**9.4. Identification of the culprit lesion**

Culprit lesion on coronary angiography usually have features suggestive of acute plaque rupture. Vulnerable plaques are usually consisted from thin-cap fibroatheroma, and when rupture of the plaque happens they are characterized morphologically by the presence of at least two of the following features: intraluminal filling defects consistent with thrombus, plaque ulceration (i.e. presence of contrast and hazy contour beyond the vessel lumen), plaque irregularity (i.e. irregular margins or overhanging edges), dissection or impaired flow [132–134]. Multiple complex plaques observed in up to 40% of NSTEMI patients with obstructive CAD [132, 134–138]. One-quarter of NSTEMI patients present with an acute occluded coronary artery and two-thirds of the occlusions are already collateralized at the time of angiographic examination [138, 139].

Identification of the culprit lesion or the differentiation between an acute/subacute and chronic occlusion may sometimes be challenging based solely on angiography data. The additive value of the information from the ECG using lead localization and the regional wall motion abnormalities by Echocardiography can help identify the culprit lesion. Intracoronary imaging like optical coherence tomography can help to identify non-obstructive thin-cap fibroatheroma while vasospasm can be provoked by test such as acetylcholine [140–142]. The value of Fractional flow reserve (FFR) guided PCI in NSTEMI patient has not been properly addressed. The achievement of maximal hyperemia may be unpredictable in NSTEMI because of the dynamic nature of coronary lesions and the associated acute microvascular dysfunction. As a result, FFR may be overestimated and the hemodynamic relevance of a coronary stenosis underestimated [142].

#### **9.5. Timing of invasive strategy**

Routine intervention has been associated with an improved outcome [143–146] however, the optimal timing of the intervention has not been well established. Early intervention might prevent ischemic events that could occur while the patient is awaiting a delayed procedure [147]. Alternatively, by treating a patient with intensive antithrombotic therapy and delaying intervention for several days, procedure-related complications might be avoided with intervention on a more stable plaque [148]. Thus, the question of when to intervene in patients with acute coronary syndromes without ST-segment elevation has not been definitively answered.

**Immediate invasive strategy** (<2 h from hospital admission) is recommended in very-highrisk NSTE-ACS patients with intent to perform vascularization because of the poor short- and long-term prognosis if left untreated.

**Early invasive strategy** (<24 h): Early invasive strategy is defined as coronary angiography performed within 24 h of hospital admission. Multiple studies showed no significant difference between early or delayed intervention groups in the rate of death, MI, stroke or major bleeds [130, 149–151].

In the early versus delayed invasive intervention in acute coronary syndromes clinical trial, prespecified analyses showed that early intervention improved the primary outcome in the third of patients who were at highest risk (GRACE risk score > 140) but not in the two thirds at low-to-intermediate risk (GRACE risk score ≤ 140) [129]. Early invasive strategy is recommended in patients with at least one high-risk criterion.

**Delayed invasive strategy** (<72 h): This is the recommended maximal delay for angiography in patients with low to intermediate risk [127, 149].

#### **9.6. Selective invasive strategy**

• Diabetes mellitus

76 Myocardial Infarction

**9.3. Pattern of coronary artery disease**

**9.4. Identification of the culprit lesion**

coronary stenosis underestimated [142].

**9.5. Timing of invasive strategy**

examination [138, 139].

• Reduced left ventricular function (ejection fraction <40%).

Angiographic patterns of CAD in NSTEMI patients are diverse, ranging from normal epicardial coronary arteries to a severely and diffusely diseased coronary arteries. Up to 20% of patients with NSTE-ACS have no lesions or non-obstructive lesions of epicardial coronary arteries, while among patients with obstructive CAD, 40–80% have multivessel disease [128–130].

Culprit lesions in the infarct-related artery are more often located within the proximal and mid segments, the left anterior descending coronary artery is the most frequent culprit vessel in both STEMI and NSTEMI-ACS (in up to 40% of patients). Left main coronary artery disease

Culprit lesion on coronary angiography usually have features suggestive of acute plaque rupture. Vulnerable plaques are usually consisted from thin-cap fibroatheroma, and when rupture of the plaque happens they are characterized morphologically by the presence of at least two of the following features: intraluminal filling defects consistent with thrombus, plaque ulceration (i.e. presence of contrast and hazy contour beyond the vessel lumen), plaque irregularity (i.e. irregular margins or overhanging edges), dissection or impaired flow [132–134]. Multiple complex plaques observed in up to 40% of NSTEMI patients with obstructive CAD [132, 134–138]. One-quarter of NSTEMI patients present with an acute occluded coronary artery and two-thirds of the occlusions are already collateralized at the time of angiographic

