Advertisement
Mayo Clinic Proceedings Home

Efficacy of Therapies for Postural Tachycardia Syndrome: A Systematic Review and Meta-analysis

  • Rachel Wells
    Affiliations
    Centre for Heart Rhythm Disorders, University of Adelaide, Adelaide, South Australia, Australia

    South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia

    Royal Adelaide Hospital, Adelaide, South Australia, Australia
    Search for articles by this author
  • Adrian D. Elliott
    Affiliations
    Centre for Heart Rhythm Disorders, University of Adelaide, Adelaide, South Australia, Australia

    South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
    Search for articles by this author
  • Rajiv Mahajan
    Affiliations
    Centre for Heart Rhythm Disorders, University of Adelaide, Adelaide, South Australia, Australia

    South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia

    Royal Adelaide Hospital, Adelaide, South Australia, Australia
    Search for articles by this author
  • Amanda Page
    Affiliations
    Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide, Adelaide, South Australia, Australia

    South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
    Search for articles by this author
  • Valeria Iodice
    Affiliations
    University College London, National Hospital for Neurology and Neurosurgery, London, United Kingdom
    Search for articles by this author
  • Prashanthan Sanders
    Affiliations
    Centre for Heart Rhythm Disorders, University of Adelaide, Adelaide, South Australia, Australia

    South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia

    Royal Adelaide Hospital, Adelaide, South Australia, Australia
    Search for articles by this author
  • Dennis H. Lau
    Correspondence
    Correspondence: Address to Dennis H. Lau, MBBS, PhD, Centre for Heart Rhythm Disorders, Department of Cardiology, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000 Australia.
    Affiliations
    Centre for Heart Rhythm Disorders, University of Adelaide, Adelaide, South Australia, Australia

    South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia

    Royal Adelaide Hospital, Adelaide, South Australia, Australia
    Search for articles by this author

      Abstract

      Objective

      To identify the evidence base and evaluate the efficacy of each treatment for postural tachycardia syndrome (POTS) in light of a recent consensus statement highlighting the lack of treatment options with clear benefit to risk ratios for this debilitating condition.

      Methods

      The CENTRAL (Cochrane Central Register of Controlled Trials), PubMed, and Embase databases from inception to May 2017 were searched using the terms postural AND tachycardia AND syndrome. A total of 135 full-text publications were screened after excluding duplicates (n=681), conference abstracts (n=467), and records that did not relate to POTS therapy (n=876). We included 28 studies with at least 4 patients with POTS in which symptomatic response was reported after more than 4 weeks of therapy. This review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Two investigators independently performed the data extraction and evaluated the quality of evidence.

      Results

      This study comprised 25 case series and 3 small randomized controlled trials that evaluated 755 and 103 patients with POTS, respectively. Interventions directed at increasing intravascular volume, increasing peripheral or splanchnic vascular tone, controlling heart rate, and increasing exercise tolerance demonstrate moderate efficacy (range, 51%-72%). Few data exist on their comparative effectiveness. Significant heterogeneities were seen in terms of patient age, symptom severity, and the measures used to evaluate treatment efficacy.

      Conclusion

      The current evidence base to guide optimal management of patients with POTS is extremely limited. More high-quality collaborative research with standardized reporting of symptom response and treatment tolerability is urgently needed.

      Abbreviations and Acronyms:

      bid (twice daily), CNHSQ (Children's National Health System Questionnaire), EPO (erythropoietin), FeSo4 (ferrous sulfate 300 mg tid), IM (intramuscular), IV (intravenous), LAR (long-acting release), NA (not available), OD (once daily), OHQ (Orthostatic Hypotension Questionnaire), POTS (postural tachycardia syndrome), QOL (quality of life), RCT (randomized controlled trial), SC (subcutaneous), SF-36 (36-item Short-Form Health Survey), SQ(10), SQ (14), SQ (28) (symptom questionnaire rating 10, 14, and 28 symptoms, respectively), SR (slow release), tid (3 times per day), WFDI (Walker Functional Disability Inventory), WSS (Winker symptom scale)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and PersonalCorporate R&D Professionals
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Low P.A.
        • Sandroni P.
        • Joyner M.
        • Shen W.K.
        Postural tachycardia syndrome (POTS).
        J Cardiovasc Electrophysiol. 2009; 20: 352-358
        • Benarroch E.E.
        Postural tachycardia syndrome: a heterogeneous and multifactorial disorder.
        Mayo Clin Proc. 2012; 87: 1214-1225
        • Raj S.R.
        Postural tachycardia syndrome (POTS).
        Circulation. 2013; 127: 2336-2342
        • Wells R.
        • Spurrier A.J.
        • Linz D.
        • et al.
        Postural tachycardia syndrome: current perspectives.
        Vasc Health Risk Manag. 2017; 14: 1-11
        • Mathias C.J.
        • Low D.A.
        • Iodice V.
        • Owens A.P.
        • Kirbis M.
        • Grahame R.
        Postural tachycardia syndrome: current experience and concepts.
        Nat Rev Neurol. 2011; 8: 22-34
        • Freeman R.
        • Wieling W.
        • Axelrod F.B.
        • et al.
        Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome.
        Clin Auton Res. 2011; 21: 69-72
        • Stewart J.M.
        Update on the theory and management of orthostatic intolerance and related syndromes in adolescents and children.
        Expert Rev Cardiovasc Ther. 2012; 10: 1387-1399
        • Ross A.J.
        • Ocon A.J.
        • Medow M.S.
        • Stewart J.M.
        A double-blind placebo-controlled cross-over study of the vascular effects of midodrine in neuropathic compared with hyperadrenergic postural tachycardia syndrome.
        Clin Sci (Lond). 2014; 126: 289-296
        • Sheldon R.S.
        • Grubb II, B.P.
        • Olshansky B.
        • et al.
        2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope.
        Heart Rhythm. 2015; 12: e41-e63
        • Chen L.
        • Wang L.
        • Sun J.
        • et al.
        Midodrine hydrochloride is effective in the treatment of children with postural orthostatic tachycardia syndrome.
        Circ J. 2011; 75: 927-931
        • Li H.
        • Wang Y.
        • Liu P.
        • et al.
        Body mass index (BMI) is associated with the therapeutic response to oral rehydration solution in children with postural tachycardia syndrome.
        Pediatr Cardiol. 2016; 37: 1313-1318
        • Moak J.P.
        • Leong D.
        • Fabian R.
        • et al.
        Intravenous hydration for management of medication-resistant orthostatic intolerance in the adolescent and young adult.
        Pediatr Cardiol. 2016; 37: 278-282
        • Ruzieh M.
        • Baugh A.
        • Dasa O.
        • et al.
        Effects of intermittent intravenous saline infusions in patients with medication-refractory postural tachycardia syndrome.
        J Interv Card Electrophysiol. 2017; 48: 255-260
        • Fortunato J.E.
        • Wagoner A.L.
        • Harbinson R.L.
        • D'Agostino Jr., R.B.
        • Shaltout H.A.
        • Diz D.I.
        Effect of fludrocortisone acetate on chronic unexplained nausea and abdominal pain in children with orthostatic intolerance.
        J Pediatr Gastroenterol Nutr. 2014; 59: 39-43
        • Lai C.C.
        • Fischer P.R.
        • Brands C.K.
        • et al.
        Outcomes in adolescents with postural orthostatic tachycardia syndrome treated with midodrine and beta-blockers.
        Pacing Clin Electrophysiol. 2009; 32: 234-238
        • Zhang F.
        • Li X.
        • Ochs T.
        • et al.
        Midregional pro-adrenomedullin as a predictor for therapeutic response to midodrine hydrochloride in children with postural orthostatic tachycardia syndrome.
