Version May 2024
INTRODUCTION — For many patients with myocardial infarction (MI), coronary angiography with stenting improves outcomes. Usually, the lesion responsible for the infarct, often referred to as the "culprit lesion," is readily identified by electrocardiography and angiography and is treated with balloon angioplasty or stenting. In addition to culprit lesions, patients with MI may have one or more obstructive lesions remote from the area of infarction referred to as "nonculprit" lesions.
This topic will address the management of nonculprit lesions in patients with ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI).
Other aspects of percutaneous coronary intervention in patients with acute coronary syndromes (ACS) can be found separately:
●(See "Periprocedural bleeding in patients undergoing percutaneous coronary intervention".)
TERMINOLOGY
Culprit lesions — A culprit lesion is the site within the epicardial coronary circulation where blood flow has been acutely interrupted or significantly reduced leading to MI and usually occurs at the site of atherosclerotic plaque rupture or thrombus formation. In addition, the presence of thrombus identifies a lesion as high-risk.
Nonculprit lesions — Lesions that are not clearly contributing to acute infarction but may be flow-limiting are referred to as nonculprit lesions. The hemodynamic significance of such lesions may be determined by angiographic assessment, intracoronary pressure measurements, or noninvasive stress testing. (See 'Assessment of nonculprit lesion anatomy' below.)
EPIDEMIOLOGY — In addition to a culprit lesion, 40 to 60 percent of patients with STEMI have multivessel coronary artery disease (CAD) with other significant lesions (≥50 percent luminal narrowing at the time of angiography or fractional flow reserve <0.80) [1,2]. Patients with ACS and significant multivessel CAD have higher rates of mortality and reinfarction than those with single-vessel disease [3,4]. As examples:
●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), respectively. The adverse impact of multivessel disease due to nonculprit lesions raises the question as to whether revascularization of these nonculprit lesions could improve outcomes [4].
●In studies of patients with STEMI and a nonculprit chronic total occlusion (CTO) lesion, mortality was generally higher than in patients without a CTO [5,6].
ASSESSMENT OF NONCULPRIT LESION ANATOMY — The approach to nonculprit percutaneous coronary intervention (PCI) in patients with MI is determined by the type of lesion, the severity of stenosis, and the number and location of residual obstructive lesions:
●Stenosis severity – Visual estimation of stenosis severity with angiography is typically sufficient. If the severity of stenosis is uncertain (eg, some lesions with 50 to 69 percent visual stenosis), intracoronary fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) measurements can be used to determine the severity stenosis. If FFR or iFR is used to assess nonculprit lesion severity, we use cut-off values <0.80 for FFR or <0.89 for iFR. (See "Clinical use of coronary artery pressure flow measurements", section on 'Intermediate severity stenosis'.)
FFR was not routinely used in trials that evaluated the effect of nonculprit PCI, and one trial found similar results among patients who underwent nonculprit PCI guided by angiographic assessment or by FFR assessment:
•The FLOW Evaluation to Guide Revascularization in Multi-vessel ST-elevation Myocardial Infarction (FLOWER-MI) study was a multicenter randomized controlled trial (n = 1171) that examined whether complete revascularization guided by FFR was superior to an angiography-guided procedure in patients with STEMI and multivessel disease following successful primary PCI [7]. The primary outcome (mortality, nonfatal MI, unplanned hospitalization with urgent revascularization) was similar in the FFR-guided and angiography-guided groups (5.5 versus 4.2 percent; hazard ratio 1.32, 95% CI 0.78-2.23).
●Lesion complexity – We evaluate for the presence of lesions that are technically difficult to address including bifurcation lesions, stenosis of the left main coronary artery, and chronic total occlusion. The approach to such lesions is discussed below. (See 'Complex lesions, chronic total occlusions' below.)
Further details on issues intrinsic to these and other complex lesions are discussed separately. (See "Percutaneous coronary intervention of specific coronary lesions".)
●Left main or multivessel disease – The approach to nonculprit PCI is influenced by whether the residual lesions are amenable to coronary artery bypass graft surgery (CABG; eg, left main stenosis, two- or three-vessel CAD). The details on the characteristics of anatomy amenable to CABG are discussed separately:
•Left main disease (See "Left main coronary artery disease".)
•Two- or three-vessel disease (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention", section on 'Multivessel disease'.)
