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European Journal of Cardio-thoracic Surgery 39 (2011) 75—80 www.elsevier.com/locate/ejcts Junctional ectopic tachycardia after surgery for congenital heart disease: incidence, risk factors and outcome§,§§ Leena Mildh a,*, Anita Hiippala b, Paula Rautiainen a, Ville Pettilä a, Heikki Sairanen c, Juha-Matti Happonen b a Department of Anaesthesia and Intensive Care, Helsinki University Hospital, Helsinki, Finland b Department of Paediatric Cardiology, Helsinki University Hospital, Helsinki, Finland c Department of Paediatric Cardiac Surgery, Helsinki University Hospital, Helsinki, Finland Received 3 December 2009; received in revised form 9 April 2010; accepted 13 April 2010 Abstract Objectives: Junctional ectopic tachycardia (JET) is a serious, haemodynamically compromising tachyarrhythmia associated with paediatric cardiac surgery, with a reported mortality up to 14%. The incidence, risk factors and outcome of this tachyarrhythmia were evaluated in this population-based, case-control patient cohort. Methods: A total of 1001 children, who underwent open-heart surgery during a 5-year period, were retrospectively analysed. The patients with haemodynamically significant tachycardia were identified, and their postoperative electrocardiograms were analysed. Three controls matched with the same type of surgery were selected for each patient with JET. Results: JET was diagnosed in 51 patients (5.0%). These patients had longer cardiopulmonary bypass time (138 vs 119 min, p = 0.002), higher body temperature (38.0 vs 37.4 8C, p = 0.013) and higher level of postoperative troponin-T (3.7 vs 2.1 mg l 1, p < 0.001) compared with controls. They also needed longer ventilatory support (3 vs 2 days, p = 0.004) and intensive care stay (7 vs 5 days, p < 0.001) as well as use of noradrenaline (23/51 vs 35/130, p = 0.019). Ventricular septal defect (VSD) closure was part of the surgery in 33/51 (64.7%) of these patients. The mortality was 8% in the JET group and 5% in the controls ( p = 0.066). In the logistic regression model, JET was not an independent risk factor for death ( p = 0.557). Conclusions: The incidence of JETwas 5.0% in this large paediatric open-heart surgery patient group. Compared with controls, these patients had longer cardiopulmonary bypass time and higher level of troponin-T, possibly reflecting the extent of surgical trauma. However, the tachycardia was not an independent risk factor for death. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. Keywords: Arrhythmia; Paediatric cardiology; Congenital heart surgery 1. Introduction Junctional ectopic tachycardia (JET) is a tachyarrhythmia associated mostly with surgery for congenital heart disease. It is usually a self-limiting condition, but can cause serious haemodynamic deterioration in the immediate postoperative phase [1]. JET is a narrow QRS complex tachycardia, usually with atrioventricular dissociation and slower atrial than ventricular rate. It can also present with 1:1 retrograde ventriculoatrial conduction. Haemodynamic instability is mostly caused by loss of atrioventricular synchrony and consequent loss of the contribution of atrial contraction to cardiac output [2,3]. The precise mechanism of JET is not known, but it is thought to result from § Presented at the 43rd Joint Annual Meeting of Association for European Paediatric Cardiology, Venice, Italy, 21—24 May 2008. §§ Funding: This study was funded in part by EVO-grant of Helsinki University Hospital. * Corresponding author. Address: Helsinki University Hospital, P.O. Box 340, 00029 Helsinki, Finland. Tel.: +358 50 4271641; fax: +358 9 471 78354. E-mail address: [email protected] (L. Mildh). mechanical trauma to the proximal conduction tissue related to suture placement or indirect stretch injury [4]. The incidence of JET has been reported to vary from 5.6% to 14% (study samples varying from 343 to 874 patients) depending on patient selection [2,5—7]. Several risk factors have been associated with this condition, both surgical and non-surgical. The surgical risk factors include resection of muscle bundles, correction of right ventricular outflow tract and correction of ventricular septum [4]. The non-surgical risk factors previously reported are young patient age, longer cardiopulmonary bypass (CPB) time, aortic crossclamp (ACC) time, low level of plasma magnesium, use of catecholamines and hyperthermia [2,6,7]. Most studies addressing the incidence and risk factors of JET are based on selected patient populations, that is, selected surgical procedures, institution-based patient groups with possible patient selection or small patient groups. The purpose of this study was to analyse the incidence, risk factors and outcome of JET in an unselected population-based patient cohort, operated upon in the only paediatric cardiac surgery centre in Finland during a 5-year period. 