Speckle-tracking echocardiographic assessment of cardiac function in children with refractory epilepsy receiving a ketogenic diet

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Therefore, assessment of cardiac performance in children receiving KD therapy is clinically relevant. This study aimed to assess cardiac function in children presenting with RE and receiving KD therapy using two-dimensional speckle tracking echocardiography (2D-STE) for early detection of myocardial dysfunction. METHODS This comparative observational study with cross-sectional cardiac evaluation included 105 children aged 2–10 years, divided into three equal groups: 35 children with RE receiving KD in addition to antiseizure medications (ASM), 35 children with RE receiving ASM only, and 35 healthy controls. All enrolled participants were subjected to comprehensive cardiac evaluation using electrocardiography (ECG), conventional echocardiography, TDI, and 2D-STE. Metabolic parameters, including lipid profile, blood glucose, and urinary ketones, were assessed. Seizure frequency was recorded before and after KD initiation. RESULTS evaluation of Left ventricular systolic and diastolic functions by conventional, TDI, and ECG were comparable among the three groups and remained within normal pediatric reference ranges. Global longitudinal strain (GLS) was statistically lower in KD group; however, values remained within normal limits, indicating no clinically relevant myocardial dysfunction. KD therapy resulted in significant decrease in seizure frequency, while changes in lipid profile remained within accepted pediatric reference ranges. Conclusion KD therapy in children with RE was not associated with adverse effects on cardiac structure, function, or electrical activity and was effective in achieving significant seizure reduction. These findings support the cardiac safety of KD when appropriately monitored. Ketogenic diet Pediatric epilepsy Cardiac functions Speckle tracking echocardiography Figures Figure 1 Figure 2 What is already known Ketogenic diet (KD) is an effective non-pharmacological therapy for children with refractory epilepsy. KD may be associated with metabolic changes, including alterations in lipid profile and micronutrient deficiencies, raising concerns about potential cardiovascular effects. Previous studies assessing cardiac safety of KD in children have largely relied on conventional echocardiography and electrocardiography, with limited data on subclinical myocardial function. What is new This study provides a comprehensive cardiac evaluation of children with refractory epilepsy receiving KD using advanced myocardial deformation imaging with two-dimensional speckle-tracking echocardiography. Global longitudinal strain was statistically lower in children on KD compared with controls, while remaining within normal pediatric reference ranges and without evidence of overt cardiac dysfunction. A moderate negative association between global longitudinal strain and duration of KD therapy was identified, suggesting subclinical myocardial adaptation detectable only by speckle-tracking echocardiography. Introduction Ketogenic diet therapy is an established, non-pharmacologic treatment option for pediatric refractory epilepsy (RE) (1). RE refers to failure of two adequately selected and well tolerated ASMs, either used individually or in combination, to achieve sustained seizure freedom (2). Approximately 20–30% of children with epilepsy developed refractory disease (3). ketogenic diet (KD) is a high-fat, low-carbohydrate, and adequate-protein dietary regimen that has demonstrated significant effectiveness in seizure control among children with RE (4). Despite its therapeutic benefits, KD may be associated with a number of adverse events included gastrointestinal disturbances, dyslipidemia, electrolyte imbalance, hypoglycemia, and persistent metabolic acidosis (5). Of particular concern is the potential impact of KD on cardiovascular function, largely due to dyslipidemia resulting from prolonged high-fat intake and metabolic acidosis. However, data regarding the cardiac effects of KD in children remain limited and inconsistent (6). Some studies have reported associations between KD use and left ventricular dilation and systolic dysfunction, often attributed to selenium deficiency (7). Children may be particularly vulnerable to these complications because of the ongoing development of myocardial structure and function, combined with the frequently extended duration of dietary therapy (8). Therefore, careful monitoring of cardiac status in children undergoing ketogenic therapy is essential to optimize seizure control and evaluate long-term safety. The present study aimed to evaluate cardiac effects of KD in pediatric patients diagnosed with RE through electrocardiography and echocardiography including 2D-STE. Subjects and methods This comparative observational study with cross-sectional cardiac evaluation was conducted between May 2024 and September 2025 in the Cardiology and neurology Unit, Pediatric Department, Kafrelsheikh University Hospitals in collaboration with the Clinical Nutrition Unit, Pediatric Department, Tanta University Hospitals. The study included a total of one hundred and five children aged between two and ten years, who were allocated into three equal groups (n = 35 each). Group I Included thirty-five children with RE receiving KD as part of their seizure management plan. These patients were enrolled during routine follow-up visits to their diet adherence & efficacy from the Pediatric Keto Clinical Nutrition Outpatient Clinic, Tanta University Hospitals, at least six months after initiation of KD. Group II included thirty-five children with RE managed solely with antiseizure medications (ASM) These patients were enrolled during follow-up visits to pediatric neurology outpatient clinic Kafrelsheikh University Hospitals. Group III served as the control group included thirty- five healthy age and sex matched children. Ethical approval for the study was granted by the Ethical Committee of the Faculty of Medicine, Kafr Elsheikh University (Approval No. KFSIRB200-180), and written informed consent was gained from the parents or legal guardians for all enrolled children prior to participation. All participating children with RE were diagnosed according to the International League Against Epilepsy (ILAE) criteria, guided by detailed medical history and confirmatory electroencephalographic findings. Children were included if they were within the specified age range and had a confirmed diagnosis of RE. children with congenital heart disease, chronic systemic illnesses (renal, hepatic, or metabolic disorders), or those without parental consent were excluded from participation. All children underwent detailed medical history, including their age, sex and past medical history. For Groups I and II, epilepsy-related characteristics were documented, including age at seizure onset, seizure type, duration of RE, and the numbers and type of ASM. For Group I the type and duration of KD received were recorded. Treatment response was assessed by comparing seizure frequency before and after initiation of KD. anthropometric measurements were performed including weight, height/length and their WHO Z-scores were calculated to assess growth parameters. (9) All enrolled children underwent laboratory investigations included complete blood count (CBC), renal function tests (serum creatinine and urea), and liver function [ serum albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST)], total serum calcium, phosphate and serum vitamin D and Lipid profile including total cholesterol, triglycerides, LDL and HDL. Group I also underwent periodic monitoring of urinary acetone using standard dipstick testing and random blood glucose to assess ketosis, metabolic status, and diet adherence. Electrocardiography (ECG) A standard 12-lead electrocardiogram (ECG) was performed to evaluate cardiac conduction, rhythm, and intervals, including PR and corrected QT (QTc) intervals. ECGs were performed in the resting, supine position and interpreted according to pediatric reference ranges to detect arrhythmias, conduction delays, or repolarization abnormalities. Echocardiography Comprehensive transthoracic echocardiography was done for all participants using a Philips Affiniti 50 ultrasound system (Philips Medical Systems, Andover, MA, USA) equipped with age-appropriate phased-array transducers. Examinations were conducted by experienced pediatric cardiologists, with patients studied in the left lateral decubitus position. Conventional echocardiography Standard two-dimensional, M-mode, and Doppler echocardiographic assessments were obtained regarding the guidelines of the American Society of Echocardiography for pediatric echocardiography. Left ventricular dimensions, wall thickness, and systolic function were measured using M-mode and two-dimensional imaging from parasternal long- and short-axis views. Trans mitral inflow velocities (E and A waves) were assessed using pulsed-wave Doppler from the apical four-chamber view, and the E/A ratio was calculated. All measurements were averaged over three consecutive cardiac cycles, and values were indexed to body size when appropriate. Tissue Doppler Imaging TDI was done from the apical four-chamber view by placing the sample volume at the lateral mitral annulus. Peak systolic (Sm), early diastolic (Em), and late diastolic (Am) myocardial velocities were recorded, and the Em/Am ratio was calculated. Isovolumic contraction time (IVCT) and isovolumic relaxation time (IVRT) were also measured. Two-dimensional speckle tracking echocardiography (2D-STE) High-quality two-dimensional grayscale images were acquired with optimized frame rates suitable for pediatric analysis. Offline analysis was performed to assess left ventricular myocardial deformation, including global longitudinal strain, using vendor-specific software. Care was taken to ensure adequate endocardial border delineation, and strain measurements were averaged over three cardiac cycles. All STE parameters were interpreted in relation to established pediatric reference values. Sample size calculation The sample size calculation was conducted by G*Power 3.1.9.2 (Universitat Kiel, Germany). We performed a pilot study (5 cases in each group), and we found that the mean (± SD) of GLS (the primary outcome) was 19.2 ± 1.64 in group I, 20.4 ± 1.67 in group II and 21.2 ± 2.86 in group III. The sample size was determined by the following considerations: 0.398 effect size, 95% confidence limit, 95% power of the study, group ratio 1:1:1, and three cases were added to overcome dropout. Therefore, we recruited 105 patients in this study. Statistical analysis The statistical analysis of the data was carried out using IBM SPSS software version 20.0 (Armonk, NY: IBM Corp, released 2011). Qualitative data were described using number and percentage. The Shapiro-Wilk test was used to verify the normality of distribution. Quantitative data were described using range (minimum and maximum), mean, standard deviation, median and interquartile range (IQR). Significance of the results obtained was judged at the 5% level. Chi-square test was used For categorical variables, to compare between different groups, Monte Carlo correction was used for Correction of chi-square when more than 20% of the cells have expected count less than 5, One way ANOVA test was used For normally distributed quantitative variables, to compare between more than two groups, and Post Hoc test (Tukey) was used for pairwise comparisons, Mann Whitney test was used For abnormally distributed quantitative variables, to compare between two studied groups and Kruskal Wallis test was used For abnormally distributed quantitative variables, to compare between more than two studied groups, and Post Hoc (Dunn's multiple comparisons test) for pairwise comparisons . Outcomes Primary outcome of this study was to assess the effect of KD on cardiac functions in children with refractory epilepsy, assessed through conventional echocardiography, tissue Doppler imaging, and two-dimensional speckle-tracking echocardiography. secondary outcomes included the assessment of seizure control after receiving KD, determined by the change in monthly seizure frequency compared with baseline, as well as the evaluation of the metabolic effects of KD through lipid parameters (total cholesterol, triglycerides, LDL and HDL), blood glucose concentration, and urinary acetone. Results A total of one hundred and five children were included in this study and allocated into three equal groups: Group I included thirty-five children with RE receiving KD, Group II comprised thirty-five children with RE receiving ASM only, and Group III included thirty-five healthy controls matched for age and sex. Baseline demographic and anthropometric data of the three studied groups are illustrated in Table 1 . Epileptic groups (Groups I and II) had significantly lower weight, and height/length Z-scores in comparison with healthy controls (Group III). Regarding epilepsy-related characteristics, generalized tonic–clonic seizures constituted the predominant type of seizure in both epileptic groups. The median age at seizure onset and duration of RE were comparable between epileptic groups. All children in Group II were receiving polytherapy (≥ 3 ASM) for seizure management in comparison with Group I (p < 0.001). Among children receiving KD (Group I), classic ketogenic diet was the most used regimen (71.4%), followed by modified Atkins diet (25.7%) and medium-chain triglyceride diet (2.9%). Median duration of KD therapy was 24 months (Table 1 ). Urinary acetone was positive in all children on KD, confirming effective ketosis, while blood glucose values remained within normal limits (mean 79.3 ± 4.6 mg/dL). KD therapy significantly reduced seizure frequency, with median monthly seizures decreasing from 90 to 30 (p < 0.001) (Table 1 ). Comparison of lipid profiles among the three groups is shown in Table 2 . Children receiving KD (Group I) exhibited statistically significant higher total cholesterol levels compared with the other groups; however, triglycerides, LDL, and HDL levels showed no significance among the three studied groups. Regarding laboratory parameters, hemoglobin levels differed significantly between groups (p < 0.001), with lower values observed in group II, while children on KD had hemoglobin levels comparable to healthy group. Other hematological indices, renal function tests, liver enzymes, serum albumin, calcium, phosphate, and vitamin D levels showed no significant intergroup differences, indicating preserved hepatic, renal, and metabolic profiles (Table 2 ). Electrocardiographic assessment revealed no significant differences among studied groups in PR interval or corrected QT (QTc) interval (Table 3 ). Conventional echocardiographic parameters, including left ventricular EF, FS, and mitral E/A ratio, as well as TDI parameters were comparable across groups. 2D-STE showed no significant intergroup differences in global circumferential or radial strain (GCS, GRS), whereas global longitudinal strain (GLS) was statistically lower in KD group (p < 0.001). (Table 3 ). Figure 1 shows a normal LV 2D-GLS from KD group (LV GLS = -21.1%) Spearman correlation analysis demonstrated no significant associations between global longitudinal strain (GLS) and anthropometric indices (height, weight, and BMI for age Z-scores) or lipid profile parameters (total cholesterol, triglycerides, LDL, and HDL) (all p > 0.05). In contrast, GLS showed a statistically significant negative correlation with duration of ketogenic diet therapy (rₛ = −0.451, p = 0.007) (Table 4 and Fig. 2 ). Table 1 Demographic data, Anthropometric Measurements, and Clinical characteristics of Studied Groups. Variable Group I (n = 35) Group II (n = 35) Group III (n = 35) p value Sex (Male:Female) 22: 13 18: 17 16: 19 0.343 Age (years) mean ± SD 5.69 ± 2.32 5.83 ± 2.02 5.86 ± 2.18 0.940 Height Z-score mean ± SD −1.70 ± 1.98 −2.14 ± 1.08 −0.45 ± 0.57 < 0.001* Weight Z-score mean ± SD −0.96 ± 1.71 −1.79 ± 0.95 −0.10 ± 0.40 < 0.001* BMI-for-age Z-score mean ± SD 0.27 ± 2.28 −0.59 ± 1.35 0.26 ± 0.88 0.028* Epilepsy characteristics (Group I and II) Duration of RE (years) median (IQR) 12.0 (12.0–24.0) 12.0 (12.0–24.0) — 0.843 Seizure type GTC, n (%) 21 (60.0) 19 (54.3) — 0.313 ≥ 3 antiseizure medications n (%) 22 (62.9) 35 (100) — < 0.001* KD profile group I Type of KD, n (%) Classic 25 (71.4) MAD 9 (25.7) MCT 1 (2.9) — — — Duration on KD (months) median (IQR) 24.0 (13.5–36.0) — — — Seizure frequency (per month), median (IQR) Before KD After KD 90.0 (30.0–210.0) 30.0 (5.0–90.0) — — < 0.001* KD ketogenic diet, RE refractory epilepsy, GTC generalized tonic clonic. Data are presented as mean ± SD (standard deviation), median (interquartile range, IQR), or number; N (%). * p value < 0.05 was considered statistically significant. Table 2 Lipid profile and laboratory parameters of studied groups Variable Group I (n = 35) Group II (n = 35) Group III (n = 35) p value Lipid profile Total cholesterol (mg/dl), mean ± SD 156.9 ± 34.88 129.9 ± 4.65 132.1 ± 4.51 < 0.001* Total cholesterol, median (IQR) 150 (140–163) 130 (126–132.5) 132 (129–135) — Triglycerides (mg/dl), mean ± SD 98.91 ± 30.90 95.06 ± 11.64 95.54 ± 9.70 0.546 LDL (mg/dl), mean ± SD 72.63 ± 35.81 58.40 ± 8.29 55.11 ± 9.17 0.275 HDL (mg/dl), mean ± SD 61.51 ± 8.02 60.09 ± 7.41 63.29 ± 6.10 0.077 Hematological parameters Hemoglobin (g/dl), mean ± SD 11.65 ± 0.69 10.59 ± 0.44 11.67 ± 0.70 < 0.001* Total leukocyte count (×10³/mm³), mean ± SD 6.66 ± 1.32 6.63 ± 1.25 6.74 ± 1.44 0.937 Platelets (×10³/mm³), mean ± SD 251.8 ± 49.09 249.1 ± 49.33 248.3 ± 47.75 0.952 Renal and liver function Urea (mg/dl), mean ± SD 11.23 ± 2.87 11.37 ± 2.98 11.34 ± 2.99 0.977 Creatinine (mg/dl), mean ± SD 0.49 ± 0.08 0.49 ± 0.08 0.49 ± 0.08 0.981 AST (U/L), mean ± SD 22.80 ± 5.23 22.86 ± 5.28 22.83 ± 5.12 0.999 ALT (U/L), mean ± SD 22.17 ± 5.82 22.49 ± 5.79 22.63 ± 5.54 0.943 Biochemical and metabolic parameters Serum albumin (g/dl), mean ± SD 4.14 ± 0.55 4.13 ± 0.59 4.13 ± 0.55 0.992 Serum calcium (mg/dl), mean ± SD 10.54 ± 0.72 10.60 ± 0.71 10.59 ± 0.70 0.940 Serum phosphate (mg/dl), mean ± SD 4.39 ± 0.59 4.52 ± 0.61 4.52 ± 0.66 0.606 Vitamin D (ng/ml), mean ± SD 35.60 ± 7.65 32.74 ± 8.66 34.77 ± 7.84 0.317 TG; Triglycerides, LDL; Low density lipoprotein, HDL; High density lipoprotein, ALT alanine aminotransferase, AST aspartate aminotransferase. Table 3 Electrocardiographic and Echocardiographic Characteristics of Studied Groups Parameter Group I (n = 35) Group II (n = 35) Group III (n = 35) p value ECG PR interval (ms) 148.3 ± 15.95 146.9 ± 16.63 149.3 ± 15.58 0.817 QTc interval (ms) 386.8 ± 4.71 386.7 ± 4.68 386.5 ± 4.91 0.962 TDI Em (cm/s) 12.28 ± 0.86 12.17 ± 0.91 12.20 ± 0.85 0.851 Am (cm/s) 7.02 ± 0.31 7.11 ± 0.26 7.06 ± 0.39 0.527 Em/Am ratio 1.74 ± 0.13 1.74 ± 0.13 1.75 ± 0.12 0.650 Sm (cm/s) 6.91 ± 0.68 6.87 ± 0.76 6.86 ± 0.78 0.885 IVRT (ms) 