Professor Junichi Ishii

I am Prof. Junichi Ishii of the Fujita Health University Joint Research Laboratory, Clinical Medicine Department.

Fujita Health University Hospital has 1435 beds and is the largest hospital in Japan. We see 2,258 outpatients per day and accept 8,915 ambulances per year. Recently, due to aging and lifestyle changes, the number of ER patients with suspected cardiovascular diseases is significantly increasing. Cardiovascular diseases, especially acute coronary syndromes, can develop suddenly. Patients in stable clinical condition can suddenly destabilize. So early diagnosis and appropriate treatment is required. Acute coronary syndrome is suspected based on clinical symptoms and ECGs in the ER. However, if the ECG change is not significant, it is very difficult to diagnose in many cases. In such cases, we are using high-sensitivity troponin I.

I present a case: 70-year old male. He had chest pain for 20 minutes at rest, so he visited our hospital. He had no symptoms on admission, but the troponin value was elevated to 0.238 ng/mL. However, his ECG did not show signs of acute coronary syndrome.

In this case, in order to distinguish if this troponin elevation is caused by chronic myocardial damage or acute myocardial infarction, we re-tested him 3 hours later. Troponin increased by 0.112, so he was diagnosed with acute myocardial infarction. We performed an angiography and detected 99% stenosis at the proximal right coronary artery. We performed intervention and inserted a stent.

As we can see in this case, the 3-hour algorithm is very useful for diagnosing acute myocardial infarction. However, in practice, it is not viable to keep patients waiting for 3 hours at the ER. Therefore, we introduced a 1-hour algorithm into clinical practice from July 2017. Before that, we investigated the Siemens High-Sensitivity Troponin I assay to see if it would meet the ESC guideline for high-sensitivity troponin assays.

We tested high-sensitivity troponin I with 988 samples from healthy volunteers receiving a health check-up and who did not have any cardiovascular disease. 59.7% of subjects had troponin levels greater than the assay’s limit of quantification. Therefore, we concluded that Siemens High-Sensitivity Troponin I assay meets the ESC guideline.

Then, we initiated a clinical study. Currently, this study is still in progress. According to the results of the interim analysis, for 504 patients with suspected NSTEMI, the negative predictive value was 100% and the sensitivity was 100%; it was an excellent result. The positive predictive value was 27.2%.

What I want everyone to keep in mind when using this 0/1h algorithm, is that you should determine a diagnosis with the combination of clinical symptoms, physical findings, and ECG.

I present another case. 65-year old male. Due to chest pain, he visited our hospital. He arrived by ambulance. His symptoms disappeared after 15 minutes. It was 45 minutes from the start of his symptoms to the time of visit. As shown, ECG did not indicate any significant ST changes.

We measured troponin. At the time of presentation, it was less than the detection limit. The troponin value was less than 3 pg/mL, but the sample was taken 45 minutes from the start of symptoms, so he was not eligible for early rule-out. We tested again after 1 hour and the change in troponin was over 12 pg/mL, we determined this as in the rule-in group. The value at 1 hour was 35.2 pg/mL, which is less than the 47.3 pg/mL upper reference limit. However, we could rule-in this patient. We performed an angiography. We detected 99% stenosis of the proximal anterior descending coronary artery, so we inserted a stent. He left hospital lightheartedly.

Here is the summary. First, the study with healthy volunteers showed that Siemens High-Sensitivity Troponin I assay complies with the definition of high-sensitivity troponin I assays by 2015 ESC Guidelines. Then, 0/1h algorithm is useful at our hospital since the negative predictive value in the rule-out group is 100%. However, I would like to emphasize that it should be used in combination with reported clinical symptoms, physical findings, and ECGs.

High-sensitivity troponin I can measure troponin I in healthy people. Therefore, we can find small myocardial damage which we have not been able to detect. Therefore, it is possible to identify not only acute coronary syndrome or severe heart failure, but also lifestyle diseases or high-risk groups in people during health checks. Additionally, we are investigating if this can be used to identify cardiotoxicity due to anti-cancer therapy.