Persistent endothelial dysfunction is associated with exercise intolerance in adults despite preserved myocardial work 3 years after SARS‐CoV‐2 infection

Abstract

Abstract Long COVID is frequently associated with persistent exercise intolerance, although the relative contributions of peripheral vascular dysfunction and myocardial function remain unclear. We investigated whether persistent endothelial dysfunction and altered myocardial work (MW) contribute to exercise intolerance approximately 3 years after SARS‐CoV‐2 infection. This case–control study included adults with Long COVID (n = 10) and controls (n = 11) who underwent cardiopulmonary exercise testing (CPET), transthoracic echocardiography with global longitudinal strain (GLS) and MW analysis, and brachial artery flow‐mediated dilation (FMD) with hyperemic shear assessment. Compared with controls, Long COVID participants exhibited lower peak V̇O2 (19.6 ± 2.5 vs. 24.3 ± 6.5 mL·kg−1·min−1, p = 0.04), percent‐predicted peak V̇O2 (61.1 ± 8.3 vs. 77.0 ± 14.2%, p = 0.006), and V̇O2 at first ventilatory threshold (11.0 ± 1.4 vs. 13.7 ± 3.8 mL·kg−1·min−1, p = 0.04). Conventional echocardiographic parameters and MW indices did not differ between groups (all p > 0.05). In contrast, endothelial function was impaired in the Long COVID group, with lower FMD (p < 0.001), peak shear rate (p = 0.01), AUCSR (p = 0.04), and AUCmax (p = 0.001). FMD correlated positively with exercise capacity in the Long COVID group (peak V̇O2: r = 0.68, p = 0.03;percent‐predicted peak V̇O2: r = 0.64, p = 0.04). In conclusion, 3 years after infection, Long COVID remains characterized by endothelial dysfunction and blunted hyperemic shear despite preserved MW, supporting a predominantly peripheral vascular basis for persistent exercise intolerance.