WASHINGTON, DC — New research suggests a novel pacing program, known as closed-loop stimulation, reduces recurrences in patients suffering from refractory, recurrent cardioinhibitory reflex vasovagal syncope.
Among 46 patients in the prospective, double-blind SPAIN trial, investigators found nearly a sevenfold reduction in recurrences in patients receiving dual-chamber pacing with closed-loop stimulation (DDD-CLS) rather than sham pacing.
The time to first syncope recurrence was also more than threefold longer with closed-loop stimulation.
Pacing has had mixed results in other syncope trials; however, closed-loop stimulation detects changes in contractility that precede syncope and responds with rapid atrioventricular pacing to prevent the syncopal episode, principal investigator Dr Gonzalo Baron-Esquivias (Hospital Universitario Virgen del Rocio, Seville, Spain) explained during his presentation at the American College of Cardiology 2017 Scientific Sessions.
Session panelist Dr Kenneth Ellenbogen (Virginia Commonwealth University Medical Center, Richmond) said "the study results are quite impressive and quite powerful" but questioned what proportion of patients presenting to the emergency department with syncope would filter through the study protocol and be considered for pacemaker implantation.
Baron-Esquivias responded that most patients who suffer syncope have just one episode in their lives and that they selected "a very exclusive patient population" who had suffered multiple syncope episodes. Importantly, the average age of this "seriously disabled" population was 56 years, whereas most syncope patients presenting to the emergency department are in their thirties or forties.
US and European guidelines don't advocate the use of permanent pacemakers in young patients, who may outgrow their tendency to vasovagal syncope, and give pacing only a class 2b indication for patients aged over 40 with refractory, recurrent syncope and cardioinhibition on head-up tilt testing.
Commenting later to heartwire from Medscape, Ellenbogen said, only a minority of patients with vasovagal syncope would be paced, but "it's a big ocean, so even if it's only 10% or less, that's still a lot of patients. So it is something for patients who have refractory syncope with multiple recurrences; there's no real good drug treatment for that."
He added, "We have used it on patients and it is somewhat dramatic how it helps patients, but the real key is selecting the right patients."
That means not only recurrent, refractory episodes, but presence of a cardioinhibitory response. "In our practice, we would try to record what their rhythm is during a syncopal episode and sometimes we see people have 30-second pauses. It's quite striking," Ellenbogen remarked.
For the study, investigators from 12 centers in Spain and Canada recruited 54 patients aged 40 years or older who had experienced five or more syncope (mean 12) episodes in their lives and at least two (mean 4.5) episodes in the past year. All had normal findings on electrocardiogram, carotid sinus massage, orthostatic test, and 24-hour Holter test but showed a drop in BP and heart rate during tilt testing. Notably, the mean asystole duration during head-up tilt testing was 15 seconds, with an interquartile range of 10 to 26 seconds.
Eight patients were lost to follow-up, leaving 46 patients (47.8% male) available for analysis who were randomized to receive DDD-CLS pacing or pacing programmed in a nonatrial tracking mode (subthreshold DDI at 30 bpm) for 12 months and then crossed over to the opposite treatment group for another 12 months. Early crossover was allowed in either group if more than three syncope episodes occurred within 1 month.
The primary efficacy end point of >50% reduction in the number of syncope episodes occurred in 72.2% of DDD-CLS patients during the first year and in 27.7% in the second year during DDI sham pacing.
None of the patients initially treated with DDI had at least a 50% reduction in syncope episodes, but 100% did after switching to DDD-CLS in the second year.
Among all 46 patients, just four (8.7%) suffered syncope during DDD-CLS compared with 21 patients (45.65%) during DDI (odds ratio 0.11, 95% CI 0.034–0.368; P=0.0001).
The risk of syncopal recurrence was 8.82 times greater with DDI than closed-loop stimulation, which translates into an absolute risk reduction of 37% and number needed to treat of 2.7 per 100 patients, Baron-Esquivias said. This was statistically significant in Cox regression modeling (hazard ratio 6.72, 95% CI 2.29–19.76; P=0.0005).
Time to first syncope recurrence after randomization was also significantly longer with DDD-CLS than DDI (29.15 vs 9.3 months, P=0.0158).
To heartwire , session cochair Dr Patrick O'Gara (Brigham and Women's Hospital and Harvard Medical School, Boston, MA) said it remains to be seen the degree to which the findings will affect practice. "This is a very small study with very small numbers of patients, and I think, especially in young patients, before obligating them to a pacemaker, one would go through an algorithm of other approaches to the problem."
Baron-Esquivias told heartwire the results are similar to those from other small studies and, if confirmed in a larger trial, point to the need for change.
"There is room to improve cardioinhibitory reflex syncope treatment," he said. "An [implantable loop recorder] ILR is not used by all cardiologists to diagnose syncope patients. Moreover, there are many cardiologists who never recommend such a study in their patients. So the 2017 US and also the 2013 European guidelines recommend treatment for those patients suffering syncope, but in an extremely small number of patients in real life and in real clinical practice."
Results are expected in 2020 from Biotronik's ongoing BioSync CLS trial comparing DDD-CLS with pacing in ODO mode in up to 128 patients with tilt-induced cardioinhibitory recurrent syncope recruited from about 25 centers in six countries.
The study was sponsored by the Spanish Society of Cardiology, which received an unrestricted grant from Biotronik Spain, the developer of the DDD-CLS program. Esquivias reported no relevant financial relationships.
Heartwire from Medscape © 2017
Cite this: 'Closed-Loop Stimulation' Pacing May Relieve Recurrent Syncope - Medscape - Mar 29, 2017.