29,30 The results were encouraging to enthusiasts, but neither the diagnosis nor the therapy became accepted practice for an extended period. CSM was not performed in many centres and was considered dangerous selleck product until the relatively benign complications incidence was reported. 19 Syncope recurrence was also considered to be a problem. That it was higher than in atrioventricular block should have been anticipated, as CSS is a form of reflex syncope involving – in every case – some degree of vasodepression. Results in the late 1980s, showing a 9% recurrence with dual chamber pacing and 18% with ventricular

pacing in 5 years gave a realistic picture at the time. 31 This was corroborated by Lopes et al in 2011, 32 using dominantly dual chamber pacing with 10.9% recurrence also in 5 years, but Brignole and Menozzi found 20% in their series over 5 years of follow-up. 33 Furthermore, in relation to current data, these figures are relatively acceptable with ∼20% in sinus node disease in 5.5 years 34 and 25% in 2 years in older vasovagal patients. 35 One randomized trial (RCT) was performed on 60 patients in 1992, with a highly significant benefit of pacing being shown (p < 0.002),

36 with a second RCT by another group in 2007 serving to confirm the earlier results. 37 CSS became fully accepted as having a strong indication for pacing and is classified as a Class 1 indication, level of evidence B in the current ESC Guidelines for Pacing. 1 The mode of pacing is advised

to be dual chamber for all those in sinus rhythm, reserving VVI pacing for those in permanent atrial fibrillation. 1 Recent earlier evidence suggests that, in both CSS and VVS, a positive tilt test implies a less positive outcome, in terms of recurrent syncope (Figure 3), from pacing, 2,38,39 which may be explained by the presence of a more potent vasodepressor component of the reflex. 40 It is in this regard that consideration of overlap between CSS and VVS is most important. Figure 3. Recurrence of syncope according to tilt-test results Figure reproduced with permission of Oxford University Press. From Solari et al. 2 CI = Cardioinhibitory. There is a case to be made for use of tilt-testing in CSS to risk stratify Drug_discovery cardioinhibitory or mixed patients in order to anticipate the likely recurrence of syncope and, perhaps, to go a step further and attempt prophylactic treatment of the vasodepressor component. However, since this treatment is less than satisfactory it may be prudent to await a first recurrence before embarking on therapy. Therapy of vasodepressor CSS Management of vasodepressor CSS has received relatively little attention. 41 Patients are advised to take increased volumes of fluid (2+litres/day) and, if safe, to increase salt consumption toward 6g/day. The principle difficulty in management is the frequent coincidence of hypertension.