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.
Table 24–2Differential diagnosis of acute chest pain in the intensive care unit. |Favorite Table|Download (.pdf) Table 24–2 Differential diagnosis of acute chest pain in the intensive care unit.
|Diagnosis ||Historical Features |
|Pulmonary embolism || |
Venous thromboembolism risk factors may be present
|Pneumonia || |
|Aortic dissection || |
Radiation to back
|Gastritis/esophageal reflux ||May vary with meals or antacids |
|Esophageal spasm ||May improve with nitrates |
|Pericarditis || |
|Musculoskeletal || |
May be elicited with palpation, motion or sometimes respiration
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.
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.
Table 24–3Differential diagnosis of ST-segment elevations. |Favorite Table|Download (.pdf) Table 24–3 Differential diagnosis of ST-segment elevations.
|Acute myocardial infarction |
|Early repolarization |
|Left ventricular hypertrophy |
|Left bundle branch block |
|Acute myopericarditis |
|Brugada syndrome |
|Pulmonary embolism |
|Ventricular aneurysm |
|Apical ballooning syndrome (Takotsubo cardiomyopathy) |
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.
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.
Kinetics of cardiac-specific biomarkers in myocardial infarction. A, myoglobin after MI; B, troponin after MI; C, CK-MB after MI; D, troponin in UA. (Reproduced with permission from Wu AH, Apple FS, Gibler WB, et al: National Academy of Clinical Biochemistry Standards of Laboratory Practice: recommendations for the use of cardiac markers in coronary artery diseases, Clin Chem 1999 Jul;45(7):1104-1121.)
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.
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).
Table 24–4Universal classification of myocardial infarction. |Favorite Table|Download (.pdf) Table 24–4 Universal classification of myocardial infarction.
|Type ||Description |
|1 ||Spontaneous |
|2 ||Secondary to an ischemic imbalance |
|3 ||Resulting in death when biomarkers are unavailable |
|4a ||Related to percutaneous coronary intervention |
|4b ||Related to stent thrombosis |
|5 ||Related to coronary artery bypass grafting |