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  • 1.
    Andell, P.
    et al.
    Department of Cardiology, Skåne University Hospital, Lund University, Lund, Sweden.
    Omerovic, E.
    Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Smokeless tobacco, snus, at admission for percutaneous coronary intervention and future risk of death2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no Suppl. 1, p. 1364-1365Article in journal (Other academic)
  • 2.
    Andell, Pontus
    et al.
    Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
    Berntorp, Karolina
    Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
    Christiansen, Evald H.
    Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
    Gudmundsdottir, Ingibjörg J.
    Department of Cardiology, University Hospital of Iceland, Reykjavik, Iceland.
    Sandhall, Lennart
    Departments of Cardiology and Radiology, Helsingborg Hospital, Helsingborg, Sweden.
    Venetsanos, Dimitrios
    Departments of Cardiology and of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Erlinge, David
    Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Koul, Sasha
    Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
    Reitan, Christian
    Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
    Gotberg, Matthias
    Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
    Reclassification of Treatment Strategy With Instantaneous Wave-Free Ratio and Fractional Flow Reserve A Substudy From the iFR-SWEDEHEART Trial2018In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, no 20, p. 2084-2094Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The authors sought to compare reclassification of treatment strategy following instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR).

    BACKGROUND: iFR was noninferior to FFR in 2 large randomized controlled trials in guiding coronary revascularization. Reclassification of treatment strategy by FFR is well-studied, but similar reports on iFR are lacking.

    METHODS: The iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome Trial) study randomized 2,037 participants with stable angina or acute coronary syndrome to treatment guided by iFR or FFR. Interventionalists entered the preferred treatment (optimal medical therapy [OMT], percutaneous coronary intervention [PCI], or coronary artery bypass grafting [CABG]) on the basis of coronary angiograms, and the final treatment decision was mandated by the iFR/FFR measurements.

    RESULTS: In the iFR/FFR (n = 1,009/n = 1,004) populations, angiogram-based treatment approaches were similar (p = 0.50) with respect to OMT (38%/35%), PCI of 1 (37%/39%), 2 (15%/16%), and 3 vessels (2%/2%) and CABG (8%/8%). iFR and FFR reclassified 40% and 41% of patients, respectively (p = 0.78). The majority of reclassifications were conversion of PCI to OMT in both the iFR/FFR groups (31.4%/29.0%). Reclassification increased with increasing number of lesions evaluated (odds ratio per evaluated lesion for FFR: 1.46 [95% confidence interval: 1.22 to 1.76] vs. iFR 1.37 [95% confidence interval: 1.18 to 1.59]). Reclassification rates for patients with 1, 2, and 3 assessed vessels were 36%, 52%, and 53% (p < 0.01).

    CONCLUSIONS: Reclassification of treatment strategy of intermediate lesions was common and occurred in 40% of patients with iFR or FFR. The most frequent reclassification was conversion from PCI to OMT regardless of physiology modality. Irrespective of the physiological index reclassification of angiogram-based treatment strategy increased with the number of lesions evaluated. (c) 2018 by the American College of Cardiology Foundation.

  • 3.
    Andell, Pontus
    et al.
    Department of Cardiology, Clinical Sciences, Skåne University Hospital, Lund, Sweden.
    Karlsson, Sofia
    Department of Cardiology, Clinical Sciences, Skåne University Hospital, Lund, Sweden.
    Mohammad, Moman A.
    Department of Cardiology, Clinical Sciences, Skåne University Hospital, Lund, Sweden.
    Götberg, Matthias
    Department of Cardiology, Clinical Sciences, Skåne University Hospital, Lund, Sweden.
    James, Stefan
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Jensen, Jens
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Unit of Medicine, Capio St Görans Sjukhus, Stockholm, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Angeras, Oskar
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden; University and Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Nilsson, Johan
    Department of Cardiology, Heart Centre, Umeå University Hospital, Umeå, Sweden.
    Omerovic, Elmir
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden; University and Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Lagerqvist, Bo
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Persson, Jonas
    Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Koul, Sasha
    Department of Cardiology, Clinical Sciences, Skåne University Hospital, Lund, Sweden.
    Erlinge, David
    Department of Cardiology, Clinical Sciences, Skåne University Hospital, Lund, Sweden.
    Intravascular Ultrasound Guidance Is Associated With Better Outcome in Patients Undergoing Unprotected Left Main Coronary Artery Stenting Compared With Angiography Guidance Alone2017In: Circulation. Cardiovascular Interventions, ISSN 1941-7640, E-ISSN 1941-7632, Vol. 10, no 5, article id e004813Article in journal (Refereed)
    Abstract [en]

    Background: Small observational studies have indicated better outcome with intravascular ultrasound (IVUS) guidance when performing unprotected left main coronary artery (LMCA) percutaneous coronary intervention (PCI), but the overall picture remains inconclusive and warrants further investigation. We studied the impact of IVUS guidance on outcome in patients undergoing unprotected LMCA PCI in a Swedish nationwide observational study.

    Methods and Results: Patients who underwent unprotected LMCA PCI between 2005 and 2014 because of stable coronary artery disease or acute coronary syndrome were included from the nationwide SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Of 2468 patients, IVUS guidance was used in 621 (25.2%). The IVUS group was younger (median age, 70 versus 75 years) and had fewer comorbidities but more complex lesions. IVUS was associated with larger stent diameters (median, 4 mm versus 3.5 mm). After adjusting for potential confounders, IVUS was associated with significantly lower occurrence of the primary composite end point of all-cause mortality, restenosis, or definite stent thrombosis (hazard ratio, 0.65; 95% confidence interval, 0.50-0.84) and all-cause mortality alone (hazard ratio, 0.62; 95% confidence interval, 0.47-0.82). In 340 propensity score-matched pairs, IVUS was also associated with significantly lower occurrence of the primary end point (hazard ratio, 0.54; 95% confidence interval, 0.37-0.80).

    Conclusions: IVUS was associated with an independent and significant outcome benefit when performing unprotected LMCA PCI. Potential mediators of this benefit include larger and more appropriately sized stents, perhaps translating into lower risk of subsequent stent thrombosis. Although residual confounding cannot be ruled out, our findings indicate a possible hazard when performing unprotected LMCA PCI without IVUS guidance.

  • 4.
    Andersson, T.
    et al.
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Bryngelsson, I. L.
    Department of Occupational and Environmental Medicine, Örebro University, Örebro, Sweden.
    Magnuson, A.
    Clinical Epidemiology and Biostatistics, Örebro University, Örebro, Sweden.
    Fröbert, Ole
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Henriksson, K.
    Department of Medical Science, Uppsala University, Uppsala, Sweden.
    Edvardsson, N.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Poci, Dritan
    Örebro University, School of Medical Sciences. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    What do patients with incident atrial fibrillation and no comorbidities at the time of diagnosis die of?2017Conference paper (Refereed)
    Abstract [en]

    Introduction: Little is known about the long-term mortality risk and the causes of death in patients without comorbidities at the time of diagnosis of atrial fibrillation (AF).

    Purposes: To identify the causes of death in patients with AF and without comorbidities at the time of AF diagnosis.

    Methods: We identified 9 519 patients with first diagnosed AF and no co-morbidities at the time of AF diagnosis in a nation-wide registry of patients hospitalized between 1995 and 2008. They represented 3.5% of the original cohort of 271186 patients hospitalized with incident AF. Patients with any diagnosis from ICD9 and ICD10 at the time of AF diagnosis wereexcluded. They were matched for age, sex and calendar year of AF diagnosis with 12 468 controls. The follow-up continued until December 2008. Causes of death were classified according to the ICD-10 codes.

    Results: During follow-up, 11.1% and 8.3% of patients with AF and controls died, HR 1.3, 95% CI 1.2–1.4. Most of the difference was explained by deaths of cardiovascular causes, 8.3% versus 3.9%, (HR 2.0, 95% CI 1.8–2.3). The cause of death pattern was the same in controls although at much lower rates. The age adjusted relative risk was higher in women than in men, HR 2.3, 95% CI 1.9–2.8 versus HR 1.7, 95% CI 1.4–2.0. Myocardial infarction was the most common cardiovascular cause of death but was less common among patients with AF than in controls, 20.5% versus 32.0%. Stroke was a more common cause among patients with AF, 13.1% versus 9.7% (HR 2.7, 95% CI 1.8–4.0), while cerebral hemorrhage was more common among controls, 4.7% versus 10.2% (HR 0.9, 95% CI 0.6–1.5). The time from AF diagnosis to death was 6.0±3.1 years, as compared to the time from inclusion to death, 5.8±3.1 years, in controls.

    Conclusions: Only cardiovascular diseases were more often causes of death than in controls. Women carried a significantly higher relative risk than men. The duration between AF diagnosis and death suggests that there is often time enough for early intervention with antithrombotic therapy, rhythm and/or rate control and treatment of risk factors as they appear. Interestingly, controls had the same cause of death pattern although at much lower rates.

  • 5.
    Andersson, Tommy
    et al.
    Dept Cardiology, Örebro Univ Hospital, Örebro, Sweden.
    Magnuson, Anders
    Bryngelsson, Ing-Liss
    Dept. Occupational & Environmental Medicine, Örebro Univ Hospital, Örebro, Sweden.
    Fröbert, Ole
    Örebro University Hospital, Örebro, Sweden.
    Henriksson, Karin M.
    Dept. Laboratory Medicine, Lund Univ, Lund, Sweden; The Sahlgrenska Academy, Sahlgrenska Univ. Hospital, Gothenburg, Sweden.
    Edvardsson, Nils
    The Sahlgrenska Academy, Sahlgrenska Univ. Hospital, Gothenburg, Sweden.
    Poci, Dritan
    Örebro University Hospital.
    All-cause mortality in 272 186 patients hospitalized with incident atrial fibrillation 1995-2008: a Swedish nationwide long-term case-control study2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 14, p. 1061-1067Article in journal (Refereed)
    Abstract [en]

    Aims To evaluate long-term all-cause risk of mortality in women and men hospitalized for the first time with atrial fibrillation (AF) compared with matched controls. Methods and results A total of 272 186 patients (44% women) <= 85 years at the time of hospitalization with incidental AF 1995-2008 and 544 344 matched controls free of in-hospital diagnosis of AF were identified. Patients were followed via record linkage of the Swedish National Patient Registry and the Cause of Death Registry. Using Cox regression models, the long-term relative all-cause mortality risk, adjusted for concomitant diseases, in women vs. controls was 2.15, 1.72, and 1.44 (P < 0.001) in the age categories <= 65, 65-74, and 75-85 years, respectively. The corresponding figures for men were 1.76, 1.36, and 1.24 (P < 0.001). Among concomitant diseases, neoplasm, chronic renal failure, and chronic obstructive pulmonary disease contributed most to the increased all-cause mortality vs. controls. In patients with AF as the primary diagnosis, the relative risk of mortality was 1.63, 1.46, and 1.28 (P < 0.001) in women and 1.45, 1.17, and 1.10 (P < 0.001) in men. Conclusion Atrial fibrillation was an independent risk factor of all-cause mortality in patients with incident AF. The concomitant diseases that contributed most were found outside the thromboembolic risk scores. The highest relative risk of mortality was seen in women and in the youngest patients compared with controls, and the differences between genders in each age category were statistically significant.

  • 6.
    Andersson, Tommy
    et al.
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Magnuson, Anders
    Örebro University Hospital.
    Bryngelsson, Ing-Liss
    Örebro University Hospital. Department of Occupational and Environmental Medicine, Örebro University Hospital, Örebro, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Henriksson, Karin M.
    Department of Medical Science, Uppsala University, Uppsala, Sweden.
    Edvardsson, Nils
    Sahlgrenska Academy at Sahlgrenska University Hospital, Göteborg, Sweden.
    Poci, Dritan
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Patients with atrial fibrillation and outcomes of cerebral infarction in those with treatment of warfarin versus no warfarin with references to CHA(2)DS(2)-VASc score, age and sex: A Swedish nationwide observational study with 48 433 patients2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0176846Article in journal (Refereed)
    Abstract [en]

    Aims: There is controversy in the guidelines as to whether patients with atrial fibrillation and a low risk of stroke should be treated with anticoagulation, especially those with a CHA(2)DS(2)-VASc score of 1 point.

    Methods: In a retrospective, nationwide cohort study, we used the Swedish National Patient Registry, the National Prescribed Drugs Registry, the Swedish Registry of Education and the Population and Housing Census Registry. 48 433 patients were identified between 1 January 2006 and 31 December 2008 with incident atrial fibrillation who were divided in age categories, sex and a CHA(2)DS(2)-VASc score of 0, 1, 2 and >= 3 and they were included in a time-varying analysis of warfarin treatment versus no treatment. The primary end-point was cerebral infarction and stroke, and patients were followed until 31 December 2009.

    Results: Patients with 1 point from the CHA(2)DS(2)-VASc score showed the following adjusted hazard ratios (HR) with a 95% confidence interval: men 65-74 years 0.46 (0.25-0.83), men < 65 years 1.11 (0.56-2.23) and women < 65 years 2.13 (0.94-4.82), where HR < 1 indicates protection with warfarin. In patients < 65 years and 2 points, HR in men was 0.35 (0.18-0.69) and in women 1.84 (0.86-3.94) while, in women with at least 3 points, HR was 0.31 (0.16-0.59). In patients 65-74 years and 2 points, HR in men was 0.37 (0.23-0.59) and in women 0.39 ( 0.21-0.73). Categories including age >= 65 years or >= 3 points showed a statistically significant protection from warfarin.