27.37 ± 1.04 27.40 ± 1.09 27.39 ± 1.18 0.996 IVCT (ms) 42.23 ± 1.24 41.70 ± 1.24 42.08 ± 1.51 0.298 Conventional ECHO FS (%) 37.86 ± 2.33 38.20 ± 2.72 38.34 ± 2.80 0.729 EF (%) 65.89 ± 3.94 66.20 ± 3.02 66.83 ± 3.65 0.531 E/A ratio 1.15 ± 0.05 1.15 ± 0.05 1.15 ± 0.05 0.963 2D STE GCS (%) 18.40 ± 3.24 19.11 ± 0.69 19.05 ± 0.66 0.442 GLS (%) 22.09 ± 0.94 22.64 ± 0.52 23.18 ± 0.47 < 0.001* GRS (%) 42.79 ± 0.96 42.61 ± 1.02 42.51 ± 1.03 0.652 QTc; corrected QT, ms; millisecond, Em; peak velocity during early ventricular diastole, Am; Late diastolic velocity, E/A = ratio between early diastolic velocity and late diastolic velocity, Sm; Systolic Velocity, IVCT; Isovolumic contraction time, IVRT; Isovolumic relaxation time, GCS; global circumferential strain, GRS; global radial strain, GLS; global longitudinal strain. Data are presented as mean ± SD Table 4 Correlation between GLS with anthropometric measurement, lipid profile and duration on KD. Group I (n = 35) GLS r s P Z-score of Height -0.004 0.982 Z-score of weight -0.084 0.633 Z-score of BMI -0.065 0.711 Total cholesterol 0.024 0.889 TG 0.021 0.905 LDL 0.144 0.409 HDL 0.248 0.151 Duration on KD (months) -0.451 0.007* r s : Spearman coefficient *: Statistically significant at p ≤ 0.05 Discussion Ketogenic diet (KD) is an established non-pharmacological therapy for children with refractory epilepsy. However, like all therapeutic strategies, KD is not free of adverse effects. Diet-related metabolic disturbances, including dyslipidemia and micronutrient deficiencies, have raised concerns regarding potential cardiovascular involvement, although available data remain limited and sometimes conflicting [ 7 , 10 , 11 , 12 ]. The principal finding of the present study is the absence of clinically significant cardiac dysfunction in children receiving KD for a median duration of 24 months. Conventional echocardiographic parameters, tissue Doppler indices, and electrocardiographic findings were comparable among children on KD, those receiving antiseizure medications alone, and healthy controls, with all values remaining within established pediatric reference ranges. These findings indicate preserved systolic and diastolic myocardial function in children receiving KD under structured medical supervision. The use of two-dimensional speckle-tracking echocardiography (STE), a sensitive modality for detecting subclinical myocardial dysfunction, strengthens these observations by providing insight into myocardial mechanics beyond conventional echocardiographic assessment [ 13 ]. Previous studies evaluating the cardiac effects of KD in children with refractory epilepsy have primarily relied on conventional echocardiography and ECG and have generally reported reassuring results. Short- and mid-term studies demonstrated preserved ventricular function, with only minor adaptive changes in diastolic indices, and long-term follow-up studies similarly confirmed preserved cardiac structure and metabolic stability [ 14 – 17 ] In the present study, speckle-tracking echocardiographic analysis demonstrated a statistically significant reduction in left ventricular global longitudinal strain (GLS) in children receiving KD, while global circumferential and radial strain parameters remained comparable across all study groups. Importantly, GLS values in the KD group remained within established pediatric reference ranges and were not accompanied by abnormalities in conventional systolic indices. These findings suggest that subtle alterations in myocardial mechanics may be detectable by STE even when conventional echocardiographic measures appear normal and are compatible with adaptive myocardial changes rather than pathological dysfunction. A moderate negative correlation was observed between GLS and duration of KD therapy; however, given the cross-sectional design and absence of baseline strain measurements, this association should be interpreted as hypothesis-generating rather than indicative of progressive myocardial impairment. From a mechanistic perspective, longitudinal myocardial fibers, predominantly located in the subendocardial layer, are particularly sensitive to metabolic and energetic alterations (18). KD induces a sustained shift in myocardial energy substrate utilization toward fatty acids and ketone bodies, which may influence myocardial contractile mechanics over prolonged periods. The absence of associations with anthropometric or lipid parameters and the preservation of circumferential and radial strain support maintained overall myocardial performance, likely through compensatory mechanisms. These findings underscore the utility of STE, particularly GLS, in detecting early myocardial functional changes during prolonged KD therapy and support the role of periodic cardiac monitoring in this population. Electrocardiographic evaluation revealed no significant differences in PR or corrected QT intervals among the studied groups, with all values within normal limits. This is consistent with previous reports demonstrating stable cardiac conduction and repolarization in children receiving KD therapy [ 19 ]. Although rare, serious cardiac complications such as QT prolongation, cardiomyopathy, and sudden cardiac death have been reported in association with KD, often related to micronutrient deficiencies, particularly selenium [ 5 , 7 ]. These observations highlight the importance of careful selection, regular monitoring of cardiac function, and appropriate micronutrient supplementation during KD therapy. Consistent with prior literature, KD was associated with sgnificant reduction in seizure frequency, with more than two-thirds of patients achieving a responder or high-responder status [ 1 , 4 , 20 ]. Regarding lipid metabolism, children on KD exhibited higher total cholesterol levels compared with other groups; however, these values remained within normal pediatric ranges and did not indicate clinically significant dyslipidemia. Similar findings have been reported previously and are generally considered adaptive metabolic changes that stabilize with ongoing dietary supervision [ 17 , 21 , 22 ]. The limitations of this study include relatively small sample size, cross-sectional design, lack of baseline cardiac assessment prior to KD initiation, and absence of systematic measurement of selenium and other micronutrient levels. Strengths include the inclusion of two epilepsy groups and a healthy control group, as well as comprehensive cardiac evaluation using ECG, conventional echocardiography, tissue Doppler imaging, and STE, allowing sensitive detection of both overt and subclinical myocardial changes. Conclusion In conclusion, KD therapy in children with RE was not associated with adverse effects on cardiac structure, function, or electrical activity ,The use of advanced echocardiographic techniques, including STE analysis provides additional reassurance regarding myocardial safety Although GLS differed significantly between groups, the observed values in KD group remained within established pediatric reference ranges, This pattern suggests the presence of subclinical longitudinal myocardial functional changes rather than overt systolic dysfunction. Declarations Statements and declarations Research funding: the authors declare that no funds, grants, or other support were received during the preparation of this research . Consent to participate : informed consent was obtained from all patient caregivers before inclusion in the study. Ethical approval :This study was conducted by the principles outlined in the Declaration of Helsinki. Ethical approval for the study was granted by the Ethical Committee of the Faculty of Medicine, Kafr Elsheikh University (Approval No. KFSIRB200-180), and written informed consent was gained from the parents or legal guardians for all enrolled children prior to participation. Data availability : The datasets generated and/or analyzed during the current study are not publicly available due to institutional and ethical restrictions but are available from the corresponding author on reasonable request. Author contributions : Hend Gamal (H.G): Patient recruitment, clinical data collection, and drafting of the initial manuscript. Amany Elbarky (A.E): Supervision of ketogenic diet implementation, nutritional monitoring, and critical revision of the manuscript. Abeer Salamah (A.S): Neurological evaluation, epilepsy classification, and antiseizure medication management. Osama Elagamy (O.E): contribution to study supervision, provided guidance on methodology and data interpretation, and assisted in critically revising the manuscript. Mohamed Abdelghafar Hussein (M.A.H): comprehensive cardiac evaluation including electrocardiography, conventional echocardiography, tissue Doppler imaging, and speckle-tracking echocardiography; interpretation of cardiac imaging data; and critical revision of the manuscript. All authors approved the final manuscript and agreed to be accountable for all aspects of the work References Henderson CB, Filloux FM, Alder SC, Lyon JL, Caplin DA (2006) Efficacy of the ketogenic diet as a treatment option for epilepsy: meta-analysis. J Child Neurol 21(3):193–198. 10.2310/7010.2006.00044 Fattorusso A, Matricardi S, Mencaroni E, Dell'Isola GB, Di Cara G, Striano P, Verrotti A (2021) The pharmacoresistant epilepsy: an overview on existent and new emerging therapies. 