Examination of Cardiac Functions During Acute Attack and Remission Period in Children With Familial Mediterranean Fever

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Cardiac involvement in FMF commonly manifests as pericarditis and pericardial effusion, however there is limited research on myocardial function. This study aimed to assess cardiac functions during active inflammation and remission periods of FMF patients and investigate the cardiac effects of inflammation during the attack period. Methods Thirty-eight FMF patients without additional cardiac diseases were included in the study. Demographic characteristics, clinical symptoms, family history, and MEFV gene analysis results were obtained retrospectively. Blood tests, blood pressure measurements, electrocardiogram evaluations, conventional echocardiography, and speckle-tracking echocardiography were performed during the attack and remission periods. Disease severity was assessed using the Pras scoring system. Results During the attack period, FMF patients exhibited significantly higher leukocyte count, neutrophil count, C-reactive protein, and erythrocyte sedimentation rate compared to the remission period (p < 0.005). Speckle-tracking echocardiography revealed decreased function in the inferior segments of the left ventricle during the attack period (p < 0.005). Right ventricular function was more affected in the moderate disease group. FMF patients with lymphopenia during the attack demonstrated more impaired right ventricular function compared to those with normal lymphocyte count. Conclusions FMF patients experience cardiac abnormalities during active inflammation, highlighting the importance of monitoring cardiac functions in these patients. Speckle-tracking echocardiography can provide valuable insights into cardiac involvement in FMF. These findings emphasize the cardiac impact of FMF inflammation and the significance of long-term cardiac function monitoring in the management of FMF patients. Familial Mediterranean Fever Attack Speckle Tracking Echocardiography Cardiac Functions Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 INTRODUCTION Familial Mediterranean fever (FMF) is an autosomal recessive, autoinflammatory disease with symptoms and clinical signs caused by serosal inflammation[ 1 – 3 ]. The disease is rare worldwide, however in the Turkish population, it’s prevalence varies between 1/400-1/1000[4; 5]. The most common forms of cardiac involvement in patients with FMF is pericarditis and pericardial effusion. There are number of studies that have assessed the pericardium and endocardium in FMF patients during the attack period; however, there are few studies that have investigated myocardial function. It is thought that diastolic functions deteriorate in long-term disease follow-up [6; 7]. Interestingly, in adult patients with FMF in the remission period, there is no difference in systolic function compared to the healthy group, whereas diastolic dysfunction is present in both right and left ventricles [ 7 – 11 ]. Finally, patients with FMF show cardiac degenerative changes including endothelial damage and an overall decline in cardiac function which result in cardiovascular morbidities. In this study, we sought to characterize the changes in cardiac function and impact of inflammatory acute phase reactants on these changes that occur during the active inflammation period and the remission period. The current literature lacks studies investigating myocardial function in the pediatric population during the attack period of this particular disease. Our objective was to assess the alterations in cardiac function during the attack and remission periods, considering clinical manifestations, disease severity, acute phase reactant levels, and mutation type. We also evaluated the pattern of cardiac involvement and the affected cardiac areas by comparing remission and attack periods. Several studies have demonstrated a rise in the prevalence of ischemic cardiac disease and mortality among individuals with FMF. Investigating cardiac involvement during the attack period in FMF patients can provide valuable insights for the prevention of long-term complications. MATERIALS AND METHODS 2.1. STUDY POPULATION In this study, we analyzed a cohort of 38 patients followed at Istanbul University-Cerrahpasa Medical Faculty Hospital. This cohort consisted of patients diagnosed with FMF according to Turkish Pediatric FMF criteria. Patients without a MEFV gene analysis were not enrolled to the study. We excluded patients with history of additional cardiac disease and/or amyloidosis and with less than one-year follow-up period. Demographic characteristics, clinical symptoms, family history and MEFV gene analysis results were retrospectively obtained from patient files. The patients were examined and blood tests, blood pressure measurements, electrocardiogram evaluations were performed both during the attack and the remission periods. Additionally, conventional and speckle tracking echocardiographic evaluations were performed during the attack and remission periods. To differentiate if patients were in the attack or remission period, complete blood count, C-reactive protein level, and erythrocyte sedimentation rates were evaluated. In addition, troponin, B natriuretic peptide, creatine kinase MB isoenzyme levels were re-measured for both periods. Patients with normal acute phase markers were not included in the cohort. During follow-up in remission periods, speckle tracking echocardiographic evaluation was postponed for the patients who had elevated acute phase markers until these markers were found to be within the normal range. 2.2. ECHOCARDIOGRAPHIC IMAGING 2.2.a. CONVENTIONAL ECHOCARDIOGRAPHY Transthoracic echocardiography was performed in the Pediatric Cardiology Department using a commercially available echocardiography machine (EPIQ CVx, Philips Medical Systems) equipped with X5-1 MHz transducer. The echocardiographic examination was performed in the left lateral decubitus/supine position. A standard trans-thoracic echocardiogram was used in M-mode with two-dimensional Doppler flow assessments and tissue Doppler imaging. All pulsed-wave Doppler and tissue Doppler imaging parameters were measured at a sweep speed of 100 mm/s at the end of expiration, and the average of three consecutive heartbeats was recorded. All measurements were performed according to the recommendations of the American Society of Echocardiography. The left ventricular ejection and shortness fractions were calculated using the Teichholz formula [ 12 ]. Right ventricular functions were analyzed with right ventricular fractional area change. Right ventricular fractional area change represents a "'surrogate'" measurement of RV ejection fraction and is expressed as the percentage change in the right ventricular chamber area from end-diastole to end-systole. Tricuspid annular plane systolic excursion is a parameter of global right ventricular function that describes apex-to-base shortening [ 13 ]. The recommended method for the assessment of ventricular diastolic dysfunctions are mitral valve and tricuspid valve inflow measurement from Doppler scan recordings. These recordings consist of peak early diastolic velocity (e wave), peak late diastolic velocity (a wave, atrial filling) and calculation of the e-to-a ratio for each ventricle (Fig. 1 , 2 ). Tissue Doppler echocardiography was performed to measure peak early and late diastolic flow velocities (e' and a', respectively, cm/s) in the lateral tricuspid/mitral annulus views (Fig. 3 ). In normal function, the e wave is bigger than the a wave, but with impaired relaxation, the e-to-a ratio will fall because of the increasing atrial filling wave (a wave). 2.2.b. SPECKLE-TRACING ECHOCARDIOGRAPHY (STRAIN IMAGING) Speckle-tracking echocardiography is a new technique that analyzes motion by tracking natural acoustic reflections within an ultrasonic window. "Speckles" are stable patterns composed of 20–40 pixels that are automatically tracked during the cardiac cycle to follow the myocardial motion and directly assess the ventricular deformation at regions of interest [ 14 ]. Longitudinal left ventricular mechanics are the most sensitive components of the left ventricular dynamics, and these components are most sensitive to the presence of myocardial disease [ 15 ]. Therefore, we measured global longitudinal strain using speckle-tracking echocardiography from three ultrasonic views. We acquired three consecutive beats using high frame-rate harmonic imaging in each echocardiographic view. Cardiac cycles were recorded as two-dimensional color video loops, and the acquired raw data were saved for offline analysis (QLab; Philips Medical Systems) (Fig. 4 ). Manual adjustment of the regions of interest was performed as necessary. The average of each measurement was calculated. 2.3. ASSESSMENT OF DISEASE SEVERITY Pras scoring system was used to determine disease severity and patients were divided into 3 subgroups according to their score [16; 17]. Patients with a score of 3–5 points were included in the mild disease activity group; 6–8 points were included in the moderate disease activity group; and 9 points or more were included in the severe disease activity group. Since there were only 2 patients with severe disease activity, these patients were excluded from the statistical analysis. 2.4. STATISTICAL ANALYSIS The data were analyzed using SPSS 23 statistical package program. The conformity of the data to normal distribution was confirmed by using Kolmogorov-Smirnov test and homogeneity of variances was proved via Levene's test. The mean difference comparisons of the measured parameters between the groups were tested by independent t test, and the mean difference comparisons of the intra-group control-attack measurements were tested by dependent t test. Chi-square test was used to analyze categorical data. Results are presented as mean ± standard deviation. Results were considered statistically significant for p < 0.05. RESULTS 3.1. Demographic Characteristics 18 female and 20 male patients were included in the cohort. The mean age of the patients in the cohort was 12.8 ± 4.8 years. The mean time to diagnosis was 15.2 ± 12.9 months in females and 22.8 ± 22.1 months in males, and no significant difference was found in the time to diagnosis (p = 0.204). The mean disease follow-up was 6.8 ± 4.7 years. Of 38 patients, 13 (34%) had a consanguineous marriage between their parents. In 31 (81.6%) of the patients, there was a family history of a relative diagnosed with FMF. Patients were divided into 7 different groups according to MEFV mutation type. Only two of our 38 patients had no MEFV mutation. Patients without a MEFV gene analysis were not enrolled to the study. M694V was homozygous in 15 patients and M694V heterozygous in 4 patients. Mutation in the M694V allele located in exon 10 was detected in 19 (50%) of our patients. 