Pathophysiology of Heart Disease

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Cleaned scanned version with corrected pagination, page orientation and bookmarks. Cover Pathophysiology of Heart Disease Copyright Dedication List of Contributors Foreword Preface Table of Contents Chapter 1: Normal Cardiac Structure and Function Cardiac Anatomy and Histology Pericardium Surface Anatomy of the Heart Internal Structure of the Heart Right Atrium and Ventricle Left Atrium and Ventricle Interventricular Septum Impulse-Conducting System Cardiac Innervation Cardiac Vessels Coronary Arteries Coronary Veins Lymphatic Vessels Histology of Ventricular Myocardial Cells Basic Electrophysiology Ion Movement and Channels Energetics Permeability Resting Potential Action Potential Cardiac Muscle Cell 1 Phase 0 Phase 1 Phase 2 Phase 3 Spedaltzed Conduction System Pacemaker Cells Refractory Periods Impulse Conduction Normal Sequence of Cardiac Depolarization Excitation–Contraction Coupling Contractile Proteins in the Myocyte Caldum-Induced Caldum Release and the Contractile Cycle Introduction to Cardiac Signaling Systems β-Adrenergic and Cholinergic Signaling Summary Acknowledgments Additional Reading Chapter 2: The Cardiac Cycle: Mechanisms of Heart Sounds and Murmurs Cardiac Cycle Heart Sounds First Heart Sound (S1) Second Heart Sound (S2) Extra Systolic Heart Sounds Early Extra Systolic Heart Sounds Mid- or Late Extra Systolic Heart Sounds Extra Diastolic Heart Sounds Opening Snap Third Heart Sound (S3) Fourth Heart Sound (S4) Quadruple Rhythm or Summation Gallop Pericardial Knock Murmurs Systolic Murmurs Diastolic Murmurs Continuous Murmurs Summary Acknowledgments Additional Reading Chapter 3: Cardiac Imaging and Catheterization Cardiac Radiography Cardiac Silhouette Pulmonary Manifestations of Heart Disease Echocardiography Ventricular Assessment Valvular Lesions Coronary Artery Disease Cardiomyopathy Pericardial Disease Cardiac Catheterization Measurement of Pressure Right Atrial Pressure Rtght Ventricular Pressure Pulmonary Artery Pressure Pulmonary Artery Wedge Pressure Measurement of Blood Flow Calculation of Vascular Resistance Contrast Angiography Nuclear Imaging Assessment of Myocardial Perfusion Radionuclide Ventriculography Assessment of Myocardial Metabolism Computed Tomography Magnetic Resonance Imaging Integration Summary Acknowledgments Additional Reading Chapter 4: The Electrocardiogram Electrical Measurement—Single-Cell Model Electrocardiographic Lead Reference System Sequence of Normal Cardiac Activation Interpretation of the Electrocardiogram Calibration Heart Rhythm Heart Rate Intervals (PR, QRS, QT) Mean QRS Axis Abnormalities of the P Wave Abnormalities of the QRS Complex Ventricular Hypertrophy Bundle Branch Blocks Fascicular Blocks Pathologic Q waves in Myocardial Infarction ST-Segment and T-Wave Abnormalities Transient Myocardial Ischemia Acute ST-Segment Elevation MI Acute Non-ST-Segment Elevation MI Summary Acknowledgments Additional Reading Chapter 5: Atherosclerosis Vascular Biology of Atherosclerosis Normal Arterial Wall Endothelial Cells Vascular Smooth Muscle Cells Extracellular Matrix Atherosclerotic Arterial Wall Fatty Streak Endothelial Dysfunction Lipoprotein Entry and Modification Leukocyte Recruitment Foam Cell Formation Plaque Progression Smooth Muscle Cell Migration Extracellular Matrix Metabolism Plaque Disruption Plaque Integrity Tnrombogenk Potential Complications of Atherosclerosis Atherosclerosis Risk Factors Genetics Traditional Risk Factors Dyslipidemia Lipid-Altering Therapy Tobacco Smoking Hypertension Antihypertensive Therapy