Adrenomedullin peptides and precursor levels in relation to haemodynamics and prognosis after heart transplantation

Abstract

Aims Heart failure (HF) is a frequent condition in the elderly, further complicated by associated pulmonary hypertension (PH), with impact on morbidity and mortality. Plasma proteins associated with cardiovascular disease, related to inflammation, neurohormonal changes, and myocyte stress, pathways recognized in the pathophysiology of HF, may provide information on disease severity and prognosis. We aimed to investigate such cardiovascular proteins and their relationship to haemodynamics before and 1 year after heart transplantation (HT), as well as their prognostic value in advanced HF with PH. Methods and results In 20 healthy controls and 67 patients with HF and PH, before and 1 year after HT, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and 18 cardiovascular proteins were analysed with proximity extension assay. Right heart catheterization was used to measure the haemodynamics of the HF patients pre‐operatively and at 1 year follow‐up after HT. Prognosis was estimated using Kaplan–Meier and Cox regression analyses. Out of 18 plasma proteins, 11 proteins including adrenomedullin peptides and precursor levels (ADM) and protein suppression of tumourigenicity 2 receptor were elevated before HT compared with healthy controls and had decreased 1 year after HT. The decrease in plasma levels 1 year after HT was towards the healthy controls' levels. The decrease in ADM levels before vs. after HT correlated with decreased mean right atrial pressure (rs = 0.61; P = 0.0077), decreased NT‐proBNP (rs = 0.75; P = 0.00025), and decreased stroke volume index (rs = −0.52; P = 0.022). High levels of pre‐operative plasma ADM were associated with worse event‐free survival (HT or death), as well as survival compared with low ADM levels (log‐rank P value = 0.023 and 0.0225, respectively). Univariable Cox regression analysis demonstrated that ADM levels were associated with survival, hazard ratio (HR) 1.007 (95% confidence interval (CI): 1.00–1.015, P = 0.049), and the association remained after adjusting for NT‐proBNP, HR 1.01 (95% CI: 1.00–1.021, P = 0.041). Conclusions Elevated plasma levels of ADM may be a marker of pressure/volume overload in HF patients with PH, as well as long‐term prognosis after HT. In line with previous studies, our findings additionally confirm that ADM may be a marker of venous congestion in HF. Further studies are encouraged to establish a deeper understanding of the properties of ADM and its relationship with HF and PH, in order to potentially facilitate clinical management of HF and associated PH.

Biologically active adrenomedullin as a marker for residual congestion and early rehospitalization in patients hospitalized for acute heart failure: Data from STRONG‐HF

“…10 Additionally, it is strongly associated with pulmonary capillary wedge pressure, right atrial pressure, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and elevated pre-discharge bio-ADM is strongly associated with HF rehospitalizations. [10][11][12] Optimal treatment to relieve congestion is currently under discussion. 8,13 Although decongestion with loop diuretics remains the first choice during the early phases of a HF hospitalization, data from STRONG-HF have shown that early initiation and fast up-titration of GDMT not only reduces congestion but improves clinical outcomes as well.…”

“…Bio‐ADM is a promising marker for residual congestion 10 . Additionally, it is strongly associated with pulmonary capillary wedge pressure, right atrial pressure, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and elevated pre‐discharge bio‐ADM is strongly associated with HF rehospitalizations 10–12 …”