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  • 1.
    Ahmad, Tariq
    et al.
    Yale Univ, CT USA; Yale Univ, CT USA.
    Lund, Lars H.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Rao, Pooja
    Qure Ai, India.
    Ghosh, Rohit
    Qure Ai, India.
    Warier, Prashant
    Qure Ai, India.
    Vaccaro, Benjamin
    Yale Univ, CT USA; Yale Univ, CT USA.
    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.
    OConnor, Christopher M.
    Duke Univ, NC USA.
    Felker, G. Michael
    Duke Univ, NC USA.
    Desai, Nihar R.
    Yale Univ, CT USA; Yale Univ, CT USA.
    Machine Learning Methods Improve Prognostication, Identify Clinically Distinct Phenotypes, and Detect Heterogeneity in Response to Therapy in a Large Cohort of Heart Failure Patients2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 8, article id e008081Article in journal (Refereed)
    Abstract [en]

    Background-Whereas heart failure (HF) is a complex clinical syndrome, conventional approaches to its management have treated it as a singular disease, leading to inadequate patient care and inefficient clinical trials. We hypothesized that applying advanced analytics to a large cohort of HF patients would improve prognostication of outcomes, identify distinct patient phenotypes, and detect heterogeneity in treatment response. Methods and Results-The Swedish Heart Failure Registry is a nationwide registry collecting detailed demographic, clinical, laboratory, and medication data and linked to databases with outcome information. We applied random forest modeling to identify predictors of 1-year survival. Cluster analysis was performed and validated using serial bootstrapping. Association between clusters and survival was assessed with Cox proportional hazards modeling and interaction testing was performed to assess for heterogeneity in response to HF pharmacotherapy across propensity-matched clusters. Our study included 44 886 HF patients enrolled in the Swedish Heart Failure Registry between 2000 and 2012. Random forest modeling demonstrated excellent calibration and discrimination for survival (C-statistic=0.83) whereas left ventricular ejection fraction did not (C-statistic=0.52): there were no meaningful differences per strata of left ventricular ejection fraction (1-year survival: 80%, 81%, 83%, and 84%). Cluster analysis using the 8 highest predictive variables identified 4 clinically relevant subgroups of HF with marked differences in 1-year survival. There were significant interactions between propensity-matched clusters (across age, sex, and left ventricular ejection fraction and the following medications: diuretics, angiotensin-converting enzyme inhibitors, )i-blockers, and nitrates, Pamp;lt;0.001, all). Conclusions-Machine learning algorithms accurately predicted outcomes in a large data set of HF patients. Cluster analysis identified 4 distinct phenotypes that differed significantly in outcomes and in response to therapeutics. Use of these novel analytic approaches has the potential to enhance effectiveness of current therapies and transform future HF clinical trials.

  • 2.
    Alabas, Oras A.
    et al.
    University of Leeds, England.
    Gale, Chris P.
    University of Leeds, England; York Teaching Hospital NHS Fdn Trust, England.
    Hall, Marlous
    University of Leeds, England.
    Rutherford, Mark J.
    University of Leicester, England.
    Szummer, Karolina
    Department Med, Sweden.
    Sederholm Lawesson, Sofia
    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.
    Alfredsson, Joakim
    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, Bertil
    Uppsala University, Sweden; Uppsala University, Sweden.
    Jernberg, Tomas
    Karolinska Institute, Sweden.
    Sex Differences in Treatments, Relative Survival, and Excess Mortality Following Acute Myocardial Infarction: National Cohort Study Using the SWEDEHEART Registry2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 12, article id e007123Article in journal (Refereed)
    Abstract [en]

