a b s t r a c t

Objectives: Carbon monoxide poisoning frequently affects repolarization, resulting in abnormal electrocardiography findings. The goal of this study was to examine the effect of CO poisoning on the novel transmyocardial repolarization parameters T peak-T end (Tp-e), Tp-e dispersion, and Tp-e/QT and the relationship of these parameters to myocardial injury (MI).

Methods: This prospective study included 94 patients with CO poisoning and 40 healthy controls. Participants received an electrocardiography and had their Blood drawn at admission and 6 and 24 hours after admission. The QT, Tp-e, Tp-e dispersion, and the Tp-e/QT ratio were calculated. Myocardial injury was determined based on an elevation in troponin any time during the first 24 hours. The patients were divided into 2 subgroups: those with and without MI.

Results: T peak-T end, Tp-e dispersion, and the Tp-e/QT ratio were higher at admission than after 6 and 24 hours of hospitalization and were higher than the control group (P b .001). There was a correlation between the Carboxyhemoglobin level at admission and Tp-e and Tp-e dispersion (P b .001). The MI subgroup (n = 14) had a higher Tp-e at admission than did the non-MI subgroup (n = 80) (96 [11] milliseconds vs 87 [12] milliseconds, P = .03). There were no any significant differences in the Tp-e dispersion or the Tp-e/QT ratio between the 2 MI subgroups. Receiver operating characteristic analysis showed that a Tp-e cutoff value for MI of 91.5 milliseconds had a sensitivity of 72.7% and a specificity of 67.2%.

Conclusion: Transmyocardial repolarization parameters indicative of arrhythmia were prolonged in patients with CO poisoning. T peak-T end was associated with MI.

(C) 2013

Introduction

Carbon monoxide (CO) causes cardiotoxicity via electrical, functional, and morphologic changes in the heart [1]. Cardiotoxicity due to CO poisoning may be silent [2]. In patients with prominent neurologic findings and respiratory symptoms, cardiotoxicity may be misdiagnosed. It has been shown that the Morbidity and mortality rates secondary to cardiotoxicity can be lowered with appropriate treatment [3,4]. Nonspecific repolarization changes and arrhythmias are seen on Electrocardiography in patients with CO poisoning. Sudden death due to CO poisoning is thought to occur because of arrhythmias originating in the ventricles [5-7]. The T wave is an ECG finding indicative of ventricular repolarization. It was recently reported that transmyocardial repolarization parameters, which include the T peak-T end interval (time from the peak to the end of the T wave [Tp-e]), Tp-e dispersion, and the Tp-e/QT ratio, are associated with an increased risk of cardiac arrhythmias [8-10]. The

* Corresponding author. Konya Egitim ve Arastirma Hastanesi Acil Servis Bolumu, 42080 Konya, Turkey. Tel.: +90 332 2236409; fax: +90 332 2237941.

E-mail address: [email protected] (N.B. Akilli).

goals of the present study were to examine the effects of CO exposure on transmyocardial repolarization parameters and to determine if there is a relationship between these parameters and myocardial injury.

Methods

Study population

The study included patients older than 17 years who presented to the our hospital with CO poisoning between 2011 and 2012 and a healthy control group. The study protocol was approved by the hospital ethics committee, and informed consent was obtained from patients who were conscious, the relatives of Unconscious patients, and Control subjects.

Study protocol

Medical history was obtained from conscious patients and the relatives of unconscious patients, and all Home medications were recorded. Demographic data and Glasgow coma scores were also

0735-6757/$ - see front matter (C) 2013 http://dx.doi.org/10.1016/j.ajem.2013.08.049

blood analysis“>recorded. Blood was drawn at the time of hospital admission to measure arterial blood gas, carboxyhemoglobin (COHb), electro- lytes, and troponin I. An ECG was performed. Exclusion criteria included age less than 17 years, history of known cardiovascular disease (such as coronary artery disease, heart failure, and atrial fibrillation), use of Antiarrhythmic drugs, electrolyte abnormalities, and a T-wave amplitude less than 1.5 mm. These laboratory studies and an ECG were repeated at 6 and 24 hours after admission. A troponin I level higher than 0.20 ng mL^-1 at anytime during the first 24 hours of hospitalization was considered to be indicative of myocardial injury. The patients were divided into 2 subgroups: those with and without myocardial injury. Healthy volunteers were included in the control group, their demographic data were recorded, and an ECG was performed.

