Ventricular-Arterial Uncoupling in Mild to Moderate COVID-19 Pneumonia: Role of A Novel Ventricular-Vascular Coupling Index

Ventricular-Arterial Uncoupling in Mild to Moderate COVID-19 Pneumonia: Role of A Novel Ventricular-Vascular Coupling Index | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Ventricular-Arterial Uncoupling in Mild to Moderate COVID-19 Pneumonia: Role of A Novel Ventricular-Vascular Coupling Index Shiyi Zhang, Lin Jin, Xinyi Li, Jianhui Zhang, Ning Wang, Jianxiong Chen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6812543/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective The physiological interaction between the left ventricle (LV) and the arterial system, known as ventricular-arterial coupling (VAC), plays a crucial role in optimizing cardiac work and overall cardiovascular performance. This study aims to investigate VAC by analyzing the ratio of the arterial velocity pulse index (AVI) to LV global longitudinal strain (GLS), in patients with mild to moderate COVID-19. Methods This study included 180 controls and 154 patients with mild to moderate COVID-19. We compared laboratory indicators, left ventricular ejection fraction (LVEF), TDI e’, effective arterial elasticity (Ea), left ventricular end-systolic elasticity (Ees), ventricular-arterial coupling index (VVI), AVI and GLS between the two groups. Correlations between AVI/GLS and clinical/laboratory indicators were assessed. Results The values of GLS ww , GLSepi were significantly lower in patients with COVID-19 than controls ( p 0.05). The AVI/GLS ratio was significantly lower in the COVID-19 group than in controls ( p < 0.05). AVI/GLS ratio was negatively correlated with age and systolic blood pressure (SBP), and positively correlated with left ventricular ejection fraction (LVEF) ( p < 0.05). Age, SBP, and LVEF were identified as independent predictors of AVI/GLS. The area under the curve (AUC) for AVI/GLS ratio in diagnosing mild to moderate COVID-19 was 0.583, with a sensitivity of 78.6%. Conclusion The AVI/GLS ratio could serve as a valuable tool for detecting altered ventricular-arterial coupling in patients mild to moderate COVID-19. echocardiography ventricular-arterial coupling arterial velocity pulse index global longitudinal strain COVID-19 Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Viral pneumonias, including Coronavirus Disease 2019 (COVID-19), trigger a range of cardiovascular responses, such as reduced endothelium-dependent dilation, increased arterial stiffness [ 1 ][ 2 ] . Systolic function of the left ventricle is also impaired [ 3 ] . Furthermore, the interaction of pathological processes, including myocardial injury, inflammation, endothelial cell dysfunction, release of proinflammatory cytokine signalling, contribute to a vicious circle of immunothrombosis, ultimately leading to tissue necrosis, fibrosis and organ failure [ 4 , 5 ] . It is known that the interaction between the ventricle and the arterial system, known as “ventricular-arterial coupling (VAC)”, could be a key determinant of cardiovascular performance. The pathophysiological and clinical implications of the arterial stiffening should be considered together with the cardiac function [ 6 , 7 ] . Current evidence suggests VAC can precede abnormalities in cardiac function [ 8 ] . The European Society of Cardiology Working Group on Aorta & Peripheral Vascular Diseases, European Association of Cardiovascular Imaging, and Heart Failure Association stated the importance of VAC and its impact on heart disease [ 9 ] . The left ventricular-vascular coupling index (VVI) is a traditional index of VAC that can be characterized as the ratio of effective arterial elastance (Ea) and left ventricular end-systolic elastance (Ees) [ 10 ] . Two-dimensional (2D) myocardial strain based on speckle tracking is a useful index of left ventricular deformation [ 11 ] , providing multidimensional myocardial mechanical information involving rotational, longitudinal, and circumferential motion. The left ventricular global longitudinal strain (GLS) provides one of the best evidence on the diagnostic and prognostic implications for cardiac dysfunction [ 12 ] . In recent years, the arterial pressure volume index (API) and arterial velocity pulse index (AVI), both non-invasive measures, have emerged as novel indices for assessing arterial stiffness. [ 13 ] [ 14 ] . AVI reflecting the stiffness of central arteries [ 15 , 16 ] , and is associated with cardiovascular events [ 17 , 18 ] . Schnaubelt et al. reported that COVID-19 causes increased arterial stiffness, and high arterial stiffness might be associated with prolonged hospitalization and increased mortality [ 19 ] . Wu et al. reported that AVI/GLS is more effective than traditional indices in detecting differences in cardiovascular function among different age groups [ 20 ] . During the progression of COVID-19 disease, the stiffer the aortic tree, the higher the AVI, while at the same time, subclinical LV dysfunction leads to lower GLS values (less negative) and further decreases the ratio. Therefore, this study aims to investigate the potential of the AVI/GLS ratio in detecting altered ventricular-arterial coupling in patients with mild to moderate COVID-19. Materials and Methods Study population A total of 341 subjects, divided into two groups labeled as mild to moderate COVID-19 infection and a control group, were included in this study. mild cases are defined as confirmed cases with mild clinical symptoms and no signs of pneumonia on chest imaging; moderate cases are defined as confirmed cases with fever, respiratory symptoms, and signs of pneumonia on imaging.The control group comprised 187 patients, with no history, symptoms, and signs of any pre-existing cardiac disease. Among them, patients with myocarditis defined by the Chinese Journal of Heart Failure [ 21 ] and Cardiomyopathy and patients with respiratory failure defined by the American Heart Association CPR and Emergency Cardiovascular Care Guide [ 21 ] were diagnosed. Inclusion and exclusion criteria All patients met the following criteria: age 18–80 years. COVID-19 group defined as Treatment Plan for novel coronavirus Infection (Trial Version 10) by the National Health Commission of China [ 21 ] and underwent echocardiography and artery stiffness examination between January 2022 to January 2023. The exclusion criteria were as follows: severe COVID-19. Clinical examinations A questionnaire was used to obtain each participant’s demographics, including age, gender, chronic medical histories. The clinical examination of the participants included measurement of systolic blood pressure (SBP), diastolic blood pressure (DBP) and body mass index (BMI). The formula for BMI was: BMI = weight (kg) ÷ height 2 (m 2 ). The laboratory variables consisted of a complete blood count, cardiac troponin (cTnT), B-type natriuretic peptide (BNP) and creatine kinase, which were all completed within 3 days from the day of the echocardiography scan. Echocardiographic examinations and 2D Speckle-Tracking Echocardiography Strain Analysis All images were obtained with a standard ultrasound machine (EPIQ7, Philips, USA). A S5-1 probe, with a frequency range of 1-5MHz, a frame rate of ≥ 60 frames/second, and an examination depth of 13–16 cm was used. The subject rested for more than 5 minutes before the examination. During the examination, the left lateral decubitus position was used, the electrocardiogram was connected and recorded simultaneously. Standard techniques were used to obtain M-mode, 2D, and Doppler measurement in accordance with American Society of Echocardiography guidelines [ 22 ] . Tissue Doppler-derived peak systolic (s’), early (e’), and late diastolic (a’) velocities were derived from the septal mitral annulus. LV end-systolic and end-diastolic volumes along with the LVEF were calculated by the biplane Simpson’s method from apical 4- and 2-chamber views. For global 2D strain analysis, the 2D echocardiographic images were obtained from three standard apical views (two-chamber, four-chamber, three-chamber) and short-axis views. Speckle-tracking analysis was determined by Automated Cardiac Motion Quantification (aCMQ) feature on the Qlab software (QLab Cardiac Analysis ver.13, Philips Healthcare Inc) using a 18-segment model for the LV. The detected region of interest (ROI) is visually assessed and manually modified, if necessary, for accurate speckle tracking. Thereafter, the software automatically provided three lines along with endocardial, mid-myocardial, and epicardial layers, which followed each myocardial layer by a speckle-tracking algorithm (Fig. 1 A). Global longitudinal strain (GLS) was calculated as the change of the whole myocardium as described previously [ 23 ] . Normal GLS is considered − 18% [ 24 ] . Left ventricular end-systolic pressure (LVESP) is calculated as 0.9×SBP, Ees is calculated as LVESP/(LVESV-V0) = LVESP/LVESV, Ea is calculated as LVESP/SV, and VVI is calculated as Ea/Ees. Artery stiffness and Ventricular-Arterial Coupling Artery stiffness was performed on a cuff-oscillometric device (PASESA AVE-2000Pro, Shenzhen, China) as described previously [ 25 ] . AVI was measured after a minimum rest of 20 min in a sitting position in a quiet room. Smoking and caffeine were not permitted 12h prior to investigation (Fig. 1 B). The index of ventricular-vascular coupling was calculated as the ratio of the arterial stiffness measured with AVI and the myocardial performance