Braunwald’s Heart Disease-A Textbook of Cardiovascular Medicine

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Cover IFC Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine Copyright Dedication Contributors Preface Preface to the First Edition Acknowledgments Contents Video Contents 1 1 - Cardiovascular Disease: Past, Present, and Future The Birth Early Stirrings Emergence of a Specialty Cardiac Imaging (see Part III) The Past The Present Cardiac Catheterization Percutaneous Coronary Intervention Cardiovascular Surgery Comments Hypertension (see Chapter 26) The Past The Present The Future Valvular Heart Disease (see Part VIII) The Past The Present Mitral Stenosis Mitral Regurgitation (MR) Transcatheter Aortic Valve Replacement Arrhythmias (SEE PART VII) The Past The Present Dyslipidemias (see ChapterS 25 and 27) The Past The Present siRNA-­inclisiran The Future Triglycerides Lipoprotein (a) Coronary Risk Factors Heart Failure (see Part VI) The Past The Present Assisted Circulation (see Chapter 58) The Past The Present The Future Genomics and Genetics (see Chapter 7) The Present The Future Precision Medicine Primordial Prevention (see Chapter 25) The Present The Future Inflammation (see Chapter 24) The Past The Present Canakinumab Colchicine The Future Clonal Hematopoiesis (see Chapter 24) Artificial Intelligence (see Chapter 11) The Present The Future Conclusions References 2 2 - Global Burden of Cardiovascular Disease Shifting Burden Epidemiologic Transitions Stage of Inactivity and Obesity: A Fifth Phase Different Patterns of Epidemiologic Transition High-­Income Countries East Asia and Pacific Demographic and Social Indices Burden of Disease Central and Eastern Europe and Central Asia Demographic and Social Indices Burden of Disease Latin America and the Caribbean Demographic and Social Indices Burden of Disease North Africa and Middle East Demographic and Social Indices Burden of Disease South Asia Demographic and Social Indices Burden of Disease Sub-­Saharan Africa Demographic and Social Indices Burden of Disease Risk Factors Tobacco Hypertension Lipids (see Chapter 27) Diabetes (see Chapter 31) Obesity (see Chapter 30) Diet (see Chapter 29) Physical Inactivity (see Chapters 30 and 32) Aging Populations (see Chapter 90) Genetic Fetal Influences Environmental Exposures (see Chapter 3) Economic Burden Cost-­Effective Solutions Risk Assessment Policy and Community Interventions Tobacco Use Salt, Dietary, and Lipid Reductions Summary and Conclusion References 3 3 - Impact of the Environment on Cardiovascular Health Air Pollution Composition and Sources of Air Pollution Particulate Air Pollutants Gaseous Pollutants Particulate Matter Sources, Composition, and Cardiovascular Risk Household Versus Ambient Air Pollution Assessment of Exposure Ischemic Heart Disease and Cerebrovascular Events Blood Pressure and Hypertension Insulin Resistance and Diabetes Heart Failure Arrhythmia Venous Thromboembolism Chronic Kidney Disease Climate Change Challenges and Outlook For the Future References 4 4 - Clinical Trials in Cardiovascular Medicine Components of Clinical Trials Rationale and Study Background Study Design Study Execution Randomization Blinding (Masking) Inclusion and Exclusion Criteria Endpoints or “Response Variables” Statistical Considerations in Trials Analysis of Primary and Secondary Endpoints Power and Sample Size Equipoise in Clinical Trials Randomization to Placebo and Standard of Care Potential for Harm in Clinical Trials Monitoring of Data and Data Safety Novel Approaches to Clinical Trial Design and Execution Pragmatic (Large Simple) Trials Use of Electronic Medical Records in Clinical Trials Adaptive Designs Interpretation of Clinical Trials Registration and Reporting of Clinical Trials Understanding the Primary Results Secondary Endpoints Interpretation of Subgroups Post-­hoc Analyses Conclusion References 5 5 - Clinical Decision-­Making in Cardiology Diagnostic Decisions Therapeutic Decisions Deciding When to Change Clinical Practice Based on New Clinical Research Findings Shared Decision-­Making System 1 and System 2 Thinking Teaching Clinical Reasoning Conclusion Classic References References Online-­Supplemental References Online-­Supplemental References 6 6 - Impact of Health Care Policy on Quality, Outcomes, and Equity in Cardiovascular Disease What is Health Policy Insurance Coverage and Access Policy Public Reporting Value-­Based Payment Programs: Hospitals Value-­Based Purchasing: Outpatient Alternative Payment Models Racial and Ethnic Minorities (see Chapter 93) Income Urban-­Rural Geography Conclusions References 7 7 - Applications of Genetics to Cardiovascular Medicine Key Principles of Human Genetics Central Dogma Heritability Genetic Architecture Genetic Variation Characterizing Human Genetic Variation Gene Discovery Family-­Based Studies Hypercholesterolemia and Coronary Artery Disease (see also Chapter 27) Metabolic Syndrome and Coronary Artery Disease Case-­Control and Population-­Based Studies Genome-­Wide Association Studies for Lipids Genome-­Wide Association Studies for Coronary Artery Disease Population-­Based Discovery of Rare Protein-­Coding Variants Associated with Coronary Artery Disease Causal Inference for Lipoproteins (see also Chapter 27) Causal Inference for Adiposity Mendelian Randomization Assumption Assessments Disease Risk Prediction Monogenic Coronary Artery Disease Polygenic Risk Scoring Polygenic Coronary Artery Disease Therapeutic Response Prediction Target Discovery and Clinical Trial Prediction On-­Target Therapeutic Side Effect Prediction Precision Medicine CYP2C19 (see also Chapter 38) Familial Hypercholesterolemia Polygenic Coronary Artery Disease Somatic Genomics (see also Chapter 24) Epigenetics Therapeutically Targeting the Genome Future Perspectives References 8 8 - Proteomics and Metabolomics in Cardiovascular Medicine Overview of the Discovery Process References 9 9 - Principles of Drug Therapeutics, Pharmacogenomics, and Biologics Risk Versus Benefit of Drug Therapy Clinical Trials Can Define Unexpected Adverse Drug Reactions Classes of Adverse Drug Reactions Pharmacokinetics and Pharmacodynamics Molecular and Genetic Basis for Variable Drug Response High-­Risk Pharmacokinetics Other Important Pharmacogenetic Effects Optimizing Drug Doses Plasma Concentration Monitoring Dose Adjustments in Disease Drug Interactions Incorporating Pharmacogenetic Information into Prescribing Future Perspectives References 10 10 - Biomarkers and Use in Precision Medicine Overview of Biomarkers Novel Technologies in Biomarker Identification Accuracy and Calibration Risk Reclassification External Validation and Impact Studies Conclusion References 11 11 - Artificial Intelligence in Cardiovascular Medicine Definitions and Key Terms Learning Supervised Learning Unsupervised Learning Reinforcement Learning Optimization and Hyperparameters Transfer Learning ECG-­Based Screening, Detection, and Prevention Image Interpretation and Procedural Guidance Nuclear Cardiology and Stress Testing Echocardiography Computed Tomography and Magnetic Resonance Imaging Coronary Arteriography Risk Scores (Deep Phenotyping) Conclusions References 12 12 - Wearable Devices in Cardiovascular Medicine Definitions and Overview Atrial Fibrillation Photoplethysmography Detection of Irregular Rhythm Electrocardiogram Hypertension Ancillary Information to the History Heart Rate and Rhythm Notifications Activity, Exercise, and Sleep Limitations The Future References 13 13 - History and Physical Examination: An Evidence-­Based Approach The History The General Physical Examination General Appearance Skin Head and Neck Extremities Chest and Abdomen The Cardiovascular Examination Jugular Venous Pressure and Waveform Assessing the Pulses Inspection and Palpation of the Heart Auscultation of the Heart First Heart Sound (S1) Second Heart Sound (S2) Systolic Sounds Diastolic Sounds Cardiac Murmurs Systolic Murmurs Diastolic Murmurs Continuous Murmurs Dynamic Auscultation Heart Failure (see Part VI) History Physical Examination Jugular Venous Pressure Third and Fourth Heart Sounds Rales and Edema Valsalva Maneuver Other Findings Patient with a Left Ventricular Assist Device Valvular Heart Disease (see also Part VIII) Mitral Stenosis Mitral Regurgitation Aortic Stenosis Aortic Regurgitation Tricuspid Valve Disease Pulmonic Valve Disease Prosthetic Heart Valves Pericardial Disease (see also Chapter 86) Pericarditis Pericardial Tamponade Constrictive Pericarditis Future Directions References 14 14 - Electrocardiography The Normal Electrocardiogram Atrial Activation and the P Wave Atrial Activation and the Normal P Wave Atrial Repolarization