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  • 1. Ahlsson, Anders
    et al.
    Jidéus, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Albåge, Anders
    Källner, Göran
    Holmgren, Anders
    Boano, Gabriella
    Hermansson, Ulf
    Kimblad, Per-Ola
    Scherstén, Henrik
    Sjögren, Johan
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Åberg, Bengt
    Berglin, Eva
    A Swedish consensus on the surgical treatment of concomitant atrial fibrillation2012In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 46, no 4, p. 212-218Article, review/survey (Refereed)
    Abstract [en]

    Atrial fibrillation (AF) is a common arrhythmia among patients scheduled for open heart surgery and is associated with increased morbidity and mortality. According to international guidelines, symptomatic and selected asymptomatic patients should be offered concomitant surgical AF ablation in conjunction with valvular or coronary surgery. The gold standard in AF surgery is the Cox Maze III ("cut-and-sew") procedure, with surgical incisions in both atria according to a specified pattern, in order to prevent AF reentry circuits from developing. Over 90% of patients treated with the Cox Maze III procedure are free of AF after 1 year. Recent developments in ablation technology have introduced several energy sources capable of creating nonconducting atrial wall lesions. In addition, simplified lesion patterns have been suggested, but results with these techniques have been unsatisfactory. There is a clear need for standardization in AF surgery. The Swedish Arrhythmia Surgery Group, represented by surgeons from all Swedish units for cardiothoracic surgery, has therefore reached a consensus on surgical treatment of concomitant AF. This consensus emphasizes adherence to the lesion pattern in the Cox Maze III procedure and the use of biatrial lesions in nonparoxysmal AF.

  • 2. Albåge, Anders
    et al.
    Jidéus, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Johansson, Birgitta
    Berglin, Eva
    Early and Long-Term Mortality in 536 Patients After the Cox-Maze III Procedure: A National Registry-Based Study2013In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 95, no 5, p. 1626-1632Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The cut-and-sew Cox-maze III procedure is the gold standard for surgical treatment of atrial fibrillation. The aim was to study early and long-term mortality based on registry analyses in Swedish Cox-maze III patients.

    METHODS: Preoperative and early postoperative data were analyzed in 536 patients (male/female (425/111), mean age 57 ± 8.6 years), operated from 1994 to 2009 in 4 centers; 422 (79%) underwent stand-alone Cox-maze III. Atrial fibrillation was paroxysmal in 38% and non-paroxysmal in 62%, mean duration was 7.8 ± 6.3 years. Patients were followed for survival or death in a validated national Cause-of-Death registry. Risk factors associated with observed survival were identified in univariable and multivariable analyses in a standard Cox proportional hazards model.

    RESULTS: Four early deaths (0.7%) occurred due to technical complications. At follow-up, 41 of 536 (7.6%) patients had died. Cause of death was cardiovascular in 19 of 536 (3.5%). No ischemic stroke-related death was registered. Univariable risk factors for all-cause mortality included hypertension (hazard ratio [HR] 2.8, confidence interval [CI] 1.5 to 5.3), heart failure (HR 2.4, CI 1.3 to 4.3), concomitant surgery (HR 2.2, CI 1.1 to 4.1), and postoperative complications (HR 2.5, CI 1.3 to 4.8). Gender, non-paroxysmal atrial fibrillation and long arrhythmia duration did not confer increased risk of death. Multivariable risk factors were hypertension (HR 2.9, CI 1.5 to 5.5) and postoperative complications (HR 2.4, CI 1.2 to 4.6). Survival for cardiovascular death at 5, 10, and 15 years was 98%, 96%, and 93%, respectively.

    CONCLUSIONS: Registry-based follow-up showed low early and long-term cardiovascular mortality and no stroke-related mortality. This is important baseline information when evaluating current surgical and nonsurgical treatment of atrial fibrillation.

  • 3.
    Alström, Ulrica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Granath, Fredrik
    Friberg, Orjan
    Ekbom, Anders
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Risk factors for re-exploration due to bleeding after coronary artery bypass grafting2012In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 46, no 1, p. 39-44Article in journal (Refereed)
    Abstract [en]

    Objective. The study aimed to investigate relevant clinical risk factors for re-exploration due to bleeding after primary coronary artery bypass graft (CABG) surgery, and to evaluate the influence of antiplatelet and antifibrinolytic drugs. Design. Three retrospective analyses were performed on patients who underwent CABG: (1) Logistic regression was used to identify clinical risk factors for re-exploration (n = 3000). (2) A case-control study (n = 228) was used to obtain information on exposure of antithrombotic and hemostatic therapy. (3) Based on exposure to antiplatelet and antifibrinolytic therapy, and odds ratios (ORs) in multivariate logistic models, the proportion of re-explorations attributed to these drugs was calculated. Results. A receiver operating characteristic curve was created for clinical risk factors. The C-index was 0.64, indicating limited ability to predict re-exploration for bleeding. Clopidogrel was the only drug influencing the risk of re-exploration (OR 3.2, 95% CI 1.7-5.9). The harmful effect of clopidogrel was confirmed in multivariate model (OR 4.7, 95% CI 2.2-9.9), and aprotinin had a protective effect of the same magnitude (OR 0.2, 95% CI 0.1-0.6). Conclusions. Clopidogrel is an essential risk factor for re-exploration due to bleeding, and attributable to at least one-quarter of surveyed cases. Aside from pharmaceuticals, there are no strong clinical risk factors.

  • 4.
    Alström, Ulrica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Levin, L-Å
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svedjeholm, R
    Friberg, Ö
    Cost analysis of re-exploration for bleeding after coronary artery bypass graft surgery2012In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 108, no 2, p. 216-222Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Re-exploration for bleeding after cardiac surgery is an indicator of substantial haemorrhage and is associated with increased hospital resource utilization. This study aimed to analyse the costs of re-exploration and estimate the costs of haemostatic prophylaxis.

    METHODS:

    A total of 4232 patients underwent isolated, first-time, coronary artery bypass graft (CABG) surgery during 2005-8. Each patient re-explored for bleeding (n=127) was matched with two controls not requiring re-exploration (n=254). Cost analysis was based on resource utilization from completion of CABG until discharge. A mean cost per patient for re-exploration was calculated. Based on this, the net cost of prophylactic treatment with haemostatic drugs for preventing re-exploration was calculated.

    RESULTS:

    Patients undergoing re-exploration had higher exposure to clopidogrel before operation, prolonged stays in the intensive care unit, and more blood transfusions than controls. The mean incremental cost for re-exploration was (sic)6290 [95% confidence interval (CI) (sic)3408-(sic)9173] per patient, of which 48% [(sic)3001 (95% CI (sic)249-(sic)2147)] was due to prolonged stay, 31% [(sic)1928 (95% CI (sic)1710-(sic)2147)] to the cost of surgery/anaesthesia, 20% [(sic)1261 (95% CI (sic)1145-(sic)1378)] to the increased number of blood transfusions, and <2% [(sic)100 (95% CI (sic)39-(sic)161)] to the cost of haemostatic drugs. A cost model, at an estimated 50% efficacy for recombinant activated clotting factor VIIa and a 50% expected risk for re-exploration without prophylaxis, demonstrated that to be cost neutral, prophylaxis of four patients needed to result in one avoided re-exploration.

    CONCLUSIONS:

    The resource utilization costs were substantially higher in patients requiring re-exploration for bleeding. From a strict cost-effectiveness perspective, clinical interventions to prevent haemorrhage might be underutilized.

  • 5.
    Alström, Ulrica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Tydén, Hans
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment2007In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 120, no 3, p. 353-359Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Addition of clopidogrel to patients treated with ASA has been shown to decrease the incidence of in-stent thrombosis after percutaneous coronary interventions. However, it has also been reported that up to 30% of patients do not achieve adequate platelet inhibition from standard dosages of ASA and clopidogrel. There is a demand for reliable methods to measure the individual platelet inhibiting effect of this combination therapy. MATERIALS AND METHODS: The primary aim of the present investigation was to compare three methods for evaluation of the platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment. Thirty patients presenting for coronary angiography/PCI were included. Two patients were excluded due to technical problems. All patients were on 75-100 mg ASA/day for at least 8 days. Blood samples were analysed before and 16 h after a 300 mg clopidogrel bolus dose. The platelet inhibiting effect was measured with (1) Whole blood flow cytometry (17 patients); (2) a bed-side test, Platelet Mapping assay for the thrombelastograph (28 patients); and (3) PFA (Platelet function analyser) -100 (26 patients). RESULTS: With flow cytometry, the percentage of platelets expressing P-selectin (p=0.03) on their surface decreased significantly after the bolus dose of clopidogrel. There was also a reduction of platelets binding fibrinogen when stimulated with ADP. A significantly (p=0.002) increased platelet inhibition could also be demonstrated with Platelet Mapping. PFA-100 could not measure any significant platelet inhibiting effect of clopidogrel. CONCLUSION: A significant platelet inhibition could be demonstrated with flow cytometry and the Platelet Mapping assay, but not with PFA-100. However, levels of response for the individual patient with these three methods were inconsistent. Further studies are needed to evaluate how the results correlate to the clinical risk of thrombosis and bleeding.

