Intro to med Chapter 2,3 and 8Paragraphs

examination of the precordium

A complete cardiovascular examination should always include careful inspection and palpation of the chest, because this may reveal valuable clues regarding the presence of cardiac disease. Abnormalities of the chest wall including skin findings should be observed. The presence of pectus excavatum is associated with Marfan's syndrome and mitral valve prolapse. Pectus carinatum can also be found in patients with Marfan's syndrome. Kyphoscoliosis can lead to right-sided heart failure and secondary pulmonary hypertension. One should also assess for visible pulsations, in particular in the regions of the aorta (second right intercostal space and suprasternal notch), pulmonary artery (third left intercostal space), right ventricle (left parasternal region), and left ventricle (fourth to fifth intercostal space at the left midclavicular line). Prominent pulsations in these areas suggest enlargement of these vessels or chambers. Retraction of the left parasternal area can be observed in patients with severe left ventricular hypertrophy, whereas systolic retraction at the apex or in the left axilla (Broadbent sign) is more characteristic of constrictive pericarditis. Palpation of the precordium is best performed when the patient, with chest exposed, is positioned supine or in a left lateral position with the examiner located on the right side of the patient. The examiner should then place the right hand over the lower left chest wall with fingertips over the region of the cardiac apex and the palm over the region of the right ventricle. The right ventricle itself is typically best palpated in the subxiphoid region with the tip of the index finger. In those patients who have chronic obstructive lung disease, are obese, or are very muscular, the normal cardiac pulsations may not be palpable. In addition, chest wall deformities may make pulsations difficult or impossible to palpate. The normal apical cardiac impulse is a brief and discrete (1 cm in diameter) pulsation located in the fourth to fifth intercostal space along the left midclavicular line. In a patient with a normal heart, this represents the point of maximal impulse (PMI). If the heart cannot be palpated with the patient supine, a left lateral position should be tried. If the left ventricle is enlarged for any reason, the PMI will typically be displaced laterally. With volume overload states such as aortic insufficiency, the left ventricle dilates, resulting in a brisk apical impulse that is increased in amplitude. With pressure overload, as in long-standing hypertension and aortic stenosis, ventricular enlargement is a result of hypertrophy, and the apical impulse is sustained. Often, it is accompanied by a palpable S4 gallop. Patients with hypertrophic cardiomyopathy can have double or triple apical impulses. Those with apical aneurysm may have an apical impulse that is larger and dyskinetic. The right ventricle is usually not palpable. However, in those with right ventricular dilation or hypertrophy, which can be related to severe lung disease, pulmonary hypertension, or congenital heart disease, an impulse may be palpated in the left parasternal region. In some cases of severe emphysema, when the distance between the chest wall and right ventricle is increased, the right ventricle is better palpated in the subxiphoid region. With severe pulmonary hypertension, the pulmonary artery may produce a palpable impulse in the second to third intercostal space to the left of the sternum. This may be accompanied by a palpable right ventricle or a palpable pulmonic component of the second heart sound (S2). An aneurysm of the ascending aorta or arch may result in a palpable pulsation in the suprasternal notch. Thrills are vibratory sensations best palpated with the fingertips; they are manifestations of harsh murmurs caused by such problems as aortic stenosis, hypertrophic cardiomyopathy, and septal defects

treatment

Acute STEMI is caused by occlusion of the epicardial coronary artery by thrombus after rupture of a vulnerable plaque. The process of myocardial necrosis is time dependent, so diagnosis and treatment of STEMI to preserve myocardium must occur as quickly as possible. More than half of deaths occur within 1 hour after onset of symptoms, before the patient can be reached for emergency care. Patients often delay seeking care for symptoms of acute MI despite efforts to alert the public to the risk of ignoring symptoms of chest discomfort. Emergency medical personnel who respond to patients with possible MI begin to institute initial therapy in the field. Patients are monitored with ECG for rhythm disturbances such as ventricular tachycardia (VT) or ventricular fibrillation (VF) that require prompt cardioversion or defibrillation. Oxygen is administered via nasal cannula, and intravenous access is established. Aspirin (162 to 325 mg) is administered to the patient, and sublingual nitroglycerin may also be given in attempt to relieve chest discomfort. Some emergency response systems perform 12-lead ECGs and telemeter the results to the emergency department, allowing for early diagnosis of STEMI and early decision making regarding revascularization strategies. Once the patient arrives in the emergency department, an ECG, if not already available, will be preformed within 5 minutes. If the ECG is nondiagnostic, a second study is obtained no more than 20 minutes after presentation. A diagnosis of STEMI triggers decision making regarding reperfusion strategies that are used by the particular institution (see Chapter 73, "ST Elevation Acute Myocardial Infarction and Complications of Myocardial Infarction," in Goldman-Cecil Medicine, 25th Edition). Hospitals that are capable of performing emergency cardiac catheterization for the purpose of reperfusion therapy have an established rapid response system to activate the catheterization laboratory for this urgent therapy. There is evidence that primary PCI therapy for STEMI is superior to fibrinolytic therapy, but its use depends on the timely availability of a well-trained catheterization team. The quality of primary PCI is signified by a so-called door-to-balloon time of less than 90 minutes. Likewise, the standard for fibrinolytic therapy is a door-to-needle time of less than 30 minutes. Regardless of the means of reperfusion, it is important for the hospital treating patients with STEMI to have a structured protocol for timely diagnosis, decision making, and initiation of therapy. In addition to aspirin, the patient should be given a loading dose of thienopyridine (clopidogrel 600 mg or prasugrel 60 mg), assuming he or she will be treated with primary PCI. Unfractionated heparin in a dose of 60 IU/kg should be administered (no more than 4000 IU bolus) with a drip rate of 12 IU/kg/hour (maximum dose, 1000 IU/hour). LMW heparin may also be used (enoxaparin 30 mg IV bolus with 1 mg/kg subcutaneously every 12 hours for patients younger than 75 years of age who have normal renal function). Other agents such as glycoprotein IIb/ IIIa inhibitors or bivalirudin are administered depending on the protocols of the catheterization laboratory. Intravenous morphine (2 to 4 mg, repeated every 5 to 15 minutes as needed) is frequently used for pain control. Patients also are commonly given sublingual nitroglycerin 0.4 mg (repeat every 5 minutes for no more than three total doses), which may help to diminish chest discomfort. Intravenous nitroglycerin may be helpful for control of both pain and hypertension if present. Intravenous β-blockers such as metoprolol (5-mg bolus every 10 minutes for a total dose of 15 mg) is indicated in the treatment of STEMI, but it should be avoided in the face of heart failure, severe COPD, hypotension, or bradycardia. β-Blockers (metoprolol, propranolol, atenolol, timolol, and carvedilol) have been shown to significantly reduce the risk of future MI and cardiovascular mortality. Statin therapy, as mentioned for NSTEMI, is recommended for all patients with STEMI as a presenting symptom regardless of their history of hypercholesterolemia. Other adjunctive measures include bedrest for the first 12 hours, ongoing oxygen by nasal cannula with pulse oximeter monitoring, continuous rhythm monitoring, anxiolytic agents as needed, and stool softeners. Atropine is kept in reserve for the treatment of hemodynamically significant bradycardia, which may occur with inferior MI. ACE-inhibitor therapy also plays an important role in the long-term survival of patients after STEMI. ACE-inhibitor therapy has been shown to reduce the incidence of heart failure, recurrent MI, and long-term mortality after STEMI. ACE inhibitors commonly used for this purpose include lisinopril, captopril, enalapril, and ramipril. The decision to initiate ACE-inhibitor therapy is directed by the patient's tolerance. Care is warranted early after STEMI, because the patient may be prone to hypotension related to ACE-inhibitor therapy. A low dose should be administered first, with gradual upward titration. Aldosterone receptor blockade with eplerenone (25 to 50 mg/ day) reduces cardiovascular mortality after MI in patients with heart failure and a reduced EF of less than 40% or diabetes. Spironolactone also reduces mortality in patients with heart failure and a history of remote MI.

clinical presentation

Angina pectoris may manifest in either stable or unstable patterns (Table 8-2), but the symptom expression is similar. Typically, patients complain of retrosternal discomfort that they may describe as pressure, tightness, or heaviness. The symptom can be subtle in its presentation, and inquiry as to the presence of "chest pain" may lead to a negative response in a patient experiencing angina pectoris. When taking a history aimed at discerning angina pectoris, one needs to seek answers to these more nuanced descriptions of symptoms. In addition to chest discomfort, patients may have associated discomfort in the arm, throat, back, or jaw. They also may experience dyspnea, diaphoresis, or nausea associated with angina pectoris. There is a good deal of variability in the expression of symptoms related to myocardial ischemia, although each person tends to have a unique signature of symptoms. Some have no chest discomfort but only radiated arm, throat, or back symptoms; dyspnea; or abdominal discomfort. Myocardial ischemia can also manifest in a "silent" form, particularly in the elderly and in patients with long-standing diabetes mellitus. The duration of angina pectoris varies, probably depending on the magnitude of the underlying myocardial ischemia. Exertion-related angina pectoris, the hallmark of stable obstructive CAD, typically resolves with rest or with decreased intensity of exercise. In stable angina pectoris, the duration of events is usually in the range of 1 to 3 minutes. Prolonged symptoms in the 20- to 30-minute range are indicative of a more serious problem such as NSTEMI or STEMI The physical examination of patients with CAD is typically normal. However, if the patient is physically examined during an episode of myocardial ischemia, either at rest or after exertion, significant changes may be present. As with any form of discomfort, there may be a reflex increase in heart rate and blood pressure. Elevated heart rate and blood pressure may act to sustain the duration of angina by increasing myocardial oxygen demand in the face of supply-limiting coronary stenosis. Acute mitral regurgitation can develop if the distribution of myocardial ischemia includes a papillary muscle, the supporting structure of the mitral valve. The physical examination in such cases would demonstrate a new systolic murmur consistent with mitral regurgitation. If severe enough in degree, this mitral regurgitation will cause decreased LV compliance and, consequently, an acute elevation in left atrial and pulmonary vein pressure leading to pulmonary congestion. In this setting, the patient will have not only the symptom of angina pectoris but also the symptom of dyspnea and the physical finding of rales. Ischemia-induced increases in LV filling pressure due to diminished compliance also can occur independently of ischemia-induced mitral regurgitation. Decreased LV compliance can produce the abnormal heart sound S4; in the case of severe diffuse myocardial ischemia causing LV systolic dysfunction, an S3 may also be perceived. Resolution of myocardial ischemia results in not only a cessation of angina pectoris but also a return to the patient's baseline physical examination status.

examination of arterial pressure and pulse

Arterial blood pressure is measured noninvasively with the use of a sphygmomanometer. Before the blood pressure is taken, the patient ideally should be relaxed, allowed to rest for 5 to 10 minutes in a quiet room, and seated or lying comfortably. The cuff is typically applied to the upper arm, approximately 1 inch above the antecubital fossa. A stethoscope is then used to auscultate under the lower edge of the cuff. The cuff is rapidly inflated to approximately 30 mm Hg above the anticipated systolic pressure and then slowly deflated (at approximately 3 mm Hg/sec) while the examiner listens for the sounds produced by blood entering the previously occluded artery. These sounds are the Korotkoff sounds. The first sound is typically a very clear tapping sound which, when heard, represents the systolic pressure. As the cuff continues to deflate, the sounds will disappear; this point represents the diastolic pressure. In normal situations, the pressure in both arms is relatively equal. If the pressure is measured in the lower extremities rather than the arms, the systolic pressure is typically 10 to 20 mm Hg higher. If the pressures in the arms are asymmetric, this may suggest atherosclerotic disease involving the aorta, aortic dissection, or obstruction of flow in the subclavian or innominate arteries. The pressure in the lower extremities can be lower than arm pressures in the setting of abdominal aortic, iliac, or femoral disease. Coarctation of the aorta can also lead to discrepant pressures between the upper and lower extremities. Leg pressure that is more than 20 mm Hg higher than the arm pressure can be found in the patient with significant aortic regurgitation, a finding called Hill's sign. A common mistake in taking the arterial blood pressure involves using a cuff of incorrect size. Use of a small cuff on a large extremity leads to overestimation of pressure. Similarly use of a large cuff on a smaller extremity underestimates the pressure Examination of the arterial pulse in a cardiovascular patient should include palpation of the carotid, radial, brachial, femoral, popliteal, posterior tibial, and dorsalis pedis pulses bilaterally. The carotid pulse most accurately reflects the central aortic pulse. One should note the rhythm, strength, contour, and symmetry of the pulses. A normal arterial pulse (Fig. 3-2A) rises rapidly to a peak in early systole, plateaus, and then falls. The descending limb of the pulse is interrupted by the incisura or dicrotic notch, which is a sharp deflection downward due to closure of the aortic valve. As the pulse moves toward the periphery, the systolic peak is higher and the dicrotic notch is later and less noticeable. The normal pattern of the arterial pulse can be altered by a variety of cardiovascular diseases (see Fig. 3-2B to F). The amplitude of the pulse increases in conditions such as anemia, pregnancy, thyrotoxicosis, and other states with high cardiac output. Aortic insufficiency, with its resultant increase in pulse pressure (difference between systolic and diastolic pressure), leads to a bounding carotid pulse often referred to as a Corrigan pulse or a water-hammer pulse. The amplitude of the pulse is diminished in low-output states such as heart failure, hypovolemia, and mitral stenosis. Tachycardia, with shorter diastolic filling times, also lowers the pulse amplitude. Aortic stenosis, when significant, leads to a delayed systolic peak and diminished carotid pulse, referred to as pulsus parvus et tardus. A bisferiens pulse is most perceptible on palpation of the carotid artery. It is characterized by two systolic peaks and can be found in patients with pure aortic regurgitation. The first peak is the percussion wave, which results from the rapid ejection of a large volume of blood early in systole. The second peak is the tidal wave, which is a reflected wave from the periphery. A bisferiens pulse may also be found in those with hypertrophic cardiomyopathy, in which the initial rapid upstroke of the pulse is interrupted by LVOT obstruction. The reflected wave produces the second impulse. Pulsus alternans is beat-to-beat variation in the pulse and can be found in patients with severe left ventricular systolic dysfunction. Pulsus paradoxus is an exaggeration of the normal inspiratory fall in systolic pressure. With inspiration, negative intrathoracic pressure is transmitted to the aorta, and systolic pressure typically drops by as much as 10 mm Hg. In pulsus paradoxus, this drop is greater than 10 mm Hg and can be palpable when marked (>20 mm Hg). It is characteristic in cardiac tamponade but can also be seen in constrictive pericarditis, pulmonary embolism, hypovolemic shock, pregnancy, and severe chronic obstructive lung disease. Because peripheral vascular disease often accompanies CAD, a detailed examination of the peripheral pulses is an absolute necessity in patients with known ischemic heart disease. In addition to the carotid, brachial, radial, femoral, popliteal, dorsalis pedis, and posterior tibial pulses, the abdominal aorta should be palpated. When the abdominal aorta is palpable below the umbilicus, the presence of an abdominal aortic aneurysm is suggested. Impaired blood flow to the lower extremities can cause claudication, a cramping pain located in the buttocks, thigh, calf, or foot, depending on the location of disease. With significant stenosis in the peripheral vasculature, the distal pulses may be significantly reduced or absent. Blood flow in a stenotic artery may be turbulent, creating an audible bruit. With normal aging, the peripheral arteries become less compliant and this change may obscure abnormal findings.

chest pain

Chest pain is one of the cardinal symptoms of cardiovascular disease, but it may also be present in many noncardiovascular diseases (Tables 3-1 and 3-2). Chest pain may be caused by cardiac ischemia but also may be related to aortic pathology such as dissection, pulmonary disease such as pneumonia, gastrointestinal pathology such as gastroesophageal reflux, or musculoskeletal pain related to chest wall trauma. Issues with organs in the abdominal cavity such as the gallbladder or pancreas can also cause chest pain. It is therefore very important to characterize the pain in terms of location, quality, quantity, location, duration, radiation, aggravating and alleviating factors, and associated symptoms. These details will help determine the origin of the pain. Myocardial ischemia due to obstructive CAD often leads to typical angina pectoris. Angina is often described as tightness, pressure, burning, or squeezing discomfort that patients may not identify as true pain. Patients frequently describe angina as a sensation of "bricks on the center of the chest" or an "elephant standing on the chest." Angina is more common in the morning, and the intensity may be affected by heat or cold, emotional stress, or eating. This discomfort is typically located in the substernal region or left side of the chest. If it is reproduced by palpation, it is unlikely to be angina. Anginal pain often radiates to the left shoulder and arm, particularly the ulnar aspect. It may also radiate to the neck, jaw, or epigastrium. Pain that radiates to the back, the right or left lower anterior chest, or below the epigastric region is less likely to be anginal in etiology. Anginal chest pain is usually brought on with exertion, in particular with more intense activity or walking up inclines, in extremes of weather, or after large meals. It is typically brief in duration, lasting 2 to 10 minutes, and resolves with rest or administration of nitroglycerine within 1 to 5 minutes. Associated symptoms often include nausea, diaphoresis, dyspnea, palpitations, and dizziness. Patients typically report a stable pattern of angina that is relatively predictable and reproducible with a given amount of exertion. When this pain begins to increase in frequency and severity or occurs with lesser amounts of exertion or at rest, one must then consider unstable angina. Anginal pain that occurs at rest with increased intensity and lasts longer than 30 minutes may represent acute myocardial infarction. Angina-like pain at rest may also occur with coronary vasospasm and noncardiac chest pain There are several other potential causes of chest pain that may be confused with angina pectoris (see Table 3-2). Pain associated with acute pericarditis is typically sharp, is located to the left of the sternum, and radiates to the neck, shoulders, and back. This may be rather severe pain that is present at rest and can last for hours. It typically improves with sitting up and forward and worsens with inspiration. Acute aortic dissection usually causes sudden onset of severe tearing chest pain which radiates to the back between the scapulae or to the lumbar region. Typically, there is a history of hypertension, and pulses may be asymmetric between the extremities. A murmur of aortic regurgitation may also be heard. Pain associated with pulmonary embolism is also acute in onset and is usually accompanied by shortness of breath. This pain is typically pleuritic, worsening with inspiration

classification of functional status

Class I Uncompromised Ordinary activity does not cause symptoms; symptoms occur only with strenuous or prolonged activity. Class II Slightly compromised Ordinary physical activity results in symptoms; no symptoms at rest. Class III Moderately compromised Less than ordinary activity results in symptoms; no symptoms at rest. Class IV Severely compromised Any activity results in symptoms; symptoms may be present at rest.

prognosis

Contemporary therapies for stable ischemic heart disease have significantly reduced the risks of cardiac events and mortality. The annual rate of major ischemic events such as MI is in the range of 1% to 2%, and the yearly mortality rate is 1% to 3%. CAD is frequently associated with systemic vascular disease, making these patients prone to a host of other events. Patients with stable ischemic heart disease have a yearly combined outcome risk for cardiovascular death, MI, or stroke in the range of 4.5%. Despite advances in medical and revascularization therapies, up to 30% of patients face some limiting symptoms of recurrent angina. Revascularization does not abolish the need for ongoing antianginal medical therapy in 80% of patients. Patients with stable ischemic heart disease should first be treated with medical therapy appropriate to reduce the risk of ischemic events (aspirin, statins) and to control symptoms of angina (nitrates, β-blockers, calcium channel antagonists). Revascularization therapy with either PCI or CABG is an option for patients who continue to have lifestyle-limiting symptoms despite the use of medical therapy and risk factor modification. The goal of all therapies for patients with stable ischemic heart disease should be individualized, taking advantage of information from controlled trials and directed at improving overall lifestyle and reducing the risk of death and disability due to progressive CAD or systemic vascular disease.

