Chapter 24: Acute Cardiac Ischemia

Acute cardiac ischemia is defined by new or worsening imbalance between myocardial oxygen supply and demand, most commonly in the setting of coronary artery disease. Despite improvements in medical therapy, the burden of coronary artery disease remains high, affecting over 15 million United States adults.¹ Acute cardiac ischemia describes a physiologic disturbance underlying a spectrum of disorders encountered in critical care, from so-called “demand ischemia” in the setting of an acute physiologic insult and stable ischemic heart disease, to acute coronary syndromes (ACS), including unstable angina (UA), non-ST segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI).

Whereas certain physiologic principles of acute cardiac ischemia are common across this spectrum, providing the basis for understanding its natural history and therapy, appropriate management varies importantly with the mechanism of disease. As such, the ability to both identify and discriminate acute cardiac ischemia is fundamental to timely selection and implementation of appropriate therapy. In this chapter, we aim to provide a practical, intuitive review of the spectrum of acute cardiac ischemia for the critical care provider.

Cardiac ischemia results from an imbalance between myocardial oxygen supply and demand. Acute disturbances in supply, demand, or both can precipitate a syndrome of acute cardiac ischemia. Major determinants of myocardial oxygen supply and demand are presented in Table 24–1.

Determinants of Myocardial Oxygen Supply

Oxygen uptake by tissue is governed by oxygen delivery and oxygen extraction. Because myocardial oxygen extraction is near-maximal, at 70% to 80%, variation in myocardial oxygen supply is primarily driven by delivery of oxygen. Delivery of oxygen is directly related to cardiac output, or blood flow, and the content of oxygen in arterial blood (Equation 24–1). Cardiac output is the product of heart rate and left ventricular stroke volume (Equation 24–2). Arterial oxygen content is determined by the hemoglobin concentration, arterial oxygen saturation, and partial pressure of oxygen in arterial blood (Equation 24–3).

Oxygenated blood is delivered to the myocardium via branches of the coronary arteries. Normal coronary anatomy consists of a right coronary artery (RCA) arising from the right sinus of Valsalva and a left main coronary artery arising from the left sinus of Valsalva, which in turn bifurcates into the left anterior descending and left circumflex arteries (Figure 24–1). The coronary arteries and their branches develop as anatomical “end arteries,” providing all or most of the blood supply to specific areas of subtended myocardium. Typically, the RCA supplies blood to the right ventricle and inferior wall of the left ventricle, the left circumflex supplies blood to the lateral and inferior walls of the left ventricle, and the left anterior descending supplies blood to the anterior wall of the left ventricle. Anatomic variations are common. Furthermore, collateral circulation can develop over time as an adaptation to chronic ischemia.

Myocardial blood flow is driven by the pressure gradient from the aortic root to the myocardial capillaries, the coronary perfusion pressure, and inversely related to coronary arterial resistance.

Coronary perfusion pressure is equal to the difference between aortic diastolic pressure and left ventricular end-diastolic pressure. Blood flow to the left ventricular myocardium occurs primarily during diastole, when aortic pressure exceeds left ventricular pressure due to closure of the aortic valve. During systole, in contrast, left ventricular pressure equals or exceeds (in the case of any left ventricular outflow tract obstruction) aortic pressure. Accordingly, decreases in aortic diastolic pressure and increases in left ventricular end-diastolic pressure will tend to decrease myocardial blood flow. In a given coronary artery, anatomic obstruction (such as by atherosclerotic plaque, thrombus or embolus) may cause limitation or complete interruption of blood flow. Clinically important obstruction may occur at the macrovascular or microvascular level. Whereas the duration of systole is fairly fixed, the duration of diastole is variable and dependent on heart rate. As such, myocardial blood flow is also heart rate dependent; other things being equal, increases in heart rate decrease diastolic filling time and tend to reduce myocardial blood flow.

Resistance to coronary arterial blood flow is dynamic. A complex array of paracrine, endocrine, neural, and mechanical factors mediate local and global increases or decreases in coronary arterial resistance, in large part through modulation of coronary vasomotor tone. The capacity for localized changes in coronary vasomotor tone permits heterogeneity in coronary arterial resistance and local adaptation to physiologic circumstances, including ischemia. Decreases in local or global coronary arterial resistance tend to increase myocardial blood flow and, in turn, myocardial oxygen delivery.

