Preoperative B-type natriuretic peptides in patients undergoing noncardiac surgery: a cumulative meta-analysis

Figures & data

Figure 1: Study selection process.

BNP: B-type natriuretic peptide; NT-proBNP: N-terminal fragment of proBNP.

Table 1: Study characteristics of eligible studies

Author, year	Surgery type	Patients	Events	Outcome definitions
Yeh, 2005	Elective non-cardiac	190	15	MACE
Dernellis, 2006	Elective non-cardiac	1590	96	MACE
Cardinale, 2007	Elective thoracic	400	72	AF
Cuthbertson, 2007	Elective major non-cardiac	204	12	MACE
Cuthbertson, 2007	Emergency hip and abdominal	40	11	MACE
Gibson, 2007	Elective major non-cardiac	190	26	MACE
Mahla, 2007	Elective vascular	218	44	MACE, acute coronary revascularisation
Hou, 2007	Elective oesophagectomy	142	11	MACE
Rajagopalan, 2008	Elective major vascular	136	28	Myocardial injury
Yun, 2008	Elective non-cardiac	279	25	MACE, non-fatal stroke
Bolliger, 2009	Elective major vascular	133	19	MACE
Oscarsson, 2009	Emergency hip	69	34	MACE
Schutt, 2009	Elective & emergency non-cardiac	25	83	Heart failure, unstable angina
Breidthardt, 2010	Elective orthopaedic	270	4	MACE, troponin elevation, ECG changes
Chong, 2010	Emergency orthopaedic	89	65	MACE
Villacorta, 2010	Elective orthopaedic	208	17	MACE
Lee, 2011	Elective thoracic	98	10	MACE, ECG changes
Nojiri, 2011	Elective thoracic	80	34	Cardiorespiratory complications
Park, 2011	Elective major non-cardiac	1923	355	MACE
Payne, 2011	Elective non-cardiac	345	111	Long term all-cause mortality
Amar, 2012	Elective thoracic	415	65	AF
Biccard, 2012	Elective vascular	788	136	Mortality, troponin elevation
Mercantini, 2012	Elective major abdominal	205	31	MACE, troponin elevation
Yang, 2012	Elective vascular	365	63	MACE
Bryce, 2013	Elective abdominal aortic aneurysm	106	29	MACE, all-cause mortality
Borges, 2013	Elective non-cardiac	145	17	Vascular death, non-fatal MI, non-fatal cardiac arrest
Scrutinio, 2014	Elective vascular	411	87	Death, ACS, acute pulmonary oedema, postoperative myocardial damage
Vetrugno, 2014	Elective orthopaedic	227	14	MACE

Notes: AF: atrial fibrillation; MACE: major adverse cardiac events (cardiac death, non-fatal myocardial infarction, congestive cardiac failure, arrhythmias); ACS: acute coronary syndrome; ECG: electrocardiograph.

