An acute coronary syndrome (ACS) encompasses a clinical spectrum of myocardial ischemia ranging from unstable angina (UA) and non–ST-segment elevation myocardial infarction (NSTEMI) to ST-segment elevation myocardial infarction (STEMI), and represents an acute phase of coronary atherosclerosis.^1-3 Early recognition, diagnosis, and prompt revascularization of the culprit lesion with percutaneous coronary intervention (PCI) is the contemporary management strategy for patients presenting with STEMI or high-risk NSTEMI.^1,2,4,5 Acute plaque rupture and subsequent atherothrombosis with consequent myocardial injury is the most common etiology for ACS; however, myocardial necrosis in the absence of unstable plaque may ensue in critically ill patients who are admitted for non–cardiac-related conditions, such as pulmonary embolism and septic shock. These patients pose a unique diagnostic and management challenge, as concomitant multiorgan failure, electrolyte derangements, and coagulopathy further complicate the clinical picture.^6-8 In this chapter, we will review the universal definition of myocardial infarction (MI) and the related patient presentations, risk stratification models, complications, and management strategies.

Acute myocardial infarction is characterized by myocardial necrosis and is diagnosed in the setting of a rise or fall in cardiac biomarkers in conjunction with clinical symptoms of ischemia, new ischemic electrocardiography (ECG) changes, new regional wall motion abnormalities on imaging, or findings on coronary angiography.^9-11 Myocardial ischemia ensues when the supply of myocardial oxygen is insufficient relative to myocardial oxygen demand. The pathophysiology of ACS is similar in STEMI, NSTEMI, and UA, and involves a milieu of factors, including endothelial dysfunction, vulnerable plaque, plaque disruption, and atherothrombosis, as summarized in Figure 6-1. It is typically precipitated by rupture or erosion of atherosclerotic plaque within a coronary artery, causing thrombosis and leading to an acute and commonly critical reduction in coronary blood flow.^1,12,13 This results in myocardial hypoperfusion, ischemia, diastolic dysfunction, systolic dysfunction, electrocardiographic changes, angina, and ultimately, necrosis.^12,14 ST-segment elevation myocardial infarctions usually represent complete occlusion of the coronary artery, while in NSTE-ACS (NSTEMI and UA), there is a critical reduction in flow.

The universal classification of myocardial infarction is summarized in Table 6-1. Patients with acute plaque rupture resulting in intraluminal thrombosis and decreased myocardial blood flow are classified as type 1 MI.^9,10 These patients need to be rapidly identified, as aggressive pharmacotherapy and immediate reperfusion are the most effective strategy for mitigating the sequelae related to myocardial infarction, including mechanical complications and death. Type 2 MI refers to myocardial injury with necrosis precipitated by an imbalance between myocardial oxygen supply and demand, or demand ischemia, as seen in tachyarrhythmias, anemia, respiratory failure, hypotension, and severe hypertension. This can occur even in normal coronaries, and is the common type of MI seen in critically ill patients.^7,9-11

Acute coronary syndromes represent an important cause of morbidity and mortality. According to the American Heart Association (AHA) heart disease and stroke statistics published in 2016, the overall rate of death attributable to cardiovascular disease was 222.9 per 100,000 Americans, and of those, 370,213 died of coronary artery disease (CAD).^12-15 While some patients have a history of stable angina, an ACS may be the initial presentation of CAD; however, not all patients with elevated troponin have ACS. Prospective studies report approximately 50% of critically ill patients to have elevated troponin, several of whom have no clinically unstable plaque or significant CAD.^16,17 In a single-center study performed in noncardiac critically ill patients, the prevalence of MI, defined as elevated troponin and ischemic ECG changes was 26% to 36%.¹⁸