    Background-This study assessed sex differences in treatments, all-cause mortality, relative survival, and excess mortality following acute myocardial infarction. Methods and Results-A population-based cohort of all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART [Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies]) from 2003 to 2013 was included in the analysis. Excess mortality rate ratios (EMRRs), adjusted for clinical characteristics and guideline-indicated treatments after matching by age, sex, and year to background mortality data, were estimated. Although there were no sex differences in all-cause mortality adjusted for age, year of hospitalization, and comorbidities for ST-segment-elevation myocardial infarction (STEMI) and non-STEMI at 1 year (mortality rate ratio: 1.01 [95% confidence interval (CI), 0.96-1.05] and 0.97 [95% CI, 0.95-.99], respectively) and 5 years (mortality rate ratio: 1.03 [95% CI, 0.99-1.07] and 0.97 [95% CI, 0.95-.99], respectively), excess mortality was higher among women compared with men for STEMI and non-STEMI at 1 year (EMRR: 1.89 [95% CI, 1.66-2.16] and 1.20 [95% CI, 1.16-1.24], respectively) and 5 years (EMRR: 1.60 [95% CI, 1.48-1.72] and 1.26 [95% CI, 1.21-1.32], respectively). After further adjustment for the use of guideline-indicated treatments, excess mortality among women with non-STEMI was not significant at 1 year (EMRR: 1.01 [95% CI, 0.97-1.04]) and slightly higher at 5 years (EMRR: 1.07 [95% CI, 1.02-1.12]). For STEMI, adjustment for treatments attenuated the excess mortality for women at 1 year (EMRR: 1.43 [95% CI, 1.26-1.62]) and 5 years (EMRR: 1.31 [95% CI, 1.19-1.43]). Conclusions-Women with acute myocardial infarction did not have statistically different all-cause mortality, but had higher excess mortality compared with men that was attenuated after adjustment for the use of guideline-indicated treatments. This suggests that improved adherence to guideline recommendations for the treatment of acute myocardial infarction may reduce premature cardiovascular death among women.

  • 3.
    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, article id e001897Article in journal (Other academic)
  • 4.
    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.

  • 5.
    Lennie, Terry A
    et al.
    College of Nursing, University of Kentucky, Lexington, KY, USA.
    Andreae, Christina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rayens, Mary K
    College of Nursing, University of Kentucky, Lexington, KY, USA.
    Song, Eun Kyeung
    Department of Nursing, College of Medicine, University of Ulsan, Korea.
    Dunbar, Sandra B
    Emory University, Atlanta, GA, USA.
    Pressler, Susan J
    Indiana University, Indianapolis, IN, USA.
    Heo, Seongkum
    College of Nursing, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
    Kim, JinShil
    Gachon University College of Nursing, Incheon, Korea.
    Moser, Debra K
    College of Nursing, University of Kentucky, Lexington, KY, USA.
    Micronutrient Deficiency Independently Predicts Time to Event in Patients with Heart Failure2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 17, p. 1-10, article id e007251Article in journal (Refereed)
    Abstract [en]

    Dietary micronutrient deficiencies have been shown to predict event‐free survival in other countries but have not been examined in patients with heart failure living in the United States. The purpose of this study was to determine whether number of dietary micronutrient deficiencies in patients with heart failure was associated with shorter event‐free survival, defined as a combined end point of all‐cause hospitalization and death.

