Class I
1. In patients whose anatomy is suitable, PCI should be performed when there is objective evidence of recur-
rent MI. (Level of Evidence: C)
2. In patients whose anatomy is suitable, PCI should be performed for moderate or severe spontaneous or provocable myocardial ischemia during recovery
from STEMI. (Level of Evidence: B)
3. In patients whose anatomy is suitable, PCI should be performed for cardiogenic shock or hemodynamic
instability. (See Section 6.3.1.6.4.6.) (Level of
Evidence: B)
Figure 26.Recommendations for initial reperfusion therapy when cardiogenic shock complicates STEMI. Early mechanical revascu- larization with PCI/CABG is a class I recommendation for candidates less than 75 years of age with ST elevation or LBBB who devel- op shock less than 36 hours from STEMI and in whom revascularization can be performed within 18 hours of shock, and a class IIa recommendation for patients 75 years of age or older with the same criteria. Eighty-five percent of shock cases are diagnosed after initial therapy for STEMI, but most patients develop shock within 24 hours. An IABP is recommended when shock is not quickly reversed with pharmacological therapy, as a stabilizing measure for patients who are candidates for further invasive care. Dashed lines indicate that the procedure should be performed in patients with specific indications only. Recommendations for staged CABG and PCI are discussed in the text, as are definitions of moderate and severe 3-vessel CAD. PCI = percutaneous coronary intervention; STEMI = ST-elevation myocardial infarction; IABP = intra-aortic balloon pump; CAD, coronary artery disease; IRA = infarct-related artery; CABG = coronary artery bypass graft surgery; LBBB = left bundle-branch block. Modified with permission from Hochman. Circulation 2003;107:2998-3002 (502).
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stable and less prone to rethrombosis and reocclusion. Thus, delaying PCI for days to weeks after fibrinolysis might improve survival, even though earlier routine PCI does not. To date, there have not been adequately sized trials to evalu- ate this treatment strategy. Two older, small, randomized tri- als (516,517) demonstrated similar LV function, rates of reinfarction, and mortality in patients randomized to PCI or conservative therapy.
6.3.1.6.5. A
CUTES
URGICALR
EPERFUSION.
Class I
Emergency or urgent CABG in patients with STEMI should be undertaken in the following circumstances: a. Failed PCI with persistent pain or hemodynamic
instability in patients with coronary anatomy suit-
able for surgery. (Level of Evidence: B)
b. Persistent or recurrent ischemia refractory to med- ical therapy in patients who have coronary anato- my suitable for surgery, have a significant area of myocardium at risk, and are not candidates for
PCI or fibrinolytic therapy. (Level of Evidence: B)
c. At the time of surgical repair of postinfarction VSR
or mitral valve insufficiency.(Level of Evidence: B)
d. Cardiogenic shock in patients less than 75 years old with ST elevation or LBBB or posterior MI who develop shock within 36 hours of STEMI, have severe multivessel or left main disease, and are suit- able for revascularization that can be performed within 18 hours of shock, unless further support is futile because of the patient’s wishes or contraindi- cations/unsuitability for further invasive care
(Level of Evidence: A)
e. Life-threatening ventricular arrhythmias in the presence of greater than or equal to 50% left main
stenosis and/or triple-vessel disease. (Level of
Evidence: B)
Class IIa
1. Emergency CABG can be useful as the primary reper- fusion strategy in patients who have suitable anatomy and who are not candidates for fibrinolysis or PCI and who are in the early hours (6 to 12 hours) of an evolv- ing STEMI, especially if severe multivessel or left
main disease is present. (Level of Evidence: B)
2. Emergency CABG can be effective in selected patients 75 years or older with ST elevation, LBBB, or posterior MI who develop shock within 36 hours of STEMI, have severe triple-vessel or left main disease, and are suitable for revascularization that can be performed within 18 hours of shock. Patients with good prior functional sta- tus who are suitable for revascularization and agree to invasive care may be selected for such an invasive strat-
egy. (Level of Evidence: B)
Class III
1. Emergency CABG should not be performed in patients with persistent angina and a small area of events, including bleeding, recurrent ischemia, emergency
CABG, and death. These studies have not been repeated in the modern interventional era with improved equipment, improved antiplatelet and anticoagulant strategies, and coro- nary stents, thus leaving the question of routine PCI early after successful fibrinolysis unresolved in contemporary practice. Studies of facilitated PCI are presently enrolling patients (36,396,471,504).
Hours to days after successful fibrinolysis. It was initially suggested that elective PCI of the stenotic infarct-related artery hours to days after fibrinolysis might allow sufficient time for development of a more stable hemostatic milieu at the site of previous thrombotic occlusion. In this setting, PCI would be safer and more effective in reducing the incidence of reocclusion and improving survival. Two large random- ized, prospective trials from an earlier PCI era tested this hypothesis, with both concluding that 1) there are fewer complications if PCI is delayed for several days after fibri- nolytic therapy and 2) routine PCI in the absence of sponta- neous or provocable ischemia does not improve LV function or survival (268,505-507). Thus, in unselected patients receiving fibrinolytic therapy, PCI of the stenotic infarct- related artery in the absence of evidence of recurrent ischemia within 48 hours did not appear to be beneficial.
Great improvements in equipment, operator experience, and adjunctive pharmacotherapy have increased PCI success rates and decreased complications. More recently, the inva- sive strategy for patients with NSTEMI has been given a Class I recommendation by the ACC/AHA 2002 Guideline Update for the Management of Patients With Unstable Angina/NSTEMI (4). Patients with STEMI are increasingly being treated similarly as an extension of this approach. Although 6 published reports (472,508-512) and 1 prelimi- nary report (Lablanche JM; oral presentation, American Heart Association 2002 Annual Scientific Sessions, November 2002, Chicago, IL) support this strategy, random- ized studies similar to those in NSTEMI need to be per- formed.
One study supports the policy of performing catheteriza- tion and subsequent revascularization for patients who do have spontaneous or inducible angina after STEMI. The DANAMI trial (515) randomly assigned 1008 survivors of a first acute MI treated with fibrinolytic therapy within 12 hours of onset of symptoms to catheterization and subse- quent revascularization or standard medical therapy if they showed evidence of spontaneous or inducible angina. Those who underwent revascularization had less unstable angina and fewer nonfatal MIs during a 2.5-year period of follow-up compared with those patients randomly assigned to medical treatment only (18% and 5.6% versus 30% and 10.5%, respectively).
Days to weeks after successful fibrinolysis. Continued thrombus lysis and remodeling of the infarct artery stenosis occur over the days to weeks after successful fibrinolysis, which makes the underlying residual coronary stenosis more
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patients with suspected STEMI who do not receive reperfu- sion therapy. Many of the studies (e.g., beta-blocker trials) that established therapies for MI patients preceded the reper- fusion era, and so their efficacy in patients with STEMI who did not receive reperfusion is clear. The acute use of aspirin was shown to be effective in patients who did and did not receive fibrinolytic therapy. Guideline-based recommenda- tions for nonreperfusion treatments should not vary whether or not patients received reperfusion therapy. The major dif- ference is that patients not receiving reperfusion therapy are considered to have a higher risk for future adverse events (261). (See Section 6.3.1.6.8.1.2 for discussion of the TETA- MI trial.)
6.3.1.6.7. A
SSESSMENT OFR
EPERFUSION.
Class IIa
It is reasonable to monitor the pattern of ST elevation, cardiac rhythm, and clinical symptoms over the 60 to 180 minutes after initiation of fibrinolytic therapy. Noninvasive findings suggestive of reperfusion include relief of symptoms, maintenance or restora- tion of hemodynamic and or electrical stability, and a reduction of at least 50% of the initial ST-segment ele- vation injury pattern on a follow-up ECG 60 to 90
minutes after initiation of therapy. (Level of Evidence:
B)
A high priority exists for the development of simple, accu- rate, readily available noninvasive techniques to assess the success of pharmacological reperfusion early, i.e., 60 to 90 minutes after administration of therapy. Prior studies evalu- ating clinical and ECG outcome measures of reperfusion used angiographic TIMI 2 or 3 flow as the “gold standard”; angiographic assessment of epicardial flow is now consid- ered inadequate to completely assess myocardial perfusion. Indeed, it is now clear that microvascular perfusion may be impaired despite achievement of TIMI 3 flow and less than 50% coronary narrowing; moreover, abnormal microperfu- sion has negative prognostic implications (395,527,528).
Myocardial contrast echocardiography, myocardial angio- graphic perfusion with assessment of angiographic blush in the myocardium, and ECG assessment of ST resolution are recognized as useful techniques for assessing myocardial perfusion. The relatively simple and readily available evalu- ation of the ECG ST-segment resolution that exceeds 50% at 60 to 90 minutes after reperfusion is a good indicator of enhanced myocardial perfusion (527). This finding is also associated with enhanced recovery of LV function, reduced infarct size, and improved prognosis (277,349,395,529-531). In the TIMI-14 study of 888 patients, those with TIMI 3 per- fusion and greater than 70% ST-segment resolution had sub- stantial enhancement of survival compared with those with- out ST-segment resolution and angiographically patent infarct arteries (531).
Santoro and colleagues (532) evaluated 158 consecutive patients with STEMI referred for direct angioplasty within 6
risk who are hemodynamically stable. (Level of
Evidence: C)
2. Emergency CABG should not be performed in patients with successful epicardial reperfusion but
unsuccessful microvascular reperfusion. (Level of
Evidence: C)
These recommendations are supplementary to those pub- lished recently in a more complete set of general guidelines and indications for CABG (518) and are restricted to patients with STEMI and associated complications. The basis for rec- ommending surgery in emergency circumstances is the doc- umented benefit of CABG for severe multivessel disease or left main coronary artery stenosis, particularly with reduced LV function (518-521), with the recognition that risk of emergency CABG is greater than that for elective operation.
The widespread use of fibrinolysis and primary PCI has largely superseded CABG for acute reperfusion of patients with STEMI. However, CABG still plays an integral role in the early reperfusion strategy for some patients. In the PAMI (Primary Angioplasty in Myocardial Infarction)-2 trial (522), of 1100 patients with MI and without cardiogenic shock, 5% underwent CABG as the primary reperfusion strategy with STEMI. Mortality was 6.4% if surgery was undertaken on an urgent or emergency basis versus 2.0% if elective. Major risk factors for death included poor LV function and advanced age. In the setting of cardiogenic shock complicating STEMI, emergency CABG has been used where other inter- ventions have failed or have not been indicated. In the SHOCK registry (523), of 136 patients undergoing emer- gency CABG for cardiogenic shock due to LV failure, mor- tality was 27.9% compared to 45.5% in 268 patients under- going PTCA. For patients undergoing CABG within 18 hours of the onset of shock, mortality was 39.6%. In a review of 25 papers reporting the outcome of CABG in 391 patients with cardiogenic shock, mortality was 35% (524). In GUSTO-I, mortality in a similar group of patients was 29% (98 of 340) after CABG and 29% (165 of 567) (422,525,526) after PTCA. On the basis of these studies, emergency CABG should only be considered for patients with STEMI with severe coronary artery disease. In the SHOCK trial, emer- gency CABG was performed at a median of 14 hours after the onset of STEMI in 40% of those who underwent early revascularization; most of the patients undergoing CABG had significant left main or 3-vessel coronary artery disease. The 30-day mortality rate was similar to those with less severe coronary artery disease who underwent PTCA (42% versus 45%).
6.3.1.6.6. P
ATIENTSW
ITHSTEMI N
OTR
ECEIVINGR
EPERFUSION. Many patients with suspected STEMI do notreceive reperfusion therapy. For some of these patients, the lack of treatment represents a missed opportunity. For others, patient preference led to a decision that the clinical benefit was not worth the risk of the therapy. Other patients may have contraindications to treatment owing to comorbid dis- ease. Few studies have examined the care and outcomes of
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2. Unfractionated heparin should be given intravenous- ly to patients undergoing reperfusion therapy with alteplase, reteplase, or tenecteplase with dosing as fol- lows: bolus of 60 U/kg (maximum 4000 U) followed by an infusion of 12 U/kg/hr (maximum 1000 U) initially adjusted to maintain activated partial thromboplastin time (aPTT) at 1.5 to 2.0 times control (approximate-
ly 50 to 70 seconds). (Level of Evidence: C)
3. Unfractionated heparin should be given intravenous- ly to patients treated with nonselective fibrinolytic agents (streptokinase, anistreplase, urokinase) who are at high risk for systemic emboli (large or anterior MI, atrial fibrillation (AF), previous embolus, or
known LV thrombus). (Level of Evidence: B)
4. Platelet counts should be monitored daily in patients
taking UFH. (Level of Evidence: C)
Class IIb
It may be reasonable to administer UFH intravenous- ly to patients undergoing reperfusion therapy with
streptokinase.(Level of Evidence: B)
Despite the use of UFH (533) in STEMI for over 40 years, there is continued controversy regarding its role. In patients who are treated with fibrinolytic therapy, recommendations for UFH therapy depend on the fibrinolytic agent chosen. The nonspecific fibrinolytic agents (streptokinase, anistre- plase, and urokinase) that produce a systemic coagulopathy, including depletion of factors V and VIII and massive pro- duction of fibrin(ogen) degradation products, are themselves anticoagulants. From this perspective, the need for conjunc- tive systemic anticoagulation with these agents conceptually is less compelling. However, the procoagulant potential of streptokinase, which induces extensive plasmin-mediated thrombin activity, has been noted as the rationale for antithrombotics (534). The rationale for UFH is clear for the more fibrin-specific agents, such as alteplase, reteplase, and tenecteplase. They induce less effect on the systemic coagu- lation system, and in many patients, very little breakdown of fibrinogen or depletion of coagulation factors is evident (535,536). Furthermore, the same procoagulant increase in thrombin activity is seen (534).
Over 60 000 patients were enrolled in the randomized ISIS-3 (357) and GISSI-2 (Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico)/International (353,354) trials comparing subcutaneous UFH with no rou- tine heparin in conjunction with streptokinase, anistreplase, and alteplase. During the period in which UFH was given, a small reduction in mortality (4 to 5 lives per 1000 treated) was observed in ISIS-3; however, by 30 days, the 2 to 3 lives saved per 1000 treated was no longer statistically significant. A small excess rate of hemorrhagic stroke (1 to 2 per 1000 treated patients) was observed together with a larger excess in systemic bleeding (3 to 5 per 1000 patients), although total stroke rate was not significantly increased. A meta-analysis of these and several smaller studies enrolling a total of 68 000 patients showed that 5 lives were saved per 1000 patients treated with UFH in addition to streptokinase (537). In the hours of symptom onset. In their observational study of
patients with TIMI grade 3 flow and less than 30% residual stenosis, 42 patients had less than 50% reduction in maximal ST elevation in a single lead versus 75 patients with at least 50% reduction in ST elevation. Those with ST-segment res- olution had enhanced infarct-zone functional recovery and improved ejection fraction. The reduction of ST-segment elevation was the only independent predictor of functional recovery.
Persistence of unrelenting ischemic chest pain, absence of resolution of the qualifying ST-segment elevation, and hemodynamic or electrical instability are generally indica- tors of failed pharmacological reperfusion and the need to consider rescue PCI. Aggressive medical support may be necessary in the interim. (See Section 6.3.1.6.4.5.)