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  • 151. Arking, Dan E
    et al.
    Pulit, Sara L
    Crotti, Lia
    van der Harst, Pim
    Munroe, Patricia B
    Koopmann, Tamara T
    Sotoodehnia, Nona
    Rossin, Elizabeth J
    Morley, Michael
    Wang, Xinchen
    Johnson, Andrew D
    Lundby, Alicia
    Gudbjartsson, Daníel F
    Noseworthy, Peter A
    Eijgelsheim, Mark
    Bradford, Yuki
    Tarasov, Kirill V
    Dörr, Marcus
    Müller-Nurasyid, Martina
    Lahtinen, Annukka M
    Nolte, Ilja M
    Smith, Albert Vernon
    Bis, Joshua C
    Isaacs, Aaron
    Newhouse, Stephen J
    Evans, Daniel S
    Post, Wendy S
    Waggott, Daryl
    Lyytikäinen, Leo-Pekka
    Hicks, Andrew A
    Eisele, Lewin
    Ellinghaus, David
    Hayward, Caroline
    Navarro, Pau
    Ulivi, Sheila
    Tanaka, Toshiko
    Tester, David J
    Chatel, Stéphanie
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kumari, Meena
    Morris, Richard W
    Naluai, Asa T
    Padmanabhan, Sandosh
    Kluttig, Alexander
    Strohmer, Bernhard
    Panayiotou, Andrie G
    Torres, Maria
    Knoflach, Michael
    Hubacek, Jaroslav A
    Slowikowski, Kamil
    Raychaudhuri, Soumya
    Kumar, Runjun D
    Harris, Tamara B
    Launer, Lenore J
    Shuldiner, Alan R
    Alonso, Alvaro
    Bader, Joel S
    Ehret, Georg
    Huang, Hailiang
    Kao, W H Linda
    Strait, James B
    Macfarlane, Peter W
    Brown, Morris
    Caulfield, Mark J
    Samani, Nilesh J
    Kronenberg, Florian
    Willeit, Johann
    Smith, J Gustav
    Greiser, Karin H
    Meyer Zu Schwabedissen, Henriette
    Werdan, Karl
    Carella, Massimo
    Zelante, Leopoldo
    Heckbert, Susan R
    Psaty, Bruce M
    Rotter, Jerome I
    Kolcic, Ivana
    Polašek, Ozren
    Wright, Alan F
    Griffin, Maura
    Daly, Mark J
    Arnar, David O
    Hólm, Hilma
    Thorsteinsdottir, Unnur
    Denny, Joshua C
    Roden, Dan M
    Zuvich, Rebecca L
    Emilsson, Valur
    Plump, Andrew S
    Larson, Martin G
    O'Donnell, Christopher J
    Yin, Xiaoyan
    Bobbo, Marco
    D'Adamo, Adamo P
    Iorio, Annamaria
    Sinagra, Gianfranco
    Carracedo, Angel
    Cummings, Steven R
    Nalls, Michael A
    Jula, Antti
    Kontula, Kimmo K
    Marjamaa, Annukka
    Oikarinen, Lasse
    Perola, Markus
    Porthan, Kimmo
    Erbel, Raimund
    Hoffmann, Per
    Jöckel, Karl-Heinz
    Kälsch, Hagen
    Nöthen, Markus M
    den Hoed, Marcel
    Loos, Ruth J F
    Thelle, Dag S
    Gieger, Christian
    Meitinger, Thomas
    Perz, Siegfried
    Peters, Annette
    Prucha, Hanna
    Sinner, Moritz F
    Waldenberger, Melanie
    de Boer, Rudolf A
    Franke, Lude
    van der Vleuten, Pieter A
    Beckmann, Britt Maria
    Martens, Eimo
    Bardai, Abdennasser
    Hofman, Nynke
    Wilde, Arthur A M
    Behr, Elijah R
    Dalageorgou, Chrysoula
    Giudicessi, John R
    Medeiros-Domingo, Argelia
    Barc, Julien
    Kyndt, Florence
    Probst, Vincent
    Ghidoni, Alice
    Insolia, Roberto
    Hamilton, Robert M
    Scherer, Stephen W
    Brandimarto, Jeffrey
    Margulies, Kenneth
    Moravec, Christine E
    Greco M, Fabiola Del
    Fuchsberger, Christian
    O'Connell, Jeffrey R
    Lee, Wai K
    Watt, Graham C M
    Campbell, Harry
    Wild, Sarah H
    El Mokhtari, Nour E
    Frey, Norbert
    Asselbergs, Folkert W
    Mateo Leach, Irene
    Navis, Gerjan
    van den Berg, Maarten P
    van Veldhuisen, Dirk J
    Kellis, Manolis
    Krijthe, Bouwe P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Franco, Oscar H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hofman, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kors, Jan A
    Uitterlinden, André G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Witteman, Jacqueline C M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kedenko, Lyudmyla
    Lamina, Claudia
    Oostra, Ben A
    Abecasis, Gonçalo R
    Lakatta, Edward G
    Mulas, Antonella
    Orrú, Marco
    Schlessinger, David
    Uda, Manuela
    Markus, Marcello R P
    Völker, Uwe
    Snieder, Harold
    Spector, Timothy D
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kivimaki, Mika
    Kähönen, Mika
    Mononen, Nina
    Raitakari, Olli T
    Viikari, Jorma S
    Adamkova, Vera
    Kiechl, Stefan
    Brion, Maria
    Nicolaides, Andrew N
    Paulweber, Bernhard
    Haerting, Johannes
    Dominiczak, Anna F
    Nyberg, Fredrik
    Whincup, Peter H
    Hingorani, Aroon D
    Schott, Jean-Jacques
    Bezzina, Connie R
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ferrucci, Luigi
    Gasparini, Paolo
    Wilson, James F
    Rudan, Igor
    Franke, Andre
    Mühleisen, Thomas W
    Pramstaller, Peter P
    Lehtimäki, Terho J
    Paterson, Andrew D
    Parsa, Afshin
    Liu, Yongmei
    van Duijn, Cornelia M
    Siscovick, David S
    Gudnason, Vilmundur
    Jamshidi, Yalda
    Salomaa, Veikko
    Felix, Stephan B
    Sanna, Serena
    Ritchie, Marylyn D
    Stricker, Bruno H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stefansson, Kari
    Boyer, Laurie A
    Cappola, Thomas P
    Olsen, Jesper V
    Lage, Kasper
    Schwartz, Peter J
    Kääb, Stefan
    Chakravarti, Aravinda
    Ackerman, Michael J
    Pfeufer, Arne
    de Bakker, Paul I W
    Newton-Cheh, Christopher
    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 8, p. 826-836Article in journal (Refereed)
    Abstract [en]

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

  • 152.
    Armaganijan, Luciana V.
    et al.
    Brazilian Clin Res Inst, Sao Paulo, Brazil..
    Alexander, Karen P.
    Duke Clin Res Inst, Durham, NC USA..
    Huang, Zhen
    Duke Clin Res Inst, Durham, NC USA..
    Tricoci, Pierluigi
    Duke Clin Res Inst, Durham, NC USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Van de Werf, Frans
    Univ Hosp Leuven, Dept Cardiol, Leuven, Belgium..
    Armstrong, Paul W.
    Univ Alberta, Edmonton, AB, Canada..
    Aylward, Philip E.
    Flinders Univ & Med Ctr, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia..
    White, Harvey D.
    Green Lane Cardiovasc Serv, Auckland, New Zealand..
    Moliterno, David J.
    Gill Heart Inst, Lexington, KY USA.;Univ Kentucky, Lexington, KY USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Chen, Edmond
    Bayer HealthCare Pharmaceut Inc, Whippany, NJ USA..
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Strony, John
    Johnson & Johnson, New Brunswick, NJ USA..
    Mahaffey, Kenneth W.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Lopes, Renato D.
    Duke Clin Res Inst, Durham, NC USA..
    Effect of age on efficacy and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 178, p. 176-184Article in journal (Refereed)
    Abstract [en]

    Background Antithrombotic therapy plays an important role in the treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS) but is associated with bleeding risk. Advanced age may modify the relationship between efficacy and safety. Methods Efficacy and safety of vorapaxar (a protease-activated receptor 1 antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate the effect of age, Cox regression models were developed to estimate hazard ratios (HRs) with the adjustment of other baseline characteristics and randomized treatment for the primary efficacy composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, and the primary safety composite of moderate or severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding. Results The median age of the population was 64 years (25th, 75th percentiles = 58, 71). Also, 1,791 patients (13.8%) were <= 54 years of age, 4,968 (38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years, and 2,206 (17.1%) were 75 years or older. Older patients had higher rates of hypertension, renal insufficiency, and previous stroke and worse Killip class. The oldest age group (>= 75 years) had substantially higher 2-year rates of the composite ischemic end point and moderate or severe GUSTO bleeding compared with the youngest age group (<= 54 years). The relationships between treatment assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89 (0.76-1.04), and 0.88 (0.74-1.06), respectively (P value for interaction = .435). Similar to what was observed for efficacy outcomes, we did not observe any interaction between vorapaxar and age on bleeding outcomes. For the composite of moderate or severe bleeding according to the GUSTO classification, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were 1.73 (0.89-3.34), 1.39 (1.04-1.86), 1.10 (0.85-1.42), and 1.73 (1.29-2.33), respectively (P value for interaction = .574). Conclusion Older patients had a greater risk for ischemic and bleeding events; however, the efficacy and safety of vorapaxar in NSTE ACS were not significantly influenced by age.

