Exercise haemodynamics and myocardial deformation in long COVID assessed using three-dimensional echocardiography

Background/Introduction Long COVID is characterised by persistent symptoms beyond three months after acute infection, frequently including fatigue and exercise intolerance. Whether cardiovascular mechanisms underlie these symptoms remains unclear. While resting cardiac assessments are often normal, the possibility of abnormalities during the physiological stress of exercise has not been thoroughly investigated. Purpose To assess left ventricular (LV) myocardial deformation and haemodynamic responses to exercise in controls versus individuals with mild and severe long COVID using three-dimensional echocardiography (3DE). Methods Participants underwent 3DE at rest and during a cardiopulmonary exercise test on a semi-recumbent cycle ergometer. Echocardiographic images were acquired at predefined exercise intensities corresponding to target heart rates (HR) expressed as percentages of the age-predicted maximum, ensuring standardised physiological stress across participants. Indexed stroke volume (iSV), indexed cardiac output (iCO), and global longitudinal, circumferential, radial and principal strain (GLS, GCS, GRS, GPS, respectively) were derived using 3D speckle tracking analysis. Exercise responses were analysed using linear mixed-effects models including exercise stage, long COVID severity, modelled as an ordered variable and their interaction, adjusted for age, sex and body mass index. Results A total of 159 individuals were included (72 controls, 57 mild long COVID, 30 severe long COVID, mean age 49±15, 21% male). Long COVID severity was associated with an attenuated increase in stroke volume with exercise (p=0.014). There was no convincing evidence of time-by-group interactions for iCO (p=0.089), GLS (p=0.149), GCS (p=0.763), GRS (p=0.302) or GPS (p=0.865). Group effects were observed suggesting lower iCO (p=0.041) and GCS (p=0.016) in severe long COVID (Figure 1). Conclusions In individuals with long COVID, augmentation of iSV with exercise is attenuated compared with controls, indicating impaired haemodynamic reserve during physiological stress. Although myocardial strain responses to exercise were largely preserved, lower iCO and GCS in severe long COVID suggest subtle baseline functional differences. These differences may contribute to exercise intolerance in patients with long COVID.ESC_Figure1.jpg