PVRI Review 3:2 2011

Call for Papers

Pulmonary

CirculationFirst Peer-Reviewed Journal Dedicated to

Pulmonary Vascular Disease

For more information see:http://www.pulmonarycirculation.org/

Submit your manuscript at:http://www.journalonweb.com/PC/

Editors-in-Chief

Senior Editor

Editors

Executive Editor

Scientific Advisory Board

Jason X.-J. Yuan, MD, PhDNicholas W. Morrell, MDHarikrishnan S., MD

Kurt R. Stenmark, MDKenneth D. Bloch, MDStephen L. Archer, MDMarlene Rabinovitch, MDJoe G.N. Garcia, MDStuart Rich, MDMartin R. Wilkins, MDHossein A. Ghofrani, MDCandice D. Fike, MDWerner Seeger, MDSheila G. Haworth, MDPatricia A. Thistlethwaite, MD, PhDChen Wang, MD, PhDAntonio A. Lopes, MD

Ghazwan Butrous, MD

Harikrishnan S., MD

Robert F. Growver, MD, PhDCharles A. Hales, MDJoseph Loscalzo, MDJohn B. West, MD, PhD, DScMagdi H. Yacoub, MD, DSc, FRS

Pulmonary Circulation is the only journal devoted to the fieldof pulmonary circulation publishing ,

, and in pulmonaryvascular disease and lung injury. The new journal stands at the

forefront of the critical collaboration between basic scientists andclinicians in research on the pulmonary circulatory system and

clinical diagnosis and treatment of pulmonary vascular diseases

original research articlesreview articles case reports perspectives

Pulmonary Vascular Research Institute (PVRI)is an international, non-profit medical research organizationdedicated to increasing the awareness and knowledge ofpulmonary vascular diseases and facilitating advances

in the treatment of affected people worldwide

First dedicated journal on the pulmonary circulationImmediate publication on acceptanceNo charge for processing manuscript

No charge for color photographsNo charge for publication

Open access

Clinical trialsClinical researchDrug developmentBasic science researchEpidemiology and biomedical informaticsDiagnostic and therapeutic guidelines

þ The first peer-‐reviewed medical journal dedicated to pulmonary vascular disease.

þ Pulmonary Circulation is the only journal devoted to the field of pulmonary circulation publishing original research articles, review articles, case reports, snapshots, and perspectives in pulmonary vascular disease and lung injury. þ The new journal stands at the forefront of the critical collaboration between basic scientists and clinicians in research on the pulmonary circulation system and clinical diagnosis and treatment of pulmonary vascular diseases. þ Topics of research articles include clinical trials, clinical research, drug development, basic science research, epidemiology and biomedical informatics, diagnostic and therapeutic guidelines. þ For more information: http:/ /www.pulmonarycirculation.org/

þ No charge for processing your manuscript

þ No charge for color photographs

þ No charge for publication

þ Immediate publication on acceptance

þ Open access

þ Submit your manuscript at: http:/ /www.journalonweb.com/PC/

The Pulmonary Vascular Research Institute (PVRI) is an international non-‐profit medical research organization dedicated to increasing the awareness and knowledge of pulmonary vascular diseases and facilitating advances in the treatment of affected people worldwide.

Call for Papers

Pulmonary

CirculationFirst Peer-Reviewed Journal Dedicated to

Pulmonary Vascular Disease

For more information see:http://www.pulmonarycirculation.org/

Submit your manuscript at:http://www.journalonweb.com/PC/

Editors-in-Chief

Senior Editor

Editors

Executive Editor

Scientific Advisory Board

Jason X.-J. Yuan, MD, PhDNicholas W. Morrell, MDHarikrishnan S., MD

Kurt R. Stenmark, MDKenneth D. Bloch, MDStephen L. Archer, MDMarlene Rabinovitch, MDJoe G.N. Garcia, MDStuart Rich, MDMartin R. Wilkins, MDHossein A. Ghofrani, MDCandice D. Fike, MDWerner Seeger, MDSheila G. Haworth, MDPatricia A. Thistlethwaite, MD, PhDChen Wang, MD, PhDAntonio A. Lopes, MD

Ghazwan Butrous, MD

Harikrishnan S., MD

Robert F. Growver, MD, PhDCharles A. Hales, MDJoseph Loscalzo, MDJohn B. West, MD, PhD, DScMagdi H. Yacoub, MD, DSc, FRS

Pulmonary Circulation is the only journal devoted to the fieldof pulmonary circulation publishing ,

, and in pulmonaryvascular disease and lung injury. The new journal stands at the

forefront of the critical collaboration between basic scientists andclinicians in research on the pulmonary circulatory system and

clinical diagnosis and treatment of pulmonary vascular diseases

original research articlesreview articles case reports perspectives

Pulmonary Vascular Research Institute (PVRI)is an international, non-profit medical research organizationdedicated to increasing the awareness and knowledge ofpulmonary vascular diseases and facilitating advances

in the treatment of affected people worldwide

First dedicated journal on the pulmonary circulationImmediate publication on acceptanceNo charge for processing manuscript

No charge for color photographsNo charge for publication

Open access

Clinical trialsClinical researchDrug developmentBasic science researchEpidemiology and biomedical informaticsDiagnostic and therapeutic guidelines

Editors-in-Chief Jason X.-‐J. Yuan, MD PhD Nicholas W. Morrell, MD Harikrishnan S., MD Senior Editor Ghazwan Butrous, MD PhD Executive Editor Harikrishnan S., MD Editors Kurt R. Stenmark, MD Kenneth D. Bloch, MD Stephen L. Archer, MD Marlene Rabinovitch, MD Joe G.N. Garcia, MD Stuart Rich, MD Martin R. Wilkins, MD Hossein A. Ghofrani, MD Candice D. Fike, MD Werner Seeger, MD Sheila G. Haworth, MD Patricia A. Thistlethwaite, MD PhD Chen Wang, MD PhD Antonio A. Lopes, MD Scientific Advisory Board Robert F. Grover, MD PhD Charles A. Hales, MD Joseph Loscalzo, MD John B. West, MD PhD DSc Magdi H. Yacoub, MD DSc FRS

Jul - Dec 2011 • Volume 3 • Issue 2 i PVRI REVIEW

ISSN 0974-6013E-ISSN 0975-1602

Editorial Board......

Chief editor

harikrishnan S. Additional Professor in Cardiology,

Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India - 695011

exeCutive editorS

Ghazwan Butrous

R. Oudiz

Ioana Preston

Mardi Gomberg-Maitland

Andrew Peacock

Alexi Crosby

Saleh Aldammas (Arabic Edition)Majdy Idrees (Arabic Edition)Jun Wang (Chinese Edition)

Maria Virginia Tavares Santana (Portuguese Edition)

Katia Stewart (Portuguese Edition)Julio Sandoval (Spanish Edition)

editorial team

Sheila Glennis Haworth Sastry Bhagavathulla R. Krishna Kumar Shyam Sunder Kothari Goverdhan Dutt Puri Anita Saxena Qadar Pasha Sivasankaran Sivasubramonian Chandrasekharan Cheranellore Kartha

editorial team for PortugueSe edition

Maria Virginia Tavares SantanaAntonio Augusto Lopes

Ângela Bandeira Vera Demarchi Aiello Maria Angélica Binoto

Daniel Waetge Jaquelina Ota Renato Maciel

Veronica Amado Frederico Thadeu Campos

Maria Ilma AraújoKátia Stewart

editorial Board/ reviewerS

PVRI Faculty

Pvri review

PVRI REVIEW ii Jul - Dec 2011 • Volume 3 • Issue 2

The JournalPVRI Review (ISSN: Print - 0974-6013, Online - 0975-1602) is peer-reviewed journal published on behalf of the Pulmonary Vascular Research Institute, supported by the Indian (South-East Asia region) task force. The journal publishes articles on the subject of Pulmonary circulation and pulmonary vascular diseases. The Journal is published quarterly (in the last week of January, April, July and October).

Abstracting and Indexing InformationThe journal is indexed/listed with Caspur, DOAJ, EBSCO Publishing’s Electronic Databases, Expanded Academic ASAP, Genamics JournalSeek, Google Scholar, Health & Wellness Research Center, Health Reference Center Academic, Hinari, Index Copernicus, OpenJGate, PrimoCentral, ProQuest, Scimago Journal Ranking, SCOLOAR, SCOPUS, SIIC databases, Summon by Serial Solutions and Ulrich’s International Periodical Directory.

Information for AuthorsThere are page charges for submissions to the journals. Please check http://www.pvrireview.org/contributors.asp for details.All manuscripts must be submitted online at www.journalonweb.com/pvri

Subscription InformationCopies are provided to the members of PVRI for free of cost.A subscription to PVRI Review comprises 4 issues. Prices include postage. Annual Subscription Rate for non-members- Institutional: INR 2000.00 for India and USD 200.00 for outside India.Personal: INR 1000.00 for India and USD 100.00 for outside India.

For mode of payment and other details, please visit www.medknow.com/subscribe.asp.

Claims for missing issues will be serviced at no charge if received within 60 days of the cover date for domestic subscribers, and 3 months for subscribers outside India. Duplicate copies cannot be sent to replace issues not delivered because of failure to notify publisher of change of address.

The journal is published and distributed by Medknow Publications and Media Pvt. Ltd. Copies are sent to subscribers directly from the publisher’s address. It is illegal to acquire copies from any other source. If a copy is received for personal use as a member of the association/society, one cannot resale or give-away the copy for commercial or library use.

The copies of the journal to the members of the association are sent by ordinary post. The editorial board, association or publisher will not be responsible for non receipt of copies. If any member/subscriber wishes to receive the copies by registered post or courier, kindly contact the publisher’s office. If a copy returns due to incomplete, incorrect or changed address of a member/subscriber on two consecutive occasions, the names of such members will be deleted from the mailing list of the journal. Providing complete, correct and up-to-date address is the responsibility of the member/subscriber.

Nonmembers: Please send change of address information to [email protected].

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The journal reserves the right to reject any advertisement considered unsuitable according to the set policies of the journal.The appearance of advertising or product information in the various sections in the journal does not constitute an endorsement or approval by the journal and/or its publisher of the quality or value of the said product or of claims made for it by its manufacturer.

CopyrightThe entire contents of the PVRI Review are protected under Indian and international copyrights. The Journal, however, grants to all users a free, irrevocable, worldwide, perpetual right of access to, and a license to copy, use, distribute, perform and display the work publicly and to make and distribute derivative works in any digital medium for any reasonable non-commercial purpose, subject to proper attribution of authorship and ownership of the rights. The journal also grants the right to make small numbers of printed copies for their personal non-commercial use.

PermissionsFor information on how to request permissions to reproduce articles/information from this journal, please visit www.pvrireview.org

Disclaimer The information and opinions presented in the Journal reflect the views of the authors and not of the Journal or its Editorial Board or the Publisher. Publication does not constitute endorsement by the journal. Neither the PVRI Review nor its publishers nor anyone else involved in creating, producing or delivering the PVRI Review or the materials contained therein, assumes any liability or responsibility for the accuracy, completeness, or usefulness of any information provided in the PVRI Review, nor shall they be liable for any direct, indirect, incidental, special, consequential or punitive damages arising out of the use of the PVRI Review. The PVRI Review, nor its publishers, nor any other party involved in the preparation of material contained in the PVRI Review represents or warrants that the information contained herein is in every respect accurate or complete, and they are not responsible for any errors or omissions or for the results obtained from the use of such material. Readers are encouraged to confirm the information contained herein with other sources.

AddressesEditorial Office

Dr. S. Harikrishnan Associate Professor in Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum - 695011, India. Tel. 91-471-2551692, FAX- 91-471-2446433 E-mail: [email protected] site: www.pvrireview.org

Published byMedknow Publications and Media Pvt. Ltd.B5-12, Kanara Business Centre, Off Link Road, Ghatkopar (E),Mumbai – 400075, India.Phone: 91-22-66491818Website: www.medknow.com

Printed at???

gENERAL iNFORMATiON

Pvri review

Jul - Dec 2011 • Volume 3 • Issue 2 iii PVRI REVIEW

July - December 2011 | Volume 3 | Issue 2

Contents.....

Editorial

From the Editor's deskS. Harikrishnan ...................................................................................................................................................................................65

MEEting PrograM

The 6th PVRI Annual General Meeting & 5th Scientific Workshops & Debates in Cape Town, South Africa, February 7–10, 2012 ........................................................................................................................................... 67

annual rEPort of PulMonary Vascular rEsEarch institutE 2011Ghazwan Butrous and Nikki Krol ......................................................................................................................................................77

announcEMEnt

Dr. Simon Campbell, FRS appointed to the PVRI Board of Directors and Advisors .........................................78

PVri confErEncE, syMPosia and MEEtings

Annual Report of Pulmonary Vascular Research Activities, 2011 .............................................................................79

PVri rEgions rEPorts

PVRI China Taskforce 2011Martin Wilkins, Chen Wang............................................................................................................................................................94

PVRI South East Asia Region TaskforceSheila G. Haworth, Harikrishnan S................................................................................................................................................94

PVRI Eastern Mediterranean Region TaskforcePaul Hassoun, Majdy Idrees ..........................................................................................................................................................95

PVRI Sub-Saharan Africa TaskforceAna Olga Mocumbi, Karen Sliwa...................................................................................................................................................96

PVri functional and disEasEs taskforcEs PVRI High-altitude TaskforceQadar Pasha, Max Gassmann ......................................................................................................................................................99

Pulmonary Hypertension associated with HIV TaskforceSonia Flores, Nicola Petrosillo, Norbert Voelkel .........................................................................................................................100

PVRI Schistosomiasis Taskforce 2011Ghazwan Butrous, Nicholas Morrell ............................................................................................................................................100

PVRI Pediatric TaskforceIan Adatia, Sheila Glennis Haworth, Maria J. del Cerro ............................................................................................................102

PVRI PH-ARC TaskforceStuart Rich ....................................................................................................................................................................................103

Pvri review

PVRI REVIEW iv Jul - Dec 2011 • Volume 3 • Issue 2

Pulmonary Hypertension Associated with Congenital Heart Disease Taskforce (PH-CHD TF) - 2011Antonio A. Lopes, Marlene Rabinovitch ......................................................................................................................................103

PVRI Publications Taskforce ................................................................................................................................................104

PVRI Review .............................................................................................................................................................................106

Administrative Activities ......................................................................................................................................................107

PVri rEsEarch grants intEriM rEPorts

Genetic Determinants of Monge’s DiseaseJean-Paul Richalet, Fabiola León-Velarde, Maria Rivera, Jose Espinoza, Anne-Paule Gimenez-Roqueplo ...........................108

Bioinformatic Analysis of Gene Expression Profiles of Pulmonary Arterial Hypertension Finding a Robust Gene Expression Signature for PAHSwapna Menon .............................................................................................................................................................................108

Does High Altitude Protect Against Irreversible Pulmonary Hypertension?Alexandra Heath, Inge von Alvensleben, Brian Graham, Rubin Tuder .....................................................................................109

Identification of Schistosoma Mansoni Antigens in the Lungs of Humans with Schistosomiasis – Associated Pulmonary Arterial HypertensionBrian Graham ...............................................................................................................................................................................110

Significant Intrapulmonary Schistosoma Egg Antigens are not Present in Schistosomiasis – Associated Pulmonary HypertensionBrian B. Graham, Jacob Chabon, Angela Bandeira, Luciano Espinheira, Ghazwan Butrous, Rubin M. Tuder ......................110

Implementation of an International Registry of Pulmonary HypertensionKaren Sliwa ................................................................................................................................................................................... 111

PVri gsk rEsEarch grants

Molecular Mechanisms of Pulmonary Microvascular Endothelial Dysfunction Under Fluid Shear StressC. C. Kartha, S. S. Binil Raj........................................................................................................................................................112

Does Non-regression of Pulmonary Hypertension Following Balloon Mitral Valvotomy Correlate with BMPR2 Mutations?Harikrishnan S., Renuka Nair, Mukund A. Prabhu .....................................................................................................................112

Telomeres in Adaptation and Maladaptation Under Hypobaric HypoxiaQadar Pasha .................................................................................................................................................................................113

intErViEw

Conversation on the PVRI- Panama Classification Of Pediatric Pulmonary Hypertensive Vascular Disease Published In Pulmonary Circulation (1,2)Ghazwan Butrous, Ian Adatia, Maria del Cerro, Sheila Haworth ..................................................................................................114

Book rEViEw

Pulmonary Hypertension in Children: The First Book Written in SpanishEduardo Oliver .................................................................................................................................................................................119

author indEx ............................................................................................................................................................................ 121

titlE indEx .................................................................................................................................................................................. 123

ErratuM ......................................................................................................................................................................................... 120

Contents..... (Contd..)

Jul - Dec 2011 • Volume 3 • Issue 2 65 PVRI REVIEW

Ed

ito

ria

l From the Editor's desk

In my previous Editorial, I mentioned how the role of PVRI Review has been redefined within the spectrum of PVRI Publications. I am pleased to say that the last issue of PVRI Review, which introduced the new content type, was generally well received by its intended audience, as the general feedback indicated. However, I must announce that with PVRI Review’s new role, my role within the Journal will also change. As of 2012, I will step down as Editor-in-Chief of PVRI Review, although I will continue to assist my successor for the year.

Change is constant, and the source of life. In that view, PVRI Review wholeheartedly embraces the future both in content and management. In practice, this means that PVRI Review will pursue a more interactive Editorial Board, which will elect an Editor-in-Chief from among its rank each year.

