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  • 1.
    Aaseth, Jan
    et al.
    Innlandet Hospital Trust, Norway; Hedmark University of Appl Science, Norway.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Bjorklund, Geir
    Council Nutr and Environm Med, Norway.
    Hestad, Knut
    Innlandet Hospital Trust, Norway; Hedmark University of Appl Science, Norway.
    Dusek, Petr
    Charles University of Prague, Czech Republic; Charles University of Prague, Czech Republic; Gen University Hospital Prague, Czech Republic.
    Roos, Per M.
    Karolinska Institute, Sweden; St Goran Hospital, Sweden.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Treatment strategies in Alzheimers disease: a review with focus on selenium supplementation2016In: Biometals, ISSN 0966-0844, E-ISSN 1572-8773, Vol. 29, no 5, 827-839 p.Article in journal (Refereed)
    Abstract [en]

    Alzheimers disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (A beta) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce A beta production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral A beta plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.

  • 2.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Baranowski, Jacek
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Dahlin, Lars-Göran
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nielsen, Niels Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Transvenous Implantation of a Stent Valve in Patients With Degenerated Mitral Prostheses and Native Mitral Stenosis2016In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 101, no 6, 2279-2284 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The purpose of this study was to report the use of a transvenous transseptal approach using a stent valve in patients with degenerated biological mitral valve prostheses, regurgitation after mitral repair, and native mitral stenosis.

    METHODS: Ten patients (median age, 74 years; range, 20-89 years; 5 men and 5 women) with degenerated mitral bioprosthetic valves (n = 7), failed mitral repair (n = 1), or calcified native stenotic valves (n = 2) underwent transvenous implantation of a stent valve.

    RESULTS: The procedure was initially successful in all patients. Predilation was performed for balloon sizing only in the 2 patients with native mitral stenosis. The stent valve was deployed during 1 period of rapid pacing. A guidewire, as a loop from the right femoral vein and through the left ventricular apex, facilitated a good angle and secure positioning of the stent valve. An ultrasonographically guided puncture of the apex was carried out in 6 patients, and in the other 4 we performed a minithoracotomy before apical puncture. All valves were implanted in a good position with improved function and without significant paravalvular leakage (PVL). There were no periprocedural deaths. The 30-day survival was 80% (8 of 10 patients), and 60% (6 of 10) of patients were still alive a median time of 290 days after the procedure.

    CONCLUSIONS: Transvenous transseptal implantation of a stent valve was performed in 10 patients with mitral valve disease, with good early functional results. These high-risk patients must be carefully selected by a multidisciplinary team because the procedure carries a high mortality.

  • 3.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nielsen, Niels Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Baranowski, Jacek
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Can predilatation in transcatheter aortic valve implantation be omitted? - a prospective randomized study2016In: Journal of Cardiothoracic Surgery, ISSN 1749-8090, E-ISSN 1749-8090, Vol. 11, no 124Article in journal (Refereed)
    Abstract [en]

    Background: The use of a balloon expandable stent valve includes balloon predilatation of the aortic stenosis before valve deployment. The aim of the study was to see whether or not balloon predilatation is necessary in transcatheter aortic valve replacement (TAVI). Methods: Sixty consecutive TAVI patients were randomized to the standard procedure or to a protocol where balloon predilatation was omitted. Results: There were no significant differences between the groups regarding early hemodynamic results or complication rates. Conclusions: TAVI can be performed safely without balloon predilatation and with the same early results as achieved with the standard procedure including balloon predilatation. The reduction in the number of pacing periods required may be beneficial for the patient.

  • 4.
    Aidemark, Jan
    et al.
    Linnaeus University, Sweden.
    Askenas, Linda
    Linnaeus University, Sweden.
    Martensson, Jan
    Jonköping University, Sweden.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Challenges for Heart Failure Patients Self-Care Systems Analysis of Patients Needs2014In: CENTERIS 2014 - CONFERENCE ON ENTERPRISE INFORMATION SYSTEMS / PROJMAN 2014 - INTERNATIONAL CONFERENCE ON PROJECT MANAGEMENT / HCIST 2014 - INTERNATIONAL CONFERENCE ON HEALTH AND SOCIAL CARE INFORMATION SYSTEMS AND TECHNOLOGIES, ELSEVIER SCIENCE BV , 2014, Vol. 16, 1256-1264 p.Conference paper (Refereed)
    Abstract [en]

    Self-care is important for heart failure patients. However, what are the views of patients on their situation when it comes to realizing self-care? The aim of the paper is to investigate the self-care needs of HF patients, by understanding the issues they embrace in their self-care processes. In this paper we make a review of 17 interviews and make a classification of what the needs are for possible information technology support systems. Based on the analysis of these interviews, we identify the diversity of needs in support of activities related to different background conditions and the dynamics of change of learning and changes in the heart failure condition. The contribution of the paper is a framework for understanding the diversity of needs and the specific situations of this group of patients.

  • 5.
    Aidemark, Jan
    et al.
    Linnaeus University, Sweden.
    Askenas, Linda
    Linnaeus University, Sweden.
    Nygardh, Anette
    Jonköping University, Sweden.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    User involvement in the co-design of self-care support systems for heart failure patients2015In: CONFERENCE ON ENTERPRISE INFORMATION SYSTEMS/INTERNATIONAL CONFERENCE ON PROJECT MANAGEMENT/CONFERENCE ON HEALTH AND SOCIAL CARE INFORMATION SYSTEMS AND TECHNOLOGIES, CENTERIS/PROJMAN / HCIST 2015, ELSEVIER SCIENCE BV , 2015, Vol. 64, 118-124 p.Conference paper (Refereed)
    Abstract [en]

    In this paper the nature of user involvement in a co-design process will be explored. The outlines of a research project aiming at developing support systems for self-care inpatients suffering from chronic heart failure will be presented. The project is planned to perform a co-design effort where users (patients and healthcare professionals) will be given the opportunity to influence the development of support systems. We will discuss a number of possibilities and challenges that lie in the design of this kind of project and also some findings from its early stages. This report presents the experiences of users input, which are discussed in the context of previous research on benefits of user contributions in systems development. (C) 2015 The Authors. Published by Elsevier B.V.

  • 6.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust and Hedmark University College, Norway.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Less increase of copeptin and MR-proADM due to intervention with selenium and coenzyme Q10 combined: Results from a 4-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.2015In: Biofactors, ISSN 0951-6433, E-ISSN 1872-8081, Vol. 41, no 6, 443-452 p.Article in journal (Refereed)
    Abstract [en]

    Intervention with selenium and coenzyme Q10 have recently been found to reduce mortality and increase cardiac function. The mechanisms behind these effects are unclear. As selenium and coenzyme Q10 is involved in the anti-oxidative defence, the present study aimed to evaluate effects of selenium and coenzyme Q10 on copeptin and adrenomedullin as oxidative stress biomarkers. Therefore 437 elderly individuals were included and given intervention for 4 years. Clinical examination and blood samples were undertaken at start and after 18 and 48 months. Evaluations of copeptin and MR-proADM changes were performed using repeated measures of variance. Cardiovascular mortality was evaluated using a 10-year-period of follow-up, and presented in Kaplan-Meier plots. A significant increase in copeptin level could be seen in the placebo group during the intervention period (from 9.4 pmol/L to 15.3 pmol/L), compared to the active treatment group. The difference between the groups was confirmed in the repeated measurement of variance analyses (P = 0.031) with less copeptin increase in the active treatment group. Furthermore, active treatment appeared to protect against cardiovascular death both in those with high and with low copeptin levels at inclusion. Less increase of MR-proADM could also be seen during the intervention in the active treatment group compared to controls (P=0.026). Both in those having an MR-proADM level above or below median level, significantly less cardiovascular mortality could be seen in the active treatment group (P=0.0001, and P=0.04 respectively). In conclusion supplementation with selenium and coenzyme Q10 during four years resulted in less concentration of both copeptin and MR-proADM. A cardioprotective effect of the supplementation was registered, irrespective of the initial levels of these biomarkers, and this protection was recognized also after 10 years of observation. © 2015 BioFactors, 41(6):443-452, 2015.

  • 7.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 12, e0141641- p.Article in journal (Refereed)
    Abstract [en]

    Background Selenium and coenzyme Q10 are important antioxidants in the body. As the intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases, an intervention trial using selenium and coenzyme Q10 for four years was performed. As previously reported, the intervention was accompanied by reduced cardiovascular mortality. The objective of the present study was to analyze cardiovascular mortality for up to 10 years after intervention, to evaluate if mortality differed in subgroups differentiated by gender, diabetes, ischemic heart disease (IHD), and functional class. Methods Four-hundred forty-three healthy elderly individuals were included from a rural municipality in Sweden. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results mortality was registered. Findings Significantly reduced cardiovascular mortality could be seen in those on selenium and coenzyme Q10 intervention. A multivariate Cox regression analysis demonstrated a reduced cardiovascular mortality risk in the active treatment group (HR: 0.51; 95% CI 0.36-0.74; P = 0.0003). The reduced mortality could be seen to persist during the 10-year period. Subgroup analysis showed positive effects in both genders. An equally positive risk reduction could be seen in those with ischemic heart disease (HR: 0.51; 95% CI 0.27-0.97; P = 0.04), but also in the different functional classes. Conclusions In a 10-year follow-up of a group of healthy elderly participants given four years of intervention with selenium and coenzyme Q10, significantly reduced cardiovascular mortality was observed. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanism explaining the persistency remains to be elucidated. Since this was a small study, the observations should be regarded as hypothesis-generating.

  • 8.
    Alehagen, Urban
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Supplementation with Selenium and Coenzyme Q10 Reduces Cardiovascular Mortality in Elderly with Low Selenium Status. A Secondary Analysis of a Randomised Clinical Trial2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 7, e0157541Article in journal (Refereed)
    Abstract [en]

    Background Selenium is needed by all living cells in order to ensure the optimal function of several enzyme systems. However, the selenium content in the soil in Europe is generally low. Previous reports indicate that a dietary supplement of selenium could reduce cardiovascular disease but mainly in populations in low selenium areas. The objective of this secondary analysis of a previous randomised double-blind placebo-controlled trial from our group was to determine whether the effects on cardiovascular mortality of supplementation with a fixed dose of selenium and coenzyme Q10 combined during a four-year intervention were dependent on the basal level of selenium. Methods In 668 healthy elderly individuals from a municipality in Sweden, serum selenium concentration was measured. Of these, 219 individuals received daily supplementation with selenium (200 mu g Se as selenized yeast) and coenzyme Q10 (200 mg) combined for four years. The remaining participants (n = 449) received either placebo (n = 222) or no treatment (n = 227). All cardiovascular mortality was registered. No participant was lost during a median follow-up of 5.2 years. Based on death certificates and autopsy results, all mortality was registered. Findings The mean serum selenium concentration among participants at baseline was low, 67.1 mu g/L. Based on the distribution of selenium concentration at baseline, the supplemented group was divided into three groups; amp;lt;65 mu g/L, 65-85 mu g/L, and amp;gt;85 mu g/L (45 and 90 percentiles) and the remaining participants were distributed accordingly. Among the non-treated participants, lower cardiovascular mortality was found in the high selenium group as compared with the low selenium group (13.0% vs. 24.1%; P = 0.04). In the group with the lowest selenium basal concentration, those receiving placebo or no supplementation had a mortality of 24.1%, while mortality was 12.1% in the group receiving the active substance, which was an absolute risk reduction of 12%. In the middle selenium concentration group a mortality of 14.0% in the non-treated group, and 6.0% in the actively treated group could be demonstrated; thus, there was an absolute risk reduction of 8.0%. In the group with a serum concentration of amp;gt;85 mu g/L, a cardiovascular mortality of 17.5% in the non-treated group, and 13.0% in the actively treated group was observed. No significant risk reduction by supplementation could thus be found in this group. Conclusions In this evaluation of healthy elderly Swedish municipality members, two important results could be reported. Firstly, a low mean serum selenium concentration, 67 mu g/L, was found among the participants, and the cardiovascular mortality was higher in the subgroup with the lower selenium concentrations amp;lt; 65 mu g/L in comparison with those having a selenium concentration amp;gt; 85 mu g/L. Secondly, supplementation was cardio-protective in those with a low selenium concentration, amp;lt;= 85 at inclusion. In those with serum seleniumamp;gt; 85 mu g/L and no apparent deficiency, there was no effect of supplementation. This is a small study, but it presents interesting data, and more research on the impact of lower selenium intake than recommended is therefore warranted.

