Exercise Testing (CPET) & Post-Infection Limitations
Filling the gaps in clinical diagnostic screening and evaluation
If you’ve been lucky enough to somehow dodge the worldwide pandemic of the COVID-19 infection, consider yourself utterly lucky. One year after the beginning of the COVID-19 pandemic, more than 100 million individuals worldwide had been infected while the total number of COVID-related deaths surpassed two million (1). Regardless of political or ideological notions you might have toward the handling of the pandemic, it’s clear that one’s degree of health doesn’t automatically rule them out, or in, for contracting the virus. The range and degree of symptoms are still up in the air as far as being truly predictive towards outcome and prognosis (2). Rest assured, this isn’t an article discussing the pandemic and our beliefs around it, although it is important to be aware that we are witnessing and still in the middle of a true historical worldwide event that will be discussed and studied for all the years to come.
The main point of this month's topic surrounds the use of exercise testing which is referred to as cardiopulmonary exercise testing (CPET) in clinical practice (3) and its recent uses in detecting acute cardiac, respiratory & pulmonary conditions in people still experiencing some lingering symptoms associated with contracting the virus. An article released in late 2021 (4) in the BMJ Post Graduate Medical Journal outlines how the authors used cardiopulmonary exercise testing (CPET) to define unexplained dyspnea in patients with post-acute sequelae (a pathological condition resulting from a disease, injury, therapy, or other trauma) of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. While also, assessing participants for criteria to diagnose myalgic encephalomyelitis/chronic fatigue syndrome.
Have you ever visited the doctor's office or immediate care provider for a certain issue? Even if you were administered a series of diagnostic tests; X-Ray, MRI or Ultrasound, nothing was found to be the cause of your chief complaint? It’s very frustrating and even disheartening. You’re sure something is going on. I personally believe diagnostic testing & screening methods that are able to identify underlying issues in acute situations can be a real paradigm shift in the way that modern medicine currently goes about its business as we stand today. Acute conditions that’re mentioned and studied here are a perfect example.
Terminology
A little education break is in order to understand and keep track of where we are with terminology. What is interesting is the term “long hauler” or “long-haul” COVID is a term completely brought on by the social networks and general discussion in the world (4). In the medical community, patients are referred to as post-acute sequelae of SARS-CoV-2 infection (PASC). Many of these patients were never admitted to a hospital. PASC symptoms can be remitting, recurring, or debilitating, and they can remain even if there is no indication of residual injury on imaging examinations, leaving the etiology of post-recovery symptoms unknown (5). Dyspnea is a subjective sense of breathing difficulty that can only be determined by a patient's report, as stated in the study's title (6).
After an acute COVID infection, cardiac magnetic resonance can reveal cardiac dysfunction, however this has not been described specifically in PASC patients (7). Severe fatigue, cognitive difficulties, unrefreshing sleep, and myalgias are all symptoms of PASC, which are all symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). After a viral infection, this symptom of unexplained exhaustion has been documented; in fact, 27% of individuals who survived the 2005 SARS pandemic four years later met the criteria for ME/CFS (8). Cardiopulmonary exercise testing (CPET) is commonly performed to assess unexplained dyspnea and may be useful in determining the source of dyspnea and exercise intolerance in these patients. When respiratory data is combined with hemodynamic monitoring, new mechanisms such as exercise-induced pulmonary hypertension and preload failure can be identified (9). If you're unfamiliar with the term "pre-load," it refers to the degree of ventricular stretch while the heart is at the end of diastole (the pause of the heart between beats to refill with blood). Preload is one of the three key elements that directly influence stroke volume (SV), the amount of blood pumped out of the heart in one cardiac cycle, together with afterload and contractility. Variations in preload are directly influenced by changes in venous tone and circulating blood volume, hence impacting cardiac output and total heart function (10).
Okay, the actual study (4)
When arriving at the exercise testing facility, patients were asked a series of interview-style questions on how getting the virus had affected their life in exertion-related ways
Measurements & parameters of testing recorded were:
Forced expiratory volume-1 second (FEV1) measured through spirometry.
Patients were seated on a bicycle ergometer with an electrocardiogram (ECG), pulse oximeter, and blood pressure cuff attached to them (think of an indoor bike). Resting data was recorded for 3 minutes using a metabolic cart (clinical grade metabolic device), and then gradual cycling exercise was started at 0 watts (W), or resting, increasing by 25 W every 3 minutes until exhaustion. At each workload and at maximal exercise, blood pressure and subjective exhaustion were measured.