estimated with GLS (AVI/GLS ratio ) calculated by echocardiography as described above. Statistical analysis Statistical analysis was performed using SPSS 26.0 (IBM, Armonk, NK, USA) statistical software.Normally distributed continuous variables are presented as mean ± SD;non-normally distributed data are reported as median (IQR)༛Categorical variables are expressed as frequencies and percentages. Between-group differences were compared by unpaired t-test, Wilcoxon rank-sum test, chi-square or Fisher’s exact test as appropriate.Linear regression analyses and Pearson’s correlation coefficients were used to assess relationships between changes in variables of interest. Multivariable adjustments were conducted in order to account for age, BMI, SBP, and LVEF, all of which have been shown to be closely associated with AVI/GLS. Receiver Operating Characteristic (ROC) curve was used to illustrate the identification ability, and the thresholds to discriminate between ventricular-vascular coupling (COVID-19) and healthy controls. Two-sided p values < 0.05 was considered statistically significant. Results Clinical characteristics Table 1 lists the general characteristics of control group (48.74 ± 14.24%) and COVID-19 infection (50.72 ± 19.82%).There was a high prevalence of medical comorbidities including hypertension (45.6%, 46.7%), diabetes (8.3%, 90.9%), cardiovascular disease (14.36%, 16.2%), stroke (3.9%, 9.1%), obesity (12.2%, 0.0%), dyslipidemia (11.7%, 2.6%), respiratory disease (18.3%, 28.6%), and hypothyroidism (2.8%, 2.6%), Myocarditis (0%, 6%), respiratory failure (0%, 3.9%). Compared with the control group, the incidence of central myositis and respiratory failure in COVID-19 patients was higher than that in the normal control group ( p < 0.001). No differences between groups were observed regarding BMI, SBP ,PP and heart rate (HR), DBP registered significant difference ( p <0.001). Patients with COVID-19 had a higher Neutrophil, Lymphocyte and cTnT level compared to the control group ( p < 0.05).and there were significant differences in diabetes and dyslipidemia between the two groups. Table 1 Baseline characteristics of study population Variables Control group (n = 187) COVID19 patients (n = 154) p value Demographics Age, years 48.74 ± 14.24 50.72 ± 19.82 0.302 Male, n (%) 85 (47.2%) 61 (39.6%) 0.185 BMI, kg/m 2 23.65 ± 3.63 23.63 ± 3.48 0.961 SBP, mmHg 127.89 ± 15.18 125.44 ± 17.52 0.172 DBP, mmHg 83.41 ± 12.39 78.67 ± 12.26 <0.001 Pulse pressure, mmHg 44.48 ± 13.53 46.77 ± 13.93 0.128 Heart rate, beats/minute 78.02 ± 12.00 79.05 ± 12.24 0.442 Comorbidities, n (%) Hypertension, n (%) 82 (45.6%) 70 (46.7%) 0.840 Diabetes, n (%) 15 (8.3%) 140 (90.9%) <0.001 Cardiovascular disease, n (%) 22 (%) 25 (16.2%) 0.209 Stroke, n (%) 7 (3.9%) 14 (9.1%) 0.046 Obesity, n (%) 1 (12.2%) 0 (0.0%) 0.536 Dyslipidemia, n (%) 21 (11.7%) 4 (2.6%) <0.001 Respiratory disease, n (%) 33 (18.3%) 44 (28.6%) 0.023 Hypothyroidism, n (%) Myocarditis, n (%) Respiratory failure, n (%) 5 (2.8%) 0(0%) 0(0%) 4 (2.6%) 1(0.6%) 6(3.9%) 0.599 <0.001 <0.001 Biochemical analysis WBC count, /L 0.82 ± 0.14 0.82 ± 0.13 0.810 Neutrophil, % 58.65 (52.35,66.83) 61.90(54.80,70.85) 0.014 Lymphocyte, % 30.95(24.58,37.33) 28.40(20.85,33.93) 0.009 cTnT, pg/mL 0.00(0.00,0.00) 0.002(0.000,0.003) <0.001 BNP, pg/mL 29.3 (13.48,44.70) 25.40(11.30,42.05) 0.431 Creatine kinase, U/L 0.70 (0.42,1.36) 0.80 (0.43,1.19) 0.922 Data are mean (SD) or median (IQR) for continuous variables or number (%) for categorized variables. SBP systolic blood pressure; DBP diastolic blood pressure; BMI Body mass index; WBC White blood cell; cTnT cardiac troponin T;BNP B-type natriuretic peptid. Echocardiographic Parameters Echocardiographic parameters and comparisons between groups are represented in Table 2 . Although no significant differences were observed between groups regarding LVEF, E/A ratio, and TDI e', GLS ww and GLS epi were significantly reduced in the COVID-19 group compared to the control group ( p < 0.05). Table 2 Echocardiographic and vascular parameters in the study population Variables Control group (n = 187) COVID19 patients (n = 154) p value Echocardiographic characteristics LVEDD (mm) 45.92 ± 3.70 45.02 ± 3.80 0.029 LVESD (mm) 28.65 ± 3.00 27.82 ± 3.07 0.013 LVEDV (mL) 71.33 ± 18.73 70.89 ± 18.59 0.829 LVESV (mL) 27.90 ± 9.41 28.18 ± 9.33 0.792 IVS (mm) 9.31 ± 1.00 9.50 ± 1.06 0.103 LVPW (mm) 9.01 ± 0.92 9.11 ± 0.99 0.350 E/A ratio 1.18 ± 0.44 1.19 ± 0.53 0.751 LVEF (%) 61.06 ± 6.22 60.39 ± 6.25 0.327 TDI e’ (cm/s) 9.49 ± 2.63 9.58 ± 3.15 0.787 E/e’ ratio 8.30 ± 2.35 8.68 ± 3.24 0.233 GLS ww (%) -20.92 ± 3.16 -21.59 ± 2.84 0.045 Layer-specific strains GLS Endo (%) -21.59 ± 3.39 -22.26 ± 3.14 0.060 GLS Epi (%) -20.22 ± 3.11 -21.00 ± 2.68 0.014 GLS Mid (%) -20.97 ± 3.22 -21.50 ± 2.80 0.107 Vascular parameters AVI 13.63 ± 5.53 16.18 ± 5.69 <0.001 Ea (mmHg/mL) 2.83 ± 0.79 2.83 ± 0.90 0.986 Ees (mmHg/mL) 4.64 ± 1.80 4.40 ± 1.50 0.193 Ventricular-arterial coupling VVI 0.65 ± 0.17 0.68 ± 0.20 0.262 AVI/GLS -0.67 ± 0.29 -0.77 ± 0.32 0.003 Note: Echocardiography, the index of left ventricular structure and function were obtained by Echocardiography; Ventricular-vascular coupling, the traditional and novel index system of ventricular-vascular coupling; LVEDD, left ventricle end-diastolic dimension; LVESD, left ventricle end-systolic dimension; LVEDV, left ventricle end-diastolic volume; LVESV, left ventricle end-systolic volume; IVS interventricular septum thickness ; LVPW LV posterior wall thickness; E/A, E and A mitral inflow waves by Doppler; LVEF left ventricular ejection fraction; TDI, Tissue Doppler Imaging; e′, early diastolic velocity of the mitral annulus by TDI; E/e’ ratio, The ratio between early mitral flow wave to early diastolic mitral annulus velocity; GCS ww global circumferential strain; GLS ww whole wall global longitudinal strain; GLS endo endomyocardial global longitudinal strain; GLS mid midmyocardial global longitudinal strain; GLS epi , epimyocardial global longitudinal strain; AVI, arterial velocity pulse index; Ea, effective arterial elastance; Ees, left ventricular end-systolic elastance; VVI, ventricular-vascular coupling index. Artery stiffness and ventricular-arterial coupling AVI values were significantly higher in the COVID-19 group (16.18 ± 5.69) compared to the control group (13.63 ± 5.53) ( p < 0.001). The AVI/GLS ratio was significantly lower in the COVID-19 group (-0.77 ± 0.32) compared to the control group (-0.67 ± 0.29) ( p = 0.0030). The boxplots in Fig. 2 illustrate the median and interquartile range for the distribution of AVI, GLS, and the AVI/GLS ratio. Association between AVI/GLS ratio and clinical parameters Among the clinical variables, age, BMI, SBP, and LVEF were all significantly associated with AVI/GLS changes. we performed a multiple logistic regression analysis to identify differences in myocardial strain associated with mild to moderate COVID-19. LVEF remained correlated with AVI/GLS ,ORs 0.0242, 1.044(p = 0.002 Table 3 , Fig. 3 )。 Table 3 Multivariate linear analysis the association between AVI/GLS and clinical parameters. Variables Regression coefficient (β) Standardized coefficients (β′) 95% Confidential interval p value Model 1 Age -0.011 -0.622 -0.013,-0.010 <0.001 BMI -0.003 -0.037 -0.010,0.004 0.366 SBP -0.003 -0.139 -0.004,-0.001 0.001 Model 2 Age -0.011 -0.600 -0.012, -0.009 <0.001 BMI -0.001 -0.015 -0.008, -0.006 0.720 SBP -0.003 -0.141 -0.004, -0.001 <0.001 LVEF 0.643 0.129 0.242, 1.044 0.002 BMI Body mass index; SBP systolic blood pressure; LVEF left ventricular ejection fraction. AVI, arterial velocity pulse index; GLS global longitudinal strains; Age, BMI, SBP in multivariable model 1. Age, BMI, SBP, LVEF in multivariable model 2. Reproducibility analysis The reproducibility of the AVI/GLS and AVI/GLS for the first time was assessed in 20 randomly selected subjects whose AVI/GLS anc AVI/GLS for the first time values were measured independently by two physicians, respectively. Bland–Altman analysis showed a unconsistent trend, and linear regression analysis showed good agreement between measurements by the two independent observers for AVI/GLS and AVI/GLS for the first time. The mean (± SD) difference was 2.23(±21.2) for repeated measurements of AVI/GLS taken by two independent observers. The mean (± SD) difference was − 1.59(±26.02)for repeated measurements of AVI/GLS for the first time taken by two independent observers (Fig. 4 ). ROC curve for predictive performance of AVI/GLS ratio The ROC curve identified a threshold of -0.504 of the AVI/GLS ratio to discriminate between COVID-19 (mild to moderate) and healthy controls AUC = 0.583, 95% CI [0.528; 0.636], with the sensitivity 78.57% (Fig. 5 ). However, by analyzing the ROC curve, the areas under the ROC curve of VVI is not statistically different. Discussion VAC plays a pivotal role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac diseases. In this study, we assessed VAC by calculating the ratio of AVI to GLS in patients with mild to moderate COVID-19 infection compared to healthy subjects. Notably, both GLS and GLS Epi strains, along with AVI values, showed slight increases in the COVID-19 cohort. Interestingly, the reduction in strain was first identified in the subepicardial region rather than the subendocardial region, which aligns with established characteristics of myocardial damage associated with myocarditis. Furthermore, the AVI/GLS ratio exhibited significantly higher values in the