Pathology and Pathophysiology
Pathology Coronary atherosclerosis is particularly prominent at branch points vessels. Atherosclerotic lesions ap-pear initially as "fatty streaks"--i, e. , lipid-laden cells, pre-sumably monocytes or macrophages, adhering to the endothe-lial surface and ultimately penetrating the intima. More ad-vanced fibrous plaques comprise not only lipid-laden ceils but also connective tissue and proliferating smooth muscle cells. The most advanced lesions, called complicated plaques, exhibit fibrocalcific degeneration with intra-and extracellular lipid, calcium, fibrous tissue, necrotic debris, extravasated blood, and a fibrous tissue cap. Platelet-rich mural thrombi are often associated with the surface. Atherogenesis may reflect en-dothelial injury; perineation of atherogenic lipoproteins such as oxidized LDL;platelet and monocyte mitogens; and impaired reverse cholesterol transport attributable to low HDL. It is un-doubtedly linked intimately to thrombosis. For example, platelet-derived growth factors may contribute to atherogene-sis, impaired endothelial cell function caused by early atherosclerosis may predispose to platelet adhesion and activa-tion, diminished endothelial elaboration of activators of fibri-nolysis or augmented release of inhibitors may apredispose to thrombosis, and vasospasm in atherosclerotic vascular seg-ments may potentiate platelet activation through augmentation of sheer forces.
The spectrum of injury manifest in myocardium depends not only on the intensity of impairment of myocardial perfusion but also on its duration. Accordingly, no conventional micro-scopic or gross changes may be evident in hearts of patients who die suddenly as a result of an acute coronary event. Typi-cal infarction is manifest by coagulation necrosis followed ulti-mately by fibrosis. Contraction-band necrosis occurs when is-chemia is followed by reperfusion or accompanied by massive a-drenergic stimulation, often with myocytolysis.
In patients who succumb with a history of preceding un-stable angina, morphologic manifestations of frank infarction may be lacking. However, platelet microemboli and vascular mural thrombosis of diverse ages are seen, indicative of the un-derlying pathophysiology involving repetitive thrombotic phe-nomena initiated by dynamic changes in complicated atherosclerotic plaques. In victims of infarction reflected by evolutionary ECG changes, the classic differentiation of trans-mural from nontransmural infarction based on ECC criteria (the presence or absence of Q waves after complete evolution of the insult) serves only as a crude generalization in view of bidirectional overlap of morphologic lesions associated with each ECG pattern.
Pathophysiology The right and left coronary arteries arise independently from individual ostia associated with right and left aortic valve cusps. The left anterior descending (LAD) and circumflex coronary arteries arise as the left main coronary artery bifurcation and supply the anterior left ventri-cle, the bulk of the interventricular septum, and the lateral and posterior left ventricular walls. The apex,lateral wall, and posterior wall may be supplied by the right posterior descend-ing coronary artery, diagonals from the LAD, and the posterior left ventricular branch of the right coronary artery, respective-ly. When the posterior descending coronary artery that sup-plies the supplies the atrioventricular (AV) node in 90 percent of subjects. Another branch (in 55 percent of subjects) sup-plies the sinuns note. The right ventricle is supplied by the right coronary artery. Although the posterior division of the left bundle branch has a dual bkood supply (from both the left and right coronary arteries), the anterior fascicle of the left bundle and the right bundle are each supplied primarily by branches of the anterior descending coronary artery.
In view of anatomic consideration it is not suiprising that right coronary artery occlusion is manifested frequently by si-nus bradycardia, AV block, right ventricular infarction, or left ventricular infarction, or left ventricular infarction of mod-est extent. Conversely impried leftfventricular function with pulmonary congestion or edema indicative of extensive injury and intraventricular conduction defects such as hemiblock are more typical of left coronary artery occlusion.
Acute insults are generally attributable to thrombosis ini-tiated by hemorrhage or rupture of complicated atheromatous plaques with deprivation of blood flow to myocardium as a final common denominator. Even if recanalization is induced rela-tively promptly (spontaneously, mechanically, or with fibri-nolytic drugs), regional myocardial perfusion may not be sus-tained ( the "no reflow" phenomenon) because of endothelial cell swelling, platelet and leukocyte plugs, or complement-me- diated microvascutar inflammation. In addition to hypoxia, de-creased removal of noxious metabolites, including potassium, calium, amphiphilic lipids, and oxygen-centered free radicals, impairs ventricular performance and may evoke lethal arrhyth-mias. Inflammation of endocardial surfaces and stasis associated with dyskinesis can lead to ventricular mural thrombi. Epicar-dial inflammation may initiate the pericardial involvement seen with as many as 20 per cent of Q-wave infarcts.
