Structure of Coronary Arteries

The coronary arteries are susceptible to atherosclerosis as well as its complications, particularly intravascular thrombosis, often resulting in myocardial infarction. Atherosclerosis is a form of arteriosclerosis characterized by initial involvement of the inner layer of the arterial wall, or intima. The intimal localization of early atheromas helps to differentiate the atherosclerosis type from other forms of arteriosclerosis, such as Mönckeberg’s medial sclerosis or periarteritis nodosa, that primarily involve the muscular or adventitial layers.

Histologic and functional characteristics of the intimal lining of the arteries help in understanding the histogenesis of spontaneous atheromas, often initiated shortly after birth, particularly the presence of different cell types in a ground substance matrix and the absence of a direct blood supply. The well-developed ath­erosclerotic plaque resulting from inflammatory and reparative processes is a complex lesion containing extracellular deposits of calcium salts, blood components, cholesterol crystals, and acid mucopolysaccharides. The initial changes, however, seem to occur at the cellular level, often accompanied by an abnormal intracellular storage of lipids, particularly cholesterol esters, fatty acids, and lipoprotein complexes. These findings on microscopy have strengthened the thesis that lipid infiltration from the bloodstream may be a significant factor in the growth of the atheromatous plaque. Furthermore, recognition by cytochemical techniques makes lipids helpful indicators of abnormal cell behavior, independent of their role in the etiology of atheroma.

Because of the frequency and severity of atherosclerosis, short-term organ culture techniques for the isolation of arterial intimal cells (intimacytes) identify susceptible cell populations, based on their response to incorporation of homologous serum lipids in vitro. Intimacytes from arteries, with and without histologic evidence of atherosclerosis, show two types of atherophils: genetically highly susceptible cells and genetically resistant cells to intracellular lipid accumulation.

In the presence of increased perfusion rates of plasma lipoproteins caused by local hemodynamic changes, hypertension, elevated serum lipids, or changes in endothelial surface permeability (trauma, fibrin deposition, platelet aggregation), genetically susceptible atherophils will be transformed into lipid-laden atherocytes. The secondary release of intracellular lipids from these cells will induce surrounding atherophils to incorporate them, creating a self-feeding process with cytologic changes that increase metabolic requirements, including oxygen consumption rates, which result in increased permeability of the cell membrane to lipids if not met. These events set up a cycle favoring further expansion of focal atherosclerotic changes. Collagen fibers are laid down by fibrophils, which are then transformed into fibrocytes surrounded by acid mucopolysaccharide deposits. This eventually results in a characteristic intimal hyperplasia after ground substance changes. These histologic lesions are self-perpetuating, resulting in the replacement of intimacytes by an acellular area of arterial intima that stimulates further surface involvement of the vascular wall in this interplay among deposition, inflammatory response, and scarring, with the eventual production of a typical atherosclerotic plaque.

In contrast, genetically resistant atherophils, even in the presence of elevated serum-lipid levels, do not respond (or respond minimally) to an increased perfusion of plasma lipids. If some atherocytes appear, they are few in number, and only superficial fatty streaks are developed, resulting in sparse intimal elevations with few fibrophils and no well-organized plaque. This type of cytologic response also seems less susceptible to the clinical complications of atherosclerosis, particularly thrombosis or rupture, because of the limited involvement of the vascular wall.

This approach to the pathogenesis of atherosclerosis emphasizes the clinical significance of the earliest possible identification of patients whose arteries are susceptible to atheroma, to modify or prevent environmental conditions that favor the acceleration of atherogenesis in the arterial intima cells. Local factors are also important in identification of the lesions, suggesting possible therapeutic approaches for their arrest or inhibition.

In terms of mortality, the most serious problem facing more developed countries is atherosclerosis of the cardiac and cerebral blood vessels. There is no single cause of atherosclerosis, which is often labeled a “multifaceted disease.” Atherosclerosis reflects the culmination of many factors acting over a lifetime and usually becomes clinically manifest only when angina pectoris, sudden cardiac death, myocardial infarction (MI), transient ischemic attack (TIA), or cerebrovascular accident (CVA, stroke) occurs. Heart failure is usually caused by MI.

Patients with a family history of premature manifestations of atherosclerosis may be at high risk for development of atherosclerotic disease. Older age, male gender, hypertension, diabetes, obesity, and tobacco smoking are associated with coronary atherosclerosis. Lack of exercise may interact with other clinical factors, and an exercise program (e.g., walking) is known to diminish symptoms in patients with known clinical manifestations of atherosclerosis. Excessive saturated fat in the diet is also involved in atherogenesis. High-fat diets increase blood lipid levels, particularly low-density lipoprotein (LDL) cholesterol. Elevated triglycerides and low levels of high-density lipoprotein (HDL) are also implicated in the etiology of atherosclerosis. Elevated serum uric acid may also contribute to atherogenesis, although further study is required. Unsaturated fatty acids with two or more double bonds help reduce cholesterol blood levels when their relationship to saturated fatty acids is increased.

Current concepts of atherogenicity are complex and involve monocytes, platelets, macrophages, foam cells, endothelial cells, smooth muscle cells, oxidized LDL, and many other subcellular substances. Interested readers should refer to current literature and textbooks on the subject. In general, the physician or clinician can profile a patient potentially prone to atherosclerosis, such as a hypertensive man who smokes cigarettes, exercises little, and has elevated blood cholesterol and triglyceride levels, low HDL levels, and abnormal glucose metabolism. Currently, in addition to diet and exercise, drugs used to treat lipid abnormalities include HMG CoA reductase inhibitors (statins), nicotinic acid preparations, ezetimibe, fibric acid derivatives, and bile acid sequestrants.

The earliest recognizable atheromatous changes in blood vessels are accumulation of aggregates of lipid-laden macrophages in the intima. The appearance of this lesion is similar to that seen in many experimental vascular lesions. Another apparently early phenomenon, difficult to correlate and possibly unrelated, is a subintimal deposit of collagen that often is primitive and thus rich in acid mucopolysaccharides. Lesions of this type shadow atherosclerosis wherever it occurs. The relationship of this vascular lesion to the type seen in Asian peoples has not been elucidated, but this disorder does occur in Asians. A further complication of this lesion is the deposition of fibrin on or within its superficial layers.

As more lipid accumulates, an atheromatous plaque with many constituents is formed. This plaque may involve only a segmental portion of the artery or its entire circumference. When the macrophages die, their lipid is released and becomes an inflammatory irritant. Fibrin accumulates, as do other blood constituents; calcium deposits form; and fibroblasts proliferate. Stenotic lesions may accumulate more surface material with deposited layers of thrombus. These lesions regress with lipid-lowering agents and antiplatelet therapy.

Even a segmental atheroma can cause atrophy of the underlying arterial wall, and the concentric type seems associated with major destruction of the lamina and parts of the media. Such changes appear secondary to interference with the nutrients permeating the intima. The stages of atheroma reveal another major feature in the lesion’s development: an inability to clear blood constituents that have permeated the media. This dynamic event is demonstrated by perfusing isolated segments of living canine arteries and observing the quantity of lipid in the vasa vasorum of the adventitia.

Hemorrhage into the lesion can result from surface blood dissecting into the plaque or from vasa vasorum bleeding. Thrombosis may occlude the artery; if the person survives, organization of the fibrin clot can progress and occasionally recanalize the artery. However, the ability of these small channels to supply any appreciable volume of blood beyond the area of obstruction is insufficient in most patients to revascularize the downstream myocardium. Rarely, an occluding thrombus completely disappears.

In addition to atheromatous and thrombus blockade of the coronary arteries, emboli can obstruct an otherwise normal coronary artery. Such emboli may consist of thrombi, valvular calcification, pieces of tumor, and occasionally even small foreign bodies. Various types of aortitis can involve the proximal vessels; syphilis of the aortic wall can occlude the ostia. The atheroma is the main disorder, however, because of its distribution. The lesions closest to the aorta (proximal) are the plaques most likely to impede flow to the cardiac microcirculation.

The cerebral circulation is particularly vulnerable in hypertensive patients. Stroke is the major cause of death. Hypertensive vascular disease is usually a combination of hypertension and atherosclerosis, the latter accelerated by elevated blood pressure. Infarction of the brain is more common than subarachnoid bleeding. Bleeding results from rupture of microaneurysms of the small arteries or from trauma. The coronary vessels are next most vulnerable. Angina pectoris and MI are common results of accelerated atherosclerosis, necessitating concurrent treatment of the hypertension and atherosclerosis. Many patients reduce their high blood pressure and return to normal levels, only to have an MI or die from complications of atherosclerosis. The results of the increased rate of atherogenesis are also seen in other large vessels besides the coronary arteries. Thus, aneurysms of the aorta and renal arteries are common, leading to distal embolization, dissection, and possible rupture. Reducing blood pressure has a beneficial action on these lesions. Drugs, surgery, and interventions are now available to treat the clinical effects of both hypertension and atherosclerosis, although the goal should be prevention.

