Pulmonary Arterial Hypertension
P re f a c e
Terence K. Trow, MD
The specific arteriopathy of pulmonary arterial hypertension (PAH) must be clearly diagnosed and distinguished from other forms of pulmonary hypertension (PH) in order to arrive at the proper therapeutic approach, which has evolved rapidly over the past 15 years. PAH is comprised of idiopathic PAH, heritable PAH, and PAH associated with identified conditions. All of these forms of PH share common features that include an elevated mean pulmonary artery pressure in the setting of a normal left ventricular end-diastolic pressure due to abnormalities in the pulmonary arterial vascular bed that impose increased resistance to blood flow with attendant increased right ventricular workload. All, with the exception of pulmonary veno-occlusive disease and pulmonary capilliary hemangiomatosis, share similar beneficial responses to PAH-specific therapies. By far the most common causes of PH that the practicing clinician will encounter is PH due to left heart disease (pulmonary venous hypertension [PVH], PH due to intrinsic pulmonary disease, and hypoxemia [be it obstructive, restrictive, or sleep-disordered breathing with or without obesity-hypoventilation syndrome]), or PH due to acute or chronic thromboembolic disease. Therapies for these conditions are markedly different and, for most, PAH-specific therapies have not been shown to be beneficial and may even be deleterious. In this issue of Clinics in Chest Medicine, PH experts from throughout the world share their experience and the most recent up-to-date findings from the literature. The value of this is heightened by the significant advances in our understanding of the diseases of the pulmonary vascular bed since the last issue of Clinics in Chest Medicine devoted to PAH in 2007.
First, Darren B. Taichman, MD, PhD and Jess Mandel, MD offer an updated discussion of the epidemiology of PAH. This discussion is followed by a review of what is known about the pathology of PAH, including exciting new observations from the Pulmonary Hypertension Breakthrough Initiative offered by Rubin M. Tuder, MD, Elvira Stracher, MD, Jeffrey Robinson, MD, Rahul Kumar, PhD, and Brian B. Graham, MD. Next C. Greg Elliott, MD reviews what is known of the genetics of PAH, including discussion of the newly discovered acid-dependent potassium-gated channel gene KCNK3 and its association with PAH. The next section of this Clinics in Chest Medicine focuses on the important principles underlying proper diagnosis and classification of PH with special detailed discussions of associated forms of PH. Paul Forfia, MD and I discuss the elements required to properly diagnose PAH, with an expanded discussion of nuances of the echocardiogram that can be helpful in distinguishing PAH from PVH. This article also emphasizes the importance ultimately of right heart catheterization in the evaluation of PH. This is followed, in turn, by thorough reviews of PH owing to left heart disease by Michael A. Mathier, MD, PH owing to lung disease and/or hypoxemia by Steven D. Nathan, MD and Paul M. Hassoun, MD, PH associated with congenital heart disease by Usha Krishnan, MD and Erika B. Rosenzweig, MD, portopulmonary hypertension by Nadine Al-Naamani, MD and Kari E. Roberts, MD, PAH associated with chronic hemolytic anemias and blood dyscrasias by Roberto F. Marchado, MD and Harrison W. Farber, MD, and PH with unclear or multifactorial mechanisms (World Health Organization Group 5) by Tim Lahm, MD and Murali M. Chakinala, MD. The
Clin Chest Med 34 (2013) xiii–xiv http://dx.doi.org/10.1016/j.ccm.2013.10.009 0272-5231/13/$ – see front matter Ó 2013 Elsevier Inc. All rights reserved.
