| 1. |
- Ahmed, Abdulla, et al.
(författare)
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Adrenomedullin peptides and precursor levels in relation to haemodynamics and prognosis after heart transplantation
- 2023
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Ingår i: ESC Heart Failure. - 2055-5822. ; 10:4, s. 2427-2437
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Ahmed, Abdulla, et al.
(författare)
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Elevated plasma sRAGE and IGFBP7 in heart failure decrease after heart transplantation in association with haemodynamics
- 2020
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Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:5, s. 2340-2353
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Tidskriftsartikel (refereegranskat)abstract
- 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 (rs = 0.7; P < 0.0001), pulmonary arterial wedge pressure (rs = 0.73; P < 0.0001), pulmonary vascular resistance (rs = 0.65; P = 0.00062), and pulmonary arterial compliance (rs = -0.52; P = 0.0074). The change in plasma IGFBP7 after HT correlated with improved mean right atrial pressure (rs = 0.71; P = 0.00011) and N-terminal pro-brain natriuretic peptide (rs = 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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| 3. |
- Ahmed, Abdulla, et al.
(författare)
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Prolargin and matrix metalloproteinase-2 in heart failure after heart transplantation and their association with haemodynamics
- 2020
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Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:1, s. 224-235
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Remodelling of the extracellular matrix (ECM) is a key mechanism involved in the development and progression of heart failure (HF) but also functional in associated pulmonary hypertension (PH). Our aim was to identify plasma ECM proteins associated to end-stage HF and secondary PH in relation to haemodynamics, before and after heart transplantation (HT).METHODS AND RESULTS: Twenty ECM plasma proteins were analysed with proximity extension assay in 20 controls and 26 HF patients pre-HT and 1 year post-HT. Right heart catherization haemodynamics were assessed in the patients during the preoperative evaluation and at the 1 year follow-up post-HT. Plasma levels of prolargin and matrix metalloproteinase-2 (MMP-2) were elevated (P < 0.0001) in HF patients compared with controls and decreased (P < 0.0001) post-HT towards controls' levels. The decrease in prolargin post-HT correlated with improved mean right atrial pressure (rs = 0.63; P = 0.00091), stroke volume index (rs = -0.73; P < 0.0001), cardiac index (rs = -0.64; P = 0.00057), left ventricular stroke work index (rs = -0.49; P = 0.015), and N-terminal pro brain natriuretic peptide (rs = 0.7; P < 0.0001). The decrease in MMP-2 post-HT correlated with improved mean pulmonary artery pressure (rs = 0.58; P = 0.0025), mean right atrial pressure (rs = 0.56; P = 0.0046), pulmonary artery wedge pressure (rs = 0.48; P = 0.016), and N-terminal pro brain natriuretic peptide (rs = 0.56; P = 0.0029).CONCLUSIONS: The normalization pattern in HF patients of plasma prolargin and MMP-2 post-HT towards controls' levels and their associations with improved haemodynamics indicate that prolargin and MMP-2 may reflect, in part, the aberrant ECM remodelling involved in the pathophysiology of HF and associated PH. Their potential clinical use as biomarkers or targets for future therapy in HF and related PH remains to be investigated.
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| 4. |
- Arvidsson, Mattias, et al.
(författare)
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Plasma proteoglycan prolargin in diagnosis and differentiation of pulmonary arterial hypertension
- 2021
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Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 8:2, s. 1230-1243
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Right ventricular dysfunction may arise because of pulmonary arterial hypertension (PAH). Development of new diagnostic methods able to identify PAH and allow for earlier treatment initiation, before the development of vascular remodelling and manifest right heart failure (HF), could potentially improve prognosis. Proteoglycans and inflammatory proteins are involved in vascular remodelling. We aimed to investigate their potential as biomarkers to differentiate PAH in a dyspnoeic population. Methods and results: Plasma from 152 patients with PAH (n = 48), chronic thrombo-embolic pulmonary hypertension (n = 20), pulmonary hypertension due to HF with reduced (n = 36) or preserved (n = 33) ejection fraction, and HF without pulmonary hypertension (n = 15) and 20 healthy controls were analysed with proximity extension assays. Haemodynamics were assessed in the patients with right heart catheterization. Plasma prolargin levels in PAH were lower compared with all the other studied disease groups (P < 0.001) but higher than the controls' levels (P = 0.003). Receiver operating characteristic curve of prolargin as a PAH-differentiating marker in a pooled population, encompassing all the other studied disease groups, had a sensitivity of 74% and a specificity of 83.3% (area under the curve = 0.84, P < 0.001). Prolargin correlated with the mean right atrial pressure (rs = 0.65, P < 0.001), N-terminal pro-brain natriuretic peptide (rs = 0.64, P < 0.001), cardiac index (rs = −0.31, P = 0.029), stroke volume index (rs = −0.41, P = 0.004), right ventricular stroke work index (rs = −0.31, P = 0.032), six-minute walking distance (rs = −0.41, P = 0.005), and mixed venous blood oxygen saturation (rs = −0.42, P = 0.003). Conclusions: Plasma prolargin levels differentiate PAH patients from controls and the other investigated dyspnoea groups including HF. Its potential in PAH differentiation may be enhanced by inclusion in a multi-marker panel. Larger studies are needed to evaluate its discriminative ability of PAH in relation to other dyspnoea aetiologies and its potential role in PAH risk stratification and pathobiology.