My resignation will be formally announced at the 6th PVRI Annual General Meeting in Cape Town, February 2012. Senior Editor Ghazwan Butrous will temporarily take over the role until a successor is appointed. I look forward to meeting interested candidates in Cape Town and seeing PVRI Review surge into the future with a new management model, new content, and new faces.

One new face that is officially presented in our Journal today is that of Dr. Simon Campbell. Dr. Campbell has recently joined the PVRI Board of Directors. An introduction can be found on page 78, and I would like to hereby welcome him to the Institute.

This current issue contains a reflection on the year that has been, in the form of the PVRI Annual Report. The report is a collective effort of PVRI Taskforces, meetings organizers and attendees, collaborators and researchers, and PVRI management alike, and details all the activities of the Pulmonary Vascular Research Institute over 2011. The current report includes detailed reports on the Panama City conference, the 2011 Leh Symposium, the joint PVRI/SAPH meeting and much more, as well as updates from the PVRI Webinars, Publications, Administrative Office, and all the Taskforces and Regions. It is heartening to read the accomplishments of the Institute over the past year, and its clear goals for the future.

This issue also contains an interview with the PVRI Pediatric Pulmonary Hypertension Taskforce, which made waves at last year’s AGM with the presentation of a new classification of Pulmonary Hypertension in Pediatric population. In PVRI Review they answer questions posed by PVRI Managing Director Ghazwan Butrous with regard to the changes that have been brought on since the presentation, and the ways in which they expect to adapt and improve the classification and its impact on the diagnosis and treatment of PPH.

Commentary is provided by Eduardo Oliver1, PhD, who reviews recent Spanish language publication Hipertensión pulmonar en niños, a product of Drs. Gabriel Diaz (FPVRI), Julio Sandoval (FPVRI), and Augusto Sola.

This PVRI Review issue also the Table of Contents of the Cape Town abstracts, which will be presented at the PVRI AGM in February. For more information on the Cape Town Agenda, please see page 67; all necessary details with regard to the Gala Dinner are given there. Finally, an erratum has been included for an error in “Impaired oxidative metabolism and enhanced glycolysis in right ventricular hypertrophy: The Warburg effect,” which was published in PVRI Review 2009, vol. 1, issue 3.

As we step forward, I am confident that PVRI Review will continue to grow and improve. Our quality content is only made possible through the efforts of the many Fellows and members of the PVRI, and although there may be changes within the publication, I do not doubt that its heart, which comprises all the people within the Pulmonary Vascular Research Institute, will continue its enthusiasm, dedication, and hard work. I feel privileged to have served as Editor-in-Chief of this flagship Journal. Dear reader, I thank you.

S. HarikrishnanEditor in Chief, PVRI Review

Fellow, Pulmonary Vascular Research InstituteCo-leader, PVRI Publication Taskforce

E-mail: [email protected]

Access this article onlineQuick response Code:

Website: www.pvrireview.org

DOi:

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How to cite this article: ???

Source of Support: Nil, Conflict of Interest: None declared.

The Pulmonary Vascular Research Instituteproudly presents

The 6th Annual General Meeting& 5th Scientific Workshops & Debates 2012,

at the Protea President Hotelin Cape Town, South Africa

Themes for the 2012 PVRI Conference program include:

• Pulmonary Vascular Disease in Africa• Clinical Trials in PVD: Ethical and Moral Issues• Translational Medicine: Challenges in the Development of

New Drugs for Pulmonary Vascular Disease

TUESDAY, 7 FEBRUARY – FRIDAY, 10 FEBRUARY 2012

For program and registration details, please go www.pvri.info

PVRI REVIEW 66 Jan - Jun 2011 • Volume 3 • Issue 1

Advertisement


The 6th PVRI Annual General Meeting & 5th Scientific Workshops & Debates in Cape Town, South Africa, February 7–10, 2012

ME

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Session Chairman underlinedMonday, 6th February09.30 – 17.30 BOARD OF DIRECTORS’ MEETING

Attendees:Stuart Rich, Sheila Glennis Haworth, Nicholas Morrell, Ahvie Herskowitz, Declan Doogan, Alec Craig, Magdi Yacoub, Pascoal Mocumbi, Ardeschir Ghofrani, Martin Wilkins, Ghazwan Butrous

09.00 – 13.00 PAPUCO (Sub-Saharan Pulmonary Vascular Diseases database registry) Meeting19.00 Board of Directors DinnerTuesday, 7th February10.30-17.00 ANNUAL GENERAL MEETING

Chair: Martin WilkinsAttendees: All PVRI Fellows

17:15 – 19:00 Press Meeting19.00 – 21.00 THE BASICS OF PULMONARY HYPERTENSION: CLASSIFICATION, DEFINITIONS AND

MANAGEMENT TEACH-IN SEMINARChair: Anne Keogh and S. Harikrishnan1. Definition and classification of pulmonary hypertension – Steve Archer (20 mins)2. Clinical diagnosis of pulmonary hypertension –Victor Tapson (20 mins)3. Assessment of RV function - Robert Frantz (20mins)4. Biomarkers in pulmonary vascular disease – Martin Wilkins (20 mins)5. Management of pulmonary hypertension – Ardeschir Ghofrani (20 mins)6. Survival data and result of most relevant clinical trials Aaron Waxman (20 mins)

Wednesday, 8th February08.30 – 09.00 PETER RAYMOND MEMORIAL LECTURE

Chair: Sheila Glennis Haworth, CC KarthaAdvances in our understanding of pulmonary vascular pathology; a global view - Rubin Tuder

09.15 – 10.45 PULMONARY VASCULAR DISEASE IN AFRICAPanellists: Ghazwan Butrous, Karen Sliwa, Ana Mocumbi1. Spectrum of Pulmonary Vascular Disease in Africa - Karen Sliwa2. Rheumatic heart disease - Liesl Zuhlke3. Endoymyocardial fibrosis - Ana Mocumbi4. Haemolytic anaemia - Ambrose Wonkam5. Managing Pulmonary Hypertension in Africa - all African colleagues

PVRI REVIEW 68 Jul - Dec 2011 • Volume 3 • Issue 2

Scientific Workshop & Debate Programs

10.45 Coffee11.00 – 12.30 THE ROLE OF INFECTION IN PULMONARY HYPERTENSION IN AFRICA

Panellists: Nicola Petrosillo, Rosie Burton, Ahmed Ibrahim, Mpiko Ntsekhe1. PVD in infectious diseases Nicholas Morrell2. PH in HIV/AIDS Jürgen Rockstroh3. Schistosomiasis Rita de Cassia dos Santos Ferreira4. Tuberculosis Graeme Meintjes

12.30 Lunch13.15 – 15.15 CLINICAL TRIALS IN PVD: ETHICAL AND PRACTICAL ISSUES

Panellists: Faber Harrison, Declan Doogan, Amany El Gazayerly, Rahul Agrawal1. Pulmonary hypertension research consortium - Stuart Rich2. Quality of trials and adherence to the Helsinki doctrine - Ardeschir Ghofrani3. Ethical issues - Solomon Benatar4. Clinical trials involving children - Maria Jesus De Cerro5. Setting up a trial with limited resources – Karen Sliwa6. Important lessons from the IMPI Study – Shaheen Pandie

15.15 Tea15.30 – 18:00 PULMONARY VASCULAR REGISTRIES OF THE WORLD

Panellists: Marius Hoeper, Ioana Preston , Simon Stewart, Debbie Quinn1. The REVEAL registry - David Badesch2. CompERA-XL - Marius Hoeper3. Heart of Africa - Karen Sliwa4. UK registries experience Paul Corris and Andrew Peacock5. Data capture in Africa to create a Pulmonary Vascular Disease database (PAPUCO Registry) – Friedrich Thienemann6. Quality standards and overview of pulmonary hypertension registries -David Pittrow

18:00 – 19:00 Pulmonary Circulation Editorial board meeting19.30 – 22.30 SPECIAL SMALL GROUP DINNER MEETINGS

1. Paediatric Taskforce (Host: Maria Jesus De Cerro)2. Pulmonary Hypertension Research Consortium (Host: Stuart Rich)3. HIV Research Group Sub-Saharan Research group (Host: Nicola Petrosillo)4. Database Taskforce: International PVRI Registry (Host: Ioana Preston)5. Schistosomiasis Taskforce-Sub-Saharan Research group ( Host: Ghazwan Butrous

Thursday, 9th February7:00 – 8:30 Posters available for viewing ALL DAY

Special database follow up meeting8.30 – 10.30 PAEDIATRIC SYMPOSIUM

Panellists: Ian Adatia, Hanaa Banjar, Anita Saxena, Peter Zartner1. Update on the PVRI classification of pulmonary vascular disease in children– Maria Jesus De Cerro2. Respiratory disease and pulmonary hypertension in children – Peter Zartner3. Pulmonary hypertension secondary to congenital heart disease in Africa - John Lawrenson4. Can we operate on this patient with pulmonary hypertension secondary to CHD? - John Hewitson

10.30 Coffee10.45 – 12.45 RIGHT VENTRICULAR PATHOBIOLOGY IN PULMONARY VASCULAR DISEASE

Chairmen: E. Kenneth Weir, Steve Archer, Srinivas Murali, 1. Be it resolved. The most important target of therapy in advanced WHO category 1 Pulmonary Hypertension is the right ventricle Pro. Harm-Jan Bogaard , Con. Evangelos Michelakis2. Be it resolved. The right ventricle in pulmonary hypertension is best imaged using advanced modalities such as MRI and PET - not echocardiography Pro. Hunter Champion Con. Anna Hemnes3. Be it resolved. Right ventricular ischemia in pulmonary hypertension is due to impaired coronary perfusion pressure Pro. Stuart Rich Con. Stephen Archer4. Be it resolved. Inotropes are beneficial in resuscitating the failing right ventricle in WHO category 1 pulmonary hypertension Pro. Paul Hassoun Con. Marius Hoeper

13.00 Lunch, followed by free time18.30 PVM History initiative talk

Chair: Stylianos Orfanos“The Story of Fen-Phen (Fenluramine)” – Stuart Rich“ historical notes: Heart and Mind” -Lionel Opie

19:30 Cocktail drink and Achievement awards ceremony20:00 GALA DINNER


Scientific Workshop & Debate Programs

Friday, 10th February8.30 – 10.00 CARDIAC CATHETERIZATION INVESTIGATION OF THE PULMONARY HYPERTENSIVE PATIENT

Panellists: Maria Jesus De Cerro, Stefano Ghio , Steven Nathan1. Investigating the adult patient – Tarek Kashour2. Investigating the paediatric patient – Ian Adatia3. Discussion

10.00 Coffee10.30 – 12.00 POSTER PRESENTATIONS AND DISCUSSION

Chairmen: Marc Pritzker, Dario Vizaa, Soni Pullamsetti, Goverdhan Puri12.00 Lunch13.00 – 14.30 TRANSLATIONAL MEDICINE: CHALLENGES IN THE DEVELOPMENT OF NEW DRUGS FOR PULMONARY

VASCULAR DISEASEPanellists: Ralph Schermuly, Konstantin G. Birukov; N Davie1. The value of animal models in pulmonary hypertension – G Maarman2. The statin story - Reda Girgis3. Bridging Biomarkers: Martin Wilkins

14:30-15:00 Concluding LectureChairman: Martin WilkinsPVD Translational Medicine, past, present and future: Werner Seeger

15.00 CLOSURE OF MEETING

Author Institution Mapping (AIM)

Please note that not all the institutions may get mapped due to non-availability of the requisite information in the Google Map. For AIM of other issues, please check the Archives/Back Issues page on the journal’s website.


5th Scientific Workshops & Debates in Cape Town, South Africa Abstracts List11Full abstract will be published in Pulmonary Circulation Vol. 1 Issue 4, December 20011

Clinical characteristics and outcome of pulmonary hypertension among admitted heart failure patientsKaraye K. M.1,3,4, Yahaya I.2,3,4, Sa’idu H.1,4, Bala M. S.1,4

1Department of Medicine and 2Department of Chemical Pathology, 3Bayero University, 4Aminu Kano Teaching Hospital, Kano, Nigeria

Address for correspondence: Dr. K. M. Karaye, PO Box 4445, Kano, Nigeria. Tel: +234 803 704 2171, E-mail: [email protected]

Heart rate recovery after 6-minute walk test in patients with pulmonary arterial hypertensionMinai O. A.1, Gudavalli R.1

1Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA

Address for correspondence: Omar Minai, Cleveland Clinic, 9500 Euclid Avenue, 44195 Cleveland Ohio, USA, Tel.: (001) 216-445-2610, E-mail: [email protected]

Does high altitude protect against irreversible pulmonary hypertension?Heath A.1, Von Alvensleben I.2, Graham B.3, Tuder R.3, Brockman C.4, Perez E.4

1Kardiozentrum – Pediatric Cardiologist, La Paz, Bolivia, PVRI fellow, Former Resident, Aachen RWTH, Germany, 2Kardiozentrum - pediatrician, La Paz, Bolivia, former resident University of Berlin, Germany, 3Department of Medicine University of Colorado at Denver, 4Centro Médico Quirúrgico Boliviano- cardiac surgeon, belga in Cochabamba, Bolivia

Address for correspondence: Dr. Alexandra Heath-Freudenthal, Kardiozentrum Fundacion Cardioinfantil La PazPo Box 100La Paz, Bolivia. E-mail: [email protected]

Long term follow up of closure of atrial septal defects in older children and adults with severe pulmonary arterial hypertensionHarikrishnan S.1, Sonney J. P.1, Randeep S.1, Venkiteswaran S.1, Krishnamoorthy K. M.1, Sivasankaran.S.1, Titus T.1, Jaganmohan T.1

1Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India

Address for correspondence: Dr. Harikrishnan S., Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum - 695011, India. Tel.: 91-471-2551692, Mob. 98951-25101, E-mail: [email protected]

Pulmonary hypertension in a tertiary health institution: a retrospective review of 24 months echocardiography registry

Sani M. U.1,2, Mijinyawa M. S.1,2, Ishaq N. A.1, Shehu M. N.1, Mohammed S.1, Ya’u J. A.1, Saidu H1

1Department of Medicine, Aminu Kano Teaching Hospital, Kano, Nigeria, 2Department of Medicine, Bayero University Kano

Address for correspondence: Mahmoud Sani, Bayero University Kano, Aminu Kano Teaching Hospital, PMB 3452, 700223, Kano, Kano State, Nigeria, Tel.: +2348033479179, E-mail: [email protected]

Overview of pulmonary hypertension registries and quality standardsPittrow D.1

1Department for Clinical Pharmacology, Technical University Dresden, Dresden, Germany

Address for correspondence: David Pittrow, Technical University Dresden, Fiedlerstr. 27, D-01307 Dresden, Germany. Tel.: +49-815-1107-31008, E-mail: [email protected]

Pulmonary hypertension at moderate altitude in children: importance of the hyperreactivity of pulmonary vascular tree (HPVT)Díaz G. F.1, Marquez A.2, Ruiz A.3

1Departamento de Pediatría, Universidad Nacional de Colombia, Bogotá, Colombia, Fundación Santa Fe de Bogotá and Hospital La Misericordia, 2Clínica de La Mujer and Centro Policlínico Del Olaya, Bogotá, 3Departamento de Ginecología y Obstetricia, Epidemiología, Universidad Nacional de Colombia

Address for correspondence: Gabriel Díaz, Titular Professor, Department of Pediatrics, Universidad Nacional de Colombia, Carrera 5 No 116-58 Apto 502, Bogotá, Colombia. E-mail: [email protected] or [email protected]

Atrial natriuretic peptide improves Staphylococcus aureus-induced lung inflammation and vascular barrier functionBirukova A. A.1, Xing J.1, Moldobaeva N.1

1Department of Medicine, University of Chicago, Chicago, Illinois, USA

Address for correspondence: Anna Birukova, MD, Section of Pulmonary and Critical Medicine, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC-6026; Office N-613, Chicago, IL 60637 USA. Tel.: 773-834-2634, E-mail: [email protected]

Oxygen sensing pathway: revealing and documenting human adaptations at high-altitudeMishra A.1,2, Thinlas T.3, Mohammad G.3, Pasha M. A. Q.1,2

1Functional Genomics Unit, Institute of Genomics and Integrative Biology, Delhi, 2Department of Biotechnology, University of Pune, Pune, 3Department of Medicine, SNM Hospital, Leh, Ladakh, J & K, India


Address for correspondence: M. A. Qadar Pasha, Functional Genomics Unit, Institute of Genomics and Integrative Biology Mall Road, Delhi 110 007, India. E-mail: [email protected]

Vasoactive mediators and ROS interactions under hypobaric hypoxiaAli Z.1,2, Mishra A.1,2, Mohammad G.3, Pasha M. A. Q.1,2


Address for correspondence: M. A. Qadar Pasha, Functional Genomics Unit, Institute of Genomics and Integrative Biology Mall Road, Delhi 110 007, India. E-mail: [email protected]

Inter-kinase communiqué: The P CodePandey P.1,2, Mohammad G.3, Pasha M. A. Q.1,2


Address for correspondence: M. A. Qadar Pasha, Functional Genomics Unit, Institute of Genomics and Integrative Biology, Mall Road, Delhi 110 007, India. E-mail: [email protected]

