Our approach

The resident is correct in recalling that the universal definition of AMI requires elevated biochemical markers of myocardial necrosis in addition to either symptoms of cardiac ischemia or ECG changes indicative of ischemia. In addition, he is correct in noting that elevated cTn levels related to cardiac ischemia are associated with an adverse prognosis and that these high-risk patients benefit from an early invasive strategy. However, the resident has made a number of errors as well. The cTn used here is a conventional assay and, with these, cTn is typically only elevated in patients with end-stage renal disease (ESRD). In this setting, raised levels increase progressively as the duration of dialysis increases and are associated with a poor prognosis. This patient may require renal replacement therapy soon, but, for the time being, his eGFR is not low enough to explain the elevated cTn. Even if it was low enough, there is no evidence that cTn is cleared renally. cTn may persist in the blood of patients with ESRD due to alternative cleavages involved in the degradation of the protein. This is also likely to be the reason why there are more elevations of cTnT than of cTnI, although both predict adverse long-term outcomes. Furthermore, concomitant changes such as LVH and other metabolic changes can often be attributed to cTn elevations.

This patient’s cTn may in fact be associated with a coronary event. A more diligent resident may have checked the patient’s chart for previous cTn levels, which, if in the normal range, would help to identify a rising pattern. The universal definition for AMI states that clinicians should look for a rising and/or falling pattern in cTn levels. This may not necessarily be synonymous with an AMI, but certainly indicates an acute event, which, along with a suggestive ECG or clinical history, should help to confirm the diagnosis of an AMI. Patients who present late (12–18 hours) after the onset of symptoms may not demonstrate a rising/falling pattern, so clinical judgment must be used. However, in this situation, the patient presented 3 hours after the onset of symptoms and one would expect a rising pattern associated with an acute coronary event. Thus, serial cTn levels should be drawn at 3 and 6 hours from the point of the patient’s arrival. A documented rising pattern in conjunction with the clinical history will confirm the diagnosis of AMI and trigger the decision for an early invasive approach, but the patient should receive full antiplatelet therapy in the meantime if suspicion of an acute coronary syndrome is high. If such a pattern is not present, alternative diagnoses should be sought. A presumptive diagnosis of AMI should not be made. This is particularly important among patients with ESRD whose cTn is elevated at baseline and who are at higher risk for bleeding as a result of their uremic state, and should not, therefore, be needlessly subjected to invasive procedures. In addition, the use of IV contrast during angiography may lead to worsening of already compromised renal function, further highlighting the need for appropriate case selection. A useful approach for these patients is to have cTn drawn routinely in outpatient settings, which can provide a baseline cTn level with which levels drawn during an acute presentation can be compared to help make a diagnosis.

Marked elevations in cTn tend to occur in only four situations: AMI, myocarditis, renal failure, and, on rare occasions, with an analytical error. Thus, serially drawn levels are still required, and a crucial facet of this problem is defining what degree of change in cTn is required. One such approach may be to define a level of change that exceeds the degree of analytical imprecision associated with a particular assay. This will vary from assay to assay and should be calculated and reported by laboratories. The changes required will be large on a percentage basis when the initial level is low, but, in ESRD where the baseline levels are elevated, lesser changes are required. Some have suggested a change of 50% when values are close to the 99% upper reference limit and 20% when they are above this.

With a high-sensitivity troponin assay, a higher proportion of elevated levels will be appreciated and will often be associated with abnormal renal function, even when it is mild. As with conventional assays, these elevations also predict poor outcomes. These observations clarify to some extent the relationship between renal dysfunction and troponin, but also create the clinical challenge of discriminating elevations related to an acute cardiac event from other pathologies.

Ultimately, an understanding of cTn testing in conjunction with Bayesian principles of diagnostic testing must inform the decision-making process. This patient’s risk factors (including the fact that he has chronic renal failure) and clinical presentation give rise to a high pretest probability of disease. The isolated elevation in cTn determined using a conventional assay is unlikely to be related to his renal failure but cannot be immediately attributed to AMI until a changing pattern is observed, at which point his post-test probability of disease will justify an early invasive approach. When in doubt, clinical judgment must be used. Lastly, but of equal importance, is the fact that the elevation is associated with an adverse prognosis. Thus, our astute resident should investigate whether there is good control of blood pressure, volume, and lipids and institute preventative pharmacotherapy as appropriate.