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Book Details
Abstract
Manage cardiovascular problems more effectively with the most comprehensive resource available! A trusted companion to Braunwald's Heart Disease, Cardiovascular Therapeutics, 4th Edition addresses pharmacological, interventional, and surgical management approaches for each type of cardiovascular disease. This practical and clinically focused cardiology reference offers a balanced, complete approach to all of the usual and unusual areas of cardiovascular disease and specific therapies in one concise volume, equipping you to make the best choices for every patient.
- Consult this title on your favorite e-reader with intuitive search tools and adjustable font sizes. Elsevier eBooks provide instant portable access to your entire library, no matter what device you're using or where you're located.
- Understand current approaches to treating and managing cardiovascular patients for long-term health, for complex problems, and for unusual cardiac events.
- Benefit from the substantial experience of Elliott M. Antman, MD, Marc S. Sabatine, MD, and a host of other respected authorities, who provide practical, evidence-based rationales for all of today's clinical therapies.
- Expand your knowledge beyond pharmacologic interventions with complete coverage of the most effective interventional and device therapies being used today.
- Easily reference Braunwald's Heart Disease, 9th Edition for further information on topics of interest.
- Make the best use of the latest genetic and molecular therapies as well as advanced therapies for heart failure.
- Cut right to the answers you need with an enhanced focus on clinically relevant information and a decreased emphasis on pathophysiology.
- Stay current with ACC/AHA/ESC guidelines and the best ways to implement them in clinical practice.
- Get an enhanced visual perspective with an all-new, full-color design throughout.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front cover | cover | ||
| Cardiovascular Therapeutics - A Companion to Braunwald's Heart Disease | iii | ||
| Copyright page | iv | ||
| Dedication | v | ||
| Half title page | i | ||
| Look for these other titles in the Braunwald Heart Disease family | ii | ||
| Braunwald’s Heart Disease Companions | ii | ||
| Braunwald’s Heart Disease Imaging Companions | ii | ||
| Contributors | vii | ||
| Foreword | xiii | ||
| Preface | xv | ||
| Acknowledgments | xvii | ||
| Table of Contents | xix | ||
| I Decision Making and Therapeutic Strategies in Cardiovascular Medicine | 1 | ||
| 1 Tools for Assessment of Cardiovascular Tests and Therapies | 1 | ||
| Interpretation of Diagnostic Tests | 1 | ||
| Clinical Trials | 3 | ||
| Need for Clinical Trials | 3 | ||
| Clinical Trial Design | 4 | ||
| Randomized Controlled Trials | 6 | ||
| Nonrandomized Concurrent Control Studies | 7 | ||
| Historic Controls | 7 | ||
| Crossover Design | 7 | ||
| Withdrawal Studies | 7 | ||
| Factorial Design | 7 | ||
| Trials that Test Equivalence of Therapies | 8 | ||
| Selection of Endpoint | 9 | ||
| Sample Size Estimations and Sequential Stopping Boundaries | 9 | ||
| False-Positive and False-Negative Error Rates and Power of Clinical Trials | 9 | ||
| How to Read and Interpret a Clinical Trial | 11 | ||
| Missing Data | 12 | ||
| Measures of Treatment Effect | 12 | ||
| Detection of Treatment Effects in Clinical Trials | 13 | ||
| Meta-Analysis | 15 | ||
| Principles of Pooling Studies | 16 | ||
| Cumulative Meta-Analysis | 16 | ||
| Meta-Regression | 17 | ||
| Future Trends in Meta-Analysis | 18 | ||
| How to Read and Interpret a Meta-Analysis | 18 | ||
| Comparative Effectiveness Research | 19 | ||
| Methods for Comparative Effectiveness Research | 20 | ||
| Balancing Risks and Benefits | 22 | ||
| Cost-Effectiveness Analysis | 23 | ||
| Types of Economic Evaluation | 23 | ||
| Methods for Performing a Cost-Effectiveness Analysis | 24 | ||
| Trial-Based Analyses | 24 | ||
| Modeling Approaches | 25 | ||
| Hybrid Approaches | 26 | ||
| Other Methodologic Considerations | 26 | ||
| Sensitivity Analysis | 26 | ||
| Perspective | 27 | ||
| Discounting | 27 | ||
| Time Horizon | 28 | ||
| Defining When a Therapy Is Cost Effective | 29 | ||
| How to Read an Economic Evaluation | 30 | ||
| References | 30 | ||
| 2 New Drug Development | 33 | ||
| Overview of the Drug Development Process | 33 | ||
| Phase I to IV Paradigm | 33 | ||
| Cycle of New Therapeutic Development | 33 | ||
| Regulation of New Drugs: Prototypical Interface with the Food and Drug Administration | 34 | ||
| Before the Investigational New Drug Application | 34 | ||
| Types of Investigational New Drug Application | 35 | ||
| Advisory Panels | 35 | ||
| Labeling | 35 | ||
| Postmarketing Surveillance | 35 | ||
| Exemptions from Investigational New Drug Application and Practice of Medicine | 36 | ||
| Investigator-Initiated Investigational New Drug Application | 36 | ||
| CDER Versus CBER: Key Differences for Biologics | 36 | ||
| International Drug Development Overview | 36 | ||
| Ethics of Drug Development in Developing Countries | 37 | ||
| Anatomy of a Clinical Trial: Operations | 37 | ||
| Protocol Development | 37 | ||
| Site Management | 38 | ||
| Data Management | 38 | ||
| Statistics | 38 | ||
| Safety Surveillance | 38 | ||
| Clinical Events Adjudication | 38 | ||
| Economics of New Drug Development | 38 | ||
| Prescription Drug User Fee Act | 38 | ||
| National Institutes of Health Roadmap Program | 39 | ||
| Patent Considerations | 39 | ||
| Summary | 39 | ||
| References | 39 | ||
| 3 Device Development for Cardiovascular Therapeutics: | 41 | ||
| Overview | 41 | ||
| Medical Device Development and Differences from Drugs | 41 | ||
| Development and Implementation of Cardiovascular Medical Devices: An Overview | 41 | ||
| Differences Between Devices and Drugs and Associated Regulatory Implications | 42 | ||
| Regulatory Fundamentals | 42 | ||
| History of Device Regulation and the Medical Device Classification System | 42 | ||
| Pathways for Regulatory Review of Cardiovascular Devices | 43 | ||
| 510(k) Premarket Notification | 43 | ||
| Premarket Approval Application | 43 | ||
| Investigational Device Exemption | 43 | ||
| Humanitarian Device Exemption | 44 | ||
| Contemporary Regulatory Issues | 44 | ||
| Randomized Versus Nonrandomized Studies in Medical Device Evaluation | 44 | ||
| Endpoints and Surrogate Endpoints in Cardiovascular Device Trials | 45 | ||
| Study Blinding in Cardiovascular Device Trials | 46 | ||
| Use of Foreign Data for U.S. Product Approval | 46 | ||
| Independent Oversight of Cardiovascular Device Trials | 46 | ||
| Labeling and Off-Label Use of Cardiovascular Devices | 46 | ||
| Risk, Benefit, and the Product Life Cycle | 47 | ||
| Total Product Life Cycle Approach | 47 | ||
| Device Safety and Failure Concepts | 47 | ||
| Ensuring the Safety of Marketed Devices | 48 | ||
| Postmarket Safety Assessment Tools | 48 | ||
| Cardiologists’ Role in Ensuring Device Safety and Performance | 50 | ||
| Product Recall and Center for Devices and Radiological Health | 50 | ||
| Other Key Regulatory Topics | 50 | ||
| Combination Products | 50 | ||
| Role of the Advisory Panel | 51 | ||
| CDRH Interactions with External Stakeholders and Government Partners | 51 | ||
| References | 51 | ||
| 4 Pharmacogenetics | 53 | ||
| Clopidogrel | 53 | ||
| Drug, Indications, Mechanism of Action, and Pharmacology | 53 | ||
| Drug Interactions | 53 | ||
| Pharmacogenetics of Clopidogrel Therapy | 53 | ||
| CYP2C19 | 54 | ||
| ABCB1 | 56 | ||
| PON1 | 56 | ||
| Therapeutic Implications | 56 | ||
| Pharmacogenetic Testing in Clopidogrel Therapy | 56 | ||
| Therapeutic modifications | 56 | ||
| Cost Effectiveness of Clopidogrel Pharmacogenetics Testing | 57 | ||
| Future Directions | 57 | ||
| Warfarin | 57 | ||
| Drug, Indications, Mechanism of Action, and Pharmacology | 57 | ||
| Drug Interactions | 57 | ||
| Pharmacogenetics of Warfarin Therapy | 57 | ||
| VKORC1 | 57 | ||
| CYP2C9 | 59 | ||
| CYP4F2 | 59 | ||
| Therapeutic Implications | 59 | ||
| Pharmacogenetic Testing in Warfarin Therapy | 59 | ||
| Cost Effectiveness of Warfarin Pharmacogenetics Testing | 59 | ||
| Therapeutic Modifications | 59 | ||
| Future Directions | 60 | ||
| Statins | 60 | ||
| Drug, Indications, Mechanism of Action, and Pharmacology | 60 | ||
| Drug Interactions | 60 | ||
| Pharmacogenetics of Statin Therapy | 61 | ||
| Key Genetic Variants Affecting Statin Efficacy | 61 | ||
| APOE | 61 | ||
| PCSK9 | 61 | ||
| HMGCR | 61 | ||
| CETP | 61 | ||
| LDLR | 62 | ||
| KIF6 | 62 | ||
| Genome-Wide Association Studies of Statin Response | 63 | ||
| Key Genetic Variants Affecting Statin Adverse Effects | 63 | ||
| SLCO1B1 | 63 | ||
| Therapeutic Implications | 63 | ||
| Future Directions | 63 | ||
| References | 63 | ||
| 5 Systems of Health Care | 67 | ||
| Systems Theory | 67 | ||
| Why Systems of Care Are Needed | 67 | ||
| Experience to Date with Cardiovascular Systems of Care | 68 | ||
| ST-Segment Elevation Myocardial Infarction | 68 | ||
| Prehospital Diagnosis, Catheterization Laboratory Activation, and Transport to Primary Percutaneous Coronary Intervention Centers | 68 | ||
| Regional Transfer Protocols | 69 | ||
| State Systems for ST-Segment Elevation Myocardial Infarction CARE | 69 | ||
| Mission: Lifeline Program to Improve ST-Segment Elevation Myocardial Infarction CARE | 69 | ||
| Heart Failure | 69 | ||
| Cardiac Arrest | 70 | ||
| Quality Improvement Theory | 70 | ||
| Experience to Date with Cardiovascular Quality Improvement | 71 | ||
| ST-Segment Elevation Myocardial Infarction | 71 | ||
| American College of Cardiology Door-to-Balloon Alliance | 71 | ||
| CRUSADE Initiative | 71 | ||
| Get with the Guidelines—Coronary Artery Disease Program | 71 | ||
| Acute Coronary Treatment and Intervention Outcomes Network | 71 | ||
| Heart Failure | 72 | ||
| Out-of-Hospital Cardiac Arrest | 72 | ||
| Lessons Learned | 72 | ||
| References | 72 | ||
| 6 Global Cardiovascular Therapy | 75 | ||
| Introduction to Global Challenges in Cardiovascular Disease Therapy | 75 | ||
| Burden of Cardiovascular Disease | 75 | ||
| Current Trends and Challenges | 75 | ||
| Acute Management and Secondary Prevention | 75 | ||
| Acute Coronary Syndrome | 75 | ||
| Secondary Prevention | 76 | ||
| Challenges to Therapeutic Usage | 77 | ||
| Current State of cardiovascular disease Drug Availability and Affordability in Low- and Middle-Income Countries | 77 | ||
| Role of the World Health Organization Essential Drug List | 78 | ||
| Human Resources Shortages | 78 | ||
| Primary Prevention | 79 | ||
| Polypill | 79 | ||
| Population Strategies | 80 | ||
| Risk Factors for Cardiovascular Disease | 80 | ||
| Tobacco | 80 | ||
| Blood Pressure | 80 | ||
| Lipids | 81 | ||
| Obesity | 81 | ||
| Summary | 81 | ||
| References | 81 | ||
| II Ischemic Heart Disease | 83 | ||
| 7 Pharmacologic Options for Treatment of Ischemic Disease | 83 | ||
| Organic Nitrates | 83 | ||
| Overview | 83 | ||
| Mechanisms of Action | 83 | ||
| Pharmacokinetics | 84 | ||
| Pharmacodynamic Effects | 84 | ||
| Side Effects of Organic Nitrates | 84 | ||
| Clinical Efficacy of Organic Nitrates | 85 | ||
| Sublingual Nitrates | 85 | ||
| Long-Acting Nitrates | 85 | ||
| Congestive Heart Failure | 87 | ||
| Other Nitrate Indications | 87 | ||
| Nitrate Tolerance | 87 | ||
| Biotransformation Hypothesis | 87 | ||
| Neurohormonal Hypothesis | 88 | ||
| Free Radical Hypothesis | 88 | ||
| Nonhemodynamic Effects of Organic Nitrates | 88 | ||
| Current Perspectives on Therapy with Organic Nitrates | 89 | ||
| Calcium Channel Blockers | 89 | ||
| Fundamental Mechanisms of Calcium Channel Blockers | 89 | ||
| Calcium Channel as Site of Action | 89 | ||
| Molecular Structure | 90 | ||
| Drug Binding Sites | 90 | ||
| Calcium Channels: L and T Types | 90 | ||
| Pharmacologic Properties of Calcium Channel Blockers | 90 | ||
| Pharmacodynamic Effects | 90 | ||
| Major Cardiovascular Actions of Calcium Channel Blockers | 91 | ||
| Classification of Calcium Channel Blockers | 91 | ||
| Vascular Selectivity | 91 | ||
| Noncardiovascular Effects | 91 | ||
| Pharmacokinetics | 91 | ||
| Major Indications for Calcium Channel Blockers | 92 | ||
| Systemic Hypertension | 92 | ||
| Angina Pectoris | 92 | ||
| Supraventricular Tachycardia | 92 | ||
| Postinfarct Protection | 92 | ||
| Specific Calcium Channel Blockers | 92 | ||
| Verapamil | 92 | ||
| Pharmacokinetics | 92 | ||
| III Heart Failure | 241 | ||
| 12 Pharmacologic Management of Heart Failure in the Ambulatory Setting | 241 | ||
| Pathophysiology and Staging System: Targets of Therapy | 241 | ||
| Diuretics and Sodium Restriction | 242 | ||
| Pathophysiologic Mechanisms | 242 | ||
| Sodium Restriction | 243 | ||
| Diuretics | 243 | ||
| Mechanisms of Action | 243 | ||
| Adverse Effects | 244 | ||
| Practical Considerations | 244 | ||
| Renin-Angiotensin System Inhibitors | 245 | ||
| Pathophysiologic Mechanisms | 245 | ||
| Clinical Efficacy | 246 | ||
| Angiotensin-Converting Enzyme Inhibitors | 246 | ||
| Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) | 246 | ||
| Vasodilator Heart Failure Trial (V-HeFT) II | 246 | ||
| Studies of Left Ventricular Dysfunction (SOLVD) | 246 | ||
| Assessment of Treatment with Lisinopril and Survival (ATLAS) | 246 | ||
| Angiotensin Receptor Blockers | 246 | ||
| Practical Considerations | 248 | ||
| Angiotensin-Converting Enzyme Inhibitors | 248 | ||
| Angiotensin Receptor Blockers | 249 | ||
| β-Blockers | 250 | ||
| Pathophysiologic Rationale | 250 | ||
| Pharmacology | 250 | ||
| Clinical Efficacy | 250 | ||
| Cardiac Insufficiency Bisoprolol Studies (CIBIS) I and II | 250 | ||
| U.S. Carvedilol Heart Failure Trials | 250 | ||
| Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) | 251 | ||
| β-Blocker Evaluation and Survival Trial (BEST) | 251 | ||
| Carvedilol Prospective Randomized Cumulative Survival Trial (COPERNICUS) | 251 | ||
| Carvedilol and Metoprolol European Trial (COMET) | 251 | ||
| Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) | 252 | ||
| Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure (SENIORS) | 252 | ||
| Practical Considerations | 252 | ||
| Choice of β-Blocker | 253 | ||
| Aldosterone Antagonists | 253 | ||
| Pathophysiology | 253 | ||
| Clinical Efficacy | 253 | ||
| Practical Considerations | 254 | ||
| Options for Patients who Remain Symptomatic Despite Standard Therapy | 254 | ||
| Hydralazine and Isosorbide Dinitrate | 255 | ||
| Practical Considerations | 255 | ||
| Digoxin | 256 | ||
| Pharmacologic and Clinical Effects | 256 | ||
| Practical Considerations | 256 | ||
| Calcium Channel Blockers | 257 | ||
| Positive Inotropic Agents | 257 | ||
| Oral Positive Inotropes | 257 | ||
| Intravenous Positive Inotropes | 257 | ||
| Bridge to Transplantation | 257 | ||
| Bridge to End of Life | 257 | ||
| Antithrombotic Therapy | 258 | ||
| Antiarrhythmic Therapy | 258 | ||
| Special Considerations | 259 | ||
| Heart Failure Patients with Preserved Ejection Fraction | 259 | ||
| Clinical Efficacy | 259 | ||
| Practical Considerations | 260 | ||
| Patients with Ischemic Heart Disease | 261 | ||
| Patients with Valvular Heart Disease | 262 | ||
| Patients with Diabetes | 262 | ||
| Gender, Race, and Ethnic Considerations | 262 | ||
| Patients with Myocarditis | 262 | ||
| Future Directions in Pharmacologic Therapy | 263 | ||
| Pharmacotherapy | 263 | ||
| Comorbidities | 264 | ||
| References | 264 | ||
| 13 Implantable Devices for the Management of Heart Failure | 270 | ||
| Implantable Cardioverter-Defibrillators in the Management of Heart Failure | 270 | ||
| MADIT II | 271 | ||
| DEFINITE | 271 | ||
| SCD-HeFT | 271 | ||
| Implantable Cardioverter-Defibrillators Early After Myocardial Infarction | 272 | ||
| DINAMIT | 272 | ||
| IRIS | 272 | ||
| Indications for Prophylactic Cardioverter-Defibrillator Implantation in Heart Failure Patients | 272 | ||
| Practical Considerations in Implantable Cardioverter-Defibrillator Therapy | 272 | ||
| Conduction Abnormalities in Heart Failure | 273 | ||
| Landmark Cardiac Resynchronization Therapy Clinical Trials | 273 | ||
| MUSTIC | 273 | ||
| MIRACLE | 273 | ||
| MIRACLE ICD | 274 | ||
| CONTAK CD | 274 | ||
| COMPANION | 274 | ||
| CARE-HF | 275 | ||
| Cardiac Resynchronization Therapy in Mild Heart Failure | 275 | ||
| REVERSE | 275 | ||
| MADIT-CRT | 275 | ||
| RAFT | 275 | ||
| Cardiac Resynchronization Therapy | 276 | ||
| Cardiac Resynchronization Therapy in Long-Term Right Ventricle Pacing | 276 | ||
| Cardiac Resynchronization Therapy in Atrial Fibrillation | 276 | ||
| Indications for Cardiac Resynchronization Therapy in Heart Failure Patients | 276 | ||
| Future Directions of Cardiac Resynchronization Therapy | 276 | ||
| Monitoring Heart Failure Through Implantable Devices | 276 | ||
| Future Directions in Implantable Devices for the Management of Heart Failure | 278 | ||
| Summary | 278 | ||
| References | 279 | ||
| 14 Strategies for Management of Acute Decompensated Heart Failure | 281 | ||
| Terminology | 281 | ||
| Epidemiology | 281 | ||
| Pathophysiology | 282 | ||
| Heart Failure with Reduced Versus Preserved Ejection Fraction | 282 | ||
| Acute Compensatory Mechanisms | 283 | ||
| Myocardial Injury | 284 | ||
| Common Precipitating Factors of Heart Failure | 284 | ||
| General Management | 285 | ||
| Initial Patient Evaluation | 285 | ||
| Risk Stratification | 285 | ||
| Clinical Assessment of Intracardiac Filling Pressures | 285 | ||
| Clinical Assessment of Systemic Perfusion | 287 | ||
| Laboratory Assessment | 287 | ||
| B-Type Natriuretic Peptide | 287 | ||
| Noninvasive Versus Invasive Management | 288 | ||
| Hemodynamic Profiles | 289 | ||
| Hemodynamic Goals of Therapy | 290 | ||
| Fluid Management | 290 | ||
| Parenteral Diuretic Therapy | 290 | ||
| Ultrafiltration | 291 | ||
| Vasoactive Therapy | 292 | ||
| Nitroglycerin | 292 | ||
| Nesiritide | 292 | ||