Oxygen is used by cells, including cardiac myocytes, as the ultimate electron acceptor in a series of redox reactions that culminate in generation of adenosine triphosphate (ATP) by oxidative phosphorylation. ATP is required to power energy-dependent cellular processes; in cardiac myocytes, this includes regulation of membrane potential, regulation of sarcoplasmic reticulum calcium concentration, and both cross-bridge formation and dissociation of actin and myosin (required for contraction and relaxation, respectively). Demand for ATP and, in turn, demand for oxygen, relates to the magnitude of this cellular work.

Accordingly, beyond myocardial basal energy expenditure, myocardial oxygen demand is driven by the work of each cardiac cycle and the number of cardiac cycles per minute (the heart rate). The work of a given cardiac cycle relates closely to wall stress—the force applied to a unit area of myocardium. As expressed by the Law of Laplace (Equation 24–4), wall stress is directly proportional to pressure and radius and inversely proportional to wall thickness. As such, wall stress and, in turn, myocardial oxygen demand will tend to increase in association with increases in contractility and systolic blood pressure (increasing left ventricular systolic pressure), obstruction to left ventricular outflow (increasing left ventricular systolic pressure), volume overload (increasing left ventricular radius and end-diastolic pressure), and decreased compliance (increasing left ventricular end-diastolic pressure).

The Ischemic Cascade

Following onset of acute cardiac ischemia, a typical sequence of events ensues, referred to as the ischemic cascade (Figure 24–2). The earliest detectable change is a local abnormality in myocardial perfusion. This is followed in course by tissue-level metabolic disturbances, regional diastolic dysfunction, regional systolic dysfunction, electrocardiographic changes, symptoms, and finally irreversible cellular injury progressing to cell death (myocardial infarction).

The pace of this cascade depends on the severity of myocardial ischemia. With acute thrombotic total occlusion of an epicardial coronary artery, contractile changes are evident within 1 to 2 minutes; within 10 minutes, alterations in membrane potential increase predisposition to malignant ventricular arrhythmias; by 20 minutes, cellular injury becomes irreversible, beginning the process of myocardial infarction.² This rapid progression to risk of life-threatening arrhythmia and irreversible myocardial injury underscores the urgency of evaluation and management of suspected acute cardiac ischemia.

Myofibrillar changes are followed within hours by acute inflammation and coagulation necrosis, which proceeds over several days, followed by removal of dead myocytes by infiltrating macrophages. During this phase of phagocytosis, cardiac tissue is particularly friable and at risk of rupture. After 1 week, granulation tissue begins to form and mature, with progressive removal of cellular tissue and deposition of collagen. The process of scarring completes over 2 months. In parallel, the healing ventricle undergoes a process of remodeling, including changes in ventricular geometry and size. Although an increase in left ventricular end-diastolic volume allows hemodynamic compensation by maintaining stroke volume despite a decrease in systolic function, this remodeling proves maladaptive, contributing to increased myocardial oxygen demand (as aforementioned), chronic heart failure and mortality. For this reason, therapies to prevent such adverse cardiac remodeling are an important component of management of acute cardiac ischemia, as will be discussed in sections to follow.

Onset of acute cardiac ischemia is accompanied by a typical constellation of symptoms, signs, and findings on laboratory and imaging investigation. Although the mechanism and severity of acute cardiac ischemia may vary across the spectrum of responsible disorders, elements of the clinical presentation are conserved, which we review here.

The cardinal symptom of acute cardiac ischemia is chest pain. Chest pain typical of cardiac ischemia (angina pectoris) is characterized by provocation by exertion or emotional upset and alleviation by rest or nitrates. Pain is typically retrosternal in location and may radiate to the jaw, throat, or arms. The quality of pain may be described as pressure-like or squeezing, and patients may even demonstrate this as a clenched fist in front of the chest (the Levine sign). Accompanying symptoms may include dyspnea, diaphoresis, and nausea. Importantly, the chest discomfort of acute cardiac ischemia may be a typical or absent, notoriously in women and patients with diabetes mellitus as well as postoperative or critically ill patients. A high index of suspicion is therefore mandatory. The angina of acute cardiac ischemia is unstable, being of new onset, occurring with rest or minimal exertion, or worsening in intensity, frequency, or duration (typically longer than 20 minutes).

