Coping with Syncope: Tilt Towards Pacing

VK Bahl, Gautam Sharma
Department of Cardiology, All India Institute of Medical Sciences, New Delhi

Syncope, defined as a transient loss of consciousness and postural tone, is one of the oldest recorded medical problems. The term syncope is derived from the Greek word "synkoptein", meaning "to cut short". One of the most frequently encountered forms of syncope, the vasovagal or the "common faint" is caused by inappropriate reflex vasodilatation and bradycardia and is rarely life threatening.1,2 Even in patients, with the so-called "malignant" form of the disease, who have profound cardioinhibition culminating in asystole during tilt tests, no death has been reported on long-term follow-up studies.3,4 However, patients with vasovagal syncope are at an increased risk of a fall, which can often result in serious injuries. Those who work as pilots, drivers, etc. can endanger others as well. Patients who develop syncope without enough warning or prodromal symptoms are unable to brace themselves for the usually inevitable "fall". Thus, patients with syncope have a level of impairment similar to that seen in patients with severe rheumatoid arthritis and psychiatric illness.5,6 The quality of life deteriorates as the frequency of syncopal spells increases. Therefore, vasovagal syncope is not "truly benign" and these patients need to be treated. At present, there is no consensus on the management of patients with vasovagal syncope. If syncopal episodes are infrequent, simple nonpharmacologic measures usually suffice. In those with severe symptoms, tilt test-guided therapy or empiric pharmacotherapy is recommended. If drugs fail, permanent pacemakers are advocated. However, this treatment algorithm has to be individualized, taking into consideration age, occupation, symptomatic status and response to head-up tilt test (HUTT).  

Non pharmacological Methods  

Salt supplementation and increased fluid intake, by increasing the extracellular fluid volume, may reduce the impact of orthostatic blood pooling. These simple measures are commonly recommended as initial therapy. Although large controlled trials are lacking, they have been shown to be of some benefit in small studies.7,8 

It may be of help to teach the patient about the pathophysiology of vasovagal syncope and ways to avoid known situational triggers. Medications such as peripherally acting alpha-antagonists and nitrates should be stopped. Several studies have demonstrated that the probability of having a syncopal recurrence is significantly reduced after a tilt test. This could be because of the counseling and education that patients receive after the first test. The benefit of "tilt training" or orthostatic training has been reported in a recent study.9 Forty-two patients were instructed to continue a program of daily tilt training at home: two 30-min sessions of upright standing against a vertical wall. No medication was prescribed. At follow-up of 15.1+7.8 months, 36 patients remained completely free of syncope.  

Pharmacotherapy  

Several pharmacologic agents targeting the afferent limb (fludrocortisone), efferent limb (beta-blockers) or both (midodrine) of this reflex-mediated syndrome have been advocated to manage these cases. Many small, nonrandomized trials have been reported using beta-blockers, clonidine, disopyrimide, angiotensin-converting enzyme inhibitors, dextroamphetamine, etilefrine, fludrocortisone, methylphenidate, midodrine, phenylephrine, propan-theline, scopolamine, serotonine-reuptake inhibitors and theophylline. However, as the natural history of this disease entity can be variable, critical assessment of the efficacy of any pharmacologic agent requires a randomized clinical trial.  

Beta-blockers : These are the most widely prescribed drugs in clinically encountered vasovagal syncope, often as empiric therapy. They presumably act by inhibiting the activation of ventricular mechanoreceptors and by blocking the effects of surging catecholamines in the circulation. 

Despite extensive clinical experience with the drug, there is a dearth of controlled studies. Several nonrandomized studies 10–19 have demonstrated its clinical efficacy with recurrence rate reduced to 6%–28% with treatment. In a large study by Cox et al.,15 296 consecutive patients were put on tilt-guided or empiric beta-blocker therapy. During a follow-up of 28±11 months, 90% of patients on tilt- guided beta-blocker therapy remained symptom-free compared with 77% on empiric therapy. Similar results were reported in another large nonrandomized study by Natale et al.19 They demonstrated a 6% recurrence rate of symptoms on tilt-guided beta-blocker therapy among 210 patients, while the recurrence rate was 36% when empiric beta-blocker therapy was given. 