examination of the jugular venous pulsations

Examination of the neck veins can provide a great deal of insight into right heart hemodynamics. The right internal jugular vein should be used, because the relatively straight course of the right innominate and jugular veins allows for a more accurate reflection of the true right atrial pressure. The longer and more winding course of the left-sided veins does not allow for as accurate a transmission of hemodynamics. For examination of the right internal jugular vein, the patient should be placed at a 45-degree angle—higher in patients with suspected elevated venous pressures and lower in those with lower venous pressures. The head should be turned to the left and light shined at an angle over the neck. Although the internal jugular vein itself is not visible, the pulsations from that vessel are transmitted to the skin and can be seen in most cases. The carotid artery lies in close proximity to the jugular vein, and its pulsations can sometimes be seen as well. Therefore, one must be certain one is observing the correct vessel. This can be accomplished by applying gentle compression at the site of pulsations. An arterial pulse will not be obliterated by this maneuver, whereas a venous pulse likely will become diminished or absent with compression. In addition, an arterial pulse is usually much more forceful and vigorous Both the level of venous pressure and the morphology of the venous waveforms should be noted. Once the pulsations have been located, the vertical distance from the sternal angle (angle of Louis) to the top of the pulsations is determined. Because the right atrium lies about 5 cm vertically below the sternal angle this number is added to the previous measurement to arrive at an estimated right atrial pressure in centimeters of water. The right atrial pressure is normally 5 to 9 cm H2O. It can be higher in patients with decompensated heart failure, disorders of the tricuspid valve (regurgitation or stenosis), restrictive cardiomyopathy, or constrictive pericarditis. With inspiration, negative intrathoracic pressure develops, venous blood drains into the thorax, and venous pressure in the normal patient falls; the opposite occurs during expiration. In a patient with conditions such as decompensated heart failure, constrictive pericarditis, or restrictive cardiomyopathy, this pattern is reversed (Kussmaul sign), and the venous pressure increases with inspiration. When the neck veins are examined, firm pressure should be applied for 10 to 30 seconds to the right upper quadrant over the liver. In a normal patient, this will cause the venous pressure to increase briefly and then return to normal. In the patient with conditions such as heart failure, constrictive pericarditis, or substantial tricuspid regurgitation, the neck veins will reveal a sustained increase in pressure due to passive congestion of the liver. This finding is called hepatojugular reflux. The normal waveforms of the jugular venous pulse are depicted in Figure 3-1A. The a wave results from atrial contraction. The x descent results from atrial relaxation after contraction and the pulling of the floor of the right atrium downward with right ventricular contraction. The c wave interrupts the x descent and is generated by bulging of the cusps of the tricuspid valve into the right atrium during ventricular systole. This occurs at the same time as the carotid pulse. Atrial pressure then increases as a result of venous return with the tricuspid valve closed during ventricular systole; this generates the v wave, which is typically smaller than the a wave. The y descent follows as the tricuspid valve opens and blood flows from the right atrium to the right ventricle during diastole Understanding of the normal jugular venous waveforms is paramount, because these waveforms can be altered in different disease states. Abnormalities of these waveforms reflect underlying structural, functional, and electrical abnormalities of the heart (see Fig. 3-1B to G). Elevation of the right atrial pressure leading to jugular venous distention can be found in heart failure (both systolic and diastolic), hypervolemia, superior vena cava syndrome, and valvular disease. The a wave is exaggerated in any condition in which a greater resistance to right atrial emptying occurs. Such conditions include pulmonary hypertension, tricuspid stenosis, and right ventricular hypertrophy or failure. Cannon a waves occur when the atrium contracts against a closed tricuspid valve, which can occur with complete heart block or any other situation involving AV dissociation. The a wave is absent during atrial fibrillation. With significant tricuspid regurgitation, the v wave becomes very prominent and may merge with the c wave, diminishing or eliminating the x descent. With tricuspid stenosis, there is impaired emptying of the right atrium, which leads to an attenuated y descent. In pericardial constriction and restrictive cardiomyopathy, the y descent occurs rapidly and deeply, and the x descent may also become more prominent, leading to a waveform with a w-shaped appearance. With pericardial tamponade, the x descent becomes very prominent while the y descent is diminished or absent

prognosis- risk stratification after myocardial infarction

Key to understanding an individual patient's risk for future coronary events or mortality related to MI is a thorough assessment of drivers for those risks: status of LV function and its impact on clinical functional status, residual myocardial ischemia, and spontaneous or exercise-induced arrhythmias. Appropriate predischarge assessments provide a comprehensive picture of the patient's risk status and prognosis

electrocardiographic monitering

Patients are routinely monitored by telemetry systems that capture arrhythmic events in the first 48 hours after MI. Late ventricular arrhythmias such as VF or sustained VT identify patients who are likely to benefit from ICD therapy. This is particularly true if EF is reduced to less than 40%. ICD implantation is also indicated for patients with persistently reduced EF (<30%).

prosthetic heart sounds

Prosthetic heart valves produce characteristic findings on auscultation. Bioprosthetic valves produce sounds that are similar to those of native heart valves, but they are typically smaller than the valves that they replace and therefore have an associated murmur. Mechanical valves have crisp, high-pitched sounds related to valve opening and closure. In most modern valves such as the St. Jude valve, which is a bileaflet mechanical valve, the closure sound is louder than the opening sound. An ejection murmur is common. If there is a change in murmur or in the intensity of the mechanical valve closure sound, dysfunction of the valve should be suspected.

angina pectoris

TYPE PATTERN ECG ABNORMALITY MEDICAL THERAPY Stable Stable pattern, induced by physical exertion, exposure to cold, eating, emotional stress Baseline often normal or nonspecific ST-T changes ≥70% Luminal narrowing of one or more coronary arteries from atherosclerosis Aspirin Sublingual nitroglycerin Lasts 5-10 min Relieved by rest or nitroglycerin Signs of previous MI ST-segment depression during angina Anti-ischemic medications Statin Unstable Increase in anginal frequency, severity, or duration Angina of new onset or now occurring at low level of activity or at rest May be less responsive to sublingual nitroglycerin Same as stable angina, although changes during discomfort may be more pronounced Occasional ST-segment elevation during discomfort Plaque rupture with platelet and fibrin thrombus, causing worsening coronary obstruction Aspirin and clopidogrel Anti-ischemic medications Heparin or LMWH Glycoprotein IIb/IIIa inhibitors Prinzmetal or variant angina Angina without provocation, typically occurring at rest Transient ST-segment elevation during pain Often with associated AV block or ventricular arrhythmias Coronary artery spasm Calcium channel blockers Nitrates

secondary prevention, patient education and rehabilitation

The goal of secondary prevention is to reduce the risk of recurrent MI and cardiovascular mortality. Risk factor modification is key to the secondary prevention strategy. All patients should have their lipid status assessed at the time of admission, but statin therapy is warranted in patients with acute MI at presentation. The target LDL level is less than 100 mg/dL, preferably closer to 70 mg/dL. Smoking cessation is of critical importance because it can reduce the risk of reinfarction, and ongoing smoking can double the risk of recurrent MI or mortality in the first year after MI. Structured smoking cessation programs and the use of pharmacologic aids (e.g., nicotine patches or gum, bupropion, varenicline) can increase the success of smoking cessation efforts. Antiplatelet therapy with aspirin (75 to 162 mg/day) is given indefinitely to all patients after MI. Regardless of whether primary PCI has been performed, patients will benefit from the use of clopidogrel 75 mg/day for the first year after MI. Those patients who have received a stent during primary PCI should continue either clopidogrel 75 mg/day or prasugrel 10 mg/day for a duration appropriate for the type of stent employed. At the least, patients should receive dual antiplatelet therapy (aspirin + thienopyridine) for 1 month for a bare metal stent, 3 months for a sirolimus-based stent, and 6 months for a paclitaxel-eluting stent. Most patients who have been treated with any type of stent receive dual antiplatelet therapy for the first year after their MI. The use of antiplatelet therapy in any form should be tempered by an individual patient's risk of hemorrhagic complications. The use of warfarin anticoagulation (target international normalized ratio [INR], 2.0 to 3.0) is indicated for patients with persistent or paroxysmal AF, guided by their CHADS-2 score (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke). Patients who have experienced pulmonary or systemic thromboembolism also warrant warfarin therapy. Patients who are at high risk for thromboembolism after acute MI, such as those with low EF related to anterior MI, should also be considered for warfarin. The concomitant use of dual antiplatelet therapy along with warfarin requires careful monitoring for bleeding complications. Acute anterior MI that has resulted in significant injury to the ventricle with an EF of less than 40% places the patient at risk for future negative remodeling of the left ventricle and potential heart failure. ACE-inhibitor therapy has been shown to reduce the risk of negative remodeling and the occurrence of heart failure in such patients. This group of patients also experiences a reduction in future recurrent MI risk with the use of ACEinhibitor therapy. This observation does not appear to carry over to patients with stable CAD. ACE-inhibitor therapy (captopril, ramipril, lisinopril) is indicated for all patients after MI. The use of ARBs (e.g., valsartan, losartan) is reasonable for patients who are intolerant of ACE-inhibitor therapy. The aldosterone receptor antagonist eplerenone (25 mg/day, titrated to 50 mg/day) is indicated as additive therapy to ACE or ARB in MI patients who have reduced EF (<40%) or diabetes. Careful monitoring of serum potassium is required after initiation of eplerenone together with ACE or ARB. ave reduced EF post-MI. This therapy should be avoided in patients with uncompensated heart failure early after MI or the presence of other contraindications. Metoprolol succinate (25 mg/day titrated up to 200 mg/day) or carvedilol (3.1256.25 mg titrated to 25 mg twice each day) should be initiated at low doses and titrated upward as tolerated. The role of beta blockers in patients with no residual myocardial ischemia, arrhythmias, or normal EF is not clear. Nitrates, either short-acting sublingual nitroglycerin or longacting versions, may be useful in the treatment of stable angina. Calcium channel blocking drugs should be avoided in patients with reduced EF (<40%). In patients with normal EF, either diltiazem or verapamil may useful as a substitute in patients who are intolerant of β-blockers when either antianginal therapy or rate control for AF is needed. The dihydropyridine, amlodipine, may be a useful adjunct for control of hypertension or treatment of angina. It should be used with caution in the face of reduced EF. therapy with estrogen or estrogen/progesterone preparations; these agents do not decrease the risk of recurrent MI but do increase the risk of thromboembolic events. The ongoing use of hormone therapy in women already receiving treatment should be individualized, with a bias toward discontinuing therapy. Diabetic patients need attention to their degree of glycemic control, with a target of hemoglobin A1c less than 7%. Vitamin supplements have no clear role in therapy for MI patients. Fish oil supplements do not appear to benefit patients who have experienced acute MI.

arrythmias

The highest risk of life-threatening arrhythmias is during the first 24 to 48 hours after the onset of acute MI. Ischemic myocardium is susceptible to arrhythmia generation, probably based on micro-re-entry associated with ischemic myocardium. The significant mortality risk in the early hours of acute MI is largely attributed to arrhythmias such as VF or VT. The risk of VF is about 3% to 5% in the early hours of MI and diminishes over 24 to 48 hours. One of the benefits of rhythm monitoring during the first 48 hours after presentation is prompt recognition and treatment of life-threatening ventricular arrhythmias. Accelerated idioventricular rhythm occurs early in the course of MI and may be associated with reperfusion. This arrhythmia is well tolerated and does not require specific therapy. Ventricular arrhythmias occurring late (>48 hours) after acute MI usually are associated with large underlying MIs and heart failure. Late episodes of VF or VT portend a poor prognosis. Immediate therapy for VF is electrical defibrillation. VT that causes hemodynamic embarrassment is treated with synchronized electrical cardioversion. β-Blocker therapy may help to suppress arrhythmias in patients who are prone to them, as may the use of amiodarone. Correction of residual ischemia may also play a role in controlling VF or VT events. Patients with late VF or hemodynamically significant VT are candidates for an implantable cardioverter defibrillator device (ICD). An ICD can also improve survival in asymptomatic patients with a persistently reduced EF less than 30% at 40 days after their acute MI. ICD therapy is also indicated if the EF is less than 35% at 40 days after MI in a patient with symptomatic heart failure. Atrial fibrillation (AF) occurs in 10% to 15% of patients after MI. Those more prone to AF include patients with older age, large MI, hypokalemia, hypomagnesemia, hypoxia, or increased sympathetic activity. Rate control with β-blockers (e.g., metoprolol), digoxin, calcium channel blockers (e.g., diltiazem) or some combination of these agents is warranted, as is the use of intravenous heparin to reduce the risk of systemic embolization. Cardioversion is warranted in the face of rapid rates that cause ischemia, heart failure, or hypotension. Amiodarone is sometimes used to help maintain sinus rhythm for the first few months after MI-related AF. Sinus bradycardia or AV block due to increased vagal tone is common in cases of inferior MI (30% to 40%). Reperfusion of the right coronary artery may be associated with significant bradycardia (Bezold-Jarisch reflex). Atropine (0.5 to 1.5 mg IV) can resolve severe inferior MI-related bradycardia. In contrast, heart block and wide-complex escape rhythms associated with anterior MI suggest an infra-AV node block. This may be worsened by the use of atropine. Advanced degrees of heart block may require the placement of a permanent pacemaker. Intermittent second-degree or third-degree AV block associated with bundle branch block or symptomatic AV block are indications for a permanent pacemaker. Type I AV block (Wenckebach) is usually not persistent and rarely causes symptoms that warrant a permanent pacemaker.

differential diagnosis

The diagnosis of STEMI is usually straightforward based on symptoms and ECG findings, but a number of conditions can mimic the ST elevation of STEMI and confound the diagnosis. The ECG changes of early repolarization, Takotsubo's syndrome, acute myocarditis, or pericarditis can be difficult or impossible to distinguish from those of STEMI. In the face of ST elevation and chest discomfort, it may be necessary to perform coronary angiography in patients who ultimately are diagnosed with a condition other than STEMI so as to not miss this critical diagnosis

prognosis

The extent and magnitude of ST depression noted on ECG in patients with NSTEMI predicts mortality risk. Patients who exhibit 2 mm or more of ST depression in multiple leads have a 10-fold increased mortality rate at 1 year. The degree of elevation in troponin also identifies patients with an increased risk of mortality during the following year. It has also been observed that the combined measurement of troponin, hsCRP, and brain natriuretic peptide (BNP) predicts an increased mortality risk better than any individual biomarker. Contemporary practice significantly reduced the risk of mortality for patients with ACS at presentation. Risk stratification with appropriate revascularization and use of antiplatelet therapy, statins, and overall coronary risk factor reduction also contribute to this decrease in mortality risk. Whereas the immediate mortality risk for patients with NSTEMI is lower than for patients with STEMI (5% vs. 7%), those with NSTEMI are more prone to subsequent recurrent coronary events. The cumulative mortality rate for STEMI and NSTEMI is similar at 6 months after presentation (12% vs.13%). NSTEMI identifies a patient group with significant long-term mortality risk who require aggressive attention to modifiable coronary risk factors.

physiology of the systemic circulation

The normal cardiovascular system delivers appropriate blood flow to each organ of the body under a wide range of conditions. This regulation is achieved by maintaining BP through adjustments in cardiac output and tissue blood flow resistance by neural and humoral factors Poiseuille's law generally describes the relationship between pressure and flow in a vessel. Fluid flow (F) through a tube is proportional (proportionality constant = K) to the pressure (P) difference between the ends of the tube: F= K * deltaP K is equivalent to the inverse of resistance to flow (R); that is, K = 1/R. Resistance to flow is determined by the properties of both the fluid and the tube. In the case of a steady, streamlined flow of fluid through a rigid tube, Poiseuille found that these factors determine resistance : R= 8 nL/pier^2 Where r is the radius of the tube, L is its length, and η is the viscosity of the fluid. Notice that changes in radius have greater influence than changes in length, because resistance is inversely proportional to the fourth power of the radius. Poiseuille's law incorporates the factors influencing flow, so that: Therefore, the most important determinants of blood flow in the cardiovascular system are ΔP and r4. Small changes in arterial radius can cause large changes in flow to a tissue or organ. Practically, systemic vascular resistance (SVR) is the total resistance to flow caused by changes in the radius of resistance vessels (small arteries and arterioles) of the systemic circulation. The SVR can be calculated as the pressure drop across the peripheral capillary beds (mean arterial pressure − right atrial pressure) divided by the blood flow across the beds (i.e., SVR = BP/CO). It is normally in the range of 800 to 1500 dynes-sec/cm−5 The autonomic nervous system alters systemic vascular tone through sympathetic and parasympathetic innervation as well as metabolic factors (local oxygen tension, carbon dioxide levels, reactive oxygen species, pH) and endothelium-derived signaling molecules (NO, endothelin). Neural regulation of BP occurs by means of constitutive and reflex changes in autonomic efferent outflow to modulate cardiac chronotropy, inotropy, and vascular resistance. The baroreflex loop is the primary mechanism by which BP is neurally modulated. Baroreceptors are stretch-sensitive nerve endings that are distributed throughout various regions of the cardiovascular system. Those located in the carotid artery (e.g., carotid sinus) and aorta are sometimes referred to as high-pressure baroreceptors and those in the cardiopulmonary areas as lowpressure baroreceptors. After afferent impulses are transmitted to the central nervous system, the signals are integrated, and the efferent arm of the reflex projects neural signals systemically through the sympathetic and parasympathetic branches of the autonomic nervous system. In general, an increase in systemic BP increases the firing rate of the baroreceptors. Efferent sympathetic outflow is inhibited (reducing vascular tone, chronotropy, and inotropy), and parasympathetic outflow is increased (reducing cardiac chronotropy). The opposite occurs when BP decreases. Please refer to Chapter 53, "Cardiac function and Circulatory Control," in Goldman-Cecil Medicine, 25th Edition

epidemiology

The occurrence of ACS represents a significant clinical event in up to 1.4 million Americans annually. One third of those categorized as having ACS are diagnosed with NSTEMI. More than half of patients with NSTEMI are 65 years of age or older, and approximately one-half are women. NSTEMI is more common in patients with diabetes, peripheral vascular disease, or chronic inflammatory disease (e.g., rheumatoid arthritis). Primary ACS is the most common form of the disease and reflects underlying plaque rupture leading to intracoronary thrombus formation and limitation of blood flow. Secondary ACS reflects imbalances in myocardial oxygen supply and demand leading to myocardial ischemia. Examples of decreased oxygen supply include profound anemia, systemic hypotension, and hypoxemia. Increased demand occurs in the face of severe systemic hypertension, fever, tachycardia, and thyrotoxicosis. Secondary ACS not uncommonly unmasks previously asymptomatic obstructive CAD, but it may also occur in the absence of CAD. Treatment of secondary ACS is directed at correcting the underlying medical condition

pathology

The process of atherosclerosis is known to begin at a young age. Autopsies of teenagers frequently demonstrate the presence of atherosclerotic changes in coronary arteries. Atherosclerosis is a process linked to the subintimal accumulation of small lipoprotein particles that are rich in LDL. Subintimal deposits of LDL are oxidized, setting off a cascade of events that culminate in not only the development of atherosclerotic plaque but also vascular inflammation. Vascular inflammation drives progression of atherosclerosis as well as the potential rupture of plaque leading to vessel occlusion. The process of lipoprotein uptake by the vessel wall is enhanced by vascular endothelial injury, which may be triggered by hypercholesterolemia, the toxic effects of cigarette smoking, sheer stresses associated with hypertension, or vascular effects of diabetes mellitus. Oxidized LDL aggregates trigger the expression of endothelial cell surface adhesion molecules, including vascular adhesion molecule-1, intracellular adhesion molecule-1, and selectins, which results in the binding of circulating macrophages to the endothelium. In response to cytokines and chemokines released by endothelial and smooth muscle cells, macrophages migrate into the subintimal region, where they ingest oxidized LDL aggregates. These LDL-laden macrophages are also called foam cells (based on the microscopic appearance), and the accumulation of foam cells represents the development of atherosclerosis. Foam cells break down, releasing pro-inflammatory substances that promote ongoing accumulation of both macrophages and T lymphocytes. This process potentiates the development of atherosclerotic plaque. Growth factors are also released that promote smooth muscle cell and fibroblast proliferation. The net result is the development of a fibrous cap, which covers a lipid-rich core Important contributors to the pathologic evolution of atherosclerotic plaque include impaired endothelial synthesis of nitric oxide and prostacyclin, both of which play major roles in vascular homeostasis. The loss of these vasodilators leads to abnormal regulation of vascular tone and also plays a role in evolving a local prothrombotic state. Platelets adhere to areas of vascular injury and are not only prothrombotic but also release growth factors that help drive the aforementioned proliferation of smooth muscle cells and fibroblasts. A key structural constituent of the fibrous cap is collagen, and its synthesis by fibroblasts is inhibited by cytokines elaborated by accumulating T lymphocytes. Foam cell degradation also releases matrix metalloproteinases that break down collagen, leading to weakening of the fibrous core and making it prone to rupture. T lymphocytes tends to accumulate at the border of plaque, which is the frequent site of plaque rupture As the fibrous cap thins through collagen degradation and eventually ruptures, blood is exposed to the thrombogenic triggers of collagen and lipid. In this setting, platelets are activated and begin to aggregate at the site of rupture. Platelets release vasoconstrictor substances thromboxane and serotonin, but more importantly, they serve as the trigger for thrombin formation, which leads to local thrombosis. Thrombin accumulation along with ongoing platelet activation can lead to rapid accumulation of thrombus in the vessel lumen. The combination of platelet-mediated thrombus accumulation and vasoconstriction can significantly limit blood flow, leading to myocardial ischemia. The degree of ischemia and its duration can culminate in MI. Complete vessel occlusion by thrombus leads to the greatest degree of myocardial ischemia and infarction, typically resulting in an ST elevation myocardial infarction (STEMI). Incomplete vessel occlusion limits blood flow enough to cause symptomatic myocardial ischemia and lesser degrees of MI, resulting in the syndromes of unstable angina or non-ST elevation myocardial infarction (NSTEMI). MI is the most profound consequence of atherosclerotic plaque pathology, but significant disability can also develop when atherosclerotic plaques expand in size, leading to obstruction of blood flow and resultant myocardial ischemia. Plaque growth, driven by smooth muscle cell proliferation, initially causes the vessel to expand toward the adventitia (Glagov remodeling). Once a limit of lateral expansion is reached, the enlarging plaque encroaches on the vessel lumen. Typically, when the diameter of the lumen is decreased by at least 70%, myocardial ischemia and symptoms of angina can develop under conditions of increasing demand for blood flow. In the case of exercise, increases in heart rate and blood pressure lead to increasing myocardial oxygen demand; when flow-limiting atherosclerotic lesions are present, oxygen demand may not be met by supply and myocardial ischemia ensues. The greater the degree of vessel obstruction, the more likely it is that myocardial ischemia and angina will occur at low workloads, even to the point of angina at rest (Fig. 8-1). Other forms of stress, such as emotional stress or cold exposure, can also cause symptoms of angina in patients with significant obstructive plaque through mechanisms such has hypertension (increased myocardial oxygen demand) or sympathetically mediated vasonstriction.

