| 1. |
- 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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| 2. |
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| 3. |
- Gjesdal, Grunde, et al.
(författare)
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Validation of cause of death classification after heart transplantation and cause-specific life expectancy compared to the general population
- 2022
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 36:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Post heart-transplant survival has increased, but information is lacking on specific causes of death and life expectancy. We aimed to assess cause-specific loss of life-years compared to the general population, evaluate classification for cause of death after heart transplantation, and assess validity of cause of death data from the International Society of Heart and Lung Transplant (ISHLT) registry. Methods: In this single center study, we included 239 heart recipients transplanted between 1988 and 2019 in Lund, Sweden (n = 239, 50% of the transplanted population where the cause of death was available). Two cardiologists retrospectively assigned causes of death according to a published classification (CLASS) in the 91 recipients who died during follow-up. Life expectancy was compared to data from the general population. Results: Compared to the average Swedish population, life expectancy for heart transplant recipients was 20 years shorter (IQR 12.9–27.2). The largest number of life-years lost were for deaths due to acute (49 years) and chronic rejection (27 years). Primary graft dysfunction (24 years) accounted for 24% of deaths, followed by malignancy (20 years) and infection (17 years), each accounting for ∼20% of deaths. Use of CLASS revealed moderate inter-rater agreement (56%) and moderate agreement with the ISHLT registry (62%). Conclusions: Survival after heart transplantation was 20 years lower than in the general population. In the young, more life-years were lost due to acute graft rejection, whereas chronic graft rejection and primary graft failure were more important causes of death in older patients. Agreement was moderate between CLASS and the ISHLT registry classifications.
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| 4. |
- Jernryd, Victoria, et al.
(författare)
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Myocardial injury biomarkers at point of care for early identification of primary graft dysfunction after heart transplantation.
- 2022
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Ingår i: Clinical transplantation. - : Wiley. - 1399-0012 .- 0902-0063. ; 36:2
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Tidskriftsartikel (refereegranskat)abstract
- Primary graft dysfunction (PGD) is a leading cause of 30- day mortality following heart transplantation, and early intervention in PGD may correlate to improved survival. Our analysis aimed to determine the feasibility of measuring cardiac biomarkers from the donor heart in the early phase for use as a predictor of PGD.Blood samples from the coronary sinus were obtained at the time of transplantation in hearts preserved by cold static storage. The samples were analyzed for CK-MB and cTnI with a point-of-care method. The primary outcome was severe PGD or the need for veno-arterial extracorporeal membrane oxygenation within 7 days, referred to as severe graft dysfunction.Of the total cohort (n = 63), eight patients (13%) were diagnosed with severe graft dysfunction within 7 days. Patients with high CK-MB had an increased risk for severe graft dysfunction with unadjusted Odds Ratio (OR) of 4.5 (95%CI 0.96-21.11 p = 0.057) and adjusted OR of 7.4 (95%CI 1.13-48.46, p = 0.037. Similar but non Clinical Transplantation For Review Only significant trends were observed for cTnI.By measuring CK-MB from the coronary effluent in the donor heart, it may be possible to identify patients at increased risk for severe PGD after heart transplantation. This article is protected by copyright. All rights reserved.
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| 5. |
- Jernryd, Victoria, et al.
(författare)
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The influence of ischemia and reperfusion time on outcome in heart transplantation
- 2020
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 34:5
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Tidskriftsartikel (refereegranskat)abstract
- Ischemia/reperfusion may lead to graft dysfunction in heart transplantation (HT). The purpose of this study was to evaluate the influence of ischemic and reperfusion time on acute cellular rejection (ACR) within the first-year post-HT and on long-term outcomes. Data were collected from 331 patients (mean age 49 ± 12 y, 28% females) who underwent HT 1988-2016. Endomyocardial biopsies obtained within the first year after HT were graded according to the 2004-ISHLT-WF. We classified the patients by ischemic time 4 hours, and of these, 31 (55%) patients had reperfusion with CPB ≥90 minutes. Ischemia >4 hours had an increased risk of ACR ≥ 2R during the first year (adjusted OR = 3.1, P =.016); however, an extended reperfusion ≥90 minutes reduced the risk (adjusted OR = 0.25, P =.024). The conditional probability of surviving 10 years post-transplant, given that the patients already survived first year, was inferior for recipients with ischemia ≥ 4 hours and reperfusion <90 minutes, 59%, compared with the other groups 83%, P =.016. Prolonged reperfusion appears to reduce the risk for ACR ≥ 2R and improve long-term survival.