Diabetes Mellitus and the uMetabolic Syndrome" Lack of Physical Activity Estrogen Status Biomarkers of Cardiovascular Risk Upoprotein (a) C-Reactive Protein (CRP) and Other Markers of Inflammation Outlook Summary Acknowledgments Additional Reading Chapter 6: Ischemic Heart Disease Determinants of Myocardial Oxygen Supply and Demand Myocardial Oxygen Supply External Compression Intrinsic Control of Coronary Arterial Tone Metabolic Factors Endothelial Factors Neural Factors Myocardial Oxygen Demand Pathophysiology of Ischemia Fixed Vessel Narrowing Fluid Mechanics Anatomy Endothelial Cell Dysfunction Inappropriate Vasoconstriction Loss of Normal Antithrombotic Properties Other Causes of Myocardial Ischemia Consequences of Ischemia Ischemic Syndromes Stable Angina Unstable Angina Variant Angina Silent Ischemia Syndrome X Clinical Features of Chronic Stable Angina History Quality Location Accompanying Symptoms Predpitants Frequency Risk Factors Differential Diagnosis Physical Examination Diagnostic Studies Electrocardiogram Stress Testing Standard Exercise Testing Nuclear Imaging Studies Exercise Echocardiography Pharmacologic Stress Tests Coronary Angiography Noninvasive Imaging of Coronary Arteries Natural History Treatment Medical Treatment of an Acute Episode of Angina Medical Treatment to Prevent Recurrent Ischemic Episodes Medical Treatment to Prevent Acute Cardiac Events Revascularization Medical versus Revascularization Therapy Summary Acknowledgments Additional Reading Chapter 7: Acute Coronary Syndromes Pathogenesis of Acute Coronary Syndromes Normal Hemostasis Endogenous Antithrombotic Mechanisms Inactivation of Clotting Factors Lysis of Fibrin Clots Endogenous Platelet Inhibition and Vasodilatation Pathogenesis of Coronary Thrombosis Significance of Coronary Thrombosis Nonatherosclerotic Causes of Acute Myocardial Infarction Pathology and Pathophysiology Pathologic Evolution of Infarction Early Changes in Infarction Late Changes in Infarction Functional Alterations Impaired Contractility and Compliance Stunned Myocardium Ischemic Preconditioning Ventricular Remodeling Clinical Features of Acute Coronary Syndromes Clinical Presentation Unstable Angina Acute Myocardial Infarction Diagnosis of Acute Coronary Syndromes ECG Abnormalities Serum Markers of Infarction Cardiac-specific Troponins Creatine Kinase Imaging Treatment of Acute Coronary Syndromes Acute Treatment of Unstable Angina and Non-ST-Elevation Myocardial Infarction Anti-ischemic Therapy Antithrombotic Therapy Antiplatelet Drugs Anticoagulant Drugs Conservative versus Early Invasive Management of UA and NSTEMI Acute Treatment of ST-Elevation Myocardial Infarction Primary Percutaneous Coronary Intervention Fibrinolytic Therapy Adjunctive Therapies Complications Recurrent Ischemia Arrhythmias Ventricular Fibrillation Supraventricular Arrhythmias Conduction Blocks Myocardial Dysfunction Heart Failure Cardiogenic Shock Right Ventricular Infarction Mechanical Complications Papillary Muscle Rupture Ventricular Free Wall Rupture Ventricular Septal Rupture True Ventricular Aneurysm Pericarditis Dressler Syndrome Thromboembolism Risk Stratification and Management Following Myocardial Infarction Summary Acknowledgments Additional Reading Chapter 8: Valvular Heart Disease Mitral Valve Disease Mitral Stenosis Etiology Pathology Pathophysiology Clinical Manifestations and Evaluation Presentation Examination Treatment Mitral Regurgitation Etiology Pathophysiology Clinical Manifestations and Evaluation Presentation Examination Natural History and Treatment Mitral Valve Prolapse Aortic Valve Disease Aortic