  • 6.
    Persson, Jonas
    et al.
    Danderyd Hospital, Sweden.
    Strawbridge, Rona J.
    Karolinska Institute, Sweden.
    McLeod, Olga
    Karolinska Institute, Sweden.
    Gertow, Karl
    Karolinska Institute, Sweden.
    Silveira, Angela
    Karolinska Institute, Sweden.
    Baldassarre, Damiano
    University of Milan, Italy.
    Van Zuydam, Natalie
    University of Dundee, Scotland.
    Shah, Sonia
    UCL, England; University of Queensland, Australia; University of Queensland, Australia.
    Fava, Cristiano
    Lund University, Sweden; University of Verona, Italy.
    Gustafsson, Stefan
    Uppsala University, Sweden.
    Veglia, Fabrizio
    University of Milan, Italy.
    Sennblad, Bengt
    Karolinska Institute, Sweden.
    Larsson, Malin
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Sabater-Lleal, Maria
    Karolinska Institute, Sweden.
    Leander, Karin
    Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Gigante, Bruna
    Danderyd Hospital, Sweden; Karolinska Institute, Sweden.
    Tabak, Adam
    Semmelweis University, Hungary.
    Kivimaki, Mika
    UCL, England.
    Kauhanen, Jussi
    University of Eastern Finland, Finland.
    Rauramaa, Rainer
    Kuopio Research Institute Exercise Med, Finland; Kuopio University Hospital, Finland.
    Smit, Andries J.
    University of Groningen, Netherlands.
    Mannarino, Elmo
    University of Perugia, Italy.
    Giral, Philippe
    Grp Hospital Pitie Salpetriere, France.
    Humphries, Steve E.
    UCL, England.
    Tremoli, Elena
    University of Milan, Italy.
    de Faire, Ulf
    Karolinska Institute, Sweden.
    Lind, Lars
    Uppsala University, Sweden.
    Ingelsson, Erik
    Uppsala University, Sweden.
    Hedblad, Bo
    Lund University, Sweden.
    Melander, Olle
    Lund University, Sweden.
    Kumari, Meena
    UCL, England.
    Hingorani, Aroon
    Karolinska Institute, Sweden; UCL, England.
    Morris, Andrew D.
    University of Dundee, Scotland.
    Palmer, Colin N. A.
    University of Dundee, Scotland.
    Lundman, Pia
    Danderyd Hospital, Sweden.
    Ohrvik, John
    Karolinska Institute, Sweden.
    Soderberg, Stefan
    Umeå University, Sweden.
    Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 8, p. e001853-Article in journal (Refereed)
    Abstract [en]

    Background-Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. Methods and Results-Baseline plasma adiponectin concentrationwas tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (beta=-0.018, Pless than0.001) in men but not in women (beta=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (beta=-0.0022, P=0.047), whereas no association was seen in women (0.0007, P=0.475; P for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82,95% CI0.54 to 1.25). Agenescore of adiponectin-raisingalleles in6loci, reported recently inalarge multi-ethnic metaanalysis, was inversely associated with baseline mean bifurcation IMT in men (beta=-0.0008, P=0.004) but not in women (beta=-0.0003, P=0.522; P for interaction=0.007). Conclusions-This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted.

  • 7.
    Pitts, Reynaria
    et al.
    VA Medical Centre, CO USA; University of Colorado, CO USA.
    Gunzburger, Elise
    University of Colorado, CO USA.
    Ballantyne, Christie M.
    Baylor Coll Med, TX 77030 USA.
    Barter, Philip J.
    University of New South Wales, Australia.
    Kallend, David
    Medicines Co, Switzerland.
    Leiter, Lawrence A.
    University of Toronto, Canada; University of Toronto, Canada.
    Leitersdorf, Eran
    Hadassah Hebrew University, Israel.
    Nicholls, Stephen J.
    University of Adelaide, Australia; University of Adelaide, Australia.
    Shah, Prediman K.
    Cedars Sinai Heart Institute, CA USA.
    Tardif, Jean-Claude
    University of Montreal, Canada.
    Olsson, Anders
    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.
    McMurray, John J. V.
    University of Glasgow, Scotland.
    Kittelson, John
    University of Colorado, CO USA.
    Schwartz, Gregory G.
    VA Medical Centre, CO USA; University of Colorado, CO USA.
    Aldosterone Does Not Predict Cardiovascular Events Following Acute Coronary Syndrome in Patients Initially Without Heart Failure2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 1, article id e004119Article in journal (Refereed)
    Abstract [en]

