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  • 1.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia2017In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 50, p. 93-99Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) later in life. In PE there is a substantial increase in levels of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1) and decreased levels of the pro-angiogenic factor placental growth factor (PlGF). Elevated levels of sFlt1 are also found in individuals with CVD. The aims of this study were to assess sFlt1, PlGF and the sFlt1/PlGF ratio and their correlation with signs of arterial aging by measuring common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.

    METHODS: Serum sFlt1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22 MHz) ultrasonography in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, with reassessment one year postpartum. A thick intima, thin media and a high I/M ratio indicate a less healthy arterial wall.

    RESULTS: During pregnancy, higher levels of sFlt1, lower levels of PlGF and thicker intima, thinner media and higher I/M ratios were found in women with PE vs. controls (all p < 0.0001). Further, sFlt1 and the sFlt1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all p < 0.0001), but negatively correlated with media thickness (p = 0.002 and 0.03, respectively). About one year postpartum, levels of sFlt1 and the sFlt1/PlGF ratio had decreased in both groups, but compared with controls women in the PE group still had higher levels (p = 0.001 and 0.02, respectively). Further, sFlt1 levels and the sFlt1/PlGF ratio were still positively correlated with intima thickness and I/M ratio.

    CONCLUSIONS: Higher sFlt1 levels and sFlt1/PlGF ratios in women with PE were positively associated with signs of arterial aging during pregnancy. About one year postpartum sFlt1 levels and the sFlt1/PlGF ratios were still higher in the PE group, and also associated with the degree of arterial aging.

  • 2.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics. Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Serum Pentraxin 3 is associated with signs of arterial alteration in women with preeclampsia.2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 241, p. 417-422Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Preeclampsia (PE) in pregnancy is a state of exaggerated inflammation and is associated with an increased risk of cardiovascular disease (CVD) later in life. Levels of pentraxin 3 (PTX3), a novel inflammation marker, are increased during PE and in individuals with CVD. The primary aim of this study was to assess whether serum PTX3 in women with PE is associated with adverse arterial effects; a thicker intima and higher intima/media (I/M) ratio in the common carotid artery (CCA).

    METHODS: Serum PTX3 levels were measured using commercially available enzyme-linked immunosorbent assay kits, and individual CCA intima and media thicknesses were estimated by 22MHz non-invasive ultrasound in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, and about one year postpartum. A thick intima, thin media and high I/M ratio indicate a less healthy artery wall.

    RESULTS: During pregnancy serum PTX3 correlated positively with intima thickness and I/M ratio but negatively with media thickness (all p<0.0001), indicating adverse arterial effects. About one year postpartum, PTX3 levels had decreased in both groups and there remained no significant group difference or significant correlation with CCA wall layers.

    CONCLUSIONS: Higher levels of serum PTX3 in women with PE were significantly associated with signs of adverse arterial effects during pregnancy, but not one year postpartum, supporting the rapid dynamics of PTX3.

  • 3.
    Antoni, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Axelsson, Jan
    Carlson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lindsjö, Lars
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Granstam, Sven-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Rosengren, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Vedin, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    In Vivo Visualization of Amyloid Deposits in the Heart with 11C-PIB and PET2013In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 54, no 2, p. 213-220Article in journal (Refereed)
    Abstract [en]

    Cardiac amyloidosis is a differential diagnosis in heart failure and is associated with high mortality. There is currently no noninvasive imaging test available for specific diagnosis. N-[methyl-11C]2-(4′-methylamino-phenyl)-6-hydroxybenzothiazole (11C-PIB) PET is used in the evaluation of brain amyloidosis. We evaluated the potential use of 11C-PIB PET in systemic amyloidosis affecting the heart.

    Methods:

    Patients (n = 10) diagnosed with systemic amyloidosis—including heart involvement of either monoclonal immunoglobulin light-chain (AL) or transthyretin (ATTR) type—and healthy volunteers (n = 5) were investigated with PET/CT using 11C-PIB to study cardiac amyloid deposits and with 11C-acetate to measure myocardial blood flow to study the impact of global and regional perfusion on PIB retention.

    Results:

    Myocardial 11C-PIB uptake was visually evident in all patients 15–25 min after injection and was not seen in any volunteer. A significant difference in 11C-PIB retention in the heart between patients and healthy controls was found. The data indicate that myocardial amyloid deposits in patients diagnosed with systemic amyloidosis could be visualized with 11C-PIB. No correlation between 11C-PIB retention index and myocardial blood flow as measured with 11C-acetate was found on the global level, whereas a positive correlation on the segmental level was seen in a single patient.

    Conclusion:

    11C-PIB and PET could be a method to study systemic amyloidosis of type AL and ATTR affecting the heart and should be investigated further both as a diagnostic tool and as a noninvasive method for treatment follow-up.

  • 4. Bergh, Claes-Håkan
    et al.
    Andersson, Bert
    Dahlström, Ulf
    Forfang, Kolbjorn
    Kivikko, Matti
    Sarapohja, Toni
    Ullman, Bengt
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Intravenous levosimendan vs. dobutamine in acute decompensated heart failure patients on beta-blockers2010In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 12, no 4, p. 404-410Article in journal (Refereed)
    Abstract [en]

    The aim of this study is to compare the effects of a 24 h intravenous infusion of levosimendan and a 48 h infusion of dobutamine on invasive haemodynamics in patients with acutely decompensated chronic NYHA class III-IV heart failure. All patients were receiving optimal oral therapy including a beta-blocker. METHODS AND RESULTS: This was a multinational, randomized, double-blind, phase IV study in 60 patients; follow-up was 1 month. There was a significant increase in cardiac index and a significant decrease in pulmonary capillary wedge pressure (PCWP) at 24 and 48 h for both dobutamine and levosimendan. The improvement in cardiac index with levosimendan was not significantly different from dobutamine at 24 h (P = 0.07), but became significant at 48 h (0.44 +/- 0.56 vs. 0.66 +/- 0.63 L/min/m(2); P = 0.04). At 24 h, the reduction in the mean change in PCWP from baseline was similar for levosimendan and dobutamine, however, at 48 h the difference was more marked for levosimendan (-3.6 +/- 7.6 vs. -8.3 +/- 6.7 mmHg; P = 0.02). No difference was observed between the groups for change in NYHA class, beta-blocker use, hospitalizations, treatment discontinuations or rescue medication use. Reduction in B-type natriuretic peptide (BNP) was significantly greater with levosimendan at 48 h (P = 0.03). According to physician's assessment, the improvement in fatigue (P = 0.01) and dyspnoea (P = 0.04) was in favour of dobutamine treatment, and hypotension was significantly more frequent with levosimendan (P = 0.007). No increase in atrial fibrillation or ventricular tachycardia was seen in either group. CONCLUSION: A 24 h levosimendan infusion achieved haemodynamic and neurohormonal improvement that was at least comparable at 24 h and superior at 48 h to a 48 h dobutamine infusion.

  • 5.
    Bjerner, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ericsson, Anders
    Briley-Soebo, Karen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bjørnerud, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    In and ex vivo MR evaluation of acute myocardial ischemia in pigs by determining R1 in steady state after the administration of the intravascular contrast agent NC100150 injection2004In: Investigative Radiology, ISSN 0020-9996, E-ISSN 1536-0210, Vol. 39, no 8, p. 479-486Article in journal (Refereed)
  • 6.
    Bjerner, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    High in-plane resolution T2-weighted magnetic resonance imaging of acute myocardial ischemia in pigs using the intravascular contrast agent NC100150 injection.2004In: Investigative Radiology, ISSN 0020-9996, E-ISSN 1536-0210, Vol. 39, no 8, p. 470-478Article in journal (Refereed)
    Abstract [en]

    Rationale and Objectives: The intravascular contrast agent NC100150 injection was tested for its ability to demarcate nonperfused myocardium in a porcine model of coronary occlusion.

    Materials and Methods: A T2-weighted fast spin echo sequence was acquired ex vivo and in vivo during first pass and steady-state circulation of the contrast agent in 2 dosages (2 and 5 mg Fe/kg bw) or saline.

    Results: Ex vivo, in the high-dose group, the volume of nonperfused myocardium determined from T2-weighted images was 99% of that determined from photographs where perfused myocardium stained with fluorescein. A significantly higher contrast to noise ratio between perfused and nonperfused myocardium was found (both ex and in vivo in steady state) compared with the control group. During first pass, a significant reduction in signal intensity (74 ± 18%) was found in perfused myocardium after contrast injection.

    Conclusion: NC100150 injection, combined with T2-weighted turbo spin echo imaging, allowed detailed visualization of non-perfused myocardium in the steady state, which corresponded to the area at risk as determined by fluorescein.

  • 7.
    Blomström, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Ekman, M.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Calvert, M. J.
    Freemantle, N.
    Lönnerholm, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Jönsson, B.
    Cost effectiveness of cardiac resynchronization therapy in the Nordic region: an analysis based on the CARE-HF trial2008In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 10, no 9, p. 869-877Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this study was to investigate the cost-effectiveness of cardiac resynchronization therapy (CRT) in Denmark, Finland and Sweden. The analysis was based on the CARE-HF trial, a randomised clinical trial investigating the efficacy of adding CRT (n=409) to optimal pharmacological treatment (n=404) in patients with moderate to severe heart failure with markers of cardiac dyssynchrony. The average follow-up time was 29.4 months. METHODS: The health effects were measured in terms of quality-adjusted life years (QALYs) gained. Data on health care resource consumption from CARE-HF was combined with costs for CRT implantation and hospitalisation from university hospitals in Denmark, Finland and Sweden. Calculations were based on patients' expected life time. The expected device lifetime (6 years) was used for CRT, and no additional gains in clinical effects were assumed after the 6 years. RESULTS: The cost-effectiveness ratio per QALY gained was 4800 euros in Denmark, 3600 euros in Finland and 6700 euros in Sweden. The 95% confidence intervals for the cost per QALY gained varied between a lower limit of 1169 euros in Finland to an upper limit of 17,482 euros in Sweden. These values were all below the threshold for being cost-effective in Denmark, Finland and Sweden. CONCLUSIONS: The study indicates that CRT is a cost-effective treatment in Scandinavian health care settings compared to traditional pharmacological therapy and can therefore be recommended for routine use in patients with moderate to severe heart failure and markers of dyssynchrony.