Only two randomized, placebo-controlled trials 20,21 have been published. In the first double-blind, randomized, placebo-controlled study by Mahanonda et al.,20 42 patients with a positive tilt test were randomized to atenolol or placebo. They were subjected to a repeat tilt test after one month. The response rates (negative HUTT) were 62% v. 5% (p=0.0004) for the atenolol and control groups, respectively. Moreover, 71% patients reported a subjective sense of well-being in the atenolol group compared with 29% in the placebo group (p=0.02). The frequency of syncopal attacks reduced from 6.0+9.4 per week to 0.6+1.6 per week in the atenolol group (p=0.025). This was the first controlled trial demonstrating the benefit with beta-blockers. However, many a question regarding the long-term efficacy of the drug, its tolerability and side-effects remained unanswered due to the short follow-up of only one month. 

The second study was published 6 years after the earlier trial. In this prospective, double-blind, randomized and placebo-controlled study,21 50 patients with syncope, of whom 20 (40%) had an abnormal tilt test, were randomized to atenolol or a placebo. During the one year of follow-up, 16 patients on atenolol and 11 patients on placebo had recurrence of syncope (61% v. 45%, p=0.09). The authors concluded that beta-blockers were no more beneficial than placebo. However, only 20 patients (40%) in this study had an abnormal response to tilt testing at baseline. Previous studies, including the favourable study by Mahanonda et al.,20 included only patients with a positive tilt test in the trial. The difference in the inclusion criteria in the two studies may have had a significant impact on the results obtained. It is indeed surprising that the investigators assigned even patients with a negative tilt test (steep angle of 80° for 45 min) to the trial. There are no prior studies in the literature showing the efficacy of elective beta-blocker therapy in patients with presumed neurocardiogenic syncope. The fact that only 5 patients included in this study had responded favorably to intravenous atenolol may also be responsible for the reported high incidence of recurrence. Previous studies 15,17,22 have demonstrated that patients who respond to intravenous beta-blockers during tilt testing, also have a favorable response to oral beta-blockers on long-term follow-up. In the study by Sra et al.,17 all patients with a negative tilt test during esmolol infusion also had a negative tilt response with oral metoprolol. Of the patients with a positive tilt test during esmolol infusion, 90% continued to have a similar response with oral therapy. Because only 5 patients (25%) had responded favorably to intravenous atenolol in the study by Madrid et al.21 it is not surprising that the response to oral atenolol was correspondingly poor. Although the authors had questioned the efficacy of beta-blockers in vasovagal syncope, the conclusions of the study need to be re-examined and interpreted critically. 

It appears that beta-blockers are effective in the treatment of patients with vasovagal syncope; however, further scrutiny is needed in large randomized trials with appropriate numbers and extended follow-up. For now, beta-blockers retain their hallowed place as the first line of treatment for vasovagal syncope. Other medications should be used if the patient does not respond or does not tolerate beta-blockers because of side-effects such as bradycardia, mpotence, bronchospasm or AV blocks.

Fludrocortisone: There is a wealth of clinical experience with fludrocortisone. Though controlled studies are lacking, it is commonly used to treat vasovagal syncope, especially in children. Fludrocortisone is a mineralocorticoid that acts by increasing the renal absorption of sodium, thereby expanding the blood volume. It may also affect the baroreceptor sensitivity and enhance the effects of circulating catecholamines by increasing the sensitivity of blood vessels to their vasconstrictive effects.23 