  • 9.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Benson, Lina
    Karolinska Institute, Sweden.
    Edner, Magnus
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of greater than= 50%2015In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 8, no 5, 862-870 p.Article in journal (Refereed)
    Abstract [en]

    Background The pathophysiology of heart failure with preserved ejection fraction is poorly understood, but may involve a systemic proinflammatory state. Therefore, statins might improve outcomes in patients with heart failure with preserved ejection fraction defined as 50%. Methods and Results Of 46 959 unique patients in the prospective Swedish Heart Failure Registry, 9140 patients had heart failure and ejection fraction 50% (age 7711 years, 54.0% women), and of these, 3427 (37.5%) were treated with statins. Propensity scores for statin treatment were derived from 40 baseline variables. The association between statin use and primary (all-cause mortality) and secondary (separately, cardiovascular mortality, and combined all-cause mortality or cardiovascular hospitalization) end points was assessed with Cox regressions in a population matched 1:1 based on age and propensity score. In the matched population, 1-year survival was 85.1% for statin-treated versus 80.9% for untreated patients (hazard ratio, 0.80; 95% confidence interval, 0.72-0.89; Pless than0.001). Statins were also associated with reduced cardiovascular death (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98; P=0.026) and composite all-cause mortality or cardiovascular hospitalization (hazard ratio, 0.89; 95% confidence interval, 0.82-0.96; P=0.003). Conclusions In heart failure with ejection fraction 50%, the use of statins was associated with improved outcomes. The mechanisms should be evaluated and the effects tested in a randomized trial.

  • 10.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Benson, Lina
    Karolinska Institute, Sweden.
    Edner, Magnus
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Association Between Use of Statins and Outcomes in Heart Failure With Reduced Ejection Fraction Prospective Propensity Score Matched Cohort Study of 21 864 Patients in the Swedish Heart Failure Registry2015In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 8, no 2, 252-260 p.Article in journal (Refereed)
    Abstract [en]

    Background-In heart failure (HF) with reduced ejection fraction, randomized trials of statins did not demonstrate improved outcomes. However, randomized trials may not always be generalizable. The aim was to determine whether statins are associated with improved outcomes in an unselected nationwide population of patients with HF with reduced ejection fraction overall and in relation to ischemic heart disease (IHD). Methods and Results-In the Swedish Heart Failure Registry, 21 864 patients with HF with reduced ejection fraction (age +/- SD, 72+/-12 years; 29% women), of whom 10 345 (47%) were treated with statins, were studied. Propensity scores for statin use were derived from 42 baseline variables. The associations between statin use and outcomes were assessed with Cox regressions in a population matched 1: 1 based on propensity score and age and in the overall population with adjustment for propensity score and age. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular mortality; HF hospitalization; and combined all-cause mortality or cardiovascular hospitalization. Survival at 1 year in the matched population was 83% for statin-treated versus 79% for untreated patients (hazard ratio, 0.81; 95% confidence interval, 0.76-0.86; Pless than0.001). In the unmatched population, 1-year survival was 85% for statin-treated versus 79% for untreated patients, hazard ratio after adjustment for propensity score and age was 0.84 (95% confidence interval, 0.80-0.89; Pless than0.001). No examined baseline variables interacted with statin use except for IHD (P=0.001), with a hazard ratio of 0.76 (95% confidence interval, 0.70-0.82, Pless than0.001) with IHD and 0.95 (95% confidence interval, 0.85-1.07; P=0.430 without IHD. Statin use was also associated with reduced risk for all 3 secondary outcomes. Conclusions-In an unselected nationwide population of patients with HF with reduced ejection fraction, statins were associated with improved outcomes, specifically in the presence of IHD. This contrasts with previous randomized controlled trials. Additional randomized controlled trials with more generalized inclusion or focused on IHD may be warranted.

  • 11.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Johansson, Peter
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Appl Science, Norway.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Brismar, Kerstin
    Karolinska University Hospital, Sweden.
    Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, e0178614Article in journal (Refereed)
    Abstract [en]

    Background Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. Methods 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. Findings After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P amp;gt; 0.0001), IGF-1 SD score (F = 29; P amp;lt; 0.0001) and of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme Q10 also on the expression of IGF-1 as one of the mechanistic effects of the intervention. Conclusion Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of intervention with selenium and coenzyme Q10 is needed.

  • 12.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Johansson, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Significant changes in circulating microRNA by dietary supplementation of selenium and coenzyme Q10 in healthy elderly males. A subgroup analysis of a prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, e0174880Article in journal (Refereed)
    Abstract [en]

    Background Selenium and coenzyme Q10 is essential for important cellular functions. A low selenium intake is reported from many European countries, and the endogenous coenzyme Q10 production is decreasing in the body with increasing age. Supplementation with selenium and coenzyme Q10 in elderly have shown reduced cardiovascular mortality and reduced levels of markers of inflammation. However, microRNA analyses could give important information on the mechanisms behind the clinical effects of supplementation. Methods Out of the 443 healthy elderly participants that were given supplementation with 200 mu g Se/ day as organic selenium yeast tablets, and 200 mg/day of coenzyme Q10 capsules, or placebo for 4 years, 25 participants from each group were randomized and evaluated regarding levels of microRNA. Isolation of RNA from plasma samples and quantitative PCR analysis were performed. Volcano- and principal component analyses (PCA)-plots were used to illustrate the differences in microRNA expression between the intervention, and the placebo groups. Serum selenium concentrations were measured before intervention. Findings On average 145 different microRNAs out of 172 were detected per sample. In the PCA plots two clusters could be identified indicating significant difference in microRNA expression between the two groups. The pre-treatment expression of the microRNAs did not differ between active treatment and the placebo groups. When comparing the post- treatment microRNAs in the active and the placebo groups, 70 microRNAs exhibited significant differences in expression, also after adjustment for multiple measurements. For the 20 microRNAs with the greatest difference in expression the difference was up to more than 4 fold and with a P-value that were less than 4.4e(-8). Conclusions Significant differences were found in expression of more than 100 different microRNAs with up to 4 fold differences as a result of the intervention of selenium and coenzyme Q10 combined. The changes in microRNA could be a part of mechanisms underlying the clinical effects earlier reported that reduced cardiovascular mortality, gave better cardiac function, and showed less signs of inflammation and oxdative stress following the intervention. However, more research is needed to understand biological mechanisms of the protective effects of selenium and Q10 supplementation.

  • 13.
    Alehagen, Urban
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Björnstedt, Mikael
    Division of Pathology F42, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Post, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust and Hedmark University College, Norway.
    Relatively high mortality risk in elderly Swedish subjects with low selenium status2016In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 70, no 1, 91-96 p.Article in journal (Refereed)
    Abstract [en]

    Background/Objectives: 

    The daily dietary intake of selenium (Se), an essential trace element, is still low in Sweden in spite of decades of nutritional information campaigns and the effect of this on the public health is presently not well known. The objective of this study was to determine the serum Se levels in an elderly Swedish population and to analyze whether a low Se status had any influence on mortality.

    Subjects/Methods: 

    Six-hundred sixty-eight (n=668) elderly participants were invited from a municipality and evaluated in an observational study. Individuals were followed for 6.8 years and Se levels were re-evaluated in 98 individuals after 48 months. Clinical examination of all individuals included functional classification, echocardiography, electrocardiogram and serum Se measurement. All mortality was registered and endpoints of mortality were assessed by Kaplan–Meier plots, and Cox proportional hazard ratios adjusted for potential confounding factors were calculated.

    Results: 

    The mean serum Se level of the study population (n=668) was 67.1 μg/l, corresponding to relatively low Se intake. After adjustment for male gender, smoking, ischemic heart disease, diabetes, chronic obstructive pulmonary disease and impaired heart function, persons with serum Se in the lowest quartile had 43% (95% confidence interval (CI): 1.02–2.00) and 56% (95% CI: 1.03–2.36) increased risk for all-cause and cardiovascular mortality, respectively. The result was not driven by inflammatory effects on Se concentration in serum.

    Conclusion: 

    The mean serum Se concentration in an elderly Swedish population was 67.1 μg/l, which is below the physiological saturation level for several selenoprotein enzymes. This result may suggest the value of modest Se supplementation in order to improve the health of the Swedish population.

  • 14.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Svensson, Erland
    Swedish Def Research Agency, Sweden.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Levels of sP-selectin and hs-CRP Decrease with Dietary Intervention with Selenium and Coenzyme Q10 Combined: A Secondary Analysis of a Randomized Clinical Trial2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, e0137680- p.Article in journal (Refereed)
    Abstract [en]

    Background/Objectives Inflammation and oxidative stress are central in many disease states. The major anti-oxidative enzymes contain selenium. The selenium intake in Europe is low, and supplementation with selenium and coenzyme Q(10) , important anti-oxidants, was evaluated in a previous study. The aim of this study was to evaluate response on the inflammatory biomarkers C-reactive protein, and sP-selectin, and their possible impact on cardiovascular mortality. Subjects/Methods 437 elderly individuals were included in the study. Clinical examination, echocardiography, electrocardiography and blood samples were drawn. The intervention time was 48 months, and median follow-up was 5.2 years. The effects on inflammation/atherosclerosis were evaluated through analyses of CRP and sP-selectin. Evaluations of the effect of the intervention was performed using repeated measures of variance. All mortality was registered, and endpoints of mortality were assessed by Kaplan-Meier plots. Results The placebo group showed a CRP level of 4.8 ng/mL at the start, and 5.1 ng/mL at the study end. The active supplementation group showed a CRP level of 4.1 ng/mL at the start, and 2.1 ng/mL at the study end. SP-selectin exhibited a level of 56.6mg/mL at the start in the placebo group and 72.3 mg/mL at the study end, and in the active group the corresponding figures were 55.9 mg/mL and 58.0 mg/mL. A significantly smaller increase was demonstrated through repeated measurements of the two biomarkers in those on active supplementation. Active supplementation showed an effect on the CRP and sP-selectin levels, irrespective of the biomarker levels. Reduced cardiovascular mortality was demonstrated in both those with high and low levels of CRP and sP-selectin in the active supplementation group. Conclusion CRP and sP-selectin showed significant changes reflecting effects on inflammation and atherosclerosis in those given selenium and coenzyme Q(10) combined. A reduced cardiovascular mortality could be demonstrated in the active group, irrespective of biomarker level. This result should be regarded as hypothesis-generating, and it is hoped it will stimulate more research in the area.

  • 15.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Matussek, Andreas
    County Hospital Ryhov, Sweden.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    PDGF-D gene polymorphism is associated with increased cardiovascular mortality in elderly men2016In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 17, no 62Article in journal (Refereed)
    Abstract [en]

    Background: Platelet-derived growth factor (PDGF) D has been reported to be active in fibroblasts, and in areas of myocardial infarction. In this longitudinal study we evaluated the association between PDGF-D polymorphism and cardiovascular mortality, and attempted to discover whether specific genotype differences regarding risk could be observed, and if gender differences could be seen. Methods: Four hundred seventy-six elderly community participants were included in this study. All participants underwent a clinical examination, echocardiography, and blood sampling including PDGF-D single nucleotide polymorphism (SNP) analyses of the rs974819 A/A, G/A and G/G SNP. The follow-up time was 6.7 years. Results: No specific genotype of rs974819 demonstrated increased cardiovascular mortality in the total population, however, the male group with genotypes A/A and G/A demonstrated an increased risk that persisted in a multivariate evaluation where adjustments were made for well-known cardiovascular risk factors (2.7 fold compared with the G/G genotype). No corresponding finding was observed in the female group. Conclusion: We report here for the first time that the genotypes G/A or A/A of the SNP rs974819 near PDGF-D exhibited a 2.7 fold increased cardiovascular mortality risk in males. Corresponding increased risk could not be observed in either the total population and thus not in the female group. However, the sample size is was small and the results should be regarded as hypothesis-generating, and thus more research in the field is recommended.

