The relationship between repolarization parameters and serum electrolyte levels in patients with J wave syndromes

Magnesium Research 2015; 28 (1): 1-13 ORIGINAL ARTICLE The relationship between repolarization parameters and serum electrolyte levels in patients with J wave syndromes Nobuyuki Sato 1, Rie Sasaki 2, Marina Imahashi 2, Eisuke Ito 2, Kumiko Saito 2, Haruyo Kubota 2, Ahmed Karim Talib 1, Naka Sakamoto 1, Kazumi Akasaka 2, Yasuaki Saijo 3, Yuichiro Kawamura 1, Satoshi Fujii 2, Naoyuki Hasebe 1 1 Department of Cardiology, Asahikawa Medical University; 2 Department of Medical Laboratory and Blood Center, Asahikawa Medical University Hospital; 3 Division of Community Medicine and Epidemiology, Department of Health Science, Asahikawa Medical University Correspondence: Nobuyuki Sato, Department of Cardiology, Asahikawa Medical University, Midorigaoka Higashi 2-1-1, Asahikawa, 078-8510, Japan <nsato@asahikawa-med.ac.jp> ABSTRACT. Background: Intravenous administration of magnesium (Mg 2+ )is effective for polymorphic ventricular tachycardia via homogenization of transmural ventricular repolarization. Mg 2+ likely plays some role in the heterogeneity of repolarization in J wave syndromes. Objective: To investigate the relationship between the repolarization parameters and serum Mg 2+, potassium (K + ), and calcium (Ca 2+ ) levels in J wave syndromes. Methods: Thirteen J-wave syndrome patients (Brugada and early repolarization [ER] syndromes), with documented episodes of ventricular fibrillation (VF), and 13 ER pattern (ERP) or Brugada type ECG patients were enrolled (25 males, mean age 48 ± 15 years). The 12-lead ECG-derived parameters including the QT, QT dispersion (QTd), Tpeak-Tend (Tp-e) interval, Tp-e dispersion (Tp-ed), Tp-e/QT ratio, and activation recovery interval (ARI) dispersion were calculated; the correlations between these parameters and electrolytes including Mg 2+,K +, and Ca 2+ were analyzed. Results: Although there was no association between serum K + or Ca 2+ and QTd, there was a strong negative correlation between serum Mg 2+ and QTd in J wave syndrome patients with a history of VF (r = -0.715, p = 0.006). Also, there was a tendency for a negative correlation between Mg 2+ and Tp-ed or ARI dispersion in J wave syndrome patients with a history of VF (r = -0.513, p = 0.072 and r = -0.53, p = 0.063, respectively). On the other hand, in 13 patients with a Brugada type ECG or ERP, no correlation was observed between serum Mg 2+ and the QTd, Tp-ed or ARI dispersion. Conclusion: Serum Mg 2+ may play an important role in the cardiac repolarization process in J wave syndromes. Key words: J wave syndrome, repolarization, magnesium doi:10.1684/mrh.2015.0379 Recently, great attention has been focused on early repolarization and the so-called J wave syndrome [1] because of the increased risk of ventricular fibrillation (VF) [2]. As for the causative genes for J wave syndromes, various genetic mutations related to sodium (Na + ), Ca 2+, and K + channels have been reported [1]. Also, the triggering of VF is affected by factors such as the autonomic nervous system, hypokalemia, and certain drugs [1]. Indeed, hypokalemia is likely a key trigger of VF in J wave syndromes, as previously reported [3, 4]. However, the triggering mechanisms underlying J wave syndromes have not been fully elucidated. Furthermore, the relationships 1 To cite this article: Sato N, Sasaki R, Imahashi M, Ito E, Saito K, Kubota H, Talib AK, Sakamoto N, Akasaka K, Saijo Y, Kawamura Y, Fujii S, Hasebe N. The relationship between repolarization parameters and serum electrolyte levels in patients with J wave syndromes. Magnes Res 2015; 28(1): 1-13 doi:10.1684/mrh.2015.0379