Causes of pulmonary arterial hypertension (PAH) in the paediatric population in a tertiary care centre in Saudi ArabiaBanjar H.1

1Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh Saudi Arabia

Address for correspondence: Hanaa Banjar, King Faisal Specialist Hospital and Research Centre, PO Box 3354, MBC-58, 11211, Riyadh Saudi Arabia. Tel.: 966-5043-93022, E-mail: [email protected]

Involvement of Immune/Inflammatory Cells to Pathology of Idiopathic Pulmonary Arterial HypertensionSavai R.1, Pullamsetti S. S.1,2, Kolbe J.2, Bieniek E.2, Ghofrani H. A.2, Weissmann N.2, Fink L.3, Klepetko W.4, Voswinckel R.1,2, Banat G. A.2, Seeger W.1,2, Grimminger F.2, Schermuly R. T.1,2

1Department of Lung Development and Remodelling, Max-Planck Institute for Heart and Lung Research, Bad Nauheim, Germany, 2Department of Internal Medicine, University of Giessen Lung Center, Giessen, 3Department of Pathology, University of Giessen Lung Center, Giessen, Germany, 4Department of Thoracic Surgery, University Hospital Vienna, Vienna, Austria

Address for correspondence: Rajkumar Savai, Molecular Mechanisms in Lung Cancer, Max Planck Institute for Heart and Lung Research, Parkstrasse 1; D-61231 Bad Nauheim; Germany. Tel.: +49 6032 705 420, E-mail: [email protected]

Non-response to acute pulmonary vasodilator challenge in Idiopathic Pulmonary Arterial Hypertension is associated with non recruitment

of Pulmonary Functional Capillary Endothelial Surface AreaLangleben D.1, Orfanos S. E.2, Giovinazzo M.1, Hirsch A.1, Sotiropoulou C.2, Armaganidis A.2, Catravas J. D.3

1Jewish General Hospital, McGill University, Montreal PQ, Canada, 2Attikon Hospital, University of Athens Medical School, Haïdari Athens, Greece, 3Medical College of Georgia, Augusta GA, USA

Address for correspondence: David Langleben, Center for Pulmonary Vascular Disease, Cardiology Division, Jewish General Hospital, H3T 1E2 Montreal, Canada. E-mail: [email protected]

Utility of the Brain Natriuretic Peptide (BNP) as a marker in the diagnosis of patients with Persistent Pulmonary Hypertension of the Newborn (PPHN)Díaz G.1, Ruiz A. I.1, Acherman R.3, Montealegre A.2, Ome L.2, Marquez A.4

1Universidad Nacional de Colombia, 2Instituto Materno Infantil, Bogotá Colombia, 3Children´s Heart Center Las Vegas, Nevada; Universidad de Nevada Las Vegas, USA, 4Clinica de La Mujer y Centro Policlínico del Olaya Bogotá Colombia

Address for correspondence: Gabriel Diaz, Titular Professor, Department of Pediatrics, Universidad Nacional de Colombia, Carrera 5 No 116-58 Apto 502, Bogotá, Colombia. E-mail: [email protected] or [email protected]

Sildenafil Plasma Concentrations in Two HIV Patients with Pulmonary Arterial Hypertension Treated with Ritonavir-Boosted Protease InhibitorsChinello P.1, Cicalini S.1, Pichini S.3, Pacifici R.3, Tempestilli M.2, Petrosillo N.1

1Second Infectious Diseases Unit, “L. Spallanzani” National Institute for Infectious Diseases, Rome, Italy, 2Clinical Biochemistry and Pharmacology Laboratory, “L. Spallanzani” National Institute for Infectious Diseases, Rome, Italy, 3Drug Abuse and Doping Unit, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy

Address for correspondence: P. Chinello, National Institute for Infectious Diseases, Via Portuense 292, 00149 Rome, Italy. Tel.: 0039-06-55170294, E-mail: [email protected]

Estimation of Pulmonary Artery pressure in patients with sickle cell anaemia in Ibadan, Nigeria: An echocardiographic studyEnakpene E. O.1, Adebiyi A.1, Ogah O. S.1, Olaniyi J. A.2, Aje A.1, Adebayo A. K.1, Ojji D. B.1, Adeoye M. A.1, Ochulor K. C.1, Oladapo O. O.1, Falase A. O.1

1Division of cardiovascular medicine, Department of Medicine, University College Hospital, Ibadan, Nigeria, 2Department of Haematology, University College Hospital, Ibadan, Nigeria

Address for correspondence: Dr. E. O. Enakpene, Division of cardiovascular medicine, Department of Medicine, University College Hospital, Ibadan, Nigeria Tel.: +234 (0) 8064121, E-mail: [email protected]

Scientific Abstracts



Pulmonary Hypertension associated with Sickle Cell Anaemia: A review of epidemiology, pathophysiology and managementOgah O.S.1, Falase A. O.1, Stewart S.2, Sliwa K.3

1Department of Medicine, University College Hospital, Ibadan, Nigeria, 2Preventative Health Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne VIC, 3004, Australia, 3Hatter Cardiovascular Research Institute, Faculty of Health Sciences,University of Cape Town, Private Bag X3, Observatory 7935, South Africa

Address for correspondence: Dr. O. S. Ogah, Division of Cardiology, Department of Medicine, University College Hospital Ibadan PMB 5116, Ibadan, Oyo State, Nigeria. Tel.: +234 806 77 47 121 E-mail: [email protected] OR [email protected]

Serotonin passes through myoendothelial gap junctions to promote pulmonary arterial smooth muscle cell differentiationGairhe S.1, Gebb S. A.2, McMurty I. F.1

1Departments of Pharmacology, 2Cell Biology and Neuroscience, and Medicine at Center for Lung Biology, College of Medicine, University of South Alabama

Address for correspondence: S. Gairhe, University of South Alabama, 307 N University Blvd, 36688 Mobile, Alabama, USA. Tel.: (001) 2514501685, E-mail: [email protected]

Doppler Echocardiographic Assessment of Pulmonary Artery Pressure in Apparently Healthy Nigerian Primary School Children in Ibadan (WESTERN NIGERIA)*Udo P. A.1, Orimadegun A. E.2, Omokhodion S. I.3

1Department of Paediatrics, University of Uyo Teaching Hospital, 2Institute of Child Health, College of Medicine, University of Ibadan, 3Department of Paediatrics, College of Medicine, University of Ibadan

Address for correspondence: Dr. Patience A. Udo, University of Uyo Teaching Hospital, PMB 1136 Uyo, Akwa Ibom, Nigeria, Tel: +2348062293723, E-mail: [email protected]

Long-term Endothelin Receptor Antagonist therapy may predispose to carcinogenesis in patients with Pulmonary Arterial HypertensionSafdar Z.1, Qureshi H.1

1Pulmonary-Critical Medicine, Baylor College of Medicine, Houston, Texas, USA

Address for correspondence: Prof. Z. Safdar, Baylor College of Medicine, 2606 Werlein Avenue, 77005, Houston, Texas, USA. Tel.: (001) 713-855-2247, E-mail: [email protected]

Non-invasive evaluation of pulmonary hypertension and its correlates among adult patients with sickle cell diseaseMbakwem A. C.1, Kehinde M. O. 2,1

1Cardiology unit, 2Haematology unit, Dept of Medicine, College of Medicine, University of Lagos

Address for correspondence: Dr Amam Mbakwem,

Cardiology unit, Dept of Medicine, College of Medicine, University of Lagos, Lagos, Nigeria. E-mail: [email protected]

Single and combinat ion therapy wi th erythropoietin (EPO) and sildenafil on hypoxia-induced PAHSamillan V.1, Haider T.1, Vogel J.1, Leuenberger C.1, Gassmann M.1, Østergaard L.1

1Department of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, Switzerland

Address for correspondence: Louise Østergaard, Department of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland. E-mail: [email protected]

A practicable risk score for pulmonary hypertensionTiede H.1, Felix J.2, Wilkins M.3, Steyerberg E.2, Seeger W.1, Grimminger F.1, Ghofrani A.1

1University of Giessen Lung Center, 2Erasmus University of Rotterdam, 3Imperial College London

Address for correspondence: Henning Tiede, University of Giessen Lung Center, Klinikstrasse 33, 35392 Giessen, Germany. Tel.: 0049-641-985-56766, E-mail: [email protected]

Use of combination therapy in postoperative persistent pulmonary arterial hypertension in childrenKulkarni S.1, Jadhav M.1, Garekar S.1, Rao S.1

1Children’s Heart Center, Kokilaben Dhirubhai Ambani Hospital, Mumbai, India

Address for correspondence: S. Kulkarni, Kokialbem Ambani Hospital, Four Bungalows, Andhere West, 40056 Mumbai, India. Tel.: 919920073200, E-mail: [email protected]

LC/MS/MS method for simultaneous analysis of arachidonic acid and its endogenous eicosanoid metabolites and prostaglandins in rodent lung tissueSagliani K.1, Hill N. S.1, Fanburg B. F.1, Dolnikowski G.2, Levy B. L.3, Preston I. R.1

1Pulmonary, Critical Care and Sleep Division, Tufts Medical Center, Boston, 2Human Nutrition Research Center of Aging, Boston, 3Brigham and Women Hospital, Boston

Address for correspondence: K. Sagliani, Tufts University School of Medicine, Tufts Medical Center 89 Chester St. Apt A2 02134 Allston/Ma, USA. Tel.: (001) 4435287801, E-mail: [email protected]

Determination of endogenous bioactive lipid profile in experimental pulmonary hypertensionSagliani K.1, Hill N. S.1, Fanburg B. F.1, Warburton R. W.1, Dolnikowski G.2, Levy B. L.3, Preston I. R.1




Lipidomic analysis of plasma from patients with pulmonary arterial hypertension: Determination of circulating arachidonic acid metabolitesSagliani K.1, Preston I. R.1, Roberts K. R.1, Fanburg B. F.1, Dolnikowski G.2, Levy B. L.3, Hill N. S.1



Echocardiographic Prediction of Pulmonary Vascular ResistanceOpotowsky A. R.1,2,3, Clair M.2, Landzberg M. J.2,3, Waxman A. B.3, Arkles J. S.1, Rogers F.1, Prasanna V., MD, Moko L.2, Maron B.3, Fields A.1, Forfia PR.1

1Department of Medicine, Cardiovascular Division, Heart Failure and Pulmonary Hypertension Program, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, 2Department of Cardiology, Children’s Hospital Boston, Boston, MA, 02115, 3Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, 02115, USA

Address for correspondence: Alexander R. Opotowsky, M.P.H, Children’s Hospital Boston, Brigham and Women’s Hospital, Harvard Medical School, 300 Longwood Avenue. Boston, MA 02115, USA. Tel.: (617) 355-6508, E-mail: [email protected]

The usefulness of cardiac MRI in understanding PAHin complex CHD, illustration in three casesKappanayil M.1, Kannan R.2, Krishna Kumar R.1

1Department of Pediatric Cardiology, Amrita Institute of Medical Sciences, Kochi, Kerala, 2Department of Radiology, Amrita Institute of Medical Sciences, Kochi, Kerala, India

Address for correspondence: Mahesh Kappanayil, Associate Professor, Pediatric Cardiology, Amrita Institute of Medical Sciences, Kochi, Kerala, India. Mob : +91-9846190020, E-mail: [email protected]

Atrial flutter and atrial fibrillation in patients with chronic pulmonary hypertensionOlsson K.1, Nickel N.1, Tongers J.2, Hoeper M.1

1Department of Respiratory Medicine, 2Department of Cardiology Hannover Medical School, Hannover, Germany

Address for correspondence: Dr. Karen Olsson, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany, Tel.: +491717774064, E-mail: [email protected]

Gene expression profiling in human pulmonary arterial smooth muscle cells in response to bone morphogenetic proteins and transforming growth

factor-βMenon S.1, Long L.2, Dunmore B. J.2, Morrell N. W.2

1Jawaharlal Nehru University, Delhi, 2Department of Medicine, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK

Address for correspondence: Swapna Menon, School of Computational & Integrative Sciences, 2547- Sector D- Pocket 2, Vasant Kunj, 110070 New Delhi, India. Tel.: -26704092, E-mail: [email protected]

Role of micro RNA 145 in vascular remodeling in pulmonary arterial hypertensionJoshi S. R.1,4, Abe K.1,2,4, Oka M.2,3,4, McMurtry I. F.2,3,4, Gerthoffer W. T.1,3,4

1Department of Biochemistry and Molecular Biology, 2Department of Pharmacology, 3Department of Medicine, 4Center for Lung Biology, University of South Alabama, College of Medicine, Mobile, AL 36688, USA

Address for correspondence: Sachindra Joshi, College of Medicine, University of South Alabama, Mobile AL 36608, USA. Tel.: (001) 251-460-6843, E-mail: [email protected]

Pulmonary capillary hemangiomatosis: an unusual histological presentation of vascular lesion in lung biopsies from patients with congenital cardiac shunts and pulmonary hypertensionAiello V. D.1, Thomaz A. M.2, Pozzan G.3, Lopes A. A. B.2

Heart Institute (InCor), São Paulo University Medical School, Brazil, 1Laboratory of Pathology, 2Clinical Division of Pediatric Cardiology, 3Santa Casa de Misericórdia de São Paulo

Address for correspondence: Vera Aiello Demarchi, Laboratory of Pathology, Heart Institute (InCor), São Paulo University Medical School, Brazil. E-mail: [email protected]

Platelet function and morphology in Idiopathic pulmonary hypertensionRamakrishnan S.1, Senguttuvan N. B.1, Lakshmy R.1, Saxena R.1, Wadhwa S.1, Khunger J. M.1, Bhargava B.1, Kothari S. S.1, Saxena A.1, Bahl V. K.1

1All India Institute of Medical Sciences, New Delhi, India

Address for correspondence: S. Ramakrishnan, Department of Cardiology, All India Institute of Medical Sciences, New Delhi 110029, India. E-mail: [email protected]

Prevalence of Pulmonary Hypertension among 6270 asymptomatic school children in India: The RHEUMATIC (Rheumatic Heart Echo Utilization and Monitoring Actuarial Trends in Indian Children) StudySaxena A.1, Ramakrishnan S.1, Roy A.1, Seth S.1, Krishnan A.1, Misra P.1, Kalaivani M.1, Bhargava B.1, Flather M.1, Poole-Wilson P.1

1All India Institute of Medical Sciences, New Delhi, Royal Brompton Hospital and Imperial College, London, UK



Address for correspondence: Prof. Anita Saxena, Department of Cardiology, All India Institute of Medical sciences, New Delhi 110029, India,. E-mail: [email protected]

A review of catheterization data for determining operability in congenital heart disease with severe pulmonary hypertension

Juneja R.1, Ramakrishnan S.1, Anju 1, Gupta S.1, Kothari S. S.1, Saxena A.1


Address for correspondence: Prof. Rajnish Juneja, Department of Cardiology, All India Institute of Medical sciences, New Delhi 110029, India. E-mail: [email protected]

Predictors of adverse clinical outcome in Eisenmenger syndromeRamakrishnan S.1, Kukreti B. B.1, Juneja R.1, Bharghava B.1, Kothari S. S.1, Saxena A.1, Bahl V. K.1

1All India Institute of Medical Sciences (AIIMS), New Delhi, India

Address for correspondence: Prof. Anita Saxena, Department of cardiology, All India Institute of Medical sciences, New Delhi 110029, India. E-mail: [email protected]

Inflammatory markers are elevated in Eisenmenger syndromeRamakrishnan S.1, Pendharkar A.1, Kukreti BB.1, Lakshmy R.1, Karthikeyan G.1, Seth S.1, Juneja R.1, Bharghava B.1, Kothari SS.1, Saxena A.1, Bahl VK.1



Nocturnal Hypoxemia in Patients with Eisenmenger SyndromeRamakrishnan S.1, Juneja R.1, Sharma A. K.1, Bardolei N.1, Shukla G.1, Guleria R.1, Bhatia M.1, Kalaivani M.1, Kothari S. S.1, Saxena A.1, Bahl V. K.1



Severe Pulmonary Hypertension associated with HIV infectionAlmodovar S., Flores S. C.1

1Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, USA

Address for correspondence: Dr. Sharilyn Almodovar, University of Colorado Denver, 12700 E 19th Avenue, Mailstop C-272, 80045 Aurora, USA. Tel.: (001) 303-724-6086, E-mail: [email protected]

Surgical treatment in congenital heart disease with pulmonary arterial hypertension (PAH-

CHD) before the era of specific therapies – A historical groupGonçalves R. C.1, Aiello V. D.1, Lopes A. A.1

1Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil

Address for correspondence: Vera Aiello Demarchi, Laboratory of Pathology, Heart Institute (InCor), São Paulo University Medical School, Brazil. E-mail: [email protected]

Loss of Tolerance and Bronchus Associated Lymphoid Tissue Expansion in Pulmonary HypertensionYeager M. E.1, Cripe P. J.1, Colvin K. L.1, Stenmark K. R.1

1University of Colorado Denver Health Sciences, Denver Colorado, USA

Address for correspondence: Michael Yeager, Dept. of Bioengineering, University of Colorado Denver Health Sciences 12700 E. 19th Ave., Box C218, Denver Colorado, USA 80045. Tel.: 303 724 4193, E-mail: [email protected]

Pulmonary hypertension amongst patients with Sickle Cell Disease in AfricaWonkam A.1

1Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Cameroon

Address for correspondence: Ambroise Wonkam, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Cameroon. E-mail: [email protected]