    Conclusions: Our results support that treatment with anticoagulation may be considered in all patients with an incident atrial fibrillation diagnosis and an age of 65 years and older, i.e. also when the CHA(2)DS(2)-VASc score is 1.

  • 7.
    Andersson, Tommy
    et al.
    Örebro University, School of Medical Sciences.
    Magnuson, Anders
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Bryngelsson, Ing-Liss
    Department of Occupational and Environmental Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Frøbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Henriksson, Karin M.
    Department of Medical Science, Uppsala University, Uppsala and AstraZeneca R&D, Mölndal, Sweden.
    Edvardsson, Nils
    Sahlgrenska Academy at Sahlgrenska University Hospital, Göteborg, Sweden.
    Poçi, Dritan
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Patients without comorbidities at the time of diagnosis of atrial fibrillation: causes of death during long-term follow-up compared to matched controls2017In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 40, no 11, p. 1076-1082Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Little is known about the long-term, cause-specific mortality risk in patients without comorbidities at the time of diagnosis of atrial fibrillation (AF).

    METHODS: From a nation-wide registry of patients hospitalized with incident AF between 1995 and 2008 we identified 9 519 patients with a first diagnosed AF and no comorbidities at the time of AF diagnosis. They were matched with 12 468 controls. The follow-up continued until December 2008. Causes of death were classified according to the ICD-10 codes.

    RESULTS: During follow-up, 11.1% of patients with AF and 8.3% of controls died. Cardiovascular diseases were the most common causes of death and the only diagnoses which showed significantly higher relative risk in patients with AF than controls (HR 2.0, 95% CI 1.8-2.3), and the relative risk was significantly higher in women than in men. Stroke was a more common cause among patients with AF, 13.1% versus 9.7% (HR 2.7, 95% CI 1.8-4.0), while cerebral hemorrhage was more common among controls, 4.7% versus 10.2% (HR 0.9, 95% CI 0.6-1.5). The time from AF diagnosis to death was 6.0 ± 3.1 years.

    CONCLUSIONS: In patients with incident AF and no known comorbidities at the time of AF diagnosis, only cardiovascular diseases were more often causes of death as compared to controls. Women carried a significantly higher relative risk than men.

  • 8.
    Angerås, Oskar
    et al.
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Haraldsson, Inger
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Redfors, Björn
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Petursson, Petur
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Albertsson, Per
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ioanes, Dan
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Odenstedt, Jacob
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Olsson, Hans
    Department of Cardiology, Karlstad Hospital, Karlstad, Sweden.
    Witt, Nils
    Department of Cardiology, South Hospital Stockholm, Stockholm, Sweden.
    Rück, Andreas
    Department of Cardiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Millgård, Jonas
    Department of Cardiology, Sunderby Hospital, Sunderbyn, Sweden.
    Nilsson, Johan
    Department of Cardiology, Heart Centre, Umeå University Hospital, Umeå, Sweden.
    Persson, Jonas
    Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden.
    Söderbom, Måns
    Department of Economics, University of Gothenburg, Gothenburg, Sweden.
    Wedel, Hans
    Health Metrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Erlinge, David
    Department of Cardiology, Lund University, Lund, Sweden.
    James, Stefan
    Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Ramunddal, Truls
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Omerovic, Elmir
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Impact of Thrombus Aspiration on Mortality, Stent Thrombosis, and Stroke in Patients With ST-Segment-Elevation Myocardial Infarction: A Report From the Swedish Coronary Angiography and Angioplasty Registry2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e007680Article in journal (Refereed)
    Abstract [en]

    Background: Thrombus aspiration is still being used in a substantial number of patients despite 2 large randomized clinical trials showing no favorable effect of routine thrombus aspiration during primary percutaneous coronary intervention in patients with STsegment- elevation myocardial infarction. The aim of this observational study was to evaluate the impact of thrombus aspiration on mortality, stent thrombosis, and stroke using all available data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

    Methods and Results: We identified 42 829 consecutive patients registered in SCAAR between January 2005 and September 2014 who underwent percutaneous coronary intervention for ST-segment-elevation myocardial infarction. Thrombus aspiration was used in 25% of the procedures. We used instrumental variable analysis with administrative healthcare region as the treatmentpreference instrumental variable to evaluate the effect of thrombus aspiration on mortality, stent thrombosis, and stroke. Thrombus aspiration was not associated with mortality at 30 days (risk reduction: -1.2; 95% confidence interval [CI], -5.4 to 3.0; P=0.57) and 1 year (risk reduction: -2.4; 95% CI, -7.6 to 3.0; P=0.37). Thrombus aspiration was associated with a lower risk of stent thrombosis both at 30 days (risk reduction: -2.7; 95% CI, -4.1 to -1.4; P<0.001) and 1 year (risk reduction: -3.5; 95% CI, -5.3 to -1.7; P<0.001). In-hospital stroke and neurologic complications did not differ between groups (risk reduction: 0.1; 95% CI, -0.8 to 1.1; P=0.76).

    Conclusions: Mortality was not different between the groups. Thrombus aspiration was associated with decreased risk of stent thrombosis. Our study provides important evidence for the external validity of previous randomized studies regarding mortality.

  • 9.
    Arevström, Lilith
    et al.
    Department of Cardiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Bergh, Cecilia
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Landberg, Rikard
    Department of Food Science, Swedish University of Agricultural Sciences, Uppsala, Sweden; Department of Biological Engineering, Food and Nutrition Science, Chalmers University of Technology, Göteborg, Sweden.
    Wu, Huaxing
    Department of Food Science, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Rodriguez-Mateos, Ana
    Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
    Waldenborg, Micael
    Örebro University, School of Health Sciences. Örebro University Hospital. Department of Cardiology.
    Magnuson, Anders
    Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Swede.
    Blanc, Stephane
    Department of Ecology, Physiology and Ethology, Hubert Curien Pluridisciplinary Institute, University of Strasbourg, Strasbourg, France.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Freeze-dried bilberry (Vaccinium myrtillus) dietary supplement improves walking distance and lipids after myocardial infarction: an open-label randomized clinical trial2019In: Nutrition Research, ISSN 0271-5317, E-ISSN 1879-0739, Vol. 62, p. 13-22Article in journal (Refereed)
    Abstract [en]

    Bilberries, Vaccinium myrtillus, have a high content of phenolic compounds including anthocyanins, which could provide cardiometabolic health benefits following acute myocardial infarction (AMI). We hypothesized that standard medical therapy supplemented with freeze-dried bilberry after AMI would have a more beneficial effect on cardiovascular risk markers and exercise capacity than medical therapy alone. Patients were allocated in a 1:1 ratio within 24 hours of percutaneous coronary intervention in an 8-week trial either to V myrtillus powder (40 g/d, equivalent to 480 g fresh bilberries) and standard medical therapy or to a control group receiving standard medical therapy alone. High-sensitivity C-reactive protein and exercise capacity measured with the 6-minute walk test were the primary biochemical and clinical end points, respectively. Fifty subjects completed the study. No statistically significant difference in high-sensitivity C-reactive protein was detected between groups. The mean 6-minute walk test distance increased significantly more in the bilberry group compared to the control group: mean difference 38 m at follow-up (95% confidence interval 14-62, P = .003). Ex vivo oxidized low-density lipoprotein was significantly lowered in the bilberry group compared to control, geometric mean ratio 0.80 (95% confidence interval 0.66-0.96, P = .017), whereas total cholesterol and low-density lipoprotein cholesterol did not differ significantly between groups. Anthocyanin-derived metabolites in blood increased significantly in the bilberry group during the intervention and were different after 8 weeks between the bilberry group and control. Findings in the present study suggest that bilberries may have clinically relevant beneficial effects following AMI; a larger, double-blind clinical trial is warranted to confirm this.

  • 10.
    Arinell, Karin
    et al.
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Acute Internal Medicine, Centralsjukhuset, Karlstad, Sweden.
    Blanc, Stéphane
    CNRS UMR 7178, Institut Pluridisciplinaire Hubert Curien, Université de Strasbourg, Strasbourg, France.
    Welinder, Karen Gjesing
    Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark.
    Støen, Ole Gunnar
    Norwegian Institute for Nature Research, Trondheim, Norway.
    Evans, Alina L.
    Department of Forestry and Wildlife Management, Inland Norway University of Applied Sciences, Koppang, Norway.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Physical inactivity and platelet function in humans and brown bears: A comparative study2018In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 29, no 1, p. 87-90Article in journal (Refereed)
    Abstract [en]

    Physical inactivity increases the risk of thromboembolism. However, good standardized human models on inactivity are in short supply and experimental models are few.

    Our objective was to investigate how standardized bed rest affects platelet aggregation in humans and to investigate if aggregation is altered in a translational model system - the hibernating brown bear (Ursus arctos). We collected blood from (1) healthy male volunteers participating in a 21-day bed rest study in head-down tilt position (-6°) 24 h a day; (2) free-ranging brown bears captured during winter hibernation and again during active state in summer. We analyzed platelet function using multiple electrode platelet aggregometry. In total, 9 healthy male volunteers (age 31.0 ± 6.4 years) and 13 brown bears (7 females and 6 males, age 2.8 ± 0.6 years) were included. In hibernating bears adenosine diphosphate, arachidonic acid, thrombin receptor activating peptide, and collagen impedance aggregometry tests were all halved compared to summer active state. In human volunteers no statistically significant changes were found between baseline and the end of bed rest. In human male volunteers 3 weeks of bed rest did not affect platelet function. In hibernating brown bears platelet aggregation was halved compared to summer and we hypothesize that this is a protective measure to avoid formation of thrombi under periods of low blood flow.

  • 11.
    Arinell, Karin
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Christensen, Kjeld
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Blanc, Stéphane
    Institut Pluridisciplinaire Hubert Curien-De'partement d'Ecologie, Physiologie, Ethologie Unite' Mixte de Recherche 7178. Centre National de la Recherche Scientifique, Universite' de Strasbourg, Strasbourg, France.
    Larsson, Anders
    Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
    Fröbert, Ole
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Effect of prolonged standardized bed rest on cystatin C and other markers of cardiovascular risk2011In: BMC Physiology, ISSN 1472-6793, E-ISSN 1472-6793, Vol. 11, article id 17Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Sedentary lifestyle is associated with coronary artery disease but even shorter periods of physical inactivity may increase cardiovascular risk. Cystatin C is independently associated with cardiovascular disease and our objective was to investigate the relation between this novel biomarker and standardized bed rest. Research of immobilization physiology in humans is challenging because good biological models are in short supply. From the Women International Space simulation for Exploration study (WISE) we studied markers of atherosclerosis and kidney function, including cystatin C, in a standardized bed rest study on healthy volunteers. Fifteen healthy female volunteers participated in a 20-day ambulatory control period followed by 60 days of bed rest in head-down tilt position (-6°) 24 h a day, finalized by 20 days of recovery. The subjects were randomized into two groups during bed rest: a control group (n = 8) that remained physically inactive and an exercise group (n = 7) that participated in both supine resistance and aerobic exercise training.

    RESULTS: Compared to baseline values there was a statistically significant increase in cystatin C in both groups after bed rest (P < 0.001). Glomerular filtration rate (GFR), calculated by both cystatin C and Cockcroft-Gault equation, decreased after bed rest while there were no differences in creatinine or creatine kinase levels. CRP did not change during bed rest in the exercise group, but there was an increase of CRP in the control group during recovery compared to both the baseline and the bed rest periods. The apo-B/apo-Ai ratio increased during bed rest and decreased again in the recovery period. Subjects experienced a small but statistically significant reduction in weight during bed rest and compared to baseline weights remained lower at day 8 of recovery.

    CONCLUSION: During and following prolonged standardized bed rest the concentrations of several clinically relevant cardiovascular risk markers change.