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Lancet Neurol 7(6):500–506. .https://doi.org/10.1016/S1474-4422(08)70092-9 Cai QY, Zhou ZJ, Luo R, Gan J, Li SP, Mu DZ, Wan CM (2017) Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies. World J Pediatr 13(6):528–536. https://doi.org/10.1007/s12519-017-0053- Kwiterovich PO Jr, Vining EP, Pyzik P, Skolasky R Jr, Freeman JM (2003) Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children. JAMA 290(7):912–920. https://doi.org/10.1001/jama.290.7.912 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 12 Apr, 2026 Reviewers invited by journal 07 Apr, 2026 Editor assigned by journal 25 Feb, 2026 Submission checks completed at journal 25 Feb, 2026 First submitted to journal 20 Feb, 2026 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8929432","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":621799913,"identity":"96a254bd-abed-40aa-8302-aa0b4b48632f","order_by":0,"name":"Hend Gamal","email":"","orcid":"","institution":"Kafrelsheikh University","correspondingAuthor":false,"prefix":"","firstName":"Hend","middleName":"","lastName":"Gamal","suffix":""},{"id":621799914,"identity":"ed853dc9-1dd8-4980-8e1a-f9e0f2466960","order_by":1,"name":"Amany Elbarky","email":"","orcid":"","institution":"Tanta University","correspondingAuthor":false,"prefix":"","firstName":"Amany","middleName":"","lastName":"Elbarky","suffix":""},{"id":621799915,"identity":"c9bbbeae-88d9-4bba-b051-09f92f850910","order_by":2,"name":"Abeer Salamah","email":"","orcid":"","institution":"Kafrelsheikh University","correspondingAuthor":false,"prefix":"","firstName":"Abeer","middleName":"","lastName":"Salamah","suffix":""},{"id":621799916,"identity":"0c7da62c-b4b4-4b49-b0d4-a4009e4ef06d","order_by":3,"name":"Osama Elagamy","email":"","orcid":"","institution":"Kafrelsheikh University","correspondingAuthor":false,"prefix":"","firstName":"Osama","middleName":"","lastName":"Elagamy","suffix":""},{"id":621799917,"identity":"faf66c08-1895-498a-b504-95a1e4f97528","order_by":4,"name":"Mohamed Abdelghafar Hussein","email":"data:image/png;base64,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","orcid":"","institution":"Kafrelsheikh University","correspondingAuthor":true,"prefix":"","firstName":"Mohamed","middleName":"Abdelghafar","lastName":"Hussein","suffix":""}],"badges":[],"createdAt":"2026-02-20 22:53:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8929432/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8929432/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107042853,"identity":"28113822-f818-43cf-80db-25bae77c0f3b","added_by":"auto","created_at":"2026-04-16 06:43:34","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":113644,"visible":true,"origin":"","legend":"\u003cp\u003eLeft ventricular longitudinal deformation analysis obtained from the apical four-chamber view demonstrates preserved myocardial mechanics. The peak endocardial longitudinal strain is −21.1%.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8929432/v1/d1c48868aaa789fbfde21768.jpeg"},{"id":107481008,"identity":"aad0ded0-6cb5-46ef-ad7d-7616688bc7ad","added_by":"auto","created_at":"2026-04-22 02:15:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":72750,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCorrelation between GLS with duration on KD in Group I (n = 35)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8929432/v1/3f448817fbf7186145738eaf.png"},{"id":107483407,"identity":"b8df7bb0-56d2-45c1-946f-f6017dd48c3a","added_by":"auto","created_at":"2026-04-22 02:27:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":820017,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8929432/v1/4a4f87e8-6f24-402b-be13-281f59296d2f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Speckle-tracking echocardiographic assessment of cardiac function in children with refractory epilepsy receiving a ketogenic diet","fulltext":[{"header":"What is already known","content":"\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u0026nbsp;Ketogenic diet (KD) is an effective non-pharmacological therapy for children with refractory epilepsy.\u003c/li\u003e\n \u003cli\u003eKD may be associated with metabolic changes, including alterations in lipid profile and micronutrient deficiencies, raising concerns about potential cardiovascular effects.\u003c/li\u003e\n \u003cli\u003ePrevious studies assessing cardiac safety of KD in children have largely relied on conventional echocardiography and electrocardiography, with limited data on subclinical myocardial function.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is new\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eThis study provides a comprehensive cardiac evaluation of children with refractory epilepsy receiving KD using advanced myocardial deformation imaging with two-dimensional speckle-tracking echocardiography.\u003c/li\u003e\n \u003cli\u003eGlobal longitudinal strain was statistically lower in children on KD compared with controls, while remaining within normal pediatric reference ranges and without evidence of overt cardiac dysfunction.\u003c/li\u003e\n \u003cli\u003eA moderate negative association between global longitudinal strain and duration of KD therapy was identified, suggesting subclinical myocardial adaptation detectable only by speckle-tracking echocardiography.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eKetogenic diet therapy is an established, non-pharmacologic treatment option for pediatric refractory epilepsy (RE) (1). RE refers to failure of two adequately selected and well tolerated ASMs, either used individually or in combination, to achieve sustained seizure freedom (2). Approximately 20\u0026ndash;30% of children with epilepsy developed refractory disease (3).\u003c/p\u003e \u003cp\u003eketogenic diet (KD) is a high-fat, low-carbohydrate, and adequate-protein dietary regimen that has demonstrated significant effectiveness in seizure control among children with RE (4). Despite its therapeutic benefits, KD may be associated with a number of adverse events included gastrointestinal disturbances, dyslipidemia, electrolyte imbalance, hypoglycemia, and persistent metabolic acidosis (5).\u003c/p\u003e \u003cp\u003eOf particular concern is the potential impact of KD on cardiovascular function, largely due to dyslipidemia resulting from prolonged high-fat intake and metabolic acidosis. However, data regarding the cardiac effects of KD in children remain limited and inconsistent (6). Some studies have reported associations between KD use and left ventricular dilation and systolic dysfunction, often attributed to selenium deficiency (7). Children may be particularly vulnerable to these complications because of the ongoing development of myocardial structure and function, combined with the frequently extended duration of dietary therapy (8). Therefore, careful monitoring of cardiac status in children undergoing ketogenic therapy is essential to optimize seizure control and evaluate long-term safety.\u003c/p\u003e \u003cp\u003eThe present study aimed to evaluate cardiac effects of KD in pediatric patients diagnosed with RE through electrocardiography and echocardiography including 2D-STE.\u003c/p\u003e"},{"header":"Subjects and methods","content":"\u003cp\u003eThis comparative observational study with cross-sectional cardiac evaluation was conducted between May 2024 and September 2025 in the Cardiology and neurology Unit, Pediatric Department, Kafrelsheikh University Hospitals in collaboration with the Clinical Nutrition Unit, Pediatric Department, Tanta University Hospitals. The study included a total of one hundred and five children aged between two and ten years, who were allocated into three equal groups (n\u0026thinsp;=\u0026thinsp;35 each).\u003c/p\u003e \u003cp\u003e \u003cb\u003eGroup I\u003c/b\u003e Included thirty-five children with RE receiving KD as part of their seizure management plan. These patients were enrolled during routine follow-up visits to their diet adherence \u0026amp; efficacy from the Pediatric Keto Clinical Nutrition Outpatient Clinic, Tanta University Hospitals, at least six months after initiation of KD.\u003c/p\u003e \u003cp\u003e\u003cb\u003eGroup II\u003c/b\u003e included thirty-five children with RE managed solely with antiseizure medications (ASM) These patients were enrolled during follow-up visits to pediatric neurology outpatient clinic Kafrelsheikh University Hospitals. \u003cb\u003eGroup III\u003c/b\u003e served as the control group included thirty- five healthy age and sex matched children. Ethical approval for the study was granted by the Ethical Committee of the Faculty of Medicine, Kafr Elsheikh University (Approval No. KFSIRB200-180), and written informed consent was gained from the parents or legal guardians for all enrolled children prior to participation.\u003c/p\u003e \u003cp\u003e All participating children with RE were diagnosed according to the International League Against Epilepsy (ILAE) criteria, guided by detailed medical history and confirmatory electroencephalographic findings. Children were included if they were within the specified age range and had a confirmed diagnosis of RE. children with congenital heart disease, chronic systemic illnesses (renal, hepatic, or metabolic disorders), or those without parental consent were excluded from participation.