  • 8.
    Boman, K.
    et al.
    Umea Univ, Res Unit, Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Lindmark, K.
    Umea Univ, Ctr Heart, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Res Unit, Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Bergman, G. J.
    QuintilesIMS, Solna, Sweden..
    Tornblom, M.
    QuintilesIMS, Solna, Sweden..
    Wirta, S. Bruce
    Novartis Sweden AB, Stockholm, Sweden..
    Costa-Scharplatz, M.
    Novartis Sweden AB, Stockholm, Sweden..
    Calado, F.
    Novartis Pharma AG, Basel, Switzerland..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Healthcare resource utilization associated with heart failure with preserved versus reduced ejection fraction: a retrospective population-based cohort study in Sweden2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, p. 346-346Article in journal (Other academic)
  • 9.
    Boman, K.
    et al.
    Umea Univ, Res Unit, Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Lindmark, K.
    Umea Univ, Ctr Heart, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Bergman, G. J.
    QuintilesIMS, Solna, Sweden..
    Tornblom, M.
    QuintilesIMS, Solna, Sweden..
    Costa-Scharplatz, M.
    Novartis Sweden AB, Stockholm, Sweden..
    Wirta, S. Bruce
    Novartis Sweden AB, Stockholm, Sweden..
    Olofsson, M.
    Umea Univ, Res Unit, Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Costs associated with heart failure with preserved versus reduced ejection fraction: a retrospective population-based cohort study in Sweden2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, p. 346-347Article in journal (Other academic)
  • 10.
    Classen, Jean-Francois
    et al.
    de Duve Institute, Universite´ Catholique de Louvain, Brussels, Belgium.
    Henrohn, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lennartsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Lauwerys, Bernard R.
    Saint-Luc University Hospital, Universite´ Catholique de Louvain, Brussels, Belgium.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rorsman, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Lenglez, Sandrine
    de Duve Institute, Universite´ Catholique de Louvain, Brussels, Belgium.
    Franck-Larsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tomasi, Jean-Paul
    Saint-Luc University Hospital, Universite´ Catholique de Louvain, Brussels, Belgium.
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vanthuyne, Marie
    Saint-Luc University Hospital, Universite´ Catholique de Louvain, Brussels, Belgium.
    Houssiau, Frédéric A.
    Saint-Luc University Hospital, Universite´ Catholique de Louvain, Brussels, Belgium.
    Demoulin, Jean-Baptiste
    de Duve Institute, Universite´ Catholique de Louvain, Brussels, Belgium.
    Lack of evidence of stimulatory autoantibodies to platelet-derived growth factor receptor in patients with systemic sclerosis2009In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, no 4, p. 1137-1144Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Systemic sclerosis (SSc) is a severe connective tissue disease of unknown etiology, characterized by fibrosis of the skin and multiple internal organs. Recent findings suggested that the disease is driven by stimulatory autoantibodies to platelet-derived growth factor receptor (PDGFR), which stimulate the production of reactive oxygen species (ROS) and collagen by fibroblasts. These results opened novel avenues of research into the diagnosis and treatment of SSc. The present study was undertaken to confirm the presence of anti-PDGFR antibodies in patients with SSc. METHODS: Immunoglobulins from 37 patients with SSc were purified by protein A/G chromatography. PDGFR activation was tested using 4 different sensitive bioassays, i.e., cell proliferation, ROS production, signal transduction, and receptor phosphorylation; the latter was also tested in a separate population of 7 patients with SSc from a different research center. RESULTS: Purified IgG samples from patients with SSc were positive when tested for antinuclear autoantibodies, but did not specifically activate PDGFRalpha or PDGFRbeta in any of the tests. Cell stimulation with PDGF itself consistently produced a strong signal. CONCLUSION: The present results raise questions regarding the existence of agonistic autoantibodies to PDGFR in SSc.

  • 11.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Nygren, Magnus
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, Tomas
    Wikström, Bernt Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    High-sensitive troponin T and I are related to invasive hemodynamic data and mortality in patients with left-ventricular dysfunction and precapillary pulmonary hypertension2011In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 412, no 17-18, p. 1582-1588Article in journal (Refereed)
    Abstract [en]

    Background: High-sensitive (hs) cardiac troponin assays are clinically useful in various cardiac conditions. We aimed to extend current evidence by assessing the relations of hs-cardiac troponin T (hs-cTnT) and I (hs-cTnI) to invasive hemodynamic data and outcome in stable patients with left-ventricular (LV) dysfunction or precapillary pulmonary hypertension (PAH). Methods: Hs-cTnT (Roche Diagnostics) and hs-cTnI (Beckman-Coulter) were measured in 103 stable patients with LV-dysfunction and 56 patients with precapillary PAH referred for right-heart catheterization. Results: Up to 47.6% of patients with LV-dysfunction, and up to 37.5% of patients with precapillary PAH had hs-troponin levels above the respective 99th percentiles. In patients with LV-dysfunction, both hs-troponins exhibited significant associations to hemodynamics, NT-proBNP and mortality (hs-cTnT: age/sex-adjusted HR 2.0 [95% CI 1.3-3.1]: hs-cTnI: age/sex-adjusted HR 1.9 [1.2-2.8]). Both hs-troponins demonstrated weaker associations to hemodynamics in patients with precapillary PAH but correlated significantly to NT-proBNP. Mortality was only predicted by hs-cTnI (age/sex-adjusted HR 3.0 [1.5-6.1]). Conclusions: Hs-troponins are related to indices of impaired myocardial performance in patients with LV-dysfunction and precapillary PAH. Both hs-troponins were also predictive for mortality in patients with LV-dysfunction. In precapillary PAH, only hs-cTnI was independently prognostic which might depend on the superior analytical performance of this assay.

  • 12.
    Fu, M.
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Sect Cardiol, Dept Med, Ostra Hosp, S-41650 Gothenburg, Sweden..
    Ahrenmark, U.
    Hosp Halmstad, Dept Med, Halmstad, Sweden..
    Berglund, S.
    Hosp Falun, Dept Med, Falun, Sweden..
    Lindholm, C. J.
    Capio City Clin, Lund, Sweden..
    Lehto, A.
    Northern Alvsborg Cty Hosp, Dept Med, Trollhattan, Sweden..
    Broberg, A. Mansson
    Karolinska Inst, Karolinska Univ Hosp Stockholm, Div Cardiol, Dept Med, Stockholm, Sweden..
    Tasevska-Dinevska, G.
    Lund Univ, Malmo Univ Hosp, Dept Cardiol, Malmo, Sweden..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Agard, A.
    Angered Hosp, Dept Med, Gothenburg, Sweden..
    Andersson, B.
    Sahlgrens Univ Hosp, Sect Cardiol, Dept Med, Ostra Hosp, S-41650 Gothenburg, Sweden..
    Adherence to optimal heart rate control in heart failure with reduced ejection fraction: insight from a survey of heart rate in heart failure in Sweden (HR-HF study)2017In: Clinical Research in Cardiology, ISSN 1861-0684, E-ISSN 1861-0692, Vol. 106, no 12, p. 960-973Article in journal (Refereed)
    Abstract [en]

    Despite that heart rate (HR) control is one of the guideline-recommended treatment goals for heart failure (HF) patients, implementation has been painstakingly slow. Therefore, it would be important to identify patients who have not yet achieved their target heart rates and assess possible underlying reasons as to why the target rates are not met. The survey of HR in patients with HF in Sweden (HR-HF survey) is an investigator-initiated, prospective, multicenter, observational longitudinal study designed to investigate the state of the art in the control of HR in HF and to explore potential underlying mechanisms for suboptimal HR control with focus on awareness of and adherence to guidelines for HR control among physicians who focus on the contributing role of beta-blockers (BBs). In 734 HF patients the mean HR was 68 +/- 12 beats per minute (bpm) (37.2% of the patients had a HR > 70 bpm). Patients with HF with reduced ejection fraction (HFrEF) (n = 425) had the highest HR (70 +/- 13 bpm, with 42% > 70 bpm), followed by HF with preserved ejection fraction and HF with mid-range ejection fraction. Atrial fibrillation, irrespective of HF type, had higher HR than sinus rhythm. A similar pattern was observed with BB treatment. Moreover, non-achievement of the recommended target HR (< 70 bpm) in HFrEF and sinus rhythm was unrelated to age, sex, cardiovascular risk factors, cardiovascular diseases, and comorbidities, but was related to EF and the clinical decision of the physician. Approximately 50% of the physicians considered a HR of > 70 bpm optimal and an equal number considered a HR of > 70 bpm too high, but without recommending further action. Furthermore, suboptimal HR control cannot be attributed to the use of BBs because there was neither a difference in use of BBs nor an interaction with BBs for HR > 70 bpm compared with HR < 70 bpm. Suboptimal control of HR was noted in HFrEF with sinus rhythm, which appeared to be attributable to physician decision making rather than to the use of BBs. Therefore, our results underline the need for greater attention to HR control in patients with HFrEF and sinus rhythm and thus a potential for improved HF care.

