A108-08 Cardiovascular Dysfunction and Proteomic Insights in Long Covid: A Cross-sectional Study on Subclinical Myocardial Injury and Pathophysiological Mechanisms

Abstract Background Cardiac symptoms are reported in over 20% of individuals with long COVID (LC), yet their underlying mechanisms remain poorly understood, creating challenges for diagnosis and management. Method We conducted a case-control analysis nested within a community-based cross-sectional study, including participants primarily infected with Omicron between December 2022 and January 2023 who completed face-to-face follow-up between December 2023 and March 2024. A total of 173 participants were included, comprising 95 individuals with persistent cardiovascular long COVID (CLC) symptoms (e.g., palpitations, chest pain, bradycardia) and 78 non-LC controls matched by age and sex. All participants underwent transthoracic echocardiography, laboratory tests, the six-minute walk test (6MWT), and questionnaires. Additionally, a subset of 34 individuals (25 with CLC and 9 controls) received cardiac magnetic resonance (CMR) imaging. The primary outcome was the prevalence of impaired global longitudinal strain (GLS), defined as GLS -18% for men and -19% for women. Secondary outcomes included CMR findings, cardiac biomarker levels, six-minute walk distance (6MWD), and health-related quality of life (HRQoL). Exploratory plasma proteomic profiling was also performed to investigate underlying mechanisms. Results Among 173 participants (mean age 43.9 years, 80.4% female), 25.4% (43/169) exhibited abnormal GLS. Compared with matched controls, participants with CLC had significantly greater impairment, with a higher prevalence of abnormal GLS (p = 0.024). Using multivariable analysis, obesity (BMI ≥ 28.0 kg/m²) was independently associated with abnormal GLS (OR 2.43; 95% CI 1.08-5.46; p = 0.032). 35.9% (59/169) of participants had 6MWD below the lower limit of normal, and after inverse probability of treatment weighting (IPTW) adjustment, GLS abnormalities were correlated with a lower percentage of predicted 6MWD (p = 0.049). As for CMR, 35.3% (12/34) exhibited late gadolinium enhancement (LGE), most commonly located in the interventricular septum (7 of 12 cases). Mechanistically, proteomic analysis linked GLS impairment in CLC to enrichment of pro-inflammatory (e.g., IL-17 signaling, cellular senescence) and metabolic (AMPK, adipocytokine signaling) pathways, suggesting that persistent inflammation and disrupted lipid metabolism may contribute to the observed myocardial dysfunction. Conclusions Persistent CLC symptoms were associated with subclinical myocardial impairment, characterized by reduced GLS and non-ischemic myocardial fibrosis on CMR. Obesity emerged as an independent risk factor. Proteomic profiling suggested that persistent inflammation and metabolic dysregulation may underlie these findings. These results highlight the importance of longitudinal cardiac monitoring in patients with LC and warrant further investigation into targeted prevention strategies. This abstract is funded by: None