Signs and Symptoms
"Typical" Q-wave infarction is manifested by prodromal symptoms of fatigue, chest discomfort, or malaise in the days preceding the event. Onset of infarction occurs often in the early morning hours, presumably in part because of the in-creased catecholamine-induced platelet aggregation and dimin-ished plasma concentrations of PAI-I after awakening. Onset is generally not directly associated with severe exertion.
Typical pain is intense, severe, unremitting for 30 to 60 minutes, crushing or squeezing in nature, retrosternal, and of-ten radiating down the ulnar aspect of left arm and into the neck, teeth, or jaw. Occasionally the pain is epigastric. Di-aphoresis, weakness, a sense of impending doom, profound restlessness, confusion, presyncope, hiccuping(presumably re-flecting irritation of the diaphragm), nausea and vomiting, and palpitations are common. Decreased systolic ventricular performance accounts for impaired perfusion of vital of vital or-gans and reflexly mediated compensatory responses to hypoten-sion such as restlessness and impaired mentation, pallor, cuta-neous vasoconstriction and sweating, tachycardia, and prerenal failure. Impaired left ventricular diastolic function leads to pul-monary vascular congestion with shortness of breath and tachypnea and pulmonary edema with orthophea. Impaired right ventricular diastolic function leads to systemic venous hy-pertension, edema, hepatomegaly, and further compromise of left ventricular cardiac output.
Myocardial infarction may be clinically silent (in as many as 1 per cent of patients), with the diagnosis established only retrospectively by ECG criteria. The patient may recall only an episode of "indigestion" or nothing. Stoicism, an unusually high pain threshold, disorders impairing function of the ner-vous system such as diabetes mellitus, or obtundation caused by medications or impaired cerebral perfusion may prevent recognition of typical chest pain.
Physical Findincs Typical of Acute Myocar-dial Infarc-tion.
Typical clinical findings can be summarized as follows:
General Appearance Pallor, diaphoresis, and restless-ness are present.
Vital Signs Heart rate is often increased secondary to sympathoadrenal discharge, ventricular ectopy, accelerated id-ioventric ular rhythm, ventricular tachycardia, atrial fibrilla-tion or flutter, or other supraventricular arrhythmias, especial-ly when atrial infarction or heart failure is present. Brad-yarrhythmias attributable to impaired sinus node function, AV nodal block, or infranodal block may be evident. The blood pressure is generally elevated initially with arterial vasocon-striction, in contrast to the case with acute pulmonary em-bolism, in which initial hypotension is frequent. However, with right ventricular infarction or severe left ventricular dys-function, hypotension occurs, The respiratory rate is usually increased in response to pulmonary congestion. Coughing, wheezing, and production of frothy sputum may occur. Fever is usually present within 24 to 48 hours and may exceed
Funduscopic Examination Manifestations of atheroselerotic vascular disease including copper wiring of arterioles, of hyperten-sion with arterial narrowing and hemorrhages, or of conditions predisposing to atherosclerosis such as diabetes with microa-neurysms may be seen, Funduscopic examination is particular-ly important to detect hemorrhage, which is a relative con-traindication to treatment with fibrinolytic agents.
Arterial and Venous Pulses Pulsus alternans, although rare, may reflect impaired left ventricular function, as may brevity of the carotid pulse secondary to decreased stroke volume, Jugular venous distention may accompany right ven-tricular infarction or right ventricular failure secondary to pro-found left ventricular dysfunction and pulmonary hyperten-sion.
Chest Rales secondary to pulmonary venous hyperten-sion are common with extensive left ventricular infarction; pleural effusions occur generally only with biventricular fail-ure.
Heart Lateral displacement of the apex impulse, dyski-nesis, a palpable $4, and a soft S1 may be indicative of dimin-ished contractility of the compromised left ventricle;paradoxi-cal split ring of S2 may reflect left bundle branch block or pro-longation of the pre-ejection period with delayed aortic valve closure despite decreased stroke volume;accentuated $4 and S may reflect diminished left ventricular complianee;a mitral re-gurgitation murmur indicative of either papillary muscle dys-function or rupture of annulus dilatation may be audible even if cardiac output is diminished markedly; a pericardial friction rub may be evident, premature ventricular beats, brief runs of ventricular tuchycardia, or accelerated idioventricular rhythm are common.
Abdomen Hepatojugular reflux may be elicited even when hepatomegaly is not marked
Extremities Peripheral cyanosis, edema, and pallor may indicate vasoconstriction, and diminished cardiac output may reflect right ventricular dysfunction or failure.
Neurologic Findings Patients with acute myocardial in-farction are prone to frank cerebrovascular insults as a result of ventricular mural thrombi and consequent embolization(with an incidence of approximately 1 per cent). Recrudescence of signs or symptoms of a prior cerebrovascular accident may oc-cur secondary to diminished cerebral perfusion. In contrast, the incidence of myocardial infarction in patients with cere-brovascular accidents in substantial.