  • 6.
    Baron, Tomasz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Orndahl, Lovisa Holm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hedin, Eva-Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Flachskampf, Frank
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Volumetric quantification of regurgitant volume in asymptomatic severe degenerative mitral regurgitation by echocardiography and cardiac mri with independent validation of forward stroke volume by positron emission tomography2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 69, no 11 Suppl, p. 1973-1973Article in journal (Other academic)
  • 7.
    Baron, Tomasz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Örndahl, Lovisa Holm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hedin, Eva-Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Flachskampf, Frank A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Comparison of left ventricular volumes and regurgitant volumes by echocardiography and magnetic resonance in patients with severe degenerative mitral regurgitation2016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, p. 1239-1239Article in journal (Refereed)
  • 8. Bourantas, Christos V.
    et al.
    Zhang, Yao-Jun
    Garg, Scot
    Mack, Michael
    Dawkins, Keith D.
    Kappetein, Arie Pieter
    Mohr, Friedrich W.
    Colombo, Antonio
    Holmes, David R.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Feldman, Ted
    Morice, Marie-Claude
    de Vries, Ton
    Morel, Marie-Angele
    Serruys, Patrick W.
    Prognostic Implications of Severe Coronary Calcification in Patients Undergoing Coronary Artery Bypass Surgery: An Analysis of the SYNTAX Study2015In: Catheterization and cardiovascular interventions, ISSN 1522-1946, E-ISSN 1522-726X, Vol. 85, no 2, p. 199-206Article in journal (Refereed)
    Abstract [en]

    ObjectivesTo investigate the prognostic implications of the presence of severe lesion calcification in patients undergoing coronary artery bypass graft (CABG) operation. BackgroundThere is robust evidence that lesion calcification is a predictor of worse prognosis in patients undergoing percutaneous coronary intervention; however, there is limited data about the prognostic implication of lesion calcium in patients treated with CABG. MethodsWe retrospectively analyzed data from 1,545 patients who underwent CABG and were recruited in the SYNTAX study and CABG registry. Two experts reviewed the angiographic data and classified patients in two groups: those with severely calcified coronary arteries and those without severe lesion calcification. Clinical outcomes at 5-year follow-up were collected and compared in the two groups. ResultsOne out of three patients exhibited severe lesion calcification (n=588). Patients with calcified coronaries had an increased mortality at 5-year follow-up (17.1% vs. 9.9%, P<0.001) and a higher event rate of death-myocardial infarction (MI) compared with those without (19.4% vs. 13.2%, P=0.003), but there was no statistical significant difference between the two groups for major adverse cardiovascular events (MACE, 26.8% vs. 21.8%, P=0.057). In multivariate Cox regression analysis severe lesion calcification was an independent predictor of an increased all-cause mortality (hazard ratio: 1.39, 95% confidence interval: 1.02-1.89; P=0.037) but it was not an independent predictor of the combined end-points death-MI or MACE. ConclusionsSevere lesion calcification is associated with an increased mortality in patients undergoing CABG, but it is not an independent predictor of death-MI or MACE. This paradox can be attributed to the fact that CABG allows perfusion of the healthy coronaries bypassing the diseased arteries and thus it minimizes the risk of coronary events due to progressive atherosclerosis. (c) 2014 Wiley Periodicals, Inc.

  • 9. Breeman, Arno
    et al.
    Hordijk-Trion, Marjo
    Lenzen, Mattie
    Hoeks, Sanne
    Ottervanger, Jan Paul
    Bertrand, Michel E.
    Sechtem, Udo
    Zaliunas, Remigijus
    Legrand, Victor
    de Boer, Menko-Jan
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Mercado, Nestor
    Wijns, William
    Boersma, Eric
    Treatment decisions in stable coronary artery disease: insights from the Euro Heart Survey on Coronary Revascularization2006In: Journal of Thoracic and Cardiovascular Surgery, ISSN 0022-5223, E-ISSN 1097-685X, Vol. 132, no 5, p. 1001-1009Article in journal (Refereed)
    Abstract [en]

    Objective: We sought to assess determinants of clinical decision making in patients with stable coronary artery disease.

    Methods: The 2936 patients with stable angina pectoris who enrolled in the Euro Heart Survey on Coronary Revascularization were the subject of this analysis. After the diagnosis has been confirmed, physicians decided on treatment: medical management or revascularization therapy by means of percutaneous coronary intervention or coronary bypass surgery. We applied logistic regression analyses to evaluate the relation between baseline characteristics and treatment decision: medical treatment versus percutaneous coronary intervention, medical treatment versus coronary bypass surgery, and percutaneous coronary intervention versus coronary bypass surgery.

    Results: The median age was 64 years, 77% were men, and 20% had diabetes. Medical therapy was intended in 690 (24%) patients, percutaneous coronary intervention in 1503 (51%) patients, and coronary bypass surgery in the remaining 743 (25%) patients, respectively. Revascularization was generally preferred in patients with more severe anginal complaints, an intermediate-to-large area of myocardium at risk, and preserved left ventricular function who had not undergone prior coronary revascularization, provided lesions were suitable for treatment. Coronary bypass surgery was preferred over percutaneous coronary intervention in multivessel or left main disease, as well as in those with concomitant valvular heart disease, provided a sufficient number of lesions were suitable for coronary bypass surgery. In those with previous coronary bypass surgeries, more often percutaneous coronary intervention was preferred than redo coronary bypass surgery. Diabetes was not associated with more frequent preference for coronary bypass surgery.

    Conclusions: In the hospitals that participated in the Euro Heart Survey on Coronary Revascularization, treatment decisions in stable coronary artery disease were largely in agreement with professional guidelines and determined by multiple factors. Most important deviations between guideline recommendations and clinical practice were seen in patients with extensive coronary disease, impaired left ventricular function, and diabetes.

  • 10. Brooks, D. R.
    et al.
    Klint, Å.
    Dickman, P. W.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Lambe, M.
    Temporal trends in non-small cell lung cancer survival in Sweden2007In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 96, no 3, p. 519-522Article in journal (Refereed)
    Abstract [en]

    We modeled temporal trends in the 1- and 5-year survival of 32 499 patients with adenocarcinoma and squamous cell carcinoma of the lung in the Swedish Cancer Register between 1961 and 2000. The 1-year relative survival for adenocarcinoma improved from 37% for patients diagnosed 1961–1965 to 45% for those diagnosed 1996–2000 and from 39 to 45% for squamous cell carcinoma. The adjusted excess mortality ratios for the period 1996–2000 compared with 1961–1965 were 0.80 for adenocarcinoma and 0.81 for squamous cell carcinoma. Thus, a previous report in a Dutch study of a relatively worsening prognosis for adenocarcinoma over time could not be confirmed.

  • 11. Carlsson, Jörg
    et al.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Höfer, Sebastian
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Outcome of percutaneous coronary intervention in hospitals with and without on-site cardiac surgery standby2007In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 93, no 3, p. 335-338Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To compare characteristics and outcome of patients undergoing percutaneous coronary intervention (PCI) in clinics with (WSB) or without (NOSB) on-site cardiac surgery backup. DESIGN: Analysis according to hospital, type of prospectively collected data of all patients who underwent PCI during 2000-3. SETTING: The Swedish Coronary Angiography and Angioplasty Registry covers all PCI procedures performed in Sweden. PATIENTS: 34,363 patients underwent PCI between January 2000 and December 2003. 8838 procedures were performed in NOSB (mean age of patients was 64.5 years) hospitals and 25,525 in WSB (mean age of patients was 64.1 years) hospitals (p = 0.002). RESULTS: More patients in NOSB hospitals had diabetes (17.8% vs 16.8%; p = 0.03). Other clinical characteristics (previous infarct, previous coronary artery bypass graft (CABG)) also showed a tendency towards worse patients being treated in NOSB hospitals. However, there was a higher percentage of patients with ST-segment elevation myocardial infarction (18% vs 9.7%; p<0.01) in WSB hospitals. After adjusting for differences in baseline risk no significant differences regarding outcome (30-day mortality, 1-year mortality, stroke and emergency CABG) were observable between WSB and NOSB hospitals. This applied to elective and non-elective procedures. CONCLUSIONS: On the basis of these data it does not seem warranted to recommend against percutaneous transluminal coronary angioplasty in NOSB hospitals.

  • 12.
    Dimberg, Axel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Alström, Ulrica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Higher Preoperative Plasma Thrombin Potential in Patients Undergoing Surgery for Aortic Stenosis Compared to Surgery for Stable Coronary Artery Disease2018In: Clinical and applied thrombosis/hemostasis, ISSN 1076-0296, E-ISSN 1938-2723, Vol. 24, no 8, p. 1282-1290Article in journal (Refereed)
    Abstract [en]

    Aortic stenosis (AS) and coronary artery disease (CAD) influence the coagulation system, potentially affecting hemostasis during cardiac surgery. Our aim was to evaluate 2 preoperative global hemostasis assays, plasma thrombin potential and thromboelastometry, in patients with severe aortic valve stenosis compared to patients with CAD. A secondary aim was to test whether the assays were associated with postoperative bleeding. Calibrated automated thrombogram (CAT) in platelet-poor plasma and rotational thromboelastometry (ROTEM) in whole blood were analyzed in patients scheduled for elective surgery due to severe AS (n = 103) and stable CAD (n = 68). Patients with AS displayed higher plasma thrombin potential, both thrombin peak with median 252 nmol/L (interquartile range 187-319) and endogenous thrombin potential (ETP) with median 1552 nmol/L/min (interquartile range 1340-1838), when compared to patients with CAD where thrombin peak was median 174 nmol/L (interquartile range 147-229) and ETP median 1247 nmol/L/min (interquartile range 1034-1448; both P < .001). Differences persisted after adjustment for age, gender, comorbidity, and antithrombotic treatment. Differences observed in thromboelastometry between the groups did not persist after adjustment for baseline characteristics. Bleeding amount showed no relationship with plasma thrombin potential but weakly to thromboelastometry (R-2 = .064, P = .001). Patients with AS exhibited preoperatively increased plasma thrombin potential compared to patients with CAD. Plasma thrombin potential was not predictive for postoperative bleeding in patients scheduled for elective surgery.

