Attenuated peripheral vascular responsiveness contributes to baroreflex dysfunction in patients with wild-type transthyretin amyloidosis

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 min per stage)-induced hypovolemia would be attenuated in patients with wtATTR (<i>n</i> = 13, 74 ± 6 yr) compared with control subjects with HFpEF of nonamyloid etiology (<i>n</i> = 13, 72 ± 4 yr). 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, whereas 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 (<i>P</i> > 0.05 for all comparisons). Vasoconstriction, as quantified by changes in FVC, was reduced in wtATTR at -30 mmHg (CON, -0.20 ± 0.20 mL/min/mmHg; wtATTR, -0.04 ± 0.17 mL/min/mmHg; <i>P</i> = 0.011) and -40 mmHg (CON, -0.26 ± 0.22 mL/min/mmHg; wtATTR, -0.02 ± 0.20 mL/min/mmHg; <i>P</i> < 0.01). MAP was unchanged across all levels of LBNP in controls, but decreased in the wtATTR group at the highest level of LBNP (<i>P</i> = 0.039). These findings provide new evidence for derangements in integrative baroreflex function beyond what is present in HFpEF from nonamyloid etiology that may contribute to blood pressure dysregulation during orthostasis in wtATTR.<b>NEW & NOTEWORTHY</b> Wild-type transthyretin amyloidosis (wtATTR) is a unique cause of heart failure typically associated with orthostatic hypotension, likely implicating baroreflex dysfunction; however, this is yet to be investigated. Using the lower-body negative pressure technique to simulate orthostatic stress, we have identified impaired peripheral vascular responsiveness, which occurred in tandem with an inability to arterial blood pressure, suggesting that diminished sympathetic vasomotor responsiveness likely contributes to baroreflex dysfunction and impaired blood pressure regulation in patients with wtATTR.