.

called “no reflow.” The term “no reflow” implies poor microvascular flow and is only used after treating all significant epicardial stenoses. TIMI flow <3 is a predictor of poor outcomes, but TIMI 3 flow does not necessarily imply appropriate microvascular flow. In fact, only ~60% of patients with TIMI 3 flow achieve significant ST-segment resolution (= cellular reperfusion), and only 70% achieve appropriate myocardial blush (= microvascular reperfusion).^63,64 “Appropriate myocardial blush,” also called “myocardial blush grade 2 or 3,” is used to describe brisk contrast staining of the myocardium followed by contrast clearance and no residual myocardial stain by the next injection. Impaired coronary flow, impaired myocardial blush, or the lack of ST resolution implies: (i) distal microembolization, (ii) microvascular spasm, or (iii) myocyte injury and swelling from ischemia or reperfusion injury, especially late reperfusion, sometimes irreversible. The best long-term outcomes (survival and LV function) are seen in patients with ST-segment resolution and good myocardial blush, while intermediate outcomes are seen in patients with discordant findings.⁶⁵

      Persistent ST elevation after successful primary or rescue PCI implies microvascular obstruction or cellular injury, and thus worse long-term prognosis. The patient may have mild persistent chest pain. Unlike persistent ST elevation after thrombolysis, persistent ST elevation after a successful PCI does not dictate any further procedure, unless the patient has severe recurrence of pain.

      Patients with no-reflow are treated with (i) intracoronary vasodilators, (ii) GPI, or (iii) IABP. After treatment of the epicardial stenosis, IABP improves coronary microvascular flow and relieves ongoing ischemia.

      When angiography is performed in patients who have been successfully reperfused with fibrinolytics, data from the pharmacoinva- sive trials suggests that ~15–20% of the infarct-related arteries have a residual stenosis <50% that does not require PCI.^30,43,66,67 While most plaques that lead to MI are <50% at baseline, fibrinolytics often partially dissolve the thrombus, not fully, hence the frequent residual obstruction.

      B. Multivessel disease in STEMI

      Approximately 50–60% of patients presenting with STEMI have multivessel CAD, and up to 40% have multiple complex plaques.^45,61,68

      The traditional teaching had been to only treat the culprit artery in hemodynamically stable patients, and to concomitantly treat culprit and non-culprit arteries in cardiogenic shock. Evidence now suggests the opposite: stable patients may safely undergo non-culprit PCI acutely, while cardiogenic shock patients with a clear culprit artery have a dramatic 8% absolute increase in mortality if non-culprit PCI is performed acutely (CULPRIT-SHOCK trial, STEMI or NSTEMI).⁶⁹ Non-culprit PCI increases procedural time and contrast load, leading to more LV volume overload and renal injury and is hazardous in the hemodynamically compromised patient. Also, non-culprit PCI may induce peri-PCI myocardial injury, distal embolization or side branch compromise, unlikely to be tolerated in the tenuous patient.

      Outside cardiogenic shock, complete revascularization of non-culprit arteries with stenoses >70%, regardless of the presence of residual symptoms or ischemia, was beneficial and reduced the 3-year risk of future MI, mainly NSTEMI, in comparison to culprit-only PCI, according to the large COMPLETE trial (5.4% vs. 7.9%); of note, mortality was not reduced. Non-culprit PCI was performed during a procedure separate from culprit PCI, within the same hospitalization or up to 45 days after discharge.⁷⁰ Other trials have suggested the safety of non-culprit PCI in the same setting as culprit PCI (PRAMI, Compare-acute) or separately during the same hospitalization (DANAMI-3 PRIMULTI).^71,72 Only COMPLETE has shown a reduction in MI, and thus, non-culprit PCI at a separate setting may be favored, during the same hospitalization (especially if critical stenosis >90%) or soon after it, as long as non-culprit PCI is feasible and the patient is not too sick to tolerate it. Immediate non-culprit PCI may be performed, while accounting for the complexity of PCIs and the total contrast load.