  • 16.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Vorkapic, Emina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Ljungberg, Liza
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Gender difference in adiponectin associated with cardiovascular mortality2015In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 16, no 9Article in journal (Refereed)
    Abstract [en]

    Background: It is important to identify cardiovascular diseases in patients at high risk. To include genetics into routine cardiological patients has therefore been discussed recently. We wanted to evaluate the association between high-molecular weight adiponectin and cardiovascular risk, and secondly in the same population evaluate if specific genotype differences regarding risk could be observed, and thirdly if gender differences could be seen. Method: Four hundred seventy-six elderly participants recruited from a rural community were included. All participants underwent a clinical examination, echocardiography, and blood sampling and the single nucleotide polymorphism (SNP) (rs266729) of adiponectin was analysed. Follow-up time was 6.7 years. Results: Those with high serum concentration of adiponectin had a more 2 fold increased cardiovascular risk, and it might be that females exhibits even higher risk where a more than 5 fold increased risk could be seen. The result could be demonstrated even in a multivariate model adjusting for well-known clinical risk factors. However, as the sample size was small the gender differences should be interpreted with caution. In the genotype evaluation the C/C carriers of the female group had a more than 9-fold increased risk of cardiovascular mortality, however the confidence interval was wide. Such genotype difference could not be found in the male group. Conclusion: High level of adiponectin was associated with increased cardiovascular risk. Also a gender difference in the genotype evaluation could be seen where the C/C carriers obtained higher risk in the female group but not in the male group. Thus, in order to identify patients at risk early, genetic analyses may add to the armamentarium used in the clinical routine. However, information should be regarded as hypothesis generating as the sample size was small and should stimulate further research in individualized cardiovascular prevention and treatment.

  • 17.
    Alfredsson, Joakim
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Duke University, NC 27710 USA.
    Alexander, Karen P.
    Duke University, NC 27710 USA.
    Multiple Chronic Conditions in Older Adults with Acute Coronary Syndromes2016In: Clinics in Geriatric Medicine, ISSN 0749-0690, E-ISSN 1879-8853, Vol. 32, no 2, 291-+ p.Article in journal (Refereed)
    Abstract [en]

    Older adults presenting with acute coronary syndromes (ACSs) often have multiple chronic conditions (MCCs). In addition to traditional cardiovascular (CV) risk factors (ie, hypertension, hyperlipidemia, and diabetes), common CV comorbidities include heart failure, stroke, and atrial fibrillation, whereas prevalent non-CV comorbidities include chronic kidney disease, anemia, depression, and chronic obstructive pulmonary disease. The presence of MCCs affects the presentation (eg, increased frequency of type 2 myocardial infarctions [MIs]), clinical course, and prognosis of ACS in older adults. In general, higher comorbidity burden increases mortality following MI, reduces utilization of ACS treatments, and increases the importance of developing individualized treatment plans.

  • 18.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Tomas L
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Gustafsson, Kerstin M
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Logander, Elisabeth
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Large early variation of residual platelet reactivity in Acute Coronary Syndrome patients treated with clopidogrel: Results from Assessing Platelet Activity in Coronary Heart Disease (APACHE).2015In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, no 2, 335-340 p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: There is a large inter-individual variation in response to clopidogrel treatment and previous studies have indicated higher risk of thrombotic events in patients with high residual platelet reactivity (HRPR), but the optimal time-point for testing is not established. The aim of this study was to investigate the optimal time-point for aggregometry testing and the risk of major adverse cardiac events associated with HRPR.

    METHOD AND RESULTS: We included 125 patients with ACS (73 with STEMI, and 71 received abciximab). The prevalence of HRPR varied substantially over time. The rate of HRPR in patients treated and not treated with abciximab were 43% vs 67% (p=0.01) before, 2% vs 23% (p=0.001) 6-8h after, 8% vs 9% (p=0.749) 3days after, and 23% vs 12% (p=0.138) 7-9 days after loading dose of clopidogrel. We found HRPR in 18% of the patients but only four ischemic events during 6months follow-up, with no significant difference between HRPR patients compared to the rest of the population. There were 3 TIMI major bleedings, all of which occurred in the low residual platelet reactivity (LRPR) group.

    CONCLUSION: There is a large variation in platelet reactivity over time, also depending on adjunctive therapy, which has a large impact on optimal time-point for assessment. We found HRPR in almost 1 in 5 patients, but very few MACE, and not significantly higher in HRPR patients. In a contemporary ACS population, with low risk for stent thrombosis, the predictive value of HRPR for ischemic events will probably be low.

  • 19.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Duke Clin Research Institute, NC USA.
    Neely, Benjamin
    Duke Clin Research Institute, NC USA.
    Neely, Megan L.
    Duke Clin Research Institute, NC USA.
    Bhatt, Deepak L.
    Brigham and Womens Hospital, MA 02115 USA; Harvard Medical Sch, MA USA.
    Goodman, Shaun G.
    St Michaels Hospital, Canada; University of Alberta, Canada; University of Alberta, Canada.
    Tricoci, Pierluigi
    Duke Clin Research Institute, NC USA; Duke University, NC 27706 USA.
    Mahaffey, Kenneth W.
    Stanford University, CA 94305 USA.
    Cornel, Jan H.
    Medical Centre Alkmaar, Netherlands.
    White, Harvey D.
    Auckland City Hospital, New Zealand.
    Fox, Keith A. A.
    University of Edinburgh, Scotland.
    Prabhakaran, Dorairaj
    Centre Chron Disease Control and Public Health Fdn India, India.
    Winters, Kenneth J.
    Eli Lilly and Co, IN 46285 USA.
    Armstrong, Paul W.
    University of Alberta, Canada; University of Alberta, Canada.
    Magnus Ohman, E.
    Duke Clin Research Institute, NC USA; Duke University, NC 27706 USA.
    Roe, Matthew T.
    Duke Clin Research Institute, NC USA; Duke University, NC 27706 USA.
    Predicting the risk of bleeding during dual antiplatelet therapy after acute coronary syndromes2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 15, 1168-1176 p.Article in journal (Refereed)
    Abstract [en]

    Objectives Dual antiplatelet therapy (DAPT) with aspirin + a P2Y12 inhibitor is recommended for at least 12 months for patients with acute coronary syndrome (ACS), with shorter durations considered for patients with increased bleeding risk. However, there are no decision support tools available to predict an individual patients bleeding risk during DAPT treatment in the post-ACS setting. Methods To develop a longitudinal bleeding risk prediction model, we analysed 9240 patients with unstable angina/non-ST segment elevation myocardial infarction (NSTEMI) from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial, who were managed without revascularisation and treated with DAPT for a median of 14.8 months. Results We identified 10 significant baseline predictors of non-coronary artery bypass grafting (CABG)-related Global Use of Strategies to Open Occluded Arteries (GUSTO) severe/life-threatening/moderate bleeding: age, sex, weight, NSTEMI (vs unstable angina), angiography performed before randomisation, prior peptic ulcer disease, creatinine, systolic blood pressure, haemoglobin and treatment with beta-blocker. The five significant baseline predictors of Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding included age, sex, angiography performed before randomisation, creatinine and haemoglobin. The models showed good predictive accuracy with Therneaus C-indices: 0.78 (SE=0.024) for the GUSTO model and 0.67 (SE=0.023) for the TIMI model. Internal validation with bootstrapping gave similar C-indices of 0.77 and 0.65, respectively. External validation demonstrated an attenuated C-index for the GUSTO model (0.69) but not the TIMI model (0.68). Conclusions Longitudinal bleeding risks during treatment with DAPT in patients with ACS can be reliably predicted using selected baseline characteristics. The TRILOGY ACS bleeding models can inform riskbenefit considerations regarding the duration of DAPT following ACS.

  • 20.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Roe, Matthew T
    Duke Clinical Research Institute, Durham, NC.
    Balancing the risks and benefits of long-term antiplatelet therapies for cardiovascular disease: clinical, research, and regulatory implications.2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 3, e001897Article in journal (Other academic)
  • 21.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Roe, Matthew T.
    Duke University of School Med, NC USA.
    Risks and Benefits of Triple Oral Anti-Thrombotic Therapies After Acute Coronary Syndromes and Percutaneous Coronary Intervention2015In: Drug Safety, ISSN 0114-5916, E-ISSN 1179-1942, Vol. 38, no 5, 481-491 p.Article, review/survey (Refereed)
    Abstract [en]

    The key pathophysiological process underlying symptomatic coronary artery disease, including acute coronary syndromes (ACS), is usually a rupture or an erosion of an atherosclerotic plaque, followed by platelet activation and subsequent thrombus formation. Early clinical trials showed benefit with long-term aspirin treatment, and later-based on large clinical trials-dual anti-platelet therapy (DAPT), initially with clopidogrel, and more recently with prasugrel or ticagrelor, has become the established treatment in the post-ACS setting and after percutaneous coronary intervention (PCI). Treatment with DAPT is recommended for both ST-elevation myocardial infarction and non-ST-elevation ACS, as well as after PCI with stenting, in American and European clinical guidelines. Notwithstanding the benefits observed with DAPT, including third-generation P2Y(12) receptor inhibitors plus aspirin, ACS patients remain at high risk for a recurrent cardiovascular event, suggesting that other treatment strategies, including the addition of a third oral anti-platelet agent or a novel oral anticoagulant (NOAC) to standard DAPT regimens, may provide additional benefit for post-ACS patients and for patients undergoing PCI. Adding a third anti-thrombotic agent to DAPT after an ACS event or a PCI procedure has been shown to have modest benefit in terms of ischemic event reduction, but has consistently been associated with increased bleeding complications. Therefore, the quest to optimize anti-thrombotic therapies post-ACS and post-PCI continues unabated but is tempered by the historical experiences to date that indicate that careful patient and dose selection will be critical features of future randomized trials.

  • 22.
    Alfredsson, Joakim
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Duke Clin Research Institute, NC 27705 USA.
    Stebbins, Amanda
    Duke Clin Research Institute, NC 27705 USA.
    Brennan, J. Matthew
    Duke University, NC USA.
    Matsouaka, Roland
    Duke University, NC USA.
    Afilalo, Jonathan
    McGill University, Canada.
    Peterson, Eric D.
    Duke Clin Research Institute, NC 27705 USA; Duke University, NC USA.
    Vemulapalli, Sreekanth
    Duke University, NC USA.
    Rumsfeld, John S.
    University of Colorado, CO USA.
    Shahian, David
    Massachusetts Gen Hospital, MA 02114 USA.
    Mack, Michael J.
    Baylor Scott and White Heatlh, TX USA.
    Alexander, Karen P.
    Duke Clin Research Institute, NC 27705 USA; Duke University, NC USA.
    Gait Speed Predicts 30-Day Mortality After Transcatheter Aortic Valve Replacement Results From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry2016In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 133, no 14, 1351-1359 p.Article in journal (Refereed)
    Abstract [en]

    Background Surgical risk scores do not include frailty assessments (eg, gait speed), which are of particular importance for patients with severe aortic stenosis considering transcatheter aortic valve replacement. Methods and Results We assessed the association of 5-m gait speed with outcomes in a cohort of 8039 patients who underwent transcatheter aortic valve replacement (November 2011-June 2014) and were included in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. We evaluated the association between continuous and categorical gait speed and 30-day all-cause mortality before and after adjustment for Society of Thoracic Surgeons-predicted risk of mortality score and key variables. Secondary outcomes included in-hospital mortality, bleeding, acute kidney injury, and stroke. The overall median gait speed was 0.63 m/s (25th-75th percentile, 0.47-0.79 m/s), with the slowest walkers (<0.5 m/s) constituting 28%, slow walkers (0.5-0.83 m/s) making up 48%, and normal walkers (>0.83 m/s) constituting 24% of the population. Thirty-day all-cause mortality rates were 8.4%, 6.6%, and 5.4% for the slowest, slow, and normal walkers, respectively (P<0.001). Each 0.2-m/s decrease in gait speed corresponded to an 11% increase in 30-day mortality (adjusted odds ratio, 1.11; 95% confidence interval, 1.01-1.22). The slowest walkers had 35% higher 30-day mortality than normal walkers (adjusted odds ratio, 1.35; 95% confidence interval, 1.01-1.80), significantly longer hospital stays, and a lower probability of being discharged to home. Conclusions Gait speed is independently associated with 30-day mortality after transcatheter aortic valve replacement. Identification of frail patients with the slowest gait speeds facilitates preprocedural evaluation and anticipation of a higher level of postprocedural care. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01737528.

