Current Status and Prospect of Bedside Detection of Cardiac Markers

Cardiovascular disease is a large class of diseases involving the heart and its blood vessels. Due to the specificity of the organs involved in this type of disease, some cardiovascular diseases (such as acute myocardial infarction) are usually fatal if they are not treated in time, and the onset is acute, so doctors need to race against time. Early diagnosis and early treatment are the keys to saving patients' lives.

The clinical guidelines require that the time from the patient's admission to the doctor to obtain the test results of the diseased heart markers should not exceed 30 minutes, and the time from the patient's admission to the doctor's initiation of thrombolytic therapy should not exceed 60-90 minutes, thereby reducing the fatality rate.

The emergence of point-of-care testing (POCT) conforms to the efficient and fast-paced working methods of modern clinical medicine, shortens the time for receipt of clinical test results, enables doctors and patients to obtain test results in time, and wins timely treatment time for patients. Therefore point-of-care testing of cardiac markers is now advocated.

1. Current status of application of cardiac marker testing

The three most commonly used indicators for the in vitro diagnostic solutions of acute myocardial infarction are cardiac troponin, creatine kinase and myoglobin.

According to the recommendations of the European Society of Cardiology/American Heart Foundation, the biochemical standard for the diagnosis of myocardial necrosis is that the maximum value of cTnT or cTnI detected by cardiac markers at least once within 24 hours of onset exceeds the 99% confidence interval of the upper limit of normal reference;

Either CK-MB exceeded the 99% confidence interval of the upper limit of normal reference for two consecutive times, or the maximum value of CK-MB exceeded twice the 99% confidence interval of the upper limit of normal reference at least once within 24 hours of onset.

The diagnostic criteria suggest that cTn is the preferred indicator, followed by CK-MB. In addition, many cardiac marker test diagnostic criteria rule out AMI by dynamically measuring cardiac markers and ECG within 24 hours.

2. Current status of point-of-care testing of cardiac markers

CK-MB, cTn and Mb are markers of myocardial necrosis, and the release kinetics of these three indicators are different, so they have different clinical values.

Mb is a small molecular substance (relative molecular weight 17000~18000). When myocardial cells are damaged, Mb is the earliest biochemical index to enter the blood, and its diffusion rate into the blood is faster than that of CK-MB or cTnI/cTnT.

Due to its early release and rapid clearance, Mb is the best early cardiac markers list for myocardial injury. However, due to the shortest window time, only 3 to 4 days, this indicator cannot be used for retrospective analysis.

It is also used as an indicator of coronary perfusion in patients undergoing thrombolysis or angioplasty. However, this index is abundant in skeletal muscle, so its specificity for the diagnosis of myocardial damage is poor.

After myocardial necrosis, the second cardiac marker test index that enters the blood is CK-MB, which has high diagnostic sensitivity for myocardial necrosis, especially dynamic detection. In 1995, CK-MB was considered as a diagnostic index for AMI. Skeletal muscle injury also has an increase in CK-MB, so its specificity is also poor. Dynamic detection of CK-MB is often used to monitor the presence or absence of reinfarction.

The third cardiac marker test to emerge is cTn, which is considered the biochemical "gold standard" for diagnosing AMI due to its excellent specificity and sensitivity. cTnI and cTnT are specific to the myocardium and are not normally present in peripheral blood.

Similar to CK-MB, it was elevated 4 hours after cardiomyocyte injury. However, the detection window of cTn is long (4 hours to 14 days), and its peak concentration is related to the infarct size. The cellular distribution and function of cTnI and cTnT are different, and the release mechanism is different, but the clinical diagnostic performance of the cardiac marker test of the two is similar.

Detection of a single marker in the early or late stage of AMI may miss the diagnosis, so dynamic detection and combined detection of multiple indicators are now advocated.

POCT has been successfully used in the diagnostic workflow of ACS and AMI. Compared with CLT, POCT shortens the return time of cardiac marker tests by 3.5-8 times. The application of POCT enables ACS or AMI patients to be diagnosed early, thereby improving their prognosis.