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| 6. |
- Martensson, T., et al.
(författare)
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Clinical relevance of endoscopy with histopathological assessment in children with suspected gastrointestinal graft-versus-host disease
- 2020
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 34:7
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Tidskriftsartikel (refereegranskat)abstract
- Endoscopy with histopathological assessment is an established practice to confirm gastrointestinal graft-versus-host disease (GI-GVHD). However, the clinical relevance of this approach in children is incompletely evaluated. In a retrospective cohort study, we investigated the frequency of treatment changes in response to histopathological findings in all children (<18 years) in Sweden who underwent endoscopy for suspected GI-GVHD (2000-2013) after receiving hematopoietic stem cell transplantation. Sixty-eight children with ninety-one endoscopic occasions were enrolled. At the time of endoscopy, anti-GI-GVHD treatment was ongoing in 71% (65/91). In 18% (12/65) with ongoing treatment, no histopathological evidence of GI-GVHD or another cause to justify anti-GI-GVHD treatment was found. In 48% (44/91), endoscopy with histopathological assessment led to changes in the treatment regimen. Re-endoscopy was more frequent among those with treatment changes, versus unchanged treatment, 39% (17/44) and 13% (6/47), respectively (P = .007). Histopathological findings generating treatment changes were as follows: GI-GVHD in 68% (30/44), normal histology in 25% (11/44), and an alternative diagnosis in 7% (3/44). In conclusion, this study supports that endoscopy with histopathological assessment should be considered in all children with suspected GI-GVHD.
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| 7. |
- Mölne, Johan, et al.
(författare)
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Glomerular macrophage index (GMI) in kidney transplant biopsies is associated with graft outcome
- 2022
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Ingår i: Clinical Transplantation. - : John Wiley & Sons. - 0902-0063 .- 1399-0012. ; 36:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Macrophages in renal transplants have been shown to participate in antibody-mediated rejection and are associated with impaired renal function. We calculated the glomerular macrophage index (GMI) in a large transplant biopsy cohort, studied its quantity in different diagnostic groups, to clarify its possible impact on graft survival.Methods: GMI, defined as the mean number of macrophages in 10 glomeruli, was prospectively quantified in 1440 renal transplant biopsies over a 10-year period. The main histopathological diagnoses were grouped into eight disease entities, and GMI was compared to normal transplant biopsies as the reference group. The impact of GMI on graft survival was analyzed.Results: GMI was highest in chronic (mean 9.4) and active (9.7) antibody mediated rejections (ABMR), mixed rejections (7.6), and recurrent or de novo glomerulonephritis (7.5) and differed significantly from normal transplants (1.3) in almost all diagnostic groups. Hazard ratios for graft loss were significantly increased for all biopsies with GMI ≥1.9 compared to GMI <.5 (reference group) in an adjusted Cox regression model and increased with higher GMI levels. Biopsies with GMI ≥ 4.6 had < 60% 10-year graft-survival, compared to > 80% with GMI ≤ 1.8.Conclusion: GMI levels were predictive of graft loss independent of histological diagnoses and may guide clinicians to decide follow-up and therapy.
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| 8. |
- Nasic, Salmir, et al.
(författare)
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Changes in numbers of glomerular macrophages between two consecutive biopsies and the association with renal transplant graft survival
- 2024
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Ingår i: Clinical Transplantation. - : John Wiley & Sons. - 0902-0063 .- 1399-0012. ; 38:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Macrophages are involved in kidney transplants. The aim of the study was to investigate if changes exist in the levels of glomerular macrophage index (GMI) between two consecutive kidney transplant biopsies, and if so to determine their potential impact on graft survival.Methods: Two consecutive biopsies were performed on the same renal graft in 623 patients. GMI was categorized into three GMI classes: ≤1.8 Low, 1.9–4.5 Medium, and ≥4.6 High. This division yielded nine possible switches between the first and second biopsies (Low-Low, Low-Medium, etc.). Cox-regressions were used and hazard ratios (HR) with 95% confidence interval (CI) are presented.Results: The worst graft survival was observed in the High-High group, and the best graft survival was observed in the Low-Low and High-Low groups. Compared to the High-High group, a reduction of risk was observed in nearly all other decreasing groups (reductions between 65% and 80% of graft loss). After adjustment for covariates, the risk for graft-loss was lower in the Low-Low (HR = 0.24, CI 0.13–0.46), Low-Medium (HR = 0.25, CI 0.11–0.55), Medium-Low (HR = 0.29, CI 0.11–0.77), and the High-Low GMI (HR = 0.31, CI 0.10–0.98) groups compared to the High-High group as the reference.Conclusions: GMI may change dynamically, and the latest finding is of most prognostic importance. GMI should be considered in all evaluations of biopsy findings since high or increasing GMI levels are associated with shorter graft survival. Future studies need to consider therapeutic strategies to lower or maintain a low GMI. A high GMI besides a vague histological finding should be considered as a warning sign requiring more frequent clinical follow up.
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| 9. |
- Nozohoor, Shahab, et al.
(författare)
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Induction immunosuppression strategies and long-term outcomes after heart transplantation
- 2020
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 34:7
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Tidskriftsartikel (refereegranskat)abstract
- Although the use of induction therapy has reduced the risk of acute rejection after heart transplantation, its use may be associated with other adverse outcomes. We aimed to examine the effect of no induction (NoInd), induction with basiliximab (BAS), or induction with antithymocyte globulin (ATG) on outcome after heart transplantation. We analyzed data from the International Society for Heart and Lung Transplantation (ISHLT) registry for adult heart transplants performed between 2000 and 2013. The primary outcome was cumulative all-cause mortality, and the secondary outcome was cause-specific death. We identified 27 369 transplants whose recipients received NoInd (n = 15 688), ATG (n = 6830), or BAS (n = 4851). Over a median follow-up of 1497 days, overall 30-day mortality was 5% and 1-year mortality was 11%. Survival after transplant was similar in patients treated with NoInd compared with ATG. The survival was improved using NoInd compared with BAS (log-rank P =.040), adjustment HR = 1.11 (95% CI, 1.04-1.19). Compared to NoInd, BAS was associated with higher risk of graft failure-related deaths, HR = 1.27 (95% CI, 1.02-1.58), and ATG was associated with higher risk of malignancy-related deaths, HR = 1.18 (95% CI, 1.01-1.39). Survival of patients who received NoInd was similar to ATG and better compared with BAS. Further, the use of ATG may be associated with increased malignancy-related mortality, compared with NoInd.
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| 10. |
- Svensson, Carl Johan, 1976, et al.
(författare)
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Donor heart dysfunction and graft survival in liver and kidney transplants-A register-based study from Sweden.
- 2024
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Ingår i: Clinical transplantation. - 0902-0063 .- 1399-0012. ; 38:5
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Tidskriftsartikel (refereegranskat)abstract
- Stress cardiomyopathy in donors can potentially affect graft function and longevity. This study aims to investigate the association between echocardiographic left ventricular ejection fraction (LVEF)<50%, and/or the presence of left ventricular regional wall motion abnormalities (RWMA) in organ donors, and short- and long-term liver and kidney graft survival. Our secondary aim was to link graft survival with donor and recipient characteristics.All donors considered for liver and kidney donation with echocardiographic records at Sahlgrenska University Hospital between 2006 and 2016 were matched with their recipients through the Scandiatransplant register. The studied outcomes were graft survival, re-transplantation, and recipient death. Kaplan-Meier curves were used to plot time to event. Multivariate Cox-regression was used to test independence.There were 370 liver donors and 312 kidney donors (matched with 458 recipients) with echocardiographic records at Sahlgrenska University Hospital between June 2006 and November 2016. Of patients with LV dysfunction by echocardiography, there were 102 liver- and 72 kidney donors. Univariate survival analyses showed no statistical difference in the short- and long-term graft survival from donors with LV dysfunction compared to donors without. Donor age>65 years, recipient re-transplantation and recipient liver tumor were predictors of worse outcome in liver transplants (p<.05). Donor age>65, donor hypertension, recipient re-transplantation, and a recipient diagnosis of diabetes or nephritis/glomerulonephritis had a negative association with graft survival in kidney transplants (p<.05).We found no significant association between donor LV dysfunction and short- and long-term graft survival in liver and kidney transplants, suggesting that livers and kidneys from such donors can be safely transplanted.
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