  • 12.
    Arinell, Karin
    et al.
    Örebro University, School of Health Sciences. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Sahdo, Berolla
    Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Evans, Alina L.
    Faculty of Forestry and Wildlife Management, Hedmark University College, Evenstad, Norway; Section of Arctic Veterinary Medicine, Norwegian School of Veterinary Science, Tromsø, Norway.
    Arnemo, Jon M.
    Faculty of Forestry and Wildlife Management, Hedmark University College, Evenstad, Norway; Department of Wildlife Fish and Environmental Studies, Faculty of Forest Sciences, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Baandrup, Ulrik
    Department of Pathology, Vendsyssel Hospital, Hjørring, Denmark; Faculty of Medical Sciences, Aalborg, Denmark.
    Fröbert, Ole
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Brown Bears (Ursus arctos) Seem Resistant to Atherosclerosis Despite Highly Elevated Plasma Lipids during Hibernation and Active State2012In: Clinical and Translational Science, ISSN 1752-8054, E-ISSN 1752-8062, Vol. 5, no 3, p. 269-272Article in journal (Refereed)
    Abstract [en]

    Hibernation is an extreme physiological challenge for the brown bear (Ursus arctos) in which metabolism is based mainly on lipids. The study objective was to compare plasma lipids in hibernating and active free-ranging brown bears and relate them to arterial histopathology. Blood was drawn from seven immobilized free-ranging brown bears (three females, 23 years old) during hibernation in February and from the same bears while active in June and analyzed by enzymatic and automated hematology methods within 48 hours of sampling. Left anterior descending coronary arteries and aortic arches from 12 bears (six females, 1.512 years old) killed in hunting were examined by histopathology. Total plasma cholesterol decreased from hibernation to the active period (11.08 +/- 1.04 mmol/L vs. 7.89 +/- 1.96 mmol/L, P= 0.0028) as did triglyceride (3.16 +/- 0.62 mmol/L vs. 1.44 +/- 0.27 mmol/L, P= 0.00012) and LDL cholesterol (4.30 +/- 0.71 mmol/L vs. 2.02 +/- 1.03 mmol/L, P= 0.0075), whereas HDL cholesterol was unchanged. No atherosclerosis, fatty streaks, foam cell infiltration, or inflammation were seen in any arterial samples. Brown bears tolerate elevated cholesterol levels, obesity, physical inactivity, and circulatory slow flow during hibernation without signs of -atherosclerosis. This species might serve as a reverse translational model for atherosclerosis resistance.

  • 13.
    Athlin, Simon
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Larsson, Emelie
    Nordenskjöld, Anna M.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Fröbert, Ole
    Örebro University, School of Medical Sciences.
    Evaluation of the novel IMMUVIEW RSV antigen test for detection of respiratory syncytial virus in adults and children2019Conference paper (Other academic)
  • 14.
    Berg von Linde, Maria Berg
    et al.
    Department of Cardiology, Faculty of Health, Örebro University, Orebro, Sweden.
    Arevström, Lilith
    Department of Cardiology, Faculty of Health, Örebro University, Orebro, Sweden.
    Fröbert, Ole
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Insights from the Den: How Hibernating Bears May Help Us Understand and Treat Human Disease2015In: Clinical and Translational Science, ISSN 1752-8054, E-ISSN 1752-8062, Vol. 8, no 5, p. 601-605Article, review/survey (Refereed)
    Abstract [en]

    Hibernating brown bears (Ursus arctos) and black bears (Ursus americanus) spend half of the year in a physically inactive state inside their winter dens without food intake and defecating and no or little urination. Under similar extreme conditions, humans would suffer from loss of lean body mass, heart failure, thrombosis, azotemia, osteoporosis, and more. However, bears exit the den in the spring strong without organ injuries. Translational animal models are used in human medicine but traditional experimental animals have several shortcomings; thus, we believe that it is time to systematically explore new models. In this review paper, we describe physiological adaptations of hibernating bears and how similar adaptations in humans could theoretically alleviate medical conditions. The bear has solved most of the health challenges faced by humans, including heart and kidney disease, atherosclerosis and thrombosis, and muscle wasting and osteoporosis. Understanding and applying this library of information could lead to a number of major discoveries that could have implications for the understanding and treatment of human disease.

  • 15.
    Bergh, Cecilia
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Fall, Katja
    Örebro University, School of Medical Sciences.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Sjöqvist, Hugo
    Örebro University, Örebro University School of Business.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Severe infections and subsequent delayed cardiovascular disease2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, no 18, p. 1958-1966Article in journal (Refereed)
    Abstract [en]

    Background: Severe infections in adulthood are associated with subsequent short-term cardiovascular disease. Whether hospital admission for sepsis or pneumonia is associated with persistent increased risk (over a year after infection) is less well established.

    Design: The design of this study was as a register-based cohort study.

    Methods: Some 236,739 men born between 1952-1956 were followed from conscription assessments in adolescence to 2010. All-cause cardiovascular disease ( n = 46,754), including coronary heart disease ( n = 10,279) and stroke ( n = 3438), was identified through national registers 1970-2010 (at ages 18-58 years).

    Results: Sepsis or pneumonia in adulthood (resulting in hospital admission) are associated with increased risk of cardiovascular disease in the years following infection. The risk is highest during the first year after the infection, with an adjusted hazard ratio (and 95% confidence intervals) of 6.33 (5.65-7.09) and a notably increased risk persisted with hazard ratios of 2.47 (2.04-3.00) for the second and 2.12 (1.71-2.62) for the third year after infection. The risk attenuated with time, but remained raised for at least five years after infection; 1.87 (1.47-2.38). The results are adjusted for characteristics in childhood, cardiovascular risk factors and medical history in adolescence. Similar statistically significant associations were found for coronary heart disease and stroke.

    Conclusions: Raised risks of cardiovascular disease following hospital admission for sepsis or pneumonia were increased for more than five years after the infection, but with the highest magnitude during the first three years following infection, suggesting a period of vulnerability when health professionals and patients should be aware of the heightened risk for cardiovascular disease.

  • 16.
    Buccheri, Sergio
    et al.
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    James, Stefan
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Lindholm, Daniel
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Olivecrona, Göran K.
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    Persson, Jonas
    Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden.
    Hambraeus, Kristina
    Department of Cardiology, Falu Lasarett, Falun, Sweden.
    Witt, Nils
    Unit of Cardiology, Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden.
    Erlinge, David
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    Angerås, Oskar
    Department of Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Lagerqvist, Bo
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Sarno, Giovanna
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Clinical and angiographic outcomes of bioabsorbable vs. permanent polymer drug-eluting stents in Sweden: a report from the Swedish Coronary and Angioplasty Registry (SCAAR)2019In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 40, no 31, p. 2607-2615Article in journal (Refereed)
    Abstract [en]

    AIMS: Randomized clinical trials have consistently demonstrated the non-inferiority of bioabsorbable polymer drug-eluting stents (BP-DES) with respect to DES having permanent polymers (PP-DES). To date, the comparative performance of BP- and PP-DES in the real world has not been extensively investigated.

    METHODS AND RESULTS: From October 2011 to June 2016, we analysed the outcomes associated with newer generation DES use in Sweden. After stratification according to the type of DES received at the index procedure, a total of 16 504 and 79 106 stents were included in the BP- and PP-DES groups, respectively. The Kaplan-Meier estimates for restenosis at 2 years were 1.2% and 1.4% in BP- and PP-DES groups, respectively. Definite stent thrombosis (ST) was low in both groups (0.5% and 0.7% in BP- and PP-DES groups, respectively). The adjusted hazard ratio (HR) for either restenosis or definite ST did not differ between BP- and PP-DES [adjusted HR 0.95, 95% confidence interval (CI) 0.74-1.21; P = 0.670 and adjusted HR 0.79, 95% CI 0.57-1.09; P = 0.151, respectively]. Similarly, there were no differences in the adjusted risk of all-cause death and myocardial infarction (MI) between the two groups (adjusted HR for all-cause death 1.01, 95% CI 0.82-1.25; P = 0.918 and adjusted HR for MI 1.05, 95% CI 0.93-1.19; P = 0.404).

    CONCLUSION: In a large, nationwide, and unselected cohort of patients, percutaneous coronary intervention with BP-DES implantation was not associated with an incremental clinical benefit over PP-DES use at 2 years follow-up.

  • 17.
    Buccheri, Sergio
    et al.
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Sarno, Giovanna
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Gudnason, Thorarinn
    Landspitali University Hospital, Reykjavik, Iceland; Department of Cardiology and Cardiovascular Research Center, University of Iceland, Iceland.
    Lagerqvist, Bo
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Lindholm, Daniel
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Maeng, Michael
    Department of Cardiology, Aarhus University Hospital, Sweden.
    Olivecrona, Göran
    Department of Cardiology, Clinical Sciences, Lund University Hospital, Switzerland.
    James, Stefan
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Assessing the Nationwide Impact of a Registry-Based Randomized Clinical Trial on Cardiovascular Practice The TASTE Trial in Perspective2019In: Circulation. Cardiovascular Interventions, ISSN 1941-7640, E-ISSN 1941-7632, Vol. 12, no 3, article id e007381Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Registry-based randomized clinical trials have emerged as useful tools to provide evidence on the comparative efficacy and safety of different therapeutic strategies. However, it remains unknown whether the results of registry-based randomized clinical trials have a sizable impact on daily clinical practice. We sought, therefore, to describe the temporal trends in thrombus aspiration (TA) use in Sweden before, during, and after dissemination of the TASTE trial (Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia) results.

    METHODS AND RESULTS: From January 1, 2006, to December 31, 2017, we included all consecutive patients with ST-segment-elevation myocardial infarction undergoing percutaneous revascularization in Sweden. All patients were registered in the Swedish Coronary Angiography and Angioplasty Registry. A total of 55 809 ST-segment-elevation myocardial infarction patients were included. TA use in Sweden substantially decreased after dissemination of TASTE results (from 39.8% to 11.8% during and after TASTE, respectively). Substantial variability in TA use across treating centers was observed before TASTE (TA use ranging from 0% to 70%), but after TASTE both the interhospital variability and the frequency of TA use were markedly reduced. A constant shift in medical practice was seen about 4 months after dissemination of the TASTE trial results. Time trends for all-cause mortality and definite stent thrombosis at 30 days were not associated with variations in TA use (P values >0.05 using the Granger test).

    CONCLUSIONS: In Sweden, the results of the TASTE trial were impactful in daily clinical practice and led to a relevant decrease in TA use in ST-segment-elevation myocardial infarction patients undergoing percutaneous revascularization.

  • 18.
    Calais, Fredrik
    et al.
    Örebro University, School of Medical Sciences.
    Eriksson Östman, Maja
    Örebro University, Faculty of Health, Department of Cardiology, Sweden.
    Hedberg, Pär
    Centre for Clinical Research, Uppsala University and Department of Clinical Physiology, Västmanland County Hospital, Västerås, Sweden.
    Rosenblad, Andreas
    Centre for Clinical Research, Uppsala University Västmanland County Hospital, Västerås, Sweden.
    Leppert, Jerzy
    Centre for Clinical Research, Uppsala University Västmanland County Hospital, Västerås, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Incremental prognostic value of coronary and systemic atherosclerosis aftermyocardial infarctionManuscript (preprint) (Other academic)
  • 19.
    Calais, Fredrik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Lagerqvist, Bo
    University Hospital Uppsala, Uppsala, Sweden.
    Leppert, Jerzy
    Uppsala University, Västerås, Sweden.
    James, Stefan
    Uppsala Clinical Research Center, Uppsala, Sweden.
    Fröbert, Ole
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden.
    Thrombus aspiration in patients with large anterior myocardial infarction: a TASTE trial substudy2015In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 66, no 15, p. B2-B2Article in journal (Other academic)
  • 20.
    Calais, Fredrik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Lagerqvist, Bo
    Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Leppert, Jerzy
    Centre for Clinical Research, Uppsala University, Central Hospital, Västerås, Sweden.
    James, Stefan K.
    Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Fröbert, Ole
    Department of Cardiology, Faculty of Health, Örebro University, Örebro, Sweden.
    Thrombus aspiration in patients with large anterior myocardial infarction: A Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia trial substudy2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 172, no 2, p. 129-134Article in journal (Refereed)
    Abstract [en]

    Background: The TASTE trial did not demonstrate clinical benefit of thrombus aspiration (TA). High-risk patients might benefit from TA.

    Methods: The TASTE trial was a multicenter, randomized, controlled, open-label trial obtaining end points from national registries. Patients (n = 7,244) with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) were randomly assigned 1: 1 to TA and PCI or to PCI alone. We assessed the 1-year clinical effect of TA in a subgroup with potentially large anterior STEMI: mid or proximal left anterior descending coronary artery infarct lesion, thrombolysis in myocardial infarction 0 to 2 flow, and symptom onset to PCI time = 5 hours. In this substudy, patient eligibility criteria corresponded to that of the INFUSE-AMI study.

    Results: In total, 1,826 patients fulfilled inclusion criteria. All-cause mortality at 1 year of patients randomized to TA did not differ from those randomized to PCI only (hazard ratio [HR] 1.05, 95% CI 0.74-1.49, P = .77). Rates of rehospitalization for myocardial infarction, heart failure, and stent thrombosis did not differ between groups (HR 0.87, 95% CI 0.51-1.46, P = .59; HR 1.10 95% CI 0.77-1.58, P = .58; and HR 0.75, 95% CI 0.30-1.86, P = .53, respectively). This was also the case for the combined end point of all-cause mortality and rehospitalization for myocardial infarction, heart failure, or stent thrombosis (HR 1.00, 95% CI 0.79-1.26, P = .99).

    Conclusion: In patients with STEMI and large area of myocardium at risk, TA did not affect outcome within 1 year.

  • 21.
    Calais, Fredrik
    et al.
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden; Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Östman, Maja Eriksson
    Department of Cardiology, Örebro, Sweden; , Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Hedberg, Pär
    Centre for Clinical Research, Uppsala University, Uppsala, Sweden; Department of Clinical Physiology, Västmanland County Hospital, Västerås, Sweden.
    Rosenblad, Andreas
    Centre for Clinical Research, Uppsala University Västmanland County Hospital, Västerås, Sweden.
    Leppert, Jerzy
    Centre for Clinical Research, Uppsala University Västmanland County Hospital, Västerås, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Incremental prognostic value of coronary and systemic atherosclerosis after myocardial infarction2018In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 261, p. 6-11Article in journal (Refereed)
    Abstract [en]

    Background: The role of systemic atherosclerosis in myocardial infarction (MI) patients is not fully understood. We investigated the incremental prognostic value of coronary and systemic atherosclerosis after acute MI by estimating extra-cardiac artery disease (ECAD) and extent of coronary atherosclerosis.