ROLE OF NONCULPRIT PCI IN SPECIFIC SCENARIOS
Unfavorable scenarios for immediate nonculprit PCI — In patients who underwent percutaneous coronary intervention (PCI) of culprit lesions and who have residual nonculprit lesions, we reassess the patient to determine the risks and benefits of additional PCI of nonculprit lesions (algorithm 1). Though PCI or coronary artery bypass graft surgery (CABG) may be an option for therapy in the future, we do not immediately perform nonculprit PCI in the following scenarios:
Cardiogenic shock — We recommend not performing nonculprit lesion PCI in patients with MI and cardiogenic shock (algorithm 1). While culprit lesion PCI in patients with cardiogenic shock is beneficial, a randomized trial suggested that immediate nonculprit PCI in similar patients is associated with harm:
●In the CULPRIT-SHOCK trial, which included 685 patients with STEMI or NSTEMI, culprit-only PCI had a lower risk of all-cause mortality compared with culprit plus nonculprit PCI (43 versus 52 percent; hazard ratio [HR] 0.84, 95% CI 0.72-0.98) [8].
Anatomy amenable to bypass grafting — In stable patients with STEMI or NSTEMI who have nonculprit lesions amenable to CABG (eg, three-vessel CAD, left main CAD), we perform a comprehensive evaluation for revascularization rather than proceed with immediate PCI (algorithm 1). The approach to choosing a revascularization strategy in the presence of left main or multivessel disease is discussed separately. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)
Complex lesions, chronic total occlusions — The approach to patients with ACS who have nonculprit stenoses that are complex (eg, complex bifurcation anatomy or chronic total occlusion [CTO]) is individualized and depends on the specific anatomy, the likelihood of technical success, and the risk of complications (algorithm 1). If we plan to perform PCI in patients with such lesions, we generally stage the PCI intervention rather than perform it during primary PCI. (See "Percutaneous coronary intervention of specific coronary lesions", section on 'Chronic total occlusion'.)
Our approach is motivated by the higher likelihood of complications associated with CTO interventions, and observational studies suggest that the benefit of CTO PCI shortly after the index MI is unclear [9]:
●The EXPLORE trial randomly assigned 204 patients with STEMI to PCI of CTO within seven days of primary PCI or no PCI of the CTO lesion [10]. Procedural success occurred in 73 percent of cases. At four months, there was no clear difference in the primary endpoints of mean left ventricular ejection fraction (44.1 versus 44.8 percent) and mean left ventricular end-diastolic volume (216 versus 213 mL) as assessed by cardiovascular magnetic resonance imaging.
Other unfavorable scenarios — Other scenarios in which the risk of the procedure or the benefit to the patient are generally not in favor of immediate nonculprit PCI include (algorithm 1):
●Less than Thrombolysis In Myocardial Infarction (TIMI) III grade flow in the nonculprit vessel after culprit PCI. (See "Suboptimal reperfusion after primary percutaneous coronary intervention in acute ST-elevation myocardial infarction".)
●Uncontrolled bleeding or other complication after PCI of the culprit lesion. (See "Periprocedural complications of percutaneous coronary intervention".)
●High risk of contrast nephropathy, adverse sedation effects, or radiation exposure injury. (See "Prevention of contrast-associated acute kidney injury related to angiography", section on 'Major risk factors'.)
●Presence of patient, operator, or healthcare team fatigue.
Approach to nonculprit PCI — In patients who do not have contraindications to additional PCI after PCI of culprit lesions, the decision to perform PCI of nonculprit lesions and the timing of such PCI is based on the type of MI:
STEMI — In patients who are stable after PCI of culprit lesions and who have anatomy amenable to PCI, we recommend performing PCI of all significant nonculprit lesions rather than PCI guided by additional tests for ischemia (eg, invasive coronary physiology, noninvasive stress testing), symptoms of ischemia, PCI after discharge, or not performing PCI of nonculprit lesions (algorithm 1). For most patients, we suggest complete revascularization during the index procedure rather than as a staged procedure.
This approach is consistent with professional guidelines [11,12].
