Clinical End Points
The primary end point of the study was in-hospital mortality, defined as death from any cause within 30 days after surgery or during the same time period of hospitalization as well as postoperative MACE during the period of hospitalization including perioperative MI (PMI) and low cardiac output syndrome (LCOS). Secondary study end points were other postoperative complications such as stroke, new-onset ventricular arrhythmia, major bleeding, necessity for rethoracotomy, and postoperative renal failure requiring temporary hemodialysis.
Selection of Patients
Patients were enrolled into the present study if they had undergone an isolated CABG procedure and a preoperative cTnI serum level had been obtained 24 h before surgery (Table 1). For risk analysis, patients were stratified into three groups according to preoperative cTnI levels, as previously described. Among these, 1,592 patients had negative preoperative cTnI serum levels 1.5 ng/mL (group 3).
The remaining 1,146 of 3,124 CABG patients were not enrolled due to no preoperative cTnI measurements within 24 h before surgery or without preoperative cTnI measurement at all, but they were statistically compared with group 1 as well as the entire study cohort with preoperative cTnI measurements to ensure that the groups with and without cTnI measurements were not different. NSTE-ACS was supposed with a positive cTnI level on hospital admission and new onset of chest pain or accelerating chest pain within the previous 24 h occurring at rest or with minimal exertion, alleviated by nitroglycerin and/or rest. Patients were excluded from the study if any of the following preoperative criteria were present: (1) preoperative MI with STEMI, (2) new-onset left bundle-branch block, (3) reoperations, and (4) any concomitant heart surgery besides CABG.
Management Strategies and Medication
Standard anesthetic and monitoring techniques were used in all patients offered by My Canadian Pharmacy. Internal thoracic artery, radial artery, and saphenous vein grafts were used as graft conduits. Heparin was administered in order to achieve an activated coagulation time > 400s. A standard cardiopulmonary bypass (CPB) technique was used with ascending aortic and two-stage venous cannulation. During CPB, moderate hemodilution with a hematocrit level between 20% and 25% using mild systemic hypothermia (> 32°C) was maintained. Myocardial protection was achieved using antegrade and optional retrograde crystalloid (Bretschneider) cardioplegic arrest and additional topical cooling, and single aortic cross-clamping for all distal anastomosis. Proximal graft anastamoses to the aorta were performed with partial occlusion of the ascending aorta.
Postoperative management of patients was standardized. Patients were monitored with respect to arterial pressure, pulmonary pressure, and central venous pressure. A 12-lead ECG was obtained preoperatively, immediately after the arrival to the ICU and at 12 h and 24 h postoperatively and once a day thereafter.
Acetylsalicylic acid, 500 mg, was administered IV within the first 6 h after surgery in the absence of significant bleeding.
Blood Sampling and Cardiac Biomarker Analysis
Venous blood samples were drawn from each patient preop-eratively on hospital admission before surgery. cTnI was measured using a specific two-sided immunoassay (Dimension Flex; Dade Behring Marburg; Marburg, Germany). The detection range for cTnI was 0.04 to 40 ng/mL, requiring further dilutions if necessary. The assays reference interval was 0.00 to 0.05 ng/mL. A cTnI value > 0.1 ng/mL was considered abnormal.
Data Collection and Definitions
Detailed in-hospital and follow-up data were obtained from the patients. All preoperative, intraoperative, and postoperative data were prospectively recorded with > 1,800 variables per case and retrospectively reviewed for the present study using the institutional database according to the Heidelberger Verein zur Multi-zentrischen Datenanalyse e.V. The study was performed with local ethics committee and institutional approval; all patients gave their informed consent.
PMI was considered to have occurred if one of the following diagnostic criteria were present: (1) a postoperative cTnI serum level > 10.5 ng/mL within the first 24 h after CABG, as previously described or elevated creatine kinase (CK)-MB values (more than two times the upper limit of normal).2 The appearance of ST-segment deviations at the J point in two or more contiguous leads with cutoff points > 0.2 mV in leads V1, V2, or V3 and > 0.1 mV in other leads or T-wave abnormalities in two or more contiguous leads or the development of new Q-waves. LCOS was present if high-dose inotropic support was necessary in the postoperative course during hospital stay with or without the need of an intra-aortic balloon pump (IABP).
