URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203.

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.

Aim The benefit of cardiac pacing in patients with severe recurrent reflex syncope and asystole induced by tilt testing has not been established. The usefulness of tilt-table test to select candidates for cardiac pacing is controversial. Methods and results We randomly assigned patients aged 40 years or older who had at least two episodes of unpredictable severe reflex syncope during the last year and a tilt-induced syncope with an asystolic pause longer than 3 s, to receive either an active (pacing ON; 63 patients) or an inactive (pacing OFF; 64 patients) dual-chamber pacemaker with closed loop stimulation (CLS). The primary endpoint was the time to first recurrence of syncope. Patients and independent outcome assessors were blinded to the assigned treatment. After a median follow-up of 11.2 months, syncope occurred in significantly fewer patients in the pacing group than in the control group [10 (16%) vs. 34 (53%); hazard ratio, 0.23; P = 0.00005]. The estimated syncope recurrence rate at 1 year was 19% (pacing) and 53% (control) and at 2 years, 22% (pacing) and 68% (control). A combined endpoint of syncope or presyncope occurred in significantly fewer patients in the pacing group [23 (37%) vs. 40 (63%); hazard ratio, 0.44; P = 0.002]. Minor device-related adverse events were reported in five patients (4%). Conclusion In patients aged 40 years or older, affected by severe recurrent reflex syncope and tilt-induced asystole, dual-chamber pacemaker with CLS is highly effective in reducing the recurrences of syncope. Our findings support the inclusion of tilt testing as a useful method to select candidates for cardiac pacing. Study registration ClinicalTrials.gov identifier NCT02324920, Eudamed number CIV-05-013546.

nus bradycardia and/or atrioventricular block.For patients with typical VVS, a combination of neural outflow and purinergic activation is likely. Letters J A C C V O L . 6 6 , N O . 2 , 2 0 1 5 J U L Y 1 4 , 2 0 1 5 : 2 0 2 -7 R E F E R E N C E S 1. Deharo JC, Mechulan A, Giorgi R, et al. Adenosine plasma level and A2A adenosine receptor expression: correlation with laboratory tests in patients with neurally mediated syncope. Heart 2012;98:855-9. 2. Deharo JC, Guieu R, Mechulan A, et al. Syncope without prodromes in patients with normal heart and normal electrocardiogram: a distinct entity. J Am Coll Cardiol 2013;62:1075-80. 3. Brignole M, Deharo JC, De Roy L, et al. Syncope due to idiopathic paroxysmal atrioventricular block: long-term follow-up of a distinct form of atrioventricular block. J Am Coll Cardiol 2011;58:167-73. 4. Saadjian AY, Gerolami V, Giorgi R, et al. Head-up tilt induced syncope and adenosine A2A receptor gene polymorphism. Eur Heart J 2009;30:1510-5. 5. Sutton R, Brignole M. Twenty-eight years of research permit reinterpretation of tilt-testing: hypotensive susceptibility rather than diagnosis. Eur Heart J 2014;35:2211-2. Early Repolarization A Risk Factor in Brugada SyndromeConte et al. (1) reported their long-term results of implantable cardioverter-defibrillator therapy in Brugada syndrome (BS). The investigators noted that 4 patients experienced an electrical storm and 1 (Patient #3) had a "fragmentation of the QRS complex (f-QRS)." In fact, this patient's electrocardiogram (ECG) showed a spike mainly at the terminal portion of all QRS complexes. After ajmaline challenge, a coved-type ECG was induced, and the spike disappeared, unmasking an S wave in leads V 4 to V 6 .We believe that the terminal QRS spike may signify early repolarization (ER) rather than f-QRS in this BS patient. Unlike in myocardial infarction, f-QRS has

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