Periprocedural MI Signals Worse Outcomes in Stented NSTE ACS Patients: MATRIX

Depending on the definition used, the incidence of periprocedural MI varies significantly when assessed in patients with ACS undergoing PCI, according to an analysis of the MATRIX trial published last week.

In a cohort that included patients with STEMI and NSTE ACS, there were no associations between periprocedural MI and either cardiovascular or all-cause death at 1 year regardless of the definition, but the mortality risks were higher in those with NSTE ACS who had a periprocedural MI classified using the Fourth Universal Definition of MI (UDMI).

Isolated increases in cardiac troponin, even up to 20 times the upper reference limit (URL), without other criteria were not associated with cardiovascular or all-cause mortality at 1 year.

“These findings are relevant for the maturation of the definition of myocardial infarction in the setting of PCI and support the distinction between myocardial injury (ie, an isolated troponin elevation) and MI, a clinical diagnosis defined by additional procedural related ischemic complications, especially if they are objective,” Sergio Leonardi, MD (University of Pavia and Fondazione IRCCS Policlinico San Matteo, Italy), and colleagues report in Circulation.

In the analysis, periprocedural MI in PCI-treated patients with STEMI was not associated with an increased risk of mortality, leading investigators to conclude that “the current data do not support the inclusion of [periprocedural] MI as an endpoint in clinical trials of patients presenting with STEMI.”

Gregg Stone, MD (Icahn School of Medicine at Mount Sinai, New York, NY), who has investigated periprocedural MI’s prognostic implications and debated its importance as part of a composite endpoint in clinical trials, emphasized that the MATRIX analysis applies only to patients with ACS, primarily NSTE ACS.

In patients with STEMI, it’s extremely challenging to diagnose a procedural MI, he said.

“The biomarkers are elevating, they’ve not peaked,” Stone told TCTMD. “It’s also very likely PCI worsens the extent of myocardial necrosis in STEMI, because it does not infrequently cause distal atherothrombotic embolization. But it’s very difficult to pick it up. The patients were having chest pain, they keep having chest pain; they had ST elevation, they keep having ST elevation.”

Stone agreed with the authors that periprocedural MI should not be used as part of a primary outcome in future trials of STEMI patients, although that’s mainly because it’s so difficult to diagnose. “I have no doubt that periprocedural MI, as defined by worsening myocardial necrosis and perhaps left ventricular dysfunction, is greater in STEMI than it is in non-STEMI and probably even more prognostically important,” he said.

In terms of clinical practice, Stone said most interventional cardiologists don’t routinely measure biomarkers after PCI unless there’s a clinical indication, such as an angiographic complication or ECG changes. These data would suggest that cardiac troponin spikes plus ancillary criteria in NSTE ACS patients should be “red lights” that would justify close patient surveillance after the procedure. 

MATRIX ACS Population

The adjudication of periprocedural MI, and what those events mean down the road, is a hotly debated topic in revascularization studies. Some cardiologists have said that the assessment of periprocedural events harkens back to an earlier time when the focus was on short-term outcomes, while others have called the collection of biomarkers an academic exercise that has little bearing on clinical practice. Still, there are many who believe that periprocedural MI remains a valid endpoint that should continue to be part of clinical trials testing different revascularization strategies.   

The MATRIX study population included 6,724 patients with ACS undergoing PCI, with procedural MI adjudicated using the Second, Third, and Fourth UDMIs.

The Second UDMI required only a troponin increase greater than three times the URL, whereas the Third, as well as the most contemporary Fourth UDMI, use a troponin threshold greater than five times the URL. Importantly, the Third and Fourth definitions also require ancillary criteria—new ischemic ECG changes, angiographic findings, or imaging findings—in addition to the biomarker elevation. The Third definition differs from the Fourth in that the ancillary criteria also included new left bundle branch block and symptoms; the Fourth UDMI instead favors new Q waves in addition to the other shared criteria.  

The overall incidence of periprocedural MI adjudicated with the Second, Third, and Fourth definitions was 9.0%, 3.0%, and 3.0%, respectively. Among those with NSTE ACS only, the incidence was 15%, 5%, and 5% with the three definitions, respectively. In patients with STEMI, procedural MI was uncommon, ranging from 1% to 4% depending on the definition.

Periprocedural infarction captured with the Fourth UDMI was associated with a twofold increased risk of all-cause mortality at 1 year (HR 2.08; 95% CI 1.00-4.30) and a roughly 2.5 times higher risk of cardiovascular mortality (HR 2.62; 95% CI 1.03-6.65) in patients with NSTE ACS. There were numerical increases in all-cause and cardiovascular deaths among those with periprocedural events based on the Third UDMI that did not reach statistical significance.

In those with STEMI, there was no association with mortality regardless of the definition used.  

There were nonsignificant increases in all-cause and cardiovascular mortality at 1 year in patients who had a troponin increase greater than five times the URL (or more than 20% from baseline) when the biomarker increase was combined with angiographic criteria. When combined with ECG changes, a troponin increase of that magnitude was associated with significantly higher risks of both mortality measures at 1 year.

Isolated thresholds of cardiac troponin, even greater than 20 times the URL, was not associated with a higher death risk in the absence of ancillary criteria.

“Our findings suggest that in patients with ACS, a diagnosis of PCI-MI based only on biomarkers may have limited discrimination and clinical significance,” say the investigators. “The integration of additional criteria for PCI-related ischemic complications may potentially increase operational complexity and costs but could help identify a minority of prognostically relevant events.”

Comparing Apples to Oranges?

To TCTMD, Stone noted that in patients with chronic coronary syndrome undergoing PCI, biomarkers are normal, or at least stable, at baseline. However, even after excluding patients with STEMI and focusing on those with NSTE ACS, there could be wide variability in baseline biomarker levels among the MATRIX patients.

“It’s hard to tease all of that out,” he said. “Depending on exactly where you started with the baseline biomarker, you may not be comparing apples to oranges in terms of the size of the [periprocedural] infarcts. That being said, I think the data are convincing: the Fourth Universal Definition of MI clearly performs better at identifying a periprocedural MI cohort in the setting of NSTE ACS which is prognostically related to subsequent cardiovascular and all-cause mortality.”

Stone noted that troponin greater than 20 times the URL without ancillary criteria wasn’t associated with adverse outcomes, but he would like to know if even larger troponin spikes—say, greater than 35 or 70 times the URL—without additional criteria would have been associated with mortality at 1 year. With the SCAI definition, for example, a marked elevation of cardiac troponin—defined as greater than 70 times the URL without ECG changes—is identified as one way to capture “clinically relevant” periprocedural MIs.

Importantly, Stone noted, the present analysis used cardiac troponin as part of the UDMI, but much of the world has moved on to high-sensitivity troponin. The latter is measured by different assays, and it’s unknown whether the same thresholds for high-sensitivity cardiac troponin can be used in a similar fashion as standard troponin, said Stone.