      CABG is rarely required acutely in STEMI (~0.2-1%),^62,63 but may be more frequently required in patients with cardiogenic shock and severe left main or three-vessel disease. In fact, in the SHOCK trial, 37% of invasively managed patients were emergently revascularized with CABG (a median of 2.7 hours after randomization, 19 hours after MI).⁷³ Acute CABG may also be required after a failed PCI.

      If staged CABG is judged necessary for full revascularization of non-culprit arteries after culprit PCI, it is preferred to wait at least 24 hours, and preferably 3–7 days. CABG mortality is increased in the first 3 days after a large MI.⁷⁴ In patients who developed RV infarct and were not successfully reperfused in the first 6 hours, it is better to delay CABG 4 weeks to let the RV heal (otherwise, there may be severe, intractable RV dilatation upon opening the pericardium during CABG). In a patient with left main or three-vessel disease and RCA-related MI, the RCA is stented and CABG performed 1 month later. If CAD is critical (e.g., > 75% left main stenosis), one may recanalize the RCA with balloon angioplasty and perform CABG sooner, a few days later.

IX. Antithrombotic therapies in STEMI

      A. Antithrombotic therapies in conjunction with primary PCI

      1 Aspirin 325 mg upon presentation.

      2 ADP-receptor antagonist is loaded at the time of PCI, or in the emergency room before catheterization if STEMI diagnosis is certain.75 Even prasugrel may be loaded before catheterization in STEMI. Yet, ATLANTIC trial failed to show a benefit of pre-cath loading vs. loading during PCI.76Ticagrelor and prasugrel are preferred as they further reduce ischemic events compared to clopidogrel, particularly in STEMI.

      3 Upstream unfractionated heparin (UFH) in the ED (60 units/kg, up to a maximum dose of 4000 units).

      4 During PCI:UFHBivalirudin vs. UFH: initial studies suggested lower bleeding with bivalirudin, but these studies were flawed by an unbalanced GPI use with UFH. A radial-access study with balanced and limited GPI use (SWEDEHEART) showed an ischemic and bleeding risk identical to UFH.77 Also, bivalirudin may be associated with a higher risk of acute stent thrombosis than UFH, which is reduced by 1-4 hours of high-dose bivalirudin post-PCI. Except for this optional brief infusion of bivalirudin, anticoagulants are stopped after PCI.GPI, in conjunction with either UFH or bivalirudin, is reserved for bailout use during PCI (large thrombus burden, thrombotic complications, or no reflow) (class IIa).78 In contemporary trials, ~15% of STEMI patients require the use of GPI.

      B. Antithrombotic therapies in patients treated with fibrinolytics (started upon presentation)

      1 Aspirin 325 mg.

      2 Clopidogrel 300 mg load if patient is <75 years old, or 75 mg if >75 years old (300 mg rather than 600 mg is the dose studied with fibrinolytics, even in pharmacoinvasive trials; 75 mg is the only dose studied with fibrinolytics in elderly patients).79,80

      3 UFH IV bolus 60 units/kg (not more than 4000 units), followed immediately by heparin drip 12 units/kg/h, adjusted Q6h to keep the PTT 1.5–2.0× the control.

      If the patient is going to have fibrinolytic reperfusion rather than PCI reperfusion, and if PCI is not expected in the next 24 hours, enoxaparin SQ or fondaparinux SQ may be used instead of UFH. In the patient receiving primary fibrinolytic reperfusion, enoxaparin or fondaparinux has a more favorable effect on reinfarction risk than UFH, with less major bleeding with fondaparinux, vs. more major bleeding with enoxaparin.^81,82 Patients undergoing standalone fibrinolytic therapy should receive anticoagulants for at least 48 hours and preferably for the duration of the hospitalization. Regimens other than UFH are preferred for anticoagulation >48 hours, because UFH is of no proven benefit beyond 48 hours.

       Dosage of enoxaparin: initial 30 mg IV dose, followed 15 minutes later by 1 mg/kg SQ Q12hFor patients >75 years old, avoid IV dose and administer 0.75 mg/kg Q12hIf GFR <30 ml/min, administer 1 mg/kg SQ Q24h

       Dosage of fondaparinux: 2.5 mg IV initially, then 2.5 mg SQ Qday. Avoid if GFR <30 ml/min.

      Clopidogrel