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  • 201.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Multimarker approach for diagnosis of acute myocardial infarction: better answers need better questions2009In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 55, no 1, p. 9-11Article in journal (Refereed)
  • 202.
    Lindahl, Bertil
    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.
    The Story of Growth Differentiation Factor 15: Another Piece of the Puzzle2013In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 59, no 11, p. 1550-1552Article in journal (Other academic)
  • 203.
    Lindahl, Bertil
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Baron, Tomasz
    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.
    Erlinge, David
    Lund Univ, Dept Cardiol, Lund, Sweden..
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Nordenskjöld, Anna
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Gard, Anton
    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.
    Jernberg, Tomas
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Epidemiol & Biostat, Dept Cardiol, Stockholm, Sweden..
    Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease2017In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 135, no 16, p. 1481-1489Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 5% to 10% of all patients with myocardial infarction. Clinical trials of secondary prevention treatment in MINOCA patients are lacking. Therefore, the aim of this study was to examine the associations between treatment with statins, renin-angiotensin system blockers, beta-blockers, dual antiplatelet therapy, and long-term cardiovascular events. METHODS: This is an observational study of MINOCA patients recorded in the SWEDEHEART registry (the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapy) between July 2003 and June 2013 and followed until December 2013 for outcome events in the Swedish Cause of Death Register and National Patient Register. Of 199 162 myocardial infarction admissions, 9466 consecutive unique patients with MINOCA were identified. Among those, the 9136 patients surviving the first 30 days after discharge constituted the study population. Mean age was 65.3 years, and 61% were women. No patient was lost to follow-up. A stratified propensity score analysis was performed to match treated and untreated groups. The association between treatment and outcome was estimated by comparing between treated and untreated groups by using Cox proportional hazards models. The exposures were treatment at discharge with statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and dual antiplatelet therapy. The primary end point was major adverse cardiac events defined as all-cause mortality, hospitalization for myocardial infarction, ischemic stroke, and heart failure. RESULTS: At discharge, 84.5%, 64.1%, 83.4%, and 66.4% of the patients were on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and dual antiplatelet therapy, respectively. During the follow-up of a mean of 4.1 years, 2183 (23.9%) patients experienced a major adverse cardiac event. The hazard ratios (95% confidence intervals) for major adverse cardiac events were 0.77 (0.68-0.87), 0.82 (0.73-0.93), and 0.86 (0.74-1.01) in patients on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and beta-blockers, respectively. For patients on dual antiplatelet therapy followed for 1 year, the hazard ratio was 0.90 (0.74-1.08). CONCLUSIONS: The results indicate long-term beneficial effects of treatment with statins and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on outcome in patients with MINOCA, a trend toward a positive effect of beta-blocker treatment, and a neutral effect of dual antiplatelet therapy. Properly powered randomized clinical trials to confirm these results are warranted.

  • 204.
    Lindahl, Bertil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Baron, Tomasz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Erlinge, David
    Lund Univ, Dept Cardiol, Lund, Sweden.
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Nordenskjöld, Anna
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Gard, Anton
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Cardiol, Stockholm, Sweden.
    Response by Lindahl et al to Letter Regarding Article, "Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease".2017In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 136, no 11, p. 1082-1083Article in journal (Other academic)
  • 205.
    Lindahl, Bertil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Diderholm, Erik
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mechanisms behind the prognostic value of troponin T in unstable coronary artery disease: a FRISC II substudy2001In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 38, no 4, p. 979-986Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study was designed to elucidate possible mechanisms for the prognostic value of troponin T (tnT).

    BACKGROUND: The reasons for the adverse prognosis associated with elevation of troponins in unstable coronary artery disease are poorly understood.

    METHODS: Patients enrolled in the Fast Revascularization during InStability in CAD (FRISC-II) trial were included. Clinical characteristics, findings at echocardiography and coronary angiography, and prognosis were evaluated in relation to different tnT levels.

    RESULTS: Absence of significant coronary stenosis was more frequent and three-vessel disease or left main stem stenosis was less frequent in patients without, compared with, detectable tnT. The occurrence of visible thrombus increased with rising levels of tnT. In the group with the highest levels of tnT, occlusion of the left circumflex artery was more common than in the three other tnT groups, as was a left ventricular ejection fraction below 0.45. The one-year risk of death in the noninvasive arm of the study increased by increasing levels of tnT (1.6% to 4.6%), whereas the risk of myocardial infarction showed an inverted U-shaped curve and was lower in the lowest (5.5%) and highest (8.4%) tnT groups than in the two intermediate groups (17.5% and 16.2%).

    CONCLUSIONS: Any detectable elevation of tnT raises the probability of significant coronary stenosis and thrombus formation and is associated with an increased risk of reinfarction and death. However, at a more pronounced elevation of troponin, a higher proportion of patients has a persistent occlusion of the culprit vessel and reduced left ventricular function, associated with a high mortality but a modest risk of reinfarction.

  • 206.
    Lindahl, Bertil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Eggers, Kai M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    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.
    Evaluation of four sensitive troponin assays for risk assessment in acute coronary syndromes using a new clinically oriented approach for comparison of assays2013In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 51, no 9, p. 1859-1864Article in journal (Refereed)
    Abstract [en]

    Background:

    Measurement of cardiac troponin T or I (cTnT; cTnI) is useful for risk prediction in acute coronary syndromes. The objective of the present study was to compare the prognostic capacity of four sensitive cardiac troponin assays using a new method for comparison.

    Methods:

    Cardiac troponin was analyzed in serum samples from 1335 patients with acute coronary syndrome using the Elecsys high sensitivity TnT (hs-cTnT), ARCHITECT STAT high sensitivity TnI (hs-cTnI), Access AccuTnI (Acc-cTnI) and Architect cTnI (Arc-cTnI) assays. All patients were followed for 30 days regarding death and acute myocardial infarction (AMI), and for 1 year regarding mortality.

    Results:

    By receiver operating characteristic (ROC) curve analyses, there were only minor differences in the area under the curves (AUC) between the assays. At a given sensitivity of 85% the hs-cTnT, Arc-cTnI and Acc-cTnI assays showed comparable specificities, while 90% or higher sensitivity was only possible to achieve with the hs-cTnT, hs-cTnI and Acc-cTnI assays. The highest odds ratios for death/AMI at 30 days and death at 1 year, respectively, were reached by cut-off levels yielding 95% sensitivity; these cut-off levels were below the respective 99th percentile levels.

    Conclusions:

    By the adoption of a new method for the comparison of cardiac troponin assays we showed that the hs-cTnT, hs-cTnI and Acc-cTnI assays had comparable prognostic properties, while the Arc-cTnI assay had inferior prognostic sensitivity.

  • 207.
    Lindahl, Bertil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Diagnostic applications of natriuretic peptides in ischemic heart disease2006In: Heart failure clinics, ISSN 1551-7136, Vol. 2, no 3, p. 311-321Article in journal (Refereed)
  • 208.
    Lindahl, Bertil
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Badertscher, Patrick
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, CRIB, Basel, Switzerland..
    Boeddinghaus, Jasper
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, CRIB, Basel, Switzerland..
    Eggers, Kai M.
    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.
    Frick, Mats
    Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden..
    Rubini Gimenez, Maria
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, CRIB, Basel, Switzerland.;UPF, Pneumol Dept, IMIM, Parc Salut Mar, Barcelona, Spain.;Emergency Dept, Parc Salut Mar, Barcelona, Spain..
    Linder, Rickard
    Danderyd Hosp, Dept Cardiol, Stockholm, Sweden..
    Ljung, Lina
    Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden..
    Martinsson, Arne
    Capio St Gorans Hosp, Stockholm, Sweden..
    Melki, Dina
    Karolinska Inst, Dept Med, Huddinge, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Nestelberger, Thomas
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, CRIB, Basel, Switzerland..
    Rentsch, Katharina
    Univ Basel Hosp, Dept Lab Med, Basel, Switzerland..
    Reichlin, Tobias
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, CRIB, Basel, Switzerland..
    Sabti, Zaid
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, CRIB, Basel, Switzerland..
    Schubera, Marie
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, CRIB, Basel, Switzerland..
    Svensson, Per
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Emergency Med, Stockholm, Sweden..
    Twerenbold, Raphael
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, CRIB, Basel, Switzerland..
    Wildi, Karin
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, CRIB, Basel, Switzerland..
    Mueller, Christian
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, CRIB, Basel, Switzerland..
    An algorithm for rule-in and rule-out of acute myocardial infarction using a novel troponin I assay2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 2, p. 125-131Article in journal (Refereed)
    Abstract [en]

    Objective To derive and validate a hybrid algorithm for rule-out and rule-in of acute myocardial infarction based on measurements at presentation and after 2 hours with a novel cardiac troponin I (cTnI) assay. Methods The algorithm was derived and validated in two cohorts (605 and 592 patients) from multicentre studies enrolling chest pain patients presenting to the emergency department (ED) with onset of last episode within 12 hours. The index diagnosis and cardiovascular events up to 30 days were adjudicated by independent reviewers. Results In the validation cohort, 32.6% of the patients were ruled out on ED presentation, 6.1% were ruled in and 61.3% remained undetermined. A further 22% could be ruled out and 9.8% ruled in, after 2 hours. In total, 54.6% of the patients were ruled out with a negative predictive value (NPV) of 99.4% (95% CI 97.8% to 99.9%) and a sensitivity of 97.7% (95% CI 91.9% to 99.7%); 15.8% were ruled in with a positive predictive value (PPV) of 74.5% (95% CI 64.8% to 82.2%) and a specificity of 95.2% (95% CI 93.0% to 96.9%); and 29.6% remained undetermined after 2 hours. No patient in the rule-out group died during the 30-day follow-up in the two cohorts. Conclusions This novel two-step algorithm based on cTnI measurements enabled just over a third of the patients with acute chest pain to be ruled in or ruled out already at presentation and an additional third after 2 hours. This strategy maximises the speed of rule-out and rule-in while maintaining a high NPV and PPV, respectively.

  • 209.
    Lindahl, Bertil
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Serial analyses of N-terminal pro-B-type natriuretic peptide in patients with non-ST-segment elevation acute coronary syndromes: a Fragmin and fast Revascularisation during In Stability in Coronary artery disease (FRISC)-II substudy2005In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 45, no 4, p. 533-541Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    The aim of this research was to describe N-terminal part of the pro-B-type natriuretic peptide (NT-proBNP) levels over time in non-ST-segment elevation acute coronary syndromes (NSTEACS), to elucidate factors associated with changes of NT-proBNP levels, and to examine association with long-term mortality.

    BACKGROUND:

    The NT-proBNP levels are associated with mortality. Long-term temporal changes of NT-proBNP levels and their relation to other factors have not been examined.

    METHODS:

    The NT-proBNP was analyzed at randomization and at 48 h, after 6 weeks, 3 and 6 months in NSTEACS patients enrolled in the Fragmin and fast Revascularisation during InStability in Coronary artery disease (FRISC)-II trial. The NT-proB-type natriuretic peptide was analyzed at least three time points in 1,216 patients.

    RESULTS:

    The median NT-proBNP level, which at randomization was 529 ng/l, decreased throughout the whole sampling period to 238 ng/l at six months. Elevated troponin T, C-reactive protein, and female gender were associated with higher reduction rates, and high age, diabetes, previous myocardial infarction, treatment with diuretics, and nitrates on admission with lower reduction rates. At each time point, the NT-proBNP level was predictive of the two-year mortality. However, the adjusted odds ratio increased for each time point.

