In a patient with hypermobile Ehlers‑Danlos syndrome who regularly does strength training with a personal trainer, brisk walks, light yoga, and physical‑therapy, should a beta‑adrenergic blocker be added to manage fatigue and orthostatic tachycardia?

Beta-Blocker Therapy for Fatigue and Orthostatic Tachycardia in hEDS

Beta-blockers should be considered for managing orthostatic tachycardia in hEDS patients who have failed conservative measures (hydration, salt intake, exercise training, compression garments), but they are not first-line therapy and should not be used primarily to target fatigue. 1

Treatment Algorithm for POTS in hEDS

Step 1: Conservative Management (First-Line)

The 2025 AGA guidelines explicitly recommend starting with non-pharmacologic interventions before considering medications 1:

• Increase fluid intake to 2-3 liters daily 1
• Increase salt intake (typically 6-10 grams daily unless contraindicated) 1
• Structured exercise training programs focusing on recumbent exercises initially, progressing to upright activities 1
• Compression garments (waist-high compression stockings, 30-40 mmHg) to reduce venous pooling 1

Step 2: Pharmacologic Therapy (When Conservative Measures Fail)

Beta-blockers and other medications should only be initiated when patients have moderate-to-severe functional impairment despite adequate trials of conservative treatments 1. The guideline specifically states that "special pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from multiple specialties (eg, cardiology, neurology) should be considered in patients who do not respond to conservative lifestyle measures" 1.

Key Considerations for Beta-Blocker Use

Mechanism and Rationale

In hEDS, abnormal connective tissue in dependent blood vessels permits excessive venous distension under normal hydrostatic pressure, leading to increased venous pooling and orthostatic symptoms 2. Beta-blockers work by controlling heart rate rather than addressing the underlying venous pooling mechanism 3.

Important Caveats

• Beta-blockers target heart rate control, not fatigue 1. Fatigue in hEDS is multifactorial and may relate to autonomic dysfunction, chronic pain, deconditioning, and sleep disturbances 3, 4
• Widespread but mild autonomic failure is present in 90% of hEDS patients 4, which may affect medication response
• Only 33% of patients with hEDS report positive outcomes from various medical interventions 5, highlighting the need for realistic expectations

Diagnostic Confirmation Before Treatment

Before initiating beta-blockers, confirm the presence of POTS through objective testing 4:

• Head-up tilt table testing to document heart rate increase ≥30 bpm (or ≥40 bpm in adolescents) within 10 minutes of standing 4
• Rule out other orthostatic disorders: orthostatic hypotension (9% prevalence), hypocapnic cerebral hypoperfusion (22%), or orthostatic cerebral hypoperfusion syndrome (18%) 4
• Assess for comorbid conditions: MCAS symptoms, gastrointestinal dysmotility, small fiber neuropathy (present in 64-82% of hEDS patients) 1, 4

Multidisciplinary Coordination

Integrated care from cardiology and/or neurology is essential when initiating pharmacologic therapy 1. Given that this patient already works with a physical therapist specializing in hEDS, coordination with that provider is critical to ensure exercise programming continues appropriately during medication titration 1, 6.

Common Pitfalls to Avoid

• Do not use beta-blockers as monotherapy without continuing conservative measures 1. Exercise training and hydration remain foundational even when medications are added
• Do not expect beta-blockers to improve fatigue directly 3. If fatigue is the primary concern rather than orthostatic tachycardia symptoms (palpitations, presyncope), beta-blockers may not provide benefit
• Do not initiate without objective POTS diagnosis 4. Subjective symptoms alone are insufficient given the 90% prevalence of autonomic dysfunction in hEDS 4