    Background- Aldosterone may have adverse effects in the myocardium and vasculature. Treatment with an aldosterone antagonist reduces cardiovascular risk in patients with acute myocardial infarction complicated by heart failure (HF) and left ventricular systolic dysfunction. However, most patients with acute coronary syndrome do not have advanced HF. Among such patients, it is unknown whether aldosterone predicts cardiovascular risk. Methods and Results- To address this question, we examined data from the dal-OUTCOMES trial that compared the cholesteryl ester transfer protein inhibitor dalcetrapib with placebo, beginning 4 to 12 weeks after an index acute coronary syndrome. Patients with New York Heart Association class II (with LVEF amp;lt; 40%), III, or IV HF were excluded. Aldosterone was measured at randomization in 4073 patients. The primary outcome was a composite of coronary heart disease death, nonfatal myocardial infarction, stroke, hospitalization for unstable angina, or resuscitated cardiac arrest. Hospitalization for HF was a secondary endpoint. Over a median follow-up of 37 months, the primary outcome occurred in 366 patients (9.0%), and hospitalization for HF occurred in 72 patients (1.8%). There was no association between aldosterone and either the time to first occurrence of a primary outcome (hazard ratio for doubling of aldosterone 0.92, 95% confidence interval 0.78-1.09, P=0.34) or hospitalization for HF (hazard ratio 1.38, 95% CI 0.96-1.99, P=0.08) in Cox regression models adjusted for covariates. Conclusions- In patients with recent acute coronary syndrome but without advanced HF, aldosterone does not predict major cardiovascular events.

  • 8.
    Savarese, Gianluigi
    et al.
    Karolinska Inst, Sweden.
    Lund, Lars H.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, 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.
    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.
    Nurse-Led Heart Failure Clinics Are Associated With Reduced Mortality but Not Heart Failure Hospitalization2019In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, no 10, article id e011737Article in journal (Refereed)
    Abstract [en]

    Background-Follow-up in a nurse-led heart failure (HF) clinic is recommended in HF guidelines, but its association with outcomes remains controversial, with previous studies including few and highly selected patients. Thus, large analyses of "real-world" samples are needed. Aims were to assess: (1) independent predictors of and (2) prognosis associated with planned referral to nurse-led HF clinics. Methods and Results-We analyzed data from the SwedeHF (Swedish HF Registry) using multivariable logistic regressions to identify independent predictors of planned referral to a nurse-led HF clinic and multivariable Cox regressions to test associations between planned referral and outcomes (all-cause death, HF hospitalization, and their composite). Of 40 992 patients, 39% were planned to be referred to a follow-up in a nurse-led HF clinic. Independent characteristics associated with planned referral were shorter duration of HF, clinical markers of more-severe HF, such as lower ejection fraction, higher New York Heart Association class and N-terminal pro-B-type natriuretic peptide, and lower blood pressure, as well as cohabitating versus living alone, male sex, fewer comorbidities, and more use of HF treatments. After adjustments, planned referral to a nurse-led HF clinic was associated with reduced mortality and mortality/HF hospitalization, but not HF hospitalization alone. Conclusions-In this nation-wide registry, 39% of our identified HF cohort was planned to be referred to a nurse-led HF clinic. Planned referral reflected more-severe HF, but also sex- and family-related factors, and it was independently associated with lower risk of death, but not of HF hospitalization.