  • 153. Arnlov, Johan
    et al.
    Ruge, Toralph
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ingelsson, Erik
    Larsson, Anders
    Sundström, Johan
    Lind, Lars
    Serum Endostatin and Risk of Mortality in the Elderly Findings From 2 Community-Based Cohorts2013In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 33, no 11, p. 2689-2695Article in journal (Refereed)
    Abstract [en]

    Objective Experimental data imply that endostatin, a proteolytically cleaved fragment of collagen XVIII, could be involved in the development of cardiovascular disease and cancer. Prospective data concerning the relation between circulating endostatin and mortality are lacking. Accordingly, we aimed to study associations between circulating endostatin and mortality risk. Approach and Results Serum endostatin was analyzed in 2 community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n=931; mean age, 70 years; median follow-up, 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=748; mean age, 77 years; median follow-up, 9.7 years). During follow-up, 90 participants died in PIVUS (1.28/100 person-years at risk), and 417 participants died in ULSAM (6.7/100 person-years at risk). In multivariable Cox regression models adjusted for age and established cardiovascular risk factors, 1 SD higher ln(serum endostatin level) was associated with a hazard ratio of mortality of 1.39 and 95% confidence interval, 1.26 to 1.53, on average in both cohorts. In the ULSAM cohort, serum endostatin was also associated with cardiovascular mortality (177 deaths; hazard ratio per SD of ln[endostatin] 1.45, 95% confidence interval [1.25-1.71]) and cancer mortality (115 deaths; hazard ratio per SD of ln[endostatin] 1.35, 95% confidence interval [1.10-1.66]). Conclusions High serum endostatin was associated with increased mortality risk in 2 independent community-based cohorts of the elderly. Our observational data support the importance of extracellular matrix remodeling in the underlying pathophysiology of cardiovascular disease and cancer.

  • 154.
    Arvidsson, Sandra
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Cardiac function in hereditary transthyretin amyloidosis: an echocardiographic study2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Hereditary transthyretin amyloidosis (ATTR) is a lethal disease in which misfolded transthyretin (TTR) proteins accumulate as insoluble aggregates in tissues throughout the body. A common mutation is the exchange of valine to methionine at place 30 (TTR V30M), a form endemically found in the northern parts of Sweden. The main treatment option for ATTR amyloidosis is liver transplantation as the procedure halts production of mutated transthyretin. The disease is associated with marked phenotypic diversity ranging from predominant cardiac complications to pure neuropathy. Two different types of fibril composition – one in which both fragmented and full-length TTR are present (type A) and one consisting of only full-length TTR (type B) have been suggested to account for some phenotypic differences. Cardiac amyloidosis is associated with increased myocardial thickness and the disease could easily be mistaken for other entities characterised by myocardial thickening, such as sarcomeric hypertrophic cardiomyopathy (HCM). The aims in this thesis were to investigate echocardiographic characteristics in Swedish ATTR amyloidosis patients, and to identify markers aiding in differentiating ATTR heart disease from HCM. Another objective was to examine the impact of fibril composition and sex on the phenotypic variation in amyloid heart disease.

    Methods: A total of 122 ATTR amyloidosis patients that had undergone thorough echocardiographic examinations were included in the studies. Analyses of ventricular geometry as well as assessment of systolic and diastolic function were performed, using both conventional echocardiographic methods and speckle tracking technique. ECG analysis was conducted in study I, allowing measurement of QRS voltage. In study I and study II ATTR patients were compared to patients with HCM. In addition, 30 healthy controls were added to study II.

    Results: When parameters from ECG and echocardiography were investigated, the results revealed that the combination of QRS voltage <30 mm (<3 mV) and an interventricular/posterior wall thickness quotient <1.6 could differentiate cardiac ATTR amyloidosis from HCM. Differences in degree of right ventricular involvement were also demonstrated between HCM and ATTR amyloidosis, where ATTR patients displayed a right ventricular apical sparing pattern whereas the inverse pattern was found in HCM. Analysis of fibril composition revealed increased LV wall thickness in type A patients compared to type B, but in addition type A women displayed both lower myocardial thickness and more preserved systolic function as compared to type A males. When cardiac geometry and function were evaluated pre and post liver transplantation in type A and B patients, significant deterioration was detected in type A but not in type B patients after liver transplantation.

    Conclusions: Increasing awareness of typical cardiac amyloidotic signs by echocardiography is important to reduce the risk of delayed diagnosis. Our classification model based on ECG and echocardiography could aid in differentiating ATTR amyloidosis from HCM. Furthermore, the apical sparing pattern found in the right ventricle may pose another clue for amyloid heart disease, although it requires to be studied further. Furthermore, we disclosed that type A fibrils, male sex and increasing age were important determinants of increased myocardial thickness. As type A fibril patients displayed rapid cardiac deterioration after liver transplantation other treatment options should probably be sought for this group of patients.

  • 155.
    Arvidsson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wikström, Gerhard
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Right ventricular involvement in transthyretin amyloidosisManuscript (preprint) (Other academic)
    Abstract [en]

    Objectives

    Right heart involvement and dysfunction is frequently encountered in cardiomyopathies. In immunoglobulin light chain (AL) amyloidosis, right ventricular (RV) function has been described as a strong determinant of survival. However, RV involvement in transthyretin related amyloidosis (ATTR) has been somewhat overlooked. We therefore sought to establish the degree of RV involvement in ATTR amyloidosis and compare the findings with sarcomeric hypertrophic cardiomyopathy (HCM).

    Patients and methods

    Forty-two patients with diagnosed ATTR and echocardiographic evidence of cardiac amyloidosis (cardiac ATTR), 19 ATTR patients with normal left ventricular (LV) wall thickness (non-cardiac ATTR), 25 patients with diagnosed sarcomeric HCM and 30 healthy controls were included in the study. Echocardiographic examinations were analysed and standard measurements of LV and RV dimensions and function were carried out. In addition, LV global and RV global and segmental strain were analysed. The degree of cardiac involvement and function was compared between non-cardiac ATTR patients and healthy controls and between cardiac ATTR patients and with those having HCM.

    Results

    Non-cardiac ATTR amyloidosis patients did not differ from healthy controls, either in geometrical or functional measurements of the LV and RV. HCM patients had significantly thicker interventricular septal thickness (p=0.017) and thinner posterior wall thickness (p=0.004) as compared to cardiac ATTR. When comparing cardiac ATTR and HCM patients by means of RV structure and function only segmental strain differed between the two patient groups. In cardiac ATTR we found an RV apex-to-base strain gradient with highest deformation in the apex whereas the pattern was inverse in patients with HCM.

    Conclusions

    RV involvement is common only in ATTR patients with concomitant LV involvement. The present study also detected an apical sparing pattern for the RV in patients with ATTR cardiomyopathy, similar to what has previously been described for the LV. This pattern was not seen in HCM patients. Further studies are warranted to assess the clinical importance of these findings.

  • 156.
    Arvidsson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Pilebro, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Westermark, Per
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Amyloid Cardiomyopathy in Hereditary Transthyretin V30M Amyloidosis - Impact of Sex and Amyloid Fibril Composition2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 11, article id e0143456Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Transthyretin V30M (ATTR V30M) amyloidosis is a phenotypically diverse disease with symptoms ranging from predominant neuropathy to exclusive cardiac manifestations. The aims of this study were to determine the dispersion of the two types of fibrils found in Swedish ATTR V30M patients -Type A consisting of a mixture of truncated and full length ATTR fibrils and type B fibrils consisting of full length fibrils, and to estimate the severity of cardiac dysfunction in relation to fibril composition and sex.

    MATERIAL AND METHODS: Echocardiographic data were analysed in 107 Swedish ATTR V30M patients with their fibril composition determined as either type A or type B. Measurements of left ventricular (LV) dimensions and evaluation of systolic and diastolic function including speckle tracking derived strain were performed. Patients were grouped according to fibril type and sex. Multivariate linear regression was utilised to determine factors of significant impact on LV thickness.

    RESULTS: There was no significant difference in proportions of the two types of fibrils between men and women. In patients with type A fibrils, women had significantly lower median septal (p = 0.007) and posterior wall thicknesses (p = 0.010), lower median LV mass indexed to height (p = 0.008), and higher septal strain (p = 0.037), as compared to males. These differences were not apparent in patients with type B fibrils. Multiple linear regression analysis revealed that fibril type, sex and age all had significant impact on LV septal thickness.

    CONCLUSION: This study demonstrates a clear difference between sexes in the severity of amyloid heart disease in ATTR V30M amyloidosis patients. Even though type A fibrils were associated with more advanced amyloid heart disease compared to type B, women with type A fibrils generally developed less cardiac infiltration than men. The differences may explain the better outcome for liver transplanted late-onset female patients compared to males.

  • 157. Asayama, Kei
    et al.
    Thijs, Lutgarde
    Li, Yan
    Gu, Yu-Mei
    Hara, Azusa
    Liu, Yan-Ping
    Zhang, Zhenyu
    Wei, Fang-Fei
    Lujambio, Ines
    Mena, Luis J.
    Boggia, Jose
    Hansen, Tine W.
    Björklund-Bodegård, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nomura, Kyoko
    Ohkubo, Takayoshi
    Jeppesen, Jorgen
    Torp-Pedersen, Christian
    Dolan, Eamon
    Stolarz-Skrzypek, Katarzyna
    Malyutina, Sofia
    Casiglia, Edoardo
    Nikitin, Yuri
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Luzardo, Leonella
    Kawecka-Jaszcz, Kalina
    Sandoya, Edgardo
    Filipovsky, Jan
    Maestre, Gladys E.
    Wang, Jiguang
    Imai, Yutaka
    Franklin, Stanley S.
    O'Brien, Eoin
    Staessen, Jan A.
    Setting Thresholds to Varying Blood Pressure Monitoring Intervals Differentially Affects Risk Estimates Associated With White-Coat and Masked Hypertension in the Population2014In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 64, no 5, p. 935-942Article in journal (Refereed)
    Abstract [en]

    Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using >= 140/>= 90, >= 130/>= 80, >= 135/>= 85, and >= 120/>= 70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion, identification of truly low-risk white-coat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice.