Statistical Analysis
Data are reported as mean ± SD, and categorical variables are presented as No. (%). For all categorical variables, the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Comparisons of categorical variables between groups were performed by a Pearson x2 test or a two-sided Cochran-Armitage trend test (using equally spaced scores); since expected frequencies < 5 occurred, all p values were calculated exactly. Comparisons of continuous variables between groups were analyzed by Kruskal-Wallis test for one-way analysis of variance or the Jonckheere-Terpstra trend test. When a significant overall effect was detected, two-group comparisons were performed with the Fisher exact test for categorical variables or the Mann-Whitney U test for continuous variables. Univariate and multivariate logistic regression analyses were performed to identify preoperative independent predictors for in-hospital mortality and MACE (PMI and LCOS) and the composite study end points, respectively. All preoperative predictor variables that were identified as significant at a two-tailed nominal p value < 0.10 in univariate regression analyses were then entered into a multivariate logistic regression analysis model. Receiver operating characteristic (ROC) curve analyses were applied to determine optimal cutoff values of cTnI and to evaluate the predictive power for in-hospital mortality and MACE. A p value < 0.05 was considered to indicate statistical significance. All statistical analyses between groups were performed using statistical software (StatXact 6.0; Cytel Software Corporation; Cambridge, MA). ROC curve analyses were calculated using statistical software (SPSS version 6.0; Chicago, IL), and logistic regression analyses were also performed (SAS System, version 8; SAS Institute; Cary, NC).
Table 1—Baseline Characteristics According to Preoperative cTnl Levels
| Characteristics | Group 1, |
s 0.1 ng/mL (n = 1592)Group 2,
0.11 to 1.5 ng/mL (n = 265)Group 3,
> 1.5 ng/mL (n = 121)OR, Group 1 vs Group 2
(95% CI)OR, Group 1 vs Group 3
(95% CI)p ValueAdmission status Elective1,210 (76)177 (67)71 (58)0.6 (0.5-0.8)0.4 (0.3-0.7)< 0.001Urgent239 (15)56 (21)30 (24)1.5 (1.1-2.1)1.9 (1.2-2.9)< 0.001Emergency143 (9)32 (12)20 (18)1.4 (0.9-2.1)2.0 (1.2-3.4)< 0.001Demographics Age, yr66 ± 967 ± 968 ± 10 0.01Female gender315 (20)66 (25)29 (24)1.3 (1.0-1.8)1.3 (0.8-2.0)0.11Body weight, kg81 ± 1482 ± 1583 ± 17 0.44Cardiovascular risk factors Diabetes mellitus478 (30)86 (32)36 (30)1.1 (0.8-1.5)1.0 (0.6-1.5)0.72Hypertension1,313 (83)226 (85)107 (88)1.2 (0.8–1.8)1.6 (0.9-3.0)0.15Hyperlipidemia1,292 (81)200 (76)95 (79)0.7 (0.5-1.0)0.8 (0.5-1.4)0.09Family history716 (45)120 (45)58 (48)1.0 (0.8-1.3)1.1 (0.8-1.7)0.82Obesity!507 (32)85 (32)38 (31)1.0 (0.8-1.3)1.0 (0.6-1.5)0.99Smoking history964 (61)133 (50)66 (55)0.7 (0.5-0.9)0.8 (0.5-1.2)0.004Comorbidities History of stroke107 (7)15 (6)7 (6)0.8 (0.5-1.5)0.9 (0.4-1.9)0.77COPD252 (16)43 (16)27 (22)1.0 (0.7-1.5)1.5 (1.0-2.4)0.18PVD234 (15)40 (15)14(12)1.0 (0.7-1.5)0.8 (0.4-1.4)0.62Renal disease!223 (14)35 (13)16(13)0.9 (0.6-1.4)0.9 (0.5-1.7)0.92Dialysis35 (2)6(2)1(1)1.0 (0.4-2.6)0.4 (0.0-2.5)0.59Cardiac history Previous MI§519 (33)114(43)75 (62)1.6 (1.2–2.1)3.4 (2.3-5.0)< 0.0001Previous PCI312 (20)44 (17)22 (18)0.8 (0.6–1.2)0.9 (0.5-1.5)0.50CCS angina class III-IV940 (59)175 (66)93 (77)1.3 (1.0-1.8)2.3 (1.5-3.6)0.0001Extent of CAD Left mainstem disease394 (25)84 (32)39 (32)1.4 (1.1-1.9)1.4 (1.0-2.2)0.02One-vessel disease42 (3)11 (4)0 (0)1.6 (0.8-3.3)0.02 (0.0-1.5)0.06Two-vessel disease234 (15)35 (14)22 (19)0.9 (0.6-1.3)1.3 (0.8-2.1)0.44Three-vessel disease1,316 (83)219 (82)99 (82)1.0 (0.7-1.4)0.9 (0.6-1.6)0.97LV ejection fraction, %60 ± 1556 ± 1455 ± 16 < 0.0001Preoperative serum marker cTnI, ng/mL0.03 ± 0.040.5 ± 0.46.6 ± 12.7 < 0.0001CK, IU/L55 ± 6368 ± 127134 ± 54 < 0.0001