Pulmonary Hypertension (eBook)

Preface 7
Contents 9
Contributors 11
List of Color Plates 15
Historical Perspective: A Century of Primary ( Idiopathic) Pulmonary Hypertension 16
1. INTRODUCTION 17
2. THE STUDY OF PULMONARY HEMODYNAMICS 18
3. CONTROL OF THE PULMONARY CIRCULATION 20
4. PULMONARY HEMODYNAMICS IN PRIMARY ( IDIOPATHIC) PULMONARY HYPERTENSION 21
5. THE AMINOREX EPIDEMIC 22
6. THE FIRST WORLD HEALTH ORGANIZATION MEETING, GENEVA, 1973 22
7. THE NATIONAL REGISTRY, 1981 23
8. THE SECOND PULMONARY HYPERTENSION EPIDEMIC 23
9. THE SECOND WORLD HEALTH ORGANIZATION MEETING, EVIAN, 1998 24
10. FAMILIAL IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION 24
11. CONCLUSION 25
REFERENCES 26
Classification of Pulmonary Hypertension 30
1. INTRODUCTION 31
2. PULMONARY ARTERIAL HYPERTENSION 33
3. PULMONARY VENOUS HYPERTENSION 39
4. PULMONARY HYPERTENSION ASSOCIATED WITH HYPOXIA 40
5. PULMONARY HYPERTENSION DUE TO CHRONIC THROMBOTIC AND/ OR EMBOLIC DISEASE 40
6. PULMONARY HYPERTENSION DUE TO MISCELLANEOUS CAUSES 41
7. FUNCTIONAL CLASSIFICATION OF PULMONARY HYPERTENSION 41
8. CONTROVERSIES 42
9. CONCLUSION 43
REFERENCES 43
Diagnostic Approach to Pulmonary Arterial Hypertension 48
1. INTRODUCTION 49
2. SUSPICION/HISTORY 49
3. PHYSICAL EXAMINATION 51
4. NONINVASIVE TESTING 52
5. INVASIVE TESTING 57
6. LABORATORY TESTING 59
7. SUMMARY 61
REFERENCES 61
Pathophysiology of Pulmonary Arterial Hypertension 66
1. INTRODUCTION 67
2. IMBALANCE OF VASOACTIVE MEDIATORS 68
3. ENVIRONMENTAL ASSOCIATIONS WITH PULMONARY ARTERIAL HYPERTENSION 71
4. CONDITIONS ASSOCIATED WITH PULMONARY ARTERIAL HYPERTENSION 74
5. GENETIC ABNORMALITIES ASSOCIATED WITH PULMONARY HYPERTENSION 78
6. CONCLUSIONS 80
REFERENCES 81
Pulmonary Hypertension Genes 88
1. INTRODUCTION 89
2. PEDIGREE ANALYSIS 89
3. BONE MORPHOGENIC PROTEIN RECEPTOR 90
2 GENE ( 90
4. 93
MUTATIONS IN IPAH 93
5. 93
IN OTHER PAH COHORTS 93
6. BIOLOGY OF 94
7. 96
AND HEREDITARY HEMORRHAGIC TELANGIECTASIA 96
8. MODIFIERS AND TRIGGERS OF PULMONARY ARTERIAL HYPERTENSION 96
9. SCREENING/COUNSELING 102
REFERENCES 103
The Right Ventricle in Pulmonary Hypertension 108
1. THE NORMAL RIGHT VENTRICLE AND PULMONARY CIRCULATION 109
2. RIGHT VENTRICULAR RESPONSE TO PULMONARY HYPERTENSION 111
3. ADAPTIVE AND MALADAPTIVE CARDIAC HYPERTROPHIC RESPONSES 112
4. SIGNALING PATHWAYS IN CARDIAC HYPERTROPHY 112
5. ADAPTIVE HYPERTROPHY 116
6. DETERMINANTS OF THE HYPERTROPHIC RESPONSE OF THE RIGHT VENTRICLE 118
7. RIGHT AND LEFT VENTRICULAR INTERACTIONS 119
8. PERICARDIAL EFFUSION 120
9. EFFECT OF RIGHT HEART FUNCTION ON PATIENT OUTCOME IN PULMONARY HYPERTENSION 121
10. MONITORING RIGHT VENTRICULAR FUNCTION 122
11. CLINICAL APPROACH TO RV DYSFUNCTION 128
12. FUTURE DIRECTIONS 131
ACKNOWLEDGMENTS 131
REFERENCES 132
Congenital Heart Disease Associated with Pulmonary Arterial Hypertension 142
1. INTRODUCTION 143
2. DYNAMIC PAH 144
3. IMMEDIATE-POSTOPERATIVE “REACTIVE” PULMONARY HYPERTENSION 146
4. LATE-POSTOPERATIVE PULMONARY HYPERTENSION 148
5. NORMAL TO MILDLY ABNORMAL PVR STATES 148
6. EISENMENGER PHYSIOLOGY 149
7. CONCLUSIONS 154
REFERENCES 154
Connective Tissue Disease Associated Pulmonary Hypertension 160
1. INTRODUCTION 161
2. EPIDEMIOLOGY 161
3. PATHOPHYSIOLOGY 165
4. CLINICAL PRESENTATION AND DIAGNOSIS 167
5. THERAPY OF SSC-PH 170
6. SURGICAL TREATMENTS 177