Features on history may suggest a noncardiac source of chest pain. Pain that is pleuritic, positional, sharp, or reproducible with palpation is less likely to represent acute cardiac ischemia. A differential diagnosis is presented in Table 24–2.

Physical Examination

Abnormalities on physical examination are insufficient to rule in or rule out acute cardiac ischemia. Careful physical diagnosis is nonetheless necessary in the setting of suspected acute cardiac ischemia to identify signs of alternative diagnoses; to assess disease severity; and to identify systemic precipitants of worsening imbalance in myocardial oxygen supply and demand.

A focused investigation for alternative diagnoses should include simultaneous palpation of the bilateral radial pulses and measurement of bilateral brachial blood pressures to look for discrepancy, as might be seen in acute aortic dissection; palpation of the locus of chest discomfort to elicit tenderness, as would be suggestive of a musculoskeletal origin of pain; and auscultation of the chest and precordium to listen for a friction rub, as might be heard in pleuritis or pericarditis, or adventitious lung sounds, as might be heard in pneumonia. It should be noted that fever, while raising the question of alternate diagnoses, does not exclude acute cardiac ischemia, as indeed fever (along with leukocytosis) may be observed during acute myocardial infarction in conjunction with a robust systemic inflammatory response, with adverse prognostic implications.

When acute cardiac ischemia is the most likely diagnosis, physical examination is useful to identify evidence of acute heart failure, hemodynamic instability, and mechanical complications of ischemia and infarction. Manifestations of acute heart failure may include a third heart sound and signs of decreased cardiac output (such as sinus tachycardia, narrow pulse pressure, hypotension, decreased alertness, cool extremities, and thready pulses) or congestion (such as jugular venous distension, tachypnea, hypoxemia, labored breathing, rales, and frank pink, frothy sputum). A new systolic murmur may represent acute mitral regurgitation, resulting from acute ischemic dysfunction of a papillary muscle or, in the setting of acute myocardial infarction, papillary muscle rupture, or formation of a ventricular septal defect. The clinical triad of hypotension, jugular venous distension, and muffled heart sounds mandates investigation for pericardial tamponade, which may result from ventricular free wall rupture.

Electrocardiogram

The surface 12-lead electrocardiogram is the sine qua non of diagnosis and triage of acute cardiac ischemia, and should be performed within 10 minutes of medical contact. While the electrocardiogram should be approached systematically, including analysis of the rhythm, rate, axis, intervals, and evidence of chamber enlargement, particular attention is paid to the ST segments, T waves, and presence or absence of pathologic Q waves.

ST-segment elevation is the defining feature of STEMI, and a red flag that emergent action may be required. When caused by acute cardiac ischemia, ST-segment elevation is indicative of severe and often transmural ischemia, most commonly secondary to an acute total obstruction to coronary blood flow. Several conditions may explain ST-segment elevations (Table 24–3). To be diagnostic of STEMI, ST-segment elevations of sufficient magnitude (at least 0.1 mV and higher in leads V2-V3) must be present in at least two contiguous leads. The ST-segment elevations of acute cardiac ischemia are characterized by a territorial distribution; elevations in leads V2-V4; V5-V6, I, aVL; and II, III, aVF reflect ischemia in the anterior, lateral and inferior walls, respectively. Ischemic ST-segment elevations are typically characterized by a convex morphology, in contrast to the concave ST-segment elevations observed in pericarditis and early repolarization.

Clinical syndromes consistent with acute cardiac ischemia with no ST-segment elevations on the surface electrocardiogram are considered non-ST elevation ACS, and comprise UA and NSTEMI. The acute cardiac ischemia of non-ST elevation ACS is typically nontransmural, but may still be extensive, often associated with multivessel coronary artery disease. ST-segment depressions or T wave inversions may be present, but these findings are not required for the diagnosis of UA or NSTEMI.