Stenosis Etiology Pathology Pathophysiology Clinical Manifestations and Evaluation Presentation Examination Natural History and Treatment Aortic Regurgitation Etiology Pathophysiology Clinical Manifestations and Assessment Presentation Examination Treatment Tricuspid Valve Disease Tricuspid Stenosis Tricuspid Regurgitation Pulmonic Valve Disease Pulmonic Stenosis Pulmonic Regurgitation Prosthetic Valves Infective Endocarditis Pathogenesis Clinical Manifestations Treatment Prevention Summary Acknowledgments Additional Reading Chapter 9: Heart Failure Physiology Determinants of Contractile Function in the Intact Heart Preload Afterload Contractility (Also Termed ulnotropic State") Pressure–Volume Loops Alterations in Preload Alterations in Afterload Alterations tn Contractutty Pathophysiology Heart Failure with Reduced EF Heart Failure with Preserved EF Right-Sided Heart Failure Compensatory Mechanisms Frank–Starling Mechanism Neurohormonal Alterations Adrenergic Nervous System Renin–Angiotensin–Aldosterone System Antidiuretic Hormone Natriuretic Peptides Other Peptides Ventricular Hypertrophy and Remodeling Myocyte Loss and Cellular Dysfunction Precipitating Factors Clinical Manifestations Symptoms Physical Signs Diagnostic Studies Prognosis Treatment of Heart Failure with Reduced Ejection Fraction Diuretics Vasodilators Positive Inotropic Drugs β-Blockers Aldosterone Antagonist Therapy Additional Therapies Arrhythmia Management Cardiac Resynchronization Therapy Cardiac Mechanical Circulatory Support and Replacement Therapy Treatment of Heart Failure with Preserved Ejection Fraction Acute Heart Failure Acute Pulmonary Edema Summary Acknowledgments Additional Reading Chapter 10: The Cardiomyopathies Dilated Cardiomyopathy Etiology Pathology Pathophysiology Clinical Findings Physical Examination Diagnostic Studies Treatment Medical Treatment of Heart Failure Symptoms Prevention and Treatment of Arrhythmias Prevention of Thromboembolic Events Cardiac Transplantation Hypertrophic Cardiomyopathy Etiology Pathology Pathophysiology HCM without Outflow Tract Obstruction HCM with Outflow Obstruction Clinical Findings Physical Examination Diagnostic Studies Treatment Prognosis Restrictive Cardiomyopathy Pathophysiology Clinical Findings Physical Examination Diagnostic Studies Treatment Other Forms of Cardiomyopathy Left Ventricular Noncompaction Arrhythmogen;c Right Ventricular Cardiomyopathy Summary Acknowledgments Additional Reading Chapter 11: Mechanisms of Cardiac Arrhythmias Normal Impulse Formation Ionic Basis of Automatidty Native and Latent Pacemakers Overdrive Suppression Electrotonic Interactions Altered Impulse Formation Alterations in Sinus Node Automatidty Increased Sinus Node Automatidty Decreased Sinus Node Automatidty Escape Rhythms Enhanced Automaticity of Latent Pacemakers Abnormal Automatidty Triggered Activity Altered Impulse Conduction Conduction Block Unidirectional Block and Reentry Accessory Pathways and the Wolff–Parkinson–White Syndrome Physiologic Basis of Antiarrhythmic Therapy Bradyarrhythmias Pharmacologic Therapy Electronic Pacemakers Tachyarrhythmias Pharmacologic Therapy Vagotonic Maneuvers Electric Cardioversion and Defibrillation Implantable Cardioversion–Defibrillators Catheter Ablation Summary Acknowledgments Additional Reading Chapter 12: Clinical Aspects of Cardiac Arrhythmias Bradyarrhythmias Sinoatrial Node Sinus Bradycardia Sick Sinus Syndrome Escape Rhythms Atrioventricular Conduction System First-Degree AV Block Second-Degree AV Block Third-Degree AV Block Tachyarrhythmias Supraventricular Arrhythmias Sinus Tachycardia Atrial