  • 9.
    Simard, Trevor
    et al.
    University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
    Hibbert, Benjamin
    University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
    Natarjan, Machu
    Hamilton Health Sciences, Hamilton, Ontario, Canada.
    Mercuri, Mathew
    Department of Medicine, Columbia University, New York, NY.
    Hetherington, Simon
    Kettering, United Kingdom.
    Wright, Robert
    James Cook University Hospital, Middlesbrough, United Kingdom.
    Delewi, Ronak
    Academic Medical Center, University of Amsterdam, The Netherlands.
    Piek, Jan
    Academic Medical Center, University of Amsterdam, The Netherlands.
    Lehmann, Ralf
    Johann Wolfgang Goethe-University Frankfurt, Frankfurt, Germany.
    Ruzsa, Zoltan
    Cardiac and Vascular Center, Semmelweis University, Budapest, Hungary.
    Lange, Helmut
    Kardiologisch-Angiologische Praxis Herzzentrum Bremen, Bremen, Germany.
    Geijer, Håkan
    Department of Radiology, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Sandborg, Michael
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Kansal, Vinay
    Faculty of Undergraduate Medicine, University of Ottawa, Ontario, Canada.
    Bernick, Jordan
    Cardiovascular Research Methods Center, Ottawa, Ontario, Canada.
    Di Santo, Pietro
    University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
    Pourdjabbar, Ali
    University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
    Ramirez, Daniel
    University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
    Chow, Benjamin
    University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
    Chong, Aun
    University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
    Labinaz, Marino
    University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
    Le May, Michel
    University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
    O’Brien, Edward
    Libin Cardiovascular Institute of Alberta, Calgary, Alberta, Canada.
    Wells, George
    Cardiovascular Research Methods Center, Ottawa, Ontario, Canada.
    So, Derek
    University of Ottawa Heart Institute, Ottawa, Ontario, Canada dso@ottawaheart.ca.
    Impact of Center Experience on Patient Radiation Exposure During Transradial Coronary Angiography and Percutaneous Intervention: A Patient-Level, International, Collaborative, Multi-Center Analysis2016In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, no 6Article in journal (Refereed)
    Abstract [en]

    Background-—The adoption of the transradial (TR) approach over the traditional transfemoral (TF) approach has been hampered by concerns of increased radiation exposure—a subject of considerable debate within the field. We performed a patient-level, multi-center analysis to definitively address the impact of TR access on radiation exposure. Methods and Results-—Overall, 10 centers were included from 6 countries—Canada (2 centers), United Kingdom (2), Germany (2), Sweden (2), Hungary (1), and The Netherlands (1). We compared the radiation exposure of TR versus TF access using measured dose-area product (DAP). To account for local variations in equipment and exposure, standardized TR:TF DAP ratios were constructed per center with procedures separated by coronary angiography (CA) and percutaneous coronary intervention (PCI). Among 57 326 procedures, we demonstrated increased radiation exposure with the TR versus TF approach, particularly in the CA cohort across all centers (weighted-average ratios: CA, 1.15; PCI, 1.05). However, this was mitigated by increasing TR experience in the PCI cohort across all centers (r=0.8; P=0.005). Over time, as a center transitioned to increasing TR experience (r=0.9; P=0.001), a concomitant decrease in radiation exposure occurred (r=0.8; P=0.006). Ultimately, when a center’s balance of TR to TF procedures approaches 50%, the resultant radiation exposure was equivalent. Conclusions-—The TR approach is associated with a modest increase in patient radiation exposure. However, this increase is  eliminated when the TR and TF approaches are used with equal frequency—a guiding principle for centers adopting the TR approach.

  • 10.
    Simonsson, Moa
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Winell, Henric
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Olsson, Henrik
    Karolinska Inst, Sweden.
    Szummer, Karolina
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Alfredsson, Joakim
    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.
    Hall, Marlous
    Univ Leeds, England.
    Dondo, Tatendashe B.
    Univ Leeds, England.
    Gale, Chris P.
    Univ Leeds, England.
    Jernberg, Tomas
    Karolinska Inst, Sweden.
    Development and Validation of a Novel Risk Score for In-Hospital Major Bleeding in Acute Myocardial Infarction:-The SWEDEHEART Score2019In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, no 5, article id e012157Article in journal (Refereed)
    Abstract [en]