Of note, in certain syndromes of myocardial infarction, ST-segment elevations may be absent from the standard electrocardiogram despite presence of acute total occlusion of a coronary artery. True lateral, posterior, and right ventricular myocardial infarctions may be occult on the standard electrocardiogram due to their peripheral locations, requiring special placement of posterior (V7-V9) or right-sided (V3R-V5R) leads to reveal the diagnostic ST-segment elevations. These myocardial infarctions are pathophysiologically indistinguishable from those with overt ST-segment elevations and require the same urgency in management. It is of particular importance to recognize right ventricular infarction when it occurs—occasionally in isolation, but most frequently in conjunction with an inferior wall myocardial infarction due to occlusion of the RCA—as acute ischemia of the right ventricle causes exquisite preload dependence and susceptibility to severe hypotension with nitroglycerin.

Serum Biomarkers

Acute cardiac ischemia associated with myocardial infarction is characterized by a typical rise and fall of serum biomarkers of cardiac injury. The most sensitive and specific of these markers are the MB-fraction of creatine kinase (CK-MB), which tends to peak in the first day and fall over the next two, and troponin I or T, which also peaks in the first day but falls more slowly over several days (Figure 24–3). Less-specific serum markers which also rise and fall with acute myocardial infarction include myoglobin, total creatine kinase, aspartate aminotransferase, and lactate dehydrogenase.

Improvements in the sensitivity of laboratory measurements of serum troponin have not only permitted superior recognition of myocardial injury in the setting of acute cardiac ischemia, but also identification of troponin elevations in the setting of other acute illnesses. This is particularly relevant in the critical care setting. Troponin elevations can be seen with nonischemic myocardial injury, as in myocarditis, toxic insults, rhabdomyolysis, defibrillator shocks, and cardiac contusion as well as severe systemic illnesses, such as sepsis, stroke, and renal failure.³ In isolation, an elevation in serum troponin is insufficient for diagnosis of acute cardiac ischemia.

Adjunctive Imaging

When laboratory studies, clinical examination, and the electrocardiogram are indeterminate for the diagnosis of cardiac ischemia, adjunctive imaging modalities with increased sensitivity to detect ischemia may be useful. The role of these tools is intuitive in the context of the ischemic cascade (see Figure 24–2). Echocardiography may detect new regional or global abnormalities in systolic or diastolic function as well as potential complications of acute cardiac ischemia, such as new onset mitral regurgitation. The transthoracic echocardiogram is a particularly useful tool in the intensive care unit as it can readily be performed portably at the bedside without requirement for radiation or nephrotoxic contrast media. For patients sufficiently stable to undergo stress testing, vasodilator testing with myocardial perfusion imaging can be used to identify regional abnormalities in myocardial perfusion.

Coronary angiography, performed either noninvasively via computed tomography or invasively via cardiac catheterization, provides an anatomic depiction of coronary arterial patency. Although a 70% or greater diameter stenosis of the lumen of a coronary artery tends to connote a hemodynamically important obstruction to blood flow, it is important to recognize that angiography, by itself, is not a physiologic test of ischemia. For lesions of uncertain hemodynamic significance in the catheterization laboratory (and soon, the computed tomography suite), fractional flow reserve may be used to verify obstruction.

Universal Definition and Classification of Myocardial Infarction

Acute myocardial infarction is defined by clinical evidence of acute cardiac ischemia and a rise and/or fall in troponin, exceeding the 99th percentile of the normal reference population for a given laboratory.³ Based on the clinical scenario, myocardial infarction may be classified into one of 6 types (1, 2, 3, 4a, 4b, or 5; see Table 24–4).

Critical care pathways differ importantly across the spectrum of acute cardiac ischemia. However, the core principle of therapy is shared: to restore balance between myocardial oxygen supply and demand. In this respect, it is fruitful to first undertake a general review of therapies used in the acute management of acute cardiac ischemia (Table 24-5) from a physiologic perspective.

