Circulation-Atherosclerosis .pptx

Circulation Calli Cook, DNP, APRN, FNP-C, FAANP Clinical Associate Professor NHWSON Objectives: Part 1 Describe the general organization and function of the systemic circulation Briefly describe the characteristics of each segment of the vascular system from arteries to veins The primary roles...

Circulation Calli Cook, DNP, APRN, FNP-C, FAANP Clinical Associate Professor NHWSON Objectives: Part 1 Describe the general organization and function of the systemic circulation Briefly describe the characteristics of each segment of the vascular system from arteries to veins The primary roles of blood: Homeostat ic Function of the Circulator System • Carry oxygen from the lungs to the tissues and carbon dioxide from the tissues for elimination from the lungs • Nutrients from the digestive tract to the tissues • Metabolic waste products from the tissues to their point of elimination • Hormones from their point of production to the site of action • Immune system components Blood Flow Pulmonary Circulation • The pulmonary circulation originates from the right ventricle with the pulmonary artery. • The primary goal of the pulmonary circulation is to oxygenate blood and remove carbon dioxide • Oxygenated blood is returned to the left atrium by means of the pulmonary veins. • Despite the same amount of total blood flow, pressure and vascular resistance are about five- to ten-fold lower in the pulmonary circulation compared with that in the systemic circuit. Systemic Circulation • Systemic circulation starts with the aorta, which receives output from the left ventricle, and branches into numerous parallel vascular circuits, each receiving a fraction of the cardiac output. • Each circuit dynamically adapts to the tissues’ metabolic needs • During exercise and rest cardiac output varies. • Redistribution of blood flow is an adaptive mechanism that ensures that blood is being directed to areas with greater metabolic need during times of increased activity. • Vital organs such as the brain are always active and receive similar blood flow under both conditions. Structure and Properties of Blood Vessels General Structure • Most vessels have three layers (from inner to outer): 1. Tunica intima: • single layer of endothelial cells forming the vessel lining, basement membrane • and a layer of elastic fibers (internal elastic lamina) 2. Tunica media: • Concentric layers of smooth muscle cells 3. Tunica externa: • Strong connective tissue • Capillaries: • Have uniquely thin walls composed of only endothelial cells and basement membrane (no elastic fibers or VSM). Comparative Structure of Blood Vessels • The size and ratio of wall components in blood vessels vary greatly • Blood flow in the systemic circulation is driven by the pumping action of the left ventricle • The pressure is highest in the aorta and falls throughout the circuit because of vascular resistance • Arteries have much thicker walls compared with veins and thus can withstand higher pressures • Arteries branch into arterioles • Representing the primary site (70% to 80%) of systemic vascular resistance • Consider diameter Endothelial Cells • The endothelial cells form a barrier that contains blood within the lumen of the vessel and controls the passage of solutes and cells from the circulation into the subendothelial space. • Endothelial cells secrete substances that modulate contraction of SMCs in the underlying medial layer. • These substances include vasodilators (e.g., NO and prostacyclin) and vasoconstrictors (e.g., endothelin) • Endothelial cells can also modulate the immune response. • In the absence of pathologic stimulation, healthy arterial endothelial cells resist leukocyte adhesion and thereby oppose local inflammation. • However, endothelial cells respond to local injury or infection by expressing cell surface adhesion molecules, which attach monocytes to the endothelium and chemokines • The normal endothelium provides a protective, nonthrombogenic surface with homeostatic vasodilatory and anti-inflammatory properties Vascular Smooth Muscle Cells • SMCs within the medial layer of normal muscular arteries have both contractile and synthetic capabilities. • SMCs produce vasoactive and inflammatory mediators, including interleukin (IL)-1 and IL-6, and tumor necrosis factor (TNF). • In normal arteries, most SMCs reside in the medial layer • During atherogenesis, medial SMCs can migrate into the intima, proliferate, and augment synthesis of extracellular matrix macromolecules while they dampen contractile protein content. EC and VSMC Properties and Disorders of Large Arteries Biophysics of Wall Tension • Blood pumped into the aorta by the left ventricle generates =a push on the vessel wall (hydrostatic pressure) • This pressure is