BOOK
Cardiac Potassium Channel Disorders, An Issue of Cardiac Electrophysiology Clinics, E-Book
Mohammad Shenasa | Stanley Nattel
(2016)
Additional Information
Book Details
Abstract
This issue of Cardiac Electrophysiology Clinics, edited by Drs. Mohammad Shenasa and Stanley Nattel, will review Cardiac Potassium Channel Disorders in depth. Topics covered include but are not limited to: Molecular Biology of Cardiac Potassium Channels; Genetic Control of Potassium Channels; Potassium Channel Remodeling in Heart Disease; Gender-specific Effects of Potassium Channel Blockers; Pharmacogenetics of Potassium Channel Blockers; Multichannel Blockers; Selective Potassium Channel Blockers; and Proarrhythmic and Torsadogenic Effects of Potassium Channel Blockers in Patients.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Cardiac PotassiumChannel Disorders | i | ||
| Copyright | ii | ||
| Contributors | iii | ||
| CONSULTING EDITORS | iii | ||
| EDITORS | iii | ||
| AUTHORS | iii | ||
| Contents | vii | ||
| Foreword: The K+ Channel: One Channel, Many Arrhythmias! | vii | ||
| Preface: Cardiac Potassium Channel Disorders: From Basics to Clinics | vii | ||
| Molecular Basis of Functional Myocardial Potassium Channel Diversity | vii | ||
| Molecular Basis of Cardiac Delayed Rectifier Potassium Channel Function and Pharmacology | vii | ||
| Genetic Control of Potassium Channels | vii | ||
| Cardiac Delayed Rectifier Potassium Channels in Health and Disease | viii | ||
| Adenosine Triphosphate-Sensitive Potassium Currents in Heart Disease and Cardioprotection | viii | ||
| Potassium Channel Remodeling in Heart Disease | viii | ||
| Modulation of Cardiac Potassium Current by Neural Tone and Ischemia | viii | ||
| Clinical Features of Genetic Cardiac Diseases Related to Potassium Channelopathies | ix | ||
| Potassium Channel Block and Novel Autoimmune-Associated Long QT Syndrome | ix | ||
| Pharmacogenetics of Potassium Channel Blockers | ix | ||
| Mechanism of Proarrhythmic Effects of Potassium Channel Blockers | ix | ||
| Atrial-Selective Potassium Channel Blockers | x | ||
| Dofetilide: Electrophysiologic Effect, Efficacy, and Safety in Patients with Cardiac Arrhythmias | x | ||
| Sotalol | x | ||
| Dronedarone: Basic Pharmacology and Clinical Use | x | ||
| Ranolazine: Electrophysiologic Effect, Efficacy, and Safety in Patients with Cardiac Arrhythmias | xi | ||
| Proarrhythmic and Torsadogenic Effects of Potassium Channel Blockers in Patients | xi | ||
| Guidelines for Potassium Channel Blocker Use | xi | ||
| CARDIAC ELECTROPHYSIOLOGY CLINICS | xii | ||
| FORTHCOMING ISSUES | xii | ||
| September 2016 | xii | ||
| December 2016 | xii | ||
| March 2017 | xii | ||
| RECENT ISSUES | xii | ||
| March 2016 | xii | ||
| December 2015 | xii | ||
| September 2015 | xii | ||
| Foreword:\rThe K+ Channel: One Channel, Many Arrhythmias! | xiii | ||
