Postoperative B-type Natriuretic Peptide for Prediction of Major Cardiac Events in Patients Undergoing Noncardiac Surgery: Systematic Review and Individual Patient Meta-analysis
Rodseth, Reitze N. M.B.Ch.B., F.C.A., M.Med.*; Biccard, Bruce M. M.B.Ch.B., F.C.A., Ph.D.†; Chu, Rong M.Sc., Ph.D.‡; Lurati Buse, Giovana A. M.D.§; Thabane, Lehana Ph.D.‖; Bakhai, Ameet M.B.B.S., M.D., F.R.C.P., M.E.S.H., F.E.S.C.#; Bolliger, Daniel M.D.**; Cagini, Lucio M.D.††; Cahill, Thomas J. M.A., M.B.B.S., M.R.C.P.‡‡; Cardinale, Daniela M.D., Ph.D., F.E.S.C.§§; Chong, Carol P. W. M.B.B.S., F.R.A.C.P., M.D.‖‖; Cnotliwy, Miłosław M.D., Ph.D.##; Di Somma, Salvatore M.D., Ph.D.***; Fahrner, René M.D.†††; Lim, Wen K. M.D., M.B.B.S., F.R.A.C.P.‡‡‡; Mahla, Elisabeth M.D.§§§; Le Manach, Yannick M.D., Ph.D.‖‖‖; Manikandan, Ramaswamy M.D.###; Pyun, Wook B. M.D.****; Rajagopalan, Sriram M.D., F.R.C.S.††††; Radovic`, Milan M.D., Ph.D.‡‡‡‡; Schutt, Robert C. M.D.§§§§; Sessler, Daniel I. M.D.‖‖‖‖; Suttie, Stuart M.B.Ch.B., M.D., F.R.C.S.Ed.####; Vanniyasingam, Thuvaraha B.Sc.*****; Waliszek, Marek M.D., Ph.D.†††††; Devereaux, P. J. M.D., Ph.D.‡‡‡‡‡
Background: It is unclear whether postoperative B-type natriuretic peptides (i.e., BNP and N-terminal proBNP) can predict cardiovascular complications in noncardiac surgery.
Methods: The authors undertook a systematic review and individual patient data meta-analysis to determine whether postoperative BNPs predict postoperative cardiovascular complications at 30 and 180 days or more.
Results: The authors identified 18 eligible studies (n = 2,051). For the primary outcome of 30-day mortality or nonfatal myocardial infarction, BNP of 245 pg/ml had an area under the curve of 0.71 (95% CI, 0.64–0.78), and N-terminal proBNP of 718 pg/ml had an area under the curve of 0.80 (95% CI, 0.77–0.84). These thresholds independently predicted 30-day mortality or nonfatal myocardial infarction (adjusted odds ratio [AOR] 4.5; 95% CI, 2.74–7.4; P < 0.001), mortality (AOR, 4.2; 95% CI, 2.29–7.69; P < 0.001), cardiac mortality (AOR, 9.4; 95% CI, 0.32–254.34; P < 0.001), and cardiac failure (AOR, 18.5; 95% CI, 4.55–75.29; P < 0.001). For greater than or equal to 180-day outcomes, natriuretic peptides independently predicted mortality or nonfatal myocardial infarction (AOR, 3.3; 95% CI, 2.58–4.3; P < 0.001), mortality (AOR, 2.2; 95% CI, 1.67–86; P < 0.001), cardiac mortality (AOR, 2.1; 95% CI, 0.05–1,385.17; P < 0.001), and cardiac failure (AOR, 3.5; 95% CI, 1.0–9.34; P = 0.022). Patients with BNP values of 0–250, greater than 250–400, and greater than 400 pg/ml suffered the primary outcome at a rate of 6.6, 15.7, and 29.5%, respectively. Patients with N-terminal proBNP values of 0–300, greater than 300–900, and greater than 900 pg/ml suffered the primary outcome at a rate of 1.8, 8.7, and 27%, respectively.
Conclusions: Increased postoperative BNPs are independently associated with adverse cardiac events after noncardiac surgery.
What We Already Know about This Topic
* Although preoperative B-type natriuretic peptides have been demonstrated to predict mortality and myocardial infarction in patients undergoing noncardiac surgery, the usefulness of postoperative natriuretic peptide has not been well established.
What This Article Tells Us That Is New
* Using individual patient data meta-analysis, patients with elevated postoperative natriuretic peptide were at increased risk of mortality, myocardial infarction, and cardiac failure at 30 days and more than 180 days after surgery
* The results further suggested that postoperative natriuretic peptide measurements may provide additional prognostic information and use in stratifying cardiovascular risk after noncardiac surgery
MORE than 200 million surgeries were performed in adults globally each year and this number is increasing.1
More than 10 million of these patients will suffer a major perioperative cardiovascular event (i.e.
, cardiovascular mortality or myocardial infarction [MI]) within 30 days of surgery.3
Effective optimization and intervention are only possible when these at-risk patients are accurately identified.