highest in the aorta and large arteries • Large arteries must withstand high pressure at a relatively large radius • To reduce wall tension and avoid rupture, large arteries have much thicker walls compared with walls of veins of similar size. • Wall tension (T) is increased by both pressure (P) and radius (r), but decreased by wall thickness (h). Clinical Examples of Vascular Wall Tension • Vascular Hypertrophy: • Increase in wall thickness helps to offset the effect of increased pressure and decrease wall tension. • However, if elevated blood pressure is sustained over time, the thicker vascular walls become fibrotic and can lead to secondary problems • Vascular Aneurysm: • Sustained high arterial pressure can cause a progressive increase in vascular radius • This sets up a vicious cycle in which the vessel begins to dilate, further increasing its radius, and therefore wall tension. • This forms a vascular aneurysm Case courtesy of The Radswiki, Radiopaedia.org, rID: Biophysics of Vascular Compliance • All blood vessels stretch under pressure • Arteries are less compliant than veins but are subjected to greater pressure changes as they receive the stroke volume of the heart during systole. • The aorta and large arteries contain an abundance of elastic fibers that stretch during systole and return to their original shape and size during diastole. • This elastic recoil of the large arteries helps to maintain diastolic blood pressure and thus tissue perfusion between heart beats. • When arterial walls become less compliant, patients may present with an increase in systolic blood pressure and a decrease in diastolic pressure and blood flow • Veins are much more compliant than arteries • 60% to 68% of the circulating blood volume is typically stored at relatively low pressures in the systemic veins and venules Elastic Recoil Biophysics of Flow Velocity • Blood flow velocity and cross-sectional area are inversely related • Blood velocity is highest in the aorta and large arteries and lowest in the capillaries. • Flow velocity is directly related to shear stress (friction of the blood sliding past and pulling on the endothelial cell surface parallel to the direction of flow) • Slow blood velocity is also the foundation for capillary function • Allows for exchange of water and bloodborne substances between blood and interstitial fluid Biophysics of Shear Stress • Laminar flow and high velocity in large arteries cause shear stress • Hydrostatic pressure further acts on the vessel wall by maintaining a perpendicular distending force that contributes to wall tension • Endothelial cell and smooth muscle layers generate and respond to a variety of biochemical mediators • Most important is the production of nitric oxide • NO promotes vasodilation, maintaining vessel patency and vascular wall health and lowering blood pressure Pathology of Flow • In turbulent flow, such as downstream from an atherosclerotic plaque and in areas of vascular branching, endothelial shear stress is reduced, leading to decreased nitric oxide production. • Decreased endothelial nitric oxide production is a hallmark of endothelial dysfunction that contributes to and accompanies atherosclerosis. • Elevated sheer stress cannot increase nitric oxide production, but rather contributes to endothelial damage and exacerbates atherosclerosis. Atheroscleros is Vessel Disease Atherosclerotic narrowing or complete obstruction of the vessel lumen, leading to tissue ischemia Weakening of the vascular wall, leading to dilation (aneurysm), rupture, and hemorrhage. The most common sites of atherosclerosis, in order of frequency, are the following: Abdominal aorta Coronary arteries Thoracic aorta, femoral and popliteal arteries Carotid arteries Vertebral, basilar, and middle cerebral arteries Stages of Development: Plaque Formation Fatty streak formation • Endothelial cell injury initiates the process of increased endothelial permeability, soon followed by movement of LDLs into the intima. • These events are promoted by elevated levels of LDLs and by systemic inflammation, associated with increased levels of the acute phase protein C-reactive protein (CRP) and the cytokine tumor necrosis factor-α (TNF-α). • Upregulation of endothelial adhesion molecules recruits monocytes to the intima, where they differentiate into macrophages they begin phagocytose LDLs. Plaque growthand begins with to recruitment of additional inflammatory cells • T lymphocytes, dendritic cells, platelets, and mast cells are recruited in response to inflammatory signals • Cholesterol accumulation continues to swell the evolving lesion Recruitment of vascular smooth muscle (VSM) cells initiates the next phase of plaque growth. • VSM cells invade the intima and become activated to proliferate and