43 ST-segment elevation MI

Acute myocardial infraction with ST-segment elevation is a common and dramatic manifestation of coronary artery disease. It is caused by the rupture of an atherosclerotic plaque in a coronary artery leading to its total thrombotic occlusion and resultant ischaemia and necrosis of downstream myocardium.

The diagnosis of ST-segment elevation is based on a syndrome of ischemic chest pain symptoms associated with typical ST-segment elevation on the electrocardiogram and an eventual rise in biomarkers of myocardial necrosis.

The treatment of ST-segment elevation is focused on re-establishing blood flow in the coronary artery involved, preferably by percutaneous coronary intervention, or by pharmacological thrombolysis in the case of expected lengthy time delays or lack of availability of facilities.

Early mortality from ST-segment elevation can be attributed to the sequelae or complications of myocardial ischaemia, or complications related to therapy. The former includes arrhythmias such as ventricular tachycardia or fibrillation; mechanical complications such as ventricular free wall, septal and mitral chordal rupture; and pump failure leading to cardiogenic shock. The latter includes hemorrhagic complications and coronary stent thrombosis.

Given that myocardial necrosis is a critically time-dependent process, the organization of a ST-segment elevation care system, and adherence to the latest clinical trial evidence and guidelines, is crucial to ensure that patients are treated in an optimal manner.

Worldwide, coronary artery disease (CAD) is the single most frequent cause of death. Over 7 million people every year die from CAD, accounting for 12.8% of all deaths. Every sixth man and every seventh woman in Europe will die from MI. Among the European Society of Cardiology (ESC) member countries, the incidence of hospital admissions for ST-segment elevation myocardial infraction (STEMI) varies [1]. One of the most comprehensive STEMI registries in Sweden showed an incidence is 66 STEMI/100,000/year. Similar figures were also reported in the Czech Republic [2], Belgium [2], and the USA [3]. The rates (per 100 000) of STEMI decreased in these countries between 1997 and 2005 from 121 to 77, whereas there was a concomitant increase in the rates of non-STEMI from 126 to 132 [4]. Mortality from STEMI is influenced by many factors, among which are: age, the Killip class, the time delay to treatment, the mode of treatment, a prior history of MI, diabetes mellitus, renal failure, the number of diseased coronary arteries, ejection fraction, and treatment. In-hospital mortality of unselected STEMI patients in the national registries of the ESC countries varies between 6 and 14% [5]. Several recent studies have highlighted a fall in acute and long-term mortality following STEMI, in parallel with greater use of reperfusion therapy, primary PCI (primary PCI), modern antithrombotic therapy, and secondary prevention treatments [2, 3, 6, 7]. Yet, mortality rates as high as 12% of patients at 6 months have been reported [8], with even higher rates in high-risk patients [9], justifying the continued efforts to improve the quality of care and adherence to guidelines.

The diagnosis and management of MI starts at the point of first medical contact (FMC), which is the point at which the patient is either initially assessed by a paramedic, physician, or other medical personnel in the pre-hospital setting, or when the patient arrives at the hospital emergency department (ED) [10] (see Chapter 42). This is the point at which a health professional is in physical contact with the patient and able to activate the chain of diagnosis and treatment, and is capable, if needed, of providing resuscitation. A working diagnosis of acute myocardial infraction (AMI) must first be made urgently to enable its optimal management. This is usually based on a history of chest pain (CP) lasting for 20 min or more, not relieved by nitroglycerin. Important clues are a history of CAD and radiation of the pain to the neck, lower jaw, or left arm. The pain may not be severe, and some patients present with less typical symptoms, such as nausea/vomiting, shortness of breath, fatigue, palpitations, or syncope. These patients tend to present later, are more likely to be women, diabetic, or elderly patients, and less frequently receive reperfusion therapy and other evidence-based therapies than patients with a typical CP presentation. Registries show that up to 30% of patients with STEMI present with atypical symptoms [11] (see Chapter 4). Awareness of these atypical presentations and ready access to emergency angiography for early diagnosis might improve outcomes in this high-risk group.

Supplemental oxygen may be administered if pulse oximetry shows an oxygen saturation of <90%, as in the registry-based DETO2X[¹²] trial, no long-term benefit was found from administering oxygen when oxygen saturation was above 90%; harm might even be done by increasing myocardial infarct size as was demonstrated in the AVOID¹³ study. Opiods such as morphine might be useful to reduce symptoms and the associated, presumably deleterious, heightened sympathetic drive.

Initially, continuous electrocardiogram (ECG) monitoring should be established as soon as possible in all patients with suspected STEMI to detect life-threatening arrhythmias and allow prompt defibrillation if indicated. A 12-lead ECG should be obtained and interpreted as soon as possible at the point of FMC [14]. The ECG is seldom normal, even at an early stage. ST-segment deviation is measured at the J point; a typical ST-elevation pattern should be present in at least two contiguous leads and be ≥0.25 mV in men below the age of 40 years, ≥0.2 mV in men over the age of 40 years, or ≥0.15 mV in women in leads V2–V3 and/or ≥0.1 mV in other leads (in the absence of left ventricular (LV) hypertrophy or left bundle branch block (LBBB) [15]. In patients with inferior MI, it is advisable to record right precordial leads (V3R and V4R) seeking ST-elevation, in order to identify concomitant right ventricular (RV) infarction [15, 16]. Likewise, ST-segment depression in leads V1–V3 suggests RV myocardial ischaemia, especially when the terminal T-wave is positive (ST-elevation equivalent), and may be confirmed by concomitant ST elevation ≥0.1 mV recorded in leads V7–V9 [15].

The ECG diagnosis may be more difficult in some cases; nevertheless, they deserve prompt management. In the presence of LBBB, the ECG diagnosis of MI is difficult, but often possible if marked ST abnormalities are present. Somewhat complex algorithms have been offered to assist in the diagnosis [15], but they do not provide diagnostic certainty [16]. The presence of concordant ST elevation (i.e. in leads with positive QRS deflections) appears to be one of the best indicators of on-going MI with an occluded infarct artery [17]. Previous data from thrombolysis trials have shown that reperfusion therapy is beneficial overall in patients with LBBB and suspected MI. However, most LBBB patients evaluated in the emergency department do not have an acute coronary occlusion, nor do they require primary PCI. A previous ECG may be helpful in determining whether the LBBB is new (and therefore highly suspicious of an on-going MI). Importantly, in patients with clinical suspicion of on-going myocardial ischaemia with new or presumed new LBBB, reperfusion therapy should be considered promptly, preferably using emergency coronary angiography with a view to primary PCI or, if unavailable, IV thrombolysis. A positive point-of-care troponin (POCT) test 1–2 hours after symptom onset in patients with bundle branch block of uncertain origin may help decide whether or not to proceed to emergency angiography, with a view to perform primary PCI.

Patients with MI and right bundle branch block (RBBB) also have a poor prognosis [18], although RBBB usually does not hamper interpretation of ST-segment elevation [19]. Prompt management should be considered when persistent ischaemic symptoms occur in the presence of RBBB, regardless of whether the latter is previously known or not. Ventricular pacing may also prevent the interpretation of ST-segment changes and may require urgent angiography to confirm diagnosis and initiate therapy. Reprogramming the pacemaker—allowing the evaluation of ECG changes during an intrinsic heart rhythm—may be considered in patients known not to be dependent on ventricular pacing, reducing delays to invasive investigation if indicated.