B-type natriuretic peptide (BNP) and its inactive cleavage product N
-terminal fragment BNP (NT-proBNP) are hormones secreted from ventricular myocytes in response to ventricular wall stretch or myocardial ischemia.4
Preoperative concentrations of BNPs are powerful predictors of mortality and MI in patients undergoing noncardiac surgery.5
Postoperative NPs may have similar prognostic abilities,6
but not all studies have demonstrated this signal.7
Many of these studies have small sample sizes, ranging from 22 to 400 patients, and have been conducted on focused patient populations, such as vascular surgery. All these factors limit the generalizability of these individual studies. Furthermore, the previous individual studies have not established specific postoperative NP thresholds that define a patient at risk of an adverse postoperative cardiac event.
We undertook a systematic review and individual patient data meta-analysis to determine whether NPs, sampled less than 7 days postoperatively, are independently associated with the individual outcomes of mortality, cardiac mortality, nonfatal MI, cardiac arrest, coronary revascularization, or heart failure within 30 days and 180 days or more of adult noncardiac surgery. The study protocol (CRD42012002054) was registered with an international prospective register of systematic reviews (PROSPERO).
Materials and Methods
Studies of noncardiac surgery patients, where postoperative BNP or NT-proBNP was measured upto 7 days after surgery, were considered eligible for inclusion. Studies were included regardless of language, design, sample size, publication status, or date of publication. Studies were excluded if patients had cardiac surgery, included pediatric patients, or used NPs (e.g., nesiritide) as therapy. Studies that met the inclusion criteria but did not report an outcome of interest (i.e., mortality, cardiac mortality, nonfatal MI, cardiac arrest, coronary revascularization, or cardiac failure) were included if authors were able to provide the unpublished data for one or more of these outcomes.
Table. No title avai...Image Tools
We searched six databases (EMBASE, OVID Health Star, Ovid Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ProQuest Dissertations and Theses A&I), used abstracts from meetings of the American Heart Association and the American Society of Anesthesiologists, consulted with experts, reviewed reference lists from identified articles, and searched for cited references of key publications in Web of Science. The search terms, including validated prognostic search terms, and databases used are listed in Appendix 1
. No language filters were used. To avoid inclusion of duplicate study data from reports publishing partial results, only the article with the largest most complete follow-up was included.
Appendix 1. Search Strategy and Databases
Database searches were conducted on January 14, 2012 using the OvidSP search engine (Ovid Technologies, Inc., New York, NY) for the following databases:
1. EMBASE 1980–2012 Week 3
2. OVID Health Star (1966 to November 2011)
3. Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and OVID MEDLINE(R) 1946 to present
4. Cochrane Central Register of Controlled Trials (January 2012)
5. Cochrane Database of Systematic Reviews (January 2012)
6. ProQuest Dissertations and Theses A&I (January 2012)
Example of search conducted on MEDLINE
Drs. Biccard and Rodseth independently screened the title and abstract of each citation identifying those that potentially could fulfill the eligibility criteria. Full texts of citations identified to undergo full-text review during the screening process were obtained, and eligibility was independently evaluated by Drs. Biccard and Rodseth. Disagreements were solved by consensus, and where this could not be reached a third reviewer (Dr. Lurati Buse) made the final eligibility decision.
Data Collection and Assessment of Study Quality
Using a standardized extraction form, we recorded the following data: study design, year of publication, sample size, type of surgery, length of follow-up, method of follow-up, type of NP assay used, and measurement frequency. Study quality was assessed using the modified Quality Assessment of Diagnostic Accuracy Studies assessment tool.8
All authors from eligible studies were contacted and invited to provide anonymous individual patient data using standardized Excel (Microsoft Corp., Redmond, WA) spreadsheets. Age, sex, individual Revised Cardiac Risk Index (RCRI) risk factors9
or if this was not available the cumulative RCRI score, type and urgency of surgery, postoperative NPs value, and predefined 30- and more than 180-day outcomes were obtained. Data sets were checked for accuracy and completeness. Only studies supplying individual patient data were included in this review. We assessed the risk of publication bias by constructing a funnel plot for the composite outcome of mortality and nonfatal MI.
Reporting of Study Outcomes
Our a priori
individual outcomes of interest included: mortality, cardiac mortality, nonfatal MI, cardiac arrest, coronary revascularization, and cardiac failure. Four studies did not differentiate between nonfatal MI and fatal MI and did not conduct routine postoperative troponin surveillance.10–13
For this reason, we were not able to report nonfatal MI; however, given that all trials collected data on mortality and MI, we were able to report this composite outcome of mortality or nonfatal MI. We deemed this outcome as the most clinically relevant and used it as our primary outcome.14
The MI definitions used are shown in Appendix 2
. Two studies collected data on cardiac mortality (Appendix 3
Eleven studies collected data on cardiac failure,7
and three of these studies explicitly defined this outcome (Appendix 4
No studies collected data on coronary revascularization or cardiac arrest.
Interobserver agreement was tested using κ statistics for study eligibility. An a priori
decision was made that when studies measured more than one postoperative NP value within the first 48 h, the highest NP measurement would be used in the analysis. For studies measuring NPs after the first 48 h, we used the NP value closest to the time of surgery. Separate data sets were created for BNP and NT-proBNP. Using receiver operating characteristic (ROC) curves, we identified the highest ROC discriminatory threshold, using Youden Index (J = sensitivity + specificity − 1 = sensitivity − false positive rate), together with its associated 95% CIs for the composite outcome of mortality and nonfatal MI at 30 days in both data sets.23
We then classified patients as falling on, above, or below this threshold, and merged the data sets.