  • 158. Asberg, Signild
    et al.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Henriksson, Karin M
    Terént, Andreas
    Reduced risk of death with warfarin: results of an observational nationwide study of 20 442 patients with atrial fibrillation and ischaemic stroke2013In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 8, no 8, p. 689-695Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Warfarin is demonstrated to be superior in efficacy over antiplatelet agents for the prevention of stroke, but the relationship between warfarin and mortality is less clear. Our aim was to investigate this relationship in a large cohort of unselected patients with atrial fibrillation and ischaemic stroke.

    METHODS: This observational study was based on patients who were discharged alive and registered in the Swedish Stroke Register in 2001 through 2005. Vital status was retrieved by linkage to the Swedish Cause of Death Register. We calculated a propensity score for the likelihood of warfarin prescription at discharge from hospital. The risk of death and 95% confidence intervals were estimated in Cox regression models.

    RESULTS: Out of the 20 442 patients with atrial fibrillation and ischaemic stroke (mean age = 79·5 years), 31% (n = 6399) were prescribed warfarin. After adjustment for the propensity score, warfarin was associated with a reduced risk of death (0·67; 95% confidence interval, 0·63-0·71). The crude rate (per 100 person-years) of fatal non-haemorrhagic stroke was lower in patients who received warfarin (1·60; 95% confidence interval, 1·34-1·89) compared to those who received antiplatelet (6·83; 95% confidence interval, 6·42-7·25). The rates (per 100 person-years) of fatal haemorrhagic stroke were 0·21 (95% confidence interval, 0·12-0·32) and 0·43 (95% confidence interval, 0·34-0·55) in patients prescribed warfarin and antiplatelet therapy, respectively.

    CONCLUSIONS: In addition to its established benefit for stroke prevention, warfarin therapy in patients with atrial fibrillation and ischaemic stroke was associated with a reduced risk of death, without an increased risk of fatal haemorrhagic stroke.

  • 159.
    Asberg, Signild
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Henriksson, Karin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Farahmand, B.
    Statin therapy and the risk of death and recurrent intracerebral hemorrhage2015In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 10, p. 43-43Article in journal (Other academic)
  • 160.
    Aspelund, Aleksanteri
    et al.
    Univ Helsinki, Wihuri Res Inst, Biomedicum Helsinki, POB 63,Haartmaninkatu 8, FIN-00014 Helsinki, Finland.;Univ Helsinki, Translat Canc Biol Program, Biomedicum Helsinki, POB 63,Haartmaninkatu 8, FIN-00014 Helsinki, Finland..
    Robciuc, Marius R.
    Univ Helsinki, Wihuri Res Inst, Biomedicum Helsinki, POB 63,Haartmaninkatu 8, FIN-00014 Helsinki, Finland.;Univ Helsinki, Translat Canc Biol Program, Biomedicum Helsinki, POB 63,Haartmaninkatu 8, FIN-00014 Helsinki, Finland..
    Karaman, Sinem
    Univ Helsinki, Wihuri Res Inst, Biomedicum Helsinki, POB 63,Haartmaninkatu 8, FIN-00014 Helsinki, Finland..
    Mäkinen, Taija
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Alitalo, Kari
    Univ Helsinki, Wihuri Res Inst, Biomedicum Helsinki, POB 63,Haartmaninkatu 8, FIN-00014 Helsinki, Finland.;Univ Helsinki, Translat Canc Biol Program, Biomedicum Helsinki, POB 63,Haartmaninkatu 8, FIN-00014 Helsinki, Finland..
    Lymphatic System in Cardiovascular Medicine2016In: Circulation Research, ISSN 0009-7330, E-ISSN 1524-4571, Vol. 118, no 3, p. 515-530Article, review/survey (Refereed)
    Abstract [en]

    The mammalian circulatory system comprises both the cardiovascular system and the lymphatic system. In contrast to the blood vascular circulation, the lymphatic system forms a unidirectional transit pathway from the extracellular space to the venous system. It actively regulates tissue fluid homeostasis, absorption of gastrointestinal lipids, and trafficking of antigen-presenting cells and lymphocytes to lymphoid organs and on to the systemic circulation. The cardinal manifestation of lymphatic malfunction is lymphedema. Recent research has implicated the lymphatic system in the pathogenesis of cardiovascular diseases including obesity and metabolic disease, dyslipidemia, inflammation, atherosclerosis, hypertension, and myocardial infarction. Here, we review the most recent advances in the field of lymphatic vascular biology, with a focus on cardiovascular disease.

  • 161. Aspelund, Aleksanteri
    et al.
    Tammela, Tuomas
    Antila, Salli
    Nurmi, Harri
    Leppanen, Veli-Matti
    Zarkada, Georgia
    Stanczuk, Lukas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Francois, Mathias
    Mäkinen, Taija
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Saharinen, Pipsa
    Immonen, Ilkka
    Alitalo, Kari
    Therapeutic Insights to Lymphangiogenic Growth Factors2015In: Journal of Vascular Research, ISSN 1018-1172, E-ISSN 1423-0135, Vol. 52, no S1, p. 19-19Article in journal (Other academic)
  • 162.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Håller vi på att vinna kampen mot hjärtinfarkt och slaganfall i norra Sverige?2004In: Skytteanska samfundets årsskrift Thule 2004, 2004, p. 75-82Chapter in book (Other (popular science, discussion, etc.))
  • 163.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The controversial snuff2014In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 276, no 1, p. 74-76Article in journal (Other academic)
  • 164. Asplund, Kjell
    et al.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sundström, G
    Stroke in the elderly1999In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 2, p. 152-157Article in journal (Refereed)
  • 165.
    Asplund, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Persson, Olle
    Umeå University, Faculty of Social Sciences, Department of Sociology.
    Country comparisons of human stroke research since 2001: a bibliometric study2012In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 43, no 3, p. 830-837Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: This is the first bibliometric comparison between countries of the development of stroke research over time.

    METHODS: Clinical and epidemiological articles on stroke published 2001 to mid-2011 were identified in Science Citation Index Expanded. Article fractions, citation fractions, h-index, and international collaboration were calculated using the BibExcel software and adjusted for population size and gross domestic product.

    RESULTS: The United States dominated with 28.7% of the sum of article fractions and 36.2% of the sum of citation fractions. The United States, Japan, the United Kingdom, and Germany together accounted for 52.1% of articles and 61.0% of citations. When adjusted for population size or gross domestic product, several small European countries, together with Israel and Taiwan, ranked the highest. Per population, there was a negative association (r=0.60) between burden of stroke (disability-adjusted life-years lost) and number of articles per population. In China, South Korea, and Singapore, the annual growth of stroke articles was more than twice the worldwide average. Whereas multinational collaboration was common within Europe and North America, it was relatively uncommon between Asian countries.

    CONCLUSIONS: The Big 4 in scientific literature on stroke, as to both number of articles and citations, are the United States, Japan, the United Kingdom, and Germany. Many small European countries have, in relation to their size, a high scientific production. Several countries with rapidly expanding economies have very fast growth of scientific production on stroke. Our results emphasize the need for stroke research in countries with a high population burden of stroke and they highlight the role of multinational collaboration.

  • 166.
    Asplund, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hulter Åsberg, Kerstin
    Appelros, Peter
    Bjarne, Daniela
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jonsson, Fredrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Norrving, Bo
    Stegmayr, Birgitta
    Terént, Andreas
    Wallin, Sari
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wester, Per-Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The Riks-Stroke story: building a sustainable national register for quality assessment of stroke care2011In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 6, no 2, p. 99-108Article in journal (Refereed)
    Abstract [en]

    Background Riks-Stroke, the Swedish Stroke Register, is the world's longest-running national stroke quality register (established in 1994) and includes all 76 hospitals in Sweden admitting acute stroke patients. The development and maintenance of this sustainable national register is described.

    Methods Riks-Stroke includes information on the quality of care during the acute phase, rehabilitation and secondary prevention of stroke, as well as data on community support. Riks-Stroke is unique among stroke quality registers in that patients are followed during the first year after stroke. The data collected describe processes, and medical and patient-reported outcome measurements. The register embraces most of the dimensions of health-care quality (evidence-based, safe, provided in time, distributed fairly and patient oriented).

    Result Annually, approximately 25 000 patients are included. In 2009, approximately 320 000 patients had been accumulated (mean age 76-years). The register is estimated to cover 82% of all stroke patients treated in Swedish hospitals. Among critical issues when building a national stroke quality register, the delicate balance between simplicity and comprehensiveness is emphasised. Future developments include direct transfer of data from digital medical records to Riks-Stroke and comprehensive strategies to use the information collected to rapidly implement new evidence-based techniques and to eliminate outdated methods in stroke care.

    Conclusions It is possible to establish a sustainable quality register for stroke at the national level covering all hospitals admitting acute stroke patients. Riks-Stroke is fulfilling its main goals to support continuous quality improvement of Swedish stroke services and serve as an instrument for following up national stroke guidelines.

  • 167.
    Asplund, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sukhova, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Diagnostic procedures, treatments, and outcomes in stroke patients admitted to different types of hospitals2015In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 46, no 3, p. 806-812Article in journal (Refereed)
    Abstract [en]

    Background and Purpose: In many countries, including Sweden, initiatives have been taken to reduce between-hospital differences in the quality of stroke services. We have explored to what extent hospital type (university, specialized nonuniversity, or community hospital) influences hospital performance. Methods: Riksstroke collects clinical data during hospital stay (national coverage 94%). Follow-up data at 3 months were collected using administrative registers and a questionnaire completed by surviving patients (response rate 88%). Structural data were collected from a questionnaire completed by hospital staff (response rate 100%). Multivariate analyses with adjustment for clustering were used to test differences between types of hospitals. Results: The proportion of patients admitted directly to a stroke unit was highest in community hospitals and lowest in university hospitals. Magnetic resonance, carotid imaging, and thrombectomy were more frequently performed in university hospitals, and the door-to-needle time for thrombolysis was shorter. Secondary prevention with antihypertensive drugs was used less often, and outpatient follow-up was less frequent in university hospitals. Fewer patients in community hospitals were dissatisfied with their rehabilitation. After adjusting for possible confounders, poor outcome (dead or activities of daily living dependency 3 months after stroke) was not significantly different between the 3 types of hospital. Conclusions: In a setting with national stroke guidelines, stroke units in all hospitals, and measurement of hospital performance and benchmarking, outcome (after case-mix adjustment) is similar in university, specialized nonuniversity, and community hospitals. There seems to be fewer barriers to organizing well-functioning stroke services in community hospitals compared with university hospitals.

