Ongoing Exercise Intolerance Following COVID‐19: A Magnetic Resonance–Augmented Cardiopulmonary Exercise Test Study, 2022, Brown et al

Abstract

Background
Ongoing exercise intolerance of unclear cause following COVID‐19 infection is well recognized but poorly understood. We investigated exercise capacity in patients previously hospitalized with COVID‐19 with and without self‐reported exercise intolerance using magnetic resonance–augmented cardiopulmonary exercise testing.

Methods and Results
Sixty subjects were enrolled in this single‐center prospective observational case‐control study, split into 3 equally sized groups: 2 groups of age‐, sex‐, and comorbidity‐matched previously hospitalized patients following COVID‐19 without clearly identifiable postviral complications and with either self‐reported reduced (COVIDreduced) or fully recovered (COVIDnormal) exercise capacity; a group of age‐ and sex‐matched healthy controls. The COVIDreducedgroup had the lowest peak workload (79W [Interquartile range (IQR), 65–100] versus controls 104W [IQR, 86–148]; P=0.01) and shortest exercise duration (13.3±2.8 minutes versus controls 16.6±3.5 minutes; P=0.008), with no differences in these parameters between COVIDnormal patients and controls. The COVIDreduced group had: (1) the lowest peak indexed oxygen uptake (14.9 mL/minper kg [IQR, 13.1–16.2]) versus controls (22.3 mL/min per kg [IQR, 16.9–27.6]; P=0.003) and COVIDnormal patients (19.1 mL/min per kg [IQR, 15.4–23.7]; P=0.04); (2) the lowest peak indexed cardiac output (4.7±1.2 L/min per m2) versus controls (6.0±1.2 L/min per m2; P=0.004) and COVIDnormal patients (5.7±1.5 L/min per m2; P=0.02), associated with lower indexed stroke volume (SVi:COVIDreduced 39±10 mL/min per m2 versus COVIDnormal 43±7 mL/min per m2 versus controls 48±10 mL/min per m2; P=0.02). There were no differences in peak tissue oxygen extraction or biventricular ejection fractions between groups. There were no associations between COVID‐19 illness severity and peak magnetic resonance–augmented cardiopulmonary exercise testing metrics. Peak indexed oxygen uptake, indexed cardiac output, and indexed stroke volume all correlated with duration from discharge to magnetic resonance–augmented cardiopulmonary exercise testing (P<0.05).

Conclusions
Magnetic resonance–augmented cardiopulmonary exercise testing suggests failure to augment stroke volume as a potential mechanism of exercise intolerance in previously hospitalized patients with COVID‐19. This is unrelated to disease severity and, reassuringly, improves with time from acute illness.

Open access, https://www.ahajournals.org/doi/10.1161/JAHA.121.024207

 

The paper also discusses the similarity of their findings with CPET findings in post-viral chronic fatigue syndrome

“Nevertheless, the differences suggest heterogeneity in the pathophysiology of persistent exercise intolerance following COVID‐19. This is in keeping with the finding of different exercise phenotypes in patients with postviral chronic fatigue syndrome, characterized as either low flow (with underlying low biventricular filling) or high flow (associated with impaired systemic oxygen extraction)”

and

“Factors that control ventricular filling (not directly assessed in this study) include blood volume and venous compliance. Indeed, blood volume is one of the most important factors in maintaining ventricular filling. Blood volume depletion is known to reduce exercise capacity,30 is depleted in postviral chronic fatigue syndrome, and correlates with exercise symptoms.31, 32Furthermore, volume expansion in these patients results in improved exercise tolerance.30 It is possible that similar mechanisms could occur in some patients following COVID‐19, reducing ventricular filling during exercise and contributing to exercise intolerance. Similar mechanistic origins of disease would perhaps be unsurprising given the symptom overlap between postviral chronic fatigue syndrome and patients following COVID‐19.

Possible causes of reduced blood volume following COVID‐19 that could be evaluated in future studies include detraining after severe illness, abnormal renal regulation of fluid balance, and reduced fluid or salt intake.33, 34 Although these causes require further investigation, they do raise the possibility of interventions tailored to volume expansion, such as increased hydration and salt intake. The other important contributor to preload is venous compliance, which controls the proportion of the total blood volume that is “stressed.” It is stressed that blood volume that directly contributes to preload and dynamic reduction of venous compliance is required to increase preload during exercise. Venous compliance is controlled by the autonomic system, and there is some evidence of dysautonomia in patients with postviral chronic fatigue syndrome34 along with small studies demonstrating dysautonomia in patients following COVID‐19.35, 36 Thus, an inability to dynamically reduce compliance may contribute to reduced exercise capacity in the COVIDreduced group and also requires further investigation”