Electrocardiographic Indices Predicting Disability in Relapsing- Remitting Multiple Sclerosis: A Cross-Sectional Study

Electrocardiographic Indices Predicting Disability in Relapsing- Remitting Multiple Sclerosis: A Cross-Sectional Study | 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 Electrocardiographic Indices Predicting Disability in Relapsing- Remitting Multiple Sclerosis: A Cross-Sectional Study Çağatay Tunca, Betül Akıncıoğlu, Etkin Elifoğlu, Leyli Can Aynal, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7924456/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Multiple sclerosis (MS) is increasingly recognized as a systemic disease with cardiovascular involvement. The frontal QRS-T angle (fQRS-T) reflects repolarization heterogeneity and is linked to arrhythmic risk in various conditions; however, its role in MS remains unclear. This study aimed to compare fQRS-T and related electrocardiographic indices between patients with relapsing–remitting MS (RRMS) and healthy controls, and to examine their association with disability severity. Methods: In this retrospective, cross-sectional study, 101 RRMS patients and 51 age- and sex-matched healthy individuals were evaluated. RRMS patients were stratified by disability severity using the Expanded Disability Status Scale (EDSS <6 vs. ≥6). Resting 12-lead ECGs were assessed for QT, Tp-e, Tp-e/QTc, fQRS-T angle, and indices of cardiac electrophysiological balance (iCEB, iCEBc) by two blinded cardiologists. Statistical analyses included univariate comparisons, logistic regression, and ROC analysis. Results: RRMS patients had significantly greater fQRS-T angles and iCEBc values compared to controls (p<0.05). Within the RRMS cohort, those with EDSS ≥6 exhibited higher fQRS-T and iCEB values (p<0.01). In multivariable analysis, fQRS-T angle (OR 1.036; p=0.010) and iCEB (OR 3.544; p=0.001) independently predicted severe disability. The fQRS-T angle demonstrated moderate diagnostic performance (AUC: 0.718; cut-off 32°). Conclusion: These findings indicate that RRMS patients exhibit subclinical ECG abnormalities that correlate with disability severity, and incorporating ECG-derived metrics into clinical monitoring may aid in risk stratification of RRMS patients with high disability burden. Trial registration: Not applicable; this was a retrospective cross-sectional observational study. Multiple Sclerosis Frontal QRS-T Angle Electrocardiography Cardiac Repolarization Expanded Disability Status Scale (EDSS) Figures Figure 1 Figure 2 Introduction Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disease of the central nervous system, predominantly affecting young adults, especially women. While traditionally defined by motor, sensory, and cognitive impairments, MS is now recognized as a systemic disease with implications for cardiovascular health. Epidemiological data indicate that patients with MS have a significantly increased risk of cardiovascular events—including myocardial infarction, stroke, heart failure, and arrhythmias—compared to the general population, even after adjusting for conventional risk factors such as hypertension and dyslipidemia [1, 2]. Multiple mechanisms may contribute to this elevated cardiovascular risk, including chronic systemic inflammation, autonomic nervous system (ANS) dysfunction, physical inactivity secondary to disability, and the cardiotoxic effects of certain disease-modifying treatments [3, 4]. Autonomic dysfunction is especially notable, as demyelinating lesions in central autonomic pathways are common in MS. This dysfunction has been linked to impairments in heart rate variability (HRV), baroreflex sensitivity, and orthostatic tolerance [5]. Electrocardiography (ECG) offers a noninvasive and cost-effective method for detecting subclinical cardiac involvement in MS. Studies have identified significant alterations in P‑wave duration and dispersion, QTc interval prolongation, and reduced HRV in MS patients—parameters associated with increased arrhythmogenic risk [6, 7]. Among newer ECG markers, the frontal QRS‑T angle (fQRS‑T)—the angle between the QRS and T vectors in the frontal plane—has emerged as a powerful predictor of ventricular depolarization–repolarization heterogeneity. An increased fQRS‑T angle correlates with adverse cardiovascular outcomes and mortality in conditions such as heart failure, coronary artery disease, and chronic inflammatory diseases [8-10]. Despite this evidence, the role of fQRS‑T angle in MS remains largely unexplored. Considering the interplay between inflammation, autonomic dysfunction, and electrical instability in MS, it is plausible that fQRS‑T angle is altered in patients with MS and may correlate with disease severity. However, current data are limited. This study aims to evaluate the frontal QRS‑T angle in patients with multiple sclerosis compared to age‑ and sex‑matched healthy controls. Furthermore, we examine whether the fQRS‑T angle is associated with clinical disease severity, as assessed by the Expanded Disability Status Scale (EDSS). We hypothesize that fQRS‑T angle may serve as a simple, ECG‑based marker of subclinical cardiovascular involvement and autonomic dysfunction in MS, aiding in risk stratification and clinical monitoring. Methodology Ethical Approval and Patient Consent This study was approved by the Institutional Ethics Committee of our hospital (Approval No: AEŞH-EK-2023-609). As this was a retrospective analysis of anonymized medical records, the requirement for written informed consent was waived. Since this was not a prospective interventional study, trial registration was not required. The study was conducted in accordance with the ethical standards of the Declaration of Helsinki. Study Design and Population This retrospective, single-center, cross-sectional study was conducted between September 2022 and October 2023 at the neurology and cardiology departments of a tertiary center. The study included 102 adult patients aged between 18 and 55 years with a confirmed diagnosis of relapsing-remitting multiple sclerosis (RRMS) according to the 2017 revised McDonald criteria. All patients were in a clinically stable phase, defined as the absence of a recent relapse and no corticosteroid use in the preceding 30 days. For comparative purposes, 102 age- and sex-matched healthy individuals without any known neurological, cardiovascular, or systemic diseases were enrolled as controls. The selection and allocation of study participants are illustrated in Figure 1. All participants were in sinus rhythm and underwent resting 12-lead ECG assessment during the study period. Neurological Evaluation and EDSS Scoring Neurological examination findings and EDSS scores were retrospectively obtained from the patients' medical records corresponding to the time of ECG acquisition. The original assessments had been performed by experienced neurologists, and when available, discrepancies in EDSS scoring were resolved through documented consensus or multidisciplinary review notes. Electrocardiographic Assessment All ECGs were recorded in the supine position following a 10-minute rest using a GE MAC 2000 electrocardiograph, with a paper speed of 25 mm/s and a calibration of 10 mm/mV. Digital ECG images were analyzed manually by two independent cardiologists blinded to clinical and neurological data. For each ECG parameter, the average of three consecutive cardiac cycles was used. If the interobserver variation exceeded 5 milliseconds, the tracings were jointly reviewed to ensure consensus. The following ECG parameters were evaluated: QT interval (from the onset of the QRS complex to the end of the T wave) and corrected QT interval (QTc) using Bazett’s formula, Tpeak–Tend (Tp-e) interval measured in leads V5 or V6, Tp-e/QT and Tp-e/QTc ratios, and the frontal QRS-T angle (calculated as the absolute angular difference between the QRS and T wave axes in the frontal plane, adjusted for values exceeding 180°). Additional indices included QRS duration, R-wave peak time (RWPT), the index of cardiac electrophysiological balance (ICEB = QT/QRS), and its corrected version (ICEBc = QTc/QRS). Atrial conduction was assessed by determining maximum and minimum P-wave durations (Pmax and Pmin), and P-wave dispersion (PWD) was calculated as the difference between these values. Inclusion and Exclusion Criteria Patients were included if they were aged 18–55 years and had a confirmed diagnosis of relapsing-remitting MS. Exclusion criteria were as follows: a history of hypertension, diabetes mellitus, coronary artery disease, moderate-to-severe valvular heart disease, heart failure (ejection fraction ≤50%), congenital heart disease, pulmonary embolism, active infection, chronic inflammatory or autoimmune diseases other than MS, or the use of disease-modifying MS therapies with known arrhythmogenic potential (e.g., fingolimod, siponimod). Patients with non-sinus rhythm, bundle branch blocks, pace rhythms or arrhythmias, those using class I or III antiarrhythmic agents, or those with electrolyte disturbances (serum potassium 5.5 mmol/L, magnesium 2.4 mg/dL), end-stage renal or hepatic dysfunction, or incomplete/unreadable ECG or EDSS data were also excluded. Statistical Analyses Statistical analyses were conducted using IBM SPSS Statistics (version 22; IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD) or median with interquartile range (IQR), depending on data distribution. Categorical variables were presented as frequencies and percentages. The normality of the data was assessed using the Shapiro–Wilk test. Comparisons between the MS and control groups were made using the independent samples t-test or Mann–Whitney U test for continuous variables, and the chi-square test for categorical data. Similarly, MS patients were divided into two subgroups based on EDSS score (<6 vs. ≥6), and intergroup comparisons were performed to evaluate the association between clinical/electrocardiographic parameters and disease severity. To identify independent predictors of severe disability in MS (defined as EDSS ≥6), univariable and multivariable logistic regression analyses were conducted among MS patients. Variables that showed significance in univariable analysis were included in the multivariable model. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Additionally, receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of significant variables in predicting MS severity. The area under the curve (AUC), optimal cut-off values, sensitivity, and specificity were reported. A p-value < 0.05 was considered statistically significant for all analyses. Results The study included 101 patients diagnosed with MS and 51 age-matched healthy controls. There were no statistically significant differences between the MS and control groups in terms of demographic or basic laboratory parameters such as age, left ventricular ejection fraction (LVEF), hemoglobin, creatinine, glucose, LDL cholesterol, serum sodium, white blood cell (WBC) count, or heart rate (all p > 0.05) (Table 1). However, several electrocardiographic indices demonstrated significant differences between the groups. Specifically, the MS group showed a significantly prolonged QT interval (372.89 ± 36.88 vs. 361.44 ± 27.28 ms, p = 0.033), increased QRS duration (p = 0.045), and elevated values of the iCEB (4.35 ± 0.64 vs. 4.08 ± 0.59, p = 0.012) and its corrected form (iCEBc: 4.66 ± 0.64 vs. 4.42 ± 0.65, p = 0.031). Additionally, Tp-e interval (88.26 ± 18.99 vs. 77.40 ± 14.15 ms, p = 0.001), Tp-e/QT ratio (p = 0.004), Tp-e/QTc ratio (p = 0.002), and QRS-T angle (p = 0.024) were all significantly higher in MS patients. When the MS cohort was stratified by disability severity based on EDSS score (EDSS <6 vs. EDSS ≥6), patients in the higher disability group (EDSS ≥6, n = 20) exhibited significantly prolonged QT (401.65 ± 49.34 vs. 365.79 ± 29.40 ms, p = 0.005) and QTc intervals (420.10 ± 40.25 vs. 393.13 ± 22.33 ms, p = 0.009), as well as higher iCEB (4.82 ± 0.94 vs. 4.24 ± 0.49, p = 0.016) and iCEBc (5.04 ± 0.90 vs. 4.57 ± 0.53, p = 0.035). Tp-e interval (102.50 ± 20.03 vs. 84.75 ± 17.10 ms, p < 0.001), Tp-e/QT ratio (p = 0.035), Tp-e/QTc ratio (p = 0.014), and QRS-T angle (p = 0.003) were also significantly elevated in the EDSS ≥6 group (Table 2). To identify independent predictors of severe disability, univariable and multivariable logistic regression analyses were performed within the MS cohort. Among all parameters, iCEB (OR = 3.544, 95% CI: 1.572–7.878, p = 0.001) and QRS-T angle (OR = 1.036, 95% CI: 1.009–1.063, p = 0.010) remained statistically significant independent predictors in the multivariable model (Table 3). Finally, ROC curve analysis demonstrated that both iCEB and QRS-T angle had moderate discriminative ability for identifying severe disability in MS. The AUC for iCEB was 0.671 (cut-off: 4.37; sensitivity: 65%, specificity: 65%), while QRS-T angle showed a higher AUC of 0.718 (cut-off: 32°; sensitivity: 70%, specificity: 71%) (Table 4; Figure 2). Discussion In this study, we demonstrated that patients with RRMS exhibit significantly greater frontal QRS-T angles compared to healthy controls. Moreover, subgroup analysis showed that patients with higher disability status (EDSS ≥6) had markedly increased QRS-T angles relative to those with lower disability scores. These findings suggest that ventricular repolarization abnormalities, as reflected by the QRS-T angle, are evident in RRMS and may worsen with disease progression. The frontal QRS-T angle represents the spatial deviation between ventricular depolarization and repolarization vectors. A wider angle indicates increased repolarization heterogeneity and has been associated with electrical instability and arrhythmia risk in various cardiac conditions, including heart failure and ischemic cardiomyopathy [11, 12]. This marker has recently gained attention in neurological conditions as well. Mikkola et al. demonstrated progressive QTc prolongation in RRMS patients with a disabling disease course, suggesting impaired autonomic regulation [13]. Similarly, de Seze et al. found QTc prolongation associated with spinal cord atrophy and autonomic dysfunction in MS [14]. Our results support and expand upon these observations, showing that QRS-T angle not only differs between RRMS patients and controls, but also correlates with disability severity. The relationship between higher EDSS scores and wider QRS-T angles may reflect cumulative structural and functional damage to central autonomic control centers such as the brainstem and insular cortex, which play key roles in modulating cardiac electrophysiology [15-18]. Neuroanatomical studies and clinical imaging have shown that demyelinating lesions in these regions can disrupt autonomic outflow, leading to altered cardiac regulation and repolarization [16-18]. In addition to QRS-T angle, Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were significantly elevated in MS patients, consistent with increased transmural dispersion of repolarization—a well-recognized substrate for ventricular arrhythmogenesis [12]. Experimental and clinical studies have confirmed that prolonged Tp-e is associated with a heightened risk of life-threatening arrhythmias such as torsades de pointes, particularly in the presence of electrical heterogeneity [19, 20]. This finding may reflect not only autonomic imbalance but also inflammatory modulation of myocardial ion channels. Indeed, pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6—prominent in MS pathophysiology—have been shown to alter cardiac potassium and calcium currents, resulting in prolonged repolarization and increased electrical instability[21, 22]. Our results further showed increased iCEB and iCEBc values in RRMS patients. These indices, reflecting the ratio between repolarization (QT or QTc) and depolarization (QRS), have been proposed as integrative markers of arrhythmic risk [23]. An increased iCEB suggests an imbalance favoring excessive repolarization duration, which has been associated with higher vulnerability to both torsades de pointes and non-torsades ventricular tachyarrhythmias [23, 24]. Ozturk et al. recently confirmed that iCEBc is significantly elevated in MS patients and proposed a cutoff value of 4.65 for distinguishing RRMS from controls, showing acceptable sensitivity and specificity [24]. Multivariate regression confirmed that QRS-T angle, Tp-e interval, and iCEB were independent predictors of MS status. Moreover, ROC analysis showed that the QRS-T angle had good discriminatory power with an AUC of 0.718 and a cutoff value of 32°, supporting its potential use as a non-invasive biomarker for detecting MS-related cardiac repolarization abnormalities. These findings are especially relevant in light of emerging evidence that MS is associated with increased cardiovascular morbidity and mortality, partly due to autonomic dysfunction and potentially arrhythmogenic substrates [1, 15, 25, 26]. The underlying mechanisms are likely multifactorial. In addition to neuroinflammation and central demyelination disrupting autonomic regulation, experimental data suggest that cytokine-mediated modulation of myocardial ion channels may directly prolong cardiac action potentials and QT intervals. Cytokines such as TNF-α and IL-6 have been shown to suppress repolarizing potassium currents and alter calcium handling, thereby increasing the likelihood of early afterdepolarizations and reentrant arrhythmias [21, 22]. Furthermore, subclinical myocardial involvement in MS has been increasingly recognized. Mincu et al. demonstrated impaired myocardial function in MS patients using echocardiography, even in the absence of overt cardiovascular disease [27]. This suggests a possible inflammatory or neurogenic cardiomyopathy component. Additionally, reduced physical activity and cardiorespiratory fitness—common in patients with advanced disability—may further impair cardiac autonomic modulation and contribute to repolarization instability [28]. Our findings thus align with a growing body of evidence that suggests MS exerts both central and peripheral effects on cardiac electrophysiology. HRV studies in MS confirm decreased vagal tone and impaired baroreflex sensitivity, particularly in patients with higher lesion burden or spinal cord involvement [7, 15, 29]. Notably, relapses and disease progression have been associated with worsened autonomic markers, including QTc prolongation and reduced HRV [30-32]. Limitations Despite the strengths of our comprehensive ECG analysis, several limitations warrant consideration. First, the cross-sectional design precludes any inference of causality or the temporal evolution of repolarization changes; longitudinal follow-up would be necessary to establish whether widening QRS-T angles or other markers predict future arrhythmic events or cardiovascular outcomes in RRMS patients. Second, our cohort was drawn from a single tertiary center, which may limit generalizability—both geographically and ethnically—and introduces potential referral bias toward more severe or atypical cases. Third, although we rigorously excluded participants with overt cardiovascular disease, subclinical myocardial pathology could only be inferred indirectly; the absence of advanced imaging modalities (e.g., cardiac MRI or strain echocardiography) means we cannot definitively separate neurogenic from inflammatory-mediated cardiomyopathic changes. Fourth, we did not systematically account for all disease-modifying therapies or concurrent medications (such as anti-spasticity agents) that might influence cardiac conduction; future studies should stratify patients by treatment regimen and examine potential drug-related effects. Finally, our sample size—while comparable to prior MS repolarization studies—remains modest, particularly in the subgroup with EDSS ≥6, and may have limited our power to detect smaller effect sizes or interactions