Electrocardiography measurement

All patients received an ECG at admission, as well as 6 and 24 hours after admission. Using a Nihon Kohden ECG 1250 Cardiofax S (2009, Tokyo, Japan) device at a velocity of 25 mm s^-1 and amplitude of 10 mm mV^-1. Electrocardiography images had a 600-dpi resolution, and measurements were made on the computer by 2 experts who were blinded to the status of each participant. ST elevation, ST depression, T-wave inversion, ST elevation in aVR lead, U wave, and the QT interval were measured. Based on these measurements, Tp-e, Tp-e dispersion, and the Tp-e/QT ratio were calculated. Ischemic ST-T- wave changes were defined as a new ST-segment elevation (>=1 mm), ST-segment depression (N0.5 mm), or T-wave inversion (>=2 mm) in 2 consecutive leads [11].

The QT interval was defined as the distance from the start of QRS to the end of the T wave in all derivations, and averages were recorded for each group. T peak-T end was measured via the tangent method in precordial leads [12]. A tangential line was drawn where the downward curve of the T wave intersected the isoelectric line (Fig. 1). In cases in which the T wave was negative or biphasic, this line was drawn by marking the lower point. If a U wave followed a T wave, the lowest point between the U and T waves was considered to be the end of the T wave. The Tp-e duration was calculated by measuring the distance between the 2 points in the isoelectric line. The difference between the maximum and the minimum Tp-e in the precordial leads was the Tp-e dispersion. To minimize the effect of the heart rate on the Tp-e/QT ratio, the patients were divided into 2 subgroups based on a heart rate at admission of 60 to 100 beats/min and more than 100 beats/min. The Tp-e/QT ratios in these 2 subgroups were separately analyzed. Intraobserver and interobserver variabil- ities in Tp-e were 4.8% and 7.1%, respectively.

Fig. 1. Measurement of Tp-e via the tangent method.

Blood analysis

Troponin I was measured using an automatic autoanalyzer. Carboxyhemoglobin was measured using a Blood gas analyzer (Rapidlab 1265) with a CO-oximetry panel developed by Siemens Healthcare Diagnostics Deerfield, IL.

Statistical analysis

Statistical analysis was performed using SPSS 15.0 for Windows (SPSS, Chicago, IL). Both visual (histogram and probability graphs) and analytical (Kolmogorov-Smirnov and Shapiro-Wilk tests) methods were used to determine if the data were normally distributed. Descriptive variables are expressed as mean +- SD for data that are normally distributed and as median and interquartile range (IQR) for variables that are not normally distributed. The ?² or Fisher exact test was used to compare categorical values. The t test was used to compare normally distributed variables, and the Mann- Whitney U test was used to compare variables that were not normally distributed. Hourly differences in the transmyocardial repolarization parameters were evaluated via repeated-measures analysis of variance for normally distributed variables, whereas the Friedman test was used for variables without normal distribution. When necessary, the Wilcoxon test with the Bonferroni correction was used to compare variables. The patient myocardial injury subgroups were compared using the Mann-Whitney U test. Correlations were determined using Pearson correlation test. The use of the Tp-e value in diagnosing Cardiac damage in patients with CO poisoning was evaluated via receiver operating characteristic curves: the cutoff value was determined using Youden index. A P value less than .05 was considered statistically significant.

Results

Ninety-four patients with CO poisoning (median age, 35.5 [24] years; male, 47.9%) and 40 controls (median age, 35.5 [19] years; male, 47.5%) were included in this study. The demographic and ECG findings of the study participants are presented in Table 1. The Tp-e, Tp-e dispersion, and Tp-e/QT ratio in the patient group at admission were significantly higher than those in the control group (Tp-e: 89.5

+- 13.2 milliseconds vs 68.5 +- 5.0 milliseconds, P b .001; Tp-e

dispersion: 27.0 [17.0] milliseconds vs 14.5 [7.0] milliseconds, P b

.001; Tp-e/QT: 0.26 +- 0.04 vs 0.18 +- 0.10, P b .001). The COHb level,

heart rate, and transmyocardial repolarization parameters in the patient group at admission and 6 and 24 hours after admission are shown in Table 2. The Tp-e, Tp-e dispersion, and Tp-e/QT ratio in the patient group were higher at admission than at 6 or 24 hours after admission. Moreover, the Tp-e, Tp-e dispersion, and Tp-e/QT ratio were higher at 6 hours compared with 24 hours after admission.