    Methods and results: The study included 544 prospective MI patients undergoing coronary angiography. For all patients, the longitudinal coronary atherosclerotic extent, expressed as Sullivan extent score (SES) was calculated. In addition, the patients underwent non-invasive screening for ECAD in the carotid, aortic, renal and lower limb. SES was found to be associated with ECAD independent of baseline clinical parameters [adjusted odds ratio (OR) 1.04 95% confidence interval (CI) 1.02-1.06, P < 0.001]. Extensive systemic atherosclerosis, defined as the combination of extensive coronary disease (SES >= 17) and ECAD, was associated with higher risk for all-cause mortality compared to limited systemic atherosclerosis (SES < 17 and no ECAD) (hazard ratio [HR] 2.9 95% CI 1.9-4.5, P < 0.001, adjusted for Global Registry of Acute Coronary Events risk score parameters 1.8, 95% CI 1.1-3.0, P = 0.019). The risk for the composite endpoint of cardiovascular death or hospitalization was significantly higher in patients with extensive systemic atherosclerosis compared to patients with limited systemic atherosclerosis (HR 3.1, 95% CI 2.1-4.7, P < 0.001, adjusted HR 1.9, 95% CI 1.2-3.1, P < 0.004).

    Conclusions: Visual estimation of the longitudinal coronary atherosclerotic extent at the time of MI predicts ECAD. Coexistence of extensive coronary disease and ECAD defines a group with particularly poor prognosis after MI.

  • 22.
    Calais, Fredrik
    et al.
    Örebro University, Faculty of Health, Department of Cardiology, Sweden.
    Östman, Maja Eriksson
    Örebro University, Faculty of Health, Department of Cardiology, Sweden.
    Hedberg, Pär
    Centre for Clinical Research, Uppsala University, Department of Clinical Physiology, Västmanland County Hospital, Västerås, Sweden.
    Rosenblad, Andreas
    Centre for Clinical Research, Uppsala University Västmanland County Hospital, Västerås, Sweden.
    Leppert, Jerzy
    Centre for Clinical Research, Uppsala University Västmanland County Hospital, Västerås, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Reply to "Letter to editor, Assessing the effect of coronary and systemic atherosclerosis following myocardial infarction" by dr Su Yueqiu et al.2018In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 271, p. 29-29Article in journal (Refereed)
  • 23.
    De Bruyne, Bernard
    et al.
    Onze-Lieve-Vrouw Clinic, Cardiovascular Center Aalst, Aalst, Belgium .
    Fröbert, Ole
    Örebro University Hospital, Region Örebro län, Örebro, Sweden.
    Fearon, William F.
    Stanford University Medical Center, Stanford CA, USA.
    Fractional Flow Reserve-Guided PCI versus Medical Therapy in Stable Coronary Disease2012In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 367, no 11, p. 991-1001Article in journal (Refereed)
    Abstract [en]

    Background: The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone.

    Methods: In patients with stable coronary artery disease for whom PCI was being considered, we assessed all stenoses by measuring FFR. Patients in whom at least one stenosis was functionally significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus the best available medical therapy (PCI group) or the best available medical therapy alone (medical-therapy group). Patients in whom all stenoses had an FFR of more than 0.80 were entered into a registry and received the best available medical therapy. The primary end point was a composite of death, myocardial infarction, or urgent revascularization.

    Results: Recruitment was halted prematurely after enrollment of 1220 patients (888 who underwent randomization and 332 enrolled in the registry) because of a significant between-group difference in the percentage of patients who had a primary endpoint event: 4.3% in the PCI group and 12.7% in the medical-therapy group (hazard ratio with PCI, 0.32; 95% confidence interval [CI], 0.19 to 0.53; P<0.001). The difference was driven by a lower rate of urgent revascularization in the PCI group than in the medical-therapy group (1.6% vs. 11.1%; hazard ratio, 0.13; 95% CI, 0.06 to 0.30; P<0.001); in particular, in the PCI group, fewer urgent revascularizations were triggered by a myocardial infarction or evidence of ischemia on electrocardiography (hazard ratio, 0.13; 95% CI, 0.04 to 0.43; P<0.001). Among patients in the registry, 3.0% had a primary end-point event.

    Conclusions: In patients with stable coronary artery disease and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to be favorable with the best available medical therapy alone. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01132495.)

  • 24.
    Erlinge, David
    et al.
    Department of Cardiology, Lund University, Sweden.
    Koul, Sasha
    Department of Cardiology, Lund University, Sweden.
    Omerovic, Elmir
    Department of Cardiology, Sahlgrenska University Hospital, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Linder, Rikard
    Department of Cardiology, Danderyd Hospital, Sweden.
    Danielewicz, Mikael
    PCI-Unit, Karlstad Hospital, Sweden.
    Hamid, Mehmet
    Department of Cardiology, Mälarsjukhuset, Sweden.
    Venetsanos, Dimitrios
    Department of Cardiology, Karolinska University Hospital, Sweden.
    Henareh, Loghman
    Department of Cardiology, Karolinska University Hospital, Sweden.
    Pettersson, Björn
    Department of Cardiology, Umeå University, Sweden.
    Wagner, Henrik
    Department of Cardiology, Helsingborg Lasarett, Sweden.
    Grimfjärd, Per
    Department of Internal Medicine, Västmanlands Sjukhus, Sweden.
    Jensen, Jens
    Department of Cardiology, Capio S:t Görans Hospital AB, Sweden.
    Hofmann, Robin
    Department of Clinical Science and Education, Södersjukhuset, Sweden.
    Ulvenstam, Anders
    Department of Cardiology, Östersund Hospital, Sweden.
    Völz, Sebastian
    Department of Cardiology, Sahlgrenska University Hospital, Sweden.
    Petursson, Petur
    Department of Cardiology, Sahlgrenska University Hospital, Sweden.
    Östlund, Ollie
    Department of Medical Sciences, Uppsala University, Sweden.
    Sarno, Giovanna
    Department of Medical Sciences, Uppsala University, Sweden.
    Wallentin, Lars
    Department of Medical Sciences, Uppsala University, Sweden.
    Scherstén, Fredrik
    Department of Cardiology, Lund University, Sweden.
    Eriksson, Peter
    Department of Cardiology, Umeå University, Sweden.
    James, Stefan
    Department of Medical Sciences, Uppsala University, Sweden.
    Bivalirudin versus heparin monotherapy in non-ST-segment elevation myocardial infarction2018In: European heart journal. Acute cardiovascular care., ISSN 2048-8726Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The optimal anti-coagulation strategy for patients with non-ST-elevation myocardial infarction treated with percutaneous coronary intervention is unclear in contemporary clinical practice of radial access and potent P2Y12-inhibitors. The aim of this study was to investigate whether bivalirudin was superior to heparin monotherapy in patients with non-ST-elevation myocardial infarction without routine glycoprotein IIb/IIIa inhibitor use.

    METHODS: In a large pre-specified subgroup of the multicentre, prospective, randomised, registry-based, open-label clinical VALIDATE-SWEDEHEART trial we randomised patients with non-ST-elevation myocardial infarction undergoing percutaneous coronary intervention, treated with ticagrelor or prasugrel, to bivalirudin or heparin monotherapy with no planned use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. The primary endpoint was the rate of a composite of all-cause death, myocardial infarction or major bleeding within 180 days.

    RESULTS: A total of 3001 patients with non-ST-elevation myocardial infarction, were enrolled. The primary endpoint occurred in 12.1% (182 of 1503) and 12.5% (187 of 1498) of patients in the bivalirudin and heparin groups, respectively (hazard ratio of bivalirudin compared to heparin treatment 0.96, 95% confidence interval 0.78-1.18, p=0.69). The results were consistent in all major subgroups. All-cause death occurred in 2.0% versus 1.7% (hazard ratio 1.15, 0.68-1.94, p=0.61), myocardial infarction in 2.3% versus 2.5% (hazard ratio 0.91, 0.58-1.45, p=0.70), major bleeding in 8.9% versus 9.1% (hazard ratio 0.97, 0.77-1.24, p=0.82) and definite stent thrombosis in 0.3% versus 0.2% (hazard ratio 1.33, 0.30-5.93, p=0.82).

    CONCLUSION: Bivalirudin as compared to heparin during percutaneous coronary intervention for non-ST-elevation myocardial infarction did not reduce the composite of all-cause death, myocardial infarction or major bleeding in non-ST-elevation myocardial infarction patients receiving current recommended treatments with modern P2Y12-inhibitors and predominantly radial access.

  • 25.
    Erlinge, David
    et al.
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    Omerovic, Elmir
    Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health, Örebro University, Örebro, Sweden.
    Linder, Rikard
    Department of Cardiology, Danderyd Hospital, Stockholm, Sweden.
    Danielewicz, Mikael
    PCI-Unit at Karlstad Hospital, Karlstad, Sweden.
    Hamid, Mehmet
    Department of Cardiology, Mälarsjukhuset, Eskilstuna, Sweden.
    Swahn, Eva
    Department of Cardiology, Linköping University Hospital, Linköping, Sweden.
    Henareh, Loghman
    Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
    Wagner, Henrik
    Department of Cardiology, Helsingborg Lasarett, Helsingborg, Sweden.
    Hårdhammar, Peter
    Department of Cardiology, Halmstad Hospital, Halmstad, Sweden.
    Sjögren, Iwar
    Department of Cardiology, Falun Hospital, Falun, Sweden.
    Stewart, Jason
    Department of Cardiology, Skaraborgs Hospital, Skövde, Sweden.
    Grimfjärd, Per
    Department of Internal Medicine, Västmanlands Sjukhus, Västerås, Sweden.
    Jensen, Jens
    Department of Cardiology, Capio St. Görans Hospital, Karolinska Institutet, Stockholm, Sweden.
    Aasa, Mikael
    Department of Cardiology, Södersjukhuset AB, Stockholm, Sweden.
    Robertsson, Lotta
    Department of Internal Medicine, Västmanlands Sjukhus, Västerås, Sweden.
    Lindroos, Pontus
    Department of Cardiology, Capio St. Görans Hospital, Karolinska Institutet, Stockholm, Sweden.
    Haupt, Jan
    Department of Cardiology, Sunderby Sjukhus, Luleå, Sweden.
    Wikström, Helena
    Department of Cardiology, Kristianstad Hospital, Kristianstad, Sweden.
    Ulvenstam, Anders
    Department of Cardiology, Östersund Hospital, Östersund, Sweden.
    Bhiladvala, Pallonji
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    Lindvall, Bo
    Department of Cardiology, Sundsvall Hospital, Sundsvall, Sweden.
    Lundin, Anders
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    Tödt, Tim
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    Ioanes, Dan
    Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Råmunddal, Truls
    Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Kellerth, Thomas
    Department of Cardiology, Faculty of Health, Örebro University, Örebro, Sweden.
    Zagozdzon, Leszek
    Department of Cardiology, Faculty of Health, Örebro University, Örebro, Sweden.
    Götberg, Matthias
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    Andersson, Jonas
    Department of Cardiology, Umeå University, Umeå, Sweden.
    Angerås, Oskar
    Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Östlund, Ollie
    Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Lagerqvist, Bo
    Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Held, Claes
    Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Wallentin, Lars
    Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Scherstén, Fredrik
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    Eriksson, Peter
    Department of Cardiology, Umeå University, Umeå, Sweden.
    Koul, Sasha
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    James, Stefan
    Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Bivalirudin versus Heparin Monotherapy in Myocardial Infarction2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 12, p. 1132-1142Article in journal (Refereed)
    Abstract [en]

    Background The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. Methods In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. Results A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). Conclusions Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).

  • 26.
    Escaned, Javier
    et al.
    Hospital Clínico San Carlos, IDISSC, Madrid, Spain; Universidad Complutense de Madrid, Madrid, Spain.
    Calais, Fredrik
    Department of Cardiology, Faculty of Health, Örebro University, Örebro, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences.
    Davies, Justin E.
    Hammersmith Hospital, Imperial College London, London, United Kingdom.
    Götberg, Matthias
    Skåne University Hospital, Lund University, Lund, Sweden.
    Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes2018In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, no 15, p. 1437-1449Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS).

    BACKGROUND: Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization.

    METHODS: The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year.

    RESULTS: Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04).

    CONCLUSIONS: Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year.

