Midregional Pro-Adrenomedullin as a Predictor for Therapeutic Response to Midodrine Hydrochloride in Children With Postural Orthostatic Tachycardia Syndrome
Open accessAbstract
Objectives This study was designed to explore the predictive value of the midregional fragment of pro-adrenomedullin (MR-proADM) in assessing the therapeutic efficacy of midodrine hydrochloride for children with postural orthostatic tachycardia syndrome (POTS). Background Midodrine hydrochloride is an important therapeutic option for children with POTS. However, there has not been any method to predict response to the drug. The MR-proADM is produced in equimolar amounts to adrenomedullin (ADM), and directly reflects levels of the rapidly degraded active peptide, ADM. Methods Fifty-seven children with POTS were designated as the POTS group. Twenty healthy children served as the control group. The children in the POTS group received midodrine hydrochloride treatment. The plasma concentration of MR-proADM was measured, using a sandwich immunoluminometric assay. A receiver-operating characteristic curve was used to explore the predictive value of MR-proADM. Results Plasma levels of MR-proADM were significantly higher in children with POTS (75.0 [62.5 to 96.0] pg/ml) than in the control group (58.5 [50.3 to 69.0] pg/ml). Plasma levels of MR-proADM in responders to midodrine hydrochloride was significantly higher than that of nonresponders (76.0 [66.0 to 91.0] pg/ml vs. 59.0 [54.0 to 65.5] pg/ml, p < 0.01]. A receiver-operating characteristic curve on the predictive value of MR-proADM showed that the area under the curve was 0.879 with a 95% confidence interval of 0.761 to 0.997. Using a cutoff value for MR-proADM of 61.5 pg/ml produced both high sensitivity (100%) and specificity (71.6%) in predicting the efficacy of midodrine hydrochloride therapy for treating POTS. Conclusions MR-proADM can help guide midodrine hydrochloride therapy in the management of POTS in children.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Midodrine is used to promote venoconstriction and vasoconstriction in POTS patients and has shown benefit in small studies.
“Midodrine, an oral alpha-adrenoceptor agonist prodrug, is used to promote venoconstriction and vasoconstriction in POTS patients and has shown benefit in small studies (Lai et al., 2009; Zhang et al., 2012).”
From Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 (2021) · cites this paper as Zhang et al., 2012
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Postural tachycardia syndrome (POTS)
LOW, P. A., SANDRONI, P., JOYNER, M., & SHEN, W. (2009) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2008.01407.x · Cited by 358 · see citing works
Grubb, B. P. (2008) · Circulation · doi:10.1161/circulationaha.107.761643 · Cited by 224 · see citing works
Flagged first, then by citations
Research works printed but not linked: 24
- Zhang F, Li X, Stella C, et al. Plasma hydrogen sulfide in differential diagnosis between vasovagal syncope and postural orthostatic tachy- cardia syndrome in children. J Pediatr 2012,160:227-31.
- Chen L, Wang L, Sun J, et al. Midodrine hydrochloride is effective in the treatment of children with postural orthostatic tachycardia syn- drome. Circ J 2011;75:927-31.
- Nishida H, Horio T, Suzuki Y, et al. Plasma adrenomedullin as an independent predictor of future cardiovascular events in high-risk patients: comparison with C-reactive protein and adiponectin. Pep- tides 2008;29:599 -605.
- Pio R, Martinez A, Unsworth EJ, et al. Complement factor H is a serum-binding protein for adrenomedullin, and the resulting complex modulates the bioactivities of both partners. J Biol Chem 2001;276: 12292-300.
- Struck J, Tao C, Morgenthaler NG, et al. Identification of an adrenomedullin precursor fragment in plasma of sepsis patients. Peptides 2004;25:1369 -72.
- Al-omari MA, Khaleghi M, Mosley TH Jr., et al. Mid-regional pro-adrenomedullin is associated with pulse pressure, left ventricular mass, and albuminuria in African Americans with hypertension. Am J Hypertens 2009;22:860 -6.
- Zhang Q, Du J, Wang C, Du Z, Wang L, Tang C. The diagnostic protocol in children and adolescents with syncope: a multi-centre prospective study. Acta Paediatr 2009;98:879 -84.
- Medow MS, Stewart JM. The postural tachycardia syndrome. Cardiol Rev 2007;15:67-75.
- Chen L, Yang YY, Wang C, et al. A multi-center study of hemody- namic characteristics exhibited by children with unexplained syncope. Chin Med J 2006;119:2062-8.
- Benditt DG, Ferguson DW, Grubb BP, et al. Tilt table testing for assessing syncope. J Am Coll Cardiol 1996;28:263-75.
- Winder R, Barth A, Bidmon D, et al . Endurance exercise training in orthostatic intolerance: a randomized, controlled trial. Hypertension 2005;45:391-8.
- Swets JA. Measuring the accuracy of diagnostic systems. Science 1988;240:1285-93. 319 JACC Vol. 60, No. 4, 2012 Zhang et al. July 24, 2012:315-20 Postural Orthostatic Tachycardia Syndrome 15. Schisterman EF, Perkins NJ, Liu A, Bondell H. Optimal cut-point and its corresponding Youden index to discriminate individuals using pooled blood samples. Epidemiology 2005;16:73-81.
- Liao Y, Chen S, Liu XQ, et al. Flow-mediated vasodilation and endothelium function in children with postural orthostatic tachycardia syndrome. Am J Cardiol 2010;106:378 -82.
