1.3).4,28–30,45,47–55 An undetectable hs-troponin, or a detectable hs-troponin with insignificant change at 1 or 2 hours rules out MI with >99.5% confidence. However, the issue is that a substantial proportion of patients who rule in for MI have non-MI troponin elevation or type 2 MI, rather than type 1 MI. ACS/type 1 MI is the diagnosis in 70-75% of the rule-in cases with no other critical illness, but is much lower in all comers (type 1 MI is the diagnosis in only 50% of patients with troponin up to 3-fold the upper reference limit).4
Note that the MI cutoff of hs-troponin is close to that of conventional troponin (eg, ~0.04 ng/ml), but is slightly lower and more precise than conventional troponin, with precision at the 3rd decimal, and the cutoff is lower in women than men with many assays.45 Thus, hs-troponin slightly increases the diagnosis of MI in comparison to conventional troponin (by 20%). More importantly, it allows delineation of a very low level and a very low risk population that cannot be delineated with conventional troponin and allows early and safe discharge of these very low risk patients. Based on this strategy, over 60% of patients may be discharged at presentation or 1 to 2 hours later. In fact, up to 50% of patients presenting with chest pain have undetectable or very low hs-troponin I (<0.005 ng/ml).51,52
If hs-troponin is not available or not used, conventional troponin is rechecked 3-6 hours after symptom onset (<3-6 hours from presentation) (ACC guidelines). Late troponin abnormality beyond 3 hours is rare, ~1%;4 rarely, troponin may need to be checked beyond 6 hours, in patients with worrisome ECG or recurrent severe symptoms (ACC).36 A negative conventional troponin is less reassuring than a low/undetectable hs-troponin, and thus, the patient frequently requires non-invasive testing for CAD; stress testing or coronary CT angiography may be performed after the second troponin, at 3-6 hours after symptom onset, or may be deferred up to 72 hours after discharge in patients with atypical symptoms and no prior CAD. The patient with persistent atypical chest pain and negative troponin has a low likelihood of CAD and may undergo stress testing while having the atypical pain.
Figure 1.3 0/1-hour or 0/2-hour ESC algorithm using hs-troponin in patients presenting to the emergency department with suspected ACS. This example uses the cutoff values specific for Roche Elecsys hs-troponin T assay. Of note, with this assay, the 99 th percentile threshold is 22 ng/L in men, and 14 ng/L in women, yet 52 ng/L is chosen as the MI rule-in value. As per ESC, this is done to improve the positive predictive value for MI, particularly that the 99th percentile threshold varies with the population studied and is not highly specific.
This algorithm may be applied to other hs-troponin assays using different cutoffs (Abbott hs-troponin I, rule-in value=64). Hs-troponin is expressed in ng/L, which may be divided by 1000 to obtain conventional values in ng/ml.
Clinical scores (eg, HEART) do not improve the safety of this algorithm and unnecessarily reduce the proportion of patients ruled out.47
Most patients who rule out with the hs-troponin strategy have non-cardiac pain. Hence, further testing is not definitely required in patients who rule out with the hs-troponin strategy, particularly when hs-troponin is undetectable. Yet some of the rule-out patients have true angina, especially those with exertional chest pain. CTA or stress imaging (>stress ECG, as per ESC) remains necessary in exertional chest pain and in patients with intermediate hs-troponin findings: a normal or low-risk stress imaging suggests no CAD, microvascular disease, or low-risk CAD for which medical therapy is appropriate. Medical therapy is tailored to how much the physician believes the chest pain is anginal, based on the exertional component, and is somewhat comparable to the management of chronic CAD. As such, coronary angiography is performed in patients whose chest pain is: (i) predominantly exertional, and (ii) occurring during low levels of activity.
Rule-in patients frequently require coronary angiogram, in the absence of a concomitant type 2 MI setting.
C. Stratification of patients who rule in for MI
In patients with elevated troponin, the most important step is to distinguish type 1 MI from secondary myocardial injury (which does not dictate acute antithrombotic therapy or coronary angiography). In a patient presenting with chest pain and no other obvious cardiac or systemic insult (HF, critical illness), any troponin elevation, even if mild (eg, 0.04 ng/ml), is a high-risk feature suggestive of type 1 MI and treated as such, with an initial invasive strategy. More severe troponin elevation or ischemic ST depression increases the likelihood of underlying CAD and, in this setting, type 1 MI (rather than MI secondary to an overlooked type 2 MI setting, hypertension, or microvascular disease). Per ESC guidelines, elevations up to 3-fold the upper reference limit (~0.15 ng/ml) have limited positive predictive value for type 1 MI (~50%). Conversely, “elevations beyond 5-fold the upper reference limit have high (>90%) positive predictive value for type 1 MI” (this corresponds to a troponin >0.25 ng/ml).4 Severe hypertension, elevated LVEDP from acute diastolic dysfunction, and vasospasm (micro- or macrovascular) are common causes of mild troponin elevation in patients with non-obstructed coronary arteries.
All patients with elevated troponin are categorized as “high risk”, but additional features imply a further increase in risk and probability of type 1 MI, such as ischemic ST changes (more extensive disease), severe troponin rise >0.5-1 ng/ml,56 elevated BNP, or high-risk scores (TIMI risk score ≥ 3 or GRACE risk score >140*).
The TIMI, HEART and GRACE risk scores are used in ACS once the diagnosis of ACS is established. These scores should not be used for the diagnosis of ACS; they have a prognostic rather than a diagnostic utility. Also, scores are one risk stratifier out of many. An elevated troponin may be associated with a TIMI risk score of only 1, yet still implies NSTEMI. In the right setting, even a mild troponin rise (e.g., 0.05 ng/ml) is a high-risk feature.
Unstable angina- Some patients qualify for an initial invasive strategy even if troponin is below MI cutoff, and may be placed under the category of “unstable angina”, although “severe stable angina” is a better nomenclature (intermediate-risk ACS per ACC, low-risk ACS per ESC):
Typical angina at mild exertion, with a typical timing and duration of angina (angina occurs with exertion, is relieved with rest, and lasts few minutes)
Typical exertional angina in a patient with diabetes, PAD, or CKD stage 3
Typical exertional angina with prior PCI <6-12 months (time frame of restenosis) or prior CABG
Low EF<40% or segmental wall motion abnormality
Hs-troponin is usually detectable in those patients, albeit below MI cut-off. This resembles the hs-troponin behaviour after a stable angina episode or a positive exercise stress testing: hs-troponin rises to detectable levels but remains well below MI cutoff, even if stress-induced ischemia is severe. Ischemia must be sustained to induce a troponin rise above MI cutoff.57
Diabetes is associated with a higher risk of adverse outcomes in NSTEMI and in typical exertional angina, and thus, an invasive strategy may be considered even with the latter case. Women with negative troponin do not generally qualify for an initial invasive strategy, as there is evidence of harm with this strategy in low-risk women.
Rest pain with negative troponin is not usually ACS and does not qualify for initial coronary angiography. Conversely, exertional pain with negative troponin may reflect CAD, a stable CAD with no plaque rupture which may, nonetheless, be severe or extensive; when