Elevated plasma tyrosine kinases VEGF-D and HER4 in heart failure patients decrease after heart transplantation in association with improved haemodynamics

Ahmed, Salaheldin; Ahmed, Abdulla; Säleby, Joanna; Bouzina, Habib; Lundgren, Jakob; Rådegran, Göran

doi:10.1007/s00380-019-01548-1

Cited by 9 publications

(11 citation statements)

References 57 publications

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“…The characteristics of the controls and heart transplant recipients have previously been described ( Table 1). 13,18 Plasma NT-proBNP levels were higher in the patients prior to HT compared with controls and decreased after HT, towards controls' levels (P < 0.001; FDR < 0.01). Plasma creatinine (P = 0.49) and the creatinine-based estimation of glomerular filtration rate (eGFR) (P = 0.15) remained unchanged following HT (FDR < 0.01) ( Table 1).…”

Section: Study Populationmentioning

confidence: 95%

Elevated plasma sRAGE and IGFBP7 in heart failure decrease after heart transplantation in association with haemodynamics

Ahmed

Arvidsson

et al. 2020

ESC Heart Failure

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Aims Metabolic derangement is implicated in the pathophysiology of heart failure (HF) and pulmonary hypertension (PH). We aimed to identify the dynamics of metabolic plasma proteins linked to end-stage HF and associated PH in relation to haemodynamics, before and after heart transplantation (HT). Methods and results Twenty-one metabolic plasma proteins were analysed with proximity extension assay in 20 controls and 26 patients before and 1 year after HT. Right heart catheterizations were performed in the HF patients pre-operatively and 1 year after HT. Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and insulin-like growth factor-binding protein 7 (IGFBP7) were higher in HF patients compared with controls (P < 0.0001) and decreased after HT (P < 0.0001), matching controls' levels. The decrease in sRAGE after HT correlated with improved mean pulmonary arterial pressure (r s = 0.7; P < 0.0001), pulmonary arterial wedge pressure (r s = 0.73; P < 0.0001), pulmonary vascular resistance (r s = 0.65; P = 0.00062), and pulmonary arterial compliance (r s = À0.52; P = 0.0074). The change in plasma IGFBP7 after HT correlated with improved mean right atrial pressure (r s = 0.71; P = 0.00011) and N-terminal pro-brain natriuretic peptide (r s = 0.71; P < 0.0001). Conclusions Our results indicate that plasma sRAGE may reflect passive pulmonary vascular congestion and the 'mechanical' state of the pulmonary vasculature in HF patients with or without related PH. Furthermore, sRAGE and IGFBP7 may provide additional insight into the pathophysiological mechanisms in HF and associated PH. Their potential clinical and therapeutic relevance in HF and associated PH need further investigation.

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Section: Study Populationmentioning

confidence: 95%

Elevated plasma sRAGE and IGFBP7 in heart failure decrease after heart transplantation in association with haemodynamics

Ahmed

Arvidsson

et al. 2020

ESC Heart Failure

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“…Notably, 84.6% of the patients had either ACEi or ARB. These data have previously been published [20] *p < 0.0001, FDR (Q = 0.01); vs. control § Nonsignificant vs. pre-HT # One patient suffered from severe orthopnea, hence the unsuccessful PAWP assessment. After optimization with furosemide and levosimendan, subsequent right heart catheterization confirmed Ipc-PH.…”

Section: Protein Analysismentioning

confidence: 62%

“…Notably, 84.6% of the patients had either ACEi or ARB. These data have previously been published [ 20 ]…”

Section: Methodsmentioning

confidence: 99%

“…Informed written consent was acquired from all participants. The population has previously been characterized, including patients' plasma creatinine and NT-proBNP, shown in Table 1 [20,21]. Briefly, 50% of the controls were male, had a median age of 41 years and a median body surface area (BSA) of (1.92 m 2 , n = 19).…”

Section: Study Populationmentioning

confidence: 99%

“…Hemodynamic data of patients before and 1-year after HT have previously been described [20,21], with an additional subgroup description of patients with HF without PH (Table 2 and supplementary Table 1, respectively).…”

Section: Hemodynamic Improvementmentioning

confidence: 99%

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Elevated plasma endocan and BOC in heart failure patients decrease after heart transplantation in association with improved hemodynamics

Ahmed

Bouzina

et al. 2020

Heart Vessels

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Background The prevalence of heart failure (HF) is rising with ageing population and constitutes a major health problem globally. A common complication of HF is pulmonary hypertension (PH) which negatively impacts survival. A pathophysiological association between HF and PH with tumorigenic processes has been suggested. We aimed to identify the plasma levels of, and the association between tumour-related proteins and hemodynamic improvements in patients with HF and PH due to left heart disease (LHD) before and 1-year after heart transplantation (HT). Methods Forty-eight tumour-related proteins were measured with proximity extension assay in plasma from 20 controls and 26 HF patients before and 1-year after HT. Patients’ hemodynamics were measured with right heart catheterization. Results Out of 48 proteins, specifically, plasma levels of endocan and brother of CDO (BOC) were elevated in end-stage HF patients compared to controls (p < 0.001), but decreased after HT (p < 0.01), towards controls’ levels. The decrease of endocan levels after HT correlated with improved mean pulmonary arterial pressure (rs = 0.80, p < 0.0001), pulmonary arterial wedge pressure (rs = 0.63, p = 0.0012), and pulmonary vascular resistance (rs = 0.70, p < 0.001). The decrease and normalization of BOC after HT correlated with decreased mean right atrial pressure (rs = 0.61 p = 0.0015) and NT-proBNP (rs = 0.57, p = 0.0022), as well as increased cardiac index (rs = − 0.51, p = 0.0086) and left-ventricular stroke work index (rs = − 0.57, p = 0.0039). Conclusion Our results suggest that (i) plasma endocan in HF may reflect the state of pulmonary vascular congestion and PH-LHD, whereas (ii) plasma BOC may reflect the cardiac function and the hemodynamic overload in HF. The exact role of these proteins and their clinical applicability as biomarkers in HF and PH-LHD ought to be investigated in larger cohorts.

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

et al. 2023

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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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Elevated plasma tyrosine kinases VEGF-D and HER4 in heart failure patients decrease after heart transplantation in association with improved haemodynamics

Cited by 9 publications

References 57 publications

Elevated plasma sRAGE and IGFBP7 in heart failure decrease after heart transplantation in association with haemodynamics

Elevated plasma sRAGE and IGFBP7 in heart failure decrease after heart transplantation in association with haemodynamics

Elevated plasma endocan and BOC in heart failure patients decrease after heart transplantation in association with improved hemodynamics

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

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