Occasionally, patients seen very early after symptom onset may have an initial ECG without ST-segment elevation (in which case, the ECG should be screened for hyper-acute T waves (Figure 43.1), which may precede ST-segment elevation). It is important to repeat the ECG or monitor the ST segment. In addition, there is a concern that some patients with a genuine acute occlusion of a coronary artery and on-going myocardial infraction (MI) (such as those with an occluded circumflex coronary artery [19, 20], acute occlusion of a coronary artery bypass graft, or left main disease), may present without ST-segment elevation and be denied reperfusion therapy, resulting in larger infarction and worse outcomes. Extending the standard 12-lead ECG with V7–V9 leads, while useful, does not always identify these patients. Consequently, persistent suspicion of myocardial ischaemia despite medical therapy, is an indication for emergency coronary angiography, with a view towards revascularization, even in patients without diagnostic ST-segment elevation [21].

The ECG finding of an isolated ST depression ≥0.05 mV in leads V1 through V3 often corresponds to an acute MI (AMI) of the inferobasal portion of the heart, commonly part of the territory of the left circumflex artery, and should be treated as a STEMI. The use of additional posterior chest wall leads V7–V9 ≥0.05 mV (≥0.1 mV in men <40 years old) is recommended to detect ST elevation related to inferobasal MI.

The presence of ST-depression of 0.1 mV in eight or more surface leads, coupled with ST elevation in a VR or V1, or both (see Figure 43.3), on an otherwise unremarkable ECG, suggests ischaemia due to multivessel or left main coronary artery obstruction, particularly if the patient presents with haemodynamic compromise [22, 23].

In patients with a suspicion of myocardial ischaemia and ST-segment elevation, or new or presumed new LBBB, reperfusion therapy needs to be initiated as soon as possible. However, the ECG may be equivocal in the early hours and, even in proven infarction, may neither show the classical features of ST-segment elevation nor new Q waves. If the ECG is equivocal or does not show evidence to support the clinical suspicion of MI, ECGs should be repeated, and compared with previous tracings when available. Additional recordings of leads V7, V8, and V9 may be helpful in making the diagnosis in selected cases.

Blood sampling for serum markers, see Chapter 36, is routinely carried out in the acute phase, but one should not wait for the results before initiating reperfusion treatment. Troponin (T or I) is the biomarker of choice, given its high sensitivity and specificity for myocardial necrosis. In patients who have both a clinically low or intermediate likelihood of on-going myocardial ischaemia and a long duration of symptoms, a negative troponin test may help to avoid unnecessary emergency angiography.

If in doubt regarding the possibility of an acute evolving MI, emergency imaging (as opposed to waiting for the biomarkers to become elevated) allows the provision of timely reperfusion therapy to these patients. If locally available, emergency coronary angiography is the modality of choice, as it can be followed immediately by primary PCI if the diagnosis is confirmed. In hospitals or settings in which coronary angiography is not immediately available—provided it does not delay transfer—a rapid confirmation of segmental wall-motion abnormalities by two-dimensional (2D) echocardiography may assist in making a decision for an emergency transfer to a PCI centre, since regional wall-motion abnormalities occur within minutes following coronary occlusion, well before necrosis. However, wall motion abnormalities are not specific for AMI and may be due to other causes such as ischaemia, an old infarction, or ventricular conduction defects. 2D echocardiography, see Chapter 20, is of particular value for the diagnosis of other causes of CP, such as pericardial effusion, massive pulmonary embolism or dissection of the ascending aorta. The absence of wall-motion abnormalities effectively excludes a major MI.

In the emergency setting, the role of CT scan, see Chapter 22, should be confined to differential diagnosis of acute aortic dissection or pulmonary embolism. Stress-induced (Takotsubo) cardiomyopathy is a recently recognized syndrome, which may be difficult to differentiate from STEMI. Symptoms and findings, ranging from slight CP to cardiogenic shock (CS), may mimic an AMI, while the ECG changes at presentation are usually modest and do not correlate with the severity of ventricular dysfunction. It is often triggered by physical or emotional stress and characterized in its typical form by transient apical or mid-LV dilation and dysfunction. Because there is no specific test to rule out MI in this setting, emergency angiography should not be delayed and, in the absence of MI, will show neither significant culprit coronary artery stenosis nor intracoronary thrombi. The diagnosis is confirmed by the finding of transient apical- to mid-ventricular ballooning, with compensatory basal hyperkinesis, and by disproportionately low plasma levels of cardiac biomarkers with respect to the severity of ventricular dysfunction and, eventually, the recovery of the LV function [24].

Prevention of delays is critical in STEMI for two reasons: first, the most critical time of an AMI is the very early phase, during which the patient is often in severe pain and liable to cardiac arrest. A defibrillator must be made available to the patient with suspected AMI as soon as possible, for immediate deVF, if needed. In addition, an early provision of therapy, particularly reperfusion therapy, is critical to its highly time-dependent benefits. Thus, minimizing delays is associated with improved outcomes. In addition, delays to treatment are the most readily available, measurable index of quality of care in STEMI; they should be recorded in every hospital providing care to STEMI patients and monitored regularly, to ensure that simple quality of care indicators are met and maintained over time. Although still debated, public reporting of delays may be a useful way of stimulating improvement in STEMI care. If targets are not met, then interventions are needed to improve performance. There are several components of delay in STEMI and several ways to record and report them, see also Chapter 42.

This is the delay between symptom onset and FMC. To minimize patient delay, the public should be made aware of how to recognize common symptoms of AMI and to call the emergency services promptly, but the effectiveness of public campaigns has not yet been clearly established [23]. Patients with a history of coronary artery disease (CAD), and their families, should receive education on the recognition of symptoms due to acute MI and the practical steps to take should a suspected acute coronary syndrome (ACS) occur. It may be wise to provide stable CAD patients with a copy of their routine baseline ECG for comparison purposes by medical personnel.

A good index of the quality of care is the time taken to record the first ECG. In hospitals and emergency medical services (EMSs) participating in the care of STEMI patients, the goal should be to reduce this delay to 10 min or less.

This is the ‘system delay’. It is more readily modifiable by organizational measures than patient delay. It is an indicator of quality of care and a predictor of outcomes [25]. If the reperfusion therapy is fibrinolysis, the goal is to reduce this delay first medical contact (FMC) to guidewire passage into the culprit artery of <90 min (and in high-risk cases with large anterior infarcsts or early presenters within 2 hours it should be <60 mins) [26, 27]. If the reperfusion therapy is fibrinolysis (FL) the goal is to reduce this delay (FMC to needle) to <30 min. In hospitals with on-site PCI capacity, the goal should be a delay (STEMI diagnosis to guidewire passage into the culprit artery) of <60 min [26, 27] in hospitals with onsite PCI capability. the goal should be to achieve a ‘door-to-reperfusion delay’ of ≤60 min between the presentation in hospital and primary PCI (defined as wire passage into the culprit artery). This delay reflects the organization and performance of the hospital with on-site PCI capacity. Importantly, while it is important to achieve the shortest possible systems delays, the choice between thrombolysis and primary PCI as reperfusion therapy is not based on these quality indicators but (as detailed later), on the predicted possibility to provide primary PCI within 120 mins.

From the patient’s perspective, the delay between symptom onset and provision of the reperfusion therapy (either starting FL or passing a wire through the culprit vessel) is possibly the most important, since it reflects total myocardial ischaemia time. It should be reduced as much as possible.

