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Original research
Development of an electrocardiogram-based risk calculator for a cardiac cause of syncope
  1. Tobias Zimmermann1,2,
  2. Jeanne du Fay de Lavallaz1,2,
  3. Joan Elias Walter1,2,3,
  4. Ivo Strebel1,2,
  5. Thomas Nestelberger1,2,
  6. Lydia Joray1,2,
  7. Patrick Badertscher1,2,
  8. Dayana Flores1,
  9. Velina Widmer1,
  10. Nicolas Geigy4,
  11. Oscar Miro2,5,
  12. Emilio Salgado5,
  13. Michael Christ6,
  14. Louise Cullen2,7,
  15. Martin Than2,8,
  16. Francisco Javier Martín-Sánchez2,9,
  17. Salvatore Di Somma2,10,
  18. W Frank Peacock2,11,
  19. Dagmar Keller12,
  20. Juan Pablo Costabel13,
  21. Desiree Nadine Wussler1,2,14,
  22. Damian Kawecki15,
  23. Jens Lohrmann1,
  24. Danielle Menosi Gualandro1,2,
  25. Michael Kuehne1,2,
  26. Tobias Reichlin2,16,
  27. Benjamin Sun17,
  28. Christian Mueller1,2
  29. the BASEL IX and SRS Investigators
    1. 1Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland
    2. 2GREAT network, Rome, Italy
    3. 3Department of Radiology, University Hospital Zurich, Zurich, Switzerland
    4. 4Emergency Department, Kantonsspital Baselland, Liestal, Switzerland
    5. 5Emergency Department, Hospital Clinic, Barcelona, Spain
    6. 6Emergency Department, Kantonsspital Luzern, Luzern, Switzerland
    7. 7Emergency and Trauma Centre, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia
    8. 8Emergency Department, Christchurch Hospital, Christchurch, New Zealand
    9. 9Emergency Department, Hospital San Carlos de Madrid, Madrid, Spain
    10. 10Emergency Medicine, Department of Medical-Surgery Sciences and Translational Medicine, University Sapienza Rome, Sant’Andrea Hospital, Rome, Italy
    11. 11Emergency Department, Baylor College of Medicine, Houston, Texas, USA
    12. 12Emergency Department, University Hospital Zurich, Zurich, Switzerland
    13. 13Instituto Cardiovascular de Buenos Aires, Buenos Aires, Argentina
    14. 14Department of Internal Medicine, University Hospital Basel, Basel, Switzerland
    15. 15Department of Cardiology, Medical University of Silesia, Zabrze, Poland
    16. 16Department of Cardiology, University Hospital Bern, Bern, Switzerland
    17. 17Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    1. Correspondence to Professor Christian Mueller, Department of Cardiology, University Hospital Basel, Basel, Switzerland; Christian.Mueller{at}usb.ch

    Abstract

    Objective To develop an ECG-based tool for rapid risk assessment of a cardiac cause of syncope in patients ≥40 years.

    Methods In a prospective international multicentre study, 2007 patients ≥40 years presenting with syncope were recruited in the emergency department (ED) of participating centres ranging from large university hospitals to smaller rural hospitals in eight countries from May 2010 to July 2017. 12-Lead ECG recordings were obtained at ED presentation following the syncopal event. The primary diagnostic outcome, a cardiac cause of syncope, was centrally adjudicated by two independent cardiologists using all available clinical information including 12-month follow-up. ECG predictors for a cardiac cause of syncope were identified using penalised backward selection and a continuous-scale likelihood was calculated based on regression analysis coefficients. Findings were validated in an independent US multicentre cohort including 2269 patients.

    Results In the derivation cohort, a cardiac cause of syncope was adjudicated in 267 patients (16%). Seven ECG criteria were identified as predictors for this outcome: heart rate and QTc-interval (continuous predictors), rhythm, atrioventricular block, ST-segment depression, bundle branch block and ventricular extrasystole/non-sustained ventricular tachycardia (categorical predictors). Diagnostic accuracy of these combined predictors for a cardiac cause of syncope was high (area under the curve 0.80, 95% CI 0.77 to 0.83). Overall, 138 patients (8%) were rapidly triaged towards rule-out and 181 patients (11%) towards rule-in of a cardiac cause of syncope. External validation showed similar performance.

