Table 1:

The best evidence papers

Author, date, journal and country Study type (level of evidence)	Patient group	Outcomes	Key results	Comments
Jang et al. (2012), Catheter Cardiovasc Intervent, UK [2] Meta-analysis (level 1a)	10 studies were identified that included 48 022 patients who underwent PCI between 1999 and 2011	Overall RR % of mortality with a CK-MB elevation >1 times the ULN RR% of mortality with a CK-MB elevation of 1 to <3 times the ULN RR% of mortality with a CK-MB elevation of 3 to <5 times the ULN RR% of mortality with a CK-MB elevation of ≥5 times the ULN	1.74% (95% CI 1.42–2.13, P < 0.001) 1.48% (95% CI 1.25–1.77, P < 0.001) 1.71% (95% CI 1.23–2.37, P = 0.001) 2.83% (1.98–4.04), P > 0.001)	This meta-analysis showed that even a small increase in CK-MB levels during PCI is associated with significantly higher risk of late mortality Monitoring cardiac enzymes during PCI may help predict long-term clinical outcome
Zimarino et al. (2012), Atherosclerosis, UK [3] Systematic review (level 1b)	14 major studies were identified which included 74 253 patients who had PCI between 2000 and 2011. (A major study defined as n > 50). Three meta-analyses with the largest sample sizes are included here used as outcomes measures	Nienhuis et al. [4] Testa et al. [5] Feldman et al. [6]	cTn elevation after PCI is associated with increased risk of death and death/MI cTn elevation >3 × URL are associated with an increased risk of death cTnT and cTnI elevation are associated with an increased all-cause mortality and death/MI	This systematic review reports that isolated cTnT/I rise after PCI over the currently proposed threshold of three times the URL—in the absence of any increase in CK-MB—appears to be over-sensitive to diagnose MI, and cannot be considered an independent predictor of late adverse outcome
Cavallini et al. (2005), Eur Heart J, Italy [7] Multicentre prospective cohort study (level 2a)	Study included 3494 consecutive patients undergoing PCI from February 2000 to October 2000 in a total of 16 Italian tertiary centres	Detection of CK-MB elevation (%) and association with increased 2-year mortality as OR Degree of CK-MB elevation as an independent predictor of risk of death as (adjusted) OR Detection of cTn and association with increased 2-year mortality as OR	CK-MB elevation detected in 16% of patient population OR: 1.9 (95% CI 1.3–2.8, P < 0.001) Adjusted OR per unit: 1.04 (95% CI 1.01–1.07, P = 0.009) cTn elevation detected in 44.2% of patient population OR: 1.2 (95% CI 0.9–1.7 P = 0.2)	This cohort study found that post-procedural elevations of CK-MB, but not cTn increase the risk of 2-year mortality
Nageh et al. (2013), BMJ Heart, UK [8] Prospective cohort study (level 2c)	Study included 316 consecutive patients who underwent PCI between 1999 and 2000	OR of association between post-procedural cTn increase and death at 18 months Post-PCI PPV for adverse events at 18 months Post-PCI NPV for adverse events at 18 months	3.28 (95% CI 1.7–6.4, P = 0.01) 0.47 (OR: 18.9, 95% CI 9.7–37, P < 0.0001) 0.96 (OR: 18.9, 95% CI 9.7–37, P < 0.0001)	This study found that a post-procedural increase in cTn was independently and significantly predictive of an increased risk of adverse events at 18 months