COVID-19 patients compared to the normal control group. This ratio demonstrated a reasonable capacity to differentiate altered VAC, suggesting its potential utility in clinical evaluation. Acute myocardial injury is a recognized complication in patients with COVID-19 [ 26 , 27 ] . In our study, we found that LVEF, the E/e’ ratio, and the E/A ratio did not exhibit significant differences among the subjects. This lack of variation may be attributed to the fact that the patients in our cohort were experiencing mild to moderate disease severity, and typical heart failure symptoms, such as orthopnea and nocturnal dyspnea, were largely absent. Nonetheless, we observed low-grade elevations in both cardiac troponin T (cTnT) and GLS, which correlate with a subclinical state of cardiac dysfunction associated with COVID-19. Myocardial deformation analysis using two-dimensional strain echocardiography, particularly through layer-specific quantification, offers a novel approach for identifying cardiac dysfunction in COVID-19 patients. Additionally, previous research has indicated preferential changes in subepicardial deformation [ 28 ] . In our study, we noted that the reduction in GLS in the subepicardial layer was more pronounced than that in the subendocardial layer. This finding suggests that cardiac dysfunction is predominantly located in the subepicardial layer of the myocardium, a critical feature that aligns with the manifestations of myocarditis. Acute myocardial injury is one of the complications observed in COVID-19 patients [ 26 , 27 ] . In our study, LVEF, E/e’ ratio and E/A ratio did not register significant differences. This may due to the patients in this study were in the mild to moderate severity of the disease and the typical symptoms of heart failure, including orthopnea and nocturnal dyspnea were largely absent in the study subjects. However, the low-grade elevation of cTnT and GLS aligns with the subclinical state of cardiac dysfunction associated with COVID-19. Myocardial deformation analysis by 2-D STE, particularly layer-specificquantification, provides a novel tool for detecting cardiac dysfunction in COVID-19 patients. In addition, previous study showed preferential changes in subepicardial deformation [ 28 ] . In our study, we noted that the reduction in GLS in the subepicardial layer was more pronounced than that in the subendocardial layer. This finding suggests that cardiac dysfunction is predominantly located in the subepicardial layer of the myocardium, a critical feature that aligns with the manifestations of myocarditis. Furthermore, pathological studies have indicated that viral infections can lead to endothelial cell infection and endotheliitis [ 29 ] . Evidence suggests that COVID-19 may accelerate vascular aging at the macrovascular level [ 30 ] , which could result in alterations in arterial stiffness [ 31 ] . The arterial velocity pulse index (AVI) is derived from the amplitude of oscillometric reflected waveforms [ 32 ] . As confirmed in the study of Stoichescu-Hogea et al [ 32 ] , arterial stiffness increased in parallel with myocardial stiffness in hypertensive patients. In this study, there was a statistically significant increase in AVI in the COVID-19 group, whereas GLS was mildly increased but within normal range. Compared with Ea, AVI provides a more direct assessment of the total elasticity of the arterial tree and the resistance of peripheral arteries, both of which are closely related to cardiac function [ 20 ] . Furthermore, early detection of subclinical disease progression in VA uncoupling using AVI/GLS ratio may be possible. Our study demonstrated that AVI/GLS ratio showed fair discrimination ability to predict altered VA coupling [ 20 ] . In addition, no difference in the incidence of AVI/GLS ratio was observed in the COVID-19 and control group. GLS has been shown to be highly sensitive to myocardial injury and to reflect cardiac contractile function. GLS, on the other hand, reflects changes in cardiac configuration and is highly specific. These mechanisms explain the preferential alteration of AVI/GLS ratio among COVID-19 patients in this study. Limitations This study has several limitations. First, this has been a retrospective cross-sectional analysis. To better explain the complex relationship between VAC, more insights could be obtained from prospective longitudinal studies in the future. Second, this study did not address changes in VAC during COVID-19 rehabilitation, thus long-term follow-up is needed. Conclusions The preferential alteration of arterial stiffness and strains in the subepicardium may underlie the cardiovascular pathology in COVID-19. The AVI/GLS ratio can be used to detect altered ventricular-arterial coupling in patients with mild to moderate COVID-19 infection. Abbreviations AVI，arterial velocity pulse index；VVI，ventricular-vascular coupling index；GLS，global longitudinal strain；VA，ventricular-arterial；EA，effective arterial elasticity Declarations Ethics statement The research plan was approved by the Ethics Committee of Shanghai General Hospital (2024SQ003). It was conducted following the Declaration of Helsinki of the World Medical Association. All participants in the project signed informed consent. Acknowledgements The authors would like to thank those researchers who contribute to the BMC Cardiovascular Disorders “Uncoupling of Ventricular and Arterial Derived from Arterial Stiffness and Global Longitudinal Strain in Mild to Moderate COVID-19” Collection. Authors' contributions Study design: ZJL. Data collection: all authors. Data verification: XYL, NW and LFD. Data analysis: LJ, JXC, and LHW. Initial draft: LJ and SYZ. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. Funding This work was supported by Natural Science Foundation of Shanghai (21ZR1451400), Shanghai Health and Family Planning Commission Fund (202240235), and Shanghai Jiading District Health and Family Planning Commission Fund (2021-KY-10). Availability of data and materials The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request. Competing Interests The authors declare that there is no conflict of interest relevant to this study. Ethics approval and consent to participate the Ethics Committee of Shanghai General Hospital (2024SQ003). Consent for publication Not applicable. References Narayan K M V, Curran J W, Foege W H. The covid-19 pandemic as an opportunity to ensure a more successful future for science and public health [J]. Jama, 2021, 325(6): 525-526. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. 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Wu L, Zhang M, Chen J, Jin L, Shen C, Sun J, Luo X, Li Z, Du L. A novel index system for assessing ventricular-vascular coupling [J]. RCM, 2023, 24(10). Diagnosis and treatment protocol for novel coronavirus pneumonia (trial version 7) [J]. Chin Med J (Engl), 2020, 133(9): 1087-1095. Lang R M, Bierig M, Devereux R B, Flachskampf F A, Foster E, Pellikka P A, Picard M H, Roman M J, Seward J, Shanewise J S, Solomon S D, Spencer K T, Sutton M S, Stewart W J. Recommendations for chamber quantification: A report from the american society of echocardiography's guidelines and standards committee and the chamber quantification writing group, developed in conjunction with the european association of echocardiography, a branch of the european society of cardiology [J]. J Am Soc Echocardiogr, 2005, 18(12): 1440-1463. Wang Y, Chen J, Jin L, Wu L, Zhang M, Sun J, Shen C, Du L, Wang B, Li Z. Sequence and directivity in cardiac muscle injury of covid-19 patients: An observational study [J]. Front Cardiovasc Med, 2023, 10: 1260971. Haji K, Marwick T H. Clinical utility of echocardiographic strain and strain rate measurements [J]. Curr Cardiol Rep, 2021, 23(3): 18. Jin L, Chen J, Wu L, Zhang M, Sun J, Shen C, Du L, Wang D, Li Z. Relative contributions of arterial stiffness to cardiovascular disease risk score in chinese women in framingham and china-par model [J]. Front Cardiovasc Med, 2023, 10: 1169250. Li R, Wang H, Ma F, Cui G L, Peng L Y, Li C Z, Zeng H S, Marian A J, Wang D W. Widespread myocardial dysfunction in covid-19 patients detected by myocardial strain imaging using 2-d speckle-tracking echocardiography [J]. Acta Pharmacol Sin, 2021, 42(10): 1567-1574. Kato S, Kitai T, Utsunomiya D, Azuma M, Fukui K, Hagiwara E, Ogura T, Ishibashi Y, Okada T, Kitakata H, Shiraishi Y, Torii S, Ohashi K, Takamatsu K, Yokoyama A, Hirata K I, Matsue Y, Node K. Myocardial injury by covid-19 infection assessed by cardiovascular magnetic resonance imaging - a prospective multicenter study [J]. Circ J, 2024. Caspar T, Germain P, El Ghannudi S, Morel O, Samet H, Trinh A, Petit-Eisenmann H, Talha S, Fichot M, Jesel L, Ohlmann P. Acute myocarditis diagnosed by layer-specific 2d longitudinal speckle tracking analysis [J]. Echocardiography, 2016, 33(1): 157-158. Varga Z, Flammer A J, Steiger P, Haberecker M, Andermatt R, Zinkernagel A S, Mehra M R, Schuepbach R A, Ruschitzka F, Moch H. Endothelial cell infection and endotheliitis in covid-19 [J]. Lancet, 2020, 395(10234): 1417-1418. Çiftel M, Ataş N, Yılmaz O. Investigation of endothelial dysfunction and arterial stiffness in multisystem inflammatory syndrome in children [J]. Eur J Pediatr, 2022, 181(1): 91-97. Jannasz I, Pruc M, Rahnama-Hezavah M, Targowski T, Olszewski R, Feduniw S, Petryka K, Szarpak L. The impact of covid-19 on carotid-femoral pulse wave velocity: A systematic review and meta-analysis [J]. J Clin Med, 2023, 12(17). Yamanashi H, Koyamatsu J, Nagayoshi M, Shimizu Y, Kawashiri S Y, Kondo H, Fukui S, Tamai M, Maeda T. Screening validity of arterial pressure-volume index and arterial velocity-pulse index for preclinical atherosclerosis in japanese community-dwelling adults: The nagasaki islands study [J]. J Atheroscler Thromb, 2018, 25(9): 792-798. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6812543","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":507269586,"identity":"7c2006c1-35eb-4563-b09a-56265d5bef81","order_by":0,"name":"Shiyi Zhang","email":"","orcid":"","institution":"Shanghai First People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shiyi","middleName":"","lastName":"Zhang","suffix":""},{"id":507269587,"identity":"dd6046d5-0f43-456c-a2e1-35c86ee57875","order_by":1,"name":"Lin Jin","email":"","orcid":"","institution":"Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Jin","suffix":""},{"id":507269588,"identity":"76dc4c0c-29d9-4a96-b2d5-bead72390e15","order_by":2,"name":"Xinyi Li","email":"","orcid":"","institution":"Shanghai First People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xinyi","middleName":"","lastName":"Li","suffix":""},{"id":507269589,"identity":"359ec66e-741d-4577-9e68-68846f4ec92e","order_by":3,"name":"Jianhui Zhang","email":"","orcid":"","institution":"Zhongshan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jianhui","middleName":"","lastName":"Zhang","suffix":""},{"id":507269590,"identity":"ee5232bd-51be-4b33-8d1f-164471f08a81","order_by":4,"name":"Ning Wang","email":"","orcid":"","institution":"Shanghai First People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ning","middleName":"","lastName":"Wang","suffix":""},{"id":507269592,"identity":"29f15184-49b9-42c3-a846-29ea9baf9303","order_by":5,"name":"Jianxiong Chen","email":"","orcid":"","institution":"Shanghai General Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jianxiong","middleName":"","lastName":"Chen","suffix":""},{"id":507269594,"identity":"87e84204-bd67-4718-a1b9-b22491104217","order_by":6,"name":"Lingheng Wu","email":"","orcid":"","institution":"Shanghai General Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lingheng","middleName":"","lastName":"Wu","suffix":""},{"id":507269598,"identity":"3fdbdf44-05d6-4865-86dc-5a64f5308b77","order_by":7,"name":"Lianfang Du","email":"","orcid":"","institution":"Shanghai First People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lianfang","middleName":"","lastName":"Du","suffix":""},{"id":507269599,"identity":"b5d742c9-c917-48dd-921a-71ce0c54d63e","order_by":8,"name":"Zhaojun Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYBACPgaGBIaEiv/1/AyMDcRpYQNpeXCGOUGygQQtDIwP25gTDA4Q6zA2/gMPGBLb2PKMzx9ue/CDwU5Ol5BlbAwHgH45x1NsdiOx3bCHIdnYjJB1bIwNQC1lEozbbjC2SfAwHEjcRlALMyjE2AwYN/cfbJP8Q5QWNpCWtoTEDUAfSRNnCw9Iy5kDxhI3gFpkDIjwCz//mQTGHxUH5Pj7jz+TfFNhJ0dQCwMDT/oPBMeAoHIQYCds6igYBaNgFIxwAADG2z6ms2TQ3wAAAABJRU5ErkJggg==","orcid":"","institution":"Shanghai First People's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Zhaojun","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2025-06-03 14:53:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6812543/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6812543/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90365213,"identity":"e5d90f1d-e95a-4a0b-9079-d8fc0d9be7ad","added_by":"auto","created_at":"2025-09-02 02:23:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":257714,"visible":true,"origin":"","legend":"\u003cp\u003e2D speckle-tracking echocardiography strain analysis (A) and AVI analysis (B). Two-dimensional speckle-tracking analyses of myocardial layer-specific strain. 18-segment bull's eye diagram of GCS\u003csub\u003eendo\u003c/sub\u003e, GCS\u003csub\u003emid\u003c/sub\u003e, and GCS\u003csub\u003eepi\u003c/sub\u003e. GCS, global circumferential strain; GLS, global longitudinal strain; LV, left ventricular.\u003c/p\u003e\n\u003cp\u003eAVI, arterial velocity pulse index; VVI, ventricular-vascular coupling index; CSBP ,Central systolic blood pressure; SYS, systolic pressure; DIA, diastolic blood pressure.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6812543/v1/06799e9ed0b47333f995ff4c.png"},{"id":90365196,"identity":"880beea3-d4b4-4019-b732-774c577520e1","added_by":"auto","created_at":"2025-09-02 02:23:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":720503,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot showing AVI (A), GLS (B) and AVI/GLS (C) in normal subjects and COVID-19 patients. AVI was higher in COVID-19 group than in control group. GLS and AVI/GLS were lower in COVID-19 group than in control group. AVI, arterial velocity pulse index; GLS global longitudinal strains;\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6812543/v1/bc7a283d220861101e4d995e.png"},{"id":90364445,"identity":"2363f073-25f0-4dcd-aba4-3864846f70fb","added_by":"auto","created_at":"2025-09-02 02:15:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":839175,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between the AVI/GLS ratio and SBP, LVEF, TDI e'.\u003c/p\u003e\n\u003cp\u003eBoth in control and COVID-19 groups, AVI/GLS exhibited a negative correlation with SBP (A) and a positive correlation with LVEF (B) and TDI e' (C). LVEF left ventricular ejection fraction; TDI e′, early diastolic velocity of the mitral annulus by TDI. AVI, arterial velocity pulse index; GLS global longitudinal strains;\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6812543/v1/50002e97620d691a82458daa.png"},{"id":90364449,"identity":"f87911e0-038b-46e4-b489-d9774d0807d8","added_by":"auto","created_at":"2025-09-02 02:15:42","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":322144,"visible":true,"origin":"","legend":"\u003cp\u003eRepeatability was analysed by Bland–Altman plots (A and C) and linear correlation analysis (B and D). Bland–Altman analysis showed a consistent trend in the difference value and the mean value of the global longitudinal strain/lobal longitudinal strains (AVI/GLS) (A, C) AVI/GLS for the first time(B、D) by repeated measurement. The results showed that intra‐group and inter-group comparison had a high degree of consistency (n = 20).\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6812543/v1/6ed1992aab01eaa9299da973.png"},{"id":90365198,"identity":"611ee203-2e49-4d7c-92d2-d1d61bff3331","added_by":"auto","created_at":"2025-09-02 02:23:42","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":245627,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for predictive performance of AVI/GLS ratio to detect altered ventricular-arterial coupling\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-6812543/v1/19abec222521c9c27afc68ab.png"},{"id":91630820,"identity":"34684e86-9849-49e8-8152-7625564b6002","added_by":"auto","created_at":"2025-09-18 13:02:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3484109,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6812543/v1/efafb6eb-f0ad-4ab6-9bde-29299d73e4cf.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Ventricular-Arterial Uncoupling in Mild to Moderate COVID-19 Pneumonia: Role of A Novel Ventricular-Vascular Coupling Index","fulltext":[{"header":"Introduction","content":"\u003cp\u003eViral pneumonias, including Coronavirus Disease 2019 (COVID-19), trigger a range of cardiovascular responses, such as reduced endothelium-dependent dilation, increased arterial stiffness \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e][\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Systolic function of the left ventricle is also impaired \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Furthermore, the interaction of pathological processes, including myocardial injury, inflammation, endothelial cell dysfunction, release of proinflammatory cytokine signalling, contribute to a vicious circle of immunothrombosis, ultimately leading to tissue necrosis, fibrosis and organ failure \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIt is known that the interaction between the ventricle and the arterial system, known as \u0026ldquo;ventricular-arterial coupling (VAC)\u0026rdquo;, could be a key determinant of cardiovascular performance. The pathophysiological and clinical implications of the arterial stiffening should be considered together with the cardiac function \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Current evidence suggests VAC can precede abnormalities in cardiac function \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. The European Society of Cardiology Working Group on Aorta \u0026amp; Peripheral Vascular Diseases, European Association of Cardiovascular Imaging, and Heart Failure Association stated the importance of VAC and its impact on heart disease \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. The left ventricular-vascular coupling index (VVI) is a traditional index of VAC that can be characterized as the ratio of effective arterial elastance (Ea) and left ventricular end-systolic elastance (Ees) \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTwo-dimensional (2D) myocardial strain based on speckle tracking is a useful index of left ventricular deformation \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e, providing multidimensional myocardial mechanical information involving rotational, longitudinal, and circumferential motion. The left ventricular global longitudinal strain (GLS) provides one of the best evidence on the diagnostic and prognostic implications for cardiac dysfunction \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. In recent years, the arterial pressure volume index (API) and arterial velocity pulse index (AVI), both non-invasive measures, have emerged as novel indices for assessing arterial stiffness. \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. AVI reflecting the stiffness of central arteries \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e, and is associated with cardiovascular events \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. Schnaubelt \u003cem\u003eet al.