\u003c/p\u003e \u003cp\u003eAll children underwent detailed medical history, including their age, sex and past medical history. For Groups I and II, epilepsy-related characteristics were documented, including age at seizure onset, seizure type, duration of RE, and the numbers and type of ASM. For Group I the type and duration of KD received were recorded. Treatment response was assessed by comparing seizure frequency before and after initiation of KD. anthropometric measurements were performed including weight, height/length and their WHO Z-scores were calculated to assess growth parameters. (9)\u003c/p\u003e \u003cp\u003eAll enrolled children underwent laboratory investigations included complete blood count (CBC), renal function tests (serum creatinine and urea), and liver function [ serum albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST)], total serum calcium, phosphate and serum vitamin D and Lipid profile including total cholesterol, triglycerides, LDL and HDL. Group I also underwent periodic monitoring of urinary acetone using standard dipstick testing and random blood glucose to assess ketosis, metabolic status, and diet adherence.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eElectrocardiography (ECG)\u003c/h2\u003e \u003cp\u003eA standard 12-lead electrocardiogram (ECG) was performed to evaluate cardiac conduction, rhythm, and intervals, including PR and corrected QT (QTc) intervals. ECGs were performed in the resting, supine position and interpreted according to pediatric reference ranges to detect arrhythmias, conduction delays, or repolarization abnormalities.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEchocardiography\u003c/strong\u003e \u003cp\u003eComprehensive transthoracic echocardiography was done for all participants using a Philips Affiniti 50 ultrasound system (Philips Medical Systems, Andover, MA, USA) equipped with age-appropriate phased-array transducers. Examinations were conducted by experienced pediatric cardiologists, with patients studied in the left lateral decubitus position.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eConventional echocardiography\u003c/h3\u003e\n\u003cp\u003e Standard two-dimensional, M-mode, and Doppler echocardiographic assessments were obtained regarding the guidelines of the American Society of Echocardiography for pediatric echocardiography. Left ventricular dimensions, wall thickness, and systolic function were measured using M-mode and two-dimensional imaging from parasternal long- and short-axis views. Trans mitral inflow velocities (E and A waves) were assessed using pulsed-wave Doppler from the apical four-chamber view, and the E/A ratio was calculated. All measurements were averaged over three consecutive cardiac cycles, and values were indexed to body size when appropriate.\u003c/p\u003e\n\u003ch3\u003eTissue Doppler Imaging\u003c/h3\u003e\n\u003cp\u003eTDI was done from the apical four-chamber view by placing the sample volume at the lateral mitral annulus. Peak systolic (Sm), early diastolic (Em), and late diastolic (Am) myocardial velocities were recorded, and the Em/Am ratio was calculated. Isovolumic contraction time (IVCT) and isovolumic relaxation time (IVRT) were also measured.\u003c/p\u003e\n\u003ch3\u003eTwo-dimensional speckle tracking echocardiography (2D-STE)\u003c/h3\u003e\n\u003cp\u003eHigh-quality two-dimensional grayscale images were acquired with optimized frame rates suitable for pediatric analysis. Offline analysis was performed to assess left ventricular myocardial deformation, including global longitudinal strain, using vendor-specific software. Care was taken to ensure adequate endocardial border delineation, and strain measurements were averaged over three cardiac cycles. All STE parameters were interpreted in relation to established pediatric reference values.\u003c/p\u003e\n\u003ch3\u003eSample size calculation\u003c/h3\u003e\n\u003cp\u003eThe sample size calculation was conducted by G*Power 3.1.9.2 (Universitat Kiel, Germany). We performed a pilot study (5 cases in each group), and we found that the mean (\u0026plusmn;\u0026thinsp;SD) of GLS (the primary outcome) was 19.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.64 in group I, 20.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.67 in group II and 21.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.86 in group III. The sample size was determined by the following considerations: 0.398 effect size, 95% confidence limit, 95% power of the study, group ratio 1:1:1, and three cases were added to overcome dropout. Therefore, we recruited 105 patients in this study.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe statistical analysis of the data was carried out using IBM SPSS software version 20.0 (Armonk, NY: IBM Corp, released 2011). Qualitative data were described using number and percentage. The Shapiro-Wilk test was used to verify the normality of distribution. Quantitative data were described using range (minimum and maximum), mean, standard deviation, median and interquartile range (IQR). Significance of the results obtained was judged at the 5% level.\u003c/p\u003e \u003cp\u003eChi-square test was used For categorical variables, to compare between different groups, Monte Carlo correction was used for Correction of chi-square when more than 20% of the cells have expected count less than 5, One way ANOVA test was used For normally distributed quantitative variables, to compare between more than two groups, and Post Hoc test (Tukey) was used for pairwise comparisons, Mann Whitney test was used For abnormally distributed quantitative variables, to compare between two studied groups and Kruskal Wallis test was used For abnormally distributed quantitative variables, to compare between more than two studied groups, and Post Hoc (Dunn's multiple comparisons test) for pairwise comparisons .\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003ePrimary outcome of this study was to assess the effect of KD on cardiac functions in children with refractory epilepsy, assessed through conventional echocardiography, tissue Doppler imaging, and two-dimensional speckle-tracking echocardiography. secondary outcomes included the assessment of seizure control after receiving KD, determined by the change in monthly seizure frequency compared with baseline, as well as the evaluation of the metabolic effects of KD through lipid parameters (total cholesterol, triglycerides, LDL and HDL), blood glucose concentration, and urinary acetone.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of one hundred and five children were included in this study and allocated into three equal groups: Group I included thirty-five children with RE receiving KD, Group II comprised thirty-five children with RE receiving ASM only, and Group III included thirty-five healthy controls matched for age and sex. Baseline demographic and anthropometric data of the three studied groups are illustrated in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Epileptic groups (Groups I and II) had significantly lower weight, and height/length Z-scores in comparison with healthy controls (Group III).\u003c/p\u003e \u003cp\u003eRegarding epilepsy-related characteristics, generalized tonic\u0026ndash;clonic seizures constituted the predominant type of seizure in both epileptic groups. The median age at seizure onset and duration of RE were comparable between epileptic groups. All children in Group II were receiving polytherapy (\u0026ge;\u0026thinsp;3 ASM) for seizure management in comparison with Group I (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eAmong children receiving KD (Group I), classic ketogenic diet was the most used regimen (71.4%), followed by modified Atkins diet (25.7%) and medium-chain triglyceride diet (2.9%). Median duration of KD therapy was 24 months (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Urinary acetone was positive in all children on KD, confirming effective ketosis, while blood glucose values remained within normal limits (mean 79.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6 mg/dL). KD therapy significantly reduced seizure frequency, with median monthly seizures decreasing from 90 to 30 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eComparison of lipid profiles among the three groups is shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Children receiving KD (Group I) exhibited statistically significant higher total cholesterol levels compared with the other groups; however, triglycerides, LDL, and HDL levels showed no significance among the three studied groups. Regarding laboratory parameters, hemoglobin levels differed significantly between groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with lower values observed in group II, while children on KD had hemoglobin levels comparable to healthy group. Other hematological indices, renal function tests, liver enzymes, serum albumin, calcium, phosphate, and vitamin D levels showed no significant intergroup differences, indicating preserved hepatic, renal, and metabolic profiles (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eElectrocardiographic assessment revealed no significant differences among studied groups in PR interval or corrected QT (QTc) interval (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Conventional echocardiographic parameters, including left ventricular EF, FS, and mitral E/A ratio, as well as TDI parameters were comparable across groups. 