with demographic factors such as age, sex, or disease duration. Conclusion In summary, RRMS patients display significant alterations in non-invasive ECG repolarization markers—including frontal QRS-T angle, Tp–e interval, and integrative indices like iCEB—which correlate with disability severity and may reflect combined central autonomic dysfunction and peripheral myocardial modulation. These findings underscore the potential utility of routine ECG screening to identify MS patients at elevated arrhythmic risk, particularly those with high EDSS scores or symptoms of dysautonomia. Incorporating such inexpensive, widely available markers into clinical practice could facilitate early detection of cardiac involvement, guide closer monitoring during relapses or therapy initiation, and ultimately inform strategies to mitigate cardiovascular morbidity. Recent guidelines also emphasize the need for proactive cardiovascular assessment in these patients, particularly during relapses or when initiating therapies like fingolimod, which may affect cardiac conduction [33, 34]. Abbreviations MS: Multiple sclerosis RRMS: Relapsing-remitting multiple sclerosis EDSS: Expanded Disability Status Scale ECG: Electrocardiography fQRS-T: Frontal QRS-T angle QTc: Corrected QT interval Tp-e: Tpeak–Tend interval iCEB: Index of cardiac electrophysiological balance (QT/QRS) iCEBc: Corrected index of cardiac electrophysiological balance (QTc/QRS) LV EF: Left ventricular ejection fraction RWPT: R-wave peak time PWD: P-wave dispersion HRV: Heart rate variability ANS: Autonomic nervous system ROC: Receiver operating characteristic AUC: Area under the curve Declarations Ethics approval and consent to participate This study was approved by the Institutional Ethics Committee of our hospital (Approval No: AEŞH-EK-2023-609). As this was a retrospective analysis of anonymized medical records, the requirement for written informed consent was waived. Since this was not a prospective interventional study, trial registration was not required. The study was conducted in accordance with the ethical standards of the Declaration of Helsinki. Consent for publication Not applicable; this study does not include any identifiable individual data. Availability of data and materials The datasets generated and analyzed during the current study are not publicly available due to patient privacy and institutional regulations but are available from the corresponding author on reasonable request. Competing Interests The authors declare that they have no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Contributions All authors meet the authorship criteria recommended by the International Committee of Medical Journal Editors (ICMJE). Each author made substantial contributions to the study design, data acquisition, analysis, or interpretation, and participated in drafting or critically revising the manuscript for important intellectual content. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work. ÇT was responsible for the study conception and overall design. ÇT, BA, EE, LCA, AT, AS, YBŞ, VOT, BÖ, BG, and KA contributed to data collection. ÇT and AT performed the statistical analyses. ÇT drafted the manuscript. BA, EE, LCA, AS, YBŞ, VOT, BÖ, BG, and KA critically reviewed the manuscript for important intellectual content. Acknowledgments The authors thank the staff of the Cardiology and Neurology Departments of Ankara Etlik City Hospital, Ahi Evran University Training and Research Hospital, and Muğla Sıtkı Koçman University for their valuable support during the study. References Christiansen CF, Christensen S, Farkas DK, Miret M, Sørensen HT, Pedersen L. 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DOI: 10.1136/jnnp-2024-335376 Mincu RI, Magda SL, Mihaila S, Florescu M, Mihalcea DJ, Velcea A, et al. Impaired Cardiac Function in Patients with Multiple Sclerosis by Comparison with Normal Subjects. Sci Rep. 2018;8(1):3300. DOI: 10.1038/s41598-018-21599-0 Motl RW, Goldman M. Physical inactivity, neurological disability, and cardiorespiratory fitness in multiple sclerosis. Acta Neurol Scand. 2011;123(2):98-104. DOI: 10.1111/j.1600-0404.2010.01361.x Benarroch EE. The central autonomic network: functional organization, dysfunction, and perspective. Mayo Clin Proc. 1993;68(10):988-1001. DOI: 10.1016/s0025-6196(12)62272-1 Ciucurel C, Iconaru EI. The Relationship between the Frontal QRS-T Angle on ECG and Physical Activity Level in Young Adults. Int J Environ Res Public Health. 2023;20(3). DOI: 10.3390/ijerph20032411 Flachenecker P, Reiners K, Krauser M, Wolf A, Toyka KV. Autonomic dysfunction in multiple sclerosis is related to disease activity and progression of disability. Mult Scler. 2001;7(5):327-34. DOI: 10.1177/135245850100700509 Gerasimova-Meigal L, Sirenev I, Meigal A. Evidence of Autonomic Dysfunction in Patients with Relapsing-Remitting Multiple Sclerosis: Heart Rate Variability and Cardiovascular Parameters. Pathophysiology. 2021;28(1):10-9. DOI: 10.3390/pathophysiology28010002 Gunay-Polatkan S, Gullu G, Sigirli D, Koc ER, Aydinlar A, Turan OF. Index of cardiac-electrophysiological balance in relapsing-remitting multiple sclerosis patients treated with fingolimod. Mult Scler Relat Disord. 2023;76:104827. DOI: 10.1016/j.msard.2023.104827 Zavarella M, Villatore A, Rocca MA, Peretto G, Filippi M. The Heart-Brain Interplay in Multiple Sclerosis from Pathophysiology to Clinical Practice: A Narrative Review. J Cardiovasc Dev Dis. 2023;10(4). DOI: 10.3390/jcdd10040153 Tables Table 1. Clinical and Laboratory Differences Between MS and Control Groups Variable MS, N=101 Control, N=51 p-value Age, years 35.19 ± 9.12 36.64 ± 9.29 0.108 LV EF, % 61.10 ± 2.27 61.30 ± 2.27 0.625 Hb, g/dl 13.67 ± 2.29 13.37 ± 2.66 0.469 Creatinine, mg/dl 0.70 ± 0.16 0.68 ± 0.16 0.424 Glucose, mg/dl 87.36 ± 8.81 87.84 ± 10.84 0.768 LDL, mg/dl 116.20 ± 35.05 122.27 ± 37.10 0.388 Sodium,mmol/l 139.91 ± 4.24 139.86 ± 5.69 0.954 WBC, 10⁹/L 6.70 ± 2.27 6.40 ± 1.92 0.417 Heart rate, atım/dk 77.09 ± 11.80 74.25 ± 10.50 0.157 S wave max amplitüde, mV 10 (5-22) 10 (5-19) 0.605 S wave min amplitüde, mV 2.0 (1.0-8.0) 2.0 (1.0-8.0) 0.974 RS max, mV 13.65 ± 3.83 13.52 ± 3.59 0.837 R vawe pik time, msn 35.41 ± 5.15 35.40 ± 4.93 0.986 RWPT V1, msn 15 (10-45) 20 (10-45) 0.516 RWPT V4-6, msn 30 (20-45) 35 (25-45) 0.171 RWPT D3, msn 25 (10-45) 22 (10-45) 0.953 QT, msn 372.89 ± 36.88 361.44 ± 27.28 0.033 QTc, msn 398.47 ± 28.69 391.18 ± 22.30 0.089 QRS, msn 86.48 ± 9.32 90.0 ± 11.44 0.045 iCEB 4.35 ± 0.64 4.08 ± 0.59 0.012 İCEBc 4.66 ± 0.64 4.42 ± 0.65 0.031 Tp-e,msn 88.26 ± 18.99 77.40 ± 14.15 0.001 Tp-e/QT 0.23 ± 0.04 0.21 ± 0.03 0.004 Tp-e/QTc 0.22 ± 0.04 0.19 ± 0.03 0.002 PR, msn 140.02 ± 20.79 140.09 ± 21.80 0.986 RR, msn 792.68 ± 118.83 788.86 ± 127.05 0.864 P min, msn 100 (30-150) 80 (40-140) 0.141 Pmax, msn 70 (30-140) 80 (40-140) 0.158 P wave dispersion, msn 56.55 ± 14.31 56.13 ± 14.97 0.876 QRS-T angle 26 (2-106) 18 (2-65) 0.024 Abbreviations: Hb, hemoglobin; iCEB, index of cardiac electrophysiological balance; LV EF, left ventricle ejection fraction; MS, multiple sclerosis; RWPT, R wave peak time; Tp-e, T wave peak to T wave end interval; WBC, white blood cell. Table 2. Comparison Based on EDSS Scores in MS Patients Variable EDSS=6, N=20 p-value Age, years 34.66 ± 8.85 37.35 ± 10.10 0.241 EDSS 1.87 ± 1.26 6.82 ± 0.65 <0.001 LV EF, % 61.07 ± 2.30 61.25 ± 2.22 0.759 Hb, g/dl 13.73 ± 2.39 13.43 ± 1.85 0.601 Creatinine, mg/dl 0.71 ± 0.15 0.66 ± 0.17 0.219 Glucose, mg/dl 87.10 ± 8.56 88.47 ± 9.94 0.545 LDL, mg/dl 116.07 ± 34.18 116.76 ± 39.59 0.942 Sodium,mmol/l 139.65 ± 4.60 140.95 ± 2.01 0.222 WBC, 10⁹/L 6.81 ± 2.33 6.22 ± 1.67 0.293 Heart rate, atım/dk 85.69 ± 11.03 84.0 ± 13.39 0.789 S wave max amplitüde, mV 10 (5-22) 8 (5-19) 0.148 S wave min amplitüde, mV 2.0 (1.0-8.0) 2.0 (1.0-4.0) 0.471 RS max, mV 13.84 ± 3.97 12.90 ± 3.19 0.329 R vawe pik time, msn 35.82 ± 5.29 33.75 ± 4.25 0.107 RWPT V1, msn 15 (10-45) 15 (10-25) 0.520 RWPT V4-6, msn 35 (20-45) 30 (25-45) 0.596 RWPT D3, msn 25 (10-45) 20 (10-40) 0.055 QT, msn 365.79 ± 29.40 401.65 ± 49.34 0.005 QTc, msn 393.13 ± 22.33 420.10 ± 40.25 0.009 QRS, msn 86.92 ± 9.24 84.70 ± 9.65 0.341 iCEB 4.24 ± 0.49 4.82 ± 0.94 0.016 iCEBc 4.57 ± 0.53 5.04 ± 0.90 0.035 Tp-e,msn 84.75 ± 17.10 102.50 ± 20.03 <0.001 Tp-e/QT 0.23 ± 0.04 0.25 ± 0.04 0.035 Tp-e/QTc 0.21 ± 0.04 0.24 ± 0.03 0.014 PR, msn 139.52 ± 19.60 142.71 ± 27.07 0.601 RR, msn 802.98 ± 117.13 736.78 ± 116.33 0.055 P min, msn 100 (30-150) 90 (40-140) 0.993 Pmax, msn 60 (30-140) 60 (40-100) 0.746 P wave dispersion, msn 57.10 ± 14.21 53.57 ± 14.99 0.399 QRS-T angle 23 (2-95) 42.50 (4-106) 0.003 Abbreviations: EDSS, Expanded Disability Status Scale; Hb, hemoglobin; iCEB, index of cardiac electrophysiological balance; LV EF, left ventricle ejection fraction; MS, multiple sclerosis; RWPT, R wave peak time; Tp-e, T wave peak to T wave end interval; WBC, white blood cell. Table 3. Regression Analysis for Identifying Parameters Associated With Multiple Sclerosis Univariable regression Multivariable regression Variables OR (%95 CI) p-value OR (%95 CI) p-value QT, msn 1.027 (1.012-1.042) <0.001 QTc, msn 1.033 (1.014-1.053) 0.001 iCEB 3.587 (1.625-7.921) 0.002 3.544 (1.572-7.878) 0.001 iCEBc 2.971 (1.365-6.466) 0.006 Tp-e,msn 1.056 (1.023-1.090) 0.001 Tp-e/QT 1.012 (1.007-1.017) 0.040 1.002 (0.991-1.013) 0.095 Tp-e/QTc 1.016 (1.006-1.026) 0.018 QRS-T angle 1.034 (1.010-1.057) 0.004 1.036 (1.009-1.063) 0.010 Abbreviations: iCEB, Index of Cardiac Electrophysiological Balance; Tp-e, T wave peak to T wave end interval Table 4. ROC Analysis of Multipl Sclerosis Related Predictive Markers Variables AUC Cut-off p-value Sensitivity Specifity iCEB 0.671 4.37 0.018 65 65 QRS-T angle 0.718 32 0.003 70 71 Abbreviations: AUC, area under the curve; iCEB, index of cardiac electrophysiological balance; QRS-T angle, frontal QRS-T angle; ROC, receiver operating characteristic. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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07:39:46","extension":"jpeg","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":126667,"visible":true,"origin":"","legend":"","description":"","filename":"MSGRAPHICALABSTRACT.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7924456/v1/dc6b6e1fae0b33d24e511b64.jpeg"},{"id":97118470,"identity":"8160eceb-fe1f-4de0-a628-03905026ddda","added_by":"auto","created_at":"2025-12-01 07:39:46","extension":"json","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":12270,"visible":true,"origin":"","legend":"","description":"","filename":"2cf5db7c01e94b069cdc8efbac03dc68.json","url":"https://assets-eu.researchsquare.com/files/rs-7924456/v1/7c58fcd593e24e27ad191625.json"},{"id":97118468,"identity":"07d1f682-d100-4234-8a37-a8f6ce4fa9ac","added_by":"auto","created_at":"2025-12-01 07:39:46","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":35669,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of participant selection and group allocation.\u003c/p\u003e","description":"","filename":"MSFigre1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7924456/v1/9af7a5c185edd54168e07068.jpeg"},{"id":97118465,"identity":"31ca90ad-e75e-4474-a6af-7cb276829a8c","added_by":"auto","created_at":"2025-12-01 07:39:46","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":29859,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves of iCEB and QRS-T angle for predicting severe disability (EDSS ≥6).\u003c/p\u003e","description":"","filename":"MSFigre2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7924456/v1/ffbb3226b4476d43eb36c414.jpg"},{"id":98780867,"identity":"79e1ec7e-4959-4562-a0f0-37e750d4371b","added_by":"auto","created_at":"2025-12-22 12:31:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1773739,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7924456/v1/0f27de74-8b29-4dea-b5d4-c07d12840173.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eElectrocardiographic Indices Predicting Disability in Relapsing- Remitting Multiple Sclerosis: A Cross-Sectional Study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMultiple sclerosis (MS) is a chronic, immune-mediated demyelinating disease of the central nervous system, predominantly affecting young adults, especially women. While traditionally defined by motor, sensory, and cognitive impairments, MS is now recognized as a systemic disease with implications for cardiovascular health. Epidemiological data indicate that patients with MS have a significantly increased risk of cardiovascular events—including myocardial infarction, stroke, heart failure, and arrhythmias—compared to the general population, even after adjusting for conventional risk factors such as hypertension and dyslipidemia [1, 2].\u003c/p\u003e\n\u003cp\u003eMultiple mechanisms may contribute to this elevated cardiovascular risk, including chronic systemic inflammation, autonomic nervous system (ANS) dysfunction, physical inactivity secondary to disability, and the cardiotoxic effects of certain disease-modifying treatments [3, 4]. Autonomic dysfunction is especially notable, as demyelinating lesions in central autonomic pathways are common in MS. This dysfunction has been linked to impairments in heart rate variability (HRV), baroreflex sensitivity, and orthostatic tolerance [5].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eElectrocardiography (ECG) offers a noninvasive and cost-effective method for detecting subclinical cardiac involvement in MS. Studies have identified significant alterations in P‑wave duration and dispersion, QTc interval prolongation, and reduced HRV in MS patients—parameters associated with increased arrhythmogenic risk [6, 7]. \u0026nbsp;Among newer ECG markers, the frontal QRS‑T angle (fQRS‑T)—the angle between the QRS and T vectors in the frontal plane—has emerged as a powerful predictor of ventricular depolarization–repolarization heterogeneity. An increased fQRS‑T angle correlates with adverse cardiovascular outcomes and mortality in conditions such as heart failure, coronary artery disease, and chronic inflammatory diseases [8-10].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDespite this evidence, the role of fQRS‑T angle in MS remains largely unexplored. Considering the interplay between inflammation, autonomic dysfunction, and electrical instability in MS, it is plausible that fQRS‑T angle is altered in patients with MS and may correlate with disease severity. However, current data are limited.\u003c/p\u003e\n\u003cp\u003eThis study aims to evaluate the frontal QRS‑T angle in patients with multiple sclerosis compared to age‑ and sex‑matched healthy controls. Furthermore, we examine whether the fQRS‑T angle is associated with clinical disease severity, as assessed by the Expanded Disability Status Scale (EDSS). We hypothesize that fQRS‑T angle may serve as a simple, ECG‑based marker of subclinical cardiovascular involvement and autonomic dysfunction in MS, aiding in risk stratification and clinical monitoring.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval and Patient Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Ethics Committee of our hospital (Approval No: AEŞH-EK-2023-609). As this was a retrospective analysis of anonymized medical records, the requirement for written informed consent was waived. Since this was not a prospective interventional study, trial registration was not required. The study was conducted in accordance with the ethical standards of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Design and Population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective, single-center, cross-sectional study was conducted between September 2022 and October 2023 at the neurology and cardiology departments of a tertiary center. The study included 102 adult patients aged between 18 and 55 years with a confirmed diagnosis of relapsing-remitting multiple sclerosis (RRMS) according to the 2017 revised McDonald criteria. All patients were in a clinically stable phase, defined as the absence of a recent relapse and no corticosteroid use in the preceding 30 days. For comparative purposes, 102 age- and sex-matched healthy individuals without any known neurological, cardiovascular, or systemic diseases were enrolled as controls. The selection and allocation of study participants are illustrated in Figure 1. All participants were in sinus rhythm and underwent resting 12-lead ECG assessment during the study period.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNeurological Evaluation and EDSS Scoring\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNeurological examination findings and EDSS scores were retrospectively obtained from the patients' medical records corresponding to the time of ECG acquisition. The original assessments had been performed by experienced neurologists, and when available, discrepancies in EDSS scoring were resolved through documented consensus or multidisciplinary review notes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eElectrocardiographic Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll ECGs were recorded in the supine position following a 10-minute rest using a GE MAC 2000 electrocardiograph, with a paper speed of 25 mm/s and a calibration of 10 mm/mV. Digital ECG images were analyzed manually by two independent cardiologists blinded to clinical and neurological data. For each ECG parameter, the average of three consecutive cardiac cycles was used. If the interobserver variation exceeded 5 milliseconds, the tracings were jointly reviewed to ensure consensus. The following ECG parameters were evaluated: QT interval (from the onset of the QRS complex to the end of the T wave) and corrected QT interval (QTc) using Bazett’s formula, Tpeak–Tend (Tp-e) interval measured in leads V5 or V6, Tp-e/QT and Tp-e/QTc ratios, and the frontal QRS-T angle (calculated as the absolute angular difference between the QRS and T wave axes in the frontal plane, adjusted for values exceeding 180°). Additional indices included QRS duration, R-wave peak time (RWPT), the index of cardiac electrophysiological balance (ICEB = QT/QRS), and its corrected version (ICEBc = QTc/QRS). Atrial conduction was assessed by determining maximum and minimum P-wave durations (Pmax and Pmin), and P-wave dispersion (PWD) was calculated as the difference between these values.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion and Exclusion Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients were included if they were aged 18–55 years and had a confirmed diagnosis of relapsing-remitting MS. Exclusion criteria were as follows: a history of hypertension, diabetes mellitus, coronary artery disease, moderate-to-severe valvular heart disease, heart failure (ejection fraction ≤50%), congenital heart disease, pulmonary embolism, active infection, chronic inflammatory or autoimmune diseases other than MS, or the use of disease-modifying MS therapies with known arrhythmogenic potential (e.g., fingolimod, siponimod). Patients with non-sinus rhythm, bundle branch blocks, pace rhythms or arrhythmias, those using class I or III antiarrhythmic agents, or those with electrolyte disturbances (serum potassium \u0026lt;3.5 or \u0026gt;5.5 mmol/L, magnesium \u0026lt;1.6 or \u0026gt;2.4 mg/dL), end-stage renal or hepatic dysfunction, or incomplete/unreadable ECG or EDSS data were also excluded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were conducted using IBM SPSS Statistics (version 22; IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD) or median with interquartile range (IQR), depending on data distribution. Categorical variables were presented as frequencies and percentages. The normality of the data was assessed using the Shapiro–Wilk test. Comparisons between the MS and control groups were made using the independent samples t-test or Mann–Whitney U test for continuous variables, and the chi-square test for categorical data. Similarly, MS patients were divided into two subgroups based on EDSS score (\u0026lt;6 vs. ≥6), and intergroup comparisons were performed to evaluate the association between clinical/electrocardiographic parameters and disease severity. To identify independent predictors of severe disability in MS (defined as EDSS ≥6), univariable and multivariable logistic regression analyses were conducted among MS patients. Variables that showed significance in univariable analysis were included in the multivariable model. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Additionally, receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of significant variables in predicting MS severity. The area under the curve (AUC), optimal cut-off values, sensitivity, and specificity were reported. A p-value \u0026lt; 0.05 was considered statistically significant for all analyses.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe study included 101 patients diagnosed with MS and 51 age-matched healthy controls. There were no statistically significant differences between the MS and control groups in terms of demographic or basic laboratory parameters such as age, left ventricular ejection fraction (LVEF), hemoglobin, creatinine, glucose, LDL cholesterol, serum sodium, white blood cell (WBC) count, or heart rate (all p \u0026gt; 0.05) (Table 1). However, several electrocardiographic indices demonstrated significant differences between the groups.\u003c/p\u003e\n\u003cp\u003eSpecifically, the MS group showed a significantly prolonged QT interval (372.89 ± 36.88 vs. 361.44 ± 27.28 ms, p = 0.033), increased QRS duration (p = 0.045), and elevated values of the iCEB (4.35 ± 0.64 vs. 4.08 ± 0.59, p = 0.012) and its corrected form (iCEBc: 4.66 ± 0.64 vs. 4.42 ± 0.65, p = 0.031). Additionally, Tp-e interval (88.26 ± 18.99 vs. 77.40 ± 14.15 ms, p = 0.001), Tp-e/QT ratio (p = 0.004), Tp-e/QTc ratio (p = 0.002), and QRS-T angle (p = 0.024) were all significantly higher in MS patients.\u003c/p\u003e\n\u003cp\u003eWhen the MS cohort was stratified by disability severity based on EDSS score (EDSS \u0026lt;6 vs. EDSS ≥6), patients in the higher disability group (EDSS ≥6, n = 20) exhibited significantly prolonged QT (401.65 ± 49.34 vs. 365.79 ± 29.40 ms, p = 0.005) and QTc intervals (420.10 ± 40.25 vs. 393.13 ± 22.33 ms, p = 0.009), as well as higher iCEB (4.82 ± 0.94 vs. 4.24 ± 0.49, p = 0.016) and iCEBc (5.04 ± 0.90 vs. 4.57 ± 0.53, p = 0.035). Tp-e interval (102.50 ± 20.03 vs. 84.75 ± 17.10 ms, p \u0026lt; 0.001), Tp-e/QT ratio (p = 0.035), Tp-e/QTc ratio (p = 0.014), and QRS-T angle (p = 0.003) were also significantly elevated in the EDSS ≥6 group (Table 2).\u003c/p\u003e\n\u003cp\u003eTo identify independent predictors of severe disability, univariable and multivariable logistic regression analyses were performed within the MS cohort. Among all parameters, iCEB (OR = 3.544, 95% CI: 1.572–7.878, p = 0.001) and QRS-T angle (OR = 1.036, 95% CI: 1.009–1.063, p = 0.010) remained statistically significant independent predictors in the multivariable model (Table 3).\u003c/p\u003e\n\u003cp\u003eFinally, ROC curve analysis demonstrated that both iCEB and QRS-T angle had moderate discriminative ability for identifying severe disability in MS. The AUC for iCEB was 0.671 (cut-off: 4.37; sensitivity: 65%, specificity: 65%), while QRS-T angle showed a higher AUC of 0.718 (cut-off: 32°; sensitivity: 70%, specificity: 71%) (Table 4; Figure 2).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we demonstrated that patients with RRMS exhibit significantly greater frontal QRS-T angles compared to healthy controls. Moreover, subgroup analysis showed that patients with higher disability status (EDSS \u0026ge;6) had markedly increased QRS-T angles relative to those with lower disability scores. These findings suggest that ventricular repolarization abnormalities, as reflected by the QRS-T angle, are evident in RRMS and may worsen with disease progression.\u003c/p\u003e\n\u003cp\u003eThe frontal QRS-T angle represents the spatial deviation between ventricular depolarization and repolarization vectors. A wider angle indicates increased repolarization heterogeneity and has been associated with electrical instability and arrhythmia risk in various cardiac conditions, including heart failure and ischemic cardiomyopathy [11, 12]. This marker has recently gained attention in neurological conditions as well. Mikkola et al. demonstrated progressive QTc prolongation in RRMS patients with a disabling disease course, suggesting impaired autonomic regulation [13]. Similarly, de Seze et al. found QTc prolongation associated with spinal cord atrophy and autonomic dysfunction in MS [14].\u003c/p\u003e\n\u003cp\u003eOur results support and expand upon these observations, showing that QRS-T angle not only differs between RRMS patients and controls, but also correlates with disability severity. The relationship between higher EDSS scores and wider QRS-T angles may reflect cumulative structural and functional damage to central autonomic control centers such as the brainstem and insular cortex, which play key roles in modulating cardiac electrophysiology [15-18]. \u003csup\u003e\u0026nbsp;\u003c/sup\u003eNeuroanatomical studies and clinical imaging have shown that demyelinating lesions in these regions can disrupt autonomic outflow, leading to altered cardiac regulation and repolarization [16-18].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn addition to QRS-T angle, Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were significantly elevated in MS patients, consistent with increased transmural dispersion of repolarization\u0026mdash;a well-recognized substrate for ventricular arrhythmogenesis [12]. Experimental and clinical studies have confirmed that prolonged Tp-e is associated with a heightened risk of life-threatening arrhythmias such as torsades de pointes, particularly in the presence of electrical heterogeneity [19, 20].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis finding may reflect not only autonomic imbalance but also inflammatory modulation of myocardial ion channels. Indeed, pro-inflammatory cytokines such as TNF-\u0026alpha;, IL-1\u0026beta;, and IL-6\u0026mdash;prominent in MS pathophysiology\u0026mdash;have been shown to alter cardiac potassium and calcium currents, resulting in prolonged repolarization and increased electrical instability[21, 22].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur results further showed increased iCEB and iCEBc values in RRMS patients. These indices, reflecting the ratio between repolarization (QT or QTc) and depolarization (QRS), have been proposed as integrative markers of arrhythmic risk [23]. \u0026nbsp;An increased iCEB suggests an imbalance favoring excessive repolarization duration, which has been associated with higher vulnerability to both torsades de pointes and non-torsades ventricular tachyarrhythmias [23, 24]. \u0026nbsp;Ozturk et al. recently confirmed that iCEBc is significantly elevated in MS patients and proposed a cutoff value of 4.65 for distinguishing RRMS from controls, showing acceptable sensitivity and specificity [24].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMultivariate regression confirmed that QRS-T angle, Tp-e interval, and iCEB were independent predictors of MS status. Moreover, ROC analysis showed that the QRS-T angle had good discriminatory power with an AUC of 0.718 and a cutoff value of 32\u0026deg;, supporting its potential use as a non-invasive biomarker for detecting MS-related cardiac repolarization abnormalities. These findings are especially relevant in light of emerging evidence that MS is associated with increased cardiovascular morbidity and mortality, partly due to autonomic dysfunction and potentially arrhythmogenic substrates [1, 15, 25, 26].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe underlying mechanisms are likely multifactorial. In addition to neuroinflammation and central demyelination disrupting autonomic regulation, experimental data suggest that cytokine-mediated modulation of myocardial ion channels may directly prolong cardiac action potentials and QT intervals. Cytokines such as TNF-\u0026alpha; and IL-6 have been shown to suppress repolarizing potassium currents and alter calcium handling, thereby increasing the likelihood of early afterdepolarizations and reentrant arrhythmias [21, 22].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurthermore, subclinical myocardial involvement in MS has been increasingly recognized. Mincu et al. demonstrated impaired myocardial function in MS patients using echocardiography, even in the absence of overt cardiovascular disease [27]. This suggests a possible inflammatory or neurogenic cardiomyopathy component. Additionally, reduced physical activity and cardiorespiratory fitness\u0026mdash;common in patients with advanced disability\u0026mdash;may further impair cardiac autonomic modulation and contribute to repolarization instability [28].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur findings thus align with a growing body of evidence that suggests MS exerts both central and peripheral effects on cardiac electrophysiology. HRV studies in MS confirm decreased vagal tone and impaired baroreflex sensitivity, particularly in patients with higher lesion burden or spinal cord involvement [7, 15, 29]. Notably, relapses and disease progression have been associated with worsened autonomic markers, including QTc prolongation and reduced HRV [30-32].