The emergency medical system (EMS), see Chapter 7, is the centrepiece of the pre-hospital management of STEMI. Trained EMS crews with ambulances equipped with defibrillators, monitors, resuscitation equipment and telecommunication equipment, can enable the rapid transport of patients suspected to have STEMI to the nearest PCI-equipped centre or emergency room (ER) for further management, while providing effective pre-hospital care. Where available, air ambulances can help to reduce transportation delays and improve outcomes. Thus, crews must be well-trained in the interpretation of ECGs, the administration of basic therapies such as oxygen and aspirin, the telecommunication with the receiving hospital and the management of complications such as VF. Physician-accompanied EMS crews are available in a few countries, but are not a pre-requisite for effective pre-hospital care.

In some countries and situations, the FMC may well be the general practitioner of the patient, in which case his role is exactly the same as that of a paramedic in an EMS—he/she should initiate all the appropriate therapies at the same time as arranging emergency transport by the EMS system to a hospital with PCI capability. Delays should again be kept to a minimum.

The term ‘STEMI care network’ describes an integrated system of hospitals and EMS services that specifically aims to provide optimal care for STEMI patients, see Chapter 42. The ideal STEMI network has hospital with and without onsite PCI capability connected by efficient, well-equipped and well-trained teams of EMS and sharing unified STEMI care pathways and protocols.

The typical journey of a patient might begin at home, at symptom onset, whereby he/she calls the easily remembered EMS number, and a road- or air-ambulance arrives rapidly. An ECG is performed, and the diagnosis of STEMI is made on the vehicle, by paramedics on-board, with the help of telecommunication with cardiologists. An estimated time-to-catheter laboratory is given, and a decision made on reperfusion modality—preferably primary PCI if available. The ambulance bypasses a non-PCI-capable hospital and heads directly for a hospital with onsite PCI capability; on arrival the patient could be sped past the ER directly to the catheter laboratory for primary PCI, as this is associated with a 20-minute reduction in time delay according to registry data [30].

The pre-hospital course of a patient with STEMI is not always so perfect, so the network provides the flexibility and structure to take variations into account. If a patient presents to a hospital without PCI capability, he/she is monitored in a well-equipped area and given FL or transported as soon as possible to a hospital with onsite PCI capability. When the diagnosis of STEMI by the EMS is uncertain, the ambulance stops by the nearest hospital for a medical opinion. In the meantime, the patient stays on the ambulance or in a safely monitored area, ready to depart rapidly for a hospital with onsite PCI capability. If the EMS expects a long travel time to a hospital with onsite PCI capability, a decision is made as to whether or not to administer a fibrinolytic agent, possibly on the ambulance.

The aim of a STEMI network is to simplify the management of an inherently complex medical condition, mainly by implementing standardized treatment protocols. Thus, the minimization of potential sources of confusion in addition to the maximization of repetition and experience are strategies that may help to achieve this objective. Ideally hospitals with onsite PCI capability are dedicated centres operating a 24-hour/7-day service with staff that are well trained in the rapid reception and treatment of STEMI patients. Centres that are unlikely to have enough volume, and which do not have the capacity to offer a sufficient independent service, should be discouraged from doing so. Irregular and inconsistent service hours might also be a source of confusion. Some networks operate on a rotational basis between hospitals with onsite PCI capability.

In a US network, it has been shown that important components for reducing delays within the hospital with PCI capability itself include having a cardiologist onsite, the ability to activate the catheterization laboratory by a single call (preferably while the patient is en route to hospital), expecting laboratory staff to arrive in the catheterization laboratory within 20 min of being paged, and using real-time data feedback between upstream care services and the catheterization laboratory [31].

To encourage and review the efficacy of the network, regular audits, exchanges of experience between networks, and reviews of targets should be conducted, as each network will require different optimizations. The Stent for Life initiative in Europe is an example of an organization dedicated to improving access to timely, effective primary PCI through focussed implementation programmes, tailored to each specific national healthcare setting and attempting to learn from failures and successes [31].

For patients with the clinical presentation of STEMI within 12 h of symptom onset and with persistent ST-segment elevation or new or presumed new LBBB, early PCI or fibrinolysis should be performed as early as possible. There is general agreement that reperfusion therapy should be considered if there is clinical or electrocardiographic evidence of on-going ischaemia or both, even if the patient reports symptom onset >12h ago. This is because the exact onset of symptoms is often unclear, and sometimes the symptoms of pain and ECG changes have been stuttering [33].

A STEMI patient presenting within 12 h of the onset of symptoms should receive reperfusion therapy as early as possible. The preferred modality of reperfusion is primary PCI, but fibrinolytic pharmacotherapy (FL) may be considered as an option in specific situations. Given the sometimes stuttering and unclear onset of symptoms, it is also generally accepted that clinical and electrocardiographic signs of on-going myocardial ischaemia may be treated with reperfusion therapy even if the time of symptom onset is >12 hrs [33].

For asymptomatic patients presenting >12 hr after symptom onset, a small randomized study showed improved myocardial salvage and 4-year survival, but the larger Occluded Artery Trial (OAT) demonstrated no benefit of PCI over medical therapy alone in patients with occluded infarct-related arteries 3–28 days after MI, including a subset of patients randomized 24–72 hrs after symptom onset [34]. A meta-analysis came to the same conclusion, with a lack of benefit in late re-canalization of occluded coronary arteries after MI [34].

Primary PCI is the preferred modality of reperfusion compared to FL, given the higher rate of successful reperfusion, long-lasting patency of the infarct-related artery and lower chances of haemorrhagic complications. However, to achieve these potential benefits, primary PCI must be delivered in a timely manner by experienced staff in high-volume centres that operate a 24/7 service. Even if a patient presents to a hospital without PCI capability, rapid transfer across a STEMI network to a hospital with onsite PCI capability can still enable timely reperfusion [36–40]. If primary PCI cannot be performed under these conditions, then FL must be considered.

The choice between primary PCI and FL often rests on estimating the delay between FMC and the implementation of primary PCI (see Figure 43.1) [38]. If this delay is expected to be >120 min, then consideration should be given to FL, ideally delivered 30 min after FMC. These guideline-recommended timings are based on post hoc analyses of randomized controlled trials (RCTs) and the NRMI 2-4 registry [37] which found that the PCI-related delay that diminishes the advantage of primary PCI over FL varied between 60 and 120 min. This apparently wide range is accounted for by variations between subgroups, from <1 hour for an anterior AMI in a patient <65 years old to 3 hours for a non-anterior AMI in a patient >65 years old. Thus, the message is that the maximum acceptable PCI-related delay should be individualized, but, for the purposes of benchmarking, patients presenting directly to a primary PCI-capable hospital should ideally have primary PCI <60 min of FMC. Intriguingly, a recent study of the USNCDR CathPCI registry revealed progressive reductions in median door-to-balloon times, from 83 min to 67 min, but without the expected improvements in mortality at 1 year. Whether other parameters, such as heart failure and angina, were affected remains to be seen [26].

Furthermore, real-world experience in Australia has shown that 40% of its population may not have timely (<120 min FMC to balloon) access to primary PCI, particularly in rural areas [27]. In light of thesedata and the results of CAPTIM and STREAM—two trials showing no difference between primary PCI and pre-hospital thrombolysis followed by planned coronary angiography [39, 40]—a pharmaco-invasive strategy can be very effective, if administered in a systematic and rapid manner.