  • 13.
    Granstam, Sven-Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Björklund, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Roos, Magnus W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Use of echocardiographic pulmonary acceleration time and estimated vascular resistance for the evaluation of possible pulmonary hypertension2013In: Cardiovascular Ultrasound, ISSN 1476-7120, E-ISSN 1476-7120, Vol. 11, p. 7-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    During ultrasound examination, tricuspid regurgitation may be absent or gives a signal that is not reliable for the estimation of systolic pulmonary pressure. The aim of this study was to evaluate the usefulness of acceleration time (AT) from the right ventricular outflow tract (RVOT) as an estimation of the trans-tricuspid valve gradient (TTVG) and to investigate the correlation between estimated and invasive pulmonary vascular resistance (PVR).

    METHODS:

    The AT was correlated to the TTVG measured with routine standard echocardiography in 121 patients. In a subgroup of 29 patients, systolic pulmonary pressure (SPAP) and mean pulmonary arterial pressure (MPAP) were obtained from recent right heart catheterization (RHC).

    RESULTS:

    We found no significant correlation between the estimation of right atrial pressure (RAP) by echocardiography and the RAP obtained by RHC. Estimated SPAP (TTGV + RAP mean from RHC) showed a good linear relation to invasively measured SPAP. TTVG and AT showed a non-linear relation, similar to SPAP and MPAP measured by catheterization and AT. For detection of SPAP above 38 mmHg a cut-off for AT of 100 ms resulted in a sensitivity of 89% and a specificity of 84%. For detection of MPAP above 25 mmHg a cut-off for AT of 100 ms resulted in similar sensitivity and specificity. Invasive PVR and the ratio of TTVG and the time velocity integral of the RVOT (TVI RVOT ) had a strong linear relation.

    CONCLUSIONS:

    Our study confirms that AT appears to be useful for the evaluation of pulmonary hypertension. In high risk patients, an AT of less than 100 ms indicates a high probability of pulmonary hypertension. Furthermore, PVR estimation by ultrasound seems preferably be done by using the ratio of TTVG and TVI RVOT.

  • 14.
    Granstam, Sven-Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Rosengren, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Vedin, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Carlson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Flachskampf, Frank A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Evaluation of patients with cardiac amyloidosis using echocardiography, ECG and right heart catheterization2013In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 20, no 1, p. 27-33Article in journal (Refereed)
    Abstract [en]

    Aims:

    To characterize patients with cardiac amyloidosis using echocardiography, electrocardiogram (ECG) and right heart catheterization (RHC).

    Methods and results:

    Fourteen patients with biopsy verified light chain or transthyretin cardiac amyloidosis were included. All patients had heart failure with markedly elevated NT-proBNP. Echocardiography demonstrated biventricular hypertrophy, left atrial enlargement and normal to slightly reduced left ventricular ejection fraction. Tissue Doppler septal e´ was low and median E/e´ was high. Within 6 months RHC was performed in eight of the patients. The restrictive filling pattern demonstrated by echocardiography corresponded well to median pulmonary wedge pressure (21 mmHg). Systolic pulmonary artery pressure (SPAP) was increased, whereas cardiac output and stroke volume were seen to be decreased with both methods. ECG demonstrated: low voltage (36%), abnormal R-progression (65%), ST-T abnormalities (71%) and high incidence of fibrillation (36%). In addition, a case report following the treatment of melphalan and dexamethasone is presented with improvement of hypertrophy, SPAP, left ventricular mass and e´.

    Conclusion:

    These findings should lead to a suspicion of cardiac amyloidosis and suggest further investigation.

  • 15.
    Henrohn, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Sandqvist, Anna
    Umea Univ, Umea Univ Hosp, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Egerod, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hedeland, Mikael
    Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, Uppsala, Sweden.;Uppsala Univ, Div Analyt Pharmaceut Chem, Dept Med Chem, SE-75185 Uppsala, Sweden..
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bondesson, Ulf
    Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, Uppsala, Sweden.;Uppsala Univ, Div Analyt Pharmaceut Chem, Dept Med Chem, SE-75185 Uppsala, Sweden..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Changes in plasma levels of asymmetric dimethylarginine, symmetric dimethylarginine, and arginine after a single dose of vardenafil in patients with pulmonary hypertension2015In: Vascular pharmacology, ISSN 1537-1891, E-ISSN 1879-3649, Vol. 73, p. 71-77Article in journal (Refereed)
    Abstract [en]

    Objective: We investigated whether vardenafil, a phosphodiesterase-5 inhibitor, alters plasma levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and arginine. Patients and methods: ADMA, SDMA, and arginine were measured (0-540 min) in 12 patients with pulmonary hypertension after a single oral dose of vardenafil. Invasive hemodynamic data were collected at baseline and after 60 min. Results: A reduction in ADMA was observed at 30 and 45 min with a median change of -11.1% (P = 0.021) and -12.5% (P = 0.002). SDMA decreased with a median -5.3% change (P = 0.032) at 45 min. An increase in arginine, median 40.3% (P = 0.002), 45.0% (P = 0.010), and 77.1% (P = 0.008) was observed at 120,300, and 540 min respectively. An increase in the arginine/ADMA ratio, median 11.7% (P = 0.012), 32.5% (P = 0.003), 26.5% (P = 0.021),33% (P = 0.007), 48.5% (P = 0.007), and 63.1% (P = 0.008) was observed at 15, 45, 60, 120, 300, and 540 min respectively. There was a positive correlation between vardenafil exposure and the percent change in the arginine/ADMA ratio from baseline to 540 min (r = 0.80; P = 0.01). A correlation between baseline mean right atrial pressure (mRAP) and baseline ADMA (r = 0.65; P = 0.023), and baseline SDMA (r = 0.61; P = 0.035) was observed. A correlation between the baseline arginine/ADMA ratio and baseline cardiac output (CO) (r = 0.59; P = 0.045) and baseline cardiac index (CI) (r = 0.61; P = 0.036) was observed. Baseline arginine/ADMA ratio correlated with baseline mRAP (r = -0.79; P = 0.002). A correlation between change (0-60 min) in CI and change in arginine (r = 0.77; P = 0.003) as well as change in the arginine/ADMA ratio (r = 0.61; P = 0.037) was observed. Conclusions: Vardenafil induced changes in ADMA, SDMA, arginine, and the arginine/ADMA ratio in patients with PH. An increase in arginine and the arginine/ADMA ratio was associated with improvement in Cl.

  • 16.
    Henrohn, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Sandqvist, Anna
    Umeå universitet.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Egeröd, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Acute haemodynamic response in relation to plasma vardenafil concentrations in patients with pulmonary hypertension2012In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 74, no 6, p. 990-998Article in journal (Refereed)
    Abstract [en]

    AIMS

    To evaluate the acute haemodynamic effects of a single oral dose of vardenafil and to study the drug concentration in relation to haemodynamic effects in patients with pulmonary hypertension (PH).

    METHODS

    Sixteen patients with PH (aged 29–85\ years), received one single oral dose of vardenafil (5, 10 or 20 mg). The haemodynamic effect was assessed over a 60 min period. Vardenafil plasma concentrations were measured after 15, 30, 45 and 60 min using liquid chromatography–tandem mass spectrometry.

    RESULTS

    At 60 min a reduction in mPAP with a median % decrease of −20.3% (range −48.3 to 3.0; P < 0.001) and an increase in cardiac output and the cardiac index with a median % change of 10.6% (range −25.0 to 88.1; P = 0.015) and 12.1% (range −24.0 to 94.4; P = 0.01) respectively was observed. The pulmonary vascular resistance (PVR) was reduced with a median % decrease of −28.9% (range −61.5 to −5.9; P < 0.001), and pulmonary selectivity was reflected by a median percent reduction of −16.9% (range −49.0 to 16.5; P = 0.002; n = 14) in the PVR/systemic vascular resistance ratio. There was a correlation between the plasma concentrations of vardenafil and change in mPAP (r = −0.579, P = 0.019) and between vardenafil concentrations and change in PVR (r = −0.662, P = 0.005).

    CONCLUSIONS

    Vardenafil causes rapid changes in cardiopulmonary haemodynamics and there is a correlation between plasma vardenafil drug concentration and the acute changes in mPAP as well as PVR in patients with PH.

  • 17. Karlsson, Lars O.
    et al.
    Grip, Lars
    Bissessar, Erik
    Bobrova, Irina
    Gustafsson, Thomas
    Kavianipour, Mohammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Odenstedt, Jacob
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gonon, Adrian T.
    Opioid receptor agonist Eribis peptide 94 reduces infarct size in different porcine models for myocardial ischaemia and reperfusion2011In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 651, no 1-3, p. 146-151Article in journal (Refereed)
    Abstract [en]

    Eribis peptide 94 (EP 94) is a novel enkephalin analog, thought to interact with the and delta-opioid receptors. The purpose of the present study was to examine the cardioprotective potential of EP 94 in two clinically relevant porcine models of myocardial ischaemia and reperfusion, and to investigate if such an effect is associated with an increased expression of endothelial nitric oxide synthase (eNOS). Forty-one anesthetized pigs underwent 40 min of coronary occlusion followed by 4 h of reperfusion. In Protocol I, balloon occlusion of the left anterior descending artery was performed with concurrent intravenous administration of (A) vehicle (n = 7), (B) EP 94 (1 ug/kg) after 5, 12, 19 and 26 min of ischaemia (n = 4) or (C) EP 94 (1 ug/kg) after 26, 33, 40 min of ischaemia (n = 6). In Protocol II, open-chest pigs were administered (D) vehicle (n = 6) or (E) 0.2 ug/kg/min of EP 94 (n = 6) through an intracoronary infusion into the jeopardized myocardium, started after 30 min of ischaemia and maintained for 15 min. The hearts were stained and the protein content of eNOS measured. EP 94 reduces infarct size when administered both early and late during ischaemia compared with vehicle (infarct size group A 61.6 +/- 2%, group B 50.2 +/- 3% and group C 49.2 +/- 2%, respectively, P < 0.05), as well as when infused intracoronary (infarct size group D 82.2 +/- 3.9% and group E 61.2 +/- 2.5% respectively, P < 0.01). Phosphorylated eNOS Ser(I177) in relation to total eNOS was significantly increased in the group administered EP 94. indicating activation of nitric oxide production.