chestmed.theclinics.com
Editor
xiv
Preface important topic of potentially curable chronic thromboembolic PH is next discussed by Peter S. Marshall, MD, Kim K. Kerr, MD, and William R. Auger. The final section of this Clinics in Chest Medicine covers the available therapeutics for PAH, both proven and novel potential therapies. Maor Sauler, MD, Wassim H. Fares, MD, and I first review the limited data on standard nonspecific therapies in the management of PAH. Next, Richard Channick, MD, Ioana Preston, MD, and James R. Klinger, MD review the data on oral therapies in the management of PAH, specifically phosphodiesterase-5 inhibitors and endothelin receptor antagonists. Harold I. Palevsky, MD, and Valerie V. McLaughlin, MD next review the use of inhaled and parenteral prostanoid therapies. Meredith E. Pugh, MD, Anna R. Hemnes, MD, and Ivan M. Robbins, MD discuss what is known about combining the aforementioned therapies in attempts to optimize treatment of this fatal disease. When medical therapies fail, options including atrial septostomy and lung transplantation can be employed and Stephanie G. Norfolk, MD, David J. Lederer, MD, MS, and Victor F. Tapson, MD review these important options. Finally, the many exciting novel therapies being explored for the treatment of these unfortunate patients are reviewed by Caroline O’Connell, MD, Dermot S. O’Callaghan, MD, and Marc Humbert, MD.
I do hope that the readers of this issue will find these contributions useful and informative in their daily approach to the finding of “PH” on an echocardiogram. I do trust the information imparted will serve to improve the evaluations and care of our courageous and unfortunate patients diagnosed with PAH, with an ultimate goal of inspiring a cure for this devastating disease. I wish to offer my sincerest gratitude to each contributing author for their thoughtful input and their time invested in the education of others. I also wish to thank Adrianne Brigido of the editorial staff at Clinics in Chest Medicine for her patience with me in putting these contributions together. Finally, I wish to thank my incredible wife and son for their support and gracious tolerance of the demands placed on my time during this editorial endeavor. Terence K. Trow, MD Director Yale Pulmonary Vascular Disease Program Yale University School of Medicine Department of Internal Medicine Section of Pulmonary Critical Care, and Sleep Medicine 333 Cedar Street, PO Box 208057 New Haven, CT 06520-8057, USA E-mail address: [email protected]
P re f a c e
Terence K. Trow, MD
The specific arteriopathy of pulmonary arterial hypertension (PAH) must be clearly diagnosed and distinguished from other forms of pulmonary hypertension (PH) in order to arrive at the proper therapeutic approach, which has evolved rapidly over the past 15 years. PAH is comprised of idiopathic PAH, heritable PAH, and PAH associated with identified conditions. All of these forms of PH share common features that include an elevated mean pulmonary artery pressure in the setting of a normal left ventricular end-diastolic pressure due to abnormalities in the pulmonary arterial vascular bed that impose increased resistance to blood flow with attendant increased right ventricular workload. All, with the exception of pulmonary veno-occlusive disease and pulmonary capilliary hemangiomatosis, share similar beneficial responses to PAH-specific therapies. By far the most common causes of PH that the practicing clinician will encounter is PH due to left heart disease (pulmonary venous hypertension [PVH], PH due to intrinsic pulmonary disease, and hypoxemia [be it obstructive, restrictive, or sleep-disordered breathing with or without obesity-hypoventilation syndrome]), or PH due to acute or chronic thromboembolic disease. Therapies for these conditions are markedly different and, for most, PAH-specific therapies have not been shown to be beneficial and may even be deleterious. In this issue of Clinics in Chest Medicine, PH experts from throughout the world share their experience and the most recent up-to-date findings from the literature. The value of this is heightened by the significant advances in our understanding of the diseases of the pulmonary vascular bed since the last issue of Clinics in Chest Medicine devoted to PAH in 2007.