  • 13.
    Djureinovic, Dijana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Dodig-Crnkovic, Tea
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden.
    Hellström, Cecilia
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden.
    Holgersson, Georg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Bergqvist, Michael
    Department of Oncology, Gavle Hospital, Gavle, Sweden..
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Schwenk, Jochen M.
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer2018In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 125, p. 157-163Article in journal (Refereed)
    Abstract [en]

    Cancer testis antigens (CTAs) are defined as proteins that are specifically expressed in testis or placenta and their expression is frequently activated in cancer. Due to their ability to induce an immune response, CTAs may serve as suitable targets for immunotherapy. The aim of this study was to evaluate if there is reactivity against CTAs in the plasma of non-small cell lung cancer (NSCLC) patients through the detection of circulating antibodies. 

    To comprehensively analyse auto-antibodies against CTAs the multiplexing capacities of suspension bead array technology was used. Bead arrays were created with 120 protein fragments, representing 112 CTAs. Reactivity profiles were measured in plasma samples from 133 NSCLC patients and 57 cases with benign lung diseases. Altogether reactivity against 69 antigens, representing 81 CTAs, was demonstrated in at least one of the analysed samples. Twenty-nine of the antigens (45 CTAs) demonstrated exclusive reactivity in NSCLC samples. Reactivity against CT47A genes, PAGE3, VCX, MAGEB1, LIN28B and C12orf54 were only found in NSCLC patients at a frequency of 1%-4%. The presence of autoantibodies towards these six antigens was confirmed in an independent group of 34 NSCLC patients.

    In conclusion, we identified autoantibodies against CTAs in the plasma of lung cancer patients. The reactivity pattern of autoantibodies was higher in cancer patients compared to the benign group, stable over time, but low in frequency of occurrence. The findings suggest that some CTAs are immunogenic and that these properties can be utilized as immune targets.

  • 14.
    Djureinovic, Dijana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Hallström, Bjorn M.
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Horie, Masafumi
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan..
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    La Fleur, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Fagerberg, Linn
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Brunnström, Hans
    Reg Labs Reg Skane, Dept Pathol, Lund, Sweden..
    Lindskog, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Madjar, Katrin
    Tech Univ Dortmund, Dept Stat, Dortmund, Germany..
    Rahnenfuehrer, Joerg
    Tech Univ Dortmund, Dept Stat, Dortmund, Germany..
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Koyi, Hirsh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Brandén, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Edlund, Karolina
    Tech Univ Dortmund, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany..
    Hengstler, Jan G.
    Tech Univ Dortmund, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany..
    Lambe, Mats
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Saito, Akira
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan..
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Uhlen, Mathias
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Profiling cancer testis antigens in non-small-cell lung cancer2016In: JCI INSIGHT, ISSN 2379-3708, Vol. 1, no 10, article id e86837Article in journal (Refereed)
    Abstract [en]

    Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies.

  • 15.
    Djureinovic, Dijana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Hallström, Björn
    Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    La Fleur, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Fagerberg, Linn
    Brunnström, Hans
    Lund Univ, Div Pathol, Lund, Sweden..
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Koyi, Hirsh
    Gavle Cent Hosp, Dept Pneumol, S-80187 Gavle, Sweden..
    Lambe, Mats
    Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden..
    Branden, Eva
    Gavle Cent Hosp, Dept Pneumol, S-80187 Gavle, Sweden..
    Lindskog, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Uhlen, Mathias
    Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    The Identification of Therapeutic Targets in Lung Cancer Based on Transcriptomic and Proteomic Characterization of Cancer-Testis Antigens2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, p. S256-S256Article in journal (Other academic)
  • 16.
    Djureinovic, Dijana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Pontén, Victor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Landelius, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Al Sayegh, Sahar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Kappert, Kai
    Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry; Center for Cardiovascular Research (CCR), Berlin, Germany.
    Kamali-Moghaddam, Masood
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung2019In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, article id 741Article in journal (Refereed)
    Abstract [en]

    Background:The overall prognosis of non-small cell lung cancer (NSCLC) is poor, and currently only patients with localized disease are potentially curable. Therefore, preferably non-invasively determined biomarkers that detect NSCLC patients at early stages of the disease are of high clinical relevance. The aim of this study was to identify and validate novel protein markers in plasma using the highly sensitive DNA-assisted multiplex proximity extension assay (PEA) to discriminate NSCLC from other lung diseases. 

    Methods:Plasma samples were collected from a total of 343 patients who underwent surgical resection for different lung diseases, including 144 patients with lung adenocarcinoma (LAC),68 patients with non-malignant lung disease, 83 with lung metastasis of colorectal cancers and 48 patients with typical carcinoid. One microliter of plasma was analyzed using PEA, allowing detection and quantification of 92 established cancer related proteins. The concentrations of the plasma proteins were compared between disease groups.

    Results:The comparison between LAC and benign samples revealed significantly different plasma levels for four proteins; CXL17, CEACAM5, VEGFR2 and ERBB3 (adjusted p-value < 0.05). A multi-parameter classifier was developed to discriminate between samples from LAC patients and from patients with non-malignant lung conditions. With a bootstrap aggregated decision tree algorithm (TreeBagger) a sensitivity of 93% and specificity of 64% was achieved to detect LAC in this risk population. 

    Conclusion:By applying the highly sensitive PEA, reliable protein profiles could be determined in microliter amounts of plasma. We further identified proteins that demonstrated different plasma concentration in defined disease groups and developed a signature that holds potential to be included in a screening assay for early lung cancer detection. 

  • 17. Ekroth, Rolf
    et al.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    High or low risk coronary patients: who gets the highest priority?2010In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 44, no 4, p. 195-196Article in journal (Refereed)
    Abstract [en]

    Coronary revascularisation is more often used in patients at small risk and with little to gain than in patients at high risk and much to gain. This is against current guide-lines and is wasteful. The problem if aggravated by socioeconomic bias. A redesigned reimbursement system, based on measured improved quality of life and survival, would encourage a more efficient use of resources.

  • 18. Ekroth, Rolf
    et al.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Randomized controlled studies: Scientific evidence or disinformation?2011In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 45, no 3, p. 131-132Article in journal (Other academic)
  • 19. Ekroth, Rolf
    et al.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Werkö, L
    Expansion of PCI at the expense of bypass surgery jeopardizes protection against premature death2002In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 36, no 4, p. 194-196Article in journal (Refereed)
  • 20. Farooq, V.
    et al.
    Serruys, P. W.
    Holmes, D. R.
    Kappetein, A. P.
    Mack, M.
    Feldman, T.
    Dawkins, K. D.
    Mohr, F. W.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    The long term (4-year) prognostic significance of abnormal cardiac enzyme rises in patients treated with surgical or percutaneous revascularisation: a substudy from the SYNTAX trial2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 500-500Article in journal (Other academic)
  • 21. Farooq, Vasim
    et al.
    Girasis, Chrysafios
    Magro, Michael
    Onuma, Yoshinobu
    Morel, Marie Angèle
    Heo, Jung Ho
    Garcia-Garcia, Hector
    Kappetein, Arie Pieter
    van den Brand, Marcel
    Holmes, David R
    Mack, Michael
    Feldman, Ted
    Colombo, Antonio
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Carrié, Didier
    Fournial, Gerard
    van Es, Gerrit-Anne
    Dawkins, Keith D
    Mohr, Friedrich W
    Morice, Marie-Claude
    Serruys, Patrick W
    The CABG SYNTAX Score - an angiographic tool to grade the complexity of coronary disease following coronary artery bypass graft surgery: from the SYNTAX Left Main Angiographic (SYNTAX-LE MANS) substudy2013In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 8, no 11, p. 1277-1285Article in journal (Refereed)
    Abstract [en]

    AIMS: The SYNTAX Score (SXscore) has established itself as an important prognostic tool in patients undergoing percutaneous coronary intervention (PCI). A limitation of the SXscore is the inability to differentiate outcomes in patients who have undergone prior coronary artery bypass graft (CABG) surgery. The CABG SXscore was devised to address this limitation.