In a study by Scott et al.,12 58 pediatric patients were randomized to receive atenolol or fludrocortisone acetate. At the end of 6 months, 48 patients (83%) showed clinical improvement (no recurrence or significant decrease in frequency/severity of episodes). Both drugs were equally effective. Neither the response to intravenous beta-blockers, nor the presence of tachycardia was predictive of long-term response to oral beta-blockers. This is contrary to earlier studies in which a positive response to intravenous beta-blockers predicted a favorable long-term response to oral beta-blockers.15,17,22 Similarly, the presence of tachycardia during the tilt test had predicted a favorable response to oral beta-blocker therapy in an earlier study by Leor et al.24 In a study18 involving 21 children who were treated with fludrocortisone, 20 experienced no recurrences of syncope on follow-up for 20 months. Although small non-randomized studies have demonstrated the usefulness of this drug, no randomized, placebo-controlled trial has been published. Despite this, fludrocortisone continues to be a popular choice amongst clinicians because of its patient-friendly profile and minimal side-effects (hypertension, edema, acne, depression and rarely, hypokalemia).

Alpha-adrenergic agonists: These agents increase the venous tone, thereby reducing the venous pooling and thus possibly the paradoxical activation of cardioreceptors. The increase they cause in arteriolar tone may counterbalance the reflex vasodilatation and hypotension that culminate in overt syncope. 

Though the initial trials showed promise, they were open-label studies with a small number of patients and used different drugs such as phenylephrine,25 methylphenidate 26 and dextroamphetamine.27 Only midodrine has proved to be of use in a randomized, placebo-controlled trial.28 Ward et al.,28 randomized 16 patients to midodrine or placebo and reported significant improvement in the frequency and recurrence of symptoms. Also, the quality of life improved significantly in the patients on midodrine. In another study with midodrine,29 11 patients were followed up for a mean of 4.3 months. There was a significant clinical improvement in 9 patients with complete resolution of symptoms in 5 of them. 

Small, nonrandomized trials had also found etilefrine, another alpha-adrenergic agonist, to be beneficial. However, recently a double-blind, randomized, placebo-controlled trial with etilefrine failed to confirm its efficacy.30 Both the treatment and placebo arms (63 patients in each) had the same recurrence rate of syncope (24%). The median time to the first syncope (106 v. 112 days) and the incidence and number of presyncopal episodes were also not significantly different. This well-crafted VASIS study 30 has put a question mark on the usefulness of alpha-adrenergic agonists in vasovagal syncope. Despite the initial promise, large randomized trials are needed to further the claims of midodrine as an agent that can be relied upon in this condition.

Serotonin-reuptake inhibitors: Serotonin is a neurotransmitter which mediates the development of hypotension and bradycardia, both of which are essential components of vasovagal syncope. Therefore, serotonin-reuptake inhibitors such as paroxetine, fluoxetine and sertraline could be of value in the treatment of this entity. Grubb et al.31 anecdotally observed that treating patients who suffered from endogenous depression as well as neurocardiogenic syncope with fluoxetine resulted in the resolution of their clinical syncope. This observation paved the way for clinical trials with this class of drugs. In their study, 16 patients with resistant vasovagal syncope and a positive tilt test were treated with fluoxetine and restudied 5–6 weeks later. Of the 13 patients (3 could not tolerate the drug) 7 (53%) were rendered tilt test negative and remained asymptomatic over a mean follow-up of 19±9 months. 

Di Girolamo et al.32 studied the effects of paroxetine hydrochloride on vasovagal syncope in a randomized, double-blind, placebo-controlled trial. The response rates (negative HUTT after 1 month) were 61.8% and 38.2% in the paroxetine and placebo groups, respectively. During the follow-up of 25.4±8 months, recurrence of syncope was seen in 17.6% in the paroxetine group as compared to 52.9% in the placebo group (p<0.0001). Only 1 patient (2.9%) discontinued the drug due to severe headache. This is a significant study; it being a placebo-controlled, randomized trial showing evidence of improvement. 

Sertraline has also been found to be effective in children with vasovagal syncope in small nonrandomized trials.33,34 Incapacitating side-effects such as anxiety, insomnia, drowsiness, anorexia and fatigue restrict the use of serotonin receptor antagonists.