1010-7940/$ — see front matter # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejcts.2010.04.002 76 L. Mildh et al. / European Journal of Cardio-thoracic Surgery 39 (2011) 75—80 2. Materials and methods This retrospective cohort study was performed at Helsinki University Hospital for Children and Adolescents, which is the only centre for paediatric heart surgery and operates all children born with congenital heart defect in Finland (population: 5.2 million). The study was reviewed and approved by the local Human Investigation Committee, which waived the need for obtain informed consent. 2.1. Subjects and data collection Data from all patients under 18 years of age, who underwent heart surgery necessitating CPB between 1 January 2000 and 31 December 2004, were included in the study. The patients with haemodynamically significant tachyarrhythmia were identified. The 12-lead electrocardiogram (ECG) and intracardiac atrial and ventricular tracings from temporary pacing wires were used to divide the patients into different diagnostic groups according to arrhythmia. Information describing surgical procedure, duration of CPB as well as ACC and survival at day 30, postoperatively, were recorded in specific paediatric heart surgery database (ProCardio, Melba Group, Finland), which obtains its information from the Finnish Population Registry Centre [8]. Surgical procedures were grouped according to the international congenital heart surgery nomenclature [9—11]. Information on patients’ demographics (sex, weight and age), intubation time, length of stay at the intensive care unit (ICU), body temperature, plasma potassium, calcium and magnesium at tachyarrhythmia onset, the use of milrinone (yes/no), adrenaline (yes/no) and noradrenaline (yes/no) as well as first postoperative day troponin-T (TnT) values were obtained from the intensive care database (Centricity Critical Care Clinisoft; GE Healthcare, Helsinki, Finland). Data tables were exported from the intensive care database, imported into a relational database (Microsoft Access; Microsoft; Seattle, WA, USA), and combined with the surgical database. Patients with solitary atrial septal defect (ASD) closure received only cold cardioplegia. All other patients received, in addition to cold cardioplegia, both warm induction cardioplegia immediately after aortic crossclamp and warm blood cardioplegia before reperfusion. The CPB circuit was primed with a solution containing magnesium. 2.4. Postoperative care Milrinone was used as the first-line inotropic drug. In the case of insufficient inotropic support (low cardiac contractility evaluated by ultrasound, profound acidosis and high blood lactate), adrenaline was added to milrinone. Noradrenaline was used in case of low systemic blood pressure. The patients were extubated when haemodynamic stability was achieved, gas exchange was satisfactory (arterial blood oxygen and carbon dioxide levels within normal individual limits according to cardiac defect) and sufficient muscle strength recovered for airway patency. Discharge criteria from the ICU included haemodynamic stability with no catecholamine support, normal sinus rhythm, normal or near to normal renal function and ability to maintain normal gas exchange with a natural airway. 2.5. Blood sampling and biochemical analysis The measurements of plasma potassium and calcium were obtained at least four times a day and performed with an ABL 700 series analyser (Radiometer Medical A/S, DK2700; Bronshoj, Denmark). Plasma magnesium was measured daily at 6 a.m. and analysed with spectrophotometric colour binding (Roche Diagnostic, Mannheim, Germany). Plasma TnT was obtained on the first postoperative morning at 6 a.m. and analysed with electrochemiluminescence immunoassay (Elecsys Troponin T STAT; Roche, Mannheim, Germany). 2.2. Arrhythmia diagnostics and treatment 2.6. Statistical methods The ECGs were retrospectively evaluated by paediatric electrophysiologists (AH, JMH) and patients were grouped according to JET or other tachyarrhythmia. For each JET patient, three controls without any arrhythmia and matched for surgical procedure and age were selected from the whole patient cohort. According to institutional treatment protocol, amiodarone was used as the first-line anti-arrhythmic drug for all patients with haemodynamically compromising tachycardia [3]. Amiodarone was given as a 5 mg kg 1 loading infusion in 0.5—1 h followed by a continuous infusion of 10— 20 mg kg 1 d 1 [12]. Other simultaneous treatments included surface cooling, sedation and, if possible, decreasing catecholamine dose. Data are presented as mean SD or median (interquartile range). Statistical analyses were performed with SPSS 10.1.315 for Windows (SPSS, Chicago, IL, USA). Differences in continuous variables between patients with JET and their controls were compared using nonparametric Mann—Whitney test. Differences in dichotomous variables were compared with Fisher’s exact test. A p-value less than 0.05 was considered significant. Univariate analysis regarding diagnosis of JET and relevant variables (CPB, ACC, plasma magnesium and TnT, use of milrinone, adrenaline and noradrenaline as well as body temperature at the onset of tachycardia) was performed with continuous variables modelled linearly. Thereafter, analysis of an independent effect of variables on incidence of JET was performed using backward stepwise logistic regression analysis with p < 0.20 to include and p > 0.10 to exclude covariates from the model. The influence of JET on 30-day mortality was studied analysing the whole patient cohort with stepwise forward multiple logistic regression. 