Notice of Special Interest (NOSI): Stimulate Research on the Diagnosis, Treatment, and Mechanistic Understanding of Postural Orthostatic Tachycardia Syndrome (POTS)
Notice Number:

Key Dates

Release Date:

March 26, 2021

First Available Due Date:
June 05, 2021
Expiration Date:
May 08, 2024

Related Announcements

PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required)
PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

Issued by

National Heart, Lung, and Blood Institute (NHLBI)

National Institute of Neurological Disorders and Stroke (NINDS)


Background and Purpose

Individuals with Postural Orthostatic Tachycardia Syndrome (POTS) suffer from an excessive increase in heart rate (tachycardia) and other symptoms that worsen upon standing or sitting up, such as light-headedness, shortness of breath, chest pain, and palpitations. It is likely that POTS has multiple underlying mechanisms resulting in subtypes of POTS that need to be identified and characterized. There is evidence that POTS can arise from abnormalities in autonomic nervous system function, immune system function including autoimmunity, regulation of blood volume and blood flow, or a combination of these factors. Genetic factors probably also affect susceptibility to POTS. Many people with POTS report a preceding medical or life-changing event such as viral infection, concussion, surgery, pregnancy, or puberty. Due to the highly variable symptoms and signs of POTS across different people, it is likely that POTS is best defined as a syndrome with several subtypes that have distinct underlying causes.

There is no cure and no standardized therapy for POTS, and current treatment options focus on addressing symptoms rather than underlying disease processes. Many individuals with POTS benefit acutely from dietary salt and volume expansion, although there are no data on the long-term effects of such therapy. Drug therapies focused on increasing blood pressure, expanding blood volume, and lowering heart rate can also be helpful. Exercise training, with a primary focus on aerobic reconditioning, has also been shown to help. Non-cardiovascular symptoms may also benefit from treatment with non-pharmacological and pharmacological approaches.

Research Objectives

POTS can be a debilitating condition that affects routine activities such as working or attending school. POTS primarily affects women of child-bearing age, with most studies reporting 80-90% female predominance. The peak incidence is at age 14 years, but half of all individuals with POTS develop it in adulthood. While there are no precise data on the prevalence of POTS, it is estimated to affect 0.2-1% of the U.S. population.

There is thus a compelling need to stimulate research to understand the causes of POTS in order to inform the development of treatments. Improving the diagnosis of POTS through the development of biomarkers or improved diagnostic tools represents another major need. Translational studies and mechanistic clinical trials to guide the development of better treatments are also important goals. This NOSI signals interest in this important area with the goal of stimulating research applications to address these critical needs.

Suggested research examples include, but are not limited to:

  • Studies to understand causes and mechanisms of POTS, e.g. neuropathology, cardiovascular structure and function, immunology, neurocognitive function
  • Diagnostic, prognostic, and monitoring biomarker studies
    • Fluid biomarkers – e.g., blood tests to diagnose POTS or monitor the effect of a therapy
    • Imaging biomarkers – e.g., functional MRI of the brain, PET and SPECT studies of cardiac sympathetic neuronal function
    • Biomarker studies of relevance to NINDS are encouraged to review the NINDS Biomarker Program
  • Longitudinal natural history of POTS
  • Genetic and epigenetic studies to understand clustering in families, female predominance, and race/ethnic predilections to POTS

Application and Submission Information

This notice applies to due dates on or after June 5, 2021 and subsequent receipt dates through May 7, 2024.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

  • PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required)
  • PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

  • For funding consideration, applicants must include NOT-HL-21-008 in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.


Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)
Denis Buxton, PhD
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0515

Vicky Whittemore, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1917

Financial/Grants Management Contact(s)
Lynn Rundhaugen
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-480-4546


Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices