Ongoing Exercise Intolerance Following COVID‐19: A Magnetic Resonance–Augmented Cardiopulmonary Exercise Test Study

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 (COVID reduced ) or fully recovered (COVID normal ) exercise capacity; a group of age‐ and sex‐matched healthy controls. The COVID reduced group 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 COVID normal patients and controls. The COVID reduced 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 COVID normal 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 m 2 ) versus controls (6.0±1.2 L/min per m 2 ; P =0.004) and COVID normal patients (5.7±1.5 L/min per m 2 ; P =0.02), associated with lower indexed stroke volume (SVi:COVID reduced 39±10 mL/min per m 2 versus COVID normal 43±7 mL/min per m 2 versus controls 48±10 mL/min per m 2 ; 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.

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

“…Szekely et al found that 75% of PASC participants had chronotropic incompetence compared to 8% of control participants; they reported that chronotropic incompetence was the most likely explanation of reduced exercise capacity in PASC. 21 They also found reduced stroke volume augmentation consistent with Brown et al 30 incompetence, present in 38% of their sample, contributed to exercise limitation, with greater limitations in exercise and heart rate among hospitalized individuals. 38 Jimeno-Almazán et al found chronotropic incompetence on CPET using a cycle ergometer and confirmed by treadmill testing among 4/32 individuals (13% of study sample) with reduced exercise capacity after COVID-19.…”

“…52–54 Endothelial dysfunction may be associated with reduced VO 2 in PASC; 55 this could be due to endothelial injury from direct viral infection, or due to effects of persistent inflammation and immune activation. 56 Elevated inflammation resulting in changes in autonomic function in PASC could explain reduced exercise capacity, chronotropic incompetence, blunted heart rate recovery, reduced heart rate variability and CPET findings others have noted in PASC including altered peripheral oxygen extraction, 57 preload failure 58 or inadequate stroke volume augmentation, 23, 24 and disordered breathing. 58–60…”

“…All reported lower peak VO 2 among those with symptoms despite differences in defining symptoms. 18–21, 29, 30 Most assessed mostly previously hospitalized individuals at 3-6 months after infection. These studies have not reached consistent conclusions regarding the etiology of reduced exercise capacity, which may be related to different study populations, exercise protocols and proportions with sub-maximal tests.…”

“…These studies have not reached consistent conclusions regarding the etiology of reduced exercise capacity, which may be related to different study populations, exercise protocols and proportions with sub-maximal tests. Two studies attributed lower peak Durstenfeld et al CPET, CMR, and Ambulatory Rhythm Findings >12 months after COVID-19 VO2 to inadequate augmentation of stroke volume 30 or chronotropic incompetence and poor stroke volume augmentation. 21 Others have attributed exercise limitations to ventilatory inefficiency from pulmonary vasculopathy, 18 respiratory abnormalities, 19 obesity and differences in cardiorespiratory fitness 29 and deconditioning.…”

“…[15][16][17][18][19] Studies using cardiopulmonary exercise testing (CPET) have demonstrated reduced exercise capacity at 3-6 months after SARS-CoV-2 infection without consistent patterns of exercise limitation. [19][20][21][22][23][24] Finally, whether arrhythmias explain palpitations in PASC is unknown beyond 3 months. 25,26 We designed the Long-Term Impact of Infection with Novel Coronavirus (LIINC) study (NCT 04362150) to evaluate physical and mental health following SARS-COV-2 infection by including individuals representing the full spectrum of acute illness (asymptomatic to severe) and post-acute-recovery (full recovery, symptomatic PASC).…”