Generalized estimating equations25
were used to analyze each outcome. All analyses were adjusted for age, cumulative RCRI score (as a categorical variable), type of surgery (vascular vs.
nonvascular), study as a clustering variable, and NP (above or below the highest ROC discriminatory threshold as determined above). Generalized estimating equations are special generalized linear models technique for clustered or correlated data. It allows for the specification of a correlation structure among patients within a study. We used an exchangeable correlation structure, which assumes the same correlation between any two patients within a study. The results are reported as adjusted odds ratio (AOR), corresponding 95% CI and associated P
values. As a sensitivity analysis, we repeated this analysis using only those studies where NPs were sampled on the first day after surgery. We assessed collinearity using the variance inflation factor. Variables with a variance inflation factor greater than 10 were considered to be collinear, and if present we excluded one of these variables from the analysis.
The NT-proBNP thresholds of less than 300 pg/ml and greater than 900 pg/ml in patients aged between 50–75 years, and BNP thresholds of 250 and greater than 400 pg/ml, have been used in the diagnosis of acute cardiac failure.26–28
We explored these thresholds to determine whether they separated patients into clinically useful risk groups for the outcome of mortality or nonfatal MI at 30 days after surgery. To determine the clinical utility of postoperative NP reclassification, we used patient age, RCRI score, and type of surgery (vascular or nonvascular) to classify them into four preoperative risk categories (<5, 5–10, >10–15, and >15) for the outcome of 30-day mortality or nonfatal MI. We then reclassified patients using these postoperative NP thresholds and tested the results using reclassification statistics.29
The criterion for statistical significance was set a priori at α = 0.05. We used IBM SPSS Statistics 19.0.0 (Chicago, IL) for descriptive analyses and SAS 9.2 2008 (Cary, NC) for generalized estimating equations and logistic regression.
Study Identification and Selection
Our literature search identified 876 citations from which our screening process identified 53 to undergo full-text evaluation and from these we identified 28 eligible studies.6
Data from five of these studies33
were contained in larger subsequent publications that we included,6
leaving 23 cohorts as shown in figure 1
Five studies were not included in the analysis as we were unable to contact authors of three studies;31
one study did not collect data on any of our outcomes of interest;36
and data from one group is under review by an institutional research committee and could not be shared.30
Authors of the remaining 18 studies provided individual patient data, and these data are included in this systematic review. Interobserver agreement for study eligibility was high (κ = 0.84). The funnel plot is shown in figure 2
Study Characteristics and Data Collection
The characteristics of the 18 study cohorts are shown in table 1
. All studies were prospective cohort studies of small sample sizes (smallest, 22 patients and largest, 400 patients). The type of surgery evaluated within studies included: six vascular surgery studies (679 vascular surgery patients), three thoracic studies (471 thoracic surgery patients), two orthopedic studies (122 orthopedic surgery patients), two urological studies (77 urology surgery patients), and five mixed or major general surgery studies (844 total patients). Most studies measured NP on day 1 after surgery. The quality of eligible studies was generally high (Appendix 5
A total of 2,051 patients were included across the 19 studies. Ten studies evaluated BNP (n = 627) and nine studies evaluated NT-proBNP (n = 1,424). The mean age of the patients was 67 ± 12 (SD) years and 66% were men. The most common surgery was vascular surgery (43% underwent this surgery), and 32% of patients had a history of coronary artery disease. Table 2
shows the clinical characteristics of all 2,051 patients and for the subgroups of patients who did and did not suffer the primary outcome.
Event Rates and Determination of NPs Cut-points
The 30-day event rates were as follows: mortality or nonfatal MI, 11.6% (n = 238 of 2,051); mortality, 3.3% (n = 67 of 2,051); cardiac mortality, 1.5% (n = 5 of 337); and cardiac failure, 3% (n = 63 of 2,051). The corresponding greater than or equal to 180-day outcomes (mean follow-up of 212 days) were 33.5% (n = 480 of 1,432) for mortality or nonfatal MI, 11.1% (n = 160 of 1,432) for mortality, 9.2% (n = 31 of 337) for cardiac mortality, and 22.7% (n = 163 of 717) for cardiac failure.
For the composite outcome of mortality or nonfatal MI at 30 days, the highest ROC postoperative NP discrimination point was 245 pg/ml for BNP with a 95% CI ranging from 195 to 468 pg/ml (ROC area under the curve, 0.71; 95% CI, 0.64–0.78) and 718 pg/ml for NT-proBNP with a 95% CI ranging from 656 to 994 pg/ml (ROC area under the curve, 0.80; 95% CI, 0.77–0.84). For the merged data set with both NPs, the ROC area under the curve was 0.76; 95% CI, 0.73–0.80.
