Table 5.

Major recent studies showing elevations in Troponin I to be associated with mortality post-coronary artery bypass grafting surgery

Study	Type of study and surgery	Number of patients	Cardiac biomarker (time)	Other features	Major findings
Greenson et al.43	Single centre prospective study; CABG or Aortic valve replacement	100	cTnI CK-MB	Pre-op, 24 h and 48 h, then daily until discharge or 1 week	Peak cTnI > 60 ng/mL (> 120× URL) predictive of cardiac events up to 30 days post op
Holmvang et al.35	Single centre prospective study, CABG only	103	cTnT cTnI CK-MB Myoglobin	Every 2 h in first 20 h, 24, 30, 36 and 48 h, 72 and 98 h	ECG changes unable to differentiate between patients with or without graft failure. CK-MB and cTnT (but not cTnI or Myoglobin) levels were significantly higher in patients with graft failure vs. those without. Optimal discrimination values were 30 mcg/L for CK-MB (sensitivity 67%, specificity 65%) and 3 mcg/L for cTnT (sensitivity 67%, specificity 76%). In multivariate analysis cTnT > 3 mcg/L was significantly associated with graft failure (sensitivity of 75% compared to 20% for clinical criteria)
Eigel et al.44	Prospective single centre study; CABG only (Excluded MI within 7 days)	540	cTnI	Prior to induction of anaesthesia and at termination of CPB	cTnI level > 0.495 ng/L (> 9.9× URL for assay) measured at the end of CPB was predictive of in-hospital adverse outcomes (MI/death)
Lasocki et al.45	Single centre prospective study; CABG or valve surgery (Acute MI < 7 days were excluded)	502	cTnI ECG changes	20 h post-op	cTnI < 32.5× URL ∼2.5% in hospital mortality cTnI ≥ 32.5× URL ∼22.5% in hospital mortality cTnI > 100× URL 44% in hospital mortality
Thielmann et al.46	Single centre prospective study: CABG only	2,078	cTnI	1, 6, 12,24 h post op	cTnI was a more sensitive and specific marker of graft failure at a level above 21.5 ng/mL (> 43× URL ng/mL) at 12 h and 33.4 ng/mL (>66.8× URL) at 24 h, compared to myoglobin and CK/CK-MB. CK-MB and EKG changes (ST-segment deviations or new Q wave) did not predict graft failure
Paparella et al.47	Prospective Single centre study; CABG only (Patients with UA/MI < 7 days included)	230	cTnI	Pre-op, 1,6,12,24 and 36 h post-op, daily from day 2 to 7	cTnI >260× URL (13 ng/L) predicted in-hospital mortality but not 2 year mortality; Peak cTnI generally observed 24 h after surgery
Onorati et al.9	Prospective single centre study; CABG only	776	cTnI ECG changes (New Q wave or reduction in R waves > 25%) & ECHO feature of MI	Pre-op and 12, 24, 48 and 72 h post-op	cTnI >3.1 μg/L (> 310× URL) at 12 h predicted increased in-hospital and 12 month mortality; Additional ECG and ECHO criteria of MI predicted worst outcome
Thielmann et al.31,48	Prospective single centre study CABG only patients undergoing re-angiography post-op	94	cTnI CK-MB	Pre-op, 1, 6, 12, 24, 36 and 48 h post-op	cTnI was the best discriminator between PMI ′in general′ and ′inherent′ release of cTnI after CABG with a cut-off value of 10.5 ng/mL (> 21× URL) and between graft-related and non-graft-related PMI with a cut-off value of 35.5 ng/mL (>71× URL). CK-MB level and ECG changes/TEE could not differentiate between those with or without graft failure.
Croal et al.49	Prospective CABG+ valve/other cardiac surgery	1365	cTnI ECG changes	2 and 24 h	cTnI at 24 h best predictor ≥53× URL 2.37 OR 30-day mortality, 2.94 OR 1 yr mortality, 1.94 OR 3 yr mortality ≥27× URL 1.05 OR 30-day mortality, 1.14 OR 1 yr mortality, 1.37 OR 3 yr mortality
