Atrial fibrillation (AF) is one of the most common

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1 Prophylactic Magnesium Does Not Prevent Atrial Fibrillation After Cardiac Surgery: A Meta-Analysis Richard C. Cook, MD, MS, Michael H. Yamashita, MDCM, MPH, Mark Kearns, MD, Krishnan Ramanathan, MB, ChB, Ken Gin, MD, and Karin H. Humphries, DSc Divisions of Cardiovascular Surgery and Cardiology, University of British Columbia, Vancouver, British Columbia, Canada Background. Atrial fibrillation (AF) is a common complication after cardiac surgery. Previous meta-analyses have concluded prophylactic magnesium (Mg) prevents postoperative AF, although with a significant degree of heterogeneity among included studies. Recently, the largest randomized, controlled trial published to date (but not included in prior published meta-analyses) concluded that Mg sulfate is not protective against AF after cardiac surgery. The objective of this study was to conduct a new meta-analysis including the results of new Mg trials not included in previous meta-analyses, and to investigate the potential causes and effects of significant heterogeneity observed in previously published meta-analyses. Methods. The MEDLINE, EMBASE, and CENTRAL databases were searched for relevant studies published up to March 31, Pooled odds ratios of occurrence of AF were calculated using random-effects models. Heterogeneity was assessed as significant using the I 2 statistic. Results. Egger s and funnel plots demonstrated biases toward stronger and more positive effects of Mg in smaller studies. When the analysis was restricted to the five double-blind, intention-to-treat studies in which AF was the primary outcome (Mg arm, n 710; control arm, n 713), Mg did not prevent postoperative AF (odds ratio, 0.94; p 0.77), and heterogeneity was no longer significant (I 2 40%; p 0.15). Conclusions. This meta-analysis, restricted to well-conducted trials, does not support the prophylactic use of Mg to prevent AF after cardiac surgery. Prior meta-analyses have drawn conclusions from simple random-effects models with significant heterogeneity. However, this approach leaves important residual heterogeneity and overemphasizes the strongly positive effects of smaller studies. (Ann Thorac Surg 2013;95:533 41) 2013 by The Society of Thoracic Surgeons Atrial fibrillation (AF) is one of the most common complications after cardiac surgery, with 25% to 40% of patients experiencing this arrhythmia [1]. Because of a demonstrated association between AF and increased risk of death [2] and stroke [3], as well as increased hospital length of stay [4], extensive efforts have been made to identify an effective method of preventing AF. Of the many potential prophylactic agents available, magnesium sulfate (MgSO 4 ) would appear to be the ideal agent because it is inexpensive, easily administered intravenously (IV), and has an excellent safety profile when infused slowly for several hours [5]. Furthermore, several small studies and previously published meta-analyses [5 11] have concluded that prophylactic administration of IV MgSO 4 is effective at preventing postoperative AF, particularly after elective coronary artery bypass grafting (CABG) surgery. The European Association for Cardiothoracic Surgery and the Canadian Cardiovascular Society have also recommended prophylaxis with IV MgSO 4 in their most recent guidelines [12, 13]. However, when we reviewed the previously published studies, we noted a lack of consistency in the results of those trials, with many showing no benefit from administration of prophylactic MgSO 4. We therefore conducted Accepted for publication Sept 4, Address correspondence to Dr Cook, St. Paul s Hospital, 1081 Burrard St, Vancouver, BC, Canada V5Z 1Y6; richard.cook@vch.ca. and completed the largest randomized, double-blind, placebo-controlled trial of IV MgSO 4 in patients undergoing CABG or valvular surgery