| Preface:\rCardiac Potassium Channel Disorders: From Basics to Clinics | xv | ||
| Molecular Basis of Functional Myocardial Potassium Channel Diversity | 257 | ||
| Key points | 257 | ||
| INTRODUCTION | 257 | ||
| MYOCARDIAL KV CHANNELS: TRANSIENT OUTWARD AND DELAYED RECTIFIER KV CHANNELS | 260 | ||
| INWARDLY RECTIFYING (KIR) MYOCARDIAL K+ CHANNELS | 262 | ||
| PORE-FORMING (α) AND ACCESSORY/AUXILIARY SUBUNITS OF MYOCARDIAL K+ CHANNELS | 262 | ||
| MOLECULAR DETERMINANTS OF NATIVE MYOCARDIAL KV CHANNELS | 264 | ||
| MOLECULAR DETERMINANTS OF NATIVE MYOCARDIAL KIR AND K2P CHANNELS | 266 | ||
| MECHANISMS CONTRIBUTING TO THE MOLECULAR REGULATION OF MYOCARDIAL K+ CHANNELS | 267 | ||
| SUMMARY, OPEN QUESTIONS, AND FUTURE CHALLENGES | 267 | ||
| REFERENCES | 268 | ||
| Molecular Basis of Cardiac Delayed Rectifier Potassium Channel Function and Pharmacology | 275 | ||
| Key points | 275 | ||
| INTRODUCTION | 275 | ||
| STRUCTURAL BASIS OF VOLTAGE-DEPENDENT POTASSIUM CHANNEL GATING | 276 | ||
| ACTIVATION GATING | 276 | ||
| INACTIVATION GATING | 277 | ||
| DEACTIVATION GATING | 277 | ||
| MOLECULAR PHARMACOLOGY OF CARDIAC DELAYED RECTIFIER POTASSIUM ION CHANNELS | 277 | ||
| Inhibitors | 277 | ||
| Activators | 279 | ||
| SUMMARY | 280 | ||
| REFERENCES | 281 | ||
| Genetic Control of Potassium Channels | 285 | ||
| Key points | 285 | ||
| INTRODUCTION | 285 | ||
| CARDIAC K+ CHANNEL GENES IN HEALTH | 286 | ||
| K+ Channels with Two Transmembrane Segments and a Single Pore | 286 | ||
| K+ Channels with Six Transmembrane Segments and a Single Pore | 287 | ||
| Voltage-gated K+ channels | 289 | ||
| Calcium-activated K+ channels | 291 | ||
| K+ Channels with Four Transmembrane Segments and Two Pores | 291 | ||
| MODULATORY SUBUNITS OF CARDIAC K+ CHANNEL GENES | 292 | ||
| CARDIAC K+ CHANNEL GENES IN HERITABLE CARDIAC DISEASES | 292 | ||
| Long QT Syndrome | 294 | ||
| IKs-related long QT syndrome: long QT1, long QT5, and Jervell and Lange-Nielsen syndrome | 294 | ||
| IKr-related long QT syndrome: long QT2 and long QT6 | 295 | ||
| IK1-related long QT syndrome: long QT7 (Andersen syndrome) | 295 | ||
| Other K+ channel genes associated with long QT syndrome | 295 | ||
| Short QT Syndrome | 295 | ||
| Brugada Syndrome and Early Repolarization Syndrome | 297 | ||
| Atrial Fibrillation | 297 | ||
| CARDIAC K+ CHANNEL GENES AS MODIFIERS OF PHENOTYPE | 298 | ||
| Cardiac K+ Channel Genes as Modifiers of Phenotype in Heritable Arrhythmia Syndromes | 298 | ||
| Cardiac K+ Channel Genes as Modifiers of Phenotype in the General Population | 300 | ||
| CARDIAC K+ CHANNEL GENES AND MICRORNAS | 301 | ||
| SUMMARY | 301 | ||
| REFERENCES | 301 | ||
| Cardiac Delayed Rectifier Potassium Channels in Health and Disease | 307 | ||
| Key points | 307 | ||
| DELAYED RECTIFIERS IN THE HEART: IKS, IKR, AND IKUR | 307 | ||
| DELAYED RECTIFIERS AND CARDIAC RHYTHM DISORDERS | 309 | ||