  • 23.
    Alhede, Christina
    et al.
    Herlev Gentofte University Hospital, Denmark.
    Lauridsen, Trine K.
    Herlev Gentofte University Hospital, Denmark.
    Johannessen, Arne
    Herlev Gentofte University Hospital, Denmark.
    Dixen, Ulrik
    Hvidovre University Hospital, Denmark.
    Jensen, Jan S.
    Herlev Gentofte University Hospital, Denmark.
    Raatikainen, Pekka
    Helsinki University Hospital, Finland.
    Hindricks, Gerhard
    Leipzig University Hospital, Germany.
    Walfridsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Kongstad, Ole
    Lund University Hospital, Sweden.
    Pehrson, Steen
    Rigshosp, Denmark.
    Englund, Anders
    Örebro University Hospital, Sweden.
    Hartikainen, Juha
    Kupio University Hospital, Finland.
    Hansen, Peter S.
    Varde Heart Centre, Denmark.
    Nielsen, Jens C.
    Aarhus University Hospital, Denmark.
    Jons, Christian
    Rigshosp, Denmark.
    Antiarrhythmic medication is superior to catheter ablation in suppressing supraventricular ectopic complexes in patients with atrial fibrillation2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 244, 186-191 p.Article in journal (Refereed)
    Abstract [en]

    Background: Supraventricular ectopic complexes (SVEC) originating in the pulmonary veins are known triggers of atrial fibrillation (AF) which led to the development of pulmonary vein isolation for AF. However, the long-term prevalence of SVEC after catheter ablation (CA) as compared to antiarrhythmic medication (AAD) is unknown. Our aims were to compare the prevalence of SVEC after AAD and CA and to estimate the association between baseline SVEC burden and AF burden during 24 months of follow-up. Methods: Patients with paroxysmal AF (N = 260) enrolled in the MANTRA PAF trial were treated with AAD (N = 132) or CA (N = 128). At baseline and 3, 6, 12, 18 and 24 months follow-up patients underwent 7-day Holter monitoring to assess SVEC and AF burden. We compared SVEC burden between treatments with Wilcoxon sum rank test. Results: Patients treated with AAD had significantly lower daily SVEC burden during follow-up as compared to CA (AAD: 19 [6-58] versus CA: 39 [14-125], p = 0.003). SVEC burden increased post-procedurally followed by a decrease after CA whereas after AAD SVEC burden decreased and stabilized after 3 months of follow-up. Patients with low SVEC burden had low AF burden after both treatments albeit this was more pronounced after CA at 24 months of follow-up. Conclusion: AAD was superior to CA in suppressing SVEC burden after treatment of paroxysmal AF. After CA SVEC burden increased immediately post-procedural followed by a decrease whereas after AAD an early decrease was observed. Lower SVEC burden was highly associated with lower AF burden during follow-up especially after CA. (C) 2017 Elsevier B.V. All rights reserved.

  • 24.
    Andreae, Christina
    et al.
    Division of Nursing Science, Department of Medical and Health Sciences, Linköping University, Uppsala University, Eskilstuna, Sweden.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Chung, Misook L
    College of Nursing, University of Kentucky, Lexington.
    Hjelm, Carina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Årestedt, Kristofer
    Linnaeus University, Kalmar, Kalmar County Hospital, Kalmar Sweden.
    Depressive Symptoms Moderate the Association Between Appetite and Health Status in Patients With Heart Failure.2017In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Decreased appetite and depressive symptoms are clinical problems in patients with heart failure. Both may result in impaired health status.

    OBJECTIVE: The aims of this study were to investigate the association between appetite and health status in patients with heart failure and to explore whether depressive symptoms moderate this association.

    METHODS: In this cross-sectional study, patients with heart failure (n = 186; mean age, 71 years), New York Heart Association class II to IV, participated. Data on appetite (Council of Nutrition Appetite Questionnaire), depressive symptoms (Patient Health Questionnaire-9), and health status (EQ-5D 3-level scale [EQ-5D-3L] descriptive system, EQ-5D-3L index, and EQ Visual Analog Scale) were collected by self-rating questionnaires. Pearson correlation was used to investigate the association between appetite and health status. Multiple regression was performed to examine whether depressive symptoms moderate the association between appetite and health status.

    RESULTS: There was a significant association between appetite and health status for EQ-5D-3L descriptive system, mobility (P < .001), pain/discomfort (P < .001), and anxiety/depression (P < .001). This association was also shown in EQ-5D-3L index (P < .001) and EQ Visual Analog Scale (P < .001). Simple slope analysis showed that the association between appetite and health status was only significant for patients without depressive symptoms (B = 0.32, t = 4.66, P < .001).

    CONCLUSIONS: Higher level of appetite was associated with better health status. In moderation analysis, the association was presented for patients without depressive symptoms. Decreased appetite is an important sign of poor health status. To improve health status, health professionals should have greater attention on appetite, as well on signs of depressive symptoms.

  • 25.
    Andreae, Christina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Chung, Misook
    College of Nursing, University of Kentucky, Lexington, Kentucky, USA.
    Lennie, Terry
    College of Nursing, University of Kentucky, Lexington, Kentucky, USA.
    Årestedt, Kristofer
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Depressive symptoms as a moderator and mediator of the relationship between physical activity, appetite and perceived health among patients with heart failure2015Conference paper (Other academic)
    Abstract [en]

    Purpose: Depressive symptoms have been shown to directly influence perceived health among persons with heart failure (HF). Decreased physical activity and appetite may also be predictive of poor perceived health.The purposes of this study were to determine whether appetite and physical activity predicted perceived health, and to determine whether depressive symptoms mediated or moderated their relationship with perceived health.

    Methods: A total of 184 patients with mild to severe HF were included. Appetite, depressive symptoms and perceived health were measured by self-report questionnaires (Council on Nutrition Appetite Questionnaire, Patient Health Questionnaire and EuroQol 5D index). Physical activity was measured by SenceWearTM for 6 days. A separate series of multiple linear regression analyses were run to determine whether depressive symptoms mediated or moderated the relationship between physical activity and perceived health, and between appetite and perceived health.

    Results: Higher physical activity predicted better perceived health (ß=0.202, p=.006) but the strength of the association decreased (ß=0.13, p=.048) when depressive symptoms were included in the model. There was a significant mediation effect for depressive symptoms on perceived health (sobel=2.03, p=.041) (Fig 1). Appetite was a significant predictor of perceived health. Examination of this association among those with and without depressive symptoms, however showed positive association between appetite and perceived health remained only for patients without depressive symptoms demonstrating a moderating effect (p<.001) (Fig 2).

    Conclusion: Identifying and treating depression simultaneously while addressing appetite and physical activity may be key to improving perceived health among persons with HF.

  • 26.
    Andreae, Christina
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Uppsala University, Sweden.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Sawatzky, Richard
    Trinity Western University, Canada; Centre Health Evaluat and Outcome Science, Canada.
    Årestedt, Kristofer
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Correction: Psychometric Evaluation of Two Appetite Questionnaires in Patients With Heart Failure (vol 21, pg 954, 2015)2016In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 22, no 3, 245-245 p.Article in journal (Other academic)
    Abstract [en]

    n/a

  • 27.
    Andreae, Christina
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Uppsala University, Sweden.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Sawatzky, Richard
    Trinity Western University, Canada; Providence Health Care Research Institute, Canada.
    Årestedt, Kristofer
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Psychometric Evaluation of Two Appetite Questionnaires in Patients With Heart Failure2015In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 21, no 12, 954-958 p.Article in journal (Refereed)
    Abstract [en]

    Background: Decreased appetite in heart failure (HF) may lead to undemutrition which could negatively influence prognosis. Appetite is a complex clinical issue that is often best measured with the use of self-report instruments. However, there is a lack of self-rated appetite instruments. The Council on Nutrition Appetite Questionnaire (CNAQ) and the Simplified Nutritional Appetite Questionnaire (SNAQ) are validated instruments developed primarily for elderly people. Yet, the psychometric properties have not been evaluated in HF populations. The aim of the present study was to evaluate the psychometric properties of CNAQ and SNAQ in patients with HE Methods and Results: A total of 186 outpatients with reduced ejection fraction and New York Heart Association (NYHA) functional classifications II-IV were included (median age 72 y; 70% men). Data were collected with the use of a questionnaire that included the CNAQ and SNAQ. The psychometric evaluation included data quality, factor structure, construct validity, known-group validity, and internal consistency. Unidimensionality was supported by means of parallel analysis and confirmatory factor analyses (CFAs). The CFA results indicated sufficient model fit. Both construct validity and known-group validity were supported. Internal consistency reliability was acceptable, with ordinal coefficient alpha estimates of 0.82 for CNAQ and 0.77 for SNAQ. Conclusions: CNAQ and SNAQ demonstrated sound psychometric properties and can be used to measure appetite in patients with HF.

  • 28.
    Andreae, Christina
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Uppsala University, Sweden.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Årestedt, Kristofer
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Linnaeus University, Sweden.
    Prevalence and associated factors for decreased appetite among patients with stable heart failure2016In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 25, no 11-12, 1703-1712 p.Article in journal (Refereed)
    Abstract [en]

    Aims and objectivesTo explore the prevalence of decreased appetite and factors associated with appetite among patients with stable heart failure. BackgroundDecreased appetite is an important factor for the development of undernutrition among patients with heart failure, but there are knowledge gaps about prevalence and the factors related to appetite in this patient group. DesignObservational, cross-sectional study. MethodsA total of 186 patients with mild to severe heart failure were consecutively recruited from three heart failure outpatient clinics. Data were obtained from medical records (heart failure diagnosis, comorbidity and medical treatment) and self-rated questionnaires (demographics, appetite, self-perceived health, symptoms of depression and sleep). Blood samples were taken to determine myocardial stress and nutrition status. Heart failure symptoms and cognitive function were assessed by clinical examinations. The Council on Nutrition Appetite Questionnaire was used to assess self-reported appetite. Bivariate correlations and multivariate linear regression analyses were conducted to explore factors associated with appetite. ResultsSeventy-one patients (38%) experienced a loss of appetite with a significant risk of developing weight loss. The final multiple regression model showed that age, symptoms of depression, insomnia, cognitive function and pharmacological treatment were associated with appetite, explaining 27% of the total variance. ConclusionIn this cross-sectional study, a large share of patients with heart failure was affected by decreased appetite, associated with demographic, psychosocial and medical factors. Relevance to clinical practiceLoss of appetite is a prevalent problem among patients with heart failure that may lead to undernutrition. Health care professionals should routinely assess appetite and discuss patients experiences of appetite, nutrition intake and body weight and give appropriate nutritional advice with respect to individual needs.

  • 29.
    Aronsson, Mattias
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Walfridsson, Håkan
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Walfridsson, Ulla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nielsen, Jens Cosedis
    Aarhus University Hospital, Denmark.
    Hansen, Peter Steen
    Aarhus University Hospital, Denmark.
    Johannessen, Arne
    Gentofte University Hospital, Denmark.
    Raatikainen, Pekka
    Tampere University Hospital, Finland.
    Hindricks, Gerhard
    Leipzig University Hospital, Germany.
    Kongstad, Ole
    Lund University Hospital, Sweden.
    Pehrson, Steen
    Rigshospitalet, Denmark.
    Englund, Anders
    University Hospital, Örebro, Sweden.
    Hartikainen, Juha
    Kuopio University Hospital, Finland.
    Mortensen, Leif Spange
    Danish Information Technology Centre for Education and Research, Aarhus, Denmark.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation: results from a MANTRA-PAF substudy.2015In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 17, no 1, 48-55 p.Article in journal (Refereed)
    Abstract [en]

    AIM: The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment.

    METHODS AND RESULTS: A decision-analytic Markov model, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the result of the subgroup analyses showed that RFA was less costly and more effective in younger patients. This implied an incremental cost-effectiveness ratio of €3434/QALY in ≤50-year-old patients respectively €108 937/QALY in >50-year-old patients.

