Aims: The Third International Study on Syncope of Uncertain Etiology (ISSUE-3) showed that dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ?40 years with severe asystolic neurally mediated syncope (NMS). Nevertheless, patients receiving pacing therapy had an estimated syncopal recurrence of 25% at 2 years. Aim of this study was to investigate the role of tilt testing (TT) response in predicting syncopal recurrence.
Methods and Results: In the ISSUE-3 registry, 162 out of 504 patients had a diagnosis of NMS documented by implantable loop recorder (ILR). TT was positive in 76 and negative in 60 (not performed in 26). An asystolic response (type 2B: VASIS classification) predicted asystole during a spontaneous NMS on ILR (type 1 of the ISSUE classification) 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). Fifty-two patients (26 TT + and 26 TT –) with asystolic, type 1 NMS were treated with 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).
TT+ recurrence rate was similar to that of 45 untreated patients (control group) which was 64%, p=0.75 (Figure 1). The recurrence rate was similar among 14 patients with asystolic and 12 non-asystolic responses during TT, p=0.53).
Conclusions: Cardiac pacing is very effective in NMS patients who have the documentation of an asystolic pause during a spontaneous event and a negative TT; conversely, there is no evidence of efficacy in patients with a positive TT. Although an asystolic response during TT predicts an asystolic spontaneous NMS, the pacing benefit is similar to that of non-asystolic responses.