| 1. |
- Arora, Satish, et al.
(författare)
-
Virtual Histology Assessment of Cardiac Allograft Vasculopathy Following Introduction of Everolimus—Results of a Multicenter Trial
- 2012
-
Ingår i: American Journal of Transplantation. - : Wiley-Blackwell. - 1600-6135 .- 1600-6143. ; 12:10, s. 2700-2709
-
Tidskriftsartikel (refereegranskat)abstract
- In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continued standard CNI-therapy underwent matched virtual histology (VH) examination to evaluate morphological progression of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 +/- 3.8% and 1.6 +/- 3.9%, respectively; p = 0.65). However, VH analysis revealed a significant increase in calcified (2.4 +/- 4.0 vs. 0.3 +/- 3.1%; p = 0.02) and necrotic component (6.5 +/- 8.5 vs. 1.1 +/- 8.6%; p = 0.01) among everolimus patients compared to controls. The increase in necrotic and calcified components was most prominent in everolimus patients with time since HTx andgt;5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal components and is more prominent in patients with a longer time since HTx. A significant increase in vWF and VCAM accompanied these qualitative changes and the prognostic implication of these findings requires further investigation.
|
|
| 2. |
- Andreassen, A. K., et al.
(författare)
-
Everolimus Initiation and Early Calcineurin Inhibitor Withdrawal in Heart Transplant Recipients: A Randomized Trial
- 2014
-
Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 14:8, s. 1828-1838
-
Tidskriftsartikel (refereegranskat)abstract
- In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (3-6 ng/mL) with reduced-exposure cyclosporine (n 56), or standard-exposure cyclosporine (n = 59), with both mycophenolate mofetil and corticosteroids. In the everolimus group, cyclosporine was withdrawn after 7-11 weeks and everolimus exposure increased (6-10 ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean +/- SD: 79.8 +/- 17.7 mL/min/1.73m 2 vs. 61.5 +/- 19.6 mL/min/1.73m 2; p<0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03 mm [95% CI 0.01, 0.05 mm] vs. 0.08 mm [95% CI 0.05, 0.12 mm], p = 0.03), and the incidence of cardiac allograft vasculopathy (CAV) was lower (50.0% vs. 64.6%, p = 0.003), with everolimus versus cyclosporine at month 12. Biopsy-proven acute rejection after weeks 7-11 was more frequent with everolimus (p = 0.03). Left ventricular function was not inferior with everolimus versus cyclosporine. Cytomegalovirus infection was less common with everolimus (5.4% vs. 30.5%, p<0.001); the incidence of bacterial infection was similar. In conclusion, everolimus-based immunosuppression with early elimination of cyclosporine markedly improved renal function after heart transplantation. Since postoperative safety was not jeopardized and development of CAV was attenuated, this strategy may benefit long-term outcome.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Arora, Satish, et al.
(författare)
-
Effect of Everolimus Introduction on Cardiac Allograft Vasculopathy-Results of a Randomized, Multicenter Trial
- 2011
-
Ingår i: Transplantation. - : Williams and Wilkins. - 0041-1337 .- 1534-6080. ; 92:2, s. 235-243
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Everolimus reduces the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant (HTx) recipients, but the influence on established CAV is unknown. Methods. In this Nordic Certican Trial in Heart and lung Transplantation substudy, 111 maintenance HTx recipients (time post-HTx 5.8 +/- 4.3 years) randomized to everolimus+reduced calcineurin inhibitor (CNI) or standard CNI had matching (intravascular ultrasound) examinations at baseline and 12 months allowing accurate assessment of CAV progression. Results. No significant difference in CAV progression was evident between the treatment groups (P=0.30). When considering patients receiving concomitant azathioprine (AZA) therapy (n=39), CAV progression was attenuated with everolimus versus standard CNI (Delta maximal intimal thickness 0.00 +/- 0.04 and 0.04 +/- 0.04 mm, Delta percent atheroma volume 0.2%+/- 3.0% and 2.6%+/- 2.5%, and Delta total atheroma volume 0.25 +/- 14.1 and 19.8 +/- 20.4 mm(3), respectively [Pless than0.05]). When considering patients receiving mycophenolate mofetil (MMF), accelerated CAV progression occurred with everolimus versus standard CNI (Delta maximal intimal thickness 0.06 +/- 0.12 vs. 0.02 +/- 0.06 mm and Delta percent atheroma volume 4.0%+/- 6.3% vs. 1.4%+/- 3.1%, respectively; Pless than0.05). The levels of C-reactive protein and vascular cell adhesion molecule-1 declined significantly with AZA+everolimus, whereas MMF+everolimus patients demonstrated a significant increase in levels of C-reactive protein, vascular cell adhesion molecule-1, and von Willebrand factor. Conclusions. Conversion to everolimus and reduced CNI does not influence CAV progression among maintenance HTx recipients. However, background immunosuppressive therapy is important as AZA+everolimus patients demonstrated attenuated CAV progression and a decline in inflammatory markers, whereas the opposite pattern was seen with everolimus +MMF. The different effect of everolimus when combined with AZA versus MMF could potentially reflect hitherto unknown interactions.
|
|
| 7. |
|
|
| 8. |
- Arora, Satish, et al.
