Relationship Between Left Atrial Spontaneous Echo Contrast and the MAPH Score in Patients With Severe Rheumatic Mitral Stenosis

Relationship Between Left Atrial Spontaneous Echo Contrast and the MAPH Score in Patients With Severe Rheumatic Mitral Stenosis | 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 Relationship Between Left Atrial Spontaneous Echo Contrast and the MAPH Score in Patients With Severe Rheumatic Mitral Stenosis Tuğba Kayhan Altuner, Nazlı Turan Şerifler, Meltem Altınsoy, Berin Ergin, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8818290/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Objective Left atrial spontaneous echo contrast (SEC) is an echocardiographic finding in which blood—normally non-contrasting—appears as a swirling, smoke-like echogenic pattern. The presence of SEC in the left atrium is associated with an increased risk of thromboembolism, and this risk increases with higher SEC grades. The MAPH score has recently been defined as a simple index of whole-blood viscosity. In this study, we aimed to evaluate the relationship between the MAPH score and the presence and grade of SEC in patients with severe rheumatic mitral stenosis in sinus rhythm. Methods This single-center, retrospective study included 96 patients in sinus rhythm who underwent percutaneous mitral balloon valvuloplasty for severe mitral stenosis. SEC presence was assessed by transesophageal echocardiography in all patients. Patients were grouped according to SEC presence (SEC+/SEC−) and SEC grade. The MAPH score (age, MPV, hematocrit, total protein) was calculated for each patient. Results Among 96 patients, 75 (78.1%) were SEC(+) and 21 (21.9%) were SEC(−). The MAPH score was higher in the SEC(+) group (Mann–Whitney U = 389.5; p < 0.001). No significant association was found between SEC severity and the MAPH score (Kruskal–Wallis p = 0.487). In ROC curve analysis, MAPH showed a significant ability to discriminate between SEC presence and absence (AUC = 0.753; 95% CI 0.639–0.866; p < 0.001). According to the Youden index, the optimal cut-off was MAPH ≥ 3, with a sensitivity of 56.0% and a specificity of 90.5%. In multivariable analysis, the MAPH score, left atrial diameter, and mitral valve area were identified as independent predictors of SEC presence. The AUC of the model built using continuous component values was 0.766 (95% CI 0.655–0.877; p < 0.001). Conclusion The MAPH score showed significant predictive performance for SEC presence but limited ability to discriminate SEC grade. rheumatic mitral stenosis spontaneous echo contrast MAPH score blood viscosity transesophageal echocardiography Figures Figure 1 INTRODUCTION Left atrial spontaneous echo contrast (SEC) is the smoke-like, swirling echogenicity of blood that is usually non-echogenic on echocardiography and is most commonly observed in patients with mitral stenosis (MS) and atrial fibrillation (AF). SEC is most easily visualized with transesophageal echocardiography (TEE) and is frequently detected within the left atrium(LA) and left atrial appendage(LAA). [ 1 , 2 ] Clinically, SEC increases the risk of left atrial thrombus formation and thromboembolic events, and greater SEC severity further increases embolic risk [ 3 – 5 ]. Therefore, improving our understanding of the mechanisms underlying SEC and identifying predictors of its presence may help reduce adverse events in patients with MS. Studies have found that SEC in the LA is influenced not only by low blood flow velocity but also by factors such as blood viscosity, erythrocyte aggregation, hematocrit, and plasma protein levels. The correlation between SEC, hematocrit, and fibrinogen levels indicates that the phenomenon is attributable to erythrocyte aggregation and elevated blood viscosity [ 5 – 7 ]. The MAPH score (mean platelet volume–age–total protein–hematocrit), developed in recent years, is a straightforward index reflecting whole-blood viscosity and correlates with coronary slow flow, thrombus burden in acute coronary syndromes, and the severity of ischemic stroke [ 8 – 10 ]. In our study, we aimed to evaluate the relationship between the MAPH score and the presence of left atrial SEC in patients with MS. MATERIALS AND METHODS Study Population This is a retrospective, single-center study of patients with severe mitral stenosis who underwent percutaneous mitral balloon valvuloplasty at our institution between October 2022 and November 2025. The study analyzed data from 156 participants. Before percutaneous mitral balloon valvuloplasty, all patients underwent TEE and transthoracic echocardiography (TTE) to rule out left atrial thrombus. The SEC in the LA was assessed using TEE. The study group was divided into two subgroups: those with SEC detected in the left atrium (SEC(+)) and those without SEC (SEC(-)). The study excluded patients with hematologic disorders, active malignancies, chronic inflammatory or autoimmune diseases, clinical or laboratory evidence of acute infection or sepsis, advanced renal or hepatic insufficiency, significant thyroid dysfunction, a history of blood transfusion in the previous three months, severe anemia (Hb < 10 g/dL), diagnosed polycythemia, or pregnancy. Additionally, patients with prior valve surgery or mitral balloon valvuloplasty, intrinsic cardiomyopathy, severe aortic stenosis or regurgitation, severe mitral regurgitation, or serious extravalvular disease were excluded. After applying these exclusion criteria, data from the remaining 96 patients were examined. Detailed records were maintained for all patients, including age, gender, diabetes, hypertension, smoking status, cerebrovascular disease, coronary artery disease, peripheral vascular disease, comorbidity history, and laboratory findings at admission. The ethics committee of our hospital approved the trial. Laboratory measurements Blood samples were drawn from the antecubital vein into EDTA tubes for a complete blood count performed on a Sysmex K-1000 (Kobe, Japan) and for biochemical analysis performed on a Roche Diagnostics Cobas 8000 c502 (Indianapolis, IN, USA). Samples were analyzed immediately to prevent platelet swelling. The MAPH score was calculated as a combination of mean platelet volume (MPV), age, total protein, and hematocrit, as defined in the literature. Cutoff points were determined using the Youden index from ROC curves that evaluated the effects of MPV, age, total protein, and hematocrit on the target outcome. 1 point was given for each parameter above the cut-off value, and an MAPH score ranging from 0 to 4 was created [ 6 ]. Glucose, urea, creatinine, liver function tests, and lipid profile were obtained using standard methods. Echocardiography All echocardiographic examinations were performed after at least 10–15 minutes of rest, using two-dimensional, M-mode, color Doppler, and spectral Doppler echocardiography (Vivid S70, GE Healthcare, USA). TTE and TEE were performed in the same session whenever possible. All measurements were performed in accordance with the American Society of Echocardiography guidelines [ 7 ]. The left ventricular ejection fraction(LVEF) was measured from the apical four-chamber view using the modified Simpson method. The mitral valve area (MVA) was measured directly from the parasternal short-axis view using planimetry. The mean mitral gradient was calculated as the average of the pressure differences obtained from transmitral flow measured by continuous-wave Doppler. Continuous-wave Doppler measured the maximum velocity of the tricuspid regurgitation jet, and the resulting trans-tricuspid gradient was added to right atrial pressure to estimate systolic pulmonary artery pressure (SPAP). The diameters of the left atrium, left ventricule and right heart chambers were measured according to standard guidelines. For TEE, after local anesthesia was applied to the pharyngeal region with topical 10% lidocaine spray, the multiplane TEE probe was advanced into the esophagus approximately 25–35 cm, and the LA and left atrial appendage (LAA) were evaluated in detail at the level where the best image was obtained. A pattern of slowly swirling, smoke-like echo densities was considered SEC. The SEC severity was graded from 0 to 4 + according to the Fatkin et al criteria [ 7 ]. All transthoracic and transesophageal echocardiographic assessments were performed by a cardiologist experienced in echocardiography. Statistical Analysis Statistical analyses were performed using IBM SPSS Statistics (Mac version, v21.0). Data showing normal distribution were presented as mean ± standard deviation, while data not showing normal distribution were presented as median (interquartile range, IQR). Categorical variables were expressed as numbers (percentages). Comparisons between SEC groups were performed using the independent-samples t-test or Mann–Whitney U test for continuous variables, depending on data distribution. The Chi-square test or Fisher's exact test was applied for categorical variables, particularly when expected cell counts were low. MAPH scores among SEC severity groups within SEC(+) patients were compared using the Kruskal–Wallis