with and without CABG [14]. Our study of 927 patients (more than double the size of all other randomized, controlled trials [RCTs]), published in 2009, concluded that prophylactic administration of IV MgSO 4 does not prevent postoperative AF (26.4% versus 24.3%, MgSO 4 versus control, respectively). We also observed that the seven meta-analyses demonstrating a protective effect of MgSO 4 against postoperative AF reported a high degree of heterogeneity among the trials included in their analyses. Furthermore, as they were published between 2004 and 2008, they did not include the results of our trial, and included relatively small numbers of patients, ranging from 1,033 [10] to 2,896 [11] patients. We therefore thought a new meta-analysis, including the results from our trial and other trials not included in the previously published meta-analyses, was warranted. Finally, we conducted a comprehensive review of the previously published meta-analyses in an effort to determine why the heterogeneity in these meta-analyses was high, and if that may have contributed to their conclusions. Material and Methods Literature Search The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were 2013 by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc

2 534 COOK ET AL Ann Thorac Surg META ANALYSIS OF MG FOR PREVENTION OF POST-OP A FIB 2013;95: searched to retrieve relevant studies published up to March 31, The MeSH search terms atrial fibrillation, atrial flutter, surgical procedures, operative, cardiac surgical procedures, magnesium, magnesium sulfate, magnesium chloride and combinations of them, as well as the terms surgery and thoracic surgery, were used in text word searches. The related articles function was used to broaden our search. Reference lists of selected articles were also examined to find additional relevant studies. Two investigators performed this literature search independently. Inclusion Criteria Only RCTs in adults clearly documenting a comparison of Mg to placebo for the prophylaxis of AF after cardiac surgery were included. Only English-language manuscripts were included. Trials of patients undergoing CABG surgery, heart valve surgery, or both were included. All study-specific definitions of AF were accepted. Both blinded and nonblinded studies were included, as well as studies using concomitant medications to prevent AF, provided the use of these medications was identical in the Mg and placebo arms. Exclusion Criteria Letters to the editor, abstracts, and studies containing insufficient data to properly conduct statistical analyses were excluded. Multiple studies published by the same author or institution were carefully evaluated to include only the study reporting the most complete set of data; the remaining studies were excluded. Studies that included patients with a history of preoperative AF were excluded. Data Extraction Each study was read independently by at least two investigators to determine the appropriateness for inclusion and to extract the data for analysis. Disagreements were resolved through discussion and consensus. Outcomes The primary outcome was the occurrence of AF after cardiac surgery during the initial hospital stay. Secondary outcomes included length of hospital stay, nonfatal cerebrovascular accident, or all-cause mortality within 30 days of surgery. Study characteristics included number of patients, year of publication, country where study took place, type of surgery (CABG, valve, or CABG valve), type, dose, route, and timing of Mg or placebo administration, use of concomitant medications for AF prophylaxis, and study-specific definition of AF. Fig 1. Flow diagram to illustrate identification, selection, and exclusion of trials used in the primary meta-analysis.

