| 1. |
- Arora, S., et al.
(author)
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The Effect of Everolimus Initiation and Calcineurin Inhibitor Elimination on Cardiac Allograft Vasculopathy in De Novo Recipients: One-Year Results of a Scandinavian Randomized Trial
- 2015
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In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 15:7, s. 1967-1975
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Journal article (peer-reviewed)abstract
- Early initiation of everolimus with calcineurin inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of calcineurin inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete calcineurin inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (SD) recipient age was 49.9 +/- 13.1 years. The everolimus group (n=47) demonstrated significantly reduced CAV progression as compared to the calcineurin inhibitor group (n=48) (Maximal Intimal Thickness 0.03 +/- 0.06 and 0.08 +/- 0.12mm, Percent Atheroma Volume 1.3 +/- 2.3 and 4.2 +/- 5.0%, Total Atheroma Volume 1.1 +/- 19.2mm(3) and 13.8 +/- 28.0mm(3) [all p-values0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the calcineurin inhibitor group (p=0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.
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| 3. |
- Esmaily, Sorosh, et al.
(author)
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Patient Outcomes after Heart Transplantation in Sweden between 1988 and 2017: Continuous Improvement in Survival.
- 2020
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In: The Journal of heart and lung transplantation. 39 (4), S284. - : Elsevier BV. - 1557-3117 .- 1053-2498.
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Conference paper (peer-reviewed)abstract
- To investigate the survival of heart transplant (HTx) recipients during different time periods in Sweden. We hypothesized that the survival for HTx recipients has improved following advancements in the management of these patients.Data was obtained through the database of the organ exchange organization Scandiatransplant. All patients who underwent HTx in Sweden between Jan 1988 and Dec 2017 were included. Patients were divided into five cohorts of six-year periods each.A total of 1137 HTx recipients were included. Main causes of transplantation were dilated cardiomyopathy (44 %) and ischemic heart disease (18 %). Retransplantation constituted a small portion of the overall total (2 %). The cohorts were similar in terms of age and gender, while later cohorts had higher BMI, lower GFR and longer ischemia time (Tab. 1). The later cohorts received organs from older donors (Tab. 1). The amount of heart transplantations performed in Sweden has increased with time (Tab. 1). Log-rank test comparing the survival curves was able to show improved survival during later eras (Fig. 1).Survival among HTx recipients has significantly improved in Sweden over time, despite less favorable recipients and donor characteristics. This was related to both reduced postoperative mortality and also improved long-time survival.
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| 6. |
- Werther Evaldsson, A., et al.
(author)
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Echocardiographic right ventricular strain from multiple apical views is superior for assessment of right ventricular systolic function
- 2019
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In: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961. ; 39:2, s. 168-176
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Journal article (peer-reviewed)abstract
- Background: Right ventricular (RV) systolic function is an important determinant of outcome in patients with pulmonary hypertension (PH). Conventional echocardiographic measures of RV are mainly based on longitudinal contractility. Recently, measurement of RV global longitudinal strain derived from multiple windows (RVGLS) has emerged as an option but has not been well evaluated. The aim of the present study was to evaluate which echocardiographic RV function parameter correlates best with RV ejection fraction derived from cardiac magnetic resonance imaging (RVEFCMR). Methods and results: Fifty-five patients evaluated for PH underwent RV assessment with echocardiography and CMR. Conventional echocardiographic parameters of RV function including tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (S′), RV fractional area change (RVFAC) and RV index of myocardial performance (RIMP). RVGLS was measured from three separate apical views using a 17-segment model and strain from the lateral free wall was calculated separately (RVfree). The study included 55 patients, whereas assessment of RVGLS could be obtained in 29 patients. The Pearson correlation coefficient with RVEFCMR was strong for RVGLS (r = 0·814, P<0·001) and RVfree (r = 0·778, P<0·001), modest for RVFAC (r = 0·681, P<0·001), TAPSE (r = 0·592, P<0·001) and RIMP (r=−0·521, P<0·01), and weak for S′ (r = 0·385, P<0·01). Conclusion: The echocardiographic RV measures, RVGLS and RVfree correlated well with RVEFCMR, whereas correlation with TAPSE, RIMP and S′ was unsatisfactory. Our findings suggest that RVGLS and RVfree are the preferred echocardiographic methods for clinical practice. RVfree is easiest to perform but RVGLS could provide incremental value in selected patients.
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| 7. |
- Andreassen, A. K., et al.
(author)
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Everolimus Initiation and Early Calcineurin Inhibitor Withdrawal in Heart Transplant Recipients: A Randomized Trial
- 2014
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In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 14:8, s. 1828-1838
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Journal article (peer-reviewed)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.
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| 8. |
- Andreassen, A. K., et al.
(author)
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Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study
- 2016
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In: American Journal of Transplantation. - : WILEY-BLACKWELL. - 1600-6135 .- 1600-6143. ; 16:4, s. 1238-1247
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Journal article (peer-reviewed)abstract
- In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6ng/mL) with reduced-exposure calcineurin inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4mL/min (standard deviation [SD] 20.2mL/min) versus 59.2mL/min (SD 17.4mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3mL/min (95% CI 11.1-25.6mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade 2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p=0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage. A follow-up study of the SCHEDULE trial, which randomized de novo heart transplant recipients to everolimus with cyclosporine discontinuation or to standard-exposure cyclosporine, shows that measured glomerular filtration rate remains significantly higher in the everolimus group at three years posttransplant, with significantly reduced progression of allograft vasculopathy compared to cyclosporine therapy.
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| 14. |
- Kylhammar, D., et al.