test. The ability of the MAPH score and other parameters to distinguish SEC presence was assessed using receiver operating characteristic (ROC) analysis. Area under the curve (AUC) values were reported with 95% confidence intervals. Optimal cut-off values were identified using the Youden index, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated at the relevant thresholds. Logistic regression was performed to identify independent determinants of SEC status. First, univariate analyses were performed; then, clinically significant variables and/or variables found to be significant or borderline significant in the univariate analyses were included in the same multivariate model. The results were reported with an odds ratio (OR) and a 95% confidence interval. Additionally, ROC analysis was performed on the predicted probabilities from a logistic model trained on continuous values of MPV, age, total protein, and hematocrit to evaluate the potential impact of dividing into two groups based on the cutoff, and the AUC was reported. p values lower than 0.05 were considered to demonstrate statistical significance. RESULTS Of the 96 patients, 21 (21.9%) were SEC(-) and 75 (78.1%) were SEC(+). In the SEC(+) group, the distribution was as follows: Grade 1: 42 (56.0%); Grade 2: 17 (22.7%); Grade 3: 9 (12.0%); and Grade 4: 7 (9.3%). Due to the small number of samples in subgroup analyses, Grade 3 and 4 cases were grouped as 'high-grade SEC (Grade 3–4)' (n = 16, 21.3%). Age was significantly higher in the SEC(+) group. The prevalence of gender, hypertension, and other comorbidities did not differ significantly between the groups (Table 1 ). Table 1 Demographic characteristics of the study populations. Variables SEC (−) (n = 21) SEC (+) (n = 75) p value Age (years), mean ± SD 45.29 ± 7.48 51.77 ± 11.29 0.003 Female sex, n (%) 14 (66.7) 59 (78.7) 0.255 Hypertension, n (%) 4 (19.0) 24 (32.0) 0.248 Diabetes mellitus, n (%) 2 (9.5) 12 (16.0) 0.728 CAD, n (%) 1 (4.8) 3 (4.0) 1.000 CVD (stroke/TIA), n (%) 1 (4.8) 8 (10.7) 0.679 Current smoker, n (%) 6 (28.6) 8 (10.7) 0.073 CAD, coronary artery disease; CVD, cerebrovascular disease Table 2 displays the differences in laboratory results between the two groups. In the comparison between SEC (−) and SEC (+) groups, creatinine, albumin, AST, and platelet count differed significantly (p 0.05). Table 2 Laboratory findings of the study populations. Variables SEC (−) (n = 21) SEC (+) (n = 75) p value Creatinine (mg/dl) 0.73 ± 0.19 0.83 ± 0.21 0.044 Sodium (mmol/L) 138.67 ± 3.40 139.13 ± 2.79 0.521 Potassium (mmol/L) 4.10 ± 0.33 4.25 ± 0.38 0.119 Albumin (g/L) 42.73 ± 2.74 40.03 ± 5.17 0.023 AST (U/L) 16.81 ± 5.49 28.33 ± 20.61 < 0.001 ALT(U/L) 17.00 ± 8.68 24.73 ± 18.21 0.063 Glucose (mg/dl) 89.38 ± 12.83 105.96 ± 38.42 0.055 LDL cholesterol (mg/dl) 105.05 ± 40.28 118.40 ± 32.38 0.124 Triglycerides (mg/dl) 100.50 ± 54.88 125.14 ± 56.65 0.087 HDL cholesterol (mg/dl) 46.90 ± 8.19 44.14 ± 13.75 0.394 Hemoglobin (g/dL) 13.25 ± 1.25 12.65 ± 1.52 0.099 Platelet count (×10³/µL) 215.00 ± 44.88 254.13 ± 71.78 0.004 Neutrophils (×10³/µL) 5.06 ± 2.01 5.11 ± 1.80 0.926 Lymphocytes (×10³/µL) 2.20 ± 0.72 2.24 ± 1.35 0.901 MPV (fL) 11.33 ± 1.42 11.21 ± 1.02 0.660 Total protein (g/L) 66.28 ± 6.06 68.74 ± 6.05 0.103 Hematocrit (%) 37.93 ± 4.20 38.59 ± 3.71 0.514 AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDL, low-density lipoprotein; HDL, high-density lipoprotein; MPV, mean platelet volume; SEC, spontaneous echo contrast. In the echocardiographic evaluation, the left atrial diameter, Left ventricular end-diastolic diameter, and systolic pulmonary artery pressure were higher in the SEC(+) group compared to the SEC(−) group, although the mitral valve area was diminished. The mean transmitral gradient, ejection fraction, and left ventricular end-systolic diameter showed no significant difference across the groups. (Table 3 ) Table 3 Echocardiographic Characteristics of the Patients Variables SEC (−) (n = 21) SEC (+) (n = 75) p value LA (cm) 4.16 ± 0.23 4.71 ± 0.70 < 0.001 LVEF (%) 63.9 ± 5.8 62 ± 4.6 0.339 LVEDD (cm) 4.40 ± 0.23 4.61 ± 0.56 0.011 LVESD (cm) 2.73 ± 0.29 2.87 ± 0.51 0.222 sPAP (mmHg) 33.52 ± 9.78 43.32 ± 18.32 0.002 Mean TMG (mmHg) 11.81 ± 2.18 11.80 ± 3.43 0.988 MVA (cm²) 1.22 ± 0.14 1.12 ± 0.17 0.014 SEC, spontaneous echo contrast; LA, left atrial diameter; LVEF, left ventricular ejection fraction; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; sPAP, systolic pulmonary artery pressure; TMG, transmitral gradient ; MVA, mitral valve area. The MAPH score was significantly higher in the SEC(+) group compared to the SEC(−) group (Mann–Whitney U = 389.5, Z = − 3.676, p < 0.001, r ≈ 0.38). No significant differences in MAPH score were observed across SEC severity grades among SEC(+) patients. (Kruskal–Wallis H = 1.440, df = 2, p = 0.487). ROC analysis showed that MAPH discriminated the presence of SEC (AUC = 0.753; 95% CI 0.639–0.866; p < 0.001). In a sensitivity analysis, the predicted probability from a logistic regression model using continuous MPV, age, total protein, and hematocrit values showed similar discriminative performance (AUC = 0.766; 95% CI 0.655–0.877; p < 0.001). (Fig. 1) Based on the Youden index, the optimal cut-off value was MAPH ≥ 3, yielding a sensitivity of 56.0% and specificity of 90.5% (PPV 95.5%, NPV 36.5%). The cut-off values for MPV, age, total protein, and hematocrit were derived using the ROC–Youden method. Among these parameters, only age showed significant discrimination for SEC presence (p = 0.008), whereas MPV, total protein, and hematocrit showed no significant discrimination (p = 0.922, p = 0.203, and p = 0.787). (Table 4 ) Table 4 ROC–Youden-derived cut-off values Variables Cut-off (ROC–Youden) p value Age (years) ≥ 46.5 0.008 MPV (fL) ≥ 10.15 0.922 Total protein (g/L) ≥ 65.55 0.203 Hematocrit (%) ≥ 39.15 0.787 MPV, mean platelet volume; ROC, receiver operating characteristic. In multivariate logistic regression analysis, the MAPH score, left atrial diameter, and mitral valve area were independent predictors of SEC (Table 5 ) Table 5 Logistic regression analyses for the presence of spontaneous echo contrast Variables Univariate analysis Multivariate analysis OR 95% CI p value OR 95% CI p value MAPH score 2.400 1.328–4.338 0.004 2.103 1.047–4.223 0.037 Left atrial diameter (cm) 1.200 1.074–1.341 0.001 1.207 1.062–1.372 0.004 Mitral valve area ( cm²) 0.648 0.501–0.930 0.019 0.576 0.501–0.895 0.015 sPAP (mmHg) 1.053 1.007–1.100 0.023 1.009 0.958–1.062 0.742 Platelet count (×10³/µL) 1.010 1.001–1.018 0.024 1.007 0.996–1.018 0.232 OR: odds ratio (Exp(B)); CI: confidence interval; SEC, spontaneous echo contrast. Odds ratios for left atrial diameter and mitral valve area are expressed per 0.1 cm and 0.1 cm², respectively. Multivariable model: all variables listed in the table were entered simultaneously into the same model. p values were calculated using the Wald test. DISCUSSION This study investigated the correlation between the MAPH score and the presence of left atrial spontaneous echo contrast in patients with severe rheumatic mitral stenosis in sinus rhythm. To our knowledge, this relationship has not been well characterized previously. MAPH was significantly higher in patients with SEC than in those without SEC. In SEC(+) patients, MAPH showed no significant variation across severity grades. These findings indicate that MAPH may be effective at detecting the presence of SEC but less useful for differentiating between levels of SEC severity. Rheumatic MS remains a major public health problem in developing countries. The incidence of AF and related thromboembolic events increases in patients with MS [ 8 ]. Studies show that thromboembolic events occur more frequently in patients with MS than in those without MS, independent of AF [ 1 ]. SEC is defined by dynamic, smoke-like echogenicity in the LA or LAA. Although LA-SEC is only occasionally detected on TTE, TEE is superior for detecting LA thrombus and SEC. Studies have also reported a higher prevalence of LA thrombus in the presence of SEC [ 9 ]. Sigel et al. demonstrated that SEC severity correlated positively with hematocrit and fibrinogen levels and negatively with shear stress, suggesting that SEC reflects red blood cell aggregation[ 10 , 11 ]. Black et al. similarly demonstrated that SEC correlated with hematocrit, fibrinogen concentration, and left atrial diameter, but showed no association with platelet count [ 12 ]. Fatkin et al. observed reduced LAA emptying velocity and lower shear rates in patients with AF and SEC [ 13 ]. A study showed that fibrinogen and gamma-globulin levels, as well as plasma/serum viscosity, were higher in patients with SEC than in those without SEC, underscoring the role of plasma proteins in SEC pathogenesis [ 14 ]. Rastegar et al. showed in vitro that fibrinogen-mediated erythrocyte aggregation may contribute to SEC formation. The strongest SEC occurred at fibrinogen 400–500 mg/dL and hematocrit 39–47%, similar to acute coronary syndrome levels [ 15 ]. The role of platelets in the pathophysiology of SEC remains incompletely