Heart Rate Variability Atrioventricular Node Conduction and the PR Segment Ventricular Activation and the QRS Complex Normal QRS Complex The Normal ST-­T Wave The QT Interval Other Repolarization Waves The U Wave The J Wave Normal Variants The Abnormal Electrocardiogram Chamber Enlargement and Hypertrophy Atrial Abnormalities Left Atrial Abnormality Diagnostic Criteria.Abnormalities in LA structure and function produce wide and notched P waves, with prominent terminal negativ... Right Atrial Abnormality Left Ventricular Hypertrophy Diagnostic Criteria Clinical Significance Right Ventricular Hypertrophy Diagnostic Criteria Clinical Significance Biventricular Hypertrophy Intraventricular Conduction Delays Fascicular Blocks Left Anterior Fascicular Block Left Posterior Fascicular Block Other Forms of Fascicular Block Left Bundle Branch Block Electrocardiogram Abnormalities Clinical Significance Right Bundle Branch Block Electrocardiogram Abnormalities Clinical Significance Multifascicular Blocks Myocardial Ischemia and Infarction Repolarization (ST-­T Wave) Abnormalities QRS Changes Evolution of Electrocardiogram Changes Other Ischemic ST-­T Patterns Electrocardiogram Localization of Myocardial Ischemia and Infarction Electrocardiogram Diagnosis of Myocardial Infarction with Bundle Branch Blocks Atrial Infarction Electrocardiogram Differential Diagnosis of Ischemia and Infarction Noninfarction Q Waves and Related Depolarization Changes ST-­T Changes Simulating Ischemia and Infarction Drug Effects Electrolyte and Metabolic Abnormalities Calcium Potassium Clinical Issues in Electrocardiographic Interpretation Indications Reading Competency Technical Errors Computer Interpretation Future Perspectives Guidelines References Patients Without Known or Suspected Cardiovascular Disease Patients with Known or Suspected Cardiovascular Disease Special Populations Persons with Dangerous or Physically Demanding Occupations Preoperative Evaluation Screening of Athletes Cardioactive Drug Administration References 15 15 - Exercise Physiology and Exercise Electrocardiographic Testing Exercise Physiology Total-­Body Oxygen Uptake Technical Components of Exercise Testing Patient Preparation Patient Assessment Symptom Rating Scales Electrocardiographic Lead Systems Exercise Test Modality and Protocols Exercise Test Supervision Risks of Exercise Testing Exercise Testing in Coronary Artery Disease Exercise-­Induced Symptoms Functional Capacity ST-­Segment Changes ST Depression Upsloping ST Depression Lead aVR ST Elevation ST Adjustments ST Elevation Pharmacologic Influences on Interpretation Digitalis Glycosides Beta Adrenoreceptor Blockers Diagnostic Value Sensitivity and Specificity (see also Chapter 10) Positive and Negative Predictive Values Pre-­Test and Post-­Test Probability of Disease Assessment of Anatomic and Functional Extent of Disease Testing in Women Prognostic Value Predictive Variables Post–Myocardial Infarction Evaluation Preoperative Evaluation in Noncardiac Surgery (see Chapter 23) Assessment of Therapy Exercise Testing in Nonatherosclerotic Heart Disease Valvular Heart Disease Aortic Stenosis Severe Acquired Aortic Valve Stenosis Moderate to Severe Congenital Valvular Aortic Stenosis Mitral Regurgitation Hypertrophic Cardiomyopathy Adult Congenital Heart Disease Additional Uses for Exercise Testing Chest Pain Units Physical Activity and Exercise Prescription Evaluation of Peripheral Artery Disease Patients with Diabetes Summary Classic References References 16 16 - Echocardiography Principles of Image Generation Physical Principles of Ultrasound Doppler Echocardiography in Practice Assessment of Flow and Continuity Equation M-­Mode Echocardiography Assessment of Cardiac Structure and Function Left Ventricular Structure: Size and Mass Left Ventricular Systolic Function Left Ventricular Diastolic Function Mitral Inflow Patterns Doppler Tissue Imaging Pulmonary Venous Doppler Flow Patterns Color M-­Mode and Flow Propagation Assessing Diastolic Function in Clinical Practice Right Ventricular Structure and Function Left and Right Atria Transesophageal Echocardiography Three-­Dimensional Echocardiography Ultrasound Enhancing Agents Myocardial Infarction Cardiomyopathies Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Other Cardiomyopathies With Regional or Global Variations in Myocardial Composition Left Ventricular Noncompaction Arrhythmogenic Cardiomyopathy Restrictive Cardiomyopathies Heart Failure Assessment of Ventricular Synchrony Assessment After Orthotopic Heart Transplantation Lung Ultrasound in Heart Failure The Athlete’s Heart Stress Echocardiography Limitations of Stress Echocardiography Risk Stratification with Stress Echocardiography Assessment of Myocardial Viability Coronary Flow Reserve and Perfusion Stress Echocardiography in Valvular Heart Disease Mitral Valve (see Chapters 75 and 76) Mitral Stenosis Echocardiographic Features Quantification of Severity Patient Selection for Balloon Valvuloplasty Mitral Regurgitation Primary (Degenerative) Mitral Regurgitation Secondary (Functional) Mitral Regurgitation Quantitation of Mitral Regurgitation Aortic Valve (see Chapters 72 to 74) Aortic Stenosis Quantitation of Severity Low-­Gradient Severe Aortic Stenosis Aortic Regurgitation (see Chapter 73) Tricuspid Valve (see Chapter 77) Acquired Disorders of the Tricuspid Valve Quantitation of Tricuspid Regurgitation Pulmonic Valve (see Chapter 77) Quantitation of Valve Dysfunction Prosthetic Valves (see Chapter 79) Pericardial Disease (see Chapter 86) Pericardial Effusion Pericardial Hematoma Constrictive Pericarditis Diseases of the Aorta (see Chapter 42) Focal Aortopathies Aortic Emergencies Pulmonary Hypertension (see Chapter 88) Infective Endocarditis (see Chapter 80) Cardiac Masses (see Chapter 98) Secondary Tumors Alternative Diagnoses Pseudoneoplasms Intracardiac Thrombus Adult Congenital Heart Disease (see Chapter 82) Atrial Septal Defect Secundum Atrial Septal Defect Primum Atrial Septal Defect Sinus Venosus Atrial Septal Defect Coronary Sinus Atrial Septal Defect Ventricular Septal Defect Membranous (Paramembranous) and Outlet Ventricular Septal Defects Inlet Ventricular Septal Defects Muscular Ventricular Septal Defects 1397256787Transcatheter Interventions (see Chapters 74 and 78) Future Directions Multimodality and Fusion Imaging Recent Echocardiography Techniques Artificial Intelligence (see Chapter 11) Appropriate Use Criteria References References 17 17 - Chest Radiography in Cardiovascular Disease Overview PA and Lateral CXR Approach to Cxr Evaluation Radiographic Densities CXR Anatomy PA Radiograph Lateral Radiograph Common Anatomic Variants Azygous Lobe Variant Aortic Arch Variants Localization Within Cardiac Silhouette Fat Calcifications Pulmonary Vasculature Support Lines and Devices Specific Cardiovascular Conditions Congenital Heart Disease Acquired Heart Disease Valvular Heart Disease Coronary Artery Disease Heart Failure Advanced Imaging in ICU References 18 18 - Nuclear Cardiology Principles of Imaging Single Photon Emission Computed Tomography Conventional SPECT Novel Image Reconstruction Software Novel SPECT Scanners Positron Emission Tomography Hybrid SPECT/CT, PET/CT, and PET/MR SPECT and PET Image Acquisition Radiotracers and Protocols Physiologic Basis for Stress Testing Stress Testing Protocols Exercise Stress Pharmacologic Stress Imaging Protocols General Principles SPECT Protocols Myocardial Perfusion Imaging Transthyretin Cardiac Amyloidosis Imaging PET Protocols Myocardial Perfusion Imaging 18F-­FDG Metabolic Imaging Protocols Reducing Radiation Dose Patient-­Centered Clinical Applications Ischemic Heart Disease Principles of Perfusion Imaging Suspected Stable Coronary Artery Disease Patients with New-­Onset Chest Pain Risk Stratification with Radionuclide Myocardial Perfusion Imaging Symptomatic Patients Without Angiographic Obstructive Coronary Artery Disease Evaluation Before Organ Transplantation Suspected Acute Coronary Syndrome Patients with Nondiagnostic Electrocardiogram and Troponin Elevation Patients with Known Stable Coronary Artery Disease Patients with Prior PCI and Recurrent Symptoms Patients with Recent Myocardial Infarction Evaluated for Potential Staged PCI Patients with Prior Myocardial Infarction and Ventricular Arrhythmias Patients with Chronic Total Coronary Artery Occlusion Heart Failure and Cardiomyopathies Patients with Newly Diagnosed Left Ventricular Systolic Dysfunction Patients with Ischemic Cardiomyopathy and Heart Failure Pathophysiology of Ischemic Left Ventricular Dysfunction Radionuclide Imaging Approaches to Assess Myocardial Ischemia and Viability Myocardial Viability Imaging to