Effect of perioperative oral sildenafil on pulmonary artery hypertension in patients undergoing mitral valve surgery: a prospective double blinded randomized trialPuri G. D.1, Kumar B.1

1Post Graduate Institute of Medical Education and Research, Chandigarh, India

Address for correspondence: Prof. Goverdhan Puri, Post Graduate Institute of Medical Education and Research, Sector 12, 160012 Chandigarh, India. Tel.: 0919815199717, E-mail: [email protected]

Adverse events of Pulmonary Hypertension Pharmacotherapy in childrenRoldan T.2, Cerro M. J.1, Romero Garrido J. A.2, Deiros L.1, Herrero A.2, Gutierrez-Larraya F.1

1Pediatric Pulmonary hypertension Unit- Pediatric Cardiology, 2Department of Pharmacy, “La Paz” Children´s Hospital. Madrid, Spain

Address for correspondence: Maria Jesus del Cerro, "La Paz" children´s hospital, C7 Paso de la Castellana, 261, 28046 Madrid, Spain. Tel.: 0034629239978, E-mail: [email protected]

Pulmonary hypertension and pulmonary vascular remodelling in mouse models of SchistosomiasisCrosby A.1

1Department of Medicine, Addenbrooke’s Hospital, Cambridge, UK



Address for correspondence: Alexi Crosby, Department of Medicine Level 5, Addenbrooke's Hospital, Box 157 Hills Road, CB2 2QQ Cambridge, United Kingdom. Tel.: 01223 762007, E-mail: [email protected]

Prognostic value of exercise cardiac index in idiopathic, heritable and anorexigen-associated pulmonary arterial hypertensionChaouat A.1

1Service des Maladies Respiratoires et Reanimation Respiratoire, Hospital de Brabois, Vandoeuvre-les-Nancy Cedex, France

Address for correspondence: Ari Chaouat, Hospital de Brabois, Allee du Morvan, 54511, Vandoeuvre-les-Nancy Cedex, France. Tel.: +33 (0) 383-153-706, E-mail: [email protected]

Blockade of TGF-beta Prevents Schistosomiasis-Associated Pulmonary HypertensionGraham B.1, Chabon J.1, Tuder R.1

1Program in Translational Lung Research, University of Colorado Denver

Address for correspondence: Brian Graham, Division of Pulmonary Sciences and Critical Care Medicine, Anschutz Medical Campus, Research 2 - 9th floor; Mail stop C-272, 12700 East 19th Avenue, Aurora, CO 80045 USA. Tel.: 1 303 724 3876, E-mail: [email protected]

Novel roles of radiation protective compound amifostine in attenuation of acute lung injuryBirukov K. G.1, Fu P.1, Sarich N.1, Birukova A. A.1

1Department of Medicine, The University of Chicago, Chicago, Illinois, USA

Address for correspondence: Konstantin Birukov, Lung Injury Center, Section of Pulmonary and Critical Medicine, Department of Medicine, University of Chicago, 5841 S. Maryland Ave, MC-6026, Office N-611, Chicago, IL 60637 USA. Tel.: 773-834-2636, E-mail: [email protected]

Subcellular mechanisms in IPAH – coordinate dysfunctions of the Golgi-ER-mitochondrial axisSehgal P. B.1

1Depts. Cell Biology & Anatomy, and Medicine, New York Medical College, New York, NY 10595, USA

Address for correspondence: Prof. Sehgal, New York Medical College, Rm. 201 Basic Sciences Building, Valhalla, 10595 NY, USA. Tel.: 914-594-4196, E-mail: [email protected]

The behavior of the right ventricular dysfunction by echocardiography and clinical Transthoracic (ECTT)Murillo C.1

1Instituto Boliviano de Biologia de la Altura, La Paz, Bolivia

Address for correspondence: Carla Murillo, Instituto Boliviano de Biologia de la Altura, Avenida los Leones 2570

Miraflores Final Saavedra, 0042, La Paz, Bolivia. Tel.: 00 591 - 2- 2242049, E-mail: [email protected]

Epidemiology of pulmonary heart disease in Nigeria: insight from the Abeokuta Heart Failure RegistryOgah O. S.1, Falase A. O.1, Stewart S.2, Sliwa K.3

1Department of Medicine, University College Hospital, Ibadan, Nigeria, 2Preventative Health Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne VIC, 3004, Australia, 3Hatter Cardiovascular Research Institute, Faculty of Health Sciences, University of Cape Town, Private Bag X3, Observatory 7935, South Africa

Address for correspondence: Dr. O. S. Ogah, Division of Cardiology, Department of Medicine, University College Hospital Ibadan PMB 5116, Ibadan, Oyo State , Nigeria. Tel.: +234 806 77 47 121, E-mail: [email protected] OR [email protected]

Therapeutic potential of HDAC inhibitors in pulmonary hypertensionZhao L.1, Chen C. N.1, Hajji N.1, Oliver E.1, Huang T. J.1, Wang D.2, Li M.2, McKinsey T.2, Stenmark K. R.2, Wilkins MR.1

1Centre for Pharmacology and Therapeutics, Experimental Medicine, ImperialCollege London, 2Department of Pediatrics, Division of Critical Care Medicine, University ofColorado Denver, USA

Address for correspondence: Prof. Lan Zhao, Burlington Danes Building, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. E-mail: [email protected]

Markers of left and right ventricular remodelling in a native African Hypertensive CohortOjji D.1,3, Lacerda L.3, Lecour S.3, Adeyemi Billyrose M.2, Sliwa K.3

1Cardiology Unit, Department of Medicine, University of Abuja Teaching Hospital, Gwagwalada, Abuja, 2Department of Medical Laboratory Sciences, University of Abuja Teaching Hospital, Gwagwalada, Abuja, 3Hatter Institute for Cardiovascular Research in Africa

Address for correspondence: Dike Ojji, Cardiology Unit, Department of Medicine, University of Abuja Teaching Hospital, PO Box 193, Gwagwalada, Abuja, Nigeria. Tel.: +234-8060094456, E-mail: [email protected]

Correlation of pulmonary arteriolar remodeling on transbronchial lung biopsies with computed tomographic indicators of pulmonary hypertensionRitu Kulshrestha1, D. Soundarya1, Seema Kumari2, Balakrishnan Menon2

Department of Pathology1, Pulmonary Medicine2, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India



PVRI Gala Dinner

The Pulmonary Vascular Research Institute is pleased to announce that this year's Gala Dinner will take place on Thursday the 9th of February at the formidable Jonkershuis Restaurant in Groot Constantia. The restaurant is nestled inside the Historic Core of the Groot Constantia Wine Estate, with panoramic views of the peninsula and the majestic Constantia Valley. The program will start at 18:30 with two talks on the PVM History Initiative, followed by cocktails and Achievement awards ceremony.

Dinner will be served from 20:00 onwards. Diners will be seated outside where they can see the sun sinking behind the mountains whilst enjoying the two lectures prepared for the occasion by professors Stuart Rich and Lionel Opie as described in the Cape Town program.

Places are restricted, so please ensure your seat by booking your reservation at www.pvri.info today.

Figure 1: Location of Jonkershuis Restaurant in Groot Constantia

Gala Dinner Program18.30 PVM in History

Chair: Stylianos Orfanos“The Story of Fen-Phen (Fenluramine)” – Stuart Rich“Historical notes: Heart and Mind” – Lionel Opie

19:30 Cocktail Drink and Achievements Award20:00 GALA DINNER


Annual Report of Pulmonary Vascular Research Institute

2011

Compiled byGhazwan Butrous and Nikki Krol1

Managing Director, 1Administrator and assistant editor, Pulmonary Vascular Research Institute


an

no

un

cE

ME

nt Dr. Simon Campbell, FRS appointed to the PVRI

Board of Directors and Advisors

The Pulmonary Vascular Research Institute Board of Directors is pleased to welcome a new member in their midst. The distinguished scientist Dr. Simon Campbell has accepted the invitation to serve as a Board member of the PVRI, and will attend the 7th Board of Directors meeting in Cape Town this year, as well as the 6th Annual General Meeting and the 5th Scientific Workshops and Debates.

Dr. Campbell received his PhD in synthetic organic chemistry from Birmingham University in the UK in 1965. He carried out postdoctoral research in Birmingham, Chile and Stanford University with W.S. Johnson, before being appointed Visiting Professor at the Universidade de Sao Paulo, Brasil in 1970.

In 1972, Dr. Campbell joined Pfizer Central Research, Sandwich, as a medicinal chemist. He retired from Pfizer as Senior Vice President for World-wide Discovery and Medicinals R&D Europe in 1998. During this time, Dr. Campbell helped play a key part in the discovery of doxazosin (CarduraTM) and amlodipine (NorvascTM), both medicines that became the leading agents worldwide in their therapeutic class. In addition, he was senior author on the research proposal that led to sildenafil (ViagraTM).

Dr. Campbell’s scientific contributions have been recognised by the Royal Society of Chemistry Award for Medicinal Chemistry (1989), the Herschberg Award from the American Chemical Society (1997), ACS Medicinal Chemistry Hall of Fame (1997), the Industry Research Institute (US) Achievement Award (1997), the CIA Individual Achievement Award (2006), and the Galen Medal (2007). He was elected Fellow of the Royal Society (1999), Fellow of the Academy of Medical Sciences (2002) and was admitted to the degree of Doctor of Science honoris causa by the University of Kent at Canterbury (1999), the University of Birmingham (2004) and St Andrews University (2008). Dr Campbell was President of the Royal Society of Chemistry (2004-06), and was awarded a CBE in the Queen’s 80th Birthday Honours List (2006) “for services to science”. He was named number 31 in the Times Eureka list of 100 top UK scientists for 2010.

Dr. Campbell has served on various professional and research bodies including SERC Organic Chemistry Sub-Committee, Science Board, LINK Asymmetric Synthesis, ABPI R&D Committee, Chemistry RAE Panel (2001) and as Visiting Professor at the University of Leeds and Birkbeck College. He also acted as the first Chair of the Expert Scientific

Advisory Committee for the Medicines for Malaria Venture (Geneva, 1999-2003) which he re-joined in 2008, and was a member of the BP Technology Advisory Council (2000-04), the Council of the University of Kent (1999-2007) and the Advisory Council for the Misuse of Drugs (2007-09).

Currently, Dr. Campbell is a member of the SABs of Astex (Cambridge), Avila (Boston), Bionomics (Adelaide) CTx (Melbourne), Ensemble (Boston) Experimental Therapeutics Centre (Singapore) Hydra (Boston) IECB (Bordeaux), Intellikine (San Diego), MRC Technology (London), and the CRUK Discovery Coordinating Committee (London). He acts as consultant to Abingworth Management (London), Apposite Capital (London), Novartis Institute for Tropical Diseases (Singapore), Wellcome Trust SDD and he also serves on Advisory Council for CaSE. Dr Campbell is a Fellow of the Royal Society of Chemistry, and is a member of the American Chemical Society and the Society for Medicines Research.

The PVRI Board of Directors received a number of recommendations suggesting Dr. Simon Campbell as a worthy and enthusiastic addition to the Board. After some review, votes were cast and Dr. Campbell was unanimously approved and invited to join in early October, which he graciously accepted. He will officially assume his role on the Board during the Board of Directors meeting in Cape Town, February 2012.

Figure 1: Dr. Simon Campbell, FRS


5th PVRI Annual General Meeting and 6th Scientific Workshops and Debates, Panama City, February 2-5, 2011

The 5th PVRI Annual General Meeting and 6th Scientific Workshops and Debates took place in Panama City, Feb 2-5 2011. The AGM functions as an opportunity to update all Fellows on the activities and initiatives of the prior year, and to set the course for the next term. Typically, Fellows are asked to vote and participate on issues regarding meeting location, taskforces, and positions within the PVRI. The Scientific Workshops & Debates focus on different approaches and activities within the field of pulmonary vascular disease research, and attracts members from Pharma, Industry and PVRI alike. It is an excellent opportunity to share and trade ideas and presentations, and discussion and active debate blooms during these days. The Panama meeting was no exception, and in many ways surpassed previous PVRI conferences. A small day-by-day breakdown is provided below. For more details, please see the PVRI website.

Wednesday, 2nd February 2011Day One of the 5th PVRI AGM began with a moment of silence for the late Peter Raymond, a highly respected founding member of the Board of Directors, who sadly passed away the week prior. PVRI President Martin Wilkins recounted Professor Raymond’s support, enthusiasm and many initiatives for the PVRI. The minute of silence ended with a round of applause in his memory.

Afterwards, Fellows focused on the PVRI achievements of the past year in order to determine the positives, learn from the negatives and stipulate the course for the coming year.

PVRI President Martin Wilkins placed particular emphasis on the FDA/PVRI meeting, the PVRI Review translation and publication in several languages, and the strong focus on schistosomiasis. Thoughts were also given to the launch of the quarterly peer-reviewed journal Pulmonary Circulation in March 2011, and ways in which to ensure enough material and articles to continue the journal full-strength. Dr. Harikrishnan S. provided an overview of PVRI Review, which was followed by a discussion regarding its future. One suggestion proposed the relegation of PVRI Review publication to twice a year, to produce issues spanning January-June and July-December.

Board of Directors Chairman Stuart Rich asked all those present to invite two friends or colleagues to join the PVRI in order to grow the membership and strengthen the base of the organisation. Managing Director Ghazwan Butrous proposed changes in the Constitution, to be put to a vote during the AGM. Absent Fellows were asked to vote online regarding the location of the 6th PVRI AGM meeting, and to record their opinions regarding the plans for the future course of the Institute.

About 40 Fellows attended the first half of the 5th PVRI Annual General Meeting. Many were deferred and had to send apologies due to the winter weather in parts of America, which shut down flights all over the country. For those unable to attend, PVRI provided a Twitter stream of live updates on the topics and happenings in Panama (www.twitter.com/pvri), images of the slides and attending Fellows at hashalbum.com/pvri and the Facebook page (http://on.fb.me/g8aLWh), as well as on the PVRI website (www.pvri.info/allblogs).

Thursday, 3rd February 2011 Day two of the 5th PVRI AGM saw a growth in the number of attendees, as nearly 60 Fellows were present for the second half of the AGM.

The discussion addressed the management of the taskforces and relocated roles where necessary. Professor John Newman suggested the creations creation of ‘Interest Groups’ on the new PVRI website, which will allow Fellows to converge and discuss topics close to their interest, so natural collaborations and initiatives can form. Managing Director Ghazwan Butrous also unveiled plans regarding a ‘PVRI e-learning website’, which will serve as an online course for medical students with an interest in pulmonary vascular diseases. For this and other initiatives, Professor Butrous requested more active involvement of key Fellows. In time, roles will be created for managerial staff to head specific projects and bring fresh ideas and perspectives to the organisation.

After coffee, Professor Butrous presented the proposed changes to the PVRI structure and hierarchy as discussed the previous day. All Fellows were asked to vote, and in addition to the present Fellows, 25 absentee votes were recorded via the internet poll. The following decisions were the result:• GhazwanButrouswillserveasManagingDirectorfor

the next 4 years• Establishment ofmanagerial staff to assistManaging

Director and the functioning Vice Presidents for Research, Education and Alliances

• EstablishmentofaPVRIBusinessUnitforClinicalandTherapeutic Excellence

• LocationofAnnualGeneralMeeting2012:CapeTown

All proposed measures were voted through unanimously or with a clear majority.

The PVRI saw a superb turn-out at the 4th Annual Workshops & Debates, and the number of attendees continued to grow throughout the day as more Fellows and delegates found their way to the hotel, with new arrivals still pouring in during the cocktail hour in the evening. About ninety people

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were present at the Workshops & Debates on the 3rd of February, despite the worldwide flight delays and cancellations caused by erratic weather conditions.

Friday, 4th February 2011The morning of the 4th of February, Dr. Ardeschir Ghofrani began the debates with a presentation on: 'The pharmacological response: The clinical response to a treatment is the best way to dissect PAH Category 1 patients into subtypes and the only practical strategy to sub-phenotype the disease'. It set the stage for a day of interested debate, discussion and examination of existing procedures and proposed alternatives. Many topics, as treated by professors Nicholas Morrell and

Ralph Schermuly in Session 3, and Kurt Stenmark, Serge Adnot, Norbert Weissmann and Ralph Schermuly again in Session 4, engaged and inspired the audience and colleagues to questions and serious debate. Professor Hassoun invited Professor Adnot to 'tell the meeting why he had been wasting his time with serotonin receptors.' Professor Adnot obliged with good humour and presented 'Abnormalities in serotonin transport have not enlightened discussions on the pathology and management of PAH'.

After lunch, the meeting continued as Professor Evangelos Michelakis started the 'Dragon's Den' themed session. Topics

Figure 1: AGM meeting

Figure 3: Scenes of the scientific meeting in Panama City

Figure 5: The Pediatric Taskforce discussing the proposed classification

Figure 2: Scene of the scientific meeting poster discussion

Figure 4: Ghazwan Butrous presenting the Gala Dinner History Talk

Figure 6: Scenes from the ‘Operability of CTEPH patients’ meetings



included IL-13, Iron, Mitochondrial targets: PDK, PPAR gamma agonists and Key features of an ideal PAH drug and were very well handled by assorted speakers. After a short coffee break, Dr. Andy Grieve sparked debate with his interactive session on alternative clinical trial design and the challenging of dosage protocols. After allowing some time for discussion, Professor Martin Wilkins declared the day’s meeting a success and invited all present to attend the Gala Dinner.

