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Assessment of atrial electromechanical delay and P-wave dispersion in patients with type 2 diabetes mellitus
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JJCC-1108; No. of Pages 6 Journal of Cardiology xxx (2015) xxx–xxx
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Original article
Assessment of atrial electromechanical delay and P-wave dispersion in patients with type 2 diabetes mellitus Kenan Demir (M.D.)a,*, Ahmet Avci (M.D.)a, Zeynettin Kaya (M.D.)b, Kamile Marakoglu (M.D.)c, Esra Ceylan (M.D.)c, Ahmet Yilmaz (M.D.)a, Ahmet Ersecgin (M.D.)a, Mustafa Armutlukuyu (M.D.)c, Bulent Behlul Altunkeser (M.D.)a a
Selcuk University Faculty of Medicine, Cardiology Department, Konya, Turkey Mevlana University Faculty of Medicine, Cardiology Department, Konya, Turkey c Selcuk University Faculty of Medicine, Department of Family Medicine, Konya, Turkey b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 31 March 2015 Received in revised form 4 June 2015 Accepted 7 June 2015 Available online xxx
Objectives: Diabetes mellitus is an independent and strong risk factor for development of atrial fibrillation (AF). Electrophysiologic and electromechanical abnormalities are associated with a higher risk of AF. In this study we aimed to determine the correlation of atrial conduction abnormalities between the surface electrocardiographic and tissue Doppler echocardiographic measurements in type 2 diabetes mellitus (T2DM) patients. Methods: A total of 88 consecutive T2DM patients and 49 age-, gender-, and body mass index-matched healthy volunteers were included in the present study. Baseline characteristics were recorded and 24hour ambulatory blood pressure monitoring, transthoracic echocardiography, and 12-lead surface electrocardiography were performed for all study participants. Atrial electromechanical delay (EMD) intervals were measured. Results: Maximum P-wave duration and P-wave dispersion (Pd) were significantly higher in patients with T2DM (105.7 10.2 ms vs. 102.2 7.5 ms, p = 0.02; 40.6 7.6 ms vs. 33.6 5.9 ms, p < 0.001, respectively). Interatrial, intraatrial, and intraleft atrial EMD were significantly higher in the T2DM patients when compared with the controls (16.5 7.8 ms vs.11.2 4.4 ms, p < 0.001; 9.0 7.3 ms vs. 6.0 3.8 ms, p = 0.002, and 7.4 5.2 ms vs. 5.1 3.2 ms, p = 0.002 respectively). Correlation analysis showed a positive correlation between interatrial EMD and Pd (r = 0.429, p < 0.001) and left atrial volume (r = 0.428, p < 0.001). Conclusions: In this study, there was significant EMD and Pd in patients with T2DM as compared with healthy volunteers. Additionally, interatrial EMD was correlated with Pd and left atrial volume index. ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Keywords: Diabetes mellitus Tissue Doppler imaging Atrial electromechanical delay P-wave dispersion
Introduction Diabetes mellitus (DM) is a chronic metabolic disorder and a major risk factor for cardiovascular disease. The frequency of cardiovascular disease, including coronary artery disease, systolic and diastolic heart failure, arrhythmia, and thromboembolism, is increased in diabetic patients. Atrial fibrillation (AF) is one of the most frequently sustained cardiac arrhythmias seen in clinical practice, and is associated with an increased risk of ischemic stroke, heart failure, and overall mortality. Many risk factors have been reported for the development of AF [1]. It was shown that DM is
* Corresponding author at: Selcuk University Faculty of Medicine, Cardiology Department, 42075 Konya, Turkey. Tel.: +90 505 506 1334; fax: +90 332 241 2151. E-mail address: [email protected] (K. Demir).
an independent and strong risk factor for development of AF. The frequency of AF development is 1.4- to 2.1-fold higher in cases with DM than cases without DM [2]. Inflammation and oxidative stress have been implicated in the pathogenesis of both the DM and AF [1]. Electrophysiologic and electromechanical (excitation–contraction coupling) abnormalities resulting from intraatrial and interatrial conduction disorders are associated with a higher risk of AF. The prolongation of intraatrial and interatrial electromechanical delay (EMD) and the inhomogeneous propagation of sinus impulses are well-known electrophysiological characteristics of the atria prone to fibrillation [3]. Atrial conduction abnormalities were evaluated with noninvasive techniques by using electrocardiography (ECG) and tissue Doppler imaging (TDI) in previous studies [4,5]. To our knowledge, there is no study that evaluated atrial conduction abnormalities using both TDI and ECG in patients with
http://dx.doi.org/10.1016/j.jjcc.2015.06.003 0914-5087/ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Demir K, et al. Assessment of atrial electromechanical delay and P-wave dispersion in patients with type 2 diabetes mellitus. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.06.003
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type 2 diabetes mellitus (T2DM). In this study we aimed to determine the correlation of atrial conduction abnormalities between the surface electrocardiographic and TDI measurements in T2DM patients.
antiarrhythmics, tricyclic antidepressants, antihistaminics, and antipsychotics were excluded from the study. Using standard laboratory methods, blood samples were drawn after an overnight 12-h fasting to determine levels of hemogram and biochemical parameters.
Methods Echocardiography Study population A total of 88 consecutive T2DM patients (45 males, 43 females; mean age, 49.5 7.9 years) and 49 age-, gender-, and body mass index-matched healthy volunteers (19 males, 30 females; mean age, 47.3 9.2 years) were included between January 2014 and June 2014 to the present study. The study protocol was approved by our local ethics committee, and all participants gave their written informed consent to participate in the study. The diagnosis of T2DM was made based on the criteria of the American Diabetes Association [6]. Medical history was obtained and physical examination was performed in all patients. All participants were evaluated with 24-hour blood pressure monitoring for diagnosing arterial hypertension. Patients and controls with a history of coronary artery disease, arterial hypertension, left ventricular (LV) wall motion, LV ejection fraction (EF) less than 50%, primary cardiomyopathy, valvular heart disease, paroxysmal AF, dysrhythmia, bundle branch block, atrioventricular conduction abnormalities on ECG, thyroid dysfunction, anemia, electrolyte imbalance, renal failure, pulmonary disease, and poor quality echocardiographic and ECG imaging were excluded from the study. All participants were in sinus rhythm and those who had been taking medications such as
All echocardiographic examinations (1.5–4.6 MHz phased array transducer, Vivid E9; GE, Horten, Norway) were performed by a cardiologist who was blinded to the clinical details and results of the other investigations of each patient and control. ECG (DII) was recorded continuously during echocardiography. M-mode measurements and conventional Doppler echocardiographic examinations were performed according to the criteria of the American Society of Echocardiography guidelines [7]. Three consecutive cycles were averaged for every parameter. Left atrium (LA) dimension and LV end-systolic and end-diastolic diameters were measured. LV ejection fraction was estimated by modified Simpson’s rule. LV mass was calculated with Devereux formula and indexed to body surface area. LA volume was calculated at end systole of the LV in the apical four- and two-chamber views using the methods of disks (Simpson’s rule). LA volume was indexed to the body surface area. Transmitral pulsed-wave Doppler velocities were recorded from the apical four-chamber view with the Doppler sample placed between the tips of the mitral leaflets. Early (E) and late (A) wave velocities, E/A ratio, E deceleration time (DT), and isovolumetric relaxation time (IVRT), isovolumetric contraction time (IVCT), and ejection time (ET) were measured from the mitral inflow profile.
Fig. 1. Measurement of time interval from the onset of P-wave on surface electrocardiogram to the beginning of Am wave (PA) interval with tissue Doppler echocardiography. (A) Lateral PA; (B) Septal PA; (C) Tricuspid PA.
Please cite this article in press as: Demir K, et al. Assessment of atrial electromechanical delay and P-wave dispersion in patients with type 2 diabetes mellitus. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.06.003
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Myocardial performance index (MPI) [MPI = (IVRT + IVCT)/ET] was calculated according to relevant guidelines. The Nyquist limit was set at 15–20 cm/s, and minimal optimal gain was used. The myocardial systolic (Sm), early diastolic (Em), and late diastolic (Am) velocities were obtained at lateral mitral annulus by placing a tissue Doppler sample volume. The E/Em and Em/Am ratios were subsequently calculated. The pulsed sample volume was placed at the level of the LV lateral mitral annulus, septal mitral annulus, and right ventricular tricuspid annulus in order to obtain electromechanical parameters. The time interval from the onset of the Pwave on surface ECG to the beginning of the late diastolic wave (Am wave) on TDI, which is named PA, was obtained from the lateral mitral annulus (lateral PA), septal mitral annulus (septal PA), and right ventricular tricuspid annulus (tricuspid PA), respectively (Fig. 1). The difference between lateral PA and tricuspid PA (lateral PA tricuspid PA) was defined as interatrial EMD, the difference between septal PA and tricuspid PA (septal PA tricuspid PA) was defined as intraatrial EMD, and the difference between lateral PA and septal PA (lateral PA septal PA) was defined as intraleft atrial EMD. In atrial EMD measurements, intraobserver variability was assessed in 20 selected subjects at random from the patient study group by repeating the measurements under the same baseline conditions. To test the interobserver variability, we performed the measurements offline from video recordings by a second observer. The intraobserver and interobserver coefficients of variation for echocardiographic measurements were found to be <5% and nonsignificant. Electrocardiography All standard 12-lead ECGs were obtained simultaneously using a recorder (Nihon Kohden Cardiofax; Model ECG-9132v, Tokyo, Japan) set at a 50 mm/s paper speed and 2 mV/cm standardization. The ECGs were analyzed by 2 qualified investigators. The onset of the P-wave was defined as the junction between the isoelectric line and the beginning of P-wave deflection. The offset was defined as the junction between the end of the P-wave deflection and the isoelectric line. The longest atrial conduction time measured on any of the 12 leads was defined as P maximum (Pmax), and the shortest time was defined as P minimum (Pmin). The difference between Pmax and Pmin was calculated and defined as P-wave dispersion (Pd = Pmax Pmin). The patients who had indiscernible P-waves in more than four leads on a baseline 12-lead ECG were not enrolled in the study.
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Statistical analysis SPSS 17.0 for Windows was used for statistical analyses (SPSS, Chicago, IL, USA). Continuous variables were presented as median or mean SD; categorical variables were defined as percentage. Differences in the continuous variables between groups were determined by Student’s t test or the Mann–Whitney U test, for variables with or without normal distribution, respectively. To test the normal distribution, the Kolmogorov– Smirnov test was used. Categorical variables were summarized as percentages and compared with the x2 test. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. A p-value <0.05 was considered statistically significant. Results Basic clinical and laboratory characteristics of 88 diabetic patients (mean age, 49.5 7.9 years) and 49 normal subjects (mean age, 47.3 9.2 years) are listed in Table 1. There was no significant difference between groups in terms of age, gender, body mass index, body surface area, smoking, systolic and diastolic blood pressures, heart rates, hemoglobin, creatinine, and low-density lipoprotein cholesterol. White blood cell count and fasting blood glucose were significantly higher in the T2DM patients [8.1 1.8 103/mL vs. 7.4 1.6 103/mL, p = 0.02; 141 (94–357) mg/dL vs. 93 (78–118) mg/dL, p < 0.001, respectively]. The mean HbA1c level was 8.0 1.9% in patients with T2DM and the median disease duration was 42 (12– 240) months. There was no correlation between HbA1c and EMD. Also, there was no correlation between duration of T2DM and EMD. The results of the echocardiographic measurements are shown in Table 2. LV end-diastolic and end-systolic diameters, LV ejection fraction, LV posterior wall thickness, LV mass index, aortic diameter, systolic pulmonary artery pressure, DT, and A and E velocities were also similar between the groups. IVRT and interventricular septum thickness were significantly higher in T2DM patients (96.3 14.3 ms vs. 90.2 14.8 ms, p = 0.02; 9.6 1.3 mm vs. 9.0 1.6 mm, p = 0.03, respectively). Also, LA diameter and LA volume index were significantly higher in T2DM patients (33.8 2.9 mm vs. 32.0 3.5 mm, p = 0.004; 31.2 7.4 mL/ m2 vs. 27.8 7.4 mL/m2, p = 0.01 respectively). E/A ratio was lower in T2DM patients, but there was no significant difference between the groups with respect to left and right ventricular Sm and Em values, Am value, Em/Am ratio, E/Em ratio, and myocardial performance index.
Table 1 Clinical and laboratory characteristics of the subjects. Patients (n = 88) Age (years) Female, n (%) BMI (kg/m2) BSA (m2) Smoking, n (%) SBP (mmHg) DBP (mmHg) Heart rate (beats/min) Hb (g/dL) WBC (103/mL) Cr (mg/dL) LDL-C (mg/dL) FBG (mg/dL) HbA1c (%) Disease duration (months)
49.5 7.9 43 (48.9) 31.2 5.1 1.99 0.2 26 (29.5) 119.7 9.6 72.7 5.3 76.7 10.2 14.3 1.9 8.1 1.8 0.8 0.1 119.3 28.8 141 (94–357) 8.0 1.9 42 (12–240)
Controls (n = 49) 47.3 9.2 30 (61.2) 30.3 5.2 1.92 0.2 14 (28.6) 117.0 9.7 71.5 6.9 75.7 11.4 14.1 1.6 7.4 1.6 0.7 0.1 130.4 39.0 93 (78–118) –
p 0.17 0.21 0.35 0.06 1.0 0.11 0.27 0.63 0.58 0.02 0.63 0.09 <0.001
BMI, body mass index; BSA, body surface area; Cr, serum creatinine; DBP, diastolic blood pressure; FBG, fasting blood glucose; Hb, hemoglobin; HbA1c, glycosylated hemoglobin A1; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure; WBC, white blood cell. The bold and italic entries are statistically significant parameters.
Please cite this article in press as: Demir K, et al. Assessment of atrial electromechanical delay and P-wave dispersion in patients with type 2 diabetes mellitus. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.06.003
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Table 2 Comparison of conventional and tissue Doppler variables between patients with type 2 diabetes mellitus and controls. Patients (N = 88) LVEDD (mm) LVESD (mm) IVS thickness (mm) PW thickness (mm) LV mass index (g/m2) Aortic diameter (mm) LA diameter (mm) LA volume index (mL/m2) LV ejection fraction (%) PAP systolic (mmHg) Conventional Doppler parameters Mitral E velocity (cm/s) Mitral A velocity (cm/s) E/A DT (ms) IVRT (ms) Tissue Doppler parameters LV lateral annulus Sm (cm/s) Am (cm/s) Em (cm/s) Em/Am E/Em MPI RV lateral annulus Sm (cm/s) Am (cm/s) Em (cm/s) Em/Am
Controls (n = 49)
p
46.9 4.6 29.0 4.5 9.6 1.3 9.4 1.4 89.9 21.8 27.6 2.9 33.8 2.9 31.2 7.4 67.4 5.2 21.8 4.6
46.3 4.6 28.8 3.9 9.0 1.6 9.4 1.2 89.6 22.8 28.6 3.0 32.0 3.5 27.8 7.4 67.1 5.2 22.0 3.6
0.46 0.79 0.03 0.86 0.93 0.07 0.004 0.01 0.79 0.74
81.48 15.7 75.7 14.9 1.11 0.30 182.3 25.3 96.3 14.3
82.9 13.1 70.8 16.1 1.23 0.34 180.1 23.1 90.2 14.8
0.55 0.08 0.05 0.6 0.02
10.4 1.9 11.4 2.5 11.0 2.8 1.0 0.34 7.8 2.3 0.58 0.07
10.4 2.4 11.0 2.4 11.4 3.0 1.0 0.33 7.5 1.8 0.56 0.08
0.92 0.36 0.35 0.22 0.48 0.13
17.0 3.0 17.9 3.8 13.2 3.3 0.77 0.32
17.0 3.3 17.2 4.3 13.6 3.6 0.83 0.30
0.88 0.38 0.49 0.32
Am, late myocardial diastolic velocity; DT, mitral E-wave deceleration time; Em, early myocardial diastolic velocity; IVRT, isovolumetric relaxation time; IVS, interventricular septum; LA, left atrium; LV, left ventricular; LVEDD, left ventricular enddiastolic diameter; LVESD, left ventricular end-systolic diameter; MPI, myocardial performance index; PAP, pulmonary artery pressure; PW, posterior wall; RV, right ventricular; Sm, systolic myocardial velocity. The bold and italic entries are statistically significant parameters.
P-wave indices and TDI parameters are shown in Table 3. Pmax duration and Pd were significantly higher in patients with T2DM (105.7 10.2 ms vs. 102.2 7.5 ms, p = 0.02; 40.6 7.6 ms vs. 33.6 5.9 ms, p < 0.001, respectively). However, Pmin duration was significantly lower in patients with T2DM (65.3 8.3 ms vs. 68.5 8.2 ms, p = 0.03). PA lateral, PA septum, and PA tricuspid durations were significantly higher in the T2DM patients when compared with the controls (64.8 14.0 ms vs. 52.1 7.3 ms, p < 0.001; 57.3 13.1 ms vs. 47.0 7.3 ms, p < 0.001, and 48.3 11.7 ms vs. 40.9 6.6 ms, p < 0.001, respectively). Also, PA divided by LA diameters was significantly higher in the T2DM patients when compared with the controls. Moreover, interatrial,
intraatrial, and intraleft atrial EMD were significantly higher in the T2DM patients when compared with the controls (16.5 7.8 ms vs. 11.2 4.4 ms, p < 0.001; 9.0 7.3 ms vs. 6.0 3.8 ms, p = 0.002 and 7.4 5.2 ms vs. 5.1 3.2 ms, p = 0.002, respectively). Correlation analysis showed a positive correlation between interatrial EMD and Pd (r = 0.429, p < 0.001) (Fig. 2) and LA volume (r = 0.428, p < 0.001) (Fig. 3). Discussion There were three major findings of this study. Interatrial, intraatrial, and left intraatrial EMD were significantly higher in
Table 3 Comparison of the electrocardiographic and tissue Doppler echocardiographic findings.
Pmax (ms) Pmin (ms) Pd (ms) PA lateral (ms) PA septum (ms) PA tricuspid (ms) PA lateral/LA diameter (ms/mm) PA septum/LA diameter (ms/mm) PA tricuspid/LA diameter (ms/mm) PA lateral PA tricuspida (ms) PA septum PA tricuspidb (ms) PA lateral PA septumc (ms)
Patients (N = 88)
Controls (n = 49)
p
105.7 10.2 65.3 8.3 40.6 7.6 64.8 14.0 57.3 13.1 48.3 11.7 1.92 0.4 1.70 0.3 1.43 0.3 16.5 7.8 9.0 7.3 7.4 5.2
102.2 7.5 68.5 8.2 33.6 5.9 52.1 7.3 47.0 7.3 40.9 6.6 1.63 0.2 1.47 0.2 1.28 0.2 11.2 4.4 6.0 3.8 5.1 3.2
0.02 0.03 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.007 <0.001 0.002 0.002
LA, left atrium; PA, time interval from the onset of P-wave on surface electrocardiogram to the beginning of Am wave interval with tissue Doppler imaging; Pd, P dispersion; Pmax, maximum P-wave duration; Pmin, minimum P-wave duration. The bold and italic entries are statistically significant parameters. a Interatrial electromechanical delay. b Intraatrial electromechanical delay. c Intraleft atrial mechanical delay.
Please cite this article in press as: Demir K, et al. Assessment of atrial electromechanical delay and P-wave dispersion in patients with type 2 diabetes mellitus. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.06.003
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Fig. 2. Correlation between interatrial electromechanical delay and P-wave dispersion.
patients with T2DM. Pd was significantly higher in patients with T2DM and there was a significant correlation between interatrial EMD and Pd. LA volume index, one of the LV diastolic function parameters, was also found to be significantly higher than in the control group, and there was a significant correlation between interatrial EMD and LA volume index. AF is the most common cardiac arrhythmia in the general population, and its prevalence is projected to increase substantially over the following decades. DM is one of the independent risk factors described for AF, and the relationship between T2DM and incident AF was evaluated in several prospective studies [1,2]. The mechanism of AF in diabetic patients is not clearly understood [1]. The increased risk of developing AF in DM may be related in part to activation of signaling pathways important in inflammation and oxidative stress. Structural remodeling and electrophysiological remodeling are critical for AF to perpetuate. The structural substrate includes atrial stretch, dilatation, loss of muscle mass, fibrosis, and disruption of cell coupling at gap junctions [8]. Increased intraatrial and interatrial EMD, atrial fibrosis and
Fig. 3. Correlation between interatrial electromechanical delay and left atrial (LA) volume.
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disturbed atrial electromechanical functions were shown as risk factors for developing AF in several diabetic animal studies. Diabetes is also associated with numerous metabolic defects including insulin resistance, impaired glucose tolerance, proinflammatory mediators, abnormalities of hemostasis, fibrinolysis, angiogenesis, and extracellular matrix turnover. All of these metabolic changes lead to endothelial dysfunction, abnormal activation of the renin-angiotensin-aldosterone system, and acceleration of atherogenesis, which could be responsible for AF occurrence. Diabetes could also cause structural, electrical, electromechanical, and autonomic remodeling [9]. These abnormalities may lead to the development of AF in diabetic people [10]. EMD has been defined as the temporal interval between the onset of cardiac electrical activity and myocardial contraction [4]. It can be easily quantified by transthoracic tissue Doppler echocardiography. Any pathologic process impairing atrial conduction may result in reentrant atrial arrhythmias [11]. Atrial conduction disorders are frequent in elderly subjects and/or those with structural heart diseases, mainly mitral valve disease, dilated cardiomyopathy, coronary slow flow, and hypertension [12– 15]. Additionally, the close relationship between EMD and metabolic syndrome, impaired fasting glucose levels, insulin resistance, type 1 DM and T2DM were demonstrated in previous studies [16–20]. It has been found that atrial EMD was independently related to new onset AF and recurrence of AF in many studies [21,22]. In the present study, we showed that interatrial, intraatrial, and left intraatrial conduction times were significantly prolonged in patients with T2DM as compared with healthy volunteers. Pd is an ECG index believed to reflect heterogeneous atrial conduction by detecting abnormal atrial conduction with ECG leads of different orientation. Pd has been studied in patients with hypertension, metabolic syndrome, and DM as a simple and noninvasive predictor of AF development [23–25]. The exact mechanism of Pd prolongation in diabetics is not well known, but it is thought that structural and electrophysiological changes in the atrial myocardium caused by diabetes might play a role. Chronic hyperglycemia causes structural and functional disorders by changing the chemical composition of the proteins present in cell membrane structure. Furthermore, extracellular protein deposition and interstitial fibrosis of myocardium can cause prolongation of Pd by forming heterogeneity in atrial conduction velocity and atrial refractoriness in diabetic patients [25]. Therefore, it has been suggested that Pd can be used to diagnose patients with a high risk of AF [26]. In this study, we found that Pmax and Pd were significantly higher in patients with T2DM and there was a significant correlation between interatrial EMD and Pd. DM is an independent risk factor with an influence on cardiac function and structure. Diastolic dysfunction is regarded as a first sign of functional abnormalities in the myocardium and is detected in up to 75% of asymptomatic diabetic patients [27]. Instead, a number of echocardiographic indices have been introduced to measure diastolic function [LV hypertrophy and mass, enlarged LA, the velocity ratio (E/A), and regional myocardial strain, etc.] [28]. In this study, we also detected greater LA diameter and LA volume index, higher IVRT and mitral A velocity, and lower E/A ratio in the T2DM patients. We found that interatrial EMD had a significant correlation with LA volume index. Our findings support that increased LA enlargement and LV early diastolic dysfunction accompanying T2DM may contribute to the prolongation of interatrial EMD. To the best of our knowledge, this is only the second report to assess the association between atrial conduction abnormalities and T2DM. This study has three different features than the previous study [20]. First, investigators did not evaluate the ambulatory blood pressure in their patient group in the previous
Please cite this article in press as: Demir K, et al. Assessment of atrial electromechanical delay and P-wave dispersion in patients with type 2 diabetes mellitus. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.06.003
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study. Hypertension is one of the major causes of EMD and LV diastolic dysfunction parameters. Therefore, in our study the patients with hypertension were excluded with ambulatory blood pressure measurements. Secondly, in the previous study, atrial conduction abnormalities were evaluated only using the TDI, but in our study atrial conduction abnormalities were assessed by both TDI and surface ECG, whereby, interatrial EMD and Pd obtained by us from both noninvasive methods were compared with each other. Thirdly, in this study we evaluated IVRT, LA diameter, and LA volume index which are parameters of LV diastolic functions. Limitations Our study was conducted in a single center with a relatively small number of participants. This was also a cross-sectional study. Patients with T2DM could not be observed prospectively for atrial arrhythmic events. In addition, although all subjects were in sinus rhythm during the study, we did not perform Holter examination to investigate presence of atrial arrhythmias in our study population. Also, we do not have data on right atrium size. Therefore, we do not know whether prolongation of interatrial EMD and impaired diastolic function, right atrium size, and increased LA diameters and volume index predict AF in T2DM patients. The other limitation of our study was that conduction times were determined with tissue Doppler echocardiography, and the gold standard technique, electrophysiological study, was not performed. The last limitation of this study is that we calculated Pmax, Pmin, and Pd manually instead of using a more reliable computer-assisted P-wave calculating system.
[6] [7]
[8]
[9] [10]
[11]
[12]
[13]
[14]
[15]
[16]
Conclusion [17]
According to our findings, there was significant EMD and Pd in patients with T2DM as compared with healthy volunteers. Additionally, interatrial EMD was correlated with Pd and LA volume index. Determining electromechanical events including the interatrial conduction time with transthoracic echocardiography is a noninvasive and simple method to measure. Large-scale and long-term follow-up prospective studies are required to establish the predictive value of atrial conduction parameters for the future development of AF in patients with T2DM. Funding This research received no grant from any funding agency in the public, commercial, or not-for-profit sectors.
[18]
[19]
[20]
[21]
[22]
Conflict of interest [23]
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Original article
Assessment of atrial electromechanical delay and P-wave dispersion in patients with type 2 diabetes mellitus Kenan Demir (M.D.)a,*, Ahmet Avci (M.D.)a, Zeynettin Kaya (M.D.)b, Kamile Marakoglu (M.D.)c, Esra Ceylan (M.D.)c, Ahmet Yilmaz (M.D.)a, Ahmet Ersecgin (M.D.)a, Mustafa Armutlukuyu (M.D.)c, Bulent Behlul Altunkeser (M.D.)a a
Selcuk University Faculty of Medicine, Cardiology Department, Konya, Turkey Mevlana University Faculty of Medicine, Cardiology Department, Konya, Turkey c Selcuk University Faculty of Medicine, Department of Family Medicine, Konya, Turkey b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 31 March 2015 Received in revised form 4 June 2015 Accepted 7 June 2015 Available online xxx
Objectives: Diabetes mellitus is an independent and strong risk factor for development of atrial fibrillation (AF). Electrophysiologic and electromechanical abnormalities are associated with a higher risk of AF. In this study we aimed to determine the correlation of atrial conduction abnormalities between the surface electrocardiographic and tissue Doppler echocardiographic measurements in type 2 diabetes mellitus (T2DM) patients. Methods: A total of 88 consecutive T2DM patients and 49 age-, gender-, and body mass index-matched healthy volunteers were included in the present study. Baseline characteristics were recorded and 24hour ambulatory blood pressure monitoring, transthoracic echocardiography, and 12-lead surface electrocardiography were performed for all study participants. Atrial electromechanical delay (EMD) intervals were measured. Results: Maximum P-wave duration and P-wave dispersion (Pd) were significantly higher in patients with T2DM (105.7 10.2 ms vs. 102.2 7.5 ms, p = 0.02; 40.6 7.6 ms vs. 33.6 5.9 ms, p < 0.001, respectively). Interatrial, intraatrial, and intraleft atrial EMD were significantly higher in the T2DM patients when compared with the controls (16.5 7.8 ms vs.11.2 4.4 ms, p < 0.001; 9.0 7.3 ms vs. 6.0 3.8 ms, p = 0.002, and 7.4 5.2 ms vs. 5.1 3.2 ms, p = 0.002 respectively). Correlation analysis showed a positive correlation between interatrial EMD and Pd (r = 0.429, p < 0.001) and left atrial volume (r = 0.428, p < 0.001). Conclusions: In this study, there was significant EMD and Pd in patients with T2DM as compared with healthy volunteers. Additionally, interatrial EMD was correlated with Pd and left atrial volume index. ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Keywords: Diabetes mellitus Tissue Doppler imaging Atrial electromechanical delay P-wave dispersion
Introduction Diabetes mellitus (DM) is a chronic metabolic disorder and a major risk factor for cardiovascular disease. The frequency of cardiovascular disease, including coronary artery disease, systolic and diastolic heart failure, arrhythmia, and thromboembolism, is increased in diabetic patients. Atrial fibrillation (AF) is one of the most frequently sustained cardiac arrhythmias seen in clinical practice, and is associated with an increased risk of ischemic stroke, heart failure, and overall mortality. Many risk factors have been reported for the development of AF [1]. It was shown that DM is
* Corresponding author at: Selcuk University Faculty of Medicine, Cardiology Department, 42075 Konya, Turkey. Tel.: +90 505 506 1334; fax: +90 332 241 2151. E-mail address: [email protected] (K. Demir).
an independent and strong risk factor for development of AF. The frequency of AF development is 1.4- to 2.1-fold higher in cases with DM than cases without DM [2]. Inflammation and oxidative stress have been implicated in the pathogenesis of both the DM and AF [1]. Electrophysiologic and electromechanical (excitation–contraction coupling) abnormalities resulting from intraatrial and interatrial conduction disorders are associated with a higher risk of AF. The prolongation of intraatrial and interatrial electromechanical delay (EMD) and the inhomogeneous propagation of sinus impulses are well-known electrophysiological characteristics of the atria prone to fibrillation [3]. Atrial conduction abnormalities were evaluated with noninvasive techniques by using electrocardiography (ECG) and tissue Doppler imaging (TDI) in previous studies [4,5]. To our knowledge, there is no study that evaluated atrial conduction abnormalities using both TDI and ECG in patients with
http://dx.doi.org/10.1016/j.jjcc.2015.06.003 0914-5087/ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Demir K, et al. Assessment of atrial electromechanical delay and P-wave dispersion in patients with type 2 diabetes mellitus. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.06.003
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type 2 diabetes mellitus (T2DM). In this study we aimed to determine the correlation of atrial conduction abnormalities between the surface electrocardiographic and TDI measurements in T2DM patients.
antiarrhythmics, tricyclic antidepressants, antihistaminics, and antipsychotics were excluded from the study. Using standard laboratory methods, blood samples were drawn after an overnight 12-h fasting to determine levels of hemogram and biochemical parameters.
Methods Echocardiography Study population A total of 88 consecutive T2DM patients (45 males, 43 females; mean age, 49.5 7.9 years) and 49 age-, gender-, and body mass index-matched healthy volunteers (19 males, 30 females; mean age, 47.3 9.2 years) were included between January 2014 and June 2014 to the present study. The study protocol was approved by our local ethics committee, and all participants gave their written informed consent to participate in the study. The diagnosis of T2DM was made based on the criteria of the American Diabetes Association [6]. Medical history was obtained and physical examination was performed in all patients. All participants were evaluated with 24-hour blood pressure monitoring for diagnosing arterial hypertension. Patients and controls with a history of coronary artery disease, arterial hypertension, left ventricular (LV) wall motion, LV ejection fraction (EF) less than 50%, primary cardiomyopathy, valvular heart disease, paroxysmal AF, dysrhythmia, bundle branch block, atrioventricular conduction abnormalities on ECG, thyroid dysfunction, anemia, electrolyte imbalance, renal failure, pulmonary disease, and poor quality echocardiographic and ECG imaging were excluded from the study. All participants were in sinus rhythm and those who had been taking medications such as
All echocardiographic examinations (1.5–4.6 MHz phased array transducer, Vivid E9; GE, Horten, Norway) were performed by a cardiologist who was blinded to the clinical details and results of the other investigations of each patient and control. ECG (DII) was recorded continuously during echocardiography. M-mode measurements and conventional Doppler echocardiographic examinations were performed according to the criteria of the American Society of Echocardiography guidelines [7]. Three consecutive cycles were averaged for every parameter. Left atrium (LA) dimension and LV end-systolic and end-diastolic diameters were measured. LV ejection fraction was estimated by modified Simpson’s rule. LV mass was calculated with Devereux formula and indexed to body surface area. LA volume was calculated at end systole of the LV in the apical four- and two-chamber views using the methods of disks (Simpson’s rule). LA volume was indexed to the body surface area. Transmitral pulsed-wave Doppler velocities were recorded from the apical four-chamber view with the Doppler sample placed between the tips of the mitral leaflets. Early (E) and late (A) wave velocities, E/A ratio, E deceleration time (DT), and isovolumetric relaxation time (IVRT), isovolumetric contraction time (IVCT), and ejection time (ET) were measured from the mitral inflow profile.
Fig. 1. Measurement of time interval from the onset of P-wave on surface electrocardiogram to the beginning of Am wave (PA) interval with tissue Doppler echocardiography. (A) Lateral PA; (B) Septal PA; (C) Tricuspid PA.
Please cite this article in press as: Demir K, et al. Assessment of atrial electromechanical delay and P-wave dispersion in patients with type 2 diabetes mellitus. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.06.003
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Myocardial performance index (MPI) [MPI = (IVRT + IVCT)/ET] was calculated according to relevant guidelines. The Nyquist limit was set at 15–20 cm/s, and minimal optimal gain was used. The myocardial systolic (Sm), early diastolic (Em), and late diastolic (Am) velocities were obtained at lateral mitral annulus by placing a tissue Doppler sample volume. The E/Em and Em/Am ratios were subsequently calculated. The pulsed sample volume was placed at the level of the LV lateral mitral annulus, septal mitral annulus, and right ventricular tricuspid annulus in order to obtain electromechanical parameters. The time interval from the onset of the Pwave on surface ECG to the beginning of the late diastolic wave (Am wave) on TDI, which is named PA, was obtained from the lateral mitral annulus (lateral PA), septal mitral annulus (septal PA), and right ventricular tricuspid annulus (tricuspid PA), respectively (Fig. 1). The difference between lateral PA and tricuspid PA (lateral PA tricuspid PA) was defined as interatrial EMD, the difference between septal PA and tricuspid PA (septal PA tricuspid PA) was defined as intraatrial EMD, and the difference between lateral PA and septal PA (lateral PA septal PA) was defined as intraleft atrial EMD. In atrial EMD measurements, intraobserver variability was assessed in 20 selected subjects at random from the patient study group by repeating the measurements under the same baseline conditions. To test the interobserver variability, we performed the measurements offline from video recordings by a second observer. The intraobserver and interobserver coefficients of variation for echocardiographic measurements were found to be <5% and nonsignificant. Electrocardiography All standard 12-lead ECGs were obtained simultaneously using a recorder (Nihon Kohden Cardiofax; Model ECG-9132v, Tokyo, Japan) set at a 50 mm/s paper speed and 2 mV/cm standardization. The ECGs were analyzed by 2 qualified investigators. The onset of the P-wave was defined as the junction between the isoelectric line and the beginning of P-wave deflection. The offset was defined as the junction between the end of the P-wave deflection and the isoelectric line. The longest atrial conduction time measured on any of the 12 leads was defined as P maximum (Pmax), and the shortest time was defined as P minimum (Pmin). The difference between Pmax and Pmin was calculated and defined as P-wave dispersion (Pd = Pmax Pmin). The patients who had indiscernible P-waves in more than four leads on a baseline 12-lead ECG were not enrolled in the study.
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Statistical analysis SPSS 17.0 for Windows was used for statistical analyses (SPSS, Chicago, IL, USA). Continuous variables were presented as median or mean SD; categorical variables were defined as percentage. Differences in the continuous variables between groups were determined by Student’s t test or the Mann–Whitney U test, for variables with or without normal distribution, respectively. To test the normal distribution, the Kolmogorov– Smirnov test was used. Categorical variables were summarized as percentages and compared with the x2 test. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. A p-value <0.05 was considered statistically significant. Results Basic clinical and laboratory characteristics of 88 diabetic patients (mean age, 49.5 7.9 years) and 49 normal subjects (mean age, 47.3 9.2 years) are listed in Table 1. There was no significant difference between groups in terms of age, gender, body mass index, body surface area, smoking, systolic and diastolic blood pressures, heart rates, hemoglobin, creatinine, and low-density lipoprotein cholesterol. White blood cell count and fasting blood glucose were significantly higher in the T2DM patients [8.1 1.8 103/mL vs. 7.4 1.6 103/mL, p = 0.02; 141 (94–357) mg/dL vs. 93 (78–118) mg/dL, p < 0.001, respectively]. The mean HbA1c level was 8.0 1.9% in patients with T2DM and the median disease duration was 42 (12– 240) months. There was no correlation between HbA1c and EMD. Also, there was no correlation between duration of T2DM and EMD. The results of the echocardiographic measurements are shown in Table 2. LV end-diastolic and end-systolic diameters, LV ejection fraction, LV posterior wall thickness, LV mass index, aortic diameter, systolic pulmonary artery pressure, DT, and A and E velocities were also similar between the groups. IVRT and interventricular septum thickness were significantly higher in T2DM patients (96.3 14.3 ms vs. 90.2 14.8 ms, p = 0.02; 9.6 1.3 mm vs. 9.0 1.6 mm, p = 0.03, respectively). Also, LA diameter and LA volume index were significantly higher in T2DM patients (33.8 2.9 mm vs. 32.0 3.5 mm, p = 0.004; 31.2 7.4 mL/ m2 vs. 27.8 7.4 mL/m2, p = 0.01 respectively). E/A ratio was lower in T2DM patients, but there was no significant difference between the groups with respect to left and right ventricular Sm and Em values, Am value, Em/Am ratio, E/Em ratio, and myocardial performance index.
Table 1 Clinical and laboratory characteristics of the subjects. Patients (n = 88) Age (years) Female, n (%) BMI (kg/m2) BSA (m2) Smoking, n (%) SBP (mmHg) DBP (mmHg) Heart rate (beats/min) Hb (g/dL) WBC (103/mL) Cr (mg/dL) LDL-C (mg/dL) FBG (mg/dL) HbA1c (%) Disease duration (months)
49.5 7.9 43 (48.9) 31.2 5.1 1.99 0.2 26 (29.5) 119.7 9.6 72.7 5.3 76.7 10.2 14.3 1.9 8.1 1.8 0.8 0.1 119.3 28.8 141 (94–357) 8.0 1.9 42 (12–240)
Controls (n = 49) 47.3 9.2 30 (61.2) 30.3 5.2 1.92 0.2 14 (28.6) 117.0 9.7 71.5 6.9 75.7 11.4 14.1 1.6 7.4 1.6 0.7 0.1 130.4 39.0 93 (78–118) –
p 0.17 0.21 0.35 0.06 1.0 0.11 0.27 0.63 0.58 0.02 0.63 0.09 <0.001
BMI, body mass index; BSA, body surface area; Cr, serum creatinine; DBP, diastolic blood pressure; FBG, fasting blood glucose; Hb, hemoglobin; HbA1c, glycosylated hemoglobin A1; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure; WBC, white blood cell. The bold and italic entries are statistically significant parameters.
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Table 2 Comparison of conventional and tissue Doppler variables between patients with type 2 diabetes mellitus and controls. Patients (N = 88) LVEDD (mm) LVESD (mm) IVS thickness (mm) PW thickness (mm) LV mass index (g/m2) Aortic diameter (mm) LA diameter (mm) LA volume index (mL/m2) LV ejection fraction (%) PAP systolic (mmHg) Conventional Doppler parameters Mitral E velocity (cm/s) Mitral A velocity (cm/s) E/A DT (ms) IVRT (ms) Tissue Doppler parameters LV lateral annulus Sm (cm/s) Am (cm/s) Em (cm/s) Em/Am E/Em MPI RV lateral annulus Sm (cm/s) Am (cm/s) Em (cm/s) Em/Am
Controls (n = 49)
p
46.9 4.6 29.0 4.5 9.6 1.3 9.4 1.4 89.9 21.8 27.6 2.9 33.8 2.9 31.2 7.4 67.4 5.2 21.8 4.6
46.3 4.6 28.8 3.9 9.0 1.6 9.4 1.2 89.6 22.8 28.6 3.0 32.0 3.5 27.8 7.4 67.1 5.2 22.0 3.6
0.46 0.79 0.03 0.86 0.93 0.07 0.004 0.01 0.79 0.74
81.48 15.7 75.7 14.9 1.11 0.30 182.3 25.3 96.3 14.3
82.9 13.1 70.8 16.1 1.23 0.34 180.1 23.1 90.2 14.8
0.55 0.08 0.05 0.6 0.02
10.4 1.9 11.4 2.5 11.0 2.8 1.0 0.34 7.8 2.3 0.58 0.07
10.4 2.4 11.0 2.4 11.4 3.0 1.0 0.33 7.5 1.8 0.56 0.08
0.92 0.36 0.35 0.22 0.48 0.13
17.0 3.0 17.9 3.8 13.2 3.3 0.77 0.32
17.0 3.3 17.2 4.3 13.6 3.6 0.83 0.30
0.88 0.38 0.49 0.32
Am, late myocardial diastolic velocity; DT, mitral E-wave deceleration time; Em, early myocardial diastolic velocity; IVRT, isovolumetric relaxation time; IVS, interventricular septum; LA, left atrium; LV, left ventricular; LVEDD, left ventricular enddiastolic diameter; LVESD, left ventricular end-systolic diameter; MPI, myocardial performance index; PAP, pulmonary artery pressure; PW, posterior wall; RV, right ventricular; Sm, systolic myocardial velocity. The bold and italic entries are statistically significant parameters.
P-wave indices and TDI parameters are shown in Table 3. Pmax duration and Pd were significantly higher in patients with T2DM (105.7 10.2 ms vs. 102.2 7.5 ms, p = 0.02; 40.6 7.6 ms vs. 33.6 5.9 ms, p < 0.001, respectively). However, Pmin duration was significantly lower in patients with T2DM (65.3 8.3 ms vs. 68.5 8.2 ms, p = 0.03). PA lateral, PA septum, and PA tricuspid durations were significantly higher in the T2DM patients when compared with the controls (64.8 14.0 ms vs. 52.1 7.3 ms, p < 0.001; 57.3 13.1 ms vs. 47.0 7.3 ms, p < 0.001, and 48.3 11.7 ms vs. 40.9 6.6 ms, p < 0.001, respectively). Also, PA divided by LA diameters was significantly higher in the T2DM patients when compared with the controls. Moreover, interatrial,
intraatrial, and intraleft atrial EMD were significantly higher in the T2DM patients when compared with the controls (16.5 7.8 ms vs. 11.2 4.4 ms, p < 0.001; 9.0 7.3 ms vs. 6.0 3.8 ms, p = 0.002 and 7.4 5.2 ms vs. 5.1 3.2 ms, p = 0.002, respectively). Correlation analysis showed a positive correlation between interatrial EMD and Pd (r = 0.429, p < 0.001) (Fig. 2) and LA volume (r = 0.428, p < 0.001) (Fig. 3). Discussion There were three major findings of this study. Interatrial, intraatrial, and left intraatrial EMD were significantly higher in
Table 3 Comparison of the electrocardiographic and tissue Doppler echocardiographic findings.
Pmax (ms) Pmin (ms) Pd (ms) PA lateral (ms) PA septum (ms) PA tricuspid (ms) PA lateral/LA diameter (ms/mm) PA septum/LA diameter (ms/mm) PA tricuspid/LA diameter (ms/mm) PA lateral PA tricuspida (ms) PA septum PA tricuspidb (ms) PA lateral PA septumc (ms)
Patients (N = 88)
Controls (n = 49)
p
105.7 10.2 65.3 8.3 40.6 7.6 64.8 14.0 57.3 13.1 48.3 11.7 1.92 0.4 1.70 0.3 1.43 0.3 16.5 7.8 9.0 7.3 7.4 5.2
102.2 7.5 68.5 8.2 33.6 5.9 52.1 7.3 47.0 7.3 40.9 6.6 1.63 0.2 1.47 0.2 1.28 0.2 11.2 4.4 6.0 3.8 5.1 3.2
0.02 0.03 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.007 <0.001 0.002 0.002
LA, left atrium; PA, time interval from the onset of P-wave on surface electrocardiogram to the beginning of Am wave interval with tissue Doppler imaging; Pd, P dispersion; Pmax, maximum P-wave duration; Pmin, minimum P-wave duration. The bold and italic entries are statistically significant parameters. a Interatrial electromechanical delay. b Intraatrial electromechanical delay. c Intraleft atrial mechanical delay.
Please cite this article in press as: Demir K, et al. Assessment of atrial electromechanical delay and P-wave dispersion in patients with type 2 diabetes mellitus. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.06.003
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Fig. 2. Correlation between interatrial electromechanical delay and P-wave dispersion.
patients with T2DM. Pd was significantly higher in patients with T2DM and there was a significant correlation between interatrial EMD and Pd. LA volume index, one of the LV diastolic function parameters, was also found to be significantly higher than in the control group, and there was a significant correlation between interatrial EMD and LA volume index. AF is the most common cardiac arrhythmia in the general population, and its prevalence is projected to increase substantially over the following decades. DM is one of the independent risk factors described for AF, and the relationship between T2DM and incident AF was evaluated in several prospective studies [1,2]. The mechanism of AF in diabetic patients is not clearly understood [1]. The increased risk of developing AF in DM may be related in part to activation of signaling pathways important in inflammation and oxidative stress. Structural remodeling and electrophysiological remodeling are critical for AF to perpetuate. The structural substrate includes atrial stretch, dilatation, loss of muscle mass, fibrosis, and disruption of cell coupling at gap junctions [8]. Increased intraatrial and interatrial EMD, atrial fibrosis and
Fig. 3. Correlation between interatrial electromechanical delay and left atrial (LA) volume.
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disturbed atrial electromechanical functions were shown as risk factors for developing AF in several diabetic animal studies. Diabetes is also associated with numerous metabolic defects including insulin resistance, impaired glucose tolerance, proinflammatory mediators, abnormalities of hemostasis, fibrinolysis, angiogenesis, and extracellular matrix turnover. All of these metabolic changes lead to endothelial dysfunction, abnormal activation of the renin-angiotensin-aldosterone system, and acceleration of atherogenesis, which could be responsible for AF occurrence. Diabetes could also cause structural, electrical, electromechanical, and autonomic remodeling [9]. These abnormalities may lead to the development of AF in diabetic people [10]. EMD has been defined as the temporal interval between the onset of cardiac electrical activity and myocardial contraction [4]. It can be easily quantified by transthoracic tissue Doppler echocardiography. Any pathologic process impairing atrial conduction may result in reentrant atrial arrhythmias [11]. Atrial conduction disorders are frequent in elderly subjects and/or those with structural heart diseases, mainly mitral valve disease, dilated cardiomyopathy, coronary slow flow, and hypertension [12– 15]. Additionally, the close relationship between EMD and metabolic syndrome, impaired fasting glucose levels, insulin resistance, type 1 DM and T2DM were demonstrated in previous studies [16–20]. It has been found that atrial EMD was independently related to new onset AF and recurrence of AF in many studies [21,22]. In the present study, we showed that interatrial, intraatrial, and left intraatrial conduction times were significantly prolonged in patients with T2DM as compared with healthy volunteers. Pd is an ECG index believed to reflect heterogeneous atrial conduction by detecting abnormal atrial conduction with ECG leads of different orientation. Pd has been studied in patients with hypertension, metabolic syndrome, and DM as a simple and noninvasive predictor of AF development [23–25]. The exact mechanism of Pd prolongation in diabetics is not well known, but it is thought that structural and electrophysiological changes in the atrial myocardium caused by diabetes might play a role. Chronic hyperglycemia causes structural and functional disorders by changing the chemical composition of the proteins present in cell membrane structure. Furthermore, extracellular protein deposition and interstitial fibrosis of myocardium can cause prolongation of Pd by forming heterogeneity in atrial conduction velocity and atrial refractoriness in diabetic patients [25]. Therefore, it has been suggested that Pd can be used to diagnose patients with a high risk of AF [26]. In this study, we found that Pmax and Pd were significantly higher in patients with T2DM and there was a significant correlation between interatrial EMD and Pd. DM is an independent risk factor with an influence on cardiac function and structure. Diastolic dysfunction is regarded as a first sign of functional abnormalities in the myocardium and is detected in up to 75% of asymptomatic diabetic patients [27]. Instead, a number of echocardiographic indices have been introduced to measure diastolic function [LV hypertrophy and mass, enlarged LA, the velocity ratio (E/A), and regional myocardial strain, etc.] [28]. In this study, we also detected greater LA diameter and LA volume index, higher IVRT and mitral A velocity, and lower E/A ratio in the T2DM patients. We found that interatrial EMD had a significant correlation with LA volume index. Our findings support that increased LA enlargement and LV early diastolic dysfunction accompanying T2DM may contribute to the prolongation of interatrial EMD. To the best of our knowledge, this is only the second report to assess the association between atrial conduction abnormalities and T2DM. This study has three different features than the previous study [20]. First, investigators did not evaluate the ambulatory blood pressure in their patient group in the previous
Please cite this article in press as: Demir K, et al. Assessment of atrial electromechanical delay and P-wave dispersion in patients with type 2 diabetes mellitus. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.06.003
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study. Hypertension is one of the major causes of EMD and LV diastolic dysfunction parameters. Therefore, in our study the patients with hypertension were excluded with ambulatory blood pressure measurements. Secondly, in the previous study, atrial conduction abnormalities were evaluated only using the TDI, but in our study atrial conduction abnormalities were assessed by both TDI and surface ECG, whereby, interatrial EMD and Pd obtained by us from both noninvasive methods were compared with each other. Thirdly, in this study we evaluated IVRT, LA diameter, and LA volume index which are parameters of LV diastolic functions. Limitations Our study was conducted in a single center with a relatively small number of participants. This was also a cross-sectional study. Patients with T2DM could not be observed prospectively for atrial arrhythmic events. In addition, although all subjects were in sinus rhythm during the study, we did not perform Holter examination to investigate presence of atrial arrhythmias in our study population. Also, we do not have data on right atrium size. Therefore, we do not know whether prolongation of interatrial EMD and impaired diastolic function, right atrium size, and increased LA diameters and volume index predict AF in T2DM patients. The other limitation of our study was that conduction times were determined with tissue Doppler echocardiography, and the gold standard technique, electrophysiological study, was not performed. The last limitation of this study is that we calculated Pmax, Pmin, and Pd manually instead of using a more reliable computer-assisted P-wave calculating system.
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[9] [10]
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Conclusion [17]
According to our findings, there was significant EMD and Pd in patients with T2DM as compared with healthy volunteers. Additionally, interatrial EMD was correlated with Pd and LA volume index. Determining electromechanical events including the interatrial conduction time with transthoracic echocardiography is a noninvasive and simple method to measure. Large-scale and long-term follow-up prospective studies are required to establish the predictive value of atrial conduction parameters for the future development of AF in patients with T2DM. Funding This research received no grant from any funding agency in the public, commercial, or not-for-profit sectors.
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Conflict of interest [23]
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Please cite this article in press as: Demir K, et al. Assessment of atrial electromechanical delay and P-wave dispersion in patients with type 2 diabetes mellitus. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.06.003