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  • 1.
    Andreassen, A. K.
    et al.
    Oslo University Hospital, Norway.
    Andersson, B.
    Sahlgrens University Hospital, Sweden.
    Gustafsson, F.
    Rigshosp, Denmark.
    Eiskjaer, H.
    Aarhus University Hospital, Denmark.
    Radegran, G.
    Lund University, Sweden; Lund University, Sweden.
    Gude, E.
    Oslo University Hospital, Norway.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Solbu, D.
    Novartis Norge AS, Norway.
    Karason, K.
    Sahlgrens University Hospital, Sweden.
    Arora, S.
    Oslo University Hospital, Norway.
    Dellgren, G.
    Sahlgrens University Hospital, Sweden.
    Gullestad, L.
    Oslo University Hospital, Norway; University of Oslo, Norway; University of Oslo, Norway.
    Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study2016In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 16, no 4, p. 1238-1247Article in journal (Refereed)
    Abstract [en]

    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.

  • 2.
    Andreassen, A.K.
    et al.
    University of Oslo, Norway .
    Andersson, B.
    Sahlgrens University Hospital, Sweden .
    Gustafsson, F.
    Rigshosp, Denmark .
    Eiskjaer, H.
    Aarhus University Hospital, Denmark .
    Rdegran, G.
    Skåne University Hospital, Sweden Lund University, Sweden .
    Gude, E.
    University of Oslo, Norway .
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Solbu, D.
    Novartis Norge AS, Norway .
    Sigurdardottir, V.
    Sahlgrens University Hospital, Sweden .
    Arora, S.
    University of Oslo, Norway .
    Dellgren, G.
    Sahlgrens University Hospital, Sweden .
    Gullestad, L.
    University of Oslo, Norway University of Oslo, Norway University of Oslo, Norway .
    Everolimus Initiation and Early Calcineurin Inhibitor Withdrawal in Heart Transplant Recipients: A Randomized Trial2014In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 14, no 8, p. 1828-1838Article in journal (Refereed)
    Abstract [en]

    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; pless than0.001). 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%, pless than0.001); 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.
    Arbring, Kerstin
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Chaireti, Roza
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    First experience of structured introduction of new oral anticoagulants in a Swedish health care district: dabigatran as an alternative to warfarin in atrial fibrillation2013Conference paper (Refereed)
  • 4.
    Arora, S
    et al.
    Oslo University Hospital, Rikshosp, Oslo, Norway .
    Erikstad, I
    Oslo University Hospital, Rikshosp, Oslo, Norway .
    Wennerblom, B
    Sahlgrens University Hospital, Gothenburg, Sweden .
    Sigurdardottir, V
    Sahlgrens University Hospital, Gothenburg, Sweden .
    Eiskjaer, H
    Skeiby University Hospital, Aarhus, Denmark .
    Botker, H
    Skeiby University Hospital, Aarhus, Denmark .
    -A Mortensen, S
    Rigshosp, Copenhagen.
    Saunameki, K
    Rigshosp, Copenhagen.
    Ekmehag, B
    Lund Hospital.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Simonsen, S
    Oslo University Hospital.
    Gude, E
    Oslo University Hospital.
    Ragnarsson, A
    Oslo University Hospital.
    Solbu, D
    Novartis Norge.
    Gullestad, L
    Oslo University Hospital.
    Effect of Everolimus Introduction and Calcineurin Inhibitor Reduction on Cardiac Allograft Vasculopathy Assessed by Virtual Histology in JOURNAL OF HEART AND LUNG TRANSPLANTATION, vol 30, issue 4, pp S33-S342011In: JOURNAL OF HEART AND LUNG TRANSPLANTATION, ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA , 2011, Vol. 30, no 4, p. S33-S34Conference paper (Refereed)
    Abstract [en]

    n/a

  • 5.
    Arora, S
    et al.
    Oslo University Hospital.
    Rundqvist, B
    Sahlgrens University Hospital.
    Mortensen, S-A
    Skeiby University Hospital.
    Eiskjaer, H
    Skeiby University Hospital.
    Riise, G
    Sahlgrens University Hospital.
    Mared, L
    Lund Hospital.
    Bjortuft, O
    Oslo University Hospital.
    Ekmehag, B
    Lund Hospital.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Simonsen, S
    Oslo University Hospital.
    Gude, E
    Oslo University Hospital.
    Solbu, D
    Novartis Norge.
    Iversen, M
    Skeiby University Hospital.
    Gullestad, L
    Oslo University Hospital.
    Everolimus Introduction and Calcineurin Reduction in Thoracic Transplant Recipients with Advanced Chronic Renal Failure in JOURNAL OF HEART AND LUNG TRANSPLANTATION, vol 30, issue 4, pp S25-S252011In: JOURNAL OF HEART AND LUNG TRANSPLANTATION, ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA , 2011, Vol. 30, no 4, p. S25-S25Conference paper (Refereed)
    Abstract [en]