(författare)
-
Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: The significance of baseline glomerular filtration rate
- 2012
-
Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier. - 1053-2498 .- 1557-3117. ; 31:3, s. 259-265
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant (FIX) recipients. Nevertheless, introduction of everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst TTx recipients with advanced renal failure. less thanbrgreater than less thanbrgreater thanMETHODS: This 12-month multicenter Scandinavian study randomized 282 maintenance TTx recipients to everolimus introduction with calcineurin inhibitor (CNI) reduction or standard CNI therapy. The measured glomerular filtration rate (mGFR) was noted at baseline and after 1-year using Cr-ethylenediarninetetraacetic acid clearance. less thanbrgreater than less thanbrgreater thanRESULTS: In 21 patients with a baseline mGFR of 20 to 29 ml/min/1.73 m(2), renal function improved in the everolimus group compared with the control group ((Delta mGFR 6.7 +/- 9.0 vs -1.6 +/- 5.1 ml/min/1.73 m(2); p = 0.03). Amongst 173 patients with moderate renal impairment (mGFR 30-59 ml/min/1.73 m(2)), renal function improvement was also greater amongst everolimus patients than in controls (Delta mGFR 5.1 +/- 11.1 vs -0.5 +/- 8.7 ml/min/1.73 m(2); p andlt; 0.01). In 55 patients with mGFR 60 to 89 ml/min/1.73 m(2), mGFR did not change significantly in either group. Improvement in mGFR was limited to patients with a median time since TTx of less than 4.6 years and was also influenced by CM reduction during the study period. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: Everolimus introduction and reduced CNI significantly improved renal function amongst maintenance TTx patients with pre-existing advanced renal failure. This beneficial effect was limited to patients undergoing conversion in less than 5 years after TTx, indicating a window of opportunity that is appropriate for pharmacologic intervention with everolimus.
|
|
| 9. |
- Cinthio, Magnus, et al.
(författare)
-
A Method for Arterial Diameter Change Measurements Using Ultrasonic B-Mode Data.
- 2010
-
Ingår i: Ultrasound in Medicine and Biology. - : Elsevier BV. - 0301-5629. ; 36:9, s. 1504-1512
-
Tidskriftsartikel (refereegranskat)abstract
- Arterial diameter change is related to distending blood pressure and is used in estimation of arterial stiffness parameters. A common technique to track the arterial walls is by integration of wall velocities estimated by different methods using cross correlation or tissue Doppler. However, because of the high pulse repetition frequency and the need for separate pulsing sequences, the B-mode image quality is affected. We have previously developed a fast algorithm for direct measurement of lumen diameter using B-mode images. In this study we have improved the technique to be more robust and also implemented measurements of diameter change, maximum differential wall velocity and relative diameter change of the common carotid artery noninvasively in vivo. The influence of the lateral width of the region of interest (ROI; 1 pixel, 0.1 mm, 0.5 mm, 1 mm, 2.5 mm and 5 mm) was evaluated. Using the optimal lateral width (2.5 mm), the systematic and random differences between two consecutive measurements were 21 mum and 105 mum, respectively, for lumen diameter measurement; -7 mum and 39 mum, respectively, for lumen diameter change measurements; -0.2 mm/s and 0.9 mm/s, respectively, for maximum relative wall velocity; and -0.2 % and 0.8 %, respectively, for measurements of the relative diameter change. The coefficient of variation (CV) was 1.9%, 5.2%, 7.9% and 6.0%, respectively. The study indicates that the reproducibility is sufficient for in vivo studies when the width of the ROI is 1.0 mm or wider. (E-mail: magnus.cinthio@elmat.lth.se).
|
|
| 10. |
- Cinthio, Magnus, et al.
(författare)
-
An automatic method for measurements of arterial intima-media thickness using ultrasonic B-mode data
- 2012
-
Ingår i: Acoustical Imaging. - Dordrecht : Springer Netherlands. - 9789400726185 - 9789400726192 ; 31, s. 115-122
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We have previously developed algorithms that use B-mode cineloops for simultaneous measurements of arterial diameter change and longitudinal movement of the arterial wall. In this study the lumen diameter algorithm was extended to also measure arterial intima-media thickness of the far wall. To optimize the algorithm the influence of the lateral width of the region-of-interest (1 pixel, 0.1 mm, 0.5 mm, 1 mm, 2.5 mm and 5 mm) was evaluated. The algorithm estimated intima-media thickness at diastole automatically by measuring the distance between the two positions where the laterally averaged B-mode intensity envelope crosses a threshold value relative to the maximum amplitudes of the intimal and adventitial echoes, respectively. The sub-pixel resolution is achieved by solving the equation of a straight line between the two samples on either side of the threshold value. The measurements were performed on 20 healthy normotensive volunteers (age 25–57 years) on the common carotid artery 2–3 cm proximal to the bifurcation. For the 2.5-mm width, which was considered the best, the intima-media thickness was mean 646 μm (SD 66) for men and 613 μm (SD 68) for women. The systematic difference was −5 μm and the random difference was 31 μm. The CV was 4.9%. The study indicates that the reproducibility is sufficient for in vivo studies when the width of the region-of-interest is 1.0 mm or wider.
|
|
