Pathophysiology of Heart Disease

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
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