Introduction

What is Postural Orthostatic Tachycardia Syndrome?

Often abbreviated to POTS, this is a long-term health condition in which the autonomic nervous system, responsible for controlling functions that we don’t think about like blood pressure and heart rate, malfunctions. POTS causes symptoms such as dizziness and a fast heart rate.

In POTS, when standing, the blood vessels fail to constrict properly, and, as a result, blood pools at the feet instead. This results in inadequate blood supply to the brain, hence leading to dizziness or fainting. To compensate, the heart accelerates, causing you to experience a pounding or fluttering sensation in your chest. This is termed ‘orthostatic intolerance’ and essentially refers to an inability to assume an upright posture because of the symptoms this causes. 

Conventional treatments

Currently, there is no definitive treatment for POTS, so management focuses on alleviating individual symptoms through both non-pharmacological and pharmacological methods. Examples include:

• Non-pharmacological – increased salt and fluid intake, compression stockings, exercise training
• Pharmacological – fludrocortisone, ivabradine, midodrine, propranolol, pyridostigmine

Many of the drugs that show some efficacy in treating POTS are not actually licensed for this particular use, and treatment methods remain elusive. With greater funding for POTS research, it is hoped that more standard treatment options will become established and subsequently integrated into wider clinical practice to provide the much-needed benefits for patients with this condition.

What new treatments could we expect in the future?

Immunotherapy

Immunotherapy uses drugs or other biological molecules to upregulate or downregulate your immune response. While traditionally associated with cancer treatment, immunotherapy has potential clinical benefits in autoimmune diseases, immunodeficiencies, and inflammatory disorders too. 

Is POTS an autoimmune condition?

Autoimmune conditions occur when your immune system mistakenly identifies healthy cells as foreign and attacks them to cause a variety of symptoms. Such examples include coeliac disease, type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. 

Evidence has suggested the presence of an autoimmune mechanism in POTS. It is thought that those with the condition have increased levels of autoantibodies, a hallmark feature of autoimmune conditions.

If POTS can be grouped under this term, immunotherapy may be a suitable treatment option. Nelson et al. demonstrated a significant reduction in autonomic symptoms following immunotherapy with immunoglobulins or plasmapheresis.¹ A similar trend was found by Schofield and Chemali in 2019.²

However, uncertainty remains over the safety and efficacy of the long-term use of immunotherapy, and under what circumstances this treatment method should be used. Further research is needed to ascertain these answers. 

Radiofrequency ablation of the sinus node

Also known as catheter ablation, this procedure involves using radiofrequency energy to destroy heart tissue responsible for abnormal heart rhythms. Doing so allows your heart to return to its normal rhythm, without causing damage to the rest of the organ.

The sinus node is an area of the heart responsible for initiating the heartbeat. Therefore, catheter ablation may prove useful in POTS to treat the fast heart rate associated with the condition, particularly if you have refractory POTS, that is, symptoms that do not improve with heart rate inhibitors, such as propranolol, ivabradine, pyridostigmine, and verapamil.

What is the current evidence?

The evidence regarding radiofrequency ablation for POTS is mixed and a reserved approach is generally taken, owing to the risks of the procedure, for example, blood clots, infection, and unexpected damage to the heart and surrounding blood vessels. Furthermore, despite the painlessness of the procedure due to administration of an anaesthetic, it is relatively invasive and needs to be performed in a hospital.

Shen et al. concluded that despite sinus node modification significantly reduced heart rate, scores measuring the participants’ autonomic symptom burden did not improve following the procedure. Hence, combined with the risks of the procedure, sinus node modification is not recommended in patients with POTS.³

Conversely, other studies have reported complete symptom resolution and normalised heart rate activity was restored following ablation of the sinus node, suggesting an efficient and safe option.⁴

Pacemaker implantation

A pacemaker is a small, battery-powered device that is surgically implanted in your chest, and sends electrical impulses to help your heart pump at a normal rate.

The evidence for pacemaker use in POTS is limited. A retrospective study concluded that a particular treatment method reduced fainting episodes in the study subjects. Despite this benefit, the fast heart rate associated with a sitting or standing position persisted, highlighting the uncertainty of the implications of pacemaker implantation in clinical practice. With further research, clarifying the guidelines for this treatment option in POTS is crucial.⁵ 

Low-dose naltrexone

Commonly administered for the prevention of relapse in opioid- and alcohol-dependent patients, low-dose naltrexone can also be used in the treatment of other disorders, like POTS.

A case study by Weinstock et al. noted that a 6-week course of low-dose naltrexone improved problems with mood, memory, and sleep.⁶

Research suggests that the drug produces chemicals known as endorphins, which act on the gastrointestinal tract to improve dysmotility. This is a feature of POTS and is related to symptoms, including constipation, bloating, and abdominal pain.⁷

Low-dose naltrexone may reduce autoantibody production. As discussed earlier, high autoantibody levels are common in POTS patients, so a treatment method that opposes this would likely be beneficial.⁶

Antibiotic therapy

Gastointestinal dysmotility in POTS can lead to small intestinal bacterial overgrowth (SIBO), manifesting as abdominal pain, bloating, and bowel dysfunction.

Rifaximin, as an antibiotic, has been shown to combat this overgrowth to provide significant relief from gastrointestinal problems, making it a potential treatment for POTS patients with digestive issues.⁶

Vagus nerve stimulation

A recent randomised clinical trial were published, investigating the use of vagus nerve stimulation for POTS. Participants were given a device to clip onto the tragus to deliver a low level of electrical stimulation to the vagus nerve, responsible for controlling involuntary functions, such as digestion, and respiratory and heart rate. Results indicated an improvement in POTS symptoms, as well as decreased levels of autoantibodies.

The non-invasive nature of this treatment method, as well as the lack of side effects, vagus nerve stimulation could be extremely promising in the future treatment of POTS.⁸

Sodium chloride 0.9% infusions

This involves delivering sodium chloride directly into a vein. The infusion works by loading you with sodium, which increases blood volume and, in turn, blood pressure, so you do not feel as dizzy. Research provides evidence that IV infusions can significantly reduce POTS symptoms and improve quality of life⁹, while also being low-cost with relatively few side effects. However, the procedure can be time-consuming and must be performed in a hospital or other care environment. It is often used with caution owing to the possible risks such as infection at the infusion site.¹⁰ 

Why is it important to develop newer treatments?

POTS is a chronic condition that often requires long-term treatment for an extended period before you notice any symptom improvement. Concerns regarding the long-term use of drugs to treat POTS allows for alternative therapies, like vagus nerve stimulation and radiofrequency ablation, to be of great use in the future.

Many of the current pharmacological treatment options for POTS, including ivabradine and fludrocortisone, are described as ‘off-label’ and evidence of their efficacy remains unclear. Left untreated, POTS could lead to decreased muscle mass from extended periods of rest, or you may sustain a head injury if you frequently faint. Therefore, this area of research must receive greater awareness and more funding so that we can conduct larger clinical trials to establish treatment options with consistent results, allowing you to control your symptoms in the best way possible.¹¹

Summary

POTS is a chronic health condition characterised by autonomic dysfunction which commonly results in dizziness and a fast heart rate upon assuming an upright posture. Although conventional treatment options exist, their efficacy and safety remain unclear. Some of the newer upcoming treatment options include radiofrequency ablation, immunotherapy, and low-dose naltrexone. Although initial research seems promising, the efficacy and safety of the long-term use of these treatments are yet to be elucidated. By doing so, more uniform methods can be implemented in medical practice to allow POTS patients to manage their symptoms well and have a good quality of life.