| Nitroprusside | 293 | ||
| Dobutamine | 293 | ||
| Milrinone | 294 | ||
| Dopamine | 295 | ||
| Epinephrine and Norepinephrine | 296 | ||
| Digoxin | 296 | ||
| Adjustment of Oral Medications | 296 | ||
| Renin-Angiotensin-Aldosterone System Inhibitors | 296 | ||
| Nitrates and Hydralazine | 297 | ||
| β-Blockers | 297 | ||
| Oral Diuretics | 297 | ||
| Other Management Issues | 297 | ||
| Sodium and Fluid Restriction | 297 | ||
| Oxygen Supplementation | 297 | ||
| Ventricular Arrhythmias | 298 | ||
| Anticoagulation | 298 | ||
| Comorbidities | 298 | ||
| Discharge Planning and Immediate Postdischarge Care | 298 | ||
| Special Considerations | 299 | ||
| Mechanical Circulatory Support | 299 | ||
| Acute Pulmonary Edema | 299 | ||
| Heart Failure with Preserved Ejection Fraction | 301 | ||
| Unfulfilled Promises and Future Directions | 301 | ||
| References | 303 | ||
| 15 Cardiac Transplantation and Circulatory Support Devices | 307 | ||
| Overview | 307 | ||
| Patient Selection for Advanced Heart Failure Therapies | 307 | ||
| Cardiac Transplantation | 307 | ||
| Patient Selection | 307 | ||
| Assessment of Cardiac Disease Severity | 307 | ||
| Assessment of the Pulmonary Vasculature | 308 | ||
| Other Cardiac Transplantation Candidacy Issues | 308 | ||
| Age | 308 | ||
| Comorbidities | 308 | ||
| Immunologic Sensitization | 308 | ||
| Listing for Cardiac Transplantation | 309 | ||
| Pretransplantation Patient Management | 309 | ||
| Cardiac Transplantation Surgical Technique | 309 | ||
| Management of the Patient After Cardiac Transplantation | 309 | ||
| Prevention and Treatment of Cardiac Rejection | 310 | ||
| Drug Interactions | 310 | ||
| Prevention and Treatment of Posttransplant Complications | 310 | ||
| Infections | 312 | ||
| Hypertension | 313 | ||
| Diabetes | 313 | ||
| Dyslipidemia | 313 | ||
| Cardiac Allograft Vasculopathy | 313 | ||
| Renal Insufficiency | 313 | ||
| Malignancy | 313 | ||
| Future Directions | 314 | ||
| Mechanical Circulatory Support | 314 | ||
| Benefits of Mechanical Circulatory Support | 314 | ||
| Hemodynamic | 314 | ||
| Biologic | 314 | ||
| Configuration of Mechanical Circulatory Support | 314 | ||
| Pulsatile Flow | 314 | ||
| Continuous Flow | 314 | ||
| Cannulation | 315 | ||
| Indications for Mechanical Circulatory Support | 315 | ||
| Univentricular Versus Biventricular Support | 315 | ||
| Timing of Support | 315 | ||
| Considerations Prior to Long-Term Mechanical Circulatory Support | 317 | ||
| Cardiac Considerations | 317 | ||
| Right Ventricular Function | 317 | ||
| Valvular Disease | 318 | ||
| Arrhythmias | 318 | ||
| Other Cardiac Abnormalities | 318 | ||
| Noncardiac Considerations | 318 | ||
| Surgical Considerations | 318 | ||
| Other Considerations | 318 | ||
| Adverse Events | 319 | ||
| References | 319 | ||
| 16 Regenerative Therapy for Heart Failure | 322 | ||
| Circulating Progenitor Cells and Myocardial Regeneration | 322 | ||
| Hematopoietic Stem Cell Transdifferentiation | 323 | ||
| Bone Marrow Cells and Clinical Studies | 324 | ||
| Endogenous Cardiac Progenitors | 326 | ||
| Age, Cardiac Disease, and Human Cardiac Stem Cell Function | 327 | ||
| References | 331 | ||
| 17 Hypertrophic, Restrictive, and Infiltrative Cardiomyopathies | 332 | ||
| Hypertrophic Cardiomyopathy | 332 | ||
| Management of Left Ventricular Outflow Tract Obstruction | 332 | ||
| Therapies for Nonobstructive Hypertrophic Cardiomyopathy | 335 | ||
| Prevention of Sudden Cardiac Death in Hypertrophic Cardiomyopathy | 335 | ||
| Management of Atrial Fibrillation in Hypertrophic Cardiomyopathy | 335 | ||
| Screening at-Risk Family Members for Hypertrophic Cardiomyopathy | 336 | ||
| Restrictive and Infiltrative Cardiomyopathies | 336 | ||
| Idiopathic Restrictive Cardiomyopathy | 336 | ||
| Cardiac Amyloidosis | 336 | ||
| Cardiac Sarcoidosis | 337 | ||
| IV Arrhythmias and Conduction Disturbances | 343 | ||
| 18 Clinical Pharmacology of Antiarrhythmic Drugs | 343 | ||
| Classification of Antiarrhythmic Drugs | 344 | ||
| Drugs | 344 | ||
| Lidocaine | 344 | ||
| Clinical Applications | 344 | ||
| Mechanism of Action | 345 | ||
| Clinical Pharmacology | 345 | ||
| Dosage and Administration | 346 | ||
| Modification of Dosage in Disease States | 346 | ||
| V Dyslipoproteinemias and Atherosclerosis | 421 | ||
| 24 Drugs for Elevated Low-Density Lipoprotein Cholesterol | 421 | ||
| Effects on Lipids and Lipoproteins | 421 | ||
| Pharmacokinetic Properties | 422 | ||
| Drug Interactions | 422 | ||