The PVRI Gala Dinner took place in the beautifully dressed Barcelona room of the Riu Panama Plaza hotel. A light pre-dinner speech was organised by Professor Ghazwan Butrous, who took meticulous care in preparing an overview of 'The Story of Pulmonary Circulation: a 2500 year History'.

During the Gala Dinner, Board of Directors Chairman Stuart Rich, PVRI President Martin Wilkins and Managing Director Ghazwan Butrous took to the stage. Professor Butrous then invited Professor Antonio Augusto Lopes to join them, and unveiled that he had been chosen to receive the first AGM PVRI award. In recognition of his efforts and achievements in education for PVRI, Professor Rich, in name of the Board, presented Professor Lopes with the trophy. Professor Lopes held a brief acceptance speech acknowledging the help and work of those involved with PVRI, and claimed his achievements would not have been possible with said support. He was met with loud applause.

Professors Martin Wilkins, Ghazwan Butrous and Miss. Nikki Krol were also commended for their work for PVRI, whilst Mrs. Andrea Rich received a round of applause for her organisational skills and eye for detail which helped the 5th PVRI AGM and 4th Workshops & Debates see great success.

Saturday, 5th February 2011The final day began early with an 8am presentation by Dr. Ian Adatia on the Classification of Pediatric Pulmonary Hypertensive Disease. Dr. Adatia’s talk included previous discussion of the Pediatric Taskforce as held in a parallel meeting on Wednesday, and was met with praise and several questions. Professor Sheila Glennis Haworth subsequently took the stage to expand on pediatric functional classification. Questions were answered by Dr. Alexandra Heath and assorted members of the Pediatric Taskforce, before Professor Brian Graham concluded the first part of the meeting with a presentation on the differences in the pathology of PAH and chronic thromboembolic pulmonary hypertension. Professor Reda Girgis brought up the rear with CTEPH case studies. Each subject provoked significant discussion, despite the meeting being in its fourth day.

During the mid-morning break Dr. Deepa Gopolan arrived after having been delayed via weather-related flight rerouting, and promptly presented the next workshop on CTEPH. All week the audience had been provided with small booklets and posters which detailed symptoms and cardiograms of 8 different cases, and were asked to diagnose the patient based on the information provided. Drs Deepa Gopolan, Ardeschir Ghofrani and Ioana Preston went through the booklet on a case by case basis, asking the audience for their initial thoughts and revealing the accurate diagnosis afterwards. This method created a very interactive workshops between all present.

The stage was then given to surgeons David Jenkins, Michael Madani and Eckhard Mayer, whilst Professor Ghazwan Butrous moderated what he predicted would be 'much fighting'. Indeed, the session ran overtime as the three engaged the audience in a debate on the 'operability of CTEPH patients'.

As President Martin Wilkins was called away early due to the tempestuous flight weather, Managing Director Ghazwan Butrous closed the meeting with a sincere thank you to all tose present who had helped make the meeting a success and a great learning experience. It was agreed that the conference had been a great success and had indeed surpassed the expectations. With that, the 5th PVRI Annual General Meeting & 4th Workshops & Debates came to an end in Panama City.

For an online recording of the meeting, please go to www.pvri.info and click on the webinars from our Panama meeting.

Figure 7: The Panama Conference as recorded on the website



Board of Directors meeting: Teleconference, April 1, 2011The PVRI Board of Directors and Advisory Committee met for a two hour teleconference on April 1st. Participants discussed the results of the Panama conference, and the agenda of the forthcoming Annual General meeting in Cape Town. Other

subjects included the progress of the educational website, the progress on the main PVRI website, Pulmonary Circulation and the Taskforces. The Board decided to meet again prior to the Cape Town conference in February, 2012.

4th Annual Joint SAPH/PVRI Pulmonary Hypertension Conference, Dubai, April 2011The 4th Annual Joint Pulmonary Hypertension conference in Dubai, April 19th-22nd 2011, continued the line of annual meetings organized by the Saudi Association of Pulmonary Hypertension (SAPH) and the Eastern Mediterranean Taskforce of the PVRI. The first meeting was held in 2008 in Dubai, followed in 2009 by a meeting in Casablanca, Morocco. In 2010, SAPH hosted the meeting in Shram el Sheik, Egypt whilst this fourth meeting was planned to take place in Beirut. However, due to the political instability in the area the organizer was forced to change the location to a more stable, easily accessible city: Dubai. This was a positive move as all interested parties were able to attend the meeting as planned. These annual conferences have proved a very successful venture as the topics as well as the attendees have increased each year. At this 4th meeting, over 140 attendees from various parts of the Middle East were in attendance. Similarly, an increase in the level of discussion and general awareness has become noticeable, both of which are strong indicators that the joint SAPH and EMR Taskforce goal of enhanced awareness of pulmonary hypertension is being met.

The 4th Annual Joint Pulmonary Hypertension conference started with a keynote talk by Professor Ghazwan Butrous on the role of Islamic scientists and physicians in the development of pulmonary hypertension, a topic which is addressed further in the Pulmonary Vascular Medicine History Initiative section of the first issue of the PVRI journal Pulmonary Circulation. The discussion was very lively with 60 people present for the meeting, and a similar atmosphere continued during cocktails and dinner.

The following morning the meeting began with a warm welcome from the chairpeople of the session, Dr. Mohamed Al Hajjaj and Dr. Mirza Al Sayegh from UAE. The word was given to Dr. Majdy Idrees, head of SAPH and organizer and chairman of this meeting. Dr. Idrees initiated this series of meetings and has been very active both within SAPH, and as vice-president of the East Mediterranean region of the PVRI, a role he shares with Dr. Paul Hassoun. Dr. Idrees started the discussion by reminding the attendees of the SAPH mission, which states that "we committed ourselves to be the pilot group to take the lead in the management of pulmonary hypertension in the region, and to serve our patients by providing optimal medical service, support and care." He reiterated that SAPH is a national not-for-profit organization, and is currently supported by the Saudi Thoracic

Society. SAPH's main goal is to address issues related to the training and education of health care professionals in the area of pulmonary vascular diseases. SAPH is a partner of the PVRI and has in the past worked with the PVRI to enhance its collaboration with other international regional associations, and will continue to do so. In the last five years, SAPH has experienced fantastic growth, going from 6 to 74 members including pulmonologists, cardiologists, intensivists, pediatricians and rheumatologists.

Dr. Idrees presented the main achievements of SAPH as a summary of three major topics: Firstly, it began and continued the tradition of the Annual Meeting. Secondly, SAPH published the Saudi guidelines for pulmonary hypertension, and thirdly, it achieved increased awareness in the kingdom of Saudi Arabia through a series of initiatives. Similarly, Dr. Idrees summarized the initial findings from the pulmonary hypertension SAPH registry. Many centers have contributed to this registry and the number of patients is growing. Dr. Idrees presented a small group of patients representatives from the Riyadh area, whose analysis was available at the time of presentation. Within this data, two main issues were highlighted; namely, how the diagnosis was performed, and when the patient was presented to the specialist centers. Unfortunately, the data was found to represent a trend of an 18 month–or more–delay before diagnosis. Obviously, this is not at all optimal and is in need of evaluation. This is a very important finding that can hopefully help guide the policy for increasing awareness for early diagnosis and treatment. Professor Gerald Simmonneau, from France, followed this enlightening presentation with his own on the clinical classification of pulmonary hypertension and the recent revision of Dana Point. Dr. Simmonneau stressed the importance of including recent clinical findings and advances in clinical classifications, and the need to clarify areas of ambiguity. The worldwide community of pulmonary hypertension hopes that this classification will be more comprehensive and more useful to clinicians in the future. For the final presentation of the Plenary Session, professor Marius Hoeper from Germany took the stand. He focused on the evidence-based treatments of pulmonary hypertension, based on the current guidelines and the findings of clinical observations and discussions from physicians. Dr. Hoeper discussed the importance of supportive therapies like diuretics, oxygen therapies and anticoagulants, and debated the issues of vaso-reactivity in pulmonary arterial hypertension and the



criteria for respondents and non-respondents. He also stressed the importance of early diagnosis and its impact in the management of pulmonary hypertension. In addition, Dr. Hoeper addressed the combination therapies. He presented some German data which showed that nearly 21% of the patients who have combination therapy are effectively on endothelin receptor and PDE5 inhibitors, whilst only 3% are on a combination of oral therapies including ERA or PDE5i and prostacyclin. The following session focused on updated issues in PH management and was chaired by Dr. Yaseem Samman (KSA) and Dr. Bassam Mahboub (UAE). The first talk was presented by Dr. Qadar Pasha from India, from the Institute of Genomics and Integrative Biology in Delhi. He summarized in a very eloquent and clear manner the molecular aspects of pulmonary hypertension, specifically regarding the role of particular genomics in vascular functions and dysfunctions. He presented the recent gene findings and different aspects of recent chromosome genes and their chromosomal localization, and the reflection of function. This was followed by a presentation from Dr. Ghazwan Butrous from the University of Kent on whether post-capillary pulmonary hypertension should be treated with the available vasodilators. Dr. Butrous defined both post-capillary pulmonary hypertension and the available so-called vasodilator treatment for pulmonary hypertension, and discussed its function in the treatment of post-capillary PH. He showed that early studies with prostacyclin and ERA were not encouraging due to various reasons. However, the experimental findings with PDE5i were more encouraging but there is no current evidence-based medicine, and the recent trial, which was mainly supported by the NIH, hasn't yet been reported. Therefore, the conclusion so far reads that an early experiment with small trials on pulmonary hypertension vasodilator therapy is encouraging, but the evidence-based medicine larger clinical trials did not show any benefit of prostacyclin and ERA. We are still awaiting the results of PDE5i inhibitors. Based on this, Dr. Butrous argued that in our current knowledge, vasodilators are not considered a standard therapy for post capillary pulmonary hypertension. Dr. Irene Lang from Austria followed this presentation by a talk on her experiences in her centre at the AKJ Vienna Hospital regarding the subcutaneous treprostinil. She discussed the value of using this method, as well as its difficulties and practical applications, and the importance of having a proper team that can help with the management of this form of modalities in the treatment of pulmonary hypertension patients. Attendees agreed that Dr. Lang's presentation was a very enlightening experience with real life examples, providing a lot of practical implications as well as demonstrating the importance of new developments in the technology of delivering drugs. After a short lunch break, a new session focused on right ventricular pathophysiolgy secondary to pulmonary hypertension chaired by Dr. Javid Khan and Manal Al Hazmi. The first presenter was Dr. Paul Hassoun from John Hopkins Medical Centre. Dr. Hassoun discussed the right ventricular response to pulmonary vascular load and he compared this to pulmonary hypertension syndrome: the IPAH versus scleroderma associated with pulmonary hypertension of the right ventricle, and described the hemodynamic serum markers and the cardiac factors that may impact on survival. He concluded that scleroderma related to pulmonary hypertension carries a grave prognosis, and several hemodynamic predictors survivors have been identified from their research group, and accordingly, dysfunction is a prominent factor in the prognosis of this condition. The possible mechanisms for this cardiac involvement could be not only the hemodynamic but neuro-

hormonal myocardial dysfunction, which includes fibrosis inflammation and perfusion defect. For the time being no medical treatment has been established.

This was followed by Dr. Abdulmajeed AlOtay from Saudi Arabia, who discussed the importance of using the new technology of the cardiac MRI in the assessment of right ventricular function and PA reactions in pulmonary hypertension. An interesting presentation, Dr. AlOtay discussed, with a lot of convincing evidence, the importance of the use of the MRI in the diagnosis of pulmonary hypertension and management of patients with pulmonary hypertension. The session on the right ventricle in PH was closed by Dr. Marius Hoeper, who discussed the therapeutic intervention in right heart failure. In this presentation, Dr. Hoeper discussed the importance of accurately identifying the role of the clinical condition of the right heart ventricle when managing a patient with pulmonary hypertension. In his conclusion, he showed that patients who have been treated aggressively with cardiac pumps also might benefit from a transplant which can have vital and successful results. Dr. Hoeper showed encouraging examples of the use of venoarterial ECMO in these patients, via the positive response to the treatment. The attendees agreed that this clinical presentation in the management of severe right ventricle failure in patients with pulmonary hypertension was very illuminating.

During the last session, Dr. Saleh al Dammas presented a well balanced treatment of the COPD bronchodilators. Dr. al Dammas stated that COPD is the fourth leading cause of death and indicated that the majority of these death happen in heavily polluted areas; for examples, 50% of these deaths were in China. Dr. al Dammas noted that COPD in the Kingdom of Saudi Arabia is still understudied. This is worrying, as there are many risk factors prevalent in Saudi Arabia. Dr. al Dammas and his group recently published small studies which found that 501 out of 1380 smokers were eligible for some form of analysis. Additionally, they found that 14% had FEV1 of less than 0.7. Almost 44% of these were on stage III COPD. This shows that trials with current PH specific agents like bosentan, sildenafil, iloprost and parentertal prostanoids and even volume reduction surgery were being used. His conclusion is that Pulmonary Hypertension is common for COPD patients, and a small percentage of COPD patients have severe pulmonary hypertension that behaves like idiopathic pulmonary arterial hypertension, This should be suspected when there is unexplained functional decline, thus right heart ventricle is a procedure of choice in the diagnosis of PH in patients with COPD. He stressed the importance of more research to evaluate the presence of pulmonary hypertension in groups of patients. Dr. Khalid Al Najashi followed with a presentation on the management of pregnant patients with pulmonary hypertension. He presented three cases on these issues and highlighted the importance of careful clinical management. He concluded that pulmonary hypertension, irrespective of the cause, is an absolute contraindication of pregnancy and once female pulmonary hypertension patients are of childbearing age, they should be counselled in a tertiary centre. If a woman with pulmonary hypertension becomes pregnant, this conceives a high alert emergency state whereby a multidisciplinary approach is needed which focuses on aggressive fluid management post-partum and initiation of vasodilators. The last presentation of the day was from Dr. Gerald Simmoneau who talked about PH registries: opportunities and difficulties, and focused on the information that may be derived from registries in pulmonary



hypertension. He also related the experience of the French PAH registry, which is one of the biggest registries in the world involving 674 patients in 17 medical centers in France. The PAH registry published that idiopathic pulmonary hypertension is the predominant cause of pulmonary arterial hypertension with 39%, followed by connective tissue diseases (15%), congenital heart diseases (11%) and portal hypertension (10%). The majority of the patients (63%) were identified as Class III. In his presentation

and the assessment of survival of PAH in the modern era, it became clear that despite our advances in treatment we still have not achieved our goal, as the majority of the mortality rates is associated with functional flaws. This indicates the importance of early diagnosis in this group of patients. Dr. Simonneau's summary reiterated that a pulmonary hypertension registry can provide important information in addition to RCTs. However, the methodology for these registries should be particularly rigorous as its subsequent data can generate new hypotheses that form the basis for prospective studies. The design is to be adapted to the questions one wants to answer.

Figure 1: Dr. Ghazwan Butrous presents at the SAPH conference

Figure 3: Dr. Irene Lang

Figure 2: SAPH 2011 meeting

Figure 4: Dr. Saleh al Dammas

Figure 6: Dr. Magdy IdressFigure 5: Achievement awards during gala dinner of SAPH 2011 meeting



The meeting was closed and followed by a very pleasant gala dinner in one of the beach hotels in Dubai. The dinner was kicked off with a welcome speech from Dr. Majdy Idrees who presented a token of appreciation to the guest speakers, the active members of the SAPH and the doctors who participated in enhancing the understanding of PH in the region. The following day the final set of meetings began with a presentation of Dr. Ghazwan Butrous on pulmonary hypertension in Clinical Year in Review. Dr. Butrous presented highlights from the important papers. The presentation can be downloaded from www.pvri.info. Next, Dr. M Omar Galal held a very interesting talk on the issues of writing a manuscript and the ethics regarding its proper execution. This was considered a very useful lesson, especially for the younger attendees. Dr. Enas Batubara presented her paper, titled 'a novel approach to the management of sub-massive pulmonary embolism', which focused on the targeting of the right ventricle in massive pulmonary hypertension. Dr. Batubara's paper included a study that was conducted at the division of Pulmonary Medicine in Riyadh Military Hospital, under the supervision of Dr. Majdy Idrees. The objective of the study was to direct their target of pulmonary vascular resistance rather than eliminate the obstruction, to improve cardiac output, and also to decrease the risk of bleeding. Their conclusion is that in sub-massive pulmonary embolism, thromboembolic therapy towards decreasing PVRI is effective in improving the heamodynamic management associated with this condition. That strategy might turn out to be the most effective approach for treating this condition and might erase the need for thromboembolic therapy. This is only the outcome of a small study and needs to be confirmed in a larger randomized placebo-controlled study.

This was followed by a presentation of Dr. Ala Eldin Ahmed who spoke about pulmonary hypertension patients treated with pulmonary tuberculosis. He presented a series of patients from studies done in Khartoum, whereby pulmonary hypertension was diagnosed by the rigorous criteria of Doppler-echo cardiography that showed that 14 patients were suffering from pulmonary tuberculosis and pulmonary hypertension. In his conclusion Pulmonary hypertension of different grades occurs even in cured pulmonary TB but all patients had an abnormal chest radiograph. They were all of a relatively young age mean age is 43 years. This is a small study which obviously needs further evaluation and more work in this area. Dr. Hanaa Banjar presented cases on pediatric pulmonary hypertension and discussed different aetiology. In particular, she is trying to implement the lessons and instruction she learned from the Panama PVRI meeting

in February 2011 on the classification of pediatric pulmonary hypertension, and stressed the importance of learning from these cases for the practical aspects of the suggested aspects of the classification.