Premature Beats Atrial Flutter Atrial Fibrillation Paroxysmal Supraventricular Tachycardias AV Nodal Reentrant Tachycardia Atrioventricular Reentrant Tachycardias Ventricular Preexdtation Syndrome Concealed Accessory Pathways Focal Atrial Tachycanna Multifocal Atrial Tachycardia Ventricular Arrhythmias Ventricular Premature Beats Ventricular Tachycardia Distinguishing Monomorphic VT from Supraventricular Tachycardia Management of Patients with VT Torsades de Pointes Ventricular Fibrillation Summary Acknowledgments Additional Reading Chapter 13: Hypertension What Is Hypertension? How Is Blood Pressure Regulated? Hemodynamic Factors Blood Pressure Reflexes Essential Hypertension Genetics and Epidemiology Experimental Findings Systemic Abnormalities Insulin Reststance, Obesity, and the Metabolic Syndrome Natural History Secondary Hypertension Patient Evaluation Exogenous Causes Renal Causes Renal Parenchymal Disease Renovascular Hypertension Mechanical Causes Coarctation of the Aorta Endocrine Causes Pheochromocytoma Adrenocortical Hormone Excess Thyroid Hormone Abnormalftfes Consequences of Hypertension Clinical Signs and Symptoms Organ Damage Caused by Hypertension Heart Left Ventricular Hypertrophy and Diastolic Dysfunction Systolic Dysfunction Coronary Artery Disease Cerebrovascular System Aorta and Peripheral Vasculature Kidney Retina Hypertensive Crisis Treatment of Hypertension Nonpharmacologic Treatment Weight Reduction Exercise Diet Sodium Potassium Alcohol Other Smoking Cessation Relaxation Therapy Pharmacologic Treatment Summary Acknowledgments Additional Reading Chapter 14: Diseases of the Pericardium Anatomy and Function Acute Pericarditis Etiology Infectious Idiopathic and Viral Pericarditis Tuberculous Pericarditis Nontuberculous Bacterial Pericarditis (Purulent Pericarditis) Noninfectious Pericarditis following Myocardial Infarction Uremic Pericarditis Neoplastic Pericarditis Radiation-Induced Pericarditis Pericarditis Associated with Connective Tissue Diseases Drug-Induced Pericarditis Pathogenesis Pathology Clinical Features History Physical Examination Diagnostic Studies Treatment Pericardial Effusion Etiology Pathophysiology Clinical Features Diagnostic Studies Treatment Cardiac Tamponade Etiology Pathophysiology Clinical Features Diagnostic Studies Treatment Constrictive Pericarditis Etiology and Pathogenesis Pathology Pathophysiology Clinical Features Diagnostic Studies Treatment Summary Acknowledgments Additional Reading Chapter 15: Diseases of the Peripheral Vasculature Diseases of the Aorta Aortic Aneurysms Etiology and Pathogenesis of True Aortic Aneurysms Clfntcal Presentation and Dtagnosts Treatment Aortic Dissection Etiology, Pathogenesis, and Classification Clinical Presentation and Diagnosis Treatment Peripheral Artery Diseases Peripheral Atherosclerotic Vascular Disease Etiology and Pathogenesis Clinical Presentation and Diagnosis Treatment Acute Arterial Occlus;on Vasculitic Syndromes Vasospasm: Raynaud Phenomenon Venous Disease Varicose Veins Chronic Venous Insuffidency Venous Thromboembolism Deep Venous Thrombosis Epidemiology, Etiology, and Pathophysiology Clinical Presentation Diagnosis Treatment Pulmonary Embolism Epidemiology, Etiology, and Pathophysiology Clinical Presentation Diagnosis Treatment Superficial Thrombophlebitis Summary Acknowledgments Additional Reading Chapter 16: Congenital Heart Disease Normal Development of the Cardiovascular System Development of the Heart Tube Formation of the Heart Loop Septation Septation of the Atria Septation of the Atrioventricular Canal Septation of the Ventricles and Ventricular Outflow