TY - JOUR
T1 - Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies
AU - Autonomic Disorders Consortium
AU - Norcliffe-Kaufmann, Lucy
AU - Kaufmann, Horacio
AU - Palma, Jose Alberto
AU - Shibao, Cyndya A.
AU - Biaggioni, Italo
AU - Peltier, Amanda C.
AU - Singer, Wolfgang
AU - Low, Phillip A.
AU - Goldstein, David S.
AU - Gibbons, Christopher H.
AU - Freeman, Roy
AU - Robertson, David
N1 - Funding Information:
Recruiting sites were part of the U.S. Autonomic Disorders Consortium and supported by the National Institutes for Health (NIH) Rare Disease Clinical Research Network (RDCRN).22 All sites had expertise in autonomic neurology. All subjects had been referred for autonomic testing to evaluate their complaints of dizziness, lightheadedness, or feeling about to faint on standing. Enrollment occurred at 5 medical centers: New York University Medical Center (New York, NY), Vanderbilt University Medical Center (Nashville, TN), Mayo Clinic (Rochester, MN), NIH Intramural Research Program (Bethesda, MD), and Beth Israel Deaconess Medical Center (Boston, MA). The National Institutes of Neurological Disorders and Stroke approved all recruiting sites. Each local institutional review board approved the study procedures. Informed consent was obtained in all cases. A detailed manual of operations was developed to standardize the autonomic function tests across sites with full operating procedures, including timings, sampling rates, and spectral analysis guidelines. Training was provided to investigators acquiring and analyzing data. All data were reviewed, verified, and audited by the RDCRN centralized
Funding Information:
Supported by the NIH Rare Disease Clinical Research Network (U54-NS065736, all authors).
Publisher Copyright:
© 2018 American Neurological Association
PY - 2018/3
Y1 - 2018/3
N2 - 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. Ann Neurol 2018;83:522–531.
AB - 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. Ann Neurol 2018;83:522–531.
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U2 - 10.1002/ana.25170
DO - 10.1002/ana.25170
M3 - Article
C2 - 29405350
AN - SCOPUS:85043470024
SN - 0364-5134
VL - 83
SP - 522
EP - 531
JO - Annals of neurology
JF - Annals of neurology
IS - 3
ER -