produce extracellular matrix, increasing the intima-media thickness (IMT). • VSM cells produce fibrous cap over the plaque, beneath which inflammatory interactions and cholesterol deposition continues. After months and years of growth, many of the foam cells die, leaving behind inflammatory debris. • The necrotic plaque core is highly thrombogenic but is initially covered by a fibrous cap and endothelial cells that keep blood from encountering it. • This is called the complex plaque (or atheroma) stage that causes vascular lumen narrowing Overview of Atherosclerosis • Atherosclerosis is the buildup of plaque within the walls of large conduit arteries • Atherosclerosis underlies the pathogenesis of coronary, cerebral, and peripheral vascular disease. • Atherosclerosis is a chronic inflammatory response to the accumulation of lipids and macrophages in the artery wall. • Progression to critical vessel narrowing can be due to: 1. Acute changes in complex plaques that trigger thrombus formation and lead to severe narrowing 2. Complete obstruction of the artery Cells and Mediators of Atherosclero sis Progression of the Fatty Streak Stages of Development: Fate of the Plaque • Endothelial cells overlying the plaque are highly dysfunctional • Diminished synthesis of nitric oxide and prostacyclin (PGI2). • As the plaque enlarges, the artery’s own blood vessels that supply the vascular wall may grow into the plaque (neovascularization). • Plaques can develop internal hemorrhages from these blood vessels, causing rapid expansion of the plaque and more severe narrowing of the lumen. • Vulnerable plaques are more likely to rupture • This causes the rapid formation of a large thrombus that can completely occlude the artery, resulting in infarction. • Ruptured plaques can heal with fibrosis, leading to a very narrow lumen that causes critical stenosis (with clinical symptoms even at rest). Extracellular Matrix Metabolism • SMCs favor fortification of the fibrous cap • Net matrix deposition depends on the balance of its synthesis by SMCs and its degradation, mediated in part by a class of proteolytic enzymes known as matrix metalloproteinases (MMP). • Inflammatory cytokines stimulate local foam cells to secrete collagen- and elastindegrading MMP, thereby weakening the fibrous cap and predisposing it to rupture Atherosclerosis Cap thickness <65 μm (based on results by Burke et al62 acquired from ruptured coronary plaques in male cadavers) Histology Thin Cap Fibroatheroma Features Large necrotic core Increased macrophage infiltration Virtual histology Focal lesion, containing necrotic core (≥10% of total plaque area) in direct contact with the lumen (cap cannot be visualized) Percent atheroma volume ≥40% Wide lipid arc (>90 degrees), suggesting increased lipid content. Lipid arc is defined the widest arc demarcating a signal poor region with diffuse borders65, 67 Necrotic lipid pools presence (signal‐poor regions poorly delineated, underlying a signal rich cap), quantified based on number of quadrants occupied Optical coherence Superficial microcalcifications (subtending a <90‐degree arc and with a border with lumen <100 μm thick) tomography Cap thickness <65 μm—although different limits have been proposed, with studies suggesting that OCT‐derived in vivo thin cap limit should be increased (postmortem/histological preparation—related alterations in previous studies) 68, 69 When virtual histology IVUS is used concomitantly to assess deeper plaque layers, OCT fibroatheromas are confirmed to have a high lipid content and low levels of fibrosis and exhibit more‐expansive remodeling.70 Stages of Developmen t: Vessel Narrowing Plaque Evolution Plaque Growth and Aneurysm Formation • A vascular aneurysm may develop just downstream from a large atherosclerotic plaque. • Narrowing due to the atherosclerotic plaque changes hemodynamic factors, causing turbulent flow just behind the plaque. • As the vascular wall stretches, it weakens and the aneurysm starts to form, causing increased vascular diameter. • This leads to further changes in hemodynamic forces that increase wall tension High blood pressure Dyslipidemia Smoking Diabetes Risk of Atheroscler osis Metabolic syndrome • Waist circumference • Blood triglycerides • HDL cholesterol • Hypertension • Hyperglycemia Unhealthy diet Family history Inflammatory diseases Older age • Plaque buildup starts in childhood and gets worse as we get older. • In males, the risk increases after age 45 • In females, the risk increases after age 55 • The risk for females is higher if there is a history of endometriosis or polycystic ovary syndrome, or if the patient had gestational diabetes or preeclampsia during pregnancy 1. Managing blood pressure with a goal of systolic <120 mm Hg and diastolic <80 mm Hg 