shows the odds ratios—adjusted for age, RCRI score, and type of surgery (vascular or nonvascular)—associated with postoperative NPs increased above the highest ROC threshold for each of the study outcomes. Patients with an increased postoperative NP measurement were at increased risk of 30-day mortality or nonfatal MI (AOR, 4.5; 95% CI, 2.74–7.4; P
< 0.001) and cardiac failure (AOR, 18.5; 95% CI, 4.55–75.29; P
< 0.001). NP increases remained predictive for greater than or equal to 180-day mortality or nonfatal MI (AOR, 3.3; 95% CI, 2.58–4.3; P
< 0.001) and cardiac failure (AOR, 3.5; 95% CI, 1.0–9.34; P
Testing the robustness of these results by performing logistic regression in which we ignored study clustering did not appreciably change the AORs (Appendix 6
). For the outcomes of mortality, and the composite of mortality and nonfatal MI, the results of the sensitivity analysis that excluded measurements obtained after the first postoperative day did not differ appreciably from the primary results (Appendix 7
). For the outcomes of cardiac mortality and cardiac failure, the AOR was lower but remained significant. No variables were found to be collinear.
Patients with BNP values of 0–250, greater than 250–400, and greater than 400 pg/ml suffered the composite of 30-day mortality or nonfatal MI at a rate of 6.6, 15.7, and 29.5%, respectively. Patients with NT-proBNP values of 0–300, greater than 300–900, and greater than 900 pg/ml suffered the same composite of 30-day mortality or nonfatal MI at a rate of 1.8, 8.7, and 27%, respectively. In the NT-proBNP group, 32% (460 of 1,421) of patients had a value greater than 900 pg/ml. In a post hoc
analysis, postoperative NP measurement improved overall net reclassification index by 20% (P
< 0.001), with 6% of patients having an event being reclassified as higher risk and 14% of patients without an event being reclassified as lower risk (table 4
). Among the 895 patients with a preoperative risk between 5 and 15% the net reclassification index improvement was 70% (P
< 0.001) with 46% of patients having an event being reclassified to a high-risk category, and 25% of patient without an event being reclassified to a low-risk category.
Due to the number of patients with an NT-proBNP greater than 900 pg/ml we decided to undertake a post hoc
analysis to determine the results for an additional NT-proBNP threshold of 3,000 pg/ml, which has been used in previous publications.44
Patients with NT-proBNP values of 900–3,000 and greater than 3,000 pg/ml had an incidence of 30-day mortality or nonfatal MI of 20.9 and 38.4%, respectively. Using 3,000 pg/ml as a threshold ensured the CIs of the two new risk groups did not overlap. These NT-proBNP and BNP results together with the associated AOR and multilevel likelihood ratios are shown in tables 5
Summary of Evidence
Our systematic review and individual patient level meta-analysis included more than 2,000 patients who had a variety of different noncardiac surgeries. Meta-analysis indicates that an increased postoperative NP is an independent predictor of mortality, cardiac mortality, mortality or nonfatal MI, and cardiac failure at 30 and greater than or equal to 180 days after noncardiac surgery.
Strengths and Weaknesses
The strengths of this review lie in the: (1) rigorous systematic review methodology, (2) success in obtaining individual patient data, and (3) the quality of the included studies. Simulation studies show that logistic regression models require at least 10 events per predictor variable to produce stable estimates of association.45
In our meta-analyses, we evaluated four independent variables, that is age, RCRI score, type of surgery (vascular vs.
nonvascular), and peak postoperative NP measurement. We surpassed 10 events per variable for all outcomes except the 30- and greater than or equal to 180-day cardiac mortality outcomes.
Our systematic review is limited by the inability to adjust for postoperative troponin measurements, which are known to be strongly associated with postoperative mortality.46
The majority of troponin increases occur within the first 48–72 h after surgery;14
the same time period during which 16 of the studies included in this review sampled NPs. Unfortunately, the data were not available to allow us to determine the temporal relationship between NP and troponin increases. As we were limited by the inability to obtain the individual preoperative RCRI risk factors for each study it is possible that our model suffers from residual confounding. The funnel plot suggests the possibility of publication bias toward studies reporting a stronger association between increased postoperative NPs and the composite outcome of mortality and nonfatal MI. This weakens our inferences.
Preoperative NPs are useful for preoperative risk stratification. This analysis did not evaluate the interaction between preoperative and postoperative NPs. It is possible that postoperative NP increases may allow clinicians to identify the most vulnerable patients among those with high preoperative NP concentrations.37
The large number of patients and deaths allowed us to evaluate all-cause mortality as an outcome. Unfortunately, cardiac mortality was only collected in two studies.6
The small number of events analyzed for this outcome make overfitting of the results possible. This, together with the results of the sensitivity analysis, demonstrates that readers should interpret the cardiac mortality and heart failure data with caution. Evaluation of postoperative MI is hampered by the varying definitions used among the studies; however, all these studies included troponin increase as part of their definitions. The definitions of cardiac failure varied widely among studies, which may limit the validity of these results.
Postoperative NPs Thresholds
Converting a continuous variable into a categorical or dichotomous variable results in a loss of information, but it may make results more practical for clinical use. The thresholds we explored separated patients into clinically useful risk groups, but in many cases CIs overlapped. This may be due to the small sample size in some of the groups. The net reclassification results suggest that in this patient population a postoperative NP measurement is of greatest value in patients with a 5–15% preoperative baseline risk of 30-day mortality or nonfatal MI.
