Evaluation of P wave and corrected QT dispersion in subarachnoid haemorrhage.
Subarachnoid haemorrhage (SAH) is considered to be a significant cause of stroke and premature deaths of patients below 45 years of age with an incidence of 6 to10/100,000 per year (1,2)
Electrocardiographic (ECG) disorders frequently emerge during the first 48 hours after SAH38. The incidence of the ECG disorders, their pathogenesis, developmental mechanisms and their prognostic importance has not been clearly elucidated (3-5). Extension of the QT interval during the acute phase of SAH is the most frequently observed ECG change (9-11).
P wave dispersion (Pwd) is an easy, basic and non-invasive electrocardiographic indicator of atrial arrhythmia (12). Atrial fibrillation was detected with 24-hour Holter monitoring in 76% of the SAH patients who experienced cardiac arrhythmia (13), but there are no data published on the impact of Pwd in SAH. In this study, we examined the ECG recordings of SAH patients and compared them with those of neurologically normal patients to determine the impact of SAH on the Pwd, QT, corrected QT (QTc), QT dispersion (QTd) and corrected QT dispersion (QTcd) intervals.
Following the approval of the hospital ethics committee, adult patients who had applied to the Polyclinic of Anaesthesiology and Reanimation at Zonguldak Karaelmas University for pre-anaesthesia assessment between January 2003 and January 2009 were retrospectively included in the study. Thirty-five SAH patients were assigned into the SAH group (Group S) and 35 neurologically normal patients were assigned into the control group (Group C).
ECG recordings, serum electrolyte levels, Glasgow Coma Scale scores and Hunt-Hess Scale scores of all patients were examined.
Standard 12 derivations ECG recordings had been obtained with a paper speed of 25 mm/second and a deflection of 10 mm/mV during the pre-anaesthesic evaluation of all the patients (Hewlett Packard, Pagewriter 300pi). The ECG recordings of Group S were performed in the first 48 hours following SAH. Heart rate was calculated using mean RR time. The QT interval was defined as between the beginning of QRS complex and the place where T wave descend onto the TP isoelectric line. When a U wave interrupted the T wave before returning to the baseline, the QT interval was measured to the nadir of the curve between the T and U waves. The QTc interval was calculated using the Bazett formula; QTc (ms) = QT measured /[square root of (RR)] (where RR is the RR interval). Extended QTc interval was defined as a duration of more than 440 ms. The QTd value was determined as the difference between the longest and shortest QT intervals in the 12 ECG leads. Extended QTd was defined as longer than 60 ms. The QTcd duration according to heart rate was identified with the Bazett formula; QTcd (ms) = QTd measured/[square root of (RR)].
The beginning of the P waves was defined as a positive deflection from the isoelectric line and the end as the point when the positive deflection return to the isoelectric line (12). Derivations where the beginning and end of the P wave were not obvious were excluded from the study. Pwd was the difference between the longest and shortest P wave duration. Extended Pwd was defined as Pwd duration longer than 40 ms.
Subjects who had fewer than nine derivations assessed in the ECG were excluded from the study. All ECG measurements were evaluated three times by two experts who did not know to which group the subject belonged and the mean values were accepted.
The serum levels of sodium, potassium, magnesium, chloride and calcium were measured from the venous blood specimens taken at their initial application to the emergency department.
Statistical Package for the Social Sciences (SPSS) 10.0 was used for data analysis. One way analysis of variance was used to compare parametric variables and chi-square was used for analysis of nonparametric variables. The Pearson's correlation coefficients were determined for Glasgow Coma Scale scores, Hunt-Hess Scale scores, serum potassium, calcium, magnesium, QTc, QTcd and Pwd intervals. P <0.05 was considered statistically significant.
There was no significant difference between study groups according to age (P=0.275) and gender (P=0.473). The incidences of hypertension (P=0.138) and diabetes mellitus (P=0.477) in both groups were also similar (Table 1). There was no incidence of coronary artery disease in any of the patients in either group.
In Group S, two patients had sinus tachycardia, two had atrial ectopic beats and two had ventricular ectopic beats. All patients in Group C were in sinus rhythm. No patient in either group had atrio-ventricular block, nor did any of the patients demonstrate branch block pattern. The average heart rate of Group S was found to be significantly higher than that of Group C (P=0.015) (Table 2).
The QT, QTc, QTd and QTcd durations of Group S were also significantly longer than Group C (P <0.001) (Table 2).
In Group S the QTc interval value was above 440 ms in 19 patients (54.3%). The QTc interval extension was observed in none of the patients in Group C (P <0.001). The QTcd interval value was found to be above 60 ms in 24 cases in Group S (68.6%) and in one case in Group C (2.9%) (p <0.001).