    CONCLUSIONS:

    The initial rise of NT-proBNP in NSTEACS is mainly reversible. Factors associated with less reversibility are related to chronically impaired left ventricular function, and factors associated with greater reversibility are related to the acute myocardial damage. The NT-proBNP level measured during a chronic, relatively stable phase is a better predictor of mortality than during an acute unstable phase. The clinical setting and timing of measurement will be important to consider when using NT-proBNP for risk assessment.

  • 210.
    Lindahl, Bertil
    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.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ristiniemi, Noora
    Wittfooth, Saara
    Pettersson, Kim
    Autoantibodies to cardiac troponin in acute coronary syndromes2010In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 411, no 21-22, p. 1793-1798Article in journal (Refereed)
    Abstract [en]

    Backgrounds In a recent small study, patients with autoantibodies to cardiac troponin (cTnaAb) had higher cardiac troponin 1 (cTnl) release during an episode of acute coronary syndrome (ACS) than patients without cTnaAb and continued to have higher long-term levels of cTnl However, the prognostic importance of the occurrence of cTnaAb is unknown Methods In 957 nonST-elevation ACS patients cTnaAb and cTnl were analyzed at randomization and after 6 months. Outcomes were assessed through 5 years Results. Seven and 11% of the patients were cTnaAb positive at inclusion and 6 months, respectively The cardiac troponin I (cTnl) concentration at inclusion was independently associated with the development of cTnaAb (OR 1 53, 95% Cl 1 25-1 88) The presence of cTnaAb was associated with an increased cTnl level at 6 months (OR 2 39, 95% CI 1 50-381) cTnaAb was not independently associated with death and AMI during follow-up (HR 0 97. 95% Cl 0.61-1 54) Conclusion Development of cTnaAb after an episode of nonST-elevation ACS is associated with the acute myocardial damage, but occurs only in a minority of patients Furthermore, the presence of cTnaAb is associated with chronically elevated cTnl concentrations However, the occurrence of cTnaAb is not associated with an adverse long-term prognosis.

  • 211.
    Lindahl, Bertil
    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.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    James, Stefan
    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.
    The new high-sensitivity cardiac troponin T assay improves risk assessment in acute coronary syndromes2010In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 160, no 2, p. 224-229Article in journal (Refereed)
    Abstract [en]

    Background Cardiac troponins are currently the markers of choice for diagnosis of acute myocardial infarction and risk assessment in acute coronary syndrome (ACS). With the introduction of the new high-sensitivity cardiac troponin T (hs-cTnT) assay, it has become possible to measure cTnT even in healthy subjects. However, how the hs-cTnT assay compares with the old cTnT assay for risk assessment in ACS is still unknown. Methods Cardiac troponin T levels were measured with the new hs-cTnT assay and the old third-generation cTnT assay in serum samples collected 48 hours after randomization in 1,452 randomly selected ACS patients enrolled in the GUSTO-IV trial. During 30 days of follow-up, deaths and myocardial infarctions were recorded. At 12 months, only all-cause mortality was collected. Results The 16% of the patients that had levels higher than the 99th percentile cutoff for hs-cTnT but less than for cTnT had a similar 1-year mortality as the 60% that were positive for both assays (9.2% vs 10.7%, P = .52) and a higher 1-year mortality compared with the 24% that were negative for both assays (9.2% vs 2.6%, P = .001). For death or acute myocardial infarction at 30 days, the group that was positive only for hs-cTnT had an intermediate risk compared with the groups negative or positive for both assays (2.4%, 5.2%, and 8.7%; P < .001). Conclusion The new hs-cTnT assay, compared with the old cTnT assay, identified more patients with myocardial damage and who were at an increased risk for new cardiac events.

  • 212.
    Ljung, Lina
    et al.
    Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden;Soder Sjukhuset, Dept Cardiol, Stockholm, Sweden.
    Lindahl, Bertil
    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.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Frick, Mats
    Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden;Soder Sjukhuset, Dept Cardiol, Stockholm, Sweden.
    Linder, Rikard
    Karolinska Inst, Dept Clin Sci, Danderyd Univ Hosp, Stockholm, Sweden.
    Löfmark, Henrik B.
    Karolinska Inst, Dept Clin Sci, Danderyd Univ Hosp, Stockholm, Sweden.
    Martinsson, Arne
    Capio St Gorans Hosp, Dept Emergency Med, Stockholm, Sweden.
    Melki, Dina
    Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden.
    Sarkar, Nondita
    Karolinska Inst, Dept Med, Stockholm, Sweden;Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden.
    Svensson, Per
    Karolinska Inst, Dept Med, Stockholm, Sweden;Karolinska Univ Hosp Solna, Funct Area Emergency Med, Stockholm, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Dept Clin Sci, Danderyd Univ Hosp, Stockholm, Sweden.
    A Rule-Out Strategy Based on High-Sensitivity Troponin and HEART Score Reduces Hospital Admissions2019In: Annals of Emergency Medicine, ISSN 0196-0644, E-ISSN 1097-6760, Vol. 73, no 5, p. 491-499Article in journal (Refereed)
    Abstract [en]

    Study objective: We evaluate whether a combination of a 1-hour high-sensitivity cardiac troponin algorithm and History, ECG, Age, Risk Factors, and Troponin (HEART) score reduces admission rate (primary outcome) and affects time to discharge, health care-related costs, and 30-day outcome (secondary outcomes) in patients with symptoms suggestive of an acute coronary syndrome.

    Methods: This prospective observational multicenter study was conducted before (2013 to 2014) and after (2015 to 2016) implementation of a strategy including level of high-sensitivity cardiac troponin T or I at 0 and 1 hour, combined with the HEART score. Patients with a nonelevated baseline high-sensitivity cardiac troponin level, a 1-hour change in high-sensitivity cardiac troponin T level less than 3 ng/L, or high-sensitivity cardiac troponin I level less than 6 ng/L and a HEART score less than or equal to 3 were considered to be ruled out of having acute coronary syndrome. A logistic regression analysis was performed to adjust for differences in baseline characteristics.

    Results: A total of 1,233 patients were included at 6 centers. There were no differences in regard to median age (64 versus 63 years) and proportion of men (57% versus 54%) between the periods. After introduction of the new strategy, the admission rate decreased from 59% to 33% (risk ratio 0.55 [95% confidence interval {CI} 0.48 to 0.63]; odds ratio 0.33 [95% CI 0.26 to 0.42]; adjusted odds ratio 0.33 [95% CI 0.25 to 0.42]). The median hospital stay was reduced from 23.2 to 4.7 hours (95% CI of difference -20.4 to -11.4); median health care-related costs, from $1,748 to $1,079 (95% CI of difference -$953 to -$391). The number of clinical events was very low.

    Conclusion: In this before-after study, clinical implementation of a 1-hour high-sensitivity cardiac troponin algorithm combined with the HEART score was associated with a reduction in admission rate and health care burden, with very low rates of adverse clinical events.

  • 213.
    Ljung, Lina
    et al.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, SE-11883 Stockholm, Sweden;Soder Sjukhuset, Dept Cardiol, SE-11883 Stockholm, Sweden.
    Reichard, Camilla
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, SE-18288 Danderyd, Sweden.
    Hagerman, Peter
    Capio St Gorans Hosp, Dept Emergency Med, SE-11281 Stockholm, Sweden.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Frick, Mats
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, SE-11883 Stockholm, Sweden;Soder Sjukhuset, Dept Cardiol, SE-11883 Stockholm, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Linder, Rikard
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, SE-18288 Danderyd, Sweden.
    Martinsson, Arne
    Capio St Gorans Hosp, Dept Emergency Med, SE-11281 Stockholm, Sweden.
    Melki, Dina
    Karolinska Univ Hosp, Heart & Vasc Theme, SE-14186 Stockholm, Sweden.
    Svensson, Per
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, SE-11883 Stockholm, Sweden;Soder Sjukhuset, Dept Cardiol, SE-11883 Stockholm, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, SE-18288 Danderyd, Sweden.
    Sensitivity of undetectable level of high-sensitivity troponin T at presentation in a large non-ST-segment elevation myocardial infarction cohort of early presenters2019In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 284, p. 6-11Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We aimed to evaluate the diagnostic sensitivity for myocardial infarction (MI) when using an undetectable level of high-sensitivity cardiac troponin T (hs-cTnT < 5 ng/L) at presentation combined with a non-ischemic electrocardiogram (ECG), to rule out MI in a non-ST-segment elevation MI (NSTEMI) cohort presenting ≤2 h from symptom onset. We also aimed to compare baseline characteristics and 30-day outcome in NSTEMI patients presenting with and without hs-cTnT < 5 ng/L.

    METHODS: All patients admitted to five centers in Sweden 2011-2015, after the introduction of hs-cTnT, who presented ≤2 h from symptom onset and received a final diagnosis of NSTEMI, were identified through the SWEDEHEART registry. These data and data of hs-cTnT levels were verified in the hospitals' medical records. The registry provided baseline and outcome data.

    RESULTS: Twenty-four (2.6%) of 911 NSTEMI patients presented with hs-cTnT < 5 ng/L. In patients presenting >1-≤2 h from symptom onset the sensitivity for MI when combining hs-cTnT and ECG was 99.4% (95% CI 98.4%-99.8%). In patients presenting ≤1 h, and in patients aged ≤65 years without prior MI, the sensitivity was insufficient. NSTEMI patients presenting with hs-cTnT < 5 ng/L were younger and had less often a prior MI. A total of 62.5 vs. 63.5% of the NSTEMI patients presenting with and without hs-cTnT < 5 ng/L underwent revascularization within 30 days and 4.5 and 3.2% died respectively.

    CONCLUSIONS: Hs-cTnT < 5 ng/L at presentation combined with a non-ischemic ECG may be used to rule out MI in patients presenting as early as >1 h from symptom onset with a sufficient sensitivity.

  • 214.
    Ljunggren, Mirjam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Does sleep disordered breathing in women promote heart failure?: A population based cohort study2014In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 23, p. 119-119Article in journal (Other academic)
  • 215.
    Ljunggren, Mirjam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    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.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Increased risk of heart failure in women with symptoms of sleep-disordered breathing2016In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 17, p. 32-37Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: An association between obstructive sleep apnea and the incidence of heart failure has been reported in men but not in women. The aim of this study was to investigate whether a combination of snoring and excessive daytime sleepiness, the two main symptoms of obstructive sleep apnea syndrome, was able to predict incident heart failure in a population-based sample of women.

    METHODS: The population-based cohort study Sleep and Health in Women (SHE; n = 5990 women born between 1901 and 1980) was used, with baseline questionnaire data from April 2000 relating to snoring, excessive daytime sleepiness, and covariates. Using data retrieved from the Swedish National Patient Register and Cause of Death Register, the follow-up of incident heart failure continued until 31 December 2011.

    RESULTS: Among women with both snoring and excessive daytime sleepiness at baseline, 5.3% developed heart failure during follow-up compared with 0.9% in the reference group with neither snoring nor excessive daytime sleepiness. After adjustment for age, waist circumference, smoking, alcohol, hypertension, diabetes, previous myocardial infarction, physical inactivity, depressive symptoms, menopausal status, and hormone replacement therapy, women with the combination of snoring and excessive daytime sleepiness had a twofold increase in the risk of incident heart failure (hazard ratio [HR] 2.2 95% confidence interval [CI] 1.1-4.4).

    CONCLUSION: Symptoms of obstructive sleep apnea, that is, the combination of snoring and excessive daytime sleepiness, are associated with an increased risk of developing heart failure in women.