Our approach is primarily influenced by trials in which nonculprit lesion PCI in patients with STEMI who are not candidates for CABG reduced the risk of subsequent MI and meta-analyses of older trials that suggest a small mortality benefit. Once the decision to perform nonculprit PCI is made and if feasible, it is reasonable to perform PCI during the index procedure; this approach reduces the burden to the patient inherent to separate (ie, staged) procedures and, as demonstrated in trials, reduces the risk of recurrent MI associated with staged procedures. The evidence includes:
●Nonculprit PCI versus no plan for additional PCI
•The FIRE trial, which included 1445 patients age 75 years or older with STEMI or NSTEMI (65 percent) who were not candidates for CABG, found that PCI of nonculprit lesions guided by physiology reduced the rate of all-cause death (9.2 versus 12.8 percent; HR 0.7, 95% CI 0.51-0.96) and MI (4.4 versus 7.0 percent; HR 0.62, 95% CI 0.4-0.97) compared with no plan for nonculprit artery PCI [13].
•In the COMPLETE trial, 4041 patients with STEMI and multivessel disease who had undergone successful culprit lesion PCI were assigned to either complete revascularization with PCI of angiographically significant nonculprit lesions or no further revascularization (culprit-only group) [14]. Patients with anatomy amenable to CABG were excluded. An angiographically significant lesion was defined by the presence of at least 70 percent stenosis on visual estimation or if there was 50 to 69 percent visual stenosis and a fractional flow reserve measurement of 0.80 or less. The following results were found at a median follow-up of three years. The rate of MI was lower in the complete revascularization group (5.4 versus 7.9 percent; HR 0.68, 95% CI 0.53-0.86) as was ischemia-driven revascularization (1.4 versus 7.9 percent; HR 0.18, 95% CI 0.12-0.26). All-cause and cardiovascular mortality were similar between the two groups. Notably, patients enrolled in the trial had a relatively low SYNTAX score of approximately 16, indicating that the chances for successful PCI were relatively high.
•In meta-analyses, there was a consistent finding of lower rates of cardiovascular mortality, recurrent MI, and repeat revascularization with nonculprit lesion PCI [15,16]:
-A 2020 meta-analysis found that nonculprit PCI was associated with lower risks of cardiovascular death (relative risk [RR] 0.68, 95% CI 0.47-0.98), MI (RR 0.65, 95% CI 0.54-0.79), and unplanned revascularization (RR 0.37, 95% CI 0.28-0.51) [15]. In addition, there were similar risks of major bleeding and contrast-induced nephropathy between the two groups.
-In another meta-analysis, patients who underwent nonculprit PCI had lower risks of cardiovascular death (HR 0.62, 95% CI 0.39-0.97), MI (HR 0.68, 95% CI 0.55-0.84), and revascularization (HR 0.29, 95% 0.22-0.38) [16].
●Timing of nonculprit PCI
•In a trial (MULTISTARS) that included 418 patients with STEMI, patients assigned to complete revascularization immediately after the culprit artery PCI had lower rates of nonfatal MI (2 versus 5.3 percent; HR 0.36, 95% CI 0.16-0.8) and unplanned ischemia-driven revascularization (4.1 versus 9.3 percent; HR 0.42, 95% CI 0.24-0.74) but similar rates of mortality compared with patients assigned to complete revascularization 19 to 45 days after the index PCI [17].
•The BIOVASC trial investigated the timing of PCI for nonculprit lesions in patients with STEMI or NSTEMI using a noninferiority design [18]. Patients were assigned to complete revascularization during the index hospital stay (n = 764) or to complete revascularization after the index hospital stay but within six weeks (n = 761). PCI of nonculprit lesions prior to discharge decreased the rate of the secondary outcomes of MI (1.9 versus 4.5 percent; HR 0.41, 95% CI 0.22-0.76) and unplanned ischemia-driven revascularization (4.2 versus 6.7 percent; HR 0.61, 95% CI 0.39-0.95). For the outcome of MI, the difference between groups was evident within days after randomization, which suggests that PCI before discharge prevented such events in the interval immediately after the index MI. The rates of cardiovascular and all-cause death were similar in each group.
NSTEMI — In patients with NSTEMI who undergo PCI of culprit lesions but who have residual nonculprit lesions, we suggest performing PCI of all significant nonculprit lesions, either angiography- or physiology-guided, during the index admission, rather than performing PCI guided by additional testing for ischemia (eg, coronary physiology study, noninvasive stress imaging) or symptoms of ischemia, not performing PCI of nonculprit lesions, or performing PCI after discharge (algorithm 1). If feasible, performance of nonculprit PCI during the index procedure may avoid the need for a separate PCI procedure.
Professional guidelines relevant to patients with NSTEMI either do not comment directly on nonculprit PCI or favor early nonculprit PCI [11,12].
