Diagnosis and Treatment of Pulmonary Hypertension: From Bench to Bedside

 

Description:

This book focuses on pulmonary arterial hypertension (PAH, Group 1) and chronic thromboembolic pulmonary hypertension (CTEPH, Group 4) among the various groups of pulmonary hypertension (PH) whose classification was updated into five major categories at the 5th World Symposium held in Nice, France, in 2013. Readers will find recent progress, methods, and up-to-date information on PH mechanisms, diagnostic images, and treatment in the management of PH. This volume, with contributions by leading researchers worldwide in the field , consists of five parts, starting with the fundamentals of PH, then pathophysiology and genetics, treatment, and right ventricular function.

 

Table of Contents:

 

Part I: Fundamentals of Pulmonary Hypertension

Chapter 1: Clinical Classification

1.1 Important Pathophysiological and Clinical Definitions of PH

1.2 Definition of Pulmonary Hypertension

1.3 How Can We Put All Types of Pulmonary Hypertension Together?

1.4 From Evian to Nice

1.5 Group 1 Modification in Nice Classification

1.6 Pre- or Postcapillary Pulmonary Hypertension

1.7 Group 1: Pulmonary Arterial Hypertension (PAH)

1.8 Other than Group 1 PAH

References

Chapter 2: Diagnosis: Imaging

2.1 Ventilation-Perfusion Lung Scintigraphy

2.2 Multidetector CTPA and Dual-Energy CTPA

2.3 Pulmonary Angiography and Intravascular Imaging

2.4 Magnetic Resonance Imaging

2.5 Molecular Imaging

References

Part II: Pathophysiology and Genetics

Chapter 3: Pathogenic and Therapeutic Role of MicroRNA in Pulmonary Arterial Hypertension

3.1 Introduction

3.2 The Biogenesis of miRNAs

3.3 Specific miRNAs Involved in the Pathogenesis of PAH

3.3.1 miR-21a and the BMP Pathway

3.3.2 miR-210 and the HIF-1α Pathway

3.3.3 MiR143/145 and the KLF4 Pathway

3.3.4 miR-124/NFAT Pathway

3.3.5 miR-124 and Other PH-Associated Pathways

3.3.6 miR-130/301, PPARγ, and miR-204 Pathway

3.3.7 miR-130/301, Apelin, and miR-424/503

3.3.8 miR-17-92 and the Cell Cycle

3.3.9 PH-Associated miRNA Cross Talk and Redundancy

3.4 General Advances in miRNA Therapeutics

3.5 Potential for miRNA Target Therapies in PAH

3.5.1 PAH miRNA Replacement Therapy

3.5.2 PAH miRNA Inhibition Therapy

3.5.3 PAH miRNA Diagnostics

3.6 Target miRNAs for Treatment

3.7 Summary and Future Research Directions

References

Chapter 4: Sex Hormones

4.1 Estrogen Paradox in PAH

4.2 Published Theories for the Estrogen Paradox in PAH

4.2.1 How Estrogens Exert Harmful Effects to the Pulmonary Circulation

4.2.1.1 Altered Estrogen Receptor (ER) Signaling

4.2.1.2 Altered Estrogen Metabolites

4.2.1.3 Microenvironment

4.2.2 How Estrogens Exert Survival Benefit in Female PAH Patients

4.2.2.1 Cardiac Protective Effect of Estrogens

4.3 The Perspective

4.4 Conclusion

References

Chapter 5: Rho-Kinase as a Therapeutic Target for Pulmonary Hypertension

5.1 Introduction

5.1.1 Roles of Rho-Kinases in the Cardiovascular System

5.1.2 Functional Differences Between ROCK1 and ROCK2

5.1.3 Roles of Rho-Kinase in VSMC Function

5.1.4 Pathological Roles of Rho-Kinase in the Cardiovascular System

5.1.5 Rho-Kinase-Mediated Development of Cardiovascular Diseases

5.1.6 Rho-Kinase in Pulmonary Hypertension

5.1.7 Rho-Kinase as a Therapeutic Target

5.1.8 Conclusions

References

Chapter 6: The Unique Property of the Pulmonary Artery Regarding the Smooth Muscle Effects of Pr

