Functionally Significant Nonculprit Lesions Pose Risk in STEMI Patients

In patients who have successfully undergone primary PCI for ST-segment elevation MI, there is an increased risk of future cardiovascular events among those with functionally significant nonculprit lesions left unstented at the time of the index procedure, according to a new look at data from Compare-Acute.  

The analysis, which evaluated the natural history of non-infarct-related arteries treated with only medical therapy in the Compare-Acute trial, showed that patients with a lower fractional flow reserve (FFR) of the non-infarct-related artery—indicating a physiologically significant lesion—had a significantly increased risk of cardiovascular disease, nonfatal MI, or revascularization during the 24 months of follow-up.

US and European guidelines, based on the results from PRAMI, CvLPRIT, COMPLETE, DANAMI-3-PRIMULTI, and Compare-Acute, already recommend revascularization of nonculprit lesions at the time of primary PCI or shortly afterwards, except in the setting of cardiogenic shock. Compare-Acute and DANAMI-3-PRIMULTI both used FFR instead of angiographic guidance to determine if the “bystander” vessels needed revascularization.

As such, the new study helps extend the prognostic value of FFR from stable coronary artery disease to the acute setting and should assist physicians in making decisions about whether to treat certain non-infarct-related arteries identified following successful primary PCI for STEMI, say investigators.

Speaking with TCTMD, senior investigator Pieter Smits, MD, PhD (Maasstad Hospital, Rotterdam, the Netherlands), said anywhere from 30% to 50% of patients with STEMI undergoing primary PCI have multivessel disease, but many of these vessels may not need revascularization.

“You can really prevent a lot of recatheterizations and second procedures if you do the FFR acutely,” said Smits, noting that 46% of patients in the main trial had no additional physiologically significant lesions beyond the infarct-related vessel. “If you do [FFR] all at once, you can also reassure your patients. In 50% of your patients, you can tell them the other lesions are negative and you don’t need to come back for more treatment.”

In the Compare-Acute study of STEMI patients with multivessel disease, patients were randomized to FFR-guided complete revascularization or treatment of the infarct-related artery only. In both groups, FFR was performed in all non-infarct-related arteries with angiographically significant stenoses, but cardiologists were blinded to the FFR outcomes when treating patients randomized to PCI of the infarct-related artery only.

“One of the reasons we did the FFR blinded in the infarct-related-artery arm was that we wanted to know what the natural outcomes of FFR values [of non-infarct-related arteries] were in STEMI patients with multivessel disease,” said Smits. “What happens when you leave FFR-positive lesions untreated? That was the main reason to have the blinded FFR in the main trial. This substudy looks at the natural course of the FFR values left untreated.”

The new study was published April 20, 2020, in JACC: Cardiovascular Interventions.  

Lower the FFR, the Higher the Risk of Future Problems

In Compare-Acute, 885 patients were randomized, including 295 to the FFR-guided complete revascularization study arm. Of these patients, 176 had nonischemic FFR in the nonculprit vessel. In the 590 patients randomized to PCI of the culprit-lesion only, 575 had FFR measurements in the nonculprit vessel. As a result, there were 751 patients with FFR data in 963 non-infarct-related arteries included in the present analysis. Of these patients, 135 developed cardiovascular disease, had an MI, or required TVR during 24 months of follow-up.

Overall, the FFR values of the non-infarct-related arteries in patients who had events was significantly lower than in those without cardiovascular disease, MI, or TVR (0.78 vs 0.84; P < 0.001).

In an analysis restricted to vessels only (and excluding CVD as an endpoint because it could not be attributed to a specific vessel with uncertainty), the median FFR value of the non-infarct-related artery was significantly in lower in those requiring revascularization (0.79 vs 0.85 in vessels not requiring revascularization; P < 0.001). Similarly, the median value of non-infarct-related arteries related to an MI was significantly lower than in those not related to the MI (0.79 vs 0.84; P = 0.016). Combined, the median FFR value was significantly lower in those vessels requiring TVR or related to an MI (0.79 vs 0.85; P < 0.001) than in those without events.

When FFR values were stratified into tertiles, there were significantly more MIs and TVRs in vessels with FFR values < 0.80 than in those with higher values. 

“Similar to chronic coronary artery disease and stable angina, we see an inverse relationship between the FFR value and events at follow-up,” said Smits. “In other words, the lower the FFR, the greater the likelihood that specific lesion will end up causing problems in long-term follow-up. There is more risk of MI, more risk of cardiovascular disease, and more risk of revascularization.” 

In the main Compare-Acute trial, which was published in the New England Journal of Medicine in 2017, the premise was to test the performance of FFR during the acute setting, given that it was initially developed for use in stable coronary artery disease. Despite concerns about its robustness in the acute setting, Smits said their new substudy shows that the FFR cutoff of 0.80 can be used to identify functionally significant coronary lesions in acute coronary syndromes.

In an editorial, Eric Van Belle, MD, PhD (Centre Hospitalier Universitaire de Lille, France), and colleagues write that the study shows that the FFR provides a “quantitative measure” of the risk of subsequent vessel-related events. Like Smits and colleagues, the editorialists agree that the FFR threshold of ≤ 0.80 initially tested in stable patients can discriminate between high- and low-risk patients in an acute setting.

“Altogether, the use of such an FFR-based risk stratification approach gives the opportunity to integrate an additional parameter in the overall appreciation of the ‘global risk’ of the patient during the primary procedure, beyond the culprit vessel and before leaving the catheterization room,” write the editorialists.

Using FFR in Clinical Practice   

With respect to clinical practice, Smits said that if FFR detects a functionally significant but nonculprit lesion in the acute setting, there are many factors which determine whether they’ll treat immediately or wait for a few weeks before bringing the patient back to the lab. Use of FFR provides definitive evidence about what should come next.

“If it’s a complex, high-risk lesion, then maybe it’s better to defer treatment,” said Smits. “You can do the FFR to determine if you need to bring the patient back, but you can defer treatment for a few weeks.”

In their editorial, Van Belle and colleagues agree that if a decision is made to stent the non-infarct-related arteries, it doesn’t have to be done during the index procedure. They suggest that the time of primary angiography for ACS or primary PCI for STEMI is an opportunity to perform the FFR testing on non-infarct-related arteries to collect information that can be used to quantify the risk of future events.