2D-STE showed no significant intergroup differences in global circumferential or radial strain (GCS, GRS), whereas global longitudinal strain (GLS) was statistically lower in KD group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows a normal LV 2D-GLS from KD group (LV GLS = -21.1%)\u003c/p\u003e \u003cp\u003eSpearman correlation analysis demonstrated no significant associations between global longitudinal strain (GLS) and anthropometric indices (height, weight, and BMI for age Z-scores) or lipid profile parameters (total cholesterol, triglycerides, LDL, and HDL) (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In contrast, GLS showed a statistically significant negative correlation with duration of ketogenic diet therapy (rₛ = \u0026minus;0.451, p\u0026thinsp;=\u0026thinsp;0.007) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic data, Anthropometric Measurements, and Clinical characteristics of Studied Groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup I\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup II\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup III\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003cp\u003e(Male:Female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22: 13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18: 17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16: 19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.343\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.69\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.86\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.940\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight Z-score\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;1.70\u0026thinsp;\u0026plusmn;\u0026thinsp;1.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;2.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight Z-score\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;0.96\u0026thinsp;\u0026plusmn;\u0026thinsp;1.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;1.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;0.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI-for-age Z-score\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;2.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;0.59\u0026thinsp;\u0026plusmn;\u0026thinsp;1.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.028*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEpilepsy characteristics\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(Group I and II)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of RE (years)\u003c/p\u003e \u003cp\u003emedian\u003c/p\u003e \u003cp\u003e(IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.0\u003c/p\u003e \u003cp\u003e(12.0\u0026ndash;24.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.0\u003c/p\u003e \u003cp\u003e(12.0\u0026ndash;24.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.843\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeizure type GTC,\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (54.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.313\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;3 antiseizure medications\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (62.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eKD profile group I\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of KD, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eClassic 25 (71.4)\u003c/p\u003e \u003cp\u003eMAD 9 (25.7)\u003c/p\u003e \u003cp\u003eMCT 1 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration on KD (months)\u003c/p\u003e \u003cp\u003emedian\u003c/p\u003e \u003cp\u003e(IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.0\u003c/p\u003e \u003cp\u003e(13.5\u0026ndash;36.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeizure frequency (per month),\u003c/p\u003e \u003cp\u003emedian (IQR)\u003c/p\u003e \u003cp\u003eBefore KD\u003c/p\u003e \u003cp\u003eAfter KD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90.0 (30.0\u0026ndash;210.0)\u003c/p\u003e \u003cp\u003e30.0 (5.0\u0026ndash;90.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eKD ketogenic diet, RE refractory epilepsy, GTC generalized tonic clonic.\u003c/p\u003e \u003cp\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (standard deviation), median (interquartile range, IQR), or number; N (%). \u003cb\u003e*\u003c/b\u003ep value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLipid profile and laboratory parameters of studied groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup I\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup II\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup III\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLipid profile\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal cholesterol (mg/dl),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e156.9\u0026thinsp;\u0026plusmn;\u0026thinsp;34.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e129.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e132.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal cholesterol,\u003c/p\u003e \u003cp\u003emedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150 (140\u0026ndash;163)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130 (126\u0026ndash;132.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e132 (129\u0026ndash;135)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTriglycerides (mg/dl),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98.91\u0026thinsp;\u0026plusmn;\u0026thinsp;30.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.06\u0026thinsp;\u0026plusmn;\u0026thinsp;11.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95.54\u0026thinsp;\u0026plusmn;\u0026thinsp;9.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.546\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL (mg/dl),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72.63\u0026thinsp;\u0026plusmn;\u0026thinsp;35.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.40\u0026thinsp;\u0026plusmn;\u0026thinsp;8.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55.11\u0026thinsp;\u0026plusmn;\u0026thinsp;9.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.275\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDL (mg/dl),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.51\u0026thinsp;\u0026plusmn;\u0026thinsp;8.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.09\u0026thinsp;\u0026plusmn;\u0026thinsp;7.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.29\u0026thinsp;\u0026plusmn;\u0026thinsp;6.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.077\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eHematological parameters\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/dl),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal leukocyte count (\u0026times;10\u0026sup3;/mm\u0026sup3;),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.66\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.937\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets (\u0026times;10\u0026sup3;/mm\u0026sup3;), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e251.8\u0026thinsp;\u0026plusmn;\u0026thinsp;49.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e249.1\u0026thinsp;\u0026plusmn;\u0026thinsp;49.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e248.3\u0026thinsp;\u0026plusmn;\u0026thinsp;47.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.952\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRenal and liver function\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrea (mg/dl),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.23\u0026thinsp;\u0026plusmn;\u0026thinsp;2.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.37\u0026thinsp;\u0026plusmn;\u0026thinsp;2.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.34\u0026thinsp;\u0026plusmn;\u0026thinsp;2.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.977\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine (mg/dl),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.981\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST (U/L),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.80\u0026thinsp;\u0026plusmn;\u0026thinsp;5.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.86\u0026thinsp;\u0026plusmn;\u0026thinsp;5.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.83\u0026thinsp;\u0026plusmn;\u0026thinsp;5.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (U/L),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.17\u0026thinsp;\u0026plusmn;\u0026thinsp;5.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.49\u0026thinsp;\u0026plusmn;\u0026thinsp;5.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.63\u0026thinsp;\u0026plusmn;\u0026thinsp;5.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.943\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBiochemical and metabolic parameters\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum albumin (g/dl),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.992\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum calcium (mg/dl),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.940\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum phosphate (mg/dl),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.606\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D (ng/ml),\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.60\u0026thinsp;\u0026plusmn;\u0026thinsp;7.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.74\u0026thinsp;\u0026plusmn;\u0026thinsp;8.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.77\u0026thinsp;\u0026plusmn;\u0026thinsp;7.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.317\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTG; Triglycerides, LDL; Low density lipoprotein, HDL; High density lipoprotein, ALT alanine aminotransferase, AST aspartate aminotransferase.