understood, and existing findings are inconsistent. Chen et al. showed that patients with MS had higher P-selectin (CD62P) expression in the LA than in the right atrium and peripheral samples, and that this expression correlated with the severity of stenosis [ 16 ]. Studies investigating the source of SEC directly in left atrial blood samples found that platelet and leukocyte aggregates contribute to SEC [ 17 ]. The correlation between platelet indices, such as MPV and SEC, is also heterogeneous in the literature, with some studies reporting a positive association and others not. Therefore, platelet activation may be a more meaningful component in terms of the prothrombotic milieu accompanying SEC and thrombus formation, rather than in the formation of SEC itself [ 18 – 20 ]. In summary, SEC is a complex issue that, in stasis, is linked to blood parameters such as hematocrit, fibrinogen/total protein, viscosity, and platelet activation. Routine, readily available parameters may help identify patients at a higher likelihood of SEC and related thrombus formation. The MAPH score—age, MPV, hematocrit, and total protein—is an accessible way to assess blood viscosity and risk of thrombosis. Previous studies have shown that the MAPH score is associated with coronary thrombus burden in patients with acute coronary syndrome and may predict high thrombus burden [ 6 , 21 ]. Akhan et al. showed that the MAPH score was an independent predictor of coronary slow flow [ 22 ]. Yurdam et al. found a negative correlation between TIMI flow grade and MAPH score [ 23 ]. Based on these findings, MAPH components are likely to overlap with the pathophysiology of SEC. In our investigation, the MAPH score was associated with SEC presence; however, it did not differ significantly across SEC grades among SEC-positive individuals. These findings suggest that the severity of SEC may be linked to left atrial stasis/flow dynamics, the hemodynamic effects of mitral stenosis, and blood rheology. In addition, the small number of cases with high SEC grades in our study may have reduced the statistical power to detect differences between grades. Therefore, in larger studies, especially in cohorts with sufficient numbers of Grade 3–4, the relationship between the MAPH score and SEC severity levels can be more clearly evaluated. In our investigation, when the components of the MAPH score were examined individually, each parameter showed limited discriminative ability; however, the composite MAPH score was significantly associated with the presence of SEC. The fact that MAPH demonstrated substantial discrimination as a 'composite' in our data supports the theory that more than one factor related to blood flow characteristics and thrombosis tendency may be effective in the pathogenesis of SEC, rather than a single parameter. The restricted discriminability of each parameter in analyses where components are assessed separately can be attributed to the composite score more effectively encapsulating the overall effect. Our echocardiographic results are also consistent with the literature. Beppu, et al. found that in individuals with MS, left atrial SEC was associated with lower cardiac output, higher LA size, and a smaller mitral valve area [ 24 ]. Other studies in patients with MS have found that LA SEC is associated with more severe stenosis, AF, older age, and the absence of moderate-to-severe mitral regurgitation [ 1 , 12 , 25 ]. In our study, the LA diameter was larger, and the MVA was smaller in patients with SEC. This finding supports the prominent role of key hemodynamic factors, such as stasis and stenosis severity, in SEC. Therefore, when evaluating SEC, it may be useful to consider echocardiographic indicators alongside composite scores that reflect blood flow characteristics and thrombotic tendency. Our study identified the MAPH score, LA diameter, and MVA as independent predictors of SEC in multivariate logistic regression. This suggests that the MAPH score is not merely a surrogate for echocardiographic severity markers and may provide additional information related to blood flow characteristics and thrombotic tendency associated with SEC. Conversely, SPAP and platelet count were not significant in the multivariate model, possibly due to overlap with key hemodynamic determinants or sample-related factors. Since the cutoff values were derived from our sample, it is important to confirm their generalizability to future studies across different patient populations. Additionally, finding similar discrimination to MAPH when using continuous component values supports the conclusion that our results are not solely dependent on the cutoff selection. According to our study, MAPH can be used clinically to risk-classify patients with a high probability of SEC and to prioritize them for further evaluation, rather than as a diagnostic test on its own, especially in settings with limited access to TEE. Study Limitations The most important limitation of our study is the relatively small sample size. Additionally, because the study had a single-center, retrospective design, the selected patient population may not be representative of the entire mitral stenosis cohort, and the generalizability of the findings may be limited. In subgroup analyses, the small number of patients with SEC(−) and, especially, high-grade SEC (Grade 3–4) may have reduced statistical power in group comparisons, making it difficult to detect potential differences. In addition, TEE parameters such as LAA emptying velocities, which reflect LAA function, could not be evaluated in our study. Because cutoff values were derived from the study cohort, their performance should be confirmed in independent populations. Conclusions In conclusion, the MAPH score, in conjunction with echocardiographic parameters, may be a simple and practical tool for estimating the likelihood of SEC in patients with rheumatic mitral stenosis in sinus rhythm. Larger, multicenter studies validating these findings in diverse patient groups are needed before clinical application. Abbreviations MS mitral stenosis AF atrial fibrillation SEC spontaneous echo contrast TEE transesophageal echocardiography TTE transthoracic echocardiography EDTA ethylenediaminetetraacetic acid Hb hemoglobin MPV mean platelet volume LVEF left ventricular ejection fraction MVA mitral valve area SPAP systolic pulmonary artery pressure LA left atrium LAA left atrial appendage AUC area under the curve ROC receiver operating characteristic NPV negative predictive value PPV positive predictive value CI confidence interval df degrees of freedom Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of Ankara Etlik City Hospital. (AEŞH-BADEK2-2025-613) The study was conducted in accordance with the principles of the Declaration of Helsinki. Patient data were anonymized prior to analysis, and the ethics committee waived the requirement for informed consent. Clinical trial number: not applicable. Consent for publication Not applicable. Availability of data and materials The datasets generated and/or analysed during the current study are not publicly available due to patient confidentiality and ethical restrictions but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding None. Authors’ contributions T.K.A., N.T.Ş., B.Y. and F.B. planned the research together. T.K.A., B.E., and M.A ensured the collection of data. T.K.A and F.B. performed statistical analysis of the data. All authors contributed to the writing of the article and approved the final version of the article. Acknowledgements Not applicable. References Black IW, et al. Left atrial spontaneous echo contrast: a clinical and echocardiographic analysis. 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Smoke-like echo in the left atrial cavity in mitral valve disease: its features and significance. J Am Coll Cardiol. 1985;6(4):744–9. Leung DY, et al. Resolution of left atrial spontaneous echocardiographic contrast after percutaneous mitral valvuloplasty: implications for thromboembolic risk. Am Heart J. 1995;129(1):65–70. Additional Declarations No competing interests reported. 