3 Ann Thorac Surg COOK ET AL 2013;95: META ANALYSIS OF MG FOR PREVENTION OF POST-OP A FIB 535 Statistical Analysis The meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) Statement [15] guidelines. Statistical analyses were performed using STATA version 10.1 software (Stata Corp, College Station, TX) The occurrences of AF, cerebrovascular accident, and all-cause mortality were treated as categorical dichotomous outcomes and reported as odds ratios (OR). Length of hospital stay was treated as a continuous outcome and reported as the weighted mean difference. In studies that only reported the mean or median, range, and the size of the trial, previously described methods were used to calculate the standard deviation [16]. Both random-effects and fixedeffects models were used; however, given the significant differences among studies only the random-effects model results are reported. Heterogeneity was calculated using the I 2 statistic. Funnel and Egger plots were used to visually evaluate for publication bias; Egger and Begg s tests were used for statistical assessment. The level of significance was set at 0.05 and corresponding 95% confidence intervals (CI) were calculated. Meta-regression was used to determine whether there was a dose response for the occurrence of AF according to the total dose of Mg given or the duration of Mg therapy. An analysis of high-quality RCTs (ie, double-blind, intention-to-treat analysis, with AF as the primary outcome) was also conducted. Results The results of the literature search, inclusions, and exclusions are summarized in Figure 1. The study and patient characteristics of the 21 included trials [14, 17 36] are summarized in Table 1. The earliest trial was published in 1988 [25] and the most recent was published in 2009 [34]. Study sample sizes varied from 20 [25] to 927 [14]. All studies except one included both sexes. Table 2 provides details of the various Mg infusion regimens, which varied widely in terms of dose, timing of administration, and duration. A fixed-effect meta-analysis was conducted, but given the heterogeneity (I %; p 0.001), only the results of the random-effects model are shown. The overall effect estimate was an OR of 0.58 (95% CI, 0.43 to 0.79), suggesting that prophylactic Mg use is associated with a 42% relative odds reduction in the incidence of AF after cardiac surgery (Fig 2). Studies were examined for evidence of publication bias and heterogeneity using the funnel plot and the Egger s plot. The funnel plot (Fig 3A) shows that among the smaller studies there are a disproportionate number of studies with positive results (in favor of Mg). The Begg s test indicates that this bias is significant (Z score 3.08; p 0.002). The Egger plot (Fig 3B) confirms the presence of significant bias. The y intercept ( 2.36; 95% CI, 3.63 to 1.09) is well below the origin, again suggesting smaller studies show more pronounced beneficial effects than larger studies. Table 1. Patient Characteristics From Selected Randomized, Controlled Trials Study (Year) Patients Blinded Assessors Blinded AF Was Primary Outcome Intention-to-Treat Analysis Number of Patients (Mg/control) Incidence (%) of AF (Mg/ control) Harris (1988) B B No No 9/11 11/9 Fanning (1991) B B Yes Yes 49/50 14/28 Colquhoun (1993) B B No No 66/64 17/23 Nurozler (1996) B B Yes Yes 25/25 4/25 Shakerinia (1996) NB NB Yes Yes 25/25 25/32 Speziale (2000) B B No Yes 72/25 3/20 Solomon (2000) NB B Yes Yes 85/82 22/20 Treggiari-Venzi (2000) B B Yes No 47/51 23/27 Bert (2001) NB B Yes Yes 63/60 38/38 Toraman (2001) NB B Yes Yes 100/100 2/21 Dagdelen (2002) NB B No Yes 93/55 2/36 Forlani (2002) B B Yes No 54/50 15/38 Kaplan (2003) B B Yes Yes 100/100 15/16 Hazelrigg (2004) B B Yes No 105/97 30/42 Geertman (2004) B B Yes Yes 74/73 34/26 Behmanesh (2006) NB NB Yes No 50/50 20/42 Bhudia (2006) B B No Yes 174/176 33/36 Najafi (2007) B B Yes No 166/179 7/12 Cook (2009) B B Yes Yes 462/465 26/24 Svagzdiene (2009) NB NB Yes No 52/106 29/26 Bakhsh (2009) NB NB Yes No 108/110 8/21 AF atrial fibrillation; B blinded; Mg magnesium; NB not blinded.

