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  • 251.
    Ekstedt, Mattias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hagström, Hannes
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Nasr, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Stål, Per
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hultcrantz, Rolf
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up2015In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 61, no 5, p. 1547-1554Article in journal (Refereed)
    Abstract [en]

    Background and rationale for the study: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e. fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. Methods: In a cohort study, data from 229 well-characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (± 5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. Main results: NAFLD patients had an increased mortality compared with the reference population (HR 1.29, CI 1.04-1.59, p=0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, p=0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, p=0.001), infectious disease (HR 2.71, CI 1.02-7.26, p=0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, p=0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, p=0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, p<0.001). Conclusions: NAFLD patients have increased risk of death, with a high risk of death from cardiovascular disease and liver-related disease. The NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease-specific mortality.

  • 252.
    Ekstrom, Magnus Pär
    et al.
    Lund Univ, Sweden.
    Blomberg, Anders
    Umea Univ, Sweden.
    Bergström, Göran
    Univ Gothenburg, Sweden.
    Brandberg, John
    Univ Gothenburg, Sweden.
    Caidahl, Kenneth
    Univ Gothenburg, Sweden.
    Engström, Gunnar
    Lund Univ, Sweden.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Eriksson, Maria
    Karolinska Inst, Sweden.
    Gränsbo, Klas
    Lund Univ, Sweden.
    Hansen, Tomas
    Uppsala Univ, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Sweden.
    Nilsson, Lars
    Umea Univ, Sweden.
    Nilsson, Ulf
    Umea Univ, Sweden.
    Olin, Anna-Carin
    Univ Gothenburg, Sweden.
    Persson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Rosengren, Annika
    Univ Gothenburg, Sweden.
    Sandelin, Martin
    Uppsala Univ, Sweden.
    Sköld, Magnus
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Sundström, Johan
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Söderberg, Stefan
    Umea Univ, Sweden.
    Tanash, Hanan A.
    Lund Univ, Sweden.
    Torén, Kjell
    Sahlgrens Univ Hosp, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Lindberg, Eva
    Uppsala Univ, Sweden.
    The association of body mass index, weight gain and central obesity with activity-related breathlessness: the Swedish Cardiopulmonary Bioimage Study2019In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 74, no 10, p. 958-964Article in journal (Refereed)
    Abstract [en]

    Introduction Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) amp;gt;30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear. Methods This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score amp;gt;= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex. Results We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; pamp;lt;0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness. Conclusion Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.

  • 253.
    Eleonora Hedlund, Eva-Maria
    et al.
    Karolinska Institute, Sweden .
    Yang, Xiaojuan
    Karolinska Institute, Sweden .
    Zhang, Yin
    Karolinska Institute, Sweden .
    Yang, Yunlong
    Karolinska Institute, Sweden .
    Shibuya, Masabumi
    Tokyo Medical and Dent University, Japan .
    Zhong, Weide
    Guangzhou Medical University, Peoples R China .
    Sun, Baocun
    Tianjin Medical University, Peoples R China .
    Liu, Yizhi
    Sun Yat Sen University, Peoples R China .
    Hosaka, Kayoko
    Karolinska Institute, Sweden .
    Cao, Yihai
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Karolinska Institute, Sweden .
    Tumor cell-derived placental growth factor sensitizes antiangiogenic and antitumor effects of anti-VEGF drugs2013In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 2, p. 654-659Article in journal (Refereed)
    Abstract [en]

    The role of placental growth factor (PlGF) in modulation of tumor angiogenesis and tumor growth remains an enigma. Furthermore, anti-PlGF therapy in tumor angiogenesis and tumor growth remains controversial in preclinical tumor models. Here we show that in both human and mouse tumors, PlGF induced the formation of dilated and normalized vascular networks that were hypersensitive to anti-VEGF and anti-VEGFR-2 therapy, leading to dormancy of a substantial number of avascular tumors. Loss-of-function using plgf shRNA in a human choriocarcinoma significantly accelerated tumor growth rates and acquired resistance to anti-VEGF drugs, whereas gain-of-function of PlGF in a mouse tumor increased anti-VEGF sensitivity. Further, we show that VEGFR-2 and VEGFR-1 blocking antibodies displayed opposing effects on tumor angiogenesis. VEGFR-1 blockade and genetic deletion of the tyrosine kinase domain of VEGFR-1 resulted in enhanced tumor angiogenesis. These findings demonstrate that tumor-derived PlGF negatively modulates tumor angiogenesis and tumor growth and may potentially serve as a predictive marker of anti-VEGF cancer therapy.

  • 254.
    Engerström, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Kramer, Andrew A.
    Prescient Healthcare Consulting, Charlottesville, VA.
    Nolin, Thomas
    The Swedish Intensive Care Registry, Karlstad, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Karlström, Göran
    The Swedish Intensive Care Registry, Karlstad, Sweden.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Academic Research Center, Linköping University, Linköping, Sweden.
    Walther, Sten M
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Comparing Time-Fixed Mortality Prediction Models and Their Effect on ICU Performance Metrics Using the Simplified Acute Physiology Score 3.2016In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 44, no 11Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To examine ICU performance based on the Simplified Acute Physiology Score 3 using 30-day, 90-day, or 180-day mortality as outcome measures and compare results with 30-day mortality as reference.

    DESIGN: Retrospective cohort study of ICU admissions from 2010 to 2014.

    SETTING: Sixty-three Swedish ICUs that submitted data to the Swedish Intensive Care Registry.

    PATIENTS: The development cohort was first admissions to ICU during 2011-2012 (n = 53,546), and the validation cohort was first admissions to ICU during 2013-2014 (n = 57,729).

    INTERVENTIONS: None.

    MEASUREMENTS AND MAIN RESULTS: Logistic regression was used to develop predictive models based on a first level recalibration of the original Simplified Acute Physiology Score 3 model but with 30-day, 90-day, or 180-day mortality as measures of outcome. Discrimination and calibration were excellent for the development dataset. Validation in the more recent 2013-2014 database showed good discrimination (C-statistic: 0.85, 0.84, and 0.83 for the 30-, 90-, and 180-d models, respectively), and good calibration (standardized mortality ratio: 0.99, 0.99, and 1.00; Hosmer-Lemeshow goodness of fit H-statistic: 66.4, 63.7, and 81.4 for the 30-, 90-, and 180-d models, respectively). There were modest changes in an ICU's standardized mortality ratio grouping (< 1.00, not significant, > 1.00) when follow-up was extended from 30 to 90 days and 180 days, respectively; about 11-13% of all ICUs.

    CONCLUSIONS: The recalibrated Simplified Acute Physiology Score 3 hospital outcome prediction model performed well on long-term outcomes. Evaluation of ICU performance using standardized mortality ratio was only modestly sensitive to the follow-up time. Our results suggest that 30-day mortality may be a good benchmark of ICU performance. However, the duration of follow-up must balance between what is most relevant for patients, most affected by ICU care, least affected by administrative policies and practically feasible for caregivers.

  • 255.
    Engerström, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nolin, Thomas
    Central Hospital Kristianstad, Sweden.
    Mårdh, Caroline
    Landstinget Värmland, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Karlström, Göran
    Landstinget Varmland, Sweden.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences, Forum Östergötland.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Impact of Missing Physiologic Data on Performance of the Simplified Acute Physiology Score 3 Risk-Prediction Model*2017In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 12, p. 2006-2013Article in journal (Refereed)
    Abstract [en]

    Objectives: The Simplified Acute Physiology 3 outcome prediction model has a narrow time window for recording physiologic measurements. Our objective was to examine the prevalence and impact of missing physiologic data on the Simplified Acute Physiology 3 models performance. Design: Retrospective analysis of prospectively collected data. Setting: Sixty-three ICUs in the Swedish Intensive Care Registry. Patients: Patients admitted during 2011-2014 (n = 107,310). Interventions: None. Measurements and Main Results: Model performance was analyzed using the area under the receiver operating curve, scaled Briers score, and standardized mortality rate. We used a recalibrated Simplified Acute Physiology 3 model and examined model performance in the original dataset and in a dataset of complete records where missing data were generated (simulated dataset). One or more data were missing in 40.9% of the admissions, more common in survivors and low-risk admissions than in nonsurvivors and high-risk admissions. Discrimination did not decrease with one to two missing variables, but accuracy was highest with no missing data. Calibration was best in the original dataset with a mix of full records and records with some missing values (area under the receiver operating curve was 0.85, scaled Brier 27%, and standardized mortality rate 0.99). With zero, one, and two data missing, the scaled Brier was 31%, 26%, and 21%; area under the receiver operating curve was 0.84, 0.87, and 0.89; and standardized mortality rate was 0.92, 1.05 and 1.10, respectively. Datasets where the missing data were simulated for oxygenation or oxygenation and hydrogen ion concentration together performed worse than datasets with these data originally missing. Conclusions: There is a coupling between missing physiologic data, admission type, low risk, and survival. Increased loss of physiologic data reduced model performance and will deflate mortality risk, resulting in falsely high standardized mortality rates.

  • 256.
    Englund, Anders
    et al.
    Arytmicenter Stockholm, Sweden.
    Walfridsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Kateterburen ablation - bättre än läkemedel.2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112Article in journal (Other academic)
    Abstract [sv]

    Randomiserade studier har visat att ablation av förmaksflimmer har bättre effekt än antiarytmisk medicinering. 

    Enligt europeiska och ameri­kanska riktlinjer kan alla typer av förmaksflimmer komma ifråga för ablation. 

    Hos patienter med paroxysmalt förmaksflimmer är lyckandefrekvensen ca 70–80 procent, medan den är något lägre vid persisterande och långvarigt flimmer. 

    Risken för allvarliga komplikationer är låg, <1,0 procent.

  • 257.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bertus Warntjes, Marcel, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. SyntheticMR AB, Linkoping, Sweden.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Multi-Parametric Representation of Voxel-Based Quantitative Magnetic Resonance Imaging2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 11, p. e111688-Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to explore the possibilities of multi-parametric representations of voxel-wise quantitative MRI data to objectively discriminate pathological cerebral tissue in patients with brain disorders. For this purpose, we recruited 19 patients with Multiple Sclerosis (MS) as benchmark samples and 19 age and gender matched healthy subjects as a reference group. The subjects were examined using quantitative Magnetic Resonance Imaging (MRI) measuring the tissue structure parameters: relaxation rates, R-1 and R-2, and proton density. The resulting parameter images were normalized to a standard template. Tissue structure in MS patients was assessed by voxel-wise comparisons with the reference group and with correlation to a clinical measure, the Expanded Disability Status Scale (EDSS). The results were visualized by conventional geometric representations and also by multi-parametric representations. Data showed that MS patients had lower R-1 and R-2, and higher proton density in periventricular white matter and in wide-spread areas encompassing central and sub-cortical white matter structures. MS-related tissue abnormality was highlighted in posterior white matter whereas EDSS correlation appeared especially in the frontal cortex. The multi-parameter representation highlighted disease-specific features. In conclusion, the proposed method has the potential to visualize both high-probability focal anomalies and diffuse tissue changes. Results from voxel-based statistical analysis, as exemplified in the present work, may guide radiologists where in the image to inspect for signs of disease. Future clinical studies must validate the usability of the method in clinical practice.

  • 258.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jan Bertus Warntje, Marcel
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Multi-Parametric Representation of Voxel-Based Quantitative Magnetic Resonance Imaging2014Conference paper (Other academic)
    Abstract [en]

    The aim of the study was to explore the possibilities of multi-parametric representations of voxel-wise quantitative MRI data to objectively discriminate pathological cerebral tissue in patients with brain disorders. For this purpose, we recruited 19 patients with Multiple Sclerosis (MS) as benchmark samples and 19 age and gender matched healthy subjects as a reference group. The subjects were examined using quantitative Magnetic Resonance Imaging (MRI) measuring the tissue structure parameters: relaxation rates, R and R, and proton density. The resulting parameter images were normalized to a standard template. Tissue structure in MS patients was assessed by voxel-wise comparisons with the reference group and with correlation to a clinical measure, the Expanded Disability Status Scale (EDSS). The results were visualized by conventional geometric representations and also by multi-parametric representations. Data showed that MS patients had lower R and R, and higher proton density in periventricular white matter and in wide-spread areas encompassing central and sub-cortical white matter structures. MS-related tissue abnormality was highlighted in posterior white matter whereas EDSS correlation appeared especially in the frontal cortex. The multi-parameter representation highlighted disease-specific features. In conclusion, the proposed method has the potential to visualize both high-probability focal anomalies and diffuse tissue changes. Results from voxel-based statistical analysis, as exemplified in the present work, may guide radiologists where in the image to inspect for signs of disease. Future clinical studies must validate the usability of the method in clinical practice.

  • 259.
    Engvall, Jan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Loyd, Dan
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Wranne, Bengt
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Coarctation of the aorta--a theoretical and experimental analysis of the effects of a centrally located arterial stenosis.1991In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 29, no 3, p. 291-296Article in journal (Refereed)
    Abstract [en]

    Aortic coarctation is a local constriction of the aorta that may severely affect haemodynamics. It is therefore important to quantify these effects. Using Bernoulli's equation and the momentum theorem, the pressure drop is described including the pressure recovery distal to the coarctation and the effects of collateral flow; both laminar and turbulent. Assuming the coarctation and collaterals to be stiff, a quadratic relationship between flow and pressure drop is expected for flow through the coarctation and for turbulent collateral flow. For laminar collateral flow, a linear relationship is expected. The coarctation flow was studied in a model consisting of a rigid tube with local constriction, connected to a flooded-level tank, containing a 36 per cent by weight solution of sucrose, with a viscosity equivalent to that of blood at body temperature. The pressure drop across the constriction showed a quadratic relationship to flow in agreement with theoretical expectations. Pressure recovery in this model was very slight (0-4 mm Hg). Nine patients with aortic coarctation were catheterised. Cardiac output and pressure drop across the coarctation were measured at rest and during supine cycle exercise at two different workloads. The relationship between mean pressure drop and cardiac output tended to be either 'parabolic' or, in some cases, approximately linear, suggesting that the flow situation in aortic coarctation can be quantified by expressions that either linearly or quadratically relate pressure and flow.