Provenchère et al.50	Prospective single centre study CABG and/or valve surgery	92	cTnI	20 h post op	cTnI levels were not predictive of 1 year mortality in a multivariate model.
Fellahi et al.51	Prospective single centre study; CABG only	202	cTnI	Per-op and 24 h post-op	cTnI ≥ 13 ng/mL (≥ 21.66 x URL) did not predict in-hospital mortality, but was predictive of 2 year mortality (18% vs. 3%; OR 7.3). Best cut off to predict death ranged from 12.1 to 13.4 ng/mL (20.16–21.66× URL)
Adabag et al.34	Retrospective analysis CABG and/or valve surgery	1186	cTnI CK-MB	Ever 8 h for 24 h post-op, longer if no peak in 24 h	cTnI level independently associated with operative (30 day) mortality; CK-MB had a weaker association with operative mortality
Muehlschlegel et al.26	Prospective single centre study CABG only surgery	1013	cTnI	Daily from day 1 to 5	24 h cTnI rise ≥ 138× URL HR 2.8 for 5 yr mortality cTnT at 24 h were independent predictors of 5 year mortality in a multivariate model (No additional benefit of measuring cTn beyond 24 h). ECG changes alone did not predict 5 year mortality.
Petaja et al.41	Meta-analysis CABG and/or Cardiac surgery	2348–3271	cTnI	Up to 7 days post op	Short-term mortality (<6 mths) 8.1% ≥ 21× URL vs. 1.5% <21× URL Long-term mortality (6–36 mths): 10.6% vs. 3.1% (RR 1.06–11.00%)
Hashemzadeh et al.52	Prospective single centre study CABG +/- Valve surgery (Excluded MI within 7 days)	320	cTnI	Immediately and 20 h post-op	20 h post-op cTnI had better prognostic value than immediate post-op levels. 20 h cTnI level was an independent predictor of in-hospital mortality above a value of 14 ng/mL (>10× URL)
Van Geene et al.53	Registry retrospective analysis;CABG and/or valve surgery	938 (Separate validation subset, n = 579)	cTnI	1 h post-op	1 h post-op cTn values correlated with hospital mortality with the best cut-off value of 4.25 μ/L (Type of assay and URL for assay not known)
Domanski et al.29	Meta-analysis CABG only	18,908	cTnI	<24 h post op	5 to < 10× URL 1.00 RR of 30 d mortality 10 to < 20× URL 1.89 RR of 30 d mortality 20 to < 40× URL 2.22 RR of 30 d mortality 40 to < 100× URL 3.61 RR of 30 d mortality ≥100× URL 10.91 RR of 30 d mortality
Ranasinghe et al.27	Retrospective analysis of 2 prospective randomized controlled clinical trials	440	cTnI	6, 12, 24, 48, 72 h post-op	cTnI levels at 12, 24, 48 and 72 h were all independent predictors of mortality HR ranging from 1.02 to 1.10 for these time points (>4.8 yr follow-up period). Cumulative area under to curve for cTn release up to 72 h was the best predictor of mortality in this model (HR 1.45). Peak cTnI of > 13 ng/mL (URL not defined) did not predict mid-term mortality.

AUC, area under the curve; CABG, coronary artery bypass grafting; CMR, cardiac MRI; CK-MB, creatine kinase-MB fraction; d, day; ECG, electrocardiogram; ECHO, echocardiocardiogram; HR, hazards ratio; h, hour; LGE, late gadolinium enhancement; LV, left ventricle; MACE, major adverse cardiac events; MI, myocardial infarction; mth, month; ng, nanogram; ONBEAT, on-pump beating heart; CABG ONSTOP, on-pump CABG; OR, odds ratio; post-op, post-operative; PMI, perioperative myocardial injury; RR, relative risk; TEE, transoesophageal echocardiogram; cTnI, Troponin I; cTnT, Troponin T; UA, unstable angina; URL, upper reference limit; yr, year.