There was no significant difference between Groups S and C in terms of minimum P wave duration (P=0.202). However, the maximum P wave and Pwd durations of Group S were found to be significantly longer than those of Group C (P <0.001) (Table 2).
The Pwd duration value was found to be above 40 ms in 20 patients in Group S (57.1%) and in one patient in Group C (2.9%) (P <0.001).
The serum potassium, calcium, magnesium and chloride values were found to be significantly low in Group S when compared with those of Group C (Table 3).
In the Pearson's correlation analysis, a positive but weak correlation was found between mortality and QTc extension (P=0.032, r=0.363). No correlation was detected between QTcd, Pwd durations and serum electrolyte levels (Table 4).
In our study, the Pwd, QT, QTc, QTd and QTcd durations in the ECG recordings of SAH patients were found to be significantly longer when compared with those of the control group. Previous studies have reported that 25 to 100% of SAH patients may have ECG disorders (4,14-16). According to a meta-analysis, ECG disorders are observed during the post-SAH period in 80 to 90% of patients (11). While these disorders can be temporary in some cases, life-threatening arrhythmias can be observed in others (8). In a case report, QT extension during cerebral arterial aneurysm clipping developed into torsade de pointes17. The extension of QT and QTc intervals at the acute period of traumatic and nontraumatic SAH is one of the most frequently observed ECG changes9,10,18. Although repolarisation disorders are observed at a rate of 60 to 70% in SAH, it is QT extension most frequently observed (11). As in previous studies, we found that the durations of QT and QTc significantly extended in the patients with non-traumatic SAH.
In an earlier study, the average QTc interval in SAH patients was found to be 456 [+ or -] 59 ms and 438 [+ or -] 48 ms with the Bazett and Hodges formulae, respectively (19). In another study, the average QTc interval in SAH was 466 [+ or -] 46 ms9. Another study revealed one or more repolarisation disorders in 41% of the SAH patients who had QTc intervals above 460 ms (20). In our study, the mean QT and QTc intervals of SAH patients were 387.06 [+ or -] 52.89 ms and 449.43 [+ or -] 37.66 ms, respectively. The QTc interval was above 440 ms in 54.3% and above 460 ms in 31.3% of the SAH patients.
Correlation between severity of SAH and QTc and QTc extension is reported to be dependent on the formula used (19), while the female gender and hypokalaemia are also independent risk factors for extension of the QTc interval (9,21). However, we could not demonstrate a significant correlation between gender and serum electrolyte levels and QTc duration (Table 4). Serious extension of QTc is one of the most effective determinants of myocardial dysfunction in SAH but some studies suggest it has no significant association with mortality (20,22). However, there are several studies reporting that QTc interval in SAH is a determinant of mortality (5,23). In our study, a correlation was found between QTc and mortality in patients with SAH.
The QTd duration significantly extends in patients with SAH with a positive correlation between QTd duration and the plasma concentration of dihydroxyphenylglycol, a metabolite of norepinephrine (24). The increase in QTd duration which is an indicator of predisposition to cardiac arrhythmia, may be related to the increased concentration of catecholamines in these patients (24). Sato et al (25) showed that QTd durations have been prolonged in patients with SAH, especially in high-grade cases. They found a positive correlation between QTd and Hunt and Hess grade and a negative correlation between QTd and serum potassium levels (25). The QTd and QTcd durations of SAH patients in our study were also found to be longer than those of the control group. However, there was no correlation between Hunt-Hess Scale scores, serum electrolyte levels and QTd interval in SAH.
Pwd is defined as the difference between maximum and minimum P wave duration, and atrial arrhythmias are regarded as simple and noninvasive electrocardiographic indicators12. The Pwd duration may extend due to coronary ischaemia (26), anxiety (27) and migraine attack (28). However, during our literature survey, we could not come across any data describing the impact of SAH on Pwd. In our study, we found that the durations of Pwd also extends.
The pathogenesis of the ECG disorders developed in SAH is not clear (3). The increased concentration of cardiogenic enzymes and plasma catecholamines, which could be associated with increased sympathetic activity (6,811,24), the stimulation of the insula cortex, which plays a role in the regulation of blood pressure (16), the increase in parasympathetic and vagal activity, which could be caused by increased intracranial pressure6, the irregularity of autonomic cardiovascular control8 and electrolyte disorders7 are among the possible causes.
