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Circulation. 2017;136:e60–e122. DOI: 10.1161/CIR.0000000000000499 August 1, 2017 e85 CLINICAL STATEMENTS AND GUIDELINES

5.2 Pacemakers in Vasovagal Syncope: Recommendation

Pacemakers might seem to be an obvious therapy for V VS, given that bradycardia and asystole are present during some spells. Numerous observational studies and RCTs have assessed whether pacemakers are efficacious in preventing syncope.404–409 It is becoming clear that strict patient selection on the basis of documented asystole during clinical syncope is important, and that observation combined with a tilt-table test that induces minimal or no vasodepressor response may increase the likelihood of a response to pacing. This is because a positive tilt-table test might identify patients who are likely to also have a vasodepressor response during V VS and therefore not respond as well to permanent pacing. As noted in Section 1.1, the recommendation in this section was based on a separately commissioned systematic review of the available evidence, the results of which were used to frame our decision making. Full details are provided in the ERC’s systematic review report.9

Recommendation for Pacemakers in V VS

COR LOE Recommendation IIb B-RSR Dual-chamber pacing might be reasonable in a select population of patients 40 years of age or older with recurrent V VS and prolonged spontaneous pauses.404–408,410

See Online Data Supplements 27 and 28. Among patients with a positive tilt-table test, a benefit of pacing for treatment of recurrent syncope was evident as compared with medical or no therapy in open-label trials,52,404,406,410–412 but this result must be interpreted with caution because of the possibility of outcome ascertainment bias. In 2 RCTs, there was no statistically significant benefit seen with active pacing.407,408 However, in a select population of patients >40 years of age with recurrent syncope and documented spontaneous pauses ≥3 seconds correlated with syncope or an asymptomatic pause ≥6 seconds, dual-chamber pacing reduced syncope recurrence. There was less benefit in patients with a positive tilt-table test that induced a vasodepressor response.405 SR indicates systematic review.

IIa B-R Midodrine is reasonable in patients with recurrent V VS with no history of hypertension, HF, or urinary retention.376–380

See Online Data Supplements 25 and 26. Midodrine is a prodrug that is metabolized to desglymidodrine, which is a peripherally active alpha-agonist used to ameliorate the reduction in peripheral sympathetic neural outflow responsible for venous pooling and vasodepression in V VS. Studies on the efficacy of midodrine support its use. In a meta-analysis of 5 RCTs in adults and children, midodrine was associated with a 43% reduction in syncope recurrence.318,376,378,379,381

IIb B-R The usefulness of orthostatic training is uncertain in patients with frequent V VS.382–386

See Online Data Supplements 25 and 26. There are 2 main methods of orthostatic training. Patients undergo repetitive tilt-table tests in a monitored setting until a negative tilt-table test occurs and then are encouraged to stand quietly against a wall for 30 to 60 minutes daily, or patients simply standing quietly against a wall at home for a prolonged period of time daily. RCTs have not shown a sustained benefit in reducing episodes of syncope recurrence with either option.382,383,385,387

IIb B-R Fludrocortisone might be reasonable for patients with recurrent V VS and inadequate response to salt and fluid intake, unless contraindicated.388,389

See Online Data Supplements 25 and 26. Fludrocortisone has mineralocorticoid activity resulting in sodium and water retention and potassium excretion, which results in increased blood volume. In a pediatric population, an RCT found more recurrent symptoms in the fludrocortisone arm than in the placebo arm.389 Serum potassium level should be monitored because of potential drug-induced hypokalemia. POST II (Prevention of Syncope Trial II) reported a marginally insignificant 31% risk reduction in adults with moderately frequent V VS, which was significant in patients after a 2-week dose stabilization period.388

IIb B-NR Beta blockers might be reasonable in patients 42 years of age or older with recurrent V VS.390–393

See Online Data Supplements 25 and 26. RCTs on the efficacy and effectiveness of beta blockers for the prevention of syncope have been negative.64,390–393 However, in a meta-analysis of a prespecified, prestratified substudy of POST I and a large observational study, an age-dependent benefit of beta blockers among patients ≥42 years of age was found, compared with those of younger age.394,395

IIb C-LD Encouraging increased salt and fluid intake may be reasonable in selected patients with V VS, unless contraindicated.396–399

N/A Evidence for the effectiveness of salt and fluid intake for patients with V VS is limited. Nonetheless, in patients with recurrent V VS and no clear contraindication, such as a history of hypertension, renal disease, HF, or cardiac dysfunction, it may be reasonable to encourage ingestion of 2 to 3 L of fluid per day and a total of 6 to 9 g (100 to 150 mmol) of salt per day, or about 1 to 2 heaping teaspoonfuls. The long-term balance of risks and benefits of a strategy of increasing salt and water intake is unknown. IIb C-LD In selected patients with V VS, it may be reasonable to reduce or withdraw medications that cause hypotension when appropriate.400

N/A A careful examination of the patient’s history for medications that may lower blood pressure (hypotensive agents) should be performed. Care should be taken to withdraw or reduce medications only where safe to do so and in conjunction with the prescribing healthcare provider. IIb C-LD In patients with recurrent V VS, a selective serotonin reuptake inhibitor might be considered.393,401,402

See Online Data Supplements 25 and 26. Serotonin has central neurophysiological effects on blood pressure and heart rate and acutely induces syncope during tilt-table testing.403 Three small RCTs on selective serotonin reuptake inhibitors have been conducted on the effectiveness of fluoxetine and paroxetine in preventing syncope, with contradictory evidence of effectiveness.393,401,402

Recommendations for V VS (Continued)

COR LOE Recommendations

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