at a fingertip area and fully reproduced with palpationc Pain > 30–60 min with consistently negative troponin Very brief pain < 15 s
a Traditional CAD risk factors are only weakly predictive of the likelihood of ACS during a given presentation.36 For example, shoulder pain that mainly occurs with shoulder movements is unlikely angina, even in a diabetic patient with prior MI. Once ACS is otherwise diagnosed, diabetes and PAD do predict a higher ACS risk.
b A new MR murmur in a patient with chest pain is considered ischemic MR until proven otherwise.
c True angina and PE pain may seem reproducible with palpation, as the chest wall is hypersensitive in those conditions. A combination of multiple low-likelihood features (e.g., reproducible pain that is also positional and sharp), rather than a sole reliance on pain reproducibility, better defines the low-likelihood group.37,38
C. Cardiac Troponin I or T
Whereas troponin I and T are also present in skeletal muscles, the muscular configuration is different and is not detected by the cardiac troponin assays. Cardiac troponin I and T are highly specific for a myocardial injury. However, this myocardial injury may not be secondary to a coronary event but to other insults (e.g., critical illness, HF, hypoxemia, hypotension), without additional clinical, ECG, or echocardiographic features of MI.
High-sensitivity troponin (hs-troponin) assays have a much lower detection cutoff than the conventional, sensitive troponin assays (eg, detection cutoff = 0.005 ng/ml vs. 0.04 ng/ml); they detect troponin in ≥50% of healthy individuals, and in fact, some very-high-sensitivity assays can measure troponin in almost all individuals. This detection cutoff is not to be confused with MI cutoff of hs-troponin, which is close to that of conventional, sensitive troponin (~0.04 ng/ml). Yet, even MI cutoff is lower and more precise with hs-troponin, with precision at the 3rd decimal; also, this fine precision allows MI cutoff to be lower in women than men, as women normally have smaller myocardial mass and troponin values.45 Thus, hs-troponin slightly increases the diagnosis of MI in comparison to sensitive troponin (by ~20%). 4 More importantly, it rises earlier and allows delineation of a very low level within the non-MI range, allowing stratification of troponin values within this non-MI range (e.g., undetectable=very low risk). Note: to avoid the confusion of decimals, hs-troponin is reported as a whole number in ng/L (e.g., detection cutoff 5 ng/L); this may be divided by 1000 to provide a conventional ng/ml value.
Troponin rises above MI cutoff within 3 hours of an episode of ischemia lasting > 20-30 min. Hs-troponin rises above detection cutoff rapidly, usually within 1 hour of ischemia.4
Kidney disease may be associated, per se, with a chronic mild elevation of troponin I. This is not related to reduced renal clearance of troponin, a marginal effect at best. It is rather due to the underlying myocardial hypertrophy, chronic CAD, and BP swings. This leads to a chronic ischemic imbalance, and, as a result, a chronic myocardial damage.
Kinetics of troponin rise and decline- In MI, troponin peaks at 18-24 hours and remains elevated for 7-14 days. However, in small MI, troponin usually normalizes within 2–3 days. Note that the troponin peak and downslope are much slower than the upslope; thus, patients presenting late after an infarct may have a plateau pattern of stable troponin (Figure 1.2).1,2 In acutely reperfused infarcts (STEMI or NSTEMI), those markers peak earlier (e.g., 12–18 hours) and sometimes peak to higher values than if not reperfused, but decline faster. Hence, the total amount of biomarkers released, meaning the area under the curve, is much smaller, and the troponin elevation resolves more quickly (e.g., 4–5 days). The area under the curve, rather than the actual biomarker peak, correlates with the infarct size.
Note on CK-MB- Troponin I or T is much more sensitive and specific than CK-MB. Frequently, NSTEMI is characterized by an elevated troponin and a normal CK-MB; CK-MB only rises with large MI, when troponin exceeds 0.5 ng/ml. CK-MB rises at 3-6 hours, peaks at 12-24 hours, and normalizes at 2-3 days. Overall, CK-MB testing is not recommended on a routine basis but has one potential application: in patients with marked troponin elevation and subacute symptom onset, CK-MB helps diagnose the age of the infarct (a normal CK-MB implies that MI is several days old).
D. Echocardiography and acute resting nuclear scan
The absence of wall motion abnormalities during active chest pain argues against ischemia. For optimal sensitivity, the patient must have active ischemia while the test is performed. Wall motion abnormalities may persist after pain resolution in case of stunning or in case of subendocardial necrosis involving > 20% of the inner myocardial thickness (< 20% subendocardial necrosis or mild troponin rise may not lead to any discernible contractile abnormality).46 Conversely, wall motion abnormalities, when present, are not very specific for acute ischemia and may reflect an old infarct. However, the patient is already in at least an intermediate risk category.
Figure 1.2 Kinetics of troponin release. Troponin rises above MI cutoff at 2-3 hours, then peaks and plateaus at ~24 hours. Note the slow decline that mimics a plateau pattern. Reperfused MI has a much narrower curve; the troponin area under the curve, rather than the peak, corresponds to the infarct size. An elevated troponin may be repeated every 8 hours until it trends down, to assess the area under the curve/infarct size.
Strain echocardiography (global or regional) improves the sensitivity and negative predictive value of echo for ACS diagnosis in patients with normal initial troponin and non-diagnostic ECG (91%), even several hours after the chest pain episode, but is non-specific and has a poor positive predictive value (13% in one study).46
Acute resting nuclear scan, with the nuclear injection performed during active chest pain or within ~3 hours of the last chest pain episode, has an even higher sensitivity than echo in detecting ischemia. An abnormal resting scan, however, is not specific, as the defect may be an old infarct or an artifact.
III. Initial approach to acute chest pain presentations and the use of conventional and high-sensitivity troponins
Only 25% of patients presenting with chest pain are eventually diagnosed with ACS. On the other hand, the ECG is normal in 20–37% of patients with ACS, and before the era of sensitive troponin, ~2-4% of patients discharged home with a presumed non-cardiac chest pain were eventually diagnosed with MI.42
A. Assess for other serious causes of chest pain at least clinically, by chest X-ray and by ECG (always think of pulmonary embolism, aortic dissection, and pericarditis).
B. Use conventional troponin and hs-troponin for MI rule-in and rule-out
According to multiple large registries and meta-analyses, a single undetectable or very low hs-troponin (eg, <0.005 ng/ml) is associated with <0.3% risk of acute MI and nearly 0% risk of cardiac death at 30 days28–30,45,47–55 Even 1-year events were very low at 0.6% in several registries, with a cardiac death ≤0.1%.28,47,51 This risk is further reduced in patients whose ECG is not suggestive of ischemia. Therefore, discharge is safe in those patients, at least as safe as in patients with negative stress tests, with no need for serial troponin measurement.
For patients acutely presenting with chest pain and no other critical illness, ESC and multiple European investigators suggest checking hs-troponin at presentation and at 1 or 2 hours after presentation (0/1 or 0/2 strategy) (Figure