Inducible Myocardial Ischemia May Be Excluded by Low Levels of High Sensitivity Cardiac Troponin Levels

In an original cohort study by Hammadah et al recently published in Annals of Internal Medicine, it has been found that very low high-sensitivity cardiac troponin(hs-cTn) levels can be used in the exclusion of inducible myocardial ischemia in patients with stable coronary artery disease (CAD).  Moreover, it identifies people with CAD who have a lower risk of ischemia during stress testing and adverse cardiovascular events.

Despite current recommendations against the use of routine surveillance cardiac stress testing in persons with known, stable ischemic heart disease, past evidence points out that the inappropriate use continues. To reduce the rate of frequent stress testing, more effective risk stratification for people with known and stable CAD is needed. US FDA had approved hs-cTn for the diagnosis of acute myocardial infarction(MI). Lower levels(<5pg/mL) can safely exclude MI and identifies lower risk population. Higher levels of hs-cTn can predict the severity of atherosclerosis and are associated with inducible MI. Hs-cTnI assay, thus, can identify a low-risk group without inducible MI.

The original cohort study conducted by Hammadah et al examined two cohorts of patients with CAD; the derivation cohort and the validation cohort. Patients recruited in the derivation cohort included an abnormal coronary angiogram demonstrating evidence of atherosclerosis with at least luminal irregularities, documented previous percutaneous or surgical coronary revascularization, documented myocardial infarction, or a positive stress test result(n=589).; and in the validation cohort included patients(n=118) who survived a myocardial infarction in the past 6 months. Myocardial perfusion imaging and hs-cTnI assays were performed and followed up for a median of 3 years. Most patients(72%) in the derivation cohort were asymptomatic during the previous 30 days, 35% had a reversible perfusion defect during stress
testing, indicating inducible MI. Patients with inducible MI had higher hs-cTnI level than those without it. The results showed higher Negative predictive values(NPVs) among patients without underlying myocardial scar. In the validation cohort, 24% developed inducible myocardial ischemia during stress testing. Patients with inducible MI had higher hs-cTnI level, and the levels increased with the percentage of ischemic defect (10% higher hs-cTnI level with each 10% increase in inducible ischemic defect size).

The study had a strong NPV and sensitivity of hs-cTnI but the specificity was 23.8% and PPV of 44.2% were low for the cutoff value of 2.5pg/mL.  Additionally, the 3-year follow-up of the derivation cohort demonstrated that patients with low hs-cTnI had a much lower risk for adverse cardiovascular outcomes suggesting that low hs-cTnI level could not only safely identify patients at low risk for inducible myocardial ischemia but also predicted a low incident adverse event.  Hence, this can emerge as a prognostic tool in patients without acute coronary syndrome. The results may not be applicable to patients with unstable angina or without known CAD. Moreover, the NPV of hs-cTnI is greater in patients with asymptomatic CAD whose left ventricular function is normal and seems to be noticeably decreased in those with a myocardial scar. Commenting on the impact of these findings in clinical cardiology, Dr. Quyyumi also notes, “I guess the findings will have to be confirmed. Once they are, and they become adopted in stress testing guidelines, then it will certainly reduce the need for stress testing. These tests are already being used in Europe for triaging patients presenting to the emergency rooms with chest pain and suspected myocardial infarction.”