  • 168. Atefi, Seyed Reza
    et al.
    Seoane, Fernando
    University of Borås, School of Health Science.
    The Emergence of Electrical Bioimpedance Monitoring for Prompt Detection of Stroke Damage2014Conference paper (Refereed)
  • 169.
    Atefi, Seyed Reza
    et al.
    KTH, School of Technology and Health (STH), Medical sensors, signals and systems (MSSS).
    Seoane, Fernando
    KTH, School of Technology and Health (STH), Medical sensors, signals and systems (MSSS).
    Lindecrantz, Kaj
    KTH, School of Technology and Health (STH), Medical sensors, signals and systems (MSSS).
    Electrical Bioimpedance cerebral monitoring. Preliminary results from measurements on stroke patients2012In: Engineering in Medicine and Biology Society (EMBC), 2012 Annual International Conference of the IEEE, IEEE , 2012, p. 126-129Conference paper (Refereed)
    Abstract [en]

    Electrical Bioimpedance Spectroscopy (EBIS) is currently used in different tissue characterization applications. In this work we aim to use EBIS to study changes in electrical properties of the cerebral tissues after an incident of hemorrhage/ischemic stroke. To do so a case-control study was conducted using six controls and three stroke cases. The preliminary results of this study show that by using Cole-based analysis on EBIS measurements and analyzing the Cole parameters R0 and R∞, it is possible to detect changes on electrical properties of cerebral tissue after stroke. 

  • 170.
    Aulin, Julia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gersh, B. J.
    Hanna, M.
    Horowitz, J. D.
    Hylek, E. M.
    Lopes, R. D.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Interleukin-6 and C-reactive protein and risk for cardiovascular events and death in anticoagulated patients with atrial fibrillation2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 1115-1116Article in journal (Refereed)
  • 171.
    Avezum, Alvaro
    et al.
    Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil.
    de Figueiredo Oliveira, Gustavo Bernardes
    Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil.
    Diaz, Rafael
    Estudios Clin Latinoamer, Rosario, Santa Fe, Argentina.
    Gonzalez Hermosillo, Jesus Antonio
    Inst Nacl Cardiol Ignacio Chavez, Rosario, Santa Fe, Argentina.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ripoll, Ernesto Ferreiros
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
    Noack, Herbert
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
    Piegas, Leopoldo Soares
    Hosp Coracao, Sao Paulo, Brazil.
    Connolly, Stuart J.
    Hamilton Hlth Sci, Hamilton, ON, Canada;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Efficacy and safety of dabigatran versus warfarin from the RE-LY trial2018In: Open heart, E-ISSN 2053-3624, Vol. 5, no 1, article id 000800Article in journal (Refereed)
    Abstract [en]

    Background Current data for atrial fibrillation (AF) and stroke are predominantly derived from North American and European patients. Although the burden of AF is high in Latin America (LA), little is known about current management of AF in the region. Methods We aimed to assess the consistency of efficacy and safety outcomes associated with dabigatran etexilate (DE) versus warfarin in patients with AF in LA from the RE-LY (Randomised Evaluation of Long-Term Anticoagulant Therapy) trial. Data from 956 LA patients and 17 157 non-LA patients were included in this analysis.chi(2) test and Cox proportional regression analysis were performed. The primary efficacy outcome included all strokes or systemic embolism (SE). Main safety outcome was major bleeding. Results LA patients were more often female, had higher proportion of permanent AF and lower creatinine clearance, among other characteristics. Vitamin K antagonist use at randomisation and time in therapeutic range were lower in LA than in non-LA patients (44% vs 63%, p<0.001; and 61.3 +/- 22.6% vs 64.6 +/- 19.6%, p=0.015, respectively). Efficacy endpoints were 0.91% versus 1.68% for DE 150 mg twice daily versus warfarin, respectively. Stroke/SE risk was lower in LA patients treated with DE 150 mg twice daily compared with warfarin, although not significant (HR 0.54; 95% CI 0.18 to 1.62). The annual stroke/SE rates for DE 110 mg twice daily versus warfarin were 1.82 versus 1.68, also not significantly different (HR 1.09; CI 0.44 to 2.67). There were no treatment-by-region interactions for either dose of DE on efficacy and safety outcomes. Conclusion Despite differences in the clinical profile and AF management, the efficacy and safety benefits of dabigatran over warfarin in LA patients relative to non-LA patients are consistent with those observed in the main RE-LY trial.

  • 172. Axelman, Elena
    et al.
    Henig, Israel
    Crispel, Yonatan
    Attias, Judith
    Li, Jin-Ping
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Brenner, Benjamin
    Vlodavsky, Israel
    Nadir, Yona
    Novel peptides that inhibit heparanase activation of the coagulation system2014In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 112, no 3, p. 466-477Article in journal (Refereed)
    Abstract [en]

    Heparanase is implicated in cell invasion, tumour metastasis and angiogenesis. It forms a complex and enhances the activity of the blood coagulation initiator tissue factor (IF). We describe new peptides derived from the solvent accessible surface of TF pathway inhibitor 2 (TFPI-2) that inhibit the heparanase procoagulant activity. Peptides were evaluated in vitro by measuring activated coagulation factor X levels and co-immunoprecipitation. Heparanase protein and/or lipopolysaccharide (LPS) were injected intra-peritoneally and inhibitory peptides were injected subcutaneously in mouse models. Plasma was analysed by ELISA for thrombin-antithrombin complex (TAT), D-dimer as markers of coagulation activation, and interleukin 6 as marker of sepsis severity. Peptides 5, 6, 7, 21 and 22, at the length of 11-14 amino acids, inhibited heparanase procoagulant activity but did not affect IF activity. Injection of newly identified peptides 5, 6 and 7 significantly decreased or abolished TAT plasma levels when heparanase or LPS were pre-injected, and inhibited clot formation in an inferior vena cava thrombosis model. To conclude, the solvent accessible surface of TFPI-2 first Kunitz domain is involved in TF/heparanase complex inhibition. The newly identified peptides potentially attenuate activation of the coagulation system induced by heparanase or LPS without predisposing to significant bleeding tendency.

  • 173.
    Axelsson, Birger
    et al.
    Örebro University, Örebro, Sweden .
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Svenmarker, Staffan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Gupta, Anil
    Örebro University, Örebro, Sweden .
    Tyden, Hans
    Örebro University, Örebro, Sweden .
    Wouters, Patrick
    Ghent, Belgium.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Effects of Combined Milrinone and Levosimendan Treatment on Systolic and Diastolic Function During Postischemic Myocardial Dysfunction in a Porcine Model2016In: Journal of Cardiovascular Pharmacology and Therapeutics, ISSN 1074-2484, E-ISSN 1940-4034, Vol. 21, no 5, p. 495-503Article in journal (Refereed)
    Abstract [en]

    It is not known whether there are positive or negative interactions on ventricular function when a calcium-sensitizing inotrope is added to a phosphodiesterase inhibitor in the clinical setting of acute left ventricular (LV) dysfunction. We hypothesized that when levosimendan is added to milrinone treatment, there will be synergetic inotropic and lusitropic effects. This was tested in an anesthetized porcine postischemic global LV injury model, where ventricular pressures and volumes (conductance volumetry) were measured. A global ischemic injury was induced by repetitive left main stem coronary artery occlusions. Load-independent indices of LV function were assessed before and after ventricular injury, after milrinone treatment, and finally after addition of levosimendan to the milrinone treatment. Nonparametric, within-group comparisons were made. The protocol was completed in 12 pigs, 7 of which received the inotrope treatment and 5 of which served as controls. Milrinone led to positive lusitropic effects seen by improvement in tau after myocardial stunning. The addition of levosimendan to milrinone further increased lusitropic state. The latter effect could however not be attributed solely to levosimendan, since lusitropic state also improved spontaneously in time-matched controls at the same rate during the corresponding period. When levosimendan was added to milrinone infusion, there was no increase in systolic function (preload recruitable stroke work) compared to milrinone treatment alone. We conclude that in this model of postischemic LV dysfunction, there appears to be no clear improvement in systolic or diastolic function after addition of levosimendan to established milrinone treatment but also no negative effects of levosimendan in this context.