circulatory physiology and the cardiac cycle

The term cardiac cycle describes the pressure changes within each cardiac chamber over time (Fig. 2-3). This cycle is divided into systole, the period of ventricular contraction, and diastole, the period of ventricular relaxation. Each cardiac valve opens and closes in response to pressure gradients generated during these periods. At the onset of systole, ventricular pressures exceeds atrial pressures, so the AV valves passively close. As myocytes contract, the intraventricular pressures rise initially, without a change in ventricular volume (isovolumic contraction), until they exceed the pressures in the aorta and pulmonary artery. At this point, the semilunar valves open, and ventricular ejection of blood occurs. When intracellular calcium levels fall, ventricular relaxation begins; arterial pressures exceed intraventricular pressures, so the semilunar valves close. Ventricular relaxation initially does not change ventricular volume (isovolumic relaxation). At the point at which intraventricular pressures fall below atrial pressures, the AV valves open. This begins the rapid and passive ventricular filling phase of diastole, during which blood in the atria empties into the ventricles. At the end of diastole, active atrial contraction augments ventricular filling. When the myocardium exhibits increased stiffness due to age, hypertension, diabetes, or systolic heart failure, the early passive phase of ventricular filling is decreased. The end result is reliance on atrial contraction to sufficiently fill the ventricle during diastole. In atrial fibrillation, the atrium does not contract; patients often have worse symptoms because this additional ventricular filling is lost. Pressure tracings obtained from the periphery complement the hemodynamic changes exhibited in the heart. In the absence of valvular disease, there is no impediment to blood flow moving from the ventricles to the arterial beds, so the systolic arterial pressure rises sharply to a peak. During diastole, no further blood volume is ejected into the aorta, so the arterial pressure gradually falls as blood flows to the distal tissue beds and elastic recoil of the arteries occurs Atrial pressure can be directly measured in the right atrium, but the left atrial pressure is indirectly measured by occluding a small pulmonary artery branch and measuring the pressure distally (the pulmonary capillary wedge pressure). An atrial pressure tracing is shown in Figure 2-3. It is composed of several waves. The a wave represents atrial contraction. As the atria subsequently relax, the atrial pressure falls, and the x descent is seen on the pressure tracing. The x descent is interrupted by a small c wave, which is generated as the AV valve bulges toward the atrium during ventricular systole. As the atria fill from venous return, the v wave is seen, after which the y descent appears as the AV valves open and blood from the atria empties into the ventricles. The normal ranges of pressures in the various cardiac chambers are shown in Table 2-1. The cardiac index is a way of normalizing the CO to body size. It is the CO divided by the body surface area and is measured in L/min/m2. The normal CO is 4 to 6 L/min at rest and can increase fourfold to sixfold during strenuous exercise The main determinants of SV are preload, afterload, and contractility (Table 2-2). Preload is the volume of blood in the ventricle at the end of diastole; it is primarily a reflection of venous return. Venous return is determined by the plasma volume and the venous compliance. Clinically, intravenous fluids increase preload, whereas diuretics or venodilators such as nitroglycerin decrease preload. When the preload is increased, the ventricle stretches, and the ensuing ventricular contraction becomes more rapid and forceful, because the increased sarcomere length facilitates actin and myosin cross-bridge kinetics by means of an increased sensitivity of troponin C to calcium. This phenomenon is known as the Frank-Starling relationship. Ventricular filling pressure (ventricular end-diastolic pressure, atrial pressure, or pulmonary capillary wedge pressure) is frequently used as a surrogate measure of preload. Afterload is the force against which the ventricles must contract to eject blood. The main determinants of afterload are the arterial pressure and the dimensions of the left ventricle. As the arterial blood pressure increases, the amount of blood that can be ejected into the aorta decreases. Wall stress, an often overlooked determinant of afterload, is directly proportional to the size of the ventricular cavity and inversely proportional to the ventricular wall thickness (Laplace's law). Therefore, ventricular wall hypertrophy is a compensatory mechanism to reduce afterload. Drugs such as angiotensin-converting enzyme (ACE) inhibitors and hydralazine reduce blood pressure (BP) by reducing afterload. Diuretics decrease left ventricular volume and size, which can reduce wall stress-mediated afterload. Contractility, or inotropy, represents the force of ventricular contraction in the presence of constant preload and afterload. Inotropy is regulated at a cellular level through stimulation of cathecholminergic (epinephrine, norepinephrine, and dopamine) receptors, intracellular signaling cascades (phosphodiesterase inhibitors), and intracellular calcium levels (affected by levosimendan and, indirectly, by digoxin). Many antihypertensive medications (e.g., β-blockers, calcium channel antagonists) interfere with adrenergic receptor activation or intracellular calcium levels, which can decrease the strength of ventricular contractions. Please refer to Chapter 53, "Cardiac Function and Circulatory Control," in Goldman-Cecil Medicine, 25th Edition In response to a change in Mvo2, the coronary arteries dilate or constrict, which changes the vascular resistance and thereby appropriately changes flow. This regulation of arterial resistance occurs at the arterioles and is mediated by several factors. Adenosine, a metabolite of ATP, is released during contraction and acts as a potent vasodilator. Other consequences of myocardial metabolism, such as decreased oxygen tension, increased carbon dioxide, acidosis, and hyperkalemia, also mediate coronary vasodilation. The endothelium produces several potent vasodilators, including nitric oxide and prostacyclin. Nitric oxide is released by the endothelium in response to acetylcholine, thrombin, adenosine diphosphate (ADP), serotonin, bradykinin, platelet aggregation, and an increase in shear stress (called flow-dependent vasodilation). Finally, the coronary arteries are innervated by the autonomic nervous system, and activation of sympathetic neurons mediates vasoconstriction or vasodilation through α- or β-receptors, respectively. Parasympathetic neurons from the vagus nerve secrete acetylcholine, which mediates vasodilation. Vasoconstricting factors, notably endothelin, are produced by the endothelium and may be important in conditions such as coronary vasospasm. Please refer to Chapter 53, "Cardiac Function and Circulatory Control," in Goldman-Cecil Medicine, 25th Edition.

treatment- medical management of stable angina

The treatment of CAD and angina pectoris is multifaceted. The presence of CAD with or without angina requires the physician to recommend risk factor modification, frequently associated with lifestyle changes. For angina pectoris, pharmacologic therapy is typically used to control symptoms, allowing for maintenance of reasonable exercise tolerance. Revascularization is commonly used to control symptoms to a degree better than what can be achieved with medications alone, but only a small group of patients with CAD benefit from revascularization in terms of increased longevity. It is also incumbent on the physician to recognize other medical conditions that can lower the threshold for angina, thus worsening symptoms and affecting quality of life. Anemia is a common medical problem that, when addressed, can significantly reduce the frequency of angina pectoris. Hyperthyroidism, with its increased metabolic demand and tachycardia, can increase the frequency of angina pectoris. Uncompensated congestive heart failure lowers the anginal threshold through the effects of LV dilation and filling pressure elevation on myocardial oxygen demand. Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea leading to hypoxemia can trigger angina pectoris. Attention to the major modifiable risk factors for CAD is a cornerstone of therapy. Poorly controlled diabetes mellitus, hypertension, hyperlipidemia, and ongoing smoking all drive the progression of CAD and increase the risk for catastrophic events such as MI or sudden death. The wealth of clinical research on preventing death and disability from CAD has led to the development of evidence-based guidelines that form the basis of contemporary therapy for CAD (Table 8-4). Complete smoking cessation is a must for patients with CAD regardless of the presence of symptoms. The use of statin medications to reduce LDL cholesterol (to <100 mg/dL, with possible additional benefit if ≤70 mg/dL) has revolutionized the therapy for CAD. Statins have been shown to reduce the risk of MI in patients with proven CAD and in those at significant risk. There is also interest low HDL levels, which appear to confer increased risk for coronary events. It is unclear whether niacin, which raises HDL, actually reduces the risk of MI or death. Exercise increases HDL levels and may confer protective effects through other mechanisms. Pharmacologic strategies to elevate HDL and hopefully reduce risk are under development. ho have known CAD or are at risk. Patients should be instructed to take aspirin, 81 to 325 mg/day (clopidogrel 75 mg/day may be used in those who are aspirin intolerant or allergic). Angiotensin-converting enzyme (ACE) inhibitors reduce the risk of recurrent MI and are also beneficial for patients with diabetes mellitus or reduced LV function. Angiotensin receptor blockers (ARBs) can be substituted in those who experience significant side effects from ACE inhibitors. Regular aerobic exercise can benefit patients with CAD by reducing their risk for complications related to the disease. Aerobic exercise also increases exercise tolerance and may reduce the frequency of exercise-related angina pectoris. Positive benefits also accrue from weight loss related to exercise and improved blood pressure control. In sedentary individuals, isometric activities such as snow shoveling can trigger MI and should be avoided. There may be some benefits to judicious weight training in patients with CAD. In addition to antiplatelet therapy, the commonly employed medications to control angina pectoris include β-blockers, nitrates, and calcium channel blockers. These agents work by correcting supply/demand blood flow mismatch that is the cause of myocardial ischemia and angina pectoris (Table 8-5). Interestingly, these drugs principally control symptoms in chronic stable angina pectoris, but they do not reduce mortality risk as therapy with aspirin or statins does Nitrates in various forms have a long history of use in patients with symptomatic CAD and can be very effective in controlling exertion-related angina. Nitrates work by venodilating largecapacitance veins and thus shifting blood out of the heart, reducing preload and myocardial oxygen demand. Nitrates are also potent coronary vasodilators and can reverse coronary spasm, allowing for improved perfusion. Short-duration but quick-acting sublingual nitroglycerin has been a mainstay both for treatment of an anginal episode and for prophylaxis against angina in situations where it is likely to occur. Patients who respond well to nitrates are frequently treated with long-acting oral or topical preparations. Both methods can effectively prevent angina pectoris, but continued use can induce tolerance. There is a recognized need for patients to have a nitrate-free period of about 8 hours every day to prevent tolerance. This usually involves cessation of use during sleep. Intravenous nitroglycerin administered by continuous drip is reserved for patients with unstable angina or acute MI. β-Blocker therapy is very effective at reducing the likelihood of exertion-related angina. β-Blockers bind to cell surface β-receptors and by so doing reduce heart rate, contractility, and blood pressure, all of which tip the balance in favor of reduced oxygen demand and less angina. The use of β-blockers can be limited by the degree of bradycardia they induce or by baseline atrioventricular (AV) conduction abnormalities. Patients with higher degrees of AV block, β-blockers can induce complete heart block. These drugs also vary in their β-receptor selectivity. Blockade of β2-adrenergic receptors can lead to bronchospasm and vasoconstriction. Even selective β1-adrenergic antagonists such as atenolol and metoprolol have some β2 activity at higher doses. Intolerance of β-blockers can limit their use in patients with significant COPD or peripheral vascular disease. β-Blockers may also add to glucose intolerance and may affect lipids by increasing triglycerides or reducing HDL. In general, these effects do not preclude their use if they prove effective in controlling angina pectoris Calcium channel blocking drugs can decrease myocardial oxygen demand by causing arterial vasodilation, bradycardia, and decreased contractility. The magnitude of these effects varies according to the class of agent used. Dihydropyridines such as nifedipine and amlodipine cause arterial vasodilation leading to a blood pressure-lowering effect. In the dose ranges administered, they have no significant effect on contractility or heart rate. In contrast, verapamil, a phenylalkylamine, has significant effects on heart rate, AV conduction, and contractility. Benzothiazepine agents such as diltiazem manifest less vasodilation than dihydropyridines and less effect on contractility than phenylalkyamine drugs. The net effect of calcium channel blocking drugs is reduced myocardial oxygen demand and less angina pectoris. Diltiazem should be used with caution in patients who are also taking a β-blocker, because severe bradycardia or heart block can occur. Verapamil should not be co-administered with a β-blocker. A newer class of antianginal drug is represented by ranolazine. This drug is a selective inhibitor of late sodium current and reduces sodium-induced calcium overload in myocytes. Although it has no effect on heart rate or blood pressure, ranolazine demonstrates antianginal properties. It is typically used when other medical therapy is insufficient in controlling angina.

other

There are other, nonspecific symptoms that may indicate cardiovascular disease. Although fatigue is present with a myriad of medical conditions, it is very common in patients with cardiac disease when low cardiac output is present. It can be seen with hypotension due to aggressive medical treatment of hypertension or with overdiuresis in patients with heart failure. Fatigue may also be a direct result of medical therapy for cardiac disease itself, such as with β-blocking agents. Although cough is commonly associated with pulmonary disease, it may also indicate high intracardiac pressures which can lead to pulmonary edema. Cough may be present in patients with heart failure or significant leftsided valve disease. A patient with congestive heart failure may describe a cough productive of frothy pink sputum, as opposed to frank bloody or blood-tinged sputum, which is seen more typically with primary lung pathology. Nausea and emesis can accompany acute myocardial infarction and may also be a reflection of heart failure leading to hepatic or intestinal congestion due to high right heart pressures. Anorexia, abdominal fullness, and cachexia may occur with end-stage heart failure. Nocturia is also a symptom described with heart failure; renal perfusion improves when the patient lies in a prone position, leading to an increase in urine output. Hoarseness of voice can occur due to compression of the recurrent laryngeal nerve. This may happen with enlarged pulmonary arteries, enlarged left atrium, or aortic aneurysm. Despite the myriad symptoms of cardiovascular disease described here, many patients with significant cardiac disease are asymptomatic. Patients with CAD may have periods of asymptomatic ischemia that can be documented on ambulatory electrocardiographic monitoring. Up to one third of patients who have suffered a myocardial infarction are unaware that they had an event. This is more common in diabetics and in older patients. A patient may have severely depressed ventricular function for some time before presenting with symptoms. In addition, patients with atrial fibrillation can be entirely asymptomatic, with this rhythm discovered only after a physical examination is performed At times, patients do not report having symptoms related to usual activities of daily living, yet symptoms are present when functional testing is performed. Therefore, assessing functional capacity is a very important part of the history in a patient with known or suspected cardiovascular disease. The ability or inability to perform various activities plays a substantial role in determining the extent of disability and in assessing response to therapy and overall prognosis, and it can influence decisions regarding the timing and type of therapy or intervention. The New York Heart Association Functional Classification is a commonly used method to assess functional status based on "ordinary activity" (Table 3-3). Patients are classified in one of four functional classes. Functional class I includes patients with known cardiac disease who have no limitations with ordinary activity. Functional classes II and III describe patients who have symptoms with less and less activity, whereas patients in functional class IV have symptoms at rest. The Canadian Cardiovascular Society has provided a similar classification of functional status specifically for patients with angina pectoris. These tools are very useful in classifying a patient's symptoms at a given time, allowing comparison at a future point and determination as to whether the symptoms are stable or progressive.

diagnosis and differential diagnosis

Three basic forms of testing have played major roles in assessing patients with chest discomfort possibly due to CAD. All of these tests capitalize on the effect of myocardial ischemia on various aspects of cardiac physiology. First, myocardial ischemia induced by exercise or by spontaneous coronary occlusion results in subendocardial ischemia, which appears on an ECG as diffuse ST depression (Fig. 8-2). Once ischemia resolves, the ECG returns to normal. Second, myocardial ischemia typically affects a segment of heart muscle, and that territory develops a wall motion abnormality that can be detected by either echocardiography or nuclear scintigraphy. Third, the basis for myocardial ischemia is a decrease in coronary and myocardial blood flow. This abnormality can be detected by assessing the distribution of radioactive tracers such as thallium 201 or technetium sestamibi using specialized detectors for imaging myocardial perfusion. All stress test techniques used in diagnosing patients with possible CAD rely on these means of detecting the impact of myocardial ischemia on cardiac electrical activity, mechanical function, or myocardial perfusion. Stress testing in its various forms frequently plays a pivotal role in the assessment of patients with possible CAD. In using stress testing, it is important to understand the significance of pretest probability of CAD in interpreting the results of any stress test method. For a patient with a high pretest probability of CAD, a positive test is highly predictive of underlying CAD, and a negative test carries the weight of being falsely negative. The opposite is true in a patient with a low pretest probability of CAD: A negative test is associated with a high negative predicative value for the presence of CAD, but a positive test is likely to be falsely positive. These factors play into a clinician's interpretation of test results and must always factor into decision making regarding the need for additional testing. Stress testing is useful not only as a diagnostic tool but also in the long-term management of established CAD. Exercise stress testing, through its ability to quantify exercise capacity, can monitor the effectiveness of medical therapy directed at reducing myocardial ischemia. The findings of an exercise stress test also have predictive value in that patients with ischemia induced at low workloads are more likely to have extensive multivessel disease, whereas those who achieve high workloads are less prone to ischemic complications of CAD. A higher risk for poor outcomes related to CAD is implied by (1) ECG changes of ST depression early during exercise and persisting late into recovery; (2) exercise-induced reduction in systolic blood pressure; and (3) poor exercise tolerance (<6 minutes on the Bruce stress test protocol). Patients with a normal resting ECG can reliably be assessed by standard exercise stress testing with ECG monitoring (Fig. 8-3). The specificity of ST changes with exertion is significantly reduced in the face of baseline ECG abnormalities related to LV hypertrophy, left bundle branch block (LBBB), pre-excitation, or use of digoxin. Various imaging techniques (echocardiography, nuclear scintigraphy, magnetic resonance imaging) have been developed to overcome the impact of baseline ECG abnormalities on the validity of stress testing. Because women also have lower specificity for ECG changes during exercise testing than men, an imaging technique is frequently used in the assessment of women. Overall, the addition of an imaging technique to stress testing significantly improves the sensitivity, specificity, and predictive value of the stress test but also greatly increases its cost. Radionuclide stress testing is a common form of imagingbased stress test. Near peak exertion, a radionuclide tracer (thallium 201, technetium 99, or tetrofosmin) is administered intravenously. The tracer is distributed to the myocardium in a quantity directly proportional to blood flow. This type of image testing relies on a disparity of tracer uptake to detect an area of ischemia. Thallium 201 redistributes over 4 hours to viable myocardium, allowing for comparison of stress-induced ischemia to a baseline state. The other tracers do not share this redistribution feature, and tests using technetium 99 or tetrofosmin require both "rest" and "stress" injections of tracer to differentiate ischemic myocardium. Patients with normal perfusion studies have a low risk of coronary events (<1%/year). The presence of a positive perfusion study confers a risk of about 7%/year for coronary events, with the risk increasing relative to the extent of perfusion abnormality. An alternative means of imaging for exercise testing is the use of echocardiography to detect ischemia-induced wall motion abnormalities. This form of testing is increasingly favored because there is no radiation associated with its use, whereas radionuclide tracers expose the patient to a significant dose of radiation. Stress echocardiography carries with it the same enhancement in sensitivity, specificity, and predictive value as radionuclide imaging. An additional benefit of echocardiography imaging is more discrete anatomic data on valve function. If it is coupled with Doppler flow imaging, information regarding exercise-induced mitral regurgitation can be obtained Another means of assessing for exercise-induced wall motion abnormalities is the use of radionuclide ventriculography or multigated acquisition scanning (MUGA). This technique is usually included as part of the interpretation of an exercise stress radionuclide study. This imaging technique does not provide the anatomic detail associated with echocardiography, and it has the negative feature of significant radiation exposure. An emerging imaging technique for stress testing is the use of magnetic resonance imaging. Radiation is not a concern, and cardiac structural imaging can match echocardiography (or exceed it in patients with poor images on echocardiography). The technique is not as easy to execute as echocardiography, but magnetic resonance imaging is likely to gain favor in exercise testing. Not all patients who require noninvasive testing for CAD are able to exercise to a degree sufficient to induce ischemia, and for some patients exercise testing is not an option at all. For these patients, pharmacologic stress testing has evolved as a viable alternative to exercise testing. The prognostic benefit of exercise workload is not available from this form of testing, but information regarding the presence of ischemia-inducing atherosclerosis is obtainable. One common form of pharmacologic testing relies on inducing coronary vasodilation (as with dipyridamole, adenosine, or regadenosine), which produces a disparity of myocardial blood flow based on the presence of coronary stenosis. Radionuclide administered during the infusion of the coronary vasodilator allows for detection of myocardial ischemia similar to that observed with exercise testing. An alternative pharmacologic approach uses the inotropic and chronotropic effects of dobutamine to increase myocardial oxygen demand and induce segmental ischemia. Echocardiography is commonly used to detect dobutamine-induced wall motion abnormalities with this approach, although radionuclide or magnetic resonance imaging could also be used. All of the stress testing techniques discussed here are able to assess for the presence of inducible myocardial ischemia associated with CAD. The presence of CAD can also be determined by assessment of coronary calcification using either EBCT or the now more common MDCT. Coronary calcification is present only because of underlying CAD. Although detecting its presence does not directly indicate the presence of obstructive CAD as would an abnormal imaging stress test, studies have shown a direct correlation between the amount of coronary calcification and the probability that a 70% stenosis is present. At the least, this type of information informs the physician that CAD is present and directs aggressive attention toward risk factor modification. MDCT scanners can reliably perform coronary angiography with the use of intravenous contrast agents and specifically timed imaging protocols. This technique is becoming increasingly used to detect the presence of obstructive CAD, although it cannot precisely define the severity of stenosis. MDCT is also valuable in defining coronary anomalies, and a negative study carries a high negative predictive value for the occurrence of coronary events. Invasive coronary angiography has been considered the "gold standard" for detecting the extent and severity of underlying CAD. This approach carries a small risk of MI, stroke, or death, so it must not be taken lightly. In the case of patients with positive stress tests, particularly those with high-risk features, coronary angiography adds more discrete information regarding the underlying disease and guides the potential use of revascularization techniques (i.e., percutaneous coronary intervention or coronary artery bypass surgery) versus medical therapy to treat CAD (Table 8-3). Additional tools, such as pressure wires used to perform fractional flow reserve studies (FFR), add to the diagnostic power of invasive catheterization by allowing one to discriminate between physiologically significant lesions and those not likely to cause ischemia. Revascularization is not indicated for lesions that do not cause ischemia. The physician must also be cognizant of the fact that not all chest discomfort is related to CAD. Although CAD as a cause of chest discomfort poses the biggest risk for poor outcomes, other considerations of chest discomfort include esophageal disease (esophageal reflux may mimic typical angina pectoris), chest wall-related pain, pulmonary embolism, pneumonia, and trauma. The clinical presentation of the patient usually points in one direction or another, but patients with chest discomfort commonly undergo an evaluation for CAD, typically with the use of stress testing. Once CAD is reliably ruled out, the physician needs to consider alternative causes of the symptom. In the acute setting of severe chest discomfort, particularly in a hemodynamically unstable patient, the differential diagnosis includes acute MI, pulmonary embolism, and aortic dissection. Prompt and accurate diagnostic evaluation, commonly with the use of invasive angiography, can be lifesaving in this situation

