Date Published: April 22, 2019
Publisher: Public Library of Science
Author(s): Caroline A. S. Humble, Stephen Huang, Ib Jammer, Jonas Björk, Michelle S. Chew, Chun Shing Kwok.
Increased postoperative cardiac troponin (cTn) independently predicts short-term mortality. Previous studies suggest that preoperative cTn also predicts major adverse cardiovascular events (MACE) and mortality after noncardiac surgery. The value of preoperative and perioperative changes in cTn as a prognostic tool for adverse outcomes has been sparsely investigated.
A systematic review and meta-analysis of the prognostic value of cTns for adverse outcome was conducted. Adverse outcome was defined as short-term (in-hospital or <30 days) and long-term (>30 days) MACE and/or all-cause mortality, in adult patients undergoing noncardiac surgery. The study protocol (CRD42018094773) was registered with an international prospective register of systematic reviews (PROSPERO). Preoperative cTn was a predictor of short- (OR 4.3, 95% CI 2.9–6.5, p<0.001, adjusted OR 5.87, 95% CI 3.24–10.65, p<0.001) and long-term adverse outcome (OR 4.2, 95% CI 1.0–17.3, p = 0.05, adjusted HR 2.0, 95% CI 1.4–3.0, p<0.001). Perioperative change in cTn was a predictor of short-term adverse outcome (OR 10.1, 95% CI 3.2–32.3, p<0.001). It was not possible to conduct pooled analyses for adjusted estimates of perioperative change in cTn as predictor of short- (a single study identified) and long-term (no studies identified) adverse outcome. Further, it was not possible to conduct pooled analyses for unadjusted estimates of perioperative change in cTn as predictor of long-term adverse outcome, since only one study was identified. Bivariate analysis of sensitivities and specificities were performed, and overall prognostic performance was summarized using summary receiver operating characteristic (SROC) curves. The pooled sensitivity and specificity for preoperative cTn and short-term adverse outcome was 0.43 and 0.86 respectively (area under the SROC curve of 0.68). There were insufficient studies to construct SROCs for perioperative changes in cTn and for long-term adverse outcome. Our study indicates that although preoperative cTn and perioperative change in cTn might be valuable predictors of MACE and/or all-cause mortality in adult noncardiac surgical patients, its overall prognostic performance remains uncertain. Future large, representative, high-quality studies are needed to establish the potential role of cTns in perioperative cardiac risk stratification.
We adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement  in conducting and reporting this systematic review. On the 23rd of January 2016, we conducted two searches in the electronic databases, Medline via PubMed and Embase via Ovid. No filters, with respect to year of publication or language, were used. The following MeSH terms were used in the Medline search: ‘Troponin’, ‘Surgical Procedures, Operative’/’surgery’/’Postoperative Complications’, ‘Cardiovascular Diseases’/’Mortality’/’Death’, ‘Prognosis’/’Risk Assessment’/’Sensitivity and Specificity’, ‘Perioperative Care’/’Perioperative Period’ (S1 File). The search strategy was developed with the assistance of a librarian at Lund University, Sweden. On the 23rd of June 2017, we conducted an updated search identical to the two searches mentioned, to identify papers published between 23rd of January 2016 to 23rd of June 2017. Two authors independently screened titles (MSC, CH or MSC, IJ), abstracts and full-text articles (IJ, CH or IJ, MSC) in accordance with predefined eligibility criteria. Differing opinions on whether to include or exclude full-text articles were resolved through discussion by two authors (IJ, CH or IJ, MSC). If consensus could not be reached, a third author (MSC or CH) reviewed the full-text article and made the final decision. Furthermore, the reference lists of the included studies [12, 17–35], in addition to three central reviews [7, 36, 37] were screened to identify additional eligible studies. The study protocol (CRD42018094773) was registered with an international prospective register of systematic reviews (PROSPERO). (S2 File).
Our search strategy identified a total of 1795 records. After an initial screening of titles and abstracts, 1739 records were eliminated, of which 394 were duplicates. Fifty-six full-text articles were assessed for eligibility. Twenty eligible studies [12, 17–35] were identified. (Fig 1). Nineteen [17–35] studies were included addressing preoperative cTn and three studies [12, 26, 29] addressing perioperative change in cTn as prognostic factor. Notably Gillman et al.  and Nagele et al.  were included in both categories.
This meta-analysis suggests that preoperative cTn predicts adverse outcome defined as MACE and/or all-cause mortality in adult noncardiac surgical patients. The effect was best demonstrated for short-term adverse outcome, and was sustained in adjusted analyses. In addition, pooled estimates show that cTn predicts adverse outcome, regardless of follow-up time, adjustment for confounders, and whether cTn was considered as preoperative values or perioperative changes. Additional subgroup meta-analysis, according to the type of troponin assay showed that preoperative cTn was clearly predictive of short-term adverse outcome in both subgroups of studies (i.e. conventional cTnT/cTnT and hs-cTnT). This is in line with the recent study by Gualandro et al. . Despite this demonstrated effect, analysis of the prognostic performance of preoperative cTns was poor for short-term adverse outcome. Thus, although this meta-analysis suggests that preoperative cTn predicts adverse outcome, SROC analysis reveals that the prognostic performance of preoperative cTn is poor. For long-term adverse outcome and perioperative change in cTn we were unable to adequately evaluate the prognostic performance.