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| 5. |
- Bergh, Niklas, 1979, et al.
(författare)
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Invasive haemodynamics in de novo everolimus vs. calcineurin inhibitor heart transplant recipients
- 2020
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Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:2, s. 567-576
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Invasive haemodynamic profiles at rest and during exercise after heart transplantation (HTx) have never been described in a randomized trial where de novo everolimus (EVR)-based therapy with early calcineurin inhibitor (CNI) withdrawal has been compared with conventional CNI treatment. We report central invasive haemodynamic parameters at rest and exercise during a 3 year follow-up after HTx in a sub-study of the SCandiavian Heart transplant Everolimus De novo stUdy with earLy calcineurin inhibitor avoidancE trial. We hypothesized that the nephroprotective properties, the less development of cardiac allograft vasculopathy (CAV), and the antifibrotic properties of EVR, in comparison with CNI-based immunosuppression, would demonstrate favourable invasive haemodynamic profiles in patients at rest and during exercise. Methods and results: Ninety of 115 HTx recipients randomized to EVR or CNI treatment performed right heart catheterization at rest and 68 performed right heart catheterization at exercise up to 3 years after HTx. Haemodynamic profiles were compared between EVR and CNI treatment groups. Resting haemodynamics improved in both groups from pre-HTx to the first follow-up at 7–11 weeks post-HTx and thereafter remained unchanged up to 3 years of follow-up. During follow-up, cardiac reserve during exercise increased with higher levels of maximum heart rate (118 to 148 b.p.m., P < 0.001), mean arterial pressure (103 to 128 mmHg, P < 0.001), and cardiac output (10.3 to 12.2 l/min, P < 0.001). No significant differences in haemodynamic parameters were observed between the EVR and CNI groups at rest or exercise. Isolated post-capillary pulmonary hypertension (mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≥ 15 mmHg, and pulmonary vascular resistance <3) were measured in 11% of the patients at 7–11 weeks, 5% at 12 months, and 6% at 36 months after HTx. The EVR group had significantly better kidney function (76 mL/min/1 vs. 60 mL/min/1, P < 0.001) and reduced CAV (P < 0.01) but an increased rate of early biopsy-proven treated rejections (21.2% vs 5.7%, P < 0.01) compared with the CNI group at any time point. The differences in renal function, CAV, or early biopsy-proven treated acute rejections were not associated with altered haemodynamics. Conclusions: De novo EVR treatment with early CNI withdrawal compared with conventional CNI therapy did not result in differences in haemodynamics at rest or during exercise up to 3 years after HTx despite significant differences in renal function, reduced CAV, and number of early biopsy-proven treated rejections.
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| 6. |
- Bobbio, Emanuele, et al.
(författare)
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Association between central haemodynamics and renal function in advanced heart failure: a nationwide study from Sweden.
- 2022
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Ingår i: ESC heart failure. - : Wiley. - 2055-5822. ; 9:4, s. 2654-2663
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Tidskriftsartikel (refereegranskat)abstract
- Renal dysfunction in patients with heart failure (HF) has traditionally been attributed to declining cardiac output and renal hypoperfusion. However, other central haemodynamic aberrations may contribute to impaired kidney function. This study assessed the relationship between invasive central haemodynamic measurements from right-heart catheterizations and measured glomerular filtration rate (mGFR) in advanced HF.All patients referred for heart transplantation work-up in Sweden between 1988 and 2019 were identified through the Scandiatransplant organ-exchange organization database. Invasive haemodynamic variables and mGFR were retrieved retrospectively. A total of 1001 subjects (49±13years; 24% female) were eligible for the study. Analysis of covariance adjusted for age, sex, and centre revealed that higher right atrial pressure (RAP) displayed the strongest relationship with impaired GFR [β coefficient -0.59; 95% confidence interval (CI) -0.69 to -0.48; P<0.001], followed by lower mean arterial pressure (MAP) (β coefficient 0.29; 95% CI 0.14-0.37; P<0.001), and finally reduced cardiac index (β coefficient 3.51; 95% CI 2.14-4.84; P<0.003). A combination of high RAP and low MAP was associated with markedly worse mGFR than any other RAP/MAP profile, and high renal perfusion pressure (RPP, MAP minus RAP) was associated with superior renal function irrespective of the degree of cardiac output.In patients with advanced HF, high RAP contributed more to impaired GFR than low MAP. A higher RPP was more closely related to GFR than was high cardiac index.