reperfusion therapy

Timely reperfusion therapy, either thrombolytic therapy or primary PCI, is critical to limiting the extent of MI and reducing the risks of future morbidity and mortality. Primary PCI has been shown to have advantages over thrombolytic therapy, with higher immediate and long-term vessel patency. Primary PCI depends on the availability of cardiac catheterization facilities and staff to conduct the reperfusion procedure quickly (see earlier discussion). If the patient has not had access to a catheterization facility for longer than 2 hours after presentation, thrombolytic therapy is a reasonable alternative. In the randomized, placebo-controlled Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto (GISSI) study, thrombolytic therapy with intravenous streptokinase was shown to reduce the risk of mortality in patients with STEMI if it was administered early after presentation. The time-dependent nature of therapy was also demonstrated, in that patients treated more than 12 hours after the onset of symptoms had no measurable benefit from thrombolysis. The next generation of thrombolytic agents, recombinant tissue-type plasminogen activators (rt-PA), improved on mortality reduction when compared with streptokinase (30-day mortality rate, 7.3% with streptokinase vs. 6.3% with rt-PA). The advantage of rt-PA appeared to be related to enhanced vessel patency at 90 minutes after administration (80% with rt-PA vs. 53% to 60% with streptokinase). Subsequent forms of rt-PA, although easier to administer, did not further reduce mortality. The major attribute of thrombolytic therapy is its ease of administration, but there is a significant risk (0.5% to 1%) of catastrophic bleeding complications in the form of intracerebral hemorrhage. Age older than 75 years, female gender, hypertension, and concomitant use of heparin increase the risk of this complication. In the case of failed thrombolytic therapy, rescue PCI may be pursued. Primary PCI has been shown to be superior to thrombolytic therapy based on lower overall mortality rates and reduced risk of recurrent nonfatal MI. It is also associated with higher vessel patency rates and a low risk of intracranial hemorrhage. Primary PCI is frequently performed by mechanical aspiration of thrombus and placement of a coronary stent. Balloon angioplasty may or may not be needed during this procedure. Patients should receive preprocedure thienopyridine (clopidogrel 600 mg or prasugrel 60 mg). Bivalirudin was shown in a clinical trial of primary PCI to be superior to both heparin- and glycoprotein IIb/IIIa-based anticoagulation with lower post-MI mortality and fewer bleeding complications. Centers that are dedicated to primary PCI as the preferred therapy are likely to have the best outcomes when operators are sufficiently skilled and the institution cares for this patient population on a regular basis. Primary PCI is the best option for patients in cardiogenic shock (within 18 hours after onset of shock), for patients with prior CABG (graft occlusion is not amenable to thrombolysis), and for patients older than 70 years of age (conferring a reduced risk of intracerebral hemorrhage compared with thrombolysis).

physical examination

A comprehensive examination should be undertaken if acute MI is suspected. Attention must be paid to vital signs, because patients may be either hypertensive or hypotensive during the course of an MI. In some cases, such as inferior MI, profound bradycardia may be present. Auscultation of the heart may reveal an S4. In the case of a large MI, the patient may have symptoms and signs of heart failure such as dyspnea, rales, elevated central venous pressure, and an S3. Severe heart failure may lead to cardiogenic shock with hypotension and vasoconstriction causing the extremities to be cool to touch. Patients with acute MI are also subject to mechanical problems such as mitral regurgitation due to papillary muscle dysfunction

pathology

A patient with cardiovascular disease may have one or more of a number of problems. Coronary artery disease, discussed in depth in Chapter 8, is a leading cause of morbidity and mortality. At presentation, patients with CAD may have stable angina or an acute coronary syndrome such as unstable angina, non-ST segment elevation myocardial infarction (NSTEMI), or ST segment elevation myocardial infarction (STEMI). For some patients, their first presentation with CAD is sudden cardiac death, the result of arrhythmia often caused by atherosclerosis of the coronary vasculature. Congestive heart failure is the end result of many cardiac disorders and is generally classified as systolic or diastolic in etiology. Various forms of cardiomyopathy, such as dilated cardiomyopathy or hypertrophic cardiomyopathy, may lead to systolic dysfunction and a decline in ejection fraction. Without proper management, this will inevitably lead to alterations in hemodynamics that result in development of pulmonary vascular congestion, edema, and a decline in functional capacity. Diastolic dysfunction can be present with systolic dysfunction and is often the result of uncontrolled hypertension or infiltrative disorders such as hemochromatosis or amyloidosis. Heart failure with a preserved ejection fraction is often caused by diastolic dysfunction. Various forms of heart failure are further discussed in Chapter 5. Stroke is caused by cerebral hypoperfusion, which can result from such problems as carotid disease, thromboembolism, or emboli of infectious origin. A more detailed discussion can be found in Chapter 116 Peripheral arterial disease (PAD), addressed in Chapter 12, includes such entities as aneurysms of the ascending, descending, and abdominal aorta; aortic dissection; carotid disease; and atherosclerosis of branch vessels of the aorta and vessels in the limbs. PAD is often present in patients with CAD Atrial fibrillation and hypertension (see Chapters 9 and 12) are not uncommon and increase in prevalence with age. Although they are not typically the primary cause of mortality, these problems often predispose to other causes of cardiovascular disease mortality, such as stroke and heart failure. Arrhythmias other than atrial fibrillation are also common and can lead to significant morbidity and mortality. Valvular heart disease may lead to cardiomyopathy and is found in all age groups Congenital heart disease includes a wide variety of disorders, ranging from valve abnormalities and coronary anomalies to cardiomyopathy and other structural abnormalities including shunts and malformations of the cardiac chambers. With advances in surgical techniques and medical therapy, these patients are often living beyond previous expectations, increasing the likelihood that they will live into adulthood. For more detailed information on congenital heart diseases, see Chapter 6.

clinical presentation

ACS may manifest as a first symptom of angina pectoris in a previously asymptomatic patient. Alternatively, patients with preexisting angina pectoris experience more frequent angina, angina at lower levels of exertion, or angina at rest. Patients who have developed ACS commonly experience their typical symptom of angina in terms of location and radiation but with increased intensity and duration. Patients with subtotal or total occlusion of a coronary artery may be much less responsive or completely unresponsive to the effects of nitroglycerin. Physical examination during myocardial ischemia may reveal a patient is who is clearly anxious and uncomfortable and who may also be experiencing dyspnea, nausea, or vomiting. Sinus tachycardia and hypertension is a common response to the discomfort of ACS, but in some instances sinus bradycardia and varying degrees of heart block may be observed. Bradyarrhythmias may also be associated with hypotension. Auscultation may reveal the presence of an S4, reflecting diminished LV compliance, or an S3 if there is extensive LV dysfunction. In the case of ischemia-induced papillary muscle dysfunction, the systolic murmur of mitral regurgitation can be heard. Patients with large areas of ischemic myocardium develop elevated LV filling pressures leading to pulmonary congestion, dyspnea, and the physical finding of rales on lung auscultation

normal heart sounds

All heart sounds should be described according to their quality, intensity, and frequency. There are two primary heart sounds heard during auscultation: S1 and S2. These are high-frequency sounds caused by closure of the valves. S1 occurs with the onset of ventricular systole and is caused by closure of the mitral and tricuspid valves. S2 is caused by closure of the aortic and pulmonic valves and marks the beginning of ventricular diastole. All other heart sounds are timed based on these two sounds S1 has two components, the first of which (M1) is usually louder, heard best at the apex, and caused by closure of the mitral valve. The second component (T1), which is softer and thought to be related to closure of the tricuspid valve, is heard best at the lower left sternal border. Although there can be two components, S1 is typically heard as a single sound. S2 also has two components, which typically can be easily distinguished. A2, the component caused by closure of the aortic valve, is usually louder and is best heard at the right upper sternal border. P2, caused by closure of the pulmonic valve, is recognized best over the left second intercostal space. With expiration, a normal S2 is perceived as a single sound. With inspiration, however, venous return to the right heart is augmented, and the increased capacitance of the pulmonary vascular bed results in a delay in pulmonic valve closure. A slight decline in pulmonary venous return to the left ventricle leads to earlier aortic valve closure. Therefore, physiologic splitting of S2, with A2 preceding P2 during inspiration, is a normal finding. Additional heart sounds can at times be heard in normal individuals. A third heart sound can sometimes be heard in healthy children and young adults. This is referred to as a physiologic S3, which is rarely heard after the age of 40 years in a normal individual. A fourth heart sound is caused by forceful atrial contraction into a noncompliant ventricle; it is rarely audible in normal young patients but is relatively common in older individuals. Murmurs are auditory vibrations generated by high flow across a normal valve or normal flow across an abnormal valve or structure. Murmurs that occur early in systole and are soft and brief in duration are not typically pathologic and are termed innocent murmurs. These usually are caused by flow across normal left ventricular or right ventricular outflow tracts and are found in children and young adults. Some systolic murmurs may be associated with high-flow states such as fever, anemia, thyroid disease, and pregnancy and are not innocent, although they are not typically associated with structural heart disease. They are called physiologic murmurs because of their association with altered physiologic states. All diastolic murmurs are pathologic.

microvascular angina with normal coronary arteries

Angina can occur in some patients in the face of normal- appearing coronary arteries and no provocable spasm. Decreased endothelium-dependent vasodilation may be the underlying pathophysiology of microvascular angina. Patients with this condition may demonstrate an increase in coronary resistance and an inability to increase coronary blood flow sufficiently when challenged by increases in myocardial oxygen demand. Women are more likely to be affected with microvascular angina, and the symptoms not uncommonly occur at rest or with emotional stress. Exercise can also trigger angina A host of diagnostic tests can detect the presence of ischemia in patients with microvascular angina. In the case of stress testing, ST changes of ischemia can be detected as well as nuclear perfusion defects and transient wall motion abnormalities on echocardiography. More sophisticated invasive testing may demonstrated the presence of stress-induced metabolic abnormalities characteristic of ischemia and endothelial dysfunction. Exercise-related ischemic symptoms may respond to β-blocker therapy. Microvascular angina also tends to respond well to nitrates, both short-acting sublingual nitroglycerin and longacting oral nitrates. Calcium channel antagonists are sometimes used together with nitrates to control angina related to microvascular ischemia.

angina pectoris and stable ischemic heart disease- definition

Angina pectoris is a clinical manifestation of obstructive CAD, which in turn is usually the result of atherosclerotic plaque formation over a number of years. The term angina pectoris refers to the symptom of chest discomfort that may be described by the patient as a sensation of chest tightness or burning. Of the 17,600,000 adults in the United States with heart disease, as many as 10,200,00 have angina pectoris. It is estimated that 785,000 people experience a new ischemic episode annually, and recurrent events occur in at least 470,000 Americans each year.

pathology

As a symptom, angina pectoris is experienced when myocardial ischemia develops. Myocardial ischemia and angina pectoris may occur in the face of obstructive atherosclerotic plaque that limits blood flow in the face of increased demand such as exertion or emotional excitement. Myocardial oxygen demand is directly related to increases in heart rate and blood pressure; these variables, in turn, can be manipulated with medical therapy to reduce the demand. Restricted oxygen supply, in the form of reduced blood flow, can also induce myocardial ischemia. Blood flow reduction is a prominent feature of acute presentations of CAD such as NSTEMI and STEMI, but atherosclerosis-mediated coronary vasoconstriction, or coronary vasospasm, is also a potential cause of flow limitation leading to myocardial ischemia. Another example of supply limitation is anemia, whereby reduced oxygen-carrying capacity coupled with obstructive lesions leads to myocardial ischemia and symptoms of angina pectoris. The term stable angina pectoris refers to myocardial ischemia caused by either plaque-mediated flow limitation in the face of excess demand or supply limitation due to coronary vasospasm

acute coronary syndrome unstable angina and NSTEMI

Asymptomatic CAD or chronic stable angina may undergo transition to a more aggressive stage of disease called acute coronary syndrome (ACS). ACS comprises a spectrum of clinical presentations, ranging from unstable angina to NSTEMI or STEMI. Unstable angina represents the new onset of angina at rest or on exertion, or an increase in frequency of previously stable anginal symptoms, particularly at rest. ACS manifesting as MI, either NSTEMI or STEMI, is differentiated from unstable angina on the basis of prolonged symptoms, characteristic ECG changes, and the presence of biomarkers in blood. Unstable angina may be a harbinger of either NSTEMI or STEMI, and the diagnosis of unstable angina identifies a patient who requires careful assessment and treatment.

auscultation- technique

Auscultation of the heart is accomplished by the use of a stethoscope with dual chest pieces. The diaphragm is ideal for high-frequency sounds, whereas the bell is better for low-frequency sounds. When one is listening for low-frequency tones, the bell should be placed gently on the skin with minimal pressure applied. If the bell is applied more firmly, the skin will stretch and higher-frequency sounds will be heard (as when using the diaphragm). Auscultation should ideally be performed in a quiet setting with the patient's chest exposed and the examiner best positioned to the right of the patient. Four major areas of auscultation are evaluated, starting at the apex and moving toward the base of the heart. The mitral valve is best heard at the apex or location of the PMI. Tricuspid valve events are appreciated in or around the left fourth intercostal space adjacent to the sternum. The pulmonary valve is best evaluated in the second left intercostal space. The aortic valve is assessed in the second right intercostal space. These areas should be evaluated from apex to base using the diaphragm and then evaluated again with the bell. Auscultation of the back, the axillae, the right side of the chest, and the supraclavicular areas should also be done. Having the patient perform maneuvers such as leaning forward, exhaling, standing, squatting, and performing a Valsalva maneuver may help to accentuate certain heart sounds (Table 3-4).

risk factors for atherosclerosis

Before delving into discussion of the pathology of atherosclerosis, a description of risk factors is warranted. There are a number of well-known risk factors for coronary artery disease (CAD), some of which are modifiable (Table 8-1). Although women ultimately also carry a significant atherosclerotic burden, men develop CAD at younger ages, and the prevalence of the disease also increases as men age. Another potent risk factor for the development of CAD is a family history of premature CAD. This speaks to a nonmodifiable, genetically based risk. Commonly, multiple family members develop symptomatic CAD before the age of 55 years (65 years for women). Risks are additive, making it very important to appreciate the modifiable risk factors such as hyperlipidemia, hypertension, diabetes mellitus, metabolic syndrome, cigarette smoking, obesity, sedentary lifestyle, and heavy alcohol intake. Metabolic syndrome deserves particular attention given that up to 25% of the adult U.S. population may satisfy the definition of the disorder as laid out by the National Cholesterol Education Program Adult Treatment Panel. The definition of metabolic syndrome requires the presence of at least three of the following five criteria: waist circumference greater than 201 cm in men or 88 cm in women, triglyceride level 150 mg/dL or higher, highdensity lipoprotein (HDL) cholesterol level lower than 40 mg/ dL in men or 50 mg/dL in women, blood pressure 130/85 mm Hg or higher, and fasting serum glucose level 110 mg/dL or higher. The features of metabolic syndrome are largely modifiable risk factors for CAD Hyperlipidemia, in particular elevated levels of low-density lipoprotein (LDL) cholesterol, plays a pivotal role in the development and evolution of atherosclerosis. HDL-cholesterol is believed to be protective, likely due to its role in transporting cholesterol from the vessel wall to the liver for degradation. Increased levels of HDL are inversely proportional to the risk of CAD-related problems. The interplay among circulating lipids is complex. Elevated levels of triglycerides are a risk factor for CAD and are frequently associated with reduced levels of protective HDL. Hyperlipidemia is highly modifiable, and clinical trials have shown that drug treatment directed at lowering LDLcholesterol significantly reduces the risk of CAD-related complications or death. as with hyperlipidemia, hypertension (systolic pressure >140 mm Hg or diastolic pressure >90 mm Hg) contributes to the risk of CAD-related complications. Hypertension, probably through sheer stress, causes vessel injury that supports the development of atherosclerotic plaque. Increasing severity of hypertension is associated with greater risk of CAD. Control of hypertension is associated with a reduced risk of CAD. Diabetes mellitus is a prominent risk factor for CAD, and the disease is becoming epidemic. Diabetes mellitus typically is associated with other risk factors, such as elevated triglycerides, reduced HDL, and hypertension, which accounts for the enhanced risk of CAD-related problems in diabetic patients. It is not clear that control of hyperglycemia in diabetic patients translates into a reduced risk of CAD, but the presence of diabetes mellitus drives the need to ensure good treatment of other modifiable risk factors. Cigarette smoking has long been known as a significant risk factor for both CAD and lung cancer. Cigarette smoking is associated with increased platelet reactivity and increased risk of thrombosis, as well as lipid abnormalities. This addictive habit is modifiable, and smoking cessation can lead to a decrease in CAD event rates by 50% in the first 2 years of cessation Similar to diabetes mellitus, obesity (body mass index >30 kg/ m2) is associated with risk factors such as hypertension, hyperlipidemia, and glucose intolerance. Although multiple risk factors are frequently present in obese people, obesity itself carries some independent risk for CAD. The location and type of adipose tissue appear to influence CAD risk, with abdominal obesity posing a greater risk for CAD in men and women Numerous clinical studies have shown the benefit of regular aerobic exercise in decreasing the risk for CAD-related problems, both in the people without known CAD and in those with the disease. Sedentary lifestyles carry an increased risk that is modifiable through exercise. Another common attribute of life, alcohol consumption, can influence the risk of CAD in both directions. One to two ounces of alcohol per day may reduce the risk for CAD-related events, but more than 2 ounces of alcohol per day is associated with an increased risk of events. Lower levels of alcohol consumption can increase HDL levels, although it is not clear that this is the mechanism of benefit. In contrast, excessive alcohol consumption is associated with hypertension, a definite risk for CAD, although other effects of high-dose alcohol may also be at play. Additional factors that may have some role in adding CAD risk include lipoprotein(a) and homocysteine. Lipoprotein(a) is structurally similar to plasminogen and may interfere with the activity of plasmin, thus contributing to a prothrombotic state. Hyperhomocysteinemia has been associated with increased vascular risks, including coronary, cerebral, and peripheral vascular disease. It is not clear that a causal link exists, and the use of folic acid supplementation to lower homocysteine levels has not been shown to reduce the risk of MI or stroke. C-reactive protein (CRP) is a marker of systemic inflammation, and it indicates an increased risk for coronary plaque rupture. High-sensitivity assays for CRP (hsCRP) have measured elevated levels that correlate with risk for MI, stroke, peripheral vascular disease, and sudden cardiac death. Another marker for the presence of CAD is coronary calcification. The process of atherosclerosis is often associated with deposition of calcium within the plaque. Coronary artery calcification can be detected by fluoroscopy during cardiac catheterization as well by computed tomography (CT) scanning using either multidetector computed tomography (MDCT) or electron beam computed tomography (EBCT). CT technology allows for a quantitative measure of coronary calcium deposits that correlates with the probability of having significant obstructive lesions. The value of routine use of either hsCRP or CT for coronary calcification remains unclear, but patients in whom coronary calcification is identified should be approached with aggressive risk-factor modification.

