Use of Troponin in Critical Illness
Cardiac biomarkers come up frequently, but to be honest these questions have generally been referring mainly to troponin. Observe:
- Question 6 from the first paper of 2017 (raised in sepsis)
- Question 10 from the second paper of 2011 (troponin)
- Question 8 from the second paper of 2006 (troponin again)
- Question 27 from the second paper of 2010 (in general)
- Question 3 from the first paper of 2003 (troponin vs CK MB)
This is an enzyme involved in the excitation-contraction coupling of the myocardium.
Troponin T serves to attach the troponin complex to actin and tropomyosin.
There is a cytosolic pool (which is released early in the infarct) and a structural pool (which is slowly released over days as the damaged myocardium decomposes)
Utility of troponin as a cardiac biomarker
In brief, troponin a sensitive and specific marker of myocardial ischaemia. It is more sensitive and specific than AST, CK and CK-MB (which are also found is skeletal muscle). Following an MI, troponin rises after 2-3 hours. The serial troponins which are taken after the onset of chest pain are sensitive and specific for myocardial infarction. This "99th centile" value is the top 1% troponin titer in a series of normal blood donors. Its taken to be the upper range of normal laboratory values. Each lab will have its own value.
Troponin use in acute coronary syndromes among critically ill patients
The ECS and AHA universal definition of an acute coronary syndrome consists of a troponin rise as well as a demonstration of ischaemic symptoms, echocardiographic evidence, or ECG changes. The troponin levels are not diagnostic, but are a risk stratification tool to be used together with echocardiography, ECG, history and examination.
In critical illness, troponin has specific useful applications. Troponin levels can be used to monitor for myocardial ischaemia in critically ill patients when history and examination are unreliable. These people can't get up and tell you about their classical left-sided crushing chest pain. Troponin levels can also be used for the late diagnosis of MI and to monitor for reinfarction. The use of troponin as a part of a risk stratification strategy is important in ICU because careful selection of patients for anticoagulation and anti-platelet therapy prevents their exposure to unnecessary bleeding risk.
Influence on prognosis of acute coronary syndromes
In STEMI, the GUSTO-III investigators found that the admission troponin level was an independent predictor of 30-day mortality. A pooled analysis of about 18,000 acute coronary syndrome patients has revealed that any troponin elevation increases the risk of death (OR = 3.44). The same goes for NSTEMI.
Influence on prognosis of non-cardiac patients
Qualitatively raised troponin is associated with a poorer outcome in the critically ill patients, irrespective of whether they have been diagnosed with an acute coronary syndrome or not. It is not quantitatively validated outside the setting of ACS / AMI, but qualitatively a troponin level raised above the diagnostic "positive" threshold is just bad news if you are a critically ill patient. Ammann et al (2003) demonstrated this among a small population (n=58); the mortality difference was quite startling, 22.4% vs 5.2%. Various other studies of similar scale have also found quite a large mortality difference. For example, Liu et al (2015) measured the mortality difference as 35% vs 12% among 40 critically ill patients in New York (remember, none of these people are having heart attacks). Perhaps the scale of the study has amplified the effects? A recent meta-analysis (Amna et al, 2014) complied the results of twenty-seven such studies, not specific to the critical care environment (all hospitalised non-cardiac patients were included). Elevated troponin was associated with increased in-hospital and 30-day mortality (n= 7255 patients, OR = 3.88) as well as increased risk of long-term mortality at 6 months (n= 5368, OR = 4.21).
Non-ischaemic causes of a raised troponin
- Renal failure - its cleared renally
- Atrial fibrillation
- Cardiac trauma
- Pulmonary embolism
- Acute stroke
- Intracranial haemorrhage
- Severe burns
Troponin elevation in sepsis and septic shock
Question 6 from the first paper of 2017 presents the candidates with a scenario where a middle-aged lady on high dose vasopressors ends up with a troponin leak, a level over 10 times higher than the normal range (i.e. about 150 nmol/L for the high sensitivity assay). What is the meaning of this, ask they examiners, and how will you manage it?
In summary, there are four possible ways to interpret a raised troponin in a septic patient.
It may be totally meaningless:
- Cardiac troponins are elevated in 85% of patients with sepsis in the absence of acute coronary syndrome.
- Overinterpretation should be guarded against; cardiac testing does have some negative impact, as it tends to increase the cost and duration of hospital stay (Suarez et al, 2016) - people end up with pointless angiograms.
It may represent an acute coronary syndrome:
- Sepsis is a high-output cardiac failure state, as it typically features a hyperdynamic circulation. As such, it represents an exercise stress test. And a raised troponin represents a failed stress test. Sepsis may therefore unmask some sort of (previously subclinical) coronary artery disease.
- In general, any proinflammatory state can give rise to an increased risk of MI just as it increases the risks of venous thrombosis (eg. among post-operative patients as in the prospective study by Donzé et al, 2014)
It may identify patients with septic cardiomyopathy:
- Significant myocardial depression is observed in sepsis (this is well explored in a good 2010 article by Hunter et al). For example, Vieillard-Baron et al (2008) did daily TOEs on their septic patients and found that around 60% had reversible global left ventricular hypokinesia.
- Patients with sepsis-associated impaired LV relaxation are particularly likely to have a troponin leak.
- Generally speaking, this does not mean that inotropes are called for in every septic patient.
It may be a predictor of increased mortality:
- Raised troponin identifies septic patients with an increased risk of mortality. This is still open for debate; for instance, Smith et al (2009) found that there was an association, but Tiruvoipati et al (2011) did not find any independent predictive value in this test. A more recent meta-analysis by Sheyin et al (2015) combined about 1800 patients worth of data into a conclusion that yes, in fact raised troponin predicts increased mortality, with a risk ratio of around 1.9.