  • 216.
    Ljunggren, Mirjam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Association between obstructive sleep apnea and elevated levels of type B natriuretic peptide in a community-based sample of women2012In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 35, no 11, p. 1521-1527Article in journal (Refereed)
    Abstract [en]

    Study Objectives:

    Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. One contributory factor may be hemodynamic stress due to the negative intrathoracic pressure during each episode of apnea. Type B natriuretic peptide (BNP) is secreted by the cardiac ventricles in response to volume expansion and pressure load and the authors hypothesized that there would be an association between indices of OSA during the night and levels of BNP in the morning.

    Setting:

    Community-based in Uppsala, Sweden.

    Participants:

    There were 349 women who participated.

    Measurements and Results:

    Participants underwent full-night polysomnography and anthropometric measurements, and answered questionnaires about medical conditions and current medication. The morning after the polysomnography, blood samples were drawn for analysis of plasma BNP, C-reactive protein, creatinine, and hemoglobin. There was an increase in mean BNP as the severity of sleep apnea increased, increasing from a mean value of 8.5 ng/L among women with an apnea-hypopnea index (AHI) < 5 to 18.0 ng/L in women with an AHI = 30. Elevated BNP levels (= 20 ng/L) were found in 29.8% of the women, whereas 70.2% had normal levels. The odds ratio was 2.2 for elevated BNP levels for women with an AHI of 5-14.9 in relation to women with an AHI < 5, 3.1 for women with an AHI of 15-29.9, and 4.6 for women with an AHI = 30 after adjustment for age, body mass index, systolic blood pressure, antihypertensive drugs, and creatinine.

    Conclusions:

    There is a dose-response relationship in women between the severity of sleep apnea during the night and the levels of BNP in the morning.

  • 217. Lopez-Sendon, Jose
    et al.
    Swedberg, Karl
    McMurray, John
    Tamargo, Juan
    Maggioni, Aldo P
    Dargie, Henry
    Tendera, Michal
    Waagstein, Finn
    Kjekshus, Jan
    Lechat, Philippe
    Torp-Pedersen, Christian
    Priori, Silvia G
    Alonso Garcia, Mari­a Angeles
    Blanc, Jean-Jacques
    Budaj, Andrzej
    Cowie, Marti­n
    Dean, V
    Deckers, Jaap
    Fernandez Burgos, Enrique
    Lekakis, John
    Lindahl, Bertil
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Mazzotta, Gianfranco
    McGregor, Keith
    Morais, Joáo
    Oto, Ali
    Smiseth, Otto A
    Ardissino, Diego
    Avendano, Cristina
    Blomström-Lundqvist, Carina
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Clément, Denis
    Drexler, Helmut
    Ferrari, Roberto
    Fox, Keith A
    Julian, Desmond
    Kearney, Peter
    Klein, Werner
    Kober, Lars
    Mancia, Giuseppe
    Nieminen, Markku
    Ruzillo, Witold
    Simoons, Maarten
    Thygesen, Kristian
    Tognoni, Gianni
    Tritto, Isabella
    Wallentin, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    [Expert Consensus document on angiotensin converting enzyme inhibitors in cardiovascular disease]2004In: Rev Esp Cardiol, ISSN 0300-8932, Vol. 57, no 12, p. 1213-32Article in journal (Refereed)
  • 218.
    Lysholm, Jack
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Strong development of research based on national quality registries in Sweden2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 9-11Article in journal (Refereed)
    Abstract [en]

    The aim of the present paper is to describe how the use of national quality registries (NQRs) for research has evolved over the past decade in Sweden. All Swedish NQRs have reported their scientific activity (publications per year in peer-reviewed scientific journals) to the Swedish Association of Local Authorities and Regions since 2009, and the present report is based on available data from 2009-2016. The yearly number of publications of the 69 registries active in 2009 has increased from 121 to 496 in 2016. Seventeen of these registries published more than 10 papers in 2016; however, 12 NQRs did not publish any papers in 2016. An additional 77 papers were published in 2016 by the 34 NQRs started after 2009. In summary, there has been a strong development of quality registry-based research in Sweden over the last decade. However, there is still room for further increase of the use of research based on NQRs in Sweden.

  • 219. Mair, Johannes
    et al.
    Jaffe, Allan
    Apple, Fred
    Lindahl, Bertil
    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.
    Cardiac Biomarkers2015In: Disease Markers, ISSN 0278-0240, E-ISSN 1875-8630, p. 1-3Article in journal (Other academic)
  • 220.
    Mair, Johannes
    et al.
    Med Univ Innsbruck, Dept Internal Med Cardiol & Angiol 3, Innsbruck, Austria..
    Lindahl, Bertil
    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.
    Giannitsis, Evangelos
    Heidelberg Univ, Med Klin 3, Heidelberg, Germany..
    Huber, Kurt
    Wilhelminen Hosp, Dept Med Cardiol & Intens Care Med, Vienna, Austria..
    Thygesen, Kristian
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark..
    Plebani, Mario
    Univ Hosp Padova, Dept Lab Med, Padua, Italy..
    Moeckel, Martin
    Charite Univ Med Berlin, Div Emergency Med, Berlin, Germany.;Charite Univ Med Berlin, Dept Cardiol, Berlin, Germany..
    Mueller, Christian
    Univ Hosp Basel, Dept Cardiol, Basel, Switzerland.;Univ Hosp Basel, Cardiovasc Res Inst Basel, Basel, Switzerland..
    Jaffe, Allan S.
    Will sacubitril-valsartan diminish the clinical utility of B-type natriuretic peptide testing in acute cardiac care?2017In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 6, no 4, p. 321-328Article in journal (Refereed)
    Abstract [en]

    Since the approval of sacubitril-valsartan for the treatment of chronic heart failure with reduced ejection fraction, a commonly raised suspicion is that a wider clinical use of this new drug may diminish the clinical utility of B-type natriuretic peptide testing as sacubitril may interfere with B-type natriuretic peptide clearance. In this education paper we critically assess this hypothesis based on the pathophysiology of the natriuretic peptide system and the limited published data on the effects of neprilysin inhibition on natriuretic peptide plasma concentrations in humans. As the main clinical application of B-type natriuretic peptide testing in acute cardiac care is and will be the rapid rule-out of suspected acute heart failure there is no significant impairment to be expected for B-type natriuretic peptide testing in the acute setting. However, monitoring of chronic heart failure patients on sacubitril-valsartan treatment with B-type natriuretic peptide testing may be impaired. In contrast to N-terminal-proBNP, the current concept that the lower the B-type natriuretic peptide result in chronic heart failure patients, the better the prognosis during treatment monitoring, may no longer be true.

  • 221.
    Mair, Johannes
    et al.
    Med Univ Innsbruck, Heart Ctr, Dept Internal Med Cardiol & Angiol 3, Innsbruck, Austria.
    Lindahl, Bertil
    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.
    Hammarsten, Ola
    Univ Gothenburg, Dept Clin Chem & Transfus Med, Gothenburg, Sweden.
    Mueller, Christian
    Univ Hosp Basel, Dept Cardiol, Basel, Switzerland; Univ Hosp Basel, Cardiovasc Res Inst Basel, Basel, Switzerland.
    Giannitsis, Evangelos
    Heidelberg Univ, Med Klin 3, Dept Cardiol, Heidelberg, Germany.
    Huber, Kurt
    Wilhelminen Hosp, Dept Med Cardiol & Intens Care Med, Vienna, Austria; Sigmund Freud Univ, Med Sch, Vienna, Austria.
    Moeckel, Martin
    Charite Univ Med Berlin, Div Emergency Med, Berlin, Germany; Charite Univ Med Berlin, Dept Cardiol, Berlin, Germany.
    Plebani, Mario
    Univ Hosp Padova, Dept Lab Med, Padua, Italy.
    Thygesen, Kristian
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
    Jaffe, Allan S.
    Mayo Clin, Rochester, MN USA; Med Sch, Rochester, MN USA.
    How is cardiac troponin released from injured myocardium?2018In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 7, no 6, p. 553-560Article in journal (Refereed)
    Abstract [en]

    Cardiac troponin I and cardiac troponin T are nowadays the criterion biomarkers for the laboratory diagnosis of acute myocardial infarction due to their very high sensitivities and specificities for myocardial injury. However, still many aspects of their degradation, tissue release and elimination from the human circulation are incompletely understood. Myocardial injury may be caused by a variety of different mechanisms, for example, myocardial ischaemia, inflammatory and immunological processes, trauma, drugs and toxins, and myocardial necrosis is preceded by a substantial reversible prelethal phase. Recent experimental data in a pig model of myocardial ischaemia demonstrated cardiac troponin release into the circulation from apoptotic cardiomyocytes as an alternative explanation for clinical situations with increased cardiac troponin without any other evidence for myocardial necrosis. However, the comparably lower sensitivities of all currently available imaging modalities, including cardiac magnetic resonance imaging for the detection of particularly non-focal myocardial necrosis in patients, has to be considered for cardiac troponin test result interpretation in clinical settings without any other evidence for myocardial necrosis apart from increased cardiac troponin concentrations as well.

  • 222.
    Mair, Johannes
    et al.
    Med Univ Innsbruck, Heart Ctr, Dept Internal Med Cardiol & Angiol 3, Innsbruck, Austria.
    Lindahl, Bertil
    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.
    Müller, Christian
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland; Univ Basel Hosp, Cardiovasc Res Inst Basel, Basel, Switzerland.
    Giannitsis, Evangelos
    Heidelberg Univ, Dept Cardiol, Med Klin 3, Heidelberg, Germany.
    Huber, Kurt
    Wilhelminen Hosp, Dept Med Cardiol & Intens Care Med, Vienna, Austria.
    Möckel, Martin
    Charite Univ Med Berlin, Div Emergency Med, Berlin, Germany; Charite Univ Med Berlin, Dept Cardiol, Berlin, Germany.
    Plebani, Mario
    Univ Hosp Padova, Dept Lab Med, Padua, Italy.
    Thygesen, Kristian
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
    Jaffe, Allan S.
    Mayo Clin & Mayo Grad Sch Med, Rochester, MN USA.
    Editor's Choice-What to do when you question cardiac troponin values2018In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 7, no 6, p. 577-586Article in journal (Refereed)
    Abstract [en]

    High-sensitivity cardiac troponin assays enable cardiac troponin measurement with a high degree of analytical sensitivity and a low level of analytical imprecision at the low measuring range. One of the most important advantages of these new assays is that they allow novel, more rapid approaches for ruling in or ruling out acute myocardial infarctions. The increase in the early diagnostic sensitivity of high-sensitivity cardiac troponin assays comes at the cost of a reduced acute myocardial infarction specificity of the biomarker, because more patients with other causes of acute or chronic myocardial injury without overt myocardial ischaemia are detected than with previous cardiac troponin assays. Increased troponin concentrations that do not fit with the clinical presentation are seen in the daily routine, mainly as a result of a variety of pathologies, and if tested in the same sample, even discrepancies between high-sensitivity cardiac troponin I and troponin T test results may sometimes be found as well. In addition, analytically false-positive test results occasionally may occur since no assay is perfect. In this review, we summarise the biochemical, pathophysiological and analytical background of the work-up for such a clinical setting.