classification of heart murmurs

CLASS DESCRIPTION CHARACTERISTIC LESIONS SYSTOLIC Ejection Begins in early systole; may extend to mid or late systole Crescendo-decrescendo pattern Often harsh in quality Begins after S1 and ends before S2 Valvular, supravalvular, and subvalvular aortic stenoses Hypertrophic cardiomyopathy Pulmonic stenosis Aortic or pulmonary artery dilation Malformed but nonobstructive aortic valve ↑ Transvalvular flow (e.g., aortic regurgitation, hyperkinetic states, atrial septal defect, physiologic flow murmur) Holosystolic Extends throughout systole* Relatively uniform in intensity Mitral regurgitation Tricuspid regurgitation Ventricular septal defect Late Variable onset and duration, often preceded by a nonejection click Mitral valve prolapse DIASTOLIC Early Begins with A2 or P2 Decrescendo pattern with variable duration Often high pitched, blowing Aortic regurgitation Pulmonic regurgitation Mid Begins after S2, often after an opening snap Low-pitched rumble heard best with bell of stethoscope Louder with exercise and left lateral position Loudest in early diastole Mitral stenosis Tricuspid stenosis ↑ Flow across atrioventricular valves (e.g., mitral regurgitation, tricuspid regurgitation, atrial septal defect) Late Presystolic accentuation of mid-diastolic murmur Mitral stenosis Tricuspid stenosis CONTINUOUS Systolic and diastolic components "Machinery murmurs" Patent ductus arteriosus Coronary atrioventricular fistula Ruptured sinus of Valsalva aneurysm into right atrium or ventricle Mammary soufflé Venous hum

cardiovascular causes of chest pain

CONDITION LOCATION QUALITY DURATION AGGRAVATING OR ALLEVIATING FACTORS ASSOCIATED SYMPTOMS OR SIGNS Angina Retrosternal region: radiates to or occasionally isolated to neck, jaw, shoulders, arms (usually left), or epigastrium Pressure, squeezing, tightness, heaviness, burning, indigestion <2-10 min Precipitated by exertion, cold weather, or emotional stress; relieved by rest or nitroglycerin; variant (Prinzmetal) angina may be unrelated to exertion, often early in the morning Dyspnea; S3, S4, or murmur of papillary dysfunction during pain Myocardial infarction Same as angina Same as angina, although more severe Variable; usually >30 min Unrelieved by rest or nitroglycerin Dyspnea, nausea, vomiting, weakness, diaphoresis Pericarditis Left of the sternum; may radiate to neck or left shoulder, often more localized than pain of myocardial ischemia Sharp, stabbing, knifelike Lasts many hours to days; may wax and wane Aggravated by deep breathing, rotating chest, or supine position; relieved by sitting up and leaning forward Pericardial friction rub Aortic dissection Anterior chest; may radiate to back, interscapular region Excruciating, tearing, knifelike Sudden onset, unrelenting Usually occurs in setting of hypertension or predisposition, such as Marfan's syndrome Murmur of aortic insufficiency; pulse or blood pressure asymmetry; neurologic deficit

Noncardiac causes of chest pain

CONDITION LOCATION QUALITY DURATION AGGRAVATING OR ALLEVIATING FACTORS ASSOCIATED SYMPTOMS OR SIGNS Pulmonary embolism (chest pain often not present) Substernal or over region of pulmonary infarction Pleuritic (with pulmonary infarction) or angina-like Sudden onset (minutes to hours) Aggravated by deep breathing Dyspnea, tachypnea, tachycardia; hypotension, signs of acute right ventricular heart failure, and pulmonary hypertension with large emboli; pleural rub; hemoptysis with pulmonary infarction Pulmonary hypertension Substernal Pressure; oppressive — Aggravated by effort Pain usually associated with dyspnea; signs of pulmonary hypertension Pneumonia with pleurisy Located over involved area Pleuritic — Aggravated by breathing Dyspnea, cough, fever, bronchial breath sounds, rhonchi, egophony, dullness to percussion, occasional pleural rub Spontaneous pneumothorax Unilateral Sharp, well localized Sudden onset; lasts many hours Aggravated by breathing Dyspnea; hyperresonance and decreased breath and voice sounds over involved lung Musculoskeletal disorders Variable Aching, well localized Variable Aggravated by movement; history of exertion or injury Tender to palpation or with light pressure Herpes zoster Dermatomal distribution Sharp, burning Prolonged None Vesicular rash appears in area of discomfort Esophageal reflux Substernal or epigastric; may radiate to neck Burning, visceral discomfort 10-60 min Aggravated by large meal, postprandial recumbency; relief with antacid Water brash Peptic ulcer Epigastric, substernal Visceral burning, aching Prolonged Relief with food, antacid — Gallbladder disease Right upper quadrant; epigastric Visceral Prolonged Spontaneous or after meals Right upper quadrant tenderness may be present Anxiety states Often localized over precordium Variable; location often moves from place to place Varies; often fleeting Situational Sighing respirations; often chest wall tenderness

muscle physiology and contraction

Calcium-induced calcium release is the primary mechanism for myocyte contraction. When a depolarizing stimulus reaches the myocyte, it enters special invaginations within the sarcolemma called T tubules. Specialized channels open in response to depolarization, permitting calcium flux into the cell (Fig. 2-2). The sarcoplasmic reticulum is in close proximity to the T tubules, and the initial calcium current triggers the release of large amounts of calcium from the sarcoplasmic reticulum into the cell cytosol. Calcium then binds to the calcium-binding regulatory subunit, troponin C, on the actin filaments of the sarcomere, resulting in a conformational change in the troponin-tropomyosin complex. The myosin binding site on actin is now exposed, to facilitate binding of actin-myosin cross-bridges, which are necessary for cellular contraction. The energy for myocyte contraction is derived from ATP. During contraction, ATP promotes dissociation of myosin from actin, thereby permitting the sliding of thick filaments past thin filaments as the sarcomere shortens. The force of myocyte contraction is regulated by the amount of free calcium released into the cell by the sarcoplasmic reticulum. More calcium allows for more frequent actin-myosin interactions, producing a stronger contraction. On repolarization of the sarcolemmal membrane, intracellular calcium is rapidly and actively resequestered into the sarcoplasmic reticulum, where it is stored by various proteins, including calsequestrin, until the next wave of depolarization occurs. Calcium is also extruded from the cytosol by various calcium pumps in the sarcolemma. The active removal of intracellular calcium by ATP ion pumps facilitates ventricular relaxation, which is necessary for proper ventricular filling during diastole

diagnostic testing

Cardiac troponins (cTnI and cTnT) are sarcomere proteins that, when measured in blood, are specific for myocardial injury. The troponin level becomes elevated 2 to 4 hours after the onset of injury, and the abnormal elevation can persist for up to 2 weeks after the event. The CK-MB isomere is not as specific for heart injury as troponin, but it can still be useful in documenting the presence of MI. CK-MB is found elevated within 4 hours after an acute MI, but it clears more rapidly than troponin. In the case of persistently elevated troponin, a measurable increase in CK-MB may herald another episode of myocardial necrosis. Chronic renal insufficiency is associated with false-positive elevations of troponin T, more so than troponin I. In addition to biomarkers of myocardial injury, other laboratory studies obtained in patients with acute MI include a complete blood count, blood chemistries, lipid panel, prothrombin time (PT), and partial thromboplastin time (PTT). Leukocytosis is a common finding in acute MI, reflecting the inflammatory nature of myocardial necrosis. At the time of admission, chest radiographs are obtained to assess for the presence of pulmonary edema or mediastinal widening suspicious for dissection. Echocardiography is important in delineating the extent of MI and assessing EF. In cases of diagnostic ambiguity, early use of echocardiography can demonstrate the presence of regional wall motion abnormalities consistent with acute MI. Echocardiography with color Doppler is also helpful in diagnosing complications of acute MI such as infarctrelated mitral regurgitation or ventricular septal defect (VSD), pericardial effusion, or evidence of pseudoaneurysm as a result of myocardial rupture. Follow-up echocardiography in the months after acute MI can also reveal recovery of LV function. Radionuclide tracer studies are not useful in diagnosing acute MI. CT, cardiac MRI, and transesophageal echocardiography are all useful in diagnosing aortic dissection when there is an increased index of suspicion. Cardiac MRI can also distinguish myopericarditis.

cardiogenic shock

Cardiogenic shock is a clinical syndrome associated with extensive loss of myocardium, which leads to a reduced cardiac index (<1.8 L/min/m2) in the face of elevated LV filling pressures (pulmonary capillary wedge pressure >18 mm Hg), resulting in systemic hypotension and reduced organ perfusion. This shock state is associated with mortality rates in the range of 70% to 80%. Aggressive diagnosis with hemodynamic monitoring and appropriate support with an intra-aortic balloon pump (IABP) and inotropic agents as indicated can help to stabilize the patient. IABP therapy is at best temporizing, and the patient's survival depends on the presence of reversible factors such as ischemia that respond to revascularization or correction of a mechanical complication of MI (e.g., mitral regurgitation or VSD. IABP therapy cannot be used in the face of significant aortic insufficiency and may not be feasible in the presence of significant peripheral vascular disease. Some centers now resort to ventricular assist devices to stabilize the patient with cardiogenic shock, but recovery of LV function is not guaranteed with this approach

definition and epidemiology

Cardiovascular disease is a major cause of morbidity and mortality around the world, and its spectrum is wide-reaching. Included in this population of patients are people with coronary artery disease (CAD), congestive heart failure, stroke, hypertension, peripheral arterial disease, atrial fibrillation and other arrhythmias, valvular disease, and congenital heart disease. In the United States alone, these diseases affect more than 82 million individuals at any given time. The impact of cardiovascular disease is unmistakable: It accounted for more inpatient hospital days in the years of 1990-2009 than other disorders such as chronic lung disease and cancer. The high number of inpatient days associated with cardiovascular disease led to a total economic cost of more than $297 billion in the year 2008 alone. Cardiovascular disease was also the number one cause of death in the United States in 2008; more than half of these deaths were from CAD, which was the top cause of mortality among individuals older than 65 years of age. Given these facts, the proper evaluation of a patient with cardiovascular disease can have a major impact on multiple fronts, from an economic standpoint as well as an individual's morbidity and mortality. Therefore, one must obtain a very thorough history and detailed physical examination to accurately assess and manage patients with cardiovascular disease.

cyanosis

Cyanosis is defined as an abnormal bluish discoloration of the skin resulting from an increase in the level of reduced hemoglobin or abnormal hemoglobin in the blood. When present, it typically represents an oxygen saturation of less than 85% (normal, >90%). There are several types of cyanosis. Central cyanosis often manifests in discoloration of the lips or trunk and usually represents low oxygen saturations due to right-to-left shunting of blood. This can occur with structural cardiac abnormalities such as large atrial or ventricular septal defects, but it also happens with impaired pulmonary function, as in with severe chronic obstructive lung disease. Peripheral cyanosis is typically secondary to vasoconstriction in the setting of low cardiac output. This can also occur with exposure to cold and can represent local arterial or venous thrombosis. When localized to the hands, peripheral cyanosis suggests Raynaud's phenomenon. Cyanosis in childhood often indicates congenital heart disease with resultant right-to-left shunting of blood.

medications for angina pectoris

DRUG CLASS EXAMPLES ANTIANGINAL EFFECT PHYSIOLOGIC SIDE EFFECTS COMMENTS Nitroglycerin Sublingual Topical Intravenous Oral Decreased preload and afterload Coronary vasodilation Increased collateral blood flow Headache Flushing Orthostasis Tolerance develops with continuous use β-Adrenergic blocking agents Metoprolol Atenolol Propranolol Nadolol Decreased heart rate Decreased blood pressure Decreased contractility Bradycardia Hypotension Bronchospasm Depression May worsen heart failure and AV conduction block; avoid in vasospastic angina Calcium channel blocking agents (non-dihydropyridine) Phenylalkylamine (verapamil) Benzothiazepine (diltiazem) Decreased heart rate Decreased blood pressure Decreased contractility Coronary vasodilation Bradycardia Hypotension Constipation with verapamil May worsen heart failure and AV conduction Calcium channel blocking agents Dihydropyridine (nifedipine, amlodipine) Decreased blood pressure Coronary vasodilation Hypotension, reflex tachycardia Peripheral edema Short-acting nifedipine is associated with increased risk for cardiovascular events. Late sodium current blocking agents Ranolazine Inhibits cardiac late INa Prevents calcium overload Dizziness Headache Constipation Nausea No effects on blood pressure or heart rate Modest QTc prolongation

dyspnea

Dyspnea is another hallmark symptom of cardiovascular disease, but it is also a primary symptom of pulmonary disease. It is defined as an uncomfortable heightened awareness of breathing. This can be an entirely normal sensation in individuals performing moderate to extreme exertion, depending on their level of conditioning. When it occurs at rest or with minimal exertion, dyspnea is considered abnormal. Dyspnea may accompany a large number of noncardiac conditions such as anemia due to a lack of oxygen-carrying capacity, pulmonary disorders such as obstructive or restrictive lung disease and asthma, obesity due to an increased work of breathing and restricted filling of the lungs, and deconditioning. In the cardiovascular patient, dyspnea is typically caused by left ventricular dysfunction, either systolic or diastolic; CAD and resultant ischemia; or valvular heart disease which, when severe, can lead to a drop in cardiac output. In cases of left ventricular dysfunction and valvular disease, the mechanism of dyspnea often involves increased intracardiac pressures that lead to pulmonary vascular congestion. Fluid then leaks into the alveolar space, impairing gas exchange and causing dyspnea. Breathing difficulties can also be secondary to a low-output state without pulmonary vascular congestion. Patients often notice dyspnea with exertion, but it can also occur at rest in patients with severe cardiac disease. Shortness of breath at rest is also a symptom in patients with pulmonary edema, large pleural effusions, anxiety, or pulmonary embolism. A patient with left ventricular systolic or diastolic failure may describe the acute onset of breathing difficulty when sleeping. This problem, called paroxysmal nocturnal dyspnea (PND), is caused by pulmonary edema that is redistributed in a prone position; it is usually secondary to left ventricular failure. These patients often notice the acute onset of dyspnea followed by coughing roughly 2 to 4 hours after going to sleep. This can be a very uncomfortable feeling, and it leads the patient to sit up immediately or get out of bed. Symptoms typically resolve over 15 to 30 minutes. Patients with left ventricular failure also often complain of orthopnea, which is dyspnea that occurs when one assumes a prone position. This is relieved by sleeping on multiple pillows or remaining seated to sleep ash pulmonary edema, which is very rapid and acute accumulation of fluid in the lungs. This can be associated with severe CAD and may also be a cause of dyspnea in patients with coarctation of the aorta and renal artery stenosis. Sudden dyspnea is associated with pulmonary embolism, and this symptom is typically accompanied by pleuritic chest pain and possibly hemoptysis in such patients. Pneumothorax can cause dyspnea accompanied by acute chest pain. Dyspnea due to lung disease is present with exertion, although in severe cases it may be present at rest. This is often accompanied by hypoxia and is relieved by pulmonary bronchodilators or steroids or both. Dyspnea may also be an "angina equivalent." Not all patients with CAD develop typical anginal chest pain. Dyspnea that comes on with exertion or emotional stress, is relieved with rest, and is relatively brief in duration might be a manifestation of significant CAD. This type of dyspnea is also usually improved with the administration of nitroglycerine.

edema

Edema often accompanies cardiovascular disease but may be a manifestation of liver disease (cirrhosis), renal disease (nephrotic syndrome), or local issues such as chronic venous insufficiency or thrombophlebitis. Edema related to cardiac disease is caused by increased venous pressures that alter the balance between hydrostatic and oncotic forces. This leads to extravasation of fluid into the extravascular space. Peripheral edema is common with right-sided heart failure, whereas the same process in left-sided heart failure leads to pulmonary edema Edema due to a cardiac etiology is typically bilateral and begins distally with progression in a proximal fashion. The feet and ankles are affected first, followed by the lower legs, thighs, and, ultimately, the abdomen, sometimes accompanied by ascites. If edema is visible, it is usually preceded by a weight gain of at least 5 to 10 pounds. Edema with heart disease is typically pitting, leaving an indentation in the skin after pressure is applied to the area. The edema is usually worse in the evening, and patients often describe an inability to fit into their shoes. While these patients are lying prone, the edema can shift to the sacral region after several hours, only to accumulate again the next day when they are on their feet again (dependent edema Total body edema, or anasarca, may be caused by heart failure but is also seen in nephrotic syndrome and cirrhosis. Unilateral edema is more likely associated with a localized issue such as deep venous thrombosis or thrombophlebitis. Other parts of the history may shed light on the etiology of edema. Patients who report PND and orthopnea are likely have a cardiac etiology. If there is a history of alcohol abuse and jaundice is present, liver disease is a probable cause. Edema of the eyes and face in addition to lower-extremity edema is more likely related to nephrotic syndrome. Edema associated with discoloration or ulcers of the lower extremities is often seen with chronic venous insufficiency. In a patient with insidious onset of edema progressing to anasarca and ascites, one must consider constrictive pericarditis.

complications of acute myocardial infarction

FUNCTIONAL Left ventricular failure Right ventricular failure Cardiogenic shock MECHANICAL Free-wall rupture Ventricular septal defect Papillary muscle rupture with acute mitral regurgitation ELECTRICAL Bradyarrhythmias (first-, second-, and third-degree atrioventricular blocks) Tachyarrhythmias (supraventricular, ventricular) Conduction abnormalities (bundle branch and fascicular blocks)

Normal values for common hemodynamic parameters

Heart rate 60-100 beats/min PRESSURES (mm Hg) Central venous ≤9 Right atrial ≤9 Right ventricular Systolic 15-30 End-diastolic ≤9 Pulmonary arterial Systolic 15-30 Diastolic 3-12 Pulmonary capillary wedge ≤12 Left atrial ≤12 Left ventricular Systolic 100-140 End-diastolic 3-12 Aortic Systolic 100-140 Diastolic 60-90 RESISTANCE Systemic vascular resistance 800-1500 dynes-sec/cm−5 Pulmonary vascular resistance 30-120 dynes-sec/cm−5 Cardiac output 4-6 L/min Cardiac index 2.5-4 L/min

thromboembolic complications

In earlier years, thromboembolism in the form of either cardioembolic stroke or pulmonary embolism contributed to 25% of post-MI in-hospital mortality, and clinical events were diagnosed in 10% of patients. The risk of thromboembolism is linked to the presence of LV mural clot, which is more likely to be found in anterior MI with associated apical akinesis and deep venous thrombosis due to prolonged bed-rest. Contemporary methods of care for acute MI have greatly reduced the risk of post-MI thromboembolism Reperfusion therapy, when applied in a timely fashion, results in less extensive MI and less impairment of LV function. Patients with anterior MI treated with reperfusion therapy are less likely to have extensive apical akinesis, which is the breeding ground for mural thrombus. It is advised that patients treated for acute MI have an echocardiogram to assess for overall LV function; in the case of anterior MI, the presence of apical mural thrombus can be detected by echocardiography. If LV mural thrombus is present, the patient should receive therapeutic anticoagulation with unfractionated or LMW heparin while oral anticoagulation with warfarin is initiated. Warfarin therapy should be continued for 6 months after MI when LV apical mural thrombus is detected. Early ambulation after MI, along with the use of compression stockings and subcutaneous heparin prophylaxis (unfractionated or LMW) for deep venous thrombosis, has greatly diminished the threat of pulmonary embolism

patient education and cardiac rehabilitation

It is important to begin the education of patients early after acute MI so that they understand the value of their various prescribed medical therapies and the need for risk factor modification. Cardiac rehabilitation programs are very useful in the ongoing education of patients; they reinforce positive lifestyle changes and provide exercise training in the post-MI period. Such programs not only educate patients but also help them to regain confidence in their ability to perform the tasks of daily living and other activities they enjoy. Early follow-up with the physician after discharge is also important to ensure clinical stability and tolerance of medical therapy and to monitor the progress of lifestyle changes.

diagnosis and physical examination- general

Like the detailed history, the physical examination is also vital when assessing a patient with cardiovascular disease. This consists of more than simply auscultating the heart. Many diseases of the cardiovascular system can affect and be affected by other organ systems. Therefore, a detailed general physical examination is essential. The general appearance of a patient is helpful: Such observations as skin color, breathing pattern, whether pain is present, and overall nutritional status can provide clues regarding the diagnosis. Examination of the head may reveal evidence of hypothyroidism, such as hair loss and periorbital edema, and examination of the eyes may reveal exophthalmos associated with hyperthyroidism. Both conditions can affect the heart. Retinal examination may reveal macular edema or flame hemorrhages which can be associated with uncontrolled hypertension. Findings such as clubbing or edema when examining the extremities, and jaundice or cyanosis when evaluating the skin, may provide clues to undiagnosed cardiovascular disease.

physiology of the pulmonary circulation

Like the systemic circulation, the pulmonary circulation consists of a branching network of progressively smaller arteries, arterioles, capillaries, and veins. The pulmonary capillaries are separated from the alveoli by a thin alveolar-capillary membrane through which gas exchange occurs. The partial pressure of oxygen (Po2) is the main regulator of pulmonary blood to optimize blood flow toward well-ventilated lung segments and away from poorly ventilated segments.