It is known that electrolyte disorders such as hypokalaemia (10), hyponatraemia (29,30) and hypomagnesemia (7,31) are frequently observed in patients with SAH. The extension of QT and QTc in patients with SAH can be associated with hypokalaemia8,14 and serious ventricular arrhythmias are more frequently observed when the QTc interval is 550 ms and above and the hypokalaemia is 3.5 mmol.[l.sup.-1] and below (15). Hypomagnesaemia is associated with ECG disorders observed in patients with SAH (7), such as formation of atrial fibrillation and extended Pwd (32,33). Dagdelen et al (33) emphasised that magnesium treatment prior to coronary artery bypass surgery shortened Pwd durations. However, we could not observe a correlation between these electrolytes and QTc, QTcd and Pwd, so ECG changes in SAH patients may not be solely attributed to electrolyte disorders.
In conclusion, we found that the Pwd, QTc and QTcd durations in SAH significantly extended. We suggest that arryhthmias may be caused by extended Pwd and QTcd durations during anaesthesia and intensive care for SAH patients.
Accepted for publication on June 5, 2009.
(1.) Linn FH, Rinkel GJ, Algra A, van Gijn J. Incidence of subarachnoid hemorrhage: role of region, year, and rate of computed tomography: a meta-analysis. Stroke 1996; 27:625-629.
(2.) Cahill J, Calvert JW, Marcantonio S, Zhang JH. p53 may play an orchestrating role in apoptotic cell death after experimental subarachnoid hemorrhage. Neurosurgery 2007; 60:531-545; discussion 545.
(3.) Schuiling WJ, Algra A, de Weerd AW, Leemans P, Rinkel GJE. ECG abnormalities in predicting secondary cerebral ischemia after subarachnoid haemorrhage. Acta Neurochir (Wien) 2006; 148:853-858; discussion 858.
(4.) Sakr YL, Lim N, Amaral ACKB, Ghosn I, Carvalho FB, Renard M et al. Relation of ECG changes to neurological outcome in patients with aneurysmal subarachnoid hemorrhage. Int J Cardiol 2004; 96:369-373.
(5.) Kawasaki T, Azuma A, Sawada T, Sugihara H, Kuribayashi T, Satoh M et al. Electrocardiographic score as a predictor of mortality after subarachnoid hemorrhage. Circ J 2002; 66:567-570.
(6.) Kawahara E, Ikeda S, Miyahara Y, Kohno S. Role of autonomic nervous dysfunction in electrocardio-graphic abnormalities and cardiac injury in patients with acute subarachnoid hemorrhage. Circ J 2003; 67:753-756.
(7.) van den Bergh WM, Algra A, Rinkel GJE. Electrocardiographic abnormalities and serum magnesium in patients with subarachnoid hemorrhage. Stroke 2004; 35:644-648.
(8.) Lanzino G, Kongable GL, Kassell NF. Electrocardiographic abnormalities after nontraumatic subarachnoid hemorrhage. J Neurosurg Anesthesiol 1994; 6:156-162.
(9.) Fukui S, Katoh H, Tsuzuki N, Ishihara S, Otani N, Ooigawa H et al. Multivariate analysis of risk factors for QT prolongation following subarachnoid hemorrhage. Crit Care 2003; 7:R7 R12.
(10.) Wong GKC, Poon WS, Chan MTV, Boet R, Gin T, Lam CW. The effect of intravenous magnesium sulfate infusion on serum levels of sodium and potassium in patients with aneurysmal subarachnoid hemorrhage. Magnes Res 2007; 20:37-42.
(11.) Sakr YL, Ghosn I, Vincent JL. Cardiac manifestations after subarachnoid hemorrhage: a systematic review of the literature. Prog Cardiovasc Dis 2002; 45:67-80.
(12.) Duru M, Seyfeli E, Kuvandik G, Kaya H, Yalcin F. Effect of weight loss on P wave dispersion in obese subjects. Obesity (Silver Spring) 2006; 14:1378-1382.
(13.) Frontera JA, Parra A, Shimbo D, Fernandez A, Schmidt JM, Peter P et al. Cardiac arrhythmias after subarachnoid hemorrhage: risk factors and impact on outcome. Cerebrovasc Dis 2008; 26:71-78.
(14.) Andreoli A, di Pasquale G, Pinelli G, Grazi P, Tognetti F, Testa C. Subarachnoid hemorrhage: frequency and severity of cardiac arrhythmias. A survey of 70 cases studied in the acute phase. Stroke 1987; 18:558-564.
(15.) Di Pasquale G, Pinelli G, Andreoli A, Manini G, Grazi P, Tognetti F. Holter detection of cardiac arrhythmias in intracranial subarachnoid hemorrhage. Am J Cardiol 1987; 59:596-600.