  • 223.
    McCord, James
    et al.
    Henry Ford Hlth Syst, Henry Ford Heart & Vasc Inst, 2799 West Grand Blvd K-14, Detroit, MI 48202 USA..
    Cabrera, Rafael
    Henry Ford Hlth Syst, Henry Ford Heart & Vasc Inst, 2799 West Grand Blvd K-14, Detroit, MI 48202 USA..
    Lindahl, Bertil
    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.
    Giannitsis, Evangelos
    Univ Heidelberg Hosp, Dept Internal Med Cardiol Angiol & Pulmonol 3, Heidelberg, Germany..
    Evans, Kaleigh
    Henry Ford Hosp Hlth Syst, Dept Internal Med, Detroit, MI USA..
    Nowak, Richard
    Henry Ford Hlth Syst, Dept Emergency Med, Detroit, MI USA..
    Frisoli, Tiberio
    Henry Ford Hlth Syst, Henry Ford Heart & Vasc Inst, 2799 West Grand Blvd K-14, Detroit, MI 48202 USA..
    Body, Richard
    Cent Manchester Univ Hosp NHS Fdn Trust, Manchester, Lancs, England..
    Christ, Michael
    Paracelsus Med Univ, Gen Hosp, Dept Emergency & Crit Care Med, Nurnberg, Germany..
    deFilippi, Christopher R.
    Inova Heart & Vasc Inst, Dept Med, Falls Church, VA USA..
    Christenson, Robert H.
    Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA..
    Jacobsen, Gordon
    Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA..
    Alquezar, Aitor
    Hosp Santa Creu & Sant Pau, Dept Emergency Med, Barcelona, Spain..
    Panteghini, Mauro
    Univ Milan, Sch Med, Dept Biomed & Clin Sci Luigi Sacco, Milan, Italy..
    Melki, Dina
    Karolinska Univ Hosp, Dept Cardiol, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Plebani, Mario
    Univ Hosp Padova, Dept Lab Med, Padua, Italy..
    Verschuren, Franck
    Clin Univ St Luc, Brussels, Belgium.;Catholic Univ Louvain, Brussels, Belgium..
    French, John
    Liverpool Hosp, Sydney, NSW, Australia.;Univ New South Wales, Sydney, NSW, Australia..
    Bendig, Garnet
    Roche Diagnost Germany, Penzberg, Germany..
    Weiser, Silvia
    Roche Diagnost Germany, Penzberg, Germany..
    Mueller, Christian
    Univ Basel Hosp, Cardiol & Cardiovasc Res Inst Basel, Basel, Switzerland..
    Prognostic Utility of a Modified HEART Score in Chest Pain Patients in the Emergency Department2017In: Circulation. Cardiovascular Quality and Outcomes, ISSN 1941-7713, E-ISSN 1941-7705, Vol. 10, no 2, article id UNSP e003101Article in journal (Refereed)
    Abstract [en]

    Background-The TRAPID-AMI trial study ( High-Sensitivity Troponin-T Assay for Rapid Rule-Out of Acute Myocardial Infarction) evaluated high-sensitivity cardiac troponin-T ( hs-cTnT) in a 1-hour acute myocardial infarction ( AMI) exclusion algorithm. Our study objective was to evaluate the prognostic utility of a modified HEART score ( m-HS) within this trial. Methods and Results-Twelve centers evaluated 1282 patients in the emergency department for possible AMI from 2011 to 2013. Measurements of hs-cTnT ( 99th percentile, 14 ng/L) were performed at 0, 1, 2, and 4 to 14 hours. Evaluation for major adverse cardiac events ( MACEs) occurred at 30 days ( death or AMI). Low-risk patients had an m-HS <= 3 and had either hs-cTnT<14 ng/L over serial testing or had AMI excluded by the 1-hour protocol. By the 1-hour protocol, 777 ( 60%) patients had an AMI excluded. Of those 777 patients, 515 ( 66.3%) patients had an m-HS <= 3, with 1 ( 0.2%) patient having a MACE, and 262 ( 33.7%) patients had an m-HS <= 4, with 6 ( 2.3%) patients having MACEs ( P=0.007). Over 4 to 14 hours, 661 patients had a hs-cTnT<14 ng/L. Of those 661 patients, 413 ( 62.5%) patients had an m-HS <= 3, with 1 ( 0.2%) patient having a MACE, and 248 ( 37.5%) patients had an m-HS >= 4, with 5 ( 2.0%) patients having MACEs ( P=0.03). Conclusions-Serial testing of hs-cTnT over 1 hour along with application of an m-HS identified a low-risk population that might be able to be directly discharged from the emergency department.

  • 224. Melki, Dina
    et al.
    Lugnegård, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Alfredsson, Joakim
    Lind, Suzanne
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jernberg, Tomas
    Implications of Introducing High-Sensitivity Cardiac Troponin T Into Clinical Practice Data From the SWEDEHEART Registry2015In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 65, no 16, p. 1655-1664Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Cardiac troponin is the preferred biomarker for diagnosing myocardial infarction (MI). OBJECTIVES The aim of this study was to examine the implications of introducing high-sensitivity cardiac troponin T (hs-cTnT) into clinical practice and to define at what hs-cTnT level risk starts to increase. METHODS We analyzed data from 48,594 patients admitted because of symptoms suggesting an acute coronary syndrome and who were entered into a large national registry. Patients were divided into Group 1, those with hs-cTnT <6 ng/l; Group 2, those with hs-cTnT 6 to 13 ng/l; Group 3, those with hs-cTnT 14 to 49 ng/l (i.e., a group in which most patients would have had a negative cardiac troponin T with older assays); and Group 4, those with hs-cTnT >= 50 ng/l. RESULTS There were 5,790 (11.9%), 6,491 (13.4%), 10,476 (21.6%), and 25,837 (53.2%) patients in Groups 1, 2, 3, and 4, respectively. In Groups 1 to 4, the proportions with MI were 2.2%, 2.6%, 18.2%, and 81.2%. There was a stepwise increase in the proportion of patients with significant coronary stenoses, left ventricular systolic dysfunction, and death during follow-up. When dividing patients into 20 groups according to hs-cTnT level, the adjusted mortality started to increase at an hs-cTnT level of 14 ng/l. CONCLUSIONS Introducing hs-cTnT into clinical practice has led to the recognition of a large proportion of patients with minor cardiac troponin increases (14 to 49 ng/l), the majority of whom do not have MI. Although a heterogeneous group, these patients remain at high risk, and the adjusted mortality rate started to increase at the level of the 99th percentile in healthy controls.

  • 225.
    Mohammad, Moman A.
    et al.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Karlsson, Sofia
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Haddad, Jonathan
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Cederberg, Bjorn
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Danderyds Univ Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lindahl, Bertil
    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.
    Frobert, Ole
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Koul, Sasha
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Christmas, national holidays, sport events, and time factors as triggers of acute myocardial infarction: SWEDEHEART observational study 1998-20132018In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 363, article id k4811Article in journal (Refereed)
    Abstract [en]

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

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

    SETTING Sweden.

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

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

    MAIN OUTCOME MEASURES Daily count of myocardial infarction.

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

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

  • 226.
    Mohammad, Moman A.
    et al.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Koul, Sasha
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Smith, J. Gustav
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Noc, Marco
    Ctr Intens Internal Med, Ljubljana, Slovenia.
    Lang, Irene
    Med Univ Vienna, Dept Cardiol, Vienna, Austria.
    Holzer, Michael
    Med Univ Vienna, Dept Emergency Med, Vienna, Austria.
    Clemmensen, Peter
    Univ Heart Ctr, Dept Gen & Intervent Cardiol, Hamburg, Germany;Univ Southern Denmark, Nykoebing F Hosp, Div Cardiol, Dept Med, Odense, Denmark.
    Jensen, Ulf
    Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Engström, Thomas
    Univ Copenhagen, Rigshosp, Heart Ctr, Copenhagen, Denmark.
    Arheden, Håkan
    Lund Univ, Skane Univ Hosp, Dept Clin Physiol, Clin Sci, Lund, Sweden.
    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.
    Lindahl, Bertil
    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.
    Metzler, Bernhard
    Dept Cardiol, Innsbruck, Austria.
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Predictive Value of High-Sensitivity Troponin T for Systolic Dysfunction and Infarct Size (Six Months) After ST-Elevation Myocardial Infarction2018In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 122, no 5, p. 735-743Article in journal (Refereed)
    Abstract [en]

    The association of markers of myocardial injury and dysfunction with infarct size (IS) and ejection fraction (EF) are well documented. However, limited data are available on the newer high-sensitivity troponin assays and comparison with morphologic and functional assessment with cardiac magnetic resonance imaging. We aimed to examine the associations of high-sensitivity cardiac Troponin-T (hs-cTnT), creatine kinase MB iso-enzyme (CKMB), and N-terminal pro B-type Natriuretic Peptide (NT-proBNP) to IS and EF at 6 months. Blood samples from 119 ST-segment elevation myocardial infarction patients from the Rapid Endovascular Catheter Core Cooling Combined With Cold Saline solution as an Adjunct to Percutaneous Coronary Intervention for the Treatment of Acute Myocardial Infarction trial were collected at baseline, 6, 24, and 48 hours after admission. Cardiac magnetic resonance was performed at 4 +/- 2 days and 6 months. The association of biomarker levels to IS and EF was tested with Pearson's correlation coefficients and linear regression models with bootstrap resampling. The correlation coefficient of biomarker to IS was (CKMB: r = 0.71); (NT-proBNP: r = 0.55); (hs-cTnT: r = 0.80); and for EF (CKMB: r = 0.57); (NT-proBNP: r = 0.48); and (peak hs-cTnT: r = 0.68). IS and EF at 4 +/- 2 days had the strongest correlations with IS and EF at 6 months respectively (IS: r = 0.84) and (EF: r = 0.74). Receiver operating characteristic of peak hs-cTnT for predicting EF <= 40% at 6 months was 0.87 compared with 0.75 for early IS. Early EF was a negative predictor of late EF <40%, 1-area under curve = 0.93. In conclusion, high-sensitivity Troponin T is a rapid, cheap, generally available tool for accurate prediction of systolic dysfunction in patients 6 months after first-time ST-segment elevation myocardial infarction.

  • 227.
    Mokhtari, Arash
    et al.
    Skane Univ Hosp, Dept Internal & Emergency Med, Lund, Sweden.;Skane Univ Hosp, Dept Cardiol, Lund, Sweden.;Lund Univ, Dept Clin Sci Lund, Lund, Sweden..
    Borna, Catharina
    Lund Univ, Dept Clin Sci Lund, Lund, Sweden.;Helsingborg Gen Hosp, Div Specialised Local Hlth Care, Helsingborg, Sweden..
    Gilje, Patrik
    Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Tyden, Patrik
    Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Lindahl, Bertil
    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.
    Nilsson, Hans-Joergen
    Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Khoshnood, Ardavan
    Skane Univ Hosp, Dept Internal & Emergency Med, Lund, Sweden.;Lund Univ, Dept Clin Sci Lund, Lund, Sweden..
    Bjork, Jonas
    Lund Univ, Occupat & Environm Med, Lund, Sweden..
    Ekelund, Ulf
    Skane Univ Hosp, Dept Internal & Emergency Med, Lund, Sweden.;Lund Univ, Dept Clin Sci Lund, Lund, Sweden..
    A 1-h Combination Algorithm Allows Fast Rule-Out and Rule-In of Major Adverse Cardiac Events2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 1531-1540Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A 1-h algorithm based on high-sensitivity cardiac troponin T (hs-cTnT) testing at presentation and again 1 h thereafter has been shown to accurately rule out acute myocardial infarction.

    OBJECTIVES: The goal of the study was to evaluate the diagnostic accuracy of the 1-h algorithm when supplemented with patient history and an electrocardiogram (ECG) (the extended algorithm) for predicting 30-day major adverse cardiac events (MACE) and to compare it with the algorithm using hs-cTnT alone (the troponin algorithm).

    METHODS: This prospective observational study enrolled consecutive patients presenting to the emergency department (ED) with chest pain, for whom hs-cTnT testing was ordered at presentation. Hs-cTnT results at 1 h and the ED physician's assessments of patient history and ECG were collected. The primary outcome was an adjudicated diagnosis of 30-day MACE defined as acute myocardial infarction, unstable angina, cardiogenic shock, ventricular arrhythmia, atrioventricular block, cardiac arrest, or death of a cardiac or unknown cause.