The radial access route primary PCI, when performed by experienced operators, is preferred over femoral access—both the RIVAL and RIFLE-STEACS trials concurred on this. STEMI patients receive multiple potent antiplatelet and anticoagulant agents and are at high risk of bleeding complications, especially at the access site. In MATRIX, 8404 ACS patients, 48% of whom who were STEMI patients, were randomised to femoral or radial access PCI. Net clinical events were significantly reduced, driven by a 33% reduction in the rate of major bleeding and a 28% reduction in all-cause mortality.

50% per cent of STEMI patients have multivessel disease. The results of the PRAMI randomised controlled trial of 467 patients demonstrated a 65% reduction in major adverse cardiac events (MACE)[46], in patients who had non-culprit lesions with >50% stenoses treated in the emergent setting in addition to culprit lesions when compared with conservative management. The CvLPRIT[47] trial, in which non-culprit lesions of >70% stenosis were treated in the intervention group, found a 53% reduction in MACE. Both the larger DANAMI-3-PRIMULTI[48] and Compare-Acute[49] trials tested a further refinement of the total revascularization strategy with PCI only to lesions causing luminal stenosis of >50% and with a fractional flow reserve (FFR) value of less than 0.80. In all four aforementioned trials, the risk of mortality or reinfarction was not reduced in the intervention group, and repeat revascularizations were reduced in PRAMI, DANAMI-3-PRIMULTI and Compare-Acute. With the current available evidence, complete revascularization at the time of pPCI may be regarded mainly as a strategy to reduce repeat procedures. Larger trials powered to determine the effect of complete revascularization are underway. In a patient with CS, however, pPCI to non-culprit vessels with critical (>90%) stenoses or angiographic signs of thrombus/plaque disruption can be justified [50].

Often the simple passage of a guidewire across the culprit lesion or a passage of a thrombus aspiration catheter is sufficient to restore flow in the IRA. Concerns about thrombus embolization can sometimes lead clinicians to defer stenting of the culprit lesion. The DAMNIMI 3-DEFER [51] trial was designed to aid in this decision. There was no significant difference in the primary endpoint of all-cause mortality, hospital admission for heart failure, recurrent MI, or unplanned revascularization of the IRA. So far, the evidence does not support a strategy of routine deferred stenting in primary PCI.

The decision between the use of bare-metal stents (BMS) and drug-eluting stents (DES) has been a compromise between the reduced restenosis risk of DES and the possibility of stent thrombosis and concerns over patient compliance with dual antiplatelet therapy (DAPT) over an extended period of time. Several recent, large trials have examined the clinical outcomes resulting from the use of DES vs. BMS. EXAMINATION[52] and COMFORTABLE-AMI[53] focused on STEMI patients, and both found that the risk of target lesion or vessel revascularization was lower; EXAMINATION found a lower risk of stent thrombosis whereas COMFORTABLE-AMI found a lower risk of target vessel-related reinfarction. Only 26% of patients had STEMI in NORSTENT[54], and the findings were also of a lower risk of repeat revascularization in the DES group, but no difference in all-cause mortality or MI. Taken together, the use of DES in pPCI is likely to reduce the need for repeat revascularization compared to BMS, and should be the first choice.

Importantly, operators should be wary of coronary spasm and the presence of thrombus during the procedure, which may confound stent sizing and result in early restenosis or stent thrombosis. Intracoronary nitrate injections can relieve spasm to some extent so as to reveal the true calibre of the vessel being treated.

Thrombus aspiration is sometimes performed prior to any angioplasty or stenting. Small trials underpowered to detect hard end-point differences, notably TAPAS[55] and INFUSE-AMI[56] gave mixed results on the use of this adjunctive therapy. The TASTE trial[57] found no difference in 30-day mortality, stent thrombosis or recurrent myocardial infarction hospitalisation. The TOTAL trial also found no difference in its primary end-point of cardiovascular death, myocardial infarction, cardiogenic shock or heart failure, and even detected significantly more strokes in the thrombus aspiration arm of 1.2% vs. 0.7% (HR 1.66; 95% CI 1.10-2.51) in the PCI-alone arm[58]. Finally a meta-analysis59 combining data from the TAPAS, TASTE and TOTAL trials found neither significant benefit nor harm associated with the use of thrombus aspiration, though in the subgroup of patients with high thrombus burden, its use was associated with fewer cardiovascular deaths at the cost of more stroke or transient ischemic attacks. Therefore, a routine strategy of thrombus aspiration is not recommended in PCI for STEMI, but it may be considered as a bail-out strategy in select patients with high thrombus-load despite conventional treatment.

A strategy of routine insertion of an intra-aortic balloon pump (IABP), see Chapter 30, during primary PCI was tested in the CRISP AMI trial [6-] involving patients with anterior MI and not in shock. In addition to a lack of benefit, IABP insertion was associated with an increase in bleeding. The attractive concepts of myocardial pre- and post-conditioning have been explored in small trials. Pre-conditioning using intermittent arm ischaemia resulted in improvements in myocardial salvage as measured by perfusion imaging at 30 days [61]. Post-conditioning with repeated intracoronary balloon inflations or cyclosporine infusions have produced conflicting result [62,63,64,65,66]. These therapies cannot be recommended until they are proven in larger randomized controlled trials.

STEMI patients undergoing primary PCI should receive a combination of aspirin and an adenosine diphosphate (ADP)-receptor blocker as early as possible before angiography (See Table 5.1), and a parenteral anticoagulant during the procedure (see Table 5.2).

Prasugrel, at a loading dose of 60 mg orally and a maintenance dose of 10 mg daily, was compared against clopidogrel in the TRITON-TIMI 38 trial in ACS patients undergoing PCI. It was shown to reduce cardiovascular death, non-fatal MI, or stroke, whilst increasing non-CABG-related bleeding risk. The results in the subset of STEMI patients were consistent, but without any clear increase in bleeding [55]. Importantly, prasugrel is contraindicated in patients who have suffered a prior stroke or transient ischaemic attack (TIA) and should be used with caution (and at a reduced dose of 5 mg, based on pharmacodynamics data [56]) in patients >75 years of age, <60 kg in weight, due to a finding of increased net harm in these groups. Alternative antiplatelet agents may be considered in these situations.

In the PLATO trial, ticagrelor, at a loading dose of 180 mg orally and maintenance dose of 90 mg twice daily, reduced cardiovascular death, stroke or non-fatal MI in a broad range of ACS patients, when compared to clopidogrel, regardless of the loading dose of the latter. While the overall bleeding rate was not different, ticagrelor increased TIMI and PLATO-defined non-CABG major bleeding [69–70]. The results were consistent in the subset of STEMI patients. Ticagrelor, presumably due to its molecular similarity to ADP, can cause self-limiting dyspnoea and bradycardia during the initial therapeutic period, but there is no evidence to suggest a deleterious effect in terms of cardiovascular outcomes [70–72].

In situations where these two more potent antiplatelet agents are not available or are contraindicated, such as in those with a history of prior bleeding, or in patients with an indication for chronic anticoagulation, or in patients with moderate-to-severe liver disease, clopidogrel can be used. In the context of primary PCI, both pharmacokinetic data and observational studies support pre-treatment compared to in-cathlab loading [72ߝ73]. A 600 mg oral loading dose followed by a 150 mg daily maintenance dose during the first week and 75 mg daily for the remaining duration of therapy was not proven to be superior to a 300 mg/75 mg regimen in CURRENT OASIS-7 [74] although such a regimen was associated with improved outcomes in the subset of patients who actually underwent PCI. This is consistent with pharmacokinetic data, as clopidogrel is a prodrug that requires metabolism to become active.