First, Darren B. Taichman, MD, PhD and Jess Mandel, MD offer an updated discussion of the epidemiology of PAH. This discussion is followed by a review of what is known about the pathology of PAH, including exciting new observations from the Pulmonary Hypertension Breakthrough Initiative offered by Rubin M. Tuder, MD, Elvira Stracher, MD, Jeffrey Robinson, MD, Rahul Kumar, PhD, and Brian B. Graham, MD. Next C. Greg Elliott, MD reviews what is known of the genetics of PAH, including discussion of the newly discovered acid-dependent potassium-gated channel gene KCNK3 and its association with PAH. The next section of this Clinics in Chest Medicine focuses on the important principles underlying proper diagnosis and classification of PH with special detailed discussions of associated forms of PH. Paul Forfia, MD and I discuss the elements required to properly diagnose PAH, with an expanded discussion of nuances of the echocardiogram that can be helpful in distinguishing PAH from PVH. This article also emphasizes the importance ultimately of right heart catheterization in the evaluation of PH. This is followed, in turn, by thorough reviews of PH owing to left heart disease by Michael A. Mathier, MD, PH owing to lung disease and/or hypoxemia by Steven D. Nathan, MD and Paul M. Hassoun, MD, PH associated with congenital heart disease by Usha Krishnan, MD and Erika B. Rosenzweig, MD, portopulmonary hypertension by Nadine Al-Naamani, MD and Kari E. Roberts, MD, PAH associated with chronic hemolytic anemias and blood dyscrasias by Roberto F. Marchado, MD and Harrison W. Farber, MD, and PH with unclear or multifactorial mechanisms (World Health Organization Group 5) by Tim Lahm, MD and Murali M. Chakinala, MD. The
Clin Chest Med 34 (2013) xiii–xiv http://dx.doi.org/10.1016/j.ccm.2013.10.009 0272-5231/13/$ – see front matter Ó 2013 Elsevier Inc. All rights reserved.
chestmed.theclinics.com
Editor
xiv
Preface important topic of potentially curable chronic thromboembolic PH is next discussed by Peter S. Marshall, MD, Kim K. Kerr, MD, and William R. Auger. The final section of this Clinics in Chest Medicine covers the available therapeutics for PAH, both proven and novel potential therapies. Maor Sauler, MD, Wassim H. Fares, MD, and I first review the limited data on standard nonspecific therapies in the management of PAH. Next, Richard Channick, MD, Ioana Preston, MD, and James R. Klinger, MD review the data on oral therapies in the management of PAH, specifically phosphodiesterase-5 inhibitors and endothelin receptor antagonists. Harold I. Palevsky, MD, and Valerie V. McLaughlin, MD next review the use of inhaled and parenteral prostanoid therapies. Meredith E. Pugh, MD, Anna R. Hemnes, MD, and Ivan M. Robbins, MD discuss what is known about combining the aforementioned therapies in attempts to optimize treatment of this fatal disease. When medical therapies fail, options including atrial septostomy and lung transplantation can be employed and Stephanie G. Norfolk, MD, David J. Lederer, MD, MS, and Victor F. Tapson, MD review these important options. Finally, the many exciting novel therapies being explored for the treatment of these unfortunate patients are reviewed by Caroline O’Connell, MD, Dermot S. O’Callaghan, MD, and Marc Humbert, MD.
I do hope that the readers of this issue will find these contributions useful and informative in their daily approach to the finding of “PH” on an echocardiogram. I do trust the information imparted will serve to improve the evaluations and care of our courageous and unfortunate patients diagnosed with PAH, with an ultimate goal of inspiring a cure for this devastating disease. I wish to offer my sincerest gratitude to each contributing author for their thoughtful input and their time invested in the education of others. I also wish to thank Adrianne Brigido of the editorial staff at Clinics in Chest Medicine for her patience with me in putting these contributions together. Finally, I wish to thank my incredible wife and son for their support and gracious tolerance of the demands placed on my time during this editorial endeavor. Terence K. Trow, MD Director Yale Pulmonary Vascular Disease Program Yale University School of Medicine Department of Internal Medicine Section of Pulmonary Critical Care, and Sleep Medicine 333 Cedar Street, PO Box 208057 New Haven, CT 06520-8057, USA E-mail address: [email protected]