| Congenital and Acquired Long QT Syndromes | 309 | ||
| KCNQ1 and long QT1 | 310 | ||
| KCNE1 and long QT syndrome variant 5 | 310 | ||
| AKAP9 and long QT syndrome variant 11 | 312 | ||
| hERG and long QT syndrome variant 2 | 312 | ||
| hERG and drug-induced long QT | 313 | ||
| Short QT Syndrome | 313 | ||
| Familial Atrial Fibrillation | 314 | ||
| DELAYED RECTIFIER CHANNELS AS THERAPEUTIC TARGETS FOR CARDIAC ARRHYTHMIA | 315 | ||
| SUMMARY AND FUTURE DIRECTIONS | 315 | ||
| REFERENCES | 316 | ||
| Adenosine Triphosphate-Sensitive Potassium Currents in Heart Disease and Cardioprotection | 323 | ||
| Key points | 323 | ||
| ADENOSINE TRIPHOSPHATE-SENSITIVE POTASSIUM CHANNEL AND CARDIOVASCULAR DISEASE: THE THEORETIC CASE | 323 | ||
| Cardiovascular Adenosine Triphosphate-Sensitive Potassium Channel and Cardioprotection | 323 | ||
| Cardiac Adenosine Triphosphate-Sensitive Potassium Channels and Arrhythmia | 324 | ||
| THE MOLECULAR BASIS OF ADENOSINE TRIPHOSPHATE-SENSITIVE POTASSIUM CHANNELS | 324 | ||
| CARDIOVASCULAR TISSUE DISTRIBUTION OF ADENOSINE TRIPHOSPHATE-SENSITIVE POTASSIUM CHANNEL SUBUNITS | 324 | ||
| CARDIOVASCULAR DISEASE AND ADENOSINE TRIPHOSPHATE-SENSITIVE POTASSIUM CHANNEL MUTATIONS | 325 | ||
| Predictions from Genetically Modified Animals | 325 | ||
| Adenosine Triphosphate-Sensitive Potassium Channel–Associated Human Disease | 326 | ||
| Cantu Syndrome: Multiple Tissue Symptoms | 327 | ||
| ADENOSINE TRIPHOSPHATE-SENSITIVE POTASSIUM CHANNEL MANIPULATION IN HEART DISEASE | 329 | ||
| Potential for Therapeutic Modulation of Cardiovascular Adenosine Triphosphate-Sensitive Potassium Channel Activity | 330 | ||
| Further Implications and Future Prospects | 330 | ||
| REFERENCES | 330 | ||
| Potassium Channel Remodeling in Heart Disease | 337 | ||
| Key points | 337 | ||
| INTRODUCTION | 337 | ||
| OVERVIEW OF THE REMODELING PROCESSES OF POTASSIUM CHANNELS IN PATHOLOGIC SITUATIONS | 338 | ||
| Remodeling of K+ Currents Associated with Hypertrophy | 338 | ||
| Hypertrophy | 338 | ||
| Exercise-induced hypertrophy | 339 | ||
| Remodeling of K+ Currents Associated with Congestive Heart Failure | 339 | ||
| Remodeling of K+ Currents Associated with Myocardial Infarction | 339 | ||
| Remodeling in the myocardial infarction border zone | 339 | ||
| Remodeling in the normal zones of hearts with prior myocardial infarction | 342 | ||
| Remodeling of K+ Currents Associated with Atrial Fibrillation | 342 | ||
| Remodeling of K+ currents in atrial fibrillation | 342 | ||
| Remodeling of K+ currents in pulmonary veins | 342 | ||
| K+ CHANNEL REMODELING: TRANSLATIONAL INTEREST AND CLINICAL IMPORTANCE | 343 | ||
| Hypokalemia and K+ Currents in Heart Disease Patients | 343 | ||
| Repolarization Reserve | 343 | ||
| Specific Targets in Atrial Fibrillation | 343 | ||
| PHARMACOLOGIC MODULATION OF K+ CHANNELS IN HEART DISEASE PATIENTS | 343 | ||