Plaques likely to rupture are called “unstable” and are the main cause of acute coronary syndromes. Plaques with a thin cap and a lipid core associated with inflammation and cap fatigue may be associated with rupture at the edges of the plaque. The plaques are rich in lipids and foam cells, found at the peripheral margins. On rupture, plaques extrude thrombogenic material, which then can trigger thrombosis on the plaque, in turn occluding the coronary artery and resulting in MI.

If the vessel only is almost occluded, a condition known as unstable angina may result. Risk factors such as cigarette smoking, hypertension, diabetes mellitus, and dyslipidemia contribute to endothelial injury, causing smooth muscle cell proliferation, inflammation, and deposition of lipid within the blood vessel wall. These events may lead to the development of unstable plaques. Other physical factors may alter plaque composition and make a plaque vulnerable to rupture; cold temperature (32°-34° C) may promote the crystallization of liquid cholesterol, and these sharp crystals may perforate the cap. Cytokines, growth factors, and oxidative stress are other factors in progression of atherosclerosis and instability.

Thrombosis related to these plaques may be caused by endothelial erosion or plaque disruption. In general, plaque erosion occurs over high-grade stenoses, whereas thrombosis related to plaque disruption is often seen in patients with few stenoses. In addition, multiple triggers of plaque disruption are probably related to increased tension, bleeding originating from the vasa vasorum, bending and twisting of the arteries, and increased systolic and pulse pressures.

Unfortunately, the terms angiogenesis and arteriogenesis are often are confused and interpreted to have the same meaning. These processes are really two separate entities representing blood vessel changes in the heart.

In patients without myocardial ischemia, myocardial oxygen demand is balanced by myocardial oxygen supply. Determinants of myocardial oxygen supply are related to aortic diastolic pressure, left ventricular end-diastolic pressure (LVEDP), and coronary artery resistance. Determinants of myocardial oxygen demand are related to heart rate, systolic blood pressure (BP), left ventricular (LV) tension, and LVEDP. Myocardial ischemia related to balloon occlusion of a coronary artery involves a sequence of decreased coronary blood flow, as detected by perfusion scintigraphy; altered regional flow/demand ratio resulting in decreased coronary sinus oxygen saturation; LV diastolic relaxation abnormalities, detected by cardiac ultrasound; systolic contraction abnormalities, detected by cardiac ultrasound or angiography; increased LVEDP; ST-segment depression on electrocardiography; and finally angina pectoris or its equivalent symptoms (e.g., breathlessness).

At the cellular level, the current hypothesis is that myocardial ischemia increases the late sodium current, which increases the sodium content of the myocardial cells. The sodium/calcium exchanger then increases the calcium content of the cell. As a result, the LV stiffens, increasing LVEDP, which decreases endomyocardial blood flow, propagating the myocardial ischemia.

Myocardial ischemia and its usual manifestation angina pectoris result from an imbalance between myocardial oxygen supply and myocardial oxygen demand. Myocardial ischemia manifested by angina pectoris can be acute or chronic. In general, patients with an acute clinical presentation have a crescendo pattern of angina and are considered to be in an unstable or “acute coronary syndrome” state.

Although most patients with myocardial ischemia are symptomatic, 25% may be asymptomatic. However, most symptomatic patients have many episodes of asymptomatic myocardial ischemia. Laboratory manifestations of myocardial ischemia other than electrocardiographic (ECG) changes are abnormalities of perfusion, as indicated by nuclear studies, and transient regional wall motion abnormalities, usually detected by echocardiographic studies or other noninvasive imaging techniques (e.g., MRI). Clinical manifestations of myocardial ischemia are generally chest discomfort (angina pectoris), arrhythmias, and LV dysfunction in both systole and diastole.

Angina pectoris (“strangling of the chest”) was first described as a serious symptom by Heberden in 1768, although he did not associate angina with coronary artery disease, as discovered later by Jenner. Angina is usually of short duration, associated with effort or emotion, and usually relieved in minutes by rest or sublingual nitroglycerin administration.

Angina pectoris varies somewhat from patient to patient, but the usual description of symptoms includes a feeling of a heavy weight, oppression, or a choking sensation under the middle of the chest and pain extending occasionally to the arms, especially the left, and almost never to the back and rarely to the neck and jaw. Many patients do not describe angina as a pain, but rather as a discomfort in the chest. It is produced, as a rule, by effort or emotion, especially in cold weather and particularly after meals or smoking. Angina rarely lasts more than 2 or 3 minutes and is relieved in a few minutes by sublingual nitroglycerin, also often used preventively, particularly if the patient knows a given situation will provoke cardiac pain. Angina must be differentiated particularly from gastrointestinal, musculoskeletal, and costochondritic origins of the discomfort.

Angina pectoris and the pain of acute MI are caused by the same disease process, but the prolonged pain in angina is associated with coronary artery occlusion and not the coronary artery stenosis of MI. The prognosis in the patient with angina pectoris varies greatly, but with medical management, many patients can continue to lead a normal life. Over months or years, their angina pectoris may diminish or disappear through natural development of collateral circulation to the ischemic zone of myocardium. However, angina is always an important symptom, and may be life threatening because of the potential for ventricular arrhythmias. Treatment of angina pectoris always includes medical therapy and often includes percutaneous coronary intervention (PCI, angioplasty/stent) or surgical bypass of a stenotic artery. Diet, blood pressure control, lipid management, nitrates, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, aspirin or other antiplatelet agents, smoking cessation, and exercise are considered optimal therapy before and after a revascularization procedure.

Prevention of the underlying disease that causes angina pectoris is paramount. For those at risk, as shown by family history and high serum cholesterol, the avoidance of obesity, a diet low in animal fat, routine exercise (if no heart disease), and smoking cessation deserve first priority in any health promotion and heart disease prevention program and should start in childhood.

The simplest and least expensive way to diagnose the presence or absence of myocardial ischemia and to quantitate functional impairment in patients with chronic stable angina is exercise stress testing with ECG monitoring. Exercise testing is typically performed using a treadmill or bicycle to provoke chest discomfort and obtain diagnostic evidence of myocardial ischemia. It is important to record 12 leads before, during, and after exercise testing in order to detect transient changes suggesting ischemia. Under resting conditions the heart rate is usually normal and the ST segment on the electrocardiogram usually isoelectric. Thus the 12-lead ECG may be normal even if a coronary artery has 70% stenosis, the usual percentage that results in myocardial ischemia when myocardial oxygen demand is increased. The ECG is normal because the myocardium is not ischemic under these resting conditions; myocardial oxygen supply is balanced by demand, and the patient does not complain of angina pectoris or equivalents such as breathlessness. The treadmill increases speed and incline progressively, thus stressing the patient, who needs to increase heart rate and blood pressure to maintain appropriate cardiac output to meet the demand. During bicycle exercise, resistance to pedaling is increased to accomplish the same increase in heart rate and blood pressure. Patients who develop myocardial ischemia show the classic ECG changes of ST-segment depression. In the patient with 70% stenosis, under conditions of increased myocardial oxygen demand, the balance of oxygen supply and increased demand will be upset, and myocardial ischemia will result. In some patients, myocardial ischemic changes on the ECG may not be accompanied by angina pectoris, termed silent myocardial ischemia. Despite the lack of symptoms, the prognostic importance of silent or asymptomatic myocardial ischemia is the same as symptomatic disease.

Chronic stable angina is often called stable ischemic heart disease. Myocardial ischemia results when the oxygen needs of the myocardium exceed the supply of oxygen derived from coronary blood flow. The oxygen needs of the myocardium are increased by aggravating or precipitating factors such as hypertension, tachycardia, heart failure, hypermetabolic state, and sympathomimetic drugs. Myocardial oxygen demand depends on heart rate, blood pressure, and LV size, thickness, and contraction. Other factors, such as severe anemia, may result in tachycardia and increased oxygen demand.