pathology

Lipid-rich coronary plaques are subject to inflammation incited by the response to oxidation of LDL-cholesterol within the plaque. A sequence of inflammatory events leads to macrophage accumulation and the elaboration of metalloproteinases that degrade collagen in the fibrous cap of the plaque. Thinning of the fibrous cap makes the plaque vulnerable to rupture and exposure of blood to thrombogenic stimuli, resulting in platelet aggregation and activation, thrombin generation, and the evolution of fibrin-based thrombus. If the occlusion is total, transmural myocardial ischemia and necrosis ensue and the ECG demonstrates ST elevation. In contrast, partially occlusive thrombus can result in unstable angina or NSTEMI (subendocardial MI). The presence of coronary collaterals can limit the extent of ischemia and necrosis in either scenario. Both STEMI and NSTEMI can set the stage for arrhythmias and LV dysfunction. Whereas coronary thrombosis is the cause of most MIs, there are patients who develop MI related to coronary embolization, coronary vasospasm, vasculitis, coronary anomalies, dissection of the aorta or a coronary artery, or trauma. One key feature of the pathology of MI is its time-dependent nature. Experimental and clinical studies have documented that coronary occlusion leads to ischemia and myonecrosis in a wavefront manner, from endocardium to epicardium. Restoration of flow to the vessel within 6 hours after occlusion is associated with limitation of infarct size and a favorable effect on mortality risk. The principle of time dependency of MI drives the need to aggressively reperfuse occluded coronary arteries, and this is the cornerstone of contemporary therapy for STEMI

effects of physiologic maneuvers on auscultatory events

MANEUVER MAJOR PHYSIOLOGIC EFFECTS USEFUL AUSCULTATORY CHANGES Respiration ↑ Venous return with inspiration ↑ Right heart murmurs and gallops with inspiration; splitting of S2 (see Fig. 3-3) Valsalva (initial ↑ BP, phase I; followed by ↓ BP, phase II) ↓ BP, ↓ venous return, ↓ LV size (phase II) ↓ HCM ↓ AS, MR MVP click earlier in systole; murmur prolongs Standing ↑ Venous return ↑ LV size ↑ HCM ↓ AS, MR MVP click earlier in systole; murmur prolongs Squatting ↑ Venous return ↑ Systemic vascular resistance ↑ LV size ↑ AS, MR, AI ↓ HCM MVP click delayed; murmur shortens Isometric exercise (e.g., handgrip) ↑ Arterial pressure ↑ Cardiac output ↑ Gallops ↑ MR, AI, MS ↓ AS, HCM Post PVC or prolonged ↑ Ventricular filling ↑ AS R-R interval ↑ Contractility Little change in MR Amyl nitrate ↓ Arterial pressure ↑ Cardiac output ↓ LV size ↑ HCM, AS, MS ↓ AI, MR, Austin Flint murmur MVP click earlier in systole; murmur prolongs Phenylephrine ↑ Arterial pressure ↑ Cardiac output ↓ LV size ↑ MR, AI ↓ AS, HCM MVP click delayed; murmur shortens

heart failure and low output states

MI involving 20% to 25% of the left ventricle can result in significant heart failure manifesting with dyspnea due to pulmonary congestion and findings of LV dysfunction such as an S3 or S4. Cardiogenic shock is associated with loss of 40% of the myocardium. This condition carries a very high risk of mortality. In the era of widespread use of reperfusion therapy, the incidence of post-MI heart failure or cardiogenic shock has declined. Early use of reperfusion therapies limits infarct size and the risk of complications related to heart failure. When acute heart failure occurs with MI, therapeutic interventions including oxygen, intravenous morphine, and diuretics can help stabilize the patient. Nitroglycerin can also help by reducing the elevated preload. Long-term therapy for heart failure related to reduced EF after acute MI includes the use of ACE inhibitors (or ARBs), appropriate β-blockers, aldosterone receptor antagonists such as eplerenone or spironolactone, and diuretics as needed. The acutely infarcted ventricle requires an increased filling pressure and volume to optimize its performance. Patients with acute MI may become relatively fluid depleted due to nausea, vomiting, or decreased fluid intake, leading to reduced LV volume and a fall in cardiac output. This can translate into hypotension that is best treated by judicious administration of fluids isk once the early arrhythmia-prone hours have passed. Occlusion of the right coronary artery and a significant acute marginal branch can lead to right ventricular infarction. Approximately 10% to 15% of patients with inferior MI have associated right ventricular infarction. This condition produces a significant increase in mortality risk (in-hospital mortality, 25% to 30% vs. <6%). Hallmarks of right ventricular infarction include elevated jugular venous pressure with Kussmaul sign and hypotension. Right ventricular function frequently recovers, but it may be necessary to administer sufficient volume to maintain right heart output. Short-term inotropic support with dobutamine in sometimes needed, and venodilators and diuretics should be avoided. High-degree AV block, usually transient with inferior MI, may worsen hemodynamics and necessitate temporary AV sequential pacing. AF may not be tolerated and may require cardioversion.

complications of myocardial infarction- recurrent chest pain

MI is associated with a number of possible problems related to the extent of injury (Table 8-6). Patients can experience postinfarction angina which may reflect re-occlusion of the infarct related vessel. This can occur either in patients who underwent primary PCI with stent placement (stent thrombosis) or thrombolysis. Post-infarction angina usually requires cardiac catheterization for appropriate diagnosis and treatment. Patients with transmural MI are also subject to pericarditis 2 to 4 days after the event. This diagnosis is usually established by the symptom nature and pattern (worse with inspiration or supine position, improved with sitting), which is different from their initial presentation with acute MI. A less common event is the development of pericarditis due to Dressler's syndrome up to 10 weeks after acute MI. This is likely an immune-mediated phenomenon. Pericarditis is treated with aspirin or nonsteroidal antiinflammatory drugs.

mechanical complications

Mechanical complications of acute MI include mitral regurgitation (due to ischemic papillary muscle dysfunction or rupture), VSD, free wall rupture, and LV aneurysm formation. These problems usually occur during the first week after MI, and they account for as much as 15% of MI-related mortality. A new murmur, sudden onset of heart failure, or hemodynamic collapse should also raise suspicion of a mechanical complication of MI. Patients who either were not reperfused or were reperfused late after onset of MI are most at risk for these problems. Echocardiography usually identifies the mechanical problem, and hemodynamic assessment with right heart catheterization can aid the diagnosis. Surgical correction of the defect is usually required. Papillary muscle rupture or dysfunction leading to acute severe mitral regurgitation results in severe heart failure and up to 75% mortality within 24 hours after onset. Afterload reduction with intravenous nitroprusside and the use of IABP can help to stabilize the patient, but surgical valve repair or replacement will be needed to provide some chance of survival. Surgery is associated with a 25% to 50% mortality risk, but that still is better than the risk with medical or IABP therapy only. Elderly patients, particularly those with hypertension, are more prone to MI-related VSD. Thrombolytic therapy may also place patients at risk for this complication. Acute VSD with resultant left-to-right shunting can produce severe hemodynamic instability. As with acute mitral regurgitation, afterload reduction and IABP may help to stabilize the patient, but ultimately surgical repair will be required. Moderate to large VSDs are not well tolerated and are associated with significant mortality risk. VSDs related to anterior MI may offer a better opportunity for surgical repair than those resulting from inferior MI. Some patients have been helped by the use of percutaneous closure devices, which can afford an opportunity to delay surgery until there is better tissue healing in the infarct area. LV free wall rupture is similar to VSD in terms of risk for occurrence and underlying myocardial pathology. Free wall rupture is usually associated with sudden death due to cardiac tamponade. On occasion, a pseudoaneurysm forms and the patient can be treated surgically.

pathology

Most patients who experience NSTEMI do so as a result of plaque rupture with subsequent thrombosis causing subtotal occlusion of the coronary artery. The limitation of coronary blood flow in this situation leads to subendocardial ischemia in the distribution of the affected coronary artery. The same pathology underlies STEMI, although in that case complete vessel occlusion occurs, leading to more extensive MI. It is possible for patients with obstructive CAD to develop collateral support of the affected artery, and in that case plaque rupture with complete vessel occlusion may lead to NSTEMI as opposed to STEMI. A smaller percentage of patients have ACS due to coronary vasospasm, which, if severe and prolonged, can lead to myocardial necrosis. Vasospasm may occur in regions of endothelial dysfunction induced by atherosclerotic plaque, or it may be triggered by exogenous vasoconstrictors such as cocaine ingestion, the use of serotonin agonists (for migraine therapy), or chemotherapeutic agents (e.g., 5-fluorouracil). Less common causes of ACS include coronary vasculitis and spontaneous coronary dissection (peripartum coronary dissection). Atherosclerotic plaques rich in LDL are prone to develop inflammation, which in turn degrades the collagen-rich fibrous cap, leading to rupture and thrombosis. Oxidized LDL within the plaque leads to accumulation of macrophages and T lymphocytes, causing inflammation within the plaque. Cytokines elaborated in the inflammatory process inhibit collage synthesis. The fibrous structure of the plaque is further compromised by matrix metalloproteinases released by macrophages. Degradation of the plaques' fibrous structure makes them prone to rupture. Systemic inflammatory conditions may also play a role in plaque rupture in some patients. It is possible to have multiple sites of plaque ulceration or rupture. Plaque rupture leads to platelet adherence and subsequent activation at the site of rupture. As platelets aggregate, the thrombosis cascade is triggered, leading to progressive accumulation of intravascular thrombus. The severity of myocardial ischemia and MI depends on the degree to which thrombus occludes the vessel. It is also possible for ACS to occur as a result of embolization of platelet aggregates or thrombus

murmurs

Murmurs are a series of auditory vibrations generated by either abnormal blood flow across a normal cardiac structure or normal flow across an abnormal cardiac structure, both of which result in turbulent flow. These sounds are longer than individual heart sounds and should be described on the basis of their location, frequency, intensity, quality, duration, shape, and timing in the cardiac cycle. The intensity of a given murmur is typically graded on a scale of 1 to 6 (Table 3-7). Murmurs of grade 4 or higher are associated with palpable thrills. The intensity or loudness of a murmur does not necessarily correlate with the severity of disease. For example, a murmur can be quite harsh when it is associated with a moderate degree of aortic stenosis. If stenosis is critical, however, the flow across the valve is diminished and the murmur becomes rather quiet. In the presence of a large atrial septal defect, flow is almost silent, whereas flow through a small ventricular septal defect is typically associated with a loud murmur The frequency of a murmur can be high or low; higherfrequency murmurs are more correlated with high velocity of flow at the site of turbulence. It is also important to notice the configuration or shape of a murmur, such as crescendo, crescendo-decrescendo, decrescendo, or plateau (Fig. 3-5). The quality of a murmur (e.g., harsh, blowing, rumbling) and the pattern of radiation are also helpful in diagnosis. Physical maneuvers can sometimes help clarify the nature of a particular murmur (see Table 3-4). Murmurs can be divided into three different categories (Table 3-8). Systolic murmurs begin with or after S1 and end with or before S2. Diastolic murmurs begin with or after S2 and end with or before S1. Continuous murmurs begin in systole and continue through diastole. Murmurs can result from abnormalities on the left or right side of the heart or in the great vessels. Right-sided murmurs become louder with inspiration because of increased venous return. This can help differentiate them from left-sided murmurs, which are unaffected by respiration. Systolic murmurs should be further differentiated based on timing (i.e., early systolic, midsystolic, late systolic, and holosystolic murmurs). Early systolic murmurs begin with S1, are decrescendo, and end typically before mid systole. Ventricular septal defects and acute mitral regurgitation may lead to early systolic murmurs. Midsystolic murmurs begin after S1 and end before S2, often in a crescendo-decrescendo shape. They are typically caused by obstruction to left ventricular outflow, accelerated flow through the aortic or pulmonic valve, or enlargement of the aortic root or pulmonary trunk. Aortic stenosis, when less than severe in degree, causes a midsystolic murmur that may be harsh and may radiate to the carotids. Pulmonic stenosis leads to a similar murmur that does not radiate to the carotid arteries but may change with inspiration. The murmur of hypertrophic cardiomyopathy may be mistaken for aortic stenosis; however, it does not radiate to the carotids and becomes exaggerated with diminished venous return. Innocent or benign murmurs may also occur as a result of aortic valve sclerosis, vibrations of a left ventricular false tendon, or vibration of normal pulmonary leaflets. They are generally less harsh and shorter in duration. High-flow states such as those found in patients with fever, during pregnancy, or with anemia may also lead to midsystolic murmurs. Holosystolic murmurs begin with S1 and end with S2; the classic examples are the murmurs associated with mitral regurgitation and tricuspid regurgitation. They may also occur with ventricular septal defects and patent ductus arteriosus. Late systolic murmurs begin in mid to late systole and end with S2. They can be characteristic of more severe aortic stenosis and are also typical of murmurs associated with mitral valve prolapse. Diastolic murmurs are also classified by timing (i.e., early diastolic, mid diastolic, and late diastolic). Early diastolic murmurs begin with S2 and can result from aortic or pulmonic regurgitation; they are usually decrescendo in shape. Shorter and quieter murmurs typically represent an acute process or mild regurgitation, whereas longer-lasting and louder murmurs are likely due to more severe regurgitation. Mid-diastolic murmurs begin after S2 and are usually caused by mitral or tricuspid stenosis. They are low pitched and are often referred to as diastolic rumbles. Because they are of low frequency, they are better auscultated with the bell of the stethoscope. Similar murmurs can be heard with obstructing atrial myxomas. Severe chronic aortic insufficiency can lead to premature closure of the mitral valve, causing a mid-diastolic rumble called an Austin-Flint murmur. Late diastolic murmurs occur immediately before S1 and reflect presystolic accentuation of the mid-diastolic murmurs resulting from augmented mitral or tricuspid flow after atrial contraction Continuous murmurs begin with S1 and last though part or all of diastole. They are generated by continuous flow from a vessel or chamber with high pressure into a vessel or chamber with lower pressure. They are referred to as machinery murmurs and are caused by aortopulmonary connections such as a patent ductus arteriosus, AV malformations, or disturbances of flow in arteries or veins.

risk factors and markers for coronary artery disease

NONMODIFIABLE RISK FACTORS Age Male sex Family history of premature coronary artery disease MODIFIABLE INDEPENDENT RISK FACTORS Hyperlipidemia Hypertension Diabetes mellitus Metabolic syndrome Cigarette smoking Obesity Sedentary lifestyle Heavy alcohol intake MARKERS Elevated lipoprotein(a) Hyperhomocysteinemia Elevated high-sensitivity C-reactive protein (hsCRP) Coronary arterial calcification detected by EBCT or MDC

silent myocardial ischemia

Not all episodes of myocardial ischemia are associated with angina. Some patients may only experience episodes of silent myocardial ischemia as evidenced by transient ST depression with ECG monitoring. Such patients can also have silent MI. It is also possible, and probably not uncommon, for patients to have both silent myocardial ischemia episodes and typical angina; this is termed mixed angina. Episodes of silent myocardial ischemia can be observed in all settings of CAD: chronic stable angina, unstable angina, and coronary vasospasm. Silent ischemia is more common in diabetic patients. Medical therapy directed at controlling symptomatic angina also reduces the number of episodes of silent ischemia.

factors affecting cardiac performance

PRELOAD (LEFT VENTRICULAR DIASTOLIC VOLUME) Total blood volume Venous (sympathetic) tone Body position Intrathoracic and intrapericardial pressures Atrial contraction Pumping action of skeletal muscle AFTERLOAD (IMPEDANCE AGAINST WHICH THE LEFT VENTRICLE MUST EJECT BLOOD) Peripheral vascular resistance Left ventricular volume (preload, wall tension) Physical characteristics of the arterial tree (elasticity of vessels or presence of outflow obstruction) CONTRACTILITY (CARDIAC PERFORMANCE INDEPENDENT OF PRELOAD OR AFTERLOAD) Sympathetic nerve impulses Increased contractility Circulating catecholamines Digitalis, calcium, other inotropic agents Increased heart rate or post-extrasystolic augmentation Anoxia, acidosis Decreased contractility Pharmacologic depression Loss of myocardium Intrinsic depression HEART RATE Autonomic nervous system Temperature, metabolic rate Medications, drugs

palpitation

Palpitation is another symptom commonly seen in the cardiovascular patient. This is the subjective sensation of rapid or forceful beating of the heart. Patients often are able to describe in detail the sensation they feel, such as jumping, skipping, racing, fluttering, or an irregularity in the heartbeat. It is important to ask the patient about the onset of the palpitations because they may begin abruptly at rest, only with exertion, with emotional stress, or with ingestion of certain foods such as chocolate. One should also inquire about associated symptoms such as chest pain, dyspnea, dizziness, and syncope. It is important to note other medical issues, such as thyroid disease, and bleeding, which can lead to anemia, because these conditions may be associated with arrhythmias. A social history focusing on drug use and intake of alcohol is important because use of these substances can lead to certain rhythm disturbances. The family history is also important, because there are many inherited disorders (e.g., long-QT syndromes) that might lead to significant arrhythmias. Potential etiologies of palpitation include premature atrial or ventricular beats, which are typically described as isolated skips and can be uncomfortable. Supraventricular tachycardias such as atrial flutter, AV nodal reentrant tachycardia, and paroxysmal atrial tachycardia often start and stop abruptly and can be rapid. Atrial fibrillation is usually rapid and very irregular. Ventricular arrhythmias are more often associated with severe dizziness or syncope. Gradual onset of tachycardia with a gradual decline in HR is more indicative of sinus tachycardia or anxiety.

diagnosis

Patients presenting with ACS require urgent care directed at rapid diagnosis and treatment. The ECG is critically important in early diagnosis of presumed ACS. The finding of ST elevation in multiple leads (Fig. 8-5) is diagnostic of STEMI and portends a more extensive MI and the need for prompt revascularization. The distribution of ST elevation reflects the region of myocardium affected by thrombotic coronary occlusion. For example, ST elevation in leads II, III, and aVF reflects an inferior MI due to occlusion of the right coronary artery (or circumflex coronary artery in some cases). ST elevation in leads V2 through V6 (see Fig. 8-5) reflects an anterior MI caused by obstruction of the left anterior descending coronary artery Unstable angina or NSTEMI is caused by subtotal vessel occlusion by thrombus leading to reduced coronary blood flow. This results in subendocardial ischemia and the characteristic ECG changes of ST depression (Fig. 8-6). It is important to recognize that up to half of patients with acute MI do not have significant ECG abnormalities on the initial study. Sequential ECGs are frequently required to establish a diagnosis. If there is a high index of suspicion for MI and ECGs are persistently nondiagnostic, the use of leads extending to the patient's back (V7 to V9) may demonstrate ST changes related to posterior LV ischemia (usually a circumflex coronary artery occlusion). Echocardiography showing regional wall motion abnormalities can also help to establish the diagnosis of acute MI Serum biomarkers also play an important role in the diagnosis of acute MI. Myocardial necrosis leads to the release of biomarkers that can be measured in serial fashion to document the occurrence of MI. The presence of specific biomarkers is definitive evidence of MI, and they are particularly helpful to provide prognostic significance when symptoms are mild and ECG changes are minimal. Common biomarkers include creatine kinase (CK), troponin I, troponin T, lactate dehydrogenase (LDH), and aspartate aminotransferase (AST). Sequential measurement of biomarkers demonstrates their various time courses for abnormal elevation after an acute MI (Fig. 8-7). This information can be helpful in retrospectively timing the occurrence of an event. In contemporary practice, troponin has become the most frequently measured biomarker, although CK is still used. LDH and AST are no longer routinely measured for the diagnosis of MI Troponins I and T are the most sensitive and most specific markers of myocardial necrosis, and as a consequence, they have become the standard in the biochemical diagnosis of acute MI. The myocardial-specific isozyme CK-MB may be in the normal range while concomitant measurement of troponin I or T reveals the presence of myocardial necrosis. Troponins I and T begin to rise within 4 hours of myocardial necrosis and remain elevated for 7 to 10 days after the MI event. Confounding elevations of troponin T occur in patients with renal failure and congestive heart failure not related to ACS. Troponin release also occurs in the case of demand ischemia not related to coronary thrombosis. This requires careful attention to the entire clinical presentation in discerning the likelihood of underlying ACS due to coronary thrombosis In the absence of clear evidence of NSTEMI (i.e., normal examination, ECG findings, and biomarkers), patients who present with the diagnosis of unstable angina should undergo stress testing. A negative exercise stress test is very helpful for distinguishing those patients who require more aggressive diagnostic testing (e.g., catheterization) from those who can be monitored as outpatients. Some centers have embraced the use of CT coronary angiography in the assessment of low-risk patients. This technique has a high negative predictive value in establishing a diagnosis of CAD. Echocardiography can be helpful in patients with equivocal ECG findings for ischemia and normal biomarkers. The presence of regional wall motion abnormalities, particularly if they correlate with the distribution of ECG abnormalities, raises the risk for underlying CAD as a cause of symptoms. The echocardiogram may also show evidence of other abnormalities as causes of chest discomfort, such as pericarditis, pulmonary embolism, or aortic dissection. directed toward coronary angiography. In the absence of contraindications, coronary angiography is indicated for patients with clear evidence of NSTEMI based on clinical presentation of symptoms, ECG changes, and positive biomarkers. Patients undergoing evaluation for unstable angina who have significant stress test abnormalities are also candidates for coronary angiography. Some patients who have ambiguous stress test findings or ongoing symptoms in the absence of other findings of NSTEMI require coronary angiography to resolve the issue as to whether underlying CAD is present. Up to 15% of patients undergoing coronary angiography for NSTEMI have no significant obstructive CAD. In a number of patients, there will be a clear "culprit" lesion showing the earmarks of plaque rupture with ulceration, associated thrombus, or reduced coronary flow. Lesions that may have played a role in symptoms, ECG findings, or biomarker release that are not clearly stenotic may be assessed for physiologic significance with the use of a fractional flow reserve (FFR) study using a pressure wire device. Patients who have new-onset chest pain require careful monitoring in an appropriate care setting that allows for rhythm monitoring as well as repeat evaluations of ECG findings and biomarker measurements. Risk assessment is aided by the use of risk scores calculated with either the Thrombolysis in Myocardial Infarction (TIMI) or the Global Registry of Acute Coronary Events (GRACE) algorithms (see Chapter 72, "Acute Coronary Syndrome: Unstable Angina and Non-ST Elevation Myocardial Infarction," in Goldman-Cecil Medicine, 25th Edition). The overall assessment in cases of new symptoms of chest discomfort aims to triage patients based on risk for coronary events. Low-risk patients can be spared aggressive anticoagulation protocols and coronary angiography, whereas high-risk patients are likely to benefit from these approaches. The use of appropriate therapies in high-risk patients (medical therapy or revascularization or both) leads to a 20% to 40% decrease in recurrent ischemic events and a 10% reduction in mortality.