Guide Revascularization in Patients with Ischemic Heart Failure Infiltrative Cardiomyopathy: Amyloidosis Inflammatory Cardiomyopathy: Sarcoidosis Infective Endocarditis Cardio-­Oncology Assessment of Ventricular Function Evaluation of Coronary Artery Disease Evaluation of Primary or Metastatic Cardiac Neoplasms Translational Molecular Imaging Aortic Valve Disease References 19 19 - Cardiovascular Magnetic Resonance Imaging Basic Physics of Magnetic Resonance Imaging Clinical Applications of Cmr Coronary Artery Disease Assessing Stable Chest Pain Syndromes CMR Assessment of Myocardial Viability and Benefit from Coronary Revascularization Cardiomyopathies Overall Approach to Undiagnosed Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Cardiomyopathy Myocarditis Cardiac Sarcoidosis Cardiac Amyloidosis Idiopathic Dilated Cardiomyopathy Other Cardiomyopathies Valvular Heart Disease (see Part VIII) Aortic Stenosis Aortic Regurgitation Mitral Regurgitation Tricuspid Regurgitation Pericardial Disease (see Chapter 86) References 20 20 - Cardiac Computed Tomography Different Types of Cardiac Computed Tomography Exams Coronary Artery Calcium Testing Test Performance and Acquisition Clinical Data Special Populations Clinical Indications and Management Recommendations Clinical Indications Management Recommendations Limitations of Coronary Artery Calcium Testing Diagnostic Accuracy Prognostic Implications Plaque Burden and Prognosis Coronary Computed Tomography Angiography in Non–ST Elevation Myocardial Infarction Selecting Appropriate Candidates for Coronary Computed Tomography Angiography Pretest Probability of Obstructive Coronary Artery Disease Patient Outcomes Following Coronary Computed Tomography Angiography Hard Clinical Outcomes Use of Invasive Angiography Following Coronary Computed Tomography Angiography High-­Risk Plaque Characteristics Low-­Attenuation Plaque Positive Remodeling Napkin-­Ring Sign Spotty Calcifications Plaque Characteristics and Incident Risk Perivascular Fat Attenuation Computed Tomography Fractional Flow Reserve Diagnostic Accuracy (see Fig. 36.17) Clinical Effectiveness Coronary Tomography Perfusion Stress Computed Tomography Perfusion Comparing and Integrating Different Techniques Patient Management Considerations Patient Management Recommendations Special Populations Guidelines Pericardial and Myocardial Disease Valvular Heart Disease (see Part VIII) Shunts Use of Cardiac Computed Tomography for Structural Heart Disease Interventions Pre-­Transcatheter Aortic Valve Replacement Post-­Transcatheter Aortic Valve Replacement (see Chapter 74) Evaluation Pre-­Transcatheter Mitral Valve Replacement (see Chapter 78) Evaluation of Left Atrial Appendage (for Thrombus, Pre-­Left Atrial Appendage Occlusion Devices) Evaluation of Cardiac Masses Future Directions References 21 21 - Coronary Angiography and Intravascular Imaging Indications for Coronary Angiography Appropriate Use Criteria Coronary Arteriography Technique Patient Preparation Access Sites (see Chapter 41) Basic Technique Catheters for Diagnostic Procedures Ventriculography Left Ventriculography Aortography Right Ventriculography Selection of Contrast Media Angiographic Projections Coronary Anatomy Coronary Artery Anomalies Pitfalls of Coronary Angiography Myocardial Bridging Coronary Artery Spasm Angiogram Evaluation Syntax Score Quantification of the Stenosis Evaluation of Microvascular Blood Flow Special Lesion Considerations Chronic Total Occlusion Calcific Lesions Thrombotic Lesions Bifurcation Lesions Coronary Dissections Coronary Intravascular Imaging Intravascular Ultrasound Procedure Interpretation Clinical Data Plaque Lipid Core Detection Optical Coherence Tomography Clinical Applications Normal Vessel Wall Stable Coronary Artery Disease Plaque Morphology Acute Coronary Syndrome Procedure Planning and Lesion Preparation Assessment After Percutaneous Coronary Intervention Co-­registration of Intravascular Imaging and X-­Ray Angiography for Patients Undergoing Percutaneous Coronary Intervention.Duri... Classic References References 22 22 - Invasive Hemodynamic Diagnosis of Cardiac Disease Complications and Risks Vascular Access Percutaneous Radial Artery Technique Percutaneous Femoral Artery Technique Venous Access Percutaneous Femoral Vein Access Percutaneous Brachial Vein Access Percutaneous Internal Jugular Vein Access Transseptal Catheterization Left-­Heart Catheterization Right-­Heart Catheterization Fluid-­Filled Pressure Systems Micromanometer Catheters and Pressure Sensor Guidewires Cardiac Output Measurements Thermodilution Method Fick Method The Cardiac Cycle and Generation of Pressure Waves Normal Pressure Waveforms Atrial Pressures Pulmonary Capillary Wedge Pressure Aortic and Pulmonary Artery Pressure Waveforms Ventricular Pressure Waveforms Evaluation of Valvular Heart Disease Calculation of Stenotic Valve Orifice Areas Aortic Valve Stenosis Low-­Flow, Low-­Gradient Aortic Stenosis Hypertrophic Obstructive Cardiomyopathy Mitral Valve Stenosis Pulmonary and Tricuspid Valve Stenosis Aortic Regurgitation Mitral Regurgitation Pulmonary and Tricuspid Valve Regurgitation Cardiac Tamponade Exercise Provocation Dynamic Exercise Static Exercise Pacing Tachycardia Physiologic Maneuvers and Volume Challenge Pharmacologic Challenges Dobutamine Isoproterenol Pulmonary Vasodilators Nitric Oxide Nitroprusside Pressure-­Volume (PV) Relationships References 23 23 - Anesthesia and Noncardiac Surgery in Patients with Heart Disease Ischemic Heart Disease 23 Anesthesia and Noncardiac Surgery in Patients with Heart Disease Hypertension Heart Failure Hypertrophic Cardiomyopathy Risk Calculators Regional Anesthesia Monitored Anesthesia Care Postoperative Management Postoperative Response to Surgery Coronary Artery Revascularization Percutaneous Coronary Intervention and Noncardiac Surgery Pharmacologic Interventions Beta-­Adrenergic Blocking Agents Statin Therapy Other Therapies Conclusion Classic References References 24 24 - The Vascular Biology of Atherosclerosis Overview and Background Structure of the Normal Artery Cell Types Composing the Normal Artery Endothelial Cells Arterial Smooth Muscle Cells Layers of the Normal Artery Intima Tunica Media Adventitia Atherosclerosis Initiation Extracellular Lipid Accumulation Leukocyte Recruitment and Retention Focality of Lesion Formation Evolution of Atheroma Innate and Adaptive Immunity: Mechanisms of Inflammation in Atherogenesis Arterial Extracellular Matrix Angiogenesis in Plaques Plaque Mineralization Complication of Atherosclerosis Arterial Stenoses and Clinical Implications Thrombosis and Atheroma Complication Plaque Rupture and Thrombosis Special Cases of Arteriosclerosis Restenosis After Arterial Intervention Aneurysmal Disease Infection, the Microbiome, and Atherosclerosis References 25 25 - Primary Prevention of Cardiovascular Disease Overview Trends in Cardiovascular Disease and Risk Factors Global Trends Trends in the United States Cardiovascular Health and Life’s Simple 7 Global Risk Lifetime Risk Traditional Risk Factors Smoking and e-­Cigarettes (see Chapter 28) Hypertension Guideline Recommendations (See Chapter 26) Interventions to Reduce Blood Pressure.The risk factors and markers for development of hypertension include increasing age, ethn... Drug Therapy (see Chapter 26).Initiation of drug therapy depends on blood pressure and the absolute level of cardiovascular risk... Metabolic Syndrome, Insulin Resistance, and Diabetes Interventions to Reduce Cardiovascular Risk among Patients with Diabetes Obesity (see Chapter 30) Family History Risk-­Enhancing Factors Social Determinants of Health (see Chapters 6 and 93) Psychosocial Factors (see Chapter 99) Ankle-­Brachial Index (see Chapter 43) Biomarkers (see Chapter 10) Lipids/Lipoproteins Standard Lipid Testing (see Chapter 27) Fasting versus nonfasting.The rationale behind using nonfasting testing is appealing physiologically. We live most of our lives ... LDL Cholesterol HDL Cholesterol Triglycerides Alternative Lipid Measures Lipoprotein(a).Lipoprotein(a) [Lp(a)] comprises a class of circulating lipoprotein particles composed of a single copy of apoB c... Homocysteine.Homocysteine is a sulfhydryl-­containing amino acid derived from the demethylation of dietary methionine. In patien... High-­Sensitivity C-­Reactive Protein and Other Biomarkers of Inflammation (see Chapter 10) Lifestyle Factors and Interventions Nutrition and Diet (see Chapters 29 and 30) Low-­Risk Populations High-­Risk Populations and Randomized Trials of the Mediterranean Diet Alcohol Consumption Physical Activity (see Chapters 32 and 33) Sedentary Behavior Interventions to Increase Physical Activity