| Amiodarone | 343 | ||
| Other Class III Antiarrhythmic Drugs and Heart Disease | 344 | ||
| Other Multichannel Blockers and Heart Diseases | 344 | ||
| Dronedarone | 344 | ||
| Vernakalant | 344 | ||
| Ranolazine | 344 | ||
| SUMMARY | 344 | ||
| REFERENCES | 345 | ||
| Modulation of Cardiac Potassium Current by Neural Tone and Ischemia | 349 | ||
| Key points | 349 | ||
| INTRODUCTION | 349 | ||
| OVERVIEW OF THE CARDIAC AUTONOMIC NERVOUS SYSTEM | 349 | ||
| CELLULAR MECHANISMS OF CARDIAC AUTONOMIC SIGNALING | 350 | ||
| AUTONOMIC EFFECTS ON ATRIAL POTASSIUM CURRENTS: SINOATRIAL NODE AND HEART RATE | 351 | ||
| ATRIAL MYOCARDIUM AND ATRIAL ARRHYTHMIAS | 352 | ||
| MODULATION OF AUTONOMIC EFFECTS ON ATRIAL POTASSIUM CURRENT AS A POSSIBLE THERAPEUTIC TARGET FOR ATRIAL FIBRILLATION | 355 | ||
| AUTONOMIC CONTROL OF POTASSIUM CURRENT IN THE VENTRICLE | 356 | ||
| MODULATION OF VENTRICULAR AUTONOMIC TONE AS A TREATMENT OF VENTRICULAR ARRHYTHMIAS | 357 | ||
| EFFECTS OF ISCHEMIA ON POTASSIUM CURRENTS | 357 | ||
| SUMMARY | 357 | ||
| REFERENCES | 358 | ||
| Clinical Features of Genetic Cardiac Diseases Related to Potassium Channelopathies | 361 | ||
| Key points | 361 | ||
| CONGENITAL LONG QT SYNDROME | 361 | ||
| Clinical Presentation | 362 | ||
| Diagnosis | 363 | ||
| Management | 363 | ||
| SHORT QT SYNDROME | 364 | ||
| Clinical Presentation | 364 | ||
| Diagnosis | 364 | ||
| Management | 366 | ||
| BRUGADA SYNDROME | 367 | ||
| Clinical Presentation | 367 | ||
| Diagnosis | 367 | ||
| Management | 367 | ||
| EARLY REPOLARIZATION SYNDROME | 368 | ||
| Clinical Presentation | 368 | ||
| Diagnosis | 368 | ||
| Management | 369 | ||
| FAMILIAL ATRIAL FIBRILLATION | 369 | ||
| SUMMARY | 369 | ||
| REFERENCES | 369 | ||
| Potassium Channel Block and Novel Autoimmune-Associated Long QT Syndrome | 373 | ||
| Key points | 373 | ||
| INTRODUCTION | 373 | ||
| Autoantibodies and the Heart | 374 | ||
| Autoimmune Anti-SSA/Ro–associated Long QT Syndrome | 374 | ||
| Clinical aspects | 374 | ||
| Autoimmune Anti-SSA/Ro–associated Long QT Syndrome | 378 | ||
| Functional and molecular aspects | 378 | ||
| Proposed Pathogenic Mechanism for Anti-SSA/Ro Antibodies in the Development of QTc Prolongation | 382 | ||
| CLINICAL SIGNIFICANCE AND SUMMARY | 382 | ||
| REFERENCES | 382 | ||
| Pharmacogenetics of Potassium Channel Blockers | 385 | ||
| Key points | 385 | ||
| PHARMACOKINETIC MECHANISMS | 386 | ||
| PHARMACODYNAMICS | 386 | ||
| METHODOLOGIC CONSIDERATIONS IN STUDYING THE GENOMICS OF DRUG-INDUCED QT INTERVAL PROLONGATION | 387 | ||
| WHAT IS THE EVIDENCE THAT DRUG-INDUCED LONG QT SYNDROME IS A GENETIC PROBLEM? | 388 | ||
| PHARMACOGENOMIC STUDIES IN THE DRUG-INDUCED LONG QT SYNDROME | 388 | ||
| CURRENT STATE OF THE ART | 390 | ||
| SUMMARY | 390 | ||
| REFERENCES | 391 | ||
| Mechanism of Proarrhythmic Effects of Potassium Channel Blockers | 395 | ||
