Reduced Stroke Volume and Brain Perfusion Drive Postural Hyperventilation in Postural Orthostatic Tachycardia Syndrome, 2024, Jacquie R. Baker et al

Highlights
POTS causes cardiovascular instability and severe symptoms.
Postural hyperventilation is thought to cause POTS, but the mechanisms are unclear.
Reduced stroke volume and brain perfusion drive postural hyperventilation in POTS.
Stroke volume and brain perfusion should be targeted as management strategies.

Summary
Postural hyperventilation has been implicated as a cause of postural orthostatic tachycardia syndrome (POTS), yet the precise mechanisms underlying the heightened breathing response remain unclear. This study challenges current hypotheses by revealing that exaggerated peripheral chemoreceptor activity is not the primary driver of postural hyperventilation. Instead, significant contributions from reduced stroke volume and compromised brain perfusion during orthostatic stress were identified. These findings shed light on our understanding of POTS pathophysiology, emphasizing the critical roles of systemic hemodynamic status. Further research should explore interventions targeting stroke volume and brain perfusion for more effective clinical management of POTS.

Participants
All studies were performed in Calgary (altitude 1,045 m above sea level). A total of 25 female patients with POTS were recruited from the Calgary Autonomic Investigation and Management Clinic, the autonomic research laboratory, and through our local study database. All patients had physician diagnoses of POTS according to the consensus statement criteria. Diagnostic orthostatic vital signs are presented.

Eleven sex- and age-matched (±3 years) control subjects were recruited from the community via local advertising. There were no baseline differences between female patients with POTS and control subjects. Study participants were excluded if they were smokers, pregnant or breastfeeding, could not tolerate wearing an oxygen mask, required portable oxygen at rest or with exercise, or had chronic heart failure or severe pulmonary disease. Additional exclusion criteria included dementia, alcohol and/or drug abuse, cerebrovascular disease, kidney or liver disease, and sympathectomy. All participants were asked to abstain from alcohol, caffeine, and exercise for 12 hours prior to testing.

Patients were asked to hold medications that modulate heart rate and blood pressure, if possible. Fourteen patients (56%) were not taking any heart rate–modulating or blood pressure–modulating medications during the study, including beta-blockers, midodrine, fludrocortisone, pyridostigmine, ivabradine, clonidine, and methyldopa. Stratified analyses were done to compare outcomes between patients who were off all relevant medications and those who remained on some of these medications.

Only baseline heart rate was different between patients on vs off medications. There were no other differences in baseline or upright ventilatory, sympathetic, or hemodynamic parameters between patients on vs off medications. Additionally, there were no differences in the supine or upright ventilatory responses to hyperoxia between patients on vs off their treatment medications

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