  • 18. Kavianipour, M
    et al.
    Ronquist, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Wikström, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Waldenström, A
    Ischaemic preconditioning alters the energy metabolism and protects the ischaemic myocardium in a stepwise fashion.2003In: Acta Physiol Scand, ISSN 0001-6772, Vol. 178, no 2, p. 129-37Article in journal (Refereed)
  • 19. Kavianipour, M
    et al.
    Wikström, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Ronquist, G
    Waldenström, A
    Validity of elevated interstitial levels of taurine as a predictor of myocardial ischemic injury.2004In: Amino Acids, ISSN 0939-4451, Vol. 27, no 1, p. 107-11Article in journal (Refereed)
  • 20. Kavianipour, M
    et al.
    Wikström, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Ronquist, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Waldenström, A
    Validity of the microdialysis technique for experimental in vivo studies of myocardial energy metabolism.2003In: Acta Physiol Scand, ISSN 0001-6772, Vol. 179, no 1, p. 61-5Article in journal (Refereed)
  • 21. Kavianipour, Mohammad
    et al.
    Ehlers, Mario R
    Malmberg, Klas
    Ronquist, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Ryden, Lars
    Wikström, Gerhard
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Gutniak, Mark
    Glucagon-like peptide-1 (7-36) amide prevents the accumulation of pyruvate and lactate in the ischemic and non-ischemic porcine myocardium.2003In: Peptides, ISSN 0196-9781, Vol. 24, no 4, p. 569-78Article in journal (Refereed)
  • 22. Kavianipour, Mohammad
    et al.
    Ronquist, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Wikström, Gerhard
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Waldenström, Anders
    8'-aminoguanosine inclusion results in enhanced efflux of taurine in preconditioned ischemic myocardium.2003In: J Cardiovasc Pharmacol, ISSN 0160-2446, Vol. 41, no 2, p. 240-8Article in journal (Refereed)
  • 23. Kjellstrom, Barbro
    et al.
    Manouras, Aristomenis
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Right ventricular wave reflection relate to clinical measures in pulmonary arterial hypertension2015In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 49, no 4, p. 235-239Article in journal (Refereed)
    Abstract [en]

    Objectives. When a forward running pressure wave from the right ventricle reaches the narrow vessels in the pulmonary circulation, it is reflected as a backward running wave. We aimed to relate changes in right ventricular waveform reflection (RVWR) to changes in clinical variables in pulmonary arterial hypertension (PAH) patients. Design. Twenty-one PAH patients with RV waveform recordings from two sequential catheterisations at least 6 months apart were included. Six-minute walked distance (6MWD) and brain natriuretic peptide (BNP) level were also available. RVWR was defined as the pressure from the inflection point on the upstroke RV pressure wave to RV peak pressure'. Direction of change in RVWR, 6MWD and BNP was classified as (+) if increased and (-) if decreased. Spearman correlations were used to analyse the relation between changes. Pearson's correlation coefficient was used to analyse relation between RVWR and pulmonary vascular resistance (PVR). Results. The correlation between change in RVWR and 6MWD was -0.67 (p < 0.01) and between RVWR and BNP was -0.53 (p < 0.05). Actual RVWR and PVR correlated both at first (0.56, p < 0.001) and at second right heart catheterisation (0.45, p < 0.001). Conclusion. RVWR might have clinical implications indicating a change in clinical status and disease progression in patients with PAH.

  • 24. Kleber, Franz X.
    et al.
    Bollmann, Tom
    Borst, Mathias M.
    Costard-Jäckle, Angelika
    Ewert, Ralf
    Kivikko, Matti
    Petterson, Tiina
    Pohjanjousi, Pasi
    Sonntag, Steffen
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Repetitive dosing of intravenous levosimendan improves pulmonary hemodynamics in patients with pulmonary hypertension: results of a pilot study2009In: Journal of clinical pharmacology, ISSN 0091-2700, E-ISSN 1552-4604, Vol. 49, no 1, p. 109-115Article in journal (Refereed)
  • 25.
    Lindmark, K.
    et al.
    Umea Univ, Ctr Heart, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Boman, K.
    Umea Univ, Res Unit, Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Res Unit, Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Bergman, G. J.
    QuintilesIMS, Solna, Sweden..
    Tornblom, M.
    QuintilesIMS, Solna, Sweden..
    Gullberg, E.
    Novartis Sweden AB, Stockholm, Sweden..
    Johansson, D.
    Novartis Sweden AB, Stockholm, Sweden..
    Schlienger, R.
    Novartis Pharma AG, Basel, Switzerland..
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Epidemiology of heart failure in Sweden: a retrospective population-based cohort study2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, p. 364-364Article in journal (Other academic)
  • 26. Lindqvist, Per
    et al.
    Henein, Michael Y.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Right ventricular myocardial velocities and timing estimate pulmonary artery systolic pressure2009In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 137, no 2, p. 130-136Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Non-invasive estimation of pulmonary artery systolic pressure (PASP) is important for identifying and following up patients. We aimed at revisiting the accuracy of various right ventricular (RV) Doppler echocardiographic measurements of PASP. METHODS: Twenty-eight patients were studied with simultaneous right heart catheterization (RHC), conventional and tissue Doppler echocardiography (TDE). We measured RV-right atrial (RA) peak pressure drop, RV spectral filling and myocardial velocities and timings. RESULTS: RV-RA peak pressure drop (r=0.89, p<0.001) strongly correlated with PASP. Both RV spectral and myocardial measurements of isovolumic relaxation time (IVRT) modestly correlated with PASP (r=0.63, p<0.01 and <0.001). Time interval measurements missed 6 and 9 cases with normal PASP by using proposed cut off values. Combining myocardial IVRT and isovolumic contraction velocity (IVCV) in a formula, predicted PASP in all but 3 of our patients. In addition, TDE measurements were obtainable in all cases compared to RV-RA gradient which were measurable in only 64% of patients. CONCLUSION: RV-RA peak pressure drop is the most accurate non-invasive method for assessing PASP. Combining myocardial IVCV and IVRT can be used accurately in estimating PASP being more feasible than RV-RA drop. Such additional measurement might be important in patients follow-up when RV-RA gradient is difficult to obtain.

  • 27. Lindqvist, Per
    et al.
    Waldenström, Anders
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kazzam, Elsadig
    Potential use of isovolumic contraction velocity in assessment of left ventricular contractility in man: A simultaneous pulsed Doppler tissue imaging and cardiac catheterization study2007In: European Journal of Echocardiography, ISSN 1525-2167, E-ISSN 1532-2114, Vol. 8, no 4, p. 252-258Article in journal (Refereed)
    Abstract [en]

    AIMS: Echocardiographic techniques have so far provided suboptimal estimates of myocardial contractility in humans. Longitudinal myocardial motion during the isovolumic contraction (IVC) phase, measured by colour tissue Doppler imaging (TDI), has recently been shown in experimental animal models to reflect the state of myocardial contractility. The aim of the present study was to investigate the relationship between left ventricular (LV) isovolumic contraction velocities (IVCv) using pulsed Doppler tissue imaging (DTI) and global LV contractility as measured during cardiac catheterization. METHODS AND RESULTS: Cardiac catheterization and pulsed DTI were simultaneously performed in 16 consecutive patients (13 males, mean age 55+/-10years) with a variety of cardiac diseases. Relationships between the peak positive IVCv as measured at basal levels of the lateral, septal, anterior and posterior walls and the first derivative of LV pressure (+dP/dt(max)), were investigated. Peak IVCv measurements were obtainable in 81-100% of the four LV wall segments. Statistically significant linear relationships were found between IVCv and +dP/dt(max) at the lateral (r=0.58, P<0.05), septal (r=0.66, P<0.01), anterior (r=0.73, P<0.01) and posterior (r=0.81, P<0.001) segments of the LV. CONCLUSION: IVCv of the basal four LV walls correlates strongly with peak +dP/dt. IVCv is a readily obtainable non-invasive parameter, which correlates with the classical invasive measurement of global LV contractility. It appears likely that there are regional differences in wall motion when DTI is used to determine state of LV contractility.

