INTRODUCTION — Coronary artery reperfusion with primary percutaneous coronary intervention, compared with either no reperfusion therapy or fibrinolysis, improves outcomes in patients with acute ST-elevation myocardial infarction (STEMI) if performed in a timely fashion. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Summary and recommendations'.)
Usually, the lesion responsible for the infarct, often referred to as the “culprit lesion,” is readily identified and an attempt is made to re-establish blood flow with the use of thrombectomy, balloon angioplasty, or placement of one or more stents. (See "Primary percutaneous coronary intervention in acute ST-elevation myocardial infarction: Periprocedural management".)
In addition to the culprit lesion(s), about 50 percent of STEMI patients have one or more obstructive lesions remote from the area of infarction (ie, "non-culprit" lesions). This topic will address the management of non-culprit lesions in patients with STEMI.
OUR APPROACH — For patients with ST-elevation myocardial infarction who have been referred for primary percutaneous coronary intervention (PCI) and who have had non-culprit lesions identified, we use the following sequential approach:
●We perform primary PCI of the culprit lesion.
●We proceed with PCI of non-culprit lesions immediately after primary PCI in patients with evidence of ongoing ischemia, particularly if the lesion subtends a large amount of myocardium or if lesions have unstable morphology (eg, thrombus, ulceration, or plaque rupture).
●For those patients who are stable after primary PCI but have non-culprit lesions that are potential causes of residual myocardial ischemia and are without plans for surgical revascularization, we perform PCI prior to discharge or within the 45 days. At this time, measurement of FFR or iFR of one or more stenoses may guide decision-making regarding additional PCI, however it is also reasonable to perform PCI of lesions that are clearly angiographically significant (severe stenoses) at the time of primary PCI.
We discuss with patients who have significant non-culprit lesions the timing of revascularization and take into account their preferences.
We generally do not perform immediate non-culprit PCI in the following patients:
●Those in cardiogenic shock. (See "Prognosis and treatment of cardiogenic shock complicating acute myocardial infarction".)
●Those at significant risk for contrast nephropathy.
●Anticipation of the need for coronary artery bypass graft (eg, significant left main disease) or valve surgery in the near future.
●Those for whom the co-morbidities outweigh the benefits of revascularization.
●Those unable to tolerate or comply with dual antiplatelet therapy.
●Those with less than TIMI III flow in the culprit vessel after optimal PCI.
●Patient, operator, or healthcare team fatigue.
●Those with non-culprit stenoses that are complex (eg, complex bifurcation anatomy or chronic total occlusion). These tend to be patients with higher SYNTAX scores. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention", section on 'Outcomes based on lesion severity'.)
●Uncontrolled bleeding or other complication after PCI of the culprit lesion.
TERMINOLOGY — A culprit lesion is the site within the epicardial coronary circulation where blood flow has been interrupted or significantly reduced, and is the etiology of the acute myocardial infarction. This usually occurs at the site of rupture of an atherosclerotic plaque; thrombus formation usually leads to complete cessation of antegrade flow. The presence of thrombus often allows for identification of the culprit lesion as thrombus has easily identified angiographic characteristics. (See "Overview of the acute management of ST-elevation myocardial infarction".)
In addition to a culprit lesion, 40 to 60 percent of ST-elevation myocardial infarction patients have multivessel coronary artery disease with other significant lesions (≥50 percent luminal narrowing at the time of angiography or fractional flow reserve <0.80) [1-4]. These are referred to as non-culprit lesions.
IMPACT OF NON-CULPRIT LESIONS — Patients with significant multivessel coronary artery disease have higher rates of mortality and reinfarction than those with single vessel disease [5,6]. In a study of 2082 patients undergoing primary percutaneous coronary intervention, the one-year cumulative incidence of death for patients with single-, double-, and triple-vessel disease was 3.2, 4.4, and 7.8 percent (p = 0.003), and of target vessel revascularization was 11.3, 15.2, and 16.2 percent (p = 0.02), respectively. The adverse impact of multivessel disease due to non-culprit lesions raises the question as to whether revascularization of these non-culprit lesions will improve outcomes.
