Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies

Lucy Norcliffe-Kaufmann, Horacio Kaufmann, Jose Alberto Palma, Cyndya A. Shibao, Italo Biaggioni, Amanda C. Peltier, Wolfgang Singer, Phillip Anson Low, David S. Goldstein, Christopher H. Gibbons, Roy Freeman, David Robertson

Research output: Contribution to journalArticle

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Abstract

Objective: Blunted tachycardia during hypotension is a characteristic feature of patients with autonomic failure, but the range has not been defined. This study reports the range of orthostatic heart rate (HR) changes in patients with autonomic failure caused by neurodegenerative synucleinopathies. Methods: Patients evaluated at sites of the U.S. Autonomic Consortium (NCT01799915) underwent standardized autonomic function tests and full neurological evaluation. Results: We identified 402 patients with orthostatic hypotension (OH) who had normal sinus rhythm. Of these, 378 had impaired sympathetic activation (ie, neurogenic OH) and based on their neurological examination were diagnosed with Parkinson disease, dementia with Lewy bodies, pure autonomic failure, or multiple system atrophy. The remaining 24 patients had preserved sympathetic activation and their OH was classified as nonneurogenic, due to volume depletion, anemia, or polypharmacy. Patients with neurogenic OH had twice the fall in systolic blood pressure (SBP; -44±25 vs -21±14 mmHg [mean±standard deviation], p<0.0001) but only one-third of the increase in HR of those with nonneurogenic OH (8±8 vs 25±11 beats per minute [bpm], p<0.0001). A ΔHR/ΔSBP ratio of 0.492 bpm/mmHg had excellent sensitivity (91.3%) and specificity (88.4%) to distinguish between patients with neurogenic from nonneurogenic OH (area under the curve=0.96, p<0.0001). Within patients with neurogenic OH, HR increased more in those with multiple system atrophy (p=0.0003), but there was considerable overlap with patients with Lewy body disorders. Interpretation: A blunted HR increase during hypotension suggests a neurogenic cause. A ΔHR/ΔSBP ratio<0.5 bpm/mmHg is diagnostic of neurogenic OH.

Original languageEnglish (US)
JournalAnnals of Neurology
DOIs
StateAccepted/In press - Jan 1 2018

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Orthostatic Hypotension
Heart Rate
Multiple System Atrophy
Hypotension
Pure Autonomic Failure
Blood Pressure
Lewy Bodies
Lewy Body Disease
Polypharmacy
Neurologic Examination
Tachycardia
Area Under Curve
Parkinson Disease
Anemia
Sensitivity and Specificity

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Norcliffe-Kaufmann, L., Kaufmann, H., Palma, J. A., Shibao, C. A., Biaggioni, I., Peltier, A. C., ... Robertson, D. (Accepted/In press). Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies. Annals of Neurology. https://doi.org/10.1002/ana.25170

Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies. / Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio; Palma, Jose Alberto; Shibao, Cyndya A.; Biaggioni, Italo; Peltier, Amanda C.; Singer, Wolfgang; Low, Phillip Anson; Goldstein, David S.; Gibbons, Christopher H.; Freeman, Roy; Robertson, David.

In: Annals of Neurology, 01.01.2018.

Research output: Contribution to journalArticle

Norcliffe-Kaufmann, L, Kaufmann, H, Palma, JA, Shibao, CA, Biaggioni, I, Peltier, AC, Singer, W, Low, PA, Goldstein, DS, Gibbons, CH, Freeman, R & Robertson, D 2018, 'Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies', Annals of Neurology. https://doi.org/10.1002/ana.25170
Norcliffe-Kaufmann, Lucy ; Kaufmann, Horacio ; Palma, Jose Alberto ; Shibao, Cyndya A. ; Biaggioni, Italo ; Peltier, Amanda C. ; Singer, Wolfgang ; Low, Phillip Anson ; Goldstein, David S. ; Gibbons, Christopher H. ; Freeman, Roy ; Robertson, David. / Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies. In: Annals of Neurology. 2018.
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abstract = "Objective: Blunted tachycardia during hypotension is a characteristic feature of patients with autonomic failure, but the range has not been defined. This study reports the range of orthostatic heart rate (HR) changes in patients with autonomic failure caused by neurodegenerative synucleinopathies. Methods: Patients evaluated at sites of the U.S. Autonomic Consortium (NCT01799915) underwent standardized autonomic function tests and full neurological evaluation. Results: We identified 402 patients with orthostatic hypotension (OH) who had normal sinus rhythm. Of these, 378 had impaired sympathetic activation (ie, neurogenic OH) and based on their neurological examination were diagnosed with Parkinson disease, dementia with Lewy bodies, pure autonomic failure, or multiple system atrophy. The remaining 24 patients had preserved sympathetic activation and their OH was classified as nonneurogenic, due to volume depletion, anemia, or polypharmacy. Patients with neurogenic OH had twice the fall in systolic blood pressure (SBP; -44±25 vs -21±14 mmHg [mean±standard deviation], p<0.0001) but only one-third of the increase in HR of those with nonneurogenic OH (8±8 vs 25±11 beats per minute [bpm], p<0.0001). A ΔHR/ΔSBP ratio of 0.492 bpm/mmHg had excellent sensitivity (91.3{\%}) and specificity (88.4{\%}) to distinguish between patients with neurogenic from nonneurogenic OH (area under the curve=0.96, p<0.0001). Within patients with neurogenic OH, HR increased more in those with multiple system atrophy (p=0.0003), but there was considerable overlap with patients with Lewy body disorders. Interpretation: A blunted HR increase during hypotension suggests a neurogenic cause. A ΔHR/ΔSBP ratio<0.5 bpm/mmHg is diagnostic of neurogenic OH.",
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AU - Biaggioni, Italo

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AU - Freeman, Roy

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