4 536 COOK ET AL Ann Thorac Surg META ANALYSIS OF MG FOR PREVENTION OF POST-OP A FIB 2013;95: Table 2. Magnesium Regimens Study Treatment Window Total Magnesium (mmol) Treatment Duration (h) Harris Intraop 16 1 Fanning Postop Colquhoun Postop Nurozler Postop NA 120 Shakerinia Intraop mmol/l in CP 2 Speziale Intraop, Postop 1 g 5 mmol/l in CP, 10 mmol/l 24 h 26 Solomon Intraop, Postop Treggiari-Venzi Postop Bert Intraop, Postop Toraman Preop, Intraop, Postop Dagdelen Preop, Postop Forlani Intraop, Postop 75 NA Kaplan Preop, Intraop, Postop Hazelrigg Intraop, Postop 80 mg/kg 8 mg kg 1 h 1 48 h 48.5 Geertman Intraop, Postop Behmanesh Postop Bhudia Intraop, Postop Najafi Intraop, Postop Cook Intraop, Postop Svagzdiene Intraop 40 mg/kg 500 mg/h NA Bakhsh Postop CP cardioplegia; Intraop intraoperative; NA not specified; Postop postoperative; Preop preoperative. Given the degree of heterogeneity and apparent publication bias, a further review of the initial 21 studies was performed. It was hypothesized that the heterogeneity might be attributable to a dose-response effect, whereby the studies that administered higher total doses of Mg or gave Mg therapy for a longer duration had a stronger protective effect against AF. However, the dose-response curve by total dose of Mg (Fig 4A) demonstrated a not significant relationship (slope of line 0.003; 95% CI, to 0.008; p 0.30). Similarly, the dose-response Fig 2. Forest plot of the random-effects metaanalysis of 21 studies of magnesium (Mg) for the prevention of atrial fibrillation after cardiac surgery. Point estimates, 95% confidence intervals (CI), and study weights are provided for each study. (ID identifier; OR odds ratio.)

5 Ann Thorac Surg COOK ET AL 2013;95: META ANALYSIS OF MG FOR PREVENTION OF POST-OP A FIB 537 for these three analyses were based on the 21 initial studies identified by the literature search to capture as many events as possible. Very few studies reported stroke as an outcome (n 3; Fig 6). As a result, the 95% CI for both the individual studies and the summary estimate (OR, 0.72; 95% CI, 0.19 to 2.78) were very wide. Nine studies examined mortality as an outcome (Fig 7). The summary OR from the random effects model was 1.07 (95% CI, 0.51 to 2.25). Nine studies evaluated length of stay. Figure 8 shows the results of the random-effects analysis with weighted mean difference as the outcome. Again, Mg administration did not significantly impact this outcome (weighted mean difference, 0.20 days; 95% CI, 0.47 to 0.07). Fig 3. (A) Funnel plot of the 21 studies included in the primary meta-analysis of magnesium for the prevention of atrial fibrillation after cardiac surgery. The precision of each study (standard error of the log odds ratio [OR]) is plotted against each study s effect estimate (OR). (B) Egger plot for the occurrence of atrial fibrillation. Egger s linear regression line, plotted on the Galbraith radial plot. Standard normal deviate (SND) is the odds ratio of each study divided by its standard error. The standard normal deviate is regressed against precision, which is the inverse of the standard error for each study. (CI confidence interval.) curve by duration of Mg therapy (Fig 4B) also showed a not significant relationship (slope of line 0.003; 95% CI, to 0.008; p 0.56). We subsequently evaluated studies with the following criteria: double-blind, intention-to-treat analysis, and AF as the primary outcome. Only 5 [14, 22, 24, 27, 29] of the 21 studies met these criteria, and the results of a second random-effects metaanalysis performed on these studies are summarized in Figure 5. The heterogeneity was substantially reduced (I %; p 0.15), and the summary OR was now 0.94 (95% CI, 0.61 to 1.44), no longer significantly in favor of Mg prophylaxis. Figures 6 through 8 summarize the results of analyses on mortality, stroke, and hospital length of stay. The data Fig 4. (A) Dose-response curve for total dose of magnesium given. Log (odds ratio [OR]) is plotted against the total dose of magnesium administered in each study. Slope of the line describes the dose-response relationship. (B) Dose-response curve for duration of magnesium therapy. Log (OR) is plotted against the duration of time magnesium was administered in each study. Slope of the line describes the dose-response relationship.