  • 260.
    Ergatoudes, Constantinos
    et al.
    Univ Gothenburg, Sweden.
    Schaufelberger, Maria
    Univ Gothenburg, Sweden.
    Andersson, Bert
    Univ Gothenburg, Sweden.
    Pivodic, Aldina
    Statistiska Konsultgruppen, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Fu, Michael
    Univ Gothenburg, Sweden.
    Non-cardiac comorbidities and mortality in patients with heart failure with reduced vs. preserved ejection fraction: a study using the Swedish Heart Failure Registry2019In: Clinical Research in Cardiology, ISSN 1861-0684, E-ISSN 1861-0692, Vol. 108, no 9, p. 1025-1033Article in journal (Refereed)
    Abstract [en]

    Background Heart failure (HF) and non-cardiac comorbidities often coexist and are known to have an adverse effect on outcome. However, the prevalence and prognostic impact of non-cardiac comorbidities in patients with HF with reduced ejection fraction (HFrEF) vs. those with preserved (HFpEF) remain inadequately studied. Methods and results We used data from the Swedish Heart Failure Registry from 2000 to 2012. HFrEF was defined as EF amp;lt; 50% and HFpEF as EF amp;gt;= 50%. Of 31 344 patients available for analysis, 79.3% (n = 24 856) had HFrEF and 20.7% (n = 6 488) HFpEF. The outcome was all-cause mortality. We examined the association between ten non-cardiac comorbidities and mortality and its interaction with EF using adjusted hazard ratio (HR). Stroke, anemia, gout and cancer had a similar impact on mortality in both phenotypes, whereas diabetes (HR 1.57, 95% confidence interval [CI] [1.50-1.65] vs. HR 1.39 95% CI [1.27-1.51], p = 0.0002), renal failure (HR 1.65, 95% CI [1.57-1.73] vs. HR 1.44, 95% CI [1.32-1.57], p = 0.003) and liver disease (HR 2.13, 95% CI [1.83-2.47] vs. HR 1.42, 95% CI [1.09-1.85] p = 0.02) had a higher impact in the HFrEF patients. Moreover, pulmonary disease (HR 1.46, 95% CI [1.40-1.53] vs. HR 1.66 95% CI [1.54-1.80], p = 0.007) was more prominent in the HFpEF patients. Sleep apnea was not associated with worse prognosis in either group. No significant variation was found in the impact over the 12-year study period. Conclusions Non-cardiac comorbidities contribute significantly but differently to mortality, both in HFrEF and HFpEF. No significant variation was found in the impact over the 12-year study period. These results emphasize the importance of including the management of comorbidities as a part of a standardized heart failure care in both HF phenotypes.

  • 261.
    Ericsson, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Angerud, Karin H.
    Umea Univ, Sweden; Umea Univ, Sweden.
    Brannstrom, Margareta
    Umea Univ, Sweden.
    Sederholm Lawesson, Sofia
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Thylén, Ingela
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Interaction between tele-nurses and callers with an evolving myocardial infarction: Consequences for level of directed care2019In: European Journal of Cardiovascular Nursing, ISSN 1474-5151, E-ISSN 1873-1953, Vol. 18, no 7, p. 545-553Article in journal (Refereed)
    Abstract [en]

    Background: Rapid contact with emergency medical services is imperative to save the lives of acute myocardial infarction patients. However, many patients turn to a telehealth advisory nurse instead, where the delivery of urgent and safe care largely depends on how the interaction in the call is established. Purpose: The purpose of this study was to explore the interaction between tele-nurses and callers with an evolving myocardial infarction after contacting a national telehealth advisory service number as their first medical contact. Method: Twenty men and 10 women (aged 46-89 years) were included. Authentic calls were analysed using inductive content analysis. Findings: One overall category, Movement towards directed level of care, labelled the whole interaction between the tele-nurse and the caller. Four categories conceptualised the different interactions: a distinct, reasoning, indecisive or irrational interaction. The interactions described how tele-nurses and callers assessed and elaborated on symptoms, context and actions. The interaction was pivotal for progress in the dialogue and affected the achievement of mutual understanding in the communicative process. An indecisive or irrational interaction could increase the risk of failing to recommend or call for acute care. Conclusion: The interaction in the communication could either lead or mislead the level of care directed in the call. This study adds new perspectives to the communicative process in the acute setting in order to identify a myocardial infarction and the level of urgency from both individuals experiencing myocardial infarction and professionals in the health system.

  • 262.
    Eriksson, B.
    et al.
    Karolinska Inst, Sweden.
    Wandell, P.
    Karolinska Inst, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nasman, P.
    KTH Royal Inst Technol, Sweden.
    Lund, L. H.
    Karolinska Univ Hosp, Sweden.
    Edner, M.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Comorbidities, risk factors and outcomes in patients with heart failure and an ejection fraction of more than or equal to 40% in primary care- and hospital care-based outpatient clinics2018In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 36, no 2, p. 207-215Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study is to describe patients with heart failure and an ejection fraction (EF) of more than or equal to 40%, managed in both Primary- and Hospital based outpatient clinks separately with their prognosis, comorbidities and risk factors. Further to compare the heart failure medication in the two groups. Design: We used the prospective Swedish Heart Failure Registry to include 9654 out-patients who had HF and EF amp;gt;= 40%, 1802 patients were registered in primary care and 7852 in hospital care. Descriptive statistical tests were used to analyze base line characteristics in the two groups and multivariate logistic regression analysis to assess mortality rate in the groups separately. Setting: The prospective Swedish Heart Failure Registry. Setting: The prospective Swedish Heart Failure Registry. Subjects: Patients with heart failure and an ejection fraction (EF) of more than or equal to 40%. Main outcome measures: Comorbidities, risk factors and mortality. Results: Mean-age was 77.5 (primary care) and 70.3 years (hospital care) p amp;lt; 0.0001, 46.7 vs. 36.3% women respectively (p amp;lt; 0.0001) and EF amp;gt;= 50% 26.1 vs. 13.4% (p amp;lt; 0.0001). Co-morbidities were common in both groups (97.2% vs. 92.3%), the primary care group having more atrial fibrillation, hypertension, ischemic heart disease and COPD. According to the multivariate logistic regression analysis smoking, COPD and diabetes were the most important independent risk factors in the primary care group and valvular disease in the hospital care group. All-cause mortality during mean follow-up of almost 4 years was 315% in primary care and 27.8% in hospital care. One year-mortality rates were 7.8%, and 7.0% respectively. Conclusion: Any co-morbidity was noted in 97% of the HF-patients with an EF of more than or equal to 40% managed at primary care based out-patient clinics and these patients had partly other independent risk factors than those patients managed in hospital care based outpatients clinics. Our results indicate that more attention should be payed to manage COPD in the primary care group.

  • 263.
    Eriksson, D.
    et al.
    Karolinska Institute, Sweden; Metab and Diabet Karolinska University Hospital, Sweden.
    Bianchi, M.
    Uppsala University, Sweden.
    Landegren, N.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Nordin, J.
    Uppsala University, Sweden.
    Dalin, F.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Mathioudaki, A.
    Uppsala University, Sweden.
    Eriksson, G. N.
    Karolinska Institute, Sweden.
    Hultin-Rosenberg, L.
    Uppsala University, Sweden.
    Dahlqvist, J.
    Uppsala University, Sweden.
    Zetterqvist, H.
    Uppsala University, Sweden; Uppsala University, Sweden.
    Karlsson, A.
    Uppsala University, Sweden.
    Hallgren, A.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Farias, F. H. G.
    Uppsala University, Sweden.
    Muren, E.
    Uppsala University, Sweden.
    Ahlgren, K. M.
    Uppsala University, Sweden.
    Lobell, A.
    Uppsala University, Sweden.
    Andersson, G.
    Swedish University of Agriculture Science, Sweden.
    Tandre, K.
    Uppsala University, Sweden.
    Dahlqvist, S. R.
    Umeå University, Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Rönnblom, L.
    Uppsala University, Sweden.
    Hulting, A. -L.
    Karolinska Institute, Sweden.
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Ekwall, O.
    University of Gothenburg, Sweden.
    Dahlqvist, P.
    Umeå University, Sweden.
    Meadows, J. R. S.
    Uppsala University, Sweden.
    Bensing, S.
    Metab and Diabet Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Lindblad-Toh, K.
    Uppsala University, Sweden; Broad Institute MIT and Harvard, MA USA.
    Kampe, O.
    Karolinska Institute, Sweden; Metab and Diabet Karolinska University Hospital, Sweden; Uppsala University, Sweden.
    Pielberg, G. R.
    Uppsala University, Sweden.
    Extended exome sequencing identifies BACH2 as a novel major risk locus for Addisons disease2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, no 6, p. 595-608Article in journal (Refereed)
    Abstract [en]

    BackgroundAutoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addisons disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. MethodsTo understand the genetic background of Addisons disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addisons disease and 1394 controls. ResultsWe identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 x 10(-15), MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addisons disease development. We also confirmed the previously known associations with the HLA complex. ConclusionWhilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addisons disease, we have identified BACH2 as a major risk locus in Addisons disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

  • 264.
    Eriksson, Daniel
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bianchi, Matteo
    Uppsala Univ, Sweden.
    Landegren, Nils
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Dalin, Frida
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Skov, Jakob
    Karolinska Inst, Sweden.
    Hultin-Rosenberg, Lina
    Uppsala Univ, Sweden.
    Mathioudaki, Argyri
    Uppsala Univ, Sweden.
    Nordin, Jessika
    Uppsala Univ, Sweden.
    Hallgren, Asa
    Karolinska Inst, Sweden.
    Andersson, Goran
    Swedish Univ Agr Sci, Sweden.
    Tandre, Karolina
    Uppsala Univ, Sweden.
    Rantapaa Dahlqvist, Solbritt
    Umea Univ, Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Ronnblom, Lars
    Uppsala Univ, Sweden.
    Hulting, Anna-Lena
    Not Found:[Eriksson, Daniel; Landegren, Nils; Dalin, Frida; Hallgren, Asa; Kampe, Olle] Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden; [Eriksson, Daniel; Bensing, Sophie; Kampe, Olle] Karolinska Univ Hosp, Dept Endocrinol Metab and Diabet, Stockholm, Sweden; [Bianchi, Matteo; Hultin-Rosenberg, Lina; Mathioudaki, Argyri; Nordin, Jessika; Meadows, Jennifer R. S.; Lindblad-Toh, Kerstin; Pielberg, Gerli Rosengren] Uppsala Univ, Dept Med Biochem and Microbiol, Sci Life Lab, Uppsala, Sweden; [Landegren, Nils; Dalin, Frida; Tandre, Karolina; Ronnblom, Lars] Uppsala Univ, Dept Med Sci, Sci Life Lab, Uppsala, Sweden; [Skov, Jakob; Bensing, Sophie] Karolinska Inst, Dept Mol Med and Surg, Stockholm, Sweden; [Andersson, Goran] Swedish Univ Agr Sci, Dept Anim Breeding and Genet, Uppsala, Sweden; [Dahlqvist, Solbritt Rantapaa; Dahlqvist, Per] Umea Univ, Dept Publ Hlth and Clin Med, Umea, Sweden; [Soderkvist, Peter; Wahlberg, Jeanette] Linkoping Univ, Dept Clin and Expt Med, Linkoping, Sweden; [Wahlberg, Jeanette] Linkoping Univ, Dept Endocrinol, Linkoping, Sweden; [Wahlberg, Jeanette] Linkoping Univ, Dept Med and Hlth Sci, Linkoping, Sweden; [Ekwall, Olov] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden; [Ekwall, Olov] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol and Inflammat Res, Gothenburg, Sweden; [Lindblad-Toh, Kerstin] Broad Inst MIT and Harvard, Cambridge, MA USA; [Kampe, Olle] KG Jebsen Ctr Autoimmune Dis, Bergen, Norway;.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Dahlqvist, Per
    Umea Univ, Sweden.
    Ekwall, Olov
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Meadows, Jennifer R. S.
    Uppsala Univ, Sweden.
    Lindblad-Toh, Kerstin
    Uppsala Univ, Sweden; Broad Inst MIT and Harvard, MA USA.
    Bensing, Sophie
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Pielberg, Gerli Rosengren
    Uppsala Univ, Sweden.
    Kampe, Olle
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; KG Jebsen Ctr Autoimmune Dis, Norway.
    Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addisons disease in Sweden2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8395Article in journal (Refereed)
    Abstract [en]

    Autoimmune Addisons disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.

  • 265.
    Eriksson, Daniel
    et al.
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm, Sweden.
    Dalin, Frida
    Karolinska Institutet, Stockholm, Uppsala University, Uppsala, Sweden.
    Eriksson, Gabriel Nordling
    Karolinska Institutet, Stockholm, Sweden.
    Landegren, Nils
    Karolinska Institutet, Stockholm, Sweden, Uppsala University, Uppsala, Sweden.
    Bianchi, Matteo
    Uppsala University, Uppsala, Sweden.
    Hallgren, Åsa
    Karolinska Institutet, Stockholm, Uppsala University, Uppsala, Sweden.
    Dahlqvist, Per
    Umeå University, Umeå, Sweden.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Clinical and Experimental Medicine.
    Ekwall, Olov
    Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Winqvist, Ola
    Karolinska Institutet, Stockholm, Sweden.
    Catrina, Sergiu-Bogdan
    Karolinska Institutet, Stockholm, Sweden.
    Rönnelid, Johan
    Uppsala University, Uppsala, Sweden.
    Hulting, Anna-Lena
    Karolinska Institutet, Stockholm, Sweden.
    Lindblad-Toh, Kerstin
    Uppsala University, Uppsala, Sweden, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.
    Alimohammadi, Mohammad
    Uppsala University, Uppsala, Sweden.
    Husebye, Eystein S
    Karolinska Institutet, Stockholm, University of Bergen, Bergen, K.G. Jebsen Center for Autoimmune Disorders, Bergen, Norway.
    Knappskog, Per Morten
    University of Bergen, Bergen, Haukeland University Hospital, Bergen, Norway.
    Rosengren Pielberg, Gerli
    Uppsala University, Uppsala, Sweden.
    Bensing, Sophie
    Karolinska University Hospital, Stockholm, Karolinska Institutet, Stockholm, Sweden.
    Kämpe, Olle
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm, Uppsala University, Uppsala, Sweden, K.G. Jebsen Center for Autoimmune Disorders, Bergen, Norway.
    Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1.2018In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 1, p. 179-186Article in journal (Refereed)
    Abstract [en]

    Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.

    Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.

    Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.

    Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.

    Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.

  • 266.
    Eriksson, Elisabet
    et al.
    Univ Gavle, Sweden.
    Berg, Sören
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Engstrom, Maria
    Univ Gavle, Sweden; Uppsala Univ, Sweden; Lishui Univ, Peoples R China.
    Internationally educated nurses and medical graduates experiences of getting a license and practicing in Sweden - a qualitative interview study2018In: BMC Medical Education, ISSN 1472-6920, E-ISSN 1472-6920, Vol. 18, article id 296Article in journal (Refereed)
    Abstract [en]

    Background: The Swedish healthcare system has an increased need for nurses and physicians, and the number of International Educated Nurses (IENs) and International Medical Graduates (IMGs) seeking job opportunities and a license to practice in Sweden is rising. This study explored how IENs and IMGs describe their experience of getting a license to practice, their perceptions of working in Sweden and of how their intercultural competence is utilized. Method: A qualitative study based on semi-structured interviews with 11 IENs and 11 IMGs. The interviews were conducted between 2015 and 2017. The data were analyzed using qualitative content analysis. Results: Three main themes were identified: Getting a license - a different story, The work is familiar, yet a lot is new, Trying to master a new language. The time to obtain a license to practice and finding a job was shorter for IENs and IMGs coming from European countries than for those from non-European countries. Some of the experiences of getting a license to practice and of entering a new workplace in another country were the same for nurses and physicians. In general, both IENs and IMGs felt welcomed and used their intercultural competence at work. Lack of language skills was regarded as the main problem for both professions, while workplace introduction was shorter for IMGs than for IENs. Conclusions: Problems related to language and culture are often underestimated, therefore organizations and managers employing IENs and IMGs should provide longer workplace introduction to facilitate the acculturation process. More time-efficient language courses specifically adapted to IENs and IMGs could make the transition easier and shorten the time to obtain a license to practice for both professions.

  • 267.
    Eriksson, Jonatan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences.
    Quantification of 4D Left Ventricular Blood Flow in Health and Disease2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The main function of the heart is to pump blood throughout the cardiovascular system by generating pressure differences created through volume changes. Although the main purpose of the heart and vessels is to lead the flowing blood throughout the body, clinical assessments of cardiac function are usually based on morphology, approximating the flow features by viewing the motion of the myocardium and vessels. Measurement of three-directional, three-dimensional and time-resolved velocity (4D Flow) data is feasible using magnetic resonance (MR). The focus of this thesis is the development and application of methods that facilitate the analysis of larger groups of data in order to increase our understanding of intracardiac flow patterns and take the 4D flow technique closer to the clinical setting.

    In the first studies underlying this thesis, a pathline based method for analysis of intra ventricular blood flow patterns has been implemented and applied. A pathline is integrated from the velocity data and shows the path an imaginary massless particle would take through the data volume. This method separates the end-diastolic volume (EDV) into four functional components, based on the position for each individual pathline at end-diastole (ED) and end-systole (ES). This approach enables tracking of the full EDV over one cardiac cycle and facilitates calculation of parameters such as e.g. volumes and kinetic energy (KE). Besides blood flow, pressure plays an important role in the cardiac dynamics. In order to study this parameter in the left ventricle, the relative pressure field was computed using the pressure Poisson equation. A comprehensive presentation of the pressure data was obtained dividing the LV blood pool into 17 pie-shaped segments based on a modification of the standard seventeen segment model. Further insight into intracardiac blood flow dynamics was obtained by studying the turbulent kinetic energy (TKE) in the LV. The methods were applied to data from a group of healthy subjects and patients with dilated cardiomyopathy (DCM). DCM is a pathological state where the cardiac function is impaired and the left ventricle or both ventricles are dilated.

    The validation study of the flow analysis method showed that a reliable user friendly tool for intra ventricular blood flow analysis was obtained. The application of this tool also showed that roughly one third of the blood that enters the LV, directly leaves the LV again in the same heart beat. The distribution of the four LV EDV components was altered in the DCM group as compared to the healthy group; the component that enters and leaves the LV during one cardiac cycle (Direct Flow) was significantly larger in the healthy subjects. Furthermore, when the kinetic energy was normalized by the volume for each component, at time of ED, the Direct Flow had the highest values in the healthy subjects. In the DCM group, however, the Retained Inflow and Delayed Ejection Flow had higher values. The relative pressure field showed to be highly heterogeneous, in the healthy heart. During diastole the predominate pressure differences in the LV occur along the long axis from base to apex. The distribution and variability of 3D pressure fields differ between early and late diastolic filling phases, but common to both phases is a relatively lower pressure in the outflow segment. In the normal LV, TKE values are low. The highest TKE values can be seen during early diastole and are regionally distributed near the basal LV regions. In contrast, in a heterogeneous group of DCM patients, total diastolic and late diastolic TKE values are higher than in normals, and increase with the LV volume.

    In conclusion, in this thesis, methods for analysis of multidirectional intra cardiac velocity data have been obtained. These methods allow assessment of data quality, intra cardiac blood flow patterns, relative pressure fields, and TKE. Using these methods, new insights have been obtained in intra cardiac blood flow dynamics in health and disease. The work underlying this thesis facilitates assessment of data from a larger population of healthy subjects and patients, thus bringing the 4D Flow MRI technique closer to the clinical setting.

    List of papers
    1. Semi-automatic quantification of 4D left ventricular blood flow
    Open this publication in new window or tab >>Semi-automatic quantification of 4D left ventricular blood flow
    Show others...
    2010 (English)In: JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE, ISSN 1097-6647, Vol. 12, no 9Article in journal (Refereed) Published
    Abstract [en]

    Background: The beating heart is the generator of blood flow through the cardiovascular system. Within the hearts own chambers, normal complex blood flow patterns can be disturbed by diseases. Methods for the quantification of intra-cardiac blood flow, with its 4D (3D+time) nature, are lacking. We sought to develop and validate a novel semi-automatic analysis approach that integrates flow and morphological data. Method: In six healthy subjects and three patients with dilated cardiomyopathy, three-directional, three-dimensional cine phase-contrast cardiovascular magnetic resonance (CMR) velocity data and balanced steady-state free-precession long- and short-axis images were acquired. The LV endocardium was segmented from the short-axis images at the times of isovolumetric contraction (IVC) and isovolumetric relaxation (IVR). At the time of IVC, pathlines were emitted from the IVC LV blood volume and traced forwards and backwards in time until IVR, thus including the entire cardiac cycle. The IVR volume was used to determine if and where the pathlines left the LV. This information was used to automatically separate the pathlines into four different components of flow: Direct Flow, Retained Inflow, Delayed Ejection Flow and Residual Volume. Blood volumes were calculated for every component by multiplying the number of pathlines with the blood volume represented by each pathline. The accuracy and inter- and intra-observer reproducibility of the approach were evaluated by analyzing volumes of LV inflow and outflow, the four flow components, and the end-diastolic volume. Results: The volume and distribution of the LV flow components were determined in all subjects. The calculated LV outflow volumes [ml] (67 +/- 13) appeared to fall in between those obtained by through-plane phase-contrast CMR (77 +/- 16) and Doppler ultrasound (58 +/- 10), respectively. Calculated volumes of LV inflow (68 +/- 11) and outflow (67 +/- 13) were well matched (NS). Low inter- and intra-observer variability for the assessment of the volumes of the flow components was obtained. Conclusions: This semi-automatic analysis approach for the quantification of 4D blood flow resulted in accurate LV inflow and outflow volumes and a high reproducibility for the assessment of LV flow components.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54610 (URN)10.1186/1532-429X-12-9 (DOI)000275445000001 ()
    Note

    The original article is: Jonatan Eriksson, Carljohan Carlhäll, Petter Dyverfeldt, Jan Engvall, Ann F Bolger and Tino Ebbers, Semi-automatic quantification of 4D left ventricular blood flow, 2010, JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE, (12), 9. http://dx.doi.org/10.1186/1532-429X-12-9

    Available from: 2010-03-26 Created: 2010-03-26 Last updated: 2014-01-15Bibliographically approved
    2. Quantification of presystolic blood flow organization and energetics in the human left ventricle
    Open this publication in new window or tab >>Quantification of presystolic blood flow organization and energetics in the human left ventricle
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    2011 (English)In: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, ISSN 0363-6135, Vol. 300, no 6, p. H2135-H2141Article in journal (Refereed) Published
    Abstract [en]

    Intracardiac blood flow patterns are potentially important to cardiac pumping efficiency. However, these complex flow patterns remain incompletely characterized both in health and disease. We hypothesized that normal left ventricular (LV) blood flow patterns would preferentially optimize a portion of the end-diastolic volume (LVEDV) for effective and rapid systolic ejection by virtue of location near and motion towards the LV outflow tract (LVOT). Three-dimensional cine velocity and morphological data were acquired in 12 healthy persons and 1 patient with dilated cardiomyopathy using MRI. A previously validated method was used for analysis in which the LVEDV was separated into four functional flow components based on the bloods locations at the beginning and end of the cardiac cycle. Each components volume, kinetic energy (KE), site, direction, and linear momentum relative to the LVOT were calculated. Of the four components, the LV inflow that passes directly to outflow in a single cardiac cycle (Direct Flow) had the largest volume. At the time of isovolumic contraction, Direct Flow had the greatest amount of KE and the most favorable combination of distance, angle, and linear momentum relative to the LVOT. Atrial contraction boosted the late diastolic KE of the ejected components. We conclude that normal diastolic LV flow creates favorable conditions for ensuing ejection, defined by proximity and energetics, for the Direct Flow, and that atrial contraction augments the end-diastolic KE of the ejection volume. The correlation of Direct Flow characteristics with ejection efficiency might be a relevant investigative target in cardiac failure.

    Place, publisher, year, edition, pages
    AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA, 2011
    Keywords
    phase-contrast magnetic resonance imaging, kinetic energy, heart, cardiac physiology
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-69186 (URN)10.1152/ajpheart.00993.2010 (DOI)000291209300019 ()
    Available from: 2011-06-17 Created: 2011-06-17 Last updated: 2013-12-17
    3. Four-dimensional blood flow-specific markers of LV dysfunction in dilated cardiomyopathy
    Open this publication in new window or tab >>Four-dimensional blood flow-specific markers of LV dysfunction in dilated cardiomyopathy
    2013 (English)In: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 14, no 5, p. 417-424Article in journal (Refereed) Published
    Abstract [en]

    Aims : Patients with mild heart failure (HF) who are clinically compensated may have normal left ventricular (LV) stroke volume (SV). Despite this, altered intra-ventricular flow patterns have been recognized in these subjects. We hypothesized that, compared with normal LVs, flow in myopathic LVs would demonstrate a smaller proportion of inflow volume passing directly to ejection and diminished the end-diastolic preservation of the inflow kinetic energy (KE).

    Methods and results : In 10 patients with dilated cardiomyopathy (DCM) (49 ± 14 years, six females) and 10 healthy subjects (44 ± 17 years, four females), four-dimensional MRI velocity and morphological data were acquired. A previously validated method was used to separate the LV end-diastolic volume (EDV) into four flow components based on the blood's locations at the beginning and end of the cardiac cycle. KE was calculated over the cardiac cycle for each component. The EDV was larger (P = 0.021) and the ejection fraction smaller (P < 0.001) in DCM compared with healthy subjects; the SV was equivalent (DCM: 77 ± 19, healthy: 79 ± 16 mL). The proportion of the total LV inflow that passed directly to ejection was smaller in DCM (P = 0.000), but the end-diastolic KE/mL of the direct flow was not different in the two groups (NS).

    Conclusion : Despite equivalent LVSVs, HF patients with mild LV remodelling demonstrate altered diastolic flow routes through the LV and impaired preservation of inflow KE at pre-systole compared with healthy subjects. These unique flow-specific changes in the flow route and energetics are detectable despite clinical compensation, and may prove useful as subclinical markers of LV dysfunction.

    Place, publisher, year, edition, pages
    Oxford University Press, 2013
    Keywords
    4D flow, Heart failure, Magnetic resonance imaging, Stroke volume
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-87616 (URN)10.1093/ehjci/jes159 (DOI)000318088300003 ()22879457 (PubMedID)
    Available from: 2013-01-19 Created: 2013-01-19 Last updated: 2017-12-06
    4. Spatial heterogeneity of 4D relative pressure fields in the human left ventricle
    Open this publication in new window or tab >>Spatial heterogeneity of 4D relative pressure fields in the human left ventricle
    2013 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Blood flow throughout the cardiovascular system is driven by pressure differences generated by the contraction and relaxation of the heart, where blood accelerates from high to low pressure areas. Absolute intracardiac pressure cannot be measured noninvasively, but relative pressure can be calculated. The aim of this study was to assess the spatial heterogeneity of the 4D relative pressure fields in the human left ventricle (LV).

    Twelve healthy subjects underwent MRI examination where 4D flow as well as morphological data were acquired. The morphological data were segmented, and the segmentation used as boundary condition when computing relative pressure fields from the pressure Poisson equation using a multi grid solver. The LV lumen was divided according to a seventeen segment model in order to assess spatial heterogeneity and present the extensive amount of data in a comprehensive manner.

    The basal anteroseptal segment shows a significantly lower median pressure than the opposite basal inferolateral segment during both early and late diastolic filling (p<0.0005 and p=0.0024, respectively). Along the long axis, the relative pressure in the apical segments are significantly higher relative to the basal segments (p<0.0005) along both the anteroseptal and inferolateral sides at and after the peaks of E-wave and A-wave.

    During diastole the main pressure differences in the LV occur along the basal-apical axis. However, pressure differences can also be found in the short-axis direction, and may also reflect important aspects of atrioventricular coupling.