Recommendations and Implications for Clinical Practice
Previous studies have shown that NP concentrations are related to the extent of myocardial injury after nonoperative MI and improve prognostic scoring systems.48
Our systematic review demonstrates the potential utility of postoperative NPs to identify patients at high risk of adverse cardiac events. These patients may benefit from close postoperative monitoring and more rigorous heart rate and fluid management; however, clinical trials are needed to determine whether this risk factor is modifiable. Postoperative NPs may also have a role in the diagnosis and management of patients with subclinical postoperative cardiac failure and may alert clinicians to those patients at risk of acute decompensation.
Before NPs can be incorporated into clinical practice they must demonstrate superiority to other more commonly used risk factors.50
For this to take place studies are required to understand the relationship between postoperative troponin and NP increases. Two questions should be addressed: (1) do increased NPs in patients without early postoperative troponin increases predict postoperative cardiac complications? and (2) do increased NPs in patients with postoperative troponin increases add additional prognostic value to troponin measurement alone? Furthermore, studies to determine the optimal timing for sampling postoperative NPs would also be useful.
Postoperative NPs increases are associated with postoperative mortality, cardiac mortality, mortality and nonfatal MI, and cardiac failure at both 30 days and 180 days or more after surgery. Clinicians may thus find postoperative NP measurements useful in stratifying cardiovascular risk after noncardiac surgery.
The authors thank Ian Glenn, M.D., Research Fellow, Department of Cardiology, Barnet and Chase Farm NHS Trust, London, United Kingdom; Ali Ansaripour, Research Fellow, Department of Cardiology Barnet and Chase Farm NHS Trust; Hence J. M. Verhagen, M.D., Ph.D., Professor and Chief of Vascular Surgery, Erasmus Medical Center, Rotterdam, The Netherlands; Sanne E. Hoeks, M.D., Ph.D., Assistant Professor, Erasmus University Medical Center, Department of Anesthesiology, Erasmus Medical Centre, Rotterdam, The Netherlands; Jan Brozek, M.D., Ph.D., Assistant Professor, Departments of Clinical Epidemiology and Biostatistics and Medicine, McMaster University, Hamilton, Ontario, Canada; Agnieszka Grudniewicz, Ph.D. Candidate, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada; David McDonagh, M.D., Associate Professor of Anesthesiology and Medicine (Neurology), Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; and John Morton, M.D., M.P.H., F.A.C.S., Associate Professor of Surgery, Section Chief, Minimally Invasive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California.
1. Weiser TG, Regenbogen SE, Thompson KD, Haynes AB, Lipsitz SR, Berry WR, Gawande AA. An estimation of the global volume of surgery: A modelling strategy based on available data. Lancet. 2008;372:139–44
2. Devereaux PJ, Goldman L, Cook DJ, Gilbert K, Leslie K, Guyatt GH. Perioperative cardiac events in patients undergoing noncardiac surgery: A review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk. CMAJ. 2005;173:627–34
3. Devereaux PJ, Chan MTV, Alonso-Coello P, Walsh M, Berwanger O, Villar JC, Wang CY, Garutti RI, Jacka MJ, Sigamani A, Srinathan S, Biccard BM, Chow CK, Abraham V, Tiboni M, Pettit S, Szczeklik W, Buse GL, Botto F, Guyatt G, Heels-Ansdell D, Sessler D, Thorlund K, Garg AX, Mrkobrada M, Thomas S, Rodseth RN, Pearse RM, Thabane L, McQueen MJ, VanHelder T, Bhandari M, Bosch J, Kurz A, Polanczky CA, Malaga G, Nagele P, Le Manach Y, Leuwer M, Yusuf S. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307:2295–304
4. Rodseth RN. B type natriuretic peptide—A diagnostic breakthrough in peri-operative cardiac risk assessment? Anaesthesia. 2009;64:165–78
5. Karthikeyan G, Moncur RA, Levine O, Heels-Ansdell D, Chan MT, Alonso-Coello P, Yusuf S, Sessler D, Villar JC, Berwanger O, McQueen M, Mathew A, Hill S, Gibson S, Berry C, Yeh HM, Devereaux PJ. Is a pre-operative brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide measurement an independent predictor of adverse cardiovascular outcomes within 30 days of noncardiac surgery? A systematic review and meta-analysis of observational studies. J Am Coll Cardiol. 2009;54:1599–606
6. Mahla E, Baumann A, Rehak P, Watzinger N, Vicenzi MN, Maier R, Tiesenhausen K, Metzler H, Toller W. N-terminal pro-brain natriuretic peptide identifies patients at high risk for adverse cardiac outcome after vascular surgery. Anesthesiology. 2007;106:1088–95