    METHODS AND RESULTS: In the SYNTAX-LE MANS substudy 115 patients with unprotected left main coronary artery disease (isolated or associated with one, two or three-vessel disease) treated with CABG were prospectively assigned to undergo a 15-month coronary angiogram. An independent core laboratory analysed the baseline SXscore prior to CABG. The 15-month CABG SXscore was calculated by a panel of three interventional cardiologists. The CABG SXscore was calculated by determining the standard SXscore in the "native" coronary vessels ("native SXscore") and deducting points based on the importance of the diseased coronary artery segment (Leaman score) that have a functioning bypass graft anastomosed distally. Points relating to intrinsic coronary disease, such as bifurcation disease or calcification, remain unaltered. The mean 15-month CABG SXscore was significantly lower compared to the mean baseline SXscore (baseline SXscore 31.6, SD 13.1; 15-month CABG SXscore 21.2, SD 11.1; p<0.001). Reproducibility analyses (kappa [k] statistics) indicated a substantial agreement between CABG SXscore measurements (k=0.70; 95% CI [0.50-0.90], p<0.001), with the points deducted to calculate the CABG SXscore the most reproducible measurement (k=0.74; 95% CI [0.53-0.95], p<0.001). Despite the limited power of the study, four-year outcome data (Kaplan-Meier curves) demonstrated a trend towards reduced all-cause death (9.1% vs. 1.8%, p=0.084) and death/CVA/MI (16.4% vs. 7.0%, p=0.126) in the low compared to the high CABG SXscore group.

    CONCLUSIONS: In this pilot study the calculation of the CABG SXscore appeared feasible, reproducible and may have a long-term prognostic role in patients with complex coronary disease undergoing surgical revascularisation. Validation of this new scoring methodology is required.

  • 22. Farooq, Vasim
    et al.
    Girasis, Chrysafios
    Magro, Michael
    Onuma, Yoshinobu
    Morel, Marie-Angele
    Heo, Jung Ho
    Garcia-Garcia, Hector M.
    Kappetein, Arie Pieter
    van den Brand, Marcel
    Holmes, David R.
    Mack, Michael
    Feldman, Ted
    Colombo, Antonio
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Carrie, Didier
    Fournial, Gerard
    van Es, Gerrit Anne
    Dawkins, Keith D.
    Mohr, Friedrich W.
    Morice, Marie-Claude
    Serruys, Patrick W.
    The coronary artery bypass graft SYNTAX Score: final five-year outcomes from the SYNTAX-LE MANS left main angiographic substudy2013In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 9, no 8, p. 1009-1010Article in journal (Refereed)
  • 23. Farooq, Vasim
    et al.
    Serruys, Patrick
    Garcia-Garcia, Hector M.
    Zhang, Yaojun
    Bourantas, Christos
    Diletti, Roberto
    Papafaklis, Michail
    Holmes, David, Jr.
    Mack, Michael
    Feldman, Ted
    Morice, Marie-Claude
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Colombo, Antonio
    de Vries, Ton
    Morel, Marie Angele
    Van Es, Gerrit Anne
    Mohr, Friedrich
    Dawkins, Keith
    Kappetein, A. Pieter
    Sianos, Georgios
    Long-Term (4-Year) Clinical Outcomes of Total Occlusions and Completeness of Revascularisation in the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery Trial2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 17, p. B25-B25Article in journal (Other academic)
  • 24. Farooq, Vasim
    et al.
    Serruys, Patrick W.
    Bourantas, Christos V.
    Zhang, Yaojun
    Muramatsu, Takashi
    Feldman, Ted
    Holmes, David R.
    Mack, Michael
    Morice, Marie Claude
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Colombo, Antonio
    de Vries, Ton
    Morel, Marie-angele
    Dawkins, Keith D.
    Kappetein, Arie Pieter
    Mohr, Friedrich W.
    Response to Letter Regarding Article, " Quantification of Incomplete Revascularization and Its Association With Five- Year Mortality in the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery ( SYNTAX) Trial: Validation of the Residual SYNTAX Score"2014In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 129, no 8, p. E355-E356Article in journal (Other academic)
  • 25. Farooq, Vasim
    et al.
    Serruys, Patrick W.
    Bourantas, Christos V.
    Zhang, Yaojun
    Muramatsu, Takashi
    Feldman, Ted
    Holmes, David R.
    Mack, Michael
    Morice, Marie Claude
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Colombo, Antonio
    de Vries, Ton
    Morel, Marie-angele
    Dawkins, Keith D.
    Kappetein, Arie-Pieter
    Mohr, Friedrich W.
    Quantification of Incomplete Revascularization and its Association With Five-Year Mortality in the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Trial Validation of the Residual SYNTAX Score2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 2, p. 141-151Article in journal (Refereed)
    Abstract [en]

    Background The residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Score is an objective measure of the degree and complexity of residual stenosis after percutaneous coronary intervention (PCI). Methods and Results In the randomized PCI cohort of the SYNTAX Trial (n=903), the baseline and residual SYNTAX Scores were calculated. Subjects with a residual SYNTAX Score of 0 were defined as having undergone complete revascularization (CR), and a residual SYNTAX Score >0 as incomplete revascularization (ICR). Five-year clinical outcomes were stratified by CR and ICR (tertiles of the residual SYNTAX Score: >0-4, >4-8, and >8). In the PCI cohort, the mean baseline and residual SYNTAX Scores were 28.4 +/- 11.5 and 4.5 +/- 6.9, respectively. The mean SYNTAX Score (representative of the burden of disease removed by PCI) was 23.8 +/- 10.9. The residual SYNTAX Score was distributed as follows: CR, 0 (n=386, 42.7%); ICR, >0 to 4 (n=184, 20.4%), >4 to 8 (n=167, 18.5%), >8 (n=153, 16.9%). A progressively higher residual SYNTAX Score was shown to be a surrogate marker of increasing clinical comorbidity and anatomic complexity. Subjects with CR or residual SYNTAX Scores 8 had comparable 5-year mortality (CR, 8.5%; residual SYNTAX Score >0-4, 8.7%; >4-8, 11.4%; P=0.60). A residual SYNTAX Score >8 was associated with 35.3% all-cause mortality at 5-years (P<0.001). Stratified analyses in the predefined medical treated diabetic and left main subgroups yielded similar results. Conclusions The residual SYNTAX Score was shown to be a powerful indicator of 5-year mortality in the SYNTAX Trial. The residual SYNTAX Score may aid in determining a reasonable level of revascularization.

  • 26. Farooq, Vasim
    et al.
    Serruys, Patrick W
    Bourantas, Christos
    Vranckx, Pascal
    Diletti, Roberto
    Garcia Garcia, Hector M
    Holmes, David R
    Kappetein, Arie-Pieter
    Mack, Michael
    Feldman, Ted
    Morice, Marie Claude
    Colombo, Antonio
    Morel, Marie-Angèle
    de Vries, Ton
    van Es, Gerrit Anne
    Steyerberg, Ewout W
    Dawkins, Keith D
    Mohr, Friedrich W
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Incidence and multivariable correlates of long-term mortality in patients treated with surgical or percutaneous revascularization in the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial.2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no 24, p. 3105-3113Article in journal (Refereed)
    Abstract [en]

    Aims The aim of this investigation was to determine the incidence and multivariable correlates of long-term (4-year) mortality in patients treated with surgical or percutaneous revascularization in the synergy between percutaneous coronary intervention (PCI) with TAXUS Express and Cardiac Surgery (SYNTAX) trial. Methods and results A total of 1800 patients were randomized to undergo coronary artery bypass graft (CABG) surgery (n = 897) or PCI (n = 903). Prospectively collected baseline and peri- and post-procedural data were used to determine independent correlates of 4-year all-cause death in the CABG and the PCI arms (Cox proportional hazards model). Four-year mortality rates in the CABG and the PCI arms were 9.0% [74 deaths (12 in-hospital)] and 11.8% [104 deaths (16 in-hospital)], respectively (log-rank P-value = 0.063). Censored data comprised 78 patients (8.7%) in the CABG arm, and 24 patients (2.7%) in the PCI arm (log-rank P-value < 0.001). Within the CABG arm, the strongest independent correlates of 4-year mortality were lack of discharge aspirin [hazard ratio (HR) 3.56; 95% CI: 2.04, 6.21; P < 0.001], peripheral vascular disease (PVD) (HR: 2.65; 95% CI: 1.49, 4.72; P = 0.001), chronic obstructive pulmonary disease, age, and serum creatinine. Within the PCI arm, the strongest independent correlate of 4-year mortality was lack of post-procedural anti-platelet therapy (HR: 152.16; 95% CI: 53.57, 432.22; P < 0.001), with 10 reported early (within 45 days) in-hospital deaths secondary to multifactorial causes precluding administration of anti-platelet therapy. Other independent correlates of mortality in the PCI arm included amiodarone therapy on discharge, pre-procedural poor left ventricular ejection fraction, a 'history of gastrointestinal bleeding or peptic ulcer disease', PVD (HR: 2.13; 95% CI: 1.26, 3.60; P = 0.005), age, female gender (HR: 1.60; 95% CI: 1.01, 2.56; P = 0.048), and the SYNTAX score (Per increase in 10 points: HR: 1.25; 95% CI: 1.06, 1.47; P = 0.007). Conclusion Independent correlates of 4-year mortality in the SYNTAX trial were multifactorial. Lack of discharge aspirin and lack of post-procedural anti-platelet therapy were the strongest independent correlates of mortality in the CABG and the PCI arms, respectively. Peripheral vascular disease is a common independent correlate of 4-year mortality and may be a marker of the severity of baseline coronary disease and risk of future native coronary disease (and extra-cardiac disease) progression.