2. Controlling cholesterol through lifestyle changes and medications as necessary How to Reduce Risk? 3. Reducing blood glucose level 4. Increasing physical activity 5. Eating a healthy diet (reasonable portions; a variety of fruits, vegetables, whole grains, poultry, and fish; and avoiding added salt, sugar, and saturated and trans fats) 6. Losing weight 7. Stopping smoking Potential Complicati ons Familial Hypercholesterolemia • Autosomal dominant disorder that is associated with lifelong elevated levels of LDL cholesterol. • The most common is a defect in the LDL receptor that reduces its ability to bind circulating LDL particles and to remove them into cells by receptor-mediated endocytosis. • Heterozygous form (HeFH) may affect as many as one in 200 to 250 persons in the US • Homozygous form (HoFH) is very rare and affects less than one in 250,000 people • For most people with HeFH, cholesterol levels are elevated the throughout life and need to be managed with statin drugs and other cholesterol-lowering medications. • Individuals with HoFH are often recognized early, based on family history and the physical findings of xanthomas on tendons and fingers, and arcus corneae, a gray ring around the cornea. • Require aggressive treatment Patient Group Guidelines for Lipid Lowering Agents Recommendation 1. High-intensity statin to achieve ≥50% LDL reduction Clinical atherosclerotic disease (ASCVD) 2. If LDL remains ≥70 mg/dL: Consider (Coronary artery disease, history of adding ezetimibe stroke, transient ischemic cerebral 3. If very high risk and LDL still ≥70 attack, peripheral vascular disease, or mg/dL on maximally tolerated statin + aortic aneurysm) ezetimibe: Consider adding PCSK9 inhibitor 1. High-intensity statin to achieve ≥50% LDL reduction 2. If <50% LDL reduction achieved or LDL remains ≥100 mg/dL: Consider adding ezetimibe 3. If LDL reduction still <50%: Consider adding bile acid sequestrant, do not add LDL cholesterol ≥190 mg/dL at baseline if triglycerides >300 mg/dL) 4. If pt has heterozygous familial hypercholesterolemia and LDL still ≥100 mg/dL 5. (or if baseline LDL ≥ 220 mg/dL, age 40-75 and LDL still ≥130 mg/dL): Consider adding PCSK9 inhibitor Diabetes Age 40-75 Moderate-intensity statinc to achieve ≥30% LDL reduction • Regardless of ASCVD risk High-intensity statina to achieve ≥50% • Multiple ASCVD risk factors LDL reduction • 10-year ASCVD riskd ≥20% High-intensity statina plus ezetimibe, if Patient Group Recommendation Diabetes Guidelines for Lipid Lowering Agents Age > 75 Data are limited; statin therapy reasonable after discussion of benefits and risks Age 20-39 Consider statin if diabetes of long duration, estimated GFR < 60 mL/min/1.73 m2, or presence of albuminuria, retinopathy, neuropathy, or reduced ankle-brachial index Primary prevention (age 40-75, nondiabetic, LDL 70-189 mg/dL): Calculate 10-year risk of cardiovascular event • Low risk (<5%) Lifestyle improvements • Borderline risk (5%-7.5%) If risk enhancers presente: Consider moderateintensity statinc • Intermediate risk (7.5%-20%) Moderate-intensity statin,c especially if risk enhancers present,e to achieve ≥30% LDL reduction (if decision to treat uncertain, consider obtaining coronary calcium scoref) If insufficient reduction of LDL due to statin intolerance, consider adding ezetimibe or bile acid sequestrant ( • High risk (≥20%) Moderate-high intensity statin to achieve ≥50% LDL reduction Lipoprotein Transport System Extrinsic and Intrinsic Pathway Exogenous (Intestinal) Pathway Dietary fats are absorbed by the small intestine and repackaged as chylomicrons Enter the circulation via the lymphatic system. Apo E and subtypes of apo C are transferred to chylomicrons from HDL particles in the bloodstream. Apo C enhances interactions of chylomicrons with lipoprotein lipase (LPL) on the endothelial surface of adipose and muscle tissue. This reaction hydrolyzes the triglycerides within chylomicrons into free fatty acids (FFAs), which are stored by adipose tissue or used for energy in cardiac and skeletal muscle. Chylomicron remnants are removed from the circulation by the liver, mediated by apo E. Endogenous (Hepatic) Pathway The liver packages cholesterol and triglycerides into VLDL particles, accompanied by apo B-100 and phospholipid. The triglyceride content of VLDL is much higher than that of cholesterol VLDL is catabolized by LPL releasing fatty acids to muscle and adipose tissue. During this process, VLDL also interacts with HDL, exchanging some of its triglyceride for apo C subtypes, apo E, and cholesteryl ester from HDL. Approximately 50% of the VLDL remnants are then cleared in the liver by hepatic receptors that recognize apo E. The remaining IDL is catabolized further by LPL and hepatic lipase (HL), which remove additional