Table 1

Demographic and ECG characteristics of the study population

	CO poisoning (n = 94)	Control (n = 40)	P
Age (y), median (IQR)	35.5 (24)	35.5 (19)	.34
Sex, n (%) Male	45 (47.9)	19 (47.5)	.97
Female	49 (49.1)	21 (52.5)
Heart rate (beats/min), mean +- SD	94.1 +- 18.5	77.3 +- 12.4	b.001
Systolic BP (mm Hg), mean +- SD	119.3 +- 16.8	115.8 +- 12.3	.25
Diastolic BP (mm Hg), mean +- SD	71.7 +- 10.2	70.4 +- 9.8	.67
Hypertension, n (%)	6 (6.4)	3 (7.5)	.56
Diabetes mellitus, n (%)	5 (5.3)	2 (5)	.87
Tp-e (ms), mean +- SD	89.5 +- 13.2	68.5 +- 5.0	b.001
Tp-e dispersion (ms), median (IQR)	27.0 (17.0)	14.5 (7.0)	b.001
Tp-e/QT, mean +- SD	0.26 +- 0.04	0.18 +- 0.1	b.001

BP, blood pressure.

Table 2

The COHb level, heart rate, and transmyocardial repolarization parameters in the patient with CO group at admission and 6 and 24 hours after admission

Table 4

A comparison of the MI and non-MI subgroup

MI (n = 14) Non-MI (n = 80) P

	Admission	6 h	24 h	P		Age (y), median (IQR)	57 (34)	34 (20)	.008
COHb (%), mean +- SD	30.6 +- 10.0a,b	6.5 +- 4.0c	1.9 +- 0.9	b.001		Sex			.86
Heart rate (beats/min),	94.7 +- 19.1a,b	80.9 +- 14.0	75.7 +- 14.5	b.001		Male, n (%)	7 (50)	38 (47.5)
mean +- SD						Female, n (%)	7 (50)	42 (52.5)
Tp-e (ms), mean +- SD	89.5 +- 13.3a,b	81.9 +- 10.1c	74.8 +- 10.0	b.001		Systolic BP (mm Hg), median (IQR)	117.5 (35)	120 (20)	.95
Tp-e dispersion (ms),	27.0 (17.0)a,b	25.5 (11.3)c	18 (10.3)	b.001		Diastolic BP (mm Hg), median (IQR)	75 (18)	70 (10)	.76
median (IQR)						GKS, median (IQR)	14 (4)	15 (0)	.003
Tp-e/QT, mean +- SD	0.26 +- 0.04a,b	0.23 +- 0.04c	0.20 +- 0.04	b.001		COHb, median (IQR)	27.5 (17.9)	30.6 (9.6)	.42

^a Statistically significant difference compared with 6-hour group at the level of

ST elevation, n (%)	3 (21.4)	4 (5)	.04
ST depression, n (%)	6 (42.9)	7 (8.7)	.001
T-wave inversion, n (%)	3 (21.4)	10 (12.5)	.41
U wave, n (%)	4 (28.6)	25 (31.3)	.75
ST elevation in aVR lead, n (%)	2 (14.3)	11 (13.8)	.98
Tp-e (ms), median (IQR)	96 (11)	87 (12)	.03
Tp-e dispersion (ms), median (IQR)	33 (28)	26 (15)	.40
Tp-e/QT, median (IQR)	0.27 (0.06)	0.26 (0.05)	.39

P b .05.

^b Statistically significant difference compared with 24-hour group at the level of

P b .05.

^c Statistically significant difference compared with 24-hour group at the level of

P b .05.

