Noninvasive detection of sympathetic neurocirculatory failure

Abstract

In sympathetic neurocirculatory failure (SNF), reflexive sympathetically mediated cardiovascular stimulation does not compensate for decreased cardiac filling. This explains orthostatic hypotension in chronic primary autonomic failure (CPAF). During phase 2 of the Valsalva maneuver (phase 2_L), blood pressure increases from its peak. During phase 4, blood pressure normally "overshoots" the baseline. Because these changes depend on sympathetically mediated cardiovascular stimulation, a progressive decrease in pressure during phase 2 and absence of the overshoot in phase 4 may indicate SNF. Moreover, because beat-to-beat blood pressure can be measured noninvasively using a photoplethysmographic or tonometric device, evaluating reflexive pressure responses might enable noninvasive diagnosis of SNF. This study assessed the relative frequencies of abnormal phase 2_L and phase 4 blood pressure in patients with CPAF and orthostatic hypotension and whether noninvasive measurement of beat-to-beat blood pressure can be used to diagnose SNF in patients. Twenty patients with chronic primary autonomic failure and orthostatic hypotension and 50 comparison patients, including several with CPAF but lacking orthostatic hypotension, underwent arterial pressure monitoring during performance of the Valsalva maneuver. Of the 20 patients with CPAF and orthostatic hypotension, all had an abnormal phase 2_L or phase 4 pressure response (sensitivity 100%), whereas only 3 of the 50 comparison patients had an abnormal response in either phase (specificity 94%). Seventeen patients with CPAF and orthostatic hypotension had abnormal responses in both phases (sensitivity 85%), but none of the comparison patients had such findings in both phases (specificity 100%). Of 13 patients in whom beat-to-beat blood pressure was recorded simultaneously invasively and noninvasively, all had abnormal blood pressure responses during phase 2_L and phase 4, whereas none of 29 comparison patients had such symptoms. Detection of abnormal blood pressure responses during phase 2_L or phase 4 of the Valsalva maneuver is a highly sensitive test for SNF. Abnormal pressure during these phases appears to identify SNF specifically. Noninvasive measurements can detect both of these abnormalities.

Association Between Supine Hypertension and Orthostatic Hypotension in Autonomic Failure

“…A progressive decline in blood pressure during Phase II and absence of pressure overshoot in Phase IV therefore characterize patients with sympathetic neurocirculatory failure ( Figure 1). 28 Antecubital venous blood was sampled through an indwelling intravenous catheter, and vital signs were measured after at least 15 minutes of supine rest and after 5 minutes of standing upright. Plasma levels of catechols were assayed by batch alumina extraction followed by liquid chromatography with electrochemical detection, as described previously.…”

Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy

“…NOH was defined by orthostatic hypotension coupled with abnormal beat-to-beat blood pressure associated with performance of the Valsalva maneuver [28].…”

Neurocirculatory Abnormalities in Chronic Orthostatic Intolerance

“…None had orthostatic hypotension, defined by a consistent, persistent fall in systolic blood pressure of 20 mm Hg or more after 5 minutes of standing up, and none had baroreflex-sympathoneural failure, detected by abnormal responses of beat-to-beat blood pressure during the Valsalva maneuver. 4 We classified patients as having POTS on the basis of an orthostatic increment of heart rate of at least 30 bpm or absolute heart rate of at least 110 bpm during orthostasis, with or without syncope or presyncope. We classified patients as having NCS by a history of chronic, repeated episodes of fainting or near-fainting, with documented tilt-evoked neurally mediated hypotension or syncope, without orthostatic tachycardia.…”

“…The pattern of beat-to-beat blood pressure excluded sympathetic neurocirculatory failure in all subjects. 4 For estimation of the rate of entry of endogenous norepinephrine into arterial plasma (total body norepinephrine spillover), 3 H-norepinephrine was infused intravenously, and total body norepinephrine spillover was calculated from the specific activity of 3 H-norepinephrine in arterial plasma. 7 Orthostasis consisted of standing upright or else upright tilting via a motorized tilt table for 5 minutes after the subject had been supine for at least 15 minutes.…”