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| 7. |
- Bouzina, Habib, et al.
(författare)
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Longitudinal changes in risk status in pulmonary arterial hypertension
- 2021
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Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 8:1, s. 680-690
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Low‐risk status in pulmonary arterial hypertension (PAH) predicts better survival. The present study aimed to describe changes in risk status and treatment approaches over multiple clinical assessments in PAH, taking age and comorbidity burden into consideration.Methods and results: The study included incident patients from the Swedish PAH registry, diagnosed with PAH in 2008–2019. Group A (n = 340) were ≤75 years old with <3 comorbidities. Group B (n = 163) were >75 years old with ≥3 comorbidities. Assessments occurred at baseline, first‐year (Y1) and third‐year (Y3) follow‐ups. The study used an explorative and descriptive approach. Group A: median age was 65 years, 70% were female, and 46% had no comorbidities at baseline. Baseline risk assessment yielded low (23%), intermediate (66%), and high risk (11%). Among patients at low, intermediate, or high risk at baseline, 51%, 18%, and 13%, respectively, were at low risk at Y3. At baseline, monotherapy was the most common therapy among low (68%) and intermediate groups (60%), while dual therapy was the most common among high risk (69%). In patients assessed as low, intermediate, or high risk at Y1, 66%, 12%, and 0% were at low risk at Y3, respectively. Of patients at intermediate or high risk at Y1, 35% received monotherapy and 13% received triple therapy. In low‐risk patients at Y1, monotherapy (40%) and dual therapy (43%) were evenly distributed. Group B: median age was 77 years, 50% were female, and 44% had ≥3 comorbidities at baseline. At baseline, 8% were at low, 80% at intermediate, and 12% at high risk. Monotherapy was the most common therapy (62%) in Group B at baseline. Few patients maintained or reached low risk at follow‐ups.Conclusions: Most patients with PAH did not meet low‐risk criteria during the 3 year follow‐up. The first year from diagnosis seems important in defining the longitudinal risk status.
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| 8. |
- Bredfelt, Anna, et al.
(författare)
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Increased right atrial volume measured with cardiac magnetic resonance is associated with worse clinical outcome in patients with pre-capillary pulmonary hypertension
- 2018
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Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 5:5, s. 864-875
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Pre-capillary pulmonary hypertension (PHpre-cap) has a poor prognosis, especially when caused by pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). Whether cardiac magnetic resonance (CMR)-based quantification of atrial volumes in PHpre-cap is beneficial in risk assessment is unknown. The aims were to investigate if (i) atrial volumes using CMR are associated with death or lung transplantation in PHpre-cap, (ii) atrial volumes differ among four unmatched major PHpre-cap subgroups, and (iii) atrial volumes differ between SSc-PAH and idiopathic/familial PAH (IPAH/FPAH) when matched for pulmonary vascular resistance (PVR). Methods and results: Seventy-five PHpre-cap patients (57 ± 19 years, 53 female, 43 de novo) with CMR and right heart catheterization were retrospectively included. Short-axis stacks of cine images were analysed, and right and left atrial maximum (RAVmax and LAVmax) and minimum volume (RAVmin and LAVmin) were indexed for body surface area. Increased (mean + 2 SD) and reduced (mean – 2 SD) volumes were predefined from CMR normal values. Transplantation-free survival was lower in patients with increased RAVmax than in those with normal [hazard ratio (HR) = 2.1, 95% confidence interval (CI) 1.1–4.0] but did not differ between those with reduced LAVmax and normal (HR 2.0, 95% CI 0.8–5.1). RAVmax and RAVmin showed no differences among unmatched or matched groups (P = ns). When matched for PVR, LAVmax, LAVmin, and pulmonary artery wedge pressure were reduced in SSc-PAH compared with IPAH/FPAH (95% CI 0.3–21.4, 95% CI 0.8–19.6, and 95% CI 2–7, respectively). Conclusions: Patients with PHpre-cap and increased right atrial volume measured with CMR had worse clinical outcome. When matched for PVR, left atrial volume was lower in SSc-PAH than in IPAH/FPAH, consistent with left-sided underfilling, indicating a potential differentiator between the groups.