Disopyramide: This class IA antiarrhythmic agent has a negative inotropic, anticholinergic and a direct peripheral vasoconstrictive effect which theoretically makes it an ideal drug to combat syncope. Small, nonrandomized studies have shown disopyramide to be beneficial. In a study by Milstein et al.,35 a repeat tilt test after oral disopyramide therapy for 3 days was performed in 10 patients. All of them had a negative test and during a subsequent follow-up after 20±5 months, all but one patient remained asymptomatic. In another study,24 of the 6 nonresponders to beta-blocker therapy, subsequently treated with disopyramide, only 1 had recurrence of syncope in the follow-up period of 9±3 months. In a double-blind, randomized trial, Morillo et al.36 studied 22 patients who were serially tilt tested with intravenous and then oral disopyramide. Neither form of disopyramide was found to be superior to placebo in preventing tilt-induced or spontaneous syncope. During follow-up of 29±8 months, syncope recurred in 27% of patients on drug therapy compared to 30% on placebo. Because of the potential for pro-arrhythmias and the presence of significant anticholinergic effects, disopyramide is not considered as first-line therapy for vasovagal syncope.

Other pharmacologic agents: Anticholinergic agents might be effective by reducing the high vagal tone that occurs during vasovagal syncope. Small numbers of patients were successfully treated with transdermal scopolamine in a few nonrandomized studies.19,37 However, Lee et al.38 found no benefit of the drug over placebo in a randomized trial of 60 patients. 

Theophylline blocks the action of adenosine which is  mediator of hypotension and bradycardia. However, two small, nonrandomized studies 39,40 have demonstrated conflicting results with the drug. 

Oral enalapril, an angiotensin-converting enzyme inhibitor, has also shown promise in 30 patients with vasovagal syncope in a randomized, double-blind, placebo-controlle trial.41 All the 15 patients given enalapril had a negative repeat tilt test. During a follow-up of 13.4+2.1 months, 14/15 (93%) patients on enalapril remained symptom-free compared with 3/15 in the placebo group. Further studies are required to assess the full potential of this class of drugs in treating patients with vasovagal syncope.

Role of tilt testing in guiding pharmacotherapy: Tilt test-guided therapy has generally been found to be more effective than empiric treatment.15,17,22 In a study of 303 patients,19 44 received empiric therapy, 210 were treated with tilt test-guided medications, and 49 refused treatment. Of the 210 patients on tilt test-guided therapy, 130 were on beta-blockers, 35 on theophylline, 10 on ephedrine, 31 on disopyramide and 4 on combination therapy. Empiric therapy consisted of beta-blockers in most of the patients. Recurrence of symptoms was seen in only 6% of the patients on tilt test-guided therapy compared with 36% on empiric therapy and 67% in no treatment group.

Conclusions: Although several pharmacologic agents have been used for the treatment of vasovagal syncope, there is a remarkable absence of scientific proof of their efficacy from large, prospective, randomized clinical trials. In fact, only three agents have shown to be of benefit in randomized clinical trials—atenolol,20 midodrine 27 and paroxitene.32 Beta-blockers are still the old favorite as the other two have significant side-effects. However, the only two randomized trials available on their efficacy have yielded conflicting results. Of late, clinicians have realized the need of looking beyond beta-blockers, and have started considering other treatment options.

Pacing for Vasovagal Syncope  

The need for a therapy beyond drugs was felt when drug-resistant fainters with "malignant syncope" were encountered. These patients form a high risk for "falls with the faint" and have a severely restricted lifestyle with significant physical and psychosocial handicap. The bradycardia or asystole component of the vasovagal syncope which along with hypotension culminates in the clinical cascade, theoretically makes pacing support during the episode seem the final answer to this vexing problem. 

