Jeanne du Fay de Lavallaz1, Patrick Badertscher2, Thomas Nestelberger2, Tobias Zimmermann3, Òscar Miró4, Emilio Salgado5, Michael Christ6, Nicolas Geigy7, Louise Cullen8, Martin Than9, F Javier Martin-Sanchez10, Salvatore Di Somma11, W Frank Peacock12, Beata Morawiec13, Joan Walter14, Raphael Twerenbold15, Christian Puelacher16, Desiree Wussler17, Jasper Boeddinghaus2, Luca Koechlin18, Ivo Strebel1, Dagmar I Keller19, Jens Lohrmann20, Eleni Michou21, Michael Kühne3, Tobias Reichlin3, Christian Mueller22. 1. University Hospital Basel, Switzerland. 2. Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland. 3. Cardiology, University Hospital Basel, Switzerland. 4. Emergency Department, Hospita Clinic, Spain. 5. Emergency Department, Hospital Clinic, Spain. 6. Emergency Medicine, Luzerner Kantonsspital, Switzerland. 7. Emergency Department, Kantonsspital Liestal, Switzerland. 8. Royal Brisbane and Women's Hospital, Australia. 9. Emergency Department, Christchurch Hospital, New Zealand. 10. Servicio de Urgencias, Hospital Clínico San Carlos, Madrid, Spain. 11. Department o MedicalSurgery sciences and Translational Medicine, Sant'Andrea Hospital University La Sapienza, Italy. 12. Department of Medicine, Section of Emergency Medicine, Baylor College of Medicine, TX. 13. 2nd Department of Cardiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland. 14. Cardiovascular Research Institute Basel, University Hospital Basel, Switzerland. 15. Cardiovascular Research Institute Basel CRIB, University Hospital Basel, Switzerland. 16. Cardiology, Cardiology Department, University Hospital Basel, Switzerland. 17. Cardiovascular Research Institute (CRIB), University Hospital Basel, Switzerland. 18. Cardiovascular Research Institute Basel (CRIB) & Cardiac surgery, University Hospital Basel, Switzerland. 19. Emergency Department, University Hospital, Switzerland. 20. Department of Cardiology, University Hospital Basel, Switzerland. 21. Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland. 22. Cardiovascular Research Institue Basel (CRIB), University Hospital Basel, Switzerland.
Abstract
BACKGROUND: The utility of B-type Natriuretic Peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin (hs-cTn) concentrations for diagnosis and risk-stratification of syncope is incompletely understood. METHODS: We evaluated the diagnostic and prognostic accuracy of BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations, alone and against the ones of clinical assessments, in patients >45years presenting with syncope to the emergency department (ED) in a prospective diagnostic multicenter study. BNP, NT-proBNP, hs-cTnT and hs-cTnI concentrations were measured in a blinded fashion. Cardiac syncope, as adjudicated by two physicians based on all information available including cardiac work-up and 1-year follow-up, was the diagnostic endpoint. The EGSYS, a syncope-specific diagnostic score, served as the diagnostic comparator. Death and MACE at 30 and 720 days were the prognostic endpoints. MACE were defined as death, cardiopulmonary resuscitation, life-threatening arrhythmia, implantation of pacemaker/implantable cardioverter defibrillator, acute myocardial infarction, pulmonary embolism, stroke/transient ischemic attack, intracranial bleeding or valvular surgery. The ROSE, OESIL, San Fransisco Syncope Rule (SFSR) and Canadian Syncope Risk Score (CSRS) served as the prognostic comparators. RESULTS: Among 1538 patients eligible for diagnostic assessment, cardiac syncope was the adjudicated diagnosis in 234 patients (15.2%). BNP, NT-proBNP, hs-cTnT, and hs-cTnI were significantly higher in cardiac syncope vs. other causes (p<0.01). The diagnostic accuracy for cardiac syncope, as quantified by the area under the curve (AUC), was 0.77-0.78 (95% confidence interval (CI) 0.74-0.81) for all four biomarkers, and superior to the one of EGSYS (AUC 0.68 [95%-CI 0.65-0.71], p<0.001). Combining BNP/NT-proBNP with hs-cTnT/hs-cTnI further improved diagnostic accuracy to an AUC of 0.81 (p<0.01). BNP, NT-proBNP, hs-cTnT, and hs-cTnI cut-offs, achieving pre-defined thresholds for sensitivity and specificity (95%), allowed for rule-in or rule-out of ~30% of all patients. A total of 450 MACE occurred during follow-up. The prognostic accuracy of BNP, NT-proBNP, hs-cTnI, and hs-cTnT for MACE was moderate-to-good (AUC 0.75-0.79), superior to ROSE, OESIL and SFSR, and inferior to the CSRS. CONCLUSIONS: BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations provide useful diagnostic and prognostic information in ED patients with syncope. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov Unique Identifier: NCT01548352.
BACKGROUND: The utility of B-type Natriuretic Peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin (hs-cTn) concentrations for diagnosis and risk-stratification of syncope is incompletely understood. METHODS: We evaluated the diagnostic and prognostic accuracy of BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations, alone and against the ones of clinical assessments, in patients >45years presenting with syncope to the emergency department (ED) in a prospective diagnostic multicenter study. BNP, NT-proBNP, hs-cTnT and hs-cTnI concentrations were measured in a blinded fashion. Cardiac syncope, as adjudicated by two physicians based on all information available including cardiac work-up and 1-year follow-up, was the diagnostic endpoint. The EGSYS, a syncope-specific diagnostic score, served as the diagnostic comparator. Death and MACE at 30 and 720 days were the prognostic endpoints. MACE were defined as death, cardiopulmonary resuscitation, life-threatening arrhythmia, implantation of pacemaker/implantable cardioverter defibrillator, acute myocardial infarction, pulmonary embolism, stroke/transient ischemic attack, intracranial bleeding or valvular surgery. The ROSE, OESIL, San Fransisco Syncope Rule (SFSR) and Canadian Syncope Risk Score (CSRS) served as the prognostic comparators. RESULTS: Among 1538 patients eligible for diagnostic assessment, cardiac syncope was the adjudicated diagnosis in 234 patients (15.2%). BNP, NT-proBNP, hs-cTnT, and hs-cTnI were significantly higher in cardiac syncope vs. other causes (p<0.01). The diagnostic accuracy for cardiac syncope, as quantified by the area under the curve (AUC), was 0.77-0.78 (95% confidence interval (CI) 0.74-0.81) for all four biomarkers, and superior to the one of EGSYS (AUC 0.68 [95%-CI 0.65-0.71], p<0.001). Combining BNP/NT-proBNP with hs-cTnT/hs-cTnI further improved diagnostic accuracy to an AUC of 0.81 (p<0.01). BNP, NT-proBNP, hs-cTnT, and hs-cTnI cut-offs, achieving pre-defined thresholds for sensitivity and specificity (95%), allowed for rule-in or rule-out of ~30% of all patients. A total of 450 MACE occurred during follow-up. The prognostic accuracy of BNP, NT-proBNP, hs-cTnI, and hs-cTnT for MACE was moderate-to-good (AUC 0.75-0.79), superior to ROSE, OESIL and SFSR, and inferior to the CSRS. CONCLUSIONS:BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations provide useful diagnostic and prognostic information in ED patients with syncope. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov Unique Identifier: NCT01548352.
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