2.3. Myocardial protection Intermittent antegrade blood cardioplegia enriched with magnesium was used for myocardial protection. L. Mildh et al. / European Journal of Cardio-thoracic Surgery 39 (2011) 75—80 Table 1 Tachycardia diagnoses other than junctional ectopic tachycardia among the 103 postoperative arrhythmia patients. Tachyarrhythmia Number of patients % Of whole cohort (1001) Atrial flutter Atrial tachycardia Sinus tachycardia Supraventricular tachycardia Ventricular fibrillation Ventricular tachycardia Other 9 3 13 12 1 1 13 0.9 0.3 1.3 1.2 0.1 0.1 1.3 3. Results 3.1. Patient characteristics During the study period, a total of 1026 patients underwent heart surgery with CPB. Patients with heart transplantation, application of ventricular assist device or age more than 18 years were excluded from the analysis (n = 25). The median age of the remaining 1001 patients was 6.7 months (interquartile (IQ) range 2.3—34.3). Of those 1001, 42 (4.2%) died within 30 days after operation. Of all the 1001, 103 (10%) patients were diagnosed with peri- or postoperative tachyarrhythmia. As many as 51 (5.0 1.36% of 1001, 95% confidence interval (CI) 3.6—6.4%) patients were diagnosed with JET, 52 patients had other tachyarrhythmia (Table 1). JET occurred mostly within 24 h postoperatively. The median age for JET patients was 3.6 (0.4—10.9) months, 31 were (61%) male and 20 (39%) were female. Of the 51 patients with JET, four (8 7.6%, 95% CI 0—15%) died within 30 days after operation. These four patients were operated for pulmonary atresia (PA) plus ventricular septal defect (VSD), tetralogy of Fallot (TOF), total anomalous pulmonary venous drainage (TAPVD) and hypoplastic left heart syndrome (HLHS). The surgical procedures associated with JET are listed in Table 2. VSD closure was part of the surgical procedure in 33/51 (65%) of JET patients. The median cycle length of the tachycardia was 325 ms (range, 280—540) and 77 Table 2 Surgical procedures associated with junctional ectopic tachycardia. Procedure Patients with JET (% of whole cohort) No of operations in whole cohort Fallot repair Arterial switch Arterial switch with VSD closure VSD closure TCPC Rastelli operation PA + VSD correction Aortic arch reconstruction + VSD correction Norwood I AVSD correction PA + Ebstein anomaly correction BDG DORV + VSD correction PA + IVS correction TAPVD correction AVR + CABG 9 6 1 11 5 4 3 3 (12%) (15%) (4%) (6%) (8%) (44%) (17%) (20%) 73 39 25 175 66 9 18 15 2 1 1 1 1 1 1 1 (3%) (1%) (100%) (1%) (13%) (10%) (7%) (100%) 70 85 1 78 8 11 14 1 In all 51 (5) % (of 1001) VSD: ventricular septum defect, ASD: atrial septum defect, TCPC: total cavopulmonary connection, PA: pulmonary atresia, AVSD: atrioventricular septum defect, BDG: bidirectional Glenn operation, DORV: double outlet right ventricle, TAPVD: total anomalous pulmonary vein drainage, AVR: aortic valve replacement, CABG: coronary artery bypass grafting. the median atrial cycle length was 380 ms (range, 280—840). A 1:1 ventruculoatrial (VA) conduction was present in 48% and VA dissociation in 52% of patients. 3.2. Comparison of JET versus control patients No differences between JET patients and their matched controls in age, gender or death within 30 days, postoperatively, could be detected. Patients with JET had longer intubation time, higher body temperature at onset of tachycardia, longer CPB time, more frequent use of noradrenaline and higher postoperative TnT compared with their matched controls (Table 3). The aim was to select three matched controls for each JET patient. However, sufficient Table 3 Patients with junctional ectopic tachycardia and the matched controls (median, interquartile range) (compared by Mann—Whitney test). Number of patients Gender (M/F) Age (years) CPB time (min) ACC time (min) Body temperature (8C) Troponin-T (mg l 1) Plasma potassium (mmol l 1) Plasma calcium (mmol l 1) Plasma magnesium (mmol l 1) Intubation time (days) Use of milrinone number of patients (%) Use of adrenaline number of patients (%) Use of noradrenalin number of patients (%) PICU stay (days) Mortality (%) JET Controls p-value 51 30/21 0.3 (0.03—0.91) 138 (104—180) 82 (60—107) 38.0 (37.0—38.0) 3.7 (2.2—6.0) 3.4 (3.2—3.7) 1.21 (1.13—1.27) 1.03 (1.03—1.17) 3 (1—6) 41 (80) 38 (75) 23 (45) 7 (5—9) 4 (7.8) 130 70/60 0.3 (0.05—1.00) 119 (79—154) 76 (39—106) 37.4 (37.0—38.0) 2.1 (1.2—3.5) 3.4 (3.0—3.8) 1.21 (1.11—1.29) 1.07 (0.81—1.23) 2 (1—4) 101 (78) 82 (63) 35 (27) 5 (3—7) 6 (4.6) 0.11 a 0.586 0.002 * 0.059 0.013 <0.001 * 0.315 0.901 0.778 0.004 * 0.953 0.238 0.019 * <0.001 * 0.066 a ACC: aortic cross-clamp, CPB: cardiopulmonary bypass, PICU: paediatric intensive care unit. a Fisher’s test. * Due to multiple comparisons p < 0.01 was considered as significant. 