6.1 Proteinase-Activated Receptor Family

6.1.1 The Activation and Signaling of the PARs

6.1.2 The Vascular Effects of PAR1 Under Physiological Conditions

6.1.3 The Upregulation and Impaired Desensitization of PAR1 in Smooth Muscle Under Pathological

6.2 The Vasoconstrictor Effect of Thrombin in the Pulmonary Artery

6.2.1 The Unique Property of the Pulmonary Artery in Regard to the Vasoconstrictor Effects of 

6.2.2 The Mechanisms Underlying PAR1-Mediated Pulmonary Vasoconstriction

6.3 The Possible Involvement of PAR1 in the Pathogenesis of Pulmonary Hypertension

References

Chapter 7: Animal Models with Pulmonary Hypertension

7.1 Pathological Findings of Pulmonary Vascular Lesions in Human PAH

7.2 Conventional Animal Models with Pulmonary Hypertension

7.2.1 Monocrotaline

7.2.2 Chronic Hypoxia

7.3 Other Animal Models with Pulmonary Hypertension

7.3.1 Fawn-Hooded Rats

7.3.2 Mice Overexpressing S100A4/Mts1

7.3.3 Mice Overexpressing IL-6

7.3.4 Murine Models with BMPR2 Mutations

7.4 What Do We Need to Establish the Preclinical Model Resembling Human Pathologic Findings?

7.5 Preclinical Animal Model with Severe PH and Complex Occlusive Lesion Formation

7.6 Conclusion

References

Chapter 8: Human Pathology

8.1 Introduction

8.2 Pathological Classification

8.2.1 Group 1: Pulmonary Arterial Hypertension (PAH) Caused by Increased Pulmonary Artery Pressure

8.2.1.1 Group 1–1.1. Idiopathic PAH

Isolated Medial Hypertrophy (Corresponds to Heath-Edwards Grade 1)

Combined Intimal Thickening and Medial Hypertrophy (Corresponds to Heath-­Edwards Grades 2 and 3

Complex Lesions

8.2.1.2 Group 1–1.4 Associated PAH (A-PAH)

Group 1–1.4.1 PAH Associated with Connective Tissue Disease [8–11]

Group 1–1.4.4. Pulmonary Hypertension Associated with CHD

8.2.2 Group 1’: Pulmonary Veno-occlusive Disease (PVOD)/Pulmonary Occlusive Venopathy (PVO)

8.2.3 Group 2: Pulmonary Hypertension Caused by Left Heart Failure

8.2.4 Group 3 Pulmonary Hypertension Due to Pulmonary Disease and Hypoxia

8.2.5 Group 4 Chronic Thromboembolic Pulmonary Hypertension (CTEPH) [17, 18]

8.3 Conclusions

References

Chapter 9: Pathophysiology and Genetics: BMPR2

9.1 Introduction

9.2 Genetics

9.2.1 Major Mutations

9.2.2 Other Rare Variants and Common Variants

9.3 Clinical Phenotype

9.4 Penetrance and Risk Factors

9.5 Pediatric PAH

9.6 Pathophysiology and Pathobiology

9.7 Therapeutic Consideration

9.8 Conclusions

References

Part III: Treatment of Pulmonary Arterial Hypertension (PAH)