    n/a

  • 6.
    Arora, S
    et al.
    Oslo University Hospital.
    Wennerblom, B
    Sahlgrens University Hospital.
    Rundqvist, B
    Sahlgrens University Hospital.
    Eiskjaer, H
    Skeiby University Hospital.
    E Botker, H
    Skeiby University Hospital.
    Mortensen, S-A
    Rigshosp, Copenhagen.
    Saunameki, K
    Rigshosp, Copenhagen.
    Ekmehag, B
    Lund Hospital.
    Jansson, Kjell
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Simonsen, S
    Oslo University Hospital.
    Gude, E
    Oslo University Hospital.
    Endresen, K
    Oslo University Hospital.
    Solbu, D
    Novartis Norge AS, Oslo.
    Gullestad, L
    Oslo University Hospital, Oslo.
    Effect of Everolimus Introduction and Calcineurin Inhibitor Reduction on Graft Vasculopathy in Heart Transplant Recipients in JOURNAL OF HEART AND LUNG TRANSPLANTATION, vol 29, issue 2, pp S50-S502010In: JOURNAL OF HEART AND LUNG TRANSPLANTATION, Elsevier Science B.V., Amsterdam. , 2010, Vol. 29, no 2, p. S50-S50Conference paper (Refereed)
    Abstract [en]

    n/a

  • 7.
    Arora, Satish
    et al.
    Oslo University Hospital Rikshospitalet, Norway.
    Erikstad, I.
    Oslo University Hospital Rikshospitalet, Norway.
    Ueland, T.
    Oslo University Hospital Rikshospitalet, Norway.
    Sigurdardottir, V.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ekmehag, B.
    Skåne University Hospital and Lund University, Lund, Sweden.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Eiskjaer, H.
    Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Bøtker, H. E.
    Skejby University Hospital, Denmark .
    Mortensen, S.-A.
    Rigshospitalet, Copenhagen, Denmark.
    Saunamaki, K.
    Rigshospitalet, Copenhagen, Denmark.
    Gude, E.
    Oslo University Hospital Rikshospitalet, Norway.
    Ragnarsson, A.
    Oslo University Hospital Rikshospitalet, Norway.
    Solbu, D.
    Medical Department, Novartis, Norway .
    Gullestad, L
    Oslo University Hospital Rikshospitalet, Norway.
    Virtual Histology Assessment of Cardiac Allograft Vasculopathy Following Introduction of Everolimus—Results of a Multicenter Trial2012In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 12, no 10, p. 2700-2709Article in journal (Refereed)
    Abstract [en]

    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.

  • 8.
    Arora, Satish
    et al.
    Oslo University Hospital.
    Gude, Einar
    Sahlgrens University Hospital.
    Aage Mortensen, Svend
    Skeiby University Hospital.
    Eiskjaer, Hans
    Skeiby University Hospital.
    Riise, Gerdt
    Sahlgrens University Hospital.
    Mared, Lena
    Lund Hospital.
    Bjortuft, Oystein
    Lund Hospital.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Simonsen, Svein
    University of Oslo.
    Solbu, Dag
    Novartis Norge.
    Iversen, Martin
    Skeiby University Hospital.
    Gullestad, Lars
    University of Oslo.
    Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: The significance of baseline glomerular filtration rate2012In: The Journal of Heart and Lung Transplantation, ISSN 1053-2498, E-ISSN 1557-3117, Vol. 31, no 3, p. 259-265Article in journal (Refereed)
    Abstract [en]

    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.
    Arora, Satish
    et al.
    Oslo University Hospital.
    Ueland, Thor
    Oslo University Hospital.
    Wennerblom, Bertil
    Sahlgrens University Hospital.
    Sigurdadottir, Vilborg
    Sahlgrens University Hospital.
    Eiskjaer, Hans
    Skejby University Hospital.
    E. Botker, Hans
    Skejby University Hospital.
    Ekmehag, Bjorn
    Skane University Hospital.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Mortensen, Svend-Aage
    Rigshosp, Copenhagen.
    Saunamaki, Kari
    Rigshosp, Copenhagen.
    Simonsen, Svein
    Oslo University Hospital.
    Gude, Einar
    Oslo University Hospital.
    Bendz, Bjorn
    Oslo University Hospital.
    Solbu, Dag
    Novartis, Oslo.
    Aukrust, Pal
    Oslo University Hospital.
    Gullestad, Lars
    Oslo University Hospital.
    Effect of Everolimus Introduction on Cardiac Allograft Vasculopathy-Results of a Randomized, Multicenter Trial2011In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 92, no 2, p. 235-243Article in journal (Refereed)
    Abstract [en]

    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.