(author)
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Angiogenic and inflammatory biomarkers for screening and follow-up in patients with pulmonary arterial hypertension
- 2018
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 47:4, s. 319-324
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Journal article (peer-reviewed)abstract
- Objective: To identify circulating angiogenic and inflammatory biomarkers with potential in screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc), and in early diagnosis and determination of treatment response in PAH. Method: Plasma samples were taken at the time of PAH diagnosis and at treatment follow-up after a median (interquartile range) of 4 months (3–9.8 months) in idiopathic (n = 9) and SSc-associated PAH (n = 11). In patients with SSc-associated PAH, plasma samples had also been gathered a median of 2 years (0.8–3 years) before PAH diagnosis (n = 10). Additional plasma samples were retrieved at two time-points separated by a median of 12 years (10–13 years) from SSc patients who did not develop PAH (n = 10) and from controls (n = 8). Angiogenic and inflammatory biomarkers were analysed by multiplex immunoassays. Results: Plasma levels of placenta growth factor (PlGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), and tumour necrosis factor-α (TNF-α) were higher (p < 0.05) in SSc patients who later developed PAH than in those who did not. Plasma vascular endothelial growth factor (VEGF)-D increased (p < 0.05) in SSc patients as PAH developed. Plasma levels of PlGF, VEGF-A, VEGF-D, sVEGFR-1, interleukin-6, and TNF-α were higher (p < 0.05) in PAH than controls. There were no significant differences in circulating biomarkers between idiopathic and SSc-associated PAH. Plasma sVEGFR-1 decreased (p < 0.05) after initiating PAH-targeted treatments. Conclusions: Plasma levels of PlGF, sVEGFR-1, TNF-α, and VEGF-D have potential in screening for SSc-associated PAH. Plasma sVEGFR-1 may be a biomarker of treatment response.
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| 15. |
- Kylhammar, D., et al.
(author)
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The principal pathways involved in the in vivo modulation of hypoxic pulmonary vasoconstriction, pulmonary arterial remodelling and pulmonary hypertension
- 2017
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In: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 219:4, s. 728-756
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Research review (peer-reviewed)abstract
- Hypoxic pulmonary vasoconstriction (HPV) serves to optimize ventilation-perfusion matching in focal hypoxia and thereby enhances pulmonary gas exchange. During global hypoxia, however, HPV induces general pulmonary vasoconstriction, which may lead to pulmonary hypertension (PH), impaired exercise capacity, right-heart failure and pulmonary oedema at high altitude. In chronic hypoxia, generalized HPV together with hypoxic pulmonary arterial remodelling, contribute to the development of PH. The present article reviews the principal pathways in the in vivo modulation of HPV, hypoxic pulmonary arterial remodelling and PH with primary focus on the endothelin-1, nitric oxide, cyclooxygenase and adenine nucleotide pathways. In summary, endothelin-1 and thromboxane A2 may enhance, whereas nitric oxide and prostacyclin may moderate, HPV as well as hypoxic pulmonary arterial remodelling and PH. The production of prostacyclin seems to be coupled primarily to cyclooxygenase-1 in acute hypoxia, but to cyclooxygenase-2 in chronic hypoxia. The potential role of adenine nucleotides in modulating HPV is unclear, but warrants further study. Additional modulators of the pulmonary vascular responses to hypoxia may include angiotensin II, histamine, serotonin/5-hydroxytryptamine, leukotrienes and epoxyeicosatrienoic acids. Drugs targeting these pathways may reduce acute and/or chronic hypoxic PH. Endothelin receptor antagonists and phosphodiesterase-5 inhibitors may additionally improve exercise capacity in hypoxia. Importantly, the modulation of the pulmonary vascular responses to hypoxia varies between species and individuals, with hypoxic duration and age. The review also define how drugs targeting the endothelin-1, nitric oxide, cyclooxygenase and adenine nucleotide pathways may improve pulmonary haemodynamics, but also impair pulmonary gas exchange by interference with HPV in chronic lung diseases.
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| 16. |
- McGlothlin, D.P., et al.
(author)
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ISHLT consensus statement: Perioperative management of patients with pulmonary hypertension and right heart failure undergoing surgery
- 2022
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In: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 41:9, s. 1135-1194
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Journal article (peer-reviewed)abstract
- Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population. This is a comprehensive document that includes common perioperative patient populations and surgical procedures with unique considerations. © 2022 International Society for Heart and Lung Transplantation
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| 17. |
- Ostenfeld, E., et al.
(author)
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Regional contribution to ventricular stroke volume is affected on the left side, but not on the right in patients with pulmonary hypertension
- 2016
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In: International Journal of Cardiovascular Imaging. - : Springer Science and Business Media LLC. - 1569-5794 .- 1573-0743. ; 32:8, s. 1243-1253
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Journal article (peer-reviewed)abstract
- To develop more sensitive measures of impaired cardiac function in patients with pulmonary hypertension (PH), since detection of impaired right ventricular (RV) function is important in these patients. With the hypothesis that a change in septal function in patients with PH is associated with altered longitudinal and lateral function of both ventricles, as a compensatory mechanism, we quantified the contributions of these parameters to stroke volume (SV) in both ventricles using cardiac magnetic resonance (CMR). Seventeen patients (10 females) evaluated for PH underwent right heart catheterization (RHC) and CMR. CMR from 33 healthy adults (13 females) were used as controls. Left ventricular (LV) atrioventricular plane displacement (AVPD) and corresponding longitudinal contribution to LVSV was lower in patients (10.8 ± 3.2 mm and 51 ± 12 %) compared to controls (16.6 ± 1.9 mm and 59 ± 9 %, p <0.0001 and p <0.01, respectively). This decrease did not differ in patient with ejection fraction (EF) >50 % and
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