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDespite the strengths of our comprehensive ECG analysis, several limitations warrant consideration. First, the cross-sectional design precludes any inference of causality or the temporal evolution of repolarization changes; longitudinal follow-up would be necessary to establish whether widening QRS-T angles or other markers predict future arrhythmic events or cardiovascular outcomes in RRMS patients. Second, our cohort was drawn from a single tertiary center, which may limit generalizability\u0026mdash;both geographically and ethnically\u0026mdash;and introduces potential referral bias toward more severe or atypical cases. Third, although we rigorously excluded participants with overt cardiovascular disease, subclinical myocardial pathology could only be inferred indirectly; the absence of advanced imaging modalities (e.g., cardiac MRI or strain echocardiography) means we cannot definitively separate neurogenic from inflammatory-mediated cardiomyopathic changes. Fourth, we did not systematically account for all disease-modifying therapies or concurrent medications (such as anti-spasticity agents) that might influence cardiac conduction; future studies should stratify patients by treatment regimen and examine potential drug-related effects. Finally, our sample size\u0026mdash;while comparable to prior MS repolarization studies\u0026mdash;remains modest, particularly in the subgroup with EDSS \u0026ge;6, and may have limited our power to detect smaller effect sizes or interactions with demographic factors such as age, sex, or disease duration.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, RRMS patients display significant alterations in non-invasive ECG repolarization markers\u0026mdash;including frontal QRS-T angle, Tp\u0026ndash;e interval, and integrative indices like iCEB\u0026mdash;which correlate with disability severity and may reflect combined central autonomic dysfunction and peripheral myocardial modulation. These findings underscore the potential utility of routine ECG screening to identify MS patients at elevated arrhythmic risk, particularly those with high EDSS scores or symptoms of dysautonomia. Incorporating such inexpensive, widely available markers into clinical practice could facilitate early detection of cardiac involvement, guide closer monitoring during relapses or therapy initiation, and ultimately inform strategies to mitigate cardiovascular morbidity. Recent guidelines also emphasize the need for proactive cardiovascular assessment in these patients, particularly during relapses or when initiating therapies like fingolimod, which may affect cardiac conduction [33, 34].\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eMS: Multiple sclerosis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRRMS: Relapsing-remitting multiple sclerosis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEDSS:\u0026nbsp;Expanded Disability Status Scale\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eECG: Electrocardiography\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003efQRS-T: Frontal QRS-T angle\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQTc: Corrected QT interval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTp-e: Tpeak\u0026ndash;Tend interval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eiCEB:\u0026nbsp;Index of cardiac electrophysiological balance (QT/QRS)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eiCEBc: Corrected index of cardiac electrophysiological balance (QTc/QRS)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLV EF: Left ventricular ejection fraction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRWPT: R-wave peak time\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePWD:\u0026nbsp;P-wave dispersion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHRV: Heart rate variability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eANS: Autonomic nervous system\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eROC: Receiver operating characteristic\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUC: Area under the curve\u003c/strong\u003e\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 Institutional Ethics Committee of our hospital (Approval No: AEŞH-EK-2023-609). As this was a retrospective analysis of anonymized medical records, the requirement for written informed consent was waived. Since this was not a prospective interventional study, trial registration was not required. The study was conducted in accordance with the ethical standards of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable; this study does not include any identifiable individual data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available due to patient privacy and institutional regulations 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\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; All authors meet the authorship criteria recommended by the International Committee of Medical Journal Editors (ICMJE). Each author made substantial contributions to the study design, data acquisition, analysis, or interpretation, and participated in drafting or critically revising the manuscript for important intellectual content. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work. ÇT was responsible for the study conception and overall design. ÇT, BA, EE, LCA, AT, AS, YBŞ, VOT, BÖ, BG, and KA contributed to data collection. ÇT and AT performed the statistical analyses. ÇT drafted the manuscript. BA, EE, LCA, AS, YBŞ, VOT, BÖ, BG, and KA critically reviewed the manuscript for important intellectual content.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the staff of the Cardiology and Neurology Departments of Ankara Etlik City\u003c/p\u003e\n\u003cp\u003eHospital, Ahi Evran University Training and Research Hospital, and Muğla Sıtkı Koçman\u003c/p\u003e\n\u003cp\u003eUniversity for their valuable support during the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eChristiansen CF, Christensen S, Farkas DK, Miret M, S\u0026oslash;rensen HT, Pedersen L. Risk of arterial cardiovascular diseases in patients with multiple sclerosis: a population-based cohort study. Neuroepidemiology. 2010;35(4):267-74. DOI: 10.1159/000320245\u003c/li\u003e\n \u003cli\u003eMarrie RA, Reider N, Cohen J, Stuve O, Trojano M, Cutter G, et al. 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Physical inactivity, neurological disability, and cardiorespiratory fitness in multiple sclerosis. Acta Neurol Scand. 2011;123(2):98-104. DOI: 10.1111/j.1600-0404.2010.01361.x\u003c/li\u003e\n \u003cli\u003eBenarroch EE. The central autonomic network: functional organization, dysfunction, and perspective. Mayo Clin Proc. 1993;68(10):988-1001. DOI: 10.1016/s0025-6196(12)62272-1\u003c/li\u003e\n \u003cli\u003eCiucurel C, Iconaru EI. The Relationship between the Frontal QRS-T Angle on ECG and Physical Activity Level in Young Adults. Int J Environ Res Public Health. 2023;20(3). DOI: 10.3390/ijerph20032411\u003c/li\u003e\n \u003cli\u003eFlachenecker P, Reiners K, Krauser M, Wolf A, Toyka KV. Autonomic dysfunction in multiple sclerosis is related to disease activity and progression of disability. Mult Scler. 2001;7(5):327-34. DOI: 10.1177/135245850100700509\u003c/li\u003e\n \u003cli\u003eGerasimova-Meigal L, Sirenev I, Meigal A. Evidence of Autonomic Dysfunction in Patients with Relapsing-Remitting Multiple Sclerosis: Heart Rate Variability and Cardiovascular Parameters. Pathophysiology. 2021;28(1):10-9. DOI: 10.3390/pathophysiology28010002\u003c/li\u003e\n \u003cli\u003eGunay-Polatkan S, Gullu G, Sigirli D, Koc ER, Aydinlar A, Turan OF. Index of cardiac-electrophysiological balance in relapsing-remitting multiple sclerosis patients treated with fingolimod. Mult Scler Relat Disord. 2023;76:104827. DOI: 10.1016/j.msard.2023.104827\u003c/li\u003e\n \u003cli\u003eZavarella M, Villatore A, Rocca MA, Peretto G, Filippi M. The Heart-Brain Interplay in Multiple Sclerosis from Pathophysiology to Clinical Practice: A Narrative Review. J Cardiovasc Dev Dis. 2023;10(4). DOI: 10.3390/jcdd10040153\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Clinical and Laboratory Differences Between MS and Control Groups\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMS, N=101\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl, N=51\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e35.19 \u0026plusmn; 9.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e36.64 \u0026plusmn; 9.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.108\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLV EF, %\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e61.10 \u0026plusmn; 2.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e61.30 \u0026plusmn; 2.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHb, g/dl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e13.67 \u0026plusmn; 2.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e13.37 \u0026plusmn; 2.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.469\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCreatinine, mg/dl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e0.70 \u0026plusmn; 0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.68 \u0026plusmn; 0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.424\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGlucose, mg/dl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e87.36 \u0026plusmn; 8.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e87.84 \u0026plusmn; 10.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.768\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDL, mg/dl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e116.20 \u0026plusmn; 35.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e122.27 \u0026plusmn; 37.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.388\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSodium,mmol/l\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e139.91 \u0026plusmn; 4.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e139.86 \u0026plusmn; 5.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.954\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWBC, 10⁹/L\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e6.70 \u0026plusmn; 2.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e6.40 \u0026plusmn; 1.