  • 174.
    Axelsson, Birger
    et al.
    Department of Cardiovascular and Thoracic Surgery, Örebro University Hospital, Örebro, Sweden; Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Häggmark, Sören
    Department of Surgical and Perioperative Sciences, Heart Centre and Anesthesiology and Intensive Care Medicine, Faculty of Medicine, Umeå University, Umeå, Sweden.
    Svenmarker, Staffan
    Department of Surgical and Perioperative Sciences, Heart Centre and Anesthesiology and Intensive Care Medicine, Faculty of Medicine, Umeå University, Umeå, Sweden.
    Johansson, Göran
    Department of Surgical and Perioperative Sciences, Anesthesiology and Intensive Care Medicine, Faculty of Medicine, Umeå University, Umeå, Sweden .
    Gupta, Anil
    Örebro University, School of Medical Sciences. Department of Anesthesiology and Intensive Care, Örebro University Hospital, Örebro, Sweden; Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    Tydén, Hans
    Örebro University, School of Health Sciences. Department of Cardiovascular and Thoracic Surgery, Örebro University Hospital, Örebro, Sweden; Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    Wouters, Patrick
    Department of Anesthesiology, University Hospital Ghent, Ghent, Belgium.
    Haney, Michael
    Department of Surgical and Perioperative Sciences, Anesthesiology and Intensive Care Medicine, Faculty of Medicine, Umeå University, Umeå, Sweden .
    Effects of Combined Milrinone and Levosimendan Treatment on Systolic and Diastolic Function During Postischemic Myocardial Dysfunction in a Porcine Model2016In: Journal of Cardiovascular Pharmacology and Therapeutics, ISSN 1074-2484, E-ISSN 1940-4034, Vol. 21, no 5, p. 495-503Article in journal (Refereed)
    Abstract [en]

    It is not known whether there are positive or negative interactions on ventricular function when a calcium-sensitizing inotrope is added to a phosphodiesterase inhibitor in the clinical setting of acute left ventricular (LV) dysfunction. We hypothesized that when levosimendan is added to milrinone treatment, there will be synergetic inotropic and lusitropic effects. This was tested in an anesthetized porcine postischemic global LV injury model, where ventricular pressures and volumes (conductance volumetry) were measured. A global ischemic injury was induced by repetitive left main stem coronary artery occlusions. Load-independent indices of LV function were assessed before and after ventricular injury, after milrinone treatment, and finally after addition of levosimendan to the milrinone treatment. Nonparametric, within-group comparisons were made. The protocol was completed in 12 pigs, 7 of which received the inotrope treatment and 5 of which served as controls. Milrinone led to positive lusitropic effects seen by improvement in tau after myocardial stunning. The addition of levosimendan to milrinone further increased lusitropic state. The latter effect could however not be attributed solely to levosimendan, since lusitropic state also improved spontaneously in time-matched controls at the same rate during the corresponding period. When levosimendan was added to milrinone infusion, there was no increase in systolic function (preload recruitable stroke work) compared to milrinone treatment alone. We conclude that in this model of postischemic LV dysfunction, there appears to be no clear improvement in systolic or diastolic function after addition of levosimendan to established milrinone treatment but also no negative effects of levosimendan in this context.

  • 175.
    Axelsson, C
    et al.
    University of Borås, School of Health Science.
    Herrera, MJ
    Fredriksson, M
    Lindqvist, J
    Herlitz, J
    University of Borås, School of Health Science.
    Implementation of mechanical chest compression in out-of-hospital carfdiac arrest in an emergency medical service system2013In: American Journal of Emergency Medicine, ISSN 0735-6757, E-ISSN 1532-8171, Vol. 31, no 8, p. 1196-1200Article in journal (Refereed)
    Abstract [en]

    AIM: The aim of this study is to describe the outcome changes after out-of-hospital cardiac arrest (OHCA) in Gothenburg, Sweden, after introduction of mechanical chest compression (MCC). METHODS: Following introduction of MCC, 1183 OHCA patients were treated from November 1, 2007, to December 31, 2011 (period 2). They were compared with 1218 OHCA patients before MCC was introduced from January 1, 1998, to May 30, 2003 (period 1). Patients in period 2 were evaluated for survival in relation to MCC use. RESULTS: The percentage of patients admitted to hospital alive increased from 25.4% to 31.9% (P < .0001). Survival to 1 month increased from 7.1% to 10.7% (P = .002) from period 1 to period 2. The proportion of ventricular fibrillation/ventricular tachycardia decreased in period 2 (P = .002). However, bystander cardiopulmonary resuscitation (P < .0001), crew-witnessed cases (P = .04), percutaneous coronary intervention (P < .0001), therapeutic hypothermia (P < .0001), and implantable cardioverter-defibrillator use (P = .01) increased, as did time from call to emergency medicine service arrival (P < .0001) and to defibrillation (P = .006). In period 2, 60% of OHCA patients were treated with MCC. The percentages admitted alive to hospital (MCC vs no MCC) were 28.6% and 36.1% (P = .008). Corresponding figures for survival to 1 month were 5.6% and 17.6% (P < .0001). In the MCC group, we found increase in the delay from collapse to defibrillation (P < .0001), greater use of adrenaline (P < .0001), and fewer crew-witnessed cases (P < .0001). CONCLUSION: Survival to 1 month after implementation of MCC was higher than before introduction. However, patients receiving MCC had low survival. Although case selection might play a role, results do not support a widespread use of MCC after OHCA.

  • 176. Axelsson, J. M.
    et al.
    Burup-Kristensen, C.
    Kesaniemi, A.
    Rossebo, A. B.
    Pedersen, T. R.
    Nienaber, C. A.
    Gohlke-Barwolf, C.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Willenheimer, R.
    Wachtell, K.
    Incidence and predictors of infective endocarditis in asymptomatic patients with mild-to-moderate aortic stenosis2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no Supplement 1, Meeting abstract P4316, p. 758-758Article in journal (Other academic)
  • 177. Axelsson, Å
    et al.
    Stibrant Sunnerhagen, K
    Herlitz, J
    University of Borås, School of Health Science.
    Comparision of respondents and non-respondents in a follow-upsurvey after cardiac arrest2013Conference paper (Refereed)
  • 178. Babu-Narayan, Sonya V
    et al.
    Prati, Daniele
    Rydman, Riikka
    Dimopoulos, Konstantinos
    Diller, Gerhard-Paul
    Uebing, Anselm
    Henein, Michael Y
    Kilner, Philip J
    Gatzoulis, Michael A
    Li, Wei
    Dyssynchrony and electromechanical delay are associated with focal fibrosis in the systemic right ventricle - Insights from echocardiography.2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 220, p. 382-388Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Systemic right ventricular (RV) dysfunction and sudden cardiac death remain problematic late after Mustard operation for transposition of the great arteries. The exact mechanism for that relationship is likely to be multifactorial including myocardial fibrosis. Doppler echocardiography gives further insights into the role of fibrosis shown by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in late morbidity.

    METHODS AND RESULTS: Twenty-two consecutive patients, mean age 28±8years, were studied with 2D echocardiography, and also assessed by LGE CMR. The presence of LGE in 13/22 patients (59%) was related to delayed septal shortening and lengthening (P=0.002 &P=0.049), prolonged systemic RV isovolumic contraction time (P=0.024) and reduced systemic RV free wall and septal excursion (P=0.027 &P=0.005). The systemic RV total isovolumic time was prolonged but not related to extent of LGE. LGE extent was related to markers of electromechanical delay and dyssynchrony (delayed onset of RV free wall shortening and lengthening; r=0.73 &P=0.004 and r=0.62 &P=0.041, respectively, and QRS duration r=0.68, P<0.01) and was inversely related to systolic RV free wall shortening velocity (r=-0.59 &P=0.042). The presence of LGE was also related to lower exercise capacity, ≥mild tricuspid regurgitation and more arrhythmia (P=0.008, P=0.014 and P=0.040). RV free wall excursion and systolic tissue Doppler velocity were related to CMR derived RV ejection fraction (r=0.51, P=0.015, and r=0.77, P=<0.001, respectively).

    CONCLUSION: Post Mustard repair, myocardial fibrosis is related to dyssynchrony, RV long axis dysfunction and tricuspid regurgitation. Echocardiographic measurements of systemic RV function can be confidently used in serial follow-up following Mustard operation.

  • 179.
    Bachoo, P.
    et al.
    Dept Vasc Surg, Aberdeen Royal Infirm, Aberdeen, UK.
    Verhoeven, E. L. G.
    Dept Vasc & Endovasc Surg, Nuernberg Clin, Nurnberg, Germany.
    Larzon, Thomas
    Örebro University Hospital.
    Early outcome of endovascular aneurysm repair in challenging aortic neck morphology based on experience from the GREAT C3 registry2013In: Journal of Cardiovascular Surgery, ISSN 0021-9509, E-ISSN 1827-191X, Vol. 54, no 5, p. 573-580Article in journal (Refereed)
    Abstract [en]

    Aim. The aim of this paper was to evaluate early outcome of the GORE (R) EXCLUDER (R) AAA Endoprosthesis featuring C3 Delivery System in subjects with aortic neck anatomy outside IFU. Methods. Individual patient data prospectively collected over a 2 year period from the Global Registry for Endovascular Aortic Treatment (GREAT). For each subject a minimum data set was collected containing demographic, pre/intra- and postoperative variables. Main outcome measures were successful exclusion of the AAA and occurrence of any major endoleak at 1 month. In this study, outside IFU was defined as aortic neck length less than 15 mm and/or aortic neck angle greater than 60 degrees. Results. A total of 400 subjects, (86.6% male, mean age 73.9 years). Primary pathology was AAA in 94.2% with 98.2% undergoing EVAR as a primary procedure. Sixty-eight subjects underwent EVAR outside IFU (neck length <15 nun N.=32, neck angle >60 degrees N.=47 and neck length <15 nun and angle >60 degrees N.=11). The graft was successfully deployed within 5 nun of its intended location in 63 (94%) cases utilising a total of 33 repositioning episodes. Eight aortic cuffs were used, 5 to treat a type 1 endoleak. At 30 days we recorded 2 type 2 endoleaks both successfully treated and 1 type 1b also successfully treated. There were 2 deaths, one in each group. Conclusion. GORE (R) EXCLUDER (R) AAA Endoprosthesis featuring C3 Delivery System allows re-positioning to be performed safely in cases outside IFU. Repositioning is an effective operative manoeuvre and facilitates EVAR in challenging anatomy. Longer follow-up is required to evaluate the durability of these results at 30 days.

  • 180.
    Backman, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Tossavainen, Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Unusual arrhythmogenic myocardial disease2014In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, no 4, p. 195-196Article in journal (Refereed)
  • 181.
    Backman, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Burned out myocardium in biventricular hypertrophic cardiomyopathy presenting with congestive heart failure: importance of ECG changes2014In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, no 3, p. 159-160Article in journal (Refereed)
  • 182. Badimon, Lina
    et al.
    Hernández Vera, Rodrigo
    Padró, Teresa
    Vilahur, Gemma
    Antithrombotic therapy in obesity2013In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 110, no 4, p. 681-688Article in journal (Refereed)
    Abstract [en]

    Clinical management of obese subjects to reduce their risk of suffering cardiovascular events is complex. Obese patients typically require preventive strategies, life-style modifications, and multi-drug therapy to address obesity-induced co-morbidities. Data regarding the effects of excess weight on the pharmacokinetics of most drugs is scarce as these individuals are often excluded from clinical trials. However, the physiological alterations observed in obese patients and their lower response to some antiplatelet agents and anticoagulants have suggested that dosage regimes need to be adjusted for these subjects. In this review we will briefly discuss platelet alterations that can contribute to increased thrombotic risk, analyse existing data regarding the effects of obesity on drug pharmacokinetics focusing on antiplatelet agents and anticoagulants, and we will describe the beneficial effects of weight loss on thrombosis.

