The Sympathetic Vasomotor Component of the Arterial Baroreflex is Impaired in Patients with Transthyretin Amyloidosis (ATTR)

Background: Transthyretin amyloidosis (ATTR) is a disease in which misfolded proteins are deposited in the myocardium and peripheral nerves, resulting in autonomic dysfunction and heart failure with preserved ejection fraction (HFpEF). One of the most common sequelae in ATTR is orthostatic hypotension, which may be related to derangements in the baroreflex. While there is emerging evidence for disease-related impairments in baroreflex responsiveness in patients with HFpEF, this pathway has not been evaluated in ATTR, thus prompting the present investigation. We hypothesized that cardiac and peripheral vasomotor responses to lower body negative pressure (LBNP)-induced central hypovolemia would be attenuated in patients with ATTR vs. HFpEF of non-amyloid etiology. Methods: Participants (HFpEF, n =4, 68±5 yr; ATTR, n =4, 74±5 yr) laid supine with the lower body (up to the iliac crest) sealed air-tight in an LBNP chamber. After baseline measurements, progressive levels of LBNP (-10, -20, -30, and -40 mmHg; 5 minutes/stage) were applied to induce central hypovolemia. Lower levels of LBNP (-10 and -20 mmHg) assessed the cardiopulmonary baroreflex, while higher levels of LBNP (-30 and -40 mmHg) evaluated integrated (arterial + cardiopulmonary) baroreflex function. Cardiac and peripheral vascular responsiveness were determined by LBNP-induced change in heart rate (∆HR) and forearm vascular conductance (∆FVC), respectively. Changes in mean arterial pressure (∆MAP) during LBNP were also assessed to quantify the degree of orthostatic intolerance. Results: There were no significant differences in HR responses between HFpEF and ATTR groups across all levels of LBNP (p>0.05). LBNP elicited progressive peripheral vasoconstriction, quantified as reductions in FVC, in patients with HFpEF, however, this response was attenuated in patients with ATTR at higher levels of LBNP (HFpEF, -16±4, -19±4; ATTR, -2±9, 0±11; p<0.05). There were no significant changes in MAP across all levels of LBNP in the HFpEF group, whereas there was a decrease in MAP in the ATTR group at higher levels of LBNP (HFpEF, -2±2, -4±1; ATTR, -6±4, -8±4; p<0.05). Conclusion and Discussion: These data provide new evidence demonstrating that the sympathetic vasomotor component of the arterial baroreflex is impaired in patients with ATTR compared to HFpEF of non-amyloid etiologies, implicating decrements in peripheral vascular control as a contributing factor to orthostatic intolerance in this patient population. Funding: Funded in part by the NIH (NIH HL170007; HL162856) and the U.S. Department of Veterans Affairs (VA CX002152). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.