| Key points | 395 | ||
| INTRODUCTION | 395 | ||
| Excitability of the Heart: Basic Cardiac Electrophysiology | 395 | ||
| Action potentials and repolarization reserve | 395 | ||
| Potassium channels | 396 | ||
| Causes of Arrhythmia | 397 | ||
| Dysfunctional impulse formation (abnormal Ca2+ handling) and impulse conduction | 397 | ||
| Reentry phenomena | 398 | ||
| Antiarrhythmic Drug Targets | 398 | ||
| Proarrhythmic Effects of Ion Channel Blockers | 398 | ||
| SPECIFIC POTASSIUM CHANNELS AND EFFECTS OF BLOCKERS | 400 | ||
| Delayed Rectifier K+ Channels | 400 | ||
| Kv11.1 (hERG1): rapid delayed outward rectifier K+ current IKr | 400 | ||
| Kv7.1 (KCNQ1): slow delayed outward rectifier K+ current IKs | 401 | ||
| Kv1.5 (KCNA5): ultrarapid delayed outward rectifier K+ current IKur | 401 | ||
| Kv4.2 (KCND2), Kv4.3 (KCND3): transient outward current Ito | 401 | ||
| Inward Rectifier K+ Channels | 402 | ||
| Kir2.1/Kir2.3: IK1 inward rectifier K+ current | 402 | ||
| Kir3.1/Kir3.4 (KCNJ3/KCNJ5): acetylcholine-activated inward rectifier K+ current IK,ACh | 402 | ||
| Kir6.1/Kir6.2 plus SUR1/SUR2: ATP-activated K+ current IK,ATP | 403 | ||
| Weak Inward Rectifiers K2P Channels | 403 | ||
| TWIK-1 (KCNK1); TREK-1 (KCNK2 or K2P2.1), TASK-1 (KCNK3 or K2P3.1); TASK-3 (KCNK9 or K2P9.1) – IK2P | 403 | ||
| Calcium-Activated K+ Channels of Small Conductance | 403 | ||
| SK1, SK2, SK3 (KCNN1, KCNN2, KCNN3) channels - Ca2+-activated K+ current ISK,Ca | 403 | ||
| SYNERGISTIC DRUG EFFECTS IN PROLONGING THE QT INTERVAL | 404 | ||
| Synergistic Pharmacodynamics Effects | 404 | ||
| Synergistic Pharmacokinetic Effects | 404 | ||
| SUMMARY | 405 | ||
| REFERENCES | 405 | ||
| Atrial-Selective Potassium Channel Blockers | 411 | ||
| Key points | 411 | ||
| INTRODUCTION | 411 | ||
| CLASSICAL ATRIAL-SELECTIVE K+ CHANNELS | 412 | ||
| Acetylcholine-Activated Inward-Rectifier K+ Current | 412 | ||
| Blockers | 412 | ||
| Ultrarapid Delayed-Rectifier K+ Current | 414 | ||
| Blockers | 414 | ||
| RECENTLY DISCOVERED ATRIAL K+ CHANNELS | 415 | ||
| Two-Pore Domain K+ Channels | 415 | ||
| Blockers | 415 | ||
| Small-Conductance Ca2+-Activated K+ Channels | 416 | ||
| Blockers | 416 | ||
| Voltage-Gated Kv1.1 Channels | 416 | ||
| Blockers | 417 | ||
| SUMMARY | 417 | ||
| REFERENCES | 417 | ||
| Dofetilide: Electrophysiologic Effect, Efficacy, and Safety in Patients with Cardiac Arrhythmias | 423 | ||
| Key points | 423 | ||
| INTRODUCTION | 423 | ||
| ELECTROPHYSIOLOGIC EFFECTS OF DOFETILIDE | 424 | ||
| EFFECT OF DOFETILIDE ON EXPERIMENTAL MODELS OF ATRIAL ARRHYTHMIAS | 424 | ||
| ANTIARRHYTHMIC EFFECTS OF DOFETILIDE | 424 | ||
| The Clinical Trials of Dofetilide | 424 | ||
| DIAMOND Trials | 424 | ||
| DIAMOND-CHF | 425 | ||
| DIAMOND-MI | 425 | ||
| DIAMOND-AF | 425 | ||
| DIAMOND Summary | 425 | ||
| The EMERALD Trial | 425 | ||