    RESULTS: In the final analysis, 1,038 patients were included. The extended algorithm identified 60% of all patients for rule-out and had a higher sensitivity than the troponin algorithm (97.5% vs. 87.6%; p < 0.001). The negative predictive value was 99.5% and the likelihood ratio was 0.04 with the extended algorithm versus 97.8% and 0.17, respectively, with the troponin algorithm. The extended algorithm ruled-in 14% of patients with a higher sensitivity (75.2% vs. 56.2%; p < 0.001) but a slightly lower specificity (94.0% vs. 96.4%; p < 0.001) than the troponin algorithm. The rule-in arms of both algorithms had a likelihood ratio >10. CONCLUSIONS A 1-h combination algorithm allowed fast rule-out and rule-in of 30-day MACE in a majority of ED patients with chest pain and performed better than the troponin-alone algorithm.

  • 228.
    Mokhtari, Arash
    et al.
    Skane Univ Hosp, Dept Internal & Emergency Med, Lund, Sweden.;Skane Univ Hosp, Dept Cardiol, Lund, Sweden.;Lund Univ, Dept Clin Sci, Lund, Sweden..
    Lindahl, Bengt
    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.
    Smith, J. Gustav
    Skane Univ Hosp, Dept Cardiol, Lund, Sweden.;Lund Univ, Dept Clin Sci, Lund, Sweden..
    Holzmann, Martin J.
    Karolinska Univ Hosp, Dept Emergency Med, Huddinge, Sweden.;Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    Khoshnood, Ardavan
    Skane Univ Hosp, Dept Internal & Emergency Med, Lund, Sweden.;Lund Univ, Dept Clin Sci, Lund, Sweden..
    Ekelund, Ulf
    Skane Univ Hosp, Dept Internal & Emergency Med, Lund, Sweden.;Lund Univ, Dept Clin Sci, Lund, Sweden..
    Diagnostic Accuracy of High-Sensitivity Cardiac Troponin T at Presentation Combined With History and ECG for Ruling Out Major Adverse Cardiac Events2016In: Annals of Emergency Medicine, ISSN 0196-0644, E-ISSN 1097-6760, Vol. 68, no 6, p. 649-658Article in journal (Refereed)
    Abstract [en]

    Study objective: We evaluate the diagnostic accuracy of a high-sensitivity cardiac troponin T (hs-cTnT) level less than 5 ng/L or less than or equal to 14 ng/L at emergency department (ED) presentation, combined with the emergency physician's assessment of history and ECG, for ruling out major adverse cardiac events within 30 days.

    Methods: This prospective observational study enrolled consecutive ED chest pain patients. Emergency physicians' assessments of patient history and ECG were collected. The primay outcome was 30-day major adverse cardiac events, defined as acute myocardial infarction, unstable angina, cardiogenic shock, ventricular arrhythmia, atrioventricular block, cardiac arrest, or death of cardiac or unknown cause.

    Results: A total of 1,138 patients were included in the final analysis. The combination of hs-cTnT less than 5 ng/L, a nonischemic ECG result, and a nonhigh risk history was present for 29.2% of all patients and had a sensitivity of 99.2% (95% confidence interval [CI] 95.6% to 100%), negative predictive value (NPV) of 99.7% (95% CI 98.3% to 100%), and a negative likelihood ratio of 0.02 (95% CI 0 to 0.17) for 30-day major adverse cardiac events. The same combination with hs-cTnT less than or equal to 14 ng/L was present in 66.7% of the patients and had a sensitivity of 92% (95% CI 85.8% to 96.1%), NPV of 98.7% (95% CI 97.6% to 99.4%), and negative likelihood ratio of 0.11 (95% CI 0.06 to 0.20).

    Conclusion: A single hs-cTnT result of less than 5 ng/L at ED presentation when combined with a nonischemic ECG result and a nonhigh risk history identified 29% of chest pain patients at a very low risk of 30-day major adverse cardiac events. A similar strategy with hs-cTnT less than or equal to 14 ng/L was associated with a higher miss rate.

  • 229.
    Mokhtari, Arash
    et al.
    Skane Univ Hosp, Dept Internal & Emergency Med, Lund, Sweden.;Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Lindahl, Bertil
    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.
    Schiopu, Alexandru
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Yndigegn, Troels
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Khoshnood, Ardavan
    Skane Univ Hosp, Dept Internal & Emergency Med, Lund, Sweden..
    Gilje, Patrik
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Ekelund, Ulf
    Skane Univ Hosp, Dept Internal & Emergency Med, Lund, Sweden..
    A 0-Hour/1-Hour Protocol for Safe, Early Discharge of Chest Pain Patients2017In: Academic Emergency Medicine, ISSN 1069-6563, E-ISSN 1553-2712, Vol. 24, no 8, p. 983-992Article in journal (Refereed)
    Abstract [en]

    Objectives: Guidelines recommend a 0-hour/1-hour high-sensitivity cardiac troponin T (hs-cTnT) diagnostic strategy in acute chest pain patients. There are, however, little data on the performance of this strategy when combined with clinical risk stratification. We aimed to evaluate the diagnostic accuracy of an accelerated diagnostic protocol (ADP) using the 0-hour/1-hour hs-cTnT strategy together with an adapted Thrombolysis In Myocardial Infarction (TIMI) score and electrocardiogram (ECG) for ruling out major adverse cardiac events (MACE) within 30 days.

    Methods: This prospective observational study enrolled consecutive emergency department (ED) chest pain patients. TIMI score variables, ED physicians' assessments of the ECG, and 0-and 1-hour hs-cTnT were collected. Thirty-day MACE was defined as acute myocardial infarction (AMI), unstable angina (UA), cardiogenic shock, ventricular arrhythmia, atrioventricular block, cardiac arrest, or death of cardiac or unknown cause.

    Results: A total of 1,020 patients were included in the final analysis. The combination of an adapted TIMI score <= 1, a nonischemic ECG, and either a 0-hour hs-cTnT < 5 ng/L or a 0-hour hs-cTnT < 12 ng/L combined with a 1-hour increase < 3 ng/L identified 432 (42.4%) patients as very low risk with a negative predictive value of 99.5% (95% confidence interval [CI] = 98.3%-99.9%) and a negative likelihood ratio of 0.04 (95% CI = 0.01-0.14) for 30-day MACE. The ADP missed only two patients with UA and no patients with AMI or other forms of MACE.

    Conclusion: An ADP using the guideline recommended 0-hour/1-hour hs-cTnT strategy rapidly identified patients with a very low risk of 30-day MACE including UA where no further cardiac testing would be needed. This could potentially allow safe early discharge of about 40% of ED chest pain patients.

  • 230.
    Mueller, Christian
    et al.
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, Cardiovasc Res Inst Basel, Basel, Switzerland..
    Giannitsis, Evangelos
    Univ Heidelberg Hosp, Heidelberg, Germany..
    Christ, Michael
    Paracelsus Med Univ, Gen Hosp, Dept Emergency & Crit Care Med, Nurnberg, Germany..
    Ordonez-Llanos, Jorge
    Inst Invest Biomed St Pau, Dept Clin Biochem, Barcelona, Spain..
    deFilippi, Christopher
    Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA..
    McCord, James
    Henry Ford Heart & Vasc Inst, Henry Ford Hlth Syst, Detroit, MI USA..
    Body, Richard
    Cent Manchester Univ Hosp NHS Fdn Trust, Manchester, Lancs, England..
    Panteghini, Mauro
    Univ Milan, Sch Med, Dept Biomed & Clin Sci Luigi Sacco, Milan, Italy..
    Jernberg, Tomas
    Karolinska Inst, Dept Med, Huddinge, Sweden..
    Plebani, Mario
    Univ Hosp Padova, Dept Lab Med, Padua, Italy..
    Verschuren, Franck
    Clin Univ St Luc, Dept Acute Med, Brussels, Belgium.;Catholic Univ Louvain, Brussels, Belgium..
    French, John
    Liverpool Hosp, Liverpool, NSW, Australia.;Univ New S Wales, Liverpool, NSW, Australia..
    Christenson, Robert
    Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA..
    Weiser, Silvia
    Roche Diagnost Germany, Penzberg, Germany..
    Bendig, Garnet
    Roche Diagnost Germany, Penzberg, Germany..
    Dilba, Peter
    Roche Diagnost Germany, Penzberg, Germany..
    Lindahl, Bertil
    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.
    Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T2016In: Annals of Emergency Medicine, ISSN 0196-0644, E-ISSN 1097-6760, Vol. 68, no 1, p. 76-87Article in journal (Refereed)
    Abstract [en]

    Study objective: We aim to prospectively validate the diagnostic accuracy of the recently developed 0-h/1-h algorithm, using high-sensitivity cardiac troponin T (hs-cTnT) for the early rule-out and rule-in of acute myocardial infarction. Methods: We enrolled patients presenting with suspected acute myocardial infarction and recent (<6 hours) onset of symptoms to the emergency department in a global multicenter diagnostic study. Hs-cTnT (Roche Diagnostics) and sensitive cardiac troponin I (Siemens Healthcare) were measured at presentation and after 1 hour, 2 hours, and 4 to 14 hours in a central laboratory. Patient triage according to the predefined hs-cTnT 0-hour/1-hour algorithm (hs-cTnT beloow 12 ng/L and Delta 1 hour below 3 ng/L to rule out; hs-cTnT at least 52 ng/L r Delta 1 hour at least 5 ng/L to rule in; remaining patients to the "observational zone") was compared against a centrally adjudicated final diagnosis by 2 independent cardiologists (reference standard). The final diagnosis was based on all available information, including coronary angiography and echocardiography results, follow-up data, and serial measurements of sensitive cardiac troponin I, whereas adjudicators remained blinded to hs-cTnT. Results: Among 1,282 patients enrolled, acute myocardial infarction was the final diagnosis for 213 (16.6%) patients. Applying the hs-cTnT 0-hour/1-hour algorithm, 813 (63.4%) patients were classified as rule out, 184 (14.4%) were classified as rule in, and 285 (22.2%) were triaged to the observational zone. This resulted in a negative predictive value and sensitivity for acute myocardial infarction of 99.1% (95% confidence interval [CI] 98.2% to 99.7%) and 96.7% (95% CI 93.4% to 98.7%) in the rule-out zone (7 patients with false-negative results), a positive predictive value and specificity for acute myocardial infarction of 77.2% (95% CI 70.4% to 83.0%) and 96.1% (95% CI 94.7% to 97.2%) in the rule-in zone, and a prevalence of acute myocardial infarction of 22.5% in the observational zone. Conclusion: The hs-cTnT 0-hour/1-hour algorithm performs well for early rule-out and rule-in of acute myocardial infarction.