Pharmacologic Therapies Shared Decision-­Making Statins (see Chapter 27) Monitoring of Therapy Aspirin N-­3 Fatty Acids Primary Prevention High-­Risk Primary Prevention Updated Meta-­Analyses and Summary The Polypill in Current Practice Precision Medicine Versus Preventive Care Community Interventions References 26 26 - Systemic Hypertension: Mechanisms, Diagnosis, and Treatment Definitions of Hypertension Epidemiology Pathophysiology Pressure Natriuresis and Salt Sensitivity Renin-­Angiotensin-­Aldosterone System Sympathetic Nervous System Natriuretic Peptides Endothelium Arterial Stiffness in Hypertension Immune System in Hypertension Genetics (see Chapter 7) Obesity History and Physical Examination Blood Pressure Measurement Office Blood Pressure Measurement Office Versus Home Blood Pressure Clinical Use of Ambulatory and Home Blood Pressure Monitoring Laboratory and Other Complementary Tests Echocardiography Evaluation of Sodium and Potassium Intake Renin Profiling Endocrine Causes (see Chapter 96) Primary Hyperaldosteronism Apparent Mineralocorticoid Excess States Hyperaldosteronism Associated with Sleep-­Disordered Breathing (see Chapter 89) Pheochromocytoma Hypercortisolism (Cushing disease) Thyroid Dysfunction Acromegaly Nonendocrine Causes Lifestyle Factors Drug-­Induced Hypertension Sleep Deprivation and Sleep-­Disordered Breathing (see Chapter 89) Nonlifestyle, Nonendocrine Causes Intrinsic Kidney Disease Renovascular Hypertension Coarctation of the Aorta Goals of Therapy Blood Pressure Guidelines Dietary Approaches Blood Pressure–Lowering Medications Pharmacologic Intervention in the Older People (>65 years) Heart Failure (see Part VI) Resistant Hypertension Nondrug Therapy for Resistant Hypertension Device Therapy Renal Denervation Baroreceptor-­Activation DEBuT-­HT Rheos Pivotal Trial Barostim Neo Trial MobiusHD Device for Baroreflex Amplification Hypertensive Urgency and Emergency References 27 27 - Lipoprotein Disorders and Cardiovascular Disease Lipoprotein Transport System Biochemistry of Lipids Lipoprotein Metabolism and Transport Low-­Density Lipoproteins High-­Density Lipoprotein and Reverse Cholesterol Transport Lipoprotein Disorders Definitions Genetic Lipoprotein Disorders Low-­Density Lipoproteins Familial Hypercholesterolemia Low-­Density Lipoprotein Receptor Gene.Defects in the low-­density lipoprotein receptor (LDLR) gene cause an accumulation of LDL... Familial Defective Apolipoprotein B.Mutations within the apolipoprotein B (APOB) gene that lead to an abnormal ligand-­receptor ... Proprotein Convertase Subtilisin/Kexin Type 9.Gain-­of-­function mutations in the PCSK9 gene decrease surface availability of th... Polygenic Hypercholesterolemia Lipoprotein(a) (Fig. 27.3) Polygenic Hypertriglyceridemia (also Known as Familial Hypertriglyceridemia, Formerly Type IV Hyperlipoproteinemia) Combined Hyperlipoproteinemia (also Known as Familial Combined Hyperlipidemia or Formerly Type 2B Hyperlipidemia) Dysbetalipoproteinemia (Formerly Type III Hyperlipoproteinemia) Monogenic Chylomicronemia Syndrome (Formerly Familial Hyperchylomicronemia Syndrome or Type I Hyperlipidemia) High-­Density Lipoproteins Disorders of High-­Density Lipoprotein Biogenesis Apolipoprotein A-­I Gene Defects Tangier Disease and Familial High-­Density Lipoprotein Deficiency Disorders of High-­Density Lipoprotein–Processing Enzymes Lecithin-­Cholesterol Acyltransferase Deficiency Cholesteryl Ester Transfer Protein Deficiency Secondary Causes of Hyperlipidemia and Metabolic Syndrome (Table 27.6) (see also Chapter 25) Hormonal Causes Metabolic Causes Renal Disorders Liver Disease Lifestyle (see also Chapters 25, 29 and 30) Alteration in Lipids by Medications Hydroxymethylglutaryl–Coenzyme A Reductase Inhibitors (Statins) Mechanisms of Action Pharmacology and Lipid Effects (Table 27.7A and B) Safety, Tolerability, and Monitoring Clinical Trials and Cardiovascular Outcomes (see also Chapter 25) Use of Statins in Particular Populations Adults with Diabetes (see also Chapter 31) Older Adults Women (see also Chapters 25 and 91) Race and Ethnicity (see also Chapter 93) Advanced Heart Failure and Chronic Kidney Disease (see Chapter 101) Pro-­Protein Convertase Subtilisin/Kexin Type 9 Inhibitors Mechanisms of Action Effects on Lipids Safety, Tolerability, and Monitoring Clinical Outcomes Trials with Monoclonal Antibodies Clinical Recommendations Ezetimibe Fibric Acid Derivatives (Fibrates) Nicotinic Acid (Niacin) Bile Acid–Binding Resins Fish Oils and Pure Eicosapentaenoic Acid Phytosterols Novel Medications78 Bempedoic Acid Rare diseases: Novel approaches for Homozygous Familial Hypercholesterolemia and Monogenic Chylomicronemia Syndrome Inhibition of APO CIII Inhibition of Angiopoietin-­Like Protein 3 (ANGPTL3) Inhibition of Lp(a) Lifestyle Changes: Diet (see also Chapters 25, 29, and 30) Treatment of Combined Lipoprotein Disorders Clinical Recommendations for Assessing Residual Risk Future Perspectives Gene Therapy Societal Changes Guidelines References 28 28 - Cardiovascular Disease Risk of Nicotine and Tobacco Products Health Effects of Tobacco Cardiovascular Effects of Tobacco Products Cigarettes Electronic Cigarettes Heated Tobacco Products Classic References References 29 29 - Nutrition and Cardiovascular and Metabolic Diseases Energy Balance (see also Chapter 30) Foods Fruits and Vegetables Nuts and Beans Whole Grains, Refined Grains, Starches, Sweets Fish Red Meats Poultry, Eggs Dairy Plant Oils Beverages Sugar-­Sweetened Beverages Milk Coffee, Tea Alcohol Macronutrients Carbohydrates Fats Total Fat Saturated Fats Monounsaturated Fats Polyunsaturated Fats n-­6 PUFA n-­3 PUFA (see Chapters 25 and 27) Trans Fats Dietary Cholesterol Protein Micronutrients Sodium, Potassium (see Chapter 26) Dietary Patterns Emerging Areas Food Processing Microbiome Personalized Nutrition Changing Behavior References 30 30 - Obesity: Medical and Surgical Management Epidemiology Traditional Definition of Obesity Visceral Obesity Marker of Ectopic Fat Deposition Portal Free Fatty Acid Hypothesis Visceral Adipose Tissue as an Endocrine Organ Visceral Adipose Tissue: Marker of Dysfunctional Subcutaneous Adipose Tissue Key Factors Associated with Visceral Obesity Age and Sex Sex Hormones Genetics Ethnicity Hypothalamic-­Pituitary-­Adrenal Axis and Endocannabinoid System Drugs Lifestyle: A Key Contributor to Visceral Obesity Key Nutritional Factors (Toward a Food-­Based Approach; see also Chapter 29) Physical Activity and Exercise Pharmacotherapy Summary and Perspectives References 31 31 - Diabetes and the Cardiovascular System Scope of the Problem Diabetes Mellitus Atherosclerotic Vascular Disease Heart Failure Atrial Fibrillation Risk Stratification Mechanistic Considerations Linking Diabetes and Atherosclerosis Lipid Management Statins Ezetimibe.Ezetimibe inhibits the intestinal cholesterol transporter Niemann-­Pick C1-­like 1 (NPC1L1). The Improved Reduction of... PCSK9 Inhibitors.Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) with antibodies such as alirocumab or evolo... Fibric acid derivatives (fibrates).Fibrates are agonists of the nuclear transcriptional regulator peroxisome proliferator–activa... Omega-13969839203 fatty acids.Omega-13969839203 fatty acids (fish oil) can reduce circulating TGs up to 40% (see Chapters 25, 27... Inclisiran.The subcutaneous injection of inclisiran, a small interfering RNA that targets PCSK9 mRNA offers a novel strategy to ... Hypertension Management Renin-­Angiotensin-­Aldosterone System Antagonists Angiotensin-­converting enzyme inhibitors.Data from randomized trials of patients with and without hypertension underpin the rec... Angiotensin Ii receptor blockers.Data on CV outcomes with ARBs are much less robust than those on ACE inhibitors, particularly i... Calcium Channel Blockers Thiazide Diuretics Beta Blockers Antihypertensive Therapy Summary Antiplatelet Therapy Daily Aspirin P2Y12 Receptor Antagonists Glucose Management Cardiovascular Effects of Selected Medications for Diabetes Metformin.Metformin, a biguanide, reduces blood glucose primarily by decreasing hepatic glucose output and perhaps by other mech... Sulfonylureas.Sulfonylureas, in clinical use since the 1950s, are the oldest oral antihyperglycemic medications. They lower gluc... Insulin.Early trials including those in both type 1 and type 2 DM suggest the CVD benefits with insulin but these studies all ha... Dipeptidyl Peptidase 4 Inhibitors.The DPP4 inhibitors selectively inhibit the action of dipeptidyl peptidase 4, a circulating en... Glucagon like peptide-­1 receptor agonists.The GLP-­1 receptor agonists (RAs) are injectable agents that enhance the incretin