A comparison of Tp-e, Tp-e dispersion, and the Tp-e/QT ratio in the patient group 24 hours after admission and in the control group is shown in Table 3. T peak-T end was significantly longer in the patient group (74.7 +- 10.0 milliseconds vs 68.5 +- 5.0 milliseconds, P b .001). There were no any differences in Tp-e dispersion or the Tp-e/QT ratio between the 2 patient and control groups (P = .06 and P = .08, respectively).

A comparison of the myocardial injury subgroup (n = 14) and non-myocardial injury subgroup (n = 80) is shown in Table 4. T peak-T end was significantly higher in the myocardial injury subgroup than in the non-myocardial injury subgroup (96 [11] milliseconds vs 87 [12] milliseconds, P = .03). The cutoff value for myocardial injury was determined using receiver operating charac- teristic curves (Tp-e >= 91.5 milliseconds; sensitivity, 73.0%; specific- ity, 67.0%; area under the curve, 0.71; 95% confidence interval, 0.57- 0.86; P = .03) (Fig. 2). The patient group was also divided into subgroups according to heart rate. Overall, 62.7% of the patients (n = 59) were in the 60 to 100 beats/min subgroup and 37.3% (n = 35) were in the greater than 100 beats/min subgroup. Carboxyhemoglo- bin, Tp-e, and Tp-e dispersion were similar in both heart rate subgroups (P N .05), whereas the Tp-e/QT ratio was significantly lower in the 60 to 100 beats/min subgroup than in the greater than 100 beats/min subgroup (0.25 +- 0.03 milliseconds vs 0.28 +- 0.04 milliseconds, P = .003). The COHb level at admission correlated with Tp-e and Tp-e dispersion (r = 0.40 [P b .01] and r = 0.30 [P b .01], respectively).

Discussion

The present study demonstrates that transmyocardial repolariza- tion parameters (noninvasive ECG indicators of ventricular arrhyth- mia) were longer in patients with CO poisoning than in control subjects and that Tp-e correlated with myocardial injury.

Carbon monoxide poisoning can lead to permanent tissue damage, including damage to the brain and heart, which are especially vulnerable to hypoxia [13]. Lippi et al [14] stated that CO leads to cardiotoxicity because it increases ischemia and has a direct toxic effect on the myocardium. Ischemic injury is caused by COHb. Carboxyhemoglobin shifts the oxygen-hemoglobin dissociation curve toward the left and causes tissue hypoxia [15]. The direct

Table 3

A comparison of Tp-e, Tp-e dispersion, and the Tp-e/QT ratio in the patient with CO poisoning group 24 hours after admission and in the control group

	CO poisoning (n = 94)	Control (n = 40)	P
Tp-e (ms), mean +- SD	74.7 +- 10.0	68.5 +- 5.0	b.001
Tp-e dispersion (ms), median (IQR)	18.0 (10.3)	14.5 (7.0)	.06
Tp-e/QT, mean +- SD	0.20 +- 0.3	0.18 +- 0.1	.08

MI, myocardial injury; BP, blood pressure; GKS, Glasgow coma score.

toxic effect of CO on the myocardium might be caused by several different mechanisms including COHb formation, cytochrome c oxidase inhibition, an increase in free radical formation, and cellular apoptosis due to nitric oxide [16-20].

Changes at the cellular and subcellular level due to CO can lead to a wide spectrum of clinical findings including cardiomyopathy, angina, acute myocardial infarction, arrhythmias, heart failure, lung edema, cardiogenic shock, and sudden death [14]. In some patients exposed to CO, there may be no cardiovascular symptoms or signs, and cardiotoxicity may be overlooked [4]. There are barriers to identifying CO-induced myocardial damage: CO poisoning may not be correctly diagnosed, the pathophysiological and clinical characteristics of CO- induced myocardial injury are not well understood, commonly used markers of myocardial damage have a low diagnostic value when skeletal muscle damage is also present, and changes in the ECG are often nonspecific [1].

After acute CO exposure, repolarization changes (ST-T changes and QT elongation) and arrhythmias are frequently observed on the ECG

Fig. 2. Receiver operating curve of Tp-e for myocardial injury. AUC, area under the curve; CI, confidence interval.

[5-7]. Although the mechanisms of arrhythmia in CO poisoning are not precisely known, some studies reported that myocardial repolar- ization heterogeneity might play an important role in the formation of arrhythmias [19]. Andre et al [21] reported that CO leads to dysregulation of calcium metabolism in epicardial myocytes (but not in endocardial cells) and thus produces a proarrhythmic effect via prolonged repolarization. That QT and QT dispersion, which are indicative of heterogenous myocardial repolarization, were reported to be high in patients with CO poisoning supports this hypothe- sis [22,23]. Nonetheless, some studies report that the Tp-e interval, Tp-e dispersion, and Tp-e/QT ratio (novel transmyocardial repolari- zation parameters) are superior to the QT interval and QT dispersion in predicting arrhythmias [24].

There are 3 layers in the myocardium associated with transmyo- cardial repolarization: the endocardial layer, M cells, and epicardial layer [25]. Rabbit studies using wedge ECG have shown that the end of repolarization in epicardial cells coincides with the T-wave peak and that the end of repolarization in endocardial cells coincides with the end of the T wave [26,27]. The repolarization phases in these regions differ, and the changes in these regions lead to transmyocardial heterogeneity, which, in turn, leads to Malignant arrhythmias. Transmyocardial heterogeneity is determined on an ECG by calculat- ing the Tp-e interval, Tp-e dispersion, and Tp-e/QT ratio [25]. Prolongation of the Tp-e interval leads to increased vulnerability to arrhythmias caused by ventricular reentry [28,29]. It was reported that the Tp-e interval, Tp-e dispersion, and Tp-e/QT ratio are high in long- and short-QT syndrome, Brugada syndrome, and myocardial infarction [8,12,30,31].

Panikkath et al [32] studied 353 cases of sudden cardiac death and reported that a prolonged Tp-e interval (Tp-e N 85 milliseconds) and a high Tp-e/QT ratio are strongly associated with sudden cardiac death. Lubinski et al [33] reported that a prolonged Tp-e and high Tp-e/QT ratio were related to ventricular tachycardia in patients with coronary artery disease. In the present study, the Tp-e in the patient group was significantly longer at admission than after 6 and 24 hours of hospitalization and longer than that in the control group. Moreover, the Tp-e was longer in the myocardial injury subgroup than in the non-myocardial injury subgroup. It has been suggested that asymp- tomatic patients presenting with CO poisoning can be discharged after 4 hours of monitoring [34]. According to the present findings, patients with a prolonged Tp-e should be monitored for arrhythmia and myocardial injury much longer than 4 hours. Many studies reported that the Tp-e/QT ratio and the length of the QT interval are related to the probability of developing arrhythmias in patients with both congenital and acquired channelopathies. In healthy individuals with heart rates between 60 and 100 beats/min, the Tp-e/QT ratio in precordial leads is 0.21 [12]. In the present study, the Tp-e/QT ratio in the subgroup of patients with a heart rate of 60 to 100 beats/min was higher than that in the control group, but there was no significant difference in the Tp-e/QT ratio between the myocardial injury and non-myocardial injury subgroups.

Whereas the Tp-e interval is indicative of transmyocardial

repolarization heterogeneity, Tp-e dispersion is indicative of varia- tion in transmyocardial repolarization in different regions of the myocardium. Castro Hevia et al [8] reported that Tp-e dispersion could be used for risk stratification in patients with Brugada syndrome. In the present study, Tp-e dispersion was greater at the time of admission than after 6 and 24 hours of hospitalization and was greater than the control group. However, there was no significant difference in the Tp-e dispersion between the myocardial and non-myocardial injury subgroups.

Limitations

The primary limitation of the present study is the small sample population, especially the myocardial injury subgroup (n = 14).

Owing to a limited number of patients with myocardial injury, logistic regression analysis was not performed, which may have negatively affected the statistical Power of the study. Despite these limitations, the authors think that the study may act as a good basis for further studies on the topic. In addition, the present study was performed at a single center. The findings must be confirmed via prospective, multicenter studies with larger populations. Owing to financial constraints, not all patients were able to undergo routine echocardi- ography, coronary angiography, scintigraphy, or magnetic resonance imaging to assess myocardial injury. Myocardial injury was deter- mined based on the troponin I level.