  • 231.
    Mueller, Christian
    et al.
    Univ Basel Hosp, Dept Cardiol, CH-4031 Basel, Switzerland.;Univ Basel Hosp, Cardiovasc Res Inst Basel, CH-4031 Basel, Switzerland..
    Giannitsis, Evangelos
    Univ Heidelberg Hosp, Heidelberg, Germany..
    Lindahl, Bertil
    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.
    Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T Reply2016In: Annals of Emergency Medicine, ISSN 0196-0644, E-ISSN 1097-6760, Vol. 67, no 6, p. 794-795Article in journal (Refereed)
  • 232.
    Mueller, Christian
    et al.
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, Cardiovasc Res Inst Basel, Basel, Switzerland..
    Giannitsis, Evangelos
    Heidelberg Univ, Med Klin III, Heidelberg, Germany..
    Möckel, Martin
    Univ Med Berlin, Div Emergency Med, Berlin, Germany.;Univ Med Berlin, Dept Cardiol Charite, Berlin, Germany..
    Huber, Kurt
    Wilhelminen Hosp, 3rd Dept Med Cardiol & Intens Care Med, Vienna, Austria..
    Mair, Johannes
    Med Univ Innsbruck, Dept Internal Med III Cardiol & Angiol, Innsbruck, Austria..
    Plebani, Mario
    Univ Hosp Padova, Dept Lab Med, Padua, Italy..
    Thygesen, Kristian
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark..
    Jaffe, Allan S.
    Mayo Clin, Rochester, MN 55905 USA.;Sch Med, Rochester, MN 55905 USA..
    Lindahl, Bertil
    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.
    Rapid rule out of acute myocardial infarction: novel biomarker-based strategies2017In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 6, no 3, p. 218-222Article in journal (Refereed)
  • 233.
    Mueller, Christian
    et al.
    Univ Hosp Basel, Dept Cardiol, Basel, Switzerland; Univ Hosp Basel, Cardiovasc Res Inst Basel, Basel, Switzerland.
    Möckel, Martin
    Charite Univ Med Berlin, Div Emergency Med, Berlin, Germany.
    Giannitsis, Evangelos
    Heidelberg Univ, Med Klin 3, Heidelberg, Germany.
    Huber, Kurt
    Wilhelminen Hosp, Dept Med Cardiol & Intens Care Med, Vienna, Austria.
    Mair, Johannes
    Innsbruck Med Univ, Dept Internal Med Cardiol & Angiol 3, Innsbruck, Austria.
    Plebani, Mario
    Univ Hosp Padova, Dept Lab Med, Padua, Italy.
    Thygesen, Kristian
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
    Jaffe, Allan S
    Mayo Clin, Rochester, MN USA; Med Sch, Rochester, MN USA.
    Lindahl, Bertil
    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.
    Use of copeptin for rapid rule-out of acute myocardial infarction2018In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 7, no 6, p. 570-576, article id 2048872617710791Article in journal (Refereed)
    Abstract [en]

    Copeptin is currently understood as a quantitative marker of endogenous stress. It rises rapidly in multiple acute disorders including acute myocardial infarction. As a single variable, it has only modest diagnostic accuracy for acute myocardial infarction. However, the use of copeptin within a dual-marker strategy together with conventional cardiac troponin increases the diagnostic accuracy and particularly the negative predictive value of cardiac troponin alone for acute myocardial infarction. The rapid rule-out of acute myocardial infarction is the only application in acute cardiac care mature enough to merit consideration for routine clinical care. However, the dual-marker approach seems to provide only very small incremental value when used in combination with sensitive or high-sensitivity cardiac troponin assays. This review aims to update and educate regarding the potential and the procedural details, as well as the caveats and challenges of using copeptin in clinical practice.

  • 234.
    Mueller-Hennessen, Matthias
    et al.
    Univ Heidelberg Hosp, Dept Internal Med Cardiol Angiol & Pulmonol 3, Heidelberg, Germany..
    Lindahl, Bertil
    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.
    Giannitsis, Evangelos
    Univ Heidelberg Hosp, Dept Internal Med Cardiol Angiol & Pulmonol 3, Heidelberg, Germany..
    Biener, Moritz
    Univ Heidelberg Hosp, Dept Internal Med Cardiol Angiol & Pulmonol 3, Heidelberg, Germany..
    Vafaie, Mehrshad
    Univ Heidelberg Hosp, Dept Internal Med Cardiol Angiol & Pulmonol 3, Heidelberg, Germany..
    deFilippi, Christopher R.
    Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA..
    Christ, Michael
    Paracelsus Med Univ, Dept Emergency & Crit Care Med, Community Hosp, Nurnberg, Germany..
    Santalo-Bel, Miguel
    Hosp Santa Creu & Sant Pau, Semicrit Unit, Barcelona, Spain.;Inst Invest Biomed St Pau, Barcelona, Spain..
    Panteghini, Mauro
    Univ Milan, Sch Med, Dept Biomed & Clin Sci Luigi Sacco, Milan, Italy..
    Plebani, Mario
    Univ Hosp Padova, Dept Lab Med, Padua, Italy..
    Verschuren, Franck
    Catholic Univ Louvain, Dept Acute Med, Clin Univ St Luc, B-1200 Brussels, Belgium..
    Jernberg, Tomas
    KarolinskaInstitutet, Dept Med, Huddinge, Sweden..
    French, John K.
    Univ New S Wales, Liverpool Hosp, Sydney, NSW, Australia..
    Christenson, Robert H.
    Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA..
    Body, Richard
    Cent Manchester Univ Hosp NHS Fdn Trust, Manchester, Lancs, England..
    McCord, James
    Henry Ford Hlth Syst, Henry Ford Heart & Vasc Inst, Detroit, MI USA..
    Dilba, Peter
    Roche Diagnost Germany, Penzberg, Germany..
    Katus, Hugo A.
    Univ Heidelberg Hosp, Dept Internal Med Cardiol Angiol & Pulmonol 3, Heidelberg, Germany..
    Mueller, Christian
    Univ Basel Hosp, Cardiol & Cardiovasc Res Inst Basel, Basel, Switzerland..
    Diagnostic and prognostic implications using age- and gender-specific cut-offs for high-sensitivity cardiac troponin T - Sub-analysis from the TRAPID-AMI study2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 209, p. 26-33Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate the impact of age-and gender-specific cut-offs for high-sensitivity cardiac troponin T (hs-cTnT) compared to the general 99th percentile hs-cTnT cut-off on diagnosis and prognosis of acute myocardial infarction (AMI).

    Methods: 1282 unselected patients presenting to the emergency department with suspected AMI were enrolled as part of the TRAPID-AMI study. In the present sub-analysis, reclassification of AMI diagnosis was performed by comparing the general hs-cTnT cut-off of 14 ng/L to previously proposed age-and gender-dependent hs-cTnT 99th percentile cut-offs (28 ng/L for >= 65 years, 9 ng/L for female and 15.5 ng/L for male patients). Patients were further clinically adjudicated into acute coronary syndrome (ACS) and non-ACS.

    Results: For patients >= 65 years, application of age-specified cut-offs resulted in a decrease of AMI from 29.8% to 18.3% in the entire cohort (n = 557) and 54.7% to 40.9% in the ACS subcohort (n = 225). Using gender-specific cut-offs, AMI-rate increased from 16.6% to 22.6% (entire cohort, n = 477) and 62.6% to 71.7% (ACS subcohort, n = 99) in women, whereas in men, rates decreased from 23.1% to 21.1% (entire cohort, n = 805) and 48.8% to 45.9% (ACS, n = 281), respectively. Age-specified cut-offs significantly reclassified patients for outcomes of 1-month and 3-month mortality in the entire and ACS cohort (14.2% net reclassification improvement, p < 0.001, respectively). Contrary, no significant differences in outcomes could be found using gender-specific cut-offs.

    Conclusions: While influence of gender-specific hs-cTnT cut-offs on diagnostic and prognostic reclassification was only modest in patients with suspected AMI, age-specific cut-offs showed a significant impact and may be considered for further validation.

  • 235. Mueller-Hennessen, Matthias
    et al.
    Lindahl, Bertil
    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.
    Giannitsis, Evangelos
    Vafaie, Mehrshad
    Biener, Moritz
    Haushofer, Alexander C
    Seier, Josef
    Christ, Michael
    Alquézar-Arbé, Aitor
    deFilippi, Christopher R
    McCord, James
    Body, Richard
    Panteghini, Mauro
    Jernberg, Tomas
    Plebani, Mario
    Verschuren, Franck
    French, John K
    Christenson, Robert H
    Dinkel, Carina
    Katus, Hugo A
    Mueller, Christian
    Combined testing of copeptin and high-sensitivity cardiac troponin T at presentation in comparison to other algorithms for rapid rule-out of acute myocardial infarction2019In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 276, p. 261-267Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We aimed to directly compare the diagnostic and prognostic performance of a dual maker strategy (DMS) with combined testing of copeptin and high-sensitivity (hs) cardiac troponin T (cTnT) at time of presentation with other algorithms for rapid rule-out of acute myocardial infarction (AMI).

    METHODS: 922 patients presenting to the emergency department with suspected AMI and available baseline copeptin measurements qualified for the present TRAPID-AMI substudy. Diagnostic measures using the DMS (copeptin <10, <14 or < 20 pmol/L and hs-cTnT≤14 ng/L), the 1 h-algorithm (hs-cTnT<12 ng/L and change <3 ng/L at 1 h), as well as the hs-cTnT limit-of-blank (LoB, <3 ng/L) and -detection (LoD, <5 ng/L) were compared. Outcomes were assessed as combined end-points of death and myocardial re-infarction.

    RESULTS: True-negative rule-out using the DMS could be achieved in 50.9%-62.3% of all patients compared to 35.0%, 45.3% and 64.5% using LoB, LoD or the 1 h-algorithm, respectively. The DMS showed NPVs of 98.1%-98.3% compared to 99.2% for the 1 h-algorithm, 99.4% for the LoB and 99.3% for the LoD. Sensitivities were 93.5%-94.8%, as well as 96.8%, 98.7% and 98.1%, respectively. Addition of clinical low-risk criteria such as a HEART-score ≤ 3 to the DMS resulted in NPVs and sensitivities of 100% with a true-negative rule-out to 33.8%-41.6%. Rates of the combined end-point of death/MI within 30 days ranged between 0.2% and 0.3% for all fast-rule-out protocols.

    CONCLUSION: Depending on the applied copeptin cut-off and addition of clinical low-risk criteria, the DMS might be an alternative to the hs-cTn-only-based algorithms for rapid AMI rule-out with comparable diagnostic measures and outcomes.

  • 236.
    Mueller-Hennessen, Matthias
    et al.
    Univ Heidelberg Hosp, Dept Internal Med 3, Cardiol Angiol & Pulmonol, Heidelberg, Germany..
    Mueller, Christian
    Univ Basel Hosp, Cardiol &Cardiovasc Res Inst Basel, Basel, Switzerland..
    Giannitsis, Evangelos
    Univ Heidelberg Hosp, Dept Internal Med 3, Cardiol Angiol & Pulmonol, Heidelberg, Germany..
    Biener, Moritz
    Univ Heidelberg Hosp, Dept Internal Med 3, Cardiol Angiol & Pulmonol, Heidelberg, Germany..
    Vafaie, Mehrshad
    Univ Heidelberg Hosp, Dept Internal Med 3, Cardiol Angiol & Pulmonol, Heidelberg, Germany..
    deFilippi, Christopher R.
    Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA..
    Christ, Michael
    Community Hosp, Dept Emergency & Crit Care Med, Nurnberg, Germany.;Paracelsus Med Univ, Nurnberg, Germany..
    Ordonez-Llanos, Jorge
    Inst Invest Biomed St Pau, Dept Clin Biochem, Barcelona, Spain..
    Panteghini, Mauro
    Univ Milan, Sch Med, Dept Biomed & Clin Sci Luigi Sacco, Milan, Italy..
    Plebani, Mario
    Univ Hosp Padova, Dept Lab Med, Padua, Italy..
    Verschuren, Franck
    Clin Univ St Luc, Dept Acute Med, Brussels, Belgium.;Catholic Univ Louvain, Brussels, Belgium..
    Melki, Dina
    Karolinska Inst, Dept Med, Huddinge, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    French, John K.
    Liverpool Hosp, Sydney, NSW, Australia.;Univ New South Wales, Sydney, NSW, Australia..
    Christenson, Robert H.
    Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA..
    Body, Richard
    Cent Manchester Univ Hosp NHS Fdn Trust, Manchester, Lancs, England..
    McCord, James
    Henry Ford Hlth Syst, Henry Ford Heart & Vasc Inst, Detroit, MI USA..
    Dinkel, Carina
    Roche Diagnost Germany, Penzberg, Germany..
    Katus, Hugo A.
    Univ Heidelberg Hosp, Dept Internal Med 3, Cardiol Angiol & Pulmonol, Heidelberg, Germany..
    Lindahl, Bertil
    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.
    Serial Sampling of High-Sensitivity Cardiac Troponin T May Not Be Required for Prediction of Acute Myocardial Infarction Diagnosis in Chest Pain Patients with Highly Abnormal Concentrations at Presentation2017In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 2, p. 542-551Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Guidelines for diagnosing acute myocardial infarction (AMI) recommend adding kinetic changes to the initial cardiac troponin (cTn) blood concentration to improve AMI diagnosis. We hypothesized that kinetic changes may not be required in patients presenting with highly abnormal cTn.