    Keywords
    Relative pressure, Magnetic resonance, 4D flow, physiology, cardiac function
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-99956 (URN)
    Available from: 2013-10-24 Created: 2013-10-24 Last updated: 2014-04-23Bibliographically approved
    5. Turbulent Kinetic Energy in Normal and Myopathic Left Ventricles
    Open this publication in new window or tab >>Turbulent Kinetic Energy in Normal and Myopathic Left Ventricles
    Show others...
    2015 (English)In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 41, no 4, p. 1021-1029Article in journal (Refereed) Published
    Abstract [en]

    Purpose: To assess turbulent kinetic energy (TKE) within the left ventricle (LV) of healthy subjects using novel 4D flow MRI methods and to compare TKE values to those from a spectrum of patients with dilated cardiomyopathy (DCM).

    Methods: 4D flow and morphological MRI-data were acquired in 11 healthy subjects and 9 patients with different degrees of diastolic dysfunction. TKELV was calculated within the LV at each diastolic time frame. At peak early (E) and late (A) diastolic filling, the TKELV was compared to transmitral peak velocity, LV diameter and mitral annular diameter.

    Results: In the majority of all subjects, peaks in TKELV could be observed at E and A. Peak TKELV at E was not different between the groups, and correlated with mitral annular dimensions. Peak TKELV at A was higher in DCM patients compared to healthy subjects, and was related to LV diameter and transmitral velocity.

    Conclusions: In normal LVs, TKE values are low. Values are highest during early diastole, and diminish with increasing LV size. In a heterogeneous group of DCM patients, late diastolic TKE values are higher than in healthy subjects. Kinetic energy loss due to elevated late diastolic TKE may reflect inefficient flow in dilated LVs.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2015
    Keywords
    Magnetic resonance imaging, blood flow, turbulent flow, cardiac function, diastolic dysfunction, heart failure
    National Category
    Medical Engineering Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-99957 (URN)10.1002/jmri.24633 (DOI)000351521700019 ()
    Note

    Contract grant sponsor: Swedish Heart-Lung Foundation; Contract grant sponsor: Swedish Research Council; Contract grant sponsor: European Research Council.

    Available from: 2013-10-24 Created: 2013-10-24 Last updated: 2017-12-06Bibliographically approved
  • 268.
    Eriksson, Jonatan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bolger, Ann F
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. University of Calif San Francisco, CA USA.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Spatial Heterogeneity of Four-Dimensional Relative Pressure Fields in the Human Left Ventricle2015In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 74, no 6, p. 1716-1725Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess the spatial heterogeneity of the four-dimensional (4D) relative pressure fields in the healthy human left ventricle (LV) and provide reference data for normal LV relative pressure. Methods: Twelve healthy subjects underwent a cardiac MRI examination where 4D flow and morphological data were acquired. The latter data were segmented and used to define the borders of the LV for computation of relative pressure fields using the pressure Poisson equation. The LV lumen was divided into 17 pie-shaped segments. Results: In the normal left ventricle, the relative pressure in the apical segments was significantly higher relative to the basal segments (P &lt; 0.0005) along both the anteroseptal and inferolateral sides after the peaks of early (E-wave) and late (A-wave) diastolic filling. The basal anteroseptal segment showed significantly lower median pressure than the opposite basal inferolateral segment during both E-wave (P &lt; 0.0005) and A-wave (P = 0.0024). Conclusion: Relative pressure in the left ventricle is heterogeneous. During diastole, the main pressure differences in the LV occur along the basal-apical axis. However, pressure differences were also found in the short axis direction and may reflect important aspects of atrioventricular coupling. Additionally, this study provides reference data on LV pressure dynamics for a group of healthy subjects. (C) 2014 Wiley Periodicals, Inc.

  • 269.
    Eriksson, Jonatan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Bolger, Ann F
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Semi-automatic quantification of 4D left ventricular blood flow2010In: JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE, ISSN 1097-6647, Vol. 12, no 9Article in journal (Refereed)
    Abstract [en]

    Background: The beating heart is the generator of blood flow through the cardiovascular system. Within the hearts own chambers, normal complex blood flow patterns can be disturbed by diseases. Methods for the quantification of intra-cardiac blood flow, with its 4D (3D+time) nature, are lacking. We sought to develop and validate a novel semi-automatic analysis approach that integrates flow and morphological data. Method: In six healthy subjects and three patients with dilated cardiomyopathy, three-directional, three-dimensional cine phase-contrast cardiovascular magnetic resonance (CMR) velocity data and balanced steady-state free-precession long- and short-axis images were acquired. The LV endocardium was segmented from the short-axis images at the times of isovolumetric contraction (IVC) and isovolumetric relaxation (IVR). At the time of IVC, pathlines were emitted from the IVC LV blood volume and traced forwards and backwards in time until IVR, thus including the entire cardiac cycle. The IVR volume was used to determine if and where the pathlines left the LV. This information was used to automatically separate the pathlines into four different components of flow: Direct Flow, Retained Inflow, Delayed Ejection Flow and Residual Volume. Blood volumes were calculated for every component by multiplying the number of pathlines with the blood volume represented by each pathline. The accuracy and inter- and intra-observer reproducibility of the approach were evaluated by analyzing volumes of LV inflow and outflow, the four flow components, and the end-diastolic volume. Results: The volume and distribution of the LV flow components were determined in all subjects. The calculated LV outflow volumes [ml] (67 +/- 13) appeared to fall in between those obtained by through-plane phase-contrast CMR (77 +/- 16) and Doppler ultrasound (58 +/- 10), respectively. Calculated volumes of LV inflow (68 +/- 11) and outflow (67 +/- 13) were well matched (NS). Low inter- and intra-observer variability for the assessment of the volumes of the flow components was obtained. Conclusions: This semi-automatic analysis approach for the quantification of 4D blood flow resulted in accurate LV inflow and outflow volumes and a high reproducibility for the assessment of LV flow components.

  • 270.
    Eriksson, Jonatan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Zajac, Jakub
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Bolger, Ann F
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. University of Calif San Francisco, CA USA.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Left ventricular hemodynamic forces as a marker of mechanical dyssynchrony in heart failure patients with left bundle branch block2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 2971Article in journal (Refereed)
    Abstract [en]

    Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified. We hypothesized that LV hemodynamic forces calculated from 4D flow MRI could serve as a marker of diastolic mechanical dyssynchrony in LBBB hearts. MRI data were acquired in heart failure patients with LBBB or matched patients without LBBB. LV pressure gradients were calculated from the Navier-Stokes equations. Integration of the pressure gradients over the LV volume rendered the hemodynamic forces. The findings demonstrate that the LV filling forces are more orthogonal to the main LV flow direction in heart failure patients with LBBB compared to those without LBBB during early but not late diastole. The greater the conduction abnormality the greater the discordance of LV filling force with the predominant LV flow direction (r(2) = 0.49). Such unique flow-specific measures of mechanical dyssynchrony may serve as an additional tool for considering the risks imposed by conduction abnormalities in heart failure patients and prove to be useful in predicting response to CRT.

  • 271. Eriksson, M
    et al.
    Isaksson, R-M
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Hellström-Ängerud, K
    Eriksson, M
    Logander, Elisabeth
    Lawesson, Sofia
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Thylén, Ingela
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Differences in symptom presentation in STEMI patients, with or without a previous history of hypertension; a survey report from the SymTime study group.2014Conference paper (Refereed)
  • 272.
    Erlinge, D.
    et al.
    Lund University, Sweden.
    Omerovic, E.
    Sahlgrens University Hospital, Sweden.
    Frobert, O.
    Örebro University, Sweden.
    Linder, R.
    Danderyd Hospital, Sweden.
    Danielewicz, M.
    Karlstad Hospital, Sweden.
    Hamid, M.
    Mälarsjukhuset, Sweden.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Henareh, L.
    Karolinska University Hospital, Sweden.
    Wagner, H.
    Helsingborg Lasarett, Sweden.
    Hardhammar, P.
    Halmstad County Hospital, Sweden.
    Sjogren, I.
    Falun Central Hospital, Sweden.
    Stewart, J.
    Skaraborgs Hospital, Sweden.
    Grimfjard, P.
    Västmanlands Sjukhus, Sweden.
    Jensen, J.
    Karolinska Institute, Sweden.
    Aasa, M.
    Södersjukhuset AB, Sweden.
    Robertsson, L.
    Södra Älvsborgs Sjukhus, Sweden.
    Lindroos, P.
    Karolinska Institute, Sweden.
    Haupt, J.
    Sunderby Sjukhus, Sweden.
    Wikstrom, H.
    Kristianstad Hospital, Sweden.
    Ulvenstam, A.
    Östersund Hospital, Sweden.
    Bhiladvala, P.
    Lund University, Sweden.
    Lindvall, B.
    Sundsvall Hospital, Sweden.
    Lundin, A.
    Lund University, Sweden.
    Todt, T.
    Lund University, Sweden.
    Ioanes, D.
    Sahlgrens University Hospital, Sweden.
    Ramunddal, T.
    Sahlgrens University Hospital, Sweden.
    Kellerth, T.
    Örebro University, Sweden.
    Zagozdzon, L.
    Örebro University, Sweden.
    Gotberg, M.
    Lund University, Sweden.
    Andersson, J.
    Umeå University, Sweden.
    Angeras, O.
    Sahlgrens University Hospital, Sweden.
    Ostlund, O.
    Uppsala University, Sweden.
    Lagerqvist, B.
    Uppsala University, Sweden.
    Held, C.
    Uppsala University, Sweden.
    Wallentin, L.
    Uppsala University, Sweden.
    Schersten, F.
    Lund University, Sweden.
    Eriksson, P.
    Umeå University, Sweden.
    Koul, S.
    Lund University, Sweden.
    James, S.
    Uppsala University, Sweden.
    Bivalirudin versus Heparin Monotherapy in Myocardial Infarction2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 12, p. 1132-1142Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y 12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y(12) inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. RESULTS A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P = 0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P = 0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P = 0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P = 0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P = 0.76). CONCLUSIONS Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others;

  • 273.
    Ernersson, Åsa
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Berggren, B.
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Hollman Frisman, Gunilla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Lower fear of hypoglycaemia in patients with type 1 diabetes of short duration2012In: 17th FEND Annual Conference 2012, page 19, 2012Conference paper (Other academic)
    Abstract [en]

    Background

    Fear of hypoglycaemia is common in patients with type 1 diabetes and many patients deliberately aim at higher blood glucose than recommended to avoid hypoglycaemia. Patient empowerment is a process whereby patients have the skills, attitudes, and self-awareness necessary to influence the quality of their lives. An empowered patient has sufficient knowledge to take relevant decisions about their illness, medical treatment and their own health.

    Aim

    The aim was to study empowerment, fear of hypoglycaemia and problem areas among patients with type1 diabetes.

    Method

    Four hundred fifty-seven patients, mean age 48.5 (±15.4) years, completed an questionnaire including questions on the duration of diabetes, episodes of severe hypoglycaemias and metabolic control, the Swedish Diabetes Empowerment Scale – 23 (Swe-DES-23), Fear of Hypoglycaemia Survey (HFS) and the Problem Areas in Diabetes scale (SWE-PAID-20) .

    Results

    The level of HbA1c was not associated with fear of hypoglycaemia while patients with newly diagnosed (0-5 years) diabetes had significantly lower (p=0.001) fear of hypoglycaemia than those with longer duration. Episodes of severe hypoglycaemia during the last year also influenced the rating on HFS. HFS was 24.7(11.6) in those with no episodes, 30.5(13.9) 1 episode, 33.0(15.4) 2-4 episodes (all p<0.01). Patients with HbA1c ≥ 8.0 % rated lower empowerment (SWE-DES-23) compared to those who had an HbA1c between 6.1-7.9% (p=0.02) and compared to those with HbA1c lower or equal to 6.0 % (p<0.001).

    On the SWE-PAID-20 patients with HbA1c ≥8 % scored in average 32.2(20.5) while those with HbA1c ≤6.0% scored 20.0(17.6) (p<0.001) (higher value indicates more emotional distress related to diabetes).

    Conclusion

    Patients with poor metabolic control, HbA1c ≥8 % are less empowered and also experiences more emotional distress related to their diabetes. Fear of hypoglycaemia was lowest in patient with up to 5 years duration of type 1 diabetes. HbA1c was not associated with fear of hypoglycaemia while repeated episodes of severe hypoglycaemia during the last year increased this fear.