MANAGEMENT APPROACHES TO NON-CULPRIT LESIONS — In patients with ST-elevation myocardial infarction (STEMI) not complicated by cardiogenic shock, the evidence provided below supports our recommendation to perform angiographically or fractional flow reserve (FFR)-guided, non-culprit PCI rather than PCI of the culprit lesion only to lower the rate of death or MI and subsequent revascularization. (See 'Our approach' above.)
There are four principal strategies to manage non-culprit lesions:
●PCI of non-culprit lesions at the time of primary PCI.
●PCI of non-culprit lesions prior to hospital discharge or soon after discharge.
●Refer for coronary artery bypass surgery (CABG) after the patient has recovered from the acute STEMI. This would be considered in patients who otherwise would undergo CABG electively. (See "Left main coronary artery disease", section on 'Summary and recommendations'.)
●Medical therapy without further revascularization, unless standard indications for revascularization in patients with stable coronary artery disease are met. (See "Chronic coronary syndrome: Indications for revascularization", section on 'Indications'.)
The best evidence to support the use of complete rather than culprit-only revascularization in STEMI patients comes from the 2019 COMPLETE study, which found a lower rate of death and MI with complete revascularization [7]. COMPLETE randomly assigned 4041 STEMI patients with multivessel disease who had undergone successful culprit-lesion PCI to either complete revascularization with PCI of angiographically significant non-culprit lesions or no further revascularization (culprit-only group). An angiographically significant lesion was present if it was associated with at least 70 percent stenosis on visual estimation or with a 50 to 69 percent stenosis accompanied by an FFR measurement of 0.80 or less (see "Clinical use of coronary artery pressure flow measurements", section on 'Intermediate severity stenosis'). Randomization was stratified according to the intended timing of non-culprit-lesion PCI (either during or after [within 45 days of randomization] hospitalization). Among those who underwent complete revascularization, the median time from randomization to non-culprit PCI was 1 and 23 days in the two stratified groups. The following results were found at a median follow-up of three years:
●The first coprimary composite outcome of cardiovascular death or MI occurred in 7.8 and 10.5 percent of the two groups, respectively (hazard ratio [HR] 0.74, 95% CI 0.60-0.91). This was driven by a lower incidence of new MI in the complete revascularization group.
●The second coprimary composite outcome of cardiovascular death, MI, or ischemia-driven revascularization occurred in 8.9 and 16.7 percent of the two groups, respectively (HR 0.51, 95% CI 0.43-0.61).
●For both primary outcomes, the benefit of complete revascularization was observed irrespective of timing.
●Patients enrolled in the trial had a relatively low SYNTAX score of about 16, indicating that the chances for successful PCI were relatively high. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention", section on 'Outcomes based on lesion severity'.)
Other evidence comes from observational studies and relatively small randomized trials. Observational studies, performed prior to the randomized trials [1,8] and their meta-analyses [1,9], concluded that culprit-only PCI, as opposed to multivessel PCI, at the time of initial reperfusion led to better outcomes. However, when patients who were treated with staged PCI during the hospitalization were analyzed separately, short- and long-term outcomes favored multivessel revascularization compared with culprit only strategy.
Nine published randomized trials of patients with multivessel disease (DANAMI-3-PRIMULTI, PRAMI, CvLPRIT, and Compare Acute being the four largest) have compared culprit only with complete revascularization with regard to composite outcomes:
●DANAMI-3-PRIMULTI randomly assigned 313 patients with one or more clinically significantly coronary stenoses in addition to the culprit lesion to either no further invasive treatment or complete, FFR-guided revascularization before discharge, usually two days after initial PCI. The primary composite end point (all-cause mortality, non-fatal infarction, and ischemia-driven revascularization of lesions in non-infarct related arteries) occurred less often in the group with complete revascularization (13 versus 22 percent; HR 0.56, 95% CI 0.38-0.83). The benefit was almost entirely attributable to a lower rate of subsequent revascularization of non-infarct related arteries (HR 0.31, 95% CI 0.18-0.53). Approximately one-third of patients who were assigned to the complete revascularization strategy did not undergo non-culprit PCI, as FFR values were above the discrimination value of 0.80 despite the fact that initial angiography suggested high-grade stenoses. (See "Clinical use of coronary artery pressure flow measurements", section on 'Intermediate severity stenosis'.)
