrenomedullin in heart failure: pathophysiology and therapeutic application

Voors

Kremer

Geven

et al. 2018

European J of Heart Fail

Self Cite

151

162

View full text Add to dashboard Cite

Adrenomedullin (ADM) is a peptide hormone first discovered in 1993 in pheochromocytoma. It is synthesized by endothelial and vascular smooth muscle cells and diffuses freely between blood and interstitium. Excretion of ADM is stimulated by volume overload to maintain endothelial barrier function. Disruption of the ADM system therefore results in vascular leakage and systemic and pulmonary oedema. In addition, ADM inhibits the renin–angiotensin–aldosterone system. ADM is strongly elevated in patients with sepsis and in patients with acute heart failure. Since hallmarks of both conditions are vascular leakage and tissue oedema, we hypothesize that ADM plays a compensatory role and may exert protective properties against fluid overload and tissue congestion. Recently, a new immunoassay that specifically measures the biologically active ADM (bio‐ADM) has been developed, and might become a biomarker for tissue congestion. As a consequence, measurement of bio‐ADM might potentially be used to guide diuretic therapy in patients with heart failure. In addition, ADM might be used to guide treatment of (pulmonary) oedema or even become a target for therapy. Adrecizumab is a humanized, monoclonal, non‐neutralizing ADM‐binding antibody with a half‐life of 15 days. Adrecizumab binds at the N‐terminal epitope of ADM, leaving the C‐terminal side intact to bind to its receptor. Due to its high molecular weight, the antibody adrecizumab cannot cross the endothelial barrier and consequently remains in the circulation. The observation that adrecizumab increases plasma concentrations of ADM indicates that ADM‐binding by adrecizumab is able to drain ADM from the interstitium into the circulation. We therefore hypothesize that administration of adrecizumab improves vascular integrity, leading to improvement of tissue congestion and thereby may improve clinical outcomes in patients with acute decompensated heart failure. A phase II study with adrecizumab in patients with sepsis is ongoing and a phase II study on the effects of adrecizumab in patients with acute decompensated heart failure with elevated ADM is currently in preparation.

show abstract

Adrenomedullin: a marker of impaired hemodynamics, organ dysfunction, and poor prognosis in cardiogenic shock

Cited by 58 publications

References 38 publications

Bio‐adrenomedullin as a marker of congestion in patients with new‐onset and worsening heart failure

Bio‐adrenomedullin as a marker of congestion in patients with new‐onset and worsening heart failure

Bioactive adrenomedullin, proenkephalin A and clinical outcomes in an acute heart failure setting

Adrenomedullin in heart failure: pathophysiology and therapeutic application

Contact Info

Product

Resources

About