The link between ventricular repolarization variables and arterial function

Available online at www.sciencedirect.com

ScienceDirect Journal of Electrocardiology 48 (2015) 145 – 149 www.jecgonline.com

The link between ventricular repolarization variables and arterial function Ioana Mozos, MD, PhD⁎ “Victor Babes” University of Medicine and Pharmacy Department of Functional Sciences, Timisoara, Romania

Abstract

Aim: To assess the relationship between repolarization variables and arterial function. Methods: A total of 54 participants, aged 33 ± 10 years, underwent arteriography and standard 12lead electrocardiography (ECG). Arteriography was performed using a noninvasive automated oscillometric method, assessing: brachial (Aix Brach) and aortic augmentation index (Aix Ao), pulse wave velocity (PWV), arterial age (AA), diastolic reflection area (DRA) and diastolic area index (DAI). Standard 12-lead ECG enabled measurement of QT and Tpeak-Tend (TpTe) intervals and TpTe/QT ratios. Results: QT interval was prolonged in patients with elevated blood pressure or body mass index. Significant associations were found between electrocardiographic repolarization parameters, such as QT intervals, TpTe and TpTe/QT and arteriography variables, such as Aix Brach, Aix Ao, PWV and AA. Conclusion: Prolonged QTc and Tpe are associated with endothelial dysfunction, arterial stiffness, impaired coronary perfusion and accelerated arterial aging. © 2015 Elsevier Inc. All rights reserved.

Keywords:

QT interval; Tpeak-Tend interval; Arterial stiffness; Augmentation index; Endothelial dysfunction; Arterial age

Introduction Several electrocardiographic (ECG) predictors of ventricular arrhythmia and sudden cardiac death risk have been described, including QT and Tpeak-Tend (TpTe) interval duration. The QT interval, the most used parameter in the electrocardiographic assessment of repolarization [1], is prolonged or borderline if it exceeds 460 and 450 ms, respectively, in women, and 450 and 430 ms, respectively, in men [2,3]. A prolonged Tpeak-Tend interval (TpTe), a readily available ECG measurement of dispersion of the end of repolarization [4,5], predisposes to life-threatening ventricular arrhythmias [6]. TpTe/QT ratio and TpTe/QTc ratio are used as indices of ventricular arrhythmogenesis [7–9]. Cardiovascular diseases continue to be the main mortality causes worldwide, and they are linked to atherosclerosis and its complications [10]. Arterial stiffness and endothelial dysfunction are markers of subclinical atherosclerosis, enabling cardiovascular risk screening [11]. Arterial age, the chronological age of a person with the same 10 years predicted risk but all risk factors at the normal levels [12], is a good predictor of cardiovascular disease.

⁎ Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, T. Vladimirescu Street 14, 300173, Timisoara, Romania. E-mail address: [email protected] http://dx.doi.org/10.1016/j.jelectrocard.2014.11.008 0022-0736/© 2015 Elsevier Inc. All rights reserved.

The aim of the present study was to assess the relationship between repolarization variables such as: QT and TpTe intervals and TpTe/QT, and arterial function. Material and methods Study population and ethical aspects A total of 54, apparently healthy participants, aged 33 ± 10 years, recruited from a general practitioners office, underwent arteriography and standard 12-lead ECG. The most important exclusion criteria were: electrolyte imbalances, atrial fibrillation, and history of myocardial infarction, stroke or diabetes mellitus, the use of drugs known to influence the QT interval or arterial stiffness. The investigations conformed to the principles outlined in the Declaration of Helsinki (Cardiovascular Research 1997; 35: 2–4) and were approved by the Ethics Committee of the University. A written informed consent was obtained from each patient. The power analysis conducted to determine the number of participants needed for the present study showed a minimum sample size required for regression analysis of 54 (anticipated effect size: 0.15; desired statistical power level: 0.8; 0.05 probability level). Arteriography Arteriography was performed by the author using a noninvasive automated oscillometric analyzer (TensioMed

146

I. Mozos / Journal of Electrocardiology 48 (2015) 145–149

Ltd, Budapest, Hungary). Brachial augmentation index (Aix Brach), aortic augmentation index (Aix Ao), pulse wave velocity (PWV), systolic blood pressure in the aorta (SBPAo), diastolic reflection area (DRA), diastolic area index (DAI) and arterial age (AA) were assessed. Pulse wave velocity (PWV) is the speed at which the pulse waveforms travel along the aorta and large arteries, calculated as the distance traveled by the pulse wave between two points, divided by the time taken to travel the distance [13], and depends on the elasticity of the arterial wall. Augmentation indices (aortic and brachial), markers of endothelial dysfunction, are calculated as the ratio of the difference between initial systolic and reflected pulse wave divided by the pulse pressure. DRA and DAI provide information about the quality of the coronary artery filling in diastole and were calculated using the mathematical model built in the software, analyzing the recorded diastolic pulse waves. Arterial age is investigated noninvasively through the measurement of arterial stiffness, central blood pressure and endothelial dysfunction. SBPAo is the central systolic blood pressure. The methodology for arteriography was previously described [14,15]. Arterial stiffness, endothelial dysfunction and early vascular aging were considered if the pulse wave velocity N 10 m/s, the brachial augmentation index greater than − 10%, and the vascular age was higher than the biological age, respectively [14]. Blood pressure values were classified according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [16]. Standard 12-lead ECG Standard 12-lead ECG was performed at a paper speed of 25 mm/s, using a Rextra, multi-channel ECG unit. ECG measurements were made independently of the arteriography results, by the same investigator. The methodology for QT interval measurement was previously described [17]. The QT interval was corrected for heart rate using the Bazett formula [18]. The Tpeak-Tend interval was calculated in each lead as the difference between the QT interval and the QTpeak interval (from the beginning of the QRS complex to the peak of the T wave) [19,20]. All intervals were measured manually. QT and TpTe were measured in each lead and the longest value was used. QT and Tpeak-Tend intervals were not measured in leads with low amplitude T waves, in which the end of the T wave could not be assessed. TpTe/QTc and TpTe/QTmax ratios were also calculated. The longest values for TpTe and QT were used to obtain TpTe/QT ratios. Mean QT interval duration (QTm) was assessed as the mean of the QT intervals in all measurable leads. Statistical analysis Categorical variables are given in numbers (percentages); continuous data are given as means ± standard deviation. Linear and multiple regression analysis, Bravais–Pearson correlations, sensitivity, specificity, positive and negative predictive value were used as statistical methods. A p b 0.05 was considered statistically significant.

Results The characteristics of the study population and the obtained ECG and arteriography variables are included in Table 1. Prolonged QTc and Tpe The patients with prolonged QTc were hypertensive, overweight, obese or with prehypertension. TpTe exceeded 100 ms in patients with elevated body mass index or increased blood pressure values. Considering the patients with a TpTe exceeding 100 ms, 38%, 34% and 14% had an impaired DRA, DAI or PWV. Most patients with a prolonged QTc had also an impaired diastolic reflection area (60%). Impaired DRA and DAI values were recorded in 48% and 35% study participants with borderline and prolonged QTc. PWV was optimal (b 7 m/s) only in 13 study participants (24%). Considering patients with a PWV exceeding 7 m/s (normal and elevated arterial stiffness), 17% (7) and 61% (25) had prolonged QTc and TpTe, respectively.

Table 1 Characteristics of the study population, electrocardiographic and arteriography variables. Variable

Reference range (means ± SD) or N (%)

Chronological age (years) Gender (male) Body mass index (kg/m2) Overweight (BMI ≥ 25 kg/m2) Obesity (BMI ≥ 30 kg/m2) Systolic blood pressure (SBP) (mmHg) Diastolic blood pressure (DBP) (mmHg) Hypertension Prehypertension Pulse pressure (PP) (mmHg) Mean arterial pressure (MAP) (mmHg) Heart rate (HR) (beats/minute) Brachial augmentation index (Aix Brach) (%) Systolic blood pressure in the aorta (SBPAo) (mmHg) Pulse pressure in the aorta (PPAo) (mmHg) Aortic augmentation index (Aix Ao) (%) Diastolic reflection area (DRA) DRA b50 Diastolic area index (DAI) (%) DAI b 50% Pulse wave velocity (PWV) (m/s) PWV b 7 m/s (optimal) PWV N 9.7 m/s Arterial age (years) QTmax (maximal QT interval duration) (ms) QTc (heart rate corrected QT interval) (ms) Prolonged QTc Borderline and prolonged QTc QTm (mean QT interval duration in all measurable leads) (ms) Tpeak-Tend interval (Tpe) (ms) Tpe N100 ms Tpe/QTmax Tpe/QTc

33 ± 10 23 (43%) 25 ± 6 25 (46%) 9 (17%) 122 ± 13 71 ± 10 6 (11%) 8 (15%) 51 ± 10 88 ± 10 76 ± 12 − 46 ± 23 111 ± 14 40 ± 9 14 ± 12 52 ± 11 21 (39%) 52 ± 5 15 (28%) 8 ± 1.4 13 (24%) 7 (13%) 41 ± 14 380 ± 25 427 ± 28 10 (19%) 23 (43%) 350 ± 24 ms 105 ± 38 29 (54%) 0.29 ± 0.08 0.26 ± 0.07

I. Mozos / Journal of Electrocardiology 48 (2015) 145–149 Table 2 Significant correlations of augmentation indices and diastolic reflection area with electrocardiographic parameters. Variables

Bravais–Pearson correlation coefficient (r)

Aix Brach − TpTe Aix Brach − TpTe/QTc Aix Ao − TpTe Aix Ao − TpTe/QTc DRA − TpTe

0.294 0.25 0.294 0.25 − 0.268

Aix Brach = brachial augmentation index, TpTe = Tpeak-Tend interval, Aix Ao = aortic augmentation index, DRA = diastolic reflection area.

Maximal QT and TpTe intervals were measured most frequent in precordial leads, and in 32 study participants (60%) in the same lead. Electrocardiographic repolarization parameters and arteriography variables: correlations, linear and multiple regression analysis Significant correlations and associations were found between TpTe and Aix Brach, TpTe and Aix Ao, TpTe N 100 ms and impaired coronary perfusion, arterial stiffness, endothelial dysfunction and early arterial aging (Tables 2 and 3). TpTe/QTc N 0.28 was also significantly associated with impaired coronary perfusion and early arterial aging (Table 3). The associations were significant even after adjusting for blood pressure, heart rate, body mass index and smoking status. Sensitivity, specificity, positive and negative predictive value of arteriography variables in predicting prolonged QT and Tpeak-Tend intervals The most sensitive arteriography variable in predicting prolonged QT or TpTe intervals is early arterial aging and the most specific is arterial stiffness (Table 4). The highest positive predicted value for TpTe exceeding 100 ms, and the highest negative predictive value for TpTe/QTc N 0.28 were obtained for DAI b 50%. Discussions The most important findings of the present study are the associations between repolarization variables (QT and TpTe

147

intervals, TpTe/QTc) and subclinical atherosclerosis, arterial stiffness, endothelial function and coronary perfusion. Several previous studies demonstrated correlations between ECG parameters, including QTc interval and ECG left ventricular hypertrophy, and arterial stiffness [21,22]. Previous studies also reported correlations between QT and QTc and markers of subclinical atherosclerosis, including intima media thickness in diabetic patients [21], in healthy subjects [15,23], and in nondiabetic patients, free of coronary artery disease [24]. It has been suggested that thickening of the carotid intima media thickness and prolonged QT intervals are the result of a common etiology, such as hypertension or coronary heart disease, and QT interval is a marker for carotid and coronary atherosclerosis [24]. Acquired forms of QT prolongation have been associated with involvement of cardiac ion channels, cardiac autonomic neuropathy and, probably, coronary atherosclerosis [24]. Endothelial dysfunction and arterial stiffness reflect systemic vascular abnormalities and endothelial function of the coronary arteries can be evaluated using the aortic augmentation index [25]. The present study, on apparently healthy subjects, with few comorbidities, draws attention to the relation between repolarization parameters, including borderline and prolonged QTc and prolonged Tpe, and endothelial dysfunction, arterial stiffness, impaired coronary perfusion and early arterial aging. As far as I know, it is the first study demonstrating an association between arterial function and the late phase of repolarization: the TpTe interval. The possible mechanisms explaining the association between subclinical arterial disease and impaired repolarization are myocardial and electrophysiological remodeling due to increased ventricular load, or subendocardial ischemia due to microvascular atherosclerosis in the coronary artery [21]. Subclinical arterial disease and coronary atherosclerosis may be parallel processes, as well [15]. The significance of the study is both clinical and pathophysiological, linking clinical and pathological aspects. Prolonged and borderline QTc and Tpe could be markers of endothelial dysfunction, arterial stiffness, impaired coronary perfusion and accelerated arterial aging. On the other hand, endothelial dysfunction, arterial stiffness, impaired coronary perfusion and accelerated arterial aging could be markers of prolonged QT and TpTe intervals.

Table 3 Linear and multiple regression analysis. Variable

Significantly associated with

R square

Adjusted R square

p

Prolonged QTc Prolonged QTc Prolonged QTc TpTe N 100 ms TpTe N 100 ms TpTe N 100 ms TpTe N 100 ms TpTe N 100 ms TpTe/QTc N 0.28 TpTe/QTc N 0.28

EAA DRA b50 DAI b50% Aix Brach greater than − 10% PWV N9.7 m/s EAA DAI b50% DRA b50, EAA EAA DAI b50%

0.16 0.119 0.106 0.071 0.124 0.725 0.246 0.751 0.112 0.075

0.141 0.100 0.087 0.052 0.105 0.706 0.227 0.727 0.093 0.056

0.024 b 0.001 0.014 0.048 0.0083 b 0.001 b 0.001 0.022, b 0.001 0.012 0.043

QTc = heart rate corrected QT interval according to the Bazett formula, TpTe = Tpeak-Tend interval, EAA = early arterial aging, DRA = diastolic reflection area, DAI = diastolic area index, Aix Brach = brachial augmentation index, PWV = pulse wave velocity, R square = coefficient of determination, adjusted R square = the coefficient of determination adjusted for the number of independent variables in the regression model.

148

I. Mozos / Journal of Electrocardiology 48 (2015) 145–149

Table 4 Sensitivity, specificity, positive and negative predictive value of arteriography variables in predicting prolonged QT and Tpeak-Tend intervals. Predictor variable

Predicted variable

Sensitivity (95% CI)

Specificity (95% CI)

Positive predictive value (95% CI)

Negative predictive value (95% CI)

PWV N9.7 m/s EAA DRA b 50 DAI b 50% PWV N9.7 m/s EAA DRA b 50 DAI b 50% EAA DRA b 50 DAI b 50%

TpTe N100 ms TpTe N100 ms TpTe N100 ms TpTe N100 ms Borderline and prolonged QTc Borderline and prolonged QTc Borderline and prolonged QTc Borderline and prolonged QTc TpTe/QTc N0.28 TpTe/QTc N0.28 TpTe/QTc N0.28

0.172 (0.076–0.345) 0.828 (0.655–0.924) 0.393 (0.236–0.576) 0.345 (0.199–0.527) 0.133 (0.037–0.379) 0.8 (0.548–0.93) 0.333 (0.152–0.583) 0.267 (0.109–0.52) 0.75 (0.409–0.929) 0.25 (0.071–0.591) 0.375 (0.137–0.694)

0.875 (0.69–0.957) 0.36 (0.202–0.555) 0.6 (0.407–0.766) 0.8 (0.609–0.911) 0.842 (0.696–0.926) 0.282 (0.165–0.438) 0.59 (0.434–0.729) 0.718 (0.562–0.835) 0.261 (0.156–0.403) 0.587 (0.443–0.717) 0.739 (0.597–0.844)

0.625 (0.306–0.863) 0.6 (0.446–0.737) 0.524 (0.324–0.717) 0.667 (0.417–0.848) 0.25 (0.071–0.591) 0.3 (0.181–0.454) 0.238 (0.106–0.451) 0.267 (0.109–0.52) 0.15 (0.07–0.291) 0.095 (0.027–0.289) 0.2 (0.07–0.452)

0.467 (0.329–0.609) 0.643 (0.388–0.837) 0.469 (0.505–1.91) 0.513 (0.68–4.373) 0.711 (0.566–0.823) 0.786 (0.524–0.924) 0.697 (0.527–0.826) 0.718 (0.562–0.835) 0.857 (0.601–0.96) 0.818 (0.656–0.914) 0.872 (0.733–0.944)

PWV = pulse wave velocity, EAA = early arterial aging, DRA = diastolic reflection area, DAI = diastolic area index, TpTe = Tpeak-Tend interval, QTc = heart rate corrected QT interval according to the Bazett formula, CI = confidence interval.

Prevention of atherosclerotic complications is extremely important, considering that the first clinical manifestations may be severe and have a poor prognosis. The present study demonstrates a significant association between subclinical atherosclerosis and repolarization variables: borderline and prolonged QT intervals and prolonged TpTe. The repolarization parameters may be used as markers of subclinical atherosclerosis. Patients with subclinical atherosclerosis should undergo standard 12-lead ECG. The QT and Tpeak-Tend interval, and arteriography variables, especially pulse wave velocity, arterial age and brachial augmentation index may identify high-cardiovascular-risk individuals who could benefit from prophylactic measures. Arterial age is considered a predictor of cardiovascular disease, associated with longevity [26], and according to the present study, it may assess also ventricular arrhythmia and sudden cardiac death risk. The most important limitations of the present study refer to the use of the Bazett formula for heart rate correction of the QT interval, the cross-sectional design, lack of a consensus on the values of TpTe interval and contradictory findings regarding its heart rate correction, the low number of patients with prolonged QTc and Tpeak-Tend interval, arterial age and coronary perfusion indices were not well validated, and no direct arrhythmia data. The Bazett formula overcorrects the QT interval at higher heart rates and under corrects at lower heart rates. However, the Bazett correction formula is very frequently used in clinical practice or research, especially for physiological heart rates. HR was up to 60 beats/minute in only two patients and exceeded 100 beats/minute in other two participants in the present study. The QT interval and arterial stiffness have many sources of variability, including advanced age, drugs, body mass index, diabetes mellitus, dyslipidemias, smoking, heart failure, impaired renal function, and hypertension. The number of patients with comorbidities was low in the present study and patients taking QT prolonging drugs and drugs known to influence arterial stiffness were excluded. Elevated blood pressure values and an increased body mass index are known to influence both repolarization and arteriography variables, reason why the associations were adjusted for blood pressure

and body mass index. No data about left ventricular mass were available, and QRS durations were not measured. Broader QRS complexes, reported in hypertensive patients with left ventricular hypertrophy [27], could affect the QT interval. On the other hand, the study population included young and middle-aged, apparently healthy participants and only 26% had elevated blood pressure values (hypertension and prehypertension). The cross-sectional design does not demonstrate cause– effect relations. Further studies are needed to demonstrate that, probably, left ventricular diastolic dysfunction and an impaired coronary perfusion are the links between arterial stiffness and impaired repolarization variables, ventricular arrhythmias and sudden cardiac death and to confirm the findings on different populations. Despite lack of consensus on the values of TpTe, the data obtained in the present study are comparable to other studies [6,19,28,29]. Despite contradictory findings regarding the need of heart rate correction of TpTe [8,30], TpTe/QT ratio remains quite constant. Considering the low number of patients with prolonged QTc and Tpeak-Tend interval exceeding 100 ms, the results need to be confirmed in larger groups. The correlation coefficients were low, but the correlations were significant. QT and TpTe interval duration are only surrogate markers of ventricular arrhythmia risk, and QT prolongation alone is insufficient to produce an arrhythmogenic response and heterogeneity of repolarization may also be necessary [31]. Conclusions Prolonged and borderline QTc and prolonged TpTe are associated with endothelial dysfunction, arterial stiffness, impaired coronary perfusion and accelerated arterial aging. References [1] Clemente D, Pereira T, Ribeiro S. Ventricular repolarization in diabetic patients: Characterization and clinical implications. Arq Bras Cardiol 2012;99(5):1015–22. [2] Rautaharju PM, Surawicz B, Gettes LS, Bailey JJ, Childers R, Deal BJ, et al. AHA/ACC/HRS recommendations for the standardization and

I. Mozos / Journal of Electrocardiology 48 (2015) 145–149

[3] [4]

[5]

[6]

[7]

[8]

[9]

[10] [11]

[12] [13]

[14]

[15]

[16]

interpretation of the electrocardiogram. Part IV: The ST segment, T and U waves, and the QT interval: A scientific statement from the American Heart association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society; Endorsed by the International Society for Computerized Electrocardiology. Circulation 2009;119:e241–50. Goldenberg I, Moss AJ, Zareba W. QT interval: How to measure it and what is “normal”. J Cardiovasc Electrophysiol 2006;17:333–6. Xia Y, Liang Y, Kongstad O, Holm M, Olsson B, Yuan S. Tpeak-Tend interval as an index of ventricular repolarization: Evaluations using monophasic action potential mapping of the epi- and endocardium in swine. J Interv Card Electrophysiol 2005;14(2):79–87. Arteyeva NV, Goshka SL, Sedova KA, Bernikova OG, Azarov JE. What does the Tpeak-Tend interval reflect? An experimental model study. J Electrocardiol 2013;46:296.e1–8. Panikkath R, Reinier K, Uy-Evanado, Teodorescu C, Hattenhauer J, Mariani R, et al. Prolonged Tpeak-Tend interval on the resting ECG is associated with increased risk of sudden cardiac death. Circ Arrhythm Electrophysiol 2011;4:441–7. Kilicasian F, Tokatli A, Ozdag F, Uzun M, Isilak Z, Yiginer O, et al. Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio are prolonged in patients with moderate and severe obstructive sleep apnea. Pacing Clin Electrophysiol 2012;35(8):966–72. Zhao X, Xie Z, Chu Y, Yang X, Liu X, Tian L. Association between Tp-e/QT ratio and prognosis in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Clin Cardiol 2012;35(9):559–64. Barbhaiya C, Po JR, Hanon S, Schweitzer P. Tpeak-Tend and Tpeak-Tend/ QT ratio as markers of ventricular arrhythmia risk in cardiac resynchronization therapy patients. Pacing Clin Electrophysiol 2013;36(1):103–8. Mozos I, Filimon L. Arterial age and shift work. Int J Collab Res Intern Med Public Health 2013;5(5):340–7. Laurent S, Cockroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. Expert consensus document on arterial stiffness: Methodological issues and clinical applications. Eur Heart J 2006;27(21):2588–605. Lee HY, Oh BH. Aging and arterial stiffness. Circ J 2010;74:2257–62. D'Agostino RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: The Framingham Heart Study. Circulation 2008;117:743–53. Mozos I, Filimon L, Gligor S, et al. Body mass index, blood pressure and arteriography variables in a middle and aged population. Health Med 2014;8(4):442–50. Mozos I, Filimon L. The QT interval, arterial stiffness, endothelial function, coronary perfusion and vascular age. In: Kennedy J, Macfarlane P, editors. Electrocardiology 2013. Proceedings of the 40th International Congress on Electrocardiology. Glasgow, August 7th-10th, 2013, VEDAPublishing House of the Slovak Academy of Sciences; 2014. p. 181–6. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL, et al. Seventh report of the Joint National Committee on

[17]

[18] [19]

[20]

[21]

[22]

[23]

[24]

[25]

[26] [27]

[28] [29] [30]

[31]

149

Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206–52. Mozos I, Costea C, Serban C, Susan L. Factors associated with a prolonged QT interval in liver cirrhosis. J Electrocardiol 2011;44:105–8. Bazett HC. An analysis of the time-relations of the electrocardiogram. Heart 1920;7:353–70. Castro Hevia J, Antzelevitch C, Tornes Barzaqa F, Dorantes Sanchez M, Dorticos Balea F, Zayas Molina R, et al. Tpeak-Tend and TpeakTend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. J Am Coll Cardiol 2006;47:1828–34. 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. Maebuchi D, Arima H, Ninomiya T, Yonemoto K, Kubo M, Doi Y, et al. Arterial stiffness and QT interval prolongation in a general population: The Hisayama study. Hypertens Res 2008;31:1339–45. Chung CM, Lin YS, Chu CM, Chang ST, Cheng HW, Yang TY, et al. Arterial stiffness is the independent factor of left ventricular hypertrophy determined by electrocardiogram. Am J Med Sci 2012;344(3):190–3. Strohmer B, Pichler M, Iglseder B, Paulweber B. Relationship of QT interval duration with carotid intima media thickness in a clinically healthy population undergoing cardiovascular risk screening. J Intern Med 2005;257(3):238–46. Festa A, DʼAgostino R, Rautaharju P, O'Leary DH, Rewers M, Mykkänen LM. Is QT interval a marker of subclinical atherosclerosis in nondiabetic subjects? The insulin resistance atherosclerosis study (IRAS). Stroke 1999;30(8):1566–71. Hlimonenko I, Meigas K, Viigimaa M, Temitski K. Aortic and arterial pulse wave velocity in patients with coronary heart disease of different severity. Estonian J Eng 2008;14(2):167–76. Nandish S, Oliveros R, Chilton R. Keeping your arteries young: Vascular health. J Clin Hypertens 2011;13:706–7. Oikarinen L, Nieminen MS, Viitasalo M, Toivonen L, Jern S, Dahlöf B, et al. QRS duration and QT interval predict mortality in hypertensive patients with left ventricular hypertrophy: The Losartan Intervention for Endpoint Reduction in Hypertension Study. Hypertension 2004;43(5):1029–34. Mozos I, Filimon L. QT and Tpeak-Tend interval in shift workers. J Electrocardiol 2013;46:60–5. Mozos I, Serban C. The relation between QT interval and T wave variables in hypertensive patients. J Pharm Bioallied Sci 2011;3(3):339–44. Gellert KS, Rautaharju P, Snyder ML, Whitsel EA, Matsushita K, Heiss G, et al. Short-term repeatability of electrocardiographic TpeakTend and QT intervals. J Electrocardiol 2014;47(3):356–61. Drew BJ, Ackerman MJ, Funk M, Gibler WB, Kligfield P, Menon V, et al. Prevention of torsade de pointes in hospital setting: A scientific statement from the American Heart Association and the American College of Cardiology Foundation. Circulation 2010;121:1047–60.