Chest pain is a frequent presenting concern for patients coming into the emergency room, and rapid identification and management of patients with an acute coronary syndrome is paramount to mitigate the sequela of myocardial necrosis. Patients in the critical care unit may not report chest pain since they are often sedated or incapacitated from other causes; therefore, other objective findings need to be utilized in the setting of strong clinical suspicion. In the absence of reported anginal symptoms, new clinical findings such as dynamic ECG changes, new ST-segment elevation, new regional wall motion abnormalities on echocardiography, or new moderate-to-severe mitral regurgitation, should prompt further investigation to rule out ACS. Nonsedated patients will likely express angina. Typical angina has 3 defining characteristics: (1) retrosternal chest pressure usually lasting more than 10 minutes that is (2) provoked by exertion or emotional stress, and (3) relieved by rest or nitroglycerin. Pain may be associated with radiation to the arm, jaw, and back, and furthermore, there may be associated diaphoresis, nausea, dyspnea, and occasionally syncope.^1,2,18,19

There is a subset of patients with atypical presentations, including women, diabetics, chronic renal failure, and the elderly (> 75 years). These patients may report sharp pain, epigastric discomfort, progressively worsening dyspnea, or pleuritic chest pain. It is important to obtain a proper history to support the diagnosis of ACS and include association of symptoms with activity, and relief with nitrates or rest, and assess change in baseline angina. Risk factors for CAD also help stratify patients presenting with suspected ACS, and are summarized in Table 6-2.^1,2

While ACS is an important cause of chest pain, the differential diagnosis of chest pain is fairly broad. It is also important to know life-threatening nonatherosclerotic conditions that may mimic acute coronary syndromes, and for which initiation of standard therapy for ACS may exacerbate the underlying condition (Table 6-3).

Electrocardiograms in Acute Coronary Syndrome

Interpretation of the ECG is an essential component of the initial diagnostic evaluation of patients with suspected ACS. In patients with high suspicion for ACS but with a nondiagnostic ECG, serial ECGs at 15- to 30-minute intervals during the first hour to evaluate dynamic ST change should be obtained. Supplemental electrocardiographic leads V₇ to V₉ to rule out posterior infarcts can also aid the diagnosis.^1,2,20,21 It should be noted that there is a myriad of nonischemic clinical scenarios that confound interpretation of the ECG, such as a left bundle branch block (LBBB), left anterior fascicular block, preexcitation, severe hyperkalemia, and left ventricular hypertrophy (LVH).^22,23

Figure 6-2 summarizes common ECG findings in patients presenting with ACS.

Cardiac Biomarkers in Acute Coronary Syndrome

In addition to careful history taking and ECG analysis, myocardial injury with necrosis can be detected with biomarkers such as cardiac troponin (cTn) I or T, creatinine kinase (CL)–muscle/brain (MB) fraction. Cardiac biomarkers are invaluable in differentiating UA from NSTEMI and also help estimate the extent of myocardial necrosis. Troponin is a complex of 3 regulatory proteins, troponin C, troponin I, and troponin T, which integrate to the contraction apparatus in skeletal and cardiac muscle. Troponin is attached to tropomycin and lies within the groove of actin filaments in muscle tissue.

Cardiac troponin I and T are the preferred diagnostic tests for acute coronary syndromes because of the tissue-specific expression within the myocardium. Troponins are more specific and sensitive than CK, CK-MB (isoenzymes of CK), and myoglobin. In patients with STEMI, troponin begins to rise within 4 hours after onset of symptoms and may be persistently elevated for up to 2 weeks post-infarct.^24-26 The gains in sensitivity are offset with the decrease in specificity. While elevated troponin is indicative of myocardial injury, it does not discriminate etiology or mechanism of injury. Myocardial infarction is consistent with the presence of elevated cTn to at least the 99th percentile of the upper reference limit, with subsequent increase or decrease (> 3 standard deviations of variance) on serial blood draws in the context of appropriate clinical criteria for ischemia, dynamic ECG changes, or imaging evidence of myocardial injury.^9-11,24