3.2. Laboratory Findings Of the laboratory tests obtained, leukocyte count, neutrophil count, C-reactive protein level, and erythrocyte sedimentation rate were found to be significantly higher in the attack period comparing to the remission period (p < 0.005). The lymphocyte count measured during the attack period was significantly lower compared to the remission period (Table 1 ). Table 1 Comparison of Laboratory Analyses in the Attack and Remission Periods TOTAL (n = 38) Attack Mean ± SD Remission Mean ± SD p value Leukocytes (/mm 3 ) 12200,0 ± 4740,8 7550,0 ± 2040,1 0,0001 Platelets (/mm 3 ) 299,1 ± 103,9 323,3 ± 85,4 0,100 Neutrophils (/mm 3 ) 9360,5 ± 4204,3 4189,5 ± 1951,8 0,0001 Lymphocytes (/mm 3 ) 1863,2 ± 1040,4 2663,2 ± 895,5 0,0001 CRP (mg/L) 98,9 ± 210,1 48,0 (median) 14,6 ± 18,1 7,5 (median) 0,020 ESR (mm/h) 25,4 ± 12,5 11,2 ± 6,2 0,0001 ProBNP (pg/ml) 251,2 ± 363,8 91,5 (median) 173,3 ± 261,3 62,5 (median) 0,250 During the attack period, the lymphocyte count was measured to be 1863.2 ± 1040.4/mm3, whereas it was 2663.2 ± 895.5/mm3 during the remission period. A significant decrease in lymphocyte count was observed during the attack period compared to the remission period (p = 0.0001). In our study, a lower limit of 1500/mm3 was defined for lymphopenia. Among the 38 patients evaluated during an attack, 14 had lymphocyte counts below the normal range, and eight of them had lymphocyte values < 1000/mm3. In this group of patients with lymphopenia (14 patients), only two were receiving biologic agents regularly (anakinra, canakinumab). During the remission period, the lymphocyte counts of patients who experienced lymphopenia during the attack returned to the normal range (Table 1 ). Table 2 Categorization of Disease Severity* Total (n = 38) Female (n = 18) Male (n = 20) p (sig.) Pras Score 6,1 ± 1,7 6,5 ± 2,1 5,7 ± 1,2 0,144 Pras Score Group Mild Disease Moderate Disease Severe Illness 17 (%44,7) 19 (%50,0) 2 (%5,3) 6 (%33,3) 10 (%55,6) 2 (%11,1) 11 (%55,0) 9 (%45,0) 0 (%0,0) 0,180 *Patients with a score of 3-5 points were included in the mild disease activity group; 6-8 points were included in the moderate disease activity group; and 9 points or more were included in the severe disease activity group. The mean Pras score of the cohort was 6.1 ± 1.7. No significant difference between genders were noted (p=0.144). The laboratory findings of patients divided into three groups (mild, moderate, and severe) according to the Pras scoring system were compared, taking into account the severity of the disease. Comparative leukocyte, neutrophil, and lymphocyte levels were presented for the attack and remission periods in Figure 5. The changes in ESR and CRP levels, based on the disease groups, are shown in Figure 6. No statistically significant difference was observed in the mean values of acute phase markers and blood count measurements between the mild and moderate disease groups (p>0.05). The schematic representation shows the comparison of measurements among the disease groups and all patients collectively (Figure 5,6). To assess cardiac function alterations between the severity subgroups electrocardiogram evaluations were performed. When evaluations of moderate and mild disease activity patients compared, a statistically significant correlation between disease severity and heart rate, PR interval, QRS width was found (p<0.005). Table 3.Evaluation of Findings in the Attack and Remission Period with Conventional Echocardiography Echocardiography Parameters Attack Mean ± SD Remission Mean ± SD p value IVSD (mm) 7,01 ± 1,5 6,89 ± 1,4 0,571 LVEDD (mm) 39,4 ± 6,3 39,9 ± 6,4 0,383 LVPWT (mm) 6,85 ± 1,4 6,92 ± 1,2 0,762 LVESD (mm) 24,78 ± 4,2 25,53 ± 4,5 0,197 EF (%) 66,82 ± 4,6 66,34 ± 5,9 0,703 CF (%) 36,28 ± 3,0 36,07 ± 5,0 0,830 E wave (mm/sec) 90,27 ± 14,1 91,5 ± 13,3 0,717 A wave (mm/sec) 58,71 ± 15,5 58,93 ± 13,2 0,949 E/A Ratio 1,77 ± 0,8 1,67 ± 0,4 0,583 E DT (msn) 161,61 ± 46,0 188,32 ± 41,1 0,046 Emi (mm/sec) 23,28 ± 13,7 22,41 ± 4,2 0,745 Ami (mm/sec) 11,65 ± 13,4 9,61 ± 2,6 0,418 E/E' 4,45 ± 1,0 4,25 ± 1,0 0,503 RV FAC 44,29 ± 8,2 43,57 ± 8,9 0,721 TAPSE (mm) 21,58 ± 3,3 20,62 ± 4,0 0,374 Etr (mm/sec) 17,14 ± 4,6 16,68 ± 4,6 0,688 Smi (mm/sec) 14,09 ± 2,5 13,31 ± 2,6 0,172 Atr (mm/sec) 10,87 ± 4,5 10,31 ± 3,4 0,572 Str (mm/sec) 18,01 ± 3,8 15,57 ± 3,8 0,354 Abbreviations Atr: Early diastolic A wave measured by tissue doppler, CF: Shortening fraction, EF: Ejection Fraction, E-DT: E-wave deseleration time, Emi: Early diastolic E wave measured by Doppler Transmitral, Etr: Early diastolic E wave measured by tissue doppler, IVSD: Diastolic diameter of the interventricular septum, LVEDD: left ventricular end-diastolic diameter, LVESD: left ventricular end-systolic diameter, LVPWT: left ventricular posterior wall thickness, RV FAC: Right ventricular functional area, Smi: Early diastolic S wave measured by Doppler Transmitral, Str: Early diastolic S wave measured by tissue doppler, TAPSE: Tricuspid Annular Plane Systolic Movements Table 4 Evaluation of Patients in the Attack-Remission Period with Speckle Tracking Echocardiography Echocardiography Parameters Attack Mean ± SD Remission Mean ± SD p value GLS_4Chs (%) 20,02 ± 5,6 22,33 ± 4,2 0,052 Basal Inferoseptum 20,02 ± 5,9 23,34 ± 9,7 0,129 Midinferoseptum 21,92 ± 5,6 22,07 ± 5,1 0,910 Apicalseptum 17,51 ± 9,7 21,07 ± 7,9 0,108 Basalanterolateral 31,89 ± 11,4 33,52 ± 10,2 0,554 Midanterolateral 17,59 ± 6,6 19,03 ± 7,2 0,434 Apical lateral 13,37 ± 9,1 18,21 ± 8,1 0,047 GLS_2Chs (%) 17,04 ± 4,9 21,76 ± 4,5 0,003 Basalinferior 19,41 ± 8,4 24,66 ± 9,5 0,003 Midinferior 18,15 ± 7,6 20,55 ± 9,1 0,337 Apicalinferior 15,92 ± 6,9 20,71 ± 7,1 0,023 Basalanterior 19,14 ± 8,1 21,93 ± 7,2 0,236 Midanterior 16,74 ± 6,0 19,57 ± 7,1 0,184 Apicalanterior 16,54 ± 6,9 20,31 ± 7,4 0,100 GLS_3Chs (%) 18,11 ± 5,0 21,38 ± 3,0 0,007 Basalinferolateral 23,68 ± 8,7 32,97 ± 12,0 0,001 Midinferolateral 18,99 ± 6,9 19,1 ± 6,7 0,954 Apicallateral 13,35 ± 6,5 16,0 ± 6,2 0,097 Basalanteroseptum 23,33 ± 9,7 25,04 ± 9,1 0,495 Midanteroseptum 17,46 ± 7,6 18,97 ± 5,7 0,405 Apicalseptum 12,45 ± 6,3 16,19 ± 5,3 0,017 Abbreviations : GLS_2Chs: Two-chamber view longitudinal strain, GLS_3Chs: Three-chamber view longitudinal strain, GLS_4Chs: Four-chamber view longitudinal strain During the attack period, speckle tracking echocardiographic evaluation demonstrated impaired function in the inferior segments of the left ventricle (Table 4). Table 5 Comparison of Strain Echocardiographic Findings in the Attack Period of Groups with Mild and Moderate Disease Activity, Based on Pras Scoring Echocardiographic Parameters Group with Mild Disease Activity (17) Mean ± SD Group with Moderate Disease Activity (19) Mean ± SD Mean Difference p value GLS 4Chs % 18,6 ± 6,1 21,3 ± 5,2 -1,75 0,381 Basal İnferoseptum 20,7 ± 6,8 18,1 ± 3,7 1,35 0,514 Midinferoseptum 20,9 ± 6,2 23,7 ± 3,5 -2,51 0,164 Apicalseptum 15,9 ± 10,4 18,8 ± 9,6 -2,89 0,418 Basalanterolateral 30,7 ± 11,8 33,5 ± 11,7 -2,38 0,572 Midanterolateral 15,5 ± 7,6 19,7 ± 5,0 -3,67 0,123 Apicallateral 12,6 ± 9,4 14,2 ± 9,7 -1,83 0,589 GLS 2Chs % 15,5 ± 4,4 18,8 ± 9,4 -2,91 0,102 Basalinferior 20,2 ± 9,1 19,0 ± 8,1 2,04 0,531 Midinferior 16,5 ± 6,7 20,1 ± 8,0 -4,12 0,133 Apicalinferior 13,8 ± 6,2 18,3 ± 7,2 -4,95 0,048 Basalanterior 17,0 ± 6,9 19,8 ± 9,0 -2,38 0,421 Midanterior 14,6 ± 5,7 18,4 ± 6,1 -4,33 0,049 Apicalanterior 15,5 ± 7,4 17,5 ± 6,8 -2,45 0,346 GLS 3Chs % 18,4 ± 6,6 18,5 ± 2,9 -0,33 0,859 Basalinferolateral 20,5 ± 6,1 25,2 ± 10,0 -3,99 0,233 Midinferolateral 19,6 ± 9,3 18,2 ± 4,8 2,01 0,451 Apicallateral 15,1 ± 8,3 11,7 ± 4,8 2,01 0,415 Basalanteroseptum 23,1 ± 9,9 23,7 ± 10,6 -0,72 0,848 Midanteroseptum 17,1 ± 9,4 18,2 ± 6,4 -1,26 0,651 Apicalceptum 13,2 ± 7,9 11,5 ± 5,3 0,66 0,785 Abbreviations : GLS_2Chs: 2 cavities global longitudinal strain, GLS_3Chs: 3 chamber view longitudinal strain, GLS_4Chs: 4 chamber view longitudinal strain Comparison between mild and moderate disease groups during the attack period showed that right ventricular function was more affected in the moderate disease group (Table 5). In patients with lymphopenia, it was observed that the right ventricular function was more severely affected during the attack phase compared to patients with normal lymphocyte count. The change in TAPSE measurements between the attack and remission periods was -16.1 ± 6.9% in the patients with lymphopenia during the attack and 3.7 ± 23.9% in the patients without lymphopenia. Statistically significant difference between the mean measurements was found (p=0.019). Comparison of Attack-Remission Changes According to Attack Treatment with Speckle Tracking Echocardiography Speckle tracking echocardiography evaluations were re-analyzed for the comparison between the patients who received anakinra treatment during the attack (17 patients) and the patients who received only symptomatic treatment (21 patients). The percentage change between the attack and remission period in the measurement of the three-chamber basalinferolateral segment in the patients who received only symptomatic treatment during the attack was 84.5 ± 96.1%. Meanwhile the change between the attack and remission period in the patients who received anakinra was 20.8 ± 51.3%. A significant difference of averages was measured between the two groups (p=0.041) Discussion In this study, we sought to establish a relationship between known markers of cardiac function and standard laboratory tests that could be easily accessed. Given our institutional access, we had a unique opportunity to obtain patient data and clinical assessment tools not easily found outside of our center. As such, this singularly positioned us to be able to ask more probing questions regarding the relationship between physiologic and anatomic changes that we see in FMF patients. We determined that this would be important, as it would help provide a clinically relevant tool that can then be re-applied to patient care without necessitating additional changes in protocol. As such, we demonstrated that there were shifts in cardiac function as noted prior and showed that this correlated to shifts in neutrophil counts, C-reactive protein, and erythrocyte sedimentation rate. Of particular note, there is a marked decrease in left and right ventricular function in FMF patients. This is especially apparent in the attack period in the left inferior segments. In addition, we found that right ventricular systolic function decreased more in the moderate disease subgroup in comparison to the mild disease subgroup (Table 1). Interestingly, there is a concurrent decrease in lymphocytes in the attack period compared to the remission period. In a previous study, 53% of the relatives of patients with FMF had a history of relatives diagnosed with FMF[1]. In our study, unlike the literature, 31 of our 38 patients (81.6%) had a family history of a relative diagnosed with FMF. In autoinflammatory diseases, acute phase reactants were found to be significantly higher during the attack period compared to the remission period. In some patients, acute phase reactants were reported to be elevated in the absence of clinical findings due to the persistence of subclinical inflammation. [1; 4; 5]Similar to the findings in the literature, C-Reactive protein, and erythrocyte sedimentation rate measurements were found to be significantly higher in the attack period compared to the remission period in our patient group when the attack and remission periods were considered. Again, similar to the findings in the literature, leukocyte and neutrophil values measured in our patients were significantly higher in the attack period compared to the control period. According to prior studies, neutrophil production increases in response to cytokines and proteins formed during attack in inflammatory diseases. Due to this increase, neutrophil/lymphocyte ratio also increases. Stress is known to be a triggering factor for attacks in patients with FMF due to its increasing effect in the cortisol levels which leads to decrease in lymphocyte count (3). In our comparative analysis of blood counts, a significant decrease in lymphocyte count in the attack period was observed. It showed that the lymphocyte count reverted to the normal range during the remission period. Since there are no prior studies in terms of the subject, no external data comparison has been performed. In this case, as a limiting point, we could not biochemically evaluate stress hormones, cortisol levels and cytokine levels in our patients during the attack period. We think that this situation can be clarified with similar studies to be conducted in the future in patients with FMF. In the speckle tracking echocardiographic evaluation of the patients, statistically significant differences were found in the global longitudinal two chamber view, inferior and anterior sections when the attack and remission periods were compared. This suggests that these differences are related to the cytokines that are released during the inflammation period. Studies on how increased TNF-α and IL-1β levels during an attack may affect cardiac functions have shown that increased TNF-α expression decreases endothelium-dependent vasodilation in coronary arterioles. The mechanism responsible for this is decreased nitric oxide bioavailability and nitric oxide-dependent vasodilation [18; 19]. Experimental studies have shown that injection of recombinant IL-1β (3 μg/kg) in experimental mice causes a decrease in myocardial contractility and systolic dysfunction [20; 21]. In clinical studies, a single dose of 100 mg anakinra given to patients with rheumatoid arthritis increased coronary flow reserve by affecting myocardial contractility and relaxation through IL-1 blockade within 3 hours [22]. In our evaluation of the speckle tracking echocardiographic measurements, we observed that patients who received anakinra treatment during the attack demonstrated faster improvement of the heart function in the three space basalinferolateral region compared to patients who did not receive anakinra. In our study, we were not able to determine whether the decrease in left ventricular function during an attack period was due to the effect of inflammatory cytokines on the