    Conclusion In patients ≥40 years with a syncopal event, a combination of seven ECG criteria enabled rapid assessment of the likelihood that syncope was due to a cardiac cause.

    Trial registration number NCT01548352 (BASEL IX), NCT01802398 (SRS study).

    • arrhythmias
    • cardiac
    • electrocardiography

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    Footnotes

    • BS and CM are joint senior authors.

    • TZ and JdFdL are joint first authors.

    • Twitter @JDFDLz, @louiseacullen

    • TZ and JdFdL contributed equally.

    • BS and CM contributed equally.

    • Collaborators Philipp Krisai, MD (Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland); Jasper Boeddinghaus, MD (Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland, GREAT network); Raphael Twerenbold, MD (Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland, GREAT network); Christian Puelacher, MD, PhD (Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland, GREAT network, Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts); Luca Koechlin, MD (Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland, GREAT network, Department of Emergency Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio); Maria Rubini Giménez, MD (Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland, GREAT network); Noemi Glarner, MD (Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland, GREAT network); Samyut Shrestha, MD (Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland, GREAT network); Beata Morawiec, MD (GREAT network, Department of Cardiology, Zabrze, Poland); Piotr Muzyk, MD (GREAT network, Department of Cardiology, Zabrze, Poland); José Bustamante Mandrión, MD (GREAT network, Servicio de Urgencias, Hospital Clínico San Carlos, Madrid, Spain); Imke Poepping, MD (University Hospital Zürich, Zürich, Switzerland); Paul David Ratmann, MD (Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland, GREAT network); Eleni Michou, MD (Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland, GREAT network); Michael Freese, RN (Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland, GREAT network); Kathrin Meissner, RN (Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland, GREAT network); Carolina Isabel Fuenzalida Inostroza (Hospital Clinic, Barcelona, Catalonia, Spain); Jaimi Greenslade (Royal Brisbane & Women's Hospital, Herston, Australia); Tracey Hawkins (Royal Brisbane & Women's Hospital, Herston, Australia); Katharina Rentsch, PhD (Laboratory Medicine, University Hospital Basel, Switzerland); Arnold von Eckardstein, MD (Laboratory Medicine, University Hospital Zürich, Switzerland); Andreas Buser, MD (Blood Transfusion Centre, Swiss Red Cross, Basel, Switzerland); Franz Bürgler, MD (Emergency Department, Kantonsspital Liestal, Switzerland); Stefan Osswald, MD (Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland); David H. Adler, MD, MPH (Department of Emergency Medicine, University of Rochester, New York); Aveh Bastani, MD (Department of Emergency Medicine, William Beaumont Hospital-Troy, Troy, Michigan); Christopher W. Baugh, MD, MBA (Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts); Jeffrey M. Caterino, MD, MPH (Department of Emergency Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio); Carol L. Clark, MD, MBA (Department of Emergency Medicine, William Beaumount Hospital-Royal Oak, Royal Oak, Michigan), Deborah B. Diercks, MD, MPH (Department of Emergency Medicine, University of Texas-Southwestern, Dallas, Texas); Judd E. Hollander, MD (Department of Emergency Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania); Bret A. Nicks, MD, MHA (Department of Emergency Medicine, Wake Forest School of Medicine, Winston, Salem, North Carolina); Daniel K. Nishijima, MD, MAS (Department of Emergency Medicine, UC Davis School of Medicine, Sacramento, California); Manish N. Shah, MD, MPH (Department of Emergency Medicine, University of Wisconsin-Madison, Madison, Wisconsin); Kirk A. Stiffler, MD (Department of Emergency Medicine, Northeast Ohio Medical University, Rootstown, Ohio); Scott T. Wilber, MD (Department of Emergency Medicine, Northeast Ohio Medical University, Rootstown, Ohio); Alan B. Storrow, MD (Department of Emergency Medicine, Vanderbilt University, Nashville, Tennessee).

    • Contributors All authors are justifiably credited with authorship, according to the authorship criteria. TZ, JD, CM: responsible for overall content; TZ, JD, JEW, TN, PB, BS, CM: conception and design; LJ, DF, VW, NG, OM, ES, MC, LC, MT, JMS, SDS, FP, DK, JPC, DNW, DK, JL, DMG, MK, TR, BS: acquisition of data; TZ, JD, JEW, IS, CM: analysis and interpretation of data; TZ, JdF, BS, CM: drafting the manuscript and final approval; JEW, IS, TN, LJ, PB, DF, VW, NG, OM, ES, MC, LC, MT, JMS, SDS, FP, DK, JPC, DNW, DK, JL, DMG, MK, TR: revision of manuscript and final approval.