triglyceride, apo E, and apo C, forming LDL particles. Plasma clearance of LDL occurs primarily via LDL receptor–mediated endocytosis in the liver and peripheral cells, directed by LDLs apo B-100 and apo E. Extrinsic and Intrinsic Pathway Ischemic Heart Disease Objectives: Part 3 • Describe the normal pattern of blood flow to the left heart and the right heard—how does it differ from other vascular beds? • List the factors that determine myocardial oxygen supply and myocardial oxygen demand • Describe different patterns of atherosclerotic coronary artery occlusion that result in the clinical syndromes of angina • Identify unique aspects of coronary artery disease presentation and pathophysiology in women, compared to men. Coronary Arteries • Oxygen and nutrients are delivered to the heart muscle by a left and a right coronary artery • The coronary arteries arise from the root of the aorta and divide into smaller vessels that penetrate the thick myocardium to provide a dense capillary supply. • RCA supplies 1. Right ventricle 2. Inferior and posterior side of the left ventricle 3. Posterior one third of the interventricular septum 4. AV node • The left coronary artery (left main), give rise to the left anterior descending (LAD) and the left circumflex (LCX) arteries. • The LAD artery provides blood to the anterior wall of the left ventricle, the apex of the heart, and the anterior two thirds of the interventricular septum. • The LCX artery provides the blood for the lateral and posterior walls of the left ventricle. • The SA nodal artery arises from the RCA in 70% of the population, from the LCX artery in 25% of people, and from both the RCA and LCX arteries in 5% of the population Coronary Veins • The coronary veins are distributed along the major coronary arteries. • These vessels return blood from the myocardial capillaries to the right atrium through the coronary sinus. Cardiac Oxygen Supply • Oxygen delivery requires adequate pulmonary function to oxygenate the blood and clear carbon dioxide, as well as adequate blood flow • Peak flow occurs during Diastole • Blood flow to the left ventricle is higher than that to the right ventricle. • During systole, the cardiac muscle contracts and compresses the coronary vasculature, increasing its local resistance and limiting blood flow. • At the onset of diastole, coronary blood flow increases. As aortic pressure drops during diastole, the ventricles are relaxing, relieving the coronary vessels from compression. • The duration of diastole affects total myocardial blood flow. • If heart rate increases, the duration of diastole shortens, while the duration of systole remains constant Blood Flow Throughou t the Cardiac Cycle Intrinsic Control of Coronary Artery Tone • The heart cannot increase oxygen extraction on demand because in its basal state, it removes nearly as much oxygen as possible from its blood supply. • Additional oxygen requirements must be met by an increase in blood flow, achieved through: • Metabolic Factors • Endothelia Factors • NO • Prostacyclin • EDHF • Endothelin 1 • Neural Factors Metabolic Factors • During states of tissue hypoxia, aerobic metabolism is impaired. • Consequently, adenosine diphosphate (ADP) and adenosine monophosphate (AMP) accumulate and are subsequently degraded to adenosine. • Adenosine is a potent vasodilator and is thought to be the primary metabolic mediator of vascular tone. • Adenosine decreases calcium entry into cells Endothelia Factors • NO: Regulates vascular tone by diffusing into and then relaxing neighboring arterial smooth muscle • Prostacyclin: Regulates vascular tone, relaxation of vascular smooth muscle • EDHF : Regulates vascular tone, relaxation of vascular smooth muscle • Endothelin 1: Potent vasoconstrictor produced by endothelial cells that partially counteracts the actions of the endothelial vasodilators Neural Factors • The neural control of vascular resistance has both sympathetic and parasympathetic components. • Coronary vessels contain both α-adrenergic and β2adrenergic receptors. • Stimulation of α-adrenergic receptors results in vasoconstriction, whereas stimulation of β2-receptors promotes vasodilatation. Cardiac Oxygen Demand • Sympathetic discharge increases heart rate and cardiac contractility, both of which increase myocardial oxygen demand. • Simultaneously, reduced duration of diastole decreases oxygen supply. • Furthermore, any condition that increases cardiac work, such as increased preload, afterload, or contractility, also increases oxygen demand. Patho of Ischemic Heart Disease Stenosis • The hemodynamic significance of a coronary artery stenosis depends on both the degree of narrowing of the epicardial portion of the vessel and the amount of compensatory vasodilatation the distal