Postural orthostatic tachycardia syndrome: pathophysiology, management, and experimental therapies

ABSTRACT

Introduction

Postural orthostatic tachycardia syndrome (POTS) is an increasingly well-recognized condition encountered in clinical practice. Diagnosis and treatment remain extremely challenging. The limited success of currently available therapies has laid the foundation for a number of experimental therapies.

Areas Covered

In this review, we will briefly outline the pathophysiology and clinical features of this syndrome, before moving on to its management, with a specific focus on experimental pharmacological therapies. Finally, we briefly discuss POTS related to the SARS CoV-2 (COVID-19) pandemic.

Expert Opinion

Despite tremendous advances, the diagnosis and management of POTS remains extremely challenging. The multitude of contributory mechanisms, which predominate to varying degrees in different patients further complicates management. Improved characterization of pathophysiological phenotypes is essential to individualize management. Lifestyle measures form the first line of therapy, followed by beta-blockers, ivabradine, fludrocortisone, and midodrine. Supplemental therapies such as iron, vitamin D and α lipoic acid are quite safe and a trial of their use is reasonable. The use of erythropoietin, IVIG, desmopressin, etc., are more specialized and nuanced alternatives. In recent years, interest has grown in the use of cardiac neuromodulation. Though preliminary, some of these therapies are quite promising.

KEYWORDS:

• POTS
• postural orthostatic tachycardia syndrome
• pathophysiology

Article highlights

• Given the multitude of overlapping pathophysiological mechanisms in these patients, better pathophysiological phenotyping is essential to permit a more tailored approach to therapy.

• Lifestyle measures form the first line of therapy in all patients.

• The mainstay of pharmacotherapy as supported by the Heart rhythm society guidelines involves beta-blockers, ivabradine, fludrocortisone, and midodrine.

• A recent randomized trial by Taub et al. indicates that Ivabradine is a safe and effective option in improving both heart rate and quality of life.

• Supplemental therapies that follow include iron, vitamin D and perhaps α lipoic acid which are quite safe options. An ongoing trial on the utility of iron in this cohort could help better define its role in this subpopulation (NCT04855266).

• The use of erythropoietin, IVIG, desmopressin, etc., are usually much more specialized and a nuanced approach is essential, often with the involvement of a specialist in the field. The results of an ongoing randomized trial (iSTAND-NCT03919773) on the use of IVIG in these patients are awaited and could prove helpful in cohorts where underlying autoimmune mechanisms could be involved.

• Increasingly, interest has grown in the use of cardiac neuromodulation in the form of stellate blockade and vagal stimulation to name a few. Though very preliminary, these therapies are quite promising and could prove very effective in POTS.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.