Chapter 10: Prostacyclin

10.1 Properties of Prostacyclin

10.2 Deficiency of Prostacyclin in Pulmonary Arterial Hypertension

10.3 Characteristics of Prostacyclin Analogues and Prostacyclin

10.3.1 Prostacyclin Analogues

10.3.2 Prostacyclin

10.4 Additional Effects of Prostacyclin Analogues and Prostacyclin

10.4.1 Antiproliferative Effects on PASMCs

10.4.2 Pro-apoptotic Effect on PASMCs

10.4.3 Reverse Remodeling Effects on Pulmonary Arteries

10.5 Prostacyclin Therapy for Patients with PAH

10.5.1 Iloprost

10.5.2 Treprostinil

10.5.3 Beraprost

10.5.4 Epoprostenol

10.6 Perspective on Prostacyclin Therapy

References

Chapter 11: Targeting the NO-sGC-cGMP Pathway in Pulmonary Arterial Hypertension

11.1 Targeting Nitric Oxide Production and Availability in PAH

11.1.1 Endothelial Nitric Oxide Synthase (eNOS)

11.1.2 Alterations in eNOS Expression in PAH

11.1.3 Alterations in eNOS Regulatory Inputs

11.1.4 Arginase

11.1.5 Nitric Oxide and Nitric Oxide Donors in PAH

11.2 Targeting Soluble Guanylyl Cyclase (sGC) in PAH

11.2.1 Stimulation of sGC with Riociguat

11.3 Targeting Phosphodiesterase Type 5 (PDE5) in PAH

11.3.1 Increasing cGMP

11.3.2 Ameliorating Ventricular Function

11.3.3 Sildenafil

11.3.4 Tadalafil

11.4 Concluding Remarks

References

Chapter 12: Endothelin Receptor Antagonist

12.1 Endothelin (ET) System

12.2 Physiology and Pathophysiology of ET System

12.2.1 ETs in Development

12.2.2 ETs in Pulmonary Arterial Hypertension (PAH)

12.2.3 Pathophysiological Roles of ET System in genetically Modified PAH Mice

12.3 ERAs

12.3.1 Structure, Specificity, Pharmacokinetics, and Drug Interactions of ERAs

12.3.1.1 Bosentan

12.3.1.2 Ambrisentan

12.3.1.3 Macitentan

12.3.2 Efficacy of ERAs in PAH

12.3.2.1 Bosentan

12.3.2.2 Ambrisentan

12.3.2.3 Macitentan

12.3.3 Safety of ERAs

12.3.3.1 General Side Effects

12.3.3.2 Liver Dysfunction

12.3.3.3 Edema

12.3.3.4 Anemia

12.3.3.5 Teratogenicity

12.4 Place of ERAs in PAH Treatment Algorithm

12.5 Conclusions

References

Chapter 13: Lung Transplantation

13.1 History

13.2 Indication for Lung Transplantation

13.2.1 Recipient Selection

13.2.1.1 Cadaveric Lung Transplantation

13.2.1.2 Living-Donor Lobar Lung Transplantation

13.2.2 Donor Selection

13.2.2.1 Cadaveric Lung Transplantation

13.2.2.2 Living-Donor Lobar Lung Transplantation

13.3 Recipient Operation

13.3.1 Bilateral Cadaveric Lung Transplantation

13.3.2 Living-Donor Lobar Lung Transplantation

13.4 Postoperative Management

13.5 Outcome and Prognosis

13.6 Summary

References

Part IV: Treatment of Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Chapter 14: Medical Therapy for Chronic Thromboembolic Pulmonary Hypertension

14.1 Preface: History of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Treatment

14.2 Types of Medical Therapy in CTEPH

14.2.1 Anticoagulants

14.2.1.1 Types of Anticoagulants

14.2.2 Oxygen, Treatment for Right Heart Failure, and Other Medical Treatment

14.2.3 Pulmonary Vasodilators

14.2.3.1 Types of Vasodilators

14.2.3.2 Mechanism of Action of Vasodilators in CTEPH

14.2.3.3 Positioning of Vasodilator Therapy in Chronic Thromboembolic Pulmonary Hypertension (CTEP

14.2.3.4 Efficacy of Vasodilators in Patients with Inoperable CTEPH

14.2.3.5 RCTs of Vasodilators in CTEPH

Riociguat

14.2.3.6 Future Direction of Pulmonary Vasodilators

References

Chapter 15: Balloon Pulmonary Angioplasty

15.1 Introduction

15.2 Indications and Contraindications of BPA

15.3 Technique of BPA

15.4 Complications after BPA and Prevention Methods

15.5 Effect of BPA

15.6 Limitations of BPA

15.7 Conclusions

References

Chapter 16: Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension

16.1 Introduction

16.2 Diagnosis Including Assessment of Operability and Indication of PEA

16.3 PEA Procedures

16.4 Perioperative Care

16.5 Outcome

16.6 Conclusions

References

Part V: Right Ventricular Function

Chapter 17: Right Ventricular Function

17.1 Introduction

17.2 Anatomy of Right Ventricle

17.3 Mechanical Aspects of Ventricular Contraction

17.4 Hemodynamic Evaluation

17.5 The Role of the RV Function in Pulmonary Hypertension

17.6 Assessment of RV Function Using Echocardiography

17.6.1 Right Ventricular Fractional Area Change

17.6.2 Tricuspid Annular Plane Systolic Excursion

17.6.3 Tissue Doppler-Derived Tricuspid Lateral Annular Systolic Velocity

17.6.4 Right Ventricular Myocardial Performance Index

17.6.5 RV Strain

17.6.6 Three-Dimensional Echocardiography

17.7 Assessment of RV Volume and Function Using Cardiac Magnetic Resonance

References

 

An aparitie	13 Jan. 2017
Autor	Yoshihiro Fukumoto
Dimensiuni	155 x 235 x 17 mm
Editura	Springer
Format	Hardcover
ISBN	9789812878397
Limba	Engleza
Nr pag	200