  • 27.
    Evans, Alina L.
    et al.
    Department of Forestry and Wildlife Management, Hedmark University College, Evenstad, Norway; Section of Arctic Veterinary Medicine, Norwegian School of Veterinary Science, Tromsø, Norway.
    Sahlén, Veronica
    Department of Ecology and Natural Resource Management, Norwegian University of Life Sciences, Ås, Norway.
    Stoen, Ole-Gunnar
    Department of Ecology and Natural Resource Management, Norwegian University of Life Sciences, Ås, Norway; Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Fahlman, Åsa
    Section of Anesthesiology, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Uppsala, Sweden; Department of Veterinary Clinical and Diagnostic Sciences, Faculty of Veterinary Medicine, University of Calgary, Calgary AB, Canada.
    Brunberg, Sven
    Department of Ecology and Natural Resource Management, Norwegian University of Life Sciences, Ås, Norway.
    Madslien, Knut
    Section for Wildlife Health, National Veterinary Institute, Oslo, Norway.
    Fröbert, Ole
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Swenson, Jon E.
    Department of Ecology and Natural Resource Management, Norwegian University of Life Sciences, Ås, Norway; Norwegian Institute for Nature Research, Trondheim, Norway.
    Arnemo, Jon M.
    Department of Forestry and Wildlife Management, Hedmark University College, Campus Evenstad, Norway; Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Capture, Anesthesia, and Disturbance of Free-Ranging Brown Bears (Ursus arctos) during Hibernation2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 7, article id e40520Article in journal (Refereed)
    Abstract [en]

    We conducted thirteen immobilizations of previously collared hibernating two-to four-year-old brown bears (Ursus arctos) weighing 21-66 kg in central Sweden in winter 2010 and 2011 for comparative physiology research. Here we report, for the first time, an effective protocol for the capture and anesthesia of free-ranging brown bears during hibernation and an assessment of the disturbance the captures caused. Bears were darted in anthill, soil, or uprooted tree dens on eleven occasions, but two bears in rock dens fled and were darted outside the den. We used medetomidine at 0.02-0.06 mg/kg and zolazepam-tiletamine at 0.9-2.8 mg/kg for anesthesia. In addition, ketamine at 1.5 mg/kg was hand-injected intramuscularly in four bears and in six it was included in the dart at 1.1-3.0 mg/kg. Once anesthetized, bears were removed from the dens. In nine bears, arterial blood samples were analyzed immediately with a portable blood gas analyzer. We corrected hypoxemia in seven bears (PaO2 57-74 mmHg) with supplemental oxygen. We placed the bears back into the dens and antagonized the effect of medetomidine with atipamezole. Capturing bears in the den significantly increased the risk of den abandonment. One of twelve collared bears that were captured remained at the original den until spring, and eleven, left their dens (mean +/- standard deviation) 3.2 +/- 3.6 (range 0.5-10.5) days after capture. They used 1.9 +/- 0.9 intermediate resting sites, during 6.2 +/- 7.8 days before entering a new permanent den. The eleven new permanent dens were located 730 +/- 589 m from the original dens. We documented that it was feasible and safe to capture hibernating brown bears, although they behaved differently than black bears. When doing so, researchers should use 25% of the doses used for helicopter darting during the active period and should consider increased energetic costs associated with den abandonment.

  • 28.
    Evans, Alina L.
    et al.
    Department of Forestry and Wildlife Management, Faculty of Applied Ecology and Agricultural Sciences, Hedmark University of Applied Sciences Evenstad (earlier University College Inland, Evenstad), Elverum, Norway.
    Singh, Navinder J.
    Department of Wildlife, Fish and Environmental Studies, Faculty of Forest Sciences, Swedish University of Agricultural Sciences (SLU), Umeå, Sweden.
    Fuchs, Boris
    Department of Forestry and Wildlife Management, Faculty of Applied Ecology and Agricultural Sciences, Hedmark University of Applied Sciences Evenstad, Elverum, Norway.
    Blanc, Stéphane
    Institut Pluridisciplinaire Hubert Curien, Université de Strasbourg, Strasbourg, France; CNRS UMR 7178, Strasbourg, France.
    Friebe, Andrea
    Department of Ecology and Natural Resources Management, Norwegian University of Life Sciences, Ås, Norway.
    Laske, Timothy G.
    Medtronic Inc., Mounds View MN, USA; University of Minnesota, Minneapolis MN, USA.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Swenson, Jon E.
    Department of Ecology and Natural Resources Management, Norwegian University of Life Sciences, Ås, Norway; Norwegian Institute for Nature Research, Trondheim, Norway.
    Arnemo, Jon M.
    Department of Forestry and Wildlife Management, Faculty of Applied Ecology and Agricultural Sciences, Hedmark University of Applied Sciences Evenstad, Elverum, Norway; Department of Wildlife, Fish and Environmental Studies, Faculty of Forest Sciences, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Physiological reactions to capture in hibernating brown bears2016In: Conservation Physiology, E-ISSN 2051-1434, Vol. 4, article id cow061Article in journal (Refereed)
    Abstract [en]

    Human disturbance can affect animal life history and even population dynamics. However, the consequences of these disturbances are difficult to measure. This is especially true for hibernating animals, which are highly vulnerable to disturbance, because hibernation is a process of major physiological changes, involving conservation of energy during a resource-depleted time of year. During the winters of 2011-15, we captured 15 subadult brown bears (Ursus arctos) and recorded their body temperatures (n = 11) and heart rates (n = 10) before, during and after capture using biologgers. We estimated the time for body temperature and heart rate to normalize after the capture event. We then evaluated the effect of the captures on the pattern and depth of hibernation and the day of den emergence by comparing the body temperature of captured bears with that of undisturbed subadult bears (n = 11). Both body temperature and heart rate increased during capture and returned to hibernation levels after 15-20 days. We showed that bears required 2-3 weeks to return to hibernation levels after winter captures, suggesting high metabolic costs during this period. There were also indications that the winter captures resulted in delayed den emergence.

  • 29.
    Fröbert, Ole
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Calais, Fredrik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    James, Stefan K.
    Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Lagerqvist, Bo
    Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    ST-Elevation Myocardial Infarction, Thrombus Aspiration, and Different Invasive Strategies: A TASTE Trial Substudy2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 6, article id e001755Article in journal (Refereed)
    Abstract [en]

    Background: The clinical effect of thrombus aspiration in ST-elevation myocardial infarction may depend on the type of aspiration catheter and stenting technique.

    Methods and Results: The multicenter, prospective, randomized, open-label trial Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE) did not demonstrate a clinical benefit of thrombus aspiration compared to percutaneous coronary intervention alone. We assessed the effect of type of aspiration device, stent type, direct stenting, and postdilatation on outcomes at 1 year. There was no difference in all-cause mortality, between the 3 most frequently used aspiration catheters (Eliminate [Terumo] 5.4%, Export [Medtronic] 5.0%, Pronto [Vascular Solutions] 4.5%) in patients randomized to thrombus aspiration. There was no difference in mortality between directly stented patients randomized to thrombus aspiration compared to patients randomized to percutaneous coronary intervention only (risk ratio 1.08, 95% CI 0.70 to 1.67, P=0.73). Similarly, there was no difference in mortality between the 2 randomized groups for patients receiving drug-eluting stents (risk ratio 0.89, 95% CI 0.63 to 1.26, P=0.50) or for those treated with postdilation (risk ratio 0.72, 95% CI 0.49 to 1.07, P=0.11). Furthermore, there was no difference in rehospitalization for myocardial infarction or stent thrombosis between the randomized arms in any of the subgroups.

    Conclusions: In patients with ST-elevation myocardial infarction randomized to thrombus aspiration, the type of aspiration catheter did not affect outcome. Stent type, direct stenting, or postdilation did not affect outcome irrespective of treatment with thrombus aspiration and percutaneous coronary intervention or percutaneous coronary intervention alone.

  • 30.
    Fröbert, Ole
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Christensen, Kjeld
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fahlman, Åsa
    Swedish University of Agricultural Sciences, Uppsala, Sweden; University of Calgary, Calgary, Canada .
    Brunberg, Sven
    The Scandinavian Brown Bear Research Project, Tackåsen, Orsa, Sweden.
    Josefsson, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Särndahl, Eva
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Swenson, Jon E
    Norwegian University of Life Sciences, Ǻs, Norway; Norwegian Institute for Nature Research, Trondheim, Norway .
    Arnemo, Jon M
    Swedish University of Agricultural Sciences, Umeå, Sweden; Hedmark University College, Stor-Elvdal, Norway .
    Platelet function in brown bear (Ursus arctos) compared to man2010In: Thrombosis journal, ISSN 1477-9560, Vol. 8, p. 11-Article in journal (Refereed)
    Abstract [en]

    Background: Information on hemostasis and platelet function in brown bear (Ursus arctos) is of importance for understanding the physiological, protective changes during hibernation.

    Objective: The study objective was to document platelet activity values in brown bears shortly after leaving the den and compare them to platelet function in healthy humans.

    Methods: Blood was drawn from immobilized wild brown bears 7-10 days after leaving the den in mid April. Blood samples from healthy human adults before and after clopidogrel and acetylsalicylic acid administration served as control. We analyzed blood samples by standard blood testing and platelet aggregation was quantified after stimulation with various agonists using multiple electrode aggregometry within 3 hours of sampling.

    Results: Blood samples were collected from 6 bears (3 females) between 1 and 16 years old and from 10 healthy humans. Results of adenosine diphosphate, aspirin, and thrombin receptor activating peptide tests in bears were all half or less of those in humans. Platelet and white blood cell counts did not differ between species but brown bears had more and smaller red blood cells compared with humans.

    Conclusion: Using three different tests, we conclude that platelet function is lower in brown bears compared to humans. Our findings represent the first descriptive study on platelet function in brown bears and may contribute to explain how bears can endure denning without obvious thrombus building. However, the possibility that our findings reflect test-dependent and not true biological variations in platelet reactivity needs further studies.

  • 31.
    Fröbert, Ole
    et al.
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Götberg, Matthias
    Department of Cardiology, University Hospital Lund, Lund, Sweden.
    Angerås, Oskar
    Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Jonasson, Lena
    Department of Cardiology, University Hospital Linkoping, Linköping, Sweden.
    Erlinge, David
    Department of Cardiology, University Hospital Lund, Lund, Sweden.
    Engström, Thomas
    Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
    Persson, Jonas
    Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Jensen, Svend E.
    Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
    Omerovic, Elmir
    Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    James, Stefan K.
    Department of Cardiology, University Hospital Uppsala, Uppsala, Sweden.
    Lagerqvist, Bo
    Department of Cardiology, University Hospital Uppsala, Uppsala, Sweden.
    Nilsson, Johan
    Cardiology, Heart Centre, department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Kåregren, Amra
    Department of Cardiology, Västerås County Hospital, Västerås, Sweden.
    Moer, Rasmus
    The Feiring Clinic, Feiring, Norway.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Evironmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Agus, David B.
    Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, United States.
    Erglis, Andrejs
    Latvian Centre of Cardiology, Pauls Stradins Clinical University Hospital, Riga, Latvia.
    Jensen, Lisette O.
    Department of Cardiology, Odense University Hospital, Odense, Denmark.
    Jakobsen, Lars
    Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
    Christiansen, Evald H.
    Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
    Pernow, John
    Cardiology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial: A registry-based randomized clinical trial2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 189, p. 94-102Article in journal (Refereed)
    Abstract [en]

    Background: Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI.

    Methods/design: The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all cause death, a new AMI, or stent thrombosis at 1 year.

    Implications: The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI.

  • 32.
    Fröbert, Ole
    et al.
    Örebro University Hospital. Department of Cardiology.
    Scherstén, Fredrik
    Department of Cardiology, Skåne University Hospital, Lund, Sweden.
    James, Stefan K.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Carlsson, Jorg
    Department of Cardiology, Kalmar Hospital, Kalmar, Sweden.
    Lagerqvist, Bo
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Long-term safety and efficacy of drug-eluting and bare metal stents in saphenous vein grafts2012In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 164, no 1, p. 87-93Article in journal (Refereed)
    Abstract [en]

    Background: Long-term safety and efficacy data of drug-eluting stents (DESs) in saphenous vein grafts (SVGs) are lacking. This study sought to compare the clinical outcomes of DES versus bare metal stents (BMS) in SVGs.

    Methods: We studied all stent implantations in SVGs in Sweden during 74 months between 2005 and 2011 registered in the Swedish Coronary Angiography and Angioplasty Registry. We evaluated outcome in patients who received DES compared with those who received BMS after adjustments for differences in clinical, vessel, and lesion characteristics.

    Results: Mean follow-up time was 3 years and 4 months. A total of 4,576 stents, implanted at 3,063 procedures, were included in the analysis of which 2,499 stents (54.6 %) were BMS and 2,077 (45.4%) were DES. The outcome analysis was based on 190 stent thromboses, 898 restenoses, and 523 deaths. The incidence of stent thrombosis did not differ between groups. When adjusted for baseline characteristics, including a propensity score for receiving DES, the incidence of restenosis was significantly lower with DES as compared with BMS (risk ratio 0.83, 95% CI 0.70-0.97, P = .019). There was a difference in mortality in the crude analysis between DES and BMS, and after multivariable adjustment, this difference remained statistically significant (risk ratio 0.80, CI 0.65-0.99, P = .038).

    Conclusions: The use of DES compared with BMS in SVGs was associated with a significantly lower adjusted incidence of restenosis and death in this large, national, all-encompassing propensity adjusted observational study. (Am Heart J 2012;164:87-93.)

  • 33.
    Götberg, Matthias
    et al.
    Department of Cardiology, Lund University, Skåne University Hospital, Lund, Sweden.
    Christiansen, Evald H.
    Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
    Gudmundsdottir, Ingibjorg
    Department of Cardiology, Reykjavik University Hospital, Reykjavik, Iceland.
    Sandhall, Lennart
    Department of Radiology, Helsingborg County Hospital, Helsingborg, Sweden.
    Omerovic, Elmir
    Department of Cardiology, Sahlgrenska University, Gothenburg, Sweden.
    James, Stefan K.
    Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Erlinge, David
    Department of Cardiology, Lund University, Skåne University Hospital, Lund, Sweden.
    Fröbert, Ole
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Instantaneous Wave-Free Ratio versus Fractional Flow Reserve guided intervention (iFR-SWEDEHEART): Rationale and design of a multicenter, prospective, registry-based randomized clinical trial2015In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 170, no 5, p. 945-950Article in journal (Refereed)
    Abstract [en]

    Background: Instantaneous wave-free ratio (iFR) is a new hemodynamic resting index for assessment of coronary artery stenosis severity. iFR uses high frequency sampling to calculate a gradient across a coronary lesion during a period of diastole. The index has been tested against fractional flow reserve (FFR) and found to have an overall classification agreement of 80% to 85%. Whether the level of disagreement is clinically relevant is unknown. Clinical outcome data on iFR are scarce. This study is a registry-based randomized clinical trial, which is a novel strategy using health quality registries as on-line platforms for randomization, case record forms, and follow-up.

    Design/Methods: iFR-SWEDEHEART is a multicenter, prospective, randomized, controlled, clinical open-label clinical trial. Two thousand patients with stable angina or acute coronary syndrome and an indication for physiology-guided assessment of one or more coronary stenoses will be randomized 1: 1 to either iFR- or FFR-guided intervention. The randomization will be conducted online in the Swedish web-based system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART) registry. The trial has a non-inferiority design, with a primary combined end point of all-cause death, non-fatal myocardial infarction, and unplanned revascularization at 12 months. End points will be identified through national registries and undergo central blind adjudication to ensure data quality.

    Discussion: The iFR-SWEDEHEART trial is an registry-based randomized clinical trial evaluating the safety and efficacy of the diagnostic method iFR compared to FFR.

  • 34.
    Götberg, Matthias
    et al.
    Department of Cardiology, Clinical Sciences, Skåne University Hospital, Lund, Sweden.
    Christiansen, Evald H.
    Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
    Gudmundsdottir, Ingibjörg J.
    Department of Cardiology, Reykjavik University Hospital, Reykjavik, Iceland.
    Sandhall, Lennart
    Departments of Cardiology and Radiology, Helsingborg Hospital, Helsingborg, Sweden.
    Danielewicz, Mikael
    Department of Cardiology, Karlstad Hospital, Karlstad, Sweden.
    Jakobsen, Lars
    Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
    Olsson, Sven-Erik
    Departments of Cardiology and Radiology, Helsingborg Hospital, Helsingborg, Sweden.
    Öhagen, Patrik
    Uppsala Clinical Research Center, Uppsala, Sweden.
    Olsson, Hans
    Department of Cardiology, Karlstad Hospital, Karlstad, Sweden.
    Omerovic, Elmir
    Department of Cardiology, Sahlgrenska University, Gothenburg, Sweden.
    Calais, Fredrik
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Lindroos, Pontus
    Department of Cardiology, St. Göran Hospital, Stockholm, Sweden.
    Maeng, Michael
    Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
    Tödt, Tim
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Venetsanos, Dimitrios
    Departments of Cardiology and of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    James, Stefan K.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Kåregren, Amra
    Department of Internal Medicine, Västmanland Hospital, Västerås, Sweden.
    Nilsson, Margareta
    Department of Cardiology, Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
    Carlsson, Jörg
    Department of Cardiology, Kalmar County Hospital, Kalmar, Sweden; Faculty of Health and Life Sciences, Linnaeus University, Kalmar, Sweden.
    Hauer, Dario
    Departments of Cardiology and of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Jensen, Jens
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet,Stockholm, Sweden; Unit of Cardiology, Capio St. Görans Sjukhus, Stockholm, Sweden; Department of Medicine, Sundsvall Hospital, Sundsvall, Sweden.
    Karlsson, Ann-Charlotte
    Department of Cardiology, Halmstad Hospital, Halmstad, Sweden.
    Panayi, Georgios
    Departments of Cardiology and of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Erlinge, David
    Department of Cardiology, Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
    Fröbert, Ole
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Cardiology, Örebro University Hospital, Örebro, Sweden .
    iFR-SWEDEHEART Investigators, Group author
    Instantaneous Wave-free Ratio versus Fractional Flow Reserve to Guide PCI2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 376, no 19, p. 1813-1823Article in journal (Refereed)
    Abstract [en]

    Background: The instantaneous wave-free ratio (iFR) is an index used to assess the severity of coronary-artery stenosis. The index has been tested against fractional flow reserve (FFR) in small trials, and the two measures have been found to have similar diagnostic accuracy. However, studies of clinical outcomes associated with the use of iFR are lacking. We aimed to evaluate whether iFR is noninferior to FFR with respect to the rate of subsequent major adverse cardiac events.

    Methods: We conducted a multicenter, randomized, controlled, open-label clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2037 participants with stable angina or an acute coronary syndrome who had an indication for physiologically guided assessment of coronary-artery stenosis were randomly assigned to undergo revascularization guided by either iFR or FFR. The primary end point was the rate of a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization within 12 months after the procedure.

    Results: A primary end-point event occurred in 68 of 1012 patients (6.7%) in the iFR group and in 61 of 1007 (6.1%) in the FFR group (difference in event rates, 0.7 percentage points; 95% confidence interval [CI], -1.5 to 2.8%; P=0.007 for noninferiority; hazard ratio, 1.12; 95% CI, 0.79 to 1.58; P=0.53); the upper limit of the 95% confidence interval for the difference in event rates fell within the prespecified noninferiority margin of 3.2 percentage points. The results were similar among major subgroups. The rates of myocardial infarction, target-lesion revascularization, restenosis, and stent thrombosis did not differ significantly between the two groups. A significantly higher proportion of patients in the FFR group than in the iFR group reported chest discomfort during the procedure.

    Conclusions: Among patients with stable angina or an acute coronary syndrome, an iFR-guided revascularization strategy was noninferior to an FFR-guided revascularization strategy with respect to the rate of major adverse cardiac events at 12 months.

  • 35.
    Götberg, Matthias
    et al.
    Lund University, Lund, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences.
    Instantaneous Wave-free Ratio versus Fractional Flow Reserve: Reply2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 16, p. 1596-1597Article in journal (Refereed)
  • 36.
    James, Stefan
    et al.
    Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Fröbert, Ole
    Örebro University Hospital.
    Lagerqvist, Bo
    Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Cardiovascular registries: a novel platform for randomised clinical trials2012In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 98, no 18, p. 1329-1331Article in journal (Other academic)
    Abstract [en]

    Registries in cardiovascular medicine ingeneral, and within interventional cardiology in particular, have gained moreattention in medical journals over thepast few years. By consecutive enrolment of complete patient populations, the methodology is a powerful tool for describing healthcare, including the complications and benefits of different therapies. However, it is very importantto be cautious in the interpretation ofthe comparison of outcomes betweendifferent treatment alternatives in obser-vational studies and always consider them non-definitive and hypothesis generating. In order to avoid selection bias, randomisation of patients may be included within a clinical registry, combining some of the most important features of a prospective randomised trial with the key strengths ofa large scale clinical registry. Thereby prospective use of quality registries could potentially revolutionise clinical trials by the fast inclusion of large patient numbers, focus on hard end points and complete follow-up, and at a fraction of the costs of today’s randomised controlled trials.

  • 37.
    Jolly, Sanjit S.
    et al.
    McMaster Univ, Hamilton ON, Canada; Populat Hlth Res Inst, Hamilton Hlth Sci, Hamilton ON, Canada.
    James, Stefan
    Uppsala Clin Res Ctr, Uppsala, Sweden.
    Dzavik, Vladimir
    Peter Munk Cardiac Ctr, Univ Hlth Network, Toronto ON, Canada.
    Cairns, John A.
    Univ British Columbia, Vancouver BC, Canada.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Response by Jolly et al to Letters Regarding Article, "Thrombus Aspiration in ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration"2017In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 135, no 22, p. E1103-E1104Article in journal (Refereed)
  • 38.
    Josefsson, Johan
    et al.
    Department of Cardiology, University Hospital of Örebro, Örebro, Sweden.
    Fröbert, Ole
    Örebro University Hospital. Department of Cardiology, University Hospital of Örebro, Örebro, Sweden.
    Losartan-induced coronary artery spasm2012In: BMJ case reports, ISSN 1757-790X, Vol. 2012, article id bcr2012006252Article in journal (Refereed)
    Abstract [en]

    We report a case of coronary artery spasm documented with angiography in a patient with severe chest pain, electrocardiographic ST-segment elevations and highly elevated troponin I. Symptom onset was 15 min after the patient's first-ever intake of losartan. Although parts of the clinical presentation suggested allergy or anaphylaxis, laboratory testing did not support this.

  • 39.
    Karlsson, Sofia
    et al.
    Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
    Andell, Pontus
    Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
    Mohammad, Moman A
    Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
    Koul, Sasha
    Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
    Olivecrona, Göran K
    Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
    James, Stefan K
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Erlinge, David
    Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.
    Heparin pre-treatment in patients with ST-segment elevation myocardial infarction and the risk of intracoronary thrombus and total vessel occlusion: Insights from the TASTE trial2019In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 8, no 1, p. 15-23Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Pre-treatment with unfractionated heparin is common in ST-segment elevation myocardial infarction (STEMI) protocols, but the effect on intracoronary thrombus burden is unknown. We studied the effect of heparin pre-treatment on intracoronary thrombus burden and Thrombolysis in Myocardial Infarction (TIMI) flow prior to percutaneous coronary intervention in patients with STEMI.

    METHODS: The Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia (TASTE) trial angiographically assessed intracoronary thrombus burden and TIMI flow, prior to percutaneous coronary intervention, in patients with STEMI. In this observational sub-study, patients pre-treated with heparin were compared with patients not pre-treated with heparin. Primary end points were a visible intracoronary thrombus and total vessel occlusion prior to percutaneous coronary intervention. Secondary end points were in-hospital bleeding, in-hospital stroke and 30-day all-cause mortality.

    RESULTS: Heparin pre-treatment was administered in 2898 out of 7144 patients (41.0%). Patients pre-treated with heparin less often presented with an intracoronary thrombus (61.3% vs. 66.0%, p<0.001) and total vessel occlusion (62.9% vs. 71.6%, p<0.001). After adjustments, heparin pre-treatment was independently associated with a reduced risk of intracoronary thrombus (odds ratio (OR) 0.73, 95% confidence interval (CI)=0.65-0.83) and total vessel occlusion (OR 0.64, 95% CI=0.56-0.73), prior to percutaneous coronary intervention. There were no significant differences in secondary end points of in-hospital bleeding (OR 0.84, 95% CI=0.55-1.27), in-hospital stroke (OR 1.17, 95% CI=0.48-2.82) or 30-day all-cause mortality (hazard ratio 0.88, 95% CI=0.60-1.30).

    CONCLUSIONS: Heparin pre-treatment was independently associated with a lower risk of intracoronary thrombus and total vessel occlusion before percutaneous coronary intervention in patients with STEMI, without evident safety concerns, in this large multi-centre observational study.

  • 40.
    Kwakkenbos, Linda
    et al.
    Behavioural Science Institute, Clinical Psychology, Radboud University, Nijmegen, Gelderland, Netherlands.
    Imran, Mahrukh
    Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal QC, Canada.
    McCord, Kimberly A.
    Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
    Sampson, Margaret
    Library Services, Children's Hospital of Eastern Ontario, Ottawa ON, Canada.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Gale, Chris
    Section of Neonatal Medicine, Department of Medicine, Imperial College London, London, United Kingdom.
    Hemkens, Lars G.
    Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
    Langan, Sinead M.
    Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
    Moher, David
    Centre for Journalology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa ON, Canada.
    Relton, Clare
    Centre for Clinical Trials and Methodology, Barts Institute of Population Health Science, Queen Mary University, London, United Kingdom.
    Zwarenstein, Merrick
    Department of Family Medicine, Western University, London, United Kingdom; Institute for Clinical Evaluative Sciences, Toronto ON, Canada.
    Benchimol, Eric I.
    Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa ON, Canada; Institute for Clinical Evaluative Sciences, Ottawa ON, Canada; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa ON, Canada.
    Boutron, Isabelle
    Sorbonne Paris Cité Epidemiology and Statistics Research Center, INSERM, UMR1153, Paris, France; Centre d'Épidémiologie Clinique, Hôpital Hôtel Dieu, Assistance Publique-Hôpitaux de Paris, Paris, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
    Campbell, Marion K.
    Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom.
    Erlinge, David
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    Jawad, Sena
    Section of Neonatal Medicine, Department of Medicine, Imperial College London, London, United Kingdom.
    Ravaud, Philippe
    Sorbonne Paris Cité Epidemiology and Statistics Research Center, INSERM, UMR1153, Paris, France; Centre d'Épidémiologie Clinique, Hôpital Hôtel Dieu, Assistance Publique-Hôpitaux de Paris, Paris, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
    Rice, Danielle B.
    Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal QC, Canada; Department of Psychology, McGill University, Montréal QC, Canada.
    Sauve, Maureen
    Scleroderma Society of Ontario, Hamilton, ON, Canada; Scleroderma Canada, Hamilton ON, Canada.
    van Staa, Tjeerd P.
    Health E-Research Centre, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom; Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, Netherlands.
    Thabane, Lehana
    Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton ON, Canada.
    Uher, Rudolf
    Department of Psychiatry, Dalhousie University, Halifax NS, Canada.
    Verkooijen, Helena M.
    Department of Epidemiology, University Medical Center Utrecht, Utrecht, Netherlands; Department of Epidemiology, University of Utrecht, Utrecht, Netherlands.
    Juszczak, Edmund
    NPEU Clinical Trials Unit, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Thombs, Brett D.
    Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal QC, Canada; Department of Psychology, McGill University, Montréal QC, Canada; Department of Psychiatry, McGill University, Montreal QC, Canada; Departments of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal QC, Canada; Department of Medicine, McGill University, Montreal QC, Canada; Departments of Educational and Counselling Psychology, McGill University, Montreal QC, Canada.
    Protocol for a scoping review to support development of a CONSORT extension for randomised controlled trials using cohorts and routinely collected health data2018In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 8, no 8, article id e025266Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Randomised controlled trials (RCTs) conducted using cohorts and routinely collected health data, including registries, electronic health records and administrative databases, are increasingly used in healthcare intervention research. The development of an extension of the CONsolidated Standards of Reporting Trials (CONSORT) statement for RCTs using cohorts and routinely collected health data is being undertaken with the goal of improving reporting quality by setting standards early in the process of uptake of these designs. To develop this extension to the CONSORT statement, a scoping review will be conducted to identify potential modifications or clarifications of existing reporting guideline items, as well as additional items needed for reporting RCTs using cohorts and routinely collected health data.

