How does Postural Orthostatic Tachycardia Syndrome (POTS) cause chronic fatigue?

From the Guidelines

Postural Orthostatic Tachycardia Syndrome (POTS) causes chronic fatigue through a complex interplay of autonomic nervous system dysfunction, deconditioning, and orthostatic intolerance, leading to reduced blood flow, increased heart rate, and energy-consuming compensatory mechanisms. The pathophysiology of POTS is debated and likely heterogeneous, involving factors such as deconditioning, immune-mediated processes, excessive venous pooling, and a hyperadrenergic state 1. When a person with POTS stands up, their heart rate increases abnormally, while their blood pressure fails to regulate properly, leading to reduced blood flow to the brain and other organs, causing fatigue.

Key mechanisms contributing to chronic fatigue in POTS include:

• Reduced blood flow to the brain and other organs due to orthostatic intolerance
• Increased heart rate and release of stress hormones, which is energy-consuming and exhausting over time
• Poor sleep quality, deconditioning from reduced activity, and blood pooling in the lower extremities, further reducing effective circulation
• Hyperadrenergic states, where excess adrenaline causes energy crashes

Management of POTS typically includes non-pharmacological interventions such as:

• Increased fluid intake (2-3 liters daily) and salt consumption (3-10g daily) to address reduction in plasma volume
• Elevation of the head of the bed with 4-6 inch blocks during sleep
• Use of support stockings (waist-high) to ensure sufficient support of central blood volume
• Gradual exercise programs, which have been shown to support long-term cardiovascular health 1

Pharmacological therapies may also be used empirically, such as:

• Low-dose beta-blockers (e.g., propranolol 10-40mg) to slow the heart rate and alleviate symptoms
• Fludrocortisone (0.1-0.2mg) to increase blood volume and help with orthostatic intolerance
• Midodrine (2.5-10mg three times daily) to help with orthostatic intolerance
• Ivabradine, which has been used in patients with severe fatigue exacerbated by beta-blockers and calcium-channel blockers, with improvement in heart rate and quality of life observed in a trial of 22 patients with POTS 1.

From the Research

Postural Orthostatic Tachycardia Syndrome (POTS) and Chronic Fatigue

• POTS is a condition characterized by an abnormally large increase in heart rate upon standing, often accompanied by physical complaints such as fatigue 2.
• Fatigue is a significant symptom frequently reported by individuals with POTS, and its management requires an individualized approach 3.
• The relationship between POTS and chronic fatigue syndrome (CFS) has been explored in several studies, with some suggesting that POTS may be an under-recognized condition in CFS patients 4.

Comorbidity of POTS and CFS

• Studies have shown that a significant proportion of CFS patients also have POTS, with estimates ranging from 5.7% to 27% 4, 5, 6.
• CFS patients with comorbid POTS tend to be younger, have a shorter length of illness, and experience greater task difficulty compared to those without POTS 5.
• However, one study found that the prevalence of POTS in CFS patients was not significantly different from that in non-CFS fatigued patients, and that POTS was not a useful diagnostic marker for CFS 6.

Mechanisms and Predictors of Fatigue in POTS

• Increasing fatigue has been associated with an increase in heart rate in POTS patients 4.
• Heart rate variability has been identified as an important marker of fatigue in CFS patients, including those with comorbid POTS 5.
• Early heart rate changes and overall heart rate change have been shown to be significant predictors of completion status and perceived task difficulty in CFS-POTS patients 5.