Cangrelor, an intravenous reversible P2Y12 inhibitor, is an option for antiplatelet therapy. A single randomized trial comparing cangrelor [75] in PCI with clopidogrel—but not ticagrelor or prasugrel—found that cangrelor reduced the risk of the primary composite ischemic end point without increasing the risk of bleeding. Although a further pooled analysis [76] of the trials in the CHAMPION series showed that periprocedural ischemic events were reduced at the cost of an increased risk of bleeding. Furthermore, only 18% of patients in the CHAMPION trial series underwent PCI for STEMI. The applicability of this medicine might be limited to patients who cannot be pre-treated with, or who are unable to absorb oral P2Y12 inhibitors.

Anticoagulant options for primary PCI include unfractionated heparin (UFH), enoxaparin, and bivalirudin, with GP IIb/IIIa inhibitors used in ‘bailout’ situations (see Table 43.2). The use of fondaparinux in the context of primary PCI was associated with potential harm in the OASIS 6 trial and is therefore not recommended [63]. (See also Chapter 44.)

There have been no placebo-controlled trials evaluating UFH in primary PCI but there is a large body of experience with this agent and UFH was part of the protocol in the trials that prove primary PCI to be superior to fibrinolysis. Dosage should follow standard recommendations for PCI (initial bolus 70–100 U/kg when no glycoprotein (GP) IIb/IIIa inhibitor is planned or 50–60 U/kg when the use of GP IIb/IIIa inhibitors is expected. The use of activated clotting time to tailor dose or monitor UFH has no strong evidence basis. If activated clotting time is used, it should not delay recanalization of the infarct-related artery. Several non-randomized studies have suggested that enoxaparin (0.5 mg/kg IV followed by SC treatment) is superior to UFH in primary PCI [78–80]. Compared with UFH in the randomized open-label ATOLL trial, the primary composite endpoint of 30-day death, complication of MI, procedural failure, and major bleeding was not significantly reduced (17% reduction, P = 0.063), although there were reductions in the composite main secondary endpoint of death, recurrent MI, or ACS or urgent revascularization, and in other secondary composite endpoints such as death, or resuscitated cardiac arrest and death, or complication of MI. Importantly, there was no indication of increased bleeding from use of enoxaparin over UFH [67–81]. Based on these considerations and on the extensive clinical experience with enoxaparin in other PCI settings [67, 70, 83], enoxaparin may be preferred over UFH.

Multiple trials have examined the choice between bivalirudin and heparin as periprocedural anticoagulation in primary PCI—HORIZONS-AMI [83], EUROMAX [84], HEAT-PRIMARY PCI [85], BRIGHT [86], MATRIX [51]. A meta-analysis [87] including the former four trials concluded that the use of bivalirudin in primary PCI had no impact on mortality, but did reduce major bleeding, at the cost of more stent thrombosis. Similar findings were made in the STEMI subgroup of the MATRIX trial [88]. Prolonging bivalirudin infusion after PCI was found to be associated with the lowest risk of bleeding and stent thrombosis in EUROMAX, but the same intervention tested specifically in MATRIX had no impact on clinical outcomes compared to only intra-procedural bivalirudin use. Taken together, the evidence suggests that it is reasonable to use bivalirudin instead of heparin in patients who are at high bleeding risk, or in whom heparin is contra-indicated, such as patients known to suffer from heparin-induced thrombocytopenia.

Several trials, performed before the routine use of DAPT, mostly using abciximab, had documented clinical benefits of GP IIb/IIIa inhibitors as adjuncts to primary PCI performed with UFH [88].

The FINESSE trial [90] found that routine upstream use of abciximab before primary PCI did not yield clinical benefit but increased bleeding risk, compared with routine use in the catheterization laboratory, suggesting that, for patients going on to primary PCI, there does not appear to be any appreciable benefit and only harm in starting GP IIb/IIIa inhibitors in the prehospital setting. A post-hoc subset analysis of the FINESSE trial, focussing on patients presenting within 4 h of symptom onset to non-PCI hospitals and requiring transfer, suggested they might derive a survival benefit from use of abciximab [91].

More recently, the ON-TIME 2 trial [92] found an improvement in surrogate markers of reperfusion from the use of tirofiban started during the pre-hospital phase, upstream of primary PCI, and continued for up to 18 h after the procedure (compared to only provisional use (i.e. not systematic use) in the catheterization laboratory). There was also a reduction in the composite secondary endpoint of death in recurrent MI in urgent target vessel revascularization and thrombotic bailout.

Finally, in the HORIZONS–AMI trial [93], there was no clear benefit from using a combination of GP IIb/IIIa inhibitor +UFH, compared to bivalirudin, and the BRAVE-3 trial did not find evidence of a reduction in infarct size from treatment with abciximab in primary PCI patients treated with 600 mg of clopidogrel [95]. Therefore, there is no definitive answer regarding the current role of routine use of GP IIb/IIIa inhibitors in primary PCI in the era of potent DAPT, particularly when prasugrel or ticagrelor is used, and the value of starting upstream of the catheterization laboratory is, at best, uncertain.

Using GP IIb/IIIa inhibitors as bailout therapy in the event of angiographic evidence of large thrombus, slow or no-reflow and other thrombotic complications is reasonable, although it has not been tested in a randomized trial.

Intracoronary (IC) rather than (IV) administration of GP IIb/IIIa inhibitors has been tested in several small studies and is associated with some benefit [1–85]. The INFUSE-AMI trial [56] randomized 452 patients undergoing PCI with bivalirudin to local delivery of abciximab vs. no abciximab. Intracoronary abciximab reduced the 30-day infarct size, evaluated by magnetic resonance imaging, but did not improve abnormal wall motion score, ST-segment resolution, post-PCI coronary flow, or myocardial perfusion. The large AIDA-4 randomized trial, which enrolled 2065 patients (i.e. more than all previous studies combined) found no clinical benefit (but also no harm) in this route of administration in terms of the composite of death, reinfarction, and heart failure, and found a borderline reduction in the secondary endpoint of heart failure [95]. Therefore, the IC route may be considered but the IV route should remain the standard of care for administration of GP IIb/IIIa inhibitors.

In conclusion, the existing data suggest that, if bivalirudin is chosen as the anticoagulant, there is no benefit of routine addition of GP IIb/IIIa blockers and a strategy of bivalirudin alone (with provisional bailout use of GP IIb/IIIa blockers) leads to lower bleeding rates and reduced mortality. If UFH or enoxaparin is chosen as the anticoagulant, the role of routine—as opposed to ‘bailout’—use of GP IIb/IIIa blockers remains debatable.

Routine post-procedural anticoagulant therapy is not indicated after primary PCI, except when there is a separate indication for either full-dose anticoagulation (due, for instance, to atrial VF, mechanical valves, or LV thrombus) or prophylactic doses for prevention of venous thromboembolism in patients requiring prolonged bed rest.

