Chapter 50

Chest Pain and Myocardial Ischemia

Evaluation of chest pain and recognition of myocardial ischemia in patients in intensive care units (ICUs) are essential skills of intensivists. Myocardial ischemia and infarction significantly increase the morbidity and mortality of ICU patients. However, effective interventions have been developed to treat myocardial ischemia and infarction. It is critical to have an understanding of how to provide prompt and appropriate treatment for this condition to effectively care for ICU patients. This chapter describes the approach to the patient with chest pain, the differential diagnosis of chest pain in the ICU, and the optimal treatment for acute coronary syndromes, with particular attention to specific issues that may arise in the ICU setting.

Pathophysiology of Myocardial Ischemia and Acute Coronary Syndromes

Myocardial ischemia and infarction result when myocardial oxygen supply is inadequate to meet myocardial oxygen demand. Myocardial oxygen supply is dependent on available oxygen, the oxygen-carrying capacity of the blood, and the perfusion pressure of and resistance to coronary blood flow. The latter is largely dependent on patency of the coronary arteries. Any fixed stenosis (≥ 70% of lumen) in an epicardial vessel may limit this augmentation of myocardial blood flow, upsetting the normal supply-demand balance and precipitating ischemia. Furthermore, oxygen-carrying capacity may be reduced as a consequence of hypoxemia or anemia, both of which can impair myocardial oxygen supply. Myocardial oxygen demand is dependent on heart rate, contractility, and wall stress. In the ICU patient, fever, pain, and endogenous or exogenous catecholamines promote tachycardia, increased myocardial contractility, and the generation of higher systolic wall tension, all of which increase myocardial oxygen demand.

In the postoperative patient, this oxygen supply may be also diminished as a result of intraoperative blood loss or iatrogenic hypotension. Like critical illness, recovery from major trauma or surgical interventions places extra demands on the myocardium by increasing total-body minute oxygen consumption (see Chapter 8). Finally, oxygen supply-demand balance may also be offset by pharmacologic interventions. For example, vasopressors and inotropic agents may cause tachycardia and augment myocardial contractility, thus increasing myocardial oxygen demand.

The pathophysiology of supply-demand mismatch leading to myocardial ischemia differs from that of acute coronary syndrome (ACS). The anatomic basis for most cases of ACS is the acute fissuring and rupture of an atherosclerotic plaque in an epicardial coronary artery with formation of superimposed thrombus. Plaques that rupture tend to have a thin fibrous coat over a central collection of foam cells, lipid, and necrotic debris. The vulnerable plaque typically ruptures near its junction with normal endothelium, and this exposes collagen and atheromatous material, which, in turn, leads to thrombosis.

The triggers of acute plaque rupture are not fully defined. Most likely, acute hemodynamic stress is the trigger, but acute and chronic endothelial inflammation may also play a role. There is a circadian variation in the occurrence of all acute cardiovascular events, including myocardial infarction (MI), sudden death, and stroke, with their peak frequency in the first 2 hours after awakening. On arising and assuming an upright posture there are a variety of acute circulatory adjustments, including the release of catecholamines, which results in increased cardiovascular tone and hemodynamic stress. In addition, in these hours there is an increase in blood viscosity and platelet aggregation. Beta-blocker therapy eliminates the higher morning incidence of acute cardiovascular events, which suggests that catecholamine release and hemodynamic stress are important causative events.

The extent of the thrombotic reaction dictates the clinical course and subsequent clinical syndrome. The plaque rupture and superimposed thrombus formation can be transient with resolution via the body’s own antithrombotic mechanisms before any permanent myocardial damage. In addition, a variety of vasoactive mediators are released from the endothelial wall that can cause vasospasm and transient complete occlusion. This leads to a syndrome of unstable angina (UA). If the injury is persistent but causes partial occlusion of the vessel, it is classified as non-ST-elevation myocardial infarction (NSTEMI). If the injury is severe and deep, the thrombotic reaction may lead to total occlusion of a coronary artery. This is classified as ST-elevation myocardial infarction (STEMI). The management of these syndromes is separated based on whether the patient is experiencing UA/NSTEMI or STEMI.