78 L. Mildh et al. / European Journal of Cardio-thoracic Surgery 39 (2011) 75—80 Table 4 Backward multiple logistic regression analysis of variables affecting occurrence of junctional ectopic tachycardia (OR with 95% CIs). Variable Univariate analysis p value Multivariate analysis p value OR 95% CI for OR 95% CI for OR Postoperative TnT (mg l 1) CPB time (min) Temperature (8C) ACC time (min) Plasma magnesium (mmol l 1) Use of milrinone Use of adrenaline Use of noradrenalin 0.041 0.028 0.06 0.038 0.93 0.91 0.51 0.09 0.037 0.032 0.050 ns ns ns ns ns 1.214 1.007 2.187 1.012 1.001 1.000 1.456 1.013 4.783 ACC: aortic cross-clamp, CI: confidence interval, CPB: cardiopulmonary bypass, OR: odds ratio, TnT: troponin-T, ns: not significant. p < 0.05 considered as statistically significant. amount of operations was not performed for certain surgical groups and, therefore, fewer controls were selected for these groups (Rastelli, PA + Ebstein and AVR + CABG). 3.3. Variables affecting the incidence of JET The stepwise backward multiple logistic regression analysis revealed longer CPB time and higher postoperative TnT to be significant prognostic factors for the incidence of JET (Table 4). Higher body temperature at the onset of JET nearly reached statistical significance (Table 4). JET was not an independent prognostic factor for death in the whole cohort of 1001 patients ( p = 0.557). 4. Discussion In this study of a nationwide paediatric cardiac surgery patient population, the incidence of postoperative JET was 5% (95% CI 3.6—6.4%). This is in accordance with recent smaller studies where the incidence has varied from 5% to 14%, depending on patient selection and study setting [2,5,7,13,14]. JET has been previously associated with several risk factors as well as with increased morbidity and mortality. Risk factors associated with JET include younger patient age, duration of CPB and ACC, electrolyte disturbances, use of inotropes and type of surgery [2,5,13—15]. Many of the earlier studies differ in their setup and thus cannot always be compared with each other. In our study, JET patients had longer CPB time, higher body temperature at the onset of JET, more frequent use of noradrenaline, higher postoperative TnT release, longer ventilator time and longer ICU stay compared with the matched controls. Most of these factors may reflect the fact that JET patients are overall more sick than their controls as speculated in the previous reports [3]. However, in the logistic regression model, only longer CPB time and higher postoperative TnT were identified as independent risk factors. Further, higher body temperature at the onset of arrhythmia was found to be nearly significant ( p = 0.050). Longer CPB time, as well as higher postoperative TnT, is probably a result of more difficult surgical correction and larger surgical trauma. In two previous case-control studies [5,7], younger patient age [5], more frequent use of inotropes [5,7], duration of CPB and elevated postoperative creatine kinase MB isoenzyme (CK-MBm) [7] were associated with JET. In these two studies, control patients were selected according to the date of surgery and could therefore include totally different type of patients and surgery, which makes the comparison of patients and the conclusion made more difficult. In our study, the use of milrinone and adrenaline did not affect the occurrence of JET. Noradrenaline was used more often in JET patients compared with their controls, but the logistic regression model was not an independent risk factor for JET. The fact that higher body temperature is associated with the occurrence of JET supports the rationale for avoiding hyperthermia in the immediate postoperative period. We matched the controls according to surgical procedure and age. This eliminates surgical risk factors, which in some studies have affected the occurrence of JET [4]. However, in our study, patients with surgery in the vicinity of atrioventricular node and bundle of His, frequently developed JET. VSD closure was part of the surgical procedure in 35/51 (65%) of JET patients. Further, almost half (44%) of Rastelli patients developed JET. This operation frequently involves extensive manipulation and resection of ventricular septum and, in our material, occasionally mandated operating through tricuspid valve annulus. The Rastelli