‘No-reflow’ describes inadequate myocardial perfusion despite successful mechanical opening of the infarct-related artery. The diagnosis of no-reflow is usually made when post-procedural thrombolysis in MI (TIMI) flow is 3, or in the case of a TIMI flow of 3 when myocardial blush grade is 0 or 1, or when ST resolution within 4 h of the procedure is <70% [96]. Other non-invasive techniques are contrast echocardiography, single-photon emission tomography, positron emission tomography (PET), and contrast-enhanced magnetic resonance imaging (MRI). There have been many attempts to treat no-reflow using intracoronary vasodilators, IV infusion of adenosine, or abciximab, but there is no conclusive proof that these therapies affect clinical outcomes. Likewise, although it is intuitively attractive and widely used in clinical practice, there is no firm evidence that manual thrombus aspiration reduces distal embolization [55–57, 97–99.

FL remains an important component in the arsenal of STEMI therapies despite the pre-eminence of primary PCI. The benefits of FL, like primary PCI, are time-dependent. FL is recommended within 12 h of symptom onset, if primary PCI cannot be performed within 120min of STEMI diagnosis. To reduce delays, paramedical staff on the ambulance could telecommunicate with Cardiologists at a hospital and initiate FL. The aim is to initiate FL within 10 min of STEMI diagnosis, whether in an ambulance or at a hospital.

For patients presenting very late (6 h or more), by extrapolation, the tolerance for PCI-related delays becomes longer, given the rapid decline in FL efficacy with time.¹⁰⁰ Meta-analyses of large FL trials have shown large mortality reductions in patients treated in pre-hospital settings [101] and <2 hrs [102] versus those treated in-hospital and later. These results have been confirmed in later registry data and post-hoc analyses of randomized trials [103–106].

Four FL agents are currently available on the market – streptokinase, reteplase, alteplase and tenecteplase. The three latter agents are recombinant tissue plasminogen activators, and are fibrin-specific. In GUSTO, alteplase with activated partial thromboplastin time-adjusted heparin (APTT) was compared against streptokinase and found to prevent 10 deaths at the cost of 3 additional strokes [107]; double-dose reteplase is easier to administer but has no additional advantage over accelerated alteplase [108]. Tenecteplase can also be given as a single weight-adjusted bolus, holding advantages in easy administration in a pre-hospital setting, and is equivalent to accelerated alteplase for 30-day mortality whilst being associated with fewer non-cerebral bleeds and blood transfusion episodes [109].

Fibrinolysis, by its nature, is unfortunately associated with haemorrhagic complications that occur in 4–13% of recipients [108–110], including an intracranial haemorrhage rate of 0.9–1.0% [108–109]. The contraindications to fibrinolysis are based on these pro-haemorrhagic properties (see Table 43.1).

As a general consideration, FL should be used with caution in patients at higher risk of bleeding such as the elderly, those with a history of bleeding complications and those with organ failure. Other complications specific to Streptokinase include hypotension, allergic reactions, and inefficacy due to neutralizing antibodies if administered a second time in the same individual.

Aspirin, when added to streptokinase in the ISIS-2 trial, had synergistic benefits, and is generally given at an oral loading dose of 150–300 mg (lower if administered IV) and a maintenance dose of 75–100 mg daily, see Chapter 44. DAPT with clopidogrel and aspirin reduced the risk of cardiovascular events in CLARITY-TIMI 28 and reduced all—cause death in COMMIT. The newer ADP-receptor antagonists prasugrel and ticagrelor should not be used in the setting of FL as there is a lack of supporting data.

Heparin should be given post-FL until revascularization (if performed), or for at least 48 hours and up to 8 days during the hospital stay of the patient. UFH improves coronary patency after alteplase, but notafter streptokinase, but needs to be monitored with activated partial thromboplastin time (aPTT), as values >70 s are associated with more bleeding, reinfarction, and death. The net clinical benefit of using enoxaparin over UFH after tenecteplase, in the large ASSENT 3 [95] and ExTRACT-TIMI 25 [96, 97] trials, was in favour of enoxaparin, in terms of in-hospital refractory ischaemia and reinfarction, and 30-day death and reinfarction, respectively. Those >75 years of age and with a creatinine clearance of <30 mL/min should receive a reduced dose of enoxaparin to reduce the probability of bleeding complications.

Fondaparinux was also superior to UFH or placebo in the OASIS-6 trial in preventing death and reinfarction [77, 114], especially in patients who received streptokinase.

Bivalirudin has only been studied as an adjunct to streptokinase [115], given for 48 hrs, and it reduced reinfarctions without reducing 30-day mortality at a cost of a small increase in non-cerebral bleeding complications. No evidence supports the use of bivalirudin with fibrin-specific agents.

Tenecteplase, aspirin, enoxaparin, and clopidogrel comprise the antithrombotic combination that has been the most extensively studied and validated, as part of a pharmaco-invasive strategy, in several large RCTs—TRANSFER [100], NORDISTEMI [101], GRACIA-2 [102], and GRACIA-3 [103].

Following the initiation of FL, patients should be immediately transferred to a PCI centre. In cases of failed FL, or if there is evidence of reocclusion or reinfarction with a recurrence of ST-segment elevation, the patient should undergo immediate angiography and rescue PCI [104]

If there are signs of successful FL (ST-segment resolution of >50% at 60–90 min, typical reperfusion arrhythmia, disappearance of CP), routine early angiography should be performed if there are no contraindications. Several randomized trials [100–102, 105–108] and two contemporary meta-analyses [106, 109] have shown that early routine post-thrombolysis angiography, with subsequent PCI (if required), reduced the rates of reinfarction and recurrent ischaemia, compared with a ‘watchful waiting’ strategy, in which angiography and revascularization were indicated only in patients with spontaneous or induced severe ischaemia or LV dysfunction, and did not increase the risk of AEs (stroke or major bleeding). Thus, early referral for angiography, with subsequent PCI (if indicated), should be the standard of care after thrombolysis, the so-called ‘pharmaco-invasive’ strategy.

The optimal delay between FL and PCI remains debated; there was a wide variation in delay in trials, from a median of 1.3 hours in the CAPITAL-AMI trial to 16.7 hours in the GRACIA-1 trial [102, 108]. Based on the three most recent trials, all of which had a median delay between the start of FL and angiography of 2–3 hours, a time window of 3–24 hours after successful FL is recommended [100, 101, 105]. The recent STREAM [38] trial showed that modern adjunctive therapies added to FL, followed by subsequent PCI, can achieve similar outcomes, compared with primary PCI.

For the small number of patients in cardiogenic shock (CS) due to coronary disease non-amenable to PCI, or with mechanical complications of AMI such as myocardial rupture, emergency open-heart coronary artery bypass grafting (CABG), and structural repair may be indicated. For those patients who have coronary occlusion non-amenable to PCI, failed PCI, and refractory symptoms after PCI, the role of CABG is uncertain, and the surgical risk is extremely high.

For those presenting with coronary anatomy not suitable for PCI, but with a patent infarct-related artery, CABG may be performed 3–5 days after stopping ticagrelor, 5 days after clopidogrel, and 7 days after prasugrel, to reduce the elevated risk of bleeding related to CABG observed in their respective clinical trials. Cangrelor, a novel IV reversible adenosine diphosphate (ADP) receptor antagonist, may play a bridging role from coronary angiography to CABG for these patients [111].

Habits of a lifetime are not easily changed, and the implementation and follow-up of these changes are a long-term undertaking. In this regard, a close collaboration between the cardiologist and the general practitioner, specialist rehabilitation nurses, pharmacists, dietitians, and physiotherapists are critically important. Detailed recommendations are available in the ESC guidelines for preventive care [112].