  • 183. Badimon, Lina
    et al.
    Hernández Vera, Rodrigo
    Vilahur, Gemma
    Atherothrombotic risk in obesity2013In: Hämostaseologie, ISSN 0720-9355, Vol. 33, no 4, p. 259-268Article in journal (Refereed)
    Abstract [en]

    A link between obesity and coronary artery disease development has been repeatedly proposed, possibly in part due to the development of a proinflammatory and prothrombotic state in obese subjects. Adipocytes secrete numerous hormones and cytokines (adipokines) which influence gene expression and cell functions in endothelial cells, arterial smooth muscle cells, and monocytes/macrophages favouring the development of an atherosclerotic vulnerable plaque. Moreover, the release of such biologically active molecules also promotes endothelial function impairment, disturbs the haemostatic and fibrinolytic systems, and produces alterations in platelet function affecting the initiation, progression, and stabilization of thrombus formation upon atherosclerotic plaque rupture. In this review we will discuss the pathophysiological mechanisms by which obesity contributes to increase atherothrombosis paying special attention to its effects over thrombosis.

  • 184.
    Baensch, Dietmar
    et al.
    Univ Hosp Rostock, Dept Internal Med 1, Div Cardiol, Heart Ctr Rostock, D-18057 Rostock, Germany..
    Bonnemeier, Hendrik
    Univ Hosp Schleswig Holstein, Dept Internal Med Cardiol & Angiol 3, Kiel, Germany..
    Brandt, Johan
    Skane Univ Hosp, Arrhythmia Dept, Lund, Sweden..
    Bode, Frank
    Univ Hosp Schleswig Holstein, Med Clin Cardiol Angiol & Intens Care Med 2, Lubeck, Germany..
    Svendsen, Jesper Hastrup
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Ctr Heart, Copenhagen, Denmark.;Univ Copenhagen, Danish Arrhythmia Res Ctr, Copenhagen, Denmark..
    Taborsky, Milos
    Fac Hosp Olomouc, Dept Internal Med Cardiol 1, Olomouc, Czech Republic..
    Kuster, Stefan
    DRK Hosp Molln Ratzeburg, Dept Internal Med, Cardiol, Ratzeburg, Germany..
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Felk, Angelika
    Biotronik, Berlin, Germany..
    Hauser, Tino
    Biotronik, Berlin, Germany..
    Suling, Anna
    Univ Med Ctr Hamburg Eppendorf, Dept Med Biometry & Epidemiol, Hamburg, Germany..
    Wegscheider, Karl
    Univ Med Ctr Hamburg Eppendorf, Dept Med Biometry & Epidemiol, Hamburg, Germany..
    Intra-operative defibrillation testing and clinical shock efficacy in patients with implantable cardioverter-defibrillators: the NORDIC ICD randomized clinical trial2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 37, p. 2500-2507Article in journal (Refereed)
    Abstract [en]

    Aims This trial was designed to test the hypothesis that shock efficacy during follow-up is not impaired in patients implanted without defibrillation (DF) testing during first implantable cardioverter-defibrillator (ICD) implantation. Methods and results Between February 2011 and July 2013, 1077 patients were randomly assigned (1 : 1) to first time ICD implantation with (n = 540) or without (n = 537) DF testing. The intra-operative DF testing was standardized across all participating centres, and all ICD shocks were programmed to 40 J irrespective of DF test results. The primary end point was the average first shock efficacy (FSE) for all true ventricular tachycardia and fibrillation (VT/VF) episodes during follow-up. The secondary end points included procedural data, serious adverse events, and mortality. During a median follow-up of 22.8 months, the model-based FSE was found to be non-inferior in patients with an ICD implanted without a DF test, with a difference in FSE of 3.0% in favour of the no DF test [confidence interval (CI) -3.0 to 9.0%, Pnon-inferiority <0.001 for the pre-defined non-inferiority margin of 210%). A total of 112 procedure-related serious adverse events occurred within 30 days in 94 patients (17.6%) tested compared with 89 events in 74 patients (13.9%) not tested (P = 0.095). Conclusion Defibrillation efficacy during follow-up is not inferior in patients with a 40 J ICD implanted without DF testing. Defibrillation testing during first time ICD implantation should no longer be recommended for routine left-sided ICD implantation.

  • 185.
    Bagai, Akshay
    et al.
    Univ Toronto, Canada.
    Goodman, Shaun G.
    Univ Toronto, Canada; Univ Toronto, Canada.
    Cantor, Warren J.
    Univ Toronto, England.
    Vicaut, Eric
    Hop Lariboisiere, France.
    Bolognese, Leonardo
    Azienda Osped Arezzo, Italy.
    Cequier, Angel
    Univ Barcelona, Spain.
    Chettibi, Mohamed
    Ctr Hosp Univ Frantz Fanon, Algeria.
    Hammett, Christopher J.
    Royal Brisbane and Womens Hosp, Australia.
    Huber, Kurt
    Wilhelminenhosp, Austria; Sigmund Freud Private Univ, 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.
    Lapostolle, Frederic
    Hop Avicenne, France.
    Lassen, Jens Flensted
    Univ Copenhagen, Denmark.
    Merkely, Bela
    Semmelweis Univ, Hungary.
    Storey, Robert F.
    Univ Sheffield, England.
    ten Berg, Jurrien M.
    St Antonius Hosp Nieuwegein, Netherlands.
    Zeymer, Uwe
    Klinikum Ludwigshafen, Germany; Inst Herzinfarktforsch Ludwigshafen, Germany.
    Diallo, Abdourahmane
    Hop Lariboisiere, France; Hop Fernand Widal, France.
    Hamm, Christian W.
    Kerckhoff Klin, Germany.
    Tsatsaris, Anne
    AstraZeneca, France.
    El Khoury, Jad
    AstraZeneca, England.
    vant Hof, Arnoud W.
    Maastricht Hart Vaat Ctr MUMC, Netherlands.
    Montalescot, Gilles
    Sorbonne Univ Paris 6, France.
    Duration of ischemia and treatment effects of pre- versus in-hospital ticagrelor in patients with ST-segment elevation myocardial infarction: Insights from the ATLANTIC study2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 196, p. 56-64Article in journal (Refereed)
    Abstract [en]

    Background Among patients with STEMI in the ATLANTIC study, pre-hospital administration of ticagrelor improved post-PCI ST-segment resolution and 30-day stent thrombosis. We investigated whether this clinical benefit with pre-hospital ticagrelor differs by ischemic duration. Methods In a post hoc analysis we compared absence of ST-segment resolution post-PCI and stent thrombosis at 30 days between randomized treatment groups (pre-versus in-hospital ticagrelor) stratified by symptom onset to first medical contact (FMC) duration [amp;lt;= 1 hour (n = 773), amp;gt;1 to amp;lt;= 3 hours (n = 772), and amp;gt;3 hours (n = 311)], examining the interaction between randomized treatment strategy and duration of symptom onset to FMC for each outcome. Results Patients presenting later after symptom onset were older, more likely to be female, and have higher baseline risk. Patients with symptom onset to FMC amp;gt;3 hours had the greatest improvement in post-PCI ST-segment elevation resolution with pre-versus in-hospital ticagrelor (absolute risk difference: amp;lt;= 1 hour, 2.9% vs. amp;gt;1 to amp;lt;= 3 hours, 3.6% vs. amp;gt;3 hours, 12.2%; adjusted p for interaction = 0.13), while patients with shorter duration of ischemia had greater improvement in stent thrombosis at 30 days with pre-versus in-hospital ticagrelor (absolute risk difference: amp;lt;= 1 hour, 1.3% vs. amp;gt;1 hour to amp;lt;= 3hours, 0.7% vs. amp;gt;3 hours, 0.4%; adjusted p for interaction = 0.55). Symptom onset to active ticagrelor administration was independently associated with stent thrombosis at 30 days (adjusted OR 1.89 per 100 minute delay, 95% CI 1.20-2.97, P amp;lt; .01), but not post-PCI ST-segment resolution (P = .41). Conclusions The effect of pre-hospital ticagrelor to reduce stent thrombosis was most evident when given early within 3 hours after symptom onset, with delay in ticagrelor administration after symptom onset associated with higher rate of stent thrombosis. These findings re-emphasize the need for early ticagrelor administration in primary PCI treated STEMI patients.

  • 186.
    Bagge, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Surgical ablation for the treatment of atrial fibrillation in different patient populations: A study of clinical outcomes including rhythm, quality of life, atrial function and safety2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Patients with atrial fibrillation (AF) have markedly reduced quality of life (QoL) and catheter ablation has become a useful tool in the rhythm control therapy. However, because of the poor outcome for patients with persistent AF, new surgical ablation strategies for rhythm control are emerging.

    The aims of this thesis were to evaluate QoL, the main indication for rhythm control, after three different types of surgical ablation for AF, two stand-alone epicardial AF ablation procedures and one concomitant procedure during mitral valve surgery (MVS), and to perform a long-term follow-up of one of the techniques with regard to rhythm outcome, left atrial function, exercise capacity and safety.

    As the first center in the Nordic countries to adopt the video-assisted epicardial pulmonary vein isolation and ganglionated plexi ablation combined with left atrial appendage excision (LAA), the  freedom from AF at one year follow-up was found to be 71% and associated with improved exercise capacity, QoL and symptoms as well as preserved left atrial function and size. The most common complication was bleeding events (14%). After 10 years, the improved symptoms and QoL remained, reaching comparable levels of the general Swedish population, despite a marked decline in the rate of freedom from AF (36%). 4 strokes appeared during follow-up despite LAA excision in 3 of these patients.