    CONCLUSION: Radiofrequency catheter ablation as first-line treatment is a cost-effective strategy for younger patients with paroxysmal AF. However, the cost-effectiveness of using RFA as first-line therapy in older patients is uncertain, and in most of these AADs should be attempted before RFA (MANTRA-PAF ClinicalTrials.gov number; NCT00133211).

  • 30.
    Bank, Ingrid E. M.
    et al.
    University of Medical Centre Utrecht, Netherlands.
    Gijsberts, Crystel M.
    University of Medical Centre Utrecht, Netherlands; ICIN Netherlands Heart Institute, Netherlands.
    Teng, Tiew-Hwa K.
    Singhealth, Singapore.
    Benson, Lina
    Karolinska Institute, Sweden.
    Sim, David
    Singhealth, Singapore.
    Shuan Daniel Yeo, Poh
    Tan Tock Seng Hospital, Singapore.
    Yee Ong, Hean
    Khoo Teck Puat Hospital, Singapore.
    Jaufeerally, Fazlur
    Singapore Gen Hospital, Singapore.
    Leong, Gerard K. T.
    Changi Gen Hospital, Singapore.
    Ling, Lieng H.
    National University, Singapore; National University of Health Syst, Singapore.
    Richards, A. Mark
    National University, Singapore; University of Otago, New Zealand.
    de Kleijn, Dominique P. V.
    University of Medical Centre Utrecht, Netherlands; National University, Singapore.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H.
    Karolinska University Hospital, Sweden.
    Lam, Carolyn S. P.
    Singhealth, Singapore; National University, Singapore; National University, Singapore; Duke NUS Medical Sch, Singapore.
    Prevalence and Clinical Significance of Diabetes in Asian Versus White Patients With Heart Failure2017In: JACC. Heart failure, ISSN 2213-1779, E-ISSN 2213-1787, Vol. 5, no 1, 14-24 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES The study sought to compare the prevalence, clinical correlates and prognostic impact of diabetes in Southeast Asian versus white patients with heart failure (HF) with preserved or reduced ejection fraction. BACKGROUND Diabetes mellitus is common in HF and is associated with impaired prognosis. Asia is home to the majority of the worlds diabetic population, yet data on the prevalence and clinical significance of diabetes in Asian patients with HF are sparse, and no studies have directly compared Asian and white patients. METHODS Two contemporary population-based HF cohorts were combined: from Singapore (n 1,002, median [25th to 75th percentile] age 62 [54 to 70] years, 76% men, 19.5% obesity) and Sweden (n =19,537, 77 [68 to 84] years, 60% men, 24.8% obesity). The modifying effect of ethnicity on the relationship between diabetes and clinical correlates or prognosis (HF hospitalization and all-cause mortality) was examined using interaction terms. RESULTS Diabetes was present in 569 (57%) Asian patients versus 4,680 (24%) white patients (p amp;lt; 0.001). Adjusting for clinical covariates, obesity was more strongly associated with diabetes in white patients (odds ratio [OR]: 3.45;. 95% confidence interval [CI]: 2.86 to 4.17) than in Asian patients (OR: 1.82; 95% CI: 1.13 to 2.96; P-interaction = 0.026). Diabetes was more strongly associated with increased HF hospitalization and all-cause mortality in Asian patients (hazard ratio: 1.50; 95% CI: 1.21 to 1.87) than in white patients (hazard ratio: 1.29; 95% CI: 1.22 to 1.36; P-interaction = 0.045). CONCLUSIONS Diabetes was 3-fold more common in Southeast Asian compared to white patients with HF, despite younger age and less obesity, and more strongly associated with poor outcomes in Asian patients than white patients. These results underscore the importance of ethnicity-tailored aggressive strategies to prevent diabetes and its complications. (C) 2017 by the American College of Cardiology Foundation.

  • 31.
    Baranowski, Jacek
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nielsen, Niels-Erik
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ahn, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    A simplified protocol for transcatheter aortic valve implantation that reduces procedure-related risk2016In: Journal of Cardiovascular Diseases & Diagnosis, E-ISSN 2329-9517, Vol. 4, no 3, 1000241Article in journal (Refereed)
    Abstract [en]

    Objectives: Transcatheter Aortic Valve Implantation is now a well-established procedure and continuous development has improved the technique. The object of this paper is to describe the successive steps taken at our department to improve our protocol, resulting in a more effective and patient-safe procedure.

    Design: An echo-guided method for aortic cusp alignment was used in 229 patients. In 139 patients pre-dilatation was excluded from the protocol. In the last 47 of the patients we exchanged the stiff guide-wire in the left ventricle with a soft wire for valve placement.

    Results: There was a significant decrease in the use of contrast medium during the period with 90% of patients receiving less than 50 ml contrast and 35% no contrast at all. In more than half the patients we only used rapid pacing in association with deployment of the stent valve. We had six cases ofpericardial bleeding due to penetration of the stiff guide wire through the left ventricular (LV) wall. This complication was avoided in all subsequent patients where we exchanged the stiff catheter to a soft guidewire in the ascending aorta before introduction of the wire and stent valve into the LV.

    Conclusions: We have successively modified our standard protocol for implantation of a balloon-expandable transcatheter aortic valve. This has simplified the procedure and reduced the risk for certain procedure-related complications.

  • 32.
    Berg, Jenny
    et al.
    Karolinska Institute, Sweden; OptumInsight, Sweden.
    Lindgren, Peter
    Karolinska Institute, Sweden; IVBAR, Sweden.
    Mejhert, Marit
    Ersta Hospital, Sweden; Karolinska Institute, Sweden.
    Edner, Magnus
    Karolinska University Hospital, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Kahan, Thomas
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Determinants of Utility Based on the EuroQol Five-Dimensional Questionnaire in Patients with Chronic Heart Failure and Their Change Over Time: Results from the Swedish Heart Failure Registry2015In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 18, no 4, 439-448 p.Article in journal (Refereed)
    Abstract [en]

    Background: There is limited information on drivers of utilities in patients with chronic heart failure (CHF). Objectives: To analyze determinants of utility in CHF and drivers of change over 1 year in a large sample from clinical practice. Methods: We included 5334 patients from the Swedish Heart Failure Registry with EuroQol five-dimensional questionnaire information available following inpatient or outpatient care during 2008 to 2010; 3495 had 1-year follow-up data Utilities based on Swedish and UK value sets were derived. We applied ordinary least squares (OLS) and two-part models for utility at inclusion and OLS regression for change over 1 year, all with robust standard errors. We assessed the predictive accuracy of both models using cross-validation. Results: Patients mean age was 73 years, 65% were men, 19% had a left ventricular ejection fraction of 50% or more, 23% had 40% to 49%, 27% had 30% to 39%, and 31% had less than 30%. For both models and value sets, utility at inclusion was affected by sex, age, New York Heart Association class, ejection fraction, hemoglobin, blood pressure, lung disease, diabetes, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, nitrates, antiplatelets, and diuretics. The OLS model performed slightly better than did the two-part model on a population level and for capturing utility ranges. Change in utility over 1 year was influenced by age, sex, and (measured at inclusion) disease duration, New York Heart Association class, blood pressure, ischemic heart disease, lung disease, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and antiplatelets. Conclusions: Utilities in CHF and their change over time are influenced by diverse demographic and clinical factors. Our findings can be used to target clinical interventions and for economic evaluations of new therapies.

  • 33.
    Berglund, Elisabeth
    et al.
    Umeå University, Sweden.
    Johansson, Bengt
    Umeå University, Sweden.
    Dellborg, Mikael
    University of Gothenburg, Sweden.
    Sörensson, Peder
    Karolinska Institute, Sweden.
    Christersson, Christina
    Uppsala University, Sweden.
    Nielsen, Niels Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Rinnstrom, Daniel
    Umeå University, Sweden.
    Thilen, Ulf
    Lund University, Sweden; Skåne University Hospital, Sweden.
    High incidence of infective endocarditis in adults with congenital ventricular septal defect2016In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 22, 1835-+ p.Article in journal (Refereed)
    Abstract [en]

    Objective Ventricular septal defects (VSDs), if haemodynamically important, are closed whereas small shunts are left without intervention. The long-term prognosis in congenital VSD is good but patients are still at risk for long-term complications. The aim of this study was to clarify the incidence of infective endocarditis (IE) in adults with VSD. Methods The Swedish registry for congenital heart disease (SWEDCON) was searched for adults with VSD. 779 patients were identified, 531 with small shunts and 248 who had the VSD previously closed. The National Patient Register was then searched for hospitalisations due to IE in adults during a 10-year period. Results Sixteen (2%) patients were treated for IE, 6 men and 10 women, with a mean age of 46.3 +/- 12.2 years. The incidence of IE was 1.7-2.7/1000 years in patients without previous intervention, 20-30 times the risk in the general population. Thirteen had small shunts without previous intervention. There was no mortality in these 13 cases. Two patients had undergone repair of their VSD and also aortic valve replacement before the episode of endocarditis and a third patient with repaired VSD had a bicuspid aortic valve, all of these three patients needed reoperation because of their IE and one patient died. No patient with isolated and operated VSD was diagnosed with IE. Conclusions A small unoperated VSD in adults carries a substantially increased risk of IE but is associated with a low risk of mortality.

  • 34.
    Bergström, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lundberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jönsson, Simon
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sarndahl, Eva
    Örebro University, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Annexin A1 in blood mononuclear cells from patients with coronary artery disease: Its association with inflammatory status and glucocorticoid sensitivity2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, e0174177Article in journal (Refereed)
    Abstract [en]

    Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of glucocorticoid actions. In atherosclerotic tissue, increased expression of AnxA1 has been associated with protective plaque-stabilizing effects. Here, we investigated the expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Blood was collected from 57 patients with stable CAD (SCAD) and 41 healthy controls. We also included a minor group (n = 10) with acute coronary syndrome (ACS). AnxA1 mRNA was measured in PBMCs. Expression of AnxA1 protein (total and surface-bound) and glucocorticoid receptors (GR) were detected in PBMC subsets by flow cytometry. Also, salivary cortisol, interleukin(IL)-6 and IL-10 in plasma, and LPS-induced cytokine secretion from PBMCs, with or without dexamethasone, were assessed. AnxA1 mRNA was found to be slightly increased in PBMCs from SCAD patients compared with controls. However, protein expression of AnxA1 or GRs in PBMC subsets did not differ between SCAD patients and controls, despite SCAD patients showing a more proinflammatory cytokine profile ex vivo. Only surface expression of AnxA1 on monocytes correlated with dexamethasone-mediated suppression of cytokines. In ACS patients, a marked activation of AnxA1 was seen involving both gene expression and translocation of protein to cell surface probably reflecting a rapid glucocorticoid action modulating the acute inflammatory response in ACS. To conclude, surface expression of AnxA1 on monocytes may reflect the degree of glucocorticoid sensitivity. Speculatively, "normal" surface expression of AnxA1 indicates that anti-inflammatory capacity is impaired in SCAD patients.

  • 35.
    Beygui, Farzin
    et al.
    Caen University Hospital, France.
    Castren, Maaret
    Helsinki University Hospital and Helsinki University, Finland; Karolinska Institutet, Stockholm, Sweden.
    Brunetti, Natale Daniele
    University of Foggia, Italy.
    Rosell-Ortiz, Fernando
    Empresa Pública de Emergencias Sanitarias de Andalucía, Spain.
    Christ, Michael
    Paracelsus Medical University, Nuremberg, Germany.
    Zeymer, Uwe
    Klinikum der Stadt Ludwigshafen am Rhein gGmbH, Germany.
    Huber, Kurt
    Cardiology and Emergency Medicine, Wilhelminenhospital, Vienna, Austria.
    Folke, Fredrik
    Copenhagen University Hospital, Gentofte, Denmark.
    Svensson, Leif
    Karolinska Institutet, Solna, Sweden.
    Bueno, Hector
    Hospital 12 de Octubre, Madrid, Spain.
    Van't Hof, Arnoud
    Interventional Cardiology, Zwolle, The Netherlands.
    Nikolaou, Nikolaos
    Konstantopouleio General Hospital, Athens, Greece.
    Nibbe, Lutz
    Medizinische Klinik m.S. Intensivmedizin und Nephrologie, Berlin, Germany.
    Charpentier, Sandrine
    University Hospital of Rangueil, Toulouse, France.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Tubaro, Marco
    San Filippo Neri Hospital, Rome, Italy.
    Goldstein, Patrick
    Lille University Hospital, France.
    Gestione pre-ospedaliera dei pazienti con dolore toracico e/o dispnea di origine cardiaca[Pre-hospital management of patients with chest pain and/or dyspnoea of cardiac origin]2017In: Recenti progressi in medicina, ISSN 2038-1840, Vol. 108, no 1, 27-51 p.Article in journal (Refereed)
    Abstract [en]

    Chest pain and acute dyspnoea are frequent causes of emergency medical services activation. The pre-hospital management of these conditions is heterogeneous across different regions of the world and Europe, as a consequence of the variety of emergency medical services and absence of specific practical guidelines. This position paper focuses on the practical aspects of the pre-hospital treatment on board and transfer of patients taken in charge by emergency medical services for chest pain and dyspnoea of suspected cardiac aetiology after the initial assessment and diagnostic work-up. The objective of the paper is to provide guidance, based on evidence, where available, or on experts' opinions, for all emergency medical services' health providers involved in the pre-hospital management of acute cardiovascular care.

