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Attenuated Peripheral Vascular Responsiveness Contributes to Baroreflex Dysfunction in Patients with Wild-Type Transthyretin Amyloidosis (wtATTR)
Journal article   Peer reviewed

Attenuated Peripheral Vascular Responsiveness Contributes to Baroreflex Dysfunction in Patients with Wild-Type Transthyretin Amyloidosis (wtATTR)

Jarred J Iacovelli, Jeremy K Alpenglow, Jill Stratford Waldron, Jonah M Simmons, Kanokwan Bunsawat, Spencer J Carter and D Walter Wray
American journal of physiology. Heart and circulatory physiology, Vol.330(3), pp.H788-H798
03/01/2026
DOI: 10.1152/ajpheart.00827.2025
PMID: 41616783

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Abstract

Autonomic dysfunction is a common clinical feature of wild-type transthyretin amyloidosis (wtATTR) that may include disease-related changes in baroreflex function. We tested the hypothesis that central and peripheral hemodynamic responses to progressive lower-body negative pressure (LBNP; -10, -20, -30, -40 mmHg; 5 minutes per stage)-induced hypovolemia would be attenuated in patients with wtATTR ( =13, 74±6 yrs) compared with control subjects with HFpEF of non-amyloid etiology ( =13, 72±4 yrs). Changes in heart rate (HR) and stroke volume (SV) during LBNP assessed central cardiac responsiveness, and changes in forearm blood flow (FBF) and vascular conductance (FVC) evaluated peripheral vascular responsiveness. Lower levels of LBNP (-10 and -20 mmHg) were used to evaluate the cardiopulmonary baroreflex, while higher levels of LBNP (-30 and -40 mmHg) assessed integrated (cardiopulmonary + arterial) baroreflex function. There were no group differences in LBNP-induced changes in HR or SV at any stage of LBNP ( >0.05 for all comparisons). Vasoconstriction, as quantified by changes in FVC, was reduced during higher levels of LBNP in wtATTR (CON -0.20 ± 0.20 mL/min/mmHg; wtATTR, -0.04 ± 0.17 mL/min/mmHg; = 0.011) and -40 mmHg (CON -0.26 ± 0.22 mL/min/mmHg; wtATTR, -0.02 ± 0.20 mL/min/mmHg; < 0.01). MAP was unchanged across all levels of LBNP in controls, but decreased in the wtATTR group at the highest level of LBNP ( =0.039). These findings provide new evidence for derangements in integrative baroreflex function beyond what is present in HFpEF from non-amyloid etiology that may contribute to blood pressure dysregulation during orthostasis in wtATTR.
 autonomic nervous system baroreflex wtATTR transthyretin amyloidosis

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