After the coffee break the focus was on 'Pharma-economic and End of Life Issues', which saw presentations by three participants: Dr. Meshal Al Mutairi, Dr. Maha al Dabbagh (KSA) and Dr. Jameel Al Ata (KSA). Dr. Al Mutairi, from Saudi Arabia, discussed the pharma-economic models of pulmonary hypertension, in particular those implemented in Saudi Arabia. There are a lot of good lessons to be learned, particularly in countries that want to establish their pulmonary hypertension service. This was followed by Dr. Maha al Dabbagh with a very exciting talk about the importance of the ethical manner in which to approach patients newly diagnosed with pulmonary hypertension. She spoke of the importance of counseling and her own experience with patients, especially those of the younger generation, and a way to communicate with patients as well as parents and guardians. This was a very illuminating talk that Dr. al Dabbagh promised to write down for the PVRI Review. The last talk was by Dr. Jameel al Ata who also discussed the ethical issues around the treatment of pulmonary hypertension. He discussed his own experiences with patients in the kingdom of Saudi Arabia. He also spoke of the implications regarding failure to comply with the guideline, or unnecessarily overusing a drug, and other such issues. In a way, this represents the great awareness and subsequent critical analysis and awareness amongst physicians regarding the way other physicians treat patients with pulmonary hypertension, especially in specialist centres. The session closed with two workshops; one focused on the haemodynamics in pulmonary hypertension, moderated by Paul Hassoun and Majdy Idrees, and a second group, which saw presentations by Ahmed Ibrahim and Omar Tamimi discussing the echocardiography in the management of PH. Overall the meeting was very successful, and showed real advances over its previous incarnations. The attendees in particular were very engaged with the discussion and debate, and this was noticeable even during the coffee breaks and lunch periods. In general, this was considered a very successful meeting which has shown that the mission of the SAPH and PVRI is being achieved: both by the increased awareness of pulmonary hypertension worldwide and by the enhancement of the understanding of illness, and its treatment, at even the local level. The 5th SAPH meeting is set for April 2012 and hopes to attract more PVRI members and Fellows, so the participation and debate between both organisations may continue to grow.

Figure 6: Attendees of SAPH 2011 meeting



The 5th National Congress on Pulmonary Embolism and Pulmonary Vascular Diseases & 3rd International Symposium on Pulmonary Circulation Disorders, Shenyang, Liaoning, July 28-30, 2011Members of PVRI worked with the CTS to arrange and deliver the programme.

The conference focused on the latest treatment guidelines based on recent clinical trials in venous thromboembolism (VTE) and pulmonary hypertension, the right ventricle and on-going research programmes.

The first part of the conference focused on the most updated guidelines of pulmonary embolism and deep venous thrombosis diagnosis, treatment and prevention and the on-going clinical

research of diagnosis, treatment and prevention of pulmonary embolism and deep venous thrombosis. Among the topics that arose in the general discussion were: 1) Systematic review of research progress of pulmonary embolism in China; 2) Prophylaxis of venous thromboembolism in patients with acute medical illness; 3) State-of-the-art diagnosis and treatment of venous thromboembolism; 4) Establishment of green channel for acute pulmonary embolism in emergency management; 5) Update on the anticoagulant treatment of venous thromboembolism; 6) D-Dimer testing in the diagnosis of acute pulmonary embolism.

Annual PVRI Get Together, Denver, May 16, 2011Each year PVRI organizes an informal meeting between its Fellows and members to coincide with the American Thoracic Society meeting. This year was no exception, and after the ATS ‘Assembly of Pulmonary Circulation Membership Meeting', PVRI delegates were invited to gather at ‘The Market’ on Larimer Square for coffee, cake and conversation.

This get-together was organized by Dr. Brian Graham, a Fellow

of the PVRI, who chose a great Denver venue for the occasion and provided a buffet of sweets for the thirty attendees. PVRI Administrator Nikki Krol made a number of announcement at the informal reception pertaining to the PVRI’s multiple projects, and directed special attention to the release of Pulmonary Circulation which had been debuted in print at the meeting. The get-together was considered a success by the attendees, who thanked Dr. Graham for his organizational effort.

Figure 1: Attendees relaxing during Annual PVRI get together in Denver Figure 2: The Market, Larimer Square



The second part of the conference described the clinical practice, diagnosis and treatment of PAH based on the recent guidelines and experiences of clinical practitioners. A brief introduction of translational research, novel target and clinical trials on pulmonary hypertension was also described. The topics included: 1) Management of pulmonary hypertension: one goal with multiple targets; 2) Clinical trials in PAH: What do they tells us? 3) New therapeutic developments in the field of pulmonary vascular disease; 4) PAH and CTEPH: “compare and contrast”; 5) Molecular Imaging – Development of New Biomarker in PH; 6) Molecular biology of chronic thromboembolic pulmonary hypertension; 7) Pathology and pathophysiology of CTEPH; 8)

Update on the pathogenesis of pulmonary vascular remodelling in PH.

A final session highlighted the most pressing issues facing the diagnosis and management of pulmonary vascular disorders such as right ventricle dysfunction, pulmonary vasculartise and related disorders.

Professors Martin Wilkins, Ardeschir Ghofrani, Luke Howard, Brian Graham and Lan Zhao from PVRI and Professors Xiansheng Cheng, Chen Wang, Weixuan Lu and other colleagues from China took part in the meeting.

Figure 1: Shenyang, Liaoning, July 28th-30th 2011 meeting

Exploratory Collaboration Meeting Between PVRI China Centre and the Pulmonary Embolism and Pulmonary Vascular Assembly of the Chinese Thoracic Society, Beijing, July 28, 2011An exploratory collaboration and strategy meeting between PVRI China Centre and the Pulmonary Embolism and Pulmonary Vascular Assembly of the CTS was held in Beijing on 8pm-10pm July 28th 2011. The fellows of PVRI China Centre (PVD assembly membership in CTS), representing all China, and international speakers from PVRI were invited to take part in the meeting. It consisted of an overview of current clinical and research projects directed at understanding pulmonary vascular diseases in China.

Prof. Martin Wilkins gave an overview of the current activities

and initiatives of the PVRI. Prof. Ardeschir Ghofrani talked about current research projects involving PVRI and China. Prof. Chen Wang spoke of future prospects of the PVRI China Centre. Among the topics that arose in the general discussion were: 1) Collaboration of clinical research for novel target for pulmonary hypertension. 2) Collaboration of translational research and basic research. 3) Education of PVD for Chinese physician. The feedback from the meeting was encouraging with the attendees reporting enthusiasm for the future of pulmonary vascular research in China.



Figure 1: Collaboration meet of Pulmonary Embolism and Pulmonary Vascular group in Chinese Thoracic Society & Pulmonary Vascular Research Institute (PVRI) -China Center on July 28, 2011, Shenyang, China

China Heart Congress 2011: Pulmonary Vascular Diseases, Beijing, August 13-14, 2011The two day PVD sessions was organised via a collaboration between Fuwai Hospi ta l ,CAMS & PUMC and the Pulmonary Vascular Research Institute. The CHC took place in Beijing mid-August 2011, and saw participation of the following PVRI Fellows: Ghazwan Butrous, Martin Wilkins, Lan Zhao, Allan Lawrie, Cheng Xiansheng and Reda Girgis. Topics

included:• Ironandpulmonaryhypertension• RoleofRightHeartinCardiovascularDiseases• HDACinhibitorinpulmonaryhypertension• AdvancesofCardio-pulmonaryExerciseGasExchangein

Pulmonary Vascular Diseases

Leh Symposium 2011, Leh, September 21-23, 2011: An Overview of High-altitude DiseasesGhulam Mohammed and Qadar Pasha (India)

The national Leh symposium took place as a PVRI initiative between 21st and 23rd of September 2011. The theme of the symposium was ‘An overview of high-altitude diseases’. The symposium began with registration of the participants who had gathered from several hospitals of Ladakh region; it was followed with inauguration. The occasion was graced by the presence of several of the stalwarts who had distinguishably served in these hospitals. Dr. Sonam Angcho, Honble Executive Councilor Health, LAHDC, Leh, Ladakh acknowledged the significance of the Leh symposium and its positive effect on the physicians of Ladakh hospitals. It was stressed to inculcate the culture of research without disturbing the routine patient-care services.

Organizing chairmans, Dr. Ghulam Mohammed from SNM Hospital, Leh and Dr. Qadar Pasha, Scientist, IGIB, Delhi, also put forward their views. Among other issues, particular attention was paid to the need for upgraded facility at the hospitals so as to improve the diagnostic approaches and avail these tools in enhancing their research skills.

Emphasis was also placed on the need to affiliate SNM Hospital with a University, so that research on High-altitude related disorders may start in earnest. Likewise, questions regarding the establishment of a High-Altitude Research Centre were raised. The latter issue was discussed in great detail and the notion was



out of its effect faster. The last speaker, Dr. Ghulam Mohd, spoke about Chronic Obstructive Airway/Pulmonary Disease (COAD/COPD) at high altitude. His observation was that life span of COPD patients at HA is shorter than their counterparts at lower altitudes (LA). He observed that there was significant difference in the levels of parameters like SPO2, pulse rate, symptoms like cough, grade of dyspnoea at HA and LA. The standard of life improves in the form of day to day activity and rehabilitation after migration to low altitude as the grade of dyspnoea falls to 2-3 from grade 4. The difference between PASP at HA and LA was significant enough to prolong the lifespan. He then suggested that COPD patients at altitude should be asked to migrate to LA, especially during the winter season. There were two young researchers from IGIB, Delhi; Ms Aastha Mishra discussed elaborately on Hypoxic pulmonary vasoconstriction at HA and

Figure 1: Leh Symposium 2011, Leh, September 21-23, 2011

seemingly supported by the local government authorities. Dr. Qadar Pasha conveyed in the inaugural and subsequent meetings that PVRI aspire to support exactly such a cause if the local and central government bodies also pledge their support. The plan was met with total agreement.

The second and third days were fully devoted to scientific presentations, of which a few are highlighted here. Dr. Spalchan, pediatrician at SNM Hospital presented an exceptional case report of a one year old Nepali baby diagnosed with Infantile Congestive Cardiac Failure (ICCF). The case was unique in the context that as all other subjects of ICCF could not survive unless they migrated to low altitude areas, this patient survived under treatment without migrating to lower altitude. The child had left sided atrial thrombus which was resolved upon administration of anti-coagulant therapy for about a year. This case was a prototype of hypoxia induced hypercoagulability at high altitude. The response to anticoagulant for a long period opened the door for additional exploration on the role of anticoagulants in HA induced pulmonary hypertension. Dr. Tashi, surgeon specialist at SNM Hospital, spoke about hollow visceral perforation, a common problem at high altitude. He corroborated this finding to hypoxia, which causes tissue damage. Dr. Norboo Angchok, a young faculty and sub-registrar at SNM hospital, presented a paper on chronic mountain sickness (CMS), a common scenario in Ladakh. CMS is a disease that can develop during extended time of living at altitude, especially in the natives who are exposed to the environment continually. The speaker had concerns regarding the Qinghai Score, and raised questions regarding the system of subjective scoring.

It was clear throughout the meeting that the initiative of the Leh Symposium has had beneficial effect. This was crystallised further in the presentation of Dr. Ghulam, who, to the surprise of many, shared the findings on physiological aspects of HAPE, undoubtedly an unthinkable act for a hardcore clinician in the past. He presented on the differential levels of biomarkers like plasma levels of aldosterone, renin, superoxide dismutase, and Endothelin 1 in High Altitude Pulmonary Edema (HAPE). Since HAPE is a multifactorial disease one could hypothesize that there was involvement of various molecules of major pathways giving rise to a particular phenotype. Thus there occurs a significant elevation of vasoconstrictors like aldosterone, renin and endothelin-1 and decrease of antioxidants such as SOD, confirming severe oxidative-stress under the hypobaric hypoxia of altitude.

Dr. T. Norboo, one of the most senior physicians of Ladakh, presented his findings on the prevalence of H. Pylori in Leh and the gastric cancer among the Ladakhis. A new topic on the high incidence of suicide in Ladakh and in other high altitude regions was introduced in the scientific session. Dr. Iqbal Ahmad, mental health officer at SNM Hospital, spoke about it at length. He acknowledged that the suicide rate at high altitude is higher, which could be attributed to the stress induced by the oxidized products at HA. Senior ophthalmologist Dr. Munshi presented on the ophthalmic disease due to the solar radiations and he sought the help of basic researchers in understanding the pathophysiology behind these diseases. Dr. Morup concern was about the problems of anaesthesia at HA. He found that more drugs for anaesthesia are consumed at HA, yet patients come



Ms Priyanka Pandey spoke about kinases in therapeutics. She discussed the future mode of treatment in HA diseases, keeping in view the role of these proteins.

The conference concluded with an end note to the youngsters to come forward to do research in addition to lending their

support to the betterment of healthcare at high altitude. The next international Lehsymposium 2012 was announced with a request to the three staunch supporters and organizers of the symposium, namely Max Gassmann, Norbert Weissman and Ghazwan Butrous, all PVRI fellows, to extend their support to the cause of developing research activities at Ladakh hospitals.

The Impact of Hypoxia on Cells, Mice and Men, Monte Verità, Ascona, Switzerland, October 9-14, 2011Max GassmannUniversity of Zürich, Winterthurerstrasse 260, CH-8057 Zürich, Switzerland

This was the third in a series of meetings held at Monte Verità designed to bring together biomedical scientists and clinician researchers who study the role of hypoxia in diverse fields. Initially, investigations into the role of hypoxia in the etiology of disease were limited to the pulmonary field particularly in relation to the effects of rapid ascent to and residence at high altitude. Over the past 20 years, it has become increasingly apparent that hypoxia plays a significant role in an enormous variety of diseases, from pregnancy disorders to formation of tumors. This meeting series was the first dedicated to bringing together basic research scientists, physiologists and clinicians from widely differing backgrounds to compare and contrast the role of hypoxia in specific cellular and animal models as well as different human disorders and diseases.

These close-knit meetings are designed such that the maximum of 100 attendees, including speakers, attend a single series of lectures throughout the day. All participants stay at the beautiful and historic Monte Verità Hotel and Conference Center, taking meals together at large community tables. This arrangement provides extensive opportunities for discussion and developing unique collaborations. The attendees embraced the spirit of the meeting with molecular biologists attending presentations on high altitude-induced disease and clinical oncologists attending sessions on the role of mitochondria in hypoxic cells.

The current meeting was divided into seminars focusing on areas such as the roles of specific molecular pathways in hypoxia (HIFs, PHDs and erythropoietin), physiological pathways (mitochondrial respiration, ventilation), specific organ responses to hypoxia (eye, placenta, gut) and clinical repercussions (exercise, high altitude cerebral and pulmonary edemas, adaptation). Despite speakers from a highly varied number of scientific fields, it became clear that there was a thread of important commonalities throughout the research presentations, tying data together into a global view of hypoxic response.

As such, the keynote lecture by Dr. William G. Kaelin, MD, describing new cancer therapies developed from recent understanding of the molecular pathways in the mammalian oxygen sensing pathways, focusing primarily on HIF prolyl

hydroxylases (PHDs), proved prophetic and provided a great foundation for the start of the conference. PHD involvement was demonstrated throughout the meeting in a wide-ranging list of diseases including, cardiomyopathy (Katschinski DM), cardiac ischemic reperfusion injury (Koivunen P), inflammatory bowel disease (Taylor, C), and Tibetan adaptation to high altitude residence (Prchal J).

Mitochondria activity was another commonality among hypoxia research presentations including generation of reactive oxygen species (Schumaker, P), hydrogen sulfide production/carotid body sensitivity (Kemp, P), placental development at high altitude (Tissot van Patot, M), adaptation to high altitude ascent (Gelfi, C), exercise (Gnaiger,E), body weight control (Aragonés, J), ischemia-reperfusion lung injury (Weissmann, N), breast cancer (Gorr, T), and ischemic cardioprotection (Koivunen, P). Mitochondrial response to hypoxia seems to be common denominator in numerous hypoxia-mediated conditions potentially providing another strong target for developing therapeutic interventions.

The more recently defined role of epigenetics in response to hypoxia was prominently discussed in a variety of conditions as well. Data were presented implicating hypoxia in altering epigenetics via chromatin remodeling (Poellinger, L), miRNAs (Gay, S), and DNA methylation (Sartori, C) in cancer, rheumatoid arthritis, and pulmonary hypertension, respectively. The potential role for the amazing capacity of epigenetics to be altered in a single generation was then further discussed in presentations focusing on adaptations in second generations at altitude, adaptation of llamas (Llanos, A), and population adaptation in Tibetans and Andeans (Prchal, J). Subsequently, evidence of hypoxia-induced rough endoplasmic reticular stress, modifications in protein synthesis and/or effects on cellular proliferation and migration was presented in association with metastasis (Johnson, R), retinal development (Grimm C) and disease (Bösch, M), as well as placental adaptation to high altitude (Burton, G). Interestingly, exposure of healthy volunteers to high altitude (Capanna Margherita) was shown to cause ulceration in the stomach (Lutz, T; Goetze, O). Finally, Jerry Dempsey reviewed the causes and consequences of hypoxic ventilatory acclimatization.



Recent evidence that erythropoietin (Epo) has multiple non-erythroid functions was expanded by data implicating Epo in exercise performance by hematological and non-hematological functions (Gassmann, M), improved cognition (Ehrenreich, H) and mood disorders (Miskowiak, K), retinal function (Rex, T), neonatal ventilation (Soliz, J), and protection from ventilator-induced lung injury (Swenson, E). An excellent debate of the mode of action of Epo protection and physiological effects was also initiated in these sessions.

Other similarities between hypoxic research areas include iron homeostasis implicated in kidney fibrosis (Haase, V.) and skeletal muscle response (Gelfi, C), nitric oxide implicated in ischemic cardioprotection (Koivunen, P), differential activation of HIF-1 and HIF-2 (Johnson, R), and control of S-glutathionylation (Bogdanova, A).

An excellent set of sessions on response to high altitude provided a valuable context in which to view the variety of hypoxia-induced pathways coming together for a global physiologic/pathophysiologic response. There were lively debates about the role of Epo in exercise, the limitations of exercise at altitude and the role of doping in climbers. The questions surrounding the doping issue included: is prevention or treatment of altitude illness doping and what constitutes doping in elite climbers? (chair: Oelz, O). There was also an interesting discussion session in which a consensus on the prevention and treatment of high altitude pulmonary edema (HAPE) was sought (chair: Maggiorini, M). Data on exercise and pulmonary capacity, pulmonary disease and altitude ascent, HAPE susceptibility and

a variety of presentations on treatments including ascent rate recommendations, oxygen, acetazolamide, phosphodiesterase 5 inhibitors, steroids and beta-3 agonist formed the context in which a consensus on HAPE was based.

While at Monte Verità, the Centro Stefano Franscini organized a public lecture in Italian by Marco Maggiorini. This event was very attractive to those interested in the pathophysiology of acute mountain sickness (AMS). The local newspapers reported accordingly next day.

Between the meeting environment, the excellent science, the novel mixture of scientific fields all surrounding hypoxia, the organization of the workshops and the excellent discussions during the presentations, the meeting was an unparalleled success. The meeting successfully achieved the projected goals of bringing together scientists to discuss the state-of-the-art in our understanding of the effects of hypoxia on the body, from development to aging as well as during pathophysiology processes, and developing new directions for future exploration.

The organizers acknowledge the generous support of the Centro Stefano Franscini (CSF) and the Swiss National Science Foundation (SNF) as well as the help of the ETHZ, UZH and USZ, the Zurich Center for Integrative Human Physiology (ZIHP), The Company of Biologist Ltd (cob), the Zürcher Universitätsverein, the Excellence Cluster Cardio-Pulmonary System (ECCPS), GlaxoSmithKline (gsk), Pfizer and exersuisse who all made it possible to organize this successful meeting.

Annual Pulmonary Hypertension Symposium, Trivandrum, October 1-2, 2011Dr. Harikrishnan S. (India)

This meeting was held on October 1st and 2nd in Trivandrum, at the Sree Chitra Tirunal Institute for Medical Sciences and Technology and the Rajiv Gandhi Centre for Bio-technology.

The meeting was organised by Dr. Harikrishnan, Prof. C. C. Kartha and Prof. S. Sivasankaran. It was supported by the Indian Association of Pathologists, the Association of Pulmonary and Critical Care Medicine and by the Trivandrum institutions. Overseas guests included Professor Rubin Tuder and Professor Patricia Thistlethwaite and Prof. Sheila Haworth.

The conference consisted of a 2 day program. The first day began with a Pathology Workshop, well-attended by 120 consultant and trainee pathologists from all over India.

An introductory session on pulmonary vascular disease was followed by a slide seminar lead by Professor Tuder from Colorado, Professor Pradeep Vaideeshwar from Mumbai and Professor Haworth from London.

The afternoon session was devoted to research initiatives in

Figure 1: Dr. Radhakrishnan, Director of the Sree Chitra, Tirunal Institute, opening the meeting



Figure 2: Dr. Yadav Bhatta from NepalFigure 3: Professor Rubin Tuder presenting the best poster award to Ritu Kulshresheta

India, under the auspices of the PVRI, following up ideas discussed at earlier meetings in 2009 in Chandigarh and in 2010 in Delhi. The poster session was very successful and there were prizes for the best clinical and basic science presentations.

A Symposium on Pulmonary Vascular Disease was held on the second day of the meeting, alongside the annual meeting of the Paediatric Cardiac Society of India. There was

considerable participation by the 100 delegates, including paediatricians, respiratory physicians and cardiologists. The highlights included a presentation on the Indian perspectives of pulmonary hypertension, both clinical (Dr. Ravindran) and research (Professor Kartha), major advances in the pathobiology of pulmonary hypertension (Professor Rubin Tuder), chronic thromboembolic pulmonary hypertension (Professor Thistlethwaite) magnetic resonance imaging (Professor Boban Thomas) and case discussions.

Figure 5: Pathology workshopFigure 4: Professor Patricia Thislethwaite

PVRI WebinarsSummary of all webmeetingsWe are pleased to report that we had 13 webinars so far. This is an important educational work of the PVRI; it would not be possible without the huge effort and collaboration of several

professors/experts from different institutions around the world, and a continued interest of the audience.

All webinars (2008-2011) will remain available at www.



Figure 1: Internet videoconferences 2008 - 2011 Figure 2: Webinar visits in all countries

Figure 3: No of participants and access Figure 4: Countries - ALL videoconferences 2008 - 2011

pahforum.com during the year of 2012. In view of the current difficulties in terms of support from private companies, we will try to apply for specific grants from governmental agencies in Brazil. The online availability of the webinars beyond the year 2012 will depend on support. There is no cost for a given conference to be kept online during the first year, but beyond that, the cost is generally 10% of the webinar cost per additional year.

Enclosed are the graphs corresponding to the statistics of all recorded webinars.

Videoconferences 2011

• Combinedclinicalandsurgicalapproachestocongenital

heart disease associated with pulmonary arterial hypertensionJune 1st, 2011

Guest: Prof. Marcelo B. Jatene, Dept. of Pediatric Cardiology and Pediatric Cardiac Surgery, Heart Institute (InCor), São Paulo, BrazilSpeakers: Antonio A. Lopes and Marcelo B. Jatene

• Exercise-induced Pulmonary HypertensionNovember 9th, 2011

Guests: Prof. Stefano Ghio, Heart Failure and Pulmonary Hypertension Unit, Policlinico San Matteo, Pavia, Italy and Prof. Michele D’Alto, Monaldi Hospital, Second University of Naples, Naples, ItalySpeakers: Stefano Ghio and Michele D’Alto



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PVRI China Taskforce 2011Leaders: Martin Wilkins (UK) and Chen Wang (China)

Significant progress has been made in 2010-2011 in collaboration with the Chinese Medical Association (CMA) and the Chinese Thoracic Society (CTS). The PVRI China Taskforce was involved in two meetings in 2011, namely:1. The 5th National Congress on Pulmonary Embolism

and Pulmonary Vascular Diseases & 3rd International Symposium on Pulmonary Circulation Disorders were held in Shenyang, Liaoning in July 28th-30th 2011.

2. An exploratory collaboration meeting between PVRI China Centre and the Pulmonary Embolism and Pulmonary Vascular Assembly of the Chinese Thoracic Society.

The Shenyang meeting covered the following broad range of topics:1. Current guidelines of pulmonary embolism, deep

venous thrombosis and chronic thromboembolic pulmonary hypertension

2. Specific issues in venous thromboembolic diseases

3. Research of pulmonary embol ism, chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension

4. Oral presentation and poster discussion5. PVRI specific topic: current diagnosis & management

of pulmonary hypertension6. Translational concept in pulmonary vascular diseases7. Pulmonary vascular diseases and related conditions8. Case series of pulmonary vascular diseases.

Full meeting reports are found at in the meetings review of this Annual Report.

SUMMARY OF OBJECTIVES FOR 2012

The taskforce intends to repeat its involvement with the meetings described above in order to create stronger collaborations between PVRI China Centre and the various local organisations.

PVRI South East Asia Region TaskforceLeaders: Sheila G. Haworth (UK) and Harikrishnan S. (India)

The leadership of this Taskforce has changed. Professor K. Kumar has been the co-leader of this Taskforce but has just handed over the position to Dr. Harikrishnan S. Professor Kumar has been an inspiring leader and all the Taskforce members are very grateful to him for his work in establishing the South East Asia Taskforce. He will remain a major figure in the PVRI India Taskforce, remaining on the Executive Committee and leading research programmes. Professor Harikrishnan S. has been very active in PVRI India since the beginning and he enjoys everyone’s confidence. He has been instrumental in establishing the PVRI journals PVRI Review and Pulmonary Circulation and is a tireless worker for PVRI India. The office of PVRI India will move to Trivandrum.

This year the Taskforce was majorly involved in the organization of the Annual Pulmonary Hypertension Symposium, Trivandrum. A full meeting report can be found in the meeting review section of this Annual Report.

Other Taskforce activities include1. Professor S K Maulik, cardiovascular pharmacologist

at the All India Institute of Medical Sciences, New Delhi. Professor S K Maulik is interested in ‘reverse pharmacology’, exploring the potential efficacy of drugs

and medicinal plants used to treat related conditions such as systemic hypertension, in pulmonary arterial hypertension.

2. Professor Sajal Chakraborti, University of Kalyani, West Bengal had been studying signal transduction in rabbit pulmonary arterial smooth muscle cells but since the Chandigarh meeting, he has been working with human cells, studying the effects of TGF-β and TNF-α through IL-13 stimulation, ion channels and Ca2+ mediated signalling.

3. Professor Harikrishnan, SCTIMST, Trivandrum: Dr. Harikrishnan has studied the influence of inflammation on restenosis of the mitral valve and non regression of pulmonary hypertension following balloon mitral valvotomy and found that a high ESR was associated with restenosis and persistence of pulmonary hypertension.

4. Dr. Bhupesh Kumar and Professor Puri, Postgraduate Institute of Medical Education and Research, Chandigarh. In a prospective, randomised double blind trial these investigators found that oral sildenafil given during induction of anaesthesia and continued for 24 hours after surgery was more effective than intravenous nitroglycerine in reducing the post-operative pulmonary arterial pressure and reduced the need for inotropic



support and duration of mechanical ventilation.5. Ms. Swapna Menon was awarded a one year PVRI grant

in 2010 for “A bioinformatic analysis of gene expression profiles of pulmonary arterial hypertension” at Jawaharlal Nehru University, Delhi. Publications and poster from this work:i. S. Menon, J. Fessel, J. West. Microarray studies in

Pulmonary Arterial Hypertension. International Journal of Clinical Practice Special Issue: The Pulmonary Hypertension Reviews: an IJCP Companion Journal Vol 65, Issue Suppl s169, pages 19–28, January 2011

ii. Eric D Austin, Swapna Menon, Anna R Hemnes, Linda R Robinson, Megha Talati, Kelly L Fox, Joy D Cogan, Rizwan Hamid, Lora K Hedges, Ivan Robbins, Kirk Lane, John H Newman, James E Loyd, and James West. Idiopathic and heritable PAH have shared molecular etiology, Pulmonary Circulation, Jul-Sep 2011 (Austin, ED and Menon, S : equal contribution)

iii. Swapna Menon,Benjamin J Dunmore, Lu Long, Nicholas W Morrell,Gene expression profiling in human pulmonary arterial smooth muscle cells in response to bone morphogenetic proteins and transforming growth factor-β. Poster submission, PVRI AGM & Scientific Debates, February 2012, Cape Town, South Africa.

6. Dr. Kashif Hanif, Central Drug Research Institute, Lucknow. Dr. Hanif was awarded a PVRI Travel grant in September 2010. He has now shown that an aqueous extract of pomegranate juice prevents the development of pulmonary hypertension in the monocrotaline rat model, reduces oxidative stress and inhibits a rise in ACE activity in the lungs.

vii. Professor K Kumar, AIMS Kochi, has completed a study of the 6-minute walking distance in healthy children aged 5-15 years, essential baseline data.

GSK Fellowships in Pulmonary Hypertension in India.

Applications for these Fellowships, generously provided by an unrestricted educational grant, were peer reviewed and awarded competitively to facilitate the work of young clinical and basic science investigators working to improve the lot of Indian people suffering from pulmonary vascular disease.

i. Professor Qadar Pasha, Institute of Genomics and Integrative Biology, Delhi. Title: Telomeres in adaptation and maladaptation under hypobaric hypoxia Postdoctoral

Fellowship for Arpana Vibhuti PhDii. Professor S. Harikrishnan Sree Chitra Tirunal Institute

Trivandrum Title: Does non-regression of pulmonary hypertension following balloon mitral valvotomy correlate with BMPRII mutations? Postdoctoral expenses for Dr. Mukund Aravind Prabhu

iii. Professor C.C. Kartha Rajiv Gandhi Centre, Trivandrum. Title: Molecular mechanisms of pulmonary microvascular endothelial dysfunction under fluid shear stress PhD Studentship expenses for Mr Binil Raj S S, M Pharm

iv. Professor Pratibha Nallari with Dr. BKS Sastry Osmania University, Hyderabad Title: Genetic insights of idiopathic pulmonary arterial hypertension The genetic status of IPAH in the Indian population is unknown, and therefore an attempt will be made to profile the genetic and phenotypic basis of this disease in an Indian cohort. Award of a PhD Studentship to Mr. ML Satyanarayana.


Future Meetingsi. At the meeting of the Executive Committee held in

Trivandrum we decided that the Annual Pulmonary Hypertension Symposium of PVRI India would be held in conjunction with that of the High Altitude Task Force and that the meeting would be held in August 2012 in Leh. Professor Qadar Pasha kindly agreed to organise this meeting

ii. Following the success of the Pathology Workshop in Trivandrum Prof. Vaideeswar is to explore the possibility of holding a similar meeting, together with a clinical pulmonary hypertension symposium in Mumbai

iii. A short 3 hour CME programme on PAH is to be held at Chennai, to encourage young investigators.

Extending PVRI Activities to other Regions of South East Asia

Colleagues from other countries in SE Asia were encouraged to attend the Trivandrum Symposium and representatives came from the Maldives and Nepal. Dr. Ali Shafeeq, a cardiologist from the Maldives wishes to organize a satellite meeting for key clinicians from South East Asian countries in the Maldives in March 2012 or 2013.

Efforts to engage colleagues from other countries in the work of the PVRI will be intensified in 2012.

PVRI Eastern Mediterranean Region TaskforceLeaders: Paul Hassoun (USA) and Majdy Idrees (Saudi Arabia)

The year 2011 saw the Eastern Mediterranean Taskforce involved in a number of different conferences, meetings and initiatives. For details on the joint PVRI/SAPH Pulmonary Hypertension conference, please see page 30.1. The 4th Annual Joint PVRI SAPH Pulmonary Hypertension

Conference – Dubai, UAE, April 2011

2. The 3rd SAPH Master Class In Pulmonary Hypertension. Riyadh, KSA, 13-14 February 2011

3. The 4th SAPH Master Class In Pulmonary Hypertension, Riyadh, KSA, 17-18 October 2011

4. Pulmonary Hypertension Awareness Day, Riyadh, KSA, 16 June 2011



5. Pulmonary Hypertension for the Nurses, Riyadh, KSA, 8 December 2011.

Research initiatives included1. Pulmonary hypertension in high altitude in Saudi Arabia.

BaDr. Al Ghamdi2. Prevalence of PAH in sickle cell disease in Saudi Patients.

Sarfraz Saleemi & Majdy Idrees3. Novel approach for the management of RV failure in

pulmonary embolism. Majdy Idrees & Tarek Kshour 4. Completing the SAPH registry for pulmonary hypertension

in Saudi Arabia. SAPH registry Taskforce

The Taskforce also strengthened its foundation with the following actions:1. It has begun to update the SAPH Guidelines on the

management of pulmonary hypertension. The work is expected to be completed by July 2012.

2. Likewise, it is in the process of building more collaborative work with pulmonary hypertension physicians and groups in EMR.

SUMMARY OF GOALS FOR 2012

1. Publish the updated SAPH guidelines on management of pulmonary hypertension

2. SAPH 2012-The 5th Joint Pulmonary Hypertension Assembly of the Eastern Mediterranean Region (SAPH/PVRI), which will be held in Istanbul 24-24 April 2012. This will be a 2-day meeting. The first day will be focused on CTEPH and the second day on CHD-PAH.

3. 5th (pediatric) and 6th (adult) Master classes will be held on February & October 2012, respectively.

4. Finalizing the SAPH pulmonary hypertension registry in Saudi Arabia Pulmonary Hypertension day for patients and public will be held in May 2012 in Jeddah, Saudi Arabia.

PVRI Sub-Saharan Africa TaskforceLeaders: Professor Ana Olga Mocumbi (Mozambique) and Professor Karen Sliwa (South Africa)

The Sub-Saharan Taskforce, under the leadership of Professor Ana Olga Mocumbi and Professor Karen Sliwa, was established in January 2010. The primary aim of this Taskforce was to establish a Sub-Saharan African Registry of Pulmonary Hypertension (PHT) and, subsequently, other research and educational awareness projects.