Table 2: Natriuretic peptide assay characteristics

Author, year	Natriuretic peptide measured	Assay, Manufacturer	Threshold (pg/ml)
Yeh, 2005	NT-proBNP	Elecsys, Roche diagnostics	450
Dernellis, 2006	BNP	AxSYM, Axis Shield diagnostics	189
Cardinale, 2007	NT-proBNP	Elecsys, Roche diagnostics	204
Cuthbertson, 2007	BNP	Bayer ADVIA Centaur, Siemens medical diagnostics	40
Cuthbertson, 2007	BNP	Bayer ADVIA Centaur, Siemens medical diagnostics	170
Gibson, 2007	BNP	Not indicated	108.5
Mahla, 2007	NT-proBNP	Elecsys, Roche diagnostics	280
Hou, 2007	NT-proBNP	Elecsys, Roche diagnostics	Not indicated
Rajagopalan, 2008	NT-proBNP	Elecsys, Roche diagnostics	308
Yun, 2008	NT-proBNP	Elecsys, Roche diagnostics	201
Bolliger, 2009	BNP	AxSYM, Axis Shield diagnostics	50
Oscarsson, 2009	NT-proBNP	Stratus CS Acute Care Diagnostic System	3984
Schutt, 2009	NT-proBNP	Elecsys, Roche diagnostics	457
Breidthardt, 2010	BNP	Fluorescence immunoassay, Biosite diagnostics	174
Chong, 2010	NT-proBNP	Elecsys, Roche diagnostics	842
Villacorta, 2010	BNP	Triage, Biosite Inc	60
Lee, 2011	NT-proBNP	Elecsys, Roche diagnostics	160
Nojiri, 2011	BNP	Shionogi BNP, Shionogi Pharmaceuticals	30
Park, 2011	NT-proBNP	Elecsys, Roche diagnostics	301
Payne, 2011	BNP	Shionoria BNP Kit (Shinogi & Co)	87.5
Amar, 2012	BNP	Not indicated	30
Biccard, 2012	BNP	Bayer ADVIA Centaur, Siemens medical diagnostics	48.1
Mercantini, 2012	BNP	Triage, Biosite Inc	36
Yang, 2012	NT-proBNP	Not indicated	302
Bryce, 2013	BNP	Shinoria BNP Kit, Shinogi & Co Ltd	99.5
Borges, 2013	NT-proBNP	Elecsys, Roche diagnostics	917
Scrutinio, 2014	NT-proBNP	Not indicated	Not indicated
Vetrugno, 2014	BNP	Bayer ADVIA Centaur, Siemens medical diagnostics	39

Table 3: Study quality characteristics

Author, year	Study design	Data collection blinded to NP value	Outcome assessment blinded to NP value	Consistent outcome definition	Routine post-operative troponin screening	Troponin assay, manufacturer & threshold used
Yeh, 2005	Prospective observational cohort	Blinded	Blinded	Yes	No, troponin testing guided by clinical signs	Not specified
Dernellis, 2006	Prospective observational cohort	Not blinded	Not blinded	Yes	No, troponin testing guided by clinical signs	Not specified
Cardinale, 2007	Prospective observational cohort	Blinded	Blinded	Yes	No	Not applicable
Cuthbertson, 2007	Prospective observational cohort	Blinded	Blinded	Yes	Yes	2nd generation, Bayer ADVIA Centaur, Troponin I > 0.32 ng/ml
Cuthbertson, 2007	Prospective observational cohort	Blinded	Blinded	Yes	Yes	2nd generation, Bayer ADVIA Centaur, Troponin I> 0.1 ng/ml
Gibson, 2007	Prospective derivation with subsequent validation study	Blinded	Blinded	Yes	Yes	2nd generation, Bayer ADVIA Centaur, no threshold indicated
Mahla, 2007	Prospective observational cohort	Blinded	Blinded	Yes	Yes	4th generation, Roche Elecsys Troponin T STAT, > 0.03 ng/ml)
Hou, 2007	Prospective observational cohort	Not indicated	Not indicated	Yes	No	Not applicable
Rajagopalan, 2008	Prospective observational cohort	Not indicated	Not indicated	Yes	Yes	2nd generation Bayer ADVIA Centaur, Troponin I > 0.1 ng/ml
Yun, 2008	Prospective observational cohort	Not indicated	Not indicated	Yes	Yes	Troponin T, assay not specified, no threshold indicated
Bolliger, 2009	Prospective prespecified secondary analysis of cohort in a placebo-controlled RCT	Blinded	Blinded	Yes	Yes	1st generation Abbott AxSYM Troponin I, > 2 ng/ml
Oscarsson, 2009	Cohort extracted from prospective observational study	Not blinded	Not blinded	Yes	Yes	High sensitivity, Siemens Stratus CS acute care Troponin I, > 0.06 ng/ml
Schutt, 2009	Prospective observational cohort	Blinded	Blinded	Yes	No	Not specified
Breidthardt, 2010	Prospective observational cohort	Not blinded	Not blinded	Yes	No, troponin testing at discretion of treating physician	1st generation Abbott AxSYM Troponin I, > 2 ng/ml
Chong, 2010	Prospective observational cohort	Blinded	Blinded	Yes	Yes	4th generation Abbott Architect STAT Troponin I, > 0.03 ng/ml
Villacorta, 2010	Prospective observational cohort	Not indicated	Not indicated	Yes	No, troponin testing guided by clinical signs	Not specified
Lee, 2011	Prospective observational cohort	Not indicated	Not indicated	Yes	No	Not specified
Nojiri, 2011	Prospective observational cohort	Not indicated	Not indicated	Yes	No	Not specified
Park, 2011	Prospective observational cohort	Not indicated	Not indicated	Yes	Yes	Troponin I (0.78 ng/ml),assay not specified
Payne, 2011	Prospective observational cohort	Blinded	Not blinded	Yes	Yes	Troponin I, assay not specified
Amar, 2012	Retrospective review of patients enrolled in a different study	Not blinded	Not blinded	Yes	No	Not applicable
Biccard, 2012	Prospective observational cohort	Not blinded	Not blinded	Yes	Yes	2nd generation Siemens Advia Centaur XP, Troponin > URL
Mercantini, 2012	Prospective observational cohort	Blinded	Blinded	Yes	Yes	4th generation Troponin T(≥ 0.06 ng/ml)
Yang, 2012	Prospective observational cohort	Not indicated	Not indicated	Yes	Yes	Troponin I (0.78 ng/ml),Roche Diagnostics, assay not specified
Bryce, 2013	Prospective multi-centre observational cohort	Blinded	Blinded	Yes	Yes	4th generation Abbott Architect STAT Troponin I, no threshold specified
Borges, 2013	Prospective observational cohort	Blinded	Blinded	Yes	Yes	2nd generation Siemens cTnI Ultra, Troponin I > 0.04 ng/ml
Scrutinio, 2014	Prospective observational cohort	Not indicated	Not indicated	Yes	Yes	2nd generation Siemens RxL immunoassay, Troponin I > 0.14 ng/ml
Vetrugno, 2014	Prospective observational cohort	Blinded	Blinded	Yes	No	Not specified