    In order to improve the rhythm outcome for patients with longstanding persistent AF a box-lesion was added to the procedure. At one year follow-up, both symptoms and QoL improved and was indistinguishable from those in the Swedish general population.

    Finally, concomitant AF ablation during MVS did not improve QoL compared to MVS alone in a double blinded randomized controlled trial. Moreover, no difference was seen between patients in AF or sinus rhythm at one year follow-up, irrespective of the allocated therapy, indicating that their preoperative symptoms were mainly related to their valve disease.

    In conclusion, the stand-alone procedures using surgical ablation was found to be effective but at the expense of procedural complications. In contrast, the concomitant surgical AF ablation did not improve QoL, a finding that raises concerns regarding current recommendations for this procedure. 

  • 187.
    Bagge, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Blomström, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Jidéus, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Lönnerholm, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Left atrial function after epicardial pulmonary vein isolation in patients with atrial fibrillation2017In: Journal of interventional cardiac electrophysiology (Print), ISSN 1383-875X, E-ISSN 1572-8595, Vol. 50, no 2, p. 195-201Article in journal (Refereed)
  • 188.
    Bagge, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Jansson, Victoria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Blomström, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    10 years follow-up of video-assisted epicardial pulmonary vein isolation and vagal denervation in patients with atrial fibrillationIn: Article in journal (Other academic)
  • 189.
    Bagge, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Probst, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Blomström, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Quality of Life Is Not Significantly Improved by Adding Epicardial Left Atrial Cryoablation to Mitral Valve Surgery Than if Performed Alone2017In: Cardiovascular Electrophysiology, ISSN 1045-3873, E-ISSN 1540-8167, Vol. 28, no 5, p. 589-590, article id MA19Article in journal (Other academic)
  • 190.
    Bagge, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Probst, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Jensen, Steen M
    Faculty of Medicine, Department of Public Health and Clinical Medicine (Heart centre) Umeå University, SE-901 87 Umeå, Sweden.
    Blomström, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Holmgren, Anders
    Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology, Umeå University, SE-901 87 Umeå, Sweden.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Quality of life is not improved after mitral valve surgery combined with epicardial left atrial cryoablation as compared with mitral valve surgery alone: a substudy of the double blind randomized SWEDish Multicentre Atrial Fibrillation study (SWEDMAF)2017In: Europace, ISSN 1099-5129, E-ISSN 1532-2092Article in journal (Refereed)
  • 191. Bahit, M C
    et al.
    Lopes, R D
    Clare, R M
    Newby, L K
    Pieper, K S
    van der Werf, F
    Armstrong, P W
    Mahaffey, K W
    Harrington, R H
    Diaz, R
    Ohman, E M
    White, H D
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, C B
    Heart failure complicating non-ST-segment elevation acute coronary syndrome: timing, predictors, and clinical outcomes2013In: JACC. Heart failure, ISSN 2213-1779, E-ISSN 2213-1787, Vol. 1, no 3, p. 223-229Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study sought to describe the occurrence and timing of heart failure (HF), associated clinical factors, and 30-day outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). BACKGROUND: Little is known about HF-complicating NSTE-ACS. METHODS: Using pooled patient-level data from 7 clinical trials from 1994 to 2008, we describe the occurrence and timing of HF, associated clinical factors, and 30-day outcomes in NSTE-ACS patients. HF at presentation was defined as Killip classes II to III; patients with Killip class IV or cardiogenic shock were excluded. New in-hospital cases of HF included new pulmonary edema. After adjusting for baseline variables, we created logistic regression models to identify clinical factors associated with HF at presentation and to determine the association between HF and 30-day mortality. RESULTS: Of 46,519 NSTE-ACS patients, 4,910 (10.6%) had HF at presentation. Of the 41,609 with no HF at presentation, 1,194 (2.9%) developed HF during hospitalization. A total of 40,415 (86.9%) had no HF at any time. Patients presenting with or developing HF during hospitalization were older, more often female, and had a higher risk of death at 30 days than patients without HF (adjusted odds ratio [OR]: 1.74; 95% confidence interval: 1.35 to 2.26). Older age, higher presenting heart rate, diabetes, prior myocardial infarction (MI), and enrolling MI were significantly associated with HF during hospitalization. CONCLUSIONS: In this large cohort of NSTE-ACS patients, presenting with or developing HF during hospitalization was associated with an increased risk of 30-day mortality. Research targeting new strategies to prevent and manage HF in this high-risk population is needed.

  • 192.
    Bahit, M. C.
    et al.
    INECO Neurociencias, Rosario, Santa Fe, Argentina..
    Lopes, R. D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Wojdyla, D. M.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hanna, M.
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Vinereanu, D.
    Univ Med & Pharm Carol Davila, Bucharest, Romania..
    Goto, S.
    Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan..
    Alexander, J. H.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Granger, C. B.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Less non-major bleeding with apixaban versus warfarin among patients with atrial fibrillation: insights from the ARISTOTLE trial2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 338-339Article in journal (Other academic)
  • 193.
    Bahit, M. Cecilia
    et al.
    INECO, Neurociencias Orono Rosario, Santa Fe, NM, Argentina..
    Lopes, Renato D.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Wojdyla, Daniel M.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hanna, Michael
    Bristol Myers Squibb, Princeton, NJ USA..
    Vinereanu, Dragos
    Univ Med & Pharm Carol Davila, Bucharest, Romania..
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA USA..
    Verheugt, Freek
    Onze Lieve Vrouwe Gasthuis OLVG, Heartctr, Amsterdam, Netherlands..
    Goto, Shinya
    Tokai Univ, Sch Med, Isehara, Kanagawa, Japan..
    Alexander, John H.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, Christopher B.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 8, p. 623-628Article in journal (Refereed)
    Abstract [en]

    Objective We describe the incidence, location and management of non-major bleeding, and assess the association between non-major bleeding and clinical outcomes in patients with atrial fibrillation (AF) receiving anticoagulation therapy enrolled in Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE). Methods We included patients who received >= 1 dose of study drug (n= 18 140). Non-major bleeding was defined as the first bleeding event considered to be clinically relevant non-major (CRNM) or minor bleeding, and not preceded by a major bleeding event. Results Non-major bleeding was three times more common than major bleeding (12.1% vs 3.8%). Like major bleeding, non-major bleeding was less frequent with apixaban (6.4 per 100 patient-years) than warfarin (9.4 per 100 patient-years) (adjusted HR 0.69, 95% CI 0.63 to 0.75). The most frequent sites of non-major bleeding were haematuria (16.4%), epistaxis (14.8%), gastrointestinal (13.3%), haematoma (11.5%) and bruising/ecchymosis (10.1%). Medical or surgical intervention was similar among patients with non-major bleeding on warfarin versus apixaban (24.7% vs 24.5%). A change in antithrombotic therapy (58.6% vs 50.0%) and permanent study drug discontinuation (5.1% (61) vs 3.6% (30), p=0.10) was numerically higher with warfarin than apixaban. CRNM bleeding was independently associated with an increased risk of overall death (adjusted HR 1.70, 95% CI 1.32 to 2.18) and subsequent major bleeding (adjusted HR 2.18, 95% CI 1.56 to 3.04). Conclusions In ARISTOTLE, non-major bleeding was common and substantially less frequent with apixaban than with warfarin. CRNM bleeding was independently associated with a higher risk of death and subsequent major bleeding. Our results highlight the importance of any severity of bleeding in patients with AF treated with anticoagulation therapy and suggest that non-major bleeding, including minor bleeding, might not be minor.

  • 194.
    Bajraktari, Gani
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    The clinical value of total isovolumic time2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The objective of this thesis is to evaluate the use of Doppler echocardiography markers ofglobal dyssynchrony [total isovolumic time (t-IVT)] in the following 6 studies: 1) Its prognostic role in predicting cardiac events in patients undergoing CABG surgery,compared with conventional global systolic and diastolic measurements. 2) Its additional value in predicting six minute walk test (6-MWT) in patients with leftventricular (LV) ejection fraction (EF) <45%. 3) Its prognostic value in comparison with other clinical, biochemical and echocardiographicvariables in patients with chronic systolic heart failure (HF). 4) The relationship between 6-MWT and cardiac function measurements in a consecutivegroup of patients, irrespective of EF and to identify predictors of exercise capacity. 5) To investigate the effect of age on LV t-IVT and Tei index compared with conventionalsystolic and diastolic parameters. 6) To assess potential additional value of markers of global LV dyssynchrony in predictingcardiac resynchronization therapy (CRT) response in HF patients.

    Study I

    Methods: This study included 74 patients before routine CABG who were followed up for18±12 months. Results: At follow-up, 29 patients were hospitalized for a cardiac event or died. LV-ESD wasgreater (P=0.003), fractional shortening (FS) lower (p<0.001), E:A ratio and Tei index higher(all P<0.001), and t-IVT longer (P<0.001) in patients with events. Low FS [0.66 (0.50–0.87),P<0.001], high E:A ratio [l4.13 (1.17–14.60), P=0.028], large LV-ESD [0.19 (0.05–0.84),P=0.029], and long t-IVT [1.37 (1.02–1.84), P=0.035] predicted events and deaths. Conclusion: Despite satisfactory surgical revascularization, long t-IVT and systolicdysfunction suggest persistent ventricular dyssynchrony that contributes to post-CABGcardiac events.