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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-8818290","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":602818599,"identity":"c8ea1a30-014c-4549-b174-4a2a1c42746d","order_by":0,"name":"Tuğba Kayhan Altuner","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBUlEQVRIiWNgGAWjYDCCA0DM2MDAIMHAwAZk2oBZBLQwo2hJI13LYcJa+G6fPyb5dYcdg2T7GbMHP3ecT+yf3XzwAUONTTQuLZLnktmkZc8kM0jz5Jgb9p65nTjjzrFkA4ZjabkNOLQYnGFmk5ZsY2aQY8gxk+Btu53YcAPIYGw4TEhLPYMc/xszyb9t5xLnE6NF8mPbYQZpiRwzad62A4kbCGmRPMNsbM145jiD5IxnZdKybcnGG2+kJRsk4PEL3xnGhzd/7qhmkDifvE3ybZud7LwbyQcffKixwakFBJh5GBjqGxg4DEAcR7DKBDzKQYDxB5hifwAi7QkoHgWjYBSMghEIADzzW5xkfJJsAAAAAElFTkSuQmCC","orcid":"","institution":"Etlik City Hospital","correspondingAuthor":true,"prefix":"","firstName":"Tuğba","middleName":"Kayhan","lastName":"Altuner","suffix":""},{"id":602818600,"identity":"90417fbd-adda-4f6c-8ccb-3e43a33726a9","order_by":1,"name":"Nazlı Turan Şerifler","email":"","orcid":"","institution":"Etlik City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nazlı","middleName":"Turan","lastName":"Şerifler","suffix":""},{"id":602818602,"identity":"578b0479-9dbb-4973-bfb3-9ebf2e3a4ff8","order_by":2,"name":"Meltem Altınsoy","email":"","orcid":"","institution":"Etlik City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Meltem","middleName":"","lastName":"Altınsoy","suffix":""},{"id":602818603,"identity":"b6a5f867-b6a2-4cc1-93ed-c8f1a9686416","order_by":3,"name":"Berin Ergin","email":"","orcid":"","institution":"Etlik City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Berin","middleName":"","lastName":"Ergin","suffix":""},{"id":602818604,"identity":"02035b0a-ea2e-44f5-b0f9-2536c6118626","order_by":4,"name":"Belma Yaman","email":"","orcid":"","institution":"Bilkent City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Belma","middleName":"","lastName":"Yaman","suffix":""},{"id":602818605,"identity":"d1bb436f-164e-497c-9e6c-ec09926e25de","order_by":5,"name":"Funda Başyiğit","email":"","orcid":"","institution":"Etlik City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Funda","middleName":"","lastName":"Başyiğit","suffix":""}],"badges":[],"createdAt":"2026-02-07 23:08:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8818290/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8818290/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104343687,"identity":"8e6928da-4858-4b62-b1c7-622afcfd44ae","added_by":"auto","created_at":"2026-03-10 17:14:47","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":153350,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8818290/v1/ac6afc9ee14d2178f4eb6aec.png"},{"id":104343712,"identity":"abe4eef7-eb06-4675-aa38-724ef863bed9","added_by":"auto","created_at":"2026-03-10 17:15:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":807222,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8818290/v1/bc1e2347-4f57-4765-9a9a-f66bb7098ea0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Relationship Between Left Atrial Spontaneous Echo Contrast and the MAPH Score in Patients With Severe Rheumatic Mitral Stenosis","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eLeft atrial spontaneous echo contrast (SEC) is the smoke-like, swirling echogenicity of blood that is usually non-echogenic on echocardiography and is most commonly observed in patients with mitral stenosis (MS) and atrial fibrillation (AF). SEC is most easily visualized with transesophageal echocardiography (TEE) and is frequently detected within the left atrium(LA) and left atrial appendage(LAA). [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Clinically, SEC increases the risk of left atrial thrombus formation and thromboembolic events, and greater SEC severity further increases embolic risk [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Therefore, improving our understanding of the mechanisms underlying SEC and identifying predictors of its presence may help reduce adverse events in patients with MS.\u003c/p\u003e \u003cp\u003eStudies have found that SEC in the LA is influenced not only by low blood flow velocity but also by factors such as blood viscosity, erythrocyte aggregation, hematocrit, and plasma protein levels. The correlation between SEC, hematocrit, and fibrinogen levels indicates that the phenomenon is attributable to erythrocyte aggregation and elevated blood viscosity [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The MAPH score (mean platelet volume\u0026ndash;age\u0026ndash;total protein\u0026ndash;hematocrit), developed in recent years, is a straightforward index reflecting whole-blood viscosity and correlates with coronary slow flow, thrombus burden in acute coronary syndromes, and the severity of ischemic stroke [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In our study, we aimed to evaluate the relationship between the MAPH score and the presence of left atrial SEC in patients with MS.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eThis is a retrospective, single-center study of patients with severe mitral stenosis who underwent percutaneous mitral balloon valvuloplasty at our institution between October 2022 and November 2025. The study analyzed data from 156 participants. Before percutaneous mitral balloon valvuloplasty, all patients underwent TEE and transthoracic echocardiography (TTE) to rule out left atrial thrombus. The SEC in the LA was assessed using TEE. The study group was divided into two subgroups: those with SEC detected in the left atrium (SEC(+)) and those without SEC (SEC(-)).\u003c/p\u003e \u003cp\u003eThe study excluded patients with hematologic disorders, active malignancies, chronic inflammatory or autoimmune diseases, clinical or laboratory evidence of acute infection or sepsis, advanced renal or hepatic insufficiency, significant thyroid dysfunction, a history of blood transfusion in the previous three months, severe anemia (Hb\u0026thinsp;\u0026lt;\u0026thinsp;10 g/dL), diagnosed polycythemia, or pregnancy. Additionally, patients with prior valve surgery or mitral balloon valvuloplasty, intrinsic cardiomyopathy, severe aortic stenosis or regurgitation, severe mitral regurgitation, or serious extravalvular disease were excluded.\u003c/p\u003e \u003cp\u003eAfter applying these exclusion criteria, data from the remaining 96 patients were examined. Detailed records were maintained for all patients, including age, gender, diabetes, hypertension, smoking status, cerebrovascular disease, coronary artery disease, peripheral vascular disease, comorbidity history, and laboratory findings at admission. The ethics committee of our hospital approved the trial.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eLaboratory measurements\u003c/h3\u003e\n\u003cp\u003eBlood samples were drawn from the antecubital vein into EDTA tubes for a complete blood count performed on a Sysmex K-1000 (Kobe, Japan) and for biochemical analysis performed on a Roche Diagnostics Cobas 8000 c502 (Indianapolis, IN, USA). Samples were analyzed immediately to prevent platelet swelling. The MAPH score was calculated as a combination of mean platelet volume (MPV), age, total protein, and hematocrit, as defined in the literature. Cutoff points were determined using the Youden index from ROC curves that evaluated the effects of MPV, age, total protein, and hematocrit on the target outcome. 1 point was given for each parameter above the cut-off value, and an MAPH score ranging from 0 to 4 was created [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Glucose, urea, creatinine, liver function tests, and lipid profile were obtained using standard methods.\u003c/p\u003e\n\u003ch3\u003eEchocardiography\u003c/h3\u003e\n\u003cp\u003eAll echocardiographic examinations were performed after at least 10\u0026ndash;15 minutes of rest, using two-dimensional, M-mode, color Doppler, and spectral Doppler echocardiography (Vivid S70, GE Healthcare, USA). TTE and TEE were performed in the same session whenever possible. All measurements were performed in accordance with the American Society of Echocardiography guidelines [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The left ventricular ejection fraction(LVEF) was measured from the apical four-chamber view using the modified Simpson method. The mitral valve area (MVA) was measured directly from the parasternal short-axis view using planimetry. The mean mitral gradient was calculated as the average of the pressure differences obtained from transmitral flow measured by continuous-wave Doppler. Continuous-wave Doppler measured the maximum velocity of the tricuspid regurgitation jet, and the resulting trans-tricuspid gradient was added to right atrial pressure to estimate systolic pulmonary artery pressure (SPAP). The diameters of the left atrium, left ventricule and right heart chambers were measured according to standard guidelines. For TEE, after local anesthesia was applied to the pharyngeal region with topical 10% lidocaine spray, the multiplane TEE probe was advanced into the esophagus approximately 25\u0026ndash;35 cm, and the LA and left atrial appendage (LAA) were evaluated in detail at the level where the best image was obtained. A pattern of slowly swirling, smoke-like echo densities was considered SEC. The SEC severity was graded from 0 to 4\u0026thinsp;+\u0026thinsp;according to the Fatkin et al criteria [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. All transthoracic and transesophageal echocardiographic assessments were performed by a cardiologist experienced in echocardiography.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using IBM SPSS Statistics (Mac version, v21.0). Data showing normal distribution were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, while data not showing normal distribution were presented as median (interquartile range, IQR). Categorical variables were expressed as numbers (percentages).\u003c/p\u003e \u003cp\u003eComparisons between SEC groups were performed using the independent-samples t-test or Mann\u0026ndash;Whitney U test for continuous variables, depending on data distribution. The Chi-square test or Fisher's exact test was applied for categorical variables, particularly when expected cell counts were low. MAPH scores among SEC severity groups within SEC(+) patients were compared using the Kruskal\u0026ndash;Wallis test.