sy... Sodium-­Glucose Cotransporter 2 Inhibitors.Sodium-­glucose cotransporter 2 (SGLT2) inhibitors, the newest class of antihyperglyc... Other Glucose-­Lowering Medications (See TABLE 31.3).Data on CVD outcomes are generally limited for other less commonly used glu... Cardiovascular Effects of More Intensive Versus Less Intensive Glucose Control Strategies Summary of Glucose Management and Treatment Guidelines Acute Coronary Syndromes Screening for Diabetes in Acute Coronary Syndrome Patients Insulin Administration and Glucose Control Antiplatelet Medications P2Y12 Receptor Antagonists Renin-­Angiotensin-­Aldosterone System Antagonists Beta-­Adrenergic Blocking Agents Primary Invasive Strategy for Non–ST-­Segment Elevation Acute Coronary Syndrome Primary Reperfusion Therapy for ST-­Segment Elevation Myocardial Infarction Coronary Revascularization Considerations Optimal Medical Therapy Versus Revascularization in Diabetes Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting Scope of the Problem Mechanistic Considerations Ischemic Heart Disease and Hypertension Therapy of Heart Failure with Preserved Ejection Fraction in Diabetes Therapy of Heart Failure with Reduced Ejection Fraction in Diabetes Modulation of the Renin-­Angiotensin-­Aldosterone System Angiotensin Receptor-­Neprilysin Inhibition (See Chapter 50) Beta Blockers Heart Failure Considerations for Glucose Management Strategies and Antihyperglycemic Medications Atrial Fibrillation Summary and Future Perspectives Guidelines References 32 32 - Exercise and Sports Cardiology Historical Perspective Cardiovascular Risks of Exercise The Pathology of Exercise-­Related Cardiovascular Events The Relative and Absolute Risk of Exercise Decreased Exercise Capacity Abnormalities Found on Screening Cardiovascular Complaints in Athletes Determining Athletic Eligibility Valve Disease Elevated “Cardiac Enzymes” Atrial Fibrillation in Endurance Athletes Accelerated Atherosclerosis Myocardial Fibrosis Noncompaction Cardiomyopathy Conclusion References 33 33 - Comprehensive Cardiac Rehabilitation Evolution of Cardiac Rehabilitation Structural Elements Multidisciplinary Team Facilities, Equipment, and Technology Tools Value of Cardiac Rehabilitation Recovery from a Cardiovascular Disease Event Physiologic Improvements (see Chapter 32) Cardiovascular Disease Risk Factor Control Cardiovascular Events Hospital Readmission Fatal and Non-­Fatal Events Safety of Cardiac Rehabilitation Cost-­Effectiveness of Cardiac Rehabilitation Additional Patient Groups Improving the Cost-­Effectiveness of Cardiac Rehabilitation Summary Classic References References 34 34 - Integrative Approaches to the Management of Patients with Heart Disease Integrative Cardiology Utilization of Additional Therapies Why Is Integrative Cardiology Important Need for Interprofessional Collaboration Ischemic Heart Disease (See Chapter 40) Nutrition Mind/Heart Connection Meditation Tai Chi Supplements Omega-­3 (see also Chapters 25, 27, and 29) Multivitamins Antioxidants Hypertension (see Chapter 26) Dietary Approaches to Stop Hypertension (DASH): Diet, Potassium, and Sodium Physical Activity Mind/Heart Connection Breathing Exercises Meditation Acupuncture Dyslipidemia (see Chapter 27) Nutrition Physical Activity (see Chapter 32) 1397256787Heart Failure (See Chapters 50 and 51) Nutrition and Lifestyle Supplements Coenzyme Q10 Arrhythmias (See Chapter 61) Comprehensive Lifestyle Approach Yoga Conclusion References 35 35 - Approach to the Patient with Chest Pain Causes of Acute Chest Pain Myocardial Ischemia or Infarction Pericardial Disease Vascular Disease Pulmonary Conditions Gastrointestinal Conditions Musculoskeletal and Other Causes Diagnostic Considerations Clinical Evaluation Initial Assessment History Physical Examination (see Chapter 13) Electrocardiography Chest Radiography (see also Chapter 17) Biomarkers Diagnostic Performance Troponin.Different genes encode troponins in cardiac muscle, slow skeletal muscle, and fast skeletal muscle; hence, assays for c... Creatine Kinase MB Isoenzyme.Until the advent of cardiac troponin assays, CK-­MB was the biomarker of choice for the diagnosis o... Testing Strategy Decision Aids Immediate Management Chest Pain Protocols and Units Early Noninvasive Testing Treadmill Electrocardiography Noninvasive Imaging Tests References 36 36 - Coronary Blood Flow and Myocardial Ischemia Control of Coronary Blood Flow Coronary Autoregulation Determinants of Coronary Vascular Resistance Nitric Oxide (Endothelium-­Derived Relaxing Factor) Endothelium-­Dependent Hyperpolarizing Factor Prostacyclin Endothelin Coronary Vasospasm Intraluminal Physical Forces Regulating Coronary Resistance Myogenic Regulation Flow-­Mediated Resistance Artery Control Right Coronary Artery Flow Stenosis Pressure-­Flow Relation Perfusion-­Based Indices of Stenosis Severity Absolute Flow Reserve Relative Flow Reserve Indices of Stenosis Severity Based on Coronary Pressure Vasodilated Pressure Measurements: Fractional Flow Reserve Resting Coronary Pressure Measurements: Instantaneous Wave-­Free Ratio Noninvasive FFRCT Using Computed Tomography and Computational Fluid Dynamics Coronary Collateral Circulation Arteriogenesis and Angiogenesis Regulation of Collateral Resistance Irreversible Injury and Myocyte Death Acute Perfusion-­Contraction Matching During Subendocardial Ischemia Short-­Term Hibernation Chronic Hibernating Myocardium Future Perspectives Classic References References 37 37 - ST-­Elevation Myocardial Infarction: Pathophysiology and Clinical Evolution Changing Patterns in Incidence And Care Improvements in Outcome Limitations of Current Therapy Pathologic Findings Plaque Formation and Disruption Acute Coronary Syndromes Heart Muscle Gross Pathologic Findings Ultrastructural and Microscopic Findings of Ischemia Patterns of Myocardial Necrosis Coagulation Necrosis Necrosis With Contraction Bands Myocytolysis Apoptosis Current Concepts of the Cellular Events During Myocardial Infarction and Healing Modification of Pathologic Changes by Reperfusion Coronary Anatomy and Location of Infarction Right Ventricular Infarction Atrial Infarction Collateral Circulation in Acute Myocardial Infarction Myocardial Infarction with Nonobstructive Coronary Arteries Nonatherosclerotic Causes of Acute Myocardial Infarction Stress (Takotsubo) Cardiomyopathy Pathophysiology Left Ventricular Function Systolic Function Diastolic Function Circulatory Regulation Ventricular Remodeling Infarct Expansion Ventricular Dilation Effects of Treatment Pathophysiology of Other Organ Systems Clinical Features Predisposing Factors Circadian Periodicity History Prodromal Symptoms Nature of the Pain Other Symptoms Differential Diagnosis “Silent” or Atypical Presentations of ST-­Elevation Myocardial Infarction Physical Examination (see also Chapters 13 and 38) General Appearance Heart Rate Blood Pressure Temperature and Respiration Jugular Venous Pulse Carotid Pulse The Chest Cardiac Examination Palpation Auscultation Heart sounds.The heart sounds, particularly the first sound, are frequently muffled and occasionally inaudible immediately after... Murmurs.Patients with STEMI typically have systolic murmurs, transient or persistent, that generally result from mitral regurgit... Friction rubs.Patients with STEMI may develop pericardial friction rubs. Rubs are notorious for their evanescence and thus are p... Extremities Neuropsychiatric Findings Laboratory Findings Serum and Plasma Markers of Cardiac Damage Recommendations for Measurement of Circulating Markers of Cardiac Injury in ST-­Segment Elevation MI Other Biomarkers (See Chapter 35) Other Laboratory Measurements Serum Lipids Hematologic Findings Electrocardiography Q Wave and Non−Q Wave Infarction Ischemia at a Distance Right Ventricular Infarction Imaging Radiography Echocardiography Magnetic Resonance Imaging Nuclear Imaging Computed Tomography Estimation of Infarct Size Electrocardiography.The sum of ST-­segment elevations measured from multiple precordial leads correlates with the extent of myoc... Cardiac markers.Estimation of infarct size by analysis of serum or plasma cardiac markers of necrosis requires accounting for th... Noninvasive imaging techniques.The imaging modalities previously discussed can aid in experimental and clinical assessment of in... Future Perspectives References 38 38 - ST-­Elevation Myocardial Infarction: Management Prehospital Management Prehospital Care Emergency Medical Service Systems Prehospital Fibrinolysis General Treatment Measures Aspirin Control of Cardiac Pain Analgesics Nitrates Beta-­Adrenergic Blocking Agents Oxygen Limitation of Infarct Size Dynamic Nature of Infarction Routine