Left-sided heart catheterization and angiography includes injection of iodinated radiopaque contrast into the aorta, left ventricle, and coronary arteries to visualize the status of the aorta and its branches, presence or absence of aortic insufficiency, patency of conduit coronary bypasses, LV function and anatomy, and condition of the coronary circulation. Coronary angiography is a precise method of determining the extent, location, and severity (percent stenosis) of CAD. Multiple views of the coronary arteries are necessary to assess the significance of a specific lesion and the distribution of the right coronary, circumflex, and anterior descending arteries and the septal and diagonal distal circulation. The classic views of the right and left coronary arteries are the right anterior oblique (RAO) and left anterior oblique (LAO) projections. Multiple angulated views (caudal and cranial) are particularly important if PCI (angioplasty) is planned. One must remember that catheter-based coronary angiography is lumenography; only the vessel’s lumen is seen. The vascular wall must be visualized by intravascular ultrasound or optical coherence tomography; despite its limitations, this is a prerequisite for coronary artery surgery and in many patients allows determination of management: medical therapy (alone or plus angioplasty/stent) or bypass surgery.

Ventriculography is part of the evaluation of patients undergoing coronary angiography, to obtain the best possible assessment of ventricular function. I prefer to have ventriculography performed in the RAO and LAO views to assess the global function of the ventricle, particularly in patients with LV dysfunction.

In the catheterization laboratory, interventional cardiologists can determine the physiologic significance of a specific coronary artery stenosis by passing a small wire (0.014-inch pressure guidewire) with a pressure transducer at the tip, through the stenosis in question, which allows them to measure systolic blood pressure (BP) proximal and distal to the stenosis. The systolic BP distal to the stenosis is divided by the pressure proximal to the stenosis; the resulting fraction is the percentage of BP decrease across the stenosis. Measurements are made at baseline and after infusion of adenosine, which increases coronary blood flow. For example, if BP across the stenosis drops by 50%, the fractional flow reserve (FFR) will be 0.50. The formula is FFR = Pd/Pa, where Pd is pressure distal to the stenosis and Pa is pressure proximal to the stenosis. This technique is particularly useful when the visual estimate of the clinical significance of a specific stenosis by angiography is uncertain.

If FFR is combined with intravascular coronary ultrasound, the interventional cardiologist will be able to determine the physiologic significance of the stenosis as well as the nature of the plaque being investigated, i.e., stable or unstable vulnerable plaque. FFR could also be called “functional flow reserve” because it supports that measurements reflect the pathophysiologic significance of a stenosis. The technique obviously requires cardiac catheterization and a specially designed pressure guidewire in which the pressure is measured proximal to and distal to a given epicardial coronary artery stenosis. Based on clinical trials, a cut-off point of 0.75—0.80 has been used to indicate a significant pathophysiologically important coronary artery stenosis. In my view, this measurement is equivalent to our measurements of noninvasively measured ankle-brachial index (ABI), in which a difference in pressure between the arm and leg suggests pathologic decrease in leg perfusion. An advantage is that this technique can provide immediate information for angioplasty/stent being considered for an epicardial stenotic vessel. If FFR is less than 0.75, the stenosis appears to be causing downstream myocardial ischemia, and angioplasty/stent seems appropriate. The DEFER clinical trial used FFR to determine if PCI with stenting was necessary in patients with FFR greater than 0.75. In these patients, stenting of the coronary stenosis did not influence clinical outcome. In another study, guided by FFR, fewer stents were used in patients who had FFR in the normal range. After 1 year, death, MI, or repeat revascularization occurred less in the FFR group, and hospital stay was shorter with less procedural cost.

Revascularization involves either percutaneous coronary intervention (PCI), as first performed by Gruenzig in 1978, or coronary artery bypass graft surgery (CABG).

Patients with acute coronary syndrome (ACS) present in three different ways: unstable angina, non–ST-segment elevation myocardial infarction, and ST-segment elevation MI. Potential causes for the development of an ACS include extracardiac factors in the patients with severe coronary atherosclerosis, such as hypertension, tachycardia, and anemia. In 1858, Virchow proposed that injury to the inner wall of a blood vessel, possibly caused by fat, might lead to inflammation and secondary plaque formation, similar to current theory. ACS is also caused by plaque disruption resulting in transient platelet aggregation and release of vasoactive substances in diseased vessels, dynamic or intermittent coronary artery thrombosis, hemorrhagic dissection into an atheromatous plaque, and progression of coronary stenoses from plaque healing.