        J Am Coll Cardiol. 2012; 60: 315-320
        • Ruzieh M.
        • Dasa O.
        • Pacenta A.
        • Karabin B.
        • Grubb B.
        Droxidopa in the treatment of postural orthostatic tachycardia syndrome.
        Am J Ther. 2017; 24: e157-e161
        • Hoeldtke R.D.
        • Bryner K.D.
        • Hoeldtke M.E.
        • Hobbs G.
        Treatment of autonomic neuropathy, postural tachycardia and orthostatic syncope with octreotide LAR.
        Clin Auton Res. 2007; 17: 334-340
        • Kanjwal K.
        • Saeed B.
        • Karabin B.
        • Kanjwal Y.
        • Grubb B.P.
        Use of octreotide in the treatment of refractory orthostatic intolerance.
        Am J Ther. 2012; 19: 7-10
        • Winker R.
        • Barth A.
        • Dorner W.
        • et al.
        Diagnostic management of orthostatic intolerance in the workplace.
        Int Arch Occup Environ Health. 2003; 76: 143-150
        • el-Sayed H.
        • Hainsworth R.
        Relationship between plasma volume, carotid baroreceptor sensitivity and orthostatic tolerance.
        Clin Sci (Lond). 1995; 88: 463-470
        • Freitas J.
        • Santos R.
        • Azevedo E.
        • Costa O.
        • Carvalho M.
        • de Freitas A.F.
        Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone.
        Clin Auton Res. 2000; 10: 293-299
        • Lin J.
        • Han Z.
        • Li H.
        • et al.
        Plasma C-type natriuretic peptide as a predictor for therapeutic response to metoprolol in children with postural tachycardia syndrome.
        PLoS One. 2015; 10: e0121913
        • Zhang Q.
        • Chen X.
        • Li J.
        • Du J.
        Orthostatic plasma norepinephrine level as a predictor for therapeutic response to metoprolol in children with postural tachycardia syndrome.
        J Transl Med. 2014; 12: 249
        • Zhao J.
        • Du S.
        • Yang J.
        • et al.
        Usefulness of plasma copeptin as a biomarker to predict the therapeutic effectiveness of metoprolol for postural tachycardia syndrome in children.
        Am J Cardiol. 2014; 114: 601-605
        • Abe H.
        • Nagatomo T.
        • Kohshi K.
        • et al.
        Heart rate and plasma cyclic AMP responses to isoproterenol infusion and effect of beta-adrenergic blockade in patients with postural orthostatic tachycardia syndrome.
        J Cardiovasc Pharmacol. 2000; 36: S79-S82
        • Fu Q.
        • Vangundy T.B.
        • Shibata S.
        • Auchus R.J.
        • Williams G.H.
        • Levine B.D.
        Exercise training versus propranolol in the treatment of the postural orthostatic tachycardia syndrome.
        Hypertension. 2011; 58: 167-175
        • McDonald C.
        • Frith J.
        • Newton J.L.
        Single centre experience of ivabradine in postural orthostatic tachycardia syndrome.
        Europace. 2011; 13: 427-430
        • Sutton R.
        • Salukhe T.V.
        • Franzen-McManus A.C.
        • Collins A.
        • Lim P.B.
        • Francis D.P.
        Ivabradine in treatment of sinus tachycardia mediated vasovagal syncope.
        Europace. 2014; 16: 284-288
        • Winker R.
        • Barth A.
        • Bidmon D.
        • et al.
        Endurance exercise training in orthostatic intolerance: a randomized, controlled trial.
        Hypertension. 2005; 45: 391-398
        • Fu Q.
        • VanGundy T.B.
        • Galbreath M.M.
        • et al.
        Cardiac origins of the postural orthostatic tachycardia syndrome.
        J Am Coll Cardiol. 2010; 55: 2858-2868
        • George S.A.
        • Bivens T.B.
        • Howden E.J.
        • et al.
        The international POTS registry: evaluating the efficacy of an exercise training intervention in a community setting.
        Heart Rhythm. 2016; 13: 943-950
        • Hoeldtke R.D.
        • Horvath G.G.
        • Bryner K.D.
        Treatment of orthostatic tachycardia with erythropoietin.
        Am J Med. 1995; 99: 525-529
        • Kanjwal K.
        • Saeed B.
        • Karabin B.
        • Kanjwal Y.
        • Sheikh M.
        • Grubb B.P.
        Erythropoietin in the treatment of postural orthostatic tachycardia syndrome.
        Am J Ther. 2012; 19: 92-95
        • Fortunato J.E.
        • Tegeler C.L.
        • Gerdes L.
        • et al.
