Hyperadrenergic postural tachycardia syndrome associated with augmented neurovascular transduction

Abstract Purpose Muscle sympathetic nerve activity (MSNA) is valuable for POTS management, but microneurography is clinically impractical. We investigated whether the Valsalva phase 2 diastolic blood pressure rise (DBP VM2l_rise ) could be a surrogate for MSNA during the Valsalva and be used to identify hyperadrenergic POTS. Methods We included 21 POTS females and 22 healthy females to perform Valsalva and microneurography. MSNA spike rate was obtained using stationary wavelet transformation. The DBP VM2l_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 DBP VM2l_rise to early phase 2 MSNA increase. We compared Valsalva responses between the identified hyperadrenergic and non-hyperadrenergic POTS. Results The DBP VM2l_rise strongly correlated with the Valsalva phase 2 MSNA spike rate percentage change from baseline in healthy (r = 0.874, p < 0.001). The DBP VM2l_rise equal 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 ± 10vs105 ± 12 mmHg, p = 0.026), shorter pressure recovery time (1.15 ± 0.75vs2.59 ± 1.17 s, p = 0.005), and higher psNVT (2.60 ± 1.02vs0.58 ± 0.46 mmHg/spike∙s − 1 , p < 0.001) than the non-hyperadrenergic POTS. Conclusion DBP VM2l_rise ≥ 15 mmHg could be a marker of hyperadrenergic response to subtype POTS. We defined this subset of POTS as functional hyperadrenergic POTS since they displayed hyperadrenergic phenotypes despite similar level of MSNA to other POTS. The higher psNVT of the hyperadrenergic group suggested a novel pathophysiology of enhanced neurovascular coupling.