Management of Patients With Unexplained Syncope: Derivation and Validation of a Simplified 2‐Step Diagnostic Approach

Abstract

Background The aim of this study was to develop a structured 2‐step approach, based on noninvasive diagnostic criteria, that led to an electrophysiology study in patients with unexplained syncope. Methods and Results Two independent cohorts were used: the derivation cohort with 665 patients based on electronic health record data to develop our 2‐step diagnostic approach, and the validation cohort based on 160 prospectively screened patients, presenting with unexplained syncope episodes. Noninvasive electrocardiographic and imaging markers and an electrophysiology study–based invasive assessment were combined. A positive diagnostic approach according to our study's prespecified criteria resulted in a decision to proceed with a permanent pacemaker/implantable cardioverter‐defibrillator. The primary end point was the time until the event of recurrent syncope (syncope‐free survival). Number needed to treat was calculated for patients with a positive diagnostic approach. The number of patients with unexplained syncope and borderline sinus bradycardia needed to treat was 5, and the number of patients with unexplained syncope and bundle branch block needed to treat was 3 over a mean follow‐up of ≈4 years. After the structured 2‐step approach, the primary outcome occurred in 14 of 82 (17.1%) with a pacemaker/implantable cardioverter‐defibrillator and 19 of 57 (33%) with a negative approach, with a mean follow‐up of ≈2.5 years (29.29±12.58 months, P =0.03). Conclusions The low number needed to treat in the derivation cohort and the low percentage of syncope recurrence in the validation cohort supports the proposed 2‐step electrophysiology‐inclusive algorithm as a potentially low‐cost, 1‐day, structured tool for these patients.