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.417\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHeart rate, atım/dk\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e77.09 \u0026plusmn; 11.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e74.25 \u0026plusmn; 10.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eS wave max amplit\u0026uuml;de, mV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e10 (5-22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e10 (5-19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.605\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eS wave min amplit\u0026uuml;de, mV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e2.0 (1.0-8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e2.0 (1.0-8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.974\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRS max, mV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e13.65 \u0026plusmn; 3.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e13.52 \u0026plusmn; 3.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.837\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR vawe pik time, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e35.41 \u0026plusmn; 5.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e35.40 \u0026plusmn; 4.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.986\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRWPT V1, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e15 (10-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e20 (10-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.516\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRWPT V4-6, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e30 (20-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e35 (25-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRWPT D3, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e25 (10-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e22 (10-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.953\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQT, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e372.89 \u0026plusmn; 36.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e361.44 \u0026plusmn; 27.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQTc, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e398.47 \u0026plusmn; 28.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e391.18 \u0026plusmn; 22.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQRS, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e86.48 \u0026plusmn; 9.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e90.0 \u0026plusmn; 11.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eiCEB\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e4.35 \u0026plusmn; 0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e4.08 \u0026plusmn; 0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eİCEBc\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e4.66 \u0026plusmn; 0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e4.42 \u0026plusmn; 0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTp-e,msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e88.26 \u0026plusmn; 18.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e77.40 \u0026plusmn; 14.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTp-e/QT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e0.23 \u0026plusmn; 0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.21 \u0026plusmn; 0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTp-e/QTc\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e0.22 \u0026plusmn; 0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.19 \u0026plusmn; 0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePR, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e140.02 \u0026plusmn; 20.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e140.09 \u0026plusmn; 21.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.986\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRR, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e792.68 \u0026plusmn; 118.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e788.86 \u0026plusmn; 127.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.864\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP min, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e100 (30-150)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e80 (40-140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.141\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePmax, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e70 (30-140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e80 (40-140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.158\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP wave dispersion, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e56.55 \u0026plusmn; 14.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e56.13 \u0026plusmn; 14.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.876\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQRS-T angle\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e26 (2-106)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e18 (2-65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviations: Hb, hemoglobin; iCEB, index of cardiac electrophysiological balance; LV EF, left ventricle ejection fraction; MS, multiple sclerosis; RWPT, R wave peak time; Tp-e, T wave peak to T wave end interval; WBC, white blood cell.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Comparison Based on EDSS Scores in MS Patients\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEDSS\u0026lt;6, N=81\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEDSS\u0026gt;=6, N=20\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e34.66 \u0026plusmn; 8.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e37.35 \u0026plusmn; 10.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.241\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEDSS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.87 \u0026plusmn; 1.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.82 \u0026plusmn; 0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLV EF, %\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e61.07 \u0026plusmn; 2.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e61.25 \u0026plusmn; 2.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.759\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHb, g/dl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13.73 \u0026plusmn; 2.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13.43 \u0026plusmn; 1.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.601\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCreatinine, mg/dl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.71 \u0026plusmn; 0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.66 \u0026plusmn; 0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.219\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGlucose, mg/dl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e87.10 \u0026plusmn; 8.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e88.47 \u0026plusmn; 9.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.545\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDL, mg/dl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e116.07 \u0026plusmn; 34.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e116.76 \u0026plusmn; 39.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.942\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSodium,mmol/l\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e139.65 \u0026plusmn; 4.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e140.95 \u0026plusmn; 2.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.222\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWBC, 10⁹/L\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.81 \u0026plusmn; 2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.22 \u0026plusmn; 1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.293\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHeart rate, atım/dk\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e85.69 \u0026plusmn; 11.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e84.0 \u0026plusmn; 13.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.789\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eS wave max amplit\u0026uuml;de, mV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10 (5-22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8 (5-19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.148\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eS wave min amplit\u0026uuml;de, mV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.0 (1.0-8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.0 (1.0-4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.471\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRS max, mV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13.84 \u0026plusmn; 3.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12.90 \u0026plusmn; 3.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.329\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eR vawe pik time, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e35.82 \u0026plusmn; 5.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e33.75 \u0026plusmn; 4.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.107\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRWPT V1, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15 (10-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15 (10-25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.520\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRWPT V4-6, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e35 (20-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30 (25-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.596\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRWPT D3, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e25 (10-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20 (10-40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eQT, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e365.79 \u0026plusmn; 29.