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Cardiac Origins of the Postural Orthostatic Tachycardia Syndrome
Open accessAbstract
Objectives To test the hypothesis that a small heart coupled with reduced blood volume contributes to the Postural Tachycardia Syndrome (POTS), while exercise training improves this syndrome. Background Patients with POTS have marked increases in heart rate during orthostasis. However, the underlying mechanisms are unknown and the effective therapy is uncertain. Methods Twenty-seven POTS patients underwent autonomic function tests, cardiac MRI, and blood volume measurements. Twenty-five of them participated in a 3-mo specially designed exercise training program with 19 completing the program; these patients were reevaluated after training. Results were compared with those of 16 healthy controls. Results Upright heart rate and total peripheral resistance were greater, while stroke volume and cardiac output were smaller in patients than controls. Baroreflex function was similar between groups. Left ventricular mass (median [25%, 75%], 1.26 [1.12, 1.37] vs 1.45 [1.34, 1.57] g/kg; P<0.01) and blood volume (60 [54, 64] vs 71 [65, 78] ml/kg; P<0.01) were smaller in patients than controls. Exercise training increased left ventricular mass and blood volume by ~12% and ~7%, and decreased upright heart rate by 9 [1, 17] bpm. Ten out of 19 patients no longer met POTS criteria after training, while patients’ Quality of Life assessed by Short-Form 36 was improved in all patients after training. Conclusions Autonomic function was intact in POTS patients. The marked tachycardia during orthostasis was attributable to a small heart coupled with reduced blood volume. Exercise training improved or even cured this syndrome in the majority of patients. It seems reasonable to offer POTS a new name based on its underlying pathophysiology – “The Grinch Syndrome”, because in this famous children’s book by Dr. Seuss, the main character had a heart that was “two sizes too small.”
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“Deconditioned patients with POTS have reduced left ventricular mass, stroke volume, and blood volume,35 which improve with exercise training.”
From 2015 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia, and Vasovagal Syncope (2015) · cites this paper as [35]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Figure 2B shows the tight relationship between stroke volume and HR in men, healthy women, and women with POTS (4,12).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“healthy women have smaller stroke volumes and higher HRs compared with healthy men, whereas women with POTS have both an exaggerated fall in stroke volume and an apparent compensatory rise in HR.”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“One feature that appears to be universally present in all POTS is cardiovascular deconditioning, a specific biological process characterized by cardiac atrophy and hypovolemia (4).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Multiple parameters associated with deconditioning have also been demonstrated in POTS patients, including reduced cardiac size and mass (by 16%), reduced blood volume (by 20%), reduced stroke volume, and reduced peak oxygen uptake (VO 2 peak) when compared with matched sedentary controls (4).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [4]
Experimental — accuracy not yet measured
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In the citing paper
“The majority of patients who complete the exercise training program no longer meet criteria for POTS, and the vast majority, if not all patients, report improved quality of life using a reliable and valid questionnaire (4,101).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [4]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Most patients with POTS have low cardiac stroke volume,26 which may cause the sinus tachycardia.”
From Diagnosis and management of postural orthostatic tachycardia syndrome (2022) · cites this paper as [26]
The cited source says what the claim attributes to it.
In the citing paper
“The findings of a 2010 case–control intervention study suggest that regular, nonupright exercise with a focus on aerobic reconditioning improves cardiovascular hemodynamics and symptoms in patients with POTS.26”
From Diagnosis and management of postural orthostatic tachycardia syndrome (2022) · cites this paper as [26]
The cited source says what the claim attributes to it.
In the citing paper
“More commonly proposed causes include partial peripheral neuropathy (“neuropathic POTS”),19 a deficit in blood volume, abnormalities in the renin-angiotensin-aldosterone system (RAAS)20, physical deconditioning,10 autoantibodies targeting peripheral adrenergic receptors21 and a hyperadrenergic state resulting from central activation of the sympathetic nervous system (“HyperPOTS”).”