  • 36.
    Bilchick, Kenneth C.
    et al.
    University of Virginia Health Syst, VA USA.
    Wang, Yongfei
    Yale New Haven Medical Centre, CT 06504 USA; Yale University, CT USA.
    Cheng, Alan
    Johns Hopkins Medical Institute, MD 21205 USA.
    Curtis, Jeptha P.
    Yale New Haven Medical Centre, CT 06504 USA; Yale University, CT USA.
    Dharmarajan, Kumar
    Yale New Haven Medical Centre, CT 06504 USA; Yale University, CT USA.
    Stukenborg, George J.
    University of Virginia, VA USA.
    Shadman, Ramin
    Southern Calif Permanente Medical Grp, CA USA.
    Anand, Inder
    University of Minnesota, MN USA.
    Lund, Lars H.
    Karolinska University Hospital, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Sartipy, Ulrik
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Maggioni, Aldo
    Italian Assoc Hospital Cardiologists, Italy.
    Swedberg, Karl
    University of Gothenburg, Sweden; Imperial Coll, England.
    OConner, Chris
    Inova Healthcare Syst, VA USA.
    Levy, Wayne C.
    University of Washington, WA USA.
    Seattle Heart Failure and Proportional Risk Models Predict Benefit From Implantable Cardioverter-Defibrillators2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 69, no 21, 2606-2618 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Recent clinical trials highlight the need for better models to identify patients at higher risk of sudden death. OBJECTIVES The authors hypothesized that the Seattle Heart Failure Model (SHFM) for overall survival and the Seattle Proportional Risk Model (SPRM) for proportional risk of sudden death, including death from ventricular arrhythmias, would predict the survival benefit with an implantable cardioverter-defibrillator (ICD). METHODS Patients with primary prevention ICDs from the National Cardiovascular Data Registry (NCDR) were compared with control patients with heart failure (HF) without ICDs with respect to 5-year survival using multivariable Cox proportional hazards regression. RESULTS Among 98,846 patients with HF (87,914 with ICDs and 10,932 without ICDs), the SHFM was strongly associated with all-cause mortality (p amp;lt; 0.0001). The ICD-SPRM interaction was significant (p amp;lt; 0.0001), such that SPRM quintile 5 patients had approximately twice the reduction in mortality with the ICD versus SPRM quintile 1 patients (adjusted hazard ratios [HR]: 0.602; 95% confidence interval [CI]: 0.537 to 0.675 vs. 0.793; 95% CI: 0.736 to 0.855, respectively). Among patients with SHFM-predicted annual mortality amp;lt;= 5.7%, those with a SPRM-predicted risk of sudden death below the median had no reduction in mortality with the ICD (adjusted ICD HR: 0.921; 95% CI: 0.787 to 1.08; p = 0.31), whereas those with SPRM above the median derived the greatest benefit (adjusted HR: 0.599; 95% CI: 0.530 to 0.677; p amp;lt; 0.0001). CONCLUSIONS The SHFM predicted all-cause mortality in a large cohort with and without ICDs, and the SPRM discriminated and calibrated the potential ICD benefit. Together, the models identified patients less likely to derive a survival benefit from primary prevention ICDs. (J Am Coll Cardiol 2017;69:2606-18) (C) 2017 by the American College of Cardiology Foundation.

  • 37.
    Borg, Sabina
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Söderlund, Anne
    Mälardalen University, Sweden.
    Bäck, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    The role of a behavioural medicine intervention in physiotherapy for the effects of rehabilitation outcomes in exercise-based cardiac rehabilitation (ECRA) - the study protocol of a randomised, controlled trial2017In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 17, 134Article in journal (Refereed)
    Abstract [en]

    Background: To help patients with coronary artery disease (CAD) benefit from the positive health effects attained by exercise-based cardiac rehabilitation (CR), adherence to these programmes according to international guidelines is important. Strategies to increase adherence to exercise-based CR are mainly an unexplored area. The objective of this study is to investigate the effects of a behavioural medicine intervention in physiotherapy, containing goal-setting, self-monitoring and feedback, with the aim of improving rehabilitation outcomes for exercise-based CR, compared with usual care. Methods: This is a randomised, controlled trial. A total of 160 patients with CAD will be included consecutively at the Coronary Care Unit at a university hospital in Sweden. Patients are randomised 1:1 using sealed envelopes to usual care or a behavioural medicine intervention in physiotherapy, in addition to usual care for 4 months. Outcome assessment at baseline, 4 and 12 months includes submaximal aerobic capacity (primary outcome), exercise adherence, muscle endurance, level of physical activity, biomarkers, anxiety and depression, health-related quality of life, patient enablement and self-efficacy (secondary outcomes). Discussion: This is the first study to evaluate the role of an integrated behavioural medicine intervention in exercise-based CR in the effects of rehabilitation outcomes. The results of this study will provide valuable information about the effect of these interventions in exercise-based CR and it has the potential to inform and assist in further treatment in secondary prevention for patients with CAD.

  • 38.
    Braunschweig, Frieder
    et al.
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm.
    Linde, Cecilia
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm.
    Benson, Lina
    Karolinska Institutet, Department of Clinical Science and Education, South Hospital, Stockholm, Sweden.
    Ståhlberg, Marcus
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm.
    New York Heart Association functional class, QRS duration, and survival in heart failure with reduced ejection fraction: implications for cardiac resychronization therapy.2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, no 3, 366-376 p.Article in journal (Refereed)
    Abstract [en]

    AIMS: Symptom severity assessed by NYHA functional class and QRS duration are essential criteria for selection of heart failure (HF) patients for CRT. This study assessed the relationship between NYHA class, QRS duration, and survival in a nationwide HF registry.

    METHODS AND RESULTS: We studied 13 423 patients with HF in NYHA class II-IV and LVEF <40% in the Swedish Heart Failure Registry. Survival was followed via the Swedish Population Registry. Of 12 534 patients without CRT (age 71 ± 12 years, 29% women), 51% and 49% were in NYHA class II and III-IV, respectively. Patients in NYHA class II compared with class III-IV were younger (69 vs. 73 years), and had a better systolic function (49% vs. 58% with LVEF <30%), P <0.001 for all, and a favourable co-morbidity profile. QRS duration was 116 ± 29 ms in NYHA class II and 119 ± 29 ms in NYHA class III-IV with QRS ≥120 ms found in 37% vs. 44%, and an LBBB in 23% vs. 28% (P < 0.001 for all). Upon multivariable Cox regression adjusting for 40 clinically relevant variables, mortality risk was higher in NYHA class III-IV vs. class II, with a hazard ratio (HR) of 1.31, 95% confidence interval (CI) 1.23-1.40. Mortality was also higher with QRS prolongation ≥120 ms vs. narrow QRS. The HR in NYHA class II patients with non-LBBB was 1.19 (95% CI 1.05 - 1.36) and in those with LBBB it was 1.16 (95% CI 1.03-1.41). The corresponding HRs in NYHA class III-IV were 1.33 (95% CI 1.21-1.47) and 1.12 (95% CI 1.02-1.22). There was no significant interaction between the effects of NYHA class and QRS duration or morphology on mortality. Applying different scenarios to estimate guideline adherence, fewer patients with NYHA class II (range 14.4-42.6%) compared with NYHA class III-IV (18.0-45.4%) had received a CRT device when indicated.

    CONCLUSIONS: In HF with reduced LVEF, QRS prolongation is common and independently linked to worse survival. The increase in mortality risk associated with QRS prolongation of both LBBB and non-LBBB morphology is similar in NYHA class II and III-IV.

  • 39.
    Bustamante, Mariana
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Petersson, Sven
    Linköping University, Department of Medical and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Jonatan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Atlas-based analysis of 4D flow CMR: Automated vessel segmentation and flow quantification2015In: Journal of Cardiovascular Magnetic Resonance, ISSN 1097-6647, E-ISSN 1532-429X, Vol. 17, no 87Article in journal (Refereed)
    Abstract [en]

    Background: Flow volume quantification in the great thoracic vessels is used in the assessment of several cardiovascular diseases. Clinically, it is often based on semi-automatic segmentation of a vessel throughout the cardiac cycle in 2D cine phase-contrast Cardiovascular Magnetic Resonance (CMR) images. Three-dimensional (3D), time-resolved phase-contrast CMR with three-directional velocity encoding (4D flow CMR) permits assessment of net flow volumes and flow patterns retrospectively at any location in a time-resolved 3D volume. However, analysis of these datasets can be demanding. The aim of this study is to develop and evaluate a fully automatic method for segmentation and analysis of 4D flow CMR data of the great thoracic vessels. Methods: The proposed method utilizes atlas-based segmentation to segment the great thoracic vessels in systole, and registration between different time frames of the cardiac cycle in order to segment these vessels over time. Additionally, net flow volumes are calculated automatically at locations of interest. The method was applied on 4D flow CMR datasets obtained from 11 healthy volunteers and 10 patients with heart failure. Evaluation of the method was performed visually, and by comparison of net flow volumes in the ascending aorta obtained automatically (using the proposed method), and semi-automatically. Further evaluation was done by comparison of net flow volumes obtained automatically at different locations in the aorta, pulmonary artery, and caval veins. Results: Visual evaluation of the generated segmentations resulted in good outcomes for all the major vessels in all but one dataset. The comparison between automatically and semi-automatically obtained net flow volumes in the ascending aorta resulted in very high correlation (r(2) = 0.926). Moreover, comparison of the net flow volumes obtained automatically in other vessel locations also produced high correlations where expected: pulmonary trunk vs. proximal ascending aorta (r(2) = 0.955), pulmonary trunk vs. pulmonary branches (r(2) = 0.808), and pulmonary trunk vs. caval veins (r(2) = 0.906). Conclusions: The proposed method allows for automatic analysis of 4D flow CMR data, including vessel segmentation, assessment of flow volumes at locations of interest, and 4D flow visualization. This constitutes an important step towards facilitating the clinical utility of 4D flow CMR.

  • 40.
    Carlén, Anna
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Åström Aneq, Meriam
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Nylander, Eva
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Gustafsson, Mikael
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Loaded treadmill walking and cycle ergometry to assess work capacity: a retrospective comparison in 424 firefighters.2017In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 37, no 1, 37-44 p.Article in journal (Refereed)
    Abstract [en]

    The fitness of firefighters is regularly evaluated using exercise tests. We aimed to compare, with respect to age and body composition, two test modalities for the assessment work capacity. A total of 424 Swedish firefighters with cycle ergometer (CE) and treadmill (TM) tests available from Jan 2004 to Dec 2010 were included. We compared results from CE (6 min at 200 W, 250 W or incremental ramp exercise) with TM (6 min at 8° inclination, 4·5 km h(-1) or faster, wearing 24-kg protective equipment). Oxygen requirements were estimated by prediction equations. It was more common to pass the TM test and fail the supposedly equivalent CE test (20%), than vice versa (0·5%), P<0·001. Low age and tall stature were significant predictors of passing both CE and TM tests (P<0·05), while low body mass predicted accomplishment of TM test only (P = 0·006). Firefighters who passed the TM but failed the supposedly equivalent CE test within 12 months had significantly lower body mass, lower BMI, lower BSA and shorter stature than did those who passed both tests. Calculated oxygen uptake was higher in TM tests compared with corresponding CE tests (P<0·001). Body constitution affected approval differently depending on the test modality. A higher approval rate in TM testing suggests lower cardiorespiratory requirements compared with CE testing, even though estimated oxygen uptake was higher during TM testing. The relevance of our findings in relation to the occupational demands needs reconsidering.