  • 274.
    Ernersson, Åsa
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Hollman Frisman, Gunilla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Löfgren, U-A
    Berggren, B
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Fear of hypoglycaemia and empowerment in patients with type 1 diabetes2012Conference paper (Other academic)
  • 275.
    Ernersson, Åsa
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Hollman Frisman, Gunilla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Young healthy individuals develop lack of energy when adopting an obesity provoking behaviour for four weeks; A phenomenological2008Conference paper (Refereed)
  • 276.
    Escaned, Javier
    et al.
    Hosp Clin San Carlos, Spain; Univ Complutense Madrid, Spain.
    Ryan, Nicola
    Hosp Clin San Carlos, Spain; Univ Complutense Madrid, Spain.
    Mejia-Renteria, Hernan
    Hosp Clin San Carlos, Spain; Univ Complutense Madrid, Spain.
    Cook, Christopher M.
    Imperial Coll London, England.
    Dehbi, Hakim-Moulay
    UCL, England.
    Alegria-Barrero, Eduardo
    Hosp Univ Torrejon, Spain; Univ Francisco de Vitoria, Spain.
    Alghamdi, Ali
    King Abdulaziz Med City Cardiac Ctr, Saudi Arabia.
    Al-Lamee, Rasha
    Imperial Coll London, England.
    Altman, John
    Colorado Heart and Vasc, CO USA.
    Ambrosia, Alphonse
    Mesa, Arizona, USA.
    Baptista, Sergio B.
    Hosp Prof Doutor Fernando Fonseca, Portugal.
    Bertilsson, Maria
    Uppsala Univ, Sweden.
    Bhindi, Ravinay
    Royal North Shore Hosp, Australia.
    Birgander, Mats
    Lund Univ, Sweden.
    Bojara, Waldemar
    Kemperhof Koblenz, Germany.
    Brugaletta, Salvatore
    Inst Invest Biomed August Pi and Sunyer, Spain.
    Buller, Christopher
    St Michaels Hosp, Canada.
    Calais, Fredrik
    Orebro Univ, Sweden.
    Silva, Pedro Canas
    Hosp Santa Maria, Portugal.
    Carlsson, Jorg
    Kalmar Cty Hosp, Sweden; Linnaeus Univ, Sweden.
    Christiansen, Evald H.
    Aarhus Univ Hosp, Denmark.
    Danielewicz, Mikael
    Karlstad Hosp, Sweden.
    Di Mario, Carlo
    Imperial Coll London, England; Univ Florence, Italy.
    Doh, Joon-Hyung
    Inje Univ, South Korea.
    Erglis, Andrejs
    Pauls Stradins Clin Univ Hosp, Latvia.
    Erlinge, David
    Lund Univ, Sweden.
    Gerber, Robert T.
    Conquest Hosp, England.
    Going, Olaf
    Sana Klinikum Lichtenberg, Germany.
    Gudmundsdottir, Ingibjorg
    Reykjavik Univ Hosp, Iceland.
    Haerle, Tobias
    Carl von Ossietzky Univ Oldenburg, Germany.
    Hauer, Dario
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Hellig, Farrel
    Sunninghill Hosp, South Africa.
    Indolfi, Ciro
    Magna Graecia Univ Catanzaro, Italy.
    Jakobsen, Lars
    Aarhus Univ Hosp, Denmark.
    Janssens, Luc
    Imelda Hosp, Belgium.
    Jensen, Jens
    Karolinska Inst, Sweden; Capio St Gorans Sjukhus, Sweden; Sundsvall Hosp, Sweden.
    Jeremias, Allen
    SUNY Stony Brook, NY 11794 USA.
    Karegren, Amra
    Vastmanland Hosp Vasteras, Sweden.
    Karlsson, Ann-Charlotte
    Halmstad Cty Hosp, Sweden.
    Kharbanda, Rajesh K.
    Oxford Univ Hosp Fdn Trust, England.
    Khashaba, Ahmed
    Ain Shams Univ, Egypt.
    Kikuta, Yuetsu
    Fukuyama Cardiovasc Hosp, Japan.
    Krackhardt, Florian
    Univ Med, Germany.
    Koo, Bon-Kwon
    Seoul Natl Univ Hosp, South Korea.
    Koul, Sasha
    Lund Univ, Sweden.
    Laine, Mika
    Helsinki Univ Hosp, Finland.
    Lehman, Sam J.
    Flinders Univ S Australia, Australia.
    Lindroos, Pontus
    St Goran Hosp, Sweden.
    Malik, Iqbal S.
    Imperial Coll London, England.
    Maeng, Michael
    Aarhus Univ Hosp, Denmark.
    Matsuo, Hitoshi
    Gifu Heart Ctr, Japan.
    Meuwissen, Martijn
    Amphia Hosp, Netherlands.
    Nam, Chang-Wook
    Keimyung Univ, South Korea.
    Niccoli, Giampaolo
    Univ Cattolica Sacro Cuore, Italy.
    Nijjer, Sukhjinder S.
    Imperial Coll London, England.
    Olsson, Hans
    Karlstad Hosp, Sweden.
    Olsson, Sven-Erik
    Helsingborg Hosp, Sweden; Helsingborg Hosp, Sweden.
    Omerovic, Elmir
    Sahlgrenska Univ Gothenburg, Sweden.
    Panayi, Georgios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Petraco, Ricardo
    Imperial Coll London, England.
    Piek, Jan J.
    Acad Med Ctr, Netherlands.
    Ribichini, Flavo
    Univ Hosp Verona, Italy.
    Samady, Habib
    Emory Univ, GA 30322 USA.
    Samuels, Bruce
    Cedars Sinai Heart Inst, CA USA.
    Sandhall, Lennart
    Helsingborg Hosp, Sweden; Helsingborg Hosp, Sweden.
    Sapontis, James
    MonashHeart, Australia; Monash Univ, Australia.
    Sen, Sayan
    Imperial Coll London, England.
    Seto, Arnold H.
    Vet Affairs Long Beach Healthcare Syst, CA USA.
    Sezer, Murat
    Istanbul Univ, Turkey.
    Sharp, Andrew S. P.
    Royal Devon and Exeter Hosp, England; Univ Exeter, England.
    Shin, Eun-Seok
    Univ Ulsan, South Korea.
    Singh, Jasvindar
    Washington Univ, MO USA.
    Takashima, Hiroaki
    Aichi Med Univ Hosp, Japan.
    Talwar, Suneel
    Royal Bournemouth Gen Hosp, England.
    Tanaka, Nobuhiro
    Tokyo Med Univ, Japan.
    Tang, Kare
    Essex Cardiothorac Ctr, England; Anglia Ruskin Univ, England.
    Van Belle, Eric
    Lille Univ Hosp, France; INSERM, France.
    van Royen, Niels
    Vrije Univ Amsterdam Med Ctr, Netherlands.
    Varenhorst, Christoph
    Uppsala Univ, Sweden.
    Vinhas, Hugo
    Hosp Garcia de Horta, Portugal.
    Vrints, Christiaan J.
    Antwerp Univ Hosp, Belgium.
    Walters, Darren
    Prince Charles Hosp, Australia.
    Yokoi, Hiroyoshi
    Fukuoka Sannou Hosp, Japan.
    Frobert, Ole
    Orebro Univ, Sweden.
    Patel, Manesh R.
    Duke Univ, NC USA.
    Serruys, Patrick
    Imperial Coll London, England.
    Davies, Justin E.
    Imperial Coll London, England.
    Gotberg, Matthias
    Lund Univ, Sweden.
    Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes2018In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, no 15, p. 1437-1449Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p amp;lt; 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

  • 277.
    Escobar Kvitting, John-Peder
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Oslo Univ Hosp, Norway.
    Hermansson, Ulf
    Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Vanhanen, Ingemar
    Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Resection of a plasma cell granuloma combining a conventional posterolateral left-sided thoracotomy with a minimally invasive valve approach2019In: GENERAL THORACIC AND CARDIOVASCULAR SURGERY, ISSN 1863-6705, Vol. 67, no 10, p. 894-896Article in journal (Refereed)
    Abstract [en]

    Plasma cell granuloma (PCG) is a rare benign tumor that is difficult to differentiate from malignancy. Depending on the location of the PCG, surgical management can be challenging. We describe a patient with a PCG involving the left lower lobe extending into the left atrium, that was resected en bloc using a conventional posterolateral thoracotomy combined with a surgical approach predominantly used for minimally invasive mitral valve surgery. This case illustrates how it is possible to utilize a technique used for cardiac surgery for tumors of pulmonary origin involving the heart.

  • 278.
    Escobar Kvitting, John-Peder
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Department of Cardiothoracic Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
    Nielsen, Niels Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Vanhanen, Ingemar
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Baranowski, Jacek
    Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Surgical management of outflow tract obstruction after transapical mitral valve implantation2018In: Journal of cardiac surgery, ISSN 0886-0440, E-ISSN 1540-8191, Vol. 33, no 9, p. 545-547Article in journal (Refereed)
    Abstract [en]

    Left ventricular outflow tract (LVOT) obstruction due to systolic anterior motion of the anterior mitral valve leaflet (AML) is a known complication after mitral valve repair or transfemoral/transapical mitral valve implantation (TMVI). We present a patient with a previous mitral valve repair who developed LVOT obstruction after TMVI in whom the AML was surgically resected using a transaortic approach.

  • 279.
    Fabris, Enrico
    et al.
    Cardiology Department, Isala Heart Center, the Netherlands, Cardiovascular Department, University of Trieste, Italy.
    van 't Hof, Arnoud
    Isala Heart Center, Maastricht University Medical Center, Zuyderland Hospital, the Netherlands,.
    Hamm, Christian W
    Kerckhoff Heart and Thorax Center, Germany.
    Lapostolle, Frédéric
    Hôpital Avicenne, France.
    Lassen, Jens F
    Aarhus University Hospital, Denmark.
    Goodman, Shaun G
    Canadian Heart Research Centre, University of Toronto, Canada.
    Ten Berg, Jurriën M
    St Antonius Hospital Nieuwegein, the Netherlands.
    Bolognese, Leonardo
    Cardiovascular and Neurological Department, Azienda Ospedaliera Arezzo, Italy.
    Cequier, Angel
    Heart Disease Institute, University of Barcelona, Spain.
    Chettibi, Mohamed
    Centre Hospito-universitaire Frantz Fanon, Algeria.
    Hammett, Christopher J
    Royal Brisbane and Women's Hospital, Australia.
    Huber, Kurt
    Wilhelminen Hospital, Austria, Sigmund Freud Private University, Austria.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Merkely, Béla
    Heart and Vascular Center, Semmelweis University, Hungary.
    Storey, Robert F
    Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK.
    Zeymer, Uwe
    Klinikum Ludwigshafen and Institut für Herzinfarktforschung, Germany.
    Cantor, Warren J
    Southlake Regional Health Centre, University of Toronto, Canada.
    Tsatsaris, Anne
    Astra Zeneca, UK.
    Kerneis, Mathieu
    ACTION Study Group, Sorbonne Université Paris 6, France.
    Diallo, Abdourahmane
    ACTION Study Group, Hospital Lariboisiere, France..
    Vicaut, Eric
    ACTION Study Group, Hospital Lariboisiere, France..
    Montalescot, Gilles
    ACTION Study Group, Sorbonne Université Paris 6, France.
    Clinical impact and predictors of complete ST segment resolution after primary percutaneous coronary intervention: A subanalysis of the ATLANTIC Trial2019In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 8, no 3, p. 208-217Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In the ATLANTIC (Administration of Ticagrelor in the catheterization laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery) trial the early use of aspirin, anticoagulation, and ticagrelor coupled with very short medical contact-to-balloon times represent good indicators of optimal treatment of ST-elevation myocardial infarction and an ideal setting to explore which factors may influence coronary reperfusion beyond a well-established pre-hospital system.

    METHODS: This study sought to evaluate predictors of complete ST-segment resolution after percutaneous coronary intervention in ST-elevation myocardial infarction patients enrolled in the ATLANTIC trial. ST-segment analysis was performed on electrocardiograms recorded at the time of inclusion (pre-hospital electrocardiogram), and one hour after percutaneous coronary intervention (post-percutaneous coronary intervention electrocardiogram) by an independent core laboratory. Complete ST-segment resolution was defined as ≥70% ST-segment resolution.

    RESULTS: Complete ST-segment resolution occurred post-percutaneous coronary intervention in 54.9% ( n=800/1456) of patients and predicted lower 30-day composite major adverse cardiovascular and cerebrovascular events (odds ratio 0.35, 95% confidence interval 0.19-0.65; p<0.01), definite stent thrombosis (odds ratio 0.18, 95% confidence interval 0.02-0.88; p=0.03), and total mortality (odds ratio 0.43, 95% confidence interval 0.19-0.97; p=0.04). In multivariate analysis, independent negative predictors of complete ST-segment resolution were the time from symptoms to pre-hospital electrocardiogram (odds ratio 0.91, 95% confidence interval 0.85-0.98; p<0.01) and diabetes mellitus (odds ratio 0.6, 95% confidence interval 0.44-0.83; p<0.01); pre-hospital ticagrelor treatment showed a favorable trend for complete ST-segment resolution (odds ratio 1.22, 95% confidence interval 0.99-1.51; p=0.06).

    CONCLUSIONS: This study confirmed that post-percutaneous coronary intervention complete ST-segment resolution is a valid surrogate marker for cardiovascular clinical outcomes. In the current era of ST-elevation myocardial infarction reperfusion, patients' delay and diabetes mellitus are independent predictors of poor reperfusion and need specific attention in the future.

  • 280.
    Fabris, Enrico
    et al.
    Isala Clinics, Zwolle, the Netherlands, University of Trieste, Trieste, Italy.
    Van't Hof, Arnoud
    Isala Clinics, Zwolle, the Netherlands.
    Hamm, Christian W
    Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
    Lapostolle, Frédéric
    Hôpital Avicenne, Bobigny, France.
    Lassen, Jens Flensted
    Aarhus University Hospital, Aarhus N, Denmark.
    Goodman, Shaun G
    St. Michael’s Hospital, University of Toronto, Toronto, Canada.
    Ten Berg, Jurriën M
    Antonius Hospital Nieuwegein, Nieuwegein, the Netherlands.
    Bolognese, Leonardo
    Cardiovascular and Neurological Department, Azienda Ospedaliera Arezzo, Arezzo, Italy.
    Cequier, Angel
    University of Barcelona, Barcelona, Spain.
    Chettibi, Mohamed
    Centre Hospitalo Universitaire Frantz Fanon, Blida, Algeria.
    Hammett, Christopher H
    Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia.
    Huber, Kurt
    Wilhelminen Hospital and Sigmund Freud Private University, Medical School, Vienna, Austria.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Merkely, Béla
    Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
    Storey, Robert F
    University of Sheffield, Sheffield, United Kingdom.
    Zeymer, Uwe
    Klinikum Ludwigshafen and Institut für Herzinfarktforschung, Ludwigshafen, Germany.
    Cantor, Warren J
    University of Toronto, Newmarket, Ontario, Canada;.
    Rousseau, Hélène
    Hospital Lariboisiere, ACTION Study Group, Paris, France.
    Vicaut, Eric
    Hospital Lariboisiere, ACTION Study Group, Paris, France.
    Montalescot, Gilles
    Sorbonne Université Paris 6, ACTION Study Group, Hospital Pitie-Salpetriere (AP-HP), Paris, France.
    Impact of presentation and transfer delays on complete ST-segment resolution before primary percutaneous coronary intervention: insights from the ATLANTIC trial.2017In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 13, no 1, p. 69-77, article id EIJ-D-16-00965Article in journal (Refereed)
    Abstract [en]

    AIMS: The aim of this study was to identify predictors of complete ST-segment resolution (STR) pre-primary percutaneous coronary intervention (PCI) in patients enrolled in the ATLANTIC trial.