        Use of an allostatic neurotechnology by adolescents with postural orthostatic tachycardia syndrome (POTS) is associated with improvements in heart rate variability and changes in temporal lobe electrical activity.
        Expl Brain Res. 2016; 234: 791-798
        • Kanjwal K.
        • Karabin B.
        • Sheikh M.
        • et al.
        Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience.
        Pacing Clin Electrophysiol. 2011; 34: 750-755
        • Kanjwal K.
        • Saeed B.
        • Karabin B.
        • Kanjwal Y.
        • Grubb B.P.
        Use of methylphenidate in the treatment of patients suffering from refractory postural tachycardia syndrome.
        Am J Ther. 2012; 19: 2-6
        • Kanjwal K.
        • Saeed B.
        • Karabin B.
        • Kanjwal Y.
        • Grubb B.P.
        Preliminary observations suggesting that treatment with modafinil improves fatigue in patients with orthostatic intolerance.
        Am J Ther. 2011; 18: 449-452
        • Shen W.K.
        • Low P.A.
        • Jahangir A.
        • et al.
        Is sinus node modification appropriate for inappropriate sinus tachycardia with features of postural orthostatic tachycardia syndrome?.
        Pacing Clin Electrophysiol. 2001; 24: 217-230
        • Kimpinski K.
        • Figueroa J.J.
        • Singer W.
        • et al.
        A prospective, 1-year follow-up study of postural tachycardia syndrome.
        Mayo Clin Proc. 2012; 87: 746-752
        • Sandroni P.
        • Opfer-Gehrking T.L.
        • McPhee B.R.
        • Low P.A.
        Postural tachycardia syndrome: clinical features and follow-up study.
        Mayo Clin Proc. 1999; 74: 1106-1110
        • Sousa A.
        • Lebreiro A.
        • Freitas J.
        • MacIel M.J.
        Long-term follow-up of patients with postural tachycardia syndrome.
        Clin Auton Res. 2012; 22: 151-153
        • Li J.
        • Zhang Q.
        • Hao H.
        • Jin H.
        • Du J.
        Clinical features and management of postural tachycardia syndrome in children: a single-center experience.
        Chin Med J (Engl). 2014; 127: 3684-3689
        • Bhatia R.
        • Kizilbash S.J.
        • Ahrens S.P.
        • et al.
        Outcomes of adolescent-onset postural orthostatic tachycardia syndrome.
        J Pediatr. 2016; 173: 149-153
        • Zhao J.
        • Tang C.
        • Jin H.
        • Du J.
        Plasma copeptin and therapeutic effectiveness of midodrine hydrochloride on postural tachycardia syndrome in children.
        J Pediatr. 2014; 165: 290-294.e1
        • Hoeldtke R.D.
        • Bryner K.D.
        • Hoeldtke M.E.
        • Hobbs G.
        Treatment of postural tachycardia syndrome: a comparison of octreotide and midodrine.
        Clin Auton Res. 2006; 16: 390-395
        • Kaufmann H.
        • Malamut R.
        • Norcliffe-Kaufmann L.
        • Rosa K.
        • Freeman R.
        The Orthostatic Hypotension Questionnaire (OHQ): validation of a novel symptom assessment scale.
        Clin Auton Res. 2012; 22: 79-90
        • Corkal J.C.
        • Kimpinski K.
        A prospective study of excessive postural heart rate change on head-up tilt.
        Clin Auton Res. 2014; 24: 253-258
        • Gordon V.M.
        • Opfer-Gehrking T.L.
        • Novak V.
        • Low P.A.
        Hemodynamic and symptomatic effects of acute interventions on tilt in patients with postural tachycardia syndrome.
        Clin Auton Res. 2000; 10: 29-33
        • Figueroa R.A.
        • Arnold A.C.
        • Nwazue V.C.
        • et al.
        Acute volume loading and exercise capacity in postural tachycardia syndrome.
        J Appl Physiol (1985). 2014; 117: 663-668
        • Jacob G.
        • Shannon J.R.
        • Black B.
        • et al.
        Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia.
        Circulation. 1997; 96: 575-580
        • Burklow T.R.
        • Moak J.P.
        • Bailey J.J.
        • Makhlouf F.T.
        Neurally mediated cardiac syncope: autonomic modulation after normal saline infusion.
        J Am Coll Cardiol. 1999; 33: 2059-2066
        • Lau D.H.
        • Mahajan R.
        • Lee G.
        • Kalman J.M.
        • Sanders P.
        Towards improved care of postural tachycardia syndrome, inappropriate sinus tachycardia and vasovagal syncope patients: a call to action in Australia.
        Heart Lung Circ. 2016; 25: 8-11