Current guidelines [112] recommend a varied diet, with calorie intake adjustment aimed at avoiding obesity, an increased consumption of fruits and vegetables, along with wholegrain cereals and bread, fish (especially oily varieties), lean meat, and low-fat dairy products. There is no evidence for the use of antioxidant supplements, low glycaemic index diets, or homocysteine-lowering therapies, following STEMI.

Obese STEMI patients with a body mass index (BMI) of ≥30 kg/m2, or a waist circumference of >102 cm in men or >88 cm in women, should aim for an optimal BMI of <25 kg/m2. Weight loss can help diminish obesity-related risk factors, though it has not been established that weight reduction per se reduces mortality.

A recent randomized trial of behavioural therapy, in addition to standard management, of patients who had AMI, PCI, or CABG within the past 12 months found a 41% lower rate of fatal and non-fatal first recurrent CVD [113].

Exercise-based rehabilitation programmes have been shown to be effective in reducing all-cause mortality and the risk of reinfarction, in the era before the introduction of modern STEMI management[114, 115], but a more recent trial did not show a superiority of this approach [116].

Aspirin should be continued indefinitely in patients who have had STEMI, generally at low doses (75–100 mg/day), due to the reduced gastrointestinal (GI) bleeding rates and an equivalent anti-ischaemic efficacy shown in CURRENT OASIS 7 [62]. The patients who are intolerant of aspirin can take clopidogrel 75 mg/day instead. The use of DAPT should be adjusted, according to the modality of treatment of the patient, see Table 43.2.

A low dose (2.5 mg) of rivaroxaban, an oral factor Xa antagonist, was shown, in the ATLAS ACS 2-TIMI 51 trial [117], to reduce all-cause mortality, cardiovascular death, AMI, and stroke, when added to aspirin and clopidogrel, at the expense of a 3-fold increase in non-CABG-related bleeding. Importantly, there is no experience of rivaroxaban with the novel oral ADP receptor blockers, and no other oral factor Xa antagonist or direct thrombin inhibitor has demonstrated an acceptable risk–benefit balance to be recommended for use with current antiplatelet therapy.

The COMMIT trial [118] showed that IV β-blockers should be used with caution in the acute phase of AMI, especially in those who are haemodynamically unstable or have early signs of heart failure. Continued oral dosing depends on its use as an antianginal agent or as part of heart failure treatment. Calcium channel blockers (CCBs) are alternatives to β-blockers in the convalescent phase, as a treatment for angina or hypertension, but should not be used in the acute phase, as there is trial evidence of harm [119].

ACE-Is and their alternative ARBs are safe in the post-STEMI setting. They both give modest benefits—captopril gave a small, but significant, 30-day mortality reduction in a systematic review of trials [120], and valsartan was similarly efficacious to captopril in VALIANT [121]. The benefit of ACE-Is or ARBs in the long term becomes more important in patients with systolic heart failure.

ACE-Is and their alternative ARBs are safe in the post-STEMI setting. They both give modest benefits—captopril gave a small, but significant, 30-day mortality reduction in a systematic review of trials [120], and valsartan was similarly efficacious to captopril in VALIANT [121]. The benefit of ACE-Is or ARBs in the long term becomes more important in patients with systolic heart failure.

In the EPHESUS trial [122], eplerenone, in addition to optimal medical therapy, in post-AMI patients with LV dysfunction reduced all-cause mortality by 15% at 16 months. When used with other medications affecting the renin–angiotensin–aldosterone axis, extra caution should be taken to monitor renal function and K+ levels.

The statin class of drugs should be used with a target low density lipoprotein (LDL) concentration of <1.8 mmol/L. A second-line option is ezetimibe for patients suffering from side effects from statins such as myopathy.

A retrospective analysis of the PROVE IT-TIMI 22 trial suggest that, after ACS, the blood pressure goal should be <140 mmHg, but no lower than 110 mmHg systolic [123].

Other pharmacotherapeutic agents, such as magnesium, glucose–insulin–potassium, lidocaine, and n-3 polyunsaturated fatty acids, do not have solid enough evidence to back their routine use in post-AMI patients.

Myocardial necrosis, due to ischaemia, sustained arrhythmias, and mechanical complications of STEMI, may lead to varying degrees of left ventricle (LV) dysfunction. The consequences could be acute and/or chronic heart failure (see Chapter 51).

The assessment of AHF in STEMI consists of physical examination, and ECG and vital signs monitoring. An echocardiogram can detect significant LV dysfunction and any mechanical complications of AMI which may require urgent treatment (see Chapter 20). The value of circulating markers, such as BNP or NT-proBNP (see Chapter 37), has not been established in the acute setting, given the rapid changes in cardiovascular physiology, and should be interpreted in conjunction with the patient’s clinical condition [121]. LV dysfunction is the strongest predictor of mortality, following STEMI, and the severity of its clinical manifestation is classified by the prognostically useful Killip classification. Mechanisms include systolic and diastolic ventricular dysfunction, often exacerbated by comorbidities such as anaemia, diabetes, infection, or pulmonary disease. Acute heart failure (AHF) can be managed using diuretics, vasodilators, inotropic support, intra-aortic balloon pump (IABP), and further revascularization interventions (see Chapter 52). In severe cases, extracorporeal membrane oxygenation and left ventricular assist device may be considered, though there has been no conclusive evidence in favour of these devices [124].

CS is a condition that complicates 6–10% of STEMIs and is associated with an in-hospital mortality of nearly 50% (see Chapter 49). Diagnostic criteria are listed in Table 43.4. The SHOCK trial registry [125] showed that this occurred in 75% of cases within 24 hours of admission. An adverse prognosis is predicted by LV systolic dysfunction, the severity of MR [126], and RV dysfunction [127]. Emergent revascularization with PCI or CABG has been shown to be better than a delayed revascularization approach [125, 128], but this may have to be supported pharmacologically or medically, and a careful fluid status titration may be necessary. A recent randomized trial of 1679 CS patients showed that those supported with noradrenaline fared better than those with dopamine, mainly due to an excess of arrhythmic events in the latter [129].

When heart failure becomes chronic, additional pharmacotherapy and device therapies may be appropriate, as detailed in the ESC guidelines for acute and chronic heart failure [130].

The COMMIT trial [118] showed that IV β-blockers should be used with caution in the acute phase of AMI, especially in those who are haemodynamically unstable or have early signs of heart failure. Continued oral dosing depends on its use as an antianginal agent or as part of heart failure treatment. Calcium channel blockers (CCBs) are alternatives to β-blockers in the convalescent phase, as a treatment for angina or hypertension, but should not be used in the acute phase, as there is trial evidence of harm [119].

ACE-Is and their alternative ARBs are safe in the post-STEMI setting. They both give modest benefits—captopril gave a small, but significant, 30-day mortality reduction in a systematic review of trials [120], and valsartan was similarly efficacious to captopril in VALIANT [121]. The benefit of ACE-Is or ARBs in the long term becomes more important in patients with systolic heart failure.

In the EPHESUS trial [122], eplerenone, in addition to optimal medical therapy, in post-AMI patients with LV dysfunction reduced all-cause mortality by 15% at 16 months. When used with other medications affecting the renin–angiotensin–aldosterone axis, extra caution should be taken to monitor renal function and K+ levels.

The statin class of drugs should be used with a target low density lipoprotein (LDL) concentration of <1.8 mmol/L. A second-line option is ezetimibe for patients suffering from side effects from statins such as myopathy.