\u003c/p\u003e \u003cp\u003eThe ability of the MAPH score and other parameters to distinguish SEC presence was assessed using receiver operating characteristic (ROC) analysis. Area under the curve (AUC) values were reported with 95% confidence intervals. Optimal cut-off values were identified using the Youden index, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated at the relevant thresholds.\u003c/p\u003e \u003cp\u003eLogistic regression was performed to identify independent determinants of SEC status. First, univariate analyses were performed; then, clinically significant variables and/or variables found to be significant or borderline significant in the univariate analyses were included in the same multivariate model. The results were reported with an odds ratio (OR) and a 95% confidence interval. Additionally, ROC analysis was performed on the predicted probabilities from a logistic model trained on continuous values of MPV, age, total protein, and hematocrit to evaluate the potential impact of dividing into two groups based on the cutoff, and the AUC was reported. p values lower than 0.05 were considered to demonstrate statistical significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eOf the 96 patients, 21 (21.9%) were SEC(-) and 75 (78.1%) were SEC(+). In the SEC(+) group, the distribution was as follows: Grade 1: 42 (56.0%); Grade 2: 17 (22.7%); Grade 3: 9 (12.0%); and Grade 4: 7 (9.3%). Due to the small number of samples in subgroup analyses, Grade 3 and 4 cases were grouped as 'high-grade SEC (Grade 3\u0026ndash;4)' (n\u0026thinsp;=\u0026thinsp;16, 21.3%). Age was significantly higher in the SEC(+) group. The prevalence of gender, hypertension, and other comorbidities did not differ significantly between the groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\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\u003eDemographic characteristics of the study populations.\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=\"char\" char=\".\" 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\u003eSEC (\u0026minus;)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSEC (+)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;75)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.29\u0026thinsp;\u0026plusmn;\u0026thinsp;7.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.77\u0026thinsp;\u0026plusmn;\u0026thinsp;11.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale sex, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (78.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.255\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\u003e4 (19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.248\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.728\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAD, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCVD (stroke/TIA), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.679\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent smoker, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.073\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCAD, coronary artery disease; CVD, cerebrovascular disease\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e displays the differences in laboratory results between the two groups. In the comparison between SEC (\u0026minus;) and SEC (+) groups, creatinine, albumin, AST, and platelet count differed significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The SEC (+) group had higher creatinine, AST, and platelet count, whereas albumin levels were lower. All other laboratory parameters were similar between groups (p\u0026thinsp;\u0026gt;\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\u003eLaboratory findings of the study populations.\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\u003eSEC (\u0026minus;)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSEC (+)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;75)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSodium (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e138.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e139.13\u0026thinsp;\u0026plusmn;\u0026thinsp;2.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.521\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePotassium (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.119\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.73\u0026thinsp;\u0026plusmn;\u0026thinsp;2.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.03\u0026thinsp;\u0026plusmn;\u0026thinsp;5.17\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\u003eAST (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.81\u0026thinsp;\u0026plusmn;\u0026thinsp;5.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.33\u0026thinsp;\u0026plusmn;\u0026thinsp;20.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT(U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.00\u0026thinsp;\u0026plusmn;\u0026thinsp;8.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.73\u0026thinsp;\u0026plusmn;\u0026thinsp;18.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucose (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89.38\u0026thinsp;\u0026plusmn;\u0026thinsp;12.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105.96\u0026thinsp;\u0026plusmn;\u0026thinsp;38.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL cholesterol (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e105.05\u0026thinsp;\u0026plusmn;\u0026thinsp;40.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e118.40\u0026thinsp;\u0026plusmn;\u0026thinsp;32.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTriglycerides (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100.50\u0026thinsp;\u0026plusmn;\u0026thinsp;54.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e125.14\u0026thinsp;\u0026plusmn;\u0026thinsp;56.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.087\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDL cholesterol (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46.90\u0026thinsp;\u0026plusmn;\u0026thinsp;8.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.14\u0026thinsp;\u0026plusmn;\u0026thinsp;13.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.394\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.65\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.099\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count (\u0026times;10\u0026sup3;/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e215.00\u0026thinsp;\u0026plusmn;\u0026thinsp;44.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e254.13\u0026thinsp;\u0026plusmn;\u0026thinsp;71.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophils (\u0026times;10\u0026sup3;/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.06\u0026thinsp;\u0026plusmn;\u0026thinsp;2.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.11\u0026thinsp;\u0026plusmn;\u0026thinsp;1.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.926\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes (\u0026times;10\u0026sup3;/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.901\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMPV (fL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.21\u0026thinsp;\u0026plusmn;\u0026thinsp;1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.660\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal protein (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.28\u0026thinsp;\u0026plusmn;\u0026thinsp;6.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.74\u0026thinsp;\u0026plusmn;\u0026thinsp;6.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.103\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematocrit (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.93\u0026thinsp;\u0026plusmn;\u0026thinsp;4.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.59\u0026thinsp;\u0026plusmn;\u0026thinsp;3.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.514\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eAST, aspartate aminotransferase; ALT, alanine aminotransferase; LDL, low-density lipoprotein; HDL, high-density lipoprotein; MPV, mean platelet volume; SEC, spontaneous echo contrast.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the echocardiographic evaluation, the left atrial diameter, Left ventricular end-diastolic diameter, and systolic pulmonary artery pressure were higher in the SEC(+) group compared to the SEC(\u0026minus;) group, although the mitral valve area was diminished. The mean transmitral gradient, ejection fraction, and left ventricular end-systolic diameter showed no significant difference across the groups. (Table\u0026nbsp;\u003cspan refid=\"Tab3\" 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\u003eEchocardiographic Characteristics of the Patients\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\u003eSEC (\u0026minus;)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSEC (+)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;75)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLA (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;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\u003e63.