Measures for Limitation of Infarct Size Reperfusion Therapy General Concepts Pathophysiology of Myocardial Reperfusion Reperfusion Injury Reperfusion Arrhythmias Late Establishment of Patency of the Infarct Vessel Fibrinolysis Effect of Fibrinolytic Therapy on Mortality Comparison of Fibrinolytic Agents Effect on Left Ventricular Function Complications of Fibrinolytic Therapy Late Therapy Intracoronary Fibrinolysis Catheter-­Based Reperfusion Strategies Surgical Reperfusion Selection of Reperfusion Strategy Referral for Angiography with Intent of Revascularization after Initial Fibrinolysis Patients Not Eligible for Reperfusion Therapy Anticoagulant and Antiplatelet Therapy Anticoagulant Therapy Effect of Heparin on Mortality Other Effects of Heparin.Several angiographic studies have examined the role of heparin therapy in establishing and maintaining ... Disadvantages of Heparin.Potential disadvantages of unfractionated heparin (UFH) include dependency on antithrombin III for inhi... Hirudin and Bivalirudin Low-­Molecular-­Weight Heparins Parenteral Factor Xa Antagonists Oral Factor IIa and Factor Xa Antagonists Recommendations for Anticoagulant Therapy Adjunctive Anticoagulation for Primary Percutaneous Coronary Intervention (see Chapter 41).Either UFH or bivalirudin is recommen... Anticoagulation with Fibrinolysis.Given the pivotal role of thrombin in the pathogenesis of STEMI (see eFig. 38.8), antithrombot... Patients Treated Without Reperfusion Therapy.Treatment with an anticoagulant is reasonable, and agents shown to be more effectiv... Antiplatelet Therapy Antiplatelet Therapy for Percutaneous Coronary Intervention in ST-­Elevation Myocardial Infarction Antiplatelet Therapy with Fibrinolysis Combination Pharmacologic Reperfusion Recommendations for Antiplatelet Therapy Hospital Management Coronary Care and Intermediate Care Units General Measures Physical Activity Pharmacologic Therapy Beta Blockers Recommendations Selection of Beta Blockers Inhibition of the Renin-­Angiotensin-­Aldosterone System Recommendations Nitrates Recommendations Calcium Channel Antagonists Other Therapies Magnesium Glucose Control During ST-­Elevation Myocardial Infarction Other Agents Hemodynamic Disturbances Hemodynamic Assessment Monitoring of Pulmonary Artery Pressure Hemodynamic Abnormalities Hemodynamic Subsets Hypotension in the Prehospital Phase Management.In the absence of HF, when hypotension is suspected to result from excessive vagotonia, patients should be placed in ... The Hyperdynamic State Left Ventricular Failure Therapeutic Implications Hypoxemia Diuretics Afterload Reduction Nitroglycerin Oral Vasodilators Glucose-­Lowering Agents(see also Chapter 31) Digitalis (see Chapter 50) Vasoactive Medications Beta-­Adrenergic Agonists Other Positive Inotropic Agents Vasopressors Cardiogenic Shock Pathologic Findings Pathophysiology Diagnosis Medical Management Mechanical Circulatory Support Intra-­Aortic Balloon Counterpulsation Percutaneous Left Ventricular Assist Devices Complications Revascularization Shock Teams Recommendations Right Ventricular Infarction Diagnosis Noninvasive Assessment Treatment Mechanical Causes of Heart Failure Free Wall Rupture Pseudoaneurysm Diagnosis Treatment Rupture of Interventricular Septum Rupture of a Papillary Muscle Differentiation Between Ventricular Septal Rupture and Mitral Regurgitation Management Arrhythmias Hemodynamic Consequences Ventricular Arrhythmias (see Chapter 67) Ventricular Premature Depolarizations Management Accelerated Idioventricular Rhythm Ventricular Tachycardia and Ventricular Fibrillation Prophylaxis Management Prognosis Bradyarrhythmias (see Chapters 68 and 69) Sinus Bradycardia Management Atrioventricular and Intraventricular Block First-­Degree Atrioventricular Block Second-­Degree Atrioventricular Block Complete (Third-­Degree) Atrioventricular Block Intraventricular Block Isolated Fascicular Blocks Right Bundle Branch Block Bifascicular Block, Including Left Bundle Branch Block Use of Pacemakers in Patients with Acute Myocardial Infarction (see Chapter 69) Temporary Pacing Asystole Permanent Pacing Supraventricular Tachyarrhythmias (see Chapters 65 and 66) Sinus Tachycardia Atrial Flutter and Fibrillation Management Other Complications Recurrent Chest Discomfort Recurrent Ischemia and Reinfarction Diagnosis Prognosis Management Pericardial Effusion and Pericarditis (see Chapter 86) Pericardial Effusion Pericarditis Dressler Syndrome Venous Thrombosis and Pulmonary Embolism Left Ventricular Aneurysm Pathogenesis Diagnosis Prognosis and Treatment Management Timing of Hospital Discharge Counseling Assessment at Hospital Discharge Assessment of Left Ventricular Function Assessment of Myocardial Ischemia Exercise Testing.An exercise test also offers an opportunity to formulate a more precise exercise prescription and helps boost p... Assessment for Electrical Instability Prophylactic Antiarrhythmic Therapy Cardiac Rehabilitation (see Chapter 33) Lifestyle Modification (see also Part IV) Depression (see Chapter 99) Modification of Lipid Profile (see Chapters 25 and 27) Antiplatelet Agents (see Chapter 95) Inhibition of the Renin-­Angiotensin-­Aldosterone System Beta-­Adrenergic Blocking Agents Nitrates Anticoagulants (see Chapters 40 and 95) Calcium Channel Antagonists Hormone Therapy (see Chapters 25 and 91) Nonsteroidal Antiinflammatory Drugs References 39 39 - Non–ST Elevation Acute Coronary Syndromes Epidemiology Pathophysiology Clinical Assessment History Physical Examination Electrocardiography Laboratory Testing: Biomarkers Imaging Noninvasive Testing Invasive Imaging Risk Assessment Residual Risk Natural History Risk Assessment Scores Management General Measures Anti-­Ischemic Therapy Nitrates Beta-­Adrenergic Receptor–Blocking Agents Intravenous Beta Blockers Oral Beta Blockers Calcium Channel Blockers Antiplatelet Therapy (see Chapter 95) Oral Antiplatelet Drugs P2Y12 Inhibitors (see eTable 39.G3) Clopidogrel Prasugrel Ticagrelor Selection and Duration of Dapt Regimen and Nste-­Acs Treatment Strategy.Patients with NSTE-­ACS are most commonly managed with P... Switching Between Oral P2y12 Inhibitors.Three common clinical scenarios in which switching between oral P2Y12 inhibitors may ari... Intravenous Antiplatelet Agents Anticoagulant Therapy (see Chapter 95) Heparin Low-­Molecular-­Weight Heparin Heparin Reversal Direct Thrombin Inhibitors Patients with Indications for Both Oral Anticoagulant and Antiplatelet Therapy Combination of Chronic Oral Anticoagulant and Antiplatelet Therapy Post NSTE-­ACS Anti-­Inflammatory Therapies Invasive Versus Conservative Management Timing of an Invasive Approach Predischarge Risk Stratification in Patients Managed with an Ischemia-­Guided Strategy Percutaneous Coronary Intervention (see Chapter 41) Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting Discharge and Posthospital Care Groups of Special Interest Older Adults (see Chapter 90) Women (see Chapter 91) 1397256787Heart Failure (see Chapters 49 to 51) Vasospastic Angina Management Cardiac Syndrome X Future Perspectives References 40 40 - Stable Ischemic Heart Disease Magnitude of the Problem Stable Angina Pectoris Clinical Manifestations Characteristics of Angina (see Chapter 35) Assessment and Classification of Angina Pectoris Differential Diagnosis of Chest Pain Esophageal Disorders Mechanisms of Anginal Pain Biliary Colic Costochondritis Other Neurologic and Musculoskeletal Disorders Other Causes of Angina-­Like Pain Physical Examination Pathophysiology Angina Caused by Increased Myocardial O2 Requirements Angina Caused by Transiently Decreased O2 Supply Importance of Pathophysiologic Considerations in Configuring Therapy Evaluation and Management Biochemical Tests Biomarkers of Myocyte Injury, Ischemia, and Hemodynamic Stress Inflammatory Biomarkers Genetic and Transcriptomic Biomarkers Noninvasive Testing Resting Electrocardiogram Resting Echocardiography (see Chapter 16) Chest Roentgenography (see Chapter 17) Stress Testing (see Chapters 15 and 18) Computed Tomography (see Chapter 20) Cardiac Magnetic Resonance Imaging (see Chapter 19) Invasive Assessment Catheterization and Coronary Angiography Limitations of Angiography Advanced Structural Coronary Imaging Functional Assessment Integrated Invasive Assessment in Patients Without Obstructive CAD High-­Risk Findings from Coronary Angiography Extent of Coronary Artery Disease Other Angiographic Findings Natural History and Risk Stratification Risk Stratification and Risk Models Medical Management Treatment of Associated Diseases Reduction of Coronary Risk Factors Hypertension (see Chapter 26) Coronary Artery Ectasia and Aneurysms.Patulous