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Diagnosis of neurally mediated syncope at initial evaluation and with tilt table testing compared with that revealed by prolonged ECG monitoring. An analysis from the Third International Study on Syncope of Uncertain Etiology (ISSUE-3)
  1. Andrea Ungar1,
  2. Paolo Sgobino2,
  3. Vitantonio Russo3,
  4. Elena Vitale4,
  5. Richard Sutton5,
  6. Donato Melissano6,
  7. Xulio Beiras7,
  8. Nicola Bottoni8,
  9. Hans H Ebert9,
  10. Michele Gulizia10,
  11. Marcella Jorfida11,
  12. Angel Moya12,
  13. Dietrich Andresen13,
  14. Nicoletta Grovale14,
  15. Michele Brignole15,
  16. on behalf of the International Study on Syncope of Uncertain Etiology 3 (ISSUE-3) Investigators
  1. 1Departments of Cardiology, Ospedale Careggi, Firenze, Italy
  2. 2Departments of Cardiology, Ospedale di Bolzano, Bolzano, Italy
  3. 3Departments of Cardiology, Ospedale di Manduria, Taranto, Italy
  4. 4Departments of Cardiology, Ospedale SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
  5. 5Departments of Cardiology, St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK
  6. 6Departments of Cardiology, Presidio Ospedaliero di Casarano, Lecce, Italy
  7. 7Departments of Cardiology, Hospital Xeral de Vigo, Vigo, Spain
  8. 8Departments of Cardiology, Arcispedale S. Maria Nuova, Reggio Emilia, Italy
  9. 9Departments of Cardiology, Kardiologische Gemeinschaftspraxis, Riesa, Germany
  10. 10Departments of Cardiology, Ospedale Garibaldi-Nesima, Catania, Italy
  11. 11Departments of Cardiology, Ospedale S. Giovanni Battista Le Molinette, Torino, Italy
  12. 12Departments of Cardiology, Hospital Universitario Vall d'Hebron, Barcelona, Spain
  13. 13Departments of Cardiology, Vivantes Klinikum Am Urban, Berlin, Germany
  14. 14Departments of Cardiology, Medtronic Italia, Rome, Italy
  15. 15Departments of Cardiology, Ospedali del Tigullio, Lavagna, Italy
  1. Correspondence to Professor Michele Brignole, Department of Cardiology, Arrhythmologic Centre, Ospedali del Tigullio, Lavagna 16033, Italy; mbrignole{at}


Objective According to the guidelines of the European Society of Cardiology, a presumed diagnosis of neurally mediated syncope (NMS) can be made when patients have a consistent history and competing diagnoses are excluded. In the present study, we compared the initial diagnosis of NMS by means of implantable loop recorder (ILR) documentation.

Methods In this prospective multicentre observational study which involved 51 hospitals in nine countries in Europe and Canada, 504 NMS patients ≥40 years, who had suffered ≥3 syncopal episodes in the previous 2 years received an ILR and were followed up for a mean of 15±11 months.

Results ILR recorded a spontaneous syncope in 187 cases, with an estimated diagnostic yield of 47% at 3 years. ILR findings were consistent with the initial diagnosis of presumed NMS in 162 (87%) patients whereas did not confirm NMS in another 25 (13%), who had an intrinsic cardiac arrhythmic cause (atrial tachyarrhythmias (#6), long pause on termination of tachyarrhythmia (#8), persistent bradycardia (#3), ventricular tachycardia (#4)) or a non-arrhythmic loss of consciousness (non-syncopal (#3), orthostatic hypotension (#1)). No clinical baseline feature was able to predict an intrinsic cardiac cause with the exception of more frequent non-syncopal atrial tachyarrhythmias on clinical history, which were present in 38% of cardiac versus 5% of NMS patients (p=0.001). Tilt table testing (TT) was positive in 76/136 (56%) presumed NMS and in 9/21 (43%) non-NMS patients (p=0.35); an asystolic response was present in 28/136 (21%) NMS and in 0/21 (0%) non-NMS patients (p=0.03).

Conclusions ILR findings showed results other than NMS in a small, although non-negligible, number of patients older than 40 years. TT was unable to discriminate between presumed NMS and non-NMS with the exception of an asystolic response which was highly specific.


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