Hypocapnic cerebral hypoperfusion: A biomarker of orthostatic intolerance

The objective of the study was to identify markers of hypocapnic cerebral hypoperfusion (HYCH) in patients with orthostatic intolerance (OI) without tachycardia and without orthostatic hypotension. This single center, retrospective study included OI patients referred for autonomic evaluation with the 10 min tilt test. Heart rate, end-tidal CO2 (ET-CO2), blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery were monitored. HYCH was defined by: (1) Symptoms of OI; (2) Orthostatic hypocapnia (low ET-CO2); (3) Abnormal decline in orthostatic CBFv due to hypocapnia; 4) Absence of tachycardia, orthostatic hypotension, or other causes of low CBFv or hypocapnia. Sixteen subjects met HYCH criteria (15/1 women/men, age 38.5 +/- 8.0 years) and were matched by age and gender to postural tachycardia patients (POTS, n = 16) and healthy controls (n = 16). During the tilt, CBFv decreased more in HYCH (-22.4 +/- 7.7%, p<0.0001) and POTS (-19.0 +/- 10.3%, p<0.0001) compared to controls (-3.0 +/- 5.0%). Orthostatic ET-CO2 was lower in HYCH (26.4 +/- 4.2 (mmHg), p<0.0001) and POTS (28.6 +/- 4.3, p<0.0001) compared to controls (36.9 +/- 2.1 mmHg). Orthostatic heart rate was normal in HYCH (89.0 +/- 10.9 (BPM), p<0.08) and controls (80.8 +/- 11.2), but was higher in POTS (123.7 +/- 11.2, p<0.0001). Blood pressure was normal and similar in all groups. It is concluded that both HYCH and POTS patients have comparable decrease in CBFv which is due to vasoconstrictive effect of hypocapnia. Blood flow velocity monitoring can provide an objective biomarker for HYCH in OI patients without tachycardia.