clinical presentation

Patients with acute MI usually have a combination of chest discomfort, ECG changes (ST elevation in contiguous leads or LBBB), and elevation in biomarkers such as CK-MB and troponin. The high sensitivity and high specificity of troponin have made it the preferred biomarker in the diagnosis of MI. The chest discomfort associated with MI is similar to angina pectoris but more severe in nature. It is usually described as substernal pressure, tightness, or fullness. Patients may have symptoms of discomfort that radiate to the neck, jaw, one or both arms, or the back. Not uncommonly, patients with symptoms of acute MI also experience nausea, vomiting, diaphoresis, apprehension, dyspnea, or weakness. In contrast to angina pectoris associated with stable CAD, acute MI symptoms last longer than 20 to 30 minutes (up to hours). occasionally, patients only have symptoms in the non-chest areas usually associated with radiation. Up to 20% of patients, particularly the elderly and diabetics, do not have typical chest discomfort at presentation. The index of suspicion for acute MI should be high in these groups if the patient exhibits profound weakness, acute dyspnea or pulmonary edema, nausea, vomiting, ventricular arrhythmias, or hypotension. The differential diagnosis for patients with chest discomfort suspicious for acute MI includes aortic dissection, pulmonary embolism, chest wall pain, esophageal reflux, acute pericarditis, pleuritis, and panic attacks. Given the life-threatening nature of aortic dissection and pulmonary embolism, these diagnoses should always be paramount, along with acute MI, in patients presenting with chest discomfort.

treatment

Patients with chest pain suggestive of ACS need urgent evaluation for evidence of ischemia (serial ECGs) and myocardial necrosis (serial biomarkers). Serial biomarker measurements, in the current era usually troponin, establish the diagnosis of MI. Continuous ECG monitoring is important given the risk of ischemia-mediated arrhythmias, and serial ECGs establish a pattern of ST changes consistent with ischemia. Patients are also prescribed bedrest and supplemental oxygen. Those with a high index of suspicion for ACS require hospital admission for observation and appropriate diagnostic testing. Chest pain lends itself well to diagnosis and treatment algorithms that guide the clinician through decision trees based on expert opinion and evidence-based medicine (see Chapter 72, "Acute Coronary Syndrome: Unstable Angina and Non-ST Elevation Myocardial Infarction," in Goldman-Cecil Medicine, 25th Edition). STEMI is typically diagnosed at the time of initial presentation. Those without evidence of ST elevation can be risk stratified, as discussed earlier, using the guidance of recurrent symptoms, ECG changes, or abnormal biomarker levels. Treatment of patients who are categorized as having unstable angina or NSTEMI is directed by their allocation to either low- or high-risk status. Once recognized as having ACS, patients require antiplatelet therapy with aspirin (75 to 162 mg per day) and clopidogrel, because plaque rupture and thrombosis is a frequent underlying pathology. Prasugrel, another thienopyridine, is an option in place of clopidogrel for those going to coronary angiography. Antiplatelet therapy significantly reduces mortality risk in patients with NSTEMI. The aspirin/clopidogrel combination is indicated as ongoing therapy in the year following diagnosis of NSTEMI. Symptoms of chest discomfort can be treated with nitrates (sublingual, topical, or intravenous drip) and β-blockers. The latter therapy slows heart rate and reduces blood pressure, effects that translate into reduced myocardial oxygen demand in the face of limited supply. It is important not to give nitrates to patients who have taken phosphodiesterase-5 inhibitors (sildenafil, tadalafil, or vardenafil) within the previous 24 to 48 hours. Attention to this detail minimizes the risk for nitrate-induced hypotension. Calcium channel antagonists may be used in lieu of β-blockers, particularly if there is a need for blood pressure control, but they should be avoided in patients with reduced EF or overt heart failure. The dihydropyridine calcium channel blocker nifedipine can be effective in controlling blood pressure and promoting coronary vasodilation, but it should be given in conjunction with a β-blocker because of the potential for the drug to induce reflex tachycardia and thereby increase myocardial oxygen demand. Glycoprotein IIb/IIIa inhibitors block platelet aggregation and can reduce ischemic events in patients undergoing PCI as treatment for NSTEMI. These drugs are usually reserved for high-risk patients at the time of PCI. They require intravenous administration and are given for 12 to 24 hours after PCI. The use of this class of drugs for PCI has decreased in light of data suggesting advantages of bivalirudin, a direct thrombin inhibitor, over the glycoprotein IIb/IIIa inhibitors. Heparin, given in its unfractionated form or as a lowmolecular-weight (LMW) preparation, has been shown to reduce the risk of ischemic complications in patients with NSTEMI. Heparin acts by activating antithrombin and thereby inhibiting the formation and activity of thrombin. The antiischemic effect of heparin is additive to that of aspirin. Unfractionated heparin is given by continuous intravenous drip for up to 48 hours. It is usually not continued after revascularization. Heparin may be associated with mild thrombocytopenia, and 1% to 5% of patients experience profound antibodymediated thrombocytopenia. These patients usually have been exposed to heparin in the past, and a known diagnosis of heparininduced thrombocytopenia necessitates the use of alternative antithrombin therapy. LMW heparins are fragments of unfractionated heparin that are more predictable in their antithrombin activity and are associated with reduced risks for thrombocytopenia and bleeding complications. The drug should be avoided in patients who have a history of heparin-induced thrombocytopenia. Clinical studies of patients with NSTEMI have shown superiority of LMW heparin over unfractionated heparin in reducing the end point of death or MI during hospitalization. LMW heparin, either enoxaparin or dalteparin, is administered subcutaneously for up to 8 days after hospitalization. As with unfractionated heparin, LMW heparin is not continued after revascularization. Dosing of LMW heparin in based on renal function status, age, and weight. LMW heparin has a long duration of action and cannot be reversed with protamine. Unfractionated heparin has a shorter duration of action and is reversible with protamine, making unfractionated heparin the preferred anticoagulant for patients who may require CABG. Fondaparinux is a selective factor Xa inhibitor that does not induce thrombocytopenia. It can reduce ischemic events in patients with NSTEMI and is associated with a lower risk of bleeding than is seen with enoxaparin. There is an increased risk of catheter-related thrombosis in patients treated with fondaparinux who are undergoing coronary angiography. This drug is reserved for cases that will be managed noninvasively and where there is a higher risk for heparin-related bleeding. Bivalirudin, a direct thrombin inhibitor, is an alternative to heparin for patients who are undergoing PCI. It is as effective as the combination of heparin and glycoprotein IIb/IIIa inhibitor in reducing the risk of ischemic complications related to PCI, and it is associated with a reduced risk of postprocedure bleeding. Bivalirudin is used preferentially in patients with a history of heparin-induced thrombocytopenia. Statin therapy is also indicated in patients with NSTEMI at presentation. Statins act to stabilize plaque and improve endothelial function. These drugs should be initiated at the time of admission to the hospital and continued after discharge. There is e evidence that high-dose atorvastatin (80 mg/day) given to patients with NSTEMI reduces the risk of subsequent ischemic events Risk stratification is important in appropriately evaluating patients with ACS. Low-risk patients (age <75 years, normal troponin levels, 0 to 2 TIMI risk factors) should be evaluated with noninvasive testing, either exercise or pharmacologic stress testing. before hospital discharge. Those with tests are positive for ischemia should be considered for predischarge coronary angiography. This approach leads to selective use of invasive testing and subsequent revascularization. Patients with high-risk ACS profiles (age >75 years, elevated troponin levels, ≥3 TIMI risk factors) are candidates for coronary angiography and, when appropriate, revascularization. The high-risk ACS patient group will have fewer subsequent ischemic events when approached in this way. Risk stratification occurs early after admission for possible ACS. An early invasive strategy (coronary angiography within 24 hours of admission) for high-risk patients has been shown to reduce the combined end point of death, MI, or stroke compared with a delayed invasive approach. The occurrence of acute heart failure, hypotension, or ventricular arrhythmias in the face of ACS prompts urgent coronary angiography to identify patients with high-risk coronary anatomy that requires urgent revascularization (see Video, Cardiac Cath, http://www.heartsite.com/html/ cardiac_cath.html). Invasive coronary angiography always carries with it a risk of bleeding complications that is no doubt enhanced by the concomitant use of potent antiplatelet and antithrombin therapies. Those at increased risk for bleeding complications include patients with female gender, low body weight, diabetes mellitus, renal insufficiency, low hematocrit, and hypertension. Some cardiologists recommend the preferential use of a radial artery approach to catheterization in order to minimize bleeding complications that are associated with the femoral artery approach.

other cardiac sound

Pericardial rubs occur in the setting of pericarditis and are coarse, scratching sounds similar to rubbing leather. They are typically heard best at the left sternal border with the patient leaning forward and holding the breath at end-expiration. A classic pericardial rub has three components: atrial systole, ventricular systole, and ventricular diastole. One might also hear a pleural rub caused by localized irritation of surrounding pleura. Continuous venous murmurs, or venous hums, are almost always present in children. They can be heard in adults during pregnancy, in the setting of anemia, or with thyrotoxicosis. They are heard best at the base of the neck with the patient's head turned to the opposite direction.

cardiac catherization and noninvasive testing

Predischarge risk stratification may involve cardiac catheterization, submaximal predischarge exercise stress testing (on days 4 to 6), or maximal exercise stress testing after discharge (at 2 to 6 weeks). The presence or absence of high-risk coronary anatomy is demonstrated for patients who have undergone primary PCI at the time presentation. Many patients who have been treated with thrombolytic therapy undergo coronary angiography before discharge to determine the extent and severity of underlying CAD as well as the status of the culprit lesion. If coronary angiography is not performed, predischarge submaximal exercise testing (up to 70% of maximal predicted heart rate) is done to identify those who are at increased risk for postdischarge coronary ischemic events. Patients who undergo submaximal exercise stress testing in lieu of coronary angiography frequently have a follow-up maximal exercise stress test within 2 to 6 weeks after discharge. During stress testing, positive results that suggest the need for coronary angiography include exercise-induced angina, ST changes of ischemia (ST depression), exercise-induced hypotension, exercise-induced ventricular arrhythmias, and low functional capacity. The sensitivity and specificity of stress testing after MI is enhanced by the use of imaging modalities such as stress echocardiography or nuclear perfusion imaging. All patients should have their EF assessed, typically by echocardiography, before discharge

goals of risk factor modification

RISK FACTOR GOAL Dyslipidemia Elevated LDL-cholesterol level Patients with CAD or CAD equivalent* LDL <70 mg/dL Without CAD, ≥2 risk factors† LDL <130 mg/dL (or <100 mg/ dL‡) Without CAD, 0-1 risk factors† LDL <160 mg/dL Elevated TG TG <200 mg/dL Reduced HDL-cholesterol level HDL >40 mg/dL Hypertension Systolic blood pressure <140 mm Hg Diastolic blood pressure <90 mm Hg Smoking Complete cessation Obesity <120% of ideal body weight for height Sedentary lifestyle 30-60 min moderately intense activity (e.g., walking, jogging, cycling, rowing) five times per week

revascularization therapy for chronic stable angina pectoris

Revascularization therapy is an option to be considered when medical therapy is not sufficiently controlling symptoms leading to impaired lifestyle. It is also frequently pursued in the face of high-risk situations such as unstable angina, STEMI, heart failure complicated by angina, arrhythmias associated with angina, or the presence of large areas of myocardial ischemia documented by noninvasive imaging. The two types of revascularization procedures are coronary bypass grafting (CABG) and percutaneous coronary intervention (PCI). Percutaneous transluminal coronary angioplasty was the initial mode of catheter-based revascularization introduced in the late 1970s (see Video, Angioplasty, http://www.heartsite.com/html/ ptca.html). In this technique, a guidewire is placed through a stenotic segment of artery, after which a balloon-tipped catheter is threaded over the wire to the area of stenosis and then inflated. Angioplasty of this form enlarges the vessel lumen in an irregular geometry through disruption of the plaque and injury to the vessel intima. Plain old balloon angioplasty (POBA), as the procedure later became to be known, was effective at improving myocardial perfusion and reducing exercise-related angina. However, because of plaque disruption, there was a 2% to 5% risk of abrupt vessel closure frequently leading to MI. In addition, there was a high incidence of injury-mediated restenosis (up to 50%) during the first 3 to 6 months after the procedure. The process of restenosis involved intimal hyperplasia and remodeling, yielding a recurrent stenosis sometimes more severe in nature than the original lesion. The innovation of coronary stents pioneered through the 1980s and clinically available in the early 1990s represented a significant advance in PCI (see Video, Intracoronary Stenting, http://www.heartsite.com/html/stent.html). Coronary stents are expandable metallic mesh tubes that are mounted on an angioplasty balloon, allowing delivery to an area of stenosis, where balloon inflation expands the stent into the vessel wall. The stent becomes permanently embedded in the vessel wall and scaffolds the artery to keep it open. This procedure not only reduces the risk of abrupt vessel occlusion to 1% or less, but it is also associated with a significant reduction in restenosis risk (20% to 25%, compared with 50% for POBA). The benefit of stenting for a patient is clear in terms of less risk of procedure-related acute MI and less need for repeat procedures. Vessels smaller than 2 mm in diameter are not good targets for stenting, because the smallest-diameter stent is 2 mm. Stents do have a risk of thrombosis, necessitating lifelong aspirin therapy and the use of clopidogrel for 4 weeks to 1 year after the procedure (there may be some advantage to longer-duration clopidogrel for 1 year). Despite the reduction achieved with coronary stents, there was still a significant risk of restenosis, leading investigators to search for a means to lower that risk. Drug-eluting stents (DES) were found to significantly reduce the risk of restenosis compared to bare metal stents. The first DES, released for use in 2003, was coated with either sirolimus or paclitaxel, both of which inhibited the hyperplastic response in the vessel wall triggered by PCI. The current generations of DES are coated with either zotarolimus or everolimus, both very effective at reducing restenosis. The predicted restenosis rate for current-generation DES is in the range of 5% to 10%. Vessel diameter affects restenosis risk, with larger-diameter vessels demonstrating less restenosis. The benefit of inhibiting tissue overgrowth within the stent is also associated with delayed endothelialization of the stent, which increases the risk of stent thrombosis for a longer time than with bare metal stents. Therefore, dual antiplatelet therapy with aspirin and clopidogrel should be maintained for at least 1 year Aspirin should never be discontinued after 1 year, to minimize the risk of late stent thrombosis. Decision making regarding the use of DES needs to take into account the patient's ability to tolerate long-term dual antiplatelet therapy, the potential for noncompliance with medications, and any need for major surgery in the near future after stent placement. The benefits of DES also confer the need for additional planning and caution. A host of other devices to treat stenotic coronary arteries have come and gone over time. In this era, rotational atherectomy plays a role in treating calcified lesions in about 5% of patients. Catheter-based aspiration of thrombus has gained a role in patients with STEMI. Intravascular ultrasound is an important imaging adjunct than can be helpful in interrogating lesions or defining the end result of stent placement. CABG emerged in the 1970s as an effective means of coronary revascularization for the control of angina. Bypass grafts take the form of saphenous vein from the leg, free radial artery segments, or intact left or right internal mammary artery grafts. The vein or radial artery grafts are placed on the ascending aorta and then anastomosed to the coronary vessels distal to the site of obstruction. In contrast, left or right internal mammary arteries are left intact at their origins and anastomosed distal to the obstruction. The left internal mammary artery is typically placed onto the left anterior descending coronary artery. This is the most important vessel to graft because of its size and distribution, and the left internal mammary artery is ideal given an expected patency rate of 90% at 10 years. Saphenous vein grafts degenerate over time, leading to episodes of symptomatic abrupt occlusion and a 50% patency rate at 10 years. Free radial artery grafts perform better than vein grafts but less well than intact mammary artery grafts. CABG is a major cardiac surgical procedure, but in skilled hands the mortality rate is expected to be 1% to 2%, with a similar risk of stroke. Periprocedural MI rates are in the range of 5% to 10%. There has been controversy over whether the use of the heartlung machine to support CABG causes more problems for patients than "beating heart" surgery does. Recent studies suggest there is no long term difference in outcomes, such as death, MI, or stroke, for patients undergoing CABG, either on- or off-pump. Most CABG procedures are performed for symptom control and are not likely to enhance longevity. The categories of patients likely to have life prolonged by CABG include those with a left main coronary artery more than 50% narrowed, those with severe three-vessel obstructive disease associated with a decrease in ejection fraction (EF, 35% to 50%), and those with two- or threeartery disease whose proximal left anterior descending artery is severely stenosed. Clinical trials comparing CABG and PCI have consistently shown that patients undergoing CABG require fewer repeat procedures during the first 2 years after surgery. In the first 2 years, it is more likely that patients with PCI will experience symptomatic restenosis than that patients with CABG will have graft failure. Over time, this advantage is lost as vein grafts begin to fail 5 to 10 years after surgery. However, there is evidence that a survival advantage exists for diabetic patients with multivessel CAD who undergo CABG as opposed to PCI. A recent study also demonstrated long-term survival benefit for CABG over PCI in the face of multivessel CAD. Some of the survival advantage in favor of CABG may be linked to the use of the left internal mammary artery as a graft. Despite the use of either revascularization technique, patients remain prone to progressive atherosclerotic disease with the potential to form plaque at previously unaffected sites. This necessitates aggressive long-term medical therapy and risk factor modification to achieve the lowest possible risk of symptomatic progression or MI. Retreatment with CABG is possible but is fraught with higher risk, and the outcome of repeat stenting for in-stent restenosis is never as good as for de novo lesions. In a small group of patients, PCI and/or CABG fails and the patient has refractory angina. Once medical therapy has been maximized, few truly effective options remain. Transmyocardial laser revascularization in areas of ischemia has been used to reduce symptoms, but this technique is now of uncertain value. External counterpulsation is a technique whereby blood pressure cuffs are placed on each leg, inflated during diastole and deflated during systole. Patients typically have a 1-hour session that may be repeated 35 times. Angina relief has been reported with this procedure and may reflect some beneficial effect on endothelial function. Spinal cord stimulation using electrodes placed in the C7-T1 dorsal epidural space can reduce anginal symptoms in the short term, although the long-term role needs definition.

acute STEMI and complications of myocardial infarction

Sustained myocardial ischemia, regardless of its cause, can result in myocardial necrosis, which underlies the clinical syndrome of MI. MI represents a spectrum of myocardial necrosis, from relatively small amounts of muscle in the case of demand ischemia, to more extensive subendocardial MI that characterizes NSTEMI, to typically large transmural MIs commonly manifesting as STEMI. The current accepted definition of acute MI accounts for clinical setting and mechanism. STEMI represents the range of large MIs that are almost always caused by total occlusion of an epicardial coronary artery resulting in extensive transmural myonecrosis (Fig. 8-8). In contrast, NSTEMI reflects subtotal coronary occlusion leading to subendocardial myonecrosis. Whereas both NSTEMI and STEMI are life-threatening, their different underlying mechanisms mandate different therapeutic strategies and affect the urgency with which they are applied. One half of all deaths in the United States and developed countries are related to cardiovascular disease. In the United States, there are approximately 1.2 million nonfatal or fatal MIs each year. CAD plays a role in 650,000 deaths each year, and 250,000 deaths are caused by acute MI. One half of patients with acute MI at presentation die within 1 hour of onset, before therapy can be instituted. Of the 5 million patients who come to emergency rooms with chest pain, 1.5 million are admitted to hospital with ACS. In this group of patients, the presence of ST elevation on ECG or an LBBB indicates the diagnosis of STEMI and the need for prompt intervention to open an occluded coronary artery. STEMI accounts for 30% of all MIs, but this mechanism of MI is associated with the highest immediate mortality risk, prompting the need for urgent therapeutic intervention.

syncope

Syncope may be caused by a variety of cardiovascular diseases. It is the transient loss of consciousness due to inadequate cerebral blood flow. In the patient presenting with syncope as a primary complaint, one must try to differentiate true cardiac causes from neurologic issues such as seizure and metabolic causes such as hypoglycemia. Determination of the timing of the syncopal event and associated symptoms is very helpful in determining the etiology. True cardiac syncope is typically very sudden, with no prodromal symptoms. It is typically caused by an abrupt drop in cardiac output which may be due to tachyarrhythmias such as ventricular tachycardia or fibrillation, bradyarrhythmias such as complete heart block, severe valvular heart disease such as aortic or mitral stenosis, or obstruction of flow due to left ventricular outflow tract (LVOT) obstruction. True cardiac syncope often has no accompanying aura. In situations such as aortic stenosis or LVOT obstruction, syncope typically occurs with exertion. Patients usually regain consciousness rather quickly with true cardiac syncope. esponse to a change in position. When one rises from a prone or seated position to a standing position, the peripheral vasculature usually constricts and the HR increases to maintain cerebral perfusion. With neurocardiogenic syncope, the peripheral vasculature abnormally dilates or the HR slows or both. This leads to a reduction in cerebral perfusion and syncope. A similar mechanism is responsible for carotid sinus syncope and syncope associated with micturition and cough. The patient usually describes a gradual onset of symptoms such as flushing, dizziness, diaphoresis, and nausea before losing consciousness, which lasts seconds. When these patients wake, they are often pale and have a lower HR. In the patient with syncope due to seizures, a prodromal aura is typically present before loss of consciousness occurs. Patients regain consciousness much more slowly and at times are incontinent, complain of headache and fatigue, and have a postictal confusional state. Syncope due to stroke is rare, because there must be significant bilateral carotid disease or disease of the vertebrobasilar system causing brainstem ischemia. Neurologic deficits accompany the physical examination findings in these patients. The history is very important in determining the cause of a syncopal episode. This was previously studied by Calkins and colleagues, who found that men older than 54 years of age who had no prodromal symptoms were more likely to have an arrhythmic cause of their episodes. However, those with prodromal symptoms such as nausea, diaphoresis, dizziness, and visual disturbances before passing out were more likely to have neurocardiogenic syncope. Many inherited disorders such as long-QT syndrome and other arrhythmias, hypertrophic cardiomyopathy with LVOT obstruction, and familial dilated cardiomyopathy lead to states conducive to syncope. For this reason, a very detailed family history is necessary.