resistance vessels can achieve. • If a stenosis narrows the lumen diameter by <60%, the maximal potential blood flow through the artery is not significantly altered and, in response to exertion, the resistance vessels can dilate to provide adequate blood flow. • When a stenosis narrows the diameter by more than 70%, resting blood flow is normal, but maximal blood flow is reduced even with full dilatation of the resistance vessels. • In this situation, when oxygen demand increases coronary flow reserve is inadequate, oxygen demand exceeds supply, and myocardial ischemia results. • If the stenosis compromises the vessel lumen by more than 90%, then even with maximal dilatation of the resistance vessels, blood flow may be inadequate to meet basal requirements and ischemia can develop at rest. Interaction Between Platelets and Endothelia Cells Patterns of Angina • Stable angina is triggered by exercise or other physically demanding activities. These symptoms resolve shortly after stopping the activity. • This symptom is often the initial clue that cardiac blood flow is not delivering enough oxygen to meet the heart’s needs. • Stable angina may show some acute improvement using a vasodilator such as nitroglycerin. • Nitroglycerin relaxes smooth muscle in the walls of the veins, increasing blood pooling in these capacitance vessels, which reduces the preload and, consequently, the work of the heart. • Unable angina represents progression. Angina does not follow a predictable pattern, can arise without physical exertion, and may not be alleviated by medication. • This indicative of deterioration of coronary blood flow and should be regarded as an emergency. Patterns of Angina • Variant angina, also known as Prinzmetal angina, is a less common condition that does not begin during exertion but characteristically occurs while resting, during the night, or during early morning hours. Pain and nausea are typically severe and are not relieved by rest. • Variant angina is triggered by coronary vasospasms and is not indicative of a coronary plaque-based restriction. • Variant angina can be treated using vasodilators such as nitroglycerin • Unfortunately, coronary arterial vasospasms are thought to be the primary event associated with triggering sudden cardiac death. Quality • “pressure,” “discomfort,” “tightness,” “burning,” or “heaviness” Location Clinical Features of Stable Angina • Diffuse • Retrosternal area or in the left precordium but may occur anywhere in the chest, back, arms, neck, lower face, or upper abdomen Accompanying symptoms • Dyspnea, weakness, and fatigue, tachycardia, diaphoresis, and nausea Precipitating Factors • Increased O2 demand • Unless strictly vasospasm Frequency • Varies based on patient activities Risks • Atherosclerosis, cigarette smoking, dyslipidemia, hypertension, diabetes, and a family history of premature coronary disease Physical Exam • If it is possible to examine a patient during an anginal attack evaluate for: • increased heart rate and blood pressure • Myocardial ischemia may lead to papillary muscle dysfunction and therefore mitral regurgitation. • Ischemia-induced regional ventricular contractile abnormalities can sometimes be detected as an abnormal bulging impulse on palpation of the left chest. • Ischemia decreases ventricular compliance, producing a stiffened ventricle and therefore an S4 heart sound on physical examination during atrial contraction • However, if the patient is free of chest discomfort during the examination, there may be no abnormal cardiac physical findings. Diagnostic Studies: ECG • During myocardial ischemia, ST-segment and T-wave changes can appear • Acute ischemia usually results in transient horizontal or downsloping ST-segment depressions and T-wave flattening or inversions • ST-segment elevations are seen can be seen, suggesting more severe transmural myocardial ischemia; however, they will quickly normalize with resolution of the patient's symptoms. Exercise Testing • The test is considered abnormal if the patient's typical chest discomfort is reproduced or if ECG abnormalities consistent with ischemia develop • The stress test is considered markedly positive if one or more of the following signs of severe ischemic heart disease occur: 1. Ischemic ECG changes develop in the first 3 minutes of exercise or persist 5 minutes after exercise has stopped 2. The magnitude of the ST-segment depressions is >2 mm 3. The systolic blood pressure abnormally falls during exercise 4. High-grade ventricular arrhythmias develop 5. The patient cannot exercise for at least 2 minutes because of cardiopulmonary limitation. Nuclear Imaging • A radionuclide is injected intravenously at peak exercise then imaging is performed • The radionuclide accumulates in proportion to the degree