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| 9. |
- Egerstedt, Anna, et al.
(författare)
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Bioactive adrenomedullin for assessment of venous congestion in heart failure
- 2022
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Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 9:5, s. 3543-3555
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Bioactive adrenomedullin (bio-ADM) is a vascular-derived peptide hormone that has emerged as a promising biomarker for assessment of congestion in decompensated heart failure (HF). We aimed to evaluate diagnostic and prognostic performance of bio-ADM for HF in comparison to amino-terminal pro-B-type natriuretic peptide (NT-proBNP), with decision thresholds derived from invasive haemodynamic and population-based studies. Methods and results: Normal reference ranges for bio-ADM were derived from a community-based cohort (n = 5060). Correlations with haemodynamic data were explored in a cohort of HF patients undergoing right heart catheterization (n = 346). Mortality and decision cutoffs for bio-ADM was explored in a cohort of patients presenting in the ER with acute dyspnoea (n = 1534), including patients with decompensated HF (n = 570). The normal reference range was 8–39 pg/mL. The area under the receiver operating characteristic curve (AUROC) for discrimination of elevated mean right atrial pressure (mRAP) and pulmonary arterial wedge pressure (PAWP) was 0.74 (95% CI = 0.67–0.79) and 0.70 (95% CI = 0.64–0.75), respectively, with optimal bio-ADM decision cutoff of 39 pg/mL, concordant with cubic spline analyses. NT-proBNP discriminated PAWP slightly better than mRAP (AUROC 0.73 [95% CI = 0.68–0.79] and 0.68 [95% CI = 0.61–0.75]). Bio-ADM correlated with (mRAP, r = 0.55) while NT-proBNP correlated with PAWP. Finally, a bio-ADM decision cutoff of 39 pg/mL associated with 30 and 90 day mortality and conferred a two-fold increased odds of HF diagnosis, independently from NT-proBNP. Conclusions: Bio-ADM tracks with mRAP and associates with measures of systemic congestion and with mortality in decompensated HF independently from NT-proBNP. Our findings support utility of bio-ADM as a biomarker of systemic venous congestion in HF and nominate a decision threshold.
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| 10. |
- Engel Sällberg, Adam, et al.
(författare)
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Plasma tumour necrosis factor-alpha-related proteins in prognosis of heart failure with pulmonary hypertension
- 2023
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Ingår i: ESC Heart Failure. - 2055-5822. ; 10:6, s. 3582-3591
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Patients with heart failure (HF) exhibit poor prognosis, which is further deteriorated by pulmonary hypertension (PH), with negative impact on morbidity and mortality. As PH due to left HF (LHF-PH) is among the most common causes of PH, there is an urge according to the 2021 European Society of Cardiology HF guidelines to find new biomarkers that aid in prognostication of this patient cohort. Given the role of tumour necrosis factor-alpha (TNF-α) in HF progression, we aimed to investigate the prognostic value of plasma proteins related to TNF-α in patients with LHF-PH, in relation to haemodynamic changes following heart transplantation (HT). Methods and results: Twenty TNF-α-related plasma proteins were analysed using proximity extension assay in healthy controls (n = 20) and patients with LHF-PH (n = 67), before and 1 year after HT (n = 19). Plasma levels were compared between the groups, and the prognostic values were determined using Kaplan–Meier and Cox regression analyses. Plasma levels of lymphotoxin-beta receptor (LTBR), TNF receptor superfamily member 6B (TNFRSF6B), and TNF-related apoptosis-inducing ligand receptors 1 and 2 (TRAIL-R1 and TRAIL-R2, respectively) were higher in LHF-PH pre-HT vs. controls (P < 0.0001), as well as higher in pre-HT vs. post-HT (P < 0.001). The elevated pre-HT levels of LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 decreased towards the levels of healthy controls after HT. Higher preoperative levels of LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 in LHF-PH were associated with worse survival rates (P < 0.002). In multivariate Cox regression models, each adjusted for age and sex, LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 predicted mortality (P < 0.002) [hazard ratio (95% confidence interval): 1.12 (1.04–1.19), 1.01 (1.004–1.02), 1.28 (1.14–1.42), and 1.03 (1.02–1.04), respectively]. Conclusions: Elevated pre-HT plasma levels of the TNF-α-related proteins LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 in LHF-PH decreased 1 year after HT, displaying a normalization pattern towards the levels of the healthy controls. These proteins were also prognostic, where higher levels were associated with worse survival rates in LHF-PH, providing new insight in their potential role as prognostic biomarkers. Larger studies are warranted to validate our findings and to investigate their possible pathobiological mechanisms in LHF-PH.
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