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. 2024 Sep 4;24(1):317.
doi: 10.1186/s12883-024-03822-w.

Blunted tachycardia and cardiac sympathetic denervation in isolated rapid eye movement sleep behavior disorder

Shota Saeda  1 , Yukiyoshi Sumi  2 , Koichi Fujiwara  3 , Hiroshi Kadotani  2
Affiliations

Blunted tachycardia and cardiac sympathetic denervation in isolated rapid eye movement sleep behavior disorder

Shota Saeda et al. BMC Neurol. .

Abstract

Background: Isolated rapid eye movement sleep behavior disorder (iRBD) serves as a prodromal phase of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Blunted tachycardia (BT) during postural changes indicates neurogenic orthostatic hypotension, a marker of autonomic dysfunction. We aimed to investigate whether BT is associated with cardiac sympathetic neurogenic denervation. Additionally, we conducted a preliminary short-term follow-up to examine the potential prognostic significance of BT regarding phenoconversion and mortality.

Methods: Forty-three patients with iRBD at Shiga University of Medical Science Hospital underwent active standing tests to identify BT, defined by a specific ratio of decrease in systolic blood pressure to inadequate increase in heart rate after standing, and orthostatic hypotension. 123I-metaiodobenzylguanidine myocardial scintigraphy (123I-MIBG) and dopamine transporter single-photon emission computed tomography (DAT-SPECT) were performed. Participants were followed up for 3.4 ± 2.4 years for phenoconversion and 4.0 ± 2.3 years for mortality assessment, and the risk of events was analyzed using log-rank tests.

Results: Among the 43 participants (mean age, 72.3 ± 7.9 years; 8 female), 17 met the BT criteria. We found no significant comorbidity-related differences in hypertension or diabetes between the BT(+) and BT(-) groups. Orthostatic hypotension was more prevalent in the BT(+) group than in the BT(-) group (47.1% vs 7.7%, p = 0.003). BT(+) patients were older with a lower early and delayed MIBG uptake; however, no significant differences were observed in DAT accumulation. Phenoconversion was observed in seven (41.2%) BT(+) and seven (26.9%) BT(-) patients. Three deaths were recorded in the BT(+) group (17.6%) and three in the BT(-) group (11.5%). No significant differences were observed in the risk of phenoconversion or mortality between the groups.

Conclusions: We have identified the possibility that BT reflects cardiac sympathetic neurogenic denervation in patients with iRBD. Future research is needed to elucidate the potential prognostic value of BT.

Keywords: Autonomic dysfunction; Blunted tachycardia; Longitudinal study; Orthostatic hypotension; Phenoconversion; Rapid eye movement sleep behavior disorder.

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Conflict of interest statement

Hiroshi Kadotani was supported by donations from Fukuda Life Tech Co., Ltd., Fukuda Life Tech Keiji Co., Ltd., and Kadotani Kids Clinic to the Shiga University of Medical Science. Hiroshi Kadotani received Merck Sharp and Dohme Corp/MSD K.K. (the Investigator-initiated Studies Program), Eisai Co., Ltd., and the SECOM Science and Technology Foundation. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp and Dohme Corp/MSD K.K. The other authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Flowchart of the patients’ inclusion and follow-up. Abbreviations: BP, blood pressure; HR, heart rate; BT, blunted tachycardia
Fig. 2
Fig. 2
Changes in BP, HR, and delta index during the active standing test. Comparison of the active standing test results in the BT(+) and BT(-) groups. (A1-C1) indicates absolute change (mean ± standard error of the mean); (A2-C2) indicates changes compared with the supine position (mean ± standard error of the mean); (D) indicates the changes in the BT criteria. Abbreviations: BP, blood pressure; BT, blunted tachycardia; HR, heart rate. x-axis: supine, mean value of the supine position, 1–15 min after standing
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