| SAFIRE-D Trial | 428 | ||
| Cleveland Clinic Report | 428 | ||
| Heart and Rhythm Medical Group Results | 428 | ||
| Results | 429 | ||
| TRIALS ON INTRAVENOUS DOFETILIDE | 429 | ||
| Post-Coronary Artery Bypass Grafting Trial | 429 | ||
| Intravenous Dofetilide | 429 | ||
| EFFECT OF DOFETILIDE ON THE ELECTROCARDIOGRAM | 431 | ||
| PHARMACOKINETICS OF DOFETILIDE | 431 | ||
| DRUG INTERACTIONS WITH DOFETILIDE | 431 | ||
| TORSADOGENIC EFFECT OF DOFETILIDE | 432 | ||
| Mechanisms of Torsadogenic Effect of Dofetilide | 432 | ||
| Management of Dofetilide-induced Torsades de Pointes | 432 | ||
| DISCUSSION | 432 | ||
| DOFETILIDE IN PREGNANCY | 433 | ||
| ADVERSE EFFECTS | 433 | ||
| GUIDELINES FOR USE OF DOFETILIDE | 433 | ||
| SUMMARY | 433 | ||
| ACKNOWLEDGMENT | 433 | ||
| REFERENCES | 434 | ||
| Sotalol | 437 | ||
| Key points | 437 | ||
| INTRODUCTION | 437 | ||
| PROPERTIES | 437 | ||
| PHARMACOKINETICS | 439 | ||
| PHARMACODYNAMICS | 440 | ||
| DRUG INTERACTIONS | 441 | ||
| NEGATIVE INOTROPIC PROPERTIES | 441 | ||
| DOSING | 441 | ||
| INDICATIONS | 443 | ||
| Premature Ventricular Contractions | 443 | ||
| Ventricular Tachycardia | 443 | ||
| ATRIAL FIBRILLATION | 443 | ||
| Acute Pharmacologic Cardioversion | 443 | ||
| Maintenance of Sinus Rhythm | 445 | ||
| Postoperative Atrial Fibrillation | 447 | ||
| SUPRAVENTRICULAR TACHYCARDIA | 447 | ||
| FETAL SUPRAVENTRICULAR ARRHYTHMIAS | 447 | ||
| PACING AND DEFIBRILLATION THRESHOLDS | 447 | ||
| REFERENCES | 449 | ||
| Dronedarone | 453 | ||
| Key points | 453 | ||
| INTRODUCTION | 453 | ||
| BASIC PHARMACOLOGY | 454 | ||
| Molecular Structure: An Amiodarone Derivative | 454 | ||
| Pharmacokinetics | 454 | ||
| Pharmacodynamics: Ion Channel Blockade | 454 | ||
| Pharmacodynamics: Cellular and Global Effects | 455 | ||
| Negative chronotropy | 455 | ||
| Negative dromotropy | 455 | ||
| Negative inotropy | 455 | ||
| Ventricular effects | 455 | ||
| Atrial effects | 455 | ||
| CLINICAL TRIAL DATA | 455 | ||
| Dronedarone Reduces Recurrence of Atrial Fibrillation | 455 | ||
| Dronedarone Reduces Hospitalizations in Nonpermanent Atrial Fibrillation | 458 | ||
| Dronedarone Increases Mortality in Heart Failure | 458 | ||
| Dronedarone Increases Mortality in Permanent Atrial Fibrillation | 459 | ||
| Dronedarone Versus Amiodarone | 459 | ||
| Systematic Reviews and Metaanalysis | 459 | ||
| REAL-WORLD EXPERIENCE | 460 | ||
| Large Cohort Studies | 460 | ||
| Postapproval Reports of Adverse Events | 460 | ||
| USE FOR OTHER INDICATIONS | 460 | ||
| DRUG INTERACTIONS | 461 | ||
| Strong CYP3A4 Inhibitors | 461 | ||
| Digoxin | 461 | ||
| Pharmacokinetic Interactions with Other Cardiovascular Drugs | 461 | ||
| QT-Prolonging Drugs | 461 | ||
| RECOMMENDATIONS FOR CONTEMPORARY USE | 461 | ||
| Clinical Practice Guidelines | 461 | ||
| When should dronedarone be used? | 461 | ||