Note: NP = B-type natriuretic peptides.

Figure 2: Cumulative risk for postoperative mortality or major adverse cardiac events associated with an elevated preoperative BNP or NT-proBNP measurement.

*Cuthbertson et al. Anaesthesia. 2007;62:875–81. Notes: **Relative risk. NP: natriuretic peptide; CI: confidence interval; MACE: major adverse cardiac event; OR: odds ratio.

Table

	Search terms	Number
1	(Natriuretic peptide OR natriureti*).mp.	90 064
2	(BNP OR B type natriureti* OR B-type natriureti* OR Brain natriureti*).mp.	42 364
3	(NT-pro BNP OR NT-proBNP OR NT-pro-BNP OR N terminal proBNP OR N terminal pro-BNP OR N-terminal proBNP N terminal pro-BNP OR N-terminal pro-brain natriureti* OR N-terminal pro-B-type natriureti*OR N-terminal pro-B type natriureti*).mp	13 484
4	(Surgery OR operative OR non-cardiac).mp.	3 308 271
5	1 or 2 or 3	94 975
6	4 and 5	4 456
7	prognosis.sh. or diagnosed.tw. or cohort:.mp. or predictor:.tw. or death.tw. or exp models, statistical/	4 837 473
8	6 and 7	1 433
9	remove duplicates from 8	876

