What is the management approach for a patient with episodes of syncope and suspected Postural Orthostatic Tachycardia Syndrome (POTS) with a negative tilt test?

Management of Suspected POTS with Negative Tilt Test

For patients with suspected Postural Orthostatic Tachycardia Syndrome (POTS) and episodes of syncope with a negative tilt test, an implantable loop recorder should be considered as the next diagnostic step, followed by a comprehensive treatment approach focusing on non-pharmacological measures including increased fluid and salt intake, physical counterpressure maneuvers, and exercise training.

Diagnostic Considerations

Understanding Negative Tilt Test Results

• A negative tilt table response does not exclude the diagnosis of reflex syncope or POTS 1
• The clinical significance of tilt test responses in predicting spontaneous syncope behavior has been questioned in recent studies 1
• Studies comparing tilt test responses with spontaneous syncope recorded by implantable loop recorders show that a negative response does not exclude the presence of asystole during spontaneous syncope 1

Further Diagnostic Testing

• When the mechanism of syncope remains unclear after initial evaluation including a negative tilt test, an implantable loop recorder is indicated in patients with recurrent syncope 1
• Implantable loop recorders have shown a diagnostic yield of over 90% in patients with unexplained syncope when monitored for approximately one year 1
• In patients with negative tilt testing and electrophysiological testing, implantable monitoring has been shown to establish a diagnosis in all patients who had recurrent episodes 2

Coexistence of POTS and Neurally Mediated Syncope

• Evidence suggests that POTS and neurally mediated syncope (NCS) may coexist in the same patient as combined forms of autonomic dysfunction 3
• Although syncope occurs in patients with POTS, it is relatively infrequent, and there is little evidence that the syncope is directly due to POTS 1
• Some patients may demonstrate a typical POTS pattern initially on tilt testing, but with continued tilting may develop a neurocardiogenic pattern 3

Treatment Approach

Non-Pharmacological Interventions

• Patient education on the diagnosis and prognosis is essential 1
• Increased fluid and salt intake may be reasonable in selected patients with vasovagal syncope (VVS), unless contraindicated 1
  • Encourage ingestion of 2-3 L of fluid per day
  • Total salt intake of 6-9 g (100-150 mmol) per day
• Physical counter-pressure maneuvers can be useful in patients who have a sufficiently long prodromal period 1
  • Leg crossing, limb/abdominal contraction, and squatting
  • These maneuvers have been shown to be superior to conventional therapy alone in preventing syncope recurrence 1
• Regular exercise training to improve orthostatic tolerance 4

Pharmacological Options

• Midodrine is reasonable in patients with recurrent vasovagal syncope who have no history of hypertension, heart failure, or urinary retention 1
  • Meta-analysis of 5 RCTs showed a 43% reduction in syncope recurrence 1
• Fludrocortisone might be reasonable for patients with recurrent vasovagal syncope and inadequate response to salt and fluid intake, unless contraindicated 1
  • Serum potassium levels should be monitored due to potential drug-induced hypokalemia 1
• Beta blockers might be reasonable in patients 42 years of age or older with recurrent vasovagal syncope 1
  • Meta-analysis showed an age-dependent benefit among patients ≥42 years of age 1

Medication Review

• In selected patients, it may be reasonable to reduce or withdraw medications that cause hypotension when appropriate 1
• Careful examination of the patient's history for medications that may contribute to hypotension is important 1

Special Considerations

Psychiatric Assessment

• Psychiatric assessment is recommended in patients with frequent recurrent syncope who have multiple other somatic complaints and when initial evaluation raises concerns for stress, anxiety, and possible psychiatric disorders 1
• In patients with suspected psychogenic pseudosyncope, a candid discussion about the diagnosis and cognitive behavioral therapy may be beneficial 1

Monitoring and Follow-up

• Regular follow-up to assess treatment effectiveness and symptom recurrence 4
• Patients should be educated on recognizing prodromal symptoms and implementing preventive measures 1
• Quality of life assessment should be part of the follow-up evaluation 4

Pitfalls and Caveats

• A negative tilt test should not exclude the diagnosis of POTS or reflex syncope if clinical suspicion is high 1
• Tilt testing has no value in assessing treatment efficacy 1
• The diagnosis of POTS requires a heart rate increase of ≥30 bpm (or ≥40 bpm in those 12-19 years old) within 10 minutes of standing, in the absence of orthostatic hypotension 1
• Treatments that improve symptoms of POTS might decrease the occurrence of syncope, although this relationship is not well established 1