operation is thus surgically challenging requiring long CPB times and producing high postoperative TnT values. Interestingly, 15% of patients with arterial switch operation, which does not include surgery near the conduction system, developed JET. This same phenomenon has been detected in other studies also [3,6,7,13,14] and indicates that direct manipulation of the conduction system is not always the triggering cause of JET. To avoid JET, surgery should be performed as gently as possible, especially in the vicinity of the conduction system, and unnecessary stretching of the tricuspid valve should be avoided. However, this cannot always be avoided and, if high postoperative TnT is detected, the patient should be kept normothermic and monitored carefully for the occurrence of JET. Plasma magnesium, calcium and potassium values did not differ between JET patients and the controls. In our study, plasma potassium was below (3.2—3.7 mmol l 1) the recommended levels at the onset of JET [3], but plasma magnesium level (1.03—1.07 mmol l 1) was within normal values. We added magnesium to our perfusion prime as well as cardioplegia solution and this could be the reason for magnesium not affecting the occurrence of JET. Both hypomagnesaemia and hypokalaemia have been reported L. Mildh et al. / European Journal of Cardio-thoracic Surgery 39 (2011) 75—80 to be risk factors for developing JET [2,16,17]. In the study of Manrique et al., magnesium supplementation decreased the incidence of JET in a dose-related manner [18]. However, in some other studies, hypomagnesaemia has not had any effect on the occurrence of JET [5,13,14]. JET has been associated with worse outcome and increased death rate compared to non-JET patients [3,7]. Again, patients with JET are possibly sicker and younger and require more extensive surgery and therefore are at higher risk of increased morbidity and mortality. In our study, there was no significant difference in mortality between JET patients and their matched controls. Due to a relatively small sample size and a nearly significant p-value, we cannot rule out the possibility of a b-type error. However, using multiple regression analysis, JET was not found to be an independent risk factor for death in the whole patient population, which supports our conclusion. Contrary to mortality, JET did affect the morbidity of these patients. JET patients had increased ventilator time and longer ICU stay, which has been shown by previous studies [2,6,7]. This can be explained by the treatment protocol for haemodynamically unstable JET patients, which include also sedation, muscle paralysis and ventilator therapy. The patients cannot be transferred to regular ward until JET has subsided. Both longer ventilator time and longer ICU stay increase other possible complications, that is, infections, and also increase the cost of treatment. In JET, ventricular rate usually exceeds that of atrial rate and there is atrioventricular dissociation. In our study, 1:1 ventriculoatrial conduction was noted in 48% of JET patients, a number exceeding the results in the study of DodgeKhatami et al. [2] JET was the most frequent tachycardia in the postoperative setting and occurred within the first 24 h after operation, which is in accordance with previous studies [3,6,13,14]. The rationale for amiodarone use differs in previous studies for treatment of JET [2,7,13,14,19]. Some institutions, like ours, use amiodarone as a primary treatment [6], because of the good response to intravenous amiodarone in patients who failed to respond to conventional therapies or are haemodynamically unstable. It has also been recommended as an early first-line treatment for JET [12,20]. There are some limitations in the present study. First, as a retrospective cohort study, no perfect standardisation of anaesthesia, cardioplegia, CPB or postoperative care could be done. However, all these procedures were performed according to the institutional protocol, which limits the patient-to-patient variation. In addition, due to a quite large sample size, we find the incidence and outcome of JET to be reliable with narrow confidence intervals. Due to continuous postoperative ECG monitoring, the number of patients with no detection of JET is supposed to be low. Yet, the exact incidence of JET might be slightly higher than 5%. This single-centre case-control study showed JET to be the most frequent haemodynamically significant tachyarrhythmia in the early postoperative period after congenital heart surgery. A prolonged CPB, high postoperative TnT and increased body temperature are independent risk factors for JET. When JET has developed, it increases ventilator time and ICU stay and, thus, hospital costs. With the current 79 recommended treatment protocol [12] with early amiodarone use, JET does not have independent impact on mortality. 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