Washington – Help is finally at hand for the subgroup of patients who have severe refractory vasovagal syncope that recurs frequently and unpredictably, and is associated with a strong cardioinhibitory response on tilt table testing, Gonzalo Baron-Esquivias, MD, said at the annual meeting of the American College of Cardiology.
Results of the randomized, multicenter, double-blind, crossover, placebo-controlled SPAIN trial showed that implantation of a permanent pacemaker programmed to a closed loop stimulation (DDD-CLS) algorithm resulted in an 89% decrease in the risk of syncopal recurrences compared with sham DDI pacing, reported Dr. Baron-Esquivias, chief of clinical cardiology at Virgen del Rocio University Hospital in Seville, Spain.
Bruce Jancin/Frontline Medical News
Dr. Gonzalvo Baron-Esquivias
Moreover, the number needed to treat with DDD-CLS pacing for 1 year to prevent a syncopal episode was a mere 2.7 patients in the SPAIN trial, he noted.
The study included 46 patients who met strict criteria for participation and received a permanent pacemaker for which they had no conventional indication. In half of the subjects, the device was programmed to DDD-CLS pacing, while the other half received sham DDI pacing, making them a placebo-treated control group. After 12 months, each group was switched over to the other form of pacing.
Dr. Baron-Esquivias emphasized that the tough SPAIN eligibility criteria enabled investigators to accurately define a specific CSL-responsive subgroup. This is not a form of therapy that’s appropriate for most patients who experience vasovagal syncope. In the right population, however, DDD-CLS pacing is life transforming. The SPAIN investigators documented severely impaired quality of life in the study population, with dramatic improvement on CLS pacing.
Vasovagal syncope is by far the most common cause of syncope. But roughly 70 out of every 100 patients who present to the emergency department with vasovagal syncope will never have a repeat episode. And of the 30 who do, perhaps only 10 will have frequent recurrences refractory to conventional measures and that impose a severe effect on quality of life. This is the subgroup for whom consideration of pacemaker therapy is appropriate.
To be eligible for the SPAIN trial, patients had to have at least five previous episodes of neuromediated vasovagal syncope, including at least two within the past year. They also had to be at least 40 years old, since CLS-responsive vasovagal syncope is skewed toward an older age group. In addition, all participants had to have normal results on a complete physical examination that included an orthostatic test, 12-lead echocardiogram, two-dimensional echocardiography, carotid sinus massage, and 24-hour Holter monitoring. Only then were they eligible for a tilt-table test. A positive head-up tilt test demonstrating a cardioinhibitory response required a heart rate drop to less than 40 bpm for at least 10 sec or a greater than 3-sec pause.
The average age of the 46 subjects who fulfilled all of these criteria was 56 years – several decades older than most patients who present with syncope. They averaged 12 prior syncopal episodes, including 4.5 during the prior 12 months. Three-quarters of the patients demonstrated asystole during the tilt test, with an average duration of 15 sec.
Four of the 46 patients experienced a syncopal recurrence during their 12 months on DDD-CLS pacing, while 21 of the same group of 46 had recurrent syncope during their year on DDI sham pacing. This translated into an absolute 37% reduction in syncopal episodes with active pacemaker therapy. Patients had an 8.8-fold greater risk of syncopal recurrence while on DDI sham pacing compared with DDD-CLS.
Dr. Baron-Esquivias explained that the DDD-CLS algorithm is designed to detect impending syncope at an early and actionable stage. The algorithm identifies the combination of increased myocardial contractility and reduced right ventricular intracardiac impedance, which heralds the first stage of vasovagal syncope. It then directs the pacemaker to activate high-rate atrioventricular sequential pacing to prevent arterial hypotension, bradycardia, and overt syncope.
Discussant Kenneth A. Ellenbogen, MD, applauded Dr. Baron-Esquivias and coinvestigators for “having the strength and conviction to attack this problem where so many prior studies have failed.”
For example, the earlier European SYNPACE trial showed no benefit for dual-chamber pacemaker therapy in DDD-RDR (rate-drop response) mode in patients with recurrent severe cardioinhibitory vasovagal syncope (Eur Heart J. 2004 Oct;25[19]:1741-8), probably due to a combination of a less robust early-syncope detection algorithm than that of DDD-CLS and less restrictive patient selection criteria, observed Dr. Ellenbogen, chairman of the division of cardiology and director of clinical cardiology electrophysiology and pacing at the Medical College of Virginia, Richmond.
The SPAIN trial was funded by the Spanish Society of Cardiology. Dr. Baron-Esquivias reported having no financial conflicts.
A considerably larger randomized trial known as BIOSync CLS, sponsored by Biotronic, which developed the CLS program, is ongoing.