Supine–Standing Echocardiography Reveals Preload Failure as the Primary Driver of POTS and Long COVID Orthostatic Intolerance

Christoper Thomas, Graham Exelby November 2025

Abstract

Background:

Orthostatic intolerance in Postural Orthostatic Tachycardia Syndrome (POTS) and Long COVID has been framed primarily as an autonomic disorder, despite weak correlations between symptoms, heart rate, and autonomic testing. Tilt-table testing does not assess venous return, ventricular filling, or thoracic inlet dynamics. We investigated whether supine–standing echocardiography could identify reproducible haemodynamic signatures that more accurately explain orthostatic symptoms.

Methods:

Consecutive patients with POTS or Long COVID underwent standardised supine and standing echocardiography assessing LVOT/AV VTI, early diastolic tissue velocities (E′), E/E′, inferior vena cava behaviour, and superior vena cava (SVC) velocity/phasicity. Echocardiographic changes were correlated with clinical features and used to define mechanistic preload-failure phenotypes.

Results:

All patients demonstrated impaired upright preload, with reduced VTI and loss of early diastolic suction. Four consistent phenotypes emerged:

1.     Mechanical–Venous Preload Failure (MVPF): thoracic inlet impedance with elevated SVC velocities and vertebral–azygos diversion.

2.     Central–Brainstem Preload Failure (C-BPF): cervical venous congestion impairing brainstem autonomic integration.

3.     RAAS-Dysregulated Preload Failure (C-BPF-R): post-viral renin–aldosterone dysfunction with microvascular instability.

4.     Hybrid phenotypes: modest impairments across multiple pathways converging to produce significant preload loss.

Across all phenotypes, tachycardia occurred after mechanical underfilling and functioned as a compensatory mechanism.

Conclusions:

Supine–standing echocardiography consistently reveals preload failure as the primary haemodynamic mechanism in POTS and Long COVID, reframing tachycardia as a secondary baroreflex response rather than a causative abnormality. This preload-first model integrates mechanical, vascular, metabolic, and central contributors to orthostatic intolerance and provides a coherent physiological basis for diagnosis and treatment. Supine–standing echocardiography should be adopted as a first-line diagnostic tool in these conditions.

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