| Efficacy | 423 | ||
| Angiographic Trials | 423 | ||
| Large-Scale Clinical Trials | 423 | ||
| Mechanism of Benefit of Statins | 424 | ||
| Safety | 424 | ||
| Liver | 424 | ||
| Muscle | 427 | ||
| Bile Acid Sequestrants | 428 | ||
| Effects on Lipids and Lipoproteins | 429 | ||
| Efficacy | 429 | ||
| Safety/Compliance Issues | 429 | ||
| Ezetimibe and Cholesterol Absorption Inhibitors | 430 | ||
| VI Hypertension | 463 | ||
| 28 Initial Evaluation and Approach to the Patient with Hypertension | 463 | ||
| Overview and Definitions | 463 | ||
| Evaluation of the Patient | 463 | ||
| History | 463 | ||
| Present Illness | 464 | ||
| Family History | 465 | ||
| Past Medical History | 465 | ||
| Review of Systems | 465 | ||
| Personal History | 465 | ||
| Physical Examination | 465 | ||
| Blood Pressure Measurement | 466 | ||
| Laboratory Evaluation | 466 | ||
| Overview of Treatment of the Hypertensive Patient | 467 | ||
| Resistant Hypertension | 467 | ||
| Adherence to Antihypertensive Medications | 468 | ||
| Lifestyle Modifications: Overview | 468 | ||
| Practical Approaches to Encouraging Lifestyle Modifications | 469 | ||
| Barriers to Lifestyle Modifications | 469 | ||
| Approaches to Increasing the Adoption of Lifestyle Modifications | 469 | ||
| Readiness for Change | 470 | ||
| Tips for Success in Adopting Healthier Dietary Practices | 471 | ||
| Tips for Success in Increasing Physical Activity | 471 | ||
| General Tips for Adopting Healthier Lifestyles | 471 | ||
| Conclusion | 472 | ||
| References | 472 | ||
| 29 Pharmacologic Management of Hypertension | 474 | ||
| Overview | 474 | ||
| Principles of Treatment | 474 | ||
| Evidence-Based Treatment | 474 | ||
| Blood Pressure Goals | 474 | ||
| Selecting Drug Therapy | 474 | ||
| Uncomplicated Hypertension | 475 | ||
| Patients with Compelling Indications | 475 | ||
| Diabetes | 475 | ||
| Chronic Kidney Disease | 476 | ||
| Coronary Artery Disease | 476 | ||
| Left Ventricular Dysfunction | 476 | ||
| Previous Ischemic Stroke | 476 | ||
| Overview of Drug Classes | 476 | ||
| Angiotensin-Converting Enzyme Inhibitors | 478 | ||
| Angiotensin Receptor Blockers | 478 | ||
| Calcium Channel Blockers | 479 | ||
| Diuretics: Thiazides | 480 | ||
| β-Blockers | 481 | ||
| Aldosterone Antagonists | 482 | ||
| Other Agents | 482 | ||
| α-Blockers | 482 | ||
| Arterial Vasodilators | 483 | ||
| Central α-Agonists | 483 | ||
| Direct Renin Inhibitor | 483 | ||
| Rauwolfia Alkaloids | 484 | ||
| Implementing Drug Therapy | 484 | ||
| Need for 24-Hour Coverage | 484 | ||
| Monotherapy Versus Combination Therapy | 484 | ||
| Monotherapy | 484 | ||
| Combination Therapy | 484 | ||
| Effects of Patient Characteristics on Blood Pressure Lowering | 484 | ||
| Monitoring | 484 | ||
| Adherence | 486 | ||
| Step-Down Therapy | 486 | ||
| Special Populations | 486 | ||
| Elderly Patients | 486 | ||
| Isolated Systolic Hypertension | 486 | ||
| Blood Pressure Goals | 486 | ||
| Orthostatic Hypotension | 486 | ||
| Selecting Drug Therapy | 487 | ||
| African-American Patients | 487 | ||
| References | 487 | ||
| 30 Endocrine Causes of Hypertension | 490 | ||
| Pheochromocytoma | 490 | ||
| Presentation | 490 | ||
| Syndromic Pheochromocytoma | 490 | ||
| Diagnosis | 490 | ||
| Principles of Treatment | 490 | ||
| Preoperative Management | 490 | ||
| α-Adrenergic Blockade | 491 | ||
| β-Adrenergic Blockade | 493 | ||
| Catecholamine Synthesis Inhibitor | 493 | ||
| Calcium Channel Blockers | 493 | ||
| Acute Hypertensive Crises | 493 | ||
| Anesthesia and Surgery | 493 | ||
| Long-Term Postoperative Follow-Up | 494 | ||
| Malignant Pheochromocytoma | 494 | ||
| Pheochromocytoma in Pregnancy | 494 | ||
| Primary Aldosteronism | 494 | ||
| Diagnosis | 495 | ||
| Case Detection | 495 | ||
| Confirming the Diagnosis | 495 | ||
| Subtype Evaluation | 495 | ||
| Principles of Treatment | 496 | ||
| Surgical Treatment of Aldosterone-Producing Adenoma and Unilateral Hyperplasia | 496 | ||
| Pharmacologic Treatment | 497 | ||
| Pharmacologic Treatment of Glucocorticoid-Remediable Aldosteronism | 497 | ||
| Other Forms of Mineralocorticoid Excess | 497 | ||
| Hyperdeoxycorticosteronism | 497 | ||
| Congenital Adrenal Hyperplasia | 497 | ||
| 11-β-Hydroxylase Deficiency | 498 | ||
| 17-α-Hydroxylase Deficiency | 498 | ||
| Deoxycorticosterone-Producing Tumor | 498 | ||
| Primary Cortisol Resistance | 498 | ||
| Apparent Mineralocorticoid Excess Syndromes | 498 | ||
| Cushing Syndrome | 498 | ||