In earlier studies, vasovagal syncope induced by tilt testingwas used as a model for clinical syncope, to determine whether pacing could be helpful. In these studies, patients who had a positive tilt test with marked bradycardia underwent a second tilt test with temporary pacing at rates of 85–100 beats/min. Fitzpatrick et al.42 using temporary dual-chamber pacing with rate hysteresis could prevent syncope in 5 out of 7 patients. In these 5 cases, syncope was prevented despite the onset of a vasovagal reaction attested to by fall in blood pressure and the development of sufficient bradycardia to initiate pacing. Similarly, Samoil et al.43 reported prevention of syncope in 3 out of 6 patients with pacing. In the study by Sra et al.,44 22 patients with bradycardia or asystole along with hypotension during tilt testing underwent a second tilt-test with dual-chamber temporary pacing at a rate of 20 beats/min above their resting rate. They found that 15 patients still had presyncope and 5 patients went on to have frank syncope during pacing. Although the authors felt that pacing was not useful in vasovagal syncope, a shift from syncope at baseline in 18 patients to syncope in just 5 patients during pacing represents a significant clinical improvement as far as frank syncope is concerned. The results were similar to the earlier study by Fitzpatrick et al.,42 in which the authors had concluded that modification of the vasovagal episode during temporary pacing could translate into a clinical advantage with permanent pacing. Overall, temporary pacing was shown to prevent syncope in more than half the patients.

The initial studies with permanent pacing were historically controlled. Peterson et al.45 reported their experience of 37 patients with vasovagal syncope who were implanted dual-chamber pacemakers with rate hysteresis. These pulse generators had sensors that detected the fall in heart rate to 40–50 beats/min and responded with pacing rates of 80–90 beats/min. During the follow-up of 39±19 months, 89% of patients reported symptomatic improvement and 62% had no recurrence of syncope. 

A similar benefit was reported using a permanent dual-chamber rate-drop response pacing algorithm by Benditt et al.46 With this feature, the pacemaker can be programmed to detect a small rapid drop of heart rate and then pace at a relatively high rate to provide chronotropic support during the time of presumed vasodilatation. All the parameters, i.e. the lowest rate, top rate and the time period are programmable. During an average follow-up of 6 months, syncope was prevented in 78% of cases. 

A third type of pulse generator with automatic rate-drop sensing mode was tested by Sheldon et al.47 In this, the dual-chamber pacemaker paces if the sensed heart rate drops by >15 beats/min/beat. The initial pacing rate is 15 beats/min below the rate preceding the rate decrease, and then slowly decreases at 0.5 beats/min/beat until the intrinsic heart rate exceeds it. With this "rate smoothening" pacing algorithm, the frequency of syncope was reduced by 93% and 50% had no recurrence. The median time to syncope recurrence before and after pacing was 7 days and 5.3 months, respectively. There was also a marked improvement in the quality of life.

Thus, irrespective of the algorithm used, benefit was demonstrated in these nonrandomized studies with permanent dual-chamber pacing, and the results were comparable. A recent study has now confirmed the benefit of dual-chamber pacing over single-chamber ventricular pacing.48 However, as these trials were historically controlled, the next step was to demonstrate the benefit in controlled studies.

Randomized pacemaker trials: There are only a few controlled trials available to study the efficacy of pacing in vasovagal syncope. 

The North American Vasovagal Pacemaker Study (VPS-I) 49 was the first randomized trial to show benefit with permanent pacing. In this trial, 54 patients with more than six lifetime episodes of syncope and a positive HUTT (with syncope or presyncope and relative bradycardia), were randomized to dual-chamber pacing with rate-drop response and no pacing. Patients in both the groups were permitted to receive medical treatment according to the judgment of treating physician. It was found that syncope recurred in 19/27 (70%) patients who did not receive pacemaker compared to 6/27 (22%) in the pacemaker group, showing a 85.4% relative risk reduction. However, there was no difference in the occurrence of presyncope, with at least one episode of presyncope reported by 74% of the no pacemaker group and 63% of the pacemaker group. The mean time from randomization to syncope also increased in the pacemaker group (112 days) compared to no pacemaker group (54 days) . However, it was an open-label study, therefore a placebo-type effect or psychological benefit from receiving a pacemaker cannot be excluded. Also, there was no standardization of medical therapy in the study. At the end of the study, it was not clear whether the conventional bradycardia support benefited the patients or the rate-drop response alogrithm. This particular aspect would become clear after publication of the results of the VPS-II trial, comparing the effectiveness of DDD pacing with and without the rate-drop response, which is currently in progress. 