6 538 COOK ET AL Ann Thorac Surg META ANALYSIS OF MG FOR PREVENTION OF POST-OP A FIB 2013;95: Fig 5. Forest plot of the five high-quality randomized, controlled trials. Model is a randomeffects model with odds ratio (OR) point estimates, 95% confidence intervals (CI), and study weights for each study. The diamond provides the summary odds ratio for the model. (ID identifier; Mg magnesium.) Comment The key conclusion of this meta-analysis is that Mg supplementation does not prevent postoperative AF after cardiac surgery, a conclusion that differs from the seven previously published meta-analyses on prophylactic Mg [5 11]. It also contradicts the European Association of Cardio-Thoracic Surgery guidelines [12], which gives a grade A recommendation to the use of prophylactic Mg in addition to other strategies, and the Canadian Cardiovascular Society guidelines [13], which suggest prophylactic IV Mg for patients who have a contraindication to -blockers and amiodarone to minimize the incidence of AF for patients undergoing cardiac surgery. Because AF is one of the most commonly encountered complications after cardiac surgery, extensive efforts have been made to identify an effective method of preventing AF. Numerous pharmacologic agents have been used, with varying degrees of success. Of these, -blockers, amiodarone, sotalol, and IV MgSO 4 have been identified as being the most promising [11, 37], with amiodarone and sotalol being the most poorly tolerated [11]. -Blockers have the most robust data supporting their prophylactic administration [11, 37], and in several centers, including our own, their use is now accepted as standard of care. Intravenous MgSO 4 would appear to be the ideal agent, given its extremely low cost and good safety profile [5]. Furthermore, serum Mg levels have been shown to drop after cardiopulmonary bypass, usually reaching their lowest levels around postoperative day 1 to 2 [22, 23], coincident with the time of most episodes of AF [23]. However, administration of any pharmacologic agent, no matter how innocuous, requires clear evidence of benefit; hence the importance of high-quality data to guide clinical practice. In the case of IV MgSO 4, the wide range in the quality of the studies that form the current evidence base likely explains the lack of consensus between our results and previous published studies and meta-analyses. In fact, the meta-analysis by Miller and colleagues [9] admitted to significant heterogeneity among the trials, Fig 6. Forest plot of the random-effects model displaying the effect of magnesium on stroke (as defined by the study authors; n 3 studies). Odds ratio (OR) point estimates, 95% confidence intervals (CI), and study weights are provided for each study. The diamond provides the summary odds ratio for the model. (ID identifier; Mg magnesium.)

7 Ann Thorac Surg COOK ET AL 2013;95: META ANALYSIS OF MG FOR PREVENTION OF POST-OP A FIB 539 Fig 7. Forest plot of the random-effects model displaying the effect of magnesium on mortality (30-day or in-hospital, as defined by the study authors; n 9 studies). Odds ratio (OR) point estimates, 95% confidence intervals (CI), and study weights are provided for each study. The diamond provides the summary odds ratio for the model. (ID identifier; Mg magnesium.) and Shepherd and associates [7], who conducted the most exhaustive meta-analysis of IV MgSO 4 for prophylaxis of AF after CABG, reported substantial heterogeneity (I %; p ), comparable to our initial analysis (I %). In reviewing the 21 RCTs included in the initial analysis, we identified several in which there were serious methodologic problems. These included lack of blinding [17, 18, 21, 30, 31, 33, 35, 36], failure to conduct an intention-to-treat analysis [23, 26, 28, 34 36], AF as a secondary end point [19 21, 25, 32], and failure to clearly define AF as an end point. Given the controversy surrounding the use of quality scores, we chose instead to remove the studies with these three important study design flaws to identify a group of studies that adhered to the modern principles of high-quality RCTs. These exclusions resulted in only five trials [14, 22, 24, 27, 29] and a random-effects model summary estimate that showed no beneficial effect associated with prophylactic administration of Mg. We believe this group of studies provides the best evidence for the effectiveness of Mg, and therefore conclude that Mg should not be administered prophylactically to prevent postoperative AF after cardiac surgery. This is not the first time that the conclusions of a meta-analysis based on a number of small studies has been shown to be erroneous after completion of a large, well-designed RCT. In the case of Mg, a meta-analysis of Fig 8. Forest plot of the weighted mean difference (WMD) for length of stay (n 9 studies). The diamond is the summary estimate from the random-effects model of the mean different length of stay associated with magnesium use. (CI confidence interval; ID identifier; Mg magnesium.)