7. SUMMARY 177
REFERENCES 178
Pulmonary Hypertension Associated with HIV, Liver Disease, Sarcoidosis, and Sickle Cell Disease 188
1. INTRODUCTION 189
2. HIV-ASSOCIATED PULMONARY HYPERTENSION 189
3. PORTOPULMONARY HYPERTENSION 198
4. SARCOIDOSIS 203
5. SICKLE CELL DISEASE 203
6. CONCLUSIONS 205
REFERENCES 206
Chronic Thromboembolic Pulmonary Hypertension 214
1. INTRODUCTION 215
2. PATHOGENESIS 216
3. CLINICAL PRESENTATION AND HISTORY 218
4. PHYSICAL EXAMINATION 219
5. DIAGNOSTIC EVALUATION 219
6. SURGICAL SELECTION 228
7. SURGICAL APPROACH 230
8. POSTOPERATIVE COURSE 232
9. SURGICAL OUTCOME 235
10. LONG-TERM OUTCOME 236
11. MEDICAL THERAPY 236
12. LUNG TRANSPLANTATION 238
13. SUMMARY 238
REFERENCES 238
General Therapeutic Approach and Traditional Therapies 246
1. INTRODUCTION 247
2. REVERSIBLE FACTORS CONTRIBUTING TO PULMONARY HYPERTENSION 247
3. SUMMARY 266
REFERENCES 266
Prostacyclin Therapy for Pulmonary Arterial Hypertension 270
1. INTRODUCTION 271
2. PHARMACOLOGICAL ACTIONS OF PROSTACYCLIN 272
3. CLINICAL APPLICATIONS OF PROSTACYLINS 273
4. SUMMARY 293
REFERENCES 293
Endothelin and Its Blockade in Pulmonary Arterial Hypertension 298
1. INTRODUCTION 299
2. PULMONARY VASCULAR ENDOTHELIN RECEPTORS IN HEALTH AND DISEASE 299
3. CLINICAL STUDIES OF ENDOTHELIN-RECEPTOR ANTAGONISTS IN PAH 302
4. SELECTION OF AN ENDOTHELIN-RECEPTOR ANTAGONIST 312
5. CONCLUSION AND FUTURE DIRECTIONS 314
REFERENCES 314
PDE5 Inhibitors and the cGMP Pathway in Pulmonary Arterial Hypertension 320
1. INTRODUCTION 321
2. MODULATION OF CGMP IN THE PULMONARY VASCULATURE 321
3. PDE5 INHIBITION IN OTHER WHO PH SUBGROUPS 330
4. COMBINATION THERAPY 331
5. COMPARING PAH THERAPIES 331
6. CONCLUSIONS 331
REFERENCES 332
Statins for Treatment of Pulmonary Hypertension 336
1. INTRODUCTION 337
2. RATIONALE FOR THE BENEFIT OF STATINS IN PULMONARY HYPERTENSION 337
3. EXPERIMENTAL EVIDENCE SUPPORTING THE HYPOTHESIS THAT STATINS AMELIORATE PULMONARY HYPERTENSION 339
4. CLINICAL APPLICATIONS OF STATINS TO TREAT PULMONARY HYPERTENSION 343
5. CONCLUSIONS 347
REFERENCES 347
Transitions and Combination Therapy for Pulmonary Arterial Hypertension 352
1. INTRODUCTION 353
2. TRANSITIONS 353
3. COMBINATIONS 359
4. CONCLUSIONS 373
REFERENCES 374
Acute Right Ventricular Dysfunction: Focus on Acute Cor Pulmonale 378
1. INTRODUCTION 379
2. PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE RIGHT VENTRICLE 379
3. ACUTE COR PULMONALE: DEFINITION, DIAGNOSIS, AND PATHOPHYSIOLOGY 380
4. A FACTOR IN WORSENING OF RV FUNCTION: MECHANICAL VENTILATION 384
5. ACUTE COR PULMONALE IN PULMONARY EMBOLISM: INCIDENCE, PROGNOSIS, AND THERAPY 385
6. ACUTE COR PULMONALE IN ARDS: INCIDENCE, PROGNOSIS, AND THERAPEUTIC IMPACT 388
7. ACUTE COR PULMONALE: PRINCIPLES OF MANAGEMENT 389
8. SUMMARY AND CONCLUSIONS 393
REFERENCES 393
Lung Transplantation and Atrial Septostomy for Pulmonary Arterial Hypertension 398
1. INTRODUCTION 399
2. LUNG TRANSPLANTATION 400
3. ATRIAL SEPTOSTOMY 411
4. SUMMARY 414
REFERENCES 414
New Directions in Pulmonary Hypertension Therapy 420
1. INTRODUCTION 421
2. GENERAL MEASURES 424
3. TARGETS: IN SEARCH OF THE MAGIC BULLET 427
4. AMMUNITION: HOW BEST TO HIT THE TARGET? 435
5. ARMOR: RECOGNIZING AND PROTECTING THE SUSCEPTIBLE 435
6. CLINICAL TRIALS AND ENDPOINTS 436
7. CONCLUSIONS 437
REFERENCES 438
Index 446