Causes of Chest Pain

The differential diagnosis of chest pain in the ICU patient is extensive and includes a number of cardiovascular and noncardiovascular causes (Table 50.1). Esophageal pain shares some features with classic angina; it is typically retrosternal and frequently relieved with nitroglycerin. Reflux pain is often burning in nature, aggravated by lying down, and related to eating. Pain aggravated by movement or by palpation of the affected area is likely to be due to musculoskeletal causes. The description of chest pain may be most helpful in differentiating other cardiopulmonary causes. For instance, the chest pain of pericarditis is typically sharp and pleuritic, relieved by leaning forward. The chest pain of aortic dissection is typically “tearing” in quality, reaches maximal intensity instantaneously, and radiates to the back or flanks. The chest pain of pulmonary embolism, when present, is more often sharp and associated with dyspnea, hypoxemia, or hemoptysis in the absence of other signs of left-sided heart failure. Pneumothorax pain is usually sharp, sudden, and accompanied by dyspnea. Frequently, many patients are admitted to the hospital with a diagnosis of “rule out MI” and are discharged after a cardiac enzyme evaluation is negative and a stress test is normal. These patients have a great deal of uncertainty regarding the actual cause of their chest discomfort, and further evaluation and intervention are essential in their postdischarge care.

TABLE 50.1

Causes of Chest Pain in the Intensive Care Unit

*Cardiovascular*	Angina Acute coronary syndrome/myocardial infarction Aortic dissection Congestive heart failure Pericarditis
*Pulmonary*	Pulmonary embolism with/without pulmonary Infarction Pneumothorax Pneumonia Pulmonary hypertension Pleurisy/pleuritis Tracheobronchitis Chest tubes
*Gastrointestinal*	Esophageal reflux Esophageal spasm Peptic ulcer disease Gallbladder disease Pancreatitis Hepatic capsular distention Subdiaphragmatic abscess
*Musculoskeletal*	Costochondritis Arthritis Postcardiopulmonary resuscitation (CPR) trauma Postoperative incisional or other related pain Cervical spine disease
*Infectious*	Herpes zoster
*Psychological*	Anxiety Panic disorder

Clinical Presentation of Angina and Chest Pain

Symptoms

Recognition and treatment of coronary ischemia in the ICU are important. Ischemia may occur spontaneously or, more often, may occur in the setting of precipitants such as anemia, fever, or postoperative stress. Typical angina may range from a minor discomfort to severe pain. The discomfort is often described as pressure, heaviness, or indigestion. If “pain” is present, it is frequently described as crushing, squeezing, or burning. Classically, angina is located substernally and radiates to the left arm, neck, or jaw. Superficial discomfort is less likely to be caused by myocardial ischemia. Moreover, the chest discomfort of myocardial ischemia does not begin suddenly at maximal intensity but rather crescendos in intensity.

Three different anginal syndromes are recognized. Provocable angina generally results from transient changes in myocardial supply and demand balance in the setting of a stable, flow-limiting atherosclerotic plaque. Unstable angina differs anatomically from provocable angina. It results from rupture of a previously stable plaque with a superimposed thrombus. A significant proportion of patients with unstable angina can progress to acute myocardial infarction, reflecting complete occlusion of a coronary artery. Variant, or Prinzmetal’s, angina, attributed to coronary vasospasm, is neither provocable nor due to plaque rupture and generally occurs at rest.

Although chest discomfort remains the most common complaint of patients with cardiac ischemia, certain associated symptoms often support the diagnosis. Patients frequently experience dyspnea as a result of increased interstitial pulmonary edema and diaphoresis resulting from autonomic instability. Nausea and vomiting caused by gastric dilatation may ensue as a consequence of cardiac sensory receptor stimulation. Dizziness or syncope may accompany ischemia or infarction, typically either vasovagally mediated or the result of tachyarrhythmia or bradyarrhythmia.

Symptoms of ischemia or myocardial infarction may be difficult to discern in the critically ill patient because of comorbid illnesses and sedating medications. Even when patients have the capacity to communicate, nearly 20% of those with acute myocardial ischemia or infarction will not develop chest discomfort. In this case, ischemia is “silent”—that is, it manifests only as objective signs in the absence of patient awareness. Recognition of ischemia in the ICU therefore requires careful scrutiny of hemodynamics, targeted physical examinations, and careful review of electrocardiographic (ECG) changes from baseline.

Physical Findings

Physical signs of myocardial ischemia are frequently nonspecific in the critically ill patient. Vital sign abnormalities can suggest a perturbation in cardiac function. When tachycardia is present and accompanied by a thready pulse, compromised cardiac output must be suspected. Alternatively, bradycardia may be seen because of excessive vagal tone or sinoatrial or atrioventricular nodal ischemia; in association with poor peripheral perfusion, this condition suggests right ventricular ischemia or infarction. Hypertension may accompany ischemia, secondary to excessive catecholamine release, whereas relative hypotension may also occur on the basis of impaired cardiac output.