8 540 COOK ET AL Ann Thorac Surg META ANALYSIS OF MG FOR PREVENTION OF POST-OP A FIB 2013;95: Mg infusion early after suspected acute myocardial infarction found a significant mortality benefit among patients treated with Mg versus control patients (3.8% versus 8.2%, respectively; p 0.001) [38]. However, a large trial of 58,050 patients published later (ISIS4) [39] demonstrated no benefit with MgSO 4 (7.64% versus 7.24% mortality, respectively), thereby disproving the results of the meta-analysis. This is the first meta-analysis of prophylactic Mg for prevention of AF after cardiac surgery that fails to demonstrate a beneficial effect of Mg (OR, 0.94; 95% CI, 0.61 to 1.44). It differs from the seven previously published meta-analyses in that it included the largest trial conducted to date and it included only high-quality trials to address the high degree of heterogeneity among the trials. The inclusion of only high-quality trials addressed the significant bias toward a positive result among the smaller trials, many of which had major design flaws. Thus, we believe that this meta-analysis is the most valid assessment of the efficacy of prophylactic Mg for postoperative AF after cardiac surgery. We therefore conclude that the routine use of prophylactic Mg does not prevent postoperative AF after cardiac surgery. References 1. Ommen S, Odell J, Stanton M. Atrial arrhythmias after cardiothoracic surgery. N Engl J Med 1997;336: Villareal RP, Hariharan R, Liu BC, et al. Postoperative atrial fibrillation and mortality after coronary artery bypass surgery. J Am Coll Cardiol 2004;43: Likosky DS, Leavitt BJ, Marrin CA, et al; Northern New England Cardiovascular Disease Study Group. Intra- and postoperative predictors of stroke after coronary artery bypass grafting. Ann Thorac Surg 2003;76: Kim MH, Deeb GM, Morady F, et al. Effect of postoperative atrial fibrillation on length of stay after cardiac surgery (The Postoperative Atrial Fibrillation in Cardiac Surgery study [PACS(2)]. Am J Cardiol 2001;87: Henyan NN, Gillespie EL, White CM, Kluger J, Coleman CI. Impact of intravenous magnesium on post-cardiothoracic surgery atrial fibrillation and length of hospital stay: a meta-analysis. Ann Thorac Surg 2005;80: Rostron A, Sanni A, Dunning J. Does magnesium prophylaxis reduce the incidence of atrial fibrillation following coronary artery bypass surgery? Interact Cardiovasc Thorac Surg 2004;4: Shepherd J, Jones J, Frampton GK, Tanajewski L, Turner D, Price A. Intravenous magnesium sulphate and sotalol for prevention of atrial fibrillation after coronary artery bypass surgery: a systematic review and economic evaluation. Health Technol Assess 2008;12:iii iv, ix Shiga T, Wajima Zi, Inoue T, Ogawa R. Magnesium prophylaxis for arrhythmias after cardiac surgery: a meta-analysis of randomized controlled trials. 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Can J Cardiol 2011;27: Cook RC, Humphries KH, Gin K, et al. Prophylactic intravenous magnesium sulphate in addition to oral -blockade does not prevent atrial arrhythmias after coronary artery or valvular heart surgery: a randomized, controlled trial. Circulation 2009;120(11 Suppl):S Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and metaanalyses: the PRISMA statement. Ann Intern Med 2009;151: Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005;5: Behmanesh S, Tossios P, Homedan H, et al. Effect of prophylactic bisoprolol plus magnesium on the incidence of atrial fibrillation after coronary bypass surgery: results of a randomized controlled trial. Curr Med Res Opin 2006;22: Bert AA, Reinert SE, Singh AK. A beta-blocker, not magnesium, is effective prophylaxis for atrial tachyarrhythmias after coronary artery bypass graft surgery. 