The higher the plasma level of MR-proADM, the more likely it is that a child with postural orthostatic tachycardia syndrome (POTS) will respond to treatment, a new study shows.
The condition is sometimes treated with midodrine hydrochloride, a vasoconstrictor — but only about 70% of patients respond to it, and there hasn't been a practical way to predict in advance which patients should receive the drug.
The investigators on the new study say circulating levels of the vasodilator adrenomedullin might provide some clues — but "unfortunately, quantifying it is almost impossible, because of its short half life" and other properties.
Instead, they've now found, they can measure plasma levels of the more stable MR-proADM (midregional fragment of pro-adrenomedullin).
"The assessment of plasma MR-proADM, reflective of ADM as a vasoactive agent, in pediatric patients is of great clinical significance in guiding the selection of midodrine hydrochloride therapy in the management of POTS in children," senior researcher Dr. Junbao Du from Peking University First Hospital in Beijing told Reuters Health in an email.
"When the plasma level of MR-proADM is over 61.5 pg/mL, the patients are suitable to take midodrine hydrochloride as a treatment," Dr. Du said.
The study, involving 57 children with POTS and 20 healthy controls, was released online July 23 in the Journal of the American College of Cardiology.
Mean plasma levels of MR-proADM were significantly higher in the children with POTS (75.0 vs 58.5 pg/mL; p<0.01).
Twenty-seven of 44 children treated with midodrine hydrochloride responded to therapy. The responders had a significantly higher mean plasma MR-proADM level than nonresponders and untreated patients (76.0 vs 59.0 pg/mL; p<0.05).
A cutoff value for MR-proADM of 61.5 pg/mL was 100% sensitive and 71.6% specific for predicting the effect of midodrine hydrochloride for treating POTS, the research team reports.
"Generally speaking, the main treatments for POTS contain non-drug therapy including health education, upright training, and oral rehydration salts and drug therapy including beta-blocker, alpha-agonists, etc.," Dr. Du said. "As indicated in our results, the POTS children who have a possible underlying mechanism involving excessive vasorelaxation demonstrated by increased plasma ADM level are suitable to take alpha-agonist, such as midodrine hydrochloride, to help vasoconstriction."
"POTS is very common in childhood and adolescence, having symptoms of orthostatic intolerance in association with excessive tachycardia," Dr. Du added. "Patients with POTS experience many difficulties with daily routines such as housework, shopping, eating, and attending work or school. Therefore, physicians should pay greater attention to this disease, in terms of its pathophysiology, diagnosis, and treatment."
In an editorial, Dr. David G. Benditt and Dr. Lin Y. Chen from the University of Minnesota Medical School in Minneapolis write, "The concept that vasoactive peptides may contribute to the clinical manifestations of POTS is potentially important. However, whether ADM and possibly other peptides are active players or simply epiphenomenon in these patients will require considerable further study."
"At a minimum," the editorial concludes, "natriuretic peptide concentrations may prove to be potentially useful markers of POTS severity that can be tracked in individual patients as treatments are introduced in an attempt to ameliorate the symptoms of this poorly understood condition."
SOURCE: Abstract for J Am Coll Cardiol 2012;60:315-320,321-323.
Will Boggs, MD • Reuters Health Information © 2012