What Actually Causes POTS? A Mechanistic Reading of Postural Orthostatic Tachycardia Syndrome — Why the standard POTS-treatment toolkit produces the response patterns it does

Returning to the variability in standard-treatment response, the four-pathway framework explains the pattern. Patients with dominant Pathway 4 respond well to standard treatment because standard treatment is designed for their pathway. Patients with dominant Pathway 3 respond partially: compression and volume expansion address some of the venous pooling, but the connective tissue substrate is not addressed by any standard intervention. Patients with dominant Pathway 1 respond minimally to standard treatment alone because the upstream lesion (NAD+ collapse and autonomic ganglion bioenergetic failure) is not addressed by symptomatic management; they often respond substantially to upstream work added to the symptomatic management. Patients with dominant Pathway 2 respond inconsistently to standard treatment because the vagal dysregulation produces variable hemodynamic compensation; they often respond substantially to vagal restoration work combined with gut treatment. This pattern is consistent with what the POTS literature documents but does not stratify. The framework provides a stratification that the literature has been moving toward but has not yet formalized.