\u003c/em\u003e reported that COVID-19 causes increased arterial stiffness, and high arterial stiffness might be associated with prolonged hospitalization and increased mortality \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Wu \u003cem\u003eet al.\u003c/em\u003e reported that AVI/GLS is more effective than traditional indices in detecting differences in cardiovascular function among different age groups \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. During the progression of COVID-19 disease, the stiffer the aortic tree, the higher the AVI, while at the same time, subclinical LV dysfunction leads to lower GLS values (less negative) and further decreases the ratio.\u003c/p\u003e\u003cp\u003eTherefore, this study aims to investigate the potential of the AVI/GLS ratio in detecting altered ventricular-arterial coupling in patients with mild to moderate COVID-19.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cb\u003eStudy population\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA total of 341 subjects, divided into two groups labeled as mild to moderate COVID-19 infection and a control group, were included in this study. mild cases are defined as confirmed cases with mild clinical symptoms and no signs of pneumonia on chest imaging; moderate cases are defined as confirmed cases with fever, respiratory symptoms, and signs of pneumonia on imaging.The control group comprised 187 patients, with no history, symptoms, and signs of any pre-existing cardiac disease. Among them, patients with myocarditis defined by the Chinese Journal of Heart Failure \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e and Cardiomyopathy and patients with respiratory failure defined by the American Heart Association CPR and Emergency Cardiovascular Care Guide\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e were diagnosed.\u003c/p\u003e\u003cp\u003e\u003cb\u003eInclusion and exclusion criteria\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAll patients met the following criteria: age 18\u0026ndash;80 years. COVID-19 group defined as Treatment Plan for novel coronavirus Infection (Trial Version 10) by the National Health Commission of China\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e and underwent echocardiography and artery stiffness examination between January 2022 to January 2023. The exclusion criteria were as follows: severe COVID-19.\u003c/p\u003e\u003cp\u003e\u003cb\u003eClinical examinations\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA questionnaire was used to obtain each participant\u0026rsquo;s demographics, including age, gender, chronic medical histories. The clinical examination of the participants included measurement of systolic blood pressure (SBP), diastolic blood pressure (DBP) and body mass index (BMI). The formula for BMI was: BMI\u0026thinsp;=\u0026thinsp;weight (kg)\u0026thinsp;\u0026divide;\u0026thinsp;height\u003csup\u003e2\u003c/sup\u003e (m\u003csup\u003e2\u003c/sup\u003e).\u003c/p\u003e\u003cp\u003eThe laboratory variables consisted of a complete blood count, cardiac troponin (cTnT), B-type natriuretic peptide (BNP) and creatine kinase, which were all completed within 3 days from the day of the echocardiography scan.\u003c/p\u003e\u003cp\u003e\u003cb\u003eEchocardiographic examinations and 2D Speckle-Tracking Echocardiography Strain Analysis\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAll images were obtained with a standard ultrasound machine (EPIQ7, Philips, USA). A S5-1 probe, with a frequency range of 1-5MHz, a frame rate of \u0026ge;\u0026thinsp;60 frames/second, and an examination depth of 13\u0026ndash;16 cm was used. The subject rested for more than 5 minutes before the examination. During the examination, the left lateral decubitus position was used, the electrocardiogram was connected and recorded simultaneously. Standard techniques were used to obtain M-mode, 2D, and Doppler measurement in accordance with American Society of Echocardiography guidelines \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Tissue Doppler-derived peak systolic (s\u0026rsquo;), early (e\u0026rsquo;), and late diastolic (a\u0026rsquo;) velocities were derived from the septal mitral annulus. LV end-systolic and end-diastolic volumes along with the LVEF were calculated by the biplane Simpson\u0026rsquo;s method from apical 4- and 2-chamber views.\u003c/p\u003e\u003cp\u003eFor global 2D strain analysis, the 2D echocardiographic images were obtained from three standard apical views (two-chamber, four-chamber, three-chamber) and short-axis views. Speckle-tracking analysis was determined by Automated Cardiac Motion Quantification (aCMQ) feature on the Qlab software (QLab Cardiac Analysis ver.13, Philips Healthcare Inc) using a 18-segment model for the LV. The detected region of interest (ROI) is visually assessed and manually modified, if necessary, for accurate speckle tracking. Thereafter, the software automatically provided three lines along with endocardial, mid-myocardial, and epicardial layers, which followed each myocardial layer by a speckle-tracking algorithm (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Global longitudinal strain (GLS) was calculated as the change of the whole myocardium as described previously \u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. Normal GLS is considered \u0026minus;\u0026thinsp;18% \u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eLeft ventricular end-systolic pressure (LVESP) is calculated as 0.9\u0026times;SBP, Ees is calculated as LVESP/(LVESV-V0)\u0026thinsp;=\u0026thinsp;LVESP/LVESV, Ea is calculated as LVESP/SV, and VVI is calculated as Ea/Ees.\u003c/p\u003e\u003cp\u003e\u003cb\u003eArtery stiffness and Ventricular-Arterial Coupling\u003c/b\u003e\u003c/p\u003e\u003cp\u003eArtery stiffness was performed on a cuff-oscillometric device (PASESA AVE-2000Pro, Shenzhen, China) as described previously \u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. AVI was measured after a minimum rest of 20 min in a sitting position in a quiet room. Smoking and caffeine were not permitted 12h prior to investigation (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB).\u003c/p\u003e\u003cp\u003eThe index of ventricular-vascular coupling was calculated as the ratio of the arterial stiffness measured with AVI and the myocardial performance estimated with GLS (AVI/GLS ratio ) calculated by echocardiography as described above.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis was performed using SPSS 26.0 (IBM, Armonk, NK, USA) statistical software.Normally distributed continuous variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD;non-normally distributed data are reported as median (IQR)༛Categorical variables are expressed as frequencies and percentages. Between-group differences were compared by unpaired t-test, Wilcoxon rank-sum test, chi-square or Fisher\u0026rsquo;s exact test as appropriate.Linear regression analyses and Pearson\u0026rsquo;s correlation coefficients were used to assess relationships between changes in variables of interest. Multivariable adjustments were conducted in order to account for age, BMI, SBP, and LVEF, all of which have been shown to be closely associated with AVI/GLS. Receiver Operating Characteristic (ROC) curve was used to illustrate the identification ability, and the thresholds to discriminate between ventricular-vascular coupling (COVID-19) and healthy controls. Two-sided \u003cem\u003ep\u003c/em\u003e values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eClinical characteristics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e lists the general characteristics of control group (48.74\u0026thinsp;\u0026plusmn;\u0026thinsp;14.24%) and COVID-19 infection (50.72\u0026thinsp;\u0026plusmn;\u0026thinsp;19.82%).There was a high prevalence of medical comorbidities including hypertension (45.6%, 46.7%), diabetes (8.3%, 90.9%), cardiovascular disease (14.36%, 16.2%), stroke (3.9%, 9.1%), obesity (12.2%, 0.0%), dyslipidemia (11.7%, 2.6%), respiratory disease (18.3%, 28.6%), and hypothyroidism (2.8%, 2.6%), Myocarditis (0%, 6%), respiratory failure (0%, 3.9%). Compared with the control group, the incidence of central myositis and respiratory failure in COVID-19 patients was higher than that in the normal control group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No differences between groups were observed regarding BMI, SBP ,PP and heart rate (HR), DBP registered significant difference (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001). Patients with COVID-19 had a higher Neutrophil, Lymphocyte and cTnT level compared to the control group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).and there were significant differences in diabetes and dyslipidemia between the two groups.