    METHODS AND RESULTS: ECGs recorded at the time of inclusion (pre-hospital [pre-H]-ECG) and in the catheterisation laboratory before angiography (pre-PCI-ECG) were analysed by an independent core laboratory. Complete STR was defined as ≥70%. Complete STR occurred pre-PCI in 12.8% (204/1,598) of patients and predicted lower 30-day composite MACCE (OR=0.10, 95% CI: 0.002-0.57, p=0.001) and total mortality (OR=0.16, 95% CI: 0.004-0.95, p=0.035). Independent predictors of complete STR included the time from index event to pre-H-ECG (OR=0.94, 95% CI: 0.89-1.00, p=0.035), use of heparins before pre-PCI-ECG (OR=1.75, 95% CI: 1.25-2.45, p=0.001) and time from pre-H-ECG to pre-PCI-ECG (OR=1.09, 95% CI: 1.03-1.16, p=0.005). In the pre-H ticagrelor group, patients with complete STR had a significantly longer delay between pre-H-ECG and pre-PCI-ECG compared to patients without complete STR (median 53 [44-73] vs. 49 [38.5-61] mins, p=0.001); however, this was not observed in the control group (in-hospital ticagrelor) (50 [40-67] vs. 49 [39-61] mins, p=0.258).

    CONCLUSIONS: Short patient delay, early administration of anticoagulant and ticagrelor if a long transfer delay is expected may help to achieve reperfusion prior to PCI. Pre-H treatment may be beneficial in patients with longer transfer delays, allowing the drug to become biologically active.

  • 281.
    Fabris, Enrico
    et al.
    Cardiology Department, Isala Heart Center, Zwolle, the Netherlands, , Cardiovascular Department, University of Trieste, Trieste, Italy.
    Van't Hof, Arnoud
    Cardiology Department, Isala Heart Center, Zwolle, the Netherlands, Maastricht University Medical Center, Maastricht, the Netherlands, Zuyderland Hospital, Heerlen, the Netherlands.
    Hamm, Christian W
    Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
    Lapostolle, Frédéric
    SAMU 93 Hôpital Avicenne, Bobigny, France.
    Lassen, Jens Flensted
    Department of Cardiology B, Aarhus University Hospital, Aarhus, Denmark.
    Goodman, Shaun G
    Canadian Heart Research Centre, Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Canada.
    Ten Berg, Jurriën M
    Department of Cardiology, St. Antonius Hospital Nieuwegein, Nieuwegein, the Netherlands.
    Bolognese, Leonardo
    Cardiovascular and Neurological Department, Azienda Ospedaliera Arezzo, Arezzo, Italy.
    Cequier, Angel
    Heart Disease Institute, Hospital Universitario de Bellvitge, University of Barcelona, Spain.
    Chettibi, Mohamed
    Centre Hospito-universitaire Frantz Fanon, Blida, Algeria.
    Hammett, Christopher J
    Department of Cardiology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
    Huber, Kurt
    3rd Department of Medicine, Cardiology and Intensive Care Medicine, Wilhelminen hospital and Sigmund Freud University, Medical School, Vienna, Austria..
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Merkely, Béla
    Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
    Storey, Robert F
    Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.
    Zeymer, Uwe
    Klinikum Ludwigshafen and Institut für Herzinfarktforschung, Ludwigshafen, Germany.
    Cantor, Warren J
    Southlake Regional Health Centre, University of Toronto, Ontario, Canada.
    Kerneis, Mathieu
    Sorbonne Université, ACTION Study Group, Hospital Pitie-Salpetriere (AP-HP), Paris, France.
    Diallo, Abdourahmane
    Hospital Lariboisiere, ACTION Study Group, Paris, France.
    Vicaut, Eric
    Hospital Lariboisiere, ACTION Study Group, Paris, France.
    Montalescot, Gilles
    Sorbonne Université, ACTION Study Group, Hospital Pitie-Salpetriere (AP-HP), Paris, France.
    Pre-hospital administration of ticagrelor in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: A sub-analysis of the ATLANTIC trial2019In: Catheterization and cardiovascular interventions, ISSN 1522-1946, E-ISSN 1522-726X, Vol. 93, no 7, p. E369-E377Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We investigated, in the contemporary era of ST-elevation myocardial infarction (STEMI) treatment, the influence of diabetes mellitus (DM) on cardiovascular outcomes, and whether pre-hospital administration of ticagrelor may affect these outcomes in a subgroup of STEMI patients with DM.

    BACKGROUND: DM patients have high platelet reactivity and a prothrombotic condition which highlight the importance of an effective antithrombotic regimen in this high-risk population.

    METHODS: In toal 1,630 STEMI patients enrolled in the ATLANTIC trial who underwent primary percutaneous coronary intervention (PCI) were included. Multivariate analysis was used to explore the association of DM with outcomes and potential treatment-by-diabetes interaction was tested.

    RESULTS: A total of 214/1,630 (13.1%) patients had DM. DM was an independent predictor of poor myocardial reperfusion as reflected by less frequent ST-segment elevation resolution (≥70%) after PCI (OR 0.59, 95% CI 0.43-0.82, P < 0.01) and was an independent predictor of the composite 30-day outcomes of death/new myocardial infarction (MI)/urgent revascularization/definite stent thrombosis (ST) (OR 2.80, 95% CI 1.62-4.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08-5.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54-28.22, P < 0.01). No significant interaction between pre-hospital ticagrelor vs in-hospital ticagrelor administration and DM was present for the clinical, electrocardiographic and angiographic outcomes as well as for thrombolysis in myocardial infarction major bleeding.

    CONCLUSIONS: DM remains independently associated with poor myocardial reperfusion and worse 30-day clinical outcomes. No significant interaction was found between pre-hospital vs in-hospital ticagrelor administration and DM status. Further approaches for the treatment of DM patients are needed.

    CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580.

  • 282.
    Feldt, Kari
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    De Palma, Rodney
    Buckinghamshire NHS Trust, England; Karolinska Inst, Sweden.
    Bjursten, Henrik
    Lund Univ, Sweden.
    Petursson, Petur
    Gothenburg Univ, Sweden.
    Nielsen, Niels Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Kellerth, Thomas
    Orebro Univ Hosp, Sweden.
    Jonsson, Anders
    Univ Hosp, Sweden.
    Nilsson, Johan
    Umea Univ Hosp, Sweden.
    Ruck, Andreas
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Settergren, Magnus
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Change in mitral regurgitation severity impacts survival after transcatheter aortic valve replacement2019In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 294, p. 32-36Article in journal (Refereed)
    Abstract [en]

    Background: The impact of a change in mitral regurgitation (MR) following TAVR is unknown. We studied the impact of baseline MR and early post-procedural change in MR on survival following TAVR. Methods: The SWEDEHEART registry included all TAVRs performed in Sweden. Patients were dichotomized into no/mild and moderate/severe MR groups. Vital status, echocardiographic data at baseline and within 7 days after TAVR were analyzed. Results: 1712 patients were included. 1404 (82%) had no/mild MR and 308 (18%) had moderate/severe MR. Baseline moderate/severe MR conferred a higher mortality rate at 5-year follow-up (adjusted HR 1.29, CI 1.01-1.65, p = 0.04). Using persistent amp;lt;= mild MR as the reference, when moderate/severe MR persisted or if MR worsened from amp;lt;= mild at baseline to moderate/severe after TAVR, higher 5-year mortality rates were seen (adjusted HR 1.66, CI 1.17-2.34, p = 0.04; adjusted HR 1.97, CI 1.29-3.00, p = 0.002, respectively). If baseline moderate/severe MR improved to = mild after TAVR no excess mortality was seen (HR 1.09, CI 0.75-1.58, p = 0.67). Paravalvular aortic regurgitation (PVL) was inversely associated with MR improvement after TAVR (OR 0.4, 95%: CI 0.17-0.94; p = 0.034). Atrial fibrillation (OR 2.1, 95% CI: 1.27-3.39, p = 0.004), self-expanding valve (OR 3.8, 95% CI: 2.08-7.14, p amp;lt; 0.0001), and PVL (4.3, 95% CI 2.32-7.78. p amp;lt; 0.0001) were associated with MR worsening. Conclusions: Moderate/severe baseline MR in patients undergoing TAVR is associated with a mortality increase during 5 years of follow-up. This risk is offset if MR improves to amp;lt;= mild, whereas worsening of MR after TAVR is associated with a 2-fold mortality increase. (C) 2019 Elsevier B.V. All rights reserved.

  • 283.
    Fernandez-Barral, Asuncion
    et al.
    University of Autonoma Madrid, Spain CSIC UAM Madrid, Spain .
    Luis Orgaz, Jose
    University of Autonoma Madrid, Spain CSIC UAM Madrid, Spain Kings Coll London, England .
    Baquero, Pablo
    University of Autonoma Madrid, Spain CSIC UAM Madrid, Spain University of Glasgow, Scotland .
    Ali, Zaheer
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Moreno, Alberto
    CSIC UAM Madrid, Spain University of Dundee, Scotland .
    Tiana, Maria
    University of Autonoma Madrid, Spain CSIC UAM Madrid, Spain .
    Gomez, Valenti
    University of Autonoma Madrid, Spain CSIC UAM Madrid, Spain UCL, England .
    Riveiro-Falkenbach, Erica
    University of Complutense Madrid, Spain Institute Invest I 12, Spain .
    Canadas, Carmen
    Capio Fdn Jimenez Diaz, Spain .
    Zazo, Sandra
    Capio Fdn Jimenez Diaz, Spain .
    Bertolotto, Corine
    CHU Nice, France CHU Nice, France .
    Davidson, Irwin
    University of Strasbourg, France .
    Luis Rodriguez-Peralto, Jose
    University of Complutense Madrid, Spain Institute Invest I 12, Spain .
    Palmero, Ignacio
    CSIC UAM Madrid, Spain .
    Rojo, Federico
    Capio Fdn Jimenez Diaz, Spain .
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    del Peso, Luis
    University of Autonoma Madrid, Spain CSIC UAM Madrid, Spain .
    Jimenez, Benilde
    University of Autonoma Madrid, Spain CSIC UAM Madrid, Spain Institute Invest I 12, Spain .
    Regulatory and Functional Connection of Microphthalmia-Associated Transcription Factor and Anti-Metastatic Pigment Epithelium Derived Factor in Melanoma2014In: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 16, no 6, p. 529-542Article in journal (Refereed)
    Abstract [en]

    Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor superfamily, has potent anti-metastatic effects in cutaneous melanoma through its direct actions on endothelial and melanoma cells. Here we show that PEDF expression positively correlates with microphthalmia-associated transcription factor ( MITF) in melanoma cell lines and human samples. High PEDF and MITF expression is characteristic of low aggressive melanomas classified according to molecular and pathological criteria, whereas both factors are decreased in senescent melanocytes and naevi. Importantly, MITF silencing down-regulates PEDF expression in melanoma cell lines and primary melanocytes, suggesting that the correlation in the expression reflects a causal relationship. In agreement, analysis of Chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq) data sets revealed three MITF binding regions within the first intron of SERPINF1, and reporter assays demonstrated that the binding of MITF to these regions is sufficient to drive transcription. Finally, we demonstrate that exogenous PEDF expression efficiently halts in vitro migration and invasion, as well as in vivo dissemination of melanoma cells induced by MITF silencing. In summary, these results identify PEDF as a novel transcriptional target of MITF and support a relevant functional role for the MITF-PEDF axis in the biology of melanoma.

  • 284.
    Fernemark, Hanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Jaredsson, Christine
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Bunjaku, Bekim
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Rosenqvist, Ulf
    Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Guldbrand, Hans
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    A Randomized Cross-Over Trial of the Postprandial Effects of Three Different Diets in Patients with Type 2 Diabetes2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, p. e79324-Article in journal (Refereed)
    Abstract [en]

    Background: In the clinic setting both fasting levels of glucose and the area under the curve (AUC) of glucose, by determination of HbA1c levels, are used for risk assessments, in type 2 diabetes (NIDDM). However little is known about postprandial levels, and hence AUC, regarding other traditional risk factors such as insulin and blood-lipids and how this is affected by different diets. less thanbrgreater than less thanbrgreater thanObjective: To study postprandial effects of three diets, during a single day, in NIDDM. less thanbrgreater than less thanbrgreater thanMethods: A low-fat diet (45-56 energy-% from carbohydrates), and a low-carbohydrate diet (16-24 energy-% from carbohydrates) was compared with a Mediterranean-style diet (black coffee for breakfast and the same total-caloric intake as the other two diets for lunch with red wine, 32-35 energy-% from carbohydrates) in a randomized cross-over design. Total-caloric intake/test-day at the clinic from food was 1025-1080 kCal in men and 905-984 kCal in women. The test meals were consumed at a diabetes ward under supervision. less thanbrgreater than less thanbrgreater thanResults: Twenty-one participants were recruited and 19 completed the studies. The low-carbohydrate diet induced lower insulin and glucose excursions compared with the low-fat diet (pandlt;0.0005 for both AUC). The insulin-response following the single Mediterranean-style lunch-meal was more pronounced than during the low-fat diet lunch (insulin increase-ratio of the low-fat diet: 4.35 +/- 2.2, of Mediterranean-style diet: 8.12 +/- 5.2, p=0.001) while postprandial glucose levels were similar. The increase-ratio of insulin correlated with the elevation of the incretin glucose-dependent insulinotropic-polypeptide following the Mediterranean-style diet lunch (Spearman, r = 0.64, p = 0.003). less thanbrgreater than less thanbrgreater thanConclusions: The large Mediterranean-style lunch-meal induced similar postprandial glucose-elevations as the low-fat meal despite almost double amount of calories due to a pronounced insulin-increase. This suggests that accumulation of caloric intake from breakfast and lunch to a single large Mediterranean style lunch-meal in NIDDM might be advantageous from a metabolic perspective.

