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April 24, 2013

Low-dose propranolol and exercise capacity in postural tachycardia syndrome
A randomized study

May 21, 2013 issue
80 (21) 1927-1933

Abstract

Objective:

To determine the effect of low-dose propranolol on maximal exercise capacity in patients with postural tachycardia syndrome (POTS).

Methods:

We compared the effect of placebo vs a single low dose of propranolol (20 mg) on peak oxygen consumption (VO2max), an established measure of exercise capacity, in 11 patients with POTS and 7 healthy subjects in a randomized, double-blind study. Subjects exercised on a semirecumbent bicycle, with increasing intervals of resistance to maximal effort.

Results:

Maximal exercise capacity was similar between groups following placebo. Low-dose propranolol improved VO2max in patients with POTS (24.5 ± 0.7 placebo vs 27.6 ± 1.0 mL/min/kg propranolol; p = 0.024), but not healthy subjects. The increase in VO2max in POTS was associated with attenuated peak heart rate responses (142 ± 8 propranolol vs 165 ± 4 bpm placebo; p = 0.005) and improved stroke volume (81 ± 4 propranolol vs 67 ± 3 mL placebo; p = 0.013). In a separate cohort of POTS patients, neither high-dose propranolol (80 mg) nor metoprolol (100 mg) improved VO2max, despite similar lowering of heart rate.

Conclusions:

These findings suggest that nonselective β-blockade with propranolol, when used at the low doses frequently used for treatment of POTS, may provide a modest beneficial effect to improve heart rate control and exercise capacity.

Classification of evidence:

This study provides Class II evidence that a single low dose of propranolol (20 mg) as compared with placebo is useful in increasing maximum exercise capacity measured 1 hour after medication.

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Information & Authors

Information

Published In

Neurology®
Volume 80Number 21May 21, 2013
Pages: 1927-1933
PubMed: 23616163

Publication History

Received: October 13, 2012
Accepted: January 29, 2013
Published online: April 24, 2013
Published in print: May 21, 2013

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Disclosure

A. Arnold is funded by American Heart Association grant 11POST7330010. L. Okamoto, A. Diedrich, and S. Paranjape report no disclosures. S. Raj is funded by NIH grant R01 HL102387 and provides expert medical consulting for law firms regarding POTS patients. I. Biaggioni is a consultant for Chelsea Therapeutics and Astra Zeneca, is funded by NIH grants P01 HL056693 and U54 NS065736, and receives research support from Astra Zeneca and Forest Laboratories. A. Gamboa is funded by NIH grant K23 HL95905. Go to Neurology.org for full disclosures.

Study Funding

Supported by NIH grants P01 HL056693, 5U54NS065736, and UL1 TR000445.

Authors

Affiliations & Disclosures

Amy C. Arnold, PhD
From the Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
American Heart Association Grant 11POST7330010
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Luis E. Okamoto, MD
From the Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
André Diedrich, MD, PhD
From the Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
emedicine online article about Multiple System Atrophy50$
Employment, Commercial Entity:
1.
Autonomic Dysfunction Center, Vanderbilt University School of Medicine Research Professor of Medicine Adjunct Research Professor of Biomedical Engineering
Consultancies:
1.
NIH external reviewerNASA reviewer
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Autonomic Dysfunction Center, Vanderbilt University School of Medicine
Research Support, Government Entities:
1.
NIH/NHLBI 5P01 HL056693-14 (Robertson) NIH/NINDS 5U54 NS065736-02 (Robertson)NIH/NHLBI 1R01 HL102387-01A1 (Raj)
Research Support, Academic Entities:
1.
Autonomic Dysfunction Center, Vanderbilt University School of Medicine
Research Support, Foundations and Societies:
1.
NIH/NHLBI 5P01 HL056693-14 (Robertson) NIH/NINDS 5U54 NS065736-02 (Robertson)NIH/NHLBI 1R01 HL102387-01A1 (Raj)
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Sachin Y. Paranjape, BS
From the Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Satish R. Raj, MD
From the Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN.
Disclosure
Scientific Advisory Boards:
1.
1. I serve on the DSMB for a phase I study sponsored by ACORDA Pharamceuticals dealing with congestive heart failure 2. I serve on the DSMB for multiple investigator initiated NIH funded studies. I have received no monetary compensation for this work.
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
1. Autonomic Neurosciences: Basic & Clinical, Editorial Board; Clinical Summary Author; 2008-present 2. Clinical Autonomic Research, Editorial Board 3. Frontiers in Autonomic Neurosciences 4. Translational Cardiology
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
1. Vanderbilt University, Assistant Professor of Medicine 2. Veterans Affairs Medical Center (VISN9), Cardiologist
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
1. NIH/NCRR K23 RR020783, Principal Investigator (2005- 2010) 2. NIH/NHLBI P01 HL056693, Co-Investigator (2007-2012) 3. NIH/NHLBI R01 HL071784, Co-Investigator (2008-2013) 4. NIH/NINDS U54 NS065736, Co-Investigator (2009-2014) 5. NIH/NCRR UL1 RR0241975 (CTSA), Scientific Review Committee Member (2009-2013) 6. NIH/NHLBI R01 HL102387, Principal Investigator, 2009- 2014
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Italo Biaggioni, MD
From the Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN.
Disclosure
Scientific Advisory Boards:
1.
1) Chelsea Pharmaceuticals, Advisory Board, unrelated to this study
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
1) Chelsea Pharmaceuticals, reimbursement to present at a meeting, unrelated to this study
Editorial Boards:
1.
NONE
Patents:
1.
1) A2B antagonists for asthma 2) Automated abdominal binder Both unrelated to this study
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
1) Chelsea Therapeutics, droxidopa 2) Astra Zeneca, ticagrelor 3) Merk, A2A antagonists All unrelated to this study
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
1) Forest Laboratories, use of nevibolol for supine hypertension in autonomic failure 2) Astra Zeneca, role of adenosine uptake blockade on the effects of ticagrelor Both unrelated to this study
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Alfredo Gamboa, MD
From the Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NIH Grant K23 HL95905
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence to Dr. Gamboa: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Amy C. Arnold: drafting/revising the manuscript, analysis or interpretation of data, acquisition of data, statistical analysis. Luis E. Okamoto: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, acquisition of data. André Diedrich: drafting/revising the manuscript, analysis or interpretation of data, acquisition of data, statistical analysis. Sachin Y. Paranjape: drafting/revising the manuscript, acquisition of data, study supervision. Satish R. Raj: drafting/revising the manuscript, study concept or design, analysis or interpretation of data. Italo Biaggioni: drafting/revising the manuscript, study concept or design, study supervision. Alfredo Gamboa: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, acquisition of data, statistical analysis.

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  9. The prevalence of headache disorders in Postural Tachycardia Syndrome: A systematic review and meta-analysis of the literature, Cephalalgia, 42, 11-12, (1274-1287), (2022).https://doi.org/10.1177/03331024221095153
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