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Combination of sotalol and magnesium prevents atrial fibrillation after coronary artery bypass grafting. Ann Thorac Surg 2002;74: Geertman H, van der Starre PJA, Sie HT, Beukema WP, van Rooyen-Butijn M. Magnesium in addition to sotalol does not influence the incidence of postoperative atrial tachyarrhythmias after coronary artery bypass surgery. J Cardiothorac Vasc Anesth 2004;18: Harris MN, Crowther A, Jupp RA, Aps C. Magnesium and coronary revascularization. Br J Anaesth 1988;60: Hazelrigg SR, Boley TM, Cetindag IB, et al. The efficacy of supplemental magnesium in reducing atrial fibrillation after coronary artery bypass grafting. Ann Thorac Surg 2004;77: Kaplan M, Kut MS, Icer UA, Demirtas MM. Intravenous magnesium sulfate prophylaxis for atrial fibrillation after coronary artery bypass surgery. J Thorac Cardiovasc Surg 2003;125: Najafi M, Hamidian R, Haghighat B, et al. 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9 Ann Thorac Surg COOK ET AL 2013;95: META ANALYSIS OF MG FOR PREVENTION OF POST-OP A FIB Shakerinia T, Ali IM, Sullivan JA. Magnesium in cardioplegia: is it necessary? Can J Surg 1996;39: Solomon AJ, Berger AK, Trivedi KK, Hannan RL, Katz NM. The combination of propranolol and magnesium does not prevent postoperative atrial fibrillation. Ann Thorac Surg 2000;69: Speziale G, Ruvolo G, Fattouch K, et al. Arrhythmia prophylaxis after coronary artery bypass grafting: regimens of magnesium sulfate administration. Thorac Cardiovasc Surg 2000;48: Toraman F, Karabulut EH, Alhan HC, Dagdelen S, Tarcan S. Magnesium infusion dramatically decreases the incidence of atrial fibrillation after coronary artery bypass grafting. Ann Thorac Surg 2001;72: Treggiari-Venzi MM, Waeber JL, Perneger TV, Suter PM, Adamec R, Romand JA. Intravenous amiodarone or magnesium sulphate is not cost-beneficial prophylaxis for atrial fibrillation after coronary artery bypass surgery. Br J Anaesth 2000;85: Svagzdiene M, Sirvinskas E, Benetis R, Raliene L, Simatoniene V. Atrial fibrillation and changes in serum and urinary electrolyte levels after coronary artery bypass grafting surgery. Medicina (Kaunas) 2009;45: Bakhsh M, Abbas S, Hussain RM, Khan SA, Naqvi SMS. Role of magnesium in preventing post-operative atrial fibrillation after coronary artery bypass surgery. J Ayub Med Coll Abbottabad 2009;21: Crystal E, Connolly SJ, Sleik K, Ginger TJ, Yusuf S. Interventions on prevention of postoperative atrial fibrillation in patients undergoing heart surgery: a meta-analysis. Circulation 2002;106: Teo KK, Yusuf S, Collins R, Held PH, Peto R. Effects of intravenous magnesium in suspected acute myocardial infarction: overview of randomised trials. BMJ 1991;303: [No authors listed]. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. Lancet 1995;345: Notice From the American Board of Thoracic Surgery The 2012 Part I (written) examination was held on Monday, November 19, To be admissible to the Part II (oral) examination, a candidate must have successfully completed the Part I (written) examination. A candidate applying for admission to the certifying examination must fulfill all the requirements of the Board in force at the time the application is received. Please address all communications to the American Board of Thoracic Surgery, 633 N St. Clair St, Suite 2320, Chicago, IL 60611; telephone: (312) ; fax: (312) ; e- mail: info@abts.org by The Society of Thoracic Surgeons Ann Thorac Surg 2013;95: /$36.00 Published by Elsevier Inc