  • 285.
    Fernlund, Eva
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Lund University, Sweden.
    Wålinder Österberg, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Kuchinskaya, Ekaterina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Gunnarsson, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics. Region Östergötland, Center for Business support and Development.
    Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death2017In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 38, no 6, p. 1262-1268Article in journal (Refereed)
    Abstract [en]

    Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy. A cascade family screening was performed in the family after identification of the TNNT2 and the BAG3 variants in the proband. The first-degree relatives underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, exercise stress test, and targeted genetic testing. The index patient presented with advanced DCM. After a severe clinical course, the baby had external left ventricular assist as a bridge to heart transplantation. 1.5 months after transplantation, the baby suffered sudden cardiac death (SCD) despite maximal treatment in the pediatric intensive care unit. The patient was shown to carry two heterozygous genetic variants in the TNNT2 gene [TNNT2 c.518G amp;gt; A(p.Arg173Gln)] and BAG3 [BAG3 c.785C amp;gt; T(p.Ala262Val)]. Two of the screened individuals (two females) appeared to carry both the familial variants. All the individuals carrying the TNNT2 variant presented with DCM, the two adult patients had mild or moderate symptoms of heart failure and reported palpitations but no syncope or presyncopal attacks prior to the genetic diagnosis. The female carriers of TNNT2 and BAG3 variants had more advanced DCM. In the family history, there were three additional cases of SCD due to DCM, diagnosed by autopsy, but no genetic analysis was possible in these cases. Our findings suggest that the variants in TNNT2 and BAG3 are associated with a high propensity to life-threatening cardiomyopathy presenting from childhood and young adulthood.

  • 286.
    Filippatos, Gerasimos
    et al.
    University of Athens, Greece.
    Sana Khan, Sadiya
    Northwestern University, IL 60611 USA.
    Ambrosy, Andrew P.
    Duke University, NC USA.
    Cleland, John G. F.
    University of London Imperial Coll Science Technology and Med, England; University of London Imperial Coll Science Technology and Med, England.
    Collins, Sean P.
    Vanderbilt University, TN 37235 USA.
    Lam, Carolyn S. P.
    National Heart Centre, Singapore.
    Angermann, Christiane E.
    University of Wurzburg, Germany; University of Wurzburg, Germany.
    Ertl, Georg
    University of Wurzburg, Germany; University of Wurzburg, Germany.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Health Sciences.
    Hu, Dayi
    Peking University, Peoples R China.
    Dickstein, Kenneth
    University of Bergen, Norway.
    Perrone, Sergio V.
    Institute Fleni, Argentina.
    Ghadanfar, Mathieu
    Novartis Pharma AG, Switzerland.
    Bermann, Georgina
    Novartis Pharma AG, Switzerland.
    Noe, Adele
    Novartis Pharma AG, Switzerland.
    Schweizer, Anja
    Novartis Pharma AG, Switzerland.
    Maier, Thomas
    Novartis Pharma AG, Switzerland.
    Gheorghiade, Mihai
    Northwestern University, IL 60611 USA.
    International REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure (REPORT-HF): rationale for and design of a global registry2015In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 17, no 5, p. 527-533Article in journal (Refereed)
    Abstract [en]

    AimsThe clinical characteristics, initial presentation, management, and outcomes of patients hospitalized with new-onset (first diagnosis) heart failure (HF) or decompensation of chronic HF are poorly understood worldwide. REPORT-HF (International REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure) is a global, prospective, and observational study designed to characterize patient trajectories longitudinally during and following an index hospitalization for HF. MethodsData collection for the registry will be conducted at approximate to 300 sites located in approximate to 40 countries. Comprehensive data including demographics, clinical presentation, co-morbidities, treatment patterns, quality of life, in-hospital and post-discharge outcomes, and health utilization and costs will be collected. Enrolment of approximate to 20 000 adult patients hospitalized with new-onset (first diagnosis) HF or decompensation of chronic HF over a 3-year period is planned with subsequent 3 years follow-up. PerspectiveThe REPORT-HF registry will explore the clinical characteristics, management, and outcomes of HF worldwide. This global research programme may have implications for the formulation of public health policy and the design and conduct of international clinical trials.

  • 287.
    Fjalldal, S.
    et al.
    Skane Univ Hosp, Sweden.
    Follin, C.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Svärd, Daniel
    Lund University, Lund, Sweden.
    Rylander, L.
    Lund Univ, Sweden.
    Gabery, S.
    Lund Univ, Sweden.
    Petersen, A.
    Lund Univ, Sweden.
    van Westen, D.
    Lund Univ, Sweden.
    Sundgren, P. C.
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Bjorkman-Burtscher, I. M.
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Latt, J.
    Skane Univ Hosp, Sweden.
    Ekman, Bertil
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Johanson, A.
    Skane Univ Hosp, Sweden.
    Erfurth, E. M.
    Skane Univ Hosp, Sweden.
    Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma2018In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 178, no 6, p. 577-587Article in journal (Refereed)
    Abstract [en]

    Context: Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown. Objective: To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP. Design: A cross-sectional study with a median follow-up time of 22 (6-49) years after operation. Setting: The South Medical Region of Sweden (2.5 million inhabitants). Participants: Included were 41 patients (24 women, amp;gt;= 17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HI was found in 23 patients. Main outcome measures: Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry. Results: Right uncinate fasciculus was significantly altered (P amp;lt;= 0.01) Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge (P = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory. Conclusions: A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP.

  • 288.
    Fjalldal, Sigridur
    et al.
    Skåne University Hospital, Sweden .
    Holmer, Helene
    Central Hospital Kristianstad, Sweden .
    Rylander, Lars
    Lund University, Sweden .
    Elfving, Maria
    Skåne University Hospital, Sweden .
    Ekman, Bertil
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Osterberg, Kai
    Lund University, Sweden .
    Erfurth, Eva Marie
    Skåne University Hospital, Sweden .
    Hypothalamic Involvement Predicts Cognitive Performance and Psychosocial Health in Long-term Survivors of Childhood Craniopharyngioma2013In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 8, p. 3253-3262Article in journal (Refereed)
    Abstract [en]

    Context: Hypothalamic damage caused by craniopharyngioma (CP) is associated with poor functional outcome. less thanbrgreater than less thanbrgreater thanObjective: To assess cognitive function and quality of life in childhood-onset CP on hormonal replacement, including GH treatment. less thanbrgreater than less thanbrgreater thanDesign: A cross-sectional study with a median follow-up time of 20 years (1-40). less thanbrgreater than less thanbrgreater thanSetting: Patients were recruited from the South Medical Region of Sweden. less thanbrgreater than less thanbrgreater thanParticipants: The study included 42 patients (20 women) surgically treated for a childhood-onset CP between 1958 and 2000. Patients were aged andgt;= 17 years. Equally many controls, matched for age, sex, residence, and smoking habits, were included. Tumor growth into the third ventricle was found in 25 patients. less thanbrgreater than less thanbrgreater thanMain Outcome Measures: All subjects were examined with a battery of cognitive tests and the following questionnaires: Symptom Checklist-90, the Interview Schedule for Social Interaction, and the Social Network concept. less thanbrgreater than less thanbrgreater thanResults: The CP patients had lower cognitive performance, reaching statistical significance in 12 of 20 test variables, including executive function and memory. Comparison of patients with tumor growth into the third ventricle to controls revealed a significant lower mean total score (P = .006). A significant negative correlation was recorded between mean z-score of cognitive performance and years since operation (r = -0.407; P = .014). No statistically significant group differences were observed across any of the 9 Symptom Checklist-90 subscales. less thanbrgreater than less thanbrgreater thanConclusions: Adults with childhood-onset CP, on hormone replacement, including GH treatment, have memory defects, disturbed attention, and impaired processing speed. Patients with hypothalamic involvement are more affected. Patients rated their quality of life as good as their matched controls.

  • 289.
    Fjälldal, S.
    et al.
    Skåne Univ Hosp, Sweden.
    Follin, C.
    Skane Univ Hosp, Sweden.
    Gabery, S.
    Lund Univ, Sweden.
    Sundgren, P. C.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Bjorkman-Burtscher, I. M.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden; Lund Univ, Sweden.
    Latt, J.
    Skane Univ Hosp, Sweden.
    Mannfolk, P.
    Skane Univ Hosp, Sweden.
    Nordstrom, C. H.
    Skane Univ Hosp, Sweden.
    Rylander, L.
    Lund Univ, Sweden.
    Ekman, Bertil
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Cheong, R.
    Lund Univ, Sweden.
    Palsson, A.
    Skane Univ Hosp, Sweden.
    Petersen, A.
    Lund Univ, Sweden.
    Erfurth, E. M.
    Skane Univ Hosp, Sweden.
    Detailed assessment of hypothalamic damage in craniopharyngioma patients with obesity2019In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 43, no 3, p. 533-544Article in journal (Refereed)
    Abstract [en]

    Background/objectives Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor craniopharyngioma (CP). Attempts have been made to predict the risk of HO based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but none have included volumetry. We performed qualitative and quantitative volumetric analyses of HT damage. The results were explored in relation to feeding related peptides and body fat. Subjects/methods A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was performed at median 22 years after first operation; 41 CPs, median age 35 (range: 17-56), of whom 23 had HT damage, were compared to 32 controls. After exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome measures were the relation of metabolic parameters to HT volume and qualitative analyses of HT damage. Results Metabolic parameters scored persistently very high in vascular risk particularly among HT damaged patients. Patients had smaller HT volumes compared to controls 769 (35-1168) mm(3) vs. 879 (775-1086) mm(3); P amp;lt; 0.001. HT volume correlated negatively with fat mass and leptin among CP patients (r(s) = -0.67; P amp;lt; .001; r(s) = -0.53; P = 0.001), and explained 39% of the variation in fat mass. For every 100 mm(3) increase in HT volume fat mass decreased by 2.7 kg (95% CI: 1.5-3.9; P amp;lt; 0.001). Qualitative assessments revealed HT damage in three out of six patients with normal volumetry, but HT damage according to operation records. Conclusions A decrease in HT volume was associated with an increase in fat mass and leptin. We present a method with a high inter-rater reliability (0.94) that can be applied by nonradiologists for the assessment of HT damage. The method may be valuable in the risk assessment of diseases involving the HT.

  • 290.
    Flaatten, H.
    et al.
    Gen ICU, Norway; University of Bergen, Norway.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Activity- or severity-based scoring in the ICU?2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 1Article in journal (Other academic)
    Abstract [en]

    n/a

  • 291.
    Foldemo, Anniqa
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Wärdig, Rikard
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Bachrach-Lindstrom, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Edman, Gunnar
    Karolinska Institute, Sweden Karolinska Institute, Sweden .
    Holmberg, Tommy
    Tiohundra AB, Sweden .
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Valter, Lars
    Tiohundra AB, Sweden .
    Osby, Urban
    Karolinska Institute, Sweden Karolinska Institute, Sweden Tiohundra AB, Sweden .
    Health-related quality of life and metabolic risk in patients with psychosis2014In: Schizophrenia Research, ISSN 0920-9964, E-ISSN 1573-2509, Vol. 152, no 1, p. 295-299Article in journal (Refereed)
    Abstract [en]

    Improved Health-related quality of life (HRQoL) is an alternative treatment goal for individuals with psychosis, who have up to two times greater prevalence of type 2 diabetes, hypertension and obesity than the general population. Aim: to compare HRQoL in patients with psychosis, especially schizophrenia, with a reference sample and explore the relationship between HRQoL and metabolic risk factors in these patients. Methods: a prospective cohort study was carried out in specialized psychiatric outpatient departments in Sweden. The patients were invited consecutively. A prospective population-based study of public health in the south-east of Sweden served as reference group. Patients were assessed with psychiatric questionnaires that included Global Assessment of Functioning (GAF). Health-related quality of life was assessed using the questionnaire EQ5D, both for patients and the population, and several other health status outcomes were used. Results: At 73%, schizophrenia and schizoaffective disorder were the most common diagnoses in the patient group. The results in patients (n = 903) and population (n = 7238) showed significant differences in lower EQ5D among patients. According to the definition by the International Diabetes Federation (IDF), elevated blood pressure was the only metabolic risk associated with lower HRQoL in patients. Raised LDL-cholesterol levels were also significantly related to lower HRQoL. Conclusion: patients suffering from psychosis had significantly lower HRQoL regarding all components in EQ5D, except for the pain/discomfort component. Almost half of the patient group met the criteria for metabolic syndrome. According to the IDF criteria, elevated blood pressure was the only metabolic risk factor that had an impact on HRQoL.

  • 292.
    Folkesson, Maggie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Sadowska, Natalia
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Matts
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Carlhäll, Carl-Johan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Differences in cardiovascular toxicities associated with cigarette smoking and snuff use revealed using novel zebrafish models2016In: Biology Open, ISSN 2046-6390, Vol. 5, no 7, p. 970-978Article in journal (Refereed)
    Abstract [en]

    Tobacco use is strongly associated with cardiovascular disease and the only avoidable risk factor associated with development of aortic aneurysm. While smoking is the most common form of tobacco use, snuff and other oral tobacco products are gaining popularity, but research on potentially toxic effects of oral tobacco use has not kept pace with the increase in its use. Here, we demonstrate that cigarette smoke and snuff extracts are highly toxic to developing zebrafish embryos. Exposure to such extracts led to a palette of toxic effects including early embryonic mortality, developmental delay, cerebral hemorrhages, defects in lymphatics development and ventricular function, and aneurysm development. Both cigarette smoke and snuff were more toxic than pure nicotine, indicating that other compounds in these products are also associated with toxicity. While some toxicities were found following exposure to both types of tobacco product, other toxicities, including developmental delay and aneurysm development, were specifically observed in the snuff extract group, whereas cerebral hemorrhages were only found in the group exposed to cigarette smoke extract. These findings deepen our understanding of the pathogenic effects of cigarette smoking and snuff use on the cardiovascular system and illustrate the benefits of using zebrafish to study mechanisms involved in aneurysm development.