| When should dronedarone not be used? | 461 | ||
| Practical Aspects | 462 | ||
| FUTURE DIRECTIONS: ANTIARRHYTHMIC DRUG COMBINATION | 462 | ||
| REFERENCES | 462 | ||
| Ranolazine: Electrophysiologic Effect, Efficacy, and Safety in Patients with Cardiac Arrhythmias | 467 | ||
| Key points | 467 | ||
| INTRODUCTION | 467 | ||
| ELECTROPHYSIOLOGIC EFFECTS OF THE LATE SODIUM CURRENT | 468 | ||
| ELECTROPHYSIOLOGIC EFFECTS OF RANOLAZINE | 469 | ||
| EVALUATION OF RANOLAZINE ON EXPERIMENTAL MODELS OF ARRHYTHMIAS | 469 | ||
| ANTIARRHYTHMIC EFFECTS OF RANOLAZINE | 469 | ||
| CLINICAL TRIALS OF RANOLAZINE | 470 | ||
| Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome–Thrombolysis in Myocardi ... | 470 | ||
| Ranolazine in Atrial Fibrillation Following an Electrical Cardioversion Trial | 470 | ||
| HARMONY Trial | 470 | ||
| Ranolazine Implantable Cardioverter-Defibrillator Trial | 470 | ||
| Ranolazine for Incomplete Vessel Revascularization Percutaneous Coronary Intervention Trial | 473 | ||
| Ranolazine in Patients with New-Onset Atrial Fibrillation in Postoperative Cardiac Surgery | 473 | ||
| Heart and Rhythm Medical Group | 473 | ||
| EFFECT OF RANOLAZINE IN EXPERIMENTAL AND CLINICAL LONG-QT SYNDROME | 473 | ||
| EFFECT OF RANOLAZINE IN PATIENTS WITH ATRIAL FIBRILLATION | 474 | ||
| EFFECT OF RANOLAZINE IN PATIENTS WITH VENTRICULAR TACHYCARDIA | 474 | ||
| RANOLAZINE IN PATIENTS WITH HEART FAILURE | 474 | ||
| EFFECT OF RANOLAZINE ON THE ELECTROCARDIOGRAM AND ECHOCARDIOGRAM | 475 | ||
| COMBINATION OF RANOLAZINE WITH OTHER ANTIARRHYTHMIC AGENTS | 475 | ||
| PHARMACOKINETICS OF RANOLAZINE | 476 | ||
| DRUG INTERACTIONS WITH RANOLAZINE | 476 | ||
| RANOLAZINE IN PREGNANCY | 476 | ||
| ADVERSE EFFECTS OF RANOLAZINE | 476 | ||
| DISCUSSION | 476 | ||
| GUIDELINES | 476 | ||
| SUMMARY | 476 | ||
| ACKNOWLEDGMENTS | 477 | ||
| REFERENCES | 477 | ||
| Proarrhythmic and Torsadogenic Effects of Potassium Channel Blockers in Patients | 481 | ||
| Key points | 481 | ||
| INTRODUCTION | 481 | ||
| A HISTORY OF PROARRHYTHMOGENIC POTENTIAL OF POTASSIUM CHANNEL BLOCKERS | 482 | ||
| RELATING RISK FACTORS TO PHARMACOLOGIC MECHANISMS | 482 | ||
| FEMALE GENDER | 484 | ||
| BRADYCARDIA | 484 | ||
| HYPOKALEMIA AND HYPOMAGNESEMIA | 485 | ||
| ATRIAL FIBRILLATION | 486 | ||
| THE ROLE OF VARIABLE DRUG CONCENTRATIONS IN TORSADES DE POINTES RISK | 489 | ||
| EFFECTS OF DRUG CONCENTRATION ON QT INTERVAL AND ARRHYTHMIA RISK | 489 | ||
| SUMMARY | 490 | ||
| REFERENCES | 490 | ||
| Guidelines for Potassium Channel Blocker Use | 495 | ||
| Key points | 495 | ||
| INTRODUCTION | 495 | ||
| ATRIAL FIBRILLATION/ATRIAL FLUTTER | 495 | ||
| PHARMACOLOGIC CARDIOVERSION OF RECENT-ONSET ATRIAL FIBRILLATION | 495 | ||
| MAINTENANCE OF SINUS RHYTHM | 497 | ||
| TREATMENT OF VENTRICULAR ARRHYTHMIAS AND PREVENTION OF SUDDEN CARDIAC DEATH | 498 | ||
| REFERENCES | 499 |