    Methods and analysis: In separate searches, we will seek publications on methods or reporting or that describe protocols or results from RCTs using cohorts, registries, electronic health records and administrative databases. Data sources will include Medline and the Cochrane Methodology Register. For each of the four main types of RCTs using cohorts and routinely collected health data, separately, two investigators will independently review included publications to extract potential checklist items. A potential item will either modify an existing CONSORT 2010, Strengthening the Reporting of Observational Studies in Epidemiology or REporting of studies Conducted using Observational Routinely collected health Data item or will be proposed as a new item. Additionally, we will identify examples of good reporting in RCTs using cohorts and routinely collected health data.

    Ethics and dissemination: The proposed scoping review will help guide the development of the CONSORT extension statement for RCTs conducted using cohorts and routinely collected health data.

  • 41.
    Lebwohl, Benjamin
    et al.
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New YorkNY, USA; Department of Medical Epidemiology and Biostatistics, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Emilsson, Louise
    Primary care research unit, Vårdcentralen Värmlands Nysäter, Värmland County, Karlstad, Sweden; Department of Medicine, Örebro University, Örebro, Sweden.
    Fröbert, Ole
    Örebro University Hospital. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Einstein, Andrew J.
    Division of Cardiology, Department of Medicine, and Department of Radiology, Columbia University College of Physicians and Surgeons, New York, USA;-Presbyterian Hospital, New York, USA.
    Green, Peter H. R.
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Mucosal healing and the risk of ischemic heart disease or atrial fibrillation in patients with celiac disease: a population-based study2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 1, article id e0117529Article in journal (Refereed)
    Abstract [en]

    Background: Patients with celiac disease (CD), characterized histologically by villous atrophy (VA) of the small intestine, have an increased risk of ischemic heart disease (IHD) and atrial fibrillation (AF), risks that persist for years after commencing the gluten-free diet. It is unknown whether persistent VA on follow-up biopsy, rather than mucosal healing, affects the risk of IHD or AF.

    Methods: We identified patients with histologic evidence of CD diagnosed at all 28 pathology departments in Sweden. Among patients who underwent a follow-up small intestinal biopsy, we compared patients with persistent VA to those who showed histologic improvement, with regard to the development of IHD (angina pectoris or myocardial infarction) or AF.

    Results: Among patients with CD and a follow-up biopsy (n = 7,440), the median age at follow-up biopsy was 25 years, with 1,063 (14%) patients who were >= 60 years at the time of follow-up biopsy. Some 196 patients developed IHD and 205 patients developed AF. After adjusting for age, gender, duration of CD, calendar period, and educational attainment, there was no significant effect of persistent VA on IHD (adjusted HR 0.97; 95%CI 0.73-1.30). Adjusting for diabetes had a negligible effect (adjusted HR 0.98; 95%CI 0.73-1.31). There was no significant association between persistent VA and the risk of AF (adjusted HR 0.98; 95%CI 0.74-1.30).

    Conclusions: In this population-based study of patients with CD, persistent VA on follow-up biopsy was not associated with an increased risk of IHD or AF. Failed mucosal healing does not influence the risk of these cardiac events.

  • 42.
    Loiske, Karin
    et al.
    Örebro University, School of Health and Medical Sciences. Clinical Physiology, Örebro University Hospital, Örebro, Sweden.
    Waldenborg, Micael
    Clinical Physiology, Örebro University Hospital, Örebro, Sweden.
    Fröbert, Ole
    Cardiology, Örebro University Hospital, Örebro, Sweden.
    Rask, Peter
    Clinical Physiology, Örebro University Hospital, Örebro, Sweden.
    Emilsson, Kent
    Clinical Physiology, Örebro University Hospital, Örebro, Sweden.
    Left and right ventricular systolic long-axis function and diastolic function in patients with takotsubo cardiomyopathy2011In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 31, no 3, p. 203-208Article in journal (Refereed)
    Abstract [en]

    Aims: Takotsubo cardiomyopathy is characterized by apical wall motion abnormalities without coronary stenosis. Limited information is available on the genesis of the underlying reversible contractile disorder. Our objective in this prospective study was to investigate biventricular changes in systolic long-axis function and diastolic parameters in the acute phase and after recovery.

    Methods and results: Thirteen consecutive patients were examined by echocardiography and coronary angiography at admission and again by echocardiography after 3 months. Amplitudes, systolic and diastolic velocities of the mitral and tricuspid annuli and conventional diastolic parameters were measured. Systolic long-axis shortening of the left ventricle (LV) and right ventricle (RV) improved from 9·6 ± 2·2 mm to 11·2 ± 1·9 mm (P = 0·02) and from 21·3 ± 3·6 mm to 24·1 ± 2·8 mm (P = 0·02), respectively. LV systolic, early and late diastolic velocities measured by pulsed-wave tissue Doppler also improved, while additional conventional diastolic parameters of the LV and RV diastolic function were unchanged.Conclusions: Takotsubo cardiomyopathy temporarily affects systolic LV and RV function, while most diastolic parameters remain unchanged

  • 43.
    Lundman, P.
    et al.
    Department of Clinical Sciences, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden.
    Karayiannides, S.
    Department of Clinical Sciences, Karolinska Institutet, Stockholm, Sweden; Department of Internal Medicine, Danderyd University Hospital, Stockholm, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    James, S.
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research center, Uppsala University, Uppsala, Sweden.
    Lagerqvist, B.
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research center, Uppsala University, Uppsala, Sweden.
    Norhammar, A.
    Cardiology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Higher one-year mortality in patients with diabetes and ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no Suppl. 1, p. S529-S530Article in journal (Other academic)
    Abstract [en]

    Background and aims: Patients with diabetes mellitus have a worse prognosis after acute coronary syndromes than patients without diabetes. Outcomes in patients with diabetes after ST-segment elevation myocar-dial infarction (STEMI) in the era of modern interventional treatment and antiplatelet therapy are less well studied. The aim is to characterise outcomes and complications in a contemporary population with diabetes and STEMI undergoing primary percutaneous coronary intervention (PCI).

    Materials and methods: In the registry-based randomised Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE) trial, 7244 patients with STEMI were randomised to undergo manual thrombus aspiration followed by PCI or to undergo PCI alone. Thrombus aspiration did not affect mortality at one year in the 1005 patients (13.9%) with diabetes [Hazard ratio (HR) 1.04; CI 0.69-1.58,p=0.839]. Therefore, all patients with diabetes, irrespective ofrandomisation in TASTE, were studied as one cohort. All patients were followed for incidence of all-cause mortality, myocardial infarction or stent thrombosis until one year after index event. HRs were calculated using a Cox proportional hazard regression model adjusted for comorbidities.

    Results: Patients with diabetes were older (mean age 67.6 vs 66.0 years, p<0.001), more often had a previous myocardial infarction (19.9 vs 10.3%, p<0.001) and undergone previous PCI (17.3 vs 8.4%, p<0.001). Thrombus grade did not differ between patients with and without diabetes (Grade 0 to Grade 5, p=0.909) and neither did the type of affected coronary vessel. Pharmacological cardiovascular treatment did not differ between groups, but the use of drug eluting stents was higher in patients with diabetes (59.0 vs 48.4%, p<0.001). After adjustment for comorbidities, diabetes independently increased the risk for mortality (HR 1.57; CI 1.23-2.00, p<0.001), but was not an independent risk factor for future myocardial infarction or stent thrombosis.

    Conclusion: Diabetes remained an adverse prognostic risk factor in this contemporary setting, resulting in increased one-year mortality in a large cohort of patients with STEMI treated with PCI. This was not influenced by thrombus aspiration and not explained by a higher thrombus burden or differences in cardiovascular medical therapy compared to patients without diabetes.

  • 44.
    Mahmoud, Karim D.
    et al.
    Department of Cardiology, Thorax Center, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Cardiology, Sint Franciscus Gasthuis, Rotterdam, The Netherlands.
    Jolly, Sanjit S.
    Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton Ontario, Canada.
    James, Stefan
    Department of Medical Science, Uppsala University and Uppsala Clinical Research Centre, Uppsala, Sweden.
    Dzavik, Vladimir
    Peter Munk Cardiac Centre, University Health Network, Toronto Ontario, Canada.
    Cairns, John A.
    University of British Columbia, Vancouver British Columbia, Canada.
    Olivecrona, Göran K.
    Skåne University Hospital, Lund University, Lund, Sweden.
    Renlund, Henrik
    Department of Medical Science, Uppsala University and Uppsala Clinical Research Centre, Uppsala, Sweden.
    Gao, Peggy
    Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton Ontario, Canada.
    Lagerqvist, Bo
    Department of Medical Science, Uppsala University and Uppsala Clinical Research Centre, Uppsala, Sweden.
    Alazzoni, Ashraf
    Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton Ontario, Canada.
    Kedev, Sasko
    University Clinic of Cardiology, Sts. Cyril and Methodius University, Skopje, Macedonia.
    Stankovic, Goran
    Department of Cardiology, Clinical Center of Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
    Meeks, Brandi
    Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton Ontario, Canada.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Zijlstra, Felix
    Department of Cardiology, Thorax Center, Erasmus Medical Center, Rotterdam, The Netherlands.
    Clinical impact of direct stenting and interaction with thrombus aspiration in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: Thrombectomy Trialists Collaboration2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 26, p. 2472-2479Article in journal (Refereed)
    Abstract [en]

    Aims: Preliminary studies suggest that direct stenting (DS) during percutaneous coronary intervention (PCI) may reduce microvascular obstruction and improve clinical outcome. Thrombus aspiration may facilitate DS. We assessed the impact of DS on clinical outcome and myocardial reperfusion and its interaction with thrombus aspiration among ST-segment elevation myocardial infarction (STEMI) patients undergoing PCI.

    Methods and results: Patient-level data from the three largest randomized trials on routine manual thrombus aspiration vs. PCI only were merged. A 1:1 propensity matched population was created to compare DS and conventional stenting. Synergy between DS and thrombus aspiration was assessed with interaction P-values in the final models. In the unmatched population (n= 17329), 32% underwent DS and 68% underwent conventional stenting. Direct stenting rates were higher in patients randomized to thrombus aspiration as compared with PCI only (41% vs. 22%; P < 0.001). Patients undergoing DS required less contrast (162 mL vs. 172 mL; P < 0.001) and had shorter fluoroscopy time (11.1 min vs. 13.3 min; P < 0.001). After propensity matching (n = 10944), no significant differences were seen between DS and conventional stenting with respect to 30-day cardiovascular death [1.7% vs. 1.9%; hazard ratio 0.88, 95% confidence interval (CI) 0.55-1.41; P=0.60; P-interaction = 0.96) and 30-day stroke or transient ischaemic attack (0.6% vs. 0.4%; odds ratio 1.02; 95% CI 0.14-7.54; P= 0.99; P-interaction = 0.81). One-year results were similar. No significant differences were seen in electrocardiographic and angiographic myocardial reperfusion measures.

    Conclusion: Direct stenting rates were higher in patients randomized to thrombus aspiration. Clinical outcomes and myocardial reperfusion measures did not differ significantly between DS and conventional stenting and there was no interaction with thrombus aspiration.