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristics of study population\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;187)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCOVID19 patients\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;154)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDemographics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e48.74\u0026thinsp;\u0026plusmn;\u0026thinsp;14.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50.72\u0026thinsp;\u0026plusmn;\u0026thinsp;19.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.302\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e85 (47.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61 (39.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.185\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.65\u0026thinsp;\u0026plusmn;\u0026thinsp;3.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.63\u0026thinsp;\u0026plusmn;\u0026thinsp;3.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.961\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSBP, mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e127.89\u0026thinsp;\u0026plusmn;\u0026thinsp;15.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e125.44\u0026thinsp;\u0026plusmn;\u0026thinsp;17.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.172\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDBP, mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e83.41\u0026thinsp;\u0026plusmn;\u0026thinsp;12.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78.67\u0026thinsp;\u0026plusmn;\u0026thinsp;12.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePulse pressure, mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44.48\u0026thinsp;\u0026plusmn;\u0026thinsp;13.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46.77\u0026thinsp;\u0026plusmn;\u0026thinsp;13.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.128\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart rate, beats/minute\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e78.02\u0026thinsp;\u0026plusmn;\u0026thinsp;12.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e79.05\u0026thinsp;\u0026plusmn;\u0026thinsp;12.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.442\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eComorbidities, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e82 (45.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e70 (46.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.840\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (8.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e140 (90.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiovascular disease, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25 (16.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.209\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStroke, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (3.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.046\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eObesity, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (12.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.536\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDyslipidemia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (11.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (2.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRespiratory disease, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33 (18.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44 (28.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.023\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypothyroidism, n (%)\u003c/p\u003e\u003cp\u003eMyocarditis, n (%)\u003c/p\u003e\u003cp\u003eRespiratory failure, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (2.8%)\u003c/p\u003e\u003cp\u003e0(0%)\u003c/p\u003e\u003cp\u003e0(0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (2.6%)\u003c/p\u003e\u003cp\u003e1(0.6%)\u003c/p\u003e\u003cp\u003e6(3.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.599\u003c/p\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBiochemical analysis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC count, /L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.810\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutrophil, %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58.65 (52.35,66.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61.90(54.80,70.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.014\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocyte, %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30.95(24.58,37.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.40(20.85,33.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.009\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecTnT, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.00(0.00,0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.002(0.000,0.003)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBNP, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29.3 (13.48,44.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25.40(11.30,42.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.431\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatine kinase, U/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.70 (0.42,1.36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.80 (0.43,1.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.922\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are mean (SD) or median (IQR) for continuous variables or number (%) for categorized variables. SBP systolic blood pressure; DBP diastolic blood pressure; BMI Body mass index; WBC White blood cell; cTnT cardiac troponin T;BNP B-type natriuretic peptid.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eEchocardiographic Parameters\u003c/b\u003e\u003c/p\u003e\u003cp\u003eEchocardiographic parameters and comparisons between groups are represented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Although no significant differences were observed between groups regarding LVEF, E/A ratio, and TDI e', GLS\u003csub\u003eww\u003c/sub\u003e and GLS\u003csub\u003eepi\u003c/sub\u003e were significantly reduced in the COVID-19 group compared to the control group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEchocardiographic and vascular parameters in the study population\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;187)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eCOVID19 patients\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;154)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eEchocardiographic characteristics\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLVEDD (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45.92\u0026thinsp;\u0026plusmn;\u0026thinsp;3.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45.02\u0026thinsp;\u0026plusmn;\u0026thinsp;3.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.029\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLVESD (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28.65\u0026thinsp;\u0026plusmn;\u0026thinsp;3.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27.82\u0026thinsp;\u0026plusmn;\u0026thinsp;3.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.013\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLVEDV (mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e71.33\u0026thinsp;\u0026plusmn;\u0026thinsp;18.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e70.89\u0026thinsp;\u0026plusmn;\u0026thinsp;18.59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.829\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLVESV (mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27.90\u0026thinsp;\u0026plusmn;\u0026thinsp;9.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.18\u0026thinsp;\u0026plusmn;\u0026thinsp;9.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.792\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIVS (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.31\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.50\u0026thinsp;\u0026plusmn;\u0026thinsp;1.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.103\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLVPW (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.350\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eE/A ratio\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.751\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLVEF (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e61.06\u0026thinsp;\u0026plusmn;\u0026thinsp;6.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60.39\u0026thinsp;\u0026plusmn;\u0026thinsp;6.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.327\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTDI e\u0026rsquo; (cm/s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.49\u0026thinsp;\u0026plusmn;\u0026thinsp;2.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.58\u0026thinsp;\u0026plusmn;\u0026thinsp;3.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.787\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eE/e\u0026rsquo; ratio\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.30\u0026thinsp;\u0026plusmn;\u0026thinsp;2.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.68\u0026thinsp;\u0026plusmn;\u0026thinsp;3.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.233\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGLS\u003csub\u003eww\u003c/sub\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-20.92\u0026thinsp;\u0026plusmn;\u0026thinsp;3.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-21.59\u0026thinsp;\u0026plusmn;\u0026thinsp;2.