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Why Standing Up Is Exhausting: The Preload-Failure Mechanism in ME/CFS and Long COVID

David Systrom, MD, of Harvard and Brigham and Women's Hospital, has run invasive cardiopulmonary exercise testing (iCPET) in ME/CFS and Long COVID patients for over a decade and found a specific circulatory finding, preload failure (the heart not filling with enough blood between beats), in roughly 90 percent of ME/CFS patients tested this way. This explains a common experience: standing and exertion feel exhausting because there is a measurable circulatory reason, not because it is 'in your head.' This is diagnostic mechanism research, not a self-directed treatment, and iCPET is a specialized test administered only by a trained clinical team. Because post-exertional malaise is central to ME/CFS and Long COVID, the safe approach is pacing first: staying within your energy envelope rather than increasing activity on a set schedule. Our Energy Envelope protocol covers what to actually do.

Not endorsed · based on the published work of David Systrom, MD

What the evidence says

Understand the finding

Preload failure means the heart is not filling with enough blood between beats, found via invasive testing in roughly 90 percent of ME/CFS patients Systrom's lab has tested n/a, education only

This gives a specific physiological name to a very common symptom experience.

Systrom, CDC-hosted presentation, 2022

Know this is diagnostic, not a home test

iCPET is a specialized, invasive test performed only by a trained clinical research team; it is not something to seek out casually or self-administer n/a

iCPET involves catheters measuring pressure directly inside the heart and lungs during exercise; it is a research/specialist-clinic procedure, not a routine or self-directed test.

Systrom, iCPET research program

This explains, it does not treat

Use this to understand the mechanism behind your symptoms, and bring it up with a clinician familiar with this research if you want to discuss it n/a

Systrom's work is diagnostic mechanism research; it identifies why symptoms happen, and does not itself prescribe a treatment.

Editorial policy

The evidence 6

Preload failure means venous blood is not returning to the heart efficiently enough, so the heart pumps out less blood per beat than it should, even though the heart muscle itself is working normally.

View sources

Systrom, CDC ME/CFS Program presentation slides Read CDC

Heart Preload Failure in ME/CFS Read Mass General Brigham

NICE NG206: Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management, recommendations Read NICE

StatPearls, Postural Orthostatic Tachycardia Syndrome: the within-10-minutes criterion, the active stand test protocol, and head-up tilt as the accepted standard Read NCBI Bookshelf

Dysautonomia International, What is POTS?: the diagnostic criteria in plain language, and the bedside stand test used where tilt testing is not available Read Dysautonomia International

2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia and vasovagal syncope Read Heart Rhythm, 2015

Not medical advice. This page is for education only and is not a substitute for professional medical care. Consult a qualified clinician before changing your health routine.
Independent curation. YourProtocol is an independent platform. This protocol is based on the publicly available work of David Systrom, MD and is not created, reviewed, endorsed by, or affiliated with David Systrom, MD or Brigham and Women's Hospital, Harvard Medical School.

Is this for you

Anyone who has been told exertion intolerance is "just anxiety" and wants the physiological explanation
People with ME/CFS or Long COVID curious what iCPET testing actually measures

Cautions

This is mechanism education, not a treatment or self-directed protocol
iCPET is a specialized, invasive research/clinical test, never self-administered
Only a clinician can order or interpret this kind of testing

Common questions

I have Long COVID or ME/CFS and want to get back to the gym. How do I start?

Preload failure explains why standing and exertion feel disproportionately hard, it does not tell you how to build activity back up, and that distinction matters most here. If exertion itself makes your symptoms worse a day or more afterward (post-exertional malaise, the hallmark of ME/CFS and many Long COVID presentations), the instinct to schedule a gradual return, a little more each week, is exactly the graded-exercise-therapy approach, and current UK clinical guidance (NICE NG206) says any programme of fixed, incremental activity increases, including graded exercise therapy, should not be offered for ME/CFS. With a heart that is not filling adequately between beats, pushing a fixed schedule on top of that risks a crash rather than building capacity. The safer approach is to pace first: stay inside your own energy envelope, with limits set by your symptoms and, where useful, a heart-rate ceiling, rather than a calendar. Our Energy Envelope pacing protocol is where to go for the how-to; this page only explains the mechanism. This is information, not medical advice, and it is never a promise of recovery.

How do I get diagnosed with POTS or ME/CFS when my doctor does not believe me? What test do I ask for?

iCPET, the invasive test this page is about, is a specialized research and clinical-trial tool run at a handful of centers, so it is not the first test to ask for and not something a general clinician can order easily. For POTS specifically, the standard diagnostic test is a tilt table test (also written tilt-table testing); where that is not available, clinicians use a bedside active stand test or the NASA Lean Test, lying down for 10 minutes, then standing for 10 more while heart rate and blood pressure are checked each minute. The threshold most guidelines use is a sustained heart-rate rise of 30 beats per minute or more within 10 minutes of standing in adults (40 bpm or more in adolescents), without the blood-pressure drop that would point to orthostatic hypotension instead. ME/CFS has no single confirmatory lab test; it is diagnosed clinically against criteria that include post-exertional malaise, unrefreshing sleep, and a substantial, lasting drop in function. If your doctor does not believe your symptoms are real, or dismisses you without testing, that is a reason to specifically ask for a referral to a cardiologist or autonomic specialist for tilt-table or autonomic testing, or to seek a second opinion; both POTS and ME/CFS are physical, measurable findings, not something you are imagining. Only a clinician can diagnose either condition; this is what to ask for walking in, not a diagnosis itself.

Why Standing Up Is Exhausting: The Preload-Failure Mechanism in ME/CFS and Long COVID

The Energy Envelope: Pacing for ME/CFS & Long COVID

Orthostatic Intolerance: Non-Drug Management