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

ObjectiveBlunted 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. MethodsPatients evaluated at sites of the U.S. Autonomic Consortium (NCT01799915) underwent standardized autonomic function tests and full neurological evaluation. ResultsWe 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; -4425 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 HR/SBP 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. InterpretationA blunted HR increase during hypotension suggests a neurogenic cause. A HR/SBP ratio<0.5 bpm/mmHg is diagnostic of neurogenic OH. Ann Neurol 2018;83:522-531