INTRODUCTION
The term early repolarization (ER) is often used to describe morphological changes called notch or slurring, where the end of the QRS junction the ST segment (with or without ST elevation) and its prevalence is reported from 2% to 31% (1). Previously, ER was mostly considered a benign electrocardiographic sign. In 2008, Haïssaguerre et al. (2) published their study, in which they reported that there may be a relationship between ER and idiopathic ventricular fibrillation. In subsequent studies, it has been reported that there is a relationship between ER and both atrial tachycardias and arrhythmic death (3,4). Furthermore, similarities in responses to physiological changes and pharmacological agents between Brugada syndrome (BrS) and ER have been demonstrated (5).
Atrioventricular nodal reentrant tachycardia (AVNRT) is a regular supraventricular tachycardia caused by dual pathways (usually slow/fast) within the atrioventricular node and in occasionally the peripheral atrial tissue. It has been reported by the study published by Hasdemir et al. (6) that BrS, which has close similarities with ER, may have co-existence with AVNRT. In our study, we investigated the relationship between the morphological changes (the ER patterns) observed in the junction region (J point) between complete depolarization and repolarization of the action potential curve with AVNRT.
METHODS
The present study was conducted as a single-centered retrospective and descriptive study. Seventy six patients who were underwent ablation therapy due to AVNRT in the electrophysiology laboratory of University of Health Sciences Türkiye, Bakırköy Dr. Sadi Konuk Hospital between 2019-2022 were included in the current study. All AVNRT patients underwent successful ablation after the diagnosis was confirmed with differential maneuvers. Of these 76 patients, 12 patients had fascicular block, branch block, or fragmented QRS on basal electrocardiogram, 2 patients had ejection fraction below 50%, 2 patients had left ventricular hypertrophy, 2 patients had frequent ventricular extra beats after the procedure and were excluded from the study. The data of the remaining 53 patients without uncontrolled hypertension, chronic kidney disease, or stenosis of any coronary artery above 50%, which are our other criteria for exclusion, were analyzed and these patients were determined as the AVNRT group. Fifty healthy volunteers, who were similar to the AVNRT group in terms of their demographic and clinical characteristics and did not have any arrhythmic complaints, were identified as a control group.
ER morphologies were defined based on a consensus report published by Macfarlane et al. (7) in 2015. Accordingly, if there was a positive deflection of at least 0.1 mV above the isoelectric line after the onset of the J point, it was defined as a notch, if there was an angulation of more than 10% in the last half of the descent of the R wave, it was defined as slurring. If there is at least 0.1 mV ST segment above the isoelectric line after 100 ms from the beginning of the J point, was defined as the ST elevation (excluding leads V1 to V3).
This study was approved by the University of Health Sciences Türkiye, Bakırköy Dr. Sadi Konuk Training and Research Hospital Clinical Research Ethics Committee (decision no: 2022-16-06, date: 15.08.2022) and conducted in accordance with the principles of the Helsinki Declaration. Written informed consent was obtained from all the participants.
Statistical Analysis
Demographic characteristics of patients and collected data were entered into IBM® SPSS® (the Statistical Package for the Social Sciences) Statistics version 23. Variables were characterized using mean and percentage values were used for qualitative variables. Categorical variables were expressed using frequency and percentage, and numerical variables expressed using mean ± standard deviation. The normality of the distribution of quantitative variables was evaluated using the Kolmogorov-Smirnov test. To compare the two independent groups, the Student t-test for parametric numerical variables and the Mann-Whitney U test for nonparametric variables were used. Categorical variables were compared with the Pearson chi-square test. Statistical significance was considered p<0.05.
RESULTS
The mean age of the 103 patients included in the study was 47.11±12.79 years in the AVNRT group and the mean age of the control group was 44.88±13.02 years. There were 34 (64.2%) female individuals in the AVNRT group and 31 (62%) female individuals in the control group. No statistically significant difference was found between the two groups in terms of demographic, clinical, echocardiographic, and laboratory parameters (Table 1).
A comparison between both genders in terms of ER and its subtypes is shown in Table 2. Of the 65 female individuals included in the study, 16 (24.6%) and 12 (31.6%) of the 38 male individuals had any type of ER morphological changing; however, this difference between both genders was not statistically significant (p=0.495). When the subgroup analysis of the detected ER types was performed, it was found that slurring with ST elevation was statistically significantly higher in males than in females (p<0.001). The slurring without ST elevation type ER was determined to be significantly higher in female individuals compared with male individuals (p=0.002). Individuals were divided into two groups by accepting the cut-off value of 40 years, and no significant difference was found between the two groups in terms of the presence of ER and its subtypes (Table 3).
While 16 (30%) patients in the AVNRT group had any type of change in ER morphology, 12 (24%) individuals in the control group had any type of change in ER morphology. Although ER patterns were numerically more frequent in the AVNRT group compared with the control group, this difference was not statistically significant (p=0.480). Notch -type ER was observed in only 1 patient in the AVNRT group. All types of ER -detected individuals in the control group was the slurring type ER. ER with ST elevation was determined in 3 patients in the AVNRT group and in 4 volunteers in the control group. There was no significant difference the ER patterns with ST elevation between the groups. In Table 4, the AVNRT and control groups were compared in terms of electrocardiographic characteristics.
Additionally, no morphological changes were observed in the ER patterns after the procedure compared to before the procedure in patients who underwent successful ablation due to AVNRT.
DISCUSSION
After the studies published by Tikkanen et al. (3,8) showing an increased frequency of cardiac arrhythmias with ER patterns, the idea has arisen that ER patterns, contrary to popular belief, may not be innocent. In addition to their clinical importance, there is still no complete consensus on the terminology and definition of ER patterns. This study aimed to investigate the coexistence of AVNRT, the most common form of paroxysmal supraventricular tachycardia, with ER patterns (9).
ER syndromes and BrS, which have pathophysiologically similar features to it, are the main components of J wave syndromes (10). It is considered that J wave abnormalities are caused by mutations that develop in a way that disrupts the inward flow functions of the Ito ion channels, especially in the inferior region of the left ventricle (11). Furthermore, several publications are associated with J-point elevations in the inferior and lateral leads, increased frequency of idiopathic VF, and cardiovascular death (2,12,13). Defects of cardiac ion channels that lead to repolarization dysfunction are not limited to the ventricular myocardium but are also likely to affect the atrial tissue. It has been reported in previously studies that there may be a coexisting between BrS and atrial fibrillation and AVNRT (6,14).
In our study, more patients in the AVNRT group had ER abnormalities than in the control group; however, this difference was not statistically significant. This may be related to the relatively small size of our sample group. AVNRT is a reentrant tachyarrhythmia that develops mainly in the presence of slow and fast pathways, in which the atrioventricular node is involved. However, some genetic variations (SCN1A, PRKAG2, RYR2, CFTR, NOS1, PIK3CB, GAD2, and HIP1R) and ion channel disorders may be responsible for the formation of pathways with different refractory periods and conduction velocities (15,16). The mutation of SCN5A, which affects INA channel functions, has been previously identified in both ER syndrome and AVNRT cases (6,17). Therefore, it is possible that these two diseases may coexist on a pathophysiological basis.
ER abnormalities are more common in men than in women because of sex hormones, especially testosterone and increased ventricular myocardial mass; on the other hand, AVNRT is more common in females (18,19). In our study, there was no statistically significant difference in the presence of ER abnormalities between male and female individuals. Nevertheless, when the comparison was performed in the subgroups, slurring with ST elevation was statistically more in men, in contrast, slurring without ST elevation was significantly higher in female individuals. Our findings are consistent with the previously reported results. However, new studies are still needed on the differences in the subtypes of ER patterns between the genders.
There are some limitations in our study. First, the study was conducted in a relatively small patient population. Additionally, the relationship between electrophysiological measurements and ER abnormalities in AVNRT patients included in the study was not examined. Finally, genetic test analyses were not available for all patients included in the study, which could be related to ER disorders and AVNRT.
CONCLUSION
To our best knowledge, the present study is the first study in the literature to investigate the co-existence of ER disorders and AVNRT. There have been many publications on the association of ER abnormalities, which have been considered benign for many years, with both ventricular and atrial arrhythmias recently. Although it is not statistically significant, we have found that the ER pattern, particularly the slurring type, is more frequent in patients with AVNRT. Additionally, determined that slurring with ST elevation type of ER is significantly more common in males, while slurring without ST elevation type is significantly more common in females. However, our findings need to be supported by larger-scale studies.
ETHICS
Ethics Committee Approval: Ethical committee approval was obtained from the Clinical Research Ethics Committee of the University of Health Sciences Türkiye, Bakırköy Dr. Sadi Konuk Training and Research Hospital (decision no: 2022-16-06, date: 15.08.2022).
Informed Consent: Written informed consent was obtained from all the participants.
Authorship Contributions
Surgical and Medical Practices: O.P., A.S.E., Concept: O.P., Design: O.P., Data Collection or Processing: O.P., A.S.E., Analysis or Interpretation: O.P., A.S.E., Literature Search: O.P., A.S.E., Writing: O.P., A.S.E.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study received no financial support.