  • 28. Lindqvist, Per
    et al.
    Waldenström, Anders
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kazzam, Elsadig
    Right ventricular myocardial isovolumic relaxation time and pulmonary pressure2006In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 26, no 1, p. 1-8Article in journal (Refereed)
    Abstract [en]

    AIMS: Non-invasive assessment of pulmonary artery systolic pressure (PASP) has several limitations. As previously described by Burstin, the right ventricular (RV) isovolumic relaxation time (IVRt) is sensitive to changes in PASP. We therefore compared RV myocardial IVRt, derived by Doppler tissue imaging (DTI), with simultaneously measured invasive PASP. METHODS AND RESULTS: Twenty-six consecutive patients (18 males, mean age 52 +/- 12 years, range 23-75) underwent a simultaneous Doppler echocardiography, including DTI, and cardiac catheterization examination for measurement of PASP and right atrial mean pressures. IVRt was measured using the myocardial velocities by pulsed DTI at both basal and mid cavity segments of the RV free wall. As diastolic time intervals are influenced by heart rate IVRt was corrected for heart rate (IVRt/RR%). A significant correlation was found between PASP and regional IVRt/RR% at both the basal (r = 0.42, P<0.05) and mid cavity segment (r = 0.71, P<0.001). Furthermore, when only patients with normal right atrial pressures (<7 mmHg) were taken into account, the correlation coefficient improved at both basal and mid cavity segments (r = 0.74, P<0.05 and r = 0.83, P<0.01). CONCLUSION: Pulsed Doppler-derived IVRt correlates well with PASP. The use of pulsed DTI for measurement of IVRt is simple, reproducible and easy to obtain. We propose this method as an additional non-invasive tool in the assessment of PASP.

  • 29. Lindqvist, Per
    et al.
    Waldenström, Anders
    Wikström, Gerhard
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Kazzam, Elsadig
    The use of isovolumic contraction velocity to determine right ventricular state of contractility and filling pressures A pulsed Doppler tissue imaging study.2005In: Eur J Echocardiogr, ISSN 1525-2167, Vol. 6, no 4, p. 264-70Article in journal (Other scientific)
  • 30. Lindqvist, Per
    et al.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Waldenström, Anders
    The use of E/Em and the time interval difference of isovolumic relaxation (TIVRT-IVRTm) in estimating left ventricular filling pressures2008In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 10, no 5, p. 490-497Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: The ratio of the transmitral and myocardial early diastolic velocities (E/Em) can be used to estimate LV filling pressures (LVFP). Additionally, the time difference between the onset of E and Em also correlates to LVFP. The aim of this study was to evaluate which of these two indices is the best marker of LVFP in a heterogeneous group of patients during a simultaneous invasive procedure. METHODS AND RESULTS: Thirty two patients were studied. Em and the isovolumic relaxation time (IVRTm) at four segments of the LV were measured using pulsed tissue Doppler echocardiography. Pulsed Doppler echocardiography was used to measure E and IVRT. E/Em and IVRT-IVRTm (T IVRT-IVRTm) were then calculated. Highly significant correlations were found between T IVRT-IVRTm and PCWP at the lateral (r= -0.80, p<0.001) and posterior (r= -0.71, p<0.001) segments whereas only a weak relationship was found between PCWP and E/Em (p<0.05). The sensitivity and specificity of using a negative T IVRT-IVRTm for identifying patients with PCWP >12 mm Hg were 89 and 90%, respectively. CONCLUSION: We found a highly significant correlation between T IVRT-IVRTm and PCWP, which was not seen for E/Em. We propose T IVRT-IVRTm as a stronger predictor of LVFP. T IVRT-IVRTm also seems to correlate to LVFP for many different clinical aetiologies of elevated LVFP.

  • 31.
    Lundgren, J.
    et al.
    Lund Univ.
    Sandqvist, A.
    Umea Univ.
    Hedeland, M.
    Statens veterinärmedicinska anstalt (SVA) .
    Bondesson, U.
    Statens veterinärmedicinska anstalt (SVA) .
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Radegran, G.
    Lund Univ.
    L-Arginine and Methylarginines Prior to and After Heart Transplantation2017In: The Journal of Heart and Lung Transplantation, ISSN 1053-2498, E-ISSN 1557-3117, Vol. 36, no 4, p. S227-S227Article in journal (Other academic)
  • 32.
    Lundgren, Jakob
    et al.
    Lund Univ, Dept Clin Sci Lund, Cardiol, Lund, Sweden; Skåne Univ Hosp, Sect Heart Failure & Valvular Dis, Hemodynam Lab, Heart & Lung Clin, Lund, Sweden.
    Sandqvist, Anna
    Umeå Univ, Dept Pharmacol & Clin Neurosci, Clin Pharmacol, Umeå, Sweden.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Science. Natl Vet Inst (SVA), Dept Chem Environm & Feed Hyg, Uppsala, Sweden.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Science. Natl Vet Inst (SVA), Dept Chem Environm & Feed Hyg, Uppsala, Sweden.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Rådegran, Göran
    Lund Univ, Dept Clin Sci Lund, Cardiol, Lund, Sweden; Skåne Univ Hosp, Sect Heart Failure & Valvular Dis, Hemodynam Lab, Heart & Lung Clin, Lund, Sweden.
    Alterations in plasma L-arginine and methylarginines in heart failure and after heart transplantation2018In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, no 4, p. 196-204Article in journal (Refereed)
    Abstract [en]

    Objective: Endothelial function, including the nitric oxide (NO)-pathway, has previously been extensively investigated in heart failure (HF). In contrast, studies are lacking on the NO pathway after heart transplantation (HT). We therefore investigated substances in the NO pathway prior to and after HT in relation to hemodynamic parameters.

    Design: 12 patients (median age 50.0 yrs, 2 females), heart transplanted between June 2012 and February 2014, evaluated at our hemodynamic lab, at rest, prior to HT, as well as four weeks and six months after HT were included. All patients had normal left ventricular function post-operatively and none had post-operative pulmonary hypertension or acute cellular rejection requiring therapy at the evaluations. Plasma concentrations of ADMA, SDMA, L-Arginine, L-Ornithine and L-Citrulline were analyzed at each evaluation.

    Results: In comparison to controls, the plasma L-Arginine concentration was low and ADMA high in HF patients, resulting in low L-Arginine/ADMA-ratio pre-HT. Already four weeks after HT L-Arginine was normalized whereas ADMA remained high. Consequently the L-Arginine/ADMA-ratio improved, but did not normalize. The biomarkers remained unchanged at the six-month evaluation and the L-Arginine/ADMA-ratio correlated inversely to pulmonary vascular resistance (PVR) six months post-HT.

    Conclusions: Plasma L-Arginine concentrations normalize after HT. However, as ADMA is unchanged, the L-Arginine/ADMA-ratio remained low and correlated inversely to PVR. Together these findings suggest that (i) the L-Arginine/ADMA-ratio may be an indicator of pulmonary vascular tone after HT, and that (ii) NO-dependent endothelial function is partly restored after HT. Considering the good postoperative outcome, the biomarker levels may be considered “normal” after HT.

  • 33.
    Malinovschi, Andrei
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Henrohn, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Eriksson, André
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lundberg, Jon O
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Increased plasma and salivary nitrite and decreased bronchial contribution to exhaled NO in pulmonary arterial hypertension2011In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 41, no 8, p. 889-897Article in journal (Refereed)
    Abstract [en]

    Background Conflicting results on exhaled NO in pulmonary hypertension (PH) exist. Therefore, we analysedexhaled NO, as well as systemic and local nitrite, a possible alternative source of NO, in PH with regard to PHaetiology.Methods Exhaled NO at multiple flow-rates, as well as plasma and salivary nitrite and nitrate, was measured in22 patients with PH and 21 healthy controls. Alveolar NO (CalvNO) and bronchial flux (J’awNO) were calculatedusing the slope–intercept model. Patients with PH were subdivided into pulmonary arterial hypertension (PAH)and PH WHO Groups II–IV, according to the WHO clinical classification of PH.Results Exhaled NO was reduced at flow-rates in the range of 20)200 mL s)1 in patients with PAH (n = 13) vs.PH WHO Group II–IV (n = 9) (P < 0Æ05 all). Patients with PAH had higher CalvNO than healthy controls [2Æ61(2Æ23, 3Æ36) vs. 1.97 ppb (1Æ22, 2Æ49), P = 0Æ03] and similar to PH WHO Group II–IV (P = 0Æ51). Patients with PAHhad lower J’awNO than patients with PH WHO Group II–IV or healthy controls [430 (371, 702) vs. 807 (557, 993)or 731 pL s)1 (580, 818), P < 0Æ05 both]. Subjects with PAH were characterized by higher levels of salivary andplasma nitrite than healthy controls (P < 0Æ05 both).Conclusions Patients with PAH have lower bronchial NO flux compared to healthy controls and patients withPH WHO Group II–IV along with elevated salivary and plasma nitrite compared to controls. This implies reducedbronchial NO synthase-derived NO formation in PAH. Increased alveolar NO levels were found in subjects withPH compared to controls, especially in subjects with PAH. This may reflect NO diffusion disturbances in thealveoli.