microvascular environment, or the changes in coronary flow velocity. In the healthy population, because of the variation in the coronary arteries that perfuse the posterior and inferior regions of the left ventricle, coronary flow velocity could not be associated with the involvement of these regions during an attack [23]. Conventional echocardiographic measurements (TAPSE) during the attack period for patients with normal lymphocyte counts, and lymphopenia showed a significant difference in right ventricular function. Moreover, TAPSE evaluations shown that the patients with lymphopenia demonstrated more changes than the patients with normal lymphocyte count, when attack and remission periods compared. Furthermore, the speckle tracking echocardiographic evaluation showed a significant alteration in three space midinferolateral area for the patients with lymphopenia. We think that right ventricular systolic function was more affected in the lymphopenia group due to increased cytokines and inflammation. We believe that future studies in different autoinflammatory diseases will clarify this. Conclusion We demonstrated that cardiac function decreased in the left ventricular inferior segments during the attack period in our study group. We found that systolic function of the right ventricle decreased more in the moderate disease group than in the mild disease group during the attack period. We also found that the patient group with lymphopenia during the attack had decreased right ventricular function compared to the normal group. Limitations 1. We evaluated our patient group within the 24-72-hour period of cardiac and biochemical findings during the attack period of the disease. We think that cardiac functions may have been detected differently in some patients because our patients were evaluated within 48 hours. We think that the results would be more meaningful if we could evaluate our patient group in a shorter and more specific period during the attack process. 2. We assumed that serum amyloid A, TNF alpha, IL 1 measurements may be more effective in evaluating the degree of inflammation during the attack period when we evaluate the cardiac involvement of our patients. In the light of this study, we plan to take these limitations into consideration in future studies. Abbreviations Atr : Early diastolic A wave measured by tissue Doppler, CF : Shortening fraction, CK-MB : Creatine kinase- myocardial band CRP : C-reactive protein E-DT : E-wave deceleration time, EF : Ejection Fraction, Emi : Early diastolic E wave measured by Doppler Transmitral ESR : Erythrocyte sedimentation rate Etr : Early diastolic E wave measured by tissue Doppler, FMF : Familial Mediterranean Fever GLS_2Chs : Two-chamber global longitudinal strain, GLS_3Chs : Three-chamber global longitudinal strain, GLS_4Chs : Four-chamber global longitudinal strain, IL : Interleukin IVSD : Diastolic diameter of the interventricular septum, LVEDD : Left ventricular end-diastolic diameter, LVESD : Left ventricular end-systolic diameter, LVPWT : Left ventricular posterior wall thickness, MEFV : Mediterranean Fever Pro-BNP : pro–B-type natriuretic peptide RV FAC : Right ventricular functional area, Smi : Early diastolic E wave measured by Doppler Transmitral, Str : Early diastolic S wave measured by tissue Doppler, TAPSE : Tricuspid Annular Plane Systolic Movements TNF : Tumor necrosis factor Declarations Funding Support and Author Disclosures This research received no specific grant from any funding agency, commercial or not-for-profit sectors. HUMAN ETHICS AND CONSENT TO PARTICIPATE The study was conducted in accordance with the Declaration of Helsinki and approved by the Istanbul University-Cerrahpasa Cerrahpasa Medical Faculty Institutional Review Board (Date:26/04/2022–No:367672). Detailed informed consent form was obtained from all patients included in the study and from the parents/legally authorized representatives of patients under 18 years of age. DATA AVAILABILITY The data that support the findings of this study are available from the corresponding author, upon reasonable request. References Barut K, Sahin S, Adrovic A, Sinoplu AB, Yucel G, Pamuk G, Aydin AK, Dasdemir S, Turanli ET, Buyru N, Kasapcopur O (2018) Familial Mediterranean fever in childhood: a single-center experience. Rheumatol Int 38:67-74 Yildiz M, Haslak F, Adrovic A, Barut K, Kasapcopur O (2020) Autoinflammatory Diseases in Childhood. 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Clin Genet 94:81-94 Lopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK, Lai WW, Geva T (2010) Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr 23:465-495; quiz 576-467 Vitarelli A, Giordano M, Germano G, Pergolini M, Cicconetti P, Tomei F, Sancini A, Battaglia D, Dettori O, Capotosto L, De Cicco V, De Maio M, Vitarelli M, Bruno P (2010) Assessment of ascending aorta wall stiffness in hypertensive patients by tissue Doppler imaging and strain Doppler echocardiography. Heart 96:1469-1474 Kaluzynski K, Chen X, Emelianov SY, Skovoroda AR, O'Donnell M (2001) Strain rate imaging using two-dimensional speckle tracking. IEEE Trans Ultrason Ferroelectr Freq Control 48:1111-1123 Reisner SA, Lysyansky P, Agmon Y, Mutlak D, Lessick J, Friedman Z (2004) Global longitudinal strain: a novel index of left ventricular systolic function. J Am Soc Echocardiogr 17:630-633 Pras E, Livneh A, Balow JE, Jr., Pras E, Kastner DL, Pras M, Langevitz P (1998) Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet 75:216-219 Ozen S, Aktay N, Lainka E, Duzova A, Bakkaloglu A, Kallinich T (2009) Disease severity in children and adolescents with familial Mediterranean fever: a comparative study to explore environmental effects on a monogenic disease. Ann Rheum Dis 68:246-248 Zhang C, Xu X, Potter BJ, Wang W, Kuo L, Michael L, Bagby GJ, Chilian WM (2006) TNF-alpha contributes to endothelial dysfunction in ischemia/reperfusion injury. Arterioscler Thromb Vasc Biol 26:475-480 Zhang C, Wu J, Xu X, Potter BJ, Gao X (2010) Direct relationship between levels of TNF-alpha expression and endothelial dysfunction in reperfusion injury. Basic Res Cardiol 105:453-464 Van Tassell BW, Arena RA, Toldo S, Mezzaroma E, Azam T, Seropian IM, Shah K, Canada J, Voelkel NF, Dinarello CA, Abbate A (2012) Enhanced interleukin-1 activity contributes to exercise intolerance in patients with systolic heart failure. PLoS One 7:e33438 Van Tassell BW, Seropian IM, Toldo S, Mezzaroma E, Abbate A (2013) Interleukin-1beta induces a reversible cardiomyopathy in the mouse. Inflamm Res 62:637-640 Ikonomidis I, Lekakis JP, Nikolaou M, Paraskevaidis I, Andreadou I, Kaplanoglou T, Katsimbri P, Skarantavos G, Soucacos PN, Kremastinos DT (2008) Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis. Circulation 117:2662-2669 Sharif D, Sharif-Rasslan A, Shahla C, Khalil A, Rosenschein U (2015) Differences in coronary artery blood velocities in the setting of normal coronary angiography and normal stress echocardiography. Heart Int 10:e6-e11 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 26 Apr, 2024 Read the published version in European Journal of Pediatrics → Version 1 posted Editorial decision: Revision requested 23 Mar, 2024 Reviews received at journal 23 Mar, 2024 Reviews received at journal 14 Mar, 2024 Reviewers agreed at journal 28 Feb, 2024 Reviewers invited by journal 13 Feb, 2024 Editor assigned by journal 12 Feb, 2024 Submission checks completed at journal 12 Feb, 2024 First submitted to journal 06 Feb, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-3933795","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":272590156,"identity":"7f3d446d-0dde-45c4-b22c-69c20c9dedb7","order_by":0,"name":"Yusuf Gunay","email":"","orcid":"","institution":"Department of Pediatrics, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine,","correspondingAuthor":false,"prefix":"","firstName":"Yusuf","middleName":"","lastName":"Gunay","suffix":""},{"id":272590157,"identity":"d5119634-4d33-4eae-9cac-d3e226f58e73","order_by":1,"name":"Fatih Karagozlu","email":"","orcid":"","institution":"Department of Pediatric Cardiology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Fatih","middleName":"","lastName":"Karagozlu","suffix":""},{"id":272590158,"identity":"3592b554-c693-4c63-b03a-bcc4c1788463","order_by":2,"name":"Sanem Gemici","email":"","orcid":"","institution":"Department of Pediatrics, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine,","correspondingAuthor":false,"prefix":"","firstName":"Sanem","middleName":"","lastName":"Gemici","suffix":""},{"id":272590159,"identity":"bc53e72b-4edc-458a-adc7-12d26f22085b","order_by":3,"name":"Sukran Seyma Yilmaz","email":"","orcid":"","institution":"Department of Pediatrics, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine,","correspondingAuthor":false,"prefix":"","firstName":"Sukran","middleName":"Seyma","lastName":"Yilmaz","suffix":""},{"id":272590160,"identity":"9774a71e-37b3-4947-997c-a67490009515","order_by":4,"name":"Sezgin Sahin","email":"","orcid":"","institution":"Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sezgin","middleName":"","lastName":"Sahin","suffix":""},{"id":272590161,"identity":"3e98a656-639f-497f-8ccc-5f5c2f3b88dd","order_by":5,"name":"Kenan Barut","email":"","orcid":"","institution":"Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kenan","middleName":"","lastName":"Barut","suffix":""},{"id":272590162,"identity":"c6f78d59-68eb-4174-9fcb-808d0f4a22ab","order_by":6,"name":"Ozgur Kasapcopur","email":"","orcid":"","institution":"Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ozgur","middleName":"","lastName":"Kasapcopur","suffix":""},{"id":272590163,"identity":"fc52e2ca-4c37-40da-a5b1-cd0ba85645c6","order_by":7,"name":"Reyhan Dedeoglu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCklEQVRIiWNgGAWjYHACNiBmZmA4AKQeMNgAScbGA8RrSWBIA2lpIEnLYbAQXi3m7T1mD37usJbjO958+EVi23m7te2HgbbU2ETj0iJz5oy5Ye+ZdGPJM8fSLBLbbidvO5MI1HIsLbcBhxYJiRwzCd62w4kbbuSYGYC0mB0AamFsOIxbi/wbM8m/bYfrN9x/A9JyLtns/EMCWiR4zKSBtiQY3OAxfpDYdsDO7AYhW3jSyqRl29INZ55JS2NIOJecYHYDaEsCPr+wH94m+bbNWp7v+OHDHz6U2dmbnU9/+OBDjQ1OLQwMHAYwFpsEkEgEq0zAqRwE2B/AWMwfgIQ9XsWjYBSMglEwIgEAvtZn5O3yG68AAAAASUVORK5CYII=","orcid":"","institution":"Department of Pediatric Cardiology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Reyhan","middleName":"","lastName":"Dedeoglu","suffix":""}],"badges":[],"createdAt":"2024-02-06 12:14:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3933795/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3933795/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00431-024-05570-y","type":"published","date":"2024-04-26T22:24:32+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":51135075,"identity":"38bb1f00-6d1f-4e5b-af21-914ddbb8dd81","added_by":"auto","created_at":"2024-02-14 18:28:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":150875,"visible":true,"origin":"","legend":"\u003cp\u003eMeasurement of right ventricular diastolic function by tissue Doppler\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3933795/v1/61b1e52f90f29eb8346743b5.png"},{"id":51135074,"identity":"6ff82e3b-66fe-4e47-8e28-81090b42e2a5","added_by":"auto","created_at":"2024-02-14 18:28:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":197717,"visible":true,"origin":"","legend":"\u003cp\u003eMeasurement of left ventricular diastolic function by tissue Doppler imaging\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3933795/v1/8bd57c5dcbeb7f48c3d36a2c.png"},{"id":51135073,"identity":"9e5f1034-861e-4d16-aebf-d166d73919a2","added_by":"auto","created_at":"2024-02-14 18:28:06","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":181315,"visible":true,"origin":"","legend":"\u003cp\u003eMeasurement of left ventricular function with M mode\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3933795/v1/343386fefb60b6c4c7865a68.png"},{"id":51137350,"identity":"f39abdef-4eeb-4fd9-b1d3-3a99c564015a","added_by":"auto","created_at":"2024-02-14 18:44:07","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":510501,"visible":true,"origin":"","legend":"\u003cp\u003eSpeckle Tracking Strain echocardiography segmental analysis of cardiac function\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-3933795/v1/798a05f90b317d96423b3611.png"},{"id":51135078,"identity":"4fa15c42-1270-43bc-be25-e132c3498158","added_by":"auto","created_at":"2024-02-14 18:28:06","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":21841,"visible":true,"origin":"","legend":"\u003cp\u003eLeukocyte, lymphocyte and neutrophil levels between the attack and remission periods\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-3933795/v1/780ca99d71d1a6378d5c7569.png"},{"id":51136547,"identity":"b8cc1461-9694-42f1-a1ed-7f49ed4d421e","added_by":"auto","created_at":"2024-02-14 18:36:06","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":29161,"visible":true,"origin":"","legend":"\u003cp\u003eESR and CRP levels between the attack and remission periods\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-3933795/v1/280e36cadab182ba8eb91c9d.png"},{"id":55690027,"identity":"90f246a8-de77-448c-b72b-6484d56369ce","added_by":"auto","created_at":"2024-05-01 22:24:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1916238,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3933795/v1/7c4bc0b0-d2d5-4dc7-81ea-efb88ad7ff7e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eExamination of Cardiac Functions During Acute Attack and Remission Period in Children With Familial Mediterranean Fever\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eFamilial Mediterranean fever (FMF) is an autosomal recessive, autoinflammatory disease with symptoms and clinical signs caused by serosal inflammation[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The disease is rare worldwide, however in the Turkish population, it\u0026rsquo;s prevalence varies between 1/400-1/1000[4; 5].