• Arrhythmias
• Interventional Techniques & Devices Clinical Trials

Michele Brignole, MD, Ospedali del Tigullio, Lavagna, Italy, presented evidence from the International Study on Syncope of Uncertain Etiology 3 Study [ISSUE3; NCT00359203], demonstrating that cardiac pacing therapy is effective for prevention of recurrent syncope in patients with neurally mediated syncope (NMS) and documented asystole. These data contradict previous data from two randomized trials [Connolly SJ et al. JAMA 2003; Raviele A et al. Eur Heart J 2004] that failed to prove the superiority of cardiac pacing over placebo for the prevention of syncopal recurrences in unselected patients who were affected by NMS. Prof. Brignole believes that the discrepancy between these findings may be explained by the current study's use of implantable loop recorders (ILRs) to document asystole in patients with NMS before beginning therapy.

This was a randomized, controlled, double–blind trial of cardiac pacing in 77 patients with NMS who had asystolic syncope ≥3 seconds or nonsyncopal asystole ≥6 seconds, as established with the use of an ILR. The primary endpoint was time to first syncope recurrence. Subjects with qualifying asystolic events had pacemakers implanted and were randomized 1:1 to either pacemaker on (PM on) or pacemaker off (PM off) groups. The study was stopped when a total of 27 primary endpoint events, irrespective of study arm, were reached. There were a total of 158 documented endpoints during the ILR screening phase; 56% patients had asystole, 23% had normal sinus rhythm, 10% had tachycardia, and 10% had bradycardia.

Baseline characteristics included a mean participant age of 63 years in each group, of which approximately half in each group was female (47% PM on, 59% PM off), and >60% had a prior hospitalization for syncope. Over 80% in the cohort had tilt table testing, with fewer patients in the PM on group having positive results than in the PM off group (42% vs 72%). Diabetes was present in 29% of patients, while 23% had structural heart disease. Overall, patients were characterized by recurrent syncope that began in middle or older age with severe presentations; mean pause, captured by an ILR of 11 seconds; and frequent injuries that were related to absence of warning symptoms.

After 24 months, 75% of PM on patients were free from recurrent syncopal episodes compared with 43% of patients who were randomized to PM off (log rank RRR, 57%; p=0.039). Complications were restricted to lead dislodgements (n=5) and 1 incidence of subclavian vein thrombosis.

The authors concluded that dual–chamber permanent pacing is effective in reducing recurrence of syncope in patients aged ≥40 years with severe asystolic NMS and suggest that the use of this invasive treatment may be effective for relatively benign NMS. The overall strategy of using an ILR in order to determine suitable patients for pacing likely contributed to the positive findings and explains the discrepancy with the negative results of previous randomized controlled trials.

In selected patients, syncope is recurrent, unpredictable, and associated with a high risk of trauma and poor quality of life. It often occurs while engaged in high–risk activity (eg, driving, machine operation, flying, competitive athletics). Prof. Brignole believes that the ILR screening phase is important in determining which patients should receive a pacemaker. Based on prior observations, 18% percent of patients who receive an ILR will be candidates for pacemaker therapy within 1 year, and approximately 40% will be candidates within 4 years.

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