Resting and Exercise-Induced Hyperventilation in Orthostatic Intolerance and Spiky-Leaky Syndrome

Amir Hashemizad Jerriel Dela Cruz Aditya Narayan Andrew James Maxwell ^*

• Heart of the Valley Pediatric Cardiology, Pleasanton, California, United States

Background: Orthostatic intolerance with or without postural orthostatic tachycardia syndrome (POTS), which we collectively term as orthostatic intolerance dysautonomia syndromes (OIDS), often presents with daytime hyperventilation thought secondary to sympathetic hyperactivity. This appears to be a key feature in a newly described subset of patients with OIDS who also exhibit craniocervical instability, mast cell activation syndrome (MCAS), hypermobility spectrum disorder (HSD), and alternating intracranial hypertension with hypotension due to cerebral spinal fluid leak, termed Spiky-Leaky Syndrome (SLS). Methods: We performed a retrospective review of clinical metabolic exercise data in young patients with SLS, comparing them to matched patients who had OIDS and with healthy controls (CTL). We assessed metabolic parameters at rest, at the anaerobic threshold (AT), and at maximal oxygen consumption (VO2max). Parameters include End-tidal CO2 (ETCO2), End-tidal O2 (ETO2), Peak Oxygen Pulse, Total Work Performed, and Peak Oxygen Uptake Efficiency Slope (OUESp).Results: From 323 reviewed exercise stress tests, 44 were from patients with SLS, 210 from those with OIDS, and 53 from CTL. VO₂ Max , AT, Peak Oxygen Pulse, Total Work Performed, and OUESp were all significantly reduced in those with OIDS and further reduced in those with SLS. ETCO2 levels were notably lower at rest, at the time of anaerobic threshold, and at time of maximal velocity of oxygen uptake in the OIDS group and even more so in the SLS group; this lower ETCO2 persisted thorough exercise. In contrast, ETO2 demonstrated an opposite but similarly pronounced trend.Compared to controls, patients with OIDS -and especially those with SLS -exhibit reduced metabolic parameters, particularly reduced peak oxygen pulse and ETCO2 during both rest and exercise. These findings suggest a reduction in ventricular preload and chronic daytime hyperventilation. These exercise parameters may serve as a markers for POTS physiology and for sympathetic hyperactivity respectively and both could play a role in a pathophysiology of SLS.