Pulmonary Hypertension

448 Pages·2008·9.409 MB·English

by  Alfred P. Fishman (auth.), Nicholas S. Hill MD, Harrison W. Farber MD (eds.)

Pulmonary Hypertension
Contemporary Cardiologytm
Christopher P. Cannon, md
SERIESEDITOR
Annemarie M. Armani, md
EXECUTIVEEDITOR
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Pulmonary
Hypertension
by
Nicholas S. Hill, md
Division of Pulmonary, Critical Care
and Sleep Medicine
Tufts Medical Center
Boston, MA
Harrison W. Farber, md
Pulmonary Center
Boston University, Boston, MA
Editors
NicholasS.Hill HarrisonW.Farber
DivisionofPulmonary,CriticalCare PulmonaryCenter
andSleepMedicine BostonUniversity
TuftsMedicalCenter Boston,MA
Boston,MA
SeriesEditor ExecutiveEditor
ChristopherP.Cannon AnnemarieArmani
SeniorInvestigator
TIMIStudyGroupCardiovascularDivision
BrighamandWomen’sHospital
AssociateProfessorofMedicine
HarvardMedicalSchool
Boston,MA
ISBN:978-1-58829-661-0 e-ISBN:978-1-60327-075-5
LibraryofCongressControlNumber:2007940760
©2008HumanaPress,apartofSpringerScience+BusinessMedia,LLC
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To the many patients with pulmonary hypertension whom we have
beenprivilegedtocareforandwhohaveinspiredustolearnasmuch
as possible about the disease, help educate others and work on the
ultimate shared goal of finding a cure.
Preface
Enormous gains have been made in the pathophysiologic
understanding and therapy of pulmonary hypertension, particularly
over the past decade. Pulmonary Hypertension aims to provide a
current, comprehensive, and clinically relevant perspective on these
gains, with contributions from accomplished experts. As background,
AlfredP.Fishman,MD,aleaderinthefieldformorethanfourdecades,
offers his unique perspective on developments in the field over the
past century, including the development of right heart catheterization
techniquesbyindividualswithwhomhesubsequentlyworked,thefirst
descriptions of “primary” pulmonary hypertension, the formation of
the NIH registry, and earlier attempts to classify the disease.
The subsequent text provides an overview of the current state
of the art. Descriptions of the present iteration of the classifi-
cation system (as refined by the World Health Organization [WHO]
consensus conference in 2003) and diagnostic approach occupy the
nexttwochapters,followedbyinsightsintopathophysiology,genetics,
and the role of the right ventricle. These provide the foundation
for Chapters 6–10, which discuss specific conditions associated with
pulmonary hypertension, including those from WHO Groups 1, 2, 4,
and 5. Chapter 10 is authored by experts from the center (University
of California, San Diego) with the greatest experience in surgical
management of the disease.
Chapters 11–16 deal with currently available therapies, starting
with a general discussion of the therapeutic approach and tradi-
tional therapies for pulmonary hypertension. The three classes of
drugs currently approved in the United States for therapy of
pulmonary hypertension—prostacyclins, endothelin receptor antago-
nists, and phosphodiesterase-5 inhibitors—are examined in separate
chapters. Results of clinical trials that have evaluated these therapies
are analyzed and critiqued, and newer potential therapies, such as
statins, are discussed. The last chapter in this grouping addresses the
issues of transitioning from one therapy to another and combining
different therapies. These are promising therapeutic avenues that are
vii
viii Preface
currently of great interest to the pulmonary hypertension community
and are undergoing intense investigation in a number of recently
completed and ongoing clinical trials.
Surgical and interventional approaches to the management of
pulmonary hypertension, including lung transplantation and atrial
septostomy, are considered in the penultimate chapter. The final
chapter casts a forward glance, as Christopher M. Carlin and Andrew
J. Peacock attempt to prognostigate on the future directions the field
is likely to follow.
The editors hope that interested readers including cardiologists,
pulmonologists, rheumatologists, medical trainees, and nurses with an
interest in the field will find the scope of the topics and the depth of
coverageusefulandinformativeintheireverydayclinicalpracticeand
thatresearcherswillgainperspectiveondevelopmentsinthefieldthat
will be helpful in charting future directions. We are deeply indebted
to all of our contributors and express our profound thanks to them for
the hard work that went into each of their outstanding contributions.
Nicholas S. Hill
Harrison W. Farber
Contents
Preface..................................................... vii
Contributors................................................ xi
List of Color Plates.......................................... xv
1 Historical Perspective: A Century of Primary (Idiopathic)
Pulmonary Hypertension................................. 1
Alfred P. Fishman
2 Classification of Pulmonary Hypertension.................. 15
C. William Hargett and Victor F. Tapson
3 Diagnostic Approach to Pulmonary Arterial Hypertension.... 33
Ronald J. Oudiz
4 Pathophysiology of Pulmonary Arterial Hypertension........ 51
Harrison W. Farber
5 Pulmonary Hypertension Genes........................... 73
Elisabeth Donlevy Willers and Ivan M. Robbins
6 The Right Ventricle in Pulmonary Hypertension............ 93
Andrew C. Stone and James R. Klinger
7 Congenital Heart Disease Associated with Pulmonary
Arterial Hypertension................................... 127
Michael J. Landzberg
8 Connective Tissue Disease Associated Pulmonary
Hypertension.......................................... 145
Kimberly A. Fisher, Nicholas S. Hill,
and Harrison W. Farber
9 Pulmonary Hypertension Associated with HIV, Liver Disease,
Sarcoidosis, and Sickle Cell Disease...................... 173
Kimberly A. Fisher and Elizabeth S. Klings
ix
x Contents
10 Chronic Thromboembolic Pulmonary Hypertension......... 199
Victor J. Test, William R. Auger, and Peter F. Fedullo
11 General Therapeutic Approach and Traditional Therapies.... 231
Nicholas S. Hill and Elizabeth S. Klings
12 Prostacyclin Therapy for Pulmonary Arterial Hypertension... 255
NicholasS.Hill,ToddF.Vardas,andVallerieMcLaughlin
13 Endothelin and Its Blockade in Pulmonary Arterial
Hypertension.......................................... 283
David Langleben
14 PDE5 Inhibitors and the cGMP Pathway in Pulmonary
Arterial Hypertension................................... 305
Ioana R. Preston
15 Statins for Treatment of Pulmonary Hypertension........... 321
John L. Faul, Peter N. Kao, Toshihiko Nishimura,
Arthur Sung, Hong Hu, and Ronald G. Pearl
16 Transitions and Combination Therapy for Pulmonary Arterial
Hypertension.......................................... 337
Todd Hirschtritt, M. Kathryn Steiner, and Nicholas S. Hill
17 Acute Right Ventricular Dysfunction: Focus on Acute Cor
Pulmonale............................................. 363
Antoine Vieillard-Baron and François Jardin
18 Lung Transplantation and Atrial Septostomy for Pulmonary
Arterial Hypertension................................... 383
E. P. Trulock
19 New Directions in Pulmonary Hypertension Therapy........ 405
Christopher M. Carlin and Andrew J. Peacock
Index...................................................... 431