Ongoing Exercise Intolerance Following COVID-19: A Magnetic Resonance-Augmented Cardiopulmonary Exercise Test Study.

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.

Prospective Case-Control Study of Cardiovascular Abnormalities 6 Months Following Mild COVID-19 in Healthcare Workers.

OBJECTIVES: The purpose of this study was to detect cardiovascular changes after mild severe acute respiratory syndrome-coronavirus-2 infection. BACKGROUND: Concern exists that mild coronavirus disease 2019 may cause myocardial and vascular disease. METHODS: Participants were recruited from COVIDsortium, a 3-hospital prospective study of 731 health care workers who underwent first-wave weekly symptom, polymerase chain reaction, and serology assessment over 4 months, with seroconversion in 21.5% (n = 157). At 6 months post-infection, 74 seropositive and 75 age-, sex-, and ethnicity-matched seronegative control subjects were recruited for cardiovascular phenotyping (comprehensive phantom-calibrated cardiovascular magnetic resonance and blood biomarkers). Analysis was blinded, using objective artificial intelligence analytics where available. RESULTS: A total of 149 subjects (mean age 37 years, range 18 to 63 years, 58% women) were recruited. Seropositive infections had been mild with case definition, noncase definition, and asymptomatic disease in 45 (61%), 18 (24%), and 11 (15%), respectively, with 1 person hospitalized (for 2 days). Between seropositive and seronegative groups, there were no differences in cardiac structure (left ventricular volumes, mass, atrial area), function (ejection fraction, global longitudinal shortening, aortic distensibility), tissue characterization (T1, T2, extracellular volume fraction mapping, late gadolinium enhancement) or biomarkers (troponin, N-terminal pro-B-type natriuretic peptide). With abnormal defined by the 75 seronegatives (2 SDs from mean, e.g., ejection fraction <54%, septal T1 >1,072 ms, septal T2 >52.4 ms), individuals had abnormalities including reduced ejection fraction (n = 2, minimum 50%), T1 elevation (n = 6), T2 elevation (n = 9), late gadolinium enhancement (n = 13, median 1%, max 5% of myocardium), biomarker elevation (borderline troponin elevation in 4; all N-terminal pro-B-type natriuretic peptide normal). These were distributed equally between seropositive and seronegative individuals. CONCLUSIONS: Cardiovascular abnormalities are no more common in seropositive versus seronegative otherwise healthy, workforce representative individuals 6 months post-mild severe acute respiratory syndrome-coronavirus-2 infection.

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance.

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.