Kini et al. (2004), Am J Cardiol, USA [9] Prospective cohort study (level 2b)	Study included 2873 patients who underwent PCI between 1999 and 2001	Kaplan–Meier estimates of death (%) for postprocedural elevation of CK-MB and cTn Group 1: normal CK-MB (<16 U/l) or cTn (<2 ng/ml) Group 2: 1–3 times the normal values of CK-MB and cTn Group 3: >3–5 times the normal values of CK-MB and cTn Group 4: >5 times the normal values of CK-MB and cTn	CK-MB: 2.1% (P = 0.002) cTn: 2.2% (P = 0.58) CK-MB: 2.7% (P = 0.002) cTn: 2.3% (P = 0.58) CK-MB: 1.7% (P = 0.002) cTn: 2.9% (P = 0.58) CK-MB: 10.3% (P = 0.002) cTn: 2.1% (P = 0.58)	This study found that periprocedural CK-MB elevation of >5 times the normal value is an independent predictor of mid-term mortality and a valuable marker for PCI prognosis in low-to-medium risk patients, whereas cTn—though frequently elevated—does not predict mortality
Nallamothu et al. (2003), Am J Cardiol, USA [10] Retrospective cohort study (level 3a)	Study identified 2796 consecutive patients who underwent PCI at a tertiary-care referral centre between 1997 and 2001. Only 1157 patients were included in the analysis	HR of post-PCI cTn levels 1–3 times normal 3–5 times normal 5–8 times normal ≥8 times normal	1.1 (95% CI 0.6–2.2, P = 0.74) 0.9 (95% CI 0.3–3.0, P = 0.85) 1.2 (95% CI 0.4–4.0, P = 0.78) 2.4 (95% CI 1.2–5.0, P = 0.018)	This study found that not only was cTn frequently elevated in patients after PCI, but that levels ≥8 times the normal value decreased long-term survival. It was concluded that patients with large elevations of cTn should be treated in a similar fashion to those with high periprocedural CK-MB levels
Natarajan et al. (2004), Am J Cardiol, USA [11] Prospective cohort study (level 3a)	Study included 1128 patients who underwent PCI between 1997 and 1999	1-year mortality (% of patient population) (n = 1128) cTnI negative (n = 9390) cTnI 1–4 times ULN (n = 86) cTnI ≥5 ULN (n = 103)	1.2% 1.0% 1.1% 2.9%	This study found that elevated cTn with concomitant CK elevations (i.e. isolated troponin elevations) posed no additional risk of 1-year mortality. It was also found that these cTnI elevations, though five times the ULN were not prognostically significant predictors of 1-year mortality
Loeb et al. (2010), Clin Cardiol, USA [12] Prospective cohort study (level 3a)	Study included 907 patients who underwent PCI between 1998 and 2006	Significant independent predicators of reduced long-term survival Significant univariate predictors of survival	Maximal post-PCI cTn (P = 0.0272) TrMX of 3.62 ng/ml or above (P = 0.0451)	This study found that the majority of low-risk patients could be expected to display cTn elevations within 24 h of PCI being carried out. It was also concluded that there was an adverse effect on long-term survival in patients with the largest post-PCI cTn elevations
Adgey et al. (1999), Clin Cardiol, USA [13] Review article (level 4a)	Study included eight studies with a total sample size of 7764 patients who underwent PCI	Kong et al., [14] 1-year mortality in patients with detected CK-MB elevation	6.6% (P = 0.02) vs 2.6% in control patients	This study found that long-term monitoring of patients with non-Q-wave MI may be appropriate, as supported by the incremental risk of death associated with a periprocedural CK-MB elevation
Grines et al. (2011), J Am Coll Cardiol, USA [15] Editorial review (level 5a)	Seven relevant papers were reviewed, these papers all examined patients who underwent PCI	Currently recommended threshold of cTn level in the diagnosis of MI Lim et al. [16] study analysis defined ‘optimal’ threshold of cTn level in the diagnosis of MI	0.15 ng/ml constitutes a Type 4a periprocedural MI 2.7 ng/ml constitutes a Type 4a periprocedural MI	This study found that CK-MB elevations were much more reliable in determining the occurrence of MI post-PCI; it was also found that cTn level elevations were—as the current guidelines stand—of limited value in the diagnosis of MI after PCI as well as prognostically