Differential Cardiopulmonary Hemodynamic Phenotypes in PASC Related Exercise Intolerance, 2023, Singh et al

Differential Cardiopulmonary Hemodynamic Phenotypes in PASC Related Exercise Intolerance
https://openres.ersjournals.com/content/early/2023/12/07/23120541.00714-2023

Background
Post-acute sequelae of COVID-19 (PASC) affects a significant portion of patients who have previously contracted SARS-CoV-2, with exertional intolerance being a prominent symptom.

Study Objective
This study aimed to characterize the invasive hemodynamic abnormalities of PASC-related exertional intolerance using a larger data set from invasive cardiopulmonary exercise testing (iCPET).

Study Design & Intervention
Fifty-five patients were recruited from the Yale Post-COVID-19-Recovery-Program, with most experiencing mild acute illness. Supine right heart catheterization (RHC) and iCPET were performed on all participants.

Main results
The majority (75%) of PASC patients exhibited impaired peak systemic oxygen extraction (pEO2) during iCPET in conjunction with supranormal cardiac output (CO) (i.e., PASC alone group), On average, the PASC alone group exhibited a “normal” peak exercise capacity, VO2 (89±18% predicted). Approximately 25% of patients had evidence of central cardiopulmonary pathology (i.e., 12 with resting and exercise HFpEF and 2 with exercise PH). PASC patient with HFpEF (i.e., PASC HFpEF group) exhibited similarly impaired pEO2 with well compensated PH (i.e., peak VO2 and cardiac output >80% respectively) despite aberrant central cardiopulmonary exercise hemodynamics. PASC patients with HFpEF also exhibited increased body mass index of 39±7 kg·m−2. To examine the relative contribution of obesity to exertional impairment in PASC HFpEF, a control group compromising of obese non-PASC group (n=61) derived from historical iCPET cohort was used. The non-PASC obese patients with preserved peak VO2 (>80% predicted) exhibited a normal peak pulmonary artery wedge pressure (17±14 versus 25±6 mmHg; p=0.03) with similar maximal voluntary ventilation (90±12 versus 86±10%predicted; p=0.53) compared to PASC HFpEF patients. Impaired pEO2 was not significantly different between PASC patients who underwent supervised rehabilitation and those who did not (p=0.19).

Conclusions
This study highlights the importance of considering impaired pEO2 in PASC patients with persistent exertional intolerance unexplained by conventional investigative testing. Results of current study also highlights the prevalence of a distinct high output failure HFpEF phenotype in PASC with a primary peripheral limitation to exercise.

 

For these patients, the next step is typically a cardiopulmonary exercise test in which the patient rides a stationary bike or runs on a treadmill while sensors track physiological activity up to the point the person feels they have to stop the exercise. However, there are still patients for whom this type of test reveals no cause of exercise intolerance.

The majority of patients just want to know that there’s something real going on. I think that’s a very valid reason to undergo a test.

Yale is one of very few places in the United States where a more advanced version of this evaluation — the invasive cardiopulmonary exercise test, or iCPET — is available. For the test, pressure sensing catheters are inserted into the pulmonary artery, a main blood vessel in the lungs, and at an artery in the wrist. As patients exercise, physicians track various measures to observe how well the heart, lungs, blood vessels, and muscles are functioning.

https://news.yale.edu/2023/12/19/study-helps-explain-post-covid-exercise-intolerance

 

More strong evidence that we need to start looking a lot more closely at muscle and microvasculature to figure out why patients aren't able to extract oxygen from their blood. Pretty clear the problem isn't in the heart or lungs.

Also, this is good:

"While deconditioning is commonly suggested to result in impaired pEO2, we did not observe a significant difference in pEO2 amongst PASC patients who underwent supervised out-patient rehabilitation program compared to those who did not undergo rehabilitation. Furthermore, the hallmark of deconditioning is reduced peak CO and bedrest studies demonstrate only a mild impairment of pEO2 24 . In contrast, in the current study PASC patients exhibited a high peak exercise CO along with a normal peak heart rate response."

 

Anecdotally, this matches my own experience very well of the early days of ME (once as a teenager, once more recently). One thing that was quite notable to me at the very start in both cases was a distinct inability to output the expected power from my muscles while biking or cross-country skiing. Normal respiration and heart rate, but my muscles clearly were unable to produce the power I was used to. I was used to being limited by my cardiovascular system, meaning I couldn't increase power output without increasing my heart and respiratory rates, but this was something quite different, where the limitation was elsewhere. This was more distinct a day after exertion as well.

This is also different from the experience of exertion at altitude, where there is a similar experience of lack of power output from the muscles, but accompanied by faster breathing and heart rate.

 

I've been gathering some papers and will post over the next few days. Some work was done on in this in ME/CFS specifically 20+ years ago, so I think it's probably good for us to have threads for those historical papers too.

 

Dead space ventilation, aka physiological dead space is the combination of anatomical (conducting airways) and alveolar (alveoli not adequately perfused by capillaries for gas exchange).

Venous oxygen saturation would be around 70-80% in HCs at rest. It will go down substantially with peak exercise as more oxygen is extracted in muscles.

 

See also our other papers tagged oxygen extraction.

 

Is there a meta-analysis on this somewhere that somehow tries to explain all different results? Personally, I feel like the results aren't consistent enough, possibly due to inconsistent methodology, varying cohorts or it not being quite as useful method as some patients believe, possibly because it only captures downstream effects of muscular or vascular problems in the oxygen extraction.

 

This quote bothered me. It's been said over and over again in the community. The patients know that something is wrong, they want to know WHAT is wrong, because that's how problems become fixable. We all know that unless the problem is understood, there is no way to fix it. This is a huge difference and the framing is just annoying.