  • 34.
    Melberg, A
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Oldfors, A
    Blomström-Lundqvist, C
    Department of Medical Sciences.
    Stålberg, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Carlsson, B
    Larsson, E
    Department of Genetics and Pathology.
    Lidell, C
    Eeg-Olofsson, K E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Wikström, G
    Henriksson, G
    Dahl, N
    Department of Genetics and Pathology.
    Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy linked to chromosome 10q.1999In: Ann Neurol, ISSN 0364-5134, Vol. 46, no 5, p. 684-92Article in journal (Refereed)
  • 35.
    Mutschler, Diana K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lagrange, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Etanercept reduces late endotoxin-induced pulmonary hypertension in the pig2006In: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 26, no 9, p. 661-667Article in journal (Refereed)
    Abstract [en]

    To evaluate whether etanercept, a tumor necrosis factor (TNF)-blocking agent, may counteract hemodynamic deterioration in endotoxemic shock, we designed a prospective, randomized placebo-controlled trial with parallel groups, consisting of 13 pigs aged 10-14 weeks receiving general anesthesia. Five pigs were given 25 mg of etanercept, 1 h before the start of a 4-h continuous infusion of endotoxin. Another 5 pigs were given the corresponding volume of saline, 1 h before the start of a 4-h continuous infusion of endotoxin. Three pigs were given 25 mg of etanercept, 1 hr before the start of a 4-h continuous infusion of saline. At 1 h of endotoxemia, mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) increased identically in both groups of pigs receiving endotoxin. Thereafter, two distinct different patterns in hemodynamics were observed. TNF-blocked pigs showed significantly lower MPAP and PVRI compared to controls. In the etanercept-treated endotoxemic pigs, Doppler analysis of the diastolic mitral inflow demonstrated a significantly increased E/A-ratio (early mitral wave inflow was divided by the atrial wave) at 2 h. The TNFblocking agent etanercept normalized two hemodynamic features of endotoxin-induced septic shock in pigs: (1) the sustained pulmonary hypertension and (2) diastolic dysfunction.

  • 36. Nieminen, M. S.
    et al.
    Altenberger, J.
    Ben-Gal, T.
    Boehmer, A.
    Comin-Colet, J.
    Dickstein, K.
    Edes, I.
    Fedele, F.
    Fonseca, C.
    Garcia-Gonzalez, M. J.
    Giannakoulas, G.
    Iakobishvili, Z.
    Jaaskelainen, P.
    Karavidas, A.
    Kettner, J.
    Kivikko, M.
    Lund, L. H.
    Matskeplishvili, S. T.
    Metra, M.
    Morandi, F.
    Oliva, F.
    Parkhomenko, A.
    Parissis, J.
    Pollesello, P.
    Poelzl, G.
    Schwinger, R. H. G.
    Segovia, J.
    Seidel, M.
    Vrtovec, B.
    Wikstrom, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Repetitive use of levosimendan for treatment of chronic advanced heart failure: Clinical evidence, practical considerations, and perspectives: An expert panel consensus2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 174, no 2, p. 360-367Article in journal (Refereed)
    Abstract [en]

    Background: The intravenous inodilator levosimendan was developed for the treatment of patients with acutely decompensated heart failure. In the last decade scientific and clinical interest has arisen for its repetitive or intermittent use in patients with advanced chronic, but not necessarily acutely decompensated, heart failure. Recent studies have suggested long-lasting favourable effects of levosimendan when administered repetitively, in terms of haemodynamic parameters, neurohormonal and inflammatory markers, and clinical outcomes. The existing data, however, requires further exploration to allow for definitive conclusions on the safety and clinical efficacy of repetitive use of levosimendan. Methods and results: A panel of 30 experts from 15 countries convened to review and discuss the existing data, and agreed on the patient groups that can be considered to potentially benefit from intermittent treatment with levosimendan. The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience. Conclusions: The current data suggest that in selected patients and support out-of-hospital care, intermittent/repetitive levosimendan can be used in advanced heart failure to maintain patient stability. Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring. Recommendations for the design of further clinical studies are made. (C) 2014 The Authors. Published by Elsevier Ireland Ltd.

  • 37.
    Nieminen, M. S.
    et al.
    Univ Helsinki, Cent Hosp, Helsinki, Finland..
    Buerke, M.
    St Marien Krankenhaus, Kardiol Angiol & Internist Intens Med, Siegen, Germany..
    Parissis, J.
    Attiko Teaching Hosp, Univ Cardiol Clin 2, Athens, Greece..
    Ben-Gal, T.
    Rabin Med Ctr, Heart Failure Unit, Petah Tiqwa, Israel.;Rabin Med Ctr, Heart Transplant Clin, Petah Tiqwa, Israel..
    Pollesello, P.
    Orion Pharma, Crit Care Proprietary Prod Div, Espoo, Finland. Gennimatas Gen Hosp Athens, Heart Failure Clin & Echo Lab, Athens, Greece..
    Kivikko, M.
    Orion Pharma, Crit Care Proprietary Prod Div, Espoo, Finland. Gennimatas Gen Hosp Athens, Heart Failure Clin & Echo Lab, Athens, Greece..
    Karavidas, A.
    Severino, P.
    Univ Roma La Sapienza, Dept Cardiovasc Resp Nephrol Anesthesiol & Geriat, Rome, Italy..
    Comin-Colet, J.
    Hosp Mar, Med Res Inst, IMIM, Barcelona, Spain..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Fedele, F.
    Univ Roma La Sapienza, Dept Cardiovasc Resp Nephrol Anesthesiol & Geriat, Rome, Italy..
    Pharmaco-economics of levosimendan in cardiology: A European perspective2015In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 199, p. 337-341Article in journal (Refereed)
    Abstract [en]

    Introduction: Heart failure places a significant economic burden on health care. Acute heart failure requires hospitalization and often frequent re-hospitalization in expensive wards where vasoactive rescue therapy is often added on top of standard medications. In these lean times, there is a growing need for cost-effective therapeutic options that supply superior support and in addition shorten the length of stay in hospital and reduce re-hospitalization rates. The inodilator levosimendan represents the latest addition to the vasoactive treatments of acute heart failure patients, and it appears to meet these expectations. Our aim was to answer the question whether the treatment efficacy of levosimendan - when selected as therapy for patients hospitalized for acute heart failure - brings savings to hospitals in various European countries representing different economies. Methods and results: We took a conservative approach and selected some a fortiori arguments to simplify the calculations. We selected seven European countries to represent different economies: Italy, Spain, Greece, Germany, Sweden, Finland and Israel. Data on the costs of medications and on the cost per day were collected and fed in a simple algorithm to detect savings. These saving varied from country to country, from a minimum of (sic)0.50 in Germany to a maximum of (sic)354.64 in Sweden. Conclusions: The use of levosimendan as a therapy for patients hospitalized for acute heart failure provides a net saving to hospitals driven by a reduction in the length of hospital stay. This finding is true in each of the countries considered in this study.

  • 38. Nieminen, Markku S.
    et al.
    Dickstein, Kenneth
    Fonseca, Candida
    Magana Serrano, Jose
    Parissis, John
    Fedele, Francesco
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Agostoni, Piergiuseppe
    Atar, Shaul
    Baholli, Loant
    Brito, Dulce
    Comin Colet, Josep
    Edes, Istvan
    Gomez Mesa, Juan E.
    Gorjup, Vojka
    Herrera Garza, Eduardo
    Gonzalez Juanatey, Jose R.
    Karanovic, Nenad
    Karavidas, Apostolos
    Katsytadze, Igor
    Kivikko, Matti
    Matskeplishvili, Simon
    Merkely, Bela
    Morandi, Fabrizio
    Novoa, Angel
    Oliva, Fabrizio
    Ostadal, Petr
    Pereira-Barretto, Antonio
    Pollesello, Piero
    Rudiger, Alain
    Schwinger, Robert H. G.
    Wieser, Manfred
    Yavelov, Igor
    Zymlinski, Robert
    The patient perspective: Quality of life in advanced heart failure with frequent hospitalisations2015In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 191, p. 256-264Article, review/survey (Refereed)
    Abstract [en]

    End of life is an unfortunate but inevitable phase of the heart failure patients' journey. It is often preceded by a stage in the progression of heart failure defined as advanced heart failure, and characterised by poor quality of life and frequent hospitalisations. In clinical practice, the efficacy of treatments for advanced heart failure is often assessed by parameters such as clinical status, haemodynamics, neurohormonal status, and echo/MRI indices. From the patients' perspective, however, quality-of-life-related parameters, such as functional capacity, exercise performance, psychological status, and frequency of re-hospitalisations, are more significant. The effects of therapies and interventions on these parameters are, however, underrepresented in clinical trials targeted to assess advanced heart failure treatment efficacy, and data are overall scarce. This is possibly due to a non-universal definition of the quality-of-life-related endpoints, and to the difficult standardisation of the data collection. These uncertainties also lead to difficulties in handling trade-off decisions between quality of life and survival by patients, families and healthcare providers. A panel of 34 experts in the field of cardiology and intensive cardiac care from 21 countries around the world convened for reviewing the existing data on quality-of-life in patients with advanced heart failure, discussing and reaching a consensus on the validity and significance of quality-of-life assessment methods. Gaps in routine care and research, which should be addressed, were identified. Finally, published data on the effects of current i.v. vasoactive therapies such as inotropes, inodilators, and vasodilators on quality-of-life in advanced heart failure patients were analysed.

  • 39.
    Nieminen, Markku S.
    et al.
    Helsinki Univ Hosp, Meilahti Tower Hosp, Heart & Lung Ctr, PL 340, Helsinki 00029, Finland..
    Fonseca, Candida
    Hosp Sao Francisco Xavier, Ctr Hosp Lisboa Ocidental, Dept Internal Med, Heart Failure Unit, P-1449005 Lisbon, Portugal..
    Brito, Dulce
    Hosp Santa Maria, Ctr Hosp Lisboa Norte, Dept Cardiol, Av Prof Egas Moniz, P-1649035 Lisbon, Portugal..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    The potential of the inodilator levosimendan in maintaining quality of life in advanced heart failure2017In: European Heart Journal, Supplement, ISSN 1520-765X, E-ISSN 1554-2815, Vol. 19, no C, p. C15-C21Article in journal (Refereed)
    Abstract [en]

    Maintaining adequate quality of life (QoL) is an important therapeutic objective for patients with advanced heart failure and, for some patients, may take precedence over prolonging life. Achieving good QoL in this context may involve aspects of patient care that lie outside the familiar limits of heart failure treatment. The inodilator levosimendan may be advantageous in this setting, not least because of its sustained duration of action, ascribed to a long-acting metabolite designated OR-1896. The possibility of using this drug in an outpatient setting is a notable practical advantage that avoids the need for patients to attend a clinic appointment. Intermittent therapy can be integrated into a wider system of outreach and patient monitoring. Practical considerations in the use of levosimendan as part of a palliative or end-of-life regimen focused on preserving QoL include the importance of starting therapy at low doses and avoiding bolus administration unless immediate effects are required and patients have adequate baseline arterial blood pressure.

