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

Ahmed, Abdulla LU orcid ; Kania, Kriss LU orcid ; Abdul Rahim, Hebba LU ; Ahmed, Salaheldin LU orcid and Rådegran, Göran LU (2023) In ESC Heart Failure 10(4). p.2427-2437
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... (More)

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.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
ESC Heart Failure
volume
10
issue
4
pages
2427 - 2437
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85160932374
  • pmid:37246315
ISSN
2055-5822
DOI
10.1002/ehf2.14399
language
English
LU publication?
yes
id
42c37e8e-0271-4d93-b0e6-1ae8519a06e8
date added to LUP
2023-06-05 21:46:19
date last changed
2024-05-03 23:47:22
@article{42c37e8e-0271-4d93-b0e6-1ae8519a06e8,
  abstract     = {{<p>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.</p><p>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).</p><p>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.</p>}},
  author       = {{Ahmed, Abdulla and Kania, Kriss and Abdul Rahim, Hebba and Ahmed, Salaheldin and Rådegran, Göran}},
  issn         = {{2055-5822}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{4}},
  pages        = {{2427--2437}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{ESC Heart Failure}},
  title        = {{Adrenomedullin peptides and precursor levels in relation to haemodynamics and prognosis after heart transplantation}},
  url          = {{http://dx.doi.org/10.1002/ehf2.14399}},
  doi          = {{10.1002/ehf2.14399}},
  volume       = {{10}},
  year         = {{2023}},
}