Chapter 1- Diseases of the cardiovascular system. Chapter 2- Diseases of the Pulmonary System. Chapter 3- Diseases of the Gastrointestinal system. Chapter 4- Endocrine and Metabolic Diseases. Chapter 5- Diseases of the Central and Peripheral Nervous Systems. Chapter 6- Connective Tissue and Joint Diseases. Chapter 7- Diseases of the Renal and Genitourinary System. Chapter 8- Fluids, Electrolytes, and Acid-Base Disorders. Chapter 9- Hematologic Diseases and Neoplasms. Chapter 10- Infectious Diseases. Chapter 11- Diseases of the skin and Hypersensitivity Disorders. Chapter 12- Ambulatory Medicine. CHAPTER 1 Diseases of the Cardiovascular System ISCHEMIC HEART DISEASE Stable Angina Pectoris A. General characteristics Stable angina pectoris is due to fixed atherosclerotic lesions that narrow the major coronary arteries. Coronary ischemia is due to an imbalance between blood supply and oxygen demand, leading to inadequate perfusion. Stable angina occurs when oxygen demand exceeds available blood supply. Risk factors o Diabetes mellitus (DM) o Hyperlipidemia—elevated LDL o Hypertension (HTN) o Cigarette smoking o Age (men >45 years; women >55 years) o Family history of premature coronary artery disease (CAD) or myocardial infarction (MI) in first-degree relative: men <45 years; women <55 years o Low levels of high-density lipoprotein (HDL) o Elevated homocysteine levels Prognostic indicators of CAD o Left ventricular function (ejection fraction [EF])  Normal >50%  If <50%, associated with increased mortality o Vessel(s) involved (severity/extent of ischemia)  Left main coronary artery–poor prognosis because it covers approximately two thirds of the heart.  Two- or three-vessel CAD–worse prognosis. Coronary artery disease (CAD) can have the following clinical presentations: Asymptomatic Stable angina pectoris Unstable angina pectoris (USA) Myocardial infarction (MI) Sudden cardiac death B. Clinical features Chest pain or substernal pressure sensation o Lasts less than 10 to 15 minutes (usually 1 to 5 minutes) o Frightening chest discomfort, usually described as heaviness, pressure, squeezing; rarely described as frank pain Brought on by exertion or emotion Relieved with rest or nitroglycerin Stress ECG (exercise testing) is used in the following situations: To confirm diagnosis of angina To evaluate response of therapy in patients with documented CAD To identify patients with CAD who may have a high risk of acute coronary events C. Diagnosis (of CAD) Resting ECG o Usually normal in patients with stable angina o Q waves are consistent with a prior myocardial infarction. P.2 o If ST segment or T wave abnormalities are present during an episode of chest pain, then treat as for unstable angina. For patients with normal resting ECG, determine whether the patient is capable of performing treadmill exercise. If so, proceed to an exercise stress test. o Stress ECG  Test involves recording ECG before, during, and after exercise on a treadmill.  75% sensitive if patients are able to exercise sufficiently to increase heart rate to 85% of maximum predicted value for age.  Exercise-induced ischemia results in subendocardial ischemia, producing ST segment depression.  Other positive findings include onset of heart failure or ventricular arrhythmia during exercise or hypotension.  Patients with a positive stress test result should undergo cardiac catheterization. o Stress echocardiography  Performed before and immediately after exercise. Exercise-induced ischemia is evidenced by wall motion abnormalities (e.g., akinesis or dyskinesis) not present at rest.  Favored by many cardiologists over stress ECG. It is more sensitive in detecting ischemia, can assess LV size and function, and can diagnose valvular disease.  Again, patients with a positive test result should undergo cardiac catheterization. P.3 o Information gained from a stress test can be enhanced by stress myocardial perfusion imaging after IV administration of a radioisotope such as thallium 201 during exercise.  Viable myocardial cells extract the radioisotope from the blood. No radioisotope uptake means no blood flow to an area of the myocardium.  It is important to determine whether the ischemia is reversible, i.e., whether areas of hypoperfusion are perfused over time as blood flow eventually equalizes. Areas of reversible ischemia may be rescued with percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG). Irreversible ischemia, however, indicates infarcted tissue that cannot be salvaged.  