The Vasovagal Syncope International Study (VASIS) investigators50 showed that plain DDI pacing with rate hysteresis reduced the likelihood of syncope in a select high-risk group. They included 42 patients who had at least three syncopal episodes in the preceding two years with a positive cardioinhibitory response to HUTT. Ninteen patients received DDI pacemakers programmed to 80 beats/min with rate hysteresis of 45 beats/min and 23 received no pacemaker. No drugs were prescribed in either group. There was recurrent syncope in 14/23 (61%) patients after a median time of 5 months in the no pacemaker group versus 1/19 (5%) in the pacemaker group (after 15 months) (p <0.0006). This benefit was maintained over a long period (mean follow-up 3.7±2.2 years). The Kaplan–Meier actuarial estimates of the first recurrence of syncope after 1, 3 and 5 years were 0%, 6% and 6% in the pacemaker group and 39%, 50% and 75% in no pacemaker group, respectively. There was recurrence in only 5%, a rate much lower than previous studies, including VPS-I. In this trial, the highest-risk category patients with a severe cardioinhibitory response to the tilt test were selected – 79% of pacemaker-treated patients and 91% of controls had an asystolic response during HUTT. Thus, in this study, patients with a more severe cardioinhibition were included, compared with the VPS-I study, in which only one-third of patients developed a heart rate of less than 40 beats/ min at baseline tilt test. Like the previous VPS trial, the placebo effect cannot be excluded as the control group did not include implantation of a device. Recurrences of presyncope and dizziness were not studied. 

Ammirati et al.51 recently published the first randomized, controlled trial comparing the effect of medical treatment with pacemaker therapy (DDD with rate-drop response) in patients with recurrent vasovagal syncope. The inclusion criteria were similar to those of the VASIS study.45 Of the 93 patients randomized, 46 received a DDD pacemaker with rate-drop response. The other 47 patients were given atenolol 100 mg/day. There was a recurrence in 2/46 (4.3%) patients in the pacemaker group after a median time of 390 days as compared with 12/47 (25.5%) patients on atenolol therapy after a median of 135 days (p=0.004). Pacemaker therapy was associated with 93% actuarial probability of remaining free of syncopal recurrence after 3 years, whereas in the medically treated group, the probability was reduced to only less than 67% for the same period of time. This study was not blinded and there was a bias towards giving the pacemaker option to older, highly symptomatic patients. Data on presyncope were not collected. Although 26% of patients in the atenolol group reported side-effects, only one patient discontinued therapy. 

In a small study of 12 severely symptomatic children, McLeod et al.48 performed a three-way, double-blind, randomized, crossover study in which the pacemakers were programmed to sensing only (no pacing), single-chamber ventricular pacing with rate hysteresis or dual-chamber pacing with rate-drop response for 4-month periods, with each patient randomized to one of the 6 possible orders of the 3 pacing modes. They found that both VVI and DDD pacing significantly reduced the episodes of syncope compared with no pacing (p=0.0078). This proved the beneficial role of pacing over and above any possible placebo effect. VVI and DDD pacing were comparable in terms of reducing syncope but the dual-pacing mode was superior when presyncope was also considered (p=0.039). 

These trials included only a highly selected group of "fainters"—high frequency of syncopal attacks, severe cardioinhibition with asystole or syncope during HUTT. Clinical improvement has been demonstrated in all the randomized studies. However, how much of this benefit is because of the psychological impact of a surgical procedure imparting a placebo effect has to be further looked into. In the VPS-I study, there was an absence of any reduction in the frequency of presyncopal attacks in the paced patients. The investigators used this negative point to eliminate any concerns regarding placebo effect, arguing that if placebo effect could decrease the incidence of syncope, it should also reduce the frequency of episodes of presyncope or light-headedness. The study by McLeod et al.48 is the only one so far that has demonstrated the superiority of pacing over no pacing. However, this was only a small study involving 12 children with documented asystole of >4 s.