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.339\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEDD (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVESD (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esPAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.52\u0026thinsp;\u0026plusmn;\u0026thinsp;9.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.32\u0026thinsp;\u0026plusmn;\u0026thinsp;18.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean TMG (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.81\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.80\u0026thinsp;\u0026plusmn;\u0026thinsp;3.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.988\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMVA (cm\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\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\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eSEC, spontaneous echo contrast; LA, left atrial diameter; LVEF, left ventricular ejection fraction; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; sPAP, systolic pulmonary artery pressure; TMG, transmitral gradient ; MVA, mitral valve area.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe MAPH score was significantly higher in the SEC(+) group compared to the SEC(\u0026minus;) group (Mann\u0026ndash;Whitney U\u0026thinsp;=\u0026thinsp;389.5, Z\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;3.676, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, r\u0026thinsp;\u0026asymp;\u0026thinsp;0.38). No significant differences in MAPH score were observed across SEC severity grades among SEC(+) patients. (Kruskal\u0026ndash;Wallis H\u0026thinsp;=\u0026thinsp;1.440, df\u0026thinsp;=\u0026thinsp;2, p\u0026thinsp;=\u0026thinsp;0.487). ROC analysis showed that MAPH discriminated the presence of SEC (AUC\u0026thinsp;=\u0026thinsp;0.753; 95% CI 0.639\u0026ndash;0.866; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In a sensitivity analysis, the predicted probability from a logistic regression model using continuous MPV, age, total protein, and hematocrit values showed similar discriminative performance (AUC\u0026thinsp;=\u0026thinsp;0.766; 95% CI 0.655\u0026ndash;0.877; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). (Fig.\u0026nbsp;1)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBased on the Youden index, the optimal cut-off value was MAPH\u0026thinsp;\u0026ge;\u0026thinsp;3, yielding a sensitivity of 56.0% and specificity of 90.5% (PPV 95.5%, NPV 36.5%). The cut-off values for MPV, age, total protein, and hematocrit were derived using the ROC\u0026ndash;Youden method. Among these parameters, only age showed significant discrimination for SEC presence (p\u0026thinsp;=\u0026thinsp;0.008), whereas MPV, total protein, and hematocrit showed no significant discrimination (p\u0026thinsp;=\u0026thinsp;0.922, p\u0026thinsp;=\u0026thinsp;0.203, and p\u0026thinsp;=\u0026thinsp;0.787). (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eROC\u0026ndash;Youden-derived cut-off values\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \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\u003eCut-off (ROC\u0026ndash;Youden)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep value\u003c/p\u003e \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\u003e\u0026ge;\u0026thinsp;46.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMPV (fL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;10.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.922\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal protein (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.203\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematocrit (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;39.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.787\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eMPV, mean platelet volume; ROC, receiver operating characteristic.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn multivariate logistic regression analysis, the MAPH score, left atrial diameter, and mitral valve area were independent predictors of SEC (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLogistic regression analyses for the presence of spontaneous echo contrast\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eVariables Univariate analysis Multivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMAPH score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.328\u0026ndash;4.338\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.047\u0026ndash;4.223\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft atrial diameter (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.074\u0026ndash;1.341\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.062\u0026ndash;1.372\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMitral valve area \u003cb\u003e(\u003c/b\u003ecm\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.648\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.501\u0026ndash;0.930\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.576\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.501\u0026ndash;0.895\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esPAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.053\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.007\u0026ndash;1.100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.958\u0026ndash;1.062\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.742\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count (\u0026times;10\u0026sup3;/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.001\u0026ndash;1.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.996\u0026ndash;1.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eOR: odds ratio (Exp(B)); CI: confidence interval; SEC, spontaneous echo contrast. Odds ratios for left atrial diameter and mitral valve area are expressed per 0.1 cm and 0.1 cm\u0026sup2;, respectively. Multivariable model: all variables listed in the table were entered simultaneously into the same model. p values were calculated using the Wald test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study investigated the correlation between the MAPH score and the presence of left atrial spontaneous echo contrast in patients with severe rheumatic mitral stenosis in sinus rhythm. To our knowledge, this relationship has not been well characterized previously. MAPH was significantly higher in patients with SEC than in those without SEC. In SEC(+) patients, MAPH showed no significant variation across severity grades. These findings indicate that MAPH may be effective at detecting the presence of SEC but less useful for differentiating between levels of SEC severity.\u003c/p\u003e \u003cp\u003eRheumatic MS remains a major public health problem in developing countries. The incidence of AF and related thromboembolic events increases in patients with MS [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Studies show that thromboembolic events occur more frequently in patients with MS than in those without MS, independent of AF [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. SEC is defined by dynamic, smoke-like echogenicity in the LA or LAA. Although LA-SEC is only occasionally detected on TTE, TEE is superior for detecting LA thrombus and SEC. Studies have also reported a higher prevalence of LA thrombus in the presence of SEC [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Sigel et al. demonstrated that SEC severity correlated positively with hematocrit and fibrinogen levels and negatively with shear stress, suggesting that SEC reflects red blood cell aggregation[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Black et al. similarly demonstrated that SEC correlated with hematocrit, fibrinogen concentration, and left atrial diameter, but showed no association with platelet count [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Fatkin et al. observed reduced LAA emptying velocity and lower shear rates in patients with AF and SEC [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. A study showed that fibrinogen and gamma-globulin levels, as well as plasma/serum viscosity, were higher in patients with SEC than in those without SEC, underscoring the role of plasma proteins in SEC pathogenesis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Rastegar et al. showed in vitro that fibrinogen-mediated erythrocyte aggregation may contribute to SEC formation. The strongest SEC occurred at fibrinogen 400\u0026ndash;500 mg/dL and hematocrit 39\u0026ndash;47%, similar to acute coronary syndrome levels [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The role of platelets in the pathophysiology of SEC remains incompletely understood, and existing findings are inconsistent. Chen et al. showed that patients with MS had higher P-selectin (CD62P) expression in the LA than in the right atrium and peripheral samples, and that this expression correlated with the severity of stenosis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Studies investigating the source of SEC directly in left atrial blood samples found that platelet and leukocyte aggregates contribute to SEC [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The correlation between platelet indices, such as MPV and SEC, is also heterogeneous in the literature, with some studies reporting a positive association and others not. Therefore, platelet activation may be a more meaningful component in terms of the prothrombotic milieu accompanying SEC and thrombus formation, rather than in the formation of SEC itself [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In summary, SEC is a complex issue that, in stasis, is linked to blood parameters such as hematocrit, fibrinogen/total protein, viscosity, and platelet activation. Routine, readily available parameters may help identify patients at a higher likelihood of SEC and related thrombus formation. The MAPH score\u0026mdash;age, MPV, hematocrit, and total protein\u0026mdash;is an accessible way to assess blood viscosity and risk of thrombosis. Previous studies have shown that the MAPH score is associated with coronary thrombus burden in patients with acute coronary syndrome and may predict high thrombus burden [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Akhan et al. showed that the MAPH score was an independent predictor of coronary slow flow [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Yurdam et al. found a negative correlation between TIMI flow grade and MAPH score [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Based on these findings, MAPH components are likely to overlap with the pathophysiology of SEC. In our investigation, the MAPH score was associated with SEC presence; however, it did not differ significantly across SEC grades among SEC-positive individuals. These findings suggest that the severity of SEC may be linked to left atrial stasis/flow dynamics, the hemodynamic effects of mitral stenosis, and blood rheology. In addition, the small number of cases with high SEC grades in our study may have reduced the statistical power to detect differences between grades. Therefore, in larger studies, especially in cohorts with sufficient numbers of Grade 3\u0026ndash;4, the relationship between the MAPH score and SEC severity levels can be more clearly evaluated. In our investigation, when the components of the MAPH score were examined individually, each parameter showed limited discriminative ability; however, the composite MAPH score was significantly associated with the presence of SEC. The fact that MAPH demonstrated substantial discrimination as a 'composite' in our data supports the theory that more than one factor related to blood flow characteristics and thrombosis tendency may be effective in the pathogenesis of SEC, rather than a single parameter. The restricted discriminability of each parameter in analyses where components are assessed separately can be attributed to the composite score more effectively encapsulating the overall effect.\u003c/p\u003e \u003cp\u003eOur echocardiographic results are also consistent with the literature. Beppu, et al. found that in individuals with MS, left atrial SEC was associated with lower cardiac output, higher LA size, and a smaller mitral valve area [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Other studies in patients with MS have found that LA SEC is associated with more severe stenosis, AF, older age, and the absence of moderate-to-severe mitral regurgitation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In our study, the LA diameter was larger, and the MVA was smaller in patients with SEC. This finding supports the prominent role of key hemodynamic factors, such as stasis and stenosis severity, in SEC. Therefore, when evaluating SEC, it may be useful to consider echocardiographic indicators alongside composite scores that reflect blood flow characteristics and thrombotic tendency.\u003c/p\u003e \u003cp\u003eOur study identified the MAPH score, LA diameter, and MVA as independent predictors of SEC in multivariate logistic regression. This suggests that the MAPH score is not merely a surrogate for echocardiographic severity markers and may provide additional information related to blood flow characteristics and thrombotic tendency associated with SEC. Conversely, SPAP and platelet count were not significant in the multivariate model, possibly due to overlap with key hemodynamic determinants or sample-related factors. Since the cutoff values were derived from our sample, it is important to confirm their generalizability to future studies across different patient populations. Additionally, finding similar discrimination to MAPH when using continuous component values supports the conclusion that our results are not solely dependent on the cutoff selection.\u003c/p\u003e \u003cp\u003eAccording to our study, MAPH can be used clinically to risk-classify patients with a high probability of SEC and to prioritize them for further evaluation, rather than as a diagnostic test on its own, especially in settings with limited access to TEE.\u003c/p\u003e\n\u003ch3\u003eStudy Limitations\u003c/h3\u003e\n\u003cp\u003eThe most important limitation of our study is the relatively small sample size. Additionally, because the study had a single-center, retrospective design, the selected patient population may not be representative of the entire mitral stenosis cohort, and the generalizability of the findings may be limited. In subgroup analyses, the small number of patients with SEC(\u0026minus;) and, especially, high-grade SEC (Grade 3\u0026ndash;4) may have reduced statistical power in group comparisons, making it difficult to detect potential differences. In addition, TEE parameters such as LAA emptying velocities, which reflect LAA function, could not be evaluated in our study. Because cutoff values were derived from the study cohort, their performance should be confirmed in independent populations.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, the MAPH score, in conjunction with echocardiographic parameters, may be a simple and practical tool for estimating the likelihood of SEC in patients with rheumatic mitral stenosis in sinus rhythm. Larger, multicenter studies validating these findings in diverse patient groups are needed before clinical application.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eMS mitral stenosis\u003c/p\u003e\n\u003cp\u003eAF atrial fibrillation\u003c/p\u003e\n\u003cp\u003eSEC spontaneous echo contrast\u003c/p\u003e\n\u003cp\u003eTEE transesophageal echocardiography\u003c/p\u003e\n\u003cp\u003eTTE transthoracic echocardiography\u003c/p\u003e\n\u003cp\u003eEDTA ethylenediaminetetraacetic acid\u003c/p\u003e\n\u003cp\u003eHb hemoglobin\u003c/p\u003e\n\u003cp\u003eMPV mean platelet volume\u003c/p\u003e\n\u003cp\u003eLVEF left ventricular ejection fraction\u003c/p\u003e\n\u003cp\u003eMVA mitral valve area\u003c/p\u003e\n\u003cp\u003eSPAP systolic pulmonary artery pressure\u003c/p\u003e\n\u003cp\u003eLA left atrium\u003c/p\u003e\n\u003cp\u003eLAA left atrial appendage\u003c/p\u003e\n\u003cp\u003eAUC area under the curve\u003c/p\u003e\n\u003cp\u003eROC receiver operating characteristic\u003c/p\u003e\n\u003cp\u003eNPV negative predictive value\u003c/p\u003e\n\u003cp\u003ePPV positive predictive value\u003c/p\u003e\n\u003cp\u003eCI confidence interval\u003c/p\u003e\n\u003cp\u003edf degrees of freedom\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Ankara Etlik City Hospital. (AEŞH-BADEK2-2025-613) The study was conducted in accordance with the principles of the Declaration of Helsinki. Patient data were anonymized prior to analysis, and the ethics committee waived the requirement for informed consent.\u0026nbsp;Clinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available due to patient confidentiality and ethical restrictions but are 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 they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eT.K.A., N.T.Ş., B.Y. and F.B. planned the research together. T.K.A., B.E., and M.A ensured the collection of data. T.K.A and F.B. performed statistical analysis of the data. All authors contributed to the writing of the article and approved the final version of the article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBlack IW, et al. Left atrial spontaneous echo contrast: a clinical and echocardiographic analysis. J Am Coll Cardiol. 1991;18(2):398\u0026ndash;404.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRittoo D, et al. A prospective study of left atrial spontaneous echo contrast and thrombus in 100 consecutive patients referred for balloon dilation of the mitral valve. J Am Soc Echocardiogr. 1994;7(5):516\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaniel WG, et al. Left atrial spontaneous echo contrast in mitral valve disease: an indicator for an increased thromboembolic risk. J Am Coll Cardiol. 