| 1. |
- 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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| 2. |
- 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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| 3. |
- Broch, Kaspar, et al.
(författare)
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Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De-novo heart transplant recipients : Design of the randomized controlled EVOLVD trial
- 2020
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 34:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiac allograft vasculopathy (CAV) is characterized by diffuse thickening of the arterial intima. Statins reduce the incidence of CAV, but despite the use of statins, CAV remains one of the leading causes of long-term death after heart transplant. Inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK9) substantially reduce cholesterol levels but have not been tested in heart transplant recipients. Methods: The Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De-novo heart transplant recipients (EVOLVD) trial (ClinicalTrials.gov Identifier: NCT03734211) is a randomized, double-blind trial designed to test the effect of the PCSK9 inhibitor evolocumab on coronary intima thickness in heart transplant recipients. Adults who have received a cardiac transplant within the past 4-8 weeks are eligible. Exclusion criteria include an estimated glomerular filtration rate < 20 mL/min/1.73 m2, renal replacement therapy, or contraindications to coronary angiography with intravascular ultrasound. 130 patients will be randomized (1:1) to 12-month treatment with evolocumab or matching placebo. The primary endpoint is the coronary artery intima thickness as measured by intravascular ultrasound. Conclusion: The EVOLVD trial is a randomized clinical trial designed to show whether treatment with the PCSK9 inhibitor evolocumab can ameliorate CAV over the first year after heart transplant.
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| 4. |
- Gustafsson, Finn, et al.
(författare)
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Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients : Long-term Follow-up From the Randomized SCHEDULE Study
- 2020
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Ingår i: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1534-6080 .- 0041-1337. ; 104:1, s. 154-164
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A calcineurin inhibitor (CNI)-free immunosuppressive regimen has been demonstrated to improve renal function early after heart transplantation, but long-term outcome of such a strategy has not been well described. METHODS: In the randomized SCHEDULE trial, de novo heart transplant recipients received (1) everolimus with reduced-exposure CNI (cyclosporine) followed by CNI withdrawal at week 7-11 posttransplant or (2) standard-exposure cyclosporine, both with mycophenolate mofetil and corticosteroids; 95/115 randomized patients were followed up at 5-7 years posttransplant. RESULTS: Mean measured glomerular filtration rate was 74.7 mL/min and 62.4 mL/min with everolimus and CNI, respectively. The mean difference was in favor of everolimus by 11.8 mL/min in the intent-to-treat population (P = 0.004) and 17.2 mL/min in the per protocol population (n = 75; P < 0.001). From transplantation to last follow-up, the incidence of biopsy-proven acute rejection (BPAR) was 77% (37/48) and 66% (31/47) (P = 0.23) with treated BPAR in 50% and 23% (P < 0.01) in the everolimus and CNI groups, respectively; no episode led to hemodynamic compromise. Coronary allograft vasculopathy (CAV) assessed by coronary intravascular ultrasound was present in 53% (19/36) and 74% (26/35) of everolimus- and CNI-treated patients, respectively (P = 0.037). Graft dimensions and function were similar between the groups. Late adverse events were comparable. CONCLUSIONS: These results suggest that de novo heart transplant patients randomized to everolimus and low-dose CNI followed by CNI-free therapy maintain significantly better long-term renal function as well as significantly reduced CAV than patients randomized to standard CNI treatment. Increased BPAR in the everolimus group during year 1 did not impair long-term graft function.
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| 5. |
- Nelson, Lærke Marie, et al.
(författare)
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Mild acute cellular rejection and development of cardiac allograft vasculopathy assessed by intravascular ultrasound and coronary angiography in heart transplant recipients—a SCHEDULE trial substudy
- 2020
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 33:5, s. 517-528
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the association between mild acute cellular rejection (ACR) and the development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). Substudy of the SCHEDULE trial (n = 115), where de novo HTx recipients were randomized to (i) everolimus with early CNI elimination or (ii) CNI-based immunosuppression. Seventy-six patients (66%) were included based on matched intravascular ultrasound (IVUS) examinations at baseline and year 3 post-HTx. Biopsy-proven ACR within year 1 post-HTx was recorded and graded (1R, 2R, 3R). Development of CAV was assessed by IVUS and coronary angiography at year 3 post-HTx. Median age was 53 years (45–61), and 71% were male. ACR was recorded in 67%, and patients were grouped by rejection profile: no ACR (33%), only 1R (42%), and ≥2R (25%). Median ∆MIT (maximal intimal thickness)BL-3Y was not significantly different between groups (P = 0.84). The incidence of CAV was 49% by IVUS and 26% by coronary angiography with no significant differences between groups. No correlation was found between number of 1R and ∆MITBL-3Y (r = −0.025, P = 0.83). The number of 1R was not a significant predictor of ∆MITBL-3Y (P = 0.58), and no significant interaction with treatment was found (P = 0.98). The burden of mild ACR was not associated with CAV development.
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Ahmed, Abdulla, et al.