  • 27. Farooq, Vasim
    et al.
    Serruys, Patrick W
    Garcia-Garcia, Hector M
    Zhang, Yaojun
    Bourantas, Christos V
    Holmes, David R
    Mack, Michael
    Feldman, Ted
    Morice, Marie-Claude
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Colombo, Antonio
    Diletti, Roberto
    Papafaklis, Michail I
    de Vries, Ton
    Morel, Marie-Angèle
    van Es, Gerrit Anne
    Mohr, Friedrich W
    Dawkins, Keith D
    Kappetein, Arie-Pieter
    Sianos, Georgios
    University Hospital Uppsala, Uppsala, Sweden.
    Boersma, Eric
    The Negative Impact of Incomplete Angiographic Revascularization on Clinical Outcomes and Its Association With Total Occlusions: The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) Trial2013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 61, no 3, p. 282-294Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    The study sought to evaluate the clinical impact of angiographic complete (CR) and incomplete (ICR) revascularization and its association with the presence of total occlusions (TO), after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery in the "all-comers" SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) trial.

    BACKGROUND:

    In patients with complex coronary artery disease undergoing PCI or CABG, the long-term prognostic implications of CR versus ICR is unsettled.

    METHODS:

    In this post hoc study, consisting of randomized (n = 1,800) and nested PCI (n = 198) and CABG (n = 649) registries, 4-year clinical outcomes were compared in groups, with and without angiographic CR, in the PCI and CABG arms. Clinical outcomes were analyzed with Kaplan-Meier estimates, log-rank comparisons, and Cox regression analyses. Multivariate predictors of ICR were determined. Similar analyses were undertaken in the TO and non-TO treated groups of both study arms.

    RESULTS:

    Angiographic CR was achieved in 52.8% of the PCI arm and 66.9% of the CABG arm. Within the PCI and CABG arms, ICR (compared with CR) seemed to be a surrogate marker of a greater burden of anatomical coronary complexity and clinical comorbidity and was associated with significantly higher frequencies of 4-year mortality, all-cause revascularization, stent thrombosis (PCI arm), and major adverse cardiac and cerebrovascular events. The presence of a TO was the strongest independent predictor of ICR after PCI (hazard ratio: 2.70, 95% confidence interval: 1.98 to 3.67, p < 0.001). Eight hundred and forty patients (PCI: 26.3%, CABG: 36.4%, p < 0.001) were identified to have 1,007 TOs, with 68.1% of TOs located in the proximal-mid coronary vasculature. The findings associating ICR (compared with CR) with higher frequencies of 4-year mortality and major adverse cardiac and cerebrovascular events remained consistent in the TO-treated groups in the PCI and CABG arms.

    CONCLUSIONS:

    Within the PCI and CABG arms of the all-comers SYNTAX trial, angiographically determined ICR has a detrimental impact on long-term clinical outcomes, including mortality. This effect remained consistent in patients with and without TOs.

  • 28. Farooq, Vasim
    et al.
    Serruys, Patrick W.
    Vranckx, Pascal
    Bourantas, Christos V.
    Girasis, Chrysafios
    Holmes, David R.
    Kappetein, Arie Pieter
    Mack, Michael
    Feldman, Ted
    Morice, Marie Claude
    Colombo, Antonio
    Morel, Marie-angele
    de Vries, Ton
    Dawkins, Keith D.
    Mohr, Friedrich W.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Incidence, correlates, and significance of abnormal cardiac enzyme rises in patients treated with surgical or percutaneous based revascularisation: A substudy from the Synergy between Percutaneous Coronary Interventions with Taxus and Cardiac Surgery (SYNTAX) Trial2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, no 6, p. 5287-5292Article in journal (Refereed)
    Abstract [en]

    Aims: The aimof the present investigationwas to determine the long-termprognostic association of post-procedural cardiac enzyme elevation within the randomised Synergy between Percutaneous Coronary Intervention (PCI) with TAXUS and Cardiac Surgery (SYNTAX) Trial. Methods: 1800 patients with unprotected left main or de novo three-vessel coronary artery disease were randomised to undergo coronary artery bypass graft (CABG) surgery or PCI. Per protocol patients underwent post-procedural blood sampling with creatine kinase (CK), and the cardiac specific MB iso-enzyme (CK-MB) only if the preceding CK ratiowas = 2x the upper limit of normal (ULN). An independent chemistry laboratory evaluated all collected blood samples. Results: Post-procedural CK sampling was available in 1629 of 1800 patients (90.5%). As per protocol, CK-MB analyses were undertaken in 474 of 491 patients (96.5%) in the CABG arm, and 53 of 61 patients (86.9%) in the PCI arm. Within the CABG arm, despite the limitations of incomplete data, a post-procedural CK-MB ratio <3/>= 3 ULNseparated 4-year mortality into low-and high-risk groups (2.3% vs. 9.5%, p = 0.03). Additionally, in the CABG arm, a post-procedural CK-MB ratio = 3 ULN was associated with an increased frequency of a high SYNTAX Score (= 33) tertile (high [>= 33] SYNTAX Score: 39.5%, intermediate [23-32] SYNTAX Score 31.0%, low [>= 22] SYNTAX Score 29.5%, p = 0.02). Within the PCI arm, a post-procedural CK ratio of >2 or >= 2 ULN separated 4-year mortality into low-and high-risk groups (10.8% vs. 23.3%, p = 0.001). Notably, there was an early (within 6 months) and late (after 2 years) peak in mortality in patients with a post-PCI CK ratio of = 2 ULN. Lack of pre-procedural thienopyridine, carotid artery disease, type 1 diabetes, andpresenceof coronary bifurcationswere independent correlates of a CK ratio = 2 ULNpost-PCI. Conclusion: Cardiac enzyme elevations post-CABG or post-PCI are associatedwith an adverse long-termmortality; the causes of which are multifactorial.

  • 29. Farooq, Vasim
    et al.
    Serruys, Patrick W.
    Zhang, Yaojun
    Mack, Michael
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Holmes, David R.
    Feldman, Ted
    Morice, Marie-Claude
    Colombo, Antonio
    Bourantas, Christos V.
    de Vries, Ton
    Morel, Marie-angele
    Dawkins, Keith D.
    Kappetein, Arie Pieter
    Mohr, Friedrich W.
    Short-Term and Long-Term Clinical Impact of Stent Thrombosis and Graft Occlusion in the SYNTAX Trial at 5 Years Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery Trial2013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 62, no 25, p. 2360-2369Article in journal (Refereed)
    Abstract [en]

    Objectives The aim of this study was to report the short-term and long-term clinical impact of stent thrombosis (ST) and graft occlusion (GO) in the final 5-year outcomes of the SYNTAX (SYNergy Between PCI With TAXUS and Cardiac Surgery) trial.

    Background The clinical effect of newer-generation drug-eluting stents and operative factors in complex coronary artery disease is uncertain.

    Methods The incidence of 5-year ST and GO, and their association with clinical outcomes, were analyzed in the randomized percutaneous coronary intervention and coronary artery bypass graft cohorts. ST and GO were defined by the SYNTAX protocol definitions (clinical presentation with acute coronary syndrome and angiographic/pathological evidence), the Academic Research Consortium (ARC) definition for ST, and the newly devised "ARC-like" definition of GO (i.e., definite, probable, or possible GO).

    Results At 5 years, 871 of 903 patients (96.5%) in the percutaneous coronary intervention cohort and 805 of 897 patients (89.7%) in the coronary artery bypass graft cohort completed follow-up. As compared with other vessel locations, protocol ST (72 lesions) occurred more frequently in the left main (14 of 72; 19%) and proximal coronary vasculature (37 of 72; 51%) and protocol GO (41 lesions) with grafts anastomosed to the distal right coronary artery (17 of 41; 42%). The incidence of 5-year ARC definite ST and ARC-like definite GO did not significantly differ (7%[n = 48] vs. 6% [n = 32], log rank p = 0.34); landmark analyses indicated significantly increased ARC definite ST within 30 days (3% [n = 19] vs. 1% [n = 6], log rank p = 0.033) but not >30 days to 5 years (4.2% [n = 29] vs. 4.5% [n = 26], log rank p = 0.78). At presentation, ARC definite ST (n = 48) and ARC-like definite GO (n = 32) were adjudicated to be linked to 4 (8%) and 0 deaths, respectively. At 5 years, ARC definite ST (n = 48) and ARC definite/probable ST (n = 75) were associated with 17 (17 of 48, 35.4%; median days to death: 0 days; interquartile range: 0 to 16 days; maximum: 321 days) and 31 (31 of 75, 41.3%; median: 0 days; interquartile range: 0 to 9 days; maximum: 721 days) cardiac deaths, respectively. At 5 years, ARC-like definite GO (n = 32) and ARC-like definite/probable GO (n = 53) were associated with 0 and 12 (12 of 52, 23.1%; median: 0 days; interquartile range: 0 to 14 days; maximum: 257 days) cardiac deaths, respectively.

    Conclusions Although the incidence of ST and GO was similar at 5 years, the clinical impact of ST appeared greater, with a negative impact on short-term to long-term mortality.