The incidence of myocardial infarction appears to be greater and its prognosis worse in patients with depression. In-farction may precipitate reactive depression whether or not a drenergic blocking agents or other central nervous system (CNS)-active agents are administered.
Hemodynamic Manifestations
Hemodynamic observations are of inestimable value in guiding therapy.
Patients Requiring Invasive Monitoring Not all patients with infarction require hemodynamic monitoring with right heart catheterization and/or invasive arterial pressure monitor-ing. Those who, are hemodynamically stable without apparent complications such as tachycardia, refractory arrhythmia, res-piratory compromise, impairment of cerebral hepatic, or renal function, or persistent or recurrent pain indicative of recurrent of refractory ischemia, pericarditis, or incipient cardiac rup-ture can generally be managed without invasive hemodynamic monitoring. Effective management may be facilitated by bal-loon flotatin right heart catheter hemodynamic monitoring in patients with pulmonary congestion indicative of pulmonary venous hypertension reflected by physical findings or chest roentgenographic abnormalities, but many patients with mild complications can be managed conservatively. Patients with peripheral hypoperfusion despite initial administration of fluids to replete or expand vascular volume and those with severe, re-fractory, or progressive congestive heart failure, potentially catastrophic complications of acute infarction refractory ar-rhythmias, persistent pain, or hemodynamic instability should be evaluated by balloon flotation right heart catheter hemody-namic monitoring.
Monitoring catheters should generally be introduced through compressible sites, particularly because of the high likelihood that thrombolytic agents will be used early in the treatment of infarction. They should remain in place for no more than 72 hours to avoid the risk of infection and can often be removed much more promptly. Sometimes ascertainment of systemic and pulmonary venous pressure, cardiac output, and peripheral vascular resistance is sufficient for subsequent man-agement without the need for continuous monitoring. In other instances the effects of vasodilators, diuretics, agents with positive inotropic effects, and therapeutic alterations of vascu-lar volume should be monitored over the ensuing 48 to 72 hours.
Hemodynamic Subsets Patients are categorized with re-spect to cardiac output (increased, normal, or diminished), systemic arterial blood pressure (increased, normal, or dimin-ished with or without increased or decreased systemic vascular resistance), and the presence or absence of pulmonary venous hypertension (augmented pulmonary arterial wedge pressure).
Patients without diminished systemic arterial blood pres-sure or pulmonary venous hypertension may have normal or hyperdynamic hemodynamics (the latter reflected by a high cardiac output with or without hypertension caused by sympa-thoadrenal stimulation). Systemic arterial hypotension may be attributable to relative or absolute hypovolemia or to right ven-tricular infarction (generally reflected by augmented systemic venous pressure). Rarely, it reflects decreased peripheral vas-cular resistance caused by vagotonia or sepsis. The noncompli-ant left ventricle requires augmented filling pressure to sustain cardiac output. Accordingly, relative hypovolemia may exist despite moderately elevated left ventricular filling pressure. Central venous pressure cannot be relied upon for assessment of vascular volume.
Right ventricular failure with or without concomitant tri-cuspid regurgitation leads to increased central venous pressure without concomitantly increased pulmonary venous or pul-monary arterial occlusive (indicative of left atrial) pressure. Pulmonary venous hypertension without systemic arterial hy-potension is often indicative of left ventricular failure (differen-tiated as mild or severe in terms of normal or depressed cardiac output). Profound hypotension and pulmonary venous hyper-tension are manifestations of cardiogenic shock. The vicious circle of cardiogenic shock--progressive infarction with declin-ing cardiac output, further compromise of perfusion, and ulti-mately extensive necrosis with profound failure and shock—is generally irreversible without prompt mechanical support of the circulation and coronary revascularization with thrombolyt-ic drugs, angioplasty, or surgery.
In general, hemodynamic status reflects the extent of left ventricular infarction. However, an infarct of modest extent superimposed on a previous infarct can profoundly compromise hemodynamics. Initial impairment of ventricular performance may exceed that attributable to irreversible injury because of myocardial stunning early after the onset of infarction. Right ventricular involvement may compromise cardiac output more than anticipated from the extent of left ventricular injury alone.
