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Hyperadrenergic postural tachycardia syndrome associated with augmented neurovascular transduction

  • Surat Kulapatana
  • , Luis E. Okamoto
  • , Stefano Rigo
  • , Vasile Urechie
  • , Thomas W. Cayton
  • , Ruijing E. Han
  • , Giris Jacob
  • , William D. Dupont
  • , Raffaello Furlan
  • , Italo Biaggioni
  • , André Diedrich*
  • *Corresponding author for this work
  • Vanderbilt University
  • Mahidol University
  • IRCCS Istituto Clinico Humanitas - Rozzano (Milano)
  • Humanitas University
  • myDoctorAngel Sagl

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Muscle sympathetic nerve activity (MSNA) is valuable for managing postural tachycardia syndrome (POTS), but microneurography is clinically impractical. We investigated whether the Valsalva phase 2 diastolic blood pressure rise (DBPVM2l_rise) serves as a sympathetic marker and proposed enhanced neurovascular transduction as a pathophysiological mechanism in hyperadrenergic POTS. Methods: We included 21 POTS women and 22 healthy women to perform Valsalva and microneurography. MSNA spike rate was obtained using stationary wavelet transformation. The DBPVM2l_rise cut point for hyperadrenergic POTS was optimized by the golden section search with its correlation to phase 2 MSNA spike rate as an objective function. We defined peripheral sympathetic neurovascular transduction (psNVT) as a ratio of DBPVM2l_rise to early phase 2 MSNA increase. We compared Valsalva responses between the identified hyperadrenergic and non-hyperadrenergic POTS. Results: The DBPVM2l_rise strongly correlated with the Valsalva phase 2 MSNA spike rate percentage change from baseline in healthy (r = 0.874, p < 0.001). The DBPVM2l_rise cutoff criterion of 15 mmHg optimally separated POTS into 7 hyperadrenergic (≥ 15 mmHg, r = 0.902, p = 0.014) and 14 non-hyperadrenergic (< 15 mmHg, r = 0.629, p = 0.021). Although similar MSNA spike rate, the hyperadrenergic group had higher baseline systolic blood pressure (118 ± 10 vs 105 ± 12 mmHg, p = 0.026), shorter pressure recovery time (1.15 ± 0.75 vs 2.59 ± 1.17 s, p = 0.048), and higher psNVT (2.60 ± 1.02 vs 0.58 ± 0.46 mmHg/spike·s−1, p < 0.001) than the non-hyperadrenergic POTS. Conclusion: DBPVM2l_rise ≥ 15 mmHg could be a sympathetic clinical marker and could identify hyperadrenergic POTS, characterized by enhanced neurovascular transduction despite comparable MSNA levels. This novel pathophysiological insight underscores the importance of sympathetic markers in POTS clinical management.

Original languageEnglish
Pages (from-to)271-283
Number of pages13
JournalClinical Autonomic Research
Volume36
Issue number2
DOIs
StatePublished - Apr 2026

Funding

FundersFunder number
Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center
National Institutes of HealthR01 HL142583
National Center for Advancing Translational Sciences5UL1TR002243-03

    Keywords

    • Hyperadrenergic
    • MSNA
    • POTS
    • Sympathetic
    • Valsalva

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