Selection of patients: Almost all trials have used tilt testing to identify patients who would benefit from permanent pacing. But the hypothesis on which this selection is based, i.e. the greater the cardioinhibition, the more the likelihood of pacing therapy being effective, has yet to be confirmed. Follow-up studies of asystolic responders on tilt testing did not reveal a more malignant outcome.3,4 In the study by Peterson et al.45 on pacing, patients with an asystolic response during tilt testing fared no better than those with less severe cardioinhibition. It is also uncertain whether bradycardia during tilt testing automatically translates into bradycardia during clinical syncope. Whether a negative test on temporary pacing can predict a long-term favorable effect on permanent pacemaker is also not proved. In the VASIS study,50 the long-term efficacy of a permanent pacemaker was clearly demonstrated despite repeat tilt testing at 15 days showing no benefit of pacing over placebo (the positive response on tilt test being 59% and 61%, respectively). Similarly, in the study by Sheldon et al.,47 the outcome of the tilt test did not have any bearing on whether patients had recurrence of syncope after pacemaker insertion. One of the 2 patients with negative tilt test results had a recurrence, compared to 5 of 10 patients with positive test results. 

The higher frequency of syncopal episodes has also been shown to be predictive of a greater probability of syncopal relapse.52,53 However, in all the randomized trials, there was a low recurrence rate despite the predicted high risk of relapse in the highly symptomatic study population. For example, in the control arm of the VASIS study, there was a recurrence rate of 0.44% per year during a follow-up of more than 3 years. Because this was lower than in the 2 years preceding enrollment, there was an obvious spontaneous decrease in the syncopal episodes even in the absence of any active or placebo treatment. The cyclic course of vasovagal syncope, the possible therapeutic effect of tilt training and patient education are confounding factors that may be responsible for the observation. Patients who are older and have a history of traumatic falls are often considered likely candidates for permanent pacing. However, logical as it seems, there is no data to substantiate this. At present, tilt testing and clinical presentation are relied upon to select patients for pacing; the future may lie in implantable loop recorders that would correctly identify the cardiac event responsible.

Type of pacing: The pacemakers used to treat vasovagal syncope detect decrease in heart rate as the sensed event in 1 of the 3 options. All the three sensing modes—rate-drop response,46,49,51 rate smoothening 47 and rate hysteresis 42,45,50 —have demonstrated comparable benefit with both temporary and permanent pacing. No large study comparing these different modes is available. Future trials such as VPS-II might show the superiority of one specialized pacing algorithm over the other.

Ideal end-point: One of the important issues is to establish a consensus for assessing the efficacy of treatment in vasovagal syncope. Syncope is known to occur in clusters with long, symptom-free intervals. Therefore, recurrence of syncope is not an ideal end-point to establish efficacy. Other end-points such as time to first recurrence, asymptomatic intervals and overall syncopal burden over a period of time should also be considered.

Conclusions: Does the demonstrable benefit in three successive randomized trials mean lowering of the threshold for permanent pacing in vasovagal syncope? At present, cautious optimism would be advisable. A careful assessment of the clinical profile, the physical, psychological and social handicap, and other factors such as occupational necessity is required. Tilt testing remains the only test that one turns to, despite its limitations. In future, implantable loop recorders would probably prove to be more useful. Larger, multicenter studies with longer follow-up are needed to resolve many unanswered questions. But for now, it seems prudent to limit pacemaker use to a few select, severely symptomatic patients who are resistant to drugs and who are particularly prone to injuries or accidents.

Correspondence: 
Dr VK Bahl, 
Professor of Cardiology, 
All India Institute of Medical Sciences, 
New Delhi 110029. 
e-mail: vkbahl@satyam.net.in  

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