Guaraldi P, Rocchi C, Cani I, Gagliardi C, Longhi S, Baschieri F, Rinaldi R, Frezza E, D'Angelo R, Barletta G, Calandra-Buonaura G, Galiè N, Massa R, Cortelli P
IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy.
Neurology Unit, Department of Systems Medicine, Policlinico Tor Vergata, Rome, Italy.
Clin Auton Res. 2023 Feb;33(1):15-22. doi: 10.1007/s10286-022-00921-x. Epub 2023 Jan 10.
Autonomic dysfunction is a distinctive but undervalued feature of hereditary transthyretin amyloidosis (ATTRv). It may predate the onset of polyneuropathy and cardiomyopathy, thereby providing crucial prognostic and therapeutic information. The objective of this study was to assess autonomic function by means of the standardized cardiovascular autonomic reflex tests (CRTs) in a cohort of subjects with genetically proven ATTRv from non-endemic areas who were in the symptomatic and pre-symptomatic stages.
All subjects enrolled in this cross-sectional study had genetically proven ATTRv. They underwent the head-up tilt test, Valsalva manoeuvre, deep breathing test, cold face test and handgrip test while under continuous blood pressure and heart rate monitoring. Based on the results of the nerve conduction study, the subjects were divided into two groups: those with polyneuropathy (ATTRv-wPN) and those without polyneuropathy (ATTRv-woPN). Age- and sex-matched healthy controls (HC) were used for comparison.
Thirty-seven ATTRv subjects (19 with ATTRv-wPN, 18 with ATTRv-woPN) and 41 HC performed the CRTs. Of these 37 subjects with ATTRv, four (11%) presented neurogenic orthostatic hypotension the during head-up tilt test. Based on the results of the CRTs, autonomic dysfunction characterized by either sympathetic or parasympathetic impairment was detected in 37% and 63% of ATTRv-wPN subjects, respectively. Subjects with ATTRv-woPN presented a significant impairment of autonomic responses to the Valsalva manoeuvre compared to the HC (overshoot p = 0.004; Valsalva ratio p = 0.001).
Autonomic dysfunctions are frequent in subjects with ATTRv when investigated by means of standardized CRTs, and are also relevant in the pre-symptomatic stage. Cardiovagal functions are the primary functions affected, among others. This may be crucial in defining the proper diagnostic workout for early diagnosis and improving the likelihood of providing the patient with prompt administration of disease-modifying treatments.
自主神经功能障碍是遗传性转甲状腺素蛋白淀粉样变性（ATTRv）的一个独特但未得到充分重视的特征。它可能早于多发性神经病和心肌病的发病，从而提供关键的预后和治疗信息。本研究的目的是通过标准化心血管自主反射测试（CRT）评估一组来自非流行地区、有基因证实的ATTRv且处于症状期和症状前期的受试者的自主神经功能。
本横断面研究纳入的所有受试者均有基因证实的ATTRv。他们在持续监测血压和心率的情况下，接受了头高位倾斜试验、瓦尔萨尔瓦动作、深呼吸试验、冷脸试验和握力试验。根据神经传导研究结果，将受试者分为两组：患有多发性神经病的（ATTRv-wPN）和未患多发性神经病的（ATTRv-woPN）。采用年龄和性别匹配的健康对照（HC）进行比较。
37名ATTRv受试者（19名ATTRv-wPN，18名ATTRv-woPN）和41名HC进行了CRT。在这37名ATTRv受试者中，有4名（11%）在头高位倾斜试验期间出现神经源性直立性低血压。根据CRT结果，在ATTRv-wPN受试者中，分别有37%和63%检测到以交感神经或副交感神经损伤为特征的自主神经功能障碍。与HC相比，ATTRv-woPN受试者对瓦尔萨尔瓦动作的自主反应存在显著损伤（过冲p = 0.004；瓦尔萨尔瓦比率p = 0.001）。
通过标准化CRT进行研究时，自主神经功能障碍在ATTRv受试者中很常见，在症状前期也很明显。迷走心血管功能是受影响的主要功能之一。这对于确定早期诊断的正确诊断方法以及提高为患者及时给予疾病修饰治疗的可能性可能至关重要。