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e401.65 \u0026plusmn; 49.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eQTc, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e393.13 \u0026plusmn; 22.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e420.10 \u0026plusmn; 40.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eQRS, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e86.92 \u0026plusmn; 9.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e84.70 \u0026plusmn; 9.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.341\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eiCEB\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.24 \u0026plusmn; 0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.82 \u0026plusmn; 0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eiCEBc\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.57 \u0026plusmn; 0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.04 \u0026plusmn; 0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTp-e,msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e84.75 \u0026plusmn; 17.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e102.50 \u0026plusmn; 20.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTp-e/QT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.23 \u0026plusmn; 0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.25 \u0026plusmn; 0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTp-e/QTc\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.21 \u0026plusmn; 0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.24 \u0026plusmn; 0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePR, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e139.52 \u0026plusmn; 19.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e142.71 \u0026plusmn; 27.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.601\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRR, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e802.98 \u0026plusmn; 117.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e736.78 \u0026plusmn; 116.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP min, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e100 (30-150)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e90 (40-140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.993\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePmax, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e60 (30-140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e60 (40-100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.746\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP wave dispersion, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e57.10 \u0026plusmn; 14.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e53.57 \u0026plusmn; 14.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.399\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eQRS-T angle\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23 (2-95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e42.50 (4-106)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviations: EDSS, Expanded Disability Status Scale; Hb, hemoglobin; iCEB, index of cardiac electrophysiological balance; LV EF, left ventricle ejection fraction; MS, multiple sclerosis; RWPT, R wave peak time; Tp-e, T wave peak to T wave end interval; WBC, white blood cell.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Regression Analysis for Identifying Parameters Associated With Multiple Sclerosis\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"623\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariable regression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 261px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariable regression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003eOR (%95 CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 185px;\"\u003e\n \u003cp\u003eOR (%95 CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQT, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e1.027 (1.012-1.042)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 185px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQTc, msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e1.033 (1.014-1.053)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 185px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eiCEB\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e3.587 (1.625-7.921)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 185px;\"\u003e\n \u003cp\u003e3.544 (1.572-7.878)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eiCEBc\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e2.971 (1.365-6.466)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 185px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTp-e,msn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e1.056 (1.023-1.090)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 185px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTp-e/QT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e1.012 (1.007-1.017)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e0.040\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 185px;\"\u003e\n \u003cp\u003e1.002 (0.991-1.013)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.095\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTp-e/QTc\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e1.016 (1.006-1.026)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 185px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQRS-T angle\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e1.034 (1.010-1.057)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 185px;\"\u003e\n \u003cp\u003e1.036 (1.009-1.063)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 623px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviations: iCEB, Index of Cardiac Electrophysiological Balance; Tp-e, T wave peak to T wave end interval\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. ROC Analysis of Multipl Sclerosis Related Predictive Markers\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAUC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCut-off\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSensitivity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpecifity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eiCEB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.671\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e4.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQRS-T angle\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.718\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 604px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviations: AUC, area under the curve; iCEB, index of cardiac electrophysiological balance; QRS-T angle, frontal QRS-T angle; ROC, receiver operating characteristic.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Multiple Sclerosis, Frontal QRS-T Angle, Electrocardiography, Cardiac Repolarization, Expanded Disability Status Scale (EDSS)","lastPublishedDoi":"10.21203/rs.3.rs-7924456/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7924456/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Multiple sclerosis (MS) is increasingly recognized as a systemic disease with cardiovascular involvement. The frontal QRS-T angle (fQRS-T) reflects repolarization heterogeneity and is linked to arrhythmic risk in various conditions; however, its role in MS remains unclear. This study aimed to compare fQRS-T and related electrocardiographic indices between patients with relapsing–remitting MS (RRMS) and healthy controls, and to examine their association with disability severity.\u003c/p\u003e\n\u003cp\u003eMethods: In this retrospective, cross-sectional study, 101 RRMS patients and 51 age- and sex-matched healthy individuals were evaluated. RRMS patients were stratified by disability severity using the Expanded Disability Status Scale (EDSS \u0026lt;6 vs. ≥6). Resting 12-lead ECGs were assessed for QT, Tp-e, Tp-e/QTc, fQRS-T angle, and indices of cardiac electrophysiological balance (iCEB, iCEBc) by two blinded cardiologists. Statistical analyses included univariate comparisons, logistic regression, and ROC analysis.\u003c/p\u003e\n\u003cp\u003eResults: RRMS patients had significantly greater fQRS-T angles and iCEBc values compared to controls (p\u0026lt;0.05). Within the RRMS cohort, those with EDSS ≥6 exhibited higher fQRS-T and iCEB values (p\u0026lt;0.01). In multivariable analysis, fQRS-T angle (OR 1.036; p=0.010) and iCEB (OR 3.544; p=0.001) independently predicted severe disability. The fQRS-T angle demonstrated moderate diagnostic performance (AUC: 0.718; cut-off 32°).\u003c/p\u003e\n\u003cp\u003eConclusion: These findings indicate that RRMS patients exhibit subclinical ECG abnormalities that correlate with disability severity, and incorporating ECG-derived metrics into clinical monitoring may aid in risk stratification of RRMS patients with high disability burden.\u003c/p\u003e\n\u003cp\u003eTrial registration: Not applicable; this was a retrospective cross-sectional observational study.\u003c/p\u003e","manuscriptTitle":"Electrocardiographic Indices Predicting Disability in Relapsing- Remitting Multiple Sclerosis: A Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-01 07:39:41","doi":"10.21203/rs.3.rs-7924456/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"816fea65-efcf-44c4-9a5c-36d4e286a644","owner":[],"postedDate":"December 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-22T10:40:05+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-01 07:39:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7924456","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7924456","identity":"rs-7924456","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}