Acute coronary syndromes result from myocardial ischemia initiated by two primary factors: platelet and thrombus formation and resulting intense vasoconstriction from accumulation of local thromboxane A₂ and serotonin, reduction of local concentrations of endothelium-derived releasing factor (EDRF), and inhibitors of platelet aggregation. These events are usually preceded by rupture or erosion of the lipid-laden plaque and involve the balance between thrombosis and thrombolysis. Patients with ACS may stabilize clinically, but this may not be associated with stabilization of the plaque. Identifying these patients requires observation for recurrent ischemia and assessment of troponin levels and possibly C-reactive protein (CRP) levels. Abnormal test results indicate increased risk for future cardiac events.

The acute coronary syndromes are not a homogeneous condition. Clinical variables evident in many patients include ECG changes, release of creatine kinase and troponins, CRP level, and differences in LV function, as well as pathology on coronary angiography. In patients with ACS, the TIMI risk score helps to predict the risk for death, MI, or recurrent ischemia at 14 days. The risks are age over 65, three risk factors for CAD, prior 50% coronary stenosis, ST-segment change on admission, angina twice in 24 hours, aspirin use within 7 days, and increased serum cardiac markers. The more risk factors present, the higher is the rate of composite endpoints in 14 days.

Myocardial infarction can result in an extensive panorama of changes. Death of the cardiac muscle may occur in a single zone or as multiple foci scattered diffusely throughout the heart. The latter can be found after suboptimal perfusion of the heart using a pump oxygenator, in which all the minute necrotic foci are of the same age. More often, however, the multiple minute foci can be found as destroyed zones of varying ages. In the acute phases, these microinfarcts may be extremely difficult to see and may be recognizable only microscopically as areas showing variable myofibril destruction and replacement by collagen. Chronically, these small foci may be minute white patches salted throughout the myocardium.

A larger myocardial infarct shows a variety of changes that depend in part on the duration of the patient’s survival after the episode. The earliest changes are associated with the resulting paralysis of vessel walls, engorgement of the capillaries, and migration of polymorphonuclear leukocytes (PMNs). Some autolytic changes then occur, and the dead muscle fibers can be recognized as showing a loss of striations and an increase in eosinophilia, fragmentation, and the gradual disappearance of nuclei. The dead muscle becomes an irritant, and more PMNs appear. Finally, the subsequent activities of repair include macrophage infiltration and replacement fibrosis. If the infarct is minute, such a sequence is of relatively short duration, but if large, remnants of necrotic muscle may be found several years later. It appears that such dead tissue has been effectively sealed away from physiologic activities.

Rapid opening of the infarcted artery is generally accepted as critical to increase patient survival, preferably using PCI. However, thrombolytic therapy remains a viable option in hospitals when PCI capability is not immediately available. Percutaneous recanalization of an occluded coronary artery by balloon angioplasty and stent placement in patients with STEMI is the standard of practice. The appropriate management of acute STEMI currently is door-to-balloon (“D2B”) time—from ED arrival to passage of a guidewire into the infarcted artery. D2B time is easily and accurately measured and documented. D2B time less than 90 minutes is an acceptable goal. The rationale is that short D2B time results in less myocardial necrosis. A favorable outcome correlates well with minimal necrosis and ejection fraction (EF) greater than 40%. An unfavorable outcome correlates with a large amount of necrosis and EF less than 40%.²

Counterpulsation is the only technique that will lower aortic systolic pressure and increase aortic diastolic pressure. To accomplish intra-aortic balloon counterpulsation (IABCP), a catheter with a cylindrical polyethylene balloon (~40 mL in adult device) is introduced into the aorta, deflated, and extended to just below the left subclavian artery and above the renal arteries, so as not to obstruct either vessel. When visualized on chest radiography or fluoroscopy, the tip of the catheter is placed at the level of the bifurcation of the right and left main bronchi, again so as not to occlude subclavian and renal arteries. Balloon expansion with helium occurs actively during diastole, and collapse of the balloon occurs actively during systole. Intra-aortic pressure is measured at the catheter tip.

Timing of balloon expansion and collapse is controlled by either ECG or pressure waveform during the cardiac cycle. When the balloon is expanded in diastole, aortic diastolic pressure increases, as does coronary perfusion pressure, which theoretically increases myocardial blood flow. When the balloon is collapsed during systole, LV afterload reduction occurs, probably a suction effect that unloads the left ventricle and increases cardiac output. When counterpulsation is working correctly, the elevated diastolic aortic pressure likely is interpreted as high blood pressure, and the baroreceptor reflexes tend to lower systolic pressure, thus decreasing myocardial oxygen demand.