Table

Author, year	Primary outcome definitions	Myocardial infarction criteria	Myocardial injury/damage/necrosis criteria
Yeh, 2005	Cardiac death, ACS including MI and unstable angina, congestive cardiac failure and serious cardiac arrhythmia	Increased cardiac enzymes (creatine kinase MB isoenzyme or troponin I) and ECG evidence of myocardial infarction (new Q waves or ST-T wave changes) in at least two adjacent leads	N/A
Dernellis, 2006	Cardiac death, non-fatal MI, acute pulmonary oedema, ventricular arrhythmia	Cardiac enzyme increase greater than twice the upper limit of normal OR new Q wave on postoperative ECG plus cardiac enzyme rise consistent with necrosis	N/A
Cardinale, 2007	Atrial fibrillation	N/A	N/A
Cuthbertson, 2007	Death or myocardial injury	N/A	cTnI > 0.32 ng/ml
Cuthbertson, 2007	Cardiac death and/or new postoperative myocardial injury and/or significant postoperative ECG changes	N/A	cTnI > 0.1 ng/ml
Gibson, 2007	Non-fatal MI and cardiac death	Typical rise and fall of cTnI plus one of: ischaemic symptoms, ECG changes (new Q waves or ST segment changes), or coronary intervention (ESC/ACC definition)	N/A
Mahla, 2007	Non-fatal MI, acute coronary revascularisation, cardiac death	Elevated cTnT and clinical or ECG changes indicative of ischaemia	N/A
Hou, 2007	Atrial fibrillation	N/A	N/A
Rajagopalan, 2008	Myocardial injury	N/A	Elevated cTnI > 0.1 ng/ml
Yun, 2008	Cardiac death, ischaemic heart disease, acute pulmonary oedema or nonfatal stroke	Not specified	Not specified
Bolliger, 2009	Any hospitalisation for myocardial revascularisation, acute coronary syndrome, acute congestive heart failure, or death by any cause	N/A	N/A
Oscarsson, 2009	Myocardial damage, acute MI, and/or death	Not specified	cTnI > 0.06 ng/ml
Schutt, 2009	Postoperative MI heart failure, unstable angina, dysrhythmia, cardiac arrest	2 out of 3 of: symptoms consistent with myocardial infarction, elevated troponin T level, or new diagnostic changes on electrocardiogram	N/A
Breidthardt, 2010	ECG changes, significant arrhythmias, myocardial necrosis, cardiac failure	N/A	cTnI > 2 ng/ml
Chong, 2010	Acute MI, congestive cardiac failure, atrial fibrillation, major arrhythmia	Standard definition ^1	cTn I > 0.03 ng/ml
Villacorta, 2010	Acute MI, unstable angina, acute pulmonary oedema, heart failure, acute atrial fibrillation, sustained ventricular tachycardia, cardiac death	Elevation of biomarkers more than 2 x upper limit of normal plus ECG changes	N/A
Lee, 2011	Myocardial injury, ECG evidence of ischaemia or arrhythmia, heart failure	N/A	cTn T > 0.1 ng/ml
Nojiri, 2011	Arrhythmias, angina pectoris, MI, congestive cardiac failure, thrombo-embolic events	Not specified	Not specified
Park, 2011	MI, pulmonary oedema, cardiovascular death	cTnI > 0.78 ng/ml (99th centile of upper reference limit)	N/A
Payne, 2011	Perioperatve death & MACE, long-term all-cause mortality	Not specified	Not specified
Amar, 2012	Atrial fibrillation	N/A	N/A
Biccard, 2012	Mortality, troponin elevation	Not specified	cTn > URL
Mercantini, 2012	Angina pectoris, STEMI, NSTEMI, troponin elevation, cardiac failure, acute hypertensive event	ST changes in two or more contiguous leads	cTnI > 0.06 ng/ml, cTnT > 0 ng/ml
Yang, 2012	MI, aggravation of cardiac failure, cardiovascular death	cTnI > 0.78 ng/ml	N/A
Bryce, 2013	Non-fatal MI, cardiac death, all-cause mortality	Troponin elevation and gradual decline plus one of: ischaemic symptoms, ECG changes (new Q waves or ST changes), or coronary artery intervention	N/A
Borges, 2013	Vascular death, non-fatal MI, non-fatal cardiac arrest	Typical rise and fall of cTnI to > 0.04 ng/ml, plus one of: ischaemic symptoms, ECG changes (new Q wave, ST changes in two or more contiguous leads, or new LBBB)	N/A
Scrutinio, 2014	Death, ACS, acute pulmonary oedema, postoperative myocardial damage	Standard definition^1	cTnI > 0.14 ng/ml
Vetrugno, 2014	New onset atrial fibrillation/flutter, acute heart failure or non-fatal/fatal MI	cTnI > 0.12 ng/ml (3 x upper reference limit)	N/A