Dietary Salt in Postural Tachycardia Syndrome

Patients with POTS may not adequately expand their plasma volume in response to a high-sodium (Na+) diet. Mechanisms involved in the regulation of plasma volume, such as the renin-angiotensin-aldosterone system and renal dopamine, 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 milliequivalents (mEq) Na+/day diet (POTS patients as inpatients; healthy control subjects with clinical research center (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 Nothing by mouth (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)

Randomization tables will be used to determine whether the 10 mEq sodium/day or 300 mEq sodium/day diet will be consumed first. Both diets will be completed on each subject (randomized crossover study), so all of the study procedures (after screening) will be repeated.

POTS and healthy controls will be randomly assigned the order of dietary sodium levels. All procedures are performed at both levels. The high sodium diet will provide 300 milliequivalents (mEq) sodium/day.

POTS and healthy controls will be randomly assigned the order of dietary sodium levels. All procedures are performed at both levels. The low sodium diet will provide 10 mEq sodium/day.

we will measure the amount of hemoglobin and myoglobin in the body by a procedure called CO rebreathing. One teaspoon of blood is taken before and after a small amount of CO has been absorbed into the bloodstream.

Using injection of iodinated I-131 tagged human serum albumin nominally 25 microcuries of radiation, blood samples are drawn before and 30 minutes after injection.

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.

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.

Plasma volume (PV) was determined by the indicator tracer-dilution technique, using the DAXOR Blood Volume Analyzer (BVA)-100 system (DAXOR Corporation), on Day 7 of the low sodium and high sodium dietary interventions. Outcome data are the absolute values for PV on Day 7 for each diet.

Whether upright plasma renin activity was modified appropriately by changes in dietary sodium in POTS & healthy controls. Outcome data are the absolute values for upright plasma renin activity on Day 7 of each diet.

Upright blood samples were collected after up to 30 minutes of standing on the 7th day of each dietary sodium intervention

Whether upright serum aldosterone was modified appropriately by changes in dietary sodium in POTS patients & healthy controls. Outcome data are the absolute values for upright serum aldosterone on Day 7 of each diet.

Upright blood samples were collected after up to 30 minutes of standing on the 7th day of each dietary sodium intervention

Whether the magnitude of the heart rate increase that occurs in patients with POTS when moving from a supine to an upright position is attenuated by a High Sodium diet relative to a Low Sodium diet. Heart rate was assessed after overnight rest and fasting after midnight, following at least 60 minutes of lying quietly. Heart rate was then measured at intervals after subjects had been standing for up to 30 minutes (as tolerated). Orthostatic tachycardia was calculated as the difference between standing and lying heart rates. Data are presented for 5 minutes standing (or maximal stand if <5 minutes) since several patients were unable to stand for 10 minutes. Data in POTS patients were compared to that of Healthy Controls.

Whether upright symptoms were improved in patients with POTS on a High Sodium diet relative to a Low Sodium diet. Patients were asked to report their standing symptom burden at the end of the Stand portion of the posture study, using the Vanderbilt Orthostatic Symptoms Scale (VOSS). They rated the severity of nine symptoms (palpitations, lightheadedness, mental confusion, blurred vision, shortness of breath, tremulousness, chest discomfort, headache, and nausea) on a scale from a minimum of 0 (reflecting an absence of symptoms) to a maximum of 10. The sum of the scores for the 9 symptoms was used to measure orthostatic symptom burden. Higher scores represent worse symptoms.

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

Garland EM, Gamboa A, Nwazue VC, Celedonio JE, Paranjape SY, Black BK, Okamoto LE, Shibao CA, Biaggioni I, Robertson D, Diedrich A, Dupont WD, Raj SR. Effect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome. J Am Coll Cardiol. 2021 May 4;77(17):2174-2184. doi: 10.1016/j.jacc.2021.03.005.