Syncope?
F. GIADA, A. RAVIELE
Introduction
Syncope is a very frequent clinical disease [1]. About 30% of the general pop- ulation undergo one syncopal episode in their lifetime, while at least 3% faint more than once. Moreover, it is the cause of about 3% of visits to hospital emergency rooms. In most cases, the aetiology of syncope is neuromediated.
Neuromediated syncope is related to bradycardia and hypotension caused by an abnormal cardiac activation of baroreceptors and of major vessels.
Baroreceptor activation produces a vagal overtone and a decrease in sympa- thetic efferents, thus leading to bradycardia, vasodilation, and hypotension.
Though neuromediated syncope does not directly cause death, it is often associated with severe trauma and, when recurrent, significantly impairs the patient’s quality of life [2–4].
In most cases, neuromediated syncope is an isolated event and patients improve after tilt testing and specialist reassurance regarding their condition [1]. However, some patients continue to have frequent fainting fits and suffer severe functional and psychological limitations which significantly under- mine their quality of life. Such patients need specific treatment.
The treatment of neuromediated syncope involves behavioural measures for all patients, drug therapy for those who are most symptomatic, and pace- maker implantation in very selected cases [1].
Studies on drugs for the treatment of neuromediated syncope have yield- ed disappointing results [5–11]. In only two brief small-scale investigations [12, 13] did the drug used prove to be more effective than placebo. Thus, drug therapy for neuromediated syncope is still controversial and remains under examination.
Cardiovascular Department, Umberto I Hospital, Mestre-Venice, Italy
Role of Pacing in the Treatment of Neuromediated Syncope
While single-chamber VVI mode pacing has proved to be ineffective in the treatment of neuromediated syncope [14], several non-randomised studies [15–17] have shown a significant decrease in syncope recurrence in patients who had undergone dual-chamber pacing. In the last few years, three ran- domised non-controlled studies revealed the efficacy of dual-chamber pace- maker implantation in reducing recurrences in patients with recurrent neu- romediated syncope. The VPS study [18] demonstrated the effectiveness of DDD with rate-drop-response pacemakers in patients affected by neurome- diated syncope who had a positive result on head-up tilt testing and present- ed a variable cardioinhibitory component. The VASIS study [19], on the other hand, showed the effectiveness of a DDI mode pacemaker with hysteresis in patients with vasovagal syncope and positive head-up tilt testing with a marked cardioinhibitory component. Finally, the SYDIT study demonstrated the superiority of DDD with rate-drop-response pacemakers with respect to drug therapy [20].
However, since the above-mentioned studies were non-controlled (patients randomised to the control arm did not receive a pacemaker), the benefits observed might have been due to the placebo effect of the pacemak- er. Indeed, the very recently published VPS II trial [21] and SYNPACE trial [22], two randomised, double-blind, placebo-controlled studies in which all enrolled patients underwent pacemaker implantation and were afterwards randomised to active pacing or inactive pacing, were unable to show any sta- tistically significant superiority of pacemaker treatment over placebo. The main finding of the SYNPACE study [22] is that active cardiac pacing is not more effective than inactive pacing in preventing syncopal recurrences in patients with severe neuromediated syncope: neither the number of patients with syncopal recurrence nor the time to the first syncopal recurrence sig- nificantly differed between pacemaker on and pacemaker off patients.
Moreover, the incidence and number of presyncopes were similar between patients with active pacing and those with inactive pacing. Furthermore, in the SYNPACE study the presence of a marked cardioinhibitory component during tilt-induced syncope did not identify patients who were likely to ben- efit from permanent pacing. These results confirm previous observations regarding the poor value of head-up tilt testing in predicting the efficacy of a given therapeutic intervention [5].
Thus, at the present time, we have insufficiently compelling data on the real efficacy of electrical therapy for the treatment of neuromediated syncope.
Future Perspectives
A crucial point in the use of permanent cardiac pacing in the treatment of neuromediated syncope is the right selection of patients. Perhaps the docu- mentation of severe bradycardia/asystole during spontaneous syncope by means of an implanted loop recorder, and not the observation of a cardioin- hibitory response during tilt-induced syncope, will identify patients who will benefit most from pacemaker implantation.
One of the most important limitations of pacing in neuromediated syn- cope is timely detection of the onset of the neuromediated reaction and trig- gering of pacing. Rate-drop response, like the other algorithms utilised in the studies mentioned above, is a sensing modality based on a reduction in the heart rate. It is possible that the use of different sensing modalities, such as those based on cardiac contractility [23] or respiratory changes [24], might yield better results in preventing syncopal relapse.
Finally, the combination of a dual-chamber pacemaker with an implantable drug delivery system using vasoactive drugs able to counteract both bradycar- dia and vasodilation could be proposed for very symptomatic patients [25].
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