Differential Diagnosis
When the history of acute myocardial infarction is typical, the initial electrocardiogram abnormal and followed by defini-tive sequential changes, and MB CK elevated in the initial or subsequent plasma samples with typical sequential changes, the diagnosis is straightforward. A presumptive diagnosis can be made when any two of these criteria are present. Unfortu-nately, however, the diagnosis may be obscure in patients seen very early after the onset of infarction and in those with EC6 manifestations of prior isehemic or other types of heart disease, electrocardiographically silent infarcts, of atypical presenta-tions. Differentiation from ischemia without infarction(unsta-ble angina, aortic stenosis in the elderly, ischemia attributable to right ventricular overload, new-onset angina, or inadequate myocardial perfusion in markedly hypertrophied left ventricles or in association with marked aortic insufficiency), and from pericarditis with pain simulating that of infarction may be dif-ficult without the aid of laboratory tests and cardiac imaging. A critical differential diagnostic consideration is aortic dissec-tion. It should be suspected whenever pain is atypical or not associated with ECG changes typical of infarction.
Pleurodynia pulmonary embolism or infarction, pneu-mothorax, pneumonitis, musculoskeletal pain associated with bursitis, the shoulder/hand syndrome, pectoral lym-phadenopathy, herpes zoster before eruption of the typical vesicles, myalgia, and costochondritis may simulate infarction superficially but can usually be differentiated easily on the basis of physical findings, results of laboratory tests, and chest ra-diography. Pain of abdominal origin that may masquerade as infarction includes that caused by cholecystitis or cholelithiasis, pancreatitis, duodenal or gastric ulcer, gastritis, esophagitis, esophageal spasm, or esophageal reflux associated with a hiatal hernia(Table 12).
Care of the Patient
The focus of treatment differs in the prehospital, hospital (coronary care unit and step-down unit), and convalescent phases despite considerable overlap of objectives in each. Most death caused by infarction occurs early and is attributable to primary ventricular fibrillation. Thus, initial objectives are im-mediate ECG monitoring and reversal of ventricular fibrillation should it occur.
Treatment in the Hospital phase Cardiac care units (CCU' s)have reduced early mortality attributable to acute myocardial infarction by approximately 50 per cent, largely by immediate implementation of defibrillation. They have proven to be optimal facilities for continuous ECG monitoring, inva-sire hemodynamic monitoring when indicated, implementation and titration of measures designed to limit the extent of infarc-tion and salvage jeopardized ischemic myocardium, and induc-tion of recanalization of infarct-related arteries pharmacologi-cally.
Care in the CCU In addition to continuous ECG moni-toring, several general measures should be implemented. Diet should include liquid only during the first 24 hours because of the risk of aspiration with the frequent nausea and vomiting, and possible cardiac arrest. Stool softeners are helpful to avoid constipation, straining, and consequent circulatory derange-ments. Patients with uncomplicated infarction need be con-fined to bed for only 1 day. Physical activity should be limited (bed-chair regimen) throughout the 2 to 3 day CCU stay, with gradual and carefully monitored resumption of ambulatory activity in the late hospital phase. Sedative, anxiolytic, and hypnotic drugs at night may be helpful but cannot replace opti-mal communication by compassionate physicians and nurses and the reassurance it provides. Oxygen should be given to avoid hypoxemia. High doses may be counterproductive be-cause of vasoconstriction and lack of augmentation of myocar-dial oxygen delivery in normoxemic patients.
Refractory or severe pain should be treated with intra-venous morphine, meperidine, or pentazocine. Repeated intra-venous doses of 4 to 8 nag of morphine at intervals of 5 to 15 minutes can be given with relative impunity until the pain is relieved or toxicity is manifest by hypotension, vomiting, or depression of respiration. Prodigious quantities are sometimes required (2 to 3 mg per kilogram). Should toxicity occur, a morphine antagonist such as naloxone can reverse it. Mor-phine-induced hypotension in a patient without incipient or overt pulmonary edema can be minimized by maintenance of the patient in a supine position, elevation of the legs, adminis-tration of fluids, and administration of atropine if heart rate is not increased.
Continuing chest pain indicative of ischemia should be treated with agents diminishing myocardial oxygen require-ments and potentiating myocardial perfusion. Intravenous ni-troglycerin titrated (10 to
Oral calcium channel blockers such as nifedipine and dilti-azem are often useful because they reduce ventricular afterload (nifedipine) and modestly reduce heart rate and contractility as well (diltiazem). However, prognosis appears to be affected adversely in patients with congestive heart failure or impaired left ventricular function that persists after myocardial infarc-tion by treatment with diltiazem and possibly other calcium channel blockers as well. Oral or intravenous conventional or ultra-short-acting adrenergic blockers such as esmolol may ameliorate ischemia and pain by lowering heart rate and hence myocardial oxygen requirements. Theoretically, calcium an-tagonists and adrenergic blockers may exert anti-injury ef-fects as well by diminishing inward calcium flux in cardiac my-ocytes.
Despite the use of effective analgesia with nitrous oxide given by inhalation in concentrations of 20 to 50 per cent com-bined with oxygen in Europe and elsewhere, this agent is not used widely in the