A positive troponin in a patient with low pretest probability for ACS may be suggestive of ACS; however, this result needs to be corroborated with ECG data and clinical presentation. Conversely, a negative troponin does not rule out ACS, and an emergent angiogram should not be delayed if there are electrocardiographic and clinical symptoms consistent with STEMI. Circulating cTnT or cTnl can be found in the plasma of patients with a transient ischemic attack (TIA) or inflammatory myocardial injury, as well as pulmonary embolus.²⁷ In addition to the absolute level of troponin, a critical component of the diagnosis of ACS is the cTn kinetics. Absolute cTn elevation is seen in multiple chronic cardiac and noncardiac conditions; however, a rise or fall in serial cTn levels supports acutely evolving cardiac injury, as seen with an acute coronary syndrome.^24,28-30

There is a high prevalence of coronary artery disease in patients with reduced glomerular filtration rate and in patients with end-stage renal disease (ESRD), and these patients tend to have worse clinical outcomes post-ACS.³¹ Troponin T levels predict short-term prognosis regardless of level of creatinine.³² Patients with advanced renal disease not yet on dialysis and presenting with STEMI should proceed to urgent angiogram, and post-procedure have close monitoring of urine output, creatinine, and electrolytes, to determine the need for dialysis, as the risk for contrast-induced nephropathy is high in this group. Additionally, acute renal insufficiency post-MI is associated with worse morbidity and mortality.^33,34

Brain (B-type) natriuretic peptide (BNP) is a peptide that is synthesized and released predominantly from the ventricular myocardium secondary to myocyte stretch and is a well-established biomarker in patients with heart failure. In patients with ACS, it is useful for prognostication and assessment of the degree of left ventricular dysfunction.^35-37 In the current guidelines, it is a class IIb indication to use BNP to provide additional prognostic information.^1,2

Risk Stratification

Prompt diagnosis of ACS is crucial to stratify patients who are at greatest risk for recurrent ischemic events and death. The HEART score uses elements of patient History, ECG, Age, Risk factors, and Troponin to stratify the risk of patients presenting to the emergency department (ED) with chest pain, and can be extrapolated to patients already admitted, such as in the critical care unit, who report chest pain, and for whom a definitive diagnosis of ACS has not been established.^38-40

Table 6-4 summarizes the components of the heart score.

Patients with ACS are a heterogeneous group and have varied risks of death and recurrent cardiac events. Several well-validated clinical prediction tools have been developed to stratify patient risk for major complications related to their myocardial infarction. The Thrombolysis In Myocardial Infarction (TIMI) and Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (PURSUIT) scores were developed from large clinical trials in patients with NSTE-ACS and predict short-term prognosis, whereas the Global Registry of Acute Coronary Events (GRACE) score was developed from a global registry and estimates in the hospital and from 6-month mortality in patients who present across the ACS spectrum.^41-44 Of note, compared to TIMI, PURSUIT and GRACE risk scores are better discriminators for in-hospital and 1-year mortality in patients presenting with NSTEMI or STEMI. The Killip classification system is used to assess the severity of heart failure in patients presenting with ACS and represents an independent predictor of all-cause mortality in patients with ACS.⁴⁵ More recently, a prospectively derived validated score for estimating 1-year mortality of STEMI at hospital discharge was proposed (Dynamic TIMI) using variables from the original TIMI risk score combined with index hospitalization clinical events that adversely affect mortality.^41,46

Table 6-5 summarizes the components of TIMI, Dynamic TIMI, PURSUIT, and GRACE scores.

Pharmacotherapy

In patients with ACS, the goal of therapy is the prevention of further myocardial ischemia/injury and death. In addition to obtaining serial ECGs and cardiac biomarkers, assessment of left ventricular function and initiation of the appropriate pharmacotherapy are paramount to the optimization of care.^1–3,47 Patients should be treated with antiplatelet, anticoagulation, and antianginal agents, and in clinically appropriate scenarios, β antagonists, angiotensin-converting enzyme inhibitors (ACEI), and nitrates. Ultimately, in patients with STEMI, prompt reperfusion should ensue in clinically appropriate settings, and in NSTE-ACS, the decision regarding early invasive strategy or an ischemia-guided strategy for coronary reperfusion needs to be established.^4,48-51

Tables 6-6, 6-7, and 6-8 summarize the most current guideline recommended antiplatelet, anticoagulation, and adjunct medications used in patients presenting with ACS.