    METHODS: Patients presenting with suspected AMI to the emergency department were enrolled in a prospective diagnostic study. We assessed the positive predictive value (PPV) of initial high-sensitivity cardiac troponin T (hs-cTnT) blood concentrations alone and in combination with kinetic changes for AMI. Predefined relative changes (delta change of >= 20%) and absolute changes (Delta change 9.2 >= ng/L) within different time intervals (1 h, 2 h, and 4-14 h after presentation) were assessed. The final diagnosis was adjudicated by 2 independent cardiologists.

    RESULTS: Among 1282 patients, 213 (16.6%) patients had a final diagnosis of AMI. For AMI prediction, PPVs increased from 48.8% for an initial hs-cTnT >14 ng/L to 87.2% for >60 ng/L, whereas PPVs remained unchanged for higher hs-cTnT concentrations at baseline (87.1% for both >80 ng/L and >100 ng/L). With addition of 20% relative Delta change, PPVs were not further improved in patients with baseline hs-cTnT >80 ng/L using the 1-h (84.0%) and 2-h (88.9%) intervals, and only minimally when extending the interval to 4-14 h (91.2% for >80 ng/L and 90.4% for >100 ng/L, respectively). Similar findings were observed when applying absolute changes.

    CONCLUSIONS: In chest pain patients with highly abnormal hs-cTnT concentrations at presentation, subsequent blood draws may not be required, as they do not provide incremental diagnostic value for prediction of AMI diagnosis.

  • 237. Mälarstig, Anders
    et al.
    Eriksson, Per
    Hamsten, Anders
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Raised Interleukin-10 is an Indicator of Poor Outcome and Enhanced Systemic Inflammation in Patients with Acute Coronary Syndrome2008In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 94, no 6, p. 724-9Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To re-evaluate the relation between plasma interleukin-10 (IL-10) concentration at hospital admission and outcome and to investigate the impact of single nucleotide polymorphisms (SNP) in the IL-10 gene in patients with non-ST elevation acute coronary syndrome (ACS). DESIGN: Determination of IL-10 plasma concentrations and genotyping of SNPs in the IL-10 gene in a prospective trial of patients with ACS and in a group of healthy controls. PATIENTS: 3179 patients in the Fragmin and fast revascularisation during InStability in Coronary artery disease II (FRISC II) trial and 393 healthy controls. MAIN OUTCOME MEASURES: Mortality and incidence of myocardial infarction (MI) at 12 months. RESULTS: The median and interquartile ranges of IL-10 were 0.8 (0.5-1.0) pg/ml in healthy controls and 1.1 (0.7-1.9) pg/ml in patients (p<0.001). In patients, IL-10 predicted a crude risk increase of death/MI, with the highest risk observed in the fourth quartile (adjusted odds ratio 1.7 (95% confidence interval 1.2 to 2.3)). Adjustment for common risk indicators, including C-reactive protein and interleukin-6, weakened the association to a non-significant level. The 1170 CC genotype weakly predicted increased plasma concentrations of IL-10 in patients (p = 0.04) and in controls (p = 0.03), which was consistent with the modest association of this variant with coronary disease (p = 0.01). CONCLUSION: In contrast with some previous reports, we conclude that IL-10 reflects a proinflammatory state in patients with ACS and we therefore suggest that IL-10 is as effective a biomarker for the risk prediction of future cardiovascular events as other markers of systemic inflammation.

  • 238.
    Mälarstig, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Soluble CD40L levels are regulated by the -3459 A>G polymorphism and predict myocardial infarction and the efficacy of antithrombotic treatment in non-ST elevation acute coronary syndrome2006In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 26, no 7, p. 1667-1673Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES - Current evidence suggests the CD40-CD40L pathway as a key process in the development, progression, and outcome of acute coronary syndrome (ACS). The aim was to investigate the prognostic importance of soluble (s) CD40L levels, single nucleotide polymorphisms (SNP) in the CD40LG gene, and the relation between sCD40L and SNPs in patients with acute coronary syndromes (ACS). METHODS AND RESULTS - Samples were obtained on admission from 2359 patients with non-ST elevation ACS randomized to an early invasive versus a conservative and to placebo controlled long-term dalteparin treatment in the FRISC-II study. The -3459 A>G SNP was identified as a novel regulator of sCD40L levels (P=0.001). In the placebo-treated group, sCD40L levels above median were associated with a 2.5-fold increased risk of myocardial infarction (MI) (P≤0.001) but not with raised mortality. In the dalteparin treated group, sCD40L showed no association with MI (P=0.75). Consequently, dalteparin treatment was effective in reducing the risk of MI only in patients with sCD40L levels above median. A combined assessment of troponin-T and sCD40L complemented the prognostic information on risk of MI. CONCLUSIONS - We identified a SNP in the CD40LG gene as a novel regulator of sCD40L plasma concentrations. Soluble CD40L levels above median reflect a prothrombotic state, which can be managed with the use of intense anti-thrombotic treatments.

  • 239.
    Möckel, Martin
    et al.
    Univ Berlin, Div Emergency Med, Berlin, Germany.;Univ Berlin, Dept Cardiol Charite, Berlin, Germany..
    Giannitsis, Evangelos
    Heidelberg Univ, Med Klin 3, Heidelberg, Germany..
    Mueller, Christian
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, Cardiovasc Res Inst Basel, Basel, Switzerland..
    Huber, Kurt
    Wilhelminen Hosp, 3rd Dept Med Cardiol & Intens Care Med, Vienna, Austria..
    Jaffe, Allan S.
    Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.;Mayo Clin, Cardiovasc Div, Rochester, MN 55905 USA.;Sch Med, Rochester, MN 55905 USA..
    Mair, Johannes
    Med Univ Innsbruck, Dept Internal Med Cardiol & Angiol 3, Innsbruck, Austria..
    Plebani, Mario
    Univ Hosp Padova, Dept Lab Med, Padua, Italy..
    Thygesen, Kristian
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark..
    Lindahl, Bertil
    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.
    Editor's Choice-Rule-in of acute myocardial infarction: Focus on troponin2017In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 6, no 3, p. 212-217Article in journal (Refereed)
  • 240. Nieminen, Markku S
    et al.
    Böhm, Michael
    Cowie, Martin R
    Drexler, Helmut
    Filippatos, Gerasimos S
    Jondeau, Guillaume
    Hasin, Yonathan
    Lopez-Sendon, José
    Mebazaa, Alexandre
    Metra, Marco
    Rhodes, Andrew
    Swedberg, Karl
    Priori, Silvia G
    Garcia, Maria Angeles Alonso
    Blanc, Jean-Jacques
    Budaj, Andrzej
    Cowie, Martin R
    Dean, Veronica
    Deckers, Jaap
    Burgos, Enrique Fernandez
    Lekakis, John
    Lindahl, Bertil
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Mazzotta, Gianfranco
    Morais, João
    Oto, Ali
    Smiseth, Otto A
    Garcia, Maria Angeles Alonso
    Dickstein, Kenneth
    Albuquerque, Anibal
    Conthe, Pedro
    Crespo-Leiro, Maria
    Ferrari, Roberto
    Follath, Ferenc
    Gavazzi, Antonello
    Janssens, Uwe
    Komajda, Michel
    Morais, Joaõ
    Moreno, Rui
    Singer, Mervyn
    Singh, Satish
    Tendera, Michal
    Thygesen, Kristian
    Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology.2005In: Eur Heart J, ISSN 0195-668X, Vol. 26, no 4, p. 384-416Article in journal (Refereed)
  • 241. Nordenskjold, A. M.
    et al.
    Hammar, P.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Frobert, P.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindahl, Bertil
    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.
    Cardiac troponin I, NT-proBNP and galactin-3 are elevated in patients with unrecognized myocardial infarction detected by cardiac magnetic resonance imaging2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 1002-1003Article in journal (Refereed)
  • 242.
    Nordenskjold, Anna M.
    et al.
    Univ Orebro, Fac Hlth, Dept Cardiol, S-70185 Orebro, Sweden..
    Hammar, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Vasteras Hosp, Dept Radiol, Vasteras, Sweden..
    Ahlström, Håkan
    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.
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eggers, Kai M.
    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.
    Frobert, Ole
    Univ Orebro, Fac Hlth, Dept Cardiol, S-70185 Orebro, Sweden..
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    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.
    Unrecognized myocardial infarctions detected by cardiac magnetic resonance imaging are associated with cardiac troponin I levels2016In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 455, p. 189-194Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 243.
    Nordenskjöld, A. M.
    et al.
    Örebro Univ, Fac Med & Hlth, Dept Cardiol, Örebro, Sweden.
    Baron, Tomasz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eggers, Kai M.
    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.
    Jernberg, T.
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Cardiol, Stockholm, Sweden.
    Lindahl, Bertil
    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.
    Predictors of adverse outcome in patients with myocardial infarction with non-obstructive coronary artery (MINOCA) disease2018In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 261, p. 18-23Article in journal (Refereed)
    Abstract [en]

    Background: Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCAs) is an increasingly recognized entity. No previous study has evaluated predictors for new major adverse cardiacvascular events (MACEs) and death in patients with MINOCA.

    Methods: We conducted an observational study of MINOCA patients recorded between July 2003 and June 2013 and followed until December 2013 for outcome events. Out of 199,163 MI admissions, 9092 consecutive unique patients with MINOCA were identified. The mean age was 65.5 years and 62% were women. MACE was defined as all-cause mortality, rehospitalization for acute MI, ischemic stroke and heart failure. Hazard ratio and 95% confidence interval (HR; 95% CI) was calculated using Cox-regression.

    Results: A total of 2147 patients (24%) experienced a new MACE and 1254 patients (14%) died during the mean follow-up of 4.5 years. Independent predictors for MACE after adjustment, were older age (1.05; 1.04–1.06), diabetes (1.44; 1.21–1.70), hypertension (1.25; 1.09–1.43), current smoking (1.38; 1.15–1.66), previous myocardial infarction (1.38; 1.04–2.82), previous stroke (1.69; 1.35–2.11), peripheral vascular disease (1.55; 1.97–2.23), chronic obstructive pulmonary disease (1.63; 1.32–2.00), reduced left ventricular ejection fraction (2.00; 1.54–2.60), lower level of total cholesterol (0.88; 0.83–0.94) and higher level of creatinine (1.01; 1.00–1.03). Independent predictors for all cause death were age, current smoking, diabetes, cancer, chronic obstructive pulmonary disease, previous stroke, reduced left ventricular fraction, lower level of total cholesterol and higher levels of creatinine and CRP.