Identification of the culprit lesion or the differentiation between an acute/subacute and chronic occlusion may sometimes be challenging based solely on angiography data. The additive value of the information from the ECG using lead localization and the regional wall motion abnormalities by Echocardiography can help identify the culprit lesion. Intracoronary imaging like optical coherence tomography can help to identify non-obstructive thin-cap fibroatheroma while vasospasm can be provoked by test such as acetylcholine [140–142]. The value of Fractional flow reserve (FFR) guided PCI in NSTEMI patient has not been properly addressed. The achievement of maximal hyperemia may be unpredictable in NSTEMI because of the dynamic nature of coronary lesions and the associated acute microvascular dysfunction. As a result, FFR may be overestimated and the hemodynamic relevance of a

Routine intervention has been associated with an improved outcome [143–146] however, the optimal timing of the intervention has not been well established. Early intervention might

may be the underlying condition in 10% and a failure of bypass graft in 5% [128–132].

Patients with no recurrence of symptoms and none of the risk criteria (low risk patient), a noninvasive stress test preferably with imaging for inducible ischemia is recommended before deciding on an invasive strategy [152].

#### **9.7. Conservative treatment**

A conservative, early medical management strategy may be appropriate in patients with a low risk score, such subpopulations may not benefit from early invasive management especially low-risk women with NSTEMI [123, 124, 126]. Older patients may be considered at high risk for invasive approach regarding complications, but the benefit may be satisfactory from such approach in this subgroup [153–155]. Patients in whom an invasive strategy may be withheld by the treating physicians may include very elderly or frail patients, patients with comorbidities such as dementia, severe chronic renal insufficiency, or cancer and patients at high risk of bleeding complication. Ultimately patients care should be individualized and left at the discretion of the treating physician.

In the medically managed NSTE-ACS patients, the CURE study demonstrated that treatment with clopidogrel in addition to aspirin for 3–12 months, significantly lower the primary outcome (a composite of death from CV causes, non-fatal MI or stroke at 1 year) but there were significantly more major bleeds [94].

The association between clopidogrel use and the composite of death or MI was significant among patients presenting with NSTEMI compared with those presenting with unstable angina [156].

**11. Revascularization strategies and outcomes**

incomplete revascularization [168, 169].

occlusions or referring to CABG.

In patients with complex, multivessel disease presenting with NSTEMI, the decision whether to do complete vs. incomplete revascularization and weather to do the complete revascularization at the index admission or to stage it is challenging and need to be tailored to age, general patient condition and comorbidities. A complete revascularization strategy of significant lesions should be pursued in multivessel disease patients with NSTE-ACS based on several studies showing the benefit of early intervention when compared with the conservative approach [143, 166, 167]. Also, recent trials have shown a detrimental prognostic effect of

Non-ST Elevation Myocardial Infarction: Diagnosis and Management

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Pursuing completeness of revascularization for some patients with complex coronary anatomy may mean increasing the risk of PCI especially in the presence of complex chronic total

The decision to treat all the significant lesions in the same setting or to stage the procedures should be based on clinical presentation, comorbidities, complexity of coronary anatomy,

With respect to outcomes, periprocedural complications of PCI as well as the long-term ischemic risk remain higher in NSTE-ACS than in stable patients, despite contemporary management. Accordingly, the risk of CV death, MI or stroke in NSTE-ACS patients in recent trials was approximately 10 and 15% at 1 and 2 years follow-up, respectively [110, 170]. For ACS patients who underwent PCI, revascularization procedures represent the most frequent, most

Approximately 10% of NSTEMI patients may require CABG during their index hospitalization [173]. The proportion of patient with NSTEMI undergoing CABG for NSTEMI decreased from 2001 to 2009, while the proportion of patients undergoing coronary angiography and PCI markedly increased [174]. CABG in the setting of NSTEMI is challenging mainly because of the difficulties in balancing ischemic and bleeding risks in relation to the timing of surgery and perioperative antithrombotic therapy. In addition, NSTEMI patients present with a higher proportion of surgical high-risk characteristics, including older age, female gender, left main coronary

disease and LV dysfunction compared with patients undergoing elective CABG [175].

**13. Percutaneous coronary intervention vs. coronary artery bypass** 

The main advantages of PCI in the setting of NSTEMI are faster revascularization of the culprit lesion, a lower risk of stroke and the absence of deleterious effects of cardiopulmonary

ventricular function, revascularization modality and patient preference.

costly and earliest cause for rehospitalization [171, 172].

**12. Coronary artery bypass surgery**

**surgery**

In the TRILOGY ACS trial, prasugrel was not associated with a statistically significant reduction in the primary endpoint (death, MI or stroke) but there were more frequent TIMI major and minor bleeding [157]. In the PLATO study, the incidence of the primary endpoint was lower with ticagrelor than with clopidogrel, but at the expense of higher incidence of TIMI major bleeds in the ticagrelor-treated patients [158].
