Why Are Troponins Ignored?

Dear Bloggers

Dyspnea has a wide differential diagnosis that can potentially involve the cardiac, respiratory, abdominal, haematologic, neuromuscular, metabolic systems etc. Because of the vast number of causes of dyspnea, it is essential to take a detailed history, as much as possible, and examine carefully for various serious causes.

Performing of a chest radiograph, electrocardiogram (ECG), cardiac biomarkers, a complete blood count and an echocardiogram, etc, are essential components for the work up of the cause of the dyspnea and on occasion, there may be several overlapping causes.

Silent myocardial infarction resulting in new onset or worsening heart failure should always be considered. New ECG changes suggestive of ischemia e.g. dynamic T wave changes, should alert the physician that there is a cardiac cause.

Checking of the Troponin-I is currently regarded as the Gold Standard test to confirm a myocardial cause. Previously, it was considered that Troponin-T (TnT) was specific for cardiac muscle but studies have shown that skeletal muscle can also release TnT e.g. rhabdomyolysis. Only Troponin-I (TnI) is considered to be most specific to cardiac muscle. It is more sensitive and more specific as a cardiac biomarker than the CK-MB fraction.

Evidence Based Medicine (EBM) texts and international guidance now make mention that TnI (or TnT) should be measured and that measurement of CK-MB is no longer necessary for the diagnosis of an acute coronary syndrome. Moreover, the TnI levels stay elevated for up to 10 days, whereas CK-MB levels drop much more quickly, making it possible to still diagnose a recent myocardial infarction even if other less sensitive or specific biomarkers are negative.

TnI can be used to examine for re-infarction too. A rise of >20% from the last measurement can assist in the diagnosis of re-infarction. CK-MB is again no longer required for making this diagnosis.

It is an unfortunate situation that many Japanese medical students and junior physicians are still being taught that they should check CK-MB and that many still are uncertain about the utility of TnI. Some physicians are not inclined to check TnI or take an elevated TnI level seriously e.g. in renal failure citing that it is purely the renal failure causing the rise.

Recent evidence has actually suggested that patients with a raised troponin level without proven acute coronary aetiology actually have a worse prognosis than in patients with an obvious acute coronary syndrome. One reason for an increased mortality rate may have been the physicians did not take such a rise seriously enough, considering it unrelated to coronary heart disease and therefore, further follow-up was not performed timely enough for such patients. The American Journal of Medicine (2011) 124, 630-635

Other common causes of elevated troponins include

•myopericarditis
•aortic dissection
•cardioversion
•cardiopulmonary resuscitation
•subarachnoid hemorrhage
•severe sepsis
•trauma / contusion
•fast atrial fibrillation
•heart failure

Stress-induced cardiomyopathy (Takotsubo) can cause heart failure, ECG changes and TnI rises. It is said that in some cases the physicians will observe the myocardial echocardiographic changes only and then (somehow) will diagnose this disorder. However, "Takotsubo Heart" cannot be diagnosed unless the patient's coronary arteries are deemed normal by angiography; thereby ruling out an acute coronary syndrome.

Essentially, we cannot ignore a potential acute coronary syndrome as evidenced by worsening dyspnea, ECG changes consistent with ischemia and a TnI rise. Although echocardiography can be useful to look for wall motion abnormalities typical of myocardial infarction, it cannot completely rule out the diagnosis especially as ultrasonographic observations have operator error and there may be poor views depending on the anatomy. In such situations emergent angiography or coronary artery computed tomography may provide the answer.

An elevated pulmonary artery pressure can be helpful to assist in the diagnosis of heart failure given a consistent history, in addition to an elevated B-Natriuretic Peptide (BNP). It is worth noting that in a recent study BNP levels were found not to be superior to physical examination of the right and left sided heart pressures by cardiology experts. The American Journal of Medicine (2011) 124, 1051-1057

Hence, it comes back to history and physical examination and understanding what common things present commonly and what important differential diagnoses should not be missed. Acute coronary syndrome is very common and Takotsubo Heart is not common at all. New onset dyspnea or worsening symptomatic heart failure should make the physician consider silent myocardial infarction in the differential diagnosis. Consistent ECG changes and elevated troponins assist in the diagnosis of this disorder.

Finally, one should not forget about pulmonary embolism (PE). This can also result in worsening heart failure and acute, sub-acute or chronic dyspnea. ECG changes can occur although they are usually right sided in origin on the ECG e.g. Tall R wave in V1 (>7mm), biphasic T waves / ST depression in V1-V3. However, a normal ECG is common and the "classic" S1Q3T3 is very unusual to see yet it seems that this is the only ECG change that students and residents seem to remember. However, BNP and TnI can both be elevated in PE, and when elevated together, they are associated with a worse prognosis.

In essence, elevated troponins should not be overlooked. Instead, further examinations should be undertaken. If silent myocardial infarction cannot be ruled out or if considered most likely, angiography is warranted. At the very least, basic cardiac treatment should be commenced for such patients on the basis that they are likely to have the problem (rather than not due to its high incidence) and that waiting is not an option especially as "time is muscle".

One should not wait for the biomarkers to become positive (which can take 4-6 hours; new highly sensitive troponin tests can provide earlier results but are still not in widespread use). Remember, and I shall say it again, "time is muscle" and the longer one waits before instituting treatment, the worse the outcome in terms of morbidity and mortality.

Remember that an essential treatment in ACS is aspirin, which reduces mortality significantly. It should never be withheld unless there is a good reason e.g. acute gastrointestinal bleeding, allergic reaction. It is said that in some institutions, some cardiologists withhold aspirin initially and proceed straight for percutaneous intervention with this drug being commenced post-procedure. This method of withholding aspirin, perhaps from the misguided belief that patients will bleed excessively during PCI, is not standard treatment according to many of the world cardiology guidelines. This needlessly puts patients at risk by delaying medical treatment of ACS.

In contrast, patients with suspicion of ACS in places such as the USA and the UK are treated more aggressively and are frequently given aspirin en route to the hospital by paramedics. In some countries e.g UK, thrombolysis by tPA for ST elevation ACS is also given en route if certain inclusion and exclusion criteria are met and they are not near to a center providing urgent PCI treatment.

It is time to take Troponins elevations more seriously and be more aggressive in the management of acute coronary syndrome in Japan rather than relying on initial PCI alone and withholding life saving drug treatment prior to such procedures.......please consider

2010 American Heart Association guidelines -- see that aspirin is given early.

2011 Summary of Guidance from the European Resuscitation Council can be obtained here