Dietary Salt in Postural Tachycardia Syndrome

Patients with POTS may not adequately expand their plasma volume in response to a high-sodium diet. Mechanisms involved in the regulation of plasma volume, such as the renin-angiotensin-aldosterone system and renal DA, may be impaired in POTS and may respond inappropriately to changes in dietary sodium.The purpose of this study is to determine (1) whether a high dietary sodium level appropriately expands plasma volume in POTS; (2) whether plasma renin activity and aldosterone are modified appropriately by changes in dietary sodium in POTS; and (3) whether patients with POTS have improvements in their orthostatic tachycardia and symptoms as a result of a high dietary sodium level.

Study Day 1

• Start 150 mEq Na+/day diet (POTS patients as inpatients; healthy control subjects with CRC provided outpatient diet)
• Start a 24h urine collection (for Na+, K+, Cr, fractionated catecholamines)
• Blood work
• Blood volume - carbon monoxide rebreathing

Study Day 2

• Complete 24h urine
• Start STUDY DIET (10 mEq Na+/day or 300 mEq Na+/day in a random order) after 3 meals of 150 mEq Na+/day are complete; water ad lib

Study Day 3 - 5

• Continue STUDY DIET; water ad lib
• On Day 5, a 24 hr holter combined ECG monitor will be placed on the subjects.

Study Day 6

• Continue STUDY DIET; water ad lib
• Remove 24h Holter combined ECG monitor and BP monitor from subject
• Start a 24h urine collection (for Na+, K+, Cr, fractionated catecholamines)
• Complete questionnaires
• NPO after midnight for study next day

Study Day 7 (BIG DAY)

• Awaken early (~6am) to void (still collecting 24h urine)
• Patient returns to bed, IV catheter inserted
• Posture Study (in morning; between 7-8am ideally)
• Blood pressure and heart rate will be measured while supine and then while standing for up to 30 minutes
• We will draw 3 tablespoons of blood in each body position to measure hormones that regulate blood pressure and blood volume
• Hormones to verify the subject's phase of menstrual cycle
• Serum/plasma aliquots for future analysis
• Subjects will rate symptoms during supine period and at end of stand using Vanderbilt Orthostatic Symptoms Score (VOSS)
• Total Blood Volume (DAXOR)- using injection of iodinated I-131 tagged human serum albumin nominally 25 micro-Ci of radiation blood samples drawn through IV catheter before injection and for ~30 minutes post-injection (total - 25 ml)
• This will be done after supine assessment, but before standing the subject up
• Autonomic Function Test with Cardiac Output and Brief Tilt
• The subject will be tilted up to 60-75 degrees head-up tilt for up to 10 minutes to measure the changes in heart rate and blood pressure and symptoms with upright challenge.
• Blood volume - carbon monoxide rebreathing
• Exercise Capacity Test (in the afternoon) Will estimate maximal oxygen consumption (VO2 max) This test will be conducted on a stationary bicycle. Effort will be gradually increase while expired air is measured during exhaustive physical work.

All procedures are repeated at least a month later with the 2nd level of dietary salt. (Randomized to high or low salt to the first phase, the second phase is the remaining level)

• Radiation: Blood Volume
  we will measure the amount of hemoglobin and myoglobin in the body by a procedure called carbon monoxide (CO) rebreathing. One teaspoon of blood is taken before and after a small amount of CO has been absorbed into the bloodstream.
  Other Name: CO-RBC Blood Volume
• Radiation: Total Blood Volume
  Using injection of iodinated I-131 tagged human serum albumin nominally 25 micro-Ci of radiation, blood samples are drawn before and 30 minutes after injection.
  Other Name: DAXOR
• Procedure: Exercise Capacity Test - Bicycle
  subjects breath room air through a mouthpiece and exhale the air into a tube that connects to a machine (metabolic cart) that analyzes carbon dioxide and oxygen content, which allows the investigator to calculate the amount of oxygen they are using under resting and exercise conditions.
  Other Name: VO2 Max (maximal oxygen consumption)
• Procedure: Posture Study
  Blood pressure and heart rate will be measured while supine and then while standing for up to 30 minutes. Blood will be drawn in each position to measure hormones that regulate blood pressure and blood volume.
  Other Name: Standing Orthostatic Challenge

• Experimental: High Sodium Level
  POTS and healthy controls will be randomly assigned the order of dietary sodium levels. All procedures are performed at both levels.
  Interventions:

  • Radiation: Blood Volume
  • Radiation: Total Blood Volume
  • Procedure: Exercise Capacity Test - Bicycle
  • Procedure: Posture Study
• Experimental: Low Sodium Dietary Level
  Interventions:

  • Radiation: Blood Volume
  • Radiation: Total Blood Volume
  • Procedure: Exercise Capacity Test - Bicycle
  • Procedure: Posture Study

Inclusion Criteria:

• Diagnosed with postural tachycardia syndrome by the Vanderbilt Autonomic Dysfunction Center
• Increase in heart rate ≥30 beats/min with position change from supine to standing (10 minutes)
• Chronic symptoms consistent with POTS that are worse when upright and get better with recumbence
• Age between 18-50 years old
• Non-smokers
• Premenopausal patients with POTS and healthy volunteers
• Only female participants are eligible.
• Since 80-90% of POTS patients are female, and there can be differences in measures with the menstrual cycle, including a small number of males might introduce a significant amount of noise.
• Able and willing to provide informed consent

Exclusion Criteria:

• Smokers
• Overt cause for postural tachycardia, i.e., acute dehydration
• Significant cardiovascular, pulmonary, hepatic, or hematological disease by history or screening results
• Pregnant (positive pregnancy test) or breastfeeding
• Hypertension defined as supine resting BP>145/95 mmHg off medications or needing antihypertensive medication
• Other factors which in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies or an unpredictable schedule
• Unable to give informed consent