From Hyperadrenergic Postural Tachycardia Syndrome: Clinical Biomarkers and Response to Guanfacine (2024) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“direct testing of autonomic function in this patient population is often normal/appropriate for the hemodynamic stress (4).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“the positive response these patients have to exercise training, which has been demonstrated to expand blood volume and increase cardiac size and mass in POTS patients and result in a prominent decrease in symptoms (4,63,64).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Research has demonstrated that physical reconditioning with a short-term (3 month) progressive exercise training program leads to improvement or remission of POTS in the majority of patients (4,64).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [4]
In the citing paper
“The three-month Dallas Program, which involves aerobic exercise coupled with resistance training, improves orthostatic and exercise tachycardia, symptoms, and quality of life [13;62;63].”
From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [13]
In the citing paper
“Although it may not be clear if deconditioning is a primary problem or secondary to POTS, many patients with POTS do have cardiovascular deconditioning and do benefit from a program of aerobic exercise and resistance training [13].”
From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [13]
In the citing paper
“One of the more consistent findings in patients with POTS is a deficit in total blood, plasma and red cell volume [45;13;46].”
From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [13]
In the citing paper
“Improvement is related to an increase in the size of the heart and increased blood volume [13]. The improved stroke volume decreases tachycardia.”
From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [13]
In the citing paper
“This finding suggests that deconditioning, with its subsequent plasma volume reduction and decreased stroke volume, may play a significant role in the development of a POTS phenotype (42).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [42]
In the citing paper
“POTS patients who participated in and completed 3 months of exercise training garnered a significant reduction in orthostatic tachycardia and experienced significant increases in blood volume (42).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [42]
In the citing paper
“In fact, 50-70% of POTS patients who complete 3 months of endurance training exhibit hemodynamic changes that no longer meet criteria for POTS (42, 62, 63).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [42]
In the citing paper
“Exercise training may be very effective and has been shown to alleviate the symptoms of POTS-related deconditioning [66,67].”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [66]
In the citing paper
“Studies that reported a plasma volume deficit in POTS patients despite a normal- to high-sodium diet (≥150 mEq sodium/day) (6, 14, 15), suggest that patients may not effectively respond to dietary sodium with plasma volume expansion.”
From Effect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome (2021) · cites this paper as [15]
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Metadata
- Authors
- Fu, Q., VanGundy, T. B., Galbreath, M. M., Shibata, S., Jain, M., Hastings, J. L., Bhella, P. S., & Levine, B. D.
- Affiliations
- Texas Health Dallas (US)
- Corresponding author
- Levine, Benjamin D.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 55
- Issue
- 25
- Pages
- 2858-2868
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC2914315
- OpenAlex
- W2130006990
- Semantic Scholar
- 7b8f40b47ff2bed4e58746aa87dd800496a2230c
- Cited by
- 329
- References
- 62
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 30 · 2023: 23 · 2022: 26 · 2021: 26 · 2020: 31 · 2019: 16 · 2018: 19 · 2017: 18 · 2016: 19 · 2015: 14 · 2014: 16 · 2013: 9 · 2012: 18
- FWCI
- 16.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (HL075283)
- National Space Biomedical Research Institute (CA00701)
- Clinical and Translational Research Center(formerly the General Clinical Research Center (RR00633)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Keywords
- postural orthostatic tachycardia syndrome, cardiac output, stroke volume, blood volume, left ventricular mass, exercise training, orthostatic tachycardia, autonomic function, baroreflex, systemic vascular resistance, quality of life
- MeSH terms
- Adult, Blood Pressure Determination, Blood Volume, Electrocardiography, Postural Balance, Female, Follow-Up Studies, Heart Diseases, Heart Rate, Hemodynamics, Humans, Magnetic Resonance Imaging, Male, Probability, Reference Values, Severity of Illness Index, Exercise, Case-Control Studies, Treatment Outcome, Risk Assessment, Tilt-Table Test, Statistics, Nonparametric, Postural Orthostatic Tachycardia Syndrome, Young Adult
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