This year Dr. Friedrich Thienemann joined the leadership team, through his role in the development and establishment of the Pan African Pulmonary Hypertension Cohort study (PAPUCO), which was initiated in 2010 and established in 2011.

The Pan African Pulmonary Hypertension Cohort study (PAPUCO), a prospective observational cohort study, was initiated by the Co-Leaders of the Sub-Saharan Taskforce (Karen Sliwa and Friedrich Thienemann). The objective of the study is to describe the epidemiology and characteristics of pulmonary hypertension in Sub-Saharan Africa (N=500), over a period of 24 months. Participants are drawn from 17 cardiovascular specialist centres in 8 African countries, namely Cameroon (1), Kenya (1), Mozambique (2), Rwanda (1), Nigeria (7), South Africa (2), Sudan (1), Tanzania (1), and Uganda (1).

The PAPUCO study is using a web-based data entry platform, in consultation with integerafrica (www.integerafrica.org), a non-governmental organization, led by Dr. Friedrich Thienemann and Christiaan Diedericks. They have committed to supply the infrastructure and to maintain and support the data entry and management side of the project (www.papuco.org).

One of the aims of the cohort study is to encourage individual physicians and cardiologists who are interested to invest time and effort to do research relevant to Africa. The PAPUCO cohort has already encouraged 3 PhD students and a Master’s student

to engage in research activities linked to PHT and linked to the study via imaging, systems, clinical and biomarker measurements that will be carried out at the Hatter Institute for Cardiovascular Research in Africa, and possibly at other collaborative centres.

The Taskforce was involved in two educational events and meetings for the PAPUCO cohort study in 2011. These include:

1. The 10th PACAR Congress, Kampala, Uganda (21st - 25th May 2011)This important meeting was attended by several PAPUCO participants. The PAPUCO study and the web-based data portal were launched at this meeting.

2. Training Tanzania, Dar Es Salaam, Tanzania (25st - 29th September 2011)At the event, on-site training was provided by Dr. Friedrich Thienemann and Prof. Karen Sliwa to the participating centre of Tanzania.

3. World Heart Day 2011, Dar Es Salaam, Tanzania, September 29th 2011Friedrich Thienemann and Prof. Karen Sliwa also gave an overview of pulmonary hypertension and heart disease in Africa at a meeting of Tanzanian Cardiologist at the World heart day 2011.

4. 12th Annual Congress of the South African Heart Association in East London, South Africa (23st - 26th October 2011)The Taskforce utilized the opportunity to dedicate a session to further training of physicians participating in the PAPUCO study. Christiaan Diedericks introduced open source technology to the attendees that allows equipping a computer with an operating system and office software. This freely available software can also be used to format multimedia content prior to uploading on the PAPUCO platform.



Figure 1: PAPUCO team during launch and training session

Figure 2: Dr. Robert Mungi (Muhimbili National Hospital, Dar Es Salaam), Professor Karen Sliwa and Dr. Friedrich Thienemann giving an overview of heart disease in Africa and the PAPUCO study

Figure 4: Dinner after a successful PAPUCO and Heart Disease in Africa meeting. From left: Dr. Dike Ojji, Dr. Kemi Tibazarwa, Prof. Karen Sliwa, Dr. Robert Mungi, Dr. Friedrich Thienemann, Dr. Mahmoud Sani, Sandra Pretorious, Dr. Peter Kisenge, Dr. Lori Blauwet

Figure 3: Dr. Robert Mungi, Dr. Peter Kisenge (Muhimbili National Hospital, Dar Es Salaam) and Professor Karen Sliwa visiting the new Tanzania Cardiac Surgery Treatment and Training Centre

Current research initiatives include the PAPUCO Registry as detailed above, as well as the following:1. Dr. Friedrich Thienemann, MSc International Health:

PAPUCO - the Pan African Pulmonary hypertension Cohort study: implementation of an online research platform for sustainable research development in an Africa context, 2011

2. Dr. Kemi Tibazarwa, PhD: Risk factor prevalence and genetic pathways in peri-partum cardiomyopathy. Registered at University of the Witwatersrand, 2011

3. Dr. Dike Ojji, PhD: The Usefulness Plasma NT pro-Brain Natriuretic Peptide and Novel Myocardial Markers in Assessing Left Ventricular Hypertrophy and Heart Failure in Hypertensive Native African Subjects. Registered at the University of Cape Town, 2011

4. Mr. Gerald Maarman, PhD: Cardioprotection in pulmonary arterial hypertension (PAH): A novel role of the SAFE pathway in a model of pulmonary arterial hypertension. Registered at the University of Cape Town, 2011.

The Taskforce initiated the following abstract and publication in 2011:• OjjiDB,LacerdaL,LecourS,BillyroseMA,SliwaK(Abstract)

Markers of left and right ventricular remodeling in a Nigerian hypertensive cohort. Presented at South African Heart Association Meeting, East London.



• StewartS,MocumbiAO,CarringtonMJ,PretoriusS,BurtonR, Sliwa K. A not-so-rare form of heart failure in urban black Africans: pathways to right heart failure in the Heart of Soweto Study cohort. Eur J Heart Fail. 2011: 13:1070-7.


• TheSub-SaharanTaskForcehasbeenelectedtohostthe6th

PVRI Annual General Meeting, Workshop and Debate. This meeting will take place in Cape Town, South Africa, from 7th-10th of February 2012. A record number of participants have registered for what promises to be a very exciting meeting and a large number of abstracts have been received

• Oneoftheprimarygoalsfor2012istoraisefurtherfundsforthePAPUCO registry, which would enable us to undertake rapid recruitment and also to facilitate storage of serum and plasma.

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PVRI High-altitude TaskforceLeaders: Qadar Pasha (India) and Max Gassmann (UK)

The High-altitude Taskforce has been very active in 2011, and has seen some changes in its organisation. Prof. Nanduri Prabhakar from Chicago has kindly agreed to be a member of the Taskforce and to be an active collaborator in the organisation of the Leh Symposium 2012. He visited India and Professor Qadar Pasha’s lab on November 5 and 6, 2011, and discussed strategies of the meeting, and the possibilities of a financial approach in the USA. Professor Prabhakar also prepared a tentative list of possible participants for submission to the funding bodies.

2011 saw the Taskforce organising a number of important and well-attended meetings as chronicled below. For more details on the Trivandrum and Leh meetings, please see the meeting review section of this Annual Report.1. DAVOS, organized by Max Gassmann2. Monte Verità, organized by Max Gassmann3. Leh Symposium, Leh, Ladakh, organized by Qadar

Pasha and Ghulam Mohd4. Presentation of proposal for current project at the PVRI

Trivandrum meeting.

Other highlights include:1. The Taskforce has been awarded an international

fellowship, namely a GSK Research Grant via PVRI. This project work will focus on the role of telomeres in high-altitude natives and sojourners. This proposal was presented at the recently concluded PVRI regional meeting in Trivandrum. It is a one year project for which the research grant will be provided by CSIR, India

2. Possible collaborations have presented themselves in form of a lengthy and fruitful discussion with Dr. Soni Pullamsetti from Giessen, Germany; and with Rubin Tuder (Denver, USA) and SG Haworth (London, UK) in the October PVRI meeting in Trivandrum

3. One of Professor Pasha’s PhD students, Ms. Aastha Mishra, became a member of PVRI on the advice of PVRI Managing Director Ghazwan Butrous and agreed to be a team member of a scientific blog. She and other scholars of the India lab will also participate in the organizational activities of Leh Symposium 2012

4. Max Gassmann, Publication of the meeting report on Oxygen 2011 in High Altitude Medicine & Biology, Volume 12, Number 2, 2011, Mary Ann Liebert, Inc. DOI: 10.1089/ham.2011.0014

5. Louise Ostergaard and Max Gassmann, Hypoxia Inducible Factor and Hypoxia-mediated pulmonary hypertension, PVRI Review, Vol 3, Issue 1 2011, pp. 5-11, DOI: 10.4103/0974-6013.85613.

In terms of research, 2011 has been a year of steady continuation, analysis, and some publication. The contribution from individual labs has continued. The High Altitude Taskforce has been able to perform few major experiments in relation to genetic understanding and the data is under analysis. Another focus is the use Sequenom facility to screen several ‘single nucleotide polymorphisms of select genes. The Taskforce’s findings on CYBA and GSTp1 have been published in the journal Clinical Science. Few of the SNPs have been put to validation. The highlight of this year’s research activities have been the identification of few novel biomarkers in relation to high-altitude adaptation and diseases; the work is currently under peer review. In addition, HIF-1 has been the focus of study from ZIHP lab.


1. Continued preparation for the next international Leh Symposium 2012:• Max Gassmann and NorbertWeissman have

submitted applications to various scientific bodies and private companies for financial support

• NanduriPrabhakarhasalsoagreedtoparticipatein the organization of Leh symposium on the suggestion of Max Gassmann. (it may be noticed that the final list of speakers will be finalized at a later date by all the organizers)

• InIndia,QadarPashaisapproachingthegovernmentorganization for financial and strategic support, which will happen only in the next financial year, i.e. after March 2012.

2. Expected audience for the Leh Symposium is 100 national and international participants- advertising will be tailored accordingly.

3. Continued work on the project focusing on the role of telomeres in high-altitude natives and sojourners.

4. Exploration of further collaborations with Dr. Soni Pullamsetti from Giessen, Germany; with Rubin Tuder (Denver, USA) and with SG Haworth (London, UK).

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Pulmonary Hypertension associated with HIV TaskforceLeaders: Sonia Flores (USA), Nicola Petrosillo (Italy) and Norbert Voelkel (USA)

2011 has been an encouraging year for this PVRI Taskforce. A number of initiatives, including meetings, publications and research have been successfully started or completed this year, inspiring subsequent goals for 2012. The Pulmonary Hypertension associated with HIV Taskforce has been involved in the following meetings:1. ICAR (Italian Conference on AIDS and Retroviruses),

Florence 27-29 March 2011. The meetings saw the attendance of all infectious disease specialists involved in HIV care and virologists from Italy, with international participation.Dr. Petrosillo was invited speaker at the Italian Conference on AIDS andRetroviruses on “Clinical role of nef protein mutations” (Pre-conference advanced course). The presentation was well-received and raised several questions, and was considered successful overall.An excerpt of the program can be found on the PVRI website.

2. CHEST 2010 The American College of Chest Physicians (ACCP), Vancouver, Canada, Oct 29th, Nov 4th, 2010, which attracted specialists and fellows in training in the area of Respiratory Medicine.Dr. Flores invited speaker at the PVRI Symposium “Global Perspective on Pulmonary Vascular Disease. “HIV and the Nef Protein: Pathogenesis of a Deadly Disease”

3. American Thoracic Society 2011, American Thoracic Society International Conference, May 2011, Denver, Colorado, USA. Dr. Flores’ research group presented a poster: Almodovar S, Allshouse A, Knight R, Roemer S, Voelkel NF, Hsue PY, Humbert M & Flores SC. ‘HIV-1 Nef Signature Sequences Are a feature of HIV-related pulmonary hypertension: A genetic translational tool?’. [Am J Respir Crit Care Med 181;2010:A5209].

Publications in 2011 include:1. Special Issue on “Pulmonary hypertension and infectious

diseases” in Clinical Microbiology Infection; published in January 2011), edited by Petrosillo N.

2. Cicalini S, Chinello P, Petrosillo N. HIV infection and pulmonary arterial hypertension. Expert Rev Respir Med. 2011 Apr;5(2):257-66.

3. Chinello P, Cicalini S, Pichini S, Pacifici R, Tempestilli

M, Petrosillo N. Sildenafil plasma concentrations in two HIV patients with pulmonary hypertension treated with Ritonavir-boosted protease inhibitors. Current HIV Res (in review).

4. Chinello P et al. Bosentan and sildenafil in the treatment of HIV-associated pulmonary hypertension. Case report and literature review. Infectious DiseaseReport (accepted).

5. Cicalini S, Almodovar S, Grilli E, Flores S. Pulmonary hypertension and human immunodeficiency virus infection: epidemiology, pathogenesis, and clinical approach. Clin Microbiol Infect. 2011 Jan;17(1):25-33.

6. Almodovar S, Hsue PY, Morelli J, Huang L & Flores SC. Pathogenesis of HIV-associated pulmonary hypertension: Potential role of HIV-1 nef. The Proceedings of the American Thoracic Society 8:308-312 (2011).

7. Almodovar S, Knight R, Allshouse AA, Roemer S, Lozupone C, McDonald D, Widmann JJ, Voelkel N, Shelton RJ, Suarez-Martinez EB, Hammer K, Goujard CM, Petrosillo N, Simonneau G, Hsue PY, Humbert M & Flores SC. Human immunodeficiency virus nef signature sequences are associated with pulmonary hypertension. AIDS Res Hum Retroviruses. 2011 Nov 9. [Epub ahead of print]. PMID:22066947.

In terms of research, the Taskforce continues to work on the development of molecular tools to gain more insights into the Pathogenesis of HIV in Pulmonary Hypertension. Specifically, the lab is cloning the nef isolates from HIV-infected patients and studying the impact of the coded Nef protein in the biology of lung endothelial cells.

SUMMARY OF GOALS FOR 2012

1. To enroll new members in the Taskforce, with a special attention to members from Africa. The PVRI Annual General Meeting and Scientific Workshops and Debates 2012 in Cape Town will present an excellent opportunity for meeting new members wishing to join the Taskforce.

2. To design a study on risk factors for pulmonary hypertension in HIV infected individuals in developing countries.

PVRI Schistosomiasis Taskforce 2011Leaders: Ghazwan Butrous (UK) and Nicholas Morrell (UK)

UNIVERSITY OF KENT LAB ACTIVITIES

(Ewa Kolosionek, Ghazwan Butrous UK)

This year the Kent UK branch started a collaboration with Dr. Brian Graham and Prof. Rubin Tuder from Denver Medical Centre, Denver University, Colorado. The project is



entitled “Whole lung transcriptome analysis of a model of Schistosomiasis-associated Pulmonary Hypertension”, and compares different methods which are microarray (Affymetrix Mouse gene ST1.0 Array) and RNA-seq (Illumina HiSeq 2000) for gene identification in Schistosomiasis murine model of Pulmonary Hypertension.

Moreover, the Schistosomiasis Taskforce has published 2 reviews this year: “Pulmonary vascular disease associated with schistosomiasis” in the Expert Review of Anti-Infective Therapy journal [Kolosionek E, Crosby A, Harhay MO, Morrell N, Butrous G.] and “Pulmonary vascular disease associated with parasitic infection--the role of schistosomiasis” in the Clinical Microbiology and Infection journal [Kolosionek E, Graham BB, Tuder RM, Butrous G.].

Another paper was published in collaboration with Dr. Alexi Crosby and Prof. Nicholas Morrell “Praziquantel reverses pulmonary hypertension and pulmonary vascular remodelling in murine schistosomiasis” in the American Journal of Respiratory and Critical Care Medicine journal [Crosby A, Jones FM, Kolosionek E, Southwood M, Purvis I, Soon E, Butrous G, Dunne DE, Morrell NW.]

At present, another manuscript is being prepared for publication, under the working title “Schistosomiasis causes remodelling of pulmonary vessels in the lung in a heterogeneous localized manner – detailed study” [E. Kolosionek, J. King, D. Rollinson, R.T. Schermuly, F. Grimminger, G. Butrous].

The above manuscript reflects the Taskforce’s work at the University of Kent, focusing specifically on the research of the last two years. The study has six salient findings that will be explored in the paper. First, cercariae infection doesn’t cause right heart hypertrophy. Second, cercariae infection causes severe inflammation, which is associated with antigen response to egg presence in the lungs. Third, severity of infection depends on length of infection and 8 weeks infection is not as severe as 12 weeks of infection. Fourth, cercariae infection and resulting inflammation cause remodelling of the vessels and this remodelling always happens in close proximity to eggs or granulomas. Fifth, size of granuloma correlates with vessel changes, where medium sized granulomas are observed to have the greatest effect. Sixth, adult worms are present in the lungs of infected animals but are not associated with granuloma formation or vessel changes. This study supports the major role of inflammation in vessel remodelling and is the first report demonstrating detailed information regarding size, localization and correlation of granuloma, eggs, adult worms and remodelled vessels and its effects on each other. Moreover, it is the first study demonstrating mapping of the lobes in respect to granuloma and changed vessel localization, and is an exciting area to further explore.


1. Publication of the manuscript “Schistosomiasis causes remodelling of pulmonary vessels in the lung in a heterogeneous localized manner – detailed study”

2. Further exploration of demonstrating mapping of the lobes in respect to granuloma and changed vessel localization

UNIVERSITY OF CAMBRIDGE LAB ACTIVITIES

(Alexi Crosby, David Dunne, Nicholas Morrell, UK)The University of Cambridge branch of the taskforce was involved with the American Thoracic Society meeting in Denver, Colorado, May 2011, British Thoracic Society 7-9 December 2011.

This year the Taskforce published a paper in the American Journal of Respiratory and Critical Care Medicine entitled ‘Praziquantel reverses pulmonary hypertension and pulmonary vascular remodelling in murine schistosomiasis’. The manuscript contains a detailed description of the effect of the anithelminthic drug, praziquantel, on schistosomiasis-induced pulmonary vascular remodelling and pulmonary arterial hypertension. By employing the established model of chronic infection the Taskforce showed that animals develop significant pulmonary hypertension and right ventricular hypertrophy 25 weeks following infection. The presence of pