P-Wave Dispersion and Left Atrial Indices As Predictors of Paroxysmal

The Egyptian Heart Journal (2014) 66, 369–374

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ORIGINAL ARTICLE P-wave dispersion and left atrial indices as predictors of paroxysmal atrial ﬁbrillation in patients with non hemorrhagic cerebrovascular strokes and transient ischemic attacks

Mohamed Elansary, Mohamed Hamdi, Hanan Zaghla, Dalia Ragab *

Critical Care Medicine Department, Cairo University, Egypt

Received 13 September 2013; accepted 20 October 2013 Available online 14 February 2014

KEYWORDS Abstract Background: One-third of stroke and Transient Ischemic Attack (TIA) are cryptogenic P-wave dispersion; requiring additional investigation and intervention. Occult Paroxysmal Atrial Fibrillation (PAF) LA volume; has been suggested as a possible cause for these cryptogenic strokes. Paroxysmal AF Objective: The aim of our study is to evaluate the role of simple ECG & bedside echocardiographic parameters for prediction of PAF in patients presenting with stroke or TIAs. Patients & methods: The study included 60 patients with non hemorrhagic stroke. During 1 week of continuous ICU monitoring, 30% of patients had PAF (group 1), the remaining 42 patients did not develop PAF (group 2). All patients were subjected to detailed history taking, thorough clinical examination including NIHSS, serial ECGs for calculation of maximum and minimum P wave

duration (Pmax, and Pmin) & P wave dispersion (Pdis), and transthoracic echocardiography for calculation of left atrial volume (LAV), and left atrial volume index (LAVI).

Results: It was found that Pmax &Pdis were signiﬁcantly higher in group 1 in comparison to group 2 (147.7 ± 9.6 mm vs 114.3 ± 9 mm, P: <0.001) and (54.1 ± 7.5 mm vs 30.2 ± 7 mm, P: <0.001), respectively. Also LAV & LAVI were signiﬁcantly higher in group 1 compared to group 2 (57.1 ± 10 mm vs 40.1 ± 12 mm, P: <0.001) & (28.9 ± 3 mm2/m2 vs 20.1 ± 8 mm2/m2, P:

<0.001), respectively. On multivariate logistic regression analysis Pmax,Pdis, and LAVI were the most signiﬁcant independent predictors of PAF. Conclusion: PAF is a possible etiology of patients with ischemic cerebrovascular accidents patients

even in those who had normal sinus rhythm on admission. Pmax P 125 mm, Pdis P 40 mm, and LAVI P 24 are highly signiﬁcant predictors of PAF with PPV of 99%, 96% and 78%, respectively,

* Corresponding author. Tel.: +20 1225424473. E-mail address: [email protected] (D. Ragab). Peer review under responsibility of Egyptian Society of Cardiology. 1110-2608 ª 2013 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology. http://dx.doi.org/10.1016/j.ehj.2013.10.004 370 M. Elansary et al.

sensitivity of 98%, 94% and 89%, respectively, speciﬁcity 96%, 93% and 75%, respectively and AUC of 0.99, 0.98 and 0.87, respectively. ª 2013 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology.

1. Introduction P-wave durations.11 Transthoracic echocardiography was done for all patients: Standard 2D, M mode, pulsed and color Stroke is the second leading cause of death worldwide and the Doppler using parasternal and apical views to measure dimen- third leading cause of death in the developed world.1 Atrial sions and evaluate global and regional left ventricular func- fibrillation (AF) is the commonest cardiac arrhythmia and tion. Assessment of left atrial volume (LAV) using the constitutes the etiology in almost 15–20% of all ischemic prolate ellipse method at apical 4-chamber and parasternal 13 strokes. A paroxysmal variant is as dangerous as permanent long-axis views at ventricular end systole (Fig. 1). 13 one, and in case of stroke, it is probably as frequent as in per- LAV was calculated as D1xD2xD3x 0.523. Left atrial manent variant in causing the most severe and disabling stroke volume index (LAVI) was calculated by relating the LAV to and might be overlooked and this might lead to depriving pa- body surface area. During ICU stay, all patients were kept tients from full anticoagulation therapy.2 Therefore, it is on continuous rhythm monitoring using monitors with trends important to diagnose AF whether permanent or paroxysmal for detection of any rhythm disturbance. variants after an ischemic stroke to provide maximal stroke Patients were divided into 2 groups: group 1: 18 patients prevention therapy. However, the diagnosis of AF especially who had PAF identified by documented history or during the paroxysmal variant poses a challenge. Some reports re- ICU stay. Group 2: 42 patients who had normal sinus rhythm vealed that the measurement of P wave duration and P wave during their whole hospital stay. dispersion in sinus rhythm, together with left atrial echocardiographic parameters might be a useful noninvasive clinical tool 3.1. Statistical analysis to identify patients at risk of developing atrial electrical insta- bility and AF.3 Computer software package SPSS 15.0 was used in the analysis. For quantitative variables, mean/median (as a measure of 2. Aim of the study central tendency), standard deviation/range, minimum, and maximum (as measures of variability) were presented. Fre- To determine whether ECG and transthoracic echocardio- quency and percentages were presented for qualitative vari- graphic LA measurements could help in detecting PAF in ables. Mann–Whitney, Kruskal Wallis and Patients & patients presenting with acute ischemic cerebrovascular Methods-83-Anova tests were used to estimate differences in accidents. quantitative variables. Chi-square and Fisher Exact tests were used to estimate differences in qualitative variables. Logistic regression analysis was performed to find out the most signif- 3. Patients and methods icant independent predictors of certain dependent variable by using backward likelihood ratio technique. ROC curve (recei- This study is a prospective observational study conducted on ver operator characteristic curve) was used to find out the best 60 patients with mean age of 64.3 ± 10.9 years admitted to cut off in addition to validity. Correlation to estimate associa- the Critical Care Medicine Department of Cairo university tion between quantitative variables was presented in the form with the diagnosis of acute ischemic cerebrovascular stroke of correlation coefficient and its significance. A probability va- or TIA during the period from July to December 2012. All pa- lue (P value) less than 0.05 was considered significant. P value tients had normal sinus rhythm at the time of admission. less than 0.001 was considered highly significant, P value high- Exclusion criteria included: patients less than 18 years old, er than 0.05 was considered insignificant. rheumatic heart disease or ICU length of stay less than one week. All patients were subjected to detailed history taking, thorough clinical examination including full neurological 4. Results assessment, routine laboratory investigation. CT brain was done on admission and 48 h later for all patients. Upon admis- During the period from July to December 2012, 60 patients sion, assessment of conscious level using Glasgo Coma Scale admitted with cryptogenic cerebrovascular accidents or TIAs (GCS), National Institute of Health & Stroke Score (NIHSS) were enrolled. Patients were then divided according to docu- & Modified Rankin Score (MRS).4–8 Twelve lead ECG was mented history or development of PAF during their hospital done on admission and regularly every 8 h for 7 days. All stay into 2 groups. Group 1 (PAF group) included 18 patients ECGs were recorded at a paper speed of 25 mm/s & 50 mm/s and group 2 (non PAF group) included 42 patients. Patients’ with a calibration of 1 mV = 10 mm and analyzed thoroughly demographic and general characteristics are shown in Table 1. for calculation of Pmax,Pmin, and Pdis. P-wave duration was de- Except for diabetes mellitus which was found to be signifi- fined as the time measured from the onset to the end of the P- cantly higher in group 2, patients in both groups were compa- wave deflection. The onset of the P-wave was considered as the rable to each others with no statistical significant difference as junction between isoelectric line and first visible upward or regards their general characteristics namely general epidemio- downward slope of the trace, the return of the trace to its iso- logical data, atherosclerotic risk factors, history of thyroid 9–12 electric line was considered to be the end of the P-wave. Pdis disease, history of previous cerebrovascular accidents or global was defined as the difference between maximum and minimum LV function. P-wave dispersion and left atrial indices as predictors of paroxysmal atrial fibrillation 371

Figure 1 Left axis parasternal, and apical 4 chambers views to measure D1,D2, and D3.D1 is obtained from apical 4 chamber view, from blood tissue interface at posterior atrial wall to level of mitral annular. D2 is obtained from the blood tissue interface of the atrial wall to the interatrial septum. D3 is obtained from the blood–tissue interface of the anterior and posterior walls.

4.1. Comparison between the studied groups regarding severity value, and diagnostic accuracy 94%, 92.7%, 78% and area un- of stroke der the curve (AUC) for these variables were 0.99 0.98, and 0.87, respectively, Fig. 2. Patients in group1 had signiﬁcantly more severe symptoms at Moreover, Pmax,Pd and LAVI were considered the most presentation compared to patients in group 2, they have lower signiﬁcant independent predictors of PAF by backward likeli- GCS (11.7 ± 3 vs 13.4 ± 2.9, P: <0.05), higher NIHSS hood ratio technique of logistic regression. Table 4. (13.8 ± 7 vs 9.5 ± 5, P: <0.05) and higher MRS (3.7 ± 1.1 vs 3.2 ± 1.2, P: <0.05), Table 2. 5. Discussion

4.2. P wave and echocardiographic left atrial indices in study Despite advances in diagnostic and interventional procedures, groups cardiac causes constitute the etiology in a high proportion of patients with ischemic stroke.14 The association between PAF and stroke has been shown to be considerably strong.15 Group 1 had a highly significantly higher values of Pmax Ischemic stroke patients – either with paroxysmal or perma- (147.7 ± 9.6 vs 114.3 ± 9, P: <0.001), Pmin (93.6 ± 8 vs nent AF – have greater mortality and morbidity rates when 83.7 ± 8, P: <0.001), Pd (54.1 ± 7.5 vs 30.2 ± 7, P: 16 <0.001), LAV (57.1 ± 10 vs 40.1 ± 12, P: <0.001) and LAVI compared to those without AF. On the other hand, poor (28.9 ± 3 vs 20.1 + 8, P: <0.001), Table 3. outcome associated with PAF is preventable with anticoagula- Receptive operator characteristics (ROC) curve was calcu- tion in nearly 40% of patients and it is clinically crucial to 17 lated to detect the highest predictive parameter of Paroxysmal detect these patients. However, unlike permanent AF, PAF might not be diagnosed readily and can be easily overlooked. AF (PAF) and it was found that Pmax,Pd, and LAVI were considered the most valid predictors of PAF. The best cutoff value 2 of Pmax,Pd, and LAVI were 125 ms, 40 ms, and 24 ml/m . These values have 98%, 94%, and 89% sensitivity, 96%, Table 2 Comparison between group 1 and 2 as regards 93%, and 75% specificity, with 99%, 96%, and 90% positive admission severity scores. predictive value, 93%, 95%, and 80% negative predictive Variables Group 1 Group 2 P Significance MRS 3.7 ± 1.1 3.2 ± 1.2 >0.05 NS GCS 11.7 ± 3 13.4 ± 2.9 <0.05 S Table 1 General characteristics of the studied groups. NIHSS 13.8 ± 7 9.5 ± 5 <0.05 S Variables Group 1 Group 2 P MRS: Modified Rankin Score, GCS: Glasgow Coma Scale, NIHSS: National Institute of Health & Stroke Score. Age 67.8 ± 10 62.7 ± 10 >0.05 Gender Male 10 (55.6%) 24 (57.1%) >0.05 Female 8 (44.4%) 18 (42.9%) Smoking 8 (44.4%) 15 (35.7%) >0.05 Table 3 P wave and echocardiographic left atrial indices in HTN 16 (88.9%) 31 (73.8%) >0.05 both groups. DM 7 (38.9%) 28 (66.7%) <0.05 Variables Group 1 Group 2 P Significance Thyroid disease 3 (16.2%) 3 (7.1%) >0.05 IHD 9 (50%) 19 (45.2%) >0.05 Pmax 147.7 ± 9.6 114.3 ± 9 <0.001 HS HF 4 (22.2%) 8 (19%) >0.05 Pmin 93.6 ± 8 83.7 ± 8 <0.001 HS Previous TIA 2 (11.1%) 3 (7.1%) >0.05 Pd 54.1 ± 7.5 30.2 ± 7 <0.001 HS Previous Stroke 5 (27.8%) 13 (31%) >0.05 LAD 4.0 ± 2.0 3.7 ± 0.4 >0.05 NS Dyslipidemia 2 (11.1%) 7 (16.7%) >0.05 LAV 57.1 ± 10 40.1 ± 12 <0.001 HS EF 54.8 ± 14 59.6 ± 8 >0.05 LAVI 28.9 ± 3 20.1 + 8 <0.001 HS 372 M. Elansary et al.

between the 2 groups regarding the presence of clinical risk factors except for diabetes that was significantly higher in group 1. This finding was in agreement with the study conducted by Archit Bhatt et al., who studied the predictors of occult PAF in cryptogenic strokes, they studied and retrospectively analyzed Figure 2 ROC curve of Pmax,Pmin,Pd and LAVI. Moreover, 62 consecutive patients with cryptogenic stroke or TIA who Pmax, Pd and LAVI were considered the most significant underwent prolonged non-invasive cardiac monitoring up to independent predictors of PAF by backward likelihood ratio 28 days after discharge & found that there was no statistical technique of logistic regression Table 4. significant difference between AF & non AF group regarding age, sex, hypertension, and heart disease.26 In contrast, Wohlfahrt et al. reported that advanced age & history of IHD could be clinical predictors to identify PAF Table 4 Relation between PAF AND different predictors by after ischemic stroke. This discrepancy may be related to the logistic regression analysis. difference in methodology implemented in their study, as their Variables Beta-coefficient P Odd’s (95% CI) patients were subjected to the intensified algorithm to detect

Pmax P 125 0.90 <0.001 2.7 (1–12.5) paroxysmal atrial fibrillation (7 days Holter ECG, and follow 27 Pd P 40 0.85 <0.001 2.2 (0.6–11.5) up investigations after 90 days & one year). LAVI P 24 0.57 <0.001 1.8 (0.2–12) Regarding the severity of stroke at presentation, our study revealed that PAF group had higher NIHSS & lower GCS compared to non AF group (13.8 ± 7 & 11.7 ± 3 vs 9.5 ± 5 & 13.4 ± 2.9, P value <0.05). Clinical guidelines recommend that patients with acute ische- In agreement to this finding, Kimura et al. found that the mic stroke should be evaluated with 24-h inpatient monitoring admission National Institutes of Health Stroke Scale (NIHSS) to detect PAF.18 But, 24-h Holter monitoring might have a low score of the AF group was higher than that of the non-AF yield diagnosing only 2.4–9.4% of these patients.19 Possibility group (median, 12 vs 5; P < 0.0001), and that The mortality of detecting PAF with 24-h Holter monitoring might be even rate within 28 days after admission was 11.3% in the AF group lower (1–5%). Moreover, it has recently been reported that and 3.4% in the non-AF group (P < 0.0001).28 there was no significant difference between Holter monitoring Our results also showed that apart from echocardiographic and serial ECG assessment in AF detection in patients with LA diameter, all other ECG & echocardiographic LA mea- 20 stroke/transient ischemic attacks. surements, Pmax,Pdis, LAV, LAVI, were significantly higher The challenges mentioned above have led to investigations in PAF group compared to non paroxysmal AF group 2 2 2 in this area. Pd is one of the most investigated parameters. Pd (147.7 mm, 54.1 mm, 57.1 mm , and 28.9 mm /m vs assessed on a single resting ECG is regarded as a noninvasive 114.3 mm, 30.2 mm, 40.1 mm2, and 20.1 mm2/m2 respectively, electrocardiographic marker which reflects the prolongation of P value <0.05). Results published by Umuttan Dogan et al. intraatrial and interatrial conduction time in addition to dis- reported the same results. In 2012, they conducted a study continuous propagation of sinus impulses.21 It has been dem- on 400 patients presenting with acute ischemic stroke, where onstrated that prolongation of Pd is a risk factor for the resting ECG, 24 h Holter monitoring & echocardiography development of PAF independent from the presence of struc- were done to all patients, results showed that Pmax tural heart diseases. It also has been shown that Pd might pre- (P = 0.002), Pdis (P < 0.001) and LA diameter (P = 0.04) dict transition from PAF to permanent AF.21,22 were significantly higher in patients with PAF when compared In previous studies, echocardiographic left atrial diameter to patients without PAF. However, in binary logistic regres- 29 (LAD) and premature atrial contractions on Holter monitoring sion analysis Pdis was the only independent predictor of PAF. were the predictors of PAF in patients with acute ischemic Moreover, Mehrdad Saravi et al. studied the different LA stroke.23 But because of high costs and technical inconvenience, indices in where 40 consecutive patients with PAF and other standard 12-lead ECG is still the most commonly used tech- 40 age and gender matched healthy controls. Their results 24 nique. P-wave dispersion (Pd) measured from a single ECG is showed that Pdis were significantly longer in PAF patients with regarded as an electrocardiographic marker of inhomogeneous either normal or increased LA diameter than in controls.30 and discontinuous propagation of sinus impulses.25 In addition, Kosropanah Sh et al. reported that ECGs of pa- Our study aimed at evaluate if P-wave measurements on tients with and without AF in pre and post-CABG showed that surface 12 lead ECG, and LA measurements on transthoracic P-wave dispersion increased by 10ms on the first postop day in echocardiography can predict PAF in patients with non-hem- thosewithAFcomparedtopre-opvalues(P = 0.018). Likewise, orrhagic cerebrovascular accidents and TIA’s. P-wave dispersion increased by 8 ms on the 3rd post-op day in To achieve this aim, we studied 60 patients admitted to the patients who developed AF (P = 0.035).31 Critical Care Medicine Department of Cairo University with In our study, echocardiographic parameters namely LAV & the diagnosis of non hemorrhagic stroke or TIAs and all had LAVI showed statistically significant higher values in group1 sinus rhythm upon admission. We found that 18 patients in comparison to group 2 (57.1 ± 10 & 28.9 ± 3 vs (30%) experienced paroxysmal attack of AF while 42 patients 40.1 ± 12 & 20.1 ± 8, respectively, P: <0.05). (70%) remained with normal sinus rhythm during their hospi- In agreement with our study, Raol stahrenberg et al. per- tal stay. Both groups showed no statistical significant differ- formed a study on 193 consecutive patients presenting with cere- ence regarding their general characteristics and demographic bral ischemia & normal sinus rhythm, patients were subjected to data. Nonetheless, there was no statistical significant difference echocardiograpic evaluation & 7 days holter monitoring for P-wave dispersion and left atrial indices as predictors of paroxysmal atrial fibrillation 373 identification of patients with paroxysmal PAF. Results showed 2. World Health Report 2000. Geneva: WHO, 2000. that LAV & LAVI were higher in paroxysmal atrial fibrillation 3. World Health Report 1998. Geneva: WHO, 1998. group in comparison to non paroxysmal atrial fibrillation 4. Teasdale G, Jennett B. Assessment of coma and impaired group.32 consciousness. Lancet 1974;81–4. 5. Rankin J. Cerebral vascular accidents in patients over the age of In our study, P in ECG is a statistically significant predic- max 60. Scott Med J 1957;2:200–15. tor of PAF & with cut off value >125 ms it predicts PAF with 6. Bonita R, Beaglehole R. Modification of Rankin scale: recovery of very high sensitivity & specificity 98% & 96%, respectively with a motor function after stroke. Stroke 1988;19(12):1497–500. positive predictive value of 99% & negative predictive value of 7. Van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn 93%. Also Pd is a statistically significant predictor of PAF & J. Interobserver agreement for the assessment of handicap in with cut off value >40 ms it predicts PAF with very high sensi- stroke patients. Stroke 1988;19(5):604–7. tivity & specificity 94% & 93%, respectively with a positive pre- 8. National Institute of Health, National Institute of Neurological dictive value of 96% & negative predictive value of 95%. Disorders and Stroke. Stroke Scale. In comparison to Umuttan Dogan et al., study in binary lo- 9. Aytemir K, Ozer N, Atalar E, Sade E. P wave dispersion on 12- gistic regression analysis P was the only independent predic- lead electrocardiography in patients with paroxysmal atrial d fibrillation. PACE 2000;23:1109–12. tor of PAF. The cut-off value of P for the detection of PAF d 10. Andrikopoulos GK, Dilaveris PE, Richter DJ. Increased variance was 57.5 ms (ms). Area under the curve was 0.80 of P wave duration on the electrocardiogram distinguishes patients (P < 0.001). On a single 12-lead ECG, a value higher than with idiopathic paroxysmal atrial fibrillation. PACE 57.5 ms predicted the presence of PAF with a sensitivity of 2000;23:1127–32. 29 80% and a specificity of 73%. 11. Dilaveris PE, Gialafos E, Sideris S. Simple electrocardiographic In our study, LAVI in echocardiography is statistically markers for the prediction of paroxysmal idiopathic atrial highly significant predictor of PAF & with cut off values high- fibrillation. Am Heart J 1998;135:18, 73–8. er than 24 ml/m2 it predicts PAF with sensitivity 89% & spec- 12. Chang CM, Lee SH, Lu MJ, Lin CH, Chao HH, Cheng JJ, et al. ificity 75% & with positive predictive value of 90% & negative The role of P wave in prediction of atrial fibrillation after coronary predictive value of 80%. artery surgery. Int J Cardiol 1999;68:303–8. 13. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, In comparison to Raol stahrenberg et al., LAD, LAV, Pellikka PA et al. Chamber Quantification Writing Group; LAVI & LAVI/a’ (LAVI divided by tissue Doppler wave) were American Society of Echo-cardiography’s Guidelines and Stan- all highly sensitive predictors with P value <0.05 but in binary dards Committee; European Associ-ation of Echocardiography. logistic regression analysis LAVI/a’ had the largest area under Recommendations for chamber quantification: a report from the the curve & with cut off value <2.3 had 92% sensitivity, American Society of Echocardiography’s Guidelines and Stan- 55.8% specificity, and 98% negative predictive value for dards Committee and the Chamber Quantification Writing Group, PAF.32 developed in conjunction with the European Association of Echocardiography, a branch of the European Society of 6. Study limitation Cardiology. 14. Weir NU. An update on cardioembolic stroke. Postgrad Med J 2008;84:133–42. In addition to the small sample size, identification of occur- 15. Friberg L, Hammar N, Rosenqvist M. Stroke in paroxysmal atrial rence of AF depended only on documented history and record- fibrillation: report from the Stockholm Cohort of atrial fibrilla- ing an AF episode during their ICU stay and none of the study tion. Eur Heart J 2010;31:967–75. patients underwent more intensified investigation as Holter or 16. Camm AJ, Kirchhof P, Lip GY, et al. Guidelines for the was subjected to long follow up. Also, the mean age of study management of atrial fibrillation: the task force for the manage- patients was a little bit high making the association of PAF ment of atrial fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010;31:2369–429. and the etiology of their cerebrovascular accidents question- 17. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic able, in other words, thrombotic etiology could not be therapy to prevent stroke in patients who have nonvalvular atrial excluded. fibrillation. Ann Intern Med 2007;146:857–67. 18. Adams Jr HP, del Zoppo G, Alberts MJ, et al. Guidelines for the 7. Conclusion early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular PAF is a possible etiology of patients with ischemic cerebro- Radiology and Intervention Council, and the Atherosclerotic vascular accidents patients even those had normal sinus Peripheral Vascular Disease and Quality of Care Outcomes in rhythm during admission. LA indices as Pmax,Pdis, and LAVI Research Interdisciplinary Working Groups: the American Acad- are highly significant independent predictors of PAF in these emy of Neurology affirms the value of this guideline as an patients. educational tool for neurologists. Stroke 2007;38:1655–711. 19. Yu EH, Lungu C, Kanner RM, Libman RB. The use of diagnostic Conflict of interest tests in patients with acute ischemic stroke. J Stroke Cerebrovasc Dis 2009;18:178–84. 20. Douen AG, Pageau N, Medic S. Serial electrocardiographic No conflict of interest. assessments significantly improve detection of atrial fibrillation 2.6-fold in patients with acute stroke. Stroke 2008;39:480–2. References 21. Dilaveris PE, Gialafos EJ, Sideris SK, et al. Simple electrocardiographic markers for the prediction of paroxysmal idiopathic 1. Sarti C, Rastenyte D, Cepaitis Z, Tuomilehto MJ. International atrial fibrillation. Am Heart J 1998;135:733–8. trends in mortality from stroke, 1968 to 1994. Stroke 22. Koide Y, Yotsukura M, Ando H, et al. Usefulness of P-wave 2000;31:1588–601, Jul. dispersion in standard twelve-lead electrocardiography to predict 374 M. Elansary et al.

transition from paroxysmal to persistent atrial fibrillation. Am J 28. Kimura K, Minematsu K, Yamaguchi T, et al. Atrial fibrillation Cardiol 2008;102:573–7. as a predictive factor for severe stroke and early death in 15831 23. Fujii S, Shibazaki K, Iguchi Y, Sakai K, Kimura K. Relationship patients with acute ischemic stroke. J Neurol Neurosurg Psychiatry between left atrial size and paroxysmal atrial fibrillation in acute 2005;76:679–83. ischemic stroke. Rinsho Shinkeigaku 2009;49:629–33. 29. Dogan U, Dogan EA, Tekinalp M, et al. P-wave dispersion for 24. Douen A, Pageau N, Medic S. Usefulness of cardiovascular predicting paroxysmal atrial fibrillation in acute ischemic Stroke. investigations in stroke management: clinical relevance and Int J Med Sci 2012;9(1):108–14. economic implications. Stroke 2007;38:1956–8. 30. Saravi M, Montazeri M, Montazeri M. Efffect of left atrial size on 25. Centurion OA. Clinical implications of the P wave duration and P wave dispersion: a study in patients with paroxysmal atrial dispersion: relationship between atrial conduction defects and fibrillation. abnormally prolonged and fractionated atrial endocardial electro- 31. Kosropanah Sh, Nemati MH, Bzargan O, et al. Effect of CABG grams. Int J Cardiol 2009;134:6–8. on P wave dispersion and the relationship between AF and P wave 26. Bhatt A, Majid A, Razak A et al. Predictors of occult paroxysmal dispersion. Int Cardiovasc Res J 2009;3(2):80–5. atrial fibrillation in cryptogenic strokes detected by long-term 32. Stahrenberg R, Edelmann F, Haase B, et al. Transthoracic noninvasive cardiac monitoring. Stroke Res Treat 2011; 2011, echocardiography to rule out paroxysmal atrial fibrillation as a Article ID: 172074. cause of stroke or transient ischemic attack. Stroke 27. Wohlfahrt J, Stahrenberg R, Weber-Kruger M et al. Clinical 2011;42:3643–5. predictors to identify paroxysmal atrial fibrillation after ischaemic stroke. Eur J Neurol 2013. doi: 10.1111/ene. 12198.