    Background-Bleeding risk stratification in acute coronary syndrome is of highest clinical interest but current risk scores have limitations. We sought to develop and validate a new in-hospital bleeding risk score for patients with acute myocardial infarction. Methods and Results-From the nationwide SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) register, 97,597 patients with acute myocardial infarction enrolled from 2009 until 2014 were selected. A full model with 23 predictor variables and 8 interaction terms was fitted using logistic regression. The full model was approximated by a model with 5 predictors and 1 interaction term. Calibration, discrimination, and clinical utility was evaluated and compared with the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) scores. Internal and temporal validity was assessed. In-hospital major bleeding, defined as fatal, intracranial, or requiring surgery or blood transfusion, occurred in 1356 patients (1.4%). The 5 predictors in the approximate model that constituted the SWEDEHEART score were hemoglobin, age, sex, creatinine, and Creactive protein. The ACTION and CRUSADE scores were poorly calibrated in the derivation cohort and therefore were recalibrated. The SWEDEHEART score showed higher discriminative ability than both recalibrated scores, overall (C-index 0.80 versus 0.73/0.72) and in all predefined subgroups. Decision curve analysis demonstrated consistently positive and higher net benefit for the SWEDEHEART score compared with both recalibrated scores across all clinically relevant decision thresholds. The original ACTION and CRUSADE scores showed negative net benefit. Conclusions-The 5-item SWEDEHEART score discriminates in-hospital major bleeding in patients with acute myocardial infarction and has superior model performance compared with the recalibrated ACTION and CRUSADE scores.

  • 11.
    Tromp, Jasper
    et al.
    University of Groningen, Netherlands.
    Khan, Mohsin A. F.
    University of Groningen, Netherlands; Academic Medical Centre, Netherlands.
    Klip, IJsbrand T.
    University of Groningen, Netherlands.
    Meyer, Sven
    University of Groningen, Netherlands; Carl von Ossietzky University of Oldenburg, Germany.
    de Boer, Rudolf A.
    University of Groningen, Netherlands.
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Hillege, Hans
    University of Groningen, Netherlands.
    van Veldhuisen, Dirk J.
    University of Groningen, Netherlands.
    van der Meer, Peter
    University of Groningen, Netherlands.
    Voors, Adriaan A.
    University of Groningen, Netherlands.
    Biomarker Profiles in Heart Failure Patients With Preserved and Reduced Ejection Fraction2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 4, article id e003989Article in journal (Refereed)
    Abstract [en]

    Background-Biomarkers may help us to unravel differences in the underlying pathophysiology between heart failure (HF) patients with a reduced ejection fraction (HFrEF) and a preserved ejection fraction (HFpEF). Therefore, we compared biomarker profiles to characterize pathophysiological differences between patients with HFrEF and HFpEF. Methods and Results-We retrospectively analyzed 33 biomarkers from different pathophysiological domains (inflammation, oxidative stress, remodeling, cardiac stretch, angiogenesis, arteriosclerosis, and renal function) in 460 HF patients (21% HFpEF, left ventricular ejection fraction amp;gt;= 45%) measured at discharge after hospitalization for acute HF. The association between these markers and the occurrence of all-cause mortality and/or HF-related rehospitalizations at 18 months was compared between patients with HFrEF and HFpEF. Patients were 70.6 +/- 11.4 years old and 37.4% were female. Patients with HFpEF were older, more often female, and had a higher systolic blood pressure. Levels of high-sensitive C-reactive protein were significantly higher in HFpEF, while levels of pro-atrial-type natriuretic peptide and N-terminal pro-brain natriuretic peptide were higher in HFrEF. Linear regression followed by network analyses revealed prominent inflammation and angiogenesis-associated interactions in HFpEF and mainly cardiac stretch-associated interactions in HrEF. The angiogenesis-specific marker, neuropilin and the remodeling-specific marker, osteopontin were predictive for all-cause mortality and/or HF-related rehospitalizations at 18 months in HFpEF, but not in HFrEF (P for interaction amp;lt;0.05). Conclusions-In HFpEF, inflammation and angiogenesis- mediated interactions are predominantly observed, while stretch-mediated interactions are found in HFrEF. The remodeling marker osteopontin and the angiogenesis marker neuropilin predicted outcome in HFpEF, but not in HFrEF.

  • 12.
    Varenhorst, Christoph
    et al.
    Uppsala Clin Res Ctr, Sweden; Uppsala Univ, Sweden.
    Hasvold, Pal
    AstraZeneca Nord Baltic, Sweden; AstraZeneca RandD, Sweden.
    Johansson, Saga
    Uppsala Clin Res Ctr, Sweden; Uppsala Univ, Sweden; AstraZeneca RandD, Sweden.
    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.
    Albertsson, Per
    Univ Gothenburg, Sweden.
    Leosdottir, Margret
    Lund Univ, Sweden.
    Hambraeus, Kristina
    Falun Cty Hosp, Sweden.
    James, Stefan
    Uppsala Clinical Research Center, Uppsala, Sweden; Uppsala University, Uppsala, Sweden.
    Jernberg, Tomas
    Solna Karolinska Univ Hosp, Sweden.
    Svennblad, Bodil
    Uppsala Clin Res Ctr, Sweden.
    Lagerqvist, Bo
    Uppsala Clin Res Ctr, Sweden; Uppsala Univ, Sweden.
    Culprit and Nonculprit Recurrent Ischemic Events in Patients With Myocardial Infarction: Data From SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies)2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e007174Article in journal (Refereed)
    Abstract [en]

    Background-Long-term disease progression after myocardial infarction (MI) is inadequately understood. We evaluated the pattern and angiographic properties (culprit lesion [CL]/non-CL [NCL]) of recurrent MI (re-MI) in a large real-world patient population. Methods and Results-Our observational study used prospectively collected data in 108 615 patients with first-occurrence MI enrolled in the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) between July 1, 2006 and November 29, 2014. During follow-up (median, 3.2 years), recurrent hospitalization for MI occurred in 11 117 patients (10.2%). Of the patients who underwent coronary angiography for the index MI, a CL was identified in 44 332 patients. Of those patients, 3464 experienced an re-MI; the infarct originated from the NCL in 1243 patients and from the CL in 655 patients. In total, 1566 re-MIs were indeterminate events and could not be classified as NCL or CL re-MIs. The risk of re-MI within 8 years related to the NCL was 0.06 (95% confidence interval [CI], 0.05-0.06), compared with 0.03 (95% CI, 0.02-0.03) for the CL. There were no large differences in baseline characteristics of patients with subsequent NCL versus CL re-MIs. Independent predictors of NCL versus CL re-MI were multivessel disease (odds ratio, 2.29; 95% CI, 1.87-2.82), male sex (odds ratio, 1.36; 95% CI, 1.09-1.71), and a prolonged time between the index and re-MI (odds ratio, 1.16; 95% CI, 1.10-1.22). Conclusions-In a large cohort of patients with first-occurrence MI undergoing percutaneous coronary intervention, the risk of re-MI originating from a previously untreated lesion was twice higher than the risk of lesions originating from a previously stented lesion.

  • 13.
    Wågsäter, Dick
    et al.
    Karolinska University hospital, Karolinska Institutet, Stockholm, Sweden .
    Paloschi, Valentina
    Karolinska University hospital, Karolinska Institutet, Stockholm, Sweden .
    Hanemaaijer, Roeland
    TNO Metabolic Health Research, Leiden, the Netherlands .
    Hultenby, Kjell
    Karolinska Institutet, Stockholm, Sweden.
    Bank, Ruud A
    University Medical Center Groningen, the Netherlands .
    Franco-Cereceda, Anders
    Karolinska Institutet, Stockholm, Sweden.
    Lindeman, Jan H N
    Leiden University Medical Center, the Netherlands .
    Eriksson, Per
    Karolinska University hospital, Karolinska Institutet, Stockholm, Sweden .
    Impaired collagen biosynthesis and cross-linking in aorta of patients with bicuspid aortic valve2013In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 2, no 1, p. e000034-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with bicuspid aortic valve (BAV) have an increased risk of developing ascending aortic aneurysm. In the present study, collagen homeostasis in nondilated and dilated aorta segments from patients with BAV was studied, with normal and dilated aortas from tricuspid aortic valve (TAV) patients as reference.