A retrospective e analysis of the PROVE IT-TIMI 22 trial suggest that, after ACS, the blood pressure goal should be <140 mmHg, but no lower than 110 mmHg systolic [123].

Other pharmacotherapeutic agents such as magnesium, glucose-insulin-potassium, lidocaine and n-3 polyunsaturated fatty acids do not have solid enough evidence to back their routine use in post-AMI patients (see Table 43.3).

Myocardial necrosis due to ischaemia, sustained arrhythmias and mechanical complications of STEMI may lead to varying degrees of LV dysfunction. The consequences could be acute and/or chronic heart failure.

The assessment of acute heart failure in STEMI consists of physical examination, ECG and vital signs monitoring. An echocardiogram, see Chapter 20, can detect significant LV dysfunction and any mechanical complications of AMI which may require urgent treatment. The value of circulating markers such as BNP or NT-proBNP, see Chapter 37, has not been established in the acute setting, given the rapid changes in cardiovascular physiology, and should be interpreted in conjunction with the patient’s clinical condition.¹³⁷. LV dysfunction is the strongest predictor of mortality following STEMI, and the severity of its clinical manifestation is classified by the prognostically useful Killip classification. Mechanisms include systolic and diastolic ventricular dysfunction, often exacerbated by co-morbidities such as anaemia, diabetes, infection or pulmonary disease. Acute heart failure can be managed using diuretics, vasodilators, inotropic support, intra-aortic balloon pumping (IABP) and further revascularization interventions. In severe cases, extracorporeal circulation membrane oxygenation and left ventricular assist devices may be considered, though there has been no conclusive evidence in favour of these devices¹⁴² (see Table 43.4).

Cardiogenic shock is a condition that complicates 6–10% of STEMI and is associated with an in-hospital mortality of nearly 50%. Diagnostic criteria are listed in Table 43.47. The SHOCK trial registry¹⁴³ showed that this occurred in 75% of cases within 24 h of admission. An adverse prognosis is predicted by LV systolic dysfunction, severity of mitral regurgitation¹⁴⁴ and right ventricular dysfunction.¹⁴⁵ Emergent revascularization with PCI or CABG has been shown to be better than a delayed revascularization approach,^{143, 146} but this may have to be supported pharmacologically or medically, and careful fluid status titration may be necessary. A recent randomized trial of 1679 cardiogenic shock patients showed that those supported with noradrenaline fared better than those with dopamine, mainly due to an excess of arrhythmic events in the latter.¹⁴⁷

When heart failure becomes chronic, additional pharmacotherapy and device therapies may be appropriate, as detailed in the ESC guidelines for acute and chronic heart failure.¹⁴⁸

Arrhythmias and conduction disturbances are common during the early hours after AMI. A cardiac rhythm monitoring study found incidences of 28% new-onset atrial VF, 13% for non-sustained VT, 10% for high-degree atrio-ventricular block (≤30 beats per minute lasting for ≥8 s), 7% for sinus bradycardia (≤30 beats per minute lasting for ≥8 s), 5% for sinus arrest (≥5 s), 3% for sustained VT, and 3% for ventricular VF.¹⁴⁹ Beta blockers given within the first 24 hours of AMI, Angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) reduce the risk of early mortality in patients with early VF/VT.^{150, 151} Patients having early VF/VT and who are successfully resuscitated have similar long-term prognoses to those who do not,¹⁵² and there is no justification to implantation of an implantable cardioverter defibrillator based on this criterion alone (Table 43.5).

These three mechanical complications usually happen in the subacute phase of AMI and can present dramatically as sudden hemodynamic decompensation. Definitive treatment requires surgery but in each case carries a very high risk of mortality. For an in-depth discussion of the mechanical complications of MI please refer to chapter 45.

Right ventricular infarction may occur in isolation or, more frequently, in connection with inferior wall STEMI. It frequently presents with the triad of hypotension, clear lung fields and raised jugular venous pressure. Elevation of the ST-segment ≥1 mV in V1 and V4R is suggestive of right ventricular infarction and should routinely be sought in patients with inferior STEMI and hypotension. Echocardiography typically demonstrates right ventricular dilatation, low pulmonary arterial pressure, dilated hepatic veins and varying degrees of inferior wall injury. Despite the jugular distension, fluid loading that maintains right ventricular filling pressure is a key therapy in avoiding or treating hypotension. In addition, diuretics and vasodilators should be avoided, as they may aggravate hypotension. Maintenance of sinus rhythm and atrio-ventricular synchrony is important and atrial VF or atrio-ventricular block should be treated early.

The incidence of pericarditis after STEMI has decreased with the advent of modern, effective reperfusion therapy [135] (see Chapter 58). Pericarditis manifests as a sharp and posture- and respiration-related CP, distinguishing it from recurrent ischaemia. It may be associated with ST-segment re-elevation. However, the ST-segment re-elevation is usually mild and progressive, as opposed to the rapid ST-segment re-elevation seen in cases of coronary reocclusion resulting from, e.g. stent thrombosis. A continuous pericardial rub may confirm the diagnosis but lacks sensitivity, especially when muffled by a pericardial effusion. Echocardiography will detect and quantify the size of theeffusion, if present, and rule out tamponade physiology. Pericarditic pain usually responds to high-dose aspirin, paracetamol, or colchicine. Steroids and long-term non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided, due to the risk of scar thinning with aneurysm development or rupture. Pericardiocentesis is rarely required but should be performed if there is haemodynamic compromise due to tamponade. Anticoagulant therapy (e.g. for the prophylaxis of venous thromboembolism (VTE)) should be interrupted, unless absolutely indicated, when a pericardial effusion is present.

Patients with a large transmural infarction—particularly if the anterolateral wall is involved—may undergo infarct expansion and a remodelling process of LV dilatation and aneurysm formation. The resultant combined systolic and diastolic dysfunction can cause volume overload and exacerbate mitral regurgitation. Echocardiography can assess LV volume, ejection fraction, the extent and degree of wall motion abnormalities, and detect mural thrombus necessitating anticoagulation. ACEi, ARB, and aldosterone antagonists have been shown to attenuate the remodelling process in transmural infarction and improve survival.

The frequency of a mural LV thrombus has decreased, largely because of the progress made in reperfusion therapy, the widespread use of multiple antithrombotic agents in STEMI, and the limitation of the myocardial infarct size produced by an effective and early myocardial reperfusion [136, 137]. Although some studies suggest that up to a quarter of anterior AMIs have detectable LV thrombi [138], LV thrombi are associated with poor prognosis, because of their association with extensive infarcts, particularly anterior infarcts with apical involvement, and a risk of systemic embolism. Relatively old trials had shown that anticoagulation in patients with large anterior wall motion abnormalities reduced the occurrence of mural thrombi [139–141]. Anticoagulation should therefore be considered in patients with large anterior wall motion abnormalities to prevent the development of thrombi, bearing in mind the risk of bleeding. The consensusonsensus is that mural thrombi, once diagnosed, require oral anticoagulant therapy with vitamin K antagonists for up to 6 months. However, this has not been revisited in the era of stenting and DAPT. Triple therapy with oral anticoagulation and DAPT substantially increases bleeding risks. The optimal duration of such triple antithrombotic therapy is unknown and should take into account the relative risks of bleeding and stent thrombosis. If repeated imaging of the left ventricle after 3 months of therapy shows the disappearance of thrombus, and particularly if there is recovery of apical wall motion, anticoagulation may be discontinued.