7. Chong CP, van Gaal WJ, Ryan JE, Burrell LM, Savige J, Lim WK. Troponin I and NT-proBNP (N-terminal pro-brain natriuretic peptide) do not predict 6-month mortality in frail older patients undergoing orthopedic surgery. J Am Med Dir Assoc. 2010;11:415–20
9. Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE, Freeman WK, Froehlich JB, Kasper EK, Kersten JR, Riegel B, Robb JF, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Buller CE, Creager MA, Ettinger SM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CWACC/AHA Task Force Members. . ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: Executive Summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): Developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. Circulation. 2007;116:1971–96
10. Cagini L, Capozzi R, Tassi V, Savignani C, Quintaliani G, Reboldi G, Puma F. Fluid and electrolyte balance after major thoracic surgery by bioimpedance and endocrine evaluation. Eur J Cardiothorac Surg. 2011;40:e71–6
11. Cardinale D, Colombo A, Sandri MT, Lamantia G, Colombo N, Civelli M, Salvatici M, Veronesi G, Veglia F, Fiorentini C, Spaggiari L, Cipolla CM. Increased perioperative N-terminal pro-B-type natriuretic peptide levels predict atrial fibrillation after thoracic surgery for lung cancer. Circulation. 2007;115:1339–44
12. Hoksch B, Fahrner R, Schmid RA. Procalcitonin and brain natriuretic peptide as parameters in the postoperative course of patients with major pulmonary resection. Interact Cardiovasc Thorac Surg. 2007;6:155–8
13. Radović M, Damjanović S, Nale D, Mićić S, Vučović D, Radović M. Modulation of aldosterone release by epidural analgesia impacts brain natriuretic peptide: A link to stress cardiomyopathy? Pilot study. Clin Endocrinol (Oxf). 2011;74:649–56
14. Devereaux PJ, Xavier D, Pogue J, Guyatt G, Sigamani A, Garutti I, Leslie K, Rao-Melacini P, Chrolavicius S, Yang H, Macdonald C, Avezum A, Lanthier L, Hu W, Yusuf S. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: A cohort study. Ann Intern Med. 2011;154:523–8
15. Rajagopalan S, Croal BL, Reeve J, Bachoo P, Brittenden J. N-terminal pro-B-type natriuretic peptide is an independent predictor of all-cause mortality and MACE after major vascular surgery in medium-term follow-up. Eur J Vasc Endovasc Surg. 2011;41:657–62
16. Chong CP, Ryan JE, van Gaal WJ, Lam QT, Sinnappu RN, Burrell LM, Savige J, Lim WK. Usefulness of N-terminal pro-brain natriuretic peptide to predict postoperative cardiac complications and long-term mortality after emergency lower limb orthopedic surgery. Am J Cardiol. 2010;106:865–72
17. Park JH, Shin GJ, Ryu JI, Pyun WB. Postoperative B-type natriuretic Peptide levels associated with prolonged hospitalization in hypertensive patients after non-cardiac surgery. Korean Circ J. 2012;42:521–7
18. Waliszek M, Waliszek-Iwanicka A, Grycewicz T, Jurowski P, Banach M, Rysz J, Goch A. Prognostic value of plasma N-terminal pro-B-type natriuretic peptide concentration in patients with normal and impaired left ventricular systolic function undergoing surgery for abdominal aortic aneurysm. Arch Med Sci. 2011;7:642–7
19. Mercantini P, Di Somma S, Magrini L, Kazemi Nava A, Scarinci A, La Torre M, Ferri M, Ferri E, Petrucciani N, Ziparo V. Preoperative brain natriuretic peptide (BNP) is a better predictor of adverse cardiac events compared to preoperative scoring system in patients who underwent abdominal surgery. World J Surg. 2012;36:24–30
20. Cahill T, Bowes P, Duncan E, Drye E, Sen S, Reshamwalla S, Andrew C, Ward M, Bakhai A. Post-operative B-type natriuretic peptide predicts mortality after gastrointestinal surgery. Eur Heart J. 2009 Paper presented at: European Society of Cardiology 2009, Barcelona, Spain, August 29, 2009–September 2, 2009
21. Cnotliwy M, Kazimierczak A, Sledz M, Biernacka J, Zukowski M. The usefulness of N-terminal pro-brain natriuretic peptide and cardiac troponin measurement in the prediction of cardiac morbidity after carotid endarterectomy. Acta Angiol. 2011;17:199–208
22. Schutt RC, Cevik C, Phy MP. Plasma N-terminal prohormone brain natriuretic peptide as a marker for postoperative cardiac events in high-risk patients undergoing noncardiac surgery. Am J Cardiol. 2009;104:137–40
23. Ray P, Le Manach Y, Riou B, Houle TT. Statistical evaluation of a biomarker. Anesthesiology. 2010;112:1023–40
24. Peat JK, Barton B Medical Statistics: A Guide To Data Analysis and Critical Appraisal. 20051st edition Malden Massachusetts, Blackwell
25. Hardin JW, Hilbe J Generalized Estimating Equations. 2003 Boca Raton Florida, Chapman & Hall/CRC
26. Januzzi JL Jr, Chen-Tournoux AA, Moe G. Amino-terminal pro-B-type natriuretic peptide testing for the diagnosis or exclusion of heart failure in patients with acute symptoms. Am J Cardiol. 2008;101:29–38
27. Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PABreathing Not Properly Multinational Study Investigators. . Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161–7
28. Ray P, Arthaud M, Birolleau S, Isnard R, Lefort Y, Boddaert J, Riou B. Comparison of brain natriuretic peptide and probrain natriuretic peptide in the diagnosis of cardiogenic pulmonary edema in patients aged 65 and older. J Am Geriatr Soc. 2005;53:643–8
29. Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS. Evaluating the added predictive ability of a new marker: From area under the ROC curve to reclassification and beyond. Stat Med. 2008;27:157–72
30. Goei D, van Kuijk JP, Flu WJ, Hoeks SE, Chonchol M, Verhagen HJ, Bax JJ, Poldermans D. Usefulness of repeated N-terminal pro-B-type natriuretic peptide measurements as incremental predictor for long-term cardiovascular outcome after vascular surgery. Am J Cardiol. 2011;107:609–14
31. Hahn R, Kettner SC. Clinical course of 40 patients with heart failure and trauma surgery treated with levosimendan. Intensive Care Med. 2011 Paper presented at: 24th Annual Congress of the European Society of Intensive Care Medicine 2011, Berlin, Germany, October 1, 2011–October 5, 2011
32. Hou JL, Gao K, Li M, Ma JY, Shi YK, Wang Y, Zhao YF. Increased N-terminal pro-brain natriuretic peptide level predicts atrial fibrillation after surgery for esophageal carcinoma. World J Gastroenterol. 2008;14:2582–5
33. Jarai R, Mahla E, Perkmann T, Jarai R, Archan S, Tentzeris I, Huber K, Metzler H. Usefulness of pre-operative copeptin concentrations to predict post-operative outcome after major vascular surgery. Am J Cardiol. 2011;108:1188–95
34. Kawaguchi M, Utada K, Yoshitani K, Uchino H, Takeda Y, Masui K, Sakabe T. Intraoperative Landiolol for Intracranial Aneurysm Surgery Trial I: Effects of a short-acting [beta]1 receptor antagonist landiolol on hemodynamics and tissue injury markers in patients with subarachnoid hemorrhage undergoing intracranial aneurysm surgery. J Neurosurg Anesthesiol. 2010;22:230–9
35. Manikandan R, Nathaniel C, Lewis P, Brough RJ, Adeyoju A, Brown SC, O’Reilly PH, Collins GN. Troponin T and N-terminal pro-brain natriuretic peptide changes in patients undergoing transurethral resection of the prostate. J Urol. 2005;174:1892–5
36. McDonagh DL, Mathew JP, White WD, Phillips-Bute B, Laskowitz DT, Podgoreanu MV, Newman MFNeurologic Outcome Research Group. . Cognitive function after major noncardiac surgery, apolipoprotein E4 genotype, and biomarkers of brain injury. Anesthesiology. 2010;112:852–9
37. Rodseth RN, de Vascocellos K, Naidoo P, Biccard BM. Early postoperative BNP does not predict postoperative cardiac events within 30 days of vascular surgery. South Afr J Anaesth Analg. 2013;19:60–5
38. Suttie S, Mofidi R, McCallum R, Christie S, Flett M, Nagy J, Griffiths G, McLeod S, Struthers A, Stonebridge P. Immediately postoperative B-type natriuretic peptide and its predictive value. Ann Vasc Surg. 2011;25:248–55
39. Talucci V, Magrini L, Scarinci A, Petrucciani N, Mercantini P, Mastrantuono A, Marino R, Di Somma S, Ziparo V. Evaluation of brain natriuretic peptide (BNP) role as prognostic factor for cardiovascular outcomes in patients undergoing non-cardiac surgery. Eur Heart J. 2010 Paper presented at: European Society of Cardiology 2010, Stockholm, Sweden, August 28, 2010–September 1, 2010
40. Talucci V, Magrini L, Petrucciani N, Scarinci A, Mercantini P, Spallotta C, Mastrantuono A, Di Somma S, Ziparo V. Bnp measurement pre- and post-noncardiac surgery as prognostic factor of cardiovascular events in hypertensive patients: Pp. 12.460. J Hypertens. 2010;28::e188–9
41. Van Kuijk JP, Flu WJ, Hoeks SE, Chonchol M, Verhagen HJM, Bax JJ, Poldermans D. Repeated N-terminal pro B-type natriuretic peptide measurements as incremental predictor for long-term cardiovascular outcome after vascular surgery. Eur Heart J. 2010 Paper presented at: European Society of Cardiology 2010, Stockholm, Sweden, August 28, 2010–September 1, 2010
42. Cahill T, Bowes P, Duncan E, Drye E, Sen S, Miller C, Reshamwalla S, Andrew C, Ward M, Bakhai A. Risk stratification by cardiac biomarkers following emergency gastrointestinal surgery. ISRN Vasc Med. 2011;2011:1–5
43. Lurati Buse GA, Schumacher P, Seeberger E, Studer W, Schuman RM, Fassl J, Kasper J, Filipovic M, Bolliger D, Seeberger MD. Randomized comparison of sevoflurane versus propofol to reduce myocardial ischemia in patients undergoing noncardiac surgery. Circulation. 2012;126:2696–704