Antithrombotic Therapy

Antithrombotic therapies, including antiplatelet and anticoagulant drugs, are useful in the acute setting when acute cardiac ischemia results from an acute coronary anatomic change (eg, atherosclerotic plaque rupture) associated with a tendency to thrombosis. This is to be contrasted with the scenario of “demand ischemia,” in which coronary anatomy is stable, but an acute physiologic change has occurred resulting in increased myocardial oxygen demand. (Initiation of dual antiplatelet therapy is not the treatment of choice for acute cardiac ischemia secondary to a gastrointestinal hemorrhage!)

Aspirin is the cornerstone of antiplatelet therapy for patients with ACS. Aspirin inhibits platelets via inhibition of cyclooxygenase and, in turn, down regulation of thromboxane A2. In the setting of ACS, aspirin should be administered as soon as possible as a chewable loading dose (162-325 mg) followed by a daily oral maintenance dose of 75 to 100 mg.

Dual antiplatelet therapy using aspirin and an antagonist of the platelet adenosine diphosphate receptor has been shown to be superior to aspirin alone in the setting of ACS with or without ST-segment elevation for the prevention of recurrent ischemic events.^4,5 Originally documented with clopidogrel, this benefit has since been extended to the newer agents prasugrel and ticagrelor.^6,7 Clopidogrel is administered as an oral loading dose (300 or 600 mg) followed by a daily oral maintenance dose of 75 mg. Prasugrel should only be initiated at the time of coronary angiography, and never in patients with active bleeding or a history of stroke; when used, it is administered as an oral loading dose (30 or 60 mg) followed by a daily oral maintenance dose of 5 or 10 mg. Ticagrelor is administered as an oral loading dose (180 mg) followed by a twice daily oral maintenance dose of 90 mg.

Anticoagulation in the setting of ACS is typically accomplished using an inhibitor of the intrinsic coagulation cascade. Options include unfractionated heparin, administered as an intravenous bolus of 60 units/kg followed by an infusion of 12 units/kg/h, titrated to an activated partial thromboplastin time of 50 to 70 seconds; the low molecular weight heparin enoxaparin, administered as a subcutaneous injection 1 mg/kg twice daily; and fondaparinux.

Glycoprotein IIb/IIIa inhibitors are potent antiplatelet agents still used, in select cases, with cardiology guidance, typically in association with invasive management. Due to an increased risk of bleeding without clear benefit, routine early use of glycoprotein IIb/IIIa inhibitors upstream of invasive angiography is not recommended.⁸

Anti-ischemic Therapy

Multimodal therapies directed at improving balance between myocardial oxygen supply and demand are useful in all forms of acute cardiac ischemia, but must be tailored carefully to an individual patient.

Beta-adrenergic blockers increase myocardial oxygen supply by increasing diastolic filling time and decrease myocardial oxygen demand by reducing heart rate, contractility, and systolic blood pressure. This mechanism explains the utility of uninterrupted beta-adrenergic blockade during the perioperative setting of patients with known coronary artery disease. When feasible, as tolerated by blood pressure, beta-adrenergic blockade should be uptitrated to achieve a resting heart rate of 60 to 80 bpm. When acute cardiac ischemia is accompanied by signs of reduced cardiac output, and in particular tachycardia and hypotension, however, caution should be taken beta-blockade may inhibit the heart's compensatory response to acute systolic dysfunction, precipitating worsening heart failure or cardiogenic shock.

Nitrates, available in transdermal, sublingual, oral, and intravenous formulations, increase myocardial oxygen supply by reducing coronary vasomotor tone and left ventricular end-diastolic pressure and reduce myocardial oxygen demand by decreasing preload and systolic blood pressure. In the setting of ACS, nitrates are useful for the treatment of refractory angina or hypertension, and should be uptitrated as tolerated by blood pressure to achieve chest pain resolution.

Nitrates should be used only with caution in patients with suspected right ventricular infarction or recent use of phosphodiesterase type 5 inhibitors, as this combination may result in hypotension.

Angiotensin converting enzyme inhibitors and angiotensin receptor blockers serve multiple purposes in the setting of ACS, among which is a reduction in myocardial oxygen demand via reduction in systolic blood pressure. As tolerated by blood pressure and renal function, an agent should be started within 24 to 48 hours of presentation with ACS.

In patients with diminished content of arterial oxygen due to anemia or hypoxemia, red blood cell transfusion or supplemental oxygen may be warranted. Liberal transfusion and superoxygenation, however, are not helpful in the setting of acute cardiac ischemia, and may be harmful.