1988;11(6):1204\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin C et al. Prognostic Implications of Left Atrial Spontaneous Echo Contrast with Catheter Ablation of Nonvalvular Atrial Fibrillation Patients with Left Atrial Dilation. J Cardiovasc Dev Dis, 2022. 9(9).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFatkin D, Herbert E, Feneley MP. Hematologic correlates of spontaneous echo contrast in patients with atrial fibrillation and implications for thromboembolic risk. Am J Cardiol. 1994;73(9):672\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbacioglu OO, et al. A New Score for Determining Thrombus Burden in STEMI Patients: The MAPH Score. Clin Appl Thromb Hemost. 2022;28:10760296211073767.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFatkin D, Feneley MP. Qualitative or quantitative assessment of spontaneous echo contrast? J Am Coll Cardiol. 1997;29(1):222\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNoubiap JJ, et al. Meta-Analysis of the Incidence, Prevalence, and Correlates of Atrial Fibrillation in Rheumatic Heart Disease. Glob Heart. 2020;15(1):38.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsai LM, et al. Role of transesophageal echocardiography in detecting left atrial thrombus and spontaneous echo contrast in patients with mitral valve disease or non-rheumatic atrial fibrillation. J Formos Med Assoc. 1990;89(4):270\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSigel B, et al. Red cell aggregation as a cause of blood-flow echogenicity. Radiology. 1983;148(3):799\u0026ndash;802.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSigel B, et al. Effect of plasma proteins and temperature on echogenicity of blood. Invest Radiol. 1982;17(1):29\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlack IW, et al. Hematologic correlates of left atrial spontaneous echo contrast and thromboembolism in nonvalvular atrial fibrillation. J Am Coll Cardiol. 1993;21(2):451\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFatkin D, Kelly RP, Feneley MP. Relations between left atrial appendage blood flow velocity, spontaneous echocardiographic contrast and thromboembolic risk in vivo. J Am Coll Cardiol. 1994;23(4):961\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBriley DP, et al. Spontaneous echo contrast and hemorheologic abnormalities in cerebrovascular disease. Stroke. 1994;25(8):1564\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRastegar R, et al. Spontaneous echo contrast videodensity isflow-related and is dependent on the relative concentrations of fibrinogen and red blood cells. J Am Coll Cardiol. 2003;41(4):603\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen MC, et al. Left atrial platelet activity with rheumatic mitral stenosis: correlation study of severity and platelet P-selectin expression by flow cytometry. Chest. 2003;124(5):1663\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZotz RJ, et al. Spontaneous echo contrast caused by platelet and leukocyte aggregates? Stroke. 2001;32(5):1127\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkpek M, et al. Relationship between platelet indices and spontaneous echo contrast in patients with mitral stenosis. Eur J Echocardiogr. 2011;12(11):865\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBayar N, et al. Relationship between spontaneous echo contrast and hematological markers in patients with rheumatic mitral stenosis. Int J Cardiovasc Acad. 2016;2(3):127\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGulcihan Balci K, et al. The association between mean platelet volume and spontaneous echocardiographic contrast or left atrial thrombus in patients with mitral stenosis. Anatol J Cardiol. 2016;16(11):863\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCakmak Karaaslan O, et al. The predictive value of MAPH score for determining thrombus burden in patients with non-ST segment elevation myocardial infarction. Egypt Heart J. 2022;74(1):60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkhan O, Kış M. A Novel Mean Platelet Volume-Age-Total Protein-Hematocrit (MAPH) Score for Blood Viscosity: Predictive Capabilities for Coronary Slow-Flow Phenomenon. J Updates Cardiovasc Med, 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYurdam FS, Kiş M. The relationship between TIMI flow and MAPH score in patients undergoing primary percutaneous coronary intervention for STEMI. Int Heart J. 2023;64(5):791\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeppu S, et al. Smoke-like echo in the left atrial cavity in mitral valve disease: its features and significance. J Am Coll Cardiol. 1985;6(4):744\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeung DY, et al. Resolution of left atrial spontaneous echocardiographic contrast after percutaneous mitral valvuloplasty: implications for thromboembolic risk. Am Heart J. 1995;129(1):65\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"rheumatic mitral stenosis, spontaneous echo contrast, MAPH score, blood viscosity, transesophageal echocardiography","lastPublishedDoi":"10.21203/rs.3.rs-8818290/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8818290/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eLeft atrial spontaneous echo contrast (SEC) is an echocardiographic finding in which blood\u0026mdash;normally non-contrasting\u0026mdash;appears as a swirling, smoke-like echogenic pattern. The presence of SEC in the left atrium is associated with an increased risk of thromboembolism, and this risk increases with higher SEC grades. The MAPH score has recently been defined as a simple index of whole-blood viscosity. In this study, we aimed to evaluate the relationship between the MAPH score and the presence and grade of SEC in patients with severe rheumatic mitral stenosis in sinus rhythm.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis single-center, retrospective study included 96 patients in sinus rhythm who underwent percutaneous mitral balloon valvuloplasty for severe mitral stenosis. SEC presence was assessed by transesophageal echocardiography in all patients. Patients were grouped according to SEC presence (SEC+/SEC\u0026minus;) and SEC grade. The MAPH score (age, MPV, hematocrit, total protein) was calculated for each patient.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 96 patients, 75 (78.1%) were SEC(+) and 21 (21.9%) were SEC(\u0026minus;). The MAPH score was higher in the SEC(+) group (Mann\u0026ndash;Whitney U\u0026thinsp;=\u0026thinsp;389.5; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant association was found between SEC severity and the MAPH score (Kruskal\u0026ndash;Wallis p\u0026thinsp;=\u0026thinsp;0.487). In ROC curve analysis, MAPH showed a significant ability to discriminate between SEC presence and absence (AUC\u0026thinsp;=\u0026thinsp;0.753; 95% CI 0.639\u0026ndash;0.866; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). According to the Youden index, the optimal cut-off was MAPH\u0026thinsp;\u0026ge;\u0026thinsp;3, with a sensitivity of 56.0% and a specificity of 90.5%. In multivariable analysis, the MAPH score, left atrial diameter, and mitral valve area were identified as independent predictors of SEC presence. The AUC of the model built using continuous component values was 0.766 (95% CI 0.655\u0026ndash;0.877; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe MAPH score showed significant predictive performance for SEC presence but limited ability to discriminate SEC grade.\u003c/p\u003e","manuscriptTitle":"Relationship Between Left Atrial Spontaneous Echo Contrast and the MAPH Score in Patients With Severe Rheumatic Mitral Stenosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-10 17:14:40","doi":"10.21203/rs.3.rs-8818290/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-03-24T06:21:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-20T01:24:39+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-18T07:42:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"98177612403903641943395167035385870291","date":"2026-03-17T14:31:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"323884947191327729104477885835410511710","date":"2026-03-15T13:39:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"323837229497668125168641341605924779341","date":"2026-03-08T23:34:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"187785320737888230979972005786969632174","date":"2026-03-08T16:24:25+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-05T11:00:38+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-11T13:50:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-10T04:13:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-10T04:11:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2026-02-07T22:51:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"69011529-7e7d-4c11-a374-0f4ab937f682","owner":[],"postedDate":"March 10th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-10T17:14:42+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-10 17:14:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8818290","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8818290","identity":"rs-8818290","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}