●The PRAMI trial planned to randomly assign 600 patients to either preventive or no preventive PCI after successful primary PCI [10]. Preventive PCI was defined as immediate (same-setting) PCI of non-infarct arteries with >50 percent diameter stenosis (staged procedures were discouraged). FFR assessment was not used. Patients with cardiogenic shock or prior CABG were excluded. The trial was terminated early by the data and safety monitoring committee after the enrollment of 465 patients for the finding of a highly significant between-group difference in the incidence of the primary outcome (a composite of cardiac death, nonfatal MI, or refractory angina) favoring non-culprit PCI (9 versus 23 percent; HR 0.35, 95% CI 0.21-0.58) during a mean follow-up of 23 months. There were a total of 21 and 53 events in the two groups, respectively, of which about half were due to refractory angina. The HRs for the individual components of the composite end point all favored non-culprit PCI. However, we believe there are limitations to PRAMI, including stopping early, liberal definition of multivessel disease, and a small number of events.
●The CvLPRIT trial randomly assigned 296 patients to complete revascularization during the hospitalization or infarct-related, artery-only revascularization [11]. Multivessel disease was defined as one or more non-culprit stenosis of >70 percent diameter stenosis in other coronary arteries. Among those assigned to treatment prior to discharge, 64 percent received complete revascularization at the time of primary PCI. FFR assessment was not used. The primary composite end point (all-cause death, recurrent MI, heart failure, and ischemia -driven revascularization at 12 months) occurred less often in the complete revascularization group (10.0 versus 21.2 percent; HR 0.45, 95% CI 0.24-0.84). All components of the primary end point were lower with complete revascularization and there was no difference in the safety end points (major bleeding, contrast-induced nephropathy, or stroke).
●The Compare-Acute trial randomly assigned 885 patients in a 1:2 ratio to undergo complete revascularization of non-infarct related coronary arteries or no revascularization [12]. FFR was performed in both groups and, in the revascularization group, PCI was performed in all lesions with a result ≤0.80. In most cases, revascularization took place during the index procedure. The primary composite end point of death from any cause, nonfatal MI, revascularization, and cerebrovascular events at 12 months occurred less often in the complete revascularization group (7.8 versus 20.5 percent; HR 0.22, 95% CI 0.22-0.55). This outcome was driven principally by many fewer revascularizations being performed in the complete revascularization group (18 versus 103). In addition, there was a trend toward a lower rate of MI (2.4 versus 4.7 percent) with complete revascularization.
The trials above were relatively small and powered only for composite outcomes that included repeat revascularization. A 2020 meta-analysis that included the above four trials plus two others (N = 6528) found that the primary outcome of cardiovascular death was significantly reduced in the group receiving complete revascularization (HR 0.62, 95% CI 0.39-0.97) [13].
UNANSWERED QUESTIONS
What is the optimal timing? — Although we often perform percutaneous coronary intervention (PCI) of significant non-culprit lesions prior to hospital discharge in patients with STEMI, there is no clear evidence favoring PCI during hospitalization over early after discharge.
One small trial suggested that there was no difference in major cardiovascular outcomes between PCI of non-culprit lesions at the time of primary PCI or staged (deferred but during hospitalization) revascularization [14]. Factors to consider for performing non-culprit PCI at the time of primary PCI include patient stability, ability to accurately assess lesion significance in the setting of acute coronary syndromes, likelihood of procedural success, risk of the intervention (eg, possibility of increased risk of contrast nephropathy), and the potential benefit of revascularization (eg, size of the ischemic territory). Nonetheless, we generally bring the patient back to the catheterization laboratory prior to hospital discharge rather than perform non-culprit PCI at the time of primary PCI.
Angiographic stenosis severity may be overestimated during angiography at the time of STEMI [15,16]. Assessment of fractional flow reserve of some of these lesions is discussed elsewhere. (See "Clinical use of coronary artery pressure flow measurements".)