  • 30. Farooq, Vasim
    et al.
    van Klaveren, David
    Steyerberg, Ewout W.
    Meliga, Emanuele
    Vergouwe, Yvonne
    Chieffo, Alaide
    Kappetein, Arie Pieter
    Colombo, Antonio
    Holmes, David R., Jr.
    Mack, Michael
    Feldman, Ted
    Morice, Marie-Claude
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Onuma, Yoshinobu
    Morel, Marie-angele
    Garcia-Garcia, Hector M.
    van Es, Gerrit Anne
    Dawkins, Keith D.
    Mohr, Friedrich W.
    Serruys, Patrick W.
    Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients: development and validation of SYNTAX score II2013In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 381, no 9867, p. 639-650Article in journal (Refereed)
    Abstract [en]

    Background The anatomical SYNTAX score is advocated in European and US guidelines as an instrument to help clinicians decide the optimum revascularisation method in patients with complex coronary artery disease. The absence of an individualised approach and of clinical variables to guide decision making between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) are limitations of the SYNTAX score. SYNTAX score II aimed to overcome these limitations. Methods SYNTAX score II was developed by applying a Cox proportional hazards model to results of the randomised all comers SYNTAX trial (n=1800). Baseline features with strong associations to 4-year mortality in either the CABG or the PCI settings (interactions), or in both (predictive accuracy), were added to the anatomical SYNTAX score. Comparisons of 4-year mortality predictions between CABG and PCI were made for each patient. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. External validation was done in the multinational all comers DELTA registry (n=2891), a heterogeneous population that included patients with three-vessel disease (26%) or complex coronary artery disease (anatomical SYNTAX score >= 33, 30%) who underwent CABG or PCI. The SYNTAX trial is registered with ClinicalTrials.gov, number NCT00114972. Findings SYNTAX score II contained eight predictors: anatomical SYNTAX score, age, creatinine clearance, left ventricular ejection fraction (LVEF), presence of unprotected left main coronary artery (ULMCA) disease, peripheral vascular disease, female sex, and chronic obstructive pulmonary disease (COPD). SYNTAX score II significantly predicted a difference in 4-year mortality between patients undergoing CABG and those undergoing PCI (p(interaction) 0.0037). To achieve similar 4-year mortality after CABG or PCI, younger patients, women, and patients with reduced LVEF required lower anatomical SYNTAX scores, whereas older patients, patients with ULMCA disease, and those with COPD, required higher anatomical SYNTAX scores. Presence of diabetes was not important for decision making between CABG and PCI (p(interaction) 0.67). SYNTAX score II discriminated well in all patients who underwent CABG or PCI, with concordance indices for internal (SYNTAX trial) validation of 0.725 and for external (DELTA registry) validation of 0.716, which were substantially higher than for the anatomical SYNTAX score alone (concordance indices of 0.567 and 0.612, respectively). A nomogram was constructed that allowed for an accurate individualised prediction of 4-year mortality in patients proposing to undergo CABG or PCI. Interpretation Long-term (4-year) mortality in patients with complex coronary artery disease can be well predicted by a combination of anatomical and clinical factors in SYNTAX score II. SYNTAX score II can better guide decision making between CABG and PCI than the original anatomical SYNTAX score.

  • 31. Grinberg, Marianna
    et al.
    Djureinovic, Dijana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Brunnström, Hans R R
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Edlund, Karolina
    Hengstler, Jan G
    La Fleur, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Koyi, Hirsh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Branden, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jirström, Karin
    Tracy, Derek K
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Rahnenführer, Jörg
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Reaching the limits of prognostication in non-small cell lung cancer: an optimized biomarker panel fails to outperform clinical parameters.2017In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 30, no 7, p. 964-977Article in journal (Refereed)
    Abstract [en]

    Numerous protein biomarkers have been analyzed to improve prognostication in non-small cell lung cancer, but have not yet demonstrated sufficient value to be introduced into clinical practice. Here, we aimed to develop and validate a prognostic model for surgically resected non-small cell lung cancer. A biomarker panel was selected based on (1) prognostic association in published literature, (2) prognostic association in gene expression data sets, (3) availability of reliable antibodies, and (4) representation of diverse biological processes. The five selected proteins (MKI67, EZH2, SLC2A1, CADM1, and NKX2-1 alias TTF1) were analyzed by immunohistochemistry on tissue microarrays including tissue from 326 non-small cell lung cancer patients. One score was obtained for each tumor and each protein. The scores were combined, with or without the inclusion of clinical parameters, and the best prognostic model was defined according to the corresponding concordance index (C-index). The best-performing model was subsequently validated in an independent cohort consisting of tissue from 345 non-small cell lung cancer patients. The model based only on protein expression did not perform better compared to clinicopathological parameters, whereas combining protein expression with clinicopathological data resulted in a slightly better prognostic performance (C-index: all non-small cell lung cancer 0.63 vs 0.64; adenocarcinoma: 0.66 vs 0.70, squamous cell carcinoma: 0.57 vs 0.56). However, this modest effect did not translate into a significantly improved accuracy of survival prediction. The combination of a prognostic biomarker panel with clinicopathological parameters did not improve survival prediction in non-small cell lung cancer, questioning the potential of immunohistochemistry-based assessment of protein biomarkers for prognostication in clinical practice.Modern Pathology advance online publication, 10 March 2017; doi:10.1038/modpathol.2017.14.

  • 32. Head, Stuart J.
    et al.
    Davierwala, Piroze M.
    Serruys, Patrick W.
    Redwood, Simon R.
    Colombo, Antonio
    Mack, Michael J.
    Morice, Marie-Claude
    Holmes, David R., Jr.
    Feldman, Ted E.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Underwood, Paul
    Dawkins, Keith D.
    Kappetein, A. Pieter
    Mohr, Friedrich W.
    Coronary artery bypass grafting vs. percutaneous coronary intervention for patients with three-vessel disease: final five-year follow-up of the SYNTAX trial2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no 40, p. 2821-2830Article in journal (Refereed)
    Abstract [en]

    Aims Coronary artery bypass grafting (CABG) has been considered the standard of care for patients with three-vessel disease (3VD), but long-term comparative results from randomized trials of CABG vs. percutaneous coronary intervention (PCI) using drug-eluting stents (DES) remain limited. Methods and results Patients with de novo 3VD or left main disease were randomly assigned to PCI with the paclitaxel-eluting first-generation stent or CABG in the SYNTAX trial. This pre-specified analysis presents the 5-year outcomes of patients with 3VD (n = 1095). The rate of major adverse cardiac and cerebrovascular events (MACCE) was significantly higher in patients with PCI compared with CABG (37.5 vs. 24.2%, respectively; P < 0.001). Percutaneous coronary intervention as opposed to CABG resulted in significantly higher rates of the composite of death/stroke/myocardial infarction (MI) (22.0 vs. 14.0%, respectively; P < 0.001), all-cause death (14.6 vs. 9.2%, respectively; P = 0.006), MI (9.2 vs. 4.0%, respectively; P = 0.001), and repeat revascularization (25.4 vs. 12.6%, respectively; P < 0.001); however, stroke was similar between groups at 5 years (3.0 vs. 3.5%, respectively; P = 0.66). Results were dependent on lesion complexity (P for interaction = 0.12); in patients with a low (022) SYNTAX score, PCI vs. CABG resulted in similar rates of MACCE (33.3% vs. 26.8%, respectively; P = 0.21) but significantly more repeat revascularization (25.4% vs. 12.6%, respectively; P = 0.038), while in intermediate (2332) or high (>= 33) SYNTAX score terciles, CABG demonstrated clear superiority in terms of MACCE, death, MI, and repeat revascularization. Differences in MACCE between PCI and CABG were larger in diabetics [hazard ratio (HR) = 2.30] than non-diabetics (HR = 1.51), although the P for interaction failed to reach significance for MACCE (P for interaction = 0.095) or any of the other endpoints. Conclusion Five-year results of patients with 3VD treated with CABG or PCI using the first-generation paclitaxel-eluting DES suggest that CABG should remain the standard of care as it resulted in significantly lower rates of death, MI, and repeat revascularization, while stroke rates were similar. For patients with low SYNTAX scores, PCI is an acceptable revascularization strategy, although at a price of significantly higher rates of repeat revascularization.

  • 33.
    Hellgren, Laila
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Granath, Fredrik
    Ekbom, Anders
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Biological versus mechanical prosthesis in 3279 patients from the Swedish in-patients register2011In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 45, no 4, p. 223-228Article in journal (Refereed)
    Abstract [en]

    Objectives. To compare valve-related morbidity among patients aged = 70 years, receiving either a mechanical or a biological prosthesis in a population-based setting. Design. In total, 3279 patients (21 644 patient-years) were followed up through the Swedish National In-Patients Register, which registers all hospital admissions. Death, thromboembolism, bleeding, endocarditis, valve thrombosis and reoperations were all captured. Results. Survival was lower among patients aged 5 years). Event-free survival was higher in younger patients with a mechanical prosthesis compared to bioprosthesis recipients (p < 0.001), but equal among older patients. Conclusions. Survival was comparable in older patients irrespective of prosthesis type. Bleeding was increased with a mechanical prosthesis, especially in the elderly. The risk of thromboembolism was higher in patients with a bioprosthesis.