Tracts Development of the Cardiac Valves Semilunar Valve Development (Aortic and Pulmonary Valves) Atrioventricular Valve Development (Mitral and Tricuspid Valves) Fetal and Transitional Circulations Fetal Circulation Transitional Circulation Common Congenital Heart Lesions Acyanotic Lesions Atrial Septal Defect Pathophysiology Symptoms Physical Examination Diagnostic Studies Treatment Ventricular Septal Defect Pathophysiology Symptoms Physical Examination Diagnostic Studies Treatment Patent Ductus Arteriosus Pathophysiology Symptoms Physical Examination Diagnostic Studies Treatment Congenital Aortic Stenosis Pathophysiology Symptoms Physical Examination Diagnostic Studies Treatment Pulmonic Stenosis Pathophysiology Symptoms Physical Examination Diagnostic Studies Treatment Coarctation of the Aorta Pathophysiology Symptoms Physical Examination Diagnostic Studies Treatment Cyanotic Lesions Tetralogy of Fallot Pathophysiology Symptoms Physical Examination Diagnostic Studies Treatment Transposition of the Great Arteries Pathophysiology Symptoms and Physical Examination Diagnostic Studies Treatment Eisenmenger Syndrome Summary Acknowledgments Additional Reading Chapter 17: Cardiovascular Drugs Inotropic Drugs and Vasopressors Cardiac Glycosides (Digitalis) Mechanism of Action Mechanical Effect Electrical Effect Clinical Uses Pharmacokinetics and Toxicity Sympathomimetic Amines Phosphodiesterase-3 Inhibitors Vasopressin Vasodilator Drugs Angiotensin-Converting Enzyme Inhibitors Clinical Uses Hypertension Heart Failure Adverse Effects Cough Hypotension Renal Insufficiency Hyperkalemia Other Effects Angiotensin II Type 1 Receptor Antagonists Direct-Acting Vasodilators Calcium Channel Blockers Mechanism of Action Vascular Smooth Muscle Cardiac Cells Clinical Uses Organic Nitrates Mechanism of Action Hemodynamic Effects and Clinical Uses Agents and Pharmacokinetics Adverse Effects Natriuretic Peptides Phosphodiesterase-5 Inhibitors Endothelin Receptor Antagonists Antiadrenergic Drugs Central Adrenergic Inhibitors (CNS α2-Agonists) Sympathetic Nerve-Ending Antagonists Peripheral α-Adrenergic Receptor Antagonists β-Adrenergic Receptor Antagonists Clinical Uses Ischemic Heart Disease Hypertension Heart Failure Adverse Effects Antiarrhythmic Drugs Class lA Antiarrhythmics Mechanism of Action Effect on Reentrant Arrhythmias Effect on Arrhythmias Caused by Increased Automaticity Effect on the Electrocardiogram Clinical Uses Specific Class lA Drugs Class IB Antiarrhythmics Mechanism of Action Clinical Uses Spedfic Class IB Drugs Class IC Antiarrhythmics Mechanism of Action Clinical Uses Specific Class IC Drugs Class II Antiarrhythmics Mechanism of Action Clinical Uses Class III Antiarrhythmics Mechanism of Action Specific Class Ill Drugs Amiodarone Other Class III Drugs Class IV Antiarrhythmics Mechanism of Action Clinical Uses Adenosine Diuretics Loop Diuretics Thiazide Diuretics Potassium-Sparing Diuretics Antithrombotic Drugs Platelet Inhibitors Aspirin Clinical Uses Adverse Effects Platelet P2Y 12 Receptor Antagonists Thienopyridines Ticagrelor Thrombin Receptor Antagonist (PAR-1 Antagonist) Glycoprotein IIb/IlIa Receptor Antagonists Dipyridamole Anticoagulant Drugs: Parenteral Agents Unfractionated Heparin Low Molecular Weight Heparins Direct Thrombin Inhibitors Factor Xa Inhibitor Anticoagulant Drugs: Oral Agents Warfarin Newer Oral Anticoagulants Lipid-Regulating Drugs HMG-CoA Reductase Inhibitors Bile Add-Binding Agents Cholesterol Absorption Inhibitors Niacin Fibrates Summary Acknowledgments Additional Reading Index A B C D E F G H I J K L M N O P Q R S T U V W X Y Z