44. Januzzi JL Jr, Rehman SU, Mohammed AA, Bhardwaj A, Barajas L, Barajas J, Kim HN, Baggish AL, Weiner RB, Chen-Tournoux A, Marshall JE, Moore SA, Carlson WD, Lewis GD, Shin J, Sullivan D, Parks K, Wang TJ, Gregory SA, Uthamalingam S, Semigran MJ. Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction. J Am Coll Cardiol. 2011;58:1881–9
45. Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49:1373–9
46. Levy M, Heels-Ansdell D, Hiralal R, Bhandari M, Guyatt G, Yusuf S, Cook D, Villar JC, McQueen M, McFalls E, Filipovic M, Schünemann H, Sear J, Foex P, Lim W, Landesberg G, Godet G, Poldermans D, Bursi F, Kertai MD, Bhatnagar N, Devereaux PJ. Prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurement after noncardiac surgery: A systematic review and meta-analysis. Anesthesiology. 2011;114:796–806
47. Devereaux PJ, Chan MT, Alonso-Coello P, Walsh M, Berwanger O, Villar JC, Wang CY, Garutti RI, Jacka MJ, Sigamani A, Srinathan S, Biccard BM, Chow CK, Abraham V, Tiboni M, Pettit S, Szczeklik W, Lurati Buse G, Botto F, Guyatt G, Heels-Ansdell D, Sessler DI, Thorlund K, Garg AX, Mrkobrada M, Thomas S, Rodseth RN, Pearse RM, Thabane L, McQueen MJ, VanHelder T, Bhandari M, Bosch J, Kurz A, Polanczyk C, Malaga G, Nagele P, Le Manach Y, Leuwer M, Yusuf S. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307:2295–304
48. Khan SQ, Narayan H, Ng KH, Dhillon OS, Kelly D, Quinn P, Squire IB, Davies JE, Ng LL. N-terminal pro-B-type natriuretic peptide complements the GRACE risk score in predicting early and late mortality following acute coronary syndrome. Clin Sci. 2009;117:31–9
49. Morrow DA, de Lemos JA, Sabatine MS, Murphy SA, Demopoulos LA, DiBattiste PM, McCabe CH, Gibson CM, Cannon CP, Braunwald E. Evaluation of B-type natriuretic peptide for risk assessment in unstable angina/non-ST-elevation myocardial infarction: B-type natriuretic peptide and prognosis in TACTICS-TIMI 18. J Am Coll Cardiol. 2003;41:1264–72
50. Ioannidis JP, Tzoulaki I. Minimal and null predictive effects for the most popular blood biomarkers of cardiovascular disease. Circ Res. 2012;110:658–62
51. Luepker RV, Apple FS, Christenson RH, Crow RS, Fortmann SP, Goff D, Goldberg RJ, Hand MM, Jaffe AS, Julian DG, Levy D, Manolio T, Mendis S, Mensah G, Pajak A, Prineas RJ, Reddy KS, Roger VL, Rosamond WD, Shahar E, Sharrett AR, Sorlie P, Tunstall-Pedoe H. Case definitions for acute coronary heart disease in epidemiology and clinical research studies: a statement from the AHA Council on Epidemiology and Prevention; AHA Statistics Committee; World Heart Federation Council on Epidemiology and Prevention; the European Society of Cardiology Working Group on Epidemiology and Prevention; Centers for Disease Control and Prevention; and the National Heart, Lung, and Blood Institute. Circulation. 2003;108:2543–2549
52. Thygesen K, Alpert JS, White HD, Jaffe AS, Apple FS, Galvani M, Katus HA, Newby LK, Ravkilde J, Chaitman B, Clemmensen PM, Dellborg M, Hod H, Porela P, Underwood R, Bax JJ, Beller GA, Bonow R, Van der Wall EE, Bassand JP, Wijns W, Ferguson TB, Steg PG, Uretsky BF, Williams DO, Armstrong PW, Antman EM, Fox KA, Hamm CW, Ohman EM, Simoons ML, Poole-Wilson PA, Gurfinkel EP, Lopez-Sendon JL, Pais P, Mendis S, Zhu JR, Wallentin LC, Fernandez-Aviles F, Fox KM, Parkhomenko AN, Priori SG, Tendera M, Voipio-Pulkki LM, Vahanian A, Camm AJ, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Widimsky P, Zamorano JL, Morais J, Brener S, Harrington R, Morrow D, Lim M, Martinez-Rios MA, Steinhubl S, Levine GN, Gibler WB, Goff D, Tubaro M, Dudek D, Al-Attar N. Universal definition of myocardial infarction. Circulation. 2007;116:2634–5353
53. McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. N Engl J Med. 1971;285:1441–144654
54. Nieminen MS, Bohm M, Cowie MR, Drexler H, Filippatos GS, Jondeau G, Hasin Y, Lopez-Sendon J, Mebazaa A, Metra M, Rhodes A, Swedberg K, Priori SG, Garcia MA, Blanc JJ, Budaj A, Dean V, Deckers J, Burgos EF, Lekakis J, Lindahl B, Mazzotta G, Morais J, Oto A, Smiseth OA, Dickstein K, Albuquerque A, Conthe P, Crespo-Leiro M, Ferrari R, Follath F, Gavazzi A, Janssens U, Komajda M, Moreno R, Singer M, Singh S, Tendera M, Thygesen K. Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology. Eur Heart J. 2005;26:384–41655
55. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Stromberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail. 2008;10:933–89
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