The clinical indications for IABCP are cardiogenic shock of any etiology, acute mitral regurgitation that does not respond to nitroprusside, acute ventricular septal defect, and refractory acute coronary syndromes (ischemia or arrhythmias). Less clear indications relate to preprocedural use in patients considered “high risk” for a revascularization procedure such as PCI or CABG (e.g., high-grade left main coronary artery stenosis). IABCP should not be used in patients with aortic insufficiency; the increase in diastolic pressure will increase the degree of aortic insufficiency. IABCP cannot be used in patients whose aorta cannot be accessed because of severe peripheral vascular disease. Complications with IABCP are fortunately rare and include leg ischemia, aortic disruption, renal artery obstruction when the balloon is not properly placed, and bleeding.

Despite the many features common to rheumatic fever and rheumatoid arthritis, notably polyarthritis and subcutaneous nodules, these are distinct nosologic entities. If differentiation is difficult in the early stages, the difference in clinical evolution rapidly distinguishes rheumatic fever from arthritis, and even in the early stages, histology of the synovium or biopsied nodule can be helpful. The lesion in rheumatic fever is capsular rather than synovial, with areas of fibrinoid necrosis accompanied by focal infiltrations of histiocytes and lymphocytes.

The joint lesions, even when severe, are entirely reversible, and permanent damage does not result. This contrasts with the cardiac lesions, which can occasionally progress to mitral stenosis and its sequelae, even when initial damage is mild. Skin rashes are uncommon but can be characteristic, especially erythema annulare, a fleeting, ring-shaped, usually flat eruption typically found on the trunk. Each lesion spreads centrifugally, leaving a slight staining in the center. Another typical feature of rheumatic fever, seen especially in severe cases, is subcutaneous nodules, mainly confined to the tissues over bony prominences, where friction combined with pressure is apparently responsible for nodule development. The nodules are most conspicuous after 2 to 3 weeks, although their impending development is often preceded by a more diffuse, boggy thickening. Histologically, a typical nodule shows an area of fibrinoid composed of parallel or interlacing bands sparsely infiltrated with histiocytes and fibroblasts. The adjacent tissue is edematous and contains groups of small vessels surrounded by similar cells. Fibrous tissue is inconspicuous.

Permanent cardiac damage correlates closely with persistent or recurrent activity of rheumatic disease, so the detection of such activity is important. The most helpful test is the erythrocyte sedimentation rate (ESR), which is almost never normal in the presence of active disease, except in patients with congestive heart failure. The converse, however—a persistently raised ESR—does not necessarily imply continued activity, especially in girls. Therefore, estimations of C-reactive protein may more accurately reflect the state of the disease activity. The greatest danger to the patient with a history of rheumatic fever is developing a new infection with β-hemolytic streptococci, because the risk of relapse is much greater than after an initial attack. The success of chemoprophylaxis has confirmed both the importance of such reinfection in the development of a relapse and the role of streptococci in rheumatic fever pathogenesis.

Environmental and genetic factors have been studied widely in an attempt to account for the considerable geographic variation in the incidence of rheumatic disease. The most impressive data are provided by Mills’ map, showing the progressive decrease in mortality from rheumatic fever as one passes from the northern to the southern latitudes of the United States. Evidence of genetic factors besides female predominance is less precise, but the increased incidence of nonsecretors of the blood group substances in patients with rheumatic fever indicates modest genetic influence. The dominant factor is environmental and related to the incidence and virulence of the local streptococci.

Rheumatic heart disease is a complication of recurrent upper-respiratory infection with group A β-hemolytic streptococci. Streptococcal products circulating from this source through the body causes a reaction in connective tissues called rheumatic inflammation. Predisposed sites include the heart, skin, and synovial membranes. In the latter two areas, inflammation usually heals by resolution, leaving no residual effects, but in the heart these recurrent respiratory infections may lead to severe deformities, usually of the valves.

Chronic rheumatic heart disease requires recurrent infections. Each attack of rheumatic inflammation goes through an active stage followed by healing. In the joints, active rheumatic involvement is characterized by migratory arthritis. In the skin, transitory subcutaneous nodules may appear. In the heart, each of the major anatomic components—the pericardium, myocardium, endocardium, and particularly the valves—may be involved.