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.045\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLayer-specific strains\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGLS \u003csub\u003eEndo\u003c/sub\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-21.59\u0026thinsp;\u0026plusmn;\u0026thinsp;3.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-22.26\u0026thinsp;\u0026plusmn;\u0026thinsp;3.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.060\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGLS \u003csub\u003eEpi\u003c/sub\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-20.22\u0026thinsp;\u0026plusmn;\u0026thinsp;3.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-21.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.014\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGLS \u003csub\u003eMid\u003c/sub\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-20.97\u0026thinsp;\u0026plusmn;\u0026thinsp;3.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-21.50\u0026thinsp;\u0026plusmn;\u0026thinsp;2.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.107\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVascular parameters\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13.63\u0026thinsp;\u0026plusmn;\u0026thinsp;5.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.18\u0026thinsp;\u0026plusmn;\u0026thinsp;5.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEa (mmHg/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.986\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEes (mmHg/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.40\u0026thinsp;\u0026plusmn;\u0026thinsp;1.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.193\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVentricular-arterial coupling\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.262\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAVI/GLS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eNote: Echocardiography, the index of left ventricular structure and function were obtained by Echocardiography; Ventricular-vascular coupling, the traditional and novel index system of ventricular-vascular coupling; LVEDD, left ventricle end-diastolic dimension; LVESD, left ventricle end-systolic dimension; LVEDV, left ventricle end-diastolic volume; LVESV, left ventricle end-systolic volume; IVS interventricular septum thickness ; LVPW LV posterior wall thickness; E/A, E and A mitral inflow waves by Doppler; LVEF left ventricular ejection fraction; TDI, Tissue Doppler Imaging; e\u0026prime;, early diastolic velocity of the mitral annulus by TDI; E/e\u0026rsquo; ratio, The ratio between early mitral flow wave to early diastolic mitral annulus velocity; GCS\u003csub\u003eww\u003c/sub\u003e global circumferential strain; GLS\u003csub\u003eww\u003c/sub\u003e whole wall global longitudinal strain; GLS\u003csub\u003eendo\u003c/sub\u003e endomyocardial global longitudinal strain; GLS\u003csub\u003emid\u003c/sub\u003e midmyocardial global longitudinal strain; GLS\u003csub\u003eepi\u003c/sub\u003e, epimyocardial global longitudinal strain; AVI, arterial velocity pulse index; Ea, effective arterial elastance; Ees, left ventricular end-systolic elastance; VVI, ventricular-vascular coupling index.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eArtery stiffness and ventricular-arterial coupling\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAVI values were significantly higher in the COVID-19 group (16.18\u0026thinsp;\u0026plusmn;\u0026thinsp;5.69) compared to the control group (13.63\u0026thinsp;\u0026plusmn;\u0026thinsp;5.53) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The AVI/GLS ratio was significantly lower in the COVID-19 group (-0.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32) compared to the control group (-0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0030). The boxplots in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e illustrate the median and interquartile range for the distribution of AVI, GLS, and the AVI/GLS ratio.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eAssociation between AVI/GLS ratio and clinical parameters\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAmong the clinical variables, age, BMI, SBP, and LVEF were all significantly associated with AVI/GLS changes. we performed a multiple logistic regression analysis to identify differences in myocardial strain associated with mild to moderate COVID-19. LVEF remained correlated with AVI/GLS ,ORs 0.0242, 1.044(p\u0026thinsp;=\u0026thinsp;0.002 Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)。\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariate linear analysis the association between AVI/GLS and clinical parameters.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRegression coefficient (β)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eStandardized coefficients (β\u0026prime;)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e95% Confidential interval\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModel 1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.622\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.013,-0.010\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.037\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.010,0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.366\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSBP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.139\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.004,-0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eModel 2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.600\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.012, -0.009\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.008, -0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.720\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSBP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.141\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.004, -0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLVEF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.643\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.129\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.242, 1.044\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eBMI Body mass index; SBP systolic blood pressure; LVEF left ventricular ejection fraction. AVI, arterial velocity pulse index; GLS global longitudinal strains; Age, BMI, SBP in multivariable model 1. Age, BMI, SBP, LVEF in multivariable model 2.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eReproducibility analysis\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe reproducibility of the AVI/GLS and AVI/GLS for the first time was assessed in 20 randomly selected subjects whose AVI/GLS anc AVI/GLS for the first time values were measured independently by two physicians, respectively. Bland\u0026ndash;Altman analysis showed a unconsistent trend, and linear regression analysis showed good agreement between measurements by the two independent observers for AVI/GLS and AVI/GLS for the first time. The mean (\u0026plusmn;\u0026thinsp;SD) difference was 2.23(\u0026plusmn;21.2)\u003c/p\u003e\u003cp\u003efor repeated measurements of AVI/GLS taken by two independent observers. The mean (\u0026plusmn;\u0026thinsp;SD) difference was \u0026minus;\u0026thinsp;1.59(\u0026plusmn;26.02)for repeated measurements of AVI/GLS for the first time taken by two independent observers (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eROC curve for predictive performance of AVI/GLS ratio\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe ROC curve identified a threshold of -0.504 of the AVI/GLS ratio to discriminate between COVID-19 (mild to moderate) and healthy controls AUC\u0026thinsp;=\u0026thinsp;0.583, 95% CI [0.528; 0.636], with the sensitivity 78.57% (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). However, by analyzing the ROC curve, the areas under the ROC curve of VVI is not statistically different.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eVAC plays a pivotal role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac diseases. In this study, we assessed VAC by calculating the ratio of AVI to GLS in patients with mild to moderate COVID-19 infection compared to healthy subjects. Notably, both GLS and GLS\u003csub\u003eEpi\u003c/sub\u003e strains, along with AVI values, showed slight increases in the COVID-19 cohort. Interestingly, the reduction in strain was first identified in the subepicardial region rather than the subendocardial region, which aligns with established characteristics of myocardial damage associated with myocarditis. Furthermore, the AVI/GLS ratio exhibited significantly higher values in the COVID-19 patients compared to the normal control group. This ratio demonstrated a reasonable capacity to differentiate altered VAC, suggesting its potential utility in clinical evaluation.