Right atrial, pulmonary artery, and pulmonary capillary wedge pressures were measured at rest, during each stage of exercise, and at peak exertion using a cardiac catheterization. At these timepoints, blood samples for pulmonary venous saturation and lactate were also taken.
The authors summarized their findings when the investigation was completed. They make a number of observations. To begin, practically all of the patients (88%) had variable ventilation, which could indicate dysfunctional breathing (DB), resting hypocapnia, or an exaggerated ventilatory response to exercise (elevated VE/VCO2 slope). Second, the majority of patients (58%) showed signs of circulatory impairment during maximal exercise performance. Finally, a significant number of people (46%) satisfied the ME/CFS criteria. This is also depicted in the diagram below.
Breaking down each area of function
Cardiac and pulmonary function
All of the subjects who had a low VO2 had a circulatory problem while they exercised. Intrinsic heart illness and/or anomalies in pulmonary or peripheral perfusion are both examples of circulatory dysfunction. Reduced lung perfusion is another symptom of circulatory impairment, which may play a role in the development of dyspnea. COVID has been linked to the production of large clots, including pulmonary emboli (11). The other patients who received invasive CPET had hemodynamic measures that indicated preload failure, including a muted increase in right atrial pressure during exercise (9). Preload failure, which has been reported in patients with unexplained dyspnea and ME/CFS (12) is thought to be caused by a decrease in plasma volume, resulting in hypovolemia. Autonomic dysfunction has also been suggested as a possible cause of PASC. Heart rate variability connected to the respiratory cycle is known as sinus arrhythmia. To explain this: Thoracic pressure drops, the chest cavity expands, air enters the lungs, arterial blood pressure drops, activating the arterial baroreceptors, vagal tone is suppressed, and heart rate rises during inspiration. During expiration, the opposite happens. This cardiopulmonary interaction can be disrupted by DB, resulting in increased dead space ventilation and intra-pulmonary blood shunting (13).
Ventilatory/Respiratory
There was no evidence of a primary ventilatory limitation to exercise in the trial. This is not surprising given that the study only included patients with normal PFTs, chest X-rays, and CT scans in our study. The use of CPET in these patients, however, revealed multiple aberrant resting and peak exercise ventilatory characteristics.
Many PASC patients had a rapid, erratic breathing pattern, which was similar to dysregulated breathing (DB). Asthmatic people are the most commonly affected by DB (14). DB can be triggered by prolonged hypoxia, metabolic imbalances, and/or anxiety. Rapid shallow breaths with or without hypocapnia are related with persistent hyperventilation disorders (15).
Many of the symptoms that people with PASC suffer, such as dyspnea, weariness, chest pain, and palpitations, are linked to DB and persistent hypocapnia. The discovery of DB and resting hypocapnia in this group is significant because it could represent a therapy target. Breathing retraining might help to alleviate symptoms (16). Years ago, Killian and Jones (17) popularized the hypothesis that dyspnea is caused by increased activity and/or labor of the respiratory muscles, or when these muscles are weak. Tachypnea at low levels of exertion in many of these PACS patients indicates increased respiratory muscle activity, which can contribute to dyspnea.
In Summary
“I’m having some trouble breathing, doctor. Normal daily tasks and especially any exercise really exacerbates it.” CT Scans, X-Rays look normal. When exposed to metabolic exercise testing, you see all the body’s systems working together (or at least trying to.) Findings from these testing modalities can alert practitioners of underlying issues that are not picked up on through common clinical diagnostic methods.
I thought the reference to breathing training, or re-training really, is a very interesting aspect of this process and takeaway. A lot of information and study has come out and is undergoing currently to see how much of a benefit this type of rehab modality can assist patients with these dysregulated breathing patterns from lingering issues due to COVID-19.
References
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Rajpal, S., Tong, M. S., Borchers, J., Zareba, K. M., Obarski, T. P., Simonetti, O. P., & Daniels, C. J. (2021). Cardiovascular Magnetic Resonance Findings in Competitive Athletes Recovering From COVID-19 Infection. JAMA cardiology, 6(1), 116–118. https://doi.org/10.1001/jamacardio.2020.4916
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