| Presentation | 498 | ||
| Diagnosis | 498 | ||
| VII Other Vascular Conditions | 539 | ||
| 35 Peripheral Artery Disease | 539 | ||
| Overview | 539 | ||
| Medical Therapy of Peripheral Artery Disease | 539 | ||
| Cardiovascular Risk Reduction | 539 | ||
| Antiplatelet Therapy | 539 | ||
| Anticoagulant Therapy | 541 | ||
| Lipid-Lowering Drugs | 541 | ||
| HMG-CoA Reductase Inhibitor (Statin) Therapy | 541 | ||
| Nonstatin Lipid-Lowering Therapy | 541 | ||
| Antihypertensive Therapy | 542 | ||
| Angiotensin-Converting Enzyme Inhibitor Therapy | 542 | ||
| β-Blocker Therapy | 542 | ||
| Smoking Cessation Therapy | 542 | ||
| Diabetes | 543 | ||
| Intermittent Claudication | 543 | ||
| Pentoxifylline | 543 | ||
| Cilostazol | 543 | ||
| Perioperative Medical Therapy for Noncardiac Vascular Surgery | 544 | ||
| β-Blockers | 544 | ||
| Statin Therapy | 544 | ||
| Antiplatelet Therapy | 544 | ||
| Interventional Management of Peripheral Artery Disease | 544 | ||
| Indications for Revascularization | 545 | ||
| Procedural Considerations | 546 | ||
| Aortoiliac Disease | 546 | ||
| Femoral-Popliteal Disease | 547 | ||
| Infrapopliteal Disease | 549 | ||
| Therapeutic Angiogenesis | 549 | ||
| Conclusions | 549 | ||
| References | 550 | ||
| 36 Cerebrovascular Disease | 553 | ||
| Atherosclerotic Carotid Artery Disease and Stroke | 553 | ||
| Risk of Stroke | 553 | ||
| Prevalence of Carotid Artery Disease | 553 | ||
| Medical Therapy of Atherosclerotic Carotid Artery Disease | 555 | ||
| Smoking Cessation | 555 | ||
| Antihypertensive Therapy | 555 | ||
| Lipid-Lowering Therapy | 556 | ||
| Antiplatelet Therapy | 557 | ||
| Revascularization for Carotid Artery Disease | 558 | ||
| Surgical Revascularization | 559 | ||
| Carotid Endarterectomy for Symptomatic Carotid Artery Stenosis | 559 | ||
| Carotid Endarterectomy for Asymptomatic Carotid Artery Stenosis | 560 | ||
| Endovascular Therapy for Carotid Artery Stenosis | 562 | ||
| Carotid Artery Stenting in Symptomatic and Asymptomatic Patients at HIGH Surgical Risk: Data From Large Registries | 563 | ||
| Carotid Artery Stenting in Patients at HIGH Surgical Risk: Data From Randomized Trials | 563 | ||
| Carotid Artery Stenting in Normal-Risk Symptomatic Patients | 563 | ||
| Carotid Artery Stenting in Normal-Risk Symptomatic and Asymptomatic Patients: CREST | 564 | ||
| Should Asymptomatic Carotid Artery Stenosis Be Revascularized? | 565 | ||
| Carotid Artery Disease and Coronary Artery Bypass Graft Surgery | 566 | ||
| References | 568 | ||
| 37 Renal Artery Stenosis | 571 | ||
| Overview | 571 | ||
| Clinical Manifestations | 571 | ||
| Natural History of Renal Artery Stenosis | 571 | ||
| Diagnosis of Renal Artery Stenosis | 571 | ||
| Treatment of Atherosclerotic Renal Artery Stenosis | 574 | ||
| Medical Therapy | 574 | ||
| Which Patients Should Be Revascularized? | 574 | ||
| Catheter-Based Intervention | 575 | ||
| Surveillance of Renovascular Disease | 577 | ||
| Catheter-Based Renal Artery Sympathetic Denervation | 578 | ||
| Conclusion | 578 | ||
| References | 578 | ||
| 38 Pulmonary Embolism and Deep Vein Thrombosis | 580 | ||
| Epidemiology and Risk Factors | 580 | ||
| Pathophysiology and Natural History | 582 | ||
| Diagnosis | 582 | ||
| Deep Vein Thrombosis | 582 | ||
| Clinical Presentation | 582 | ||
| Clinical Likelihood Assessment | 582 | ||
| Laboratory Testing | 582 | ||
| Imaging | 583 | ||
| Overall Diagnostic Algorithm | 583 | ||
| Pulmonary Embolism | 583 | ||
| Clinical Presentation | 583 | ||
| Laboratory Testing | 583 | ||
| Electrocardiogram | 583 | ||
| Chest Radiography | 583 | ||
| Chest Computed Tomography for Diagnosis and Risk Stratification | 584 | ||
| Echocardiography for Diagnosis and Risk Stratification | 584 | ||
| Lung Scanning | 584 | ||
| Magnetic Resonance Imaging | 585 | ||
| Overall Diagnostic Algorithm | 585 | ||
| Overall Risk Stratification of Pulmonary Embolism | 586 | ||
| Management | 586 | ||
| Spectrum of Disease: Superficial Venous Thrombosis, Deep Vein Thrombosis, and Pulmonary Embolism | 586 | ||
| Anticoagulation | 587 | ||
| Unfractionated Heparin | 587 | ||
| Heparin-Induced Thrombocytopenia | 587 | ||
| Low-Molecular-Weight Heparin | 588 | ||
| Fondaparinux | 588 | ||
| Warfarin | 588 | ||
| Direct Factor XA and Factor IIA Inhibitors | 589 | ||
| Basic Versus Advanced Therapy for Venous Thromboembolism | 589 | ||
| Deep Vein Thrombosis | 589 | ||
| Advanced Therapy for Pulmonary Embolism | 590 | ||
| Duration of Anticoagulation | 590 | ||
