E2 ModerateModerate confidencePEM ?ObservationalPeer-reviewedMachine draft
The Relation Between Cardiac Output and Cerebral Blood Flow in ME/CFS Patients with a POTS Response During a Tilt Test.
van Campen, C Linda M C, Visser, Frans C · Journal of clinical medicine · 2025 · DOI
Quick Summary
When people with ME/CFS and POTS stand up, their blood pressure and heart rate don't respond normally, causing symptoms like dizziness and fatigue. This study looked at 260 ME/CFS patients during a tilt test to understand how the heart's output of blood relates to blood flow in the brain. The researchers found two different patterns: about two-thirds of patients showed their brain blood flow dropped at roughly the same rate as their heart's output decreased, while about one-third had a different pattern where their heart was racing but their heart output wasn't dropping as much, and their brain blood flow didn't follow the expected pattern.
Why It Matters
Understanding why some ME/CFS patients with POTS don't maintain adequate brain blood flow during position changes is crucial for explaining orthostatic symptoms and could guide personalized treatment approaches. The identification of two distinct hemodynamic patterns suggests that ME/CFS with POTS may not be a single disease mechanism, potentially explaining why treatments work differently for different patients.
Observed Findings
- Approximately two-thirds of ME/CFS patients with POTS showed proportional reductions in both cardiac output and cerebral blood flow during tilt testing.
- Approximately one-third showed limited cardiac output reduction despite substantial heart rate increase, with no corresponding proportional cerebral blood flow reduction.
- End-tilt heart rate and heart rate increase were significantly higher in patients with ≥15% cardiac output reduction.
- Cardiac output reduction percentage was more discriminative than heart rate increase or stroke volume reduction for categorizing patient groups.
- Cerebral blood flow measurements (supine, end-tilt, and percent reduction) did not differ significantly between the two patient groups despite different cardiac output patterns.
Inferred Conclusions
- ME/CFS patients with POTS demonstrate at least two distinct hemodynamic response patterns to orthostatic stress, suggesting heterogeneous underlying pathophysiology.
- Approximately one-third of POTS-phenotype ME/CFS patients may exhibit a hyperadrenergic response characterized by excessive heart rate elevation that does not proportionally maintain cardiac output or cerebral blood flow.
- Cardiac output reduction is a more reliable physiological marker than heart rate response for characterizing hemodynamic patterns in this population.
- The dissociation between cardiac output and cerebral blood flow in some patients suggests dysfunction in cerebral autoregulation or additional pathophysiological mechanisms beyond simple hemodynamic reduction.
What This Study Does Not Prove
This study does not prove causation—it only describes associations observed during tilt testing. The cross-sectional design cannot determine whether the hyperadrenergic pattern is a primary cause or a compensatory response to another underlying problem. It also does not establish which hemodynamic pattern is more harmful or whether either pattern responds better to specific treatments.
Tags
Symptom:Orthostatic IntoleranceFatigue
Biomarker:Blood Biomarker
Method Flag:Weak Case DefinitionNo ControlsExploratory Only
Metadata
- DOI
- 10.3390/jcm14113648
- PMID
- 40507411
- Review status
- Machine draft
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 8 April 2026