Perfusion imaging increases the sensitivity and specificity of exercise stress tests, but is also more expensive. If the patient cannot exercise, perform a pharmacologic stress test. o IV adenosine, dipyramidole, or dobutamine can be used. The cardiac stress induced by these agents takes the place of exercise. This can be combined with an ECG, an echocardiogram, or nuclear perfusion imaging. o IV adenosine and dipyramidole cause generalized coronary vasodilation. Because diseased coronary arteries are already maximally dilated at rest to increase blood flow, they receive relatively less blood flow when the entire coronary system is pharmacologically vasodilated. o Dobutamine increases myocardial oxygen demand by increasing heart rate, blood pressure, and cardiac contractility. Holter monitoring (ambulatory ECG) can be useful in detecting silent ischemia (i.e., ECG changes not accompanied by symptoms). Cardiac catheterization with coronary angiography (see Box 1-2) o Coronary angiography–definitive test for CAD. Indicated for patients being considered for revascularization (PTCA or CABG). o Contrast is injected into coronary vessels to visualize any stenotic lesions. This defines the location and extent of coronary disease. o If coronary artery disease is severe (e.g., left main or three-vessel disease), refer patient for surgical revascularization (CABG). Box 1-1 There Are Two Conditions Termed Syndrome X Metabolic Syndrome X o Any combination of hypercholesterolemia, hypertriglyceridemia, impaired glucose tolerance, diabetes, hyperuricemia, HTN o Key underlying factor is insulin resistance (due to obesity) Syndrome X o Exertional angina with normal coronary arteriogram: Patients present with chest pain after exertion but have no coronary stenoses at cardiac catheterization. o Exercise testing and nuclear imaging show evidence of myocardial ischemia. o Prognosis is excellent. Box 1-2 Cardiac Catheterization Most accurate method of determining a specific cardiac diagnosis Provides information on hemodynamics, intracardiac pressure measurements, cardiac output, oxygen saturation, etc. Coronary angiography (see below) is almost always performed as well for visualization of coronary arteries. There are many indications for cardiac catheterization (generally performed when revascularization or other surgical intervention are being considered): o After a positive stress test o In a patient with angina in any of the following situations: when noninvasive tests are nondiagnostic, angina that occurs despite medical therapy, angina that occurs soon after MI, and any angina that is a diagnostic dilemma. o If patient is severely symptomatic and urgent diagnosis and management are necessary o For evaluation of valvular disease, and to determine the need for surgical intervention Coronary Arteriography (Angiography) Most accurate method of identifying the presence and severity of CAD; the standard test for delineating coronary anatomy Main purpose is to identify patients with severe coronary disease to determine whether revascularization is needed Coronary stenosis >70% may be significant (i.e., it can produce angina) A stress test is generally considered positive if the patient develops any of the following during exercise: S-T segment depression, chest pain, hypotension, or significant arrhythmias. D. Treatment Risk factor modification o Smoking cessation cuts coronary heart disease (CHD) risk in half by 1 year after quitting. o HTN—vigorous BP control reduces the risk of CHD, especially in diabetic patients. o Hyperlipidemia—reduction in serum cholesterol with lifestyle modifications and HMG-CoA reductase inhibitors reduces CHD risk. o DM—strict glycemic control is thought to have less effect on macrovascular disease risk than microvascular disease risk but should still be emphasized. o Obesity—weight loss modifies other risk factors (diabetes, HTN, and hyperlipidemia) and provides other health benefits. o Exercise is critical; it minimizes emotional stress, promotes weight loss, and helps reduce other risk factors. o Diet: Reduce intake of saturated fat (<7% total calories) and cholesterol (<200 mg/day). o Hyperhomocystinemia–value of treating yet to be established. Medical therapy o Aspirin  Indicated in all patients with CAD  Decreases morbidity—reduces risk of MI o β-Blockers—block sympathetic stimulation of heart  Reduce HR, BP, and contractility, thereby decreasing cardiac work (i.e., β-blockers lower myocardial oxygen consumption)  Have been shown to reduce the frequency of coronary events P.4 FIGURE 1-1 Coronary angiogram. injection of the right coronary artery shows a stenosis in the midportion of the vessel, indicated by the arrow. (From Lilly LS. Pathophysiology of Heart Disease. 