- Kato J, Tsuruda T, Kita T, et al. Adrenomedullin: a protective factor for blood vessels. Arterioscler Thromb Vasc Biol 2005;25:2480 -7.
- Wei YJ, Tian Q, Li QH, et al. Hemodynamic effects of centrally administered adrenomedullin (13-52) in anesthetized rats. Biol Signals 1995;4:338-44.
- Saita M, Shimokawa A, Kunitake T, et al. Central actions of adrenomedullin on cardiovascular parameters and sympathetic outflow in conscious rats. Am J Physiol 1998;274:R979 -84.
- Gordon VM, Opfer-Gehrking TL, Novak V, Low PA. Hemody- namic and symptomatic effects of acute interventions on tilt in patients with postural tachycardia syndrome. Clin Auton Res 2000;10:29 -33.
- Hoeldtke RD, Bryner KD, Hoeldtke ME, Hobbs G. Treatment of postural tachycardia syndrome: a comparison of octreotide and mido- drine hydrochloride. Clin Auton Res 2006;16:390 -5.
- von Haehling S, Filippatos GS, Papassotiriou J, et al. Mid-regional pro-adrenomedullin as a novel predictor of mortality in patients with chronic heart failure. Eur J Heart Fail 2010;12:484 -91.
- Serban IL, Serban DN, Haulica ˘I. Relaxing effects of adrenomedullin in rat mesenteric resistance arteries. Rev Med Chir Soc Med Nat Iasi 2007;111:696 -701.
- Thulesius O, Gjöres JE, Berlin E. Vasoconstrictor effect of midodrine, ST 1059, noradrenaline, etilefrine and dihydroergotamine on isolated human veins. Eur J Clin Pharmacol 1979;16:423-4.
- Mack KJ, Johnson JN, Rowe PC. Orthostatic intolerance and the headache patient. Semin Pediatr Neurol 2010;17:109 -16.
- Carew S, Connor MO, Cooke J, et al. A review of postural orthostatic tachycardia syndrome. Europace 2009;11:18 -25.
- Stewart JM. Postural tachycardia syndrome and reflex syncope: simi- larities and differences. J Pediatr 2009;154:481-5. Key Words: children y midodrine hydrochloride y midregional fragment of pro-adrenomedullin y postural orthostatic tachycardia syndrome.
Cited by
Sorted by citations
Vernino, S., Bourne, K. M., Stiles, L. E., Grubb, B. P., Fedorowski, A., Stewart, J. M., Arnold, A. C., Pace, L. A., Axelsson, J., Boris, J. R., et al. (2021) · Autonomic Neuroscience · doi:10.1016/j.autneu.2021.102828 · Cited by 304 · see citing works
Efficacy of Therapies for Postural Tachycardia Syndrome: A Systematic Review and Meta-analysis
Wells, R., Elliott, A. D., Mahajan, R., Page, A., Iodice, V., Sanders, P., & Lau, D. H. (2018) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2018.01.025 · Cited by 67 · see citing works
Moon, J., Kim, D.-Y., Byun, J.-I., Sunwoo, J.-S., Lim, J.-A., Kim, T.-J., Shin, J.-W., Lee, W.-J., Lee, H. S., Jun, J.-S., et al. (2016) · Health and Quality of Life Outcomes · doi:10.1186/s12955-016-0548-x · Cited by 66 · see citing works
Moon, J., Kim, D.-Y., Lee, W.-J., Lee, H. S., Lim, J.-A., Kim, T.-J., Jun, J.-S., Park, B., Byun, J.-I., Sunwoo, J.-S., et al. (2018) · Neurotherapeutics · doi:10.1007/s13311-018-0612-9 · Cited by 40 · see citing works
Zhao, J., Tang, C., Jin, H., & Du, J. (2014) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2014.04.032 · Cited by 27 · see citing works
Self-citation
- Authors
- Zhang, F., Li, X., Ochs, T., Chen, L., Liao, Y., Tang, C., Jin, H., & Du, J.
- Affiliations
- Peking University First Hospital (CN)
- Northwestern University (US)
- Peking University (CN)
- Ministry of Education of the People's Republic of China (CN)
- Corresponding author
- Jin, Hongfang
- Du, Junbao
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 60
- Issue
- 4
- Pages
- 315-320
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2027027558
- Cited by
- 66
- References
- 2
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 7 · 2019: 2 · 2018: 6 · 2017: 6 · 2016: 6 · 2015: 3 · 2014: 12 · 2013: 4 · 2012: 1
- FWCI
- 6.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Major Basic Research Project of China (2011CB503904, 2012CB517806)
- National Twelfth Five-Year Plan for Science & Technology (2012BA103B03)
- Beijing Science and Technology Project (D10100050010059)
- National Natural Science Foundation of China (81121061)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- postural orthostatic tachycardia syndrome, midodrine, treatment response prediction, adrenomedullin, pediatric patients, biomarkers
- MeSH terms
- Adolescent, Blood Pressure, Child, Female, Heart Rate, Humans, Male, Midodrine, Peptide Fragments, Predictive Value of Tests, Protein Precursors, ROC Curve, Sympathomimetics, Biomarkers, Treatment Outcome, Tilt-Table Test, Adrenomedullin, Postural Orthostatic Tachycardia Syndrome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