    METHODS AND RESULTS: Ascending aortas from 56 patients were used for biochemical and morphological analyses of collagen. mRNA expression was analyzed in 109 patients. Collagen turnover rates were similar in nondilated and dilated aortas of BAV patients, showing that aneurysmal formation in BAV is, in contrast to TAV, not associated with an increased collagen turnover. However, BAV in general was associated with an increased aortic collagen turnover compared with nondilated aortas of TAV patients. Importantly, the ratio of hydroxylysyl pyridinoline (HP) to lysyl pyridinoline (LP), 2 distinct forms of collagen cross-linking, was lower in dilated aortas from patients with BAV, which suggests that BAV is associated with a defect in the posttranslational collagen modification. This suggests a deficiency at the level of lysyl hydroxylase (PLOD1), which was confirmed by mRNA and protein analyses that showed reduced PLOD1 expression but normal lysyl oxidase expression in dilated aortas from patients with BAV. This suggests that impaired collagen cross-linking in BAV patients may be attributed to changes in the expression and/or activity of PLOD1.

    CONCLUSIONS: Our results demonstrate an impaired biosynthesis and posttranslational modification of collagen in aortas of patients with BAV, which may explain the increased aortic aneurysm formation in BAV patients.

  • 14.
    Zamani, Payman
    et al.
    Hospital University of Penn, PA USA .
    Schwartz, Gregory G.
    University of Colorado, CO USA .
    Olsson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Rifai, Nader
    Childrens Hospital, MA USA .
    Bao, Weihang
    Pfizer Pharmaceut Grp, NY USA .
    Libby, Peter
    VA Boston Healthcare Syst, MA USA .
    Ganz, Peter
    San Francisco Gen Hospital, CA USA .
    Kinlay, Scott
    VA Boston Healthcare Syst, MA USA .
    Inflammatory Biomarkers, Death, and Recurrent Nonfatal Coronary Events After an Acute Coronary Syndrome in the MIRACL Study2013In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 2, no 1Article in journal (Refereed)
    Abstract [en]

    Background-In acute coronary syndromes, C-reactive protein (CRP) strongly relates to subsequent death, but surprisingly not to recurrent myocardial infarction. Other biomarkers may reflect different processes related to these outcomes. We assessed 8 inflammatory and vascular biomarkers and the risk of death and recurrent nonfatal cardiovascular events in the 16 weeks after an acute coronary syndrome. less thanbrgreater than less thanbrgreater thanMethods and Results-We measured blood concentrations of CRP, serum amyloid A (SAA), interleukin-6 (IL-6), soluble intercellular adhesion molecule (ICAM), soluble vascular cell adhesion molecule (VCAM), E-selectin, P-selectin, and tissue plasminogen activator antigen (tPA) 24 to 96 hours after presentation with acute coronary syndrome in 2925 subjects participating in a multicenter study. Biomarkers were related to the risk of death, and recurrent nonfatal acute coronary syndromes (myocardial infarction or unstable angina) over 16 weeks using Cox proportional hazard models. On univariate analyses, baseline CRP (P=0.006), SAA (P=0.012), and IL-6 (Pandlt;0.001) were related to death, but not to recurrent nonfatal acute coronary syndromes. VCAM and tPA related to the risk of death (Pandlt;0.001, P=0.021, respectively) and to nonfatal acute coronary syndromes (P=0.021, P=0.049, respectively). Adjusting for significant covariates reduced the strength of the associations; however, CRP and SAA continued to relate to death. less thanbrgreater than less thanbrgreater thanConclusions-In acute coronary syndromes, the CRP inflammatory axis relates to the risk of death and may reflect myocardial injury. VCAM and tPA may have greater specificity for processes reflecting inflammation and thrombosis in the epicardial arteries, which determine recurrent coronary events.

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