DDD Pacing Can Help Suppress Asystolic Neurally Mediated Syncope: ISSUE-3

March 27, 2012

March 26, 2012 (Chicago, Illinois) — Contrary to previous clinical trials that suggested otherwise, pacemaker therapy can cut the risk of fainting spells in patients with demonstrated asystolic neurally mediated syncope (NMS), according to the authors of a randomized, controlled trial reported here today at the American College of Cardiology 2012 Scientific Sessions.

Pacing therapy succeeded in their trial, but not the others, at least partly because the study differed in requiring patients to have demonstrated asystolic NMS at implantable loop-recorder (ILR) screening, said principal investigator Dr Michele Brignole (Ospedali del Tigullio, Lavagna, Italy) when presenting the results of the third International Study on Syncope of Uncertain Etiology (ISSUE-3). The trial was conducted at 29 centers in Canada and Western Europe.

All patients in the trial had a dual-chamber pacemaker implanted and were then randomized to having it "on" or "off." The pacemaker-on group showed a 57% reduction in relative risk of fainting within two years of randomization (p=0.039).

During his formal presentation of the trial, Brignole concluded that the degree of syncope reduction supports the use of therapy with a dual-chamber pacemaker "for the relatively benign neurally mediated syncope," despite the therapy's invasiveness.

That's in highly selected patients like those in the trial, Brignole told heartwire . ISSUE-3 included only patients screened with an ILR with a "severe presentation of syncope" due to a high frequency of episodes and who had failed to respond to more conservative interventions. Also, 45% to 55% of randomized patients had a history of often major fainting-related injuries. "The point is that in these patients, there has been no [treatment] with proven efficacy for this form [of syncope] before this trial."

With the results of ISSUE-3, according to Brignole, "the efficacy of pacing is established" without the need for replication in further trials. He told heartwire that pacing therapy in such patients is now standard at his center.

The trial's 77 patients were at least 40 years old and had a clinical history that suggested NMS (including at least three episodes of syncope in the preceding two years) and in whom other forms of syncope had been largely excluded. At ILR monitoring, they had to have demonstrated at least three seconds of asystole associated with clinical syncope or an asystolic nonsyncopal episode of at least six seconds.

Patients were randomized to receive a dual-chamber pacemaker that was activated to DDD-RDR mode or left off.

Pacemaker-related complications during the trial included dislodgment of the right-atrial lead in two patients, of the right-ventricular lead in two patients, and a subclavian vein thrombosis in one patient.

Rate of a First Postrandomization Episode of Syncope in Screened Patients With Asystolic Neurally Mediated Syncope

Follow-up interval Pacemaker on, n=38 (%) Pacemaker off, n=39 (%)
12 mo 25 37
24 mo 25 57*

*p=0.039 vs pacemaker-on

Electrophysiologist Dr Peter A Brady (Mayo Clinic, Rochester, MN), who comoderated the session during which ISSUE-3 was presented, told heartwire that he is "a little bit skeptical" that the patient selection and screening measures used in the trial actually selected a population in whom an asystolic vasovagal response was the predominant syncope mechanism. And that, he said, is important to whether the trial justifies an invasive therapy in patients like those enrolled.

Even so, in patients with "truly a neurocardiogenic mechanism for their syncope," according to Brady, "I would say that other therapies are probably well worth trying first, in aggressive fashion, before proceeding with an invasive approach."

The trial was supported by Medtronic Bakken Research Center. Brignole had no disclosures.

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