    Study II

    Methods: We studied 77 patients (60±12 year, and 33.3% females) with stable HF using 6-MWT.iii Results: E’ wave (r=0.61, p<0.001), E/e’ ratio (r=-0.49, p<0.001), t-IVT (r=-0.44, p<0.001),Tei index (r=-0.43, p<0.001) and NYHA class (r=-0.53, p<0.001) had the highest correlationwith the 6-MWT distance. In multivariate analysis, only E/e’ ratio [0.800 (0.665-0.961),p=0.017], and t-IVT [0.769 (0.619-0.955), p=0.018] independently predicted poor 6-MWTperformance (<300m). Conclusions: In HF, the higher the filling pressures and the more dyssynchronous the LV, thepoorer is the patient’s exercise capacity.

    Study III

    Methods: We studied 107 systolic HF patients; age 68±12 year, 25% females and measuredplasma NT-pro-BNP. Results: Over a follow-up period of 3718 months, t-IVT ≥12.3 sec/min, mean E/Em ratio≥10, log NT-pro-BNP levels ≥2.47 pg/ml and LV EF ≤32.5% predicted clinical events. Theaddition of t-IVT and NT-pro-BNP to conventional clinical and echocardiographic variablessignificantly improved the χ2 for the prediction of outcome from 33.1 to 38.0, (p<0.001). Conclusions: Prolonged t-IVT adds to the prognostic stratification of patients with systolicHF.

    Study IV

    Methods: We studied 147 HF patients (61±11 year, 50.3% male) with 6-MWT.Results: The 6-MWT correlated with t-IVT (r=-0.49, p<0.001) and Tei index (r=-0.43,p<0.001) but not with any of the other clinical or echocardiographic parameters. Group Ipatients (<300m) had lower Hb (p=0.02), lower EF (p=0.003), larger left atrium (p=0.02),thicker septum (p=0.02), lower A wave (p=0.01) and lateral wall a’ (p=0.047), longerisovolumic relaxation time (r=0.003) and longer t-IVT (p= 0.03), compared with Group II(>300m). Only t-IVT ratio [1.257 (1.071-1.476), p=0.005], LV EF [0.947 (0.903-0.993),p=0.02], and E/A ratio [0.553 (0.315-0.972), p=0.04] independently predicted poor 6-MWTperformance. Conclusion: In HF, the limited 6-MWT is related mostly to severity of global LVdyssynchrony, more than EF or raised filling pressures.

    Study V

    Methods: We studied 47 healthy individuals (age 62±12 year, 24 female), arbitrarilyclassified into: M (middle age), S (seniors), and E (elderly). Results: Age strongly correlated with t-IVT (r=0.8, p<0.001) and with Tei index (r=0.7,p<0.001), E/A ratio (r=-0.6, p<0.001), but not with global or segmental systolic function measurements or QRS duration. The normal upper limit of the t-IVT (95% CI) for the three groups was 8.3 s/min, 10.5 s/min and 14.5 s/min, respectively, being shorter in the S compared with the E group (p=0.001). T-IVT correlated with A wave (r=0.66, p<0.001), E/Aratio (r=-0.56, p<0.001), septal e’ (r=-0.49, p=0.001) and septal a’ (r=0.4, p=0.006), but notwith QRS. Conclusions: In normals, age is associated with exaggerated LV global dyssynchrony anddiastolic function disturbances, but systolic function remains unaffected.

    Study VI

    Methods: We studied 103 HF patients (67±12 year, 82.5% male) recruited for CRTtreatment. Results: Prolonged t-IVT [0.878 (0.802-0.962), p=0.005], long QRS duration [0.978 (0.960-0.996), p=0.02] and high tricuspid regurgitation pressure drop (TRPD) [1.047 (1.001-1.096),p=0.046] independently predicted response to CRT. A t-IVT ≥11.6 s/min was 67% sensitiveand 62% specific (AUC 0.69, p=0.001) in predicting CRT response. Respective values for aQRS ≥ 151ms were 66% and 62% (AUC 0.65, p=0.01). Combining the two variables had asensitivity of 67% but higher specificity of 88% in predicting CRT response. In atrialfibrillation (AF) patients, only prolonged t-IVT ≥11 s/min [0.690 (0.509-0.937), p=0.03]independently predicted CRT response with a sensitivity of 69% and specificity of 79% (AUC0.78, p=0.015). Conclusion: Combining prolonged t-IVT and broad QRS had higher specificity in predictingresponse to CRT, with the former the sole predictor of response in AF patients.

  • 195.
    Bajraktari, Gani
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Batalli, A.
    Poniku, A.
    Ahmeti, A.
    Olloni, R.
    Hyseni, V.
    Vela, Z.
    Morina, B.
    Tafarshiku, R.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Left ventricular dyssynchrony predicts limited exercise capacity in heart failure irrespective of ejection fraction2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl. 1, p. 34-34Article in journal (Other academic)
  • 196.
    Bajraktari, Gani
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Batalli, Arlind
    Poniku, Afrim
    Ahmeti, Artan
    Olloni, Rozafa
    Hyseni, Violeta
    Vela, Zana
    Morina, Besim
    Tafarshiku, Rina
    Vela, Driton
    Rashiti, Premtim
    Haliti, Edmond
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Left ventricular markers of global dyssynchrony predict limited exercise capacity in heart failure, but not in patients with preserved ejection fraction2012In: Cardiovascular Ultrasound, ISSN 1476-7120, E-ISSN 1476-7120, Vol. 10, p. 36-Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional capacity assessed by 6 min walk test (6-MWT) in patients with heart failure (HF), irrespective of ejection fraction (EF).

    Methods: In 147 HF patients (mean age 61 +/- 11 years, 50.3% male), a 6-MWT and an echo-Doppler study were performed in the same day. Global LV dyssynchrony was indirectly assessed by total isovolumic time - t-IVT [in s/min; calculated as: 60 - (total ejection time + total filling time)], and Tei index (t-IVT/ejection time). Patients were divided into two groups based on the 6-MWT distance (Group I: <= 300 m and Group II: > 300 m), and also in two groups according to EF (Group A: LVEF >= 45% and Group B: LVEF <45%).

    Results: In the cohort of patients as a whole, the 6-MWT correlated with t-IVT (r = -0.49, p < 0.001) and Tei index (r = -0.43, p < 0.001) but not with any of the other clinical or echocardiographic parameters. Group I had lower hemoglobin level (p = 0.02), lower EF (p = 0.003), larger left atrium (p = 0.02), thicker interventricular septum (p = 0.02), lower A wave (p = 0.01) and lateral wall late diastolic myocardial velocity a' (p = 0.047), longer isovolumic relaxation time (r = 0.003) and longer t-IVT (p = 0.03), compared with Group II. In the patients cohort as a whole, only t-IVT ratio [1.257 (1.071-1.476), p = 0.005], LV EF [0.947 (0.903-0.993), p = 0.02], and E/A ratio [0.553 (0.315-0.972), p = 0.04] independently predicted poor 6-MWT performance (< 300 m) in multivariate analysis. None of the echocardiographic measurements predicted exercise tolerance in HFpEF.

    Conclusion: In patients with HF, the limited exercise capacity, assessed by 6-MWT, is related mostly to severity of global LV dyssynchrony, more than EF or raised filling pressures. The lack of exercise predictors in HFpEF reflects its multifactorial pathophysiology.

  • 197.
    Bajraktari, Gani
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Berisha, G.
    Bytyci, I.
    Haliti, E.
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ahmeti, A.
    Poniku, A.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    The presence of metabolic syndrome predicts long-term outcome in heart failure patients2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, p. 831-831Article in journal (Other academic)
  • 198.
    Bajraktari, Gani
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bytyci, I.
    Ahmeti, A.
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Poniku, A.
    Haliti, E.
    Batalli, A.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Left atrial emptying function predicts long-term outcome in HFpEF patients2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, p. 1183-1183Article in journal (Other academic)
  • 199.
    Bajraktari, Gani
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bytyci, I.
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hyseni, V.
    Berisha, G.
    Rexhepaj, N.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    The relationship between left atrial emptying function and exercise capacity in heart failure2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no Supplement 1, Meeting abstract P2776, p. 510-510Article in journal (Other academic)
  • 200.
    Bajraktari, Gani
    et al.
    Service of Cardiology, Internal Medicine Clinic, University Clinical Centre of Kosova, Prishtina, Kosovo.
    Dini, Frank Lloyd
    Fontanive, Paolo
    Elezi, Shpend
    Berisha, Venera
    Napoli, Anna Maria
    Ciuti, Manrico
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Independent and incremental prognostic value of Doppler-derived left ventricular total isovolumic time in patients with systolic heart failure2011In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 148, no 3, p. 271-275Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A prolonged total isovolumic time (T-IVT) has been shown to be associated with worsening survival in patients submitted to coronary artery surgery. However, it is not known whether it has prognostic significance in patients with chronic systolic heart failure (HF).

    AIM: To determine the prognostic value of T-IVT in comparison with other clinical, biochemical and echocardiographic variables in patients with chronic systolic HF.

    METHODS: Patients (n=107; age 68+/-12years, 25% women) with chronic systolic HF, left ventricular ejection fraction (EF) <45%, and sinus rhythm, underwent a complete Doppler echocardiographic study, that included tissue Doppler long axis velocities and total isovolumic time (T-IVT), determined as [60-(total ejection time+total filling time)]. Plasma N-terminal pro-B natriuretic peptide (NT-pro-BNP) was also measured. The associations of dichotomous variables selected according to the Receiver Operator Characteristic analysis were assessed using the Cox proportional hazard model.

    RESULTS: Follow-up period was 37+/-18months. Multivariate predictors of events were T-IVT >/=12.3% s/min, mean E/E(m) ratio >/=10, log NT-pro-BNP levels >/=2.47pg/ml and LV EF</=32.5%. On Kaplan-Meier analysis, patients with prolonged T-IVT, high mean E/E(m) ratio, increased NT-pro-BNP levels and decreased LV EF had a worse outcome compared with those without. The addition of T-IVT and NT-pro-BNP to conventional clinical and echocardiographic variables significantly improved the chi-square for the prediction of the outcome from 33.1 to 38.0, (P<0.001).

    CONCLUSIONS: Prolonged T-IVT added to the prognostic stratification of patients with systolic HF.

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