(16.) Di Pasquale G, Lusa AM, Manini GL, Dominici P, Andreoli A, Limoni P et al. [Cardiac arrhythmias associated with subarachnoid hemorrhage. Prospective study with dynamic electrocardiography]. G Ital Cardiol 1984; 14:323-329.'
(17.) Takenaka I, Aoyama K, Iwagaki T, Ishimura H, Kadoya T. Development of torsade de pointes caused by exacerbation of QT prolongation during clipping of cerebral artery aneurysm in a patient with subarachnoid haemorrhage. Br J Anaesth 2006; 97:533-535.
(18.) Collier BR, Miller SL, Kramer GS, Balon JA, Gonzalez LS 3rd. Traumatic subarachnoid hemorrhage and QTc prolongation. J Neurosurg Anesthesiol 2004; 16:196-200.
(19.) Colkesen AY, Sen O, Giray S, Acil T, Ozin B, Muderrisoglu H. Correlation between QTc interval and clinical severity of subarachnoid hemorrhage depends on the QTc formula used. Pacing Clin Electrophysiol 2007; 30:1482-1486.
(20.) Sommargren CE, Zaroff JG, Banki N, Drew BJ. Electrocardiographic repolarization abnormalities in subarach noid hemorrhage. J Electrocardiol 2002; 35:257-262.
(21.) Fukui S, Otani N, Katoh H, Tsuzuki N, Ishihara S, Ohnuki A et al. Female gender as a risk factor for hypokalemia and QT prolongation after subarachnoid hemorrhage. Neurology 2002; 59:134-136.
(22.) Mayer SA, LiMandri G, Sherman D, Lennihan L, Fink ME, Solomon RA et al. Electrocardiographic markers of abnormal left ventricular wall motion in acute subarachnoid hemorrhage. J Neurosurg 1995; 83:889-896.
(23.) Sugimoto K, Watanabe E, Yamada A, Iwase M, Sano H, Hishida H et al. Prognostic implications of left ventricular wall motion abnormalities associated with subarachnoid hemorrhage. Int Heart J 2008; 49:75-85.
(24.) Randell T, Tanskanen P, Scheinin M, Kytta J, Ohman J, Lindgren L. QT dispersion after subarachnoid hemorrhage. J Neurosurg Anesthesiol 1999; 11:163-166.
(25.) Sato K, Kato M, Yoshimoto T. QT intervals and QT dispersion in patients with subarachnoid hemorrhage. J Anesth 2001; 15:74-77.
(26.) Dilaveris PE, Andrikopoulos GK, Metaxas G, Richter DJ, Avgeropoulou CK, Androulakis AM et al. Effects of ischemia on P wave dispersion and maximum P wave duration during spontaneous anginal episodes. Pacing Clin Electrophysiol 1999; 22:1640-1647.
(27.) Uyarel H, Kasikcioglu H, Dayi SU, Tartan Z, Karabulut A, Uzunlar B et al. Anxiety and P wave dispersion in a healthy young population. Cardiology 2005; 104:162-168.
(28.) Duru M, Melek I, Seyfeli E, Duman T, Kuvandik G, Kaya H et al. QTc dispersion and P-wave dispersion during migraine attacks. Cephalalgia 2006; 26:672-677.
(29.) Segatore M. Hyponatremia after aneurysmal subarachnoid hemorrhage. J Neurosci Nurs 1993; 25:92-99.
(30.) Miyasaka Y, Asahi S, Nakayama K, Matsumori K, Beppu T. [Etiology of water and electrolyte metabolism imbalance following the rupture of cerebral aneurysms--with special reference to preoperative condition]. No Shinkei Geka 1984; 12:699-706.
(31.) van den Bergh WM, Algra A, van der Sprenkel JWB, Tulleken CAF, Rinkel GJE. Hypomagnesemia after aneurysmal subarachnoid hemorrhage. Neurosurgery 2003; 52:276-281; discussion 281-282.
(32.) Najafi M, Hamidian R, Haghighat B, Fallah N, Tafti HA, Karimi A et al. Magnesium infusion and postoperative atrial fibrillation: a randomized clinical trial. Acta Anaesthesiol Taiwan 2007; 45:89-94.
(33.) Dagdelen S, Yuce M, Toraman F, Karabulut H, Alhan C. The value of P dispersion on predicting atrial fibrillation after coronary artery bypass surgery; effect of magnesium on P dispersion. Card Electrophysiol Rev 2002; 7:162-164.