  • 45.
    Mohammad, Moman A.
    et al.
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Andell, Pontus
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Koul, Sasha
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Desta, Liyew
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Jernberg, Tomas
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Omerovic, Elmir
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Spaak, Jonas
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Fröbert, Ole
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Jensen, Jens
    Department of Medicine, Capio S:t Görans Sjukhus, Karolinska Institutet, Stockholm, Sweden.
    Engström, Thomas
    The Heart Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
    Hofman-Bang, Claes
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Persson, Hans
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Erlinge, David
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Intravenous beta-blocker therapy in ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention is not associated with benefit regarding short-term mortality: a Swedish nationwide observational study2017In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 13, no 2, p. E210-E218Article in journal (Refereed)
    Abstract [en]

    Aims: Our aim was to investigate the impact of intravenous (IV) beta-blocker therapy on short-term mortality and other in-hospital events in patients with ST-segment elevation myocardial infarction (STEMI) treated with dual antiplatelet therapy (DAPT) and primary percutaneous coronary intervention (PCI).

    Methods and results: Using the nationwide Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, we identified all patients with STEMI undergoing PCI between 2006 and 2013. Patients with cardiogenic shock and cardiac arrest at presentation were excluded. The primary endpoint was mortality within 30 days. Secondary endpoints were in-hospital events (mortality, cardiogenic shock and left ventricular ejection fraction [LVEF] <40% at discharge). We adjusted for confounders with a multivariable model and propensity score matching. Out of 16,909 patients, 2,876 (17.0%) were treated with an IV beta-blocker. After adjusting for confounders, the IV beta-blocker group had higher 30-day all-cause mortality (HR: 1.44, 95% CI: 1.14-1.83), more in-hospital cardiogenic shock (OR: 1.53, 95% CI: 1.09-2.16) and were more often discharged with an LVEF <40% (OR: 1.70, 95% CI: 1.51-1.92).

    Conclusions: In this large nationwide observational study, the use of IV beta-blockers in patients with STEMI treated with primary PCI was associated with higher short-term mortality, lower LVEF at discharge, as well as a higher risk of in-hospital cardiogenic shock.

  • 46.
    Mohammad, Moman A
    et al.
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Karlsson, Sofia
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Haddad, Jonathan
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Cederberg, Björn
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Jernberg, Tomas
    Department of clinical sciences, Danderyd's University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Lindahl, Bertil
    Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Koul, Sasha
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Erlinge, David
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Christmas, national holidays, sport events, and time factors as triggers of acute myocardial infarction: SWEDEHEART observational study 1998-20132018In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 363, article id k4811Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To study circadian rhythm aspects, national holidays, and major sports events as triggers of myocardial infarction.

    DESIGN: Retrospective observational study using the nationwide coronary care unit registry, SWEDEHEART.

    SETTING: Sweden.

    PARTICIPANTS: 283 014 cases of myocardial infarction reported to SWEDEHEART between 1998 and 2013. Symptom onset date was documented for all cases, and time to the nearest minute for 88%.

    INTERVENTIONS: Myocardial infarctions with symptom onset on Christmas/New Year, Easter, and Midsummer holiday were identified. Similarly, myocardial infarctions that occurred during a FIFA World Cup, UEFA European Championship, and winter and summer Olympic Games were identified. The two weeks before and after a holiday were set as a control period, and for sports events the control period was set to the same time one year before and after the tournament. Circadian and circaseptan analyses were performed with Sunday and 24:00 as the reference day and hour with which all other days and hours were compared. Incidence rate ratios were calculated using a count regression model.

    MAIN OUTCOME MEASURES: Daily count of myocardial infarction.

    RESULTS: Christmas and Midsummer holidays were associated with a higher risk of myocardial infarction (incidence rate ratio 1.15, 95% confidence interval 1.12 to 1.19, P<0.001, and 1.12, 1.07 to 1.18, P<0.001, respectively). The highest associated risk was observed for Christmas Eve (1.37, 1.29 to 1.46, P<0.001). No increased risk was observed during Easter holiday or sports events. A circaseptan and circadian variation in the risk of myocardial infarction was observed, with higher risk during early mornings and on Mondays. Results were more pronounced in patients aged over 75 and those with diabetes and a history of coronary artery disease.

    CONCLUSIONS: In this nationwide real world study covering 16 years of hospital admissions for myocardial infarction with symptom onset documented to the nearest minute, Christmas, and Midsummer holidays were associated with higher risk of myocardial infarction, particularly in older and sicker patients, suggesting a role of external triggers in vulnerable individuals.

  • 47.
    Mohammad, Moman A.
    et al.
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    Koul, Sasha
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    Rylance, Rebecca
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Alfredsson, Joakim
    Department of Cardiology, Linköping University Hospital, Linköping, Sweden.
    Sahlen, Anders
    Karolinska Institutet, Department of Medicine, Huddinge, Sweden; National Heart Centre Singapore, Singapore.
    Witt, Nils
    Department of Cardiology, Clinical Science and Education, Södersjukhuset, Stockholm, Sweden.
    Jernberg, Tomas
    Danderyds University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Muller, James
    Cardiovascular Division, Brigham and Women's Hospital, Boston Massachusetts, USA.
    Erlinge, David
    Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
    Association of Weather With Day-to-Day Incidence of Myocardial Infarction: A SWEDEHEART Nationwide Observational Study2018In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 3, no 11, p. 1081-1089Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: Whether certain weather conditions modulate the onset of myocardial infarction (MI) is of great interest to clinicians because it could be used to prevent MIs as well as guide allocation of health care resources.

    OBJECTIVE: To determine if weather is associated with day-to-day incidence of MI.

    DESIGN, SETTING, AND PARTICIPANTS: In this prospective, population-based and nationwide setting, daily weather data from the Swedish Meteorological and Hydrological Institute were extracted for all MIs reported to the Swedish nationwide coronary care unit registry, Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART), during 1998 to 2013 and then merged with each MI on date of symptom onset and coronary care unit. All patients admitted to any coronary care unit in Sweden owing to MI were included, A total of 280 873 patients were included, of whom 92 044 were diagnosed as having ST-elevation MI. Weather data were available for 274 029 patients (97.6%), which composed the final study population. Data were analyzed between February 2017 and April 2018.

    EXPOSURES: The nationwide daily mean air temperature, minimum air temperature, maximum air temperature, wind velocity, sunshine duration, atmospheric air pressure, air humidity, snow precipitation, rain precipitation, and change in air temperature.

    MAIN OUTCOMES AND MEASURES: The nationwide daily counts of MI as outcome.

    RESULTS: In 274 029 patients, mean (SD) age was 71.7 (12) years. Incidence of MI increased with lower air temperature, lower atmospheric air pressure, higher wind velocity, and shorter sunshine duration. The most pronounced association was observed for air temperature, where a 1-SD increase in air temperature (7.4 degrees C) was associated with a 2.8% reduction in risk of MI (unadjusted incidence ratio, 0.972; 95% CI, 0.967-0.977; P <.001). Results were consistent for non-ST-elevation MI as well as ST-elevation MI and across a large range of subgroups and health care regions.

    CONCLUSIONS AND RELEVANCE: In this large, nationwide study, low air temperature, low atmospheric air pressure, high wind velocity, and shorter sunshine duration were associated with risk of MI with the most evident association observed for air temperature.

  • 48.
    Nordenskjöld, Anna M.
    et al.
    Department of Cardiology, Faculty of Health, Örebro University, Örebro, Sweden .
    Hammar, Per
    Department of Radiology, Västmanland Hospital Västerås, Västerås, Sweden.
    Ahlström, Håkan
    Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden.
    Bjerner, Tomas
    Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden.
    Duvernoy, Olov
    Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden.
    Eggers, Kai M.
    Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Hadziosmanovic, Nermin
    Uppsala Clinical Research Centre, Uppsala, Sweden.
    Lindahl, Bertil
    Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
    Unrecognized myocardial infarction assessed by cardiac magnetic resonance imaging: prognostic implications2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 2, article id e0148803Article in journal (Refereed)
    Abstract [en]

    Background: Clinically unrecognized myocardial infarctions (UMI) are not uncommon and may be associated with adverse outcome. The aims of this study were to determine the prognostic implication of UMI in patients with stable suspected coronary artery disease (CAD) and to investigate the associations of UMI with the presence of CAD.

    Methods and Findings: In total 235 patients late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging and coronary angiography were performed. For each patient with UMI, the stenosis grade of the coronary branch supplying the infarcted area was determined. UMIs were present in 25% of the patients and 67% of the UMIs were located in an area supplied by a coronary artery with a stenosis grade >= 70%. In an age-and gender-adjusted model, UMI independently predicted the primary endpoint (composite of death, myocardial infarction, resuscitated cardiac arrest, hospitalization for unstable angina pectoris or heart failure within 2 years of follow-up) with an odds ratio of 2.9; 95% confidence interval 1.1-7.9. However, this association was abrogated after adjustment for age and presence of significant coronary disease. There was no difference in the primary endpoint rates between UMI patients with or without a significant stenosis in the corresponding coronary artery.

    Conclusions: The presence of UMI was associated with a threefold increased risk of adverse events during follow up. However, the difference was no longer statistically significant after adjustments for age and severity of CAD. Thus, the results do not support that patients with suspicion of CAD should be routinely investigated by LGE-CMR for UMI. However, coronary angiography should be considered in patients with UMI detected by LGE-CMR.

  • 49.
    Nordenskjöld, Anna M.
    et al.
    Department of Cardiology, Faculty of Health, Örebro University, Örebro, Sweden.
    Hammar, Per
    Department of Radiology, Västerås Hospital, Västerås, Sweden; Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden.
    Ahlström, Håkan
    Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden.
    Bjerner, Tomas
    Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden.
    Duvernoy, Olov
    Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden.
    Eggers, Kai M.
    Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Centre, Uppsala, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Hadziosmanovic, Nermin
    Uppsala Clinical Research Centre, Uppsala, Sweden.
    Lindahl, Bertil
    Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Centre, Uppsala, Sweden.
    Unrecognized myocardial infarctions detected by cardiac magnetic resonance imaging are associated with cardiac troponin I levels2016In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 455, p. 189-194Article in journal (Refereed)
    Abstract [en]

    Background: Both unrecognized myocardial infarction (UMI) and elevated levels of biomarkers are common in patients with stable coronary artery disease (CAD). The objective of this study was to determine the association between levels of cardiac biomarkers, UMI and extent of CAD in patients with stable CAD.

    Methods: A total of 235 patients (median age: 65years; 34% women) with stable CAD without previously known myocardial infarction were examined with late gadolinium enhancement cardiovascular magnetic resonance imaging and coronary angiography. Blood samples were drawn at enrolment and high sensitivity cardiac troponin I (cTnI), NT-proBNP and Galectin-3 were analyzed.

    Results: UMI was detected in 58 patients (25%). The median levels of cTnI, NT-proBNP and Galectin-3 were significantly higher in patients with UMI compared to those without, (p<0.001, p=0.006 and p=0.033, respectively). After adjustment for cardiovascular risk factors, left ventricular ejection fraction and renal function, cTnI remained independently associated with the presence of UMI (p=0.031) and the extent of CAD (p=0.047). Neither NT-proBNP, nor Galectin-3, was independently associated with UMI or extent of CAD.

    Conclusions: The independent association between levels of cTnI and UMI indicates a common pathophysiological pathway for the cTnI elevation and development of UMI.

    Clinical trial registration: ClinicalTrials.gov (NCT01257282).

  • 50.
    Nyström, Thomas
    et al.
    Division of Endocrinology, Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden.
    James, Stefan K.
    Cardiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Lindahl, Bertil
    Cardiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Östlund, Ollie
    Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Erlinge, David
    Cardiology, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Herlitz, Johan
    Department of Health Sciences, University of Borås, Borås, Sweden.
    Omerovic, Elmir
    Department of Molecular and Clinical Medicine and Sahlgrenska University Hospital, Department of Cardiology, University of Gothenburg, Gothenburg, Sweden.
    Mellbin, Linda
    Division of Cardiology, Department of Medicine, Solna, Karolinska Institutet and Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden.
    Alfredsson, Joakim
    Department of Medical and Health Sciences and Department of Cardiology, Linköping University, Linköping, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Jernberg, Tomas
    Cardiology, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Hofmann, Robin
    Division of Cardiology, Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden.
    Oxygen Therapy in Myocardial Infarction Patients With or Without Diabetes: A Predefined Subgroup Analysis From the DETO2X-AMI Trial2019In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, article id dc190590Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine the effects of oxygen therapy in myocardial infarction (MI) patients with and without diabetes.

    RESEARCH DESIGN AND METHODS: In the Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction (DETO2X-AMI) trial, 6,629 normoxemic patients with suspected MI were randomized to oxygen at 6 L/min for 6-12 h or ambient air. In this prespecified analysis involving 5,010 patients with confirmed MI, 934 had known diabetes. Oxidative stress may be of particular importance in diabetes, and the primary objective was to study the effect of supplemental oxygen on the composite of all-cause death and rehospitalization with MI or heart failure (HF) at 1 year in patients with and without diabetes.

    RESULTS: = 0.81). There was no statistically significant difference for the individual components of the composite end point or the rate of cardiovascular death up to 1 year. Likewise, corresponding end points in patients without diabetes were similar between the treatment groups.

    CONCLUSIONS: Despite markedly higher event rates in patients with MI and diabetes, oxygen therapy did not significantly affect 1-year all-cause death, cardiovascular death, or rehospitalization with MI or HF, irrespective of underlying diabetes, in line with the results of the entire study.

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