| Inferior Vena Cava Filters | 591 | ||
| Prevention | 591 | ||
| Prevention of Venous Thromboembolism in Patients with Cancer | 591 | ||
| Implementation of in-Hospital Prophylaxis | 592 | ||
| Hip Replacement, Knee Replacement, and Hip Fracture | 592 | ||
| Mechanical Prophylaxis | 592 | ||
| Unconventional Prophylaxis | 592 | ||
| Vitamin E | 592 | ||
| Statins | 593 | ||
| Duration of Prophylaxis and Extension of Prophylaxis after Hospital Discharge | 593 | ||
| Conclusions | 593 | ||
| References | 593 | ||
| 39 Treatment of Pulmonary Arterial Hypertension | 596 | ||
| Current State of Diagnosis | 596 | ||
| Epidemiologic Associations | 596 | ||
| Current Pathobiologic Paradigm of Pulmonary Arterial Hypertension | 596 | ||
| Diagnosis and Risk Stratification | 596 | ||
| Current State of Therapy | 599 | ||
| Prostanoids | 599 | ||
| Endothelin Receptor Antagonism | 601 | ||
| Phosphodiesterase Inhibition | 601 | ||
| Atrial Septostomy | 602 | ||
| Transplantation for Idiopathic Pulmonary Arterial Hypertension | 602 | ||
| Medical Therapy Algorithms | 602 | ||
| New Pathobiologic and Care Paradigms | 604 | ||
| Pregnancy and Contraception | 604 | ||
| References | 604 | ||
| 40 Aortic Disease | 606 | ||
| Abdominal Aortic Aneurysms | 606 | ||
| Surgical Management | 606 | ||
| Medical Management | 607 | ||
| Thoracic Aortic Aneurysms | 608 | ||
| Surgical Management | 608 | ||
| Medical Management | 613 | ||
| Aortic Dissection | 613 | ||
| Definitive Therapy | 614 | ||
| Long-Term Therapy and Late Follow-up | 616 | ||
| Intramural Hematoma | 617 | ||
| Penetrating Atherosclerotic Ulcer | 617 | ||
| Thoracic Aortic Atheroembolism | 617 | ||
| References | 618 | ||
| VIII Other Cardiovascular Conditions | 621 | ||
| 41 Pharmacologic Options for Treating Cardiovascular Disease During Pregnancy | 621 | ||
| Hypertension | 621 | ||
| Edema | 623 | ||
| Valvular Heart Disease | 623 | ||
| Thromboembolic Disease During Pregnancy | 624 | ||
| Fibrinolysis | 626 | ||
| Ischemic Heart Disease | 626 | ||
| Lipid Disorders | 627 | ||
| Heart Failure | 627 | ||
| Cardiac Arrhythmias | 628 | ||
| Marfan Syndrome | 629 | ||
| Pulmonary Hypertension | 629 | ||
| Antibiotic Prophylaxis | 630 | ||
| References | 630 | ||
| 42 Care for Adults with Congenital Heart Disease | 632 | ||
| Issues for the Care Provider | 632 | ||
| Endocarditis | 632 | ||
| Left-to-Right Shunting: General Principles | 632 | ||
| Cyanosis | 633 | ||
| Major Cyanotic Organ Complications | 634 | ||
| Musculoskeletal Changes | 634 | ||
| Hematologic Changes | 634 | ||
| Renal Changes | 634 | ||
| Cardiopulmonary Exercise | 634 | ||
| Neurologic Effects | 634 | ||
| Recommendations for Management of the Cyanotic Patient | 635 | ||
| Pregnancy | 635 | ||
| IX Appendix | 747 | ||
| Appendix Cardiovascular Devices | 747 | ||
| Pulmonary Artery Catheters | 747 | ||
| Indications | 747 | ||
| Design | 747 | ||
| Technical Aspects of Placement | 747 | ||
| Interpretation of Waveforms | 747 | ||
| Troubleshooting and Complications | 747 | ||
| Intraaortic Balloon Pump Counterpulsation | 749 | ||
| Indications | 749 | ||
| Design | 749 | ||
| Technical Aspects of Placement | 749 | ||
| Timing and Waveforms | 750 | ||
| Complications | 750 | ||
| Pericardiocentesis | 750 | ||
| Indications | 750 | ||
| Technical Aspects | 750 | ||
| Electrical Cardioversion and Defibrillation | 751 | ||
| Equipment | 751 | ||
| Setup and Patient Preparation | 751 | ||
| Technical Considerations | 751 | ||
| Permanent Pacemakers | 752 | ||
| Leads | 752 | ||
| Basic Pacing Concepts | 752 | ||
| Pacemaker Programming Considerations | 752 | ||
| Mode | 752 | ||
| Rate-Responsive Pacing | 752 | ||
| Pseudo Pacemaker Malfunction | 752 | ||
| Temporary Pacemakers | 752 | ||
| Indications | 752 | ||
| Placement | 758 | ||
| Complications and Troubleshooting | 758 | ||
| Implantable Cardioverter-Defibrillators | 758 | ||
| Programmed Therapies for Ventricular Arrhythmias | 759 | ||
| Magnet Operation | 759 | ||
| Inappropriate Shocks | 759 | ||
| Routine Follow-up | 760 | ||
| References | 760 | ||
| Index | 761 | ||
| A | 761 | ||
| B | 766 | ||
| C | 768 | ||
| D | 774 | ||
| E | 776 | ||
| F | 778 | ||
| G | 778 | ||
| H | 779 | ||
| I | 783 | ||
| J | 785 | ||
| K | 785 | ||
| L | 785 | ||
| M | 787 | ||
| N | 789 | ||
| O | 791 | ||
| P | 791 | ||
| Q | 796 | ||
| R | 796 | ||
| S | 799 | ||
| T | 802 | ||
| U | 804 | ||
| V | 804 | ||
| W | 807 | ||
| X | 807 | ||
| Y | 807 | ||
| Z | 807 |