Analgesic therapy with morphine may indirectly decrease myocardial oxygen demand via reduction in pain and, in turn, heart rate. As morphine may also mask ongoing ischemia, however, it is reserved as a second-line to more direct anti-ischemic therapies. Nonsteroidal anti-inflammatory therapies should be avoided in the setting of ACS.

In select cases of acute cardiac ischemia refractory to medical therapies, mechanical support may be warranted to optimize balance of myocardial oxygen supply and demand. Positive pressure ventilation may reduce myocardial oxygen demand via reduction in work of breathing and preload. Intra-aortic balloon counterpulsation improves myocardial oxygen supply by augmenting coronary perfusion pressure during diastole and reduces myocardial oxygen demand by reducing afterload during systole.

When acute cardiac ischemia results from acute interruption of blood flow in a coronary artery, reperfusion therapy restores myocardial oxygen supply via restoration of myocardial blood flow. Reperfusion therapy may be accomplished via fibrinolytic therapy, percutaneous coronary intervention, or coronary artery bypass graft surgery. Whereas fibrinolytic therapy is appropriate only for STEMI, percutaneous coronary intervention or bypass grafting may be used in cases of ACS with or without ST-segment elevation.

While not strictly an anti-ischemic therapy, inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (statins) are a fundamental component of management of ACS. Through not only lipid lowering, but also pleiotropic effects, statins stabilize atherosclerotic plaque and reduce risk of recurrent ischemic events in patients with ACS. As soon as possible upon diagnosis of ACS, in the absence of contraindications, patients should be treated with a high-potency statin, examples of which include atorvastatin 80 mg and rosuvastatin 40 mg.

In patients with suspected acute cardiac ischemia, prompt evaluation and triage is mandatory to permit assignment to syndrome-specific critical care pathways (Figure 24–4). For detailed, up-to-date discussion of management considerations particular to UA/NSTEMI and STEMI, readers are encouraged to refer directly to current American College of Cardiology/American Heart Association guidelines.^9,10

Acute Cardiac Ischemia in the Setting of Stable Coronary Artery Disease

Myocardial infarction “type 2” may result from anatomically stable coronary artery disease when physiologic derangements result in an acute imbalance between myocardial oxygen supply and demand and elevation in serum biomarkers of myocardial injury. The key to management of this syndrome is identification and correction of the underlying cause of increased myocardial oxygen demand. Potential etiologies of myocardial infarction type 2 are listed in Table 24–6. In conjunction with this disease-directed approach, supportive measures to mitigate cardiac ischemia include use of anti-ischemic therapies, as discussed earlier.

Of note, demand-mediated acute ischemia in the intensive care unit may not present with classical angina. Symptoms may be atypical or absent (“silent ischemia”). Among patients with known coronary artery disease or coronary risk factors, such silent ischemia is common in the intensive care unit, often unrecognized, and linked with increased morbidity and mortality.¹¹ Reported incidence has varied in series studying different settings and using test modalities with different sensitivities, with ischemic ST changes observed in 11% to 21% and troponin elevations noted in 15% to 38% of patients in published series.^11,12,13 Continuous electrocardiographic monitoring using 5 electrodes and 2 leads (typically II and V5) has a low sensitivity in comparison with a standard 12-lead electrocardiogram and may miss clinically important ischemia.¹³ It is important to recognize, however, that elevation in serum biomarkers of myocardial infarction may occur in the absence of epicardial coronary artery disease, deriving instead from direct effects of catecholamines or other circulating toxins on myocardial cells.

NSTE-ACS (UA/NSTEMI)

UA and NSTEMI account for the majority of ACS. When a diagnosis of UA/NSTEMI is suspected, the early priority of management is risk stratification. High-risk cases of UA/NSTEMI benefit from an early invasive management strategy, whereas lower-risk cases may be managed with an initial conservative strategy and provisional invasive angiography. Clinical features indicating high risk include refractory angina, hemodynamic or electrical instability, left ventricular systolic dysfunction, elevated serum biomarkers of cardiac injury, and ST-segment deviation. Global risk scores are also useful for risk stratification; commonly used scores include the TIMI, GRACE, and PURSUIT risk scores.