aneurysmal dilation involving most of the length of a major epicardial coronary a... Coronary Collateral Vessels (See Chapter 36).Provided that they are of adequate size, collateral vessels may protect against MI ... Myocardial Bridging.Bridging of coronary arteries (see Chapter 21) is observed during coronary angiography at a rate of less tha... Cigarette Smoking Management of Dyslipidemia (see Chapter 27) Low High-­Density Lipoprotein Cholesterol.Patients with established CAD and low levels of HDL cholesterol represent a subgroup a... High Triglycerides.Hypertriglyceridemia (TG >150 mg/dL [1.7 mmol/L]) is commonly associated with obesity, physical inactivity in... Management of Diabetes Mellitus (See Chapter 31).Patients with diabetes mellitus are at significantly higher risk for atheroscle... Estrogen THERAPY.In view of the collective data from randomized clinical trials, it is not advised that hormone replacement ther... Exercise (see Chapters 25, 32, and 33) Obesity (see Chapters 29 and 30) Inflammation (see Chapters 24 and 25) Counseling and Changes in Lifestyle (see Chapter 25) Pharmacologic Management of Angina Beta Adrenoceptor–Blocking Agents Adverse Effects and Contraindications Calcium Antagonists Mechanism of Action First-­Generation Calcium Antagonists Nifedipine.Nifedipine, a dihydropyridine, is a particularly effective dilator of vascular smooth muscle and is a more potent vas... Adverse Effects.These occur in 15% to 20% of patients and require discontinuation of medication in approximately 5%. Most advers... Characteristics of Different Beta-­Blocking Agents (Table 40.6) Selectivity Intrinsic Sympathomimetic Activity Lipid Solubility Alpha Adrenoceptor–Blocking Activity Effects on Serum Lipid Levels Verapamil.Verapamil dilates systemic and coronary resistance vessels and large coronary conductance vessels. It slows the heart ... Diltiazem.Diltiazem’s actions are intermediate between those of nifedipine and verapamil. In clinically useful doses its vasodil... Second-­Generation Calcium Antagonists Amlodipine.This agent, which is less lipid soluble than nifedipine, has a slow, smooth onset and ultralong duration of action (p... Nicardipine.This drug has a half-­life similar to that of nifedipine (2 to 4 hours) but appears to have greater vascular selecti... Felodipine and Isradipine.In the United States, both of these drugs are approved by the U.S. Food and Drug Administration for th... Nitrates Mechanism of Action Pharmacology of Nitrates Effects on the Coronary Circulation (See Table 40.4).Nitroglycerin causes dilation of epicardial stenoses. Even a small increase... Redistribution of Blood Flow.Nitroglycerin causes blood flow to be redistributed from normally perfused segments to ischemic are... Cellular Mechanism of Action.Nitrates have the ability to cause vasodilation, regardless of whether the endothelium is intact. A... Nitrate Tolerance.A major problem with the use of nitrates is the development of nitrate tolerance, which has been demonstrated ... Mechanisms.Several mechanisms of nitrate tolerance have been proposed. Evidence has supported the hypothesis that increased gene... Management.The primary strategy for managing nitrate tolerance is to prevent it by providing a nitrate-­free interval. The optim... Nitrate Withdrawal.A common form of nitrate withdrawal (rebound) is observed in patients whose angina is intensified after disco... Types of Preparations and Routes of Administration Adverse Reactions.Adverse reactions are common and include headache, flushing, and hypotension. The last is rarely severe, but i... Short-­Acting Nitroglycerin (Nitroglycerin Tablets and Oral Spray).Nitrate preparations are available in sublingual, buccal, ora... Isosorbide Dinitrate.This drug is available in tablets for sublingual use, in chewable form, in tablets for oral use, and in sus... Isosorbide 5-­Mononitrate.Plasma levels of isosorbide 5-­mononitrate reach their peak between 30 minutes and 2 hours after inges... Topical Nitroglycerin.Nitroglycerin may be applied as a transdermal patch. Application of a silicone gel or polymer matrix impre... Other Issues Related to Oral Nitrates Interaction With Cyclic Guanosine Monophosphate–Specific Phosphodiesterase Type 5 Inhibitors.The combination of nitrates and pho... Other Pharmacologic Agents Ranolazine Other Antianginal Therapies Other Considerations of Medical Management of Angina Pectoris Choice of Initial Therapy Relative Advantages of Beta-­Blocking Agents and Calcium Antagonists (Table 40.10) Selection of Therapy Other Antianginal Agents Ivabradine.Ivabradine is a specific and selective inhibitor of the If ion channel, the principal determinant of the sinoatrial n... Nicorandil.Nicorandil is a nicotinamide ester that dilates peripheral and coronary resistance vessels via action on ATP-­sensiti... Metabolic Agents.Agents aimed at increasing the metabolic efficiency of cardiac myocytes have also been studied in patients with... Combination Therapy Synthesis of an Integrated Approach to Management of Patients with Stable Angina ?Nonpharmacologic Treatment Approaches.These therapies are generally considered only for patients who have refractory ischemic s... Revascularization Approaches in Stable Ischemic Heart Disease (see Chapter 41) Approach to Decision Making Regarding Revascularization Other Antianginal Strategies Enhanced External Counterpulsation.The use of enhanced external counterpulsation (EECP) is another largely historical alternativ... Spinal Cord Stimulation.An option for patients with refractory angina who are not candidates for coronary revascularization is s... Patient Selection for Revascularization Presence and Severity of Symptoms Significance of Coronary Lesions (and Other Anatomic Considerations) Fractional Flow Reserve (see Invasive Assessment; see Chapters 20 and 41) Presence of Left Ventricular Dysfunction and Extent of Ischemia Risks Associated with the Procedure Restenosis and Late Stent Thrombosis(see Chapter 41) Comparisons between Percutaneous Coronary Intervention and Medical Therapy PCI Guided by Coronary Artery Hemodynamic Data Selection of Percutaneous Coronary Intervention for Revascularization Coronary Artery Bypass Grafting Minimally Invasive Coronary Artery Bypass Surgery Arterial and Venous Conduits Patency of Venous and Arterial Grafts.Early occlusion (before hospital discharge) occurs in 8% to 12% of venous grafts, and by 1... Distal vasculature.The state of the distal coronary vasculature is important for the fate of bypass grafts. Late patency of graf... Progression of Disease in Native Arteries Effects of Therapy on Vein Graft Occlusion and Native Vessel Progression.Measures aimed at enhancing long-­term patency are gene... Antiplatelet Therapy Lipid-­Lowering Therapy Patient Selection Surgical Outcomes and Long-­Term Results Operative Mortality Perioperative Complications Relief of Angina Effects on Survival Perioperative Complications.Perioperative morbidity has increased because of a larger fraction of higher-­risk patients. The rat... Myocardial Infarction.Perioperative MI, particularly if associated with hemodynamic or arrhythmic complications or with preexist... Cerebrovascular Complications.Neurologic abnormalities following cardiac surgery are dreaded complications and are associated wi... Atrial Fibrillation.This arrhythmia is one of the most frequent complications of CABG.229,230 It occurs in up to 40% of patients... Renal Dysfunction.The incidence of renal failure requiring dialysis after CABG remains low (0.5% to 2.0%), but it is associated ... Surgical Treatment in Special Groups Women (see Chapter 91) Older Patients (See Chapter 90) Renal Disease Patients with Diabetes (See Chapter 31) ?Patients with Associated Other Vascular Disease.The management of patients with peripheral artery disease and cerebrovascular d... Patients Requiring Reoperation Comparisons between Percutaneous Coronary Intervention and Coronary Artery Bypass Surgery Observational Studies Randomized Trials Coronary Bypass Surgery in Patients With Associated Vascular Disease.Management of patients with combined CAD and peripheral vas... Implications of Combined Coronary Artery Disease and Peripheral Artery Disease.Clinically apparent CAD occurs frequently in pati... Carotid Artery Disease.In patients with stable CAD and carotid artery disease in whom carotid endarterectomy or stenting is plan... Management of Patients With Associated Vascular Disease.Patients with severe or unstable CAD requiring revascularization can be ... Choosing between Percutaneous Coronary Intervention, Coronary Artery Bypass Surgery, and Medical Therapy Single-­Vessel Disease Multivessel