\u003c/p\u003e\u003cp\u003eAcute myocardial injury is a recognized complication in patients with COVID-19 \u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. In our study, we found that LVEF, the E/e\u0026rsquo; ratio, and the E/A ratio did not exhibit significant differences among the subjects. This lack of variation may be attributed to the fact that the patients in our cohort were experiencing mild to moderate disease severity, and typical heart failure symptoms, such as orthopnea and nocturnal dyspnea, were largely absent. Nonetheless, we observed low-grade elevations in both cardiac troponin T (cTnT) and GLS, which correlate with a subclinical state of cardiac dysfunction associated with COVID-19. Myocardial deformation analysis using two-dimensional strain echocardiography, particularly through layer-specific quantification, offers a novel approach for identifying cardiac dysfunction in COVID-19 patients. Additionally, previous research has indicated preferential changes in subepicardial deformation \u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. In our study, we noted that the reduction in GLS in the subepicardial layer was more pronounced than that in the subendocardial layer. This finding suggests that cardiac dysfunction is predominantly located in the subepicardial layer of the myocardium, a critical feature that aligns with the manifestations of myocarditis.\u003c/p\u003e\u003cp\u003eAcute myocardial injury is one of the complications observed in COVID-19 patients \u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. In our study, LVEF, E/e\u0026rsquo; ratio and E/A ratio did not register significant differences. This may due to the patients in this study were in the mild to moderate severity of the disease and the typical symptoms of heart failure, including orthopnea and nocturnal dyspnea were largely absent in the study subjects. However, the low-grade elevation of cTnT and GLS aligns with the subclinical state of cardiac dysfunction associated with COVID-19. Myocardial deformation analysis by 2-D STE, particularly layer-specificquantification, provides a novel tool for detecting cardiac dysfunction in COVID-19 patients. In addition, previous study showed preferential changes in subepicardial deformation \u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. In our study, we noted that the reduction in GLS in the subepicardial layer was more pronounced than that in the subendocardial layer. This finding suggests that cardiac dysfunction is predominantly located in the subepicardial layer of the myocardium, a critical feature that aligns with the manifestations of myocarditis.\u003c/p\u003e\u003cp\u003eFurthermore, pathological studies have indicated that viral infections can lead to endothelial cell infection and endotheliitis \u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. Evidence suggests that COVID-19 may accelerate vascular aging at the macrovascular level \u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e, which could result in alterations in arterial stiffness \u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. The arterial velocity pulse index (AVI) is derived from the amplitude of oscillometric reflected waveforms \u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e. As confirmed in the study of Stoichescu-Hogea et al\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e, arterial stiffness increased in parallel with myocardial stiffness in hypertensive patients. In this study, there was a statistically significant increase in AVI in the COVID-19 group, whereas GLS was mildly increased but within normal range.\u003c/p\u003e\u003cp\u003eCompared with Ea, AVI provides a more direct assessment of the total elasticity of the arterial tree and the resistance of peripheral arteries, both of which are closely related to cardiac function \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Furthermore, early detection of subclinical disease progression in VA uncoupling using AVI/GLS ratio may be possible. Our study demonstrated that AVI/GLS ratio showed fair discrimination ability to predict altered VA coupling\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. In addition, no difference in the incidence of AVI/GLS ratio was observed in the COVID-19 and control group. GLS has been shown to be highly sensitive to myocardial injury and to reflect cardiac contractile function. GLS, on the other hand, reflects changes in cardiac configuration and is highly specific. These mechanisms explain the preferential alteration of AVI/GLS ratio among COVID-19 patients in this study.\u003c/p\u003e\u003cp\u003e\u003cb\u003eLimitations\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, this has been a retrospective cross-sectional analysis. To better explain the complex relationship between VAC, more insights could be obtained from prospective longitudinal studies in the future. Second, this study did not address changes in VAC during COVID-19 rehabilitation, thus long-term follow-up is needed.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe preferential alteration of arterial stiffness and strains in the subepicardium may underlie the cardiovascular pathology in COVID-19. The AVI/GLS ratio can be used to detect altered ventricular-arterial coupling in patients with mild to moderate COVID-19 infection.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAVI，arterial velocity pulse index；VVI，ventricular-vascular coupling index；GLS，global longitudinal strain；VA，ventricular-arterial；EA，effective arterial elasticity\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research plan was approved by the Ethics Committee of Shanghai General Hospital (2024SQ003). It was conducted following the Declaration of Helsinki of the World Medical Association. All participants in the project signed informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank those researchers who contribute to the BMC Cardiovascular Disorders \u0026ldquo;Uncoupling of Ventricular and Arterial Derived from Arterial Stiffness and Global Longitudinal Strain in Mild to Moderate COVID-19\u0026rdquo; Collection.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy design: ZJL. Data collection: all authors. Data verification: XYL, NW and LFD. Data analysis: LJ, JXC, and LHW. Initial draft: LJ and SYZ. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Natural Science Foundation of Shanghai (21ZR1451400), Shanghai Health and Family Planning Commission Fund (202240235), and Shanghai Jiading District Health and Family Planning Commission Fund (2021-KY-10).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest relevant to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ethe Ethics Committee of Shanghai General Hospital (2024SQ003).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNarayan K M V, Curran J W, Foege W H. 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J Atheroscler Thromb, 2018, 25(9): 792-798.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"echocardiography, ventricular-arterial coupling, arterial velocity pulse index, global longitudinal strain, COVID-19","lastPublishedDoi":"10.21203/rs.3.rs-6812543/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6812543/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThe physiological interaction between the left ventricle (LV) and the arterial system, known as ventricular-arterial coupling (VAC), plays a crucial role in optimizing cardiac work and overall cardiovascular performance. This study aims to investigate VAC by analyzing the ratio of the arterial velocity pulse index (AVI) to LV global longitudinal strain (GLS), in patients with mild to moderate COVID-19.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis study included 180 controls and 154 patients with mild to moderate COVID-19. We compared laboratory indicators, left ventricular ejection fraction (LVEF), TDI e\u0026rsquo;, effective arterial elasticity (Ea), left ventricular end-systolic elasticity (Ees), ventricular-arterial coupling index (VVI), AVI and GLS between the two groups. Correlations between AVI/GLS and clinical/laboratory indicators were assessed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe values of GLS\u003csub\u003eww\u003c/sub\u003e, GLSepi were significantly lower in patients with COVID-19 than controls (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, there were no significant differences in GLS\u003csub\u003emid\u003c/sub\u003e and GLS\u003csub\u003eendo\u003c/sub\u003e between the two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The AVI/GLS ratio was significantly lower in the COVID-19 group than in controls (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). AVI/GLS ratio was negatively correlated with age and systolic blood pressure (SBP), and positively correlated with left ventricular ejection fraction (LVEF) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Age, SBP, and LVEF were identified as independent predictors of AVI/GLS. The area under the curve (AUC) for AVI/GLS ratio in diagnosing mild to moderate COVID-19 was 0.583, with a sensitivity of 78.6%.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThe AVI/GLS ratio could serve as a valuable tool for detecting altered ventricular-arterial coupling in patients mild to moderate COVID-19.\u003c/p\u003e","manuscriptTitle":"Ventricular-Arterial Uncoupling in Mild to Moderate COVID-19 Pneumonia: Role of A Novel Ventricular-Vascular Coupling Index","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-02 02:15:37","doi":"10.21203/rs.3.rs-6812543/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8664e7d8-a38b-4d62-97ad-304b0647e076","owner":[],"postedDate":"September 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-18T12:53:57+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-02 02:15:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6812543","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6812543","identity":"rs-6812543","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}