Conclusion

Identifying cardiotoxicity in patients with CO poisoning can be difficult, especially in asymptomatic patients. In the present study, the novel transmyocardial repolarization parameters Tp-e, Tp-e dispersion, and the Tp-e/QT ratio were longer in the patients with CO poisoning than in controls subjects. Moreover, a prolonged Tp-e interval was a marker of myocardial injury. Based on these findings, ECG-a simple, inexpensive, and noninvasive technique-can be used to help determine the risk of developing myocardial injury and Life-threatening arrhythmias after CO poisoning. Patients with prolonged transmyocardial repolarization parameters should be monitored for more than 4 hours to not miss the symptoms and signs of cardiotoxicity.

References

1. Gandini C, Castoldi AF, Candura SM, Locatelli C, Butera R, Priori S, et al. Carbon monoxide cardiotoxicity. J Toxicol Clin Toxicol 2001;39:35-44.
2. Fiorista F, Casazza F, Comolatti G. Silent myocardial infarction caused by acute carbon monoxide poisoning. G Ital Cardiol 1993;23:583-7.
3. Adir Y, Merdler A, Ben Haim S, Front A, Harduf R, Bitterman H. Effects of exposure to low concentrations of carbon monoxide on exercise performance and myocardial perfusion in young healthy men. Occup Environ Med 1999;56:535-8.
4. Aslan S, Uzkeser M, Seven B, Gundogdu F, Acemoglu H, Aksakal E, et al. The evaluation of myocardial damage in 83 young adults with carbon monoxide poisoning in the East Anatolia region in Turkey. Hum Exp Toxicol 2006;25:439-46.
5. Thiels H, Van Durme JP, Vermeire P, Pannier R. Immediate and late electrocar- diographic changes in the course of acute carbon monoxide poisoning. Lille Med 1972;17:191-5.
6. Cosby RS, Bergeron M. Electrocardiographic changes in carbon monoxide poisoning. Am J Cardiol 1963;11:93-6.
7. Carnevali R, Omboni E, Rossati M, Villa A, Checchini M. Electrocardiographic changes in acute carbon monoxide poisoning. Minerva Med 1987;78:175-8.
8. Castro Hevia J, Antzelevitch C, Tornes Barzaga F, Dorantes Sanchez M, Dorticos Balea F, Zayas Molina R, et al. Tpeak-Tend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. J Am Coll Cardiol 2006;47:1828-34.
9. Savelieva I, Yap YG, Yi G, Guo X, Camm AJ, Malik M. Comparative reproducibility of QT, QT peak, and T peak-T end intervals and dispersion in normal subjects, patients with myocardial infarction, and patients with hypertrophic cardiomy- opathy. Pacing Clin electrophysiol 1998;21:2376-81.
10. Hlaing T, Guo D, Zhao X, DiMino T, Greenspon L, Kowey PR, et al. The QT and Tp-e intervals in left and right chest leads: comparison between patients with systemic and pulmonary hypertension. J Electrocardiol 2005;38:154-8.
11. Satran D, Henry CR, Adkinson C, Nicholson CI, Bracha Y, Henry TD. Cardiovascular manifestations of moderate to severe carbon monoxide poisoning. J Am Coll Cardiol 2005;45:1513-6.
12. Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol 2008;41:567-74.
13. Cevik Y, Tanriverdi F, Delice O, Kavalci C, Sezigen S. Reversible increases in QT dispersion and P wave dispersion during carbon monoxide intoxication. Hong Kong J Emerg Med 2010;17:441-50.
14. Lippi G, Rastelli G, Meschi T, Borghi L, Cervellin G. Pathophysiology, clinics, diagnosis and treatment of heart involvement in carbon monoxide poisoning. Clin Biochem 2012;45:1278-85.
15. Douglas CG, Haldane JS, Haldane JB. The laws of combination of haemoglobin with carbon monoxide and oxygen. J Physiol 1912;44:275-304.