Disease Need for Complete Revascularization Prinzmetal (Variant) Angina Microvascular Dysfunction Evidence of Ischemia Abnormal Pain Perception Clinical Features Clinical and Diagnostic Assessment Prognosis Management Silent Myocardial Ischemia Ischemic Cardiomyopathy Mechanisms of Silent Myocardial Ischemia Prognosis Detection and Management of Silent Ischemia Left Ventricular Aneurysm Mitral Regurgitation Secondary to Coronary Artery Disease Management Left Ventricular Aneurysm Detection.Clues to the presence of an aneurysm include persistent ST-­segment elevations on the resting ECG (in the absence of c... Detection.Clues to the presence of an aneurysm include persistent ST-­segment elevations on the resting ECG (in the absence of c... Left Ventricular Aneurysmectomy.True LV aneurysms do not rupture, and operative excision may be carried out to improve the clini... Cardiac Transplantation–Associated Coronary Arteriopathy Future Perspectives References EFIGURE 40.12Commonly asked questions about stable angina. (From Joshi PH, de Lemos JA. Diagnosis and management of stable angin... EFIGURE 40.13Common diagnostic tests for stable angina. (From Joshi PH, de Lemos JA. Diagnosis and management of stable angina: ... EFIGURE 40.15Common antianginal therapies used in the United States. (From Joshi PH, de Lemos JA. Diagnosis and management of st... EFIGURE 40.16Key randomized clinical trials of revascularization in patients with stable angina. (From Joshi PH, de Lemos JA. Di... EFIGURE 40.17Approach to diagnosis and management of stable angina. (From Joshi PH, de Lemos JA. Diagnosis and management of sta... 41 41 - Percutaneous Coronary Intervention Background Indications Clinical Presentations Stable Ischemic Heart Disease and Stable Angina Acute Coronary Syndromes Asymptomatic or Minimally Symptomatic Patients Preoperative Considerations (see Chapter 23) Patient-­Specific Considerations Extent of Jeopardized Myocardium Specific Lesion Subsets Left Main Disease Multivessel Disease Chronic Total Occlusions Saphenous Vein Grafts (Fig. 41.2) Bifurcation Lesions Lesion Calcification Thrombotic Lesions Diabetes Mellitus (see Chapter 31) Cardiomyopathy/Left Ventricular Dysfunction Ischemic Cardiomyopathy Role of Left Ventricular Dysfunction in PCI Role of PCI in Cardiogenic Shock Renal Dysfunction and Other Comorbidities Coronary Devices Balloon Angioplasty Coronary Stents (see eFig. 41.2) ?Drug-­Eluting Stents (also see the online chapter for further discussion) Zotarolimus-­Eluting Stents Everolimus-­Eluting Stents Sirolimus-­Eluting Stents Paclitaxel-­Eluting Stents Zotarolimus-­Eluting Stents Everolimus-­Eluting Stents ?Bioabsorbable Polymer Drug-­Eluting Stents (also see the online chapter for further discussion) Bioresorbable Vascular Scaffolds Coronary Atherectomy Rotational Atherectomy (Fig. 41.5) Orbital Atherectomy Excimer Laser Angioplasty Thrombectomy and Aspiration Devices Drug-­Coated Balloons Coronary Physiology (see Chapter 36) Mechanical Aspiration Intravascular Imaging (see Chapter 21) Vascular Access ?Complications Vascular Closure Devices Aspirin Complications of Femoral Access Glycoprotein IIb/IIIa Inhibitors Antithrombin Agents (see CHAPTERS 9, 38,AND 39) Unfractionated Heparin Low-­Molecular-­Weight Heparin Bivalirudin Factor Xa Inhibitors Early Clinical Outcomes Mortality Myocardial Infarction Urgent Revascularization Angiographic Complications Stent Thrombosis Late Clinical Outcomes Future Perspectives References 42 42 - Diseases of the Aorta The Normal Aorta Anatomy and Physiology Physiology Evaluation of the Aorta Aortic Aneurysms Abdominal Aortic Aneurysms Pathogenesis Clinical Features Diagnostic Imaging Ultrasound/Computed Tomography/Magnetic Resonance Imaging/Aortography Screening Genetics/Molecular Genetics Natural History Ruptured Abdominal Aortic Aneurysm Management Surveillance/Medical Therapy Surgery Techniques and Outcomes.For OSR of infrarenal AAAs, the abdominal aorta is approached through either a transperitoneal or a left... Endovascular Abdominal Aortic Aneurysm Repair.In patients with suitable anatomy, EVAR offers a less invasive alternative to OSR.... Thoracic Aortic Aneurysms Cause and Pathogenesis Genetically Triggered Thoracic Aortic Aneurysm Diseases Degenerative Aneurysms Aortic Dissection Kommerell Diverticulum Syphilis and Aortitis Clinical Manifestations Diagnosis Natural History Management Ascending Thoracic Aortic Aneurysms.Treatment of ascending TAAs involves opening the ascending aorta and placement of a prosthet... Aortic Arch Aneurysms.Aortic arch aneurysms are more difficult to treat surgically because reconstruction of the aortic arch ves... Descending Thoracic Aneurysms.Treatment paradigms for descending TAAs have changed due to the rapid development of TEVAR with en... Thoracoabdominal Aneurysms.Thoracoabdominal aneurysms (TAAAs) can extend from the subclavian artery to the iliac vessels. The Cr... Endovascular Repair of Thoracic Aneurysms.TEVAR, a far less invasive alternative to OSR of descending TAAs, has lower morbidity ... Anchor 616 Medical Management Aortic Dissection Classification Cause and Pathogenesis Clinical Manifestations Symptoms Physical Findings Laboratory Findings Diagnostic Techniques Computed Tomography Magnetic Resonance Imaging Echocardiogram (see also Chapter 16) Transthoracic Echocardiography Transesophageal Echocardiography Aortography Selecting an Imaging Modality The Role of Coronary Angiography Management Blood Pressure Reduction Management of Cardiac Tamponade Definitive Therapy Long-­Term Therapy and Follow-­Up Aortic Dissection Variants Aortic Intramural Hematoma Penetrating Atherosclerotic Aortic Ulcer Aortoarteritis Syndromes Bacterial Infections of the Aorta (see Chapter 80) Primary Tumors of the Aorta Future Perspectives References 43 43 - Peripheral Artery Diseases Epidemiology Risk Factors for Peripheral Artery Disease Pathophysiology of Peripheral Artery Disease Factors Regulating Blood Supply Clinical Features Symptoms Physical Findings Categorization Testing for Peripheral Artery Disease Segmental Pressure Measurement Ankle-­Brachial Index Treadmill Exercise Testing (see Chapter 15) Pulse Volume Recording Doppler Ultrasonography Duplex Ultrasound Imaging Magnetic Resonance Angiography (see Chapter 19) Contrast-­Enhanced Angiography Other Measurement Tools Prognosis Treatment Risk Factor Modification (see also Chapter 25) Diet Smoking Cessation Treatment of Diabetes (see also Chapter 31) Blood Pressure Control Lipid-­Lowering Therapy (see also Chapter 27) Antithrombotic Therapy for Reduction of Major Adverse Cardiovascular and Limb Events Antiplatelet Monotherapy Dual Antiplatelet Therapy with Aspirin and P2Y12 Inhibition Combination Antiplatelet and Anticoagulant Therapy Other Combination Therapies Smoking Cessation Supervised and Home-­Based Exercise Training Pharmacotherapy to Improve Claudication Vasodilators Other Medical Therapies Peripheral Artery Surgery Vasculitis (See also Chapter 97) Thromboangiitis Obliterans Pathology and Pathogenesis Clinical Features Diagnosis Treatment Fibromuscular Dysplasia Popliteal Artery Entrapment Syndrome Acute Limb Ischemia Prognosis Pathogenesis Diagnostic Tests Treatment Atheroembolism Pathogenesis Clinical Features Diagnostic Tests Treatment References 44 44 - Treatment of Noncoronary Obstructive Vascular Disease Endovascular Technologies Balloon Angioplasty Bare-­Metal Stents Drug-­Eluting Peripheral Stents Drug-­Coated Balloons Controversy About Paclitaxel-­Coated Balloons and Stents Covered Stents Thrombolysis Mechanical and Aspiration Thrombectomy Rotational, Orbital, and Directional Atherectomy Laser Atherectomy Cryoplasty and Intravascular Lithotripsy Medical Therapy to Improve Endovascular Durability Planning an Intervention Vascular Imaging Vascular Access Peripheral Artery Disease of the Lower Extremities Aortoiliac Disease Femoral-­Popliteal Artery Disease Tibial Disease Cervical Artery Disease Extracranial Carotid Disease Vertebral and Subclavian Artery Disease Mesenteric and Renal Artery Disease Mesenteric Artery Renal Artery Extremity Deep Venous Thrombosis Superior Vena Cava Syndrome Future Perspectives References 45 45 - Prevention and Management of Ischemic Stroke Classification of Ischemic Stroke Stroke Risk Factors and Prevention Antiplatelet Therapy for Primary Prevention Stroke Prevention in Atrial Fibrillation Secondary Prevention of Ischemic Stroke Antiplatelet Therapy Anticoagulant Therapy Management of Acute Ischemic Stroke Endovascular Therapy Infective Endocarditis Conclusions Classic References References Disclosure Index RELATIONSHIP CODES Institution and Company Codes Contributors Index IBC