electrocardiogram

The ECG is an important tool in the diagnosis of acute MI. ST elevation of 1 mm or greater in contiguous leads is seen in most patients with acute MI. The initial ECG may be nondiagnostic, so it is important to obtain serial tracings no more than 20 minutes apart to detect the evolutionary changes characteristic of STEMI. The first stage of ECG presentation is ST elevation that subtends the region of the heart affected by transmural ischemia. ST depression may be present in opposing leads, and these are termed reciprocal changes (see Chapter 73, "ST Elevation Acute Myocardial Infarction and Complications of Myocardial Infarction," in Goldman-Cecil Medicine, 25th Edition). The presence of reciprocal changes may indicate a larger and more threatening MI. As the MI progresses, ST elevation gives way to T wave inversion. Varying degrees of resolution of ST and T wave changes occur over time, but patients with transmural MI develop pathologic Q waves in the leads subtending the infarcted muscle. Other causes of ST elevation include pericarditis and a chronic repolarization finding of "early repolarization." The presence of either cause of ST elevation can confound the early ECG diagnosis of acute MI. Approximately 30% of acute MIs originate from the circumflex coronary artery on the posterior wall of the heart. This type of MI appears on the ECG as precordial ST depression. The presence of precordial ST depression should raise suspicion of the presence of "true posterior MI," and additional leads placed through the axilla to the back may reveal the presence of posterior ST elevation. Echocardiography demonstrating posterior hypokinesis is also useful in discriminating true posterior MI. Acute inferior MI due to occlusion of the right coronary artery can also be associated with right ventricular infarction if the right coronary artery's acute marginal branch is compromised. Right ventricular infarction can lead to some challenging management issues, and its diagnosis is aided by the use of right precordial leads to detect ST elevation. LBBB can mask ST elevation due to acute MI. Patients with clinical features of acute MI who have an LBBB (particularly a new LBBB) should be presumed to have STEMI and treated appropriately. Right bundle branch block (RBBB) does not mask the ST elevation of STEM

neural innervation

The autonomic nervous system is an integral component in the regulation of cardiac function. In general, sympathetic stimulation increases the heart rate (HR) (chronotropy) and the force of myocardial contraction (inotropy). Sympathetic stimulation commences in preganglionic neurons located within the superior five or six thoracic segments of the spinal cord. They synapse with second-order neurons in the cervical sympathetic ganglia and then propagate the signal through cardiac nerves that innervate the SA node, AV node, epicardial vessels, and myocardium. The parasympathetic system produces an opposite physiologic effect by decreasing HR and contractility. Its neural supply originates in preganglionic neurons within the dorsal motor nucleus of the medulla oblongata, which reach the heart through the vagus nerve. These efferent neural fibers synapse with second-order neurons located in ganglia within the heart which terminate in the SA node, AV node, epicardial vessels, and myocardium to decrease HR and contractility. Conversely, afferent vagal fibers from the inferior and posterior aspects of the ventricles, the aortic arch, and the carotid sinus conduct sensory information back to the medulla, which mediates important cardiac reflexes

Definition

The circulatory system comprises the heart, which is connected in series to the arterial and venous vascular networks, which are arranged in parallel and connect at the level of the capillaries (Fig. 2-1). The heart is composed of two atria, which are low-pressure capacitance chambers that function to store blood during ventricular contraction (systole) and then fill the ventricles with blood during ventricular relaxation (diastole). The two ventricles are high-pressure chambers responsible for pumping blood through the lungs (right ventricle) and to the peripheral tissues (left ventricle). The left ventricle is thicker than the right, in order to generate the higher systemic pressures required for perfusio There are four cardiac valves that facilitate unidirectional blood flow through the heart. Each of the four valves is surrounded by a fibrous ring, or annulus, that forms part of the structural support of the heart. Atrioventricular (AV) valves separate the atria and ventricles. The mitral valve is a bileaflet valve that separates the left atrium and left ventricle. The tricuspid valve is a trileaflet valve that separates the right atrium and right ventricle. Strong chords (chordae tendineae) attach the ventricular aspects of these valves to the papillary muscles of their respective ventricles. Semilunar valves separate the ventricles from the arterial chambers: the aortic valve separates the left ventricle from the aorta, and the pulmonic valve separates the right ventricle from the pulmonary artery A thin, double-layered membrane called the pericardium surrounds the heart. The inner, or visceral, layer adheres to the outer surface of the heart, also known as the epicardium. The outer layer is the parietal pericardium, which attaches to the sternum, vertebral column, and diaphragm to stabilize the heart in the chest. Between these two membranes is a pericardial space filled with a small amount of fluid (<50 mL). This fluid serves to lubricate contact surfaces and limit direct tissue-surface contact during myocardial contraction. A normal pericardium exerts minimal external pressure on the heart, thereby facilitating normal movement of the interventricular septum during the cardiac cycle. Too much fluid in this space (i.e., pericardial effusion), can cause impaired ventricular filling and abnormal septal movement. Please refer to Chapter 77, "Pericardial Diseases," in Goldman-Cecil Medicine, 25th Edition.

clinical presentation of coronary artery disease

The clinical syndromes that patients experience due to the presence of CAD principally relate to the occurrence of myocardial ischemia. Myocardial ischemia develops when there is a mismatch of oxygen delivery and oxygen demand. Given that extraction of oxygen by the myocardium is very high, any increase in oxygen demand must be met with an increase in coronary blood flow. Oxygen demand is directly related to increases in heart rate, myocardial contractility, and wall stress (which are related to blood pressure and cardiac dimensions). There is a reflex increase in myocardial oxygen demand driven by these factors as the heart is required to deliver more systemic blood flow in the face of various stresses, the most common of which is increased exertion. Coronary blood flow also depends on the vascular tone of arterioles that are under the control of vasodilators derived from normal functioning endothelium and autonomic tone Coronary blood flow increases to meet an increase in myocardial oxygen demand through endothelium-mediated vasodilation. In the face of atherosclerosis, endothelial dysfunction may develop, resulting in reduced endothelium-mediated vasodilation. Endothelial dysfunction coupled with a flow-limiting stenosis sets the stage for the development of myocardial ischemia. The coronary vessel distal to a flow-limiting stenosis tends to be maximally dilated. As myocardial oxygen demand increases, the myocardium distal to a flow-limiting stenosis is no longer able to augment flow by additional dilation. An overall limitation in the ability to increase coronary blood flow due to flow-limiting stenosis and endothelial dysfunction results in supply/demand mismatch and myocardial ischemia The major clinical manifestation of myocardial ischemia is chest discomfort (angina pectoris), which is usually described as a pressure or sensation of midsternal tightness. It may be quite pronounced in intensity or relatively subtle. Myocardial ischemia produces not only the sensation of angina pectoris but also a number of derangements in myocyte function. As in any tissue, inadequate oxygen delivery leads to a transition to anaerobic glycolysis, increased lactate production causing cellular acidosis, and abnormal calcium homeostasis. The net consequences of these cellular abnormalities include reductions in myocardial contractility and relaxation. Decreased myocardial contractility results in systolic wall motion abnormalities in the area of ischemia, and the abnormality of relaxation causes reduced ventricular compliance. These changes cause an increase in LV filling pressures above the normal range. The cellular abnormalities related to myocardial ischemia also translate into changes in cellular electrical activity that appear as abnormalities in the electrocardiogram (ECG). Myocardial ischemia may result in either ST depression or ST elevation, depending on the duration, severity, and location of the ischemia. The cellular, mechanical, and electrical abnormalities caused by ischemia typically precede the patient's perception of angina. Myocardial dysfunction due to ischemia may recover quickly to normal if the duration of ischemia is brief. Prolonged myocardial ischemia can lead to conditions of myocardial stunning or myocardial hibernation. In the case of stunning, the mechanical dysfunction induced by prolonged ischemia persists for hours or days until function returns to normal. In the face of chronic ischemia, myocyte viability may be maintained, but because of ischemia, mechanical dysfunction persists; in this condition, known as hibernation, restoration of blood flow can result in recovery of myocardial function The heart's conduction system is less prone to ischemic injury, but ischemia can lead to impaired conduction. Ischemic disruption of myocyte electrical homeostasis also sets the stage for potentially life-threatening arrhythmias.

differential diagnosis

The initial assessment of patients with possible ACS should include consideration of other potentially life-threatening conditions such as pulmonary embolism and aortic dissection. These considerations are particularly important if the patient's presentation does not entirely fit that of ACS. Pulmonary embolism can be associated with ECG changes and troponin elevation, and such findings lead to early use of coronary angiography. If there is no CAD-related explanation of the patient's presentation, prompt investigation for pulmonary embolism is warranted. If the patient has findings suggestive of aortic dissection, that diagnosis should be aggressively pursued with appropriate imaging techniques, given the high risk of mortality associated with that disease. Valvular heart diseases such as aortic stenosis or regurgitation and hypertrophic cardiomyopathy can manifest with symptoms and ECG findings suggestive of ACS. Physical examination should aid in consideration of these conditions. Pericarditis and myopericarditis can also present diagnostic dilemmas related to chest pain, ECG abnormalities (ST and T-wave changes mimicking ischemia), and positive biomarkers. Stress cardiomyopathy (Takotsubo's syndrome) also manifests with chest pain, T-wave inversion, and positive biomarkers. Patients with this diagnosis frequently undergo urgent catheterization to assess for CAD. The absence of a culprit lesion and findings of characteristic wall motion abnormalities establish the diagnosis

physiology of the coronary circulation

The normally functioning heart maintains equilibrium between the amount of oxygen delivered to myocytes and the amount of oxygen consumed by them (myocardial oxygen consumption, or Mvo2). If a myocyte works harder because it is contracting with increased frequency (HR), with increased intensity (contractility), or against an increased load (wall stress), then it will use more oxygen and its Mvo2 will increase. In order to meet this increase in demand for more oxygen, the heart will have to either increase blood flow or increase its efficiency in extracting oxygen. The heart is unique in that its oxygen extraction is almost maximal at resting conditions. Therefore, increasing blood flow is the only reasonable means of increasing oxygen supply Microvascular blood flow in the coronary circulation is impaired during systole because the intramyocardial blood vessels are compressed by contracting myocardium. Therefore, most coronary flow occurs during diastole. Accordingly, the diastolic pressure is the major pressure driving flow within the coronary circulation. Systolic pressure impedes intramyocardial arterial blood flow but augments venous flow. On a clinical note, tachycardia is particularly detrimental because coronary flow is reduced when the diastolic filling time is abbreviated, and the Mvo2 increases with increasing HR. In order to sustain constant perfusion to the myocardium, coronary blood flow is maintained constant over a wide range of pressures in a process called autoregulatio

myocardium

The proper cellular organization of cardiac tissue (myocardium) is critical for the generation of efficient myocardial contraction. Disruptions in this structure and organization lead to cardiac dyssynchrony and arrhythmias, which cause significant morbidity and mortality. Atrial and ventricular myocytes are specialized, branching muscle cells that are connected end to end by intercalated disks. These disks aid in the transmission of mechanical tension between cells. The myocyte plasma membrane, or sarcolemma, facilitates excitation and contraction through small transverse tubules (T tubules). Subcellular features specific for myocytes include increased mitochondria number for production of adenosine triphosphate (ATP); an extensive network of intracellular tubules, called the sarcoplasmic reticulum, for calcium storage; and sarcomeres, which are myofibrils comprised of repeating units of overlapping thin actin filaments and thick myosin filaments and their regulatory proteins troponin and tropomyosin. Specialized myocardial cells form the cardiac conduction system (described earlier) and are responsible for the generation of an electrical impulse and organized propagation of that impulse to cardiac myocytes, which, in turn, respond by mechanical contraction.

circulatory pathway

The purpose of the circulatory system is to bring deoxygenated blood, carbon dioxide, and other waste products from the tissues to the lungs for disposal and reoxygenation (see Fig. 2-1A). Deoxygenated blood drains from peripheral tissues through venules and veins, eventually entering the right atrium through the superior and inferior venae cavae during ventricular systole. Venous drainage from the heart enters the right atrium through the coronary sinus. During ventricular diastole, the blood in the right atrium flows across the tricuspid valve and into the right ventricle. Blood in the right ventricle is ejected across the pulmonic valve and into the main pulmonary artery, which bifurcates into the left and right pulmonary arteries and perfuses the lungs. After multiple bifurcations, blood reaches the pulmonary capillaries, where carbon dioxide is exchanged for oxygen across the alveolar-capillary membrane. Oxygenated blood then enters the left atrium from the lungs via the four pulmonary veins. Blood flows across the open mitral valve and into the left ventricle during diastole and is ejected across the aortic valve and into the aorta during systole. The blood reaches various organs, where oxygen and nutrients are exchanged for carbon dioxide and metabolic wastes, and the cycle begins again. The heart receives its blood supply through the left and right coronary arteries, which originate in outpouchings of the aortic root called the sinuses of Valsalva. The left main coronary artery is a short vessel that bifurcates into the left anterior descending (LAD) and the left circumflex (LCx) coronary arteries. The LAD supplies blood to the anterior and anterolateral left ventricle through diagonal branches and to the anterior interventricular septum through septal perforator branches. The LAD travels anteriorly in the anterior interventricular groove and terminates at the cardiac apex. The LCx traverses posteriorly in the left AV groove (between left atrium and left ventricle) to perfuse the lateral aspect of the left ventricle (through obtuse marginal branches) and the left atrium. The right coronary artery (RCA) courses down the right AV groove to the crux of the heart, the point at which the left and right AV grooves and the inferior interventricular groove meet. The RCA gives off branches to the right atrium and acute marginal branches to the right ventricle The blood supply to the diaphragmatic and posterior aspects of the left ventricle varies. In 85% of individuals, the RCA bifurcates at the crux to form the posterior descending coronary artery (PDA), which travels in the inferior interventricular groove to supply the inferior left ventricule and the inferior third of the interventricular septum, and the posterior left ventricular (PLV) branches. This course is termed a right-dominant circulation. In 10% of individuals, the RCA terminates before reaching the crux, and the LCx supplies the PLV and PDA. This course is termed a left-dominant circulation. In the remaining individuals, the RCA gives rise to the PDA and the LCx gives rise to the PLV in a co-dominant circulation.

conduction system

The sinoatrial (SA) node is a collection of specialized pacemaker cells, 1 to 2 cm long, that is located in the right atrium between the superior vena cava and the right atrial appendage (see Fig. 2-1B). The SA node is supplied by the SA nodal artery, which is a branch of the RCA in about 60% of the population and a branch of the LCx in about 40%. An electrical impulse originates in the SA and is conducted to the AV node by internodal tracts within the atria. The AV node is a critical electrical interface between the atria and ventricles, because it facilitates electromechanical coupling. The AV node is a located at the inferior aspect of the right atrium, between the coronary sinus and the septal leaflet of the tricuspid valve. The AV node is supplied by the AV nodal artery, which is a branch of the RCA in about 90% of the population and a branch of the LCx in 10%. Electrical impulse conduction slows through the AV node and continues to the ventricles by means of the HisPurkinje system. The increased impulse time through the AV node allows for adequate ventricular filling The bundle of His extends from the AV node down the membranous interventricular septum to the muscular septum, where it divides into the left and right bundle branches, finally terminating in Purkinje cells, which are specialized cells that facilitate the rapid propagation of electrical impulses. The Purkinje cells directly stimulate myocytes to contract. The right bundle and the left bundle are supplied by septal perforator branches from the LAD. The distal and posterior portion of the left bundle has an additional blood supply from the AV nodal artery (PDA origin); for that reason, it is more resistant to ischemia. Conduction can be impaired at any point, from ischemia, medications (e.g., β-blockers, calcium channel blockers), infection, or congenital abnormalities. Please refer to Chapter 61, "Principles of Electrophysiology," in Goldman-Cecil Medicine, 25th Edition.

definition and epidemiology

The term coronary heart disease (CHD) describes a number of cardiac conditions that result from the presence of atherosclerotic lesions in the coronary arteries. The development of atherosclerotic plaque within the coronary arteries can result in obstruction to blood flow, producing ischemia, which can be acute or chronic in nature. Atherosclerosis is a disease process that starts at a young age and can be present for years in an asymptomatic form until the degree of vessel obstruction leads to ischemic symptoms. Obstructive atherosclerotic lesions can cause chronic symptoms of exercise- or stress-related angina; or, in the case of plaque rupture and acute thrombosis, sudden death, unstable angina, or myocardial infarction (MI) may ensue. In the United States, more than 17 million people experience some form of CHD. Approximately 10 million suffer from symptoms of angina, and at least 380,000 deaths occur each year from acute MI or CHD-related sudden death. Despite progress in therapy and overall reductions in CHD-related mortality, CHD remains the number one cause of death in both men and women, accounting for 27% of deaths in women (more than deaths due to cancer). The incidence of CHD increases with age for both men and women. There are at least 1.2 million MIs per year in the United States, and many more cases of unstable angina. CHD frequently results in lifestyle-limiting symptoms due to angina or impairment of left ventricular (LV) function. The cost of care related directly to CHD and indirectly to lost productivity from CHD is in the range of $156 billion per year. CHD remains a major life-threatening disease process associated with significant economic impact.

clinical presentation

There have been major advances in technology over the years that allow for specialized testing to assist in the diagnosis of cardiovascular diseases. We now rely on such tests as angiography, ultrasound scanning, and advanced imaging modalities such as high-resolution computed tomography and magnetic resonance imaging to determine how to manage an individual case. However, these techniques should be used not as a primary method of assessment but rather to supplement the findings from a thorough history and physical examination. Despite the availability of rather costly imaging techniques and laboratory tests, a relatively inexpensive but detailed history and physical examination is often all that is required to establish a diagnosis. When evaluating patients with cardiovascular disease, it is important to allow them to express their symptoms in their own words. For example, many patients who deny chest pain when asked specifically about this symptom, will, in their very next breath, describe the chest pressure they feel, which they do not consider to be "pain." It is very important to delve into details regarding the setting in which the symptom occurs (e.g., at rest, with activity, with extreme emotional stress). The location, quality, intensity, and radiation of the symptom should be elicited. One should ask whether there are aggravating or alleviating factors and whether there are other symptoms that accompany the primary symptom. It is also important to note the pattern of the symptom in terms of stability or progression in intensity or frequency over time. An assessment of functional status should always be a part of the history in a patient with cardiovascular disease, because a recent decline in exercise tolerance can be very telling in regard to severity of disease. A detailed past medical history and review of systems are necessary because cardiovascular conditions can be associated with other medical conditions; for example, patient may have arrhythmias in the setting of hyperthyroidism. A comprehensive list of medications must be reviewed, and a social history must be taken detailing alcohol use, smoking, and occupational history. Patients should also be questioned regarding major risk factors such as hypertension, hyperlipidemia, and diabetes mellitus. A thorough family history is needed, not only to identify such entities as early-onset CAD but also to assess for other potentially inherited disorders, such as familial cardiomyopathy or arrhythmic disorders (e.g., long-QT syndrome).

indications for coronary angiography in patients with stable angina pectoris

Unacceptable angina despite medical therapy (for consideration of revascularization) Noninvasive testing results with high-risk features Angina or risk factors for coronary artery disease in the setting of depressed left ventricular systolic function For diagnostic purposes, in the individual in whom the results of noninvasive testing are unclear

other anginal syndromes variant angina

Whereas typical angina pectoris is usually triggered by physical or emotional stress, some patients experience a syndrome termed variant angina. Variant angina was first described in 1959 by Prinzmetal and colleagues, who observed patients with chest discomfort at rest, not triggered by physical or emotional stress, and associated with ST segment elevation (Fig. 8-4). Episodes of AV block and ventricular ectopy were observed, but MI was not a common feature. These patients typically did not have the common CAD risk factors other than smoking. Coronary angiography demonstrated these patients to be experiencing transient coronary vasospasm. The vasospasm tended to occur in an area of atherosclerotic plaque, but some patients had spasm in angiographically normal segments of coronary artery. In the course of investigating the pathophysiology of variant angina, a number of provocative tests were developed to induce coronary spasm in susceptible individuals. Intracoronary ergonovine or acetylcholine can induce spasm in patients with variant angina, probably as a result of underlying endothelial dysfunction. Other spasm-inducing provocations include the cold pressor test (placing a hand in an ice bath), the induction of alkalosis (hyperventilation or intravenous bicarbonate), and histamine infusion. Provocative testing to induce coronary vasospasm has fallen out of favor in the routine assessment of patients with angina. Coronary vasospasm usually resolves promptly with the administration of nitroglycerin (sublingual, intravenous, or intraarterial). The combination of oral nitrates and calcium channel blockers is often used to prevent spasm. β-Blockers may aggravate coronary spasm by inhibiting the action of vasodilating β2receptors, allowing for unopposed α-receptor induced vasoconstriction. Rare patients do not respond to vasodilator medical therapy and may benefit from coronary stent placement in spasmprone atherosclerotic lesions.