  • 293.
    Folkesson, Maggie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Vorkapic, Emina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Gulbins, Erich
    University of Duisburg-Essen, University of Cincinnati.
    Japtok, Lukasz
    The department of Toxicology, Institute of Nutritional Science, University of Potsdam.
    Kleuser, Burkhard
    The department of Toxicology, Institute of Nutritional Science, University of Potsdam.
    Welander, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Inflammatory cells, ceramides, and expression of proteases in perivascular adipose tissue adjacent to human abdominal aortic aneurysms2017In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 65, no 4, p. 1171-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Abdominal aortic aneurysm (AAA) is a deadly irreversible weakening and distension of the abdominal aortic wall. The pathogenesis of AAA remains poorly understood. Investigation into the physical and molecular characteristics of perivascular adipose tissue (PVAT) adjacent to AAA has not been done before and is the purpose of this study.

    METHODS AND RESULTS: Human aortae, periaortic PVAT, and fat surrounding peripheral arteries were collected from patients undergoing elective surgical repair of AAA. Control aortas were obtained from recently deceased healthy organ donors with no known arterial disease. Aorta and PVAT was found in AAA to larger extent compared with control aortas. Immunohistochemistry revealed neutrophils, macrophages, mast cells, and T-cells surrounding necrotic adipocytes. Gene expression analysis showed that neutrophils, mast cells, and T-cells were found to be increased in PVAT compared with AAA as well as cathepsin K and S. The concentration of ceramides in PVAT was determined using mass spectrometry and correlated with content of T-cells in the PVAT.

    CONCLUSIONS: Our results suggest a role for abnormal necrotic, inflamed, proteolytic adipose tissue to the adjacent aneurysmal aortic wall in ongoing vascular damage.

  • 294.
    Forsberg, Lena M
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Nylander, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tamés, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Exercise echocardiography predicts postoperative left ventricular remodeling in aortic regurgitation2014In: SCANDINAVIAN CARDIOVASCULAR JOURNAL, ISSN 1401-7431, Vol. 48, no 1, p. 4-12Article in journal (Refereed)
    Abstract [en]

    Objective. We aimed to investigate if preoperative left ventricular (LV) function assessed by exercise echocardiography could predict late postoperative LV function in aortic regurgitation (AR) patients and to evaluate how LV long-axis function is affected late after aortic valve surgery. Design. A total of 21 male chronic AR patients, aged 49 (12) years, accepted for surgery were examined preoperatively, 6 months-, and 4 years postoperatively, at rest and during exercise. Besides conventional echocardiographic parameters, the atrioventricular plane displacement (AVPD) by M-mode and peak systolic velocity (s) in the basal LV by color tissue Doppler were measured. Results. Preoperatively EFrest and EFexercise, were 55(7)% and 54(9)%, respectively, and Delta EF 0(8)%. LV dimensions and volumes indexed to BSA had decreased at the 6-month follow-up and were stable at late follow-up. s(rest), s(exercise), AVPD(rest), and AVPD(exercise) were unchanged at both the postoperative examinations (all P >= 0.05). Preoperative EFexercise and AVPD(exercise) showed inverse correlation to late postoperative indexed LV enddiastolic volume (r = -0.68, p < 0.004 and r = -0.86, P < 0.001) and indexed LV endsystolic volume (r = -0.68, P = 0.004 and r = -0.81, P < 0.001), while there was no correlation to preoperative EFrest and AVPD(rest) (all r < 0.2). Conclusions. Preoperative exercise echocardiography can detect AR patients with suboptimal LV remodeling late postoperatively.

  • 295.
    Forsell, Claes
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Åberg, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Preoperative Topical Hypothermia used in Prolonged Severe Lower Limb Ischemia to Avoid Ischemic Damage - The First Clinical Experience2013In: International Journal of Biomedical Science, ISSN 1550-9702, E-ISSN 1555-2810, Vol. 9, no 3, p. 181-184Article in journal (Refereed)
    Abstract [en]

    Severe lower limb ischemia TASC IIB/III with sensory and motor neurologic deficiencies leads to prolonged hospital care, amputation, and death in 20-70 % of cases. We present our first clinical experience of the use of preoperative topical hypothermia to improve muscular viability in these patients. Two hours after onset of symptoms, six 4-liter plastic bags were filled with snow and packed against the ischemic leg which was protected from frost injury by a layer of towels. After surgical revascularization four hours later muscular and neural functions in the leg were completely restored. A maximum serum myoglobin of 6500 ng/L (median 12000 ng/L in similar but untreated patients) postoperatively decreased to 1400 ng/L after 27 hours.

  • 296.
    Forsgren, Mikael
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Karlsson, Markus
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlström, Nils
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Norén, Bengt
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Ekstedt, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Cedersund, Gunnar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Model-inferred mechanisms of liver function from magnetic resonance imaging data: Validation and variation across a clinically relevant cohort2019In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 15, no 6, article id e1007157Article in journal (Refereed)
    Abstract [en]

    Estimation of liver function is important to monitor progression of chronic liver disease (CLD). A promising method is magnetic resonance imaging (MRI) combined with gadoxetate, a liver-specific contrast agent. For this method, we have previously developed a model for an average healthy human. Herein, we extended this model, by combining it with a patient-specific non-linear mixed-effects modeling framework. We validated the model by recruiting 100 patients with CLD of varying severity and etiologies. The model explained all MRI data and adequately predicted both timepoints saved for validation and gadoxetate concentrations in both plasma and biopsies. The validated model provides a new and deeper look into how the mechanisms of liver function vary across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate. These mechanisms are shared across many liver functions and can now be estimated from standard clinical images.

    Author summary

    Being able to accurately and reliably estimate liver function is important when monitoring the progression of patients with liver disease, as well as when identifying drug-induced liver injury during drug development. A promising method for quantifying liver function is to use magnetic resonance imaging combined with gadoxetate. Gadoxetate is a liver-specific contrast agent, which is taken up by the hepatocytes and excreted into the bile. We have previously developed a mechanistic model for gadoxetate dynamics using averaged data from healthy volunteers. In this work, we extended our model with a non-linear mixed-effects modeling framework to give patient-specific estimates of the gadoxetate transport-rates. We validated the model by recruiting 100 patients with liver disease, covering a range of severity and etiologies. All patients underwent an MRI-examination and provided both blood and liver biopsies. Our validated model provides a new and deeper look into how the mechanisms of liver function varies across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate.

  • 297.
    Forsgren, Mikael
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Norén, Bengt
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Kihlberg, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Comparing 2D and 3D Magnetic Resonance Elastography Techniques in a Clinical Setting: Initial Experiences2014Conference paper (Other academic)
    Abstract [en]

    Purpose: It has been shown that liver fibrosis, and even cirrhosis, may be reversible in humans. For this reason there is a great need for the imminent introduction of non-invasive and clinically useful methods in order to monitor fibrosis in patients [1, 2]. A body of evidence points to the fact that MRE is a highly useful candidate towards this end [3]. However, before using such techniques more widely, it is important to verify that comparable physical measures are provided by alternative and clinically relevant MRE approaches. The aim of this pilot study was to compare 2D and 3D MRE, also known as MR Rheology, using a commercially available 2D system, with an acoustic transducer, and 3D MRE research system, with an electromagnetic transducer, with respect to liver stiffness and elasticity in patients with diffuse or suspected diffuse liver disease. Materials and Methods: Seven patients, referred to our hospital for evaluation of elevated serum alanine aminotransferase (ALT) and/or alkaline phosphatase (ALP) levels but without signs of cirrhosis on physical examination, were recruited from a previous study [4], and examined in the course of one day. Fibrosis staging from prior biopsy were gained from [4], see Table 1. The 3D MRE method included an active electromagnetic transducer generating waves at 56 Hz, and a 1.5 T Philips Achieva MR-scanner, with a phased array body coil (Sense TorsoXL, all 16 coil elements), GRE sequence parameters include; FOV = 320x256 mm2, matrix = 80x38, slice thickness = 4 mm, # slices = 9, FA = 15°, TR = 112 ms, TE = 9.21 ms, SENSE = 2. The 2D MRE method included a passive acoustic transducer generating waves at 60 Hz, and a 1.5 T GE 450W MR-scanner, with a phased array body coil (HD8 Torso, all 8 coil elements), GRE sequence parameters include; FOV = 440x440 mm2, matrix = 256x64, slice thickness = 10 mm, # slices = 4, FA = 30°, TR = 50 ms, TE = 21.7 ms, ASSET = 2. The transducers were on both systems placed on the anterior chest wall to the right of xiphoid process (patient in a supine position), the time between each MRE acquisition was dependent on how long it took to transfer the patient between the two MR systems in the hospital (<10 min) A region of interest (ROI) was placed in an appropriate single 10 mm slice acquired using the GE MR-scanner. A corresponding ROI for the Philips system, covering the same anatomical region, was placed over three slices (4 mm thickness each). This yielded a total cranio-caudal coverage of the ROIs equal to 10 mm (on the GE data) and 12 mm (on the Philips data). The mean and standard deviations of the stiffness (GE), elasticity (Philips) and Gabs,Elastic (Philips) were calculated. Gabs,Elastic is the absolute value of the shear modulus, which in principle is equivalent to the viscoelastic property, shear stiffness. In the 3D method the shear waves were obtained by applying the curl operator and using the Voigt rheological model to obtain shear elasticity maps [5, 6]. In the 2D method the GE system provided the stiffness maps. Statistics was performed using Mathematica 9. ROI drawing and quantification of the data from the GE system was performed using Sectra PACS IDS7, and ROI drawing and quantification of the data from the Philips system was performed using a custom software package implemented in ROOT, generously provided by R. Sinkus (Kings College, London, UK). Results: The measured values are presented in Table 1. Both elasticity and Gabs,Elastic correlates well with the stiffness measurement carried out in the GE system (Fig. 1), as was shown by the elasticity and stiffness correlation R2 = 0.96 (P < 0.001) slope = 1.08 (P < 0.001), intercept = 0.61 kPa (P = 0.08), Gabs,Elastic and stiffness correlation R2 = 0.96 (P < 0.001), slope = 0.95 (P< 0.001) intercept = 0.28 kPa (P = 0.43)

  • 298.
    Forsgren, Mikael
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Wolfram MathCore AB, Linköping, Sweden.
    Norén, Bengt
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Kihlberg, Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Comparing hepatic 2D and 3D magnetic resonance elastography methods in a clinical setting – Initial experiences2015In: European Journal of Radiology Open, E-ISSN 2352-0477, Vol. 2, p. 66-70Article in journal (Refereed)
    Abstract [en]

    Purpose

    Continuous monitoring of liver fibrosis progression in patients is not feasible with the current diagnostic golden standard (needle biopsy). Recently, magnetic resonance elastography (MRE) has emerged as a promising method for such continuous monitoring. Since there are different MRE methods that could be used in a clinical setting there is a need to investigate whether measurements produced by these MRE methods are comparable. Hence, the purpose of this pilot study was to evaluate whether the measurements of the viscoelastic properties produced by 2D (stiffness) and 3D (elasticity and ‘Gabs,Elastic’) MRE are comparable.

    Materials and methods

    Seven patients with diffuse or suspect diffuse liver disease were examined in the same day with the two MRE methods. 2D MRE was performed using an acoustic passive transducer, with a 1.5 T GE 450 W MR system. 3D MRE was performed using an electromagnetic active transducer, with a 1.5 T Philips Achieva MR system. Finally, mean viscoelastic values were extracted from the same anatomical region for both methods by an experienced radiologist.

    Results

    Stiffness correlated well with the elasticity, R2 = 0.96 (P < 0.001; slope = 1.08, intercept = 0.61 kPa), as well as with ‘Gabs,ElasticR2 = 0.96 (P < 0.001; slope = 0.95, intercept = 0.28 kPa).

    Conclusion

    This pilot study shows that different MRE methods can produce comparable measurements of the viscoelastic properties of the liver. The existence of such comparable measurements is important, both from a clinical as well as a research perspective, since it allows for equipment-independent monitoring of disease progression.

  • 299.
    Forsum, Elisabet
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Janerot Sjöberg, Birgitta
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Löf, Marie
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    MET-values of standardised activities in relation to body fat: studies in pregnant and non-pregnant women2018In: Nutrition & Metabolism, ISSN 1743-7075, E-ISSN 1743-7075, Vol. 15, article id 45Article in journal (Refereed)
    Abstract [en]

    Background: Physical activity is associated with health in women. Published MET-values (MET: metabolic equivalent of task) may assess physical activity and energy expenditure but tend to be too low for subjects with a high total body fat (TBF) content and therefore inappropriate for many contemporary women. The MET-value for an activity is the energy expenditure of a subject performing this activity divided by his/her resting energy expenditure, often assumed to be 4.2 kJ/kg/h. Relationships between TBF and MET have been little studied although overweight and obesity is common in women. Available data indicate that MET-values decrease during pregnancy but more studies in pregnant contemporary women are needed. Subjects and methods: Using indirect calorimetry we measured energy expenditure and assessed MET-values in women, 22 non-pregnant (BMI: 18-34) and 22 in gestational week 32 (non-pregnant BMI: 18-32) when resting, sitting, cycling (30 and 60 watts), walking (3.2 and 5.6 km/h) and running (8 km/h). Relationships between TBF and MET-values were investigated and used to predict modified MET-values. The potential of such values to improve calculations of total energy expenditure of women was investigated. Results: The resting energy expenditure was below 4.2 kJ/kg/h in both groups of women. Women in gestational week 32 had a higher resting energy metabolism (p amp;lt; 0.001) and 7-15% lower MET-values (p amp;lt; 0.05) than non-pregnant women. MET-values of all activities were correlated with TBF (p amp;lt; 0.05) in non-pregnant women and modified MET-values improved estimates of total energy expenditure in such women. In pregnant women, correlations (p amp;lt;= 0.03) between TBF and MET were found for running (8 km/h) and for walking at 5.6 km/h. Conclusions: Our results are relevant when attempts are made to modify the MET-system in contemporary pregnant and non-pregnant women. MET-values were decreased in gestational week 32, mainly due to an increased resting energy metabolism and studies describing how body composition affects the one MET-value (i.e. the resting energy metabolism in kJ/kg/h) during pregnancy are warranted. Studies of how pregnancy and TBF affect MET-values of high intensity activities are also needed. Corrections based on TBF may have a potential to improve the MET-system in non-pregnant women.

  • 300.
    Forte, Mari Nieves Velasco