\u003c/p\u003e \u003cp\u003eThe most common forms of cardiac involvement in patients with FMF is pericarditis and pericardial effusion. There are number of studies that have assessed the pericardium and endocardium in FMF patients during the attack period; however, there are few studies that have investigated myocardial function. It is thought that diastolic functions deteriorate in long-term disease follow-up [6; 7]. Interestingly, in adult patients with FMF in the remission period, there is no difference in systolic function compared to the healthy group, whereas diastolic dysfunction is present in both right and left ventricles [\u003cspan additionalcitationids=\"CR8 CR9 CR10\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Finally, patients with FMF show cardiac degenerative changes including endothelial damage and an overall decline in cardiac function which result in cardiovascular morbidities.\u003c/p\u003e \u003cp\u003eIn this study, we sought to characterize the changes in cardiac function and impact of inflammatory acute phase reactants on these changes that occur during the active inflammation period and the remission period.\u003c/p\u003e \u003cp\u003eThe current literature lacks studies investigating myocardial function in the pediatric population during the attack period of this particular disease. Our objective was to assess the alterations in cardiac function during the attack and remission periods, considering clinical manifestations, disease severity, acute phase reactant levels, and mutation type. We also evaluated the pattern of cardiac involvement and the affected cardiac areas by comparing remission and attack periods.\u003c/p\u003e \u003cp\u003eSeveral studies have demonstrated a rise in the prevalence of ischemic cardiac disease and mortality among individuals with FMF. Investigating cardiac involvement during the attack period in FMF patients can provide valuable insights for the prevention of long-term complications.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. STUDY POPULATION\u003c/h2\u003e \u003cp\u003eIn this study, we analyzed a cohort of 38 patients followed at Istanbul University-Cerrahpasa Medical Faculty Hospital. This cohort consisted of patients diagnosed with FMF according to Turkish Pediatric FMF criteria. Patients without a \u003cem\u003eMEFV\u003c/em\u003e gene analysis were not enrolled to the study. We excluded patients with history of additional cardiac disease and/or amyloidosis and with less than one-year follow-up period.\u003c/p\u003e \u003cp\u003eDemographic characteristics, clinical symptoms, family history and \u003cem\u003eMEFV\u003c/em\u003e gene analysis results were retrospectively obtained from patient files. The patients were examined and blood tests, blood pressure measurements, electrocardiogram evaluations were performed both during the attack and the remission periods. Additionally, conventional and speckle tracking echocardiographic evaluations were performed during the attack and remission periods. To differentiate if patients were in the attack or remission period, complete blood count, C-reactive protein level, and erythrocyte sedimentation rates were evaluated. In addition, troponin, B natriuretic peptide, creatine kinase MB isoenzyme levels were re-measured for both periods. Patients with normal acute phase markers were not included in the cohort. During follow-up in remission periods, speckle tracking echocardiographic evaluation was postponed for the patients who had elevated acute phase markers until these markers were found to be within the normal range.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. ECHOCARDIOGRAPHIC IMAGING\u003c/h2\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.2.a. CONVENTIONAL ECHOCARDIOGRAPHY\u003c/h2\u003e \u003cp\u003eTransthoracic echocardiography was performed in the Pediatric Cardiology Department using a commercially available echocardiography machine (EPIQ CVx, Philips Medical Systems) equipped with X5-1 MHz transducer. The echocardiographic examination was performed in the left lateral decubitus/supine position. A standard trans-thoracic echocardiogram was used in M-mode with two-dimensional Doppler flow assessments and tissue Doppler imaging. All pulsed-wave Doppler and tissue Doppler imaging parameters were measured at a sweep speed of 100 mm/s at the end of expiration, and the average of three consecutive heartbeats was recorded. All measurements were performed according to the recommendations of the American Society of Echocardiography. The left ventricular ejection and shortness fractions were calculated using the Teichholz formula [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Right ventricular functions were analyzed with right ventricular fractional area change. Right ventricular fractional area change represents a \"'surrogate'\" measurement of RV ejection fraction and is expressed as the percentage change in the right ventricular chamber area from end-diastole to end-systole. Tricuspid annular plane systolic excursion is a parameter of global right ventricular function that describes apex-to-base shortening [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The recommended method for the assessment of ventricular diastolic dysfunctions are mitral valve and tricuspid valve inflow measurement from Doppler scan recordings. These recordings consist of peak early diastolic velocity (e wave), peak late diastolic velocity (a wave, atrial filling) and calculation of the e-to-a ratio for each ventricle (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e1\u003c/span\u003e,\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Tissue Doppler echocardiography was performed to measure peak early and late diastolic flow velocities (e' and a', respectively, cm/s) in the lateral tricuspid/mitral annulus views (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In normal function, the e wave is bigger than the a wave, but with impaired relaxation, the e-to-a ratio will fall because of the increasing atrial filling wave (a wave).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.2.b. SPECKLE-TRACING ECHOCARDIOGRAPHY (STRAIN IMAGING)\u003c/h2\u003e \u003cp\u003eSpeckle-tracking echocardiography is a new technique that analyzes motion by tracking natural acoustic reflections within an ultrasonic window. \"Speckles\" are stable patterns composed of 20\u0026ndash;40 pixels that are automatically tracked during the cardiac cycle to follow the myocardial motion and directly assess the ventricular deformation at regions of interest [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Longitudinal left ventricular mechanics are the most sensitive components of the left ventricular dynamics, and these components are most sensitive to the presence of myocardial disease [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Therefore, we measured global longitudinal strain using speckle-tracking echocardiography from three ultrasonic views. We acquired three consecutive beats using high frame-rate harmonic imaging in each echocardiographic view. Cardiac cycles were recorded as two-dimensional color video loops, and the acquired raw data were saved for offline analysis (QLab; Philips Medical Systems) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Manual adjustment of the regions of interest was performed as necessary. The average of each measurement was calculated.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.3. ASSESSMENT OF DISEASE SEVERITY\u003c/h2\u003e \u003cp\u003e Pras scoring system was used to determine disease severity and patients were divided into 3 subgroups according to their score [16; 17]. Patients with a score of 3\u0026ndash;5 points were included in the mild disease activity group; 6\u0026ndash;8 points were included in the moderate disease activity group; and 9 points or more were included in the severe disease activity group. Since there were only 2 patients with severe disease activity, these patients were excluded from the statistical analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.4. STATISTICAL ANALYSIS\u003c/h2\u003e \u003cp\u003eThe data were analyzed using SPSS 23 statistical package program. The conformity of the data to normal distribution was confirmed by using Kolmogorov-Smirnov test and homogeneity of variances was proved via Levene's test. The mean difference comparisons of the measured parameters between the groups were tested by independent t test, and the mean difference comparisons of the intra-group control-attack measurements were tested by dependent t test. Chi-square test was used to analyze categorical data. Results are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Results were considered statistically significant for p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec10\"\u003e\n \u003ch2\u003e3.1. Demographic Characteristics\u003c/h2\u003e\n \u003cp\u003e18 female and 20 male patients were included in the cohort. The mean age of the patients in the cohort was 12.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8 years. The mean time to diagnosis was 15.2\u0026thinsp;\u0026plusmn;\u0026thinsp;12.9 months in females and 22.8\u0026thinsp;\u0026plusmn;\u0026thinsp;22.1 months in males, and no significant difference was found in the time to diagnosis (p\u0026thinsp;=\u0026thinsp;0.204). The mean disease follow-up was 6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7 years.\u003c/p\u003e\n \u003cp\u003eOf 38 patients, 13 (34%) had a consanguineous marriage between their parents. In 31 (81.6%) of the patients, there was a family history of a relative diagnosed with FMF.\u003c/p\u003e\n \u003cp\u003ePatients were divided into 7 different groups according to \u003cem\u003eMEFV\u003c/em\u003e mutation type. Only two of our 38 patients had no \u003cem\u003eMEFV\u003c/em\u003e mutation. Patients without a \u003cem\u003eMEFV\u003c/em\u003e gene analysis were not enrolled to the study. M694V was homozygous in 15 patients and M694V heterozygous in 4 patients. Mutation in the M694V allele located in exon 10 was detected in 19 (50%) of our patients.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003e3.2. Laboratory Findings\u003c/h2\u003e\n \u003cp\u003eOf the laboratory tests obtained, leukocyte count, neutrophil count, C-reactive protein level, and erythrocyte sedimentation rate were found to be significantly higher in the attack period comparing to the remission period (p\u0026thinsp;\u0026lt;\u0026thinsp;0.005). The lymphocyte count measured during the attack period was significantly lower compared to the remission period (Table \u003cspan\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eComparison of Laboratory Analyses in the Attack and Remission Periods\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTOTAL (n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAttack\u003c/p\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRemission\u003c/p\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLeukocytes (/mm\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12200,0\u0026thinsp;\u0026plusmn;\u0026thinsp;4740,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7550,0\u0026thinsp;\u0026plusmn;\u0026thinsp;2040,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlatelets (/mm\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e299,1\u0026thinsp;\u0026plusmn;\u0026thinsp;103,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e323,3\u0026thinsp;\u0026plusmn;\u0026thinsp;85,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeutrophils (/mm\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9360,5\u0026thinsp;\u0026plusmn;\u0026thinsp;4204,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4189,5\u0026thinsp;\u0026plusmn;\u0026thinsp;1951,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLymphocytes (/mm\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1863,2\u0026thinsp;\u0026plusmn;\u0026thinsp;1040,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2663,2\u0026thinsp;\u0026plusmn;\u0026thinsp;895,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCRP (mg/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e98,9\u0026thinsp;\u0026plusmn;\u0026thinsp;210,1\u003c/p\u003e\n \u003cp\u003e48,0 (median)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14,6\u0026thinsp;\u0026plusmn;\u0026thinsp;18,1\u003c/p\u003e\n \u003cp\u003e7,5 (median)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eESR (mm/h)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25,4\u0026thinsp;\u0026plusmn;\u0026thinsp;12,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11,2\u0026thinsp;\u0026plusmn;\u0026thinsp;6,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eProBNP (pg/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e251,2\u0026thinsp;\u0026plusmn;\u0026thinsp;363,8\u003c/p\u003e\n \u003cp\u003e91,5 (median)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e173,3\u0026thinsp;\u0026plusmn;\u0026thinsp;261,3\u003c/p\u003e\n \u003cp\u003e62,5 (median)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,250\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eDuring the attack period, the lymphocyte count was measured to be 1863.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1040.4/mm3, whereas it was 2663.2\u0026thinsp;\u0026plusmn;\u0026thinsp;895.5/mm3 during the remission period. A significant decrease in lymphocyte count was observed during the attack period compared to the remission period (p\u0026thinsp;=\u0026thinsp;0.0001). In our study, a lower limit of 1500/mm3 was defined for lymphopenia. Among the 38 patients evaluated during an attack, 14 had lymphocyte counts below the normal range, and eight of them had lymphocyte values\u0026thinsp;\u0026lt;\u0026thinsp;1000/mm3. In this group of patients with lymphopenia (14 patients), only two were receiving biologic agents regularly (anakinra, canakinumab). During the remission period, the lymphocyte counts of patients who experienced lymphopenia during the attack returned to the normal range (Table \u003cspan\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eCategorization of Disease Severity*\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep (sig.)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePras Score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6,1\u0026thinsp;\u0026plusmn;\u0026thinsp;1,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6,5\u0026thinsp;\u0026plusmn;\u0026thinsp;2,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5,7\u0026thinsp;\u0026plusmn;\u0026thinsp;1,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,144\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePras Score Group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMild Disease\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eModerate Disease\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSevere Illness\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (%44,7)\u003c/p\u003e\n \u003cp\u003e19 (%50,0)\u003c/p\u003e\n \u003cp\u003e2 (%5,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (%33,3)\u003c/p\u003e\n \u003cp\u003e10 (%55,6)\u003c/p\u003e\n \u003cp\u003e2 (%11,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (%55,0)\u003c/p\u003e\n \u003cp\u003e9 (%45,0)\u003c/p\u003e\n \u003cp\u003e0 (%0,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0,180\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e*Patients with a score of 3-5 points were included in the mild disease activity group; 6-8 points were included in the moderate disease activity group; and 9 points or more were included in the severe disease activity group.\u003c/p\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eThe mean Pras score of the cohort was 6.1 \u0026plusmn; 1.7. No significant difference between genders were noted (p=0.144).\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eThe laboratory findings of patients divided into three groups (mild, moderate, and severe) according to the Pras scoring system were compared, taking into account the severity of the disease. Comparative leukocyte, neutrophil, and lymphocyte levels were presented for the attack and remission periods in Figure 5. The changes in ESR and CRP levels, based on the disease groups, are shown in Figure 6.\u003c/p\u003e\n \u003cp\u003eNo statistically significant difference was observed in the mean values of acute phase markers and blood count measurements between the mild and moderate disease groups (p\u0026gt;0.05). The schematic representation shows the comparison of measurements among the disease groups and all patients collectively (Figure 5,6).\u003c/p\u003e\n \u003cp\u003eTo assess cardiac function alterations between the severity subgroups electrocardiogram evaluations were performed. When evaluations of moderate and mild disease activity patients compared, a statistically significant correlation between disease severity and heart rate, PR interval, QRS width was found (p\u0026lt;0.005).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3.Evaluation of Findings in the Attack and Remission Period with Conventional Echocardiography\u003c/strong\u003e\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"80%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003e\u003cstrong\u003eEchocardiography Parameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAttack\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e\u003cstrong\u003eRemission\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;p value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eIVSD (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e7,01 \u0026plusmn; 1,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e6,89 \u0026plusmn; 1,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,571\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eLVEDD (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e39,4 \u0026plusmn; 6,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e39,9 \u0026plusmn; 6,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,383\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eLVPWT (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e6,85 \u0026plusmn; 1,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e6,92 \u0026plusmn; 1,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,762\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eLVESD (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e24,78 \u0026plusmn; 4,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e25,53 \u0026plusmn; 4,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,197\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eEF (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e66,82 \u0026plusmn; 4,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e66,34 \u0026plusmn; 5,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,703\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eCF (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e36,28 \u0026plusmn; 3,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e36,07 \u0026plusmn; 5,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,830\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eE wave (mm/sec)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e90,27 \u0026plusmn; 14,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e91,5 \u0026plusmn; 13,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,717\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eA wave (mm/sec)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e58,71 \u0026plusmn; 15,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e58,93 \u0026plusmn; 13,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,949\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eE/A Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e1,77 \u0026plusmn; 0,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e1,67 \u0026plusmn; 0,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,583\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eE DT (msn)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e161,61 \u0026plusmn; 46,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e188,32 \u0026plusmn; 41,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,046\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eEmi (mm/sec)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e23,28 \u0026plusmn; 13,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e22,41 \u0026plusmn; 4,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,745\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eAmi (mm/sec)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e11,65 \u0026plusmn; 13,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e9,61 \u0026plusmn; 2,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,418\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eE/E\u0026apos;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e4,45 \u0026plusmn; 1,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e4,25 \u0026plusmn; 1,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,503\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eRV FAC\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e44,29 \u0026plusmn; 8,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e43,57 \u0026plusmn; 8,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,721\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eTAPSE (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e21,58 \u0026plusmn; 3,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e20,62 \u0026plusmn; 4,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,374\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eEtr (mm/sec)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e17,14 \u0026plusmn; 4,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e16,68 \u0026plusmn; 4,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,688\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eSmi (mm/sec)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e14,09 \u0026plusmn; 2,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e13,31 \u0026plusmn; 2,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,172\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eAtr (mm/sec)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e10,87 \u0026plusmn; 4,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e10,31 \u0026plusmn; 3,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,572\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.272727272727273%\"\u003e\n \u003cp\u003eStr (mm/sec)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e18,01 \u0026plusmn; 3,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e15,57 \u0026plusmn; 3,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003e0,354\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e Atr: Early diastolic A wave measured by tissue doppler, CF: Shortening fraction, \u0026nbsp;EF: Ejection Fraction, E-DT: E-wave deseleration time, Emi: Early diastolic E wave measured by Doppler Transmitral, Etr: Early diastolic E wave measured by tissue doppler, \u0026nbsp;IVSD: Diastolic diameter of the interventricular septum, LVEDD: left ventricular end-diastolic diameter, LVESD: left ventricular end-systolic diameter, LVPWT: left ventricular posterior wall thickness, RV FAC: Right ventricular functional area, Smi: Early diastolic S wave measured by Doppler Transmitral, Str: Early diastolic S wave measured by tissue doppler, TAPSE: Tricuspid Annular Plane Systolic Movements\u003c/p\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 4\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eEvaluation of Patients in the Attack-Remission Period with Speckle Tracking Echocardiography\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEchocardiography Parameters\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAttack\u003c/p\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRemission\u003c/p\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGLS_4Chs (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20,02\u0026thinsp;\u0026plusmn;\u0026thinsp;5,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22,33\u0026thinsp;\u0026plusmn;\u0026thinsp;4,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,052\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasal Inferoseptum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20,02\u0026thinsp;\u0026plusmn;\u0026thinsp;5,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23,34\u0026thinsp;\u0026plusmn;\u0026thinsp;9,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,129\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMidinferoseptum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21,92\u0026thinsp;\u0026plusmn;\u0026thinsp;5,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22,07\u0026thinsp;\u0026plusmn;\u0026thinsp;5,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,910\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eApicalseptum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17,51\u0026thinsp;\u0026plusmn;\u0026thinsp;9,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21,07\u0026thinsp;\u0026plusmn;\u0026thinsp;7,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,108\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasalanterolateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31,89\u0026thinsp;\u0026plusmn;\u0026thinsp;11,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33,52\u0026thinsp;\u0026plusmn;\u0026thinsp;10,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,554\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMidanterolateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17,59\u0026thinsp;\u0026plusmn;\u0026thinsp;6,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19,03\u0026thinsp;\u0026plusmn;\u0026thinsp;7,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,434\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eApical lateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13,37\u0026thinsp;\u0026plusmn;\u0026thinsp;9,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,21\u0026thinsp;\u0026plusmn;\u0026thinsp;8,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,047\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGLS_2Chs (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17,04\u0026thinsp;\u0026plusmn;\u0026thinsp;4,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21,76\u0026thinsp;\u0026plusmn;\u0026thinsp;4,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasalinferior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19,41\u0026thinsp;\u0026plusmn;\u0026thinsp;8,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24,66\u0026thinsp;\u0026plusmn;\u0026thinsp;9,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMidinferior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,15\u0026thinsp;\u0026plusmn;\u0026thinsp;7,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20,55\u0026thinsp;\u0026plusmn;\u0026thinsp;9,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,337\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eApicalinferior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15,92\u0026thinsp;\u0026plusmn;\u0026thinsp;6,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20,71\u0026thinsp;\u0026plusmn;\u0026thinsp;7,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,023\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasalanterior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19,14\u0026thinsp;\u0026plusmn;\u0026thinsp;8,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21,93\u0026thinsp;\u0026plusmn;\u0026thinsp;7,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,236\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMidanterior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16,74\u0026thinsp;\u0026plusmn;\u0026thinsp;6,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19,57\u0026thinsp;\u0026plusmn;\u0026thinsp;7,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,184\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eApicalanterior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16,54\u0026thinsp;\u0026plusmn;\u0026thinsp;6,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20,31\u0026thinsp;\u0026plusmn;\u0026thinsp;7,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGLS_3Chs (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,11\u0026thinsp;\u0026plusmn;\u0026thinsp;5,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21,38\u0026thinsp;\u0026plusmn;\u0026thinsp;3,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasalinferolateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23,68\u0026thinsp;\u0026plusmn;\u0026thinsp;8,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e32,97\u0026thinsp;\u0026plusmn;\u0026thinsp;12,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMidinferolateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,99\u0026thinsp;\u0026plusmn;\u0026thinsp;6,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19,1\u0026thinsp;\u0026plusmn;\u0026thinsp;6,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,954\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eApicallateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13,35\u0026thinsp;\u0026plusmn;\u0026thinsp;6,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16,0\u0026thinsp;\u0026plusmn;\u0026thinsp;6,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,097\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasalanteroseptum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23,33\u0026thinsp;\u0026plusmn;\u0026thinsp;9,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25,04\u0026thinsp;\u0026plusmn;\u0026thinsp;9,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,495\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMidanteroseptum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17,46\u0026thinsp;\u0026plusmn;\u0026thinsp;7,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,97\u0026thinsp;\u0026plusmn;\u0026thinsp;5,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,405\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eApicalseptum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12,45\u0026thinsp;\u0026plusmn;\u0026thinsp;6,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16,19\u0026thinsp;\u0026plusmn;\u0026thinsp;5,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,017\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: GLS_2Chs: Two-chamber view longitudinal strain, GLS_3Chs: Three-chamber view longitudinal strain, GLS_4Chs: Four-chamber view longitudinal strain\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eDuring the attack period, speckle tracking echocardiographic evaluation demonstrated impaired function in the inferior segments of the left ventricle (Table 4).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 5\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eComparison of Strain Echocardiographic Findings in the Attack Period of Groups with Mild and Moderate Disease Activity, Based on Pras Scoring\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEchocardiographic Parameters\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup with Mild Disease Activity (17)\u003c/p\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup with Moderate Disease Activity (19)\u003c/p\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean Difference\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGLS 4Chs %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,6 \u0026plusmn; 6,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21,3 \u0026plusmn; 5,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1,75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,381\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasal İnferoseptum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20,7 \u0026plusmn; 6,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,1 \u0026plusmn; 3,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,514\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMidinferoseptum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20,9 \u0026plusmn; 6,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23,7 \u0026plusmn; 3,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-2,51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,164\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eApicalseptum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15,9 \u0026plusmn; 10,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,8 \u0026plusmn; 9,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-2,89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,418\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasalanterolateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30,7 \u0026plusmn; 11,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33,5 \u0026plusmn; 11,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-2,38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,572\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMidanterolateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15,5 \u0026plusmn; 7,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19,7 \u0026plusmn; 5,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-3,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,123\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eApicallateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12,6 \u0026plusmn; 9,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14,2 \u0026plusmn; 9,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1,83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,589\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGLS 2Chs %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15,5 \u0026plusmn; 4,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,8 \u0026plusmn; 9,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-2,91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,102\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasalinferior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20,2 \u0026plusmn; 9,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19,0 \u0026plusmn; 8,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2,04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,531\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMidinferior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16,5 \u0026plusmn; 6,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20,1 \u0026plusmn; 8,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-4,12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,133\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eApicalinferior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13,8 \u0026plusmn; 6,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,3 \u0026plusmn; 7,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-4,95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,048\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasalanterior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17,0 \u0026plusmn; 6,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19,8 \u0026plusmn; 9,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-2,38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,421\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMidanterior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14,6 \u0026plusmn; 5,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,4 \u0026plusmn; 6,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-4,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,049\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eApicalanterior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15,5 \u0026plusmn; 7,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17,5 \u0026plusmn; 6,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-2,45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,346\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGLS 3Chs %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,4 \u0026plusmn; 6,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,5 \u0026plusmn; 2,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,859\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasalinferolateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20,5 \u0026plusmn; 6,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25,2 \u0026plusmn; 10,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-3,99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,233\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMidinferolateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19,6 \u0026plusmn; 9,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,2 \u0026plusmn; 4,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2,01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,451\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eApicallateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15,1 \u0026plusmn; 8,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11,7 \u0026plusmn; 4,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2,01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,415\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasalanteroseptum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23,1 \u0026plusmn; 9,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23,7 \u0026plusmn; 10,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0,72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,848\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMidanteroseptum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17,1 \u0026plusmn; 9,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18,2 \u0026plusmn; 6,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1,26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,651\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eApicalceptum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13,2 \u0026plusmn; 7,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11,5 \u0026plusmn; 5,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0,66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,785\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: GLS_2Chs: 2 cavities global longitudinal strain, GLS_3Chs: 3 chamber view longitudinal strain, GLS_4Chs: 4 chamber view longitudinal strain\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eComparison between mild and moderate disease groups during the attack period showed that right ventricular function was more affected in the moderate disease group (Table 5).\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;In patients with lymphopenia, it was observed that the right ventricular function was more severely affected during the attack phase compared to patients with normal lymphocyte count. The change in TAPSE measurements between the attack and remission periods was -16.1 \u0026plusmn; 6.9% in the patients with lymphopenia during the attack and 3.7 \u0026plusmn; 23.9% in the patients without lymphopenia. Statistically significant difference between the mean measurements was found (p=0.019).\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eComparison of Attack-Remission Changes According to Attack Treatment with Speckle Tracking Echocardiography\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSpeckle tracking echocardiography evaluations were re-analyzed for the comparison between the patients who received anakinra treatment during the attack (17 patients) and the patients who received only symptomatic treatment (21 patients). The percentage change between the attack and remission period in the measurement of the three-chamber basalinferolateral segment in the patients who received only symptomatic treatment during the attack was 84.5 \u0026plusmn; 96.1%. Meanwhile the change between the attack and remission period in the patients who received anakinra was 20.8 \u0026plusmn; 51.3%. A significant difference of averages was measured between the two groups (p=0.041)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we sought to establish a relationship between known markers of cardiac function and standard laboratory tests that could be easily accessed. Given our institutional access, we had a unique opportunity to obtain patient data and clinical assessment tools not easily found outside of our center. As such, this singularly positioned us to be able to ask more probing questions regarding the relationship between physiologic and anatomic changes that we see in FMF patients. \u0026nbsp;We determined that this would be important, as it would help provide a clinically relevant tool that can then be re-applied to patient care without necessitating additional changes in protocol. As such, we demonstrated that there were shifts in cardiac function as noted prior and showed that this correlated to shifts in neutrophil counts, C-reactive protein, and erythrocyte sedimentation rate.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOf particular note, there is a marked decrease in left and right ventricular function in FMF patients. This is especially apparent in the attack period in the left inferior segments. In addition, we found that right ventricular systolic function decreased more in the moderate disease subgroup in comparison to the mild disease subgroup (Table 1). Interestingly, there is a concurrent decrease in lymphocytes in the attack period compared to the remission period. In a previous study, 53% of the relatives of patients with FMF had a history of relatives diagnosed with FMF[1]. In our study, unlike the literature, 31 of our 38 patients (81.6%) had a family history of a relative diagnosed with FMF.\u003c/p\u003e\n\u003cp\u003eIn autoinflammatory diseases, acute phase reactants were found to be significantly higher during the attack period compared to the remission period. In some patients, acute phase reactants were reported to be elevated in the absence of clinical findings due to the persistence of subclinical inflammation.\u0026nbsp;[1; 4; 5]Similar to the findings in the literature, C-Reactive protein, and erythrocyte sedimentation rate\u0026nbsp;measurements were found to be significantly higher in the attack period compared to the remission period in our patient group when the attack and remission periods were considered. Again, similar to the findings in the literature, leukocyte and neutrophil values measured in our patients were significantly higher in the attack period compared to the control period.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAccording to prior studies, neutrophil production increases in response to cytokines and proteins formed during attack in inflammatory diseases. Due to this increase, neutrophil/lymphocyte ratio also increases. Stress is known to be a triggering factor for attacks in patients with FMF due to its increasing effect in the cortisol levels which leads to decrease in lymphocyte count (3). In our comparative analysis of blood counts, a significant decrease in lymphocyte count in the attack period was observed. It showed that the lymphocyte count reverted to the normal range during the remission period. Since there are no prior studies in terms of the subject, no external data comparison has been performed. In this case, as a limiting point, we could not biochemically evaluate stress hormones, cortisol levels and cytokine levels in our patients during the attack period. We think that this situation can be clarified with similar studies to be conducted in the future in patients with FMF.\u003c/p\u003e\n\u003cp\u003eIn the speckle tracking echocardiographic evaluation of the patients, statistically significant differences were found in the global longitudinal two chamber view, inferior and anterior sections when the attack and remission periods were compared. This suggests that these differences are related to the cytokines that are released during the inflammation period.\u0026nbsp;Studies on how\u0026nbsp;increased TNF-\u0026alpha; and\u0026nbsp;IL-1\u0026beta; levels\u0026nbsp;during an attack\u0026nbsp;may affect cardiac functions have shown that increased\u0026nbsp;TNF-\u0026alpha; expression decreases endothelium-dependent vasodilation in coronary arterioles. The mechanism responsible for this is decreased nitric oxide bioavailability and nitric oxide-dependent vasodilation\u0026nbsp;[18; 19]. Experimental studies have shown that injection of recombinant IL-1\u0026beta; (3 \u0026mu;g/kg) in experimental mice causes a decrease in myocardial contractility and systolic dysfunction\u0026nbsp;[20; 21].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn clinical studies, a single dose of 100 mg anakinra given to patients with rheumatoid arthritis increased coronary flow reserve by affecting myocardial contractility and relaxation through IL-1 blockade within 3 hours\u0026nbsp;[22].\u0026nbsp;In our evaluation of the speckle tracking echocardiographic measurements, we observed that patients who received anakinra treatment during the attack demonstrated faster improvement of the heart function in the three space basalinferolateral region compared to patients who did not receive anakinra.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn our study, we were not able to determine whether the decrease in left ventricular function during an attack period was due to the effect of inflammatory cytokines on the microvascular environment, or the changes in coronary flow velocity. In the healthy population, because of the variation in the coronary arteries that perfuse the posterior and inferior regions of the left ventricle, coronary flow velocity could not be associated with the involvement of these regions during an attack\u0026nbsp;[23].\u003c/p\u003e\n\u003cp\u003eConventional echocardiographic measurements (TAPSE) during the attack period for patients with normal lymphocyte counts, and lymphopenia showed a significant difference in right ventricular function. Moreover, TAPSE evaluations shown that the patients with lymphopenia demonstrated more changes than the patients with normal lymphocyte count, when attack and remission periods compared. Furthermore, the speckle tracking echocardiographic evaluation showed a significant alteration in three space midinferolateral area for the patients with lymphopenia.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe think that right ventricular systolic function was more affected in the lymphopenia group due to increased cytokines and inflammation. We believe that future studies in different autoinflammatory diseases will clarify this.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e\u0026nbsp;We demonstrated that cardiac function decreased in the left ventricular inferior segments during the attack period in our study group. We found that systolic function of the right ventricle decreased more in the moderate disease group than in the mild disease group during the attack period. We also found that the patient group with lymphopenia during the attack had decreased right ventricular function compared to the normal group.\u003c/p\u003e\n"},{"header":"Limitations","content":"\u003cp\u003e1. We evaluated our patient group within the 24-72-hour period of cardiac and biochemical findings during the attack period of the disease. We think that cardiac functions may have been detected differently in some patients because our patients were evaluated within 48 hours. We think that the results would be more meaningful if we could evaluate our patient group in a shorter and more specific period during the attack process.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2. We assumed that serum amyloid A, TNF alpha, IL 1 measurements may be more effective in evaluating the degree of inflammation during the attack period when we evaluate the cardiac involvement of our patients. In the light of this study, we plan to take these limitations into consideration in future studies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eAtr\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Early diastolic A wave measured by tissue Doppler,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCF\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;:\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eShortening fraction,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCK-MB\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;:\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eCreatine kinase-\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003emyocardial band\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;:\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eC-reactive protein\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eE-DT\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;:\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eE-wave deceleration time,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEF \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp; Ejection Fraction,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEmi\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;:\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eEarly diastolic E wave measured by Doppler Transmitral\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eESR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Erythrocyte sedimentation rate\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEtr\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Early diastolic E wave measured by tissue Doppler,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFMF \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;:\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eFamilial Mediterranean Fever\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGLS_2Chs\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Two-chamber global longitudinal strain,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGLS_3Chs\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp;Three-chamber global longitudinal strain,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGLS_4Chs\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Four-chamber global longitudinal strain,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIL \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;:\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eInterleukin\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIVSD\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;:\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eDiastolic diameter of the interventricular septum,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLVEDD\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Left ventricular end-diastolic diameter,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLVESD\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Left ventricular end-systolic diameter,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLVPWT\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Left ventricular posterior wall thickness,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMEFV \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Mediterranean Fever\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePro-BNP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;pro\u0026ndash;B-type natriuretic peptide\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRV FAC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026nbsp; : \u0026nbsp; \u0026nbsp;\u003c/strong\u003eRight ventricular\u0026nbsp;functional area,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSmi\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;:\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eEarly diastolic E wave measured by Doppler Transmitral,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStr\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Early diastolic S wave measured by tissue Doppler,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTAPSE \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; :\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Tricuspid Annular Plane Systolic Movements\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTNF \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;:\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Tumor necrosis factor\u003cstrong\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding Support and Author Disclosures\u003c/h2\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency, commercial or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHUMAN ETHICS AND CONSENT TO PARTICIPATE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki and approved by the\u0026nbsp;Istanbul University-Cerrahpasa Cerrahpasa Medical Faculty Institutional Review Board (Date:26/04/2022\u0026ndash;No:367672).\u0026nbsp;Detailed informed consent form was obtained from all patients included in the study and from the parents/legally authorized representatives of patients under 18 years of age.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eDATA AVAILABILITY\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author, upon reasonable request.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBarut K, Sahin S, Adrovic A, Sinoplu AB, Yucel G, Pamuk G, Aydin AK, Dasdemir S, Turanli ET, Buyru N, Kasapcopur O (2018) Familial Mediterranean fever in childhood: a single-center experience. Rheumatol Int 38:67-74\u003c/li\u003e\n\u003cli\u003eYildiz M, Haslak F, Adrovic A, Barut K, Kasapcopur O (2020) Autoinflammatory Diseases in Childhood. Balkan Med J 37:236-246\u003c/li\u003e\n\u003cli\u003eOzen S, Bilginer Y (2014) A clinical guide to autoinflammatory diseases: familial Mediterranean fever and next-of-kin. Nat Rev Rheumatol 10:135-147\u003c/li\u003e\n\u003cli\u003ePepper RJ, Lachmann HJ (2016) Autoinflammatory Syndromes in Children. Indian J Pediatr 83:242-247\u003c/li\u003e\n\u003cli\u003eBen-Chetrit E, Touitou I (2009) Familial mediterranean Fever in the world. Arthritis Rheum 61:1447-1453\u003c/li\u003e\n\u003cli\u003eOzdemir O, Agras PI, Aydin Y, Abaci A, Hizli S, Akkus HI, Fidan C (2012) Assessment of cardiac functions using tissue Doppler imaging in children with familial Mediterranean fever. Cardiol Young 22:188-193\u003c/li\u003e\n\u003cli\u003eKoca B, Kasapcopur O, Bakari S, Sonmez E, Oztunc F, Eroglu AG, Saltik L, Calay O (2012) QT dispersion and cardiac involvement in children with Familial Mediterranean fever. Cardiol Young 22:404-409\u003c/li\u003e\n\u003cli\u003eKalkan GY, Bayram NA, Erten S, Keles T, Durmaz T, Akcay M, Bozkurt E (2010) Evaluation of left ventricle function by strain imaging in patients with familial Mediterranean fever. Echocardiography 27:1056-1060\u003c/li\u003e\n\u003cli\u003eSari I, Arican O, Can G, Akdeniz B, Akar S, Birlik M, Tunca M, Akkoc N, Guneri S, Onen F (2008) Assessment of aortic stiffness and ventricular functions in familial Mediterranean fever. Anadolu Kardiyol Derg 8:271-278\u003c/li\u003e\n\u003cli\u003eBaysal T, Peru H, Oran B, Sahin TK, Koksal Y, Karaaslan S (2009) Left ventricular diastolic function evaluated with tissue Doppler imaging in children with familial Mediterranean fever. Clin Rheumatol 28:23-28\u003c/li\u003e\n\u003cli\u003eGangemi S, Manti S, Procopio V, Casciaro M, Di Salvo E, Cutrupi M, Ganci G, Salpietro C, Chimenz R, Cuppari C (2018) Lack of clear and univocal genotype-phenotype correlation in familial Mediterranean fever patients: A systematic review. Clin Genet 94:81-94\u003c/li\u003e\n\u003cli\u003eLopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK, Lai WW, Geva T (2010) Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr 23:465-495; quiz 576-467\u003c/li\u003e\n\u003cli\u003eVitarelli A, Giordano M, Germano G, Pergolini M, Cicconetti P, Tomei F, Sancini A, Battaglia D, Dettori O, Capotosto L, De Cicco V, De Maio M, Vitarelli M, Bruno P (2010) Assessment of ascending aorta wall stiffness in hypertensive patients by tissue Doppler imaging and strain Doppler echocardiography. Heart 96:1469-1474\u003c/li\u003e\n\u003cli\u003eKaluzynski K, Chen X, Emelianov SY, Skovoroda AR, O\u0026apos;Donnell M (2001) Strain rate imaging using two-dimensional speckle tracking. IEEE Trans Ultrason Ferroelectr Freq Control 48:1111-1123\u003c/li\u003e\n\u003cli\u003eReisner SA, Lysyansky P, Agmon Y, Mutlak D, Lessick J, Friedman Z (2004) Global longitudinal strain: a novel index of left ventricular systolic function. J Am Soc Echocardiogr 17:630-633\u003c/li\u003e\n\u003cli\u003ePras E, Livneh A, Balow JE, Jr., Pras E, Kastner DL, Pras M, Langevitz P (1998) Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet 75:216-219\u003c/li\u003e\n\u003cli\u003eOzen S, Aktay N, Lainka E, Duzova A, Bakkaloglu A, Kallinich T (2009) Disease severity in children and adolescents with familial Mediterranean fever: a comparative study to explore environmental effects on a monogenic disease. Ann Rheum Dis 68:246-248\u003c/li\u003e\n\u003cli\u003eZhang C, Xu X, Potter BJ, Wang W, Kuo L, Michael L, Bagby GJ, Chilian WM (2006) TNF-alpha contributes to endothelial dysfunction in ischemia/reperfusion injury. Arterioscler Thromb Vasc Biol 26:475-480\u003c/li\u003e\n\u003cli\u003eZhang C, Wu J, Xu X, Potter BJ, Gao X (2010) Direct relationship between levels of TNF-alpha expression and endothelial dysfunction in reperfusion injury. 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Circulation 117:2662-2669\u003c/li\u003e\n\u003cli\u003eSharif D, Sharif-Rasslan A, Shahla C, Khalil A, Rosenschein U (2015) Differences in coronary artery blood velocities in the setting of normal coronary angiography and normal stress echocardiography. Heart Int 10:e6-e11\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"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":"Familial Mediterranean Fever Attack, Speckle Tracking Echocardiography, Cardiac Functions","lastPublishedDoi":"10.21203/rs.3.rs-3933795/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3933795/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eFamilial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease characterized by recurring serosal inflammation. Cardiac involvement in FMF commonly manifests as pericarditis and pericardial effusion, however there is limited research on myocardial function. This study aimed to assess cardiac functions during active inflammation and remission periods of FMF patients and investigate the cardiac effects of inflammation during the attack period.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThirty-eight FMF patients without additional cardiac diseases were included in the study. Demographic characteristics, clinical symptoms, family history, and \u003cem\u003eMEFV\u003c/em\u003e gene analysis results were obtained retrospectively. Blood tests, blood pressure measurements, electrocardiogram evaluations, conventional echocardiography, and speckle-tracking echocardiography were performed during the attack and remission periods. Disease severity was assessed using the Pras scoring system.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eDuring the attack period, FMF patients exhibited significantly higher leukocyte count, neutrophil count, C-reactive protein, and erythrocyte sedimentation rate compared to the remission period (p\u0026thinsp;\u0026lt;\u0026thinsp;0.005). Speckle-tracking echocardiography revealed decreased function in the inferior segments of the left ventricle during the attack period (p\u0026thinsp;\u0026lt;\u0026thinsp;0.005). Right ventricular function was more affected in the moderate disease group. FMF patients with lymphopenia during the attack demonstrated more impaired right ventricular function compared to those with normal lymphocyte count.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eFMF patients experience cardiac abnormalities during active inflammation, highlighting the importance of monitoring cardiac functions in these patients. Speckle-tracking echocardiography can provide valuable insights into cardiac involvement in FMF. These findings emphasize the cardiac impact of FMF inflammation and the significance of long-term cardiac function monitoring in the management of FMF patients.\u003c/p\u003e","manuscriptTitle":"Examination of Cardiac Functions During Acute Attack and Remission Period in Children With Familial Mediterranean Fever","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-14 18:28:02","doi":"10.21203/rs.3.rs-3933795/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-03-23T23:21:56+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-23T21:55:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-14T12:24:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"9c5cfb66-d99c-4f48-9b27-d52514555d9b","date":"2024-02-28T16:22:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-02-13T07:17:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-02-12T13:50:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-12T13:49:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Pediatrics","date":"2024-02-06T12:01:20+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":"edc198cd-f353-4caa-920f-74498d6c1e2e","owner":[],"postedDate":"February 14th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-05-01T22:24:32+00:00","versionOfRecord":{"articleIdentity":"rs-3933795","link":"https://doi.org/10.1007/s00431-024-05570-y","journal":{"identity":"european-journal-of-pediatrics","isVorOnly":false,"title":"European Journal of Pediatrics"},"publishedOn":"2024-04-26 22:24:32","publishedOnDateReadable":"April 26th, 2024"},"versionCreatedAt":"2024-02-14 18:28:02","video":"","vorDoi":"10.1007/s00431-024-05570-y","vorDoiUrl":"https://doi.org/10.1007/s00431-024-05570-y","workflowStages":[]},"version":"v1","identity":"rs-3933795","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3933795","identity":"rs-3933795","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}