16. Prockop LD, Chichkova RI. Carbon monoxide intoxication: an updated review. J Neurol Sci 2007;262:122-30.
17. Tibbles PM, Edelsberg JS. Hyperbaric-oxygen therapy. N Engl J Med 1996;334: 1642-8.
18. Tritapepe L, Macchiarelli G, Rocco M, Scopinaro F, Schillaci O, Martuscelli E, et al. Functional and ultrastructural evidence of Myocardial stunning after acute carbon monoxide poisoning. Crit Care Med 1998;26:797-801.
19. Hajsadeghi S, Tavakkoli N, Jafarian Kerman SR, Shahabadi A, Khojandi M. electrocardiographic findings and serum troponin I in carbon monoxide Poisoned patients. Acta Med Iran 2012;50:185-91.
20. Dallas ML, Yang Z, Boyle JP, Boycott HE, Scragg JL, Milligan CJ, et al. Carbon monoxide induces cardiac arrhythmia via induction of the late Na+ current. Am J Respir Crit Care Med 2012;186:648-56.
21. Andre L, Boissiere J, Reboul C, Perrier R, Zalvidea S, Meyer G, et al. Carbon monoxide pollution promotes cardiac remodeling and ventricular arrhythmia in healthy rats. Am J Respir Crit Care Med 2010;181:587-95.
22. Yelken B, Tanriverdi B, Cetinbas F, Memis D, Sut N. The assessment of QT intervals in acute carbon monoxide poisoning. Anadolu Kardiyol Derg 2009;9:397-400.
23. Hanci V, Ayoglu H, Yurtlu S, Yildirim N, Okyay D, Erdogan G, et al. Effects of acute carbon monoxide poisoning on the P-wave and QT interval dispersions. Anadolu Kardiyol Derg 2011;11:48-52.
24. Mozos I, Serban C. The relation between QT interval and T-wave variables in Hypertensive patients. J Pharm Bioallied Sci 2011;3:339-44.
25. Kayrak M, Acar K, Gul EE, Ozbek O, Abdulhalikov T, Sonmez O, et al. The association between myocardial iron load and ventricular repolarization parameters in asymptomatic beta-thalassemia patients. Adv Hematol 2012;2012:170510.
26. Yan GX, Wu Y, Liu T, Wang J, Marinchak RA, Kowey PR. Phase 2 early afterdepolarization as a trigger of Polymorphic ventricular tachycardia in acquired long-QT syndrome: direct evidence from intracellular recordings in the intact left ventricular wall. Circulation 2001;103:2851-6.
27. Yan GX, Martin J. Electrocardiographic T wave: a symbol of transmural dispersion of repolarization in the ventricles. J Cardiovasc Electrophysiol 2003;14:639-40.
28. Yan GX, Antzelevitch C. Cellular basis for the normal T wave and the electrocardiographic manifestations of the long-QT syndrome. Circulation 1998;98:1928-36.
29. Antzelevitch C, Shimizu W, Yan GX, Sicouri S. Cellular basis for QT dispersion. J Electrocardiol 1998;30(Suppl):168-75.
30. Letsas KP, Weber R, Astheimer K, Kalusche D, Arentz T. Tpeak-Tend interval and Tpeak-Tend/QT ratio as markers of ventricular tachycardia inducibility in subjects with Brugada ECG phenotype. Europace 2010;12:271-4.
31. Zhao Z, Yuan Z, Ji Y, Wu Y, Qi Y. Left ventricular hypertrophy amplifies the QT, and Tp-e intervals and the Tp-e/QT ratio of left chest ECG. J Biomed Res 2010;24: 69-72.
32. Panikkath R, Reinier K, Uy-Evanado A, Teodorescu C, Hattenhauer J, Mariani R, et al. Prolonged Tpeak-to-tend interval on the resting ECG is associated with increased risk of sudden cardiac death. Circ Arrhythm Electrophysiol 2011;4: 441-7.
33. Lubinski A, Kornacewicz-Jach Z, Wnuk-Wojnar AM, Adamus J, Kempa M, Krolak T, et al. The terminal portion of the T wave: a new electrocardiographic marker of risk of ventricular arrhythmias. Pacing Clin Electrophysiol 2000;23: 1957-9.
34. Tintinalli JD, Stapczynski JS, Ma OJ. Tintinalli’s emergency medicine: a compre- hensive study guide. 7th ed. New York, NY: Mc Graw-Hill Professional; 2010.