After evaluation of vital signs, physical examination should include a thorough cardiovascular, pulmonary, and extremity exam. Examination of the heart may reveal a new S3 or S4 gallop from acute systolic or diastolic dysfunction. Precordial examination may reveal an ectopic impulse from a bulging akinetic myocardial segment. There may be a murmur of mitral regurgitation caused by ischemia of the papillary muscle. Jugular venous pressure may be elevated if right ventricular failure is present. When ischemia is accompanied by left ventricular heart failure, auscultation of the lungs may reveal crackles, resulting from opening of fluid-filled alveoli, or wheezes, resulting from reflex bronchoconstriction. Peripheral signs of ischemia include diaphoresis with cool, clammy skin, ashen skin caused by peripheral vasoconstriction or cyanosis, slow capillary filling, and livedo reticularis resulting from poor cardiac output.

Diagnostic Evaluation

Electrocardiogram (ECG)

The electrocardiogram (ECG) is a crucial source of data in the evaluation of chest pain. It should be obtained as soon as possible after presentation in patients with chest discomfort. In addition, it should be obtained in the ICU patient routinely, particularly if there are unexplained changes in vital signs or physical signs, such as tachypnea, hypotension, or tachycardia. Either transient ischemia or frank myocardial infarction may be identified. The key changes of myocardial ischemia or infarction on the ECG are repolarization abnormalities, arrhythmias, or conduction blocks.

Repolarization Abnormalities

Most commonly, myocardial ischemia is accompanied by changes in the T waves or ST segments on the standard 12-lead ECG. These include transient T-wave inversion or ST-segment depression. Right coronary artery ischemia is best visualized in leads II, III, and aVF; circumflex artery ischemia in leads I, aVL, V₅, and V₆; and left anterior descending (LAD) artery ischemia in the precordial leads, V₁ to V₄. Leads V₁ and V₂ may also reflect posterior wall ischemia or infarction by recording electrical forces opposite in direction to the forces of anterior ischemia. This is attributable to ischemia of the right coronary artery or the left circumflex artery (whichever is dominant).

The classic ECG manifestation of ischemia is downward displacement of the ST segment (Figure 50.1). Horizontal and downward-sloping ST segments are generally more specific than upsloping ST segments. Although less specific, flattening of the ST segment with increased angulation at the ST-segment/T-wave junction also suggests ischemia. With resolution of ischemia, ST segments typically return to baseline. When ST segments remain depressed, subendocardial myocardial infarction should be suspected. ST-segment elevation is consistent with acute transmural myocardial infarction and is often followed by T-wave inversion and the appearance of Q waves (Figure 50.2A). A new left bundle branch block (LBBB) is felt to be equivalent to an ST-segment elevation infarction as it may represent complete occlusion of the LAD prior to septal branches that perfuse the left bundle branch. Less often, ST-segment elevation reflects transient myocardial ischemia secondary to vasospasm (Prinzmetal’s angina). Diffuse, widespread ST elevation may be secondary to pericarditis.

Figure 50.1 Twelve-lead electrocardiogram (ECG) from a 76-year-old diabetic, hypertensive man with excellent exercise tolerance, who developed asymptomatic ECG changes on the first postoperative day after total hip replacement. He ruled in for myocardial infarction and developed heart failure; cardiac catheterization revealed left main and three-vessel disease. Note ST-segment depression in leads I, II, III, aVF, and V₃ through V₆, with reciprocal ST-segment elevation in lead aVR.

Figure 50.2 A, Twelve-lead electrocardiogram (ECG) from a 51-year-old man with a history of hypertension and hyperlipidemia who presented with 2 hours of chest pain. ECG revealed ST-elevation myocardial infarction, and he was referred for emergent cardiac catheterization. Note ST elevations in leads II, III, and avF with reciprocal ST-segment depression in leads I and avL. There is also an R-wave in V1 and V2 with ST-segment depression. This is consistent with an inferoposterior myocardial infarction. B, Cardiac catheterization revealed a completely occluded right coronary artery. Successful percutaneous coronary intervention was performed on this lesion with a good outcome for the patient. C, Following percutaneous coronary intervention and stent placement, the patient achieved complete reperfusion of the infarcted territory and his symptoms resolved.