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eElectrocardiographic and Echocardiographic Characteristics of Studied Groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup I\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup II\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup III\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eECG\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePR interval (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e148.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e146.9\u0026thinsp;\u0026plusmn;\u0026thinsp;16.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e149.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.817\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQTc interval (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e386.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e386.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e386.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.962\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTDI\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEm (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.851\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAm (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.527\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEm/Am ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.650\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSm (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.885\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVRT (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.37\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.40\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.39\u0026thinsp;\u0026plusmn;\u0026thinsp;1.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.996\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVCT (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.23\u0026thinsp;\u0026plusmn;\u0026thinsp;1.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.70\u0026thinsp;\u0026plusmn;\u0026thinsp;1.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.298\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eConventional ECHO\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.86\u0026thinsp;\u0026plusmn;\u0026thinsp;2.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.20\u0026thinsp;\u0026plusmn;\u0026thinsp;2.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.34\u0026thinsp;\u0026plusmn;\u0026thinsp;2.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.729\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEF (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.89\u0026thinsp;\u0026plusmn;\u0026thinsp;3.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.20\u0026thinsp;\u0026plusmn;\u0026thinsp;3.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66.83\u0026thinsp;\u0026plusmn;\u0026thinsp;3.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.531\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE/A ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.963\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2D STE\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.40\u0026thinsp;\u0026plusmn;\u0026thinsp;3.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.442\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGLS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGRS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42.51\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.652\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eQTc; corrected QT, ms; millisecond, Em; peak velocity during early ventricular diastole, Am; Late diastolic velocity, E/A\u0026thinsp;=\u0026thinsp;ratio between early diastolic velocity and late diastolic velocity, Sm; Systolic Velocity, IVCT; Isovolumic contraction time, IVRT; Isovolumic relaxation time, GCS; global circumferential strain, GRS; global radial strain, GLS; global longitudinal strain.\u003c/p\u003e \u003cp\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation between GLS with anthropometric measurement, lipid profile and duration on KD.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGroup I\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGLS\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u003csub\u003es\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eZ-score of Height\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.982\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eZ-score of weight\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.084\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.633\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eZ-score of BMI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.065\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.711\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal cholesterol\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.889\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTG\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.905\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLDL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.409\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHDL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.248\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.151\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration on KD (months)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.451\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.007*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003er\u003csub\u003es\u003c/sub\u003e: Spearman coefficient\u003c/h2\u003e \u003cp\u003e*: Statistically significant at p\u0026thinsp;\u0026le;\u0026thinsp;0.05\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eKetogenic diet (KD) is an established non-pharmacological therapy for children with refractory epilepsy. However, like all therapeutic strategies, KD is not free of adverse effects. Diet-related metabolic disturbances, including dyslipidemia and micronutrient deficiencies, have raised concerns regarding potential cardiovascular involvement, although available data remain limited and sometimes conflicting [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe principal finding of the present study is the absence of clinically significant cardiac dysfunction in children receiving KD for a median duration of 24 months. Conventional echocardiographic parameters, tissue Doppler indices, and electrocardiographic findings were comparable among children on KD, those receiving antiseizure medications alone, and healthy controls, with all values remaining within established pediatric reference ranges. These findings indicate preserved systolic and diastolic myocardial function in children receiving KD under structured medical supervision.\u003c/p\u003e \u003cp\u003eThe use of two-dimensional speckle-tracking echocardiography (STE), a sensitive modality for detecting subclinical myocardial dysfunction, strengthens these observations by providing insight into myocardial mechanics beyond conventional echocardiographic assessment [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Previous studies evaluating the cardiac effects of KD in children with refractory epilepsy have primarily relied on conventional echocardiography and ECG and have generally reported reassuring results. Short- and mid-term studies demonstrated preserved ventricular function, with only minor adaptive changes in diastolic indices, and long-term follow-up studies similarly confirmed preserved cardiac structure and metabolic stability [\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn the present study, speckle-tracking echocardiographic analysis demonstrated a statistically significant reduction in left ventricular global longitudinal strain (GLS) in children receiving KD, while global circumferential and radial strain parameters remained comparable across all study groups. Importantly, GLS values in the KD group remained within established pediatric reference ranges and were not accompanied by abnormalities in conventional systolic indices. These findings suggest that subtle alterations in myocardial mechanics may be detectable by STE even when conventional echocardiographic measures appear normal and are compatible with adaptive myocardial changes rather than pathological dysfunction. A moderate negative correlation was observed between GLS and duration of KD therapy; however, given the cross-sectional design and absence of baseline strain measurements, this association should be interpreted as hypothesis-generating rather than indicative of progressive myocardial impairment.\u003c/p\u003e \u003cp\u003eFrom a mechanistic perspective, longitudinal myocardial fibers, predominantly located in the subendocardial layer, are particularly sensitive to metabolic and energetic alterations (18). KD induces a sustained shift in myocardial energy substrate utilization toward fatty acids and ketone bodies, which may influence myocardial contractile mechanics over prolonged periods. The absence of associations with anthropometric or lipid parameters and the preservation of circumferential and radial strain support maintained overall myocardial performance, likely through compensatory mechanisms. These findings underscore the utility of STE, particularly GLS, in detecting early myocardial functional changes during prolonged KD therapy and support the role of periodic cardiac monitoring in this population.\u003c/p\u003e \u003cp\u003eElectrocardiographic evaluation revealed no significant differences in PR or corrected QT intervals among the studied groups, with all values within normal limits. This is consistent with previous reports demonstrating stable cardiac conduction and repolarization in children receiving KD therapy [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Although rare, serious cardiac complications such as QT prolongation, cardiomyopathy, and sudden cardiac death have been reported in association with KD, often related to micronutrient deficiencies, particularly selenium [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These observations highlight the importance of careful selection, regular monitoring of cardiac function, and appropriate micronutrient supplementation during KD therapy.\u003c/p\u003e \u003cp\u003eConsistent with prior literature, KD was associated with sgnificant reduction in seizure frequency, with more than two-thirds of patients achieving a responder or high-responder status [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Regarding lipid metabolism, children on KD exhibited higher total cholesterol levels compared with other groups; however, these values remained within normal pediatric ranges and did not indicate clinically significant dyslipidemia. Similar findings have been reported previously and are generally considered adaptive metabolic changes that stabilize with ongoing dietary supervision [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe limitations of this study include relatively small sample size, cross-sectional design, lack of baseline cardiac assessment prior to KD initiation, and absence of systematic measurement of selenium and other micronutrient levels. Strengths include the inclusion of two epilepsy groups and a healthy control group, as well as comprehensive cardiac evaluation using ECG, conventional echocardiography, tissue Doppler imaging, and STE, allowing sensitive detection of both overt and subclinical myocardial changes.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, KD therapy in children with RE was not associated with adverse effects on cardiac structure, function, or electrical activity ,The use of advanced echocardiographic techniques, including STE analysis provides additional reassurance regarding myocardial safety Although GLS differed significantly between groups, the observed values in KD group remained within established pediatric reference ranges, This pattern suggests the presence of subclinical longitudinal myocardial functional changes rather than overt systolic dysfunction.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatements and declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResearch funding: the authors declare that no funds, grants, or other \u0026nbsp; \u0026nbsp;support were received during the preparation of this research .\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e : informed consent was obtained from all patient caregivers before inclusion in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e :This study was conducted by the principles outlined in the Declaration of Helsinki. Ethical approval for the study was granted by the Ethical Committee of the Faculty of Medicine, Kafr Elsheikh University (Approval No. KFSIRB200-180), and written informed consent was gained from the parents or legal guardians for all enrolled children prior to participation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e:\u0026nbsp;The datasets generated and/or analyzed during the current study are not publicly available due to institutional and ethical restrictions but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHend Gamal (H.G):\u003c/strong\u003e Patient recruitment, clinical data collection, and drafting of the initial manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAmany Elbarky (A.E):\u003c/strong\u003e Supervision of ketogenic diet implementation, nutritional monitoring, and critical revision of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbeer Salamah (A.S):\u003c/strong\u003e Neurological evaluation, epilepsy classification, and antiseizure medication management.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOsama Elagamy (O.E):\u003c/strong\u003e contribution to study supervision, provided guidance on methodology and data interpretation, and assisted in critically revising the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMohamed Abdelghafar Hussein (M.A.H):\u003c/strong\u003e comprehensive cardiac evaluation including electrocardiography, conventional echocardiography, tissue Doppler imaging, and speckle-tracking echocardiography; interpretation of cardiac imaging data; and \u0026nbsp;critical revision of the manuscript.\u003c/p\u003e\n\u003cp\u003eAll authors approved the final manuscript and agreed to be accountable for all aspects of the work\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHenderson CB, Filloux FM, Alder SC, Lyon JL, Caplin DA (2006) Efficacy of the ketogenic diet as a treatment option for epilepsy: meta-analysis. 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Lancet Neurol 7(6):500\u0026ndash;506. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e.https://doi.org/10.1016/S1474-4422(08)70092-9\u003c/span\u003e\u003cspan address=\".10.1016/S1474-4422(08)70092-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCai QY, Zhou ZJ, Luo R, Gan J, Li SP, Mu DZ, Wan CM (2017) Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies. World J Pediatr 13(6):528\u0026ndash;536. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s12519-017-0053-\u003c/span\u003e\u003cspan address=\"10.1007/s12519-017-0053-\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwiterovich PO Jr, Vining EP, Pyzik P, Skolasky R Jr, Freeman JM (2003) Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children. JAMA 290(7):912\u0026ndash;920. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/jama.290.7.912\u003c/span\u003e\u003cspan address=\"10.1001/jama.290.7.912\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Ketogenic diet, Pediatric epilepsy, Cardiac functions, Speckle tracking echocardiography","lastPublishedDoi":"10.21203/rs.3.rs-8929432/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8929432/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBACKGROUND\u003c/h2\u003e \u003cp\u003eRefractory epilepsy (RE) in childhood remains a major therapeutic challenge. ketogenic diet (KD) is widely used as an effective non-pharmacological therapy; however, KD-related metabolic changes may potentially affect myocardial structure and function. Therefore, assessment of cardiac performance in children receiving KD therapy is clinically relevant. This study aimed to assess cardiac function in children presenting with RE and receiving KD therapy using two-dimensional speckle tracking echocardiography (2D-STE) for early detection of myocardial dysfunction.\u003c/p\u003e\u003ch2\u003eMETHODS\u003c/h2\u003e \u003cp\u003eThis comparative observational study with cross-sectional cardiac evaluation included 105 children aged 2\u0026ndash;10 years, divided into three equal groups: 35 children with RE receiving KD in addition to antiseizure medications (ASM), 35 children with RE receiving ASM only, and 35 healthy controls. All enrolled participants were subjected to comprehensive cardiac evaluation using electrocardiography (ECG), conventional echocardiography, TDI, and 2D-STE. Metabolic parameters, including lipid profile, blood glucose, and urinary ketones, were assessed. Seizure frequency was recorded before and after KD initiation.\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e \u003cp\u003eevaluation of Left ventricular systolic and diastolic functions by conventional, TDI, and ECG were comparable among the three groups and remained within normal pediatric reference ranges. Global longitudinal strain (GLS) was statistically lower in KD group; however, values remained within normal limits, indicating no clinically relevant myocardial dysfunction. KD therapy resulted in significant decrease in seizure frequency, while changes in lipid profile remained within accepted pediatric reference ranges.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eKD therapy in children with RE was not associated with adverse effects on cardiac structure, function, or electrical activity and was effective in achieving significant seizure reduction. These findings support the cardiac safety of KD when appropriately monitored.\u003c/p\u003e","manuscriptTitle":"Speckle-tracking echocardiographic assessment of cardiac function in children with refractory epilepsy receiving a ketogenic diet","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-16 06:43:30","doi":"10.21203/rs.3.rs-8929432/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"130733500388941165995755422772196024196","date":"2026-04-12T20:50:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-07T18:48:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-25T22:44:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-25T12:44:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Pediatrics","date":"2026-02-20T22:46:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"97a945ec-5209-4d2f-9149-8cfb52479e9b","owner":[],"postedDate":"April 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-16T06:43:30+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-16 06:43:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8929432","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8929432","identity":"rs-8929432","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}