3rd Ed. Philadelphia: Lippincott Williams & Wilkins, 2003:148, Figure 6.8. Courtesy of Dr. William Daley.) View Figure o Nitrates—cause generalized vasodilation  Relieve angina; reduce preload, therefore the load and oxygen demand.  May prevent angina when taken before exertion  Effect on prognosis is unknown; main benefit is symptomatic relief  Can be administered orally, sublingually, transdermally, or intravenously o Calcium channel blockers  Cause coronary vasodilation and afterload reduction  Now considered a secondary treatment when β-blockers and/or nitrates are not fully effective. o If CHF is also present, treatment with ACE inhibitors and/or diuretics may be indicated as well. Revascularization o May be preferred for high-risk patients, although there is some controversy whether revascularization is superior to medical management for a patient with stable angina and stenosis >70%. o Two methods—PTCA and CABG—see Box 1-3 P.5 o Revascularization does not reduce incidence of MI, but does result in significant improvement in symptoms. Management decisions (general guidelines)—Risk factor modification and aspirin are indicated in all patients. Manage patients according to overall risk: o Mild disease (normal EF, mild angina, single-vessel disease)  Nitrates (for symptoms and as prophylaxis) and a β-blocker are appropriate.  Consider calcium channel blockers if symptoms continue despite nitrates and β-blockers. o Moderate disease (normal EF, moderate angina, two-vessel disease)  If the above regimen does not control symptoms, consider coronary angiography to assess suitability for revascularization (either PTCA or CABG). o Severe disease (decreased EF, severe angina, and three-vessel/left main or left anterior descending disease)  Coronary angiography and consider for CABG Box 1-3 Percutaneous Transluminal Coronary Angioplasty (PTCA) Should be considered in patients with one- or two-vessel disease Best if used for proximal lesions Restenosis is a significant problem (up to 40% within first 6 months); however, if there is no evidence of restenosis at 6 months, it usually does not occur. Stents significantly reduce the rate of restenosis. Coronary Artery Bypass Grafting (CABG) Treatment of choice in patients with high-risk disease Indicated in patients with left main disease, three-vessel disease with reduced left ventricular function, two-vessel disease with proximal LAD stenosis, or severe ischemia for palliation of symptoms Side effects of nitrates Headache Orthostatic hypotension Tolerance Syncope Unstable Angina Pectoris A. General characteristics Pathophysiology o With unstable angina (USA), oxygen demand is unchanged. Supply is decreased secondary to reduced resting coronary flow. This is in contrast to stable angina, which is due to increased demand. o USA is significant because it indicates stenosis that has enlarged via thrombosis, hemorrhage, or plaque rupture. It may lead to total occlusion of a coronary vessel. The following patients may be said to have USA: o Patients with chronic angina with increasing frequency, duration, or intensity of chest pain o Patients with new-onset angina that is severe and worsening o Patients with angina at rest Acute coronary syndrome The clinical manifestations of atherosclerotic plaque rupture and coronary occlusion Term generally refers to unstable angina or acute MI B. Diagnosis (see stable angina) Perform a diagnostic workup to exclude MI in all patients. Patients with USA have a higher risk of adverse events during stress testing. These patients should be stabilized with medical management before stress testing or should undergo cardiac catheterization initially. USA and non-ST-segment elevation MI are often considered together because it is very difficult to distinguish the two based on patient presentation. If cardiac enzymes are elevated, then the patient has non-ST segment elevation MI. The ESSENCE trial showed that in USA and non-ST segment-elevation MI, risk of death, MI, or recurrent angina was lower in the enoxaparin group than in the heparin group at 14 days, 30 days, and 1 year. The need for revascularization was also lower in the enoxaparin group. Thrombolytic therapy and calcium channel blockers have not been proven to be beneficial in unstable angina. C. Treatment Hospital admission on a floor with continuous cardiac monitoring. Establish IV access and give supplemental oxygen. Provide pain control with nitrates (below) and morphine.