  • 41.
    Cermakova, Pavla
    et al.
    Karolinska Institute, Sweden; Int Clin Research Centre, Czech Republic; St Annes University Hospital, Czech Republic.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Fereshtehnejad, Seyed-Mohammad
    Karolinska Institute, Sweden.
    Johnell, Kristina
    Karolinska Institute, Sweden; Stockholm University, Sweden.
    Winblad, Bengt
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Eriksdotter, Maria
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Religa, Dorota
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Heart failure and dementia: survival in relation to types of heart failure and different dementia disorders2015In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 17, no 6, 612-619 p.Article in journal (Refereed)
    Abstract [en]

    AimsHeart failure (HF) and dementia frequently coexist, but little is known about their types, relationships to each other and prognosis. The aims were to (i) describe patients with HF and dementia, assess (ii) the proportion of specific dementia disorders in types of HF based on ejection fraction and (iii) the prognostic role of types of HF and dementia disorders. Methods and resultsThe Swedish Heart Failure Registry (RiksSvikt) and The Swedish Dementia Registry (SveDem) were record-linked. Associations between dementia disorders and HF types were assessed with multinomial logistic regression and survival was investigated with Kaplan-Meier analysis and multivariable Cox regression. We studied 775 patients found in both registries (55% men, mean age 82years). Ejection fraction was preserved in 38% of patients, reduced in 34%, and missing in 28%. The proportions of dementia disorders were similar across HF types. Vascular dementia was the most common dementia disorder (36%), followed by other dementias (28%), mixed dementia (20%), and Alzheimer disease (16%). Over a mean follow-up of 1.5years, 76% of patients survived 1year. We observed no significant differences in survival with regard to HF type (P=0.2) or dementia disorder (P=0.5). After adjustment for baseline covariates, neither HF types nor dementia disorders were independently associated with survival. ConclusionsHeart failure with preserved ejection fraction was the most common HF type and vascular dementia was the most common dementia disorder. The proportions of dementia disorders were similar across HF types. Neither HF types nor specific dementia disorders were associated with survival.

  • 42.
    Charitakis, Emmanouil
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Walfridsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Short‐Term Influence of Radiofrequency Ablation on NT‐proBNP, MR‐proANP, Copeptin, and MR‐proADM in Patients With Atrial Fibrillation: Data From the Observational SMURF Study2016In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, no 9Article in journal (Refereed)
    Abstract [en]

    Background There is limited knowledge on the short‐term influence of radiofrequency ablation (RFA) of atrial fibrillation (AF) on 2 cardiac biomarkers; the N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and the midregional fragment of the N‐terminal of pro‐ANP (MR‐proANP) and 2 extracardiac biomarkers; the c‐terminal provasopressin (copeptin) and the midregional portion of proadrenomedullin (MR‐proADM). There are also limited data concerning cardiac production of the latter two.

    Methods and Results We studied 192 consecutive patients eligible for RFA of AF referred to the University Hospital, Linköping, Sweden. NT‐proBNP, MR‐proANP, copeptin, and MR‐proADM levels were measured in peripheral blood, the coronary sinus (CS), and the left atrium before ablation, and in peripheral blood immediately and the day after RFA. The level of NT‐proBNP decreased the day after RFA in participants in AF at the time of RFA, compared to the participants in sinus rhythm who showed a slight increase (P<0.001). Furthermore, regardless of the actual rhythm, the level of MR‐proANP showed an increase immediately after RFA (P<0.001), followed by a decrease the day after ablation (P<0.001). Copeptin level showed a 6‐fold increase immediately after RFA compared to baseline (P<0.001), whereas MR‐proADM level increased the day after RFA (P<0.001). Levels of copeptin and MR‐proADM were not higher in the CS compared to peripheral blood.

    Conclusions RFA of AF is a strong stimulus with a significant and direct impact on different neurohormonal systems. We found no sign of a cardiac release of MR‐proADM or copeptin.

  • 43.
    Charitakis, Emmanouil
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Walfridsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Nylander, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Neurohormonal Activation After Atrial Fibrillation Initiation in Patients Eligible for Catheter Ablation: A Randomized Controlled Study2016In: JOURNAL OF THE AMERICAN HEART ASSOCIATION, ISSN 2047-9980, Vol. 5, no 12, e003957Article in journal (Refereed)
    Abstract [en]

    Background-Biomarker activation in atrial fibrillation (AF) has been widely studied, but the immediate effect of AF initiation remains unclear. We studied the effect of AF initiation on 2 cardiac biomarkers: the N-terminal fragment of the proB-type natriuretic peptide (NT-proBNP), the midregional fragment of the N-terminal of pro-atrial natriuretic peptide (MR-proANP), and 2 extracardiac biomarkers-the copeptin and the midregional portion of proadrenomedullin (MR-proADM). Methods and Results-This was a randomized controlled study, including 45 patients with AF who had been referred for radiofrequency ablation to the University Hospital, Link_ oping, Sweden, between February 2012 and April 2014. Freedom from AF during the 4 days prior to radiofrequency ablation was confirmed by transtelephonic ECGs. Biomarkers were collected from the femoral vein (fv), coronary sinus (CS), and left atrium (LA) prior to AF initiation (baseline) and 30 minutes later. The MR-proANP and NT-proBNP concentrations increased in the intervention group compared with the control group 30 minutes after the initiation of AF (MR-proANP: P-fvamp;lt;0.001, P-CSamp;lt;0.001, P-LAamp;lt;0.001; NT-proBNP: P-LAamp;lt;0.001). Copeptin levels in patients without ischemic heart disease were decreased after the initiation of AF (P-fv= 0.003, P-CS= 0.015, P-LA= 0.011). Conclusions-AF is a strong stimulus that results in immediate activation of different biomarkers.

  • 44.
    Charitakis, Emmanouil
    et al.
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Walfridsson, Ulla
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Nylander, Eva
    Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Strömberg, Anna
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Walfridsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Symptom burden, Metabolic profile, Ultrasound findings, Rhythm, neurohormonal activation, haemodynamics and health-related quality of life in patients with atrial Fibrillation (SMURF): a protocol for an observational study with a randomised interventional component2015In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, no 12, e008723Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with an estimated prevalence of 1.5-2%. It is an independent risk factor for ischaemic stroke and is estimated to cause about 20-25% of all stroke cases. AF has a great impact on health-related quality of life (HRQoL); however, one unresolved issue related to AF is the wide variation in its symptoms.

    METHODS AND ANALYSIS: The symptom burden, metabolic profile, ultrasound findings, rhythm, neurohormonal activation, haemodynamics and HRQoL in patients with AF (Symptom burden, Metabolic profile, Ultrasound findings, Rhythm, neurohormonal activation, haemodynamics and health-related quality of life in patients with atrial Fibrillation, SMURF) study is a prospective observational, cohort study, with a randomised interventional part. The aim of the study is to investigate, in patients with AF, the relationship between symptom burden and metabolic aspects, atrial function and different neurohormones, and the effect of radiofrequency ablation (RFA). The interventional part of the study will give an insight into the neurohormonal and intracardiac pressure changes directly after initiation of AF. Consecutive patients with symptomatic AF accepted for treatment with RFA for the first time at Linköping University Hospital are eligible for participation. The enrolment started in January 2012, and a total of 200 patients are to be included into the study, with 45 of them being enrolled into the interventional study with initiation of AF. The sample size of the interventional study is based on a small pilot study with 5 patients induced to AF while 2 served as controls. The results indicated that, in order to find a statistically significant difference, there was a need to include 28 patients; for safety reasons, 45 patients will be included.

    ETHICS AND DISSEMINATION: The SMURF study is approved by the Regional Ethical Review Board at the Faculty of Health Sciences, Linköping, Sweden. The results will be presented through peer-review journals and conference presentation.

    TRIAL REGISTRATION NUMBER: NCT01553045; Pre-results.

  • 45.
    Chung, Rosanna W S
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Leandersson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Lundberg, Anna K
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lutein exerts anti-inflammatory effects in patients with coronary artery disease.2017In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 262, 87-93 p., S0021-9150(17)30197-1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Many coronary artery disease (CAD) patients exhibit chronic low-grade inflammation. Carotenoids are anti-oxidants with potential anti-inflammatory properties. Here, we first assessed relationships between interleukin (IL)-6 and individual carotenoids in plasma from CAD patients. Based on the results, we proceeded to assess anti-inflammatory effects of one carotenoid, lutein, in peripheral blood mononuclear cells (PBMCs) from CAD patients.

    METHODS: Lutein + zeaxanthin (isomers with lutein being dominant), β-cryptoxanthin, lycopene, α- and β-carotene and IL-6 were measured in plasma from 134 patients with stable angina (SA) and 59 patients with acute coronary syndrome. In 42 patients, plasma measurements were also performed 3 months after coronary intervention. PBMCs from SA patients were pre-treated with lutein (1, 5 and 25 μM) for 24 h followed by 24 h incubation ± lipopolysaccharide (LPS). Cell pellets were collected for IL-6, IL-1β and TNF mRNA and intracellular lutein. Cytokine secretion was measured in cell media.

    RESULTS: Only lutein + zeaxanthin were inversely correlated with IL-6 in SA patients at baseline (r = -0.366, p < 0.001) and follow-up (r = -0.546, p < 0.001). Ex vivo, lutein was taken up by PBMCs from SA patients in a dose- and time-dependent manner. Pre-treatment with lutein dose-dependently lowered LPS-induced secretion of IL-6, IL-1β (p < 0.01) and TNF (p < 0.05), and also reduced IL-6, IL-1β and TNF mRNA expression (p < 0.05).

    CONCLUSIONS: Clinical findings highlighted the inverse association between lutein and IL-6 in CAD patients. Anti-inflammatory effects of lutein in PBMCs from CAD patients were consolidated in ex vivo experiments. Taken together, these results show that lutein has the potential to play a role in resolution of chronic inflammation in CAD patients.

    The full text will be freely available from 2018-05-06 14:18
  • 46.
    Cortez, Daniel
    et al.
    Lund University, Sweden; Penn State Milton S Hershey Medical Centre, PA 17033 USA.
    Svensson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Carlson, Jonas
    Lund University, Sweden.
    Graw, Sharon
    University of Colorado Denver AMC, CO USA.
    Sharma, Nandita
    Penn State Milton S Hershey Medical Centre, PA 17033 USA.
    Brun, Francesca
    University of Colorado Denver AMC, CO USA; Osped Riuniti, Italy; University of Trieste, Italy.
    Spezzacatene, Anita
    University of Colorado Denver AMC, CO USA; Osped Riuniti, Italy; University of Trieste, Italy.
    Mestroni, Luisa
    University of Colorado Denver AMC, CO USA; Osped Riuniti, Italy; University of Trieste, Italy.
    Platonov, Pyotr G.
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Right precordial-directed electrocardiographical markers identify arrhythmogenic right ventricular cardiomyopathy in the absence of conventional depolarization or repolarization abnormalities2017In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 17, 261Article in journal (Refereed)
    Abstract [en]

    Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carries a risk of sudden death. We aimed to assess whether vectorcardiographic (VCG) parameters directed toward the right heart and a measured angle of the S-wave would help differentiate ARVD/C with otherwise normal electrocardiograms from controls. Methods: Task Force 2010 definite ARVD/C criteria were met for all patients. Those who did not fulfill Task Force depolarization or repolarization criteria (-ECG) were compared with age and gender-matched control subjects. Electrocardiogram measures of a 3-dimentional spatial QRS-T angle, a right-precordial-directed orthogonal QRS-T (RPD) angle, a root mean square of the right sided depolarizing forces (RtRMS-QRS), QRS duration (QRSd) and the corrected QT interval (QTc), and a measured angle including the upslope and downslope of the S-wave (S-wave angle) were assessed. Results: Definite ARVD/C was present in 155 patients by 2010 Task Force criteria (41.7 +/- 17.6 years, 65.2% male). -ECG ARVD/C patients (66 patients) were compared to 66 control patients (41.7 +/- 17.6 years, 65.2% male). All parameters tested except the QRSd and QTc significantly differentiated -ECG ARVD/C from control patients (p amp;lt; 0.004 to p amp;lt; 0.001). The RPD angle and RtRMS-QRS best differentiated the groups. Combined, the 2 novel criteria gave 81.8% sensitivity, 90.9% specificity and odds ratio of 45.0 (95% confidence interval 15.8 to 128.2). Conclusion: ARVD/C disease process may lead to development of subtle ECG abnormalities that can be distinguishable using right-sided VCG or measured angle markers better than the spatial QRS-T angle, the QRSd or QTc, in the absence of Taskforce ECG criteria.

  • 47.
    Cosedis Nielsen, Jens
    et al.
    Aarhus University Hospital, Denmark.
    Johannessen, Arne
    Gentofte University Hospital, Copenhagen, Denmark .
    Raatikainen, Pekka
    Heart Center Co. Tampere University Hospital, Tampere, Finland .
    Hindricks, Gerhard
    Leipzig University Hospital, Leipzig, Germany .
    Walfridsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Pehrson, Steen Michael
    Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark .
    Englund, Anders
    Department of Medicine, University Hospital, Örebro, Sweden .
    Hartikainen, Juha
    Kuopio University Hospital, Kuopio, Finland .
    Spange Mortensen, Leif
    UNI-C, Danish Information Technology Centre for Education and Research, Aarhus, Denmark .
    Steen Hansen, Peter
    MANTRA-PAF Investigators. UNI-C, Danish Information Technology Centre for Education and Research, Aarhus, Denmark .
    Long-term efficacy of catheter ablation as first-line therapy for paroxysmal atrial fibrillation: 5-year outcome in a randomised clinical trial2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 5, 370-378 p.Article in journal (Refereed)
    Abstract [en]

    Objective The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial compared radiofrequency catheter ablation (RFA) with antiarrhythmic drug therapy (AAD) as first-line treatment for paroxysmal atrial fibrillation (AF). Endpoint of ablation was elimination of electrical activity inside pulmonary veins. We present the results of the 5-year follow-up.

    Methods This pre-specified 5-year follow-up included assessment of any AF and symptomatic AF burden by one 7-day Holter recording and quality of life (QoL) assessment, using SF-36 questionnaire physical and mental component scores. Analysis was intention-to-treat. Imputation was used to compensate for missing Holter data.

    Results 245 of 294 patients (83%) randomised to RFA (n=125) or AAD (n=120) attended the 5-year follow-up, 227 with Holter recording. Use of class I or III AAD was more frequent in AAD group (N=61 vs 13, p<0.001). More patients in the RFA group were free from AF (126/146 (86%) vs 105/148 (71%), p=0.001, relative risk (RR) 0.82; 95% CI 0.73 to 0.93) and symptomatic AF (137/146 (94%) vs 126/148 (85%), p=0.015, χ2 test, RR 0.91; 95% CI 0.84 to 0.98) in 7-day Holter recording. AF burden was significantly lower in the RFA group (any AF: p=0.003; symptomatic AF: p=0.02). QoL scores did not differ between randomisation groups. QoL scores remained improved from baseline (both components p<0.001), and did not differ from 2-year scores.

    Conclusions At 5 years, the occurrence and burden of any AF and symptomatic AF were significantly lower in the RFA group than in the AAD group. Improved QoL scores observed after 2 years persisted after 5 years without between-group differences.

  • 48.
    Cowper, Patricia A.
    et al.
    Duke University, NC USA.
    Pan, Wenqin
    Duke University, NC USA.
    Anstrom, Kevin J.
    Duke University, NC USA.
    Kaul, Padma
    University of Alberta, Canada.
    Wallentin, Lars
    Uppsala University, Sweden.
    Davidson-Ray, Linda
    Duke University, NC USA.
    Lundborg, Elisabet
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Cannon, Christopher P.
    Brigham and Womens Hospital, MA 02115 USA.
    Harrington, Robert A.
    Stanford University, CA 94305 USA.
    Mark, Daniel B.
    Duke University, NC USA.
    Economic Analysis of Ticagrelor Therapy From a US Perspective2015In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 65, no 5, 465-476 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Based on results of the PLATO (Platelet Inhibition and Patient Outcomes) trial comparing ticagrelor with clopidogrel therapy, the U.S. Food and Drug Administration approved ticagrelor in 2011 for reducing thrombotic cardiovascular events in patients with acute coronary syndrome (ACS) with the proviso that it be taken with low-dose aspirin. OBJECTIVES This study sought to assess the cost and cost effectiveness of ticagrelor therapy relative to clopidogrel in treating ACS patients from the perspective of the U.S. health care system. METHODS We estimated within-trial resource use and costs using U.S. low-dose aspirin patients in PLATO (n = 547). Quality-adjusted life expectancy was estimated using the total PLATO population (n = 18,624), combined with baseline risk and long-term survival data from an external ACS patient cohort. Study drugs were valued at current costs. Cost effectiveness was assessed, as was the sensitivity of results to sampling and methodological uncertainties. RESULTS One year of ticagrelor therapy, relative to that of generic clopidogrel, cost $29,665/quality-adjusted life-year gained, with 99% of bootstrap estimates falling under a $100,000 willingness-to-pay threshold. Results were robust to extensive sensitivity analyses, including variations in clopidogrel cost, exclusion of costs in extended years of life, and a recalibrated estimate of survival reflecting a lower underlying mortality risk in the United States. CONCLUSIONS For PLATO-eligible ACS patients, a U.S. perspective comparison of the current standard of dual antiplatelet therapy of aspirin with clopidogrel versus aspirin plus ticagrelor showed that the ticagrelor regimen increased life expectancy at an incremental cost well within accepted benchmarks of good value for money. (C) 2015 by the American College of Cardiology Foundation.

  • 49.
    Crespo-Leiro, Maria G.
    et al.
    Complexo Hospital University of A Coruna, Spain.
    Anker, Stefan D.
    University of Medical Centre Gottingen UMG, Germany.
    Maggioni, Aldo P.
    European Soc Cardiol, France; ANMCO Research Centre, Italy.
    Coats, Andrew J.
    Monash University, Australia.
    Filippatos, Gerasimos
    Athens University Hospital Attikon, Greece.
    Ruschitzka, Frank
    University of Heart Centre Zurich, Switzerland.
    Ferrari, Roberto
    University Hospital Ferrara, Italy; Maria Cecilia Hospital, Italy.
    Francesco Piepoli, Massimo
    AUSL Piacenza, Italy.
    Delgado Jimenez, Juan F.
    University Hospital 12 Octubre, Spain.
    Metra, Marco
    University of Brescia, Italy.
    Fonseca, Candida
    University of Nova Lisboa, Portugal.
    Hradec, Jaromir
    Charles University of Prague, Czech Republic.
    Amir, Offer
    Bar Ilan University, Israel.
    Logeart, Damien
    University of Paris Diderot, France.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Merkely, Bela
    Semmelweis University, Hungary.
    Drozdz, Jaroslaw
    Medical University of Lodz, Poland.
    Goncalvesova, Eva
    National Cardiovasc Institute, Slovakia.
    Hassanein, Mahmoud
    University of Alexandria, Egypt.
    Chioncel, Ovidiu
    University of Medicina Carol Davila, Romania.
    Lainscak, Mitja
    Gen Hospital Celje, Slovenia.
    Seferovic, Petar M.
    University of Belgrade, Serbia.
    Tousoulis, Dimitris
    University of Athens, Greece.
    Kavoliuniene, Ausra
    Lithuanian University of Health Science, Lithuania.
    Fruhwald, Friedrich
    Medical University, Austria.
    Fazlibegovic, Emir
    Clin Hospital Mostar, Bosnia and Herceg.
    Temizhan, Ahmet
    Turkey Yuksek Ihtisas Hospital, Turkey.
    Gatzov, Plamen
    University Hospital Lozenets, Bulgaria.
    Erglis, Andrejs
    Pauls Stradins Clin University Hospital, Latvia.
    Laroche, Cecile
    European Soc Cardiol, France.
    Mebazaa, Alexandre
    University of Paris Diderot, France.
    European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT): 1-year follow-up outcomes and differences across regions2016In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 18, no 6, 613-625 p.Article in journal (Refereed)
    Abstract [en]

    AimsThe European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT-R) was set up with the aim of describing the clinical epidemiology and the 1-year outcomes of patients with heart failure (HF) with the added intention of comparing differences between participating countries. Methods and resultsThe ESC-HF-LT-R is a prospective, observational registry contributed to by 211 cardiology centres in 21 European and/or Mediterranean countries, all being member countries of the ESC. Between May 2011 and April 2013 it collected data on 12440 patients, 40.5% of them hospitalized with acute HF (AHF) and 59.5% outpatients with chronic HF (CHF). The all-cause 1-year mortality rate was 23.6% for AHF and 6.4% for CHF. The combined endpoint of mortality or HF hospitalization within 1year had a rate of 36% for AHF and 14.5% for CHF. All-cause mortality rates in the different regions ranged from 21.6% to 36.5% in patients with AHF, and from 6.9% to 15.6% in those with CHF. These differences in mortality between regions are thought reflect differences in the characteristics and/or management of these patients. ConclusionThe ESC-HF-LT-R shows that 1-year all-cause mortality of patients with AHF is still high while the mortality of CHF is lower. This registry provides the opportunity to evaluate the management and outcomes of patients with HF and identify areas for improvement.

  • 50.
    Das, Debraj
    et al.
    University of Alberta, Canada.
    Savarese, Gianluigi
    Karolinska Institute, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Fu, Michael
    Department Med, Sweden.
    Howlett, Jonathan
    University of Calgary, Canada.
    Ezekowitz, Justin A.
    University of Alberta, Canada.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Ivabradine in Heart Failure The Representativeness of SHIFT (Systolic Heart Failure Treatment With the IF Inhibitor Ivabradine Trial) in a Broad Population of Patients With Chronic Heart Failure2017In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 10, no 9, e004112Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The sinus node inhibitor ivabradine was approved for patients with heart failure (HF) after the ivabradine and outcomes in chronic HF (SHIFT [Systolic Heart Failure Treatment With the IF Inhibitor Ivabradine Trial]) trial. Our objective was to characterize the proportion of patients with HF eligible for ivabradine and the representativeness of the SHIFT trial enrollees compared with those in the Swedish Heart Failure Registry. METHODS AND RESULTS: We examined 26 404 patients with clinical HF from the Swedish Heart Failure Registry and divided them into SHIFT type (left ventricular ejection fraction amp;lt; 40%, New York Heart Association class II-IV, sinus rhythm, and heart rate amp;gt;= 70 beats per minute) and nonSHIFT type. Baseline characteristics and medication use were compared and change in eligibility over time was reported at 6 months and 1 year in a subset of patients. Overall, 14.2% (n= 3741) of patients were SHIFT type. These patients were more likely to be younger, men, have diabetes mellitus, ischemic heart disease, lower left ventricular ejection fraction, and more recent onset HF (amp;lt; 6 months; all, Pamp;lt; 0.001). Although 88.9% of SHIFT type and 88.5% of non-SHIFT type (P= 0.421) were receiving selected beta-blockers, only 58.8% and 67.3% (Pamp;lt; 0.001) were on amp;gt; 50% of target dose. From those patients who had repeated visits within 6 months (n= 5420) and 1 year (n= 6840), respectively, 10.2% (n= 555) and 10.6% (n= 724) of SHIFT-type patients became ineligible, 77.3% (n= 4188) and 77.3% (n= 5287) remained ineligible, and 4.6% (n= 252) and 4.9% (n= 335) of non-SHIFT-type patients became eligible for initiation of ivabradine. CONCLUSIONS: From the Swedish Heart Failure Registry, 14.2% of patients with HF were eligible for ivabradine. These patients more commonly were not receiving target beta-blocker dose. Over time, a minority of patients became ineligible and an even smaller minority became eligible.

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