Which non-culprit lesions? — Non-culprit lesions should be treated during the initial hospitalization if angiographic or intracoronary imaging suggests unstable morphology (ulceration, thrombus) or in patients with recurrent ischemic symptoms. In the absence of unprovoked ischemia, PCI of non-culprit lesions should be treated soon after PCI if the stenosis severity is >70 percent, or >50 percent with an abnormal fractional flow reserve (FFR) or iFR [17], and the location of the lesion is proximal or in a vessel that subtends a significant area of myocardium. If the burden of ischemia is unclear or the viability of the territory is in question, further assessment with noninvasive imaging prior to PCI can be considered. Vessels not suitable for stenting, due to small diameter or distal location, should not be treated routinely.
Chronic total occlusions — The optimal approach to STEMI patients with chronic total occlusion (CTO) of a non-culprit lesion, identified at the time of primary PCI, is not known. We perform PCI of non-culprit CTO in STEMI patients if the occluded vessel subtends a significant area of potentially viable myocardium and the anatomic complexity predicts a high likelihood of success with an antegrade approach or the procedure can be performed by an operator proficient in more advanced chronic total occlusion techniques, including re-entry and retrograde approaches, such that the risks of the procedure are low. In general, we stage the CTO intervention rather than perform during the index primary PCI. Timing can be prior to discharge or electively after discharge, depending on the severity of symptoms and objective evidence of ischemic burden. (See "Percutaneous coronary intervention of specific coronary lesions", section on 'Chronic total occlusion'.)
Up to 15 percent of patients with STEMI are found to have CTO of a non-culprit artery at coronary angiography. The presence of an occlusion of another epicardial artery significantly increases mortality and this is particularly true if CTO is present [18,19].
Observational studies have suggested that PCI of CTO improves outcomes, particularly in patients with STEMI [20]. The EXPLORE trial randomly assigned 204 STEMI patients to PCI of CTO within seven days of primary PCI or no PCI [21]. At four months, there was no difference in the primary end points of the mean left ventricular ejection fraction (44.1 versus 44.8 percent) and left ventricular end diastolic volume (215.6 versus 212.8 mL), both assessed by cardiac magnetic resonance imaging. Core laboratory adjudicated procedural success was 73 percent.
Role of invasive hemodynamic assessment — We consider measurement of FFR or iFR for non-culprit lesions of intermediate or indeterminate severity (40 to 70 percent) seen at the time of angiography. These measurements are made at the time of culprit vessel angiography if the plan is to perform multivessel PCI at the time of primary PCI or if the need for additional revascularization is unclear. For patients in whom there is at least one severe stenosis (>70 percent) and staged PCI in a separate setting is planned, we perform FFR or iFR during the subsequent procedure. We use the same cut-off values in the setting of STEMI <0.80 for FFR or <0.89 for iFR. (See "Clinical use of coronary artery pressure flow measurements", section on 'Intermediate severity stenosis'.)
RECOMMENDATIONS OF OTHERS — Many relevant studies were published after the guidelines presented below were released.
In the 2015 American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions focused update (of prior guidelines) on primary percutaneous coronary intervention (PCI) for patients with ST-elevation myocardial infarction, the guideline to perform PCI of a noninfarct artery either at the time of primary PCI or as a planned staged procedure was changed from a class III to IIb recommendation [22,23].
The guideline from the European Society of Cardiology recommends against non-culprit PCI [24].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: ST-elevation myocardial infarction (STEMI)".)
SUMMARY AND RECOMMENDATIONS
●For patients with ST-elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI) and who are found to have significant non-culprit lesions, we recommend PCI of these lesions rather than revascularization for symptoms only (Grade 1A). (See 'Our approach' above.)
●For STEMI patients found to have non-culprit lesions at the time of primary PCI and who do not have one or more high-risk features (eg, cardiogenic shock or ongoing ischemia, particularly if the lesion subtends a large amount of myocardium, or lesions with unstable morphology [eg, thrombus, ulceration, plaque rupture]), we suggest PCI of these non-culprit lesions during a separate visit to the catheterization laboratory prior to hospital discharge or soon after hospital discharge rather than at the time of the primary PCI (Grade 2C). (See 'Our approach' above.)