of perfusion of viable myocardial cells • Ischemic areas appear as “cold spots” • To differentiate between transient ischemia and infarcted tissue • Imaging is also performed at rest If the cold spot fills in a region of transient ischemia has been identified but if the cold spot remains unchanged, a region of irreversible infarction is likely Condition Differentiating Features Cardiac Differentia l Diagnosis Myocardial ischemia • Retrosternal tightness or pressure; typically radiates to the neck, jaw, or left shoulder and arm • Lasts a few minutes (usually <10) • Brought on by exertion, relieved by rest or nitroglycerin • ECG: transient ST depressions or elevations, or flattened or inverted T waves Pericarditis • Sharp, pleuritic pain that varies with position; friction rub may be present on auscultation • Can last for hours to days • ECG: diffuse ST elevations and PR deviation (see Chapter 14) Gastrointestinal Gastroesophageal reflux • Retrosternal burning • Precipitated by certain foods, worsened by supine position, unaffected by exertion • Relieved by antacids Condition Differentiating Features Gastrointestinal Differentia l Diagnosis Peptic ulcer disease • Epigastric ache or burning • Occurs after meals, unaffected by exertion • Relieved by antacids, not by nitroglycerin Esophageal spasm • Retrosternal pain accompanied by dysphagia • Precipitated by meals, unaffected by exertion • May be relieved by nitroglycerin Biliary colic • Constant, deep pain in right upper quadrant; can last for hours • Brought on by fatty foods, unaffected by exertion • Not relieved by antacids or nitroglycerin Musculoskeletal Costochondral syndrome • Sternal pain worsened by chest movement • Costochondral junctions tender to palpation • Relieved by anti-inflammatory drugs, not by nitroglycerin Cervical radiculitis • Constant ache or shooting pains; may be in a dermatomal distribution • Worsened by neck motion Pattern of Ischemic Heart Disease in Females: Symptoms • Females are more likely overall to report angina. • Females are less likely to report exertional angina and more likely to report emotional stress-induced angina and persistent angina, as well as angina at rest. • Females are more likely to report that their angina is associated with decreased quality of life. • Females with angina are more likely than males to have an array of associated symptoms, including pain in the back, neck, and jaw; shortness of breath; nausea or indigestion; and fatigue. Pattern of Ischemic Heart Disease in Females: Pathology • Pathological analysis reveals a disconnect between the extent to which the coronary arteries are narrowed and the amount of myocardial ischemia. • Although many females have severely narrowed coronary arteries on coronary angiography, other females with severe myocardial ischemia may have no angiographic signs of lumen narrowing. • Recent studies have identified coronary microvascular dysfunction in both males and females who have angina and even myocardial infarction without the signs of disease in the large coronary arteries. Pattern of Ischemic Heart Disease in Females Medical Treatment Drug Class Mechanism of Action Organic nitrates** ↓ ↓ ↑ ↑ ↓ Adverse Effects Myocardial O2 demand Preload (venodilatation) • Headache • Hypotension O2 supply • Reflex tachycardia Coronary perfusion Coronary vasospasm β-Blockers ↓ Myocardial O2 demand ↓ Contractility ↓ Heart rate • Excessive bradycardia • ↓ LV contractile function • Bronchoconstriction • May mask hypoglycemic symptoms • Fatigue Calcium channel blockers (agent specific; see footnote) ↓ ↓ ↓ ↓ ↓ ↑ ↑ ↓ • Headache, flushing • ↓↓ LV contractility (V, D) • Marked bradycardia (V, D) • Edema (especially N, D) • Constipation (especially V) Ranolazine ↓ Late phase inward sodium current Myocardial O2 demand Preload (venodilatation) Wall stress (↓BP) Contractility (V, D) Heart rate (V, D) O2 supply Coronary perfusion Coronary vasospasm • Dizziness, headache • Constipation, nausea BP, blood pressure; D, diltiazem; LV, left ventricular; N, nifedipine and other dihydropyridine calcium channel antagonists; V, verapamil. Drug Class Aspirin Medical Treatment to Prevent Acute Events Platelet P2Y12 ADP receptor antagonists Lipid-lowering therapy Angiotensin-converting enzyme (ACE) inhibitors Mechanism of Action • Inhibition of synthesis of thromboxane A • anti-inflammatory properties that may be important in stabilizing atheromatous plaque • Prevent platelet activation and aggregation • Can be used in combo with ASA • Help stabilize existing atherosclerosis • Reduces preload and afterload Percutaneous Coronary Interventions (PCI) Interventio nal Treatment Coronary Artery Bypass Graft Surgery (CABG) More effective for long-term Less invasive than CABG relief of angina than PCI or pharmacologic