Interpretation of T-wave changes in the absence of ST-segment changes is more difficult, owing to lack of specificity. T-wave inversion is most suggestive of ischemia when deep and symmetric in several leads; less specific are T waves that invert asymmetrically, with a gentle downslope and a rapid upslope. Such T-wave morphologies are typical of repolarization abnormalities seen in association with ventricular hypertrophy or bundle branch block. In patients whose baseline ECG demonstrates inverted T waves, ischemia may result in pseudonormalization of T waves to the upright position.

In the ICU, postural adjustments, hyperventilation, neurologic events (e.g., subarachnoid hemorrhage), and anxiety can produce T-wave changes identical to those precipitated by ischemia. A number of pharmacologic agents often used in the ICU may also produce T-wave changes, including digitalis, antiarrhythmic drugs, sympathomimetic and sympatholytic agents, tricyclic antidepressants, barbiturates, lithium, and insulin. A variety of reversible extracardiac illnesses frequently seen in the ICU have also been implicated in T-wave changes, including allergic reactions, hemorrhage, viral infections, hypothyroidism or hyperthyroidism, adrenal insufficiency, hypokalemia, strokes, pulmonary embolism, and intra-abdominal diseases, such as acute pancreatitis or acute cholecystitis.

Arrhythmias (see Chapters 33 and 34 for more details)

Arrhythmias may be additional ECG manifestations of myocardial ischemia or infarction, although they may also occur as a manifestation of structural heart disease (hypertension, left atrial abnormalities, etc.). These can include atrial arrhythmias (atrial tachycardia, atrial fibrillation, and atrial flutter), sinus tachycardia, and ventricular tachycardia/fibrillation. Conduction blocks ranging from first-degree atrioventricular (AV) block to complete heart block can also be seen.

Chest Radiography

In the setting of myocardial ischemia, chest radiographs frequently demonstrate evidence of interstitial or alveolar edema. When it appears in an interstitial pattern, edema manifests as haziness among pulmonary vascular markings, owing to pulmonary venous engorgement as well as peribronchial cuffing. This is accompanied by thickening of interlobular septa with engorged lymphatic vessels, known as Kerley B lines, which appear as short, horizontal, linear densities at the lung periphery. If interstitial fluid accumulates rapidly, it may flood alveoli, resulting in confluent opacification, usually in a perihilar or “batwing” distribution. Unilateral or bilateral pleural effusions may also accompany acute ischemic cardiac failure.

Cardiac Enzymes

Myocardial injury results in the release of a variety of intracellular biochemical markers. The most commonly measured of these include creatine kinase (CK), its dimeric isoform CK-MB (isoenzyme of creatine kinase with muscle and brain subunits), and troponins I and T (Table 50.2). Typically, postinfarction CK and CK-MB appear within 4 to 6 hours and peak within 18 to 24 hours. Both remain elevated for 48 to 72 hours following infarction, but, as a result of faster clearance, CK-MB usually returns to baseline before total CK. Measurement of CK and its isoenzymes is very sensitive, but trace amounts of CK-MB are also found in a number of other tissues, so care must be taken in interpreting rises in CK-MB after surgery or trauma.

TABLE 50.2

Assessment and Management of Chest Pain in the Intensive Care Unit

History	Character, timing, radiation of pain Associated symptoms Cardiac risk factors
Physical Exam	Vital signs Focused cardiac and pulmonary examination Signs of congestive heart failure
Diagnostic Evaluation	ECG (ST-T new wave changes consistent with ischemia/infarction; Q waves; arrhythmias) Cardiac biomarkers (troponin, CK, CK-MB)
Risk Stratification	TIMI risk score Echocardiography
Contributing Causes	Consider precipitants for ischemia other than acute coronary syndrome —Sepsis —Hypovolemia —Trauma —Anemia —Stress from postoperative state
Medical Therapy	Anti-ischemic therapy —Oxygen —Analgesia —Beta-blockers —Nitrates Antiplatelet therapy —Aspirin —Thienopyridines (i.e., clopidogrel) —Glycoprotein IIb/IIIa inhibitors Anticoagulant therapy —Heparin, low-molecular-weight heparin Statins ACE inhibitors
Invasive Therapy	STEMI —Prompt angioplasty/PCI —Thrombolytics if PCI not available NSTEMI/UA —Consider invasive approach within 24–48 hours