Address for correspondence: Dr V. Hanci, Bahcelievler Mahallesi, Isik Yonder Caddesi, Alay Apt. Kat: 4, Daire:7, Zonguldak, Turkey.
V. HANCI *, S. GUL ([dagger]), S. M. DOGAN ([double dagger]), I. O. TURAN ([section]), M. KALAYCI ([double dagger]), B. ACIKGOZ **
Departments of Anesthesiology and Reanimation, Neurosurgery and Cardiology, Zonguldak Karaelmas University, School of Medicine, Zonguldak, Turkey
* M.D., Assistant Professor Doctor, Department of Anesthesiology and Reanimation.
([dagger]) M.D., Assistant Professor Doctor, Department of Neurosurgery.
([double dagger]) M.D., Associate Professor Doctor, Department of Cardiology.
([section]) M.D., Associate Professor Doctor, Department of Anesthesiology and Reanimation.
** M.D., Professor Doctor, Department of Neurosurgery.
TABLE 1 Demographic data of groups Group S (n = 35) Group C (n = 35) P Age (y) 53.42 [+ or -] 13.00 49.94 [+ or -] 13.47 0.275 Gender (F/M) 19/16 16/19 0.473 HT (Yes/No) 16/19 10/25 0.138 DM (Yes/No) 6/29 3/32 0.477 F = female, M = male, HT = hypertension, DM = diabetes mellitus. Table 2 Electrocardiographic data of groups Group S Group C (n = 35) (n = 35) Heart rate (beats. 81.05 [+ or -] 13.34 74. 06 [+ or -] 9.75 [min.sup.-1]) PR interval (ms) 160.94 [+ or -] 18.68 158.25 [+ or -] 13.49 Max P wave duration 112.28 [+ or -] 14.56 94.28 [+ or -] 12.43 (ms) Min P wave duration 63.42 [+ or -] 12.58 67.14 [+ or -] 11.52 (ms) P wave dispersion (ms) 48.85 [+ or -] 19.21 27.14 [+ or -] 11.00 QT interval (ms) 387.06 [+ or -] 52.89 356.34 [+ or -] 24.67 QTc interval (ms) 449.43 [+ or -] 37.66 385.86 [+ or -] 13.95 QTd interval (ms) 66.86 [+ or -] 23.48 41.14 [+ or -] 11.31 QTcd interval (ms) 79.77 [+ or -] 29.41 44.54 [+ or -] 12.90 P Heart rate (beats. 0.015 [min.sup.-1]) PR interval (ms) 0.493 Max P wave duration 0.000 (ms) Min P wave duration 0.202 (ms) P wave dispersion (ms) 0.000 QT interval (ms) 0.003 QTc interval (ms) 0.000 QTd interval (ms) 0.000 QTcd interval (ms) 0.000 Max = maximum, Min = minumum, QTc = corrected QT, QTd = QT dispersion, QTcd = corrected QT dispersion. TABLE 3 Biochemical data of groups Normal Group S values (n = 35) Sodium 136-145 140.92 [+ or -] 4.23 (mmol.[l.sup.-1]) Potassium 3.5-5.5 3.83 [+ or -] 0.48 (mmol.[l.sup.-1]) Calcium 8.4-10.2 8.99 [+ or -] 0.62 (mg.[dl.sup.-1]) Chloride 98-110 101.96 [+ or -] 4.88 (mmol.[l.sup.-1]) Magnesium 1.3-2.7 1.92 [+ or -] 0.26 (mg.[dl.sup.-1]) Group C P (n = 35) Sodium 141.92 [+ or -] 3.31 0.280 (mmol.[l.sup.-1]) Potassium 4.38 [+ or -] 0.38 <0.001 (mmol.[l.sup.-1]) Calcium 9.51 [+ or -] 0.50 <0.001 (mg.[dl.sup.-1]) Chloride 104.01 [+ or -] 2.0 0.037 (mmol.[l.sup.-1]) Magnesium 2.30 [+ or -] 0.21 <0.001 (mg.[dl.sup.-1]) TABLE 4 Pearson correlations in Group S between GCS, HHS, serum electrolyte and QTc, QTcd and Pwd intervals QTc interval QTcd interval Pwd GCS -0.265 -0.088 -0.093 HHS 0.252 0.116 0.113 Sodium -0.097 -0.011 -0.032 Potassium -0.277 -0.035 -0.211 Chloride -0.265 -0.214 -0.265 Calcium -0.209 -0.204 -0.199 Magnesium -0.018 -0.239 -0.109 GCS = Glasgow coma scales, HHS = Hunt-Hess scale, QTc = corrected QT, QTcd = corrected QT dispersion, Pwd = P wave dispersion.