No 73 (2013)
ORIGINAL ARTICLES
A. G. Strelnikov,
A. B. Romanov,
S. N. Artemenko,
I. G. Stenin,
D. A. Elesin,
R. T. Kamiev,
D. V. Losik,
S. A. Bayramova,
A. M. Chernyavsky,
E. A. Pokushalov
5-9 133
Abstract
To compare effectiveness of management of subjects with newly diagnosed atrial fibrillation (AF) after aorto-coronary bypass grafting surgery (ACBG) alone and in combination with epicardial pulmonary vein isolation (PVI), 35 patients aged 62±5 years (28 men) were examined and surgically treated. The patients were randomized into two following groups: ACBG alone (Group I, n=17) and ACBG accompanied by epicardial PVI (Group II, n=18). Freedom from AF (AF burden <0.5% according to the loop recorder data) within 18 month study period was the primary endpoint. Secondary endpoints were as follows: AF burden according to the loop recorder data within the study, occurrence of thromboembolic and post-operative complications. In the course of the surgery, bipolar ablation clamp was put on the right pulmonary veins and their circular ablation was carried out. On the left side, ablation was performed using a similar technique on an “inverted” heart. All ablations were performed on the left atrial myocardium. No additional ablative lines or the left auricle resection were performed. Intra-operational assessment of the entrance block and exit block was carried out in all study subjects. Then, the ABCG surgery was carried out according to the commonly accepted technique. As the final step of surgery, Reveal XT device (Medtronic, Inc.) was implanted. All patients were free from antiarrhythmic therapy before and after the surgery within the entire study period; however all patients took β blockers. Besides, all patients received anticoagulant therapy for no less than 6 months. Within the 18 month follow-up period, total freedom from paroxysms of atrial fibrillation/flutter/tachycardia (i.e., AF burden <0.5% according to the loop recorded data; log-rank criterion, p=0.007) was detected in 16 patients (88.9%) of 18 ones of Group II and 8 patients (47.1%) of 17 ones of Group I. None of the above patients took antiarrhythmics. No significant correlation was found between the pre-operative subject data and AF recurrence. At the end of follow-up period, the AF burden according to the loop recorder data was 7.8±5.1ΰ/ο and 1.6±1.8ΰ/ο in Group I and Group II, respectively (p<0.001). Two patients of 11 (18.2% of both groups) with AF recurrence had asymptomatic AF. During the follow-up period, no thromboembolic events in the study subjects were documented. Thus, in patients with newly diagnosed AF and indications for direct myocardial revascularization, ACBG in combination with epicardial PVI can prevent recurrence of AF.
10-15 142
Abstract
To improve outcomes of surgical treatment of patients with post-infarction left ventricular aneurysms (LVA) and ventricular arrhythmias by means of radiofrequency ablation (RFA) and optimal excision of the damaged myocardium, 168 patients were examined and surgically treated. Before aneurysmectomy, the electrophysiological study with electro-anatomic CARTO reconstruction of the left ventricle (LV) was performed. The arrhythmogenic zones revealed were labeled using radiofrequency labels with the aid of ablative electrode (power of radiofrequency current: 45 W; irrigation with normal saline: 17 ml/min). During the operation, resection of the damaged endocardium was performed according to the radiofrequency labels. As the next step of the surgery, the LV endoventricular plastic repair was performed in accordance with the commonly accepted technique. Endocardectomy was performed in 74 patients of study group. The control group consisted of 94 patients with no endocardectomy performed. The patients of study and control groups aged 54.4±2.1 years and 56.2±1.6 years, respectively. All patients had a history of myocardial infarction complicated by LVA which occurred 3.7±0.9 years and 3.9±1.2 years before the surgery. In 130 patients of both groups, the aneurysm resection and LV reconstruction were carried out according to the Dor technique in 130 patients, using the modification by Menicanti in 38 patients. In 26 patients of both groups, the mitral annuloplasty was made. Aorto-coronary bypass grafting was performed in all subjects. One patient (1.4%) of study group died in hospital, the mortality in control group made up 6.4%. In 8 patients of the same group, ventricular arrhythmias in early post-operation period were detected. The late mortality (one year after surgery) was 4.1% in study group and 12.8% in control group. When analyzing the study data, subgroups of subjects in whom the electrophysiological study was performed post-operatively were additionally considered. Subgroup A consisted of 38 patients of study group, Subgroup B, of 32 patients of control group. In the Subgroup A subjects, an improvement of electrophysiological indices was revealed: areas of “electric scar” were located only in the endocardial patch, areas with the decreased potential totally disappeared, transition zones (0.5 1.5 mV) were local, without possibility of both development of re-entry and induction of ventricular tachycardia. In only one patient of Subgroup A with incomplete endocardectomy, monomorphic ventricular tachycardia was induced. In Group B, spontaneous episodes of ventricular tachycardia were documented in 5 cases; ventricular tachycardia was induced during the electrophysiological study in 7 cases (35% of subjects). In 11 ones of them, cardioverters-defibrillators were implanted. Thus, when treating surgically post-infarction LVA, endocardial, resection of scar and transition areas of LV is critical for preventing episodes of ventricular tachycardia. Endocardial electrophysiological study and electro-anatomic LV reconstruction permit one to reveal potential sites of the re-entry development. Radiofrequency labels made during the endocardial electrophysiological study permit one to locate precisely the damage area during the open-heart surgery to carry out endocardectomy in an optimal way.
16-24 259
Abstract
To assess parameters pertinent to duration and dispersion of ventricular repolarization in patients with Types 1 and 2 of the long QT syndrome during the changing heart rate at the background of gradual physical exercise test, 74 pediatric patients were examined. Group I consisted of 45 pediatric patients aged 13.9±3.6 years (4 17 years; boys: 36%) with genetically confirmed long QT syndrome of Type 1 (LQT1). Group II consisted of 29 patients with the KCNH2 gene mutations (long QT syndrome of Type 2, LQT2) aged 12.8±3.1 years (5 17 years; boys: 35%). By the study inclusion, 26 patients of Group LQT1 and 18 subjects of Group LQT2 have received specific antiarrhythmic therapy. The stress test was performed on treadmill according to the Bruce protocol until reaching target heart rate of 170 bpm or development of fatigue. QT interval was measured in Lead II at rest and on exertion. QTC was calculated according to the Bazett’s formula. Measured were the QTP interval from the QRS complex onset to the T-wave peak and the peak-end QT interval (QTP-E) as the difference between QT and QTP. The QT interval dispersion (QTD) was calculated as the difference between the longest and shortest QT intervals in 12 leads. The ΔQTC index was used for assessment of the heart rate response to physical exertion ^QTC1 is QTC at exertion minus QTC pre-exertion) and of recovery of the initial QTC levels ^QTC2 is QTC at exertion minus QTC in the recovery period; ΔQTC3 is QTC pre-exertion minus QTC in the recovery period). The QT and QTC interval duration before exertion were significantly longer in Group LQT2, whereas longer peak exertion QT and QTC intervals were found in Group LQT1. Thus, the QTC dynamics at exertion in Groups LQT1 and LQT2 were differently directed: it increased in the patients of Group LQT1 and decreased in Group LQT2. ΔQTC1 was significantly higher in Group LQT1 due to an increased QTC interval at exertion. The QTP interval did not differ initially in the groups and became significantly longer at exertion in Group LQT1. The same trend was found for the QTPC interval. QTD at baseline and pre-load was more pronounced in the patients of Group LQT2; however, with the heart rate rise, the difference diminished and, at exertion, the index did not significantly differ in both groups. The QTP-E index at baseline in Group LQT2 was higher than in Group LQT1; however, with the heart rate increase at exertion, similar values were observed in both groups. The ΔQTC2 values were significantly higher in Group LQT1. In the Group LQT1 subjects with a history of syncope, the following indices were higher than in children without syncope: QT pre-exertion, QTP pre-exertion, QT exertion, QTP exertion, QTD exertion, QT recovery, and QTP recovery. The values of heart rate at exertion and in the recovery period were significantly lower in the above group. The peculiar feature revealed is related to use of β-blockers in a majority of patients with syncope. Thus, the most widespread type of the long QT syndrome (LQT1) is characterized by a considerably increased QTC interval at the background of heart rate increase at exertion, which is also reflected in increased ΔQTC and QTPC indices. In LQT2, the QTC interval shortening is more pronounced than in LQT1. For LQT2 subjects, a decreased dispersion of repolarization at exertion (intervals QTD and QTP-E) was shown.
25-29 180
Abstract
To assess total cholesterol and total phospholipids as well as the platelet calcium ion kinetics, 197 children aged 9.4±3.3 years (2 13 years) were examined, including 167 patients with the sinus node dysfunction (SND) and 30 healthy children. Based on the autonomic nervous system state, the following groups were identified: Group I consisted of pediatric patients with idiopathic SND, Group II, of children with SND at the background of the autonomic dysfunction syndrome. In all children, blood hematology and chemistry tests were performed; special chemistry tests were performed in 155 children. Total cholesterol in platelets of children with SND was higher 1.8 times in patients with idiopathic SND and 2.3 times in patients with SND at the background of autonomic dysfunction as compared with healthy children. Phospholipids in both groups of pediatric patients with SND had no significant difference with that in healthy children. The cholesterol/phospholipids coefficient in both groups of children with SND was significantly higher than in healthy children. In Group II, IO as an index of initial (para-membrane) level of ionized calcium had a tendency to an increased level as compared with Group I. Thus, in pediatric patients with SND at the background of autonomic dysfunction, as opposed to the patients with idiopathic SND, increased total cholesterol was observed, which gives evidence of an increased membrane microviscosity. A lower Ca++ concentration at the first minute, the maximal one at the 15 th minute, and an increased time to the peak intensity of fluorescence are peculiar features of platelets in pediatric patients with idiopathic SND. Slow Ca++ kinetics as compared with the data of pediatric patients with SND at the background of autonomic dysfunction gives evidence about a depressed transmembrane Ca++ transport.
30-33 144
Abstract
To study electrophysiological peculiar features of the heart conduction system parameters in pediatric patients with supraventricular tachycardias (SVT) with different PQ interval duration, 172 children were examined. Group I consisted of 55 children with short PQ interval, Group II, of 117 children with the normal PQ interval. Transesophageal electrophysiological study was performed in all patients. In the short PQ interval group, patients with paroxysmal atrio-ventricular nodal reciprocal tachycardia (PAVNRT) constituted Group 1 and patients with paroxysmal orthodromic atrio-ventricular reciprocal tachycardia (PAVRT), Group 2. In control group with the normal PQ interval, patients with PAVNRT constituted Group 3 and patients with PAVRT, Group 4. In the children with the short PQ interval, the Wenckebach point was significantly higher than in those with the normal PQ interval (200±30 bpm and 180.5±30.6 bpm, respectively; p=0.01). In the children with the short PQ interval, presence of fast atrio-ventricular conduction (Wenckebach point >200 bpm) was significantly more widespread (54.2% and 31.2%, respectively; p<0.05). In the children with PAVRT, its rate did not significantly differ in both groups (RR: 294.5±37.9 ms and 309.3±39.3 ms, respectively, p>0.05). In the pediatric patients with the short PQ interval, a statistically significantly shorter PAVNRT cycle duration was revealed as opposed to the patients with the normal PQ interval (279.2±57.9 ms and 322.9±54.3 ms; p=0.002). Thus, presence of the short PQ interval has no effect on the PAVRT cycle length but contributes to a shorter PAVNRT cycle length. In the pediatric patients with SVT, occurrence of atrial fibrillation and heart rate during atrial fibrillation did not significantly differ in the case of short and normal QT intervals.
34-42 220
Abstract
To study peculiar features of heart rate turbulence (HRT) and microvolt T-wave alternations (mTWA) in patients with hypertrophic cardiomyopathy and arterial hypertension with the left ventricular hypertrophy (LVH), examined were 50 patients aged 40.6±18.3 years with hypertrophic cardiomyopathy (25 men and 25 women), 71 patients aged 59.2±10.9 years with arterial hypertension (34 men and 37 women), and 90 subjects aged 47.8±20.7 years (48 men and 42 women) free of cardiovascular diseases. The examination was carried out, which included collection of historical data, physical examination, echocardiography, and ECG Holter monitoring. During ECG Holter monitoring, mTWA and HRT were assessed. The turbulence onset (TO) and turbulence slope (TS) indices were calculated when assessing HRT. Based on the results of echocardiographic assessment, the patients with arterial hypertension were distributed into two following subgroups: subjects with LVH (14 men and 21 women aged 59.3±10.4 years) and patients without LVH (20 men and 16 women aged 59.1±11.4 years). The control group was divided into 2 subgroups, as well. Subgroup 1 (24 men and 26 women aged 38.6±20 years) was used for comparison with the hypertrophic cardiomyopathy subjects, Subgroup 2 (24 men and 16 women aged 59±16 years), for comparison with arterial hypertension subjects. Alterations of the first HRT were noted in 18% of patients with hypertrophic cardiomyopathy and 1 patient of control group (2%, p<0.05%). The analysis of mTWA parameters showed that the hypertrophic cardiomyopathy subjects were characterized by higher values of mTWA05:00 as compared with the control group. The correlation analysis in the patients with hypertrophic cardiomyopathy did not show significant correlation of mTWA indices with the width of the left ventricular (LV) myocardium, excluding mild negative correlation of the inter-ventricular septum width and mTWA100 in Lead II in FA 1/32 (rS=-0.320, p<0.05). Thus, the patients with hypertrophic cardiomyopathy as as opposed to control group are characterized by a higher occurrence of HRT disturbances (mainly, TO) and higher levels of mTWA recorded in early pre-morning hours. However, the correlation of the alterations observed with the LVH extent either was not revealed or was of the minimal extent. In patients with arterial hypertension and LVH, the HRT alterations were revealed more frequently than in control group (40% and 12.5%, respectively; p<0.05). The correlation analysis in the overall patient group with arterial hypertension (n=71) showed a slight positive correlation of TO with the posterior wall width (rS=0.376, p<0.05). The analysis of mTWA parameters showed significantly higher levels of mTWA05:00 (FA 1/8 and 1/32, Lead I) in the patients with arterial hypertension and LVH as compared with control group. Thus, the patients with LVH due to arterial hypertension and hypertrophic cardiomyopathy are characterized by a higher incidence of HRT alterations and higher levels of mTWA05:00 as opposed to the subjects free of cardiovascular diseases; however, the correlation of the above alterations with the LVH extent is either absent (mTWA05:00) or is minimal (TO).
43-48 340
Abstract
To reveal main signs of the sinus node dysfunction (SND) in premature newborns after perinatal hypoxia according to the Hotel monitoring data (heart rate analysis), 139 newborns were examined. Group I consisted of 54 premature newborns, gestational age: 30 36 weeks, of body mass of no less than 1,300 g (2,145.3±566.41 g). Group II included 43 premature newborns of 31 36 weeks of gestation and body mass of no less than 1,700 g (2,460.8±369.97 g). Group III (control) included 42 mature newborns. The instrumental examination included neurosonoraphy, standard ECG at rest, echocardiography, and ECG Holter monitoring performed at 18 30 days of life. In Group I as compared with Group III, a higher minimal and mean heart rate during sleep and wakefulness and a lower difference between maximal and minimal heart rate (AHR) were revealed. Circadian index was significantly lower in Group I than in Group II. The significant difference was found for mean, maximal, and minimal heart rate during sleep between Group II and Group III, they were significantly higher in Group II. Circadian index in Group III (mature newborns) was significantly higher than in Groups I and II. No diagnostically significant cardiac arrhythmia was observed in any group of children examined. Among the conduction disturbances revealed, pauses mainly due to sinus arrhythmia and second-degree sino-atrial block were of a special interest. The time-domain indices of heart rate variability were significantly lower in Groups I and II, as opposed to Group III. No significant inter-group differences in spectral heart rate variability indices were revealed. Thus, heart rate in premature newborns, as opposed to mature newborns, is characterized by tachycardia, rigidity, and decreased rate dispersion. The maximal duration of the heart rate pauses in mature newborns was 786 ms, in premature newborns without severe perinatal hypoxia, 816 ms. In premature newborns after severe perinatal hypoxia, at the background of pronounced tachycardia during the entire day and night as well as rigid circadian heart rate profile, long heart rate pauses were revealed, in some patients up to asystole; this can be considered SND.
49-53 165
Abstract
To compare accuracy of non-invasive topical diagnosis of ventricular arrhythmias using the results of epicardial and combined epi-endocardial mapping and the data of intra-cardiac electrophysiological study, 94 patients (35 men and 59 women) aged 20 67 years (mean age: 43.5 years) with ventricular arrhythmias of different origin and location were examined. In all patients, the non-invasive electrophysiological study was carried out, which included surface ECG in 240 leads, spiral computed tomography with the data processing to locate an area of the earliest activation, corresponding to the arrhythmogenic focus projection. According to the data of intra-cardiac electrophysiological study and successful radiofrequency ablation, in 58 patients, the arrhythmogenic focus was located in the right ventricle outflow tract (RVOT): in 3 patients, in the anterolateral area of RVOT; in 8 patients, on the anterior wall of RVOT; in 20 subjects, in the antero-septal area of RVOT; in 23 patients, in the septal area of RVOT; and in 4 subjects, in the postero-septal area of RVOT. The combined epi-endocardial mapping in 56 cases showed the same arrhythmogenic focus location, in 2 patients, discrepancies were revealed. When using epicardial mapping, the arrhythmogenic focus was precisely located in 48 patients. In 8 patients, according to the data of the intra-cardiac electrophysiological study and successful radiofrequency ablation, the arrhythmogenic focus was located in the right ventricle inflow tract (RVIT): in 2 patients, in basal segments of the free wall; in 1 patient, in apical segments of the free wall; in 1 patient, in the antero-septal area on the border between apical and medial segments of the right ventricle; and in 4 patients, in parahisian area, under the tricuspid valve annulus. The epi-endocardial mapping in 6 cases showed the same arrhythmogenic focus location, in 2 patients, discrepancies were revealed. When using epicardial mapping, the arrhythmogenic focus was precisely located in 3 patients. In 12 patients, according to the data of intra-cardiac electrophysiological study and successful radiofrequency ablation, the arrhythmogenic focus was located in the left ventricle outflow tract (LVOT): in 3 patients, in the projection of non-coronary aortic sinus; in 2 patients, on the border between of the right and left aortic sinuses; in 2 patients, in the projection of the right aortic sinus; and in 5 patients, in the projection of the left aortic sinus. The epi-endocardial mapping showed the same arrhythmogenic focus location in 11 cases. During epicardial mapping, it was possible to locate the arrthythmogenic focus precisely in 7 patients only. In 16 patients, according to the data of intra-cardiac electrophysiological study and successful radiofrequency ablation, the arrhythmogenic focus was located in the left ventricle inflow tract (LVIT): in 2 patients, on the boundary between medial apical segments in the postero-septal position of the left ventricle; in 2 patients, in the apical part of intra-ventricular septum; in 1 patient, in basal parts of the anterior wall; in 1 patient, in basal parts of the lateral wall; in 4 patients, in basal parts of the posterior wall; in 3 patients, in basal parts of LV, in postero-septal location; and in 3 patients, ventricular extrasystoles originated from the left ventricle papillary muscle. The epi-endocardial mapping showed the same arrhythmogenic focus location in 10 cases, epicardial pacing showed the same results. Thus, the topical diagnostics of ventricular arrhythmias based on the epi-endocardial mapping data permits one to locate arrhythmogenic foci with a rather high accuracy.
E. V. Lyan,
G. A. Gromyko,
A. S. Klyukvin,
F. A. Tursunova,
A. N. Morozov,
A. I. Kazakov,
A. B. Merkuryeva,
S. M. Yashin
54-57 145
Abstract
To assess acute recurrence and concealed conduction in the pulmonary vein (PV) antrum, 134 patients aged 56±8.6 years with paroxysmal and persistent atrial fibrillation (AF) with documented indications to radiofrequency ablation (RFA) were examined. During the operation, the anatomic map of the left atrium (LA) was constructed; radiofrequency applications were made on the perimeter of the PV antrums. Ipsilateral PVs were isolated as a single whole (en bloc). Upon isolating pulmonary veins, the “point of final isolation” (PFI) was marked. In case of development of acute recurrence in PVs, during the observational period (30 min), additional radiofrequency applications were made in the “break” area. After the observational period, the ATP test was carried out. In the case of recording of concealed conduction in PV, additional radiofrequency applications were made in the area of transitory “break”. The duration of the procedure was 123±18 min, of the X-ray exposure (fluoroscopy), 23±6.7 min. In all 134 cases, all PVs were isolated (268 ipsilateral couples). In the left antrum, PFI were located in the left atrium crest in more than in 50% of cases. In the right antrum, PFI were located on the posterior wall and were adjacent to the left atrium “roof’ in more than 60% of cases. In the observational period, acute recurrence was noted in 84 of 134 patients (63%), in total in 94 of 238 couples (35%) of ipsilateral PVs. During the ATP test, in 31 of 134 patients (23%), the concealed conduction into at least one ipsilateral vein was revealed, in total in 33 of 268 couples (12%). Thus, acute recurrence takes place in a considerable number of patients who receive RFA of AF. The location of acute recurrence and concealed conduction is inhomogeneous and is related to the peculiar features of RFA.
58-63 246
Abstract
To clarify advantages of the method of long-term ECG monitoring, assess its diagnostic value with regard to rare arrhythmic events, and document its correlation (or lack of correlation) with clinical symptoms, 84 patients (27 women and 57 men) aged 48.3±22.6 years (7 months - 80 years) were examined. Twenty nine patients had arterial hypertension, 22 ones had coronary artery disease; cardiomyopathy of undetermined origin was diagnosed in 4 patients, dilated cardiomyopathy, in 2 ones, and hypertrophic cardiomyopathy, in 2 ones. The systemic connective tissue dysplasia was revealed in 1 patient, idiopathic pulmonary hypertension, in 1 patient, and syndrome X, in 1 patient. In 23 subjects, cardiac arrhythmias were considered idiopathic. Before long-term ECG monitoring, the patients were counseled in depth in ECG transfer through the Internet, the diary was given for recording subjective feelings, additional electrodes for replacement and recommendations for daily activities during long-term ECG monitoring were given, as well. The long-term ECG monitoring device with telemetric control was installed to study subjects, in which the system of 3 canal ECG recording of 7 leads was used. A laptop was also given to the study patients to be used for ECG upload into the server. When receiving the information on the server via the Internet, a physician analyzed it using the KTResult 3 software product. Indications to long-term ECG monitoring were as follows: symptomatic palpitations and painful irregular heartbeats, which were not recorded during previous Holter monitoring, in 69 patients and syncope/pre-syncope of unknown origin, in 15 patients. The duration of long-term ECG monitoring with the telemetric control was 7.9±3.2 days (4 39 days). During long-term ECG monitoring, the correlation of palpitations and irregular heartbeats with cardiac arrhythmias was documented in all 69 study subjects: ventricular tachycardia was documented in 31 subjects, paroxysmal atrial fibrillation/flutter, in 14 patients, paroxysms of sustained atrial tachycardia, in 8 subjects, and sinus tachycardia, in 16 patients. In 15 patients with complaints of syncope or pre-syncope, their correlation with cardiac arrhythmias was confirmed only in 5 cases. No complications during long-term ECG monitoring were documented. The authors’ experience in the long-term ECG monitoring gives evidence that a novel effective technique has been introduced which permits one to speed up the diagnosis of severe cardiac arrhythmia, contributes to confirmation/exclusion of arrhythmic origin of rare syncope and episodes of palpitations. This, in its turn, can contribute to selection of the optimal treatment strategy, including timeliness of surgical procedures (implantation of pacemakers and cardioverters-defibrillators, radiofrequency catheter ablation). The novel method will be indeed of importance in case of conservative management of arrhythmic patients.
ПИСЬМО В НОМЕР
CASE REPORTS
A. V. Yakovlev,
N. A. Andryushina,
S. V. Ponomarev,
A. K. Snegirkova,
I. M. Felikov,
N. F. Yakovleva,
A. N. Turov
65-66 191
Abstract
A clinical case report is given of a 65 year old female patient with obesity, arterial hypertension, diabetes mellitus, and syndrome of obstructive sleep apnoe associated with multiple episodes of non-sustained ventricular tachycardia, with a positive effect of CPAP therapy.
67-70 146
Abstract
A clinical case report is given of a 55 year old female patient with dilated cardiomyopathy, in whom, during implantation of cardiac resynchronization device with defibrillating function, a bimetallic stent was used for fixation of the left ventricular electrode in the coronary sinus vein.
71-74 185
Abstract
A clinical case report is given of a patient with a history of myocardial infarction with episodes of palpitations leading to syncope, in whom, in the course of endocardial electrophysiological study, stimulation entrainment mapping was used, which permitted one to conduct radiofrequency catheter ablation of re-entry ventricular tachycardia.
REPORT
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ISSN 1561-8641 (Print)
ISSN 2658-7327 (Online)
ISSN 2658-7327 (Online)