Benefit of pacemaker therapy in patients with presumed neurally mediated syncope and documented asystole is greater when tilt test is negative: an analysis from the third International Study on Syncope of Uncertain Etiology (ISSUE-3)

Circ Arrhythm Electrophysiol. 2014 Feb;7(1):10-6. doi: 10.1161/CIRCEP.113.001103. Epub 2013 Dec 12.

Abstract

Background: In the Third International Study on Syncope of Uncertain Etiology (ISSUE-3), cardiac pacing was effective in reducing recurrence of syncope in patients with presumed neurally mediated syncope (NMS) and documented asystole but syncope still recurred in 25% of them at 2 years. We have investigated the role of tilt testing (TT) in predicting recurrences.

Methods and results: In 136 patients enrolled in the ISSUE-3, TT was positive in 76 and negative in 60. An asystolic response predicted a similar asystolic form during implantable loop recorder monitoring, with a positive predictive value of 86%. The corresponding values were 48% in patients with non-asystolic TT and 58% in patients with negative TT (P=0.001 versus asystolic TT). Fifty-two patients (26 TT+ and 26 TT-) with asystolic neurally mediated syncope received a pacemaker. Syncope recurred in 8 TT+ and in 1 TT- patients. At 21 months, the estimated product-limit syncope recurrence rates were 55% and 5%, respectively (P=0.004). The TT+ recurrence rate was similar to that seen in 45 untreated patients (control group), which was 64% (P=0.75). The recurrence rate was similar between 14 patients with asystolic and 12 with non-asystolic responses during TT (P=0.53).

Conclusions: Cardiac pacing was effective in neurally mediated syncope patients with documented asystolic episodes in whom TT was negative; conversely, there was insufficient evidence of efficacy from this data set in patients with a positive TT even when spontaneous asystole was documented. Present observations are unexpected and need to be confirmed by other studies. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01463358.

Keywords: arrhythmias, cardiac; autonomic effect; baroreflexes; biological pacemakers; cardiology; nervous system; syncope; tilt-table test.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Cardiac Pacing, Artificial*
  • Double-Blind Method
  • Europe
  • Female
  • Heart Arrest / diagnosis
  • Heart Arrest / physiopathology
  • Heart Arrest / therapy*
  • Heart Rate*
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Recurrence
  • Syncope, Vasovagal / diagnosis
  • Syncope, Vasovagal / physiopathology
  • Syncope, Vasovagal / therapy*
  • Tilt-Table Test*
  • Time Factors
  • Treatment Outcome

Associated data

  • ClinicalTrials.gov/NCT01463358