Our approach is based on direct data from the BIOVASC trial and indirect data from trials that evaluated nonculprit revascularization in patients with STEMI. Another small trial suggested that PCI immediately following culprit PCI and PCI before discharge had similar outcomes. The data include:
●The BIOVASC trial included patients with NSTEMI; the benefit of early revascularization on reducing recurrent MI did not differ based on the patient's initial presentation [18]. Additional details of this trial are presented elsewhere in this topic. (See 'STEMI' above.)
●The SMILE trial randomly assigned 584 patients with NSTEMI to nonculprit lesion PCI during the initial PCI or to nonculprit lesion prior to discharge [19]. The rates of mortality and MI were similar between the two groups, while target vessel revascularization was higher in the delayed PCI group (8.3 versus 15.2 percent). All patients underwent revascularization before discharge; the short time between PCI in the two groups may have resulted in similar rates of recurrent MI.
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
●Epidemiology – In addition to a culprit lesion, 40 to 60 percent of patients with ST-elevation myocardial infarction (STEMI) have multivessel coronary artery disease (CAD) with other significant lesions. The presence of such lesions increases the likelihood of mortality and reinfarction. (See 'Epidemiology' above.)
●Role of nonculprit PCI in specific scenarios – After culprit lesion percutaneous coronary intervention (PCI), a decision must be made on how to manage any remaining nonculprit lesions. The decision to revascularize such lesions depend on the following factors (algorithm 1):
•Unfavorable scenarios for immediate nonculprit PCI – Though PCI or coronary artery bypass graft surgery (CABG) may be an option for therapy in the future, immediate nonculprit PCI is typically not performed in the following scenarios:
-Presence of cardiogenic shock – We recommend not performing nonculprit lesion PCI in patients with myocardial infarction (MI) and cardiogenic shock (Grade 1B) (algorithm 1). While culprit lesion PCI in patients with cardiogenic shock is beneficial, a randomized trial suggested that nonculprit PCI in similar patients is associated with harm. (See 'Cardiogenic shock' above.)
-Anatomy amenable to coronary artery bypass grafting –In stable patients with STEMI or non-ST-elevation MI (NSTEMI) who have nonculprit lesions amenable to CABG (eg, three-vessel CAD, left main CAD), we perform a comprehensive evaluation for revascularization rather than proceed with PCI. The approach to choosing a revascularization strategy in the presence of left main or multivessel disease is discussed separately (algorithm 1). (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)
-Complex lesions, chronic total occlusions – If we plan to perform PCI in patients with complex lesions, including chronic total occlusions (CTO), we generally stage the PCI intervention rather than perform it during primary PCI (algorithm 1). (See 'Complex lesions, chronic total occlusions' above.)
-Other unfavorable scenarios – Other scenarios in which the risk of the procedure or the benefit to the patient are generally not in favor of nonculprit PCI include less than Thrombolysis In Myocardial Infarction (TIMI) III grade flow in the culprit vessel after optimal PCI; uncontrolled bleeding or other major complication after PCI of the culprit lesion; high risk of contrast nephropathy, adverse sedation effects, or radiation exposure injury; and presence of patient, operator, or healthcare team fatigue (algorithm 1). (See 'Other unfavorable scenarios' above.)
•Approach to patients without contraindications to additional PCI – In patients who do not have contraindications to additional PCI, the decision to perform PCI of nonculprit lesions and the timing of such PCI is determined by the presence of unstable lesions characteristics or, in the absence of unstable lesions, the clinical presentation:
-ST-elevation myocardial infarction – In patients who are stable after PCI of culprit lesions and who have anatomy amenable to PCI, we recommend performing PCI of all significant nonculprit lesions rather than PCI guided by additional tests for ischemia or symptoms of ischemia, PCI after discharge, or not performing PCI of nonculprit lesions (Grade 1B) (algorithm 1). For most patients, we suggest complete revascularization during the index procedure rather than as a staged procedure (Grade 2B). (See 'STEMI' above.)
-Non-ST-elevation myocardial infarction – In patients with NSTEMI who undergo PCI of culprit lesions but who have residual nonculprit lesions, we suggest performing PCI of all significant nonculprit lesions during the index admission rather than perform PCI guided by additional testing for ischemia or symptoms of ischemia or not performing PCI of nonculprit lesions (Grade 2C) (algorithm 1). (See 'NSTEMI' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Paul Sorajja, MD, who contributed to earlier versions of this topic review.
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