(författare)
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Evaluation of the European Society of Cardiology/European Respiratory Society derived three-and four-strata risk stratification models in pulmonary arterial hypertension : Introducing an internet-based risk stratification calculator
- 2023
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Ingår i: European Heart Journal Open. - : Oxford University Press (OUP). - 2752-4191. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Estimation of prognosis in pulmonary arterial hypertension (PAH) has been influenced by that various risk stratification models use different numbers of prognostic parameters, as well as the lack of a comprehensive and time-saving risk assessment calculator. We therefore evaluated the various European Society of Cardiology (ESC)-/European Respiratory Society (ERS)-based three-and four-strata risk stratification models and established a comprehensive internet-based calculator to facilitate risk assessment. Methods and results: Between 1 January 2000 and 26 July 2021, 773 clinical assessments on 169 incident PAH patients were evaluated at diagnosis and follow-ups. Risk scores were calculated using the original Swedish Pulmonary Arterial Hypertension Registry (SPAHR)/Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) three-strata model, the updated SPAHR three-strata model with divided intermediate risk, and the simplified three-parameter COMPERA 2.0 four-strata model. The original SPAHR/COMPERA and the updated SPAHR models were tested for both 3-6 and 7-11 available parameters, respectively. Prognostic accuracy [area under the receiver operating characteristic (ROC) curve (AUC)] and Uno's cumulative/time-dependent C-statistics (uAUC) were calculated for 1-, 3-, and 5-year mortality. At baseline, both the original SPAHR/COMPERA and the updated SPAHR models, using up to six parameters, provided the highest accuracy (uAUC = 0.73 for both models) in predicting 1-, 3-, and 5-year mortality. At follow-ups, the updated SPAHR model with divided intermediate risk (7-11 parameters) provided the highest accuracy for 1-, 3-, and 5-year mortality (uAUC = 0.90), followed by the original SPAHR/COMPERA model (7-11 parameters) (uAUC = 0.88) and the COMPERA 2.0 model (uAUC = 0.85). Conclusions: The present study facilitates risk assessment in PAH by introducing a comprehensive internet-based risk score calculator (https://www.svefph.se/risk-stratification). At baseline, utilizing the original or the updated SPAHR models using up to six parameters was favourable, the latter model additionally offering sub-characterization of the intermediate risk group. Our findings support the 2022 ESC/ERS pulmonary hypertension guidelines' strategy for risk stratification suggesting the utilization of a three-strata model at baseline and a simplified four-strata model at follow-ups. Our findings furthermore support the utility of the updated SPAHR model with divided intermediate risk, when a more comprehensive assessment is needed at follow-ups, complementing the three-parameter COMPERA 2.0 model. Larger multi-centre studies are encouraged to validate the utility of the updated SPAHR model. Take home message: By introducing an internet-based risk score calculator (https://www.svefph.se/risk-stratification), risk assessment is facilitated. Our results support the 2022 ESC/ERS pulmonary hypertension guidelines' risk stratification strategy, additionally suggesting the updated SPAHR three-strata model with divided intermediate risk, as a promising complement to the new simplified three-parameter COMPERA 2.0 four-strata strategy, when a more comprehensive overview is needed.
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| 9. |
- Ahmed, Abdulla, et al.
(författare)
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Plasma ADAMTS13 and von Willebrand factor in diagnosis and prediction of prognosis in pulmonary arterial hypertension
- 2021
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Ingår i: Pulmonary Circulation. - : Wiley. - 2045-8932 .- 2045-8940. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- To improve outcome in pulmonary arterial hypertension, earlier diagnosis and better prognostic assessments are required. We aimed to investigate the diagnostic and prognostic potential of plasma proteins related to pathways recognized in pulmonary arterial hypertension including coagulation, inflammation, and metabolism. Forty-two proteins were analysed with proximity extension assay from plasma of 20 healthy controls and 150 patients, including (pulmonary arterial hypertension, n = 48, whereof 33 also during early treatment follow-ups); chronic thromboembolic pulmonary hypertension (CTEPH, n = 20); pulmonary hypertension (PH) due to heart failure (HF) with preserved ejection fraction (HFpEF-PH, n = 31); PH due to HF with reduced ejection fraction (HFrEF-PH, n = 36); and HF without PH (Dyspnoea/HF-non-PH, n = 15). Patients’ haemodynamics were assessed by right heart catheterization. Plasma ADAMTS13 in incident pulmonary arterial hypertension was lower compared to the healthy controls (p = 0.055), as well as CTEPH (p < 0.0001), HFrEF-PH (p < 0.0001), HFrEF-PH (p < 0.0001), and Dyspnoea/HF-non-PH (p < 0.0001). Adjusted for age and sex, ADAMTS13 discriminated pulmonary arterial hypertension from the other disease groups with an AUC of 0.91 (sensitivity = 87.5%, and specificity = 78.4%). Higher plasma von Willebrand factor was associated with worse survival (log-rank p = 0.0029), and a higher mortality rate (adjusted hazard ratio 1.002, 95% confidence interval 1–1.004; p = 0.041). Adjusted for age, sex, and combined with the ESC/ERS risk score, von Willebrand factor predicted mortality (median follow-up 3.6 years) in pulmonary arterial hypertension with an AUC of 0.94 (sensitivity = 81.3%, and specificity=93.8%). ADAMTS13 may be a promising biomarker for early detection of PAH and von Willebrand factor as a candidate prognostic biomarker. The putative additional value of von Willebrand factor to the European multiparametric risk assessment strategy remains to be elucidated.
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| 10. |
- Ahmed, Abdulla, et al.
(författare)
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Prognostisk riskstratifiering vid pulmonell arteriell hypertension
- 2023
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Ingår i: Lakartidningen. - 0023-7205. ; 120
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Tidskriftsartikel (refereegranskat)abstract
- The 2022 ESC/ERS pulmonary hypertension guidelines recommend multiparametric risk stratification at diagnosis and follow-up to guide treatment in pulmonary arterial hypertension (PAH). The goal is to maintain or achieve a low-risk status, corresponding to a 1-year mortality < 5%. Risk assessment is, however, underutilized in clinical practice, and applied only by 60% of clinicians. To overcome the barrier of underutilization and facilitate risk assessment, we have established a comprehensive internet-based risk stratification calculator (https://www.svefph.se/risk-stratification).
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