therapy Shorter hospital stay and easier recuperation than CABG Most complete revascularization Superior to pharmacologic therapy for relief of angina •Survival advantage in patients with >50% left main coronary artery stenosis • Multivessel coronary disease, especially if LV contractile function is impaired Case 1 • Patient Complaint: “My legs swell up every day after work. This didn’t happen to me until I started that new medication. I was feeling fine before. My blood pressure never made me feel bad.” • History of Present Illness: A 43-year-old man was diagnosed with essential hypertension 2 weeks ago at his previous visit. Amlodipine, 5 mg, was initiated, and he has been taking this daily as prescribed. He has continued to obtain home blood pressure readings: Mean blood pressure values are now <130 mm Hg systolic and <80 mm Hg diastolic. He is feeling well; however, he reports bilateral lower extremity edema and fullness. The swelling is worse in the evening, after standing on his feet most of the day at work. It improves after elevating his legs. Laboratory values obtained at his last visit were all unremarkable, and the review of systems is similarly unchanged. • Past Medical/Family History: His past medical history is significant for obesity and osteoarthritis of his right knee. His family history, as noted previously, is significant for prostate cancer, hypertension and hyperlipidemia on his father’s side, and hypertension, hyperlipidemia, and diabetes mellitus type 2 on his mother’s side. He currently takes naproxen, 500 mg twice a day as needed, for knee pain. Case 1 • Physical Examination: You observe a wellappearing obese man in no acute distress. The patient is alert and oriented. • Cardiovascular examination reveals regular rate and rhythm, with no murmurs, thrills, or gallops. Lungs are clear to auscultation bilaterally. • Abdomen is soft, nontender, and nondistended, with no renal masses or aortic or renal artery bruits. • Examination of the extremities now reveals +1 pitting edema bilaterally, with normal peripheral pulses. • Laboratory and Diagnostic Findings: You perform baseline tests, including electrolytes and serum creatinine, fasting glucose, urinalysis, CBC, TSH, and lipids; obtain an ECG Questions • What role do calcium channels play in VSM cell function? • How might blocking calcium channels lead to increased capillary filtration manifested as edema? Case 2 • Patient Complaint: “I keep having this pressure all over my chest and I feel short of breath. It started while I was raking leaves in the yard this morning. It went on for about 5 minutes before it finally got better. It seemed to help if I sat down for a bit, but it came right back if I tried to rake again.” • History of Present Illness/Review of Systems: The patient is a 54-year-old man who presents to the ED with complaints of two episodes of chest pressure and dyspnea on exertion that occurred this morning while working in his yard. He noted some radiation to the left lower jaw. During the episode, his discomfort was a 6 out of 10. The symptoms lasted about 5 minutes and were relieved by rest. He denies any symptoms currently. He has never experienced anything similar before. Chest pain and shortness of breath are reported; all other systems negative. • Past Medical/Family/Social History: The patient has a history of hypertension. He has smoked 1 pack of cigarettes per day for 20 years. He reports a family history of ischemic stroke in his mother at age 62. He takes lisinopril, 5 mg daily. Case 2 • Physical Examination: • Temperature of 98.4°F; blood pressure of 138/76 mm Hg, heart rate of 92 beats/min, and respirations of 12 breaths/min. • The patient is alert and oriented. Skin color is normal with no rashes. Head is normocephalic. Pupils are equal, round, reactive to light, and accommodating. • Neck is supple with no carotid bruits, jugular venous distention, lymphadenopathy, or tenderness. Oral mucous membranes are moist and without lesions. • Lungs are clear to auscultation. Chest is without tenderness to palpation, with no masses. • Heart rate is regular, with no murmurs, thrills, or gallops noted. • Abdomen is soft, nondistended, and nontender. No peripheral edema is noted, with 1+ radial and pedal pulses. • Laboratory and Diagnostic Findings: The ECG: see next slide. Posteroanterior and lateral chest radiographs show no cardiopulmonary abnormalities. Laboratory tests of CBC, CMP, and troponin are unremarkable. Case 2 ECG Case 2 Questions • What aspects of the patient’s history, physical, and laboratory and diagnostic findings provide support for a diagnosis of myocardial ischemia? • What are the patient’s risk factors for coronary artery disease? What additional tests might the provider request to evaluate this risk?