N. SATO, ET AL. Abbreviation list QTd: QT dispersion Tp-e: Tpeak-Tend Tp-ed: Tpeak-Tend dispersion ARI: activation recovery interval ARId: activation recovery interval dispersion between the repolarization parameters and electrolytes other than K +, in patients with J wave syndromes have not been reported to date. Mg 2+ is the second most abundant intracellular cation and the fourth most abundant cation in the body [5]. Although only 1% of the Mg 2+ in the body is in the plasma and interstitial fluid, Mg 2+ is indispensable for normal physiological functions, including myocardial function; in fact, reduced Mg 2+ levels could cause cardiovascular events [5]. Intravenous administration of Mg 2+ has been shown to be effective for many types of arrhythmias including torsade de pointes (Tdp). One of the important anti-arrhythmic mechanisms of Mg 2+ is thought to be a homogenizing, ventricular repolarization process [6]. Indeed, the heterogeneity of the ventricular repolarization across the ventricular wall is reported to be important for initiating and perpetuating polymorphic ventricular tachyarrhythmias. Intravenous Mg 2+ has been shown to be effective in a prolonged QT interval model of polymorphic ventricular tachycardia via homogenization of transmural ventricular repolarization [7]. Because ventricular fibrillation in J wave syndromes is initiated by phase 2 re-entry leading to polymorphic ventricular tachyarrhythmias, there is a possibility that Mg 2+ has some role or contributes to the heterogeneity of the repolarization in J wave syndromes. Hence, we sought to investigate the relationship between the repolarization parameters and serum Mg 2+,K +, and Ca 2+ levels in J wave syndromes. Methods A total of 26 patients were enrolled (25 males, mean age 48 ± 15 years). Thirteen patients who met the diagnosis of J-wave syndrome (Brugada and ER syndromes) with documented episodes of VF, and thirteen early repolarization pattern (ERP) or Brugada type ECG patients were enrolled. A Brugada type ECG was defined in those patients who had a coved-type or saddleback type ST-segment elevation in leads V1 to V3. An ERP was defined in those patients who had a J-wave elevation of >0.1 mv in at least two leads within the inferior and/or lateral chest leads. Serum electrolytes measurements The serum Mg2+ and Ca2+ were measured by a colormetric method. The serum K+ was measured by an ion selective electrode method. All measurements were performed with an auto-analyzer (LABOSPECT 008, Hitachi Inc. Tokyo, Japan). ECG recordings and analyses In 13 patients who had the diagnosis of J-wave syndrome, with documented episodes of VF, a standard investigation protocol was performed in each patient including a 12-lead surface ECG, blood sampling, chest X-rays, 2-dimensional echocardiography, 24-hour Holter recordings, myocardial perfusion imaging, cardiac magnetic resonance imaging, cardiac catheterization when indicated, and an electrophysiology study when appropriate during their first admission. In the 13 ERP or Brugada type ECG patients, the standard investigation protocol was performed either in the outpatient clinic or during admission. The 12-lead ECG-derived parameters including the QT, QT dispersion (QTd), Tpeak-Tend (Tp-e) interval, Tp-e dispersion (Tp-ed), Tp-e /QT ratio, and activation recovery interval (ARI) dispersion were calculated using the QT observer Version 3.0 software (Nihon Kohden, Tokyo, Japan; figure 1). The QT interval was defined as the interval from the onset of the QRS complex to the end of the T wave, which was the intersection of the isoelectric line and T wave. If a U wave existed, the end of the QT interval was taken to be the nadir between the T and U wave peaks. For QTd, the difference between the maximum and minimum intervals on the 12-lead ECG was calculated. ARI was defined as the time from the onset of the intrinsic deflection of the QRS (time of the minimum dv/dt) to the timing of the maximum upstroke velocity near the peak of the T wave (time of the maximum dv/dt). ARI was measured for each lead, and ARI dispersion was defined as the maximum ARI difference among the 12 leads. Tp-e, measured for each lead, was obtained by calculating the difference between the QT interval and QT peak interval, as measured from the beginning of 2

J wave syndrome and electrolytes A QT dispersion QTc dispersion QT Maximum 16 ms 16 356 ms (VI) QT apex dispersion QTc apex dispersion QT apex Maximum 48 ms 51 310 ms (avl) Tp-e dispersion Tp-e c dispersion Tp-e Maximum 52 ms 55 94 ms (V1) QT Minimum 340 ms (V4) QT apex Minimum 262 ms (V1) Tp-e Minimum 42 ms (avl) I avr V1 V4 QTa Tp-e 272 74 QT 346 I 278 70 348 II QTa/Tpe QT 272/ 74 ms 346 ms 272/ 70 ms 342 ms 262 / 94 ms 272 / 356 ms MAX 68 ms 356 ms MIN 290 64 354 III II avl V2 V5 272 70 342 avr 310 42 352 avl 284 68 352 avf QTa/Tpe QT 278/ 70 ms 348 ms 310/ 42 ms 352 ms 264/ 86 ms 350 ms III avf V3 V6 278/ 66 ms 344 ms 262 264 270 34 356 86 350 74 344 V1 V2 V3 272 68 340 V4 278 66 344 V5 QTa/Tpe QT 290/ 64 ms 354 ms 284/ 68 ms 352 ms 270/ 74 ms 344 ms 280/ 66 ms 346 ms 280 66 346 V6 Figure 1. The method used for the measurement of the QT parameters is illustrated. A) Repolarization parameters. B) ARI dispersion. QRS to the peak of the T-wave. Tp-e dispersion was defined as the difference between the maximum and minimum Tp-e intervals of the 12 leads. The measurements were performed by two investigators blinded to the results of the other studies, and the average values were used. Then the correlations between these parameters and the electrolyte analyses, including Mg 2+,K +, and Ca 2+, were determined. As for the patients whose electrolytes could be measured immediately after VF, those values were also evaluated. All participants gave their written informed consent. The local institutional ethics review board approved this study. Statistical analysis The values are presented as the mean ± standard deviation. Variable differences between the two groups were analyzed using Student s t-test, and to test the association between two variables, the Pearson correlation method was used. All statistical analyses were performed on a personal computer with the Sigma Plot for Windows statistical package (version 11.2, Synstat Software, Inc., San Jose, CA, USA). A P-value <0.05 was considered significant. Results Tables 1 and 2 show the serum K +,Ca 2+, and Mg 2+ concentrations, and the QT maximum (max), QT minimum (min), QTd, Tp-e max, Tp-e min, Tp-ed, Tp-e/QT, and ARI dispersion in the J wave syndrome patients and Brugada type ECG or ERP patients, respectively. There was no significant difference between the two groups regarding serum K +,Ca 2+, and Mg 2+ concentrations. Also, there was no significant difference between the two groups 3

N. SATO, ET AL. B RT dispersion : RTc dispersion : RT Maximum : RT Minimum : ARI dispersion : ARIc dispersion : ARI Maximum : ARI Minimum : 122 ms 130 346 ms (avl) 224 ms (V1) I avr V1 V4 II avl V2 V5 III avf V3 V6 96 ms 102 280 ms (avr) 184 ms (V3) AT/RT ARI AT/RT ARI AT/RT ARI Figure 1. (Continued). regarding the QT max, QT min, QTd, Tp-e max, Tp-e min, Tp-ed, Tp-e /QT, and ARI dispersion. Although there was no association between serum K+ or Ca2+ and QTd (data not shown), there was a strong negative correlation between serum Mg and QTd in the J wave syndrome patients who had a history of VF (r = -0.715, p = 0.006, n = 13) (figure 2). Also, there was a tendency for a negative correlation between Mg2+ and Tp-ed or ARI dispersion in the J wave syndrome patients who had a history of VF (r = -0.513, p = 0.072 and r = -0.53, p = 0.063, respectively, n = 13: figures 3 and 4). On the other hand, in 13 patients with 4 a Brugada type ECG or ERP, no correlation was observed between serum Mg2+ and QTd, Mg2+, and Tp-ed, and Mg2+ and ARI dispersion (figures 2-4). Furthermore, the serum K+ and Mg2+ exhibited relatively low values just after VF in the J wave syndrome patients who had a history of VF (3.2 ± 0.4 meq/l and 1.97 ± 0.6 mg/dl, respectively, n = 7). Figure 5 shows a representative example from a 64-year-old male who was referred to our department for the treatment of Brugada syndrome. His QTd and ARId values were high, but the serum Mg2+ value was low.

J wave syndrome and electrolytes Table 1. Serum electrolytes and QT parameters in J wave syndrome patients Case Mg 2+ K + Ca 2+ QT maximum QT minimum QTd Tp-e maximum Tp-e minimum Tp-ed Tp-e/QT ARId (mg/dl) (mmol/l) (mg/dl) (ms) (ms) (ms) (ms) (ms) (ms) (ms) 1 2.5 4.1 8.7 384 362 22 86 68 18 0.22 98 2 2.3 3.9 9.3 386 328 58 86 54 32 0.22 98 3 2 4 8.9 402 352 50 118 75 43 0.29 136 4 2.1 4 9.6 410 348 62 98 66 32 0.24 122 5 1.9 3.5 9 442 368 74 108 70 38 0.24 114 6 1.8 4.4 9.6 458 377 81 102 58 44 0.22 200 7 2.3 4.4 9.1 386 336 50 80 60 20 0.21 110 8 2.2 3.9 9.4 494 458 36 154 100 54 0.31 174 9 2.3 3.7 9.6 380 318 62 108 64 44 0.28 124 10 2 4.6 10 377 305 72 106 63 43 0.28 205 11 2 4 8.8 432 346 86 82 53 29 0.19 114 12 2 4.2 10 356 289 67 98 50 48 0.28 154 13 2.3 4.2 9.9 430 402 28 150 54 96 0.29 150 Mean ± SD 2.1 ± 0.2 4.1 ± 0.3 9.4 ± 0.5 411 ± 39 353 ± 44 58 ± 20 106 ± 23 64 ± 13 42 ± 19 0.25 ± 0.04 138 ± 36 QTd: QT dispersion; Tp-e: Tpeak-Tend; Tp-ed: Tp-e dispersion; ARId: activation recovery interval dispersion; ms: millisecond; SD: standard deviation 5

N. SATO, ET AL. Table 2. Serum electrolytes and QT parameters in ER pattern or Brugada type ECG patients Case Mg 2+ K + Ca 2+ QT maximum QT minimum QTd Tp-e maximum Tp-e minimum Tp-ed Tp-e/QT ARId (mg/dl) (mmol/l) (mg/dl) (ms) (ms) (ms) (ms) (ms) (ms) (ms) 1 2 3.8 8.9 404 362 42 92 56 36 0.23 224 2 1.9 4.4 9.4 380 347 33 104 60 44 0.27 190 3 2 4 9.4 368 332 36 92 68 24 0.25 96 4 2 4.4 9.5 380 324 56 88 40 48 0.23 104 5 2 4.4 9.6 356 340 16 94 42 52 0.26 96 6 2 4.1 9.5 372 310 62 104 85 19 0.28 102 7 2.1 3.9 9.5 403 366 37 137 91 46 0.34 110 8 1.9 4 9.4 452 397 55 107 57 50 0.24 114 9 2.2 4.5 10.2 382 321 61 86 29 57 0.23 188 10 2 3.9 9.5 430 372 58 92 50 42 0.21 122 11 2.2 4.3 9 448 379 69 117 60 57 0.26 140 12 2.1 3.9 9.3 380 326 54 106 78 28 0.28 116 13 2.1 4 9.7 450 360 90 90 50 40 0.2 252 Mean ± SD 2.0 ± 0.1 4.1 ± 0.2 9.5 ± 0.3 400 ± 34 349 ± 26 51 ± 19 101 ± 14 59 ± 18 42 ± 12 0.25 ± 0.04 143 ± 53 QTd: QT dispersion; Tp-e: Tpeak-Tend; Tp-ed: Tp-e dispersion; ARId: activation recovery interval dispersion; ms: millisecond; SD: standard deviation 6

J wave syndrome and electrolytes A 100 80 r = -0.715 p = 0.006 n = 13 QTd (ms) 60 40 20 0 1.6 1.8 2.0 2.2 2.4 2.6 Mg 2+ (mg/dl) B QTd (ms) 80 70 60 50 40 30 r = 0.022 p = 0.941 n = 13 20 10 1.8 1.9 2.0 2.1 2.2 2.3 2.4 Mg 2+ (mg/dl) Figure 2. Correlation between the serum Mg 2+ and QT dispersion (QTd) in J wave syndrome patients who had a history of VF (A) and Brugada type ECG, or ERP patients (B). Discussion In the present study, we demonstrated that the serum Mg 2+ level may play an important role in the cardiac repolarization process in J wave syndromes. To the best of our knowledge, this is the first study to demonstrate that Mg 2+ may be related to the arrhythmogenesis in J wave syndromes. It has been suggested that the serum Mg 2+ levels do not correlate with the tissue levels, and that a significant cardiac depletion exists even with normal concentrations in patients with heart disease. Indeed, Haigney et al. demonstrated that the sublingual Mg 2+ level, but the not the serum Mg level, correlated inversely with the QT interval dispersion [8]. On the other hand, a recent metaanalysis by Qu et al. suggested that a rise in the serum Mg 2+ concentration was linearly associated with a reduction in the risk of total cardiovascular events [9], suggesting that a very slight change in the serum Mg 2+ concentration has some role in controlling physiological function. Although the serum Mg 2+ concentrations in the present J wave syndrome patients were not very low compared to the physiological range, the significant correlation between the repolarization 7

N. SATO, ET AL. A Tp-ed (ms) 60 50 40 30 r = 0.513 p = 0.072 n = 13 20 0 1.6 1.8 2.0 2.2 2.4 2.6 Mg 2+ (mg/dl) B Tp-ed (ms) 60 50 40 30 r = 0.431 p = 0.141 n = 13 20 0 1.8 1.9 2.0 2.1 Mg 2+ (mg/dl) 2.2 2.3 2.4 Figure 3. Correlation between the serum Mg 2+ and Tp-ed in J wave syndrome patients who had a history of VF (A) and Brugada type ECG, or ERP patients (B). parameters and Mg 2+ concentration may indicate some pathophysiological role of Mg 2+ in J wave syndromes. Mg 2+ has been reported to exert its antiarrhythmic effect via modulation of cardiac ion channels. Although there is little or no effect on the Na + channels, it has been shown that the L-type Ca 2+ current is inhibited by extracellular Mg 2+ in a dose-dependent manner and the cardiac membrane stabilizing action of Mg 2+ is mainly due to its modulation of the amplitude, and the activation/inactivation kinetics of the Ca 2+ channels [5]. Furthermore, Mg 2+ can also influence the inward and delayed-rectifier K + channels, and Mg 2+ -induced rectification is influenced by extracellular K + levels, which may also contribute to the membrane stabilizing effect [5]. Regarding the causative channels for J wave syndromes, in addition to decreases in the Na + or L-type Ca 2+ currents and increases in the outward K + currents, the transient outward current (Ito) is thought to be an important current for the genesis of a gradient between the epicardium and endocardium [1]. The Ito current is also known to be modified by intracellular Mg 2+ [10], and the ventricular action potential duration is reported to be shortened by a low intracellular Mg 2+ level. Collectively, there is the possibility that those multichannel effects caused by Mg 2+ may contribute to the membrane stabilizing action and 8

J wave syndrome and electrolytes A ARId (ms) 220 200 180 160 140 120 100 r = 0.53 p = 0.063 n = 13 80 1.6 1.8 2.0 2.2 2.4 2.6 Mg 2+ (mg/dl) B ARId (ms) 260 240 220 200 180 160 140 120 100 r = -0.192 p = 0.529 n = 13 80 1.85 1.90 1.95 2.00 2.05 2.10 2.15 2.20 2.25 Mg 2+ (mg/dl) Figure 4. Correlation between the serum Mg 2+ and ARI dispersion (ARId) in J wave syndrome patients who had a history of VF (A) and Brugada type ECG, or ERP patients (B). homogenizing effects on repolarization in J wave syndromes. Chinushi et al. reported that intravenous Mg 2+ shortened the ARI slightly, and decreased the transmural dispersion of the repolarization in a prolonged QT interval canine model of polymorphic ventricular tachycardia [7]. In fact, from the clinical point of view, it has been shown that Mg 2+ has little effect on the QT interval. In addition, from the cellular electrophysiological point of view, Mg 2+ has little effect or only a mild effect on the shortening of the ventricular repolarization [11-13]. On the other hand, in guinea pig ventricular myocytes, dual effects of Mg 2+ on the action potential duration have been reported, and its mechanism is explained by different degrees of inhibition of the Ca 2+ current (I Ca ) and K + current (I K ) [14]. In clinical practice, it is widely accepted that intravenous Mg 2+ is effective for polymorphic ventricular tachycardia via homogenization of transmural ventricular repolarization [6]. Therefore, it is necessary to elucidate the mechanism of Mg 2+ in the homogenization of repolarization. Regarding the underlying mechanism of the homogenizing activity of ventricular repolarization, Haigney et al. presented important data and a discussion [8]. They demonstrated that the sublingual epithelial Mg 2+ level correlated inversely with the QT interval dispersion in patients with 9

N. SATO, ET AL. A 64-year-old male, Brugada syndrome patient (4LSB) (3LSB) (2LSB) Figure 5. A representative example of the ECG and repolarization parameters in a 64-year-old male who was referred to our department for close examination of a syncopal attack. He was diagnosed with Brugada syndrome and an implantable cardioverter defibrillator was inserted. The findings from the (A) ECG, (B) repolarization parameters, and (C) ARI dispersion. LSB: left sternal border; ms: millisecond Tp-ed: Tp-e dispersion. ventricular tachyarrhythmias and the change in Mg2+ also correlated inversely with the change in the QT dispersion. They discussed the postulated mechanism underlying the action of Mg2+ as a regulator of repolarization. Their speculation was based on previous reports as follows: A reduction in cytosolic Mg2+ results in a relative increase in the ICa, leading to a prolongation of the action potential duration in one beat, whereas the subsequent increase in cytosolic calcium may suppress the ICa and enhance the calcium-sensitive repolarizing currents resulting in shortening of the action potential duration in the next beat. Additionally, delayed rectifier K+ currents would also increase due to the low Mg2+ situation, further hastening repolarization [8]. In our study, 10 although we did not demonstrate a correlation between the QT interval dispersion and a change in the Mg2+ concentration, we found a correlation between the serum Mg2+ levels and QTd, Tp-ed or ARI dispersion in J wave syndrome patients who had a history of VF, suggesting a similar homogenizing effect of Mg2+ on the repolarization in J wave syndromes. There is some controversy regarding the normal value of the QT interval. In a literature review, QT dispersion was reported to vary generally between 30 and 60 ms in normal subjects [15, 16]. The weighted mean ± SD value of the QT dispersion from studies in normal subjects is reported to be 33.4 ± 20.3 ms [15]. In our study comparing serum Mg2+ concentration in J wave syndrome patients,

J wave syndrome and electrolytes B QTa Tp-e QT Mg 1.8 mg/dl 335 74 409 I K 4.4 mmol/l 345 68 413 II Ca 9.6 mg/dl 317 88 405 III QT dispersion 81 ms 338 70 408 avr QT maximum 458 ms 327 78 405 avl QT minimum 377 ms 382 76 458 avf Tp-ed 44 ms 319 58 377 V1 Tp-Te maximum 102 ms 330 86 416 V2 Tp-Te minimum 58 ms 326 90 416 V3 338 102 440 V4 350 76 426 V5 360 74 434 V6 Figure 5. (Continued). Table 3. Comparison of the serum Mg 2+ concentration according to the QTd values in J wave syndrome patients QTd 50 ms (n =5) QTd >50 ms (n =8) Mean SD Mean SD Serum Mg 2+ (mg/dl) 2.26 0.18 2.05 0.18 0.064 QTd 60ms QTd >60 ms P* (n =6) (n =7) Mean SD Mean SD Serum Mg 2+ (mg/dl) 2.27 0.16 2.01 0.16 0.016 QTd: QT dispersion; ms: millisecond; SD: standard deviation *t-test P* there was a statistically significant difference in Mg 2+ levels with a QTd cut-off value of 60 ms, as shown in table 3. Verduyn et al. demonstrated that the suppression or prevention of Tdp by MgSO 4 is related to the diminution of the interventricular delta 11

N. SATO, ET AL. C RT dispersion : 188 ms RTc dispersion : 186 RT Maximum : 368 ms (avr) RT Minimum : 180 ms (V1) ARI dispersion : ARIc dispersion : ARI Maximum : ARI Minimum : I avr V1 V4 II avl V2 V5 III avf V3 V6 200 ms 198 352 ms (avr) 152 ms (V1) AT/RT ARI AT/RT ARI AT/RT ARI Figure 5. (Continued). action potential duration using an animal model of Tdp [17]. Since the interventricular dispersion of the repolarization may also be responsible for the pathogenesis in J wave syndromes [1], Mg2+ might have some beneficial effects for the prevention of polymorphic tachycardia in J wave syndromes. It is widely accepted that the K+ level is critical for the development of ventricular tachyarrhyth- 12 mias, including Tdp. Also, hypomagnesemia has been shown to exacerbate the proarrhythmogenic effect of hypokalemia, and Mg2+ has an additive effect, together with K+, on the prevention of various arrhythmias [1]. In our study, serum K+ and Mg2+ levels exhibited relatively low values just after VF in the J wave syndrome patients who had a history of VF. Therefore, it is also suggested that

J wave syndrome and electrolytes serum Mg 2+ and K + levels might have some important, additive role in the repolarization process in J wave syndromes. Conclusion The serum Mg 2+ level, which can cause homogenization of the ventricular repolarization, may play some important role in the cardiac repolarization process in J wave syndromes. Study limitations The results of this study should be interpreted in light of their limitations. First, the number of patients in the study group was small. Second, although the intracellular Mg 2+ level is important for cardiac physiological activity including ionic channels, we could not evaluate the values in the present study. Third, because we did not use MgSO 4 to treat polymorphic ventricular tachycardia in J wave syndrome patients, we could not evaluate the direct effect of Mg 2+ on tachyarrhythmias in J wave syndromes. Disclosure Financial support: none. Conflict of interest: none. References 1. Antzelevitch C. Genetic, molecular and cellular mechanisms underlying the J wave syndromes. Circ J 2012; 76: 1054-65. 2. Haïssaguerre M, Derval N, Sacher F, et al. Sudden cardiac death associated with early repolarization. N Engl J Med 2008; 358: 2016-23. 3. Araki T, Konno T, Itoh H, Ino H, Shimizu M. Brugada syndrome with ventricular tachycardia and fibrillation related to hypokalemia. Circ J 2003; 67: 93-5. 4. Myojo T, Sato N, Nimura A, et al. Recurrent ventricular fibrillation related to hypokalemia in early repolarization syndrome. Pacing Clin Electrophysiol 2012; 35: e234-238. 5. Kolte D, Vijayaraghavan K, Khera S, Sica DA, Frishman WH. Role of magnesium in cardiovascular diseases. Cardiol Rev 2014; 22: 182-92. 6. Ho KM. Intravenous magnesium for cardiac arrhythmias: jack of all trades. Magnes Res 2008; 21: 65-8. 7. Chinushi M, Sugiura H, Komura S, et al. Effects of intravenous magnesium in a prolonged QT interval model of polymorphic ventricular tachycardia focus on transmural ventricular repolarization. Pacing Clin Electrophysiol 2005; 28: 844-50. 8. Haigney MC, Berger R, Schulman S, et al. Tissue magnesium levels and the arrhythmic substrate in humans. J Cardiovasc Electrophysiol 1997; 8: 980-6. 9. Qu X, Jin F, Hao Y, Li H, Tang T, Wang H, Yan W, Dai K. Magnesium and the risk of cardiovascular events: a meta-analysis of prospective cohort studies. PLoS One 2013; 8: e57720. 10. Zhang DY, Lau CP, Li GR. Human Kir2.1 channel carries a transient outward potassium current with inward rectification. Pflugers Arch 2009; 457: 1275-85. 11. Satoh Y, Sugiyama A, Tamura K, Hashimoto K. Effect of magnesium sulfate on the haloperidolinduced QT prolongation assessed in the canine in vivo model under the monitoring of monophasic action potential. Jpn Circ J 2000; 64: 445-51. 12. Bailie DS, Inoue H, Kaseda S, Ben-David J, Zipes DP. Magnesium suppression of early after-depolarizations and ventricular tachyarrhythmias induced by cesium in dogs. Circulation 1988; 77: 1395-402. 13. Kaseda S, Gilmour Jr. RF, Zipes DP. Depressant effect of magnesium on early after-depolarizations and triggered activity induced by cesium, quinidine, and 4-aminopyridine in canine cardiac Purkinje fibers. Am Heart J 1989; 118: 458-66. 14. Zhang S, Sawanobori T, Adaniya H, Hirano Y, Hiraoka M. Dual effects of external magnesium on action potential duration in guinea pig ventricular myocytes. Am J Physiol 1995; 268: H2321-2328. 15. Malik M, Batchvarov VN. Measurement, interpretation and clinical potential of QT dispersion. JAm Coll Cardiol 2000 15; 36: 1749-66. 16. Franz MR, Zabel M. Electrophysiological basis of QT dispersion measurements. Prog Cardiovasc Dis 2000; 42: 311-24. 17. Verduyn SC, Vos MA, van der Zande J, van der Hulst FF, Wellens HJ. Role of interventricular dispersion of repolarization in acquired torsade-de-pointes arrhythmias: reversal by magnesium. Cardiovasc Res 1997; 34: 453-63. 13