Cardiovagal Baroreflex Deficits Impair Neurovascular Coupling and Cognition in POTS

• Status: Active, not recruiting
• Trial end date: 2022-06-01
• Target enrollment: 0
• Participant gender: Female

Summary

Postural tachycardia syndrome (POTS), is the chronic form of orthostatic intolerance associated with excessive upright tachycardia, and occurs predominantly in young females (>85%). Among its most troubling symptoms are lightheadedness, fatigue, and decreased memory often called "brain fog" by patients. Task-related neurovascular coupling (NVC) links neural activity to an increase in CBF known as "functional hyperemia". Although memory task performance and NVC deteriorated with angle of tilt in POTS but not healthy controls, cerebral blood flow (CBF) remained similar to control. Instead, the investigators observed extensive narrow band low frequency (0.07-0.13 Hz) oscillations in BP (OBP) that entrained and amplified oscillations in CBF (OCBF). OBP and OCBF increased with tilt angle and caused impaired working memory and reduced functional hyperemia. The cardiovagal baroreflex couples BP to HR to buffer BP changes. The investigators hypothesize that the cardiovagal baroreflex becomes progressively impaired with orthostasis in POTS, but not in healthy volunteers, and accounts for OBP, OCBF, and loss of NVC; further, improving the baroreflex reduces OBP, OCBF and Brain Fog in POTS.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: New York Medical College
• Collaborator: National Institutes of Health (NIH)
• Treatments: Digoxin; Lactulose; Pyridostigmine Bromide

Criteria

Inclusion Criteria for POTS patients:

POTS patients referred for day to day orthostatic intolerance with greater than 3 symptoms for greater than 3 months and will have the diagnosis of symptomatic postural tachycardia made during a screening tilt table test :

• dizziness

• nausea and vomiting

• palpitations

• fatigue

• headache

• exercise intolerance

• blurred vision

• abnormal sweating heat.

Healthy control subjects:

• normal physical examination, and normal electrocardiographic and echocardiographic evaluations.

• Only those free from heart disease, and from systemic illness will be eligible to participate.

• This excludes patients with illnesses and disease states known to be associated with endothelial cell dysfunction such as diabetes, renal disease, congestive heart failure, systemic hypertension, acute and chronic inflammatory diseases, neoplasm, immune mediated disease, trauma, morbid obesity and peripheral vascular disease.

At the time of testing all patients and control subjects must refrain from vasoactive drugs for two weeks.

Exclusion Criteria for both POTS and healthy controls:

• An active medical condition that may explain the diagnosis

• A previous medical condition with undocumented resolution that may explain the diagnosis

• any systemic or overt structural, arrhythmic or myopathic cardiovascular disease

• any illnesses known to produce autonomic dysfunction such as diabetes, heart disease, renal disease, systemic hypertension, acute and chronic inflammatory diseases, neoplastic disease, immune mediated disease, major trauma and burns, morbid obesity and peripheral vascular disease will also be excluded.

• Cigarette smokers will be excluded.

• Past or present major psychiatric disorder

• Substance abuse within 2 years before onset of symptoms.