  • 40.
    Poelzl, Gerhard
    et al.
    Univ Klin Innsbruck, Innsbruck, Austria..
    Altenberger, Johann
    Rehabil Zentrum Grossgmain, Salzburg, Austria..
    Baholli, Loant
    Klinikum Dortmund Mitte, Dortmund, Germany..
    Beltran, Paola
    HM Broggi, Barcelona, Spain..
    Borbely, Attila
    Univ Debrecen, Fac Med, Div Clin Physiol, Debrecen, Hungary..
    Comin-Colet, Josep
    Univ Hosp Bellvitge, Barcelona, Spain..
    Delgado, Juan F.
    Hosp 12 Octubre, Madrid, Spain..
    Fedele, Francesco
    Sapienza Univ, Policlin Umberto 1, Rome, Italy..
    Fontana, Antonella
    Orion Pharma Srl, Milan, Italy..
    Fruhwald, Friedrich
    Med Univ Klin, Graz, Austria..
    Giamouzis, Gregory
    Univ Thessaly, Larissa Univ Hosp, Larisa, Greece..
    Giannakoulas, George
    Aristotle Univ Thessaloniki, Thessaloniki, Greece..
    Garcia-Gonzalez, Martin J.
    H La Laguna, Tenerife, Spain..
    Gustafsson, Finn
    Rigshosp, Copenhagen, Denmark..
    Kaikkonen, Kari
    Oulu Univ Hosp, Oulu, Finland..
    Kivikko, Matti
    Orion Pharma, Espoo, Finland..
    Kubica, Jacek
    Nicolaus Copernicus Univ, Coll Med, Bydgoszcz, Poland..
    von Lewinski, Dirk
    Med Univ Klin, Graz, Austria..
    Lofman, Ida
    Karolinska Univ Sjukhus Huddinge, Huddinge, Sweden..
    Malfatto, Gabriella
    Ist Auxol Italiano, Milan, Italy..
    Manito, Nicolas
    Univ Hosp Bellvitge, Barcelona, Spain..
    Martinez-Selles, Martin
    H Gregorio Maranon, Madrid, Spain..
    Masip, Josep
    HM Broggi, Barcelona, Spain..
    Merkely, Bela
    Semmelweis Univ, Heart & Vasc Ctr, Budapest, Hungary..
    Morandi, Fabrizio
    Circolo Hosp & Macchi Fdn, Varese, Italy..
    Molgaard, Henning
    Aarhus Univ Hosp, Skejby, Denmark..
    Oliva, Fabrizio
    Osped Niguarda Ca Granda, Milan, Italy..
    Pantev, Emil
    Helsingborgs Iasarett, Helsingborg, Sweden..
    Papp, Zoltan
    Univ Debrecen, Fac Med, Div Clin Physiol, Debrecen, Hungary..
    Perna, Gian Piero
    Osped Riuniti, Dipartimento Sci Cardiol Med Chirurg, Ancona, Italy..
    Pfister, Roman
    Univ Cologne, Herzzentrum, Klin Innere Med 3, Cologne, Germany..
    Piazza, Vito
    Azienda Osped San Camillo Forlanini, Rome, Italy..
    Bover, Ramon
    H Clin San Carlos, Madrid, Spain..
    Rangel-Sousa, Diego
    H Virgen Rocio, Seville, Spain..
    Recio-Mayoral, Alejandro
    Hosp Univ Virgen Macarena, Seville, Spain..
    Reinecke, Alexander
    Uni Klinikum Schleswig Holstein, Kiel, Germany..
    Rieth, Andreas
    Kerckhoff Klin, Bad Nauheim, Germany..
    Sarapohja, Toni
    Orion Pharma, Espoo, Finland..
    Schmidt, Gunter
    CHARITE Univ Med Berlin, Berlin, Germany..
    Seidel, Mirko
    Unfallkrankenhaus Berlin, Innere Med Klin, Berlin, Germany..
    Stoerk, Stefan
    Univ Wurzburg, Comprehens Heart Failure Ctr, Wurzburg, Germany.;Univ Hosp, Wurzburg, Germany..
    Vrtovec, Bojan
    Univ Clin Ctr, Ljubljana, Slovenia..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Yerly, Patrik
    CHU Vaudois, Lausanne, Switzerland..
    Pollesello, Piero
    Orion Pharma, Espoo, Finland..
    Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 243, p. 389-395Article in journal (Refereed)
    Abstract [en]

    Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminalprohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.

  • 41.
    Rådegran, Göran
    et al.
    Lund Univ, Dept Clin Sci Lund, Cardiol, Lund, Sweden.;Skåne Univ Hosp, Haemodynam Lab, Sect Heart Failure & Valvular Dis, VO Heart & Lung Med, S-22185 Lund, Sweden..
    Kjellström, Barbro
    Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Ekmehag, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Univ Uppsala Hosp, Uppsala, Sweden..
    Larsen, Flemming
    Karolinska Inst, Dept Mol Med & Surg, Sect Clin Physiol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Physiol, Stockholm, Sweden..
    Rundqvist, Bengt
    Gothenburg Univ, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Cardiol, Gothenburg, Sweden..
    Berg Blomquist, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Gustafsson, Carola
    Gothenburg Univ, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Cardiol, Gothenburg, Sweden..
    Hesselstrand, Roger
    Lund Univ, Dept Clin Sci, Rheumatol, Lund, Sweden.;Skane Univ Hosp, Rheumatol Clin, Lund, Sweden..
    Karlsson, Monica
    Linkoping Univ, Inst Med & Hlth Sci, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Inst Med & Hlth Sci, Dept Clin Physiol, Linkoping, Sweden..
    Kornhall, Björn
    Lund Univ, Dept Clin Sci Lund, Cardiol, Lund, Sweden.;Skane Univ Hosp, Haemodynam Lab, Sect Heart Failure & Valvular Dis, VO Heart & Lung Med, S-22185 Lund, Sweden..
    Nisell, Magnus
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Clin Pulm Med, Stockholm, Sweden..
    Persson, Liselotte
    Lund Univ, Dept Clin Sci Lund, Cardiol, Lund, Sweden.;Skåne Univ Hosp, Haemodynam Lab, Sect Heart Failure & Valvular Dis, VO Heart & Lung Med, S-22185 Lund, Sweden..
    Ryftenius, Henrik
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Clin Pulm Med, Stockholm, Sweden..
    Selin, Maria
    Umeå Univ, Dept Publ Hlth & Clin Med, Cardiol, Umeå, Sweden.;Umea Univ, Ctr Heart, Umea, Sweden..
    Ullman, Bengt
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden.;Söder Sjukhuset, Dept Cardiol, Stockholm, Sweden..
    Wall, Kent
    Univ Örebro, Dept Clin Physiol, Örebro, Sweden.;Örebro Univ Hosp, Örebro, Sweden..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Willehadson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jansson, Kjell
    Linköping Univ, Inst Med & Hlth Sci, Dept Cardiol, Linköping, Sweden.;Linköping Univ, Inst Med & Hlth Sci, Dept Clin Physiol, Linköping, Sweden..
    Söderberg, Stefan
    Umeå Univ, Dept Publ Hlth & Clin Med, Cardiol, Umeå, Sweden.;Umeå Univ, Ctr Heart, Umeå, 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.

  • 42.
    Salehpour, Mehran
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Håkansson, Karl
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Possnert, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Life science application utilizing radiocarbon tracing2013In: Radiocarbon, ISSN 0033-8222, E-ISSN 1945-5755, Vol. 55, no 2-3, p. 865-873Article in journal (Refereed)
    Abstract [en]

    Radiocarbon-based accelerator mass spectrometry (AMS) facilities at Uppsala University include a measurement center for archaeological applications and a separate entity dedicated to life science research. This paper addresses the latter, with the intention of giving a brief description of the biomedical activities at our laboratory, as well as presenting new data. The ultra-small sample preparation method, which can be used down to a few µg C samples, is outlined and complemented with new results. Furthermore, it is shown that the average secondary ion current performance for small samples can be improved by increasing the distance between the cathode surface and the pressed graphite surface. Finally, data is presented for a new application: Amyloidoses are a group of diseases where the conformational changes in specific proteins’ structure lead to the formation of extracellular deposits that spread and increase in mass and eventually may lead to total organ failure and death. The formation timeframe is unknown and yet it is an important clue for the elucidation of the mechanism. We present results on bomb-peak dating of 4 different types of purified amyloid proteins from human postmortem heart and spleen samples. The data indicates that the average measured age of the carbon originating from the systemic amyloid types studied here correspond to a few years before the death of the subject. This suggests that a major part of the fibril formation takes place during the last few years before death, rather than as an accumulation of amyloid deposits over decades.

  • 43.
    Salehpour, Mehran
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Håkansson, Karl
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Possnert, Possnert
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Life science applications utilizing radiocarbon tracing2013In: Radiocarbon, ISSN 0033-8222, E-ISSN 1945-5755, Vol. 55, no 2-3, p. 865-873Article in journal (Refereed)
    Abstract [en]

    Radiocarbon-based accelerator mass spectrometry (AMS) facilities at Uppsala University include a measurement center for archaeological applications and a separate entity dedicated to life science research. This paper addresses the latter, with the intention of giving a brief description of the biomedical activities at our laboratory, as well as presenting new data. The ultra-small sample preparation method, which can be used down to a few μg C samples, is outlined and complemented with new results. Furthermore, it is shown that the average secondary ion current performance for small samples can be improved by increasing the distance between the cathode surface and the pressed graphite surface. Finally, data is presented for a new application: Amyloidoses are a group of diseases where the conformational changes in specific proteins’ structure lead to the formation of extracellular deposits that spread and increase in mass and eventually may lead to total organ failure and death. The formation timeframe is unknown and yet it is an important clue for the elucidation of the mechanism. We present results on bomb-peak dating of 4 different types of purified amyloid proteins from human postmortem heart and spleen samples. The data indicates that the average measured age of the carbon originating from the systemic amyloid types studied here correspond to a few years before the death of the subject. This suggests that a major part of the fibril formation takes place during the last few years before death, rather than as an accumulation of amyloid deposits over decades.

  • 44.
    Sandqvist, Anna
    et al.
    Umea Univ, Div Clin Pharmacol, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Henrohn, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Egeröd, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst SVA, Dept Chem, Uppsala, Sweden..
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst SVA, Dept Chem, Uppsala, Sweden..
    Schneede, Jorn
    Umea Univ, Div Clin Pharmacol, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Acute vasodilator response to vardenafil and clinical outcome in patients with pulmonary hypertension2015In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 71, no 10, p. 1165-1173Article in journal (Refereed)
    Abstract [en]

    Purpose Acute vasodilator testing is recommended in patients with pulmonary arterial hypertension to identify individuals who may benefit from long-term treatment with oral calcium channel blockers. The aim of this study was to investigate the use of vardenafil in acute vasoreactivity testing compared to adenosine. Methods A total of 20 patients eligible for right heart catheterisation were enrolled. Acute vasoreactivity testing was carried out with intravenous (iv) adenosine (n = 18) followed by oral vardenafil (n = 20). Haemodynamic responses were recorded at baseline and after 60 min (vardenafil). Responders were defined according to consensus guideline criteria. Results Both vardenafil and adenosine significantly decreased mean pulmonary arterial pressure (mPAP, p < 0.001 and p = 0.026, respectively) and pulmonary vascular resistance (p < 0.001 and p > 0.001, respectively), and significantly increased cardiac output (p = 0.001 and p = 0.005, respectively). Vardenafil reduced mPAP more than adenosine (p = 0.044), while adenosine resulted in higher responses of cardiac index (p = 0.009) and pulmonary arterial oxygen saturation (p = 0.042). Acute adverse reactions were common with adenosine, while no side effects were observed after a single oral dose vardenafil. Vardenafil identified five responders (out of 20), while adenosine identified three responders (out of 18). During a 7-year follow-up, vardenafil responders had significantly lower NT-proBNP levels compared to non-responders. Conclusions Vardenafil may be safely used for acute vasoreactivity testing in patients with PH. A single oral dose of vardenafil is better tolerated than iv adenosine and may identify additional responders who could benefit from long-term vasodilator treatment.

  • 45.
    Sandqvist, Anna
    et al.
    Umea Univ, Clin Pharmacol, Dept Pharmacol & Clin Neurosci, S-90187 Umea, Sweden..
    Schneede, Jörn
    Umea Univ, Clin Pharmacol, Dept Pharmacol & Clin Neurosci, S-90187 Umea, Sweden..
    Kylhammar, David
    Lund Univ, Dept Clin Sci Lund, Cardiol, Lund, Sweden.;Skane Univ Hosp, Sect Heart Failure & Valvular Dis, Lund, Sweden..
    Henrohn, D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lundgren, Jakob
    Lund Univ, Dept Clin Sci Lund, Cardiol, Lund, Sweden.;Skane Univ Hosp, Sect Heart Failure & Valvular Dis, Lund, Sweden..
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Science. Natl Vet Inst SVA, Dept Chem, Uppsala, Sweden..
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Science. Natl Vet Inst SVA, Dept Chem, Uppsala, Sweden..
    Rådegran, Göran
    Lund Univ, Dept Clin Sci Lund, Cardiol, Lund, Sweden.;Skane Univ Hosp, Sect Heart Failure & Valvular Dis, Lund, Sweden..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden..
    Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction2018In: Heart and Vessels, ISSN 0910-8327, E-ISSN 1615-2573, Vol. 33, no 3, p. 255-263Article in journal (Refereed)
    Abstract [en]

    Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from l-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, l-arginine, l-ornithine, and l-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas l-arginine and l-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p < 0.001). Patients with PAH also had lower levels of l-arginine than patients with LVSD (p < 0.05). l-Arginine correlated to 6 min walking distance (6MWD) (r (s) = 0.58, p = 0.006) and l-arginine/ADMA correlated to WHO functional class (r (s) = -0.46, p = 0.043) in PAH. In conclusion, l-arginine levels were significantly lower in treatment na < ve PAH patients compared to patients with LVSD. Furthermore, l-arginine correlated with 6MWD in PAH. l-arginine may provide useful information in differentiating PAH from LVSD.

  • 46. Sartipy, Ulrik
    et al.
    Kjellman, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Samuelsson, Sten
    Hagerman, Inger
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Thomas
    Albåge, Anders
    Lindblom, Dan
    Left ventricular reconstruction as an alternative to heart transplantation: a case report2006In: Heart Surgery Forum, ISSN 1098-3511, E-ISSN 1522-6662, Vol. 9, no 3, p. E638-E640Article in journal (Refereed)
    Abstract [en]

    A 57-year-old man with dilated cardiomyopathy was referred to our institution to be assessed for heart transplantation. He had symptoms of severe heart failure and left ventricular dysfunction. We proposed surgical ventricular restoration (the Dor procedure) as an alternative to heart transplantation. The patient underwent successful surgery and an uneventful postoperative course. Pre- and postoperative investigations are presented. One year after surgery, the patient is in good clinical and functional condition. This case illustrates that surgical ventricular restoration can be an alternative to heart transplantation.

  • 47. Selimovic, N.
    et al.
    Lövgren Ekmehag, B.
    Jansson, K.
    Larsen, F.
    Söderberg, S.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pulmonary Arterial Hypertension in Sweden: First Data from a National Registry2012In: The Journal of Heart and Lung Transplantation, ISSN 1053-2498, E-ISSN 1557-3117, Vol. 31, no 4, p. S284-S284Article in journal (Other academic)
  • 48.
    Stålhammar, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Boman, K.
    Umea Univ, Res Unit, Skelleftea Cty Hosp, Med & Geriatr,Dept Publ Hlth, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Res Unit, Skelleftea Cty Hosp, Med & Geriatr,Dept Publ Hlth, Umea, Sweden..
    Lindmark, K.
    Umea Univ, Ctr Heart, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Lahoz, R.
    Novartis Pharma AG, Basel, Switzerland..
    Corda, S.
    Novartis Pharma AG, Basel, Switzerland..
    Wintzell, V.
    IMS Hlth Sweden, Stockholm, Sweden..
    Linder, R.
    IMS Hlth Sweden, Stockholm, Sweden..
    Gondos, A.
    IMS Hlth Germany, Berlin, Germany..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    A description of unselected patients with heart failure: a swedish population-based study2016In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 18, p. 195-195Article in journal (Other academic)
  • 49.
    Stålhammar, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Boman, K.
    Umea Univ, Res Unit, Med & Geriatr, Skelleftea Cty Hosp,Dept Publ Hlth, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Res Unit, Med & Geriatr, Skelleftea Cty Hosp,Dept Publ Hlth, Umea, Sweden..
    Lindmark, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Ctr Heart, Umea, Sweden..
    Lahoz, R.
    Novartis Pharma AG, Basel, Switzerland..
    Corda, S.
    Novartis Pharma AG, Basel, Switzerland..
    Wintzell, V.
    IMS Hlth Sweden, Stockholm, Sweden..
    Linder, R.
    IMS Hlth Sweden, Stockholm, Sweden..
    Gondos, A.
    IMS Hlth Germany, Berlin, Germany..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Recent trends in diagnostic work-up among unselected patients newly diagnosed with heart failure: a Swedish population-based study2016In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 18, p. 54-55Article in journal (Other academic)
  • 50.
    Stålhammar, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Boman, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Res Unit, Med, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Dept Publ Hlth & Clin Med, Res Unit, Med, Umea, Sweden..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Bergman, G. J.
    QuintilesIMS, Solna, Sweden..
    Tornblom, M.
    QuintilesIMS, Solna, Sweden..
    Wintzell, V.
    QuintilesIMS, Solna, Sweden..
    Wirta, S. Bruce
    Novartis Sweden AB, Stockholm, Sweden..
    Proenca, C. C.
    Wellmera AG, Basel, Switzerland..
    Schlienger, R.
    Novartis Pharma AG, Basel, Switzerland..
    Lindmark, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Ctr Heart, Umea, Sweden..
    Management of patients with heart failure with preserved versus reduced ejection fraction: a retrospective population-based cohort study in Sweden2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, p. 54-55Article in journal (Other academic)
12 1 - 50 of 67
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