    • Funding The BASEL IX study was supported by research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel (Switzerland), the University Basel (Switzerland), the University Hospital Basel (Switzerland), the Freiwillige Akademische Gesellschaft Basel (Switzerland), Abbott, BRAHMS, Singulex, Roche, the Emergency Medicine Foundation (Australia) and the Emergency Care Foundation (New Zealand). The Syncope Risk Score study was supported by the National Institutes of Health grant R01HL111033 (USA). Roche donated hs-cTnT test kits to support the Syncope Risk Stratification study.

    • Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

    • Competing interests The authors designed the study, gathered and analysed the data, vouch for the data and analysis, wrote the paper and decided to publish. TZ, JD and CM had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors have read and approved the manuscript. The sponsors had no role in designing or conducting the study and no role in gathering or analysing the data or writing the manuscript. The manuscript and its contents have not been published previously and are not being considered for publications elsewhere in whole or in part in any language, including publicly accessible websites or e-print servers. TZ has received research support from the Freiwillige Akademische Gesellschaft Basel (Switzerland). JEW reports a research grant from the Swiss Heart Foundation, the Swiss Academy of Medical Sciences and the Bangerter Foundation (YTCR 23/17). PB has received research funding from the University of Basel, the "Stiftung für Herzschrittmacher und Elektrophysiologie" and the Freiwillige Akademische Gesellschaft Basel. LC reports grants and personal fees from Abbott Diagnostics, grants and personal fees from Beckman Coulter, grants and personal fees from Siemens, outside the submitted work. MT reports grants and personal fees from Abbott, grants and personal fees from Alere, grants from Beckman, grants and personal fees from Roche, outside the submitted work. FJM-S received speaker, advisory or consulting fees from Novartis, MSD, Bristol-Myers Squibb, Pfizer, The Medicine Company, Otsuka, Thermo Fisher, Cardiorentis, Sanofi, and research grants from the Spanish Ministry of Health and FEDER, Mapfre, Novartis, Bayer, MSD, Abbot and Orion-Pharma, outside the submitted work. WFP reports research grants from Abbott, Braincheck, Immunarray, Janssen, Roche and ZS Pharma, having served as a consultant for Abbott, AstraZeneca, Bayer, Beckman, Boehrhinger-Ingelheim, Ischemia Care, Dx, Immunarray, Instrument Labs, Janssen, Ortho Clinical Diagnostics, Relypsa, Roche and Siemens, having provided expert testimony for Johnson and Johnson, and having ownership interests in Comprehensive Research Associates, and Emergencies in Medicine, Ischemia DX. MK reports personal fees from Bayer, personal fees from Daiichi-Sankyo, personal fees from Pfizer-BMS, personal fees from Böhringer-Ingelheim, outside the submitted work. TR has received research grants from the Goldschmidt-Jacobson Foundation, the Swiss National Science Foundation (PASMP3-136995), the Swiss Heart Foundation, the Professor Max Cloëtta Foundation, the University of Basel and the University Hospital Basel as well as speaker honoraria from Abbott, Bayer, Biosense, Brahms, Medtronic, Pfizer-BMS and Roche. BS has received consulting honoraria from Medtronic, outside the submitted work. CM has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union, the KTI, the Cardiovascular Research Foundation Basel, the University Basel, the University Hospital Basel, Abbott, AstraZeneca, Beckman Coulter, BRAHMS, Critical Diagnostics, Idorsia, Novartis, Ortho Clinical Diagnostics, Roche, Sanofi, Siemens and Singulex, as well as speaker/consulting honoraria or travel support from Acon, Amgen, Bayer, BMS, Boehringer Ingelheim, Idorsia, Medtronic, Novartis, Osler, Roche, Sanofi, Siemens and Singulex.

    • Patient consent for publication Not required.

    • Ethics approval Both studies (BAsel Syncope EvaLuation (BASEL IX) and Improving Syncope Risk Stratification in Older Adults (SRS)) were conducted according to the principles of the Declaration of Helsinki and approved by all local ethics committees. Written informed consent was obtained from all patients enrolled.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement No data are available. The data underlying this article cannot be shared publicly due to the lack of approval by the participating patients and institutions.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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