    Conclusions: The clinical factors predicting new MACE and death of MINOCA patients seem to be strikingly similar to factors previously shown to predict new cardiovascular events in patients with MI and obstructive coronary artery disease.

  • 244. Nordenskjöld, Anna M
    et al.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Eggers, Kai M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Fröbert, Ole
    Jaffe, Allan S
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Short- and Long-term Individual Variation in Cardiac Troponin in Patients with Stable Coronary Artery Disease2013In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 59, no 2, p. 401-409Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    A rise or fall of cardiac troponin is a prerequisite for the diagnosis of acute myocardial infarction. Defining significant changes requires knowledge of both biological and analytical variation. The short-term biological variation of cardiac troponin in healthy individuals is 3%-48%. However, healthy individuals may not be representative for patients in whom cardiac troponin measurement is often of clinical importance. Therefore, we studied the individual variation of cardiac troponin in patients with symptoms of stable coronary artery disease.

    METHODS:

    Twenty-four patients scheduled for elective coronary angiography were included. Blood samples were drawn once at enrollment and serially at six 4-h intervals on the day before coronary angiography. Cardiac troponin was measured with hs-cTn assays from Abbott Laboratories (premarket cTnI assay) and Roche Diagnostics (Elecsys® cTnT assay with two different lots).

    RESULTS:

    The short-term individual variation in cardiac troponin I (cTnI) was 14%, the reference change value (RCV) 49%, and RCV-log-normal (rise/fall) 54%/-35%. The corresponding values for cTnT were 7%, 23%, and 26%/-21%. The long-term variation for cTnI was 24%, RCV 69%, and RCV-log-normal (rise/fall) 97%/-49%. The corresponding values for cTnT were 11%, 32%, and 37%/-27%.

    CONCLUSIONS:

    The short-term individual variation of cardiac troponin in patients with symptoms of stable coronary artery disease is similar to the biological variation previously demonstrated in healthy individuals. Our results suggest that a change in cardiac troponin concentrations of >50% can be used in attempting to diagnose acute myocardial injury. To detect significant long-term changes in cardiac troponin concentrations, larger changes will be required.

  • 245. Nordenskjöld, Anna M.
    et al.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Fröbert, Ole
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Short-and long-term individual variation in NT-proBNP levels in patients with stable coronary artery disease2013In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 422, p. 15-20Article in journal (Refereed)
    Abstract [en]

    Background: In addition to diagnosis of heart failure (HF) natriuretic peptides (BNP and NT-proBNP) may be used for risk prediction in stable and acute coronary artery disease. The aim of the study was to evaluate the short- and long-term individual variation of NT-proBNP in patients with stable coronary artery disease. Methods: Twenty-four patients with suspected stable coronary artery disease and scheduled for elective coronary angiography were included. Blood samples were drawn at enrolment and, on average 3 weeks later, serially the day prior to coronary angiography. NT-proBNP was determined using Elecsys proBNP sandwich immunoassay (Roche Diagnostics). Results: The individual variation in NT-proBNP over 4 h was 11.8%, over 20 h 12.4% and over 3 weeks 20.4%. The corresponding positive and negative lognormal reference change values (RCV) were +41/-29%, +42/-30% and + 76/-43%, respectively. No significant circadian variation was found. Conclusions: Our results suggest that an increase in NT-proBNP levels of >42% or a decrease of >30% is needed to indicate a reliable short-term change; and for a long-term change an increase of >76% or a decrease of >43% is required. This should be considered when interpreting changes in NT-proBNP levels. 

  • 246.
    Nordenskjöld, Anna M.
    et al.
    Orebro Univ, Dept Cardiol, Fac Med & Hlth, Orebro, Sweden.
    Eggers, Kai M.
    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.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Mohammad, Moman A.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Lindahl, Bertil
    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.
    Circadian onset and prognosis of myocardial infarction with non-obstructive coronary arteries (MINOCA)2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 4, article id e0216073Article in journal (Refereed)
    Abstract [en]

    Background: Many acute cardiovascular events such as myocardial infarction (MI) follow circadian rhythms. Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a newly noticed entity with limited data on onset pattern and its impact on prognosis.

    Material and methods: In this observational study of Swedish MINOCA patients registered in the SWEDEHEART registry between 2003-2013 and followed until December 2013 we identified 9,092 unique patients with MINOCA out of 199,163 MI admissions in total. Incidence rate ratios (IRR) were calculated for whole hours, parts of the day, weekdays, months, seasons and major holidays.

    Results: The mean age was 65.5 years, 62.0% were women and 16.6% presented with STEMI. The risk for MINOCA proved to be most common in the morning (IRR = 1.70, 95% CI [1.63-1.84]) with a peak at 08.00 AM (IRR = 2.25, 95% CI [1.96-2.59]) and on Mondays (IRR = 1.28, 95% CI [1.18-1.38]). No altered risk was detected during the different seasons, the Christmas and New Year holidays or the Swedish Midsummer festivities. There was no association between time of onset of MINOCA and short-or long-term prognosis.

    Conclusion: The onset of MINOCA shows a circadian and circaseptan variation with increased risk at early mornings and Mondays, similar to previous studies on all MI, suggesting stress related triggering. However, during holidays were traditional MI increase, we did not see any increase for MINOCA. No association was detected between time of onset and prognosis, indicating that the underlying pathological mechanisms of MINOCA and the quality of care are similar at different times of onset but triggering mechanism may be more active early mornings and Mondays.

  • 247.
    Nordenskjöld, Anna M.
    et al.
    Univ Orebro, Fac Hlth, Dept Cardiol, SE-70182 Orebro, Sweden.;Univ Orebro, Fac Hlth, Dept Cardiol, Sodra Grev Rosengatan, SE-70182 Orebro, Sweden..
    Hammar, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Vastmanland Hosp Vasteras, Dept Radiol, Vasteras, Sweden..
    Ahlström, Håkan
    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.
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Frobert, Ole
    Univ Orebro, Fac Hlth, Dept Cardiol, SE-70182 Orebro, Sweden..
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Unrecognized Myocardial Infarction Assessed by Cardiac Magnetic Resonance Imaging - Prognostic Implications2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 2, article id e0148803Article in journal (Refereed)
    Abstract [en]

    Background Clinically unrecognized myocardial infarctions (UMI) are not uncommon and may be associated with adverse outcome. The aims of this study were to determine the prognostic implication of UMI in patients with stable suspected coronary artery disease (CAD) and to investigate the associations of UMI with the presence of CAD. Methods and Findings In total 235 patients late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging and coronary angiography were performed. For each patient with UMI, the stenosis grade of the coronary branch supplying the infarcted area was determined. UMIs were present in 25% of the patients and 67% of the UMIs were located in an area supplied by a coronary artery with a stenosis grade >= 70%. In an age-and gender-adjusted model, UMI independently predicted the primary endpoint (composite of death, myocardial infarction, resuscitated cardiac arrest, hospitalization for unstable angina pectoris or heart failure within 2 years of follow-up) with an odds ratio of 2.9; 95% confidence interval 1.1-7.9. However, this association was abrogated after adjustment for age and presence of significant coronary disease. There was no difference in the primary endpoint rates between UMI patients with or without a significant stenosis in the corresponding coronary artery. Conclusions The presence of UMI was associated with a threefold increased risk of adverse events during follow up. However, the difference was no longer statistically significant after adjustments for age and severity of CAD. Thus, the results do not support that patients with suspicion of CAD should be routinely investigated by LGE-CMR for UMI. However, coronary angiography should be considered in patients with UMI detected by LGE-CMR.

  • 248. Nordenskjöld, Anna M
    et al.
    Hammar, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    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.
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lindahl, Bertil
    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.
    Unrecognized myocardial infarction assessed by cardiac magnetic resonance imaging is associated with adverse long-term prognosis2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 7, article id e0200381Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Unrecognized myocardial infarctions (UMIs) are common. The study is an extension of a previous study, aiming to investigate the long-term (>5 year) prognostic implication of late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) detected UMI in patients with suspected stable coronary artery disease (CAD) without previously diagnosed myocardial infarction (MI).

    METHODS: In 235 patients with suspected stable CAD without previous MI, LGE-CMR imaging and coronary angiography were performed. LGE with a subendocardial component detectable in more than one imaging plane was required to indicate UMI. The stenosis grade of the coronary arteries was determined, including in the artery supplying an infarcted area. Stenosis ≥70% stenosis was considered significant. Patients were followed for 5.4 years in mean regarding a composite endpoint of cardiovascular death, MI, hospitalization due to heart failure, stable or unstable angina.

    RESULTS: UMI were present in 58 of 235 patients (25%). Thirty-nine of the UMIs were located downstream of a significant coronary stenosis. During the follow-up 40 patients (17.0%) reached the composite endpoint. Of patients with UMI, 34.5% (20/58) reached the primary endpoint compared to 11.3% (20/177) of patients with no UMI (HR 3.7, 95% CI 2.0-6.9, p<0.001). The association between UMI and outcome remained (HR 2.3, 95% CI 1.2-4.4, p = 0.012) after adjustments for age, gender, extent of CAD and all other variables univariate associated with outcome. Sixteen (41%) of the patients with an UMI downstream of a significant stenosis reached the endpoint compared to four (21%) patients with UMI and no relation to a significant stenosis (HR 2.4, 95% CI 0.8-7.2, p = 0.12).

    CONCLUSION: The presence of UMI was independently associated with an increased risk of cardiovascular events during long-term follow up.

  • 249. Nordenskjöld, Anna M
    et al.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Baron, Tomasz
    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.
    Jernberg, Tomas
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Reynolds, Harmony R
    Tornvall, Per
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Reinfarction in Patients with Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA): Coronary Findings and Prognosis.2019In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 132, no 3, p. 335-346Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is common. There are limited data on the mechanisms and prognosis for reinfarction in MINOCA patients.

    METHODS: In this observational study of MINOCA patients hospitalized in Sweden and registered in the SWEDEHEART registry between July 2003 and June 2013 and followed until December 2013, we identified 9092 unique patients with MINOCA of 199,163 MI admissions in total. The 570 (6.3%) MINOCA patients who were hospitalized due to a recurrent MI constituted the study group.

    RESULTS: The mean age was 69.1 years and 59.1% were women. The median time to readmission was 17 months. A total of 340 patients underwent a new coronary angiography and 180 (53%) had no obstructive coronary artery disease (CAD) and 160 (47%) had obstructive CAD; 123 had 1-vessel, 26 had 2-vessel, 9 had 3-vessel disease, and 2 had left main together with 1-vessel disease. Male sex, diabetes, peripheral vascular disease, higher levels of creatinine, and ST elevation at presentation were more common in patients with MI with obstructive CAD than in patients with a recurrent MINOCA. Mortality during a median follow-up of 38 months was similar whether the reinfarction event was MINOCA or MI with obstructive CAD 13.9% vs 11.9% (P = .54).

    CONCLUSIONS: About half of patients with reinfarction after MINOCA who underwent coronary angiography had progression of coronary stenosis. Angiography should be strongly considered in patients with MI after MINOCA. Mortality associated with recurrent events was substantial, though there was no difference in mortality between those with or without significant CAD.

  • 250. Norhammar, Anna
    et al.
    Malmberg, Klas
    Diderholm, Erik
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Lagerqvist, Bo
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Rydén, Lars
    Wallentin, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Diabetes mellitus: the major risk factor in unstable coronary artery disease even after consideration of the extent of coronary artery disease and benefits of revascularization.2004In: J Am Coll Cardiol, ISSN 0735-1097, Vol. 43, no 4, p. 585-91Article in journal (Refereed)
234567 201 - 250 of 309
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