A new definition of acute myocardial infarction (MI) that separates it from myocardial injury presents an opportunity for laboratories to fully leverage high-sensitivity cardiac troponin (hs-cTn) assays and provide better guidance to physicians on interpreting cTn results. “Studies have shown that myocardial injury, defined by an elevated cTn value, is frequently encountered clinically and is associated with an adverse prognosis. Although myocardial injury is a prerequisite for the diagnosis of MI, it is also an entity in itself,” according to the Fourth Universal Definition of Myocardial Infarction guidance issued by the European Society of Cardiology, American College of Cardiology, and American Heart Association.

MI represents the death of myocardial cells and is characterized by acute myocardial ischemia. Nonischemic myocardial injury by comparison is often associated with other conditions such as renal failure or heart conditions like myocarditis. “For patients with increased cTn values, clinicians must distinguish whether patients have suffered a nonischemic myocardial injury or one of the MI subtypes. If there is no evidence to support the presence of myocardial ischemia, a diagnosis of myocardial injury should be made,” the authors advised.

Biomarkers cTn I and T help define who has acute MI. Myocardial injury reflects an elevated cTn value above the 99th percentile upper reference limit. When cTn values rise and fall due to myocardial ischemia with at least one value exceeding the 99th percentile, then the definition changes to acute MI. The advent of hs-cTn assays underscores the need to create this differentiation between heart attack and injury, guideline co-author Allan Jaffe, MD, a cardiologist and chair of the division of clinical core laboratory services at Mayo Clinic in Rochester, Minnesota, told CLN Stat.

“The more sensitive the assay, the more increases in troponin you will find,” Jaffe, a leading researcher and educator involving the use and interpretation of cTn assays, observed.

While heart attack usually gives off bigger signals than other conditions, clinicians are always going see those lower level signals and ask themselves: Is this a small MI, or is it myocardial injury? Patients often complain of very nonspecific symptoms. “It’s hard to distinguish whether or not the funny feeling in their chest is ischemia or not,” Jaffe said. “When you have increasing sensitivity of the assays, then this becomes a more frequent problem.” hs-cTn assays indicate myocardial injury, but the physician still doesn’t know the cause. “That’s the reason why there’s a lot of emphasis on myocardial injury and the fact that to make a diagnosis of infarction, one needs to see ischemia,” he elaborated.

The Fourth Universal Definition of MI also comments on multiple approaches that use early data to predict who will have an acute MI and who will rule out. The document lists these various screening and triage approaches for rapid rule in and rule out, listing some of the pros and cons of each approach. “At present we do not endorse a specific approach. In addition, the values needed will vary significantly between hs-cTn assays,” Jaffe said.

Clinical laboratorians in the wake of this new definition could take several measures to help physicians appropriately use and interpret hs-cTn results, Jaffe continued. Consistent use of the 99th percentile protocol is one such approach. Labs sometimes decide that the 99th percentile is something else and use their own cutoffs. This undermines the guidance the Universal Fourth Definition is trying to achieve, Jaffe said. “It’s hard to suggest approaches to evaluate changing patterns or results or when to consider other possibilities when these are set up as if one is using the assays properly and someone else is using different cutoffs. Then it doesn’t work well. It’s important that labs start to come together and stop deciding that the 99th percentile is something else.”

Quality control is another factor to consider. “Our studies have seen a high degree of ‘flyers’ where little things cause big changes in value. This is why labs need a level of quality control that is much more intensive than before,” he said. For the same reason, Jaffe also advised that labs avoid protocols that have “tight windows,” i.e. protocols that rely on small differences in readings as being totally determinative.

Labs also need to work on turnaround time to prevent emergency department overcrowding. When the emergency department is overloaded, all patients suffer, Jaffe emphasized.“Finally, the lab needs to participate in development of protocols so that whatever approaches clinicians take reflect the joint input of the emergency department, lab, cardiology, and surgery departments that use these assays,” he said.