  • 34.
    Hellgren, Laila
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Kvidal, Per
    Department of Medical Sciences.
    Hörte, Lars-Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Krusemo, Ulla-Brith
    Ståhle, Elisabeth
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Survival after mitral valve replacement: rationale for surgery before occurrence of severe symptoms.2004In: Ann Thorac Surg, ISSN 1552-6259, Vol. 78, no 4, p. 1241-7Article in journal (Other scientific)
  • 35. Hellgren, Laila
    et al.
    Kvidal, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Ståhle, Elisabeth
    Improved early results after heart valve surgery over the last decade.2002In: Eur J Cardiothorac Surg, ISSN 1010-7940, Vol. 22, no 6, p. 904-11Article in journal (Other scientific)
  • 36.
    Hellgren, Laila
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Kvidal, Per-David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Landelius, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hansson, E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Optimal timing of aortic valve replacement for aortic stenosis: are we operating late?2003In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 37, no 5, p. 266-269Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the adherence to current guidelines for surgery in patients with aortic valve stenosis.

    DESIGN: From 1 January 1997 to 31 May 1999, 99 patients were accepted for aortic valve surgery with preserved left ventricular function and normal coronary angiogram. On admission for operation, 20 patients were evaluated regarding symptoms, exercise capacity, and left ventricular morphology and function.

    RESULTS: There were 14 men and 6 women, mean age 64.3 years. Years from symptom onset varied from 2.1 to 3.2. Dyspnoea was the most common limiting symptom. Thirty per cent of the patients were classified as NYHA IIIB. Physical capacity was reduced to 79% of the expected. Left ventricular hypertrophy was present in 14/20 patients. Left ventricular systolic function was reduced with mean ejection fraction of 0.46. Diastolic dysfunction (E/A ratio <1) was present in 12 patients.

    CONCLUSION: Many patients accepted for aortic valve replacement due to aortic stenosis show advanced disease and are referred for surgery later in the disease process than is recommended in the current guidelines.

  • 37.
    Hellgren, Laila
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Landelius, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Kvidal, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Severe mitral regurgitation: relations between magnetic resonance imaging, echocardiography and natriuretic peptides2008In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 42, no 1, p. 48-55Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Assessment of the severity of mitral regurgitation by echocardiography can be technically demanding in certain patients and supplementary methods are therefore desirable. This study addressed the agreement between magnetic resonance imaging (MRI) and echocardiography, and their relations to natriuretic peptides (NT-proANP and NT-proBNP), in quantifying severe mitral regurgitation.

    METHODS:

    Eighteen patients with severe mitral regurgitation scheduled for surgery underwent MRI, echocardiography and assay of natriuretic peptides preoperatively for clinical assessment.

    RESULTS:

    MRI and echocardiography were comparable in measuring severity of regurgitation qualitatively but not quantitatively, mitral regurgitant fraction (mean difference 27.5 (11) ml). There was a correlation between increasing regurgitant fraction on MRI and increased levels of plasma NT-proANP and NT-proBNP. In echocardiography, increasing vena contracta width and increasing PISA correlated to increased levels of plasma NT-proANP and NT-proBNP. No other correlation was found between measures on MRI and echocardiography and natriuretic peptides.

    CONCLUSIONS:

    MRI and echocardiography were comparable grading the severity of mitral regurgitation with qualitative measures but not with quantitative measures. MRI might be a complement to echocardiography when a more distinct measure of the regurgitant volume is needed, as in paravalvular leakage.

  • 38.
    Hellgren, Laila
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Quality of life after heart valve surgery with prolonged intensive care2005In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 80, no 5, p. 1693-1698Article in journal (Refereed)
    Abstract [en]

    ACKGROUND:

    A small proportion of patients undergoing heart valve operations require prolonged intensive care after surgery. Little is known about the quality of life that such patients attain after hospital discharge.

    METHODS:

    All consecutive patients who underwent primary heart valve surgery from 1998 to 2003 and required 8 days or more of treatment in an intensive care unit (ICU) were included (n = 225). At follow-up on August 31, 2004, 154 of these patients were alive. A cohort (n = 154) matched for sex, age, type of procedure, and week of operation, with an uncomplicated postoperative course (ICU stay of 2 days or less), served as the control group. All patients received the Medical Outcomes Study Short-Form 36, the Nottingham Health Profile, and the Hospital Depression and Anxiety scale to evaluate their quality of life.

    RESULTS:

    Survival at 5 years in the total ICU group was 68% (154 of 225). According to SF-36, the ICU study cohort reported poorer physical health but equal mental health compared with controls. On the Nottingham Health Profile, the ICU group reported more problems in all domains except emotional reactions and sleep. There was no difference in anxiety or depression between the groups. The ICU patients were in more advanced New York Heart Association functional classes preoperatively and postoperatively. No patient in the ICU study cohort regretted undergoing the operation, and 80% experienced improvement after surgery.

    CONCLUSIONS:

    This study showed reduced quality of life in terms of physical health and equal mental health in patients who required prolonged intensive care after heart valve surgery compared with controls without complications.

  • 39. Husted, S E
    et al.
    Wallentin, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Lagerqvist, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Kontny, F
    Ståhle, E
    Department of Surgical Sciences.
    Swahn, E
    Benefits of extended treatment with dalteparin in patients with unstable coronary artery disease eligible for revascularization.2002In: Eur Heart J, ISSN 0195-668X, Vol. 23, no 15, p. 1213-8Article in journal (Refereed)
  • 40. Iqbal, Javaid
    et al.
    Zhang, Yao-Jun
    Holmes, David R.
    Morice, Marie-Claude
    Mack, Michael J.
    Kappetein, Arie Pieter
    Feldman, Ted
    Ståhle, Elizabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Escaned, Javier
    Banning, Adrian P.
    Gunn, Julian P.
    Colombo, Antonio
    Steyerberg, Ewout W.
    Mohr, Friedrich W.
    Serruys, Patrick W.
    Optimal Medical Therapy Improves Clinical Outcomes in Patients Undergoing Revascularization With Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting Insights From the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) Trial at the 5-Year Follow-Up2015In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 131, no 14, p. 1269-1277Article in journal (Refereed)
    Abstract [en]

    Background-There is a paucity of data on the use of optimal medical therapy (OMT) in patients with complex coronary artery disease undergoing revascularization with percutaneous coronary intervention or coronary artery bypass grafting (CABG) and its long-term prognostic significance. Methods and Results-The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial is a multicenter, randomized, clinical trial of patients (n=1800) with complex coronary disease randomized to revascularization with percutaneous coronary intervention or CABG. Detailed drug history was collected for all patients at discharge and at the 1-month, 6-month, 1-year, 3-year, and 5-year follow-ups. OMT was defined as the combination of at least 1 antiplatelet drug, statin, beta-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Five-year clinical outcomes were stratified by OMT and non-OMT. OMT was underused in patients treated with coronary revascularization, especially CABG. OMT was an independent predictor of survival. OMT was associated with a significant reduction in mortality (hazard ratio, 0.64; 95% confidence interval, 0.48-0.85; P=0.002) and composite end point of death/myocardial infarction/stroke (hazard ratio, 0.73; 95% confidence interval, 0.58-0.92; P=0.007) at the 5-year follow-up. The treatment effect with OMT (36% relative reduction in mortality over 5 years) was greater than the treatment effect of revascularization strategy (26% relative reduction in mortality with CABG versus percutaneous coronary intervention over 5 years). On stratified analysis, all the components of OMT were important for reducing adverse outcomes regardless of revascularization strategy. Conclusions-The use of OMT remains low in patients with complex coronary disease requiring coronary intervention with percutaneous coronary intervention and even lower in patients treated with CABG. Lack of OMT is associated with adverse clinical outcomes. Targeted strategies to improve OMT use in postrevascularization patients are warranted.

  • 41. Jacobsen, Michael D
    et al.
    Wagner, Galen S
    Holmvang, Lene
    Kontny, Frederic
    Wallentin, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Husted, Steen
    Swahn, Eva
    Ståhle, Elisabeth
    Department of Surgical Sciences.
    Steffensen, Rolf
    Clemmensen, Peter
    Quantitative T-wave analysis predicts 1 year prognosis and benefit from early invasive treatment in the FRISC II study population.2005In: Eur Heart J, ISSN 0195-668X, Vol. 26, no 2, p. 112-8Article in journal (Refereed)
  • 42. Kappetein, Arie Pieter
    et al.
    Feldman, Ted E.
    Mack, Michael J.
    Morice, Marie-Claude
    Holmes, David R.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Dawkins, Keith D.
    Mohr, Friedrich W.
    Serruys, Patrick W.
    Colombo, Antonio
    Comparison of coronary bypass surgery with drug-eluting stenting for the treatment of left main and/or three-vessel disease: 3-year follow-up of the SYNTAX trial2011In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 32, no 17, p. 2125-2134Article in journal (Refereed)
    Abstract [en]

    Aims: Long-term randomized comparisons of percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) in left main coronary (LM) disease and/or three-vessel disease (3VD) patients have been limited. This analysis compares 3-year outcomes in LM and/or 3VD patients treated with CABG or PCI with TAXUS Express stents.

    Methods and results: SYNTAX is an 85-centre randomized clinical trial (n = 1800). Prospectively screened, consecutive LM and/or 3VD patients were randomized if amenable to equivalent revascularization using either technique; if not, they were entered into a registry. Patients in the randomized cohort will continue to be followed for 5 years. At 3 years, major adverse cardiac and cerebrovascular events [MACCE: death, stroke, myocardial infarction (MI), and repeat revascularization; CABG 20.2% vs. PCI 28.0%, P < 0.001], repeat revascularization (10.7 vs. 19.7%, P < 0.001), and MI (3.6 vs. 7.1%, P = 0.002) were elevated in the PCI arm. Rates of the composite safety endpoint (death/stroke/MI 12.0 vs. 14.1%, P = 0.21) and stroke alone (3.4 vs. 2.0%, P = 0.07) were not significantly different between treatment groups. Major adverse cardiac and cerebrovascular event rates were not significantly different between arms in the LM subgroup (22.3 vs. 26.8%, P = 0.20) but were higher with PCI in the 3VD subgroup (18.8 vs. 28.8%, P < 0.001).

    Conclusions: At 3 years, MACCE was significantly higher in PCI-compared with CABG-treated patients. In patients with less complex disease (low SYNTAX scores for 3VD or low/intermediate terciles for LM patients), PCI is an acceptable revascularization, although longer follow-up is needed to evaluate these two revascularization strategies.

  • 43.
    Kvidal, Per
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Bergström,
    Hörte,
    Ståhle, Elisabeth
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Observed and relative survival after aortic valve replacement.2000In: J Am Coll Cardiol, ISSN 0735-1097, Vol. 35, no 3, p. 747-56Article in journal (Other scientific)
  • 44.
    Kvidal, Per
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Bergström, Reinhold
    Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Information Science.
    Malm, Torsten
    Ståhle, Elisabeth
    Department of Surgical Sciences.
    Long-term follow-up of morbidity and mortality after aortic valve replacement with a mechanical valve prosthesis2000In: Eur Heart J, Vol. 21, p. 1099-1111Article in journal (Refereed)
  • 45.
    Kvidal, Per
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Stahle, Elisabeth
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Nygren,
    Landelius,
    Thuren,
    Enghoff,
    Long-term follow up study on 64 elderly patients after balloon aortic valvuloplasty.1997In: J Heart Valve Dis, ISSN 0966-8519, Vol. 6, no 5, p. 480-6Article in journal (Other scientific)
  • 46.
    Lagerqvist, B
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Diderholm, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Husted, S
    Kontny, F
    Ståhle, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Swahn, E
    Venge, P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Siegbahn, A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    FRISC score for selection of patients for an early invasive treatment strategy in unstable coronary artery disease2005In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 91, no 8, p. 1047-1052Article in journal (Refereed)
    Abstract [en]

    Objective: To develop a scoring system for risk stratification and evaluation of the effect of an early invasive strategy for treatment of unstable coronary artery disease (CAD).

    Design: Retrospective analysis of a randomised study (FRISC II; fast revascularisation in instability in coronary disease).

    Setting: 58 Scandinavian hospitals.

    Patients: 2457 patients with unstable CAD from the FRISC II study.

    Main outcome measures: One year rates of mortality and death/myocardial infarction (MI).

    Methods: Patients were randomly assigned to an early invasive or a non-invasive strategy. From the non-invasive cohort independent variables of death or death/MI were identified.

    Results: Seven factors, age > 70 years, male sex, diabetes, previous MI, ST depression, and increased concentrations of troponins and markers of inflammation (interleukin 6 or C reactive protein), were associated with an independent increased risk for death or death/MI. In patients with ≥ 5 of these factors the invasive strategy reduced mortality from 15.4% (20 of 130) to 5.2% (7 of 134) (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.15 to 0.78, p  =  0.006). Death/MI was also reduced in patients with 3–4 factors from 15.7% (80 of 511) to 10.8% (58 of 538) (RR 0.69, 95% CI 0.50 to 0.94, p  =  0.02). Neither death nor death/MI was reduced in patients with 0–2 risk factors.

    Conclusion: In unstable CAD, this scoring system based on factors independently associated with an adverse outcome can be used shortly after admission to the hospital for risk stratification and for selection of patients to an early invasive treatment strategy.

  • 47. Lagerqvist, Bo
    et al.
    Husted, Steen
    Kontny, Fredrik
    Näslund, Ulf
    Ståhle, Elisabeth
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Swahn, Eva
    Wallentin, Lars
    A long-term perspective on the protective effects of an early invasive strategy in unstable coronary artery disease: two-year follow-up of the FRISC-II invasive study.2002In: J Am Coll Cardiol, ISSN 0735-1097, Vol. 40, no 11, p. 1902-14Article in journal (Refereed)
  • 48.
    Lagerqvist, Bo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Husted, Steen
    Kontny, Fredrik
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Swahn, Eva
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    5-year outcomes in the FRISC-II randomised trial of an invasive versus a non-invasive strategy in non-ST-elevation acute coronary syndrome: a follow-up study2006In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 368, no 9540, p. 998-1004Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The FRISC-II invasive trial compared an early invasive with a non-invasive strategy in terms of death and myocardial infarction in non-ST-elevation acute coronary syndrome. We present 5-year follow-up results, overall and in subgroups based on recommended risk stratification criteria. METHODS: In the FRISC-II trial, 2457 patients with non-ST-elevation acute coronary syndrome were randomised to early invasive strategy (coronary angiography and, if appropriate, revascularisation, within 7 days from admission) or non-invasive primarily medical strategy. Risk stratification was done on the basis of risk indicators at randomisation: age older than 65 years, male sex, diabetes mellitus, previous myocardial infarction, ST-segment depression, raised troponin concentration (>0.03 mug/L), and raised C-reactive protein or interleukin 6. Information on events after 24 months was taken from national registries. Analyses were done on an intention-to-treat basis. FINDINGS: At 5 years the groups differed in terms of the primary composite endpoint of death, myocardial infarction, or both (invasive 217, 19.9 %; noninvasive 270, 24.5 %; risk ratio 0.81; 95% CI 0.69-0.95; p=0.009). 5-year mortality was 117 (9.7%) in the invasive group compared with 124 (10.1%) in the noninvasive group (0.95; 0.75 -1.21; p=0.693). Rates of myocardial infarction were 141 (12.9 %) in the invasive and 195 (17.7%) in the non-invasive group (0.73; 0.60-0.89; p=0.002). The benefit of the invasive strategy was confined to male patients, non-smokers, and patients with two or more risk indicators. INTERPRETATION: The 5-year outcome of this trial indicates sustained benefit of an early invasive strategy in patients with non-ST-elevation acute coronary syndrome at moderate to high risk.

  • 49. Lenzen, M J
    et al.
    Boersma, E
    Bertrand, M E
    Maier, W
    Moris, C
    Piscione, F
    Sechtem, U
    Ståhle, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Widimsky, P
    de Jaegere, P
    Scholte op Reimer, W J M
    Mercado, N
    Wijns, W
    Management and outcome of patients with established coronary artery disease: the Euro Heart Survey on coronary revascularization.2005In: Eur Heart J, ISSN 0195-668X, Vol. 26, no 12, p. 1169-79Article in journal (Refereed)
  • 50. Mack, Michael J
    et al.
    Head, Stuart J
    Holmes, David R
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Feldman, Ted E
    Colombo, Antonio
    Morice, Marie-Claude
    Unger, Felix
    Erglis, Andrejs
    Stoler, Robert
    Dawkins, Keith D
    Serruys, Patrick W
    Mohr, Friedrich W
    Kappetein, A Pieter
    Analysis of Stroke Occurring in the SYNTAX Trial Comparing Coronary Artery Bypass Surgery and Percutaneous Coronary Intervention in the Treatment of Complex Coronary Artery Disease2013In: JACC. Cardiovascular interventions, ISSN 1936-8798, Vol. 6, no 4, p. 344-354Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study sought to analyze stroke rates in the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial's randomized and registry cohorts of patients being treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) for treatment of complex coronary artery disease.

    BACKGROUND: The SYNTAX trial compared PCI to CABG in patients with de novo 3-vessel and/or left main coronary disease.

    METHODS: The SYNTAX randomized trial was conducted at 85 U.S. and European sites (n = 1,800). All strokes (up to 4 years) were independently adjudicated by a clinical events committee that included a neurologist. An additional 1,077 (of which 644 were followed for 5 years) and 198 patients were included in the CABG and PCI registries, respectively.

    RESULTS: In the randomized cohort, 31 CABG and 19 PCI patients experienced 33 and 20 strokes post-randomization at 4-year follow-up, respectively (p = 0.062). Three strokes occurred pre-procedurally but following randomization in CABG-treated patients. After CABG, a large proportion of strokes occurred acutely (0 to 30 days: 9 of 33), whereas in the PCI arm, most strokes occurred >30 days after the procedure (18 of 20). Stroke resulted in death in 3 patients in both the PCI and CABG groups. Of the patients who developed stroke, 68% (21 of 31) in the CABG group had residual deficits at discharge; in the PCI group, 47% (9 of 19) had residual deficits. In a multivariate analysis, treatment with CABG was not significantly associated with increased stroke rates (odds ratio: 1.67, 95% confidence interval: 0.93 to 3.01, p = 0.089). The incidence and outcomes of stroke were similar in the randomized trial and registries.

    CONCLUSIONS: There is a higher risk of periprocedural stroke in patients undergoing CABG versus PCI; however, the risk converges over the first 4 years of follow-up. (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972).

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