  • 10.
    Granfeldt, Hans
    et al.
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Holmberg, Erica
    Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Träff, Stefan
    Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Jansson, Kjell
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Ahn, Henrik
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Long-term Quality-of-Life (QoL) in patients with progressive chronic heart failure after surgical ventricular restoration with passive ventricular constraint (CorCap-CSDTM): Comparison with a patient-matched reference group from the general populationManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Chronic heart failure have a poor prognosis with high morbidity and reduced quality of life. Ventricular constraint, the CorCap Cardiac Support Device (CSD) has been introduced with the intention of inducing reverse remodeling. Studies have shown sustained improvement in left ventricular dimensions and function after three years, but quality-of-life (QoL) has been poorly studied.

    Methods and Results: Since 2003, 26 patients with chronic progressive heart failure met the inclusion criteria for CSD. They were prospectively followed each year for five years postoperatively. Nineteen patients were scheduled for concomitant cardiac surgery.

    In a cross-sectional study, 18 patients were investigated regarding QoL using SF-36. A reference group was randomly selected from the Swedish SF-36 general population reference group.

    One-year survival for CSD-patients was 86%, three-year survival was 76%. After a mean follow-up time after surgery of 3.9 years (range; 0.9 to 7 years), no difference in QoL measured with SF-36 was found. Echocardiographic dimensions and QoL improved significantly after three years for isolated CSD patients.

    Conclusions: QoL in patients operated with CSD, measured with SF-36-questionnaire, more than three years after implantation, is comparable to a matched general population reference group. In the CSD group alone, QoL improved significantly after three years.

  • 11.
    Granfeldt, Hans
    et al.
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Peterzén, Bengt
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Hubbert, Laila
    Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Casimir Ahn, Henrik
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    A single center experience with the HeartMate II (TM) Left Ventricular Assist Device (LVAD)2009In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 43, no 6, p. 360-365Article in journal (Refereed)
    Abstract [en]

    Objectives. Left ventricular assist devices (LVAD), used in the setting bridge-to-transplantation and destination therapy, for patients with deteriorating severe heart failure are continuously developing. The second generation, the axial flow pumps, have been introduced since some years. Design. Eleven consecutive patients, seven male, with severe heart failure due to ischemic cardiomyopathy (n = 5), dilated cardiomyopathy (n = 5) and cytotoxic ethiology (n = 1) were implanted with the HeartMate-II (TM). They were preoperatively treated with inotropic support (n = 9), ventricular assist device (n = 2) and mechanical ventilation (n = 4). Results. Eight patients were bridged to transplant after median 155 days (range, 65 to 316 days). One patient is ongoing for 748 days, intended for destination therapy. Ten of eleven patients were discharged after median 64 days (range, 40 to 105 days). Four patients were reoperated due to bleeding. Two embolic events were recorded. One perioperative death. Conclusion. Eleven HM-II (TM) LVADs have been implanted in our institution with good early results. Eight patients were successfully bridged to heart transplantation. One patient is intended for destination therapy and is ongoing since November 2006. In these severely ill patients, this technique offers a good chance surviving until heart transplantation. In selected cases the technique also offers the possibility of a permanent support and longevity.

  • 12.
    Gullestad, L
    et al.
    Oslo University Hospital.
    Rundqvist, B
    Sahlgrens University Hospital.
    A Mortensen, S
    Rigshosp, Copenhagen.
    Eiskjaer, H
    Aarhus University Hospital.
    C Riise, G
    Sahlgrens University Hospital.
    Mared, L
    Lund University.
    Bjortuft, O
    Oslo University Hospital.
    Ekmehag, B
    Lund University.
    Jansson, Kjell
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Simonsen, S
    Oslo University Hospital.
    Gude, E
    Oslo University Hospital.
    Fagertun, H
    Oslo University Hospital.
    Solbu, D
    Oslo University Hospital.
    Iversen, M
    Rigshosp, Copenhagen.
    Everolimus Introduction with CNI Minimization Significantly Improves Renal Function in Thoracic Transplant Recipients: A Scandinavian Multicenter, Randomized Study in JOURNAL OF HEART AND LUNG TRANSPLANTATION, vol 29, issue 2, pp S49-S492010In: JOURNAL OF HEART AND LUNG TRANSPLANTATION, Elsevier Science B.V., Amsterdam. , 2010, Vol. 29, no 2, p. S49-S49Conference paper (Refereed)
    Abstract [en]

    n/a

  • 13.
    Gullestad, Lars
    et al.
    Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.
    Eiskjaer, Hans
    Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
    Gustafsson, Finn
    Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
    Riise, Gerdt C
    Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Karason, Kristjan
    Department of Cardiology and Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Dellgren, Göran
    Department of Cardiology and Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Rådegran, Göran
    Department of Clinical Sciences Lund, Cardiology, Lund University and the Section for Heart Failure and Valvular Disease, Skåne University Hospital, Lund, Sweden.
    Hansson, Lennart
    Department of Respiratory Medicine, Lund University Hospital and Skåne University Hospital, Lund, Sweden.
    Gude, Einar
    Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.
    Bjørtuft, Øystein
    Department of Respiratory Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Schultz, Hans Henrik
    Division of Lung Transplantation, Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
    Solbu, Dag
    Novartis Norge AS, Oslo, Norway.
    Iversen, Martin
    Division of Lung Transplantation, Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
    Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial2016In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 29, no 7, p. 819-829Article in journal (Refereed)
    Abstract [en]

    The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years postrandomization (mean: 5.6 years) was attended by 72/140 everolimus patients (51.4%) and 91/142 controls (64.1%). Mean measured GFR remained stable in the everolimus group from randomization (51.3 ml/min) to last visit (51.4 ml/min) but decreased in controls (from 50.5 ml/min to 45.3 ml/min) and was significantly higher with everolimus at last follow-up (P = 0.004). The least squares mean (SE) change from randomization was -1.5 (1.7)ml/min with everolimus versus -7.2 (1.7)ml/min for controls (difference: 5.7 [95% CI 1.7; 9.6]ml/min; P = 0.006). The difference was accounted for by heart transplant patients (difference: 6.9 [95% 2.3; 11.5]ml/min; P = 0.004). Lung transplant patients showed no between-group difference at last follow-up. Rates of rejection, death, and major cardiac events were similar between groups, as was graft function. Pneumonia was more frequent with everolimus (18.3% vs. 6.4%). In conclusion, introducing everolimus in maintenance heart transplant patients, with reduced CNI, achieves a significant improvement in renal function which is maintained for at least 5 years, but an early renal benefit in lung transplant patients was lost. Long-term immunosuppressive efficacy was maintained.

  • 14.
    Gullestad, Lars
    et al.
    University of Oslo.
    Iversen, Martin
    Rigshospital, Copenhagen.
    Mortensen, Svend-Aage
    University of Oslo.
    Eiskjaer, Hans
    Aarhus University Hospital.
    C. Riise, Gerdt
    Sahlgrens University Hospital.
    Mared, Lena
    Lund University Hospital.
    Bjortuft, Oystein
    University of Oslo.
    Ekmehag, Bjorn
    Lund University Hospital.
    Jansson, Kjell
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Simonsen, Svein
    University of Oslo.
    Gude, Einar
    University of Oslo.
    Rundqvist, Bengt
    University of Gothenburg.
    E. Fagertun, Hans
    Capturo AS Stat Kjeller.
    Solbu, Dag
    Novartis Norge AS.
    Bergh, Claes-Hakan
    University of Gothenburg.
    Everolimus With Reduced Calcineurin Inhibitor in Thoracic Transplant Recipients With Renal Dysfunction: A Multicenter, Randomized Trial2010In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 89, no 7, p. 864-872Article in journal (Refereed)
    Abstract [en]

    Background. The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. Methods. In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate greater than= 20 mL/min/1.73m(2) and less than90 mL/min/1.73 m(2)) greater than1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. Results. Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and tacrolimus trough levels in the everolimus cohort decreased by 57% and 56%, respectively. The primary endpoint, mean change in measured glomerular filtration rate from baseline to month 12, was 4.6 mL/min with everolimus and -0.5 mL/min in controls (Pless than0.0001). Everolimus-treated heart and lung transplant patients in the lowest tertile for time posttransplant exhibited mean increases of 7.8 mL/min and 4.9 mL/min, respectively. Biopsy-proven treated acute rejection occurred in six everolimus and four control heart transplant patients (P=0.54). In total, 138 everolimus patients (98.6%) and 127 control patients (89.4%) experienced one or more adverse event (P=0.002). Serious adverse events occurred in 66 everolimus patients (46.8%) and 44 controls (31.0%) (P=0.02). Conclusion. Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation.

  • 15.
    Gullestad, Lars
    et al.
    Oslo University Hospital.
    Mortensen, Svend-Aage
    Rigshospital, Copenhagen, Denmark .
    Eiskjoer, Hans
    Aarhus University Hospital.
    Riise, Gerdt C
    Sahlgrens University Hospital.
    Mared, Lena
    Lund University.
    Bjortuft, Oystein
    Oslo University Hospital.
    Ekmehag, Bjorn
    Lund University.
    Jansson, Kjell
    Linköping University, Department of Medicine and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Simonsen, Svein
    Oslo University Hospital.
    Gude, Einar
    Oslo University Hospital.
    Rundqvist, Bengt
    University Goteborg.
    Fagertun, Hansn E
    Novartis Norge AS.
    Iversen, Martin
    Rigshospital, Copenhagen, Denmark .
    Two-Year Outcomes in Thoracic Transplant Recipients After Conversion to Everolimus With Reduced Calcineurin Inhibitor Within a Multicenter, Open-Label, Randomized Trial2010In: TRANSPLANTATION, ISSN 0041-1337, Vol. 90, no 12, p. 1581-1589Article in journal (Refereed)
    Abstract [en]

    Background. Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required. Methods. In a prospective, open-label, multicenter study, thoracic transplant recipients more than or equal to 1 year posttransplant with mild-to-moderate renal insufficiency were randomized to continue their current CNI-based immunosuppression or convert to everolimus with predefined CNI exposure reduction. After a 12-month core trial, patients were followed up to month 24 after randomization. Results. Of 245 patients who completed the month 12 visit, 235 patients (108 everolimus and 127 controls) entered the 12-month extension phase. At month 24, mean measured glomerular filtration rate had increased by 3.2 +/- 12.3 mL/min from the point of randomization in everolimus-treated patients and decreased by 2.4 +/- 9.0 mL/min in controls (Pandlt;0.001), a difference that was significant within both the heart and lung transplant subpopulations. During months 12 to 24, 5.6% of everolimus patients and 3.1% of controls experienced biopsy-proven acute rejection (P=0.76). There were no significant differences in the rate of adverse events or serious adverse events (including pneumonia) between groups during months 12 to 24. Conclusions. Converting maintenance thoracic transplant recipients to everolimus with low-exposure CNI results in a renal benefit that is sustained to 2 years postconversion, with significantly improved measured glomerular filtration rate in both heart and lung transplant patients. Despite reductions of more than 50% in CNI exposure, there was no marked loss of efficacy. The safety profile of the everolimus-based regimen was acceptable.

  • 16.
    Gustafsson, Finn
    et al.
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Andreassen, Arne K.
    Oslo Univ Hosp, Norway.
    Andersson, Bert
    Sahlgrens Univ Hosp, Sweden.
    Eiskjaer, Hans
    Aarhus Univ Hosp, Denmark.
    Radegran, Goran
    Lund Univ, Sweden; Lund Univ, Sweden.
    Gude, Einar
    Oslo Univ Hosp, Norway.
    Jansson, Kjell
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Solbu, Dag
    Novartis Norge AS, Norway.
    Karason, Kristjan
    Sahlgrens Univ Hosp, Sweden.
    Arora, Satish
    Oslo Univ Hosp, Norway.
    Dellgren, Goran
    Sahlgrens Univ Hosp, Sweden.
    Gullestad, Lars
    Oslo Univ Hosp, Norway; Univ Oslo, Norway; Univ Oslo, Norway.
    Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Long-term Follow-up From the Randomized SCHEDULE Study2020In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 104, no 1, p. 154-164Article in journal (Refereed)
    Abstract [en]

    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.

  • 17.
    Jansson, Kjell
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Treatment in Dilated Cardiomyopathy: with special emphasis on beta-adrenergic receptor blockade and angiotensin-converting enzyme inhibition1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Dilated cardiomyopathy (DCM) is a heart muscle disease of unknown origin, characterised by ventricular dilatation and impairment of systolic function. The basic treattnent is medical, according to different pharmacological principles. Evaluation of the severity of the disease and the effects of medication are important for optimal management.

    Fifty-four patients (42 male and 12 female) with DCM were randomized to receive treatment with either a beta-adrenergic receptor blocker (metoprolol) or an angiotensin-converting enzyme (ACE) inhibitor (captopril). Almost all patients had a history of congestive heart failure and were therefore treated with furosemide. Baseline characteristics and the effects of therapy were studied by invasive haemodynamics, echocardiography, neurohormonal function, heart rate variability and quality of life evaluation.

    There were favourable effects on left ventricular (LV) function with both drugs but metoprolol seemed to be superior to captopril in improving LV stroke volume and reducing LV filling pressure. There was a reduction in both systolic and diastolic dimensions and the non-invasive findings were in accordance with invasive results. Neurohormonal activation was less than expected and the levels of plasma renin activity and angiotensin II were within the normal range while the levels of atrial natriuretic peptide were increased. Urinary excretion of Aldosterone was reduced with both metoprolol and captopril therapy, but treatment with petoprolol reduced the level of ANP during exercise.

    Both drugs increased heart rate variability but petoprolol was superior to captopril in increasing totaol power and power in the low and very low frequency.

    Quality of life was assessed by a disease-specific questionnaire and wsa improved in the dimension "emotion" in both groups during treatment. In the captopril group there were also improvements in total score and in the dimension "physical activity". Improvements in quality of life dimensions, however, did not correlate to improvement in LV function.

    In conclusion both metoprolol and captopril were well tolerated. There were effects of beta-adrenergic receptor blockade on LV performance that were not obtained, at least not equally, during therapy with ACE inhibitor. Itreatment of patients with DCM should therefore include a beta-receptor blocker. Carefully performed, non-invasive methods can be used to evaluate the effects of therapy.

  • 18.
    Jansson, Kjell
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Karlberg, B E
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine.
    Karlsson, E
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Nylander, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Nyqvist, O
    Karlberg, K-E
    The circulating renin-angiotensin system during treatment with mteprlol or captopril in patients with heart failure due to non-ischaemic dilated cardiomyopathy.1999In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 245, p. 435-443Article in journal (Refereed)
  • 19.
    Jansson, Kjell
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Karlberg, Karl-Erik
    Karlsson, Erling
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Nyquist, Olof
    Nylander, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    The value of repeated echocardiographic evaluation in patients with idiopathic dilated cardiomyopathy during treatment with metoprolol or captopril2000In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 34, no 3, p. 293-300Article in journal (Refereed)
    Abstract [en]

    Serial echocardiographic investigations were carried out on patients with idiopathic dilated cardiomyopathy, to evaluate treatment effects on left ventricular (LV) performance during therapy with either metoprolol or captopril. Thirty-two patients (23 males and 9 females) with mild to moderate symptoms of heart failure (NYHA II-III) and a mean age of 49 years were included in the investigation. The patients were investigated with Doppler echocardiography before treatment, after 3 and 6 months of treatment (either metoprolol or captopril) and 1 month after withdrawal of treatment. Intra- and inter-investigator reproducibility was acceptable, with a coefficient of variation of less than 5% for LV dimensions. A reduction in LV dimensions was seen in both treatment groups. In the metoprolol group there was also an increase in LV stroke volume and fractional shortening. The non-invasive data were in accordance with invasive measurements of stroke volume and LV filling pressure. In patients with idiopathic dilated cardiomyopathy and mild to moderate symptoms of heart failure, echocardiography seemed to be sufficiently reproducible to be used for determination of treatment effects in a longitudinal heart failure study. Both metoprolol and captopril were well tolerated and had favourable effects on LV performance.

  • 20.
    Jansson, Kjell
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Hagerman, I
    Östlund, R
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Karlberg, K-E
    Nylander, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Nyqvist, O
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    The effects of Metoprolol and Captopril on heart rate variability in patients with idiopathic dilated cardiomyopathy.1999In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 22, p. 397-402Article in journal (Refereed)
  • 21.
    Malinovschi, Andrei
    et al.
    Uppsala Univ, Sweden.
    Zhou, Xingwu
    Uppsala Univ, Sweden; Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Bake, Bjorn
    Univ Gothenburg, Sweden.
    Bergstrom, Goran
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Blomberg, Anders
    Umea Univ, Sweden.
    Brisman, Jonas
    Univ Gothenburg, Sweden.
    Caidahl, Kenneth
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Engstrom, Gunnar
    Lund Univ, Sweden.
    Eriksson, Maria J.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Frolich, Andreas
    Umea Univ, Sweden.
    Janson, Christer
    Uppsala Univ, Sweden.
    Jansson, Kjell
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Vikgren, Jenny
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Lindberg, Anne
    Umea Univ, Sweden.
    Linder, Robert
    Umea Univ, Sweden.
    Mannila, Maria
    Karolinska Univ Hosp, Sweden.
    Persson, Hans L.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Skold, C. Magnus
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Toren, Kjell
    Univ Gothenburg, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ekholmen.
    Wollmer, Per
    Lund Univ, Sweden.
    Engvall, Jan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Assessment of Global Lung Function Initiative (GLI) reference equations for diffusing capacity in relation to respiratory burden in the Swedish CArdioPulmonary bioImage Study (SCAPIS)2020In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 56, no 2, article id 1901995Article in journal (Refereed)
    Abstract [en]

    The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (DLCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired DLCO. We examined if the GLI LLN for DLCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.

    Spirometry, DLCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50–64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).

    Both the median and LLN for DLCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of DLCO <GLI LLN (and also <SCAPIS LLN) was 3.9%, while the prevalence of DLCO >GLI LLN but <SCAPIS LLN was 5.7%. Subjects with DLCO >GLI LLN but <SCAPIS LLN (n=860) had more emphysema (14.3% versus 4.5%, p<0.001), chronic airflow limitation (8.5% versus 3.9%, p<0.001) and chronic bronchitis (8.3% versus 4.4%, p<0.01) than subjects (n=13 600) with normal DLCO (>GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma.

    The GLI LLN for DLCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with DLCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.

  • 22. Peterze, B.
    et al.
    Lonn, U.
    Jansson, Kjell
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Rutberg, H.
    Casimir-Ahn, H.
    Nylander, E.
    Long-term follow-up of thoratec ventricular assist device bridge-to-recovery patients successfully removed from support after recovery of ventricular function2002In: The Journal of Heart and Lung Transplantation, ISSN 1053-2498, E-ISSN 1557-3117, Vol. 21, no 5, p. 516-521Article in journal (Refereed)
    Abstract [en]

    Background: In certain forms of severe heart failure there is sufficient improvement in cardiac function during ventricular assist device (VAD) support to allow removal of the device. However, it is critical to know whether there is sustained recovery of the heart and long-term patient survival if VAD bridging to recovery is to be considered over the option of transplantation. Methods: To determine long-term outcome of survivors of VAD bridge-to-recovery procedures, we retrospectively evaluated 22 patients with non-ischemic heart failure successfully weaned from the Thoratec left ventricular assist device (LVAD) or biventricular assist device (BVAD) after recovery of ventricular function at 14 medical centers. All patients were in imminent risk of dying and were selected for VAD support using standard bridge-to-transplant requirements. There were 12 females and 10 males with an average age of 32 (range, 12-49). The etiologies were 12 with myocarditis, 7 with cardiomyopathies (4 post-partum [PPCM], 1 viral [VCM], and 2 idiopathic [IDCM]), and 3 with a combination of myocarditis and cardiomyopathy. BVADs were used in 13 patients and isolated LVADs in 9 patients, for an average duration of 57 days (range, 11-190 days), before return of ventricular function and successful weaning from the device. Post-VAD survival was compared with 43 VAD bridge-to-transplant patients with the same etiologies who underwent cardiac transplantation instead of device weaning. Results: Nineteen of the 22 patients are currently alive. Three patients required heart transplantation, 1 within 1 day, 2 at 12 and 13 months post-weaning, and 2 died at 2.5 and 6 months. The remaining 17 patients are alive with their native hearts after an average of 3.2 years (range, 1.2-10 years). The actuarial survival of native hearts (transplant-free survival) post-VAD support is 86% at 1 year and 77% at 5 years, which was not significantly different (p = 0.94) from that of post-VAD transplanted patients, also at 86% and 77%, respectively. Conclusion: Long-term survival for bridge-to-recovery with VADs for acute cardiomyopathies and myocarditis is equivalent to that for cardiac transplantation. Recovery of the native heart, which can take weeks to months of VAD support, is the most desirable clinical outcome and should be actively sought, with transplantation used only after recovery of ventricular function has been ruled out.

  • 23.
    Peterzén, Bengt
    et al.
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Lönn, Urban
    Jansson, Kjell
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Ruthberg, Hans
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Casimir Ahn, Hans
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Nylander, Eva
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Long-term follow-up of patients treated with an implantable left ventricular assist device as an extended bridge to heart transplantation2002In: The Journal of Heart and Lung Transplantation, ISSN 1053-2498, Vol. 21, no 5, p. 604-607Article in journal (Refereed)
    Abstract [en]

    Four patients were given the TCI implantable left ventricular assist device as a bridge to heart transplantation. The median treatment time was 541 days (range 462 to 873 days), with a total of 2,417 treatment days. The patients were followed with exercise tests and echocardiography 3 to 18 months after implantation. An invasive method was used for quantification of inflow valve incompetence.

  • 24.
    Rådegran, Göran
    et al.
    Department of Clinical Sciences Lund, Cardiology, Lund University, Lund, Sweden; Haemodynamic Laboratory, the Section for Heart Failure and Valvular Disease, VO Heart and Lung Medicine, Skåne University Hospital, Lund, Sweden.
    Kjellström, Barbro
    Cardiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
    Ekmehag, Björn
    Department of Public Health and Caring Science, Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
    Larsen, Flemming
    Department of Molecular Medicine and Surgery, Section of Clinical Physiology, Karolinska Institute, Stockholm, Sweden; Department of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden.
    Rundqvist, Bengt
    Department of Cardiology , Sahlgrenska University Hospital, the Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Berg Blomquist, Sofia
    Department of Medical Sciences Cardiology, Uppsala University, Uppsala, Sweden.
    Gustafsson, Carola
    Department of Cardiology, Sahlgrenska University Hospital, the Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Hesselstrand, Roger
    Department of Clinical Sciences Lund, Rheumatology, Lund University, and the Rheumatology Clinic, Skåne University Hospital, Lund, Sweden.
    Karlsson, Monica
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Kornhall, Björn
    Department of Clinical Sciences Lund, Cardiology, Lund University, Lund, Sweden; Haemodynamic Laboratory, the Section for Heart Failure and Valvular Disease, VO Heart and Lung Medicine, Skåne University Hospital, Lund, Sweden.
    Nisell, Magnus
    Department of Medicine, Karolinska Institute, Stockholm, Sweden; Clinic for Pulmonary Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Persson, Liselotte
    Department of Clinical Sciences Lund, Cardiology, Lund University, Lund, Sweden; Haemodynamic Laboratory, the Section for Heart Failure and Valvular Disease, VO Heart and Lung Medicine, Skåne University Hospital, Lund, Sweden.
    Ryftenius, Henrik
    Department of Medicine, Karolinska Institute, Stockholm, Sweden; Clinic for Pulmonary Medicine, Karolinska University Hospital, Stockholm, Sweden .
    Selin, Maria
    Department of Public Health and Clinical Medicine, Cardiology and the Heart Centre, Umeå University, Umeå, Sweden.
    Ullman, Bengt
    Department of Cardiology, Karolinska Institute, Stockholm, Sweden; Department of Cardiology, Södersjukhuset, Sweden, Stockholm.
    Wall, Kent
    Department of Clinical Physiology, Örebro University, and Örebro University Hospital, Örebro, Sweden.
    Wikström, Gerhard
    Department of Medical Sciences Cardiology, Uppsala University, Uppsala, Sweden.
    Willehadson, Maria
    Department of Medical Sciences Cardiology, Uppsala University, Uppsala, Sweden.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Söderberg, Stefan
    Department of Medicine, Karolinska Institute, Stockholm, Sweden; Clinic for Pulmonary Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Characteristics and survival of adult Swedish PAH and CTEPH patients 2000-20142016In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 50, no 4, p. 243-250Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The Swedish Pulmonary Arterial Hypertension Register (SPAHR) is an open continuous register, including pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients from 2000 and onwards. We hereby launch the first data from SPAHR, defining baseline characteristics and survival of Swedish PAH and CTEPH patients.

    DESIGN: Incident PAH and CTEPH patients 2008-2014 from all seven Swedish PAH-centres were specifically reviewed.

    RESULTS: There were 457 PAH (median age: 67 years, 64% female) and 183 CTEPH (median age: 70 years, 50% female) patients, whereof 77 and 81%, respectively, were in functional class III-IV at diagnosis. Systemic hypertension, diabetes, ischaemic heart disease and atrial fibrillation were common comorbidities, particularly in those >65 years. One-, 3- and 5-year survival was 85%, 71% and 59% for PAH patients. Corresponding numbers for CTEPH patients with versus without pulmonary endarterectomy were 96%, 89% and 86% versus 91%, 75% and 69%, respectively. In 2014, the incidence of IPAH/HPAH, associated PAH and CTEPH was 5, 3 and 2 per million inhabitants and year, and the prevalence was 25, 24 and 19 per million inhabitants.

    CONCLUSION: The majority of the PAH and CTEPH patients were diagnosed at age >65 years, in functional class III-IV, and exhibiting several comorbidities. PAH survival in SPAHR was similar to other registers.

  • 25.
    Selimovic, N
    et al.
    Sahlgrens University Hospital.
    Lovgren Ekmehag, B
    Norrtalje Hospital.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Larsen, F
    Karolinska University Hospital.
    Soderberg, S
    Umeå University Hospital.
    Wikstrom, G
    Uppsala University.
    Pulmonary Arterial Hypertension in Sweden: First Data from a National Registry in JOURNAL OF HEART AND LUNG TRANSPLANTATION, vol 31, issue 4, pp S284-S2842012In: JOURNAL OF HEART AND LUNG TRANSPLANTATION, Elsevier , 2012, Vol. 31, no 4, p. S284-S284Conference paper (Refereed)
    Abstract [en]

    n/a

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