Regardless of risk profile, all patients diagnosed with UA/NSTEMI should be managed with dual antiplatelet therapy, anticoagulation, a high-potency statin, and optimal anti-ischemic therapy, as discussed earlier. Useful markers of therapeutic efficacy include resolution of chest pain and ST-segment deviations and a downward trend in serum CK-MB. Patients judged to be at high-risk and assigned to an early invasive strategy should undergo invasive angiography to define coronary anatomy and facilitate triage to an appropriate revascularization strategy. Patients deemed to be at low risk may be evaluated first using noninvasive stress testing, with subsequent triage to invasive angiography as warranted.

STEMI

STEMI is a medical emergency. Most commonly resulting from acute thrombotic occlusion of a coronary artery in the setting of coronary atherosclerosis, STEMI reflects severe, acute often transmural cardiac ischemia. “Time is muscle”: reperfusion therapy is time-sensitive to save jeopardized myocardium. As such, management algorithms for STEMI, including interhospital systems of care, are designed to minimize time to reperfusion therapy, for which primary percutaneous coronary intervention is preferred. Reperfusion therapy is indicated in all eligible patients within 12 hours of symptom onset; between 12 and 24 hours after symptom onset, reperfusion therapy may still be indicated for patients with clinical or electrocardiographic evidence of ongoing ischemia. Current time to reperfusion therapy systems goals include a door-to-needle time of 30 minutes (for fibrinolytic therapy) and a door-to-device time of 90 minutes (for primary percutaneous coronary intervention). In conjunction with expeditious reperfusion therapy, patients diagnosed with STEMI should receive dual antiplatelet therapy, anticoagulation, a high-potency statin, and optimal anti-ischemic therapy, as discussed above. In a limited proportion of cases, patients ineligible for reperfusion therapy will be managed with these medical therapies alone.

Complications of STEMI are of particular concern, and become the focus of critical care following reperfusion therapy. These may be grouped in terms of ischemic, electrical, and mechanical complications.

Ischemic complications include reinfarction and, following percutaneous coronary intervention with stent implantation, acute or subacute stent thrombosis. Symptoms and signs may include recurrent ischemic chest discomfort, ST-segment deviations, and a new rise in serum biomarkers of cardiac injury. Management may require intensification of antithrombotic and anti-ischemic therapy and may include repeat invasive angiography.

Electrical complications may include new onset bradyarrhythmias (including conduction blocks) and tachyarrhythmias, and in particular within the first 24 to 48 hours, ventricular tachycardia. Continuous electrocardiographic monitoring is mandatory to permit prompt identification and acute management of dysrhythmia; indeed, facilitation of prompt defibrillation was a primary motivating factor in the creation of coronary care units.

Mechanical complications include pump failure and cardiogenic shock; acute mitral regurgitation; ventricular septal defect formation; and free wall rupture with pericardial tamponade. Clinicians must maintain a high index of suspicion for these mechanical complications, which may manifest as fulminant clinical deterioration and which, importantly, may present late, 3 to 7 days following myocardial infarction.

In addition to these complications of STEMI itself, attention must be paid to the complications of our therapy. In particular, patients with both STEMI and UA/NSTEMI are exposed to risk of bleeding as a consequence of the acute provision of antiplatelet, anticoagulant, and invasive vascular therapies. Bleeding complications of ACS are important, with adverse prognostic implications. Patients who bleed are at risk for morbidity and mortality related to bleeding itself as well as heightened risk of recurrent ischemic events, which may relate to withholding of antithrombotic therapies or adverse effects of transfusion.

While the emphasis of critical care for acute cardiac ischemia is expeditious restoration of balance between myocardial oxygen supply and demand, also of critical importance is the transition from this acute phase to the work of preventing recurrent ischemic events. The critical care provider has a unique chance to “set the ship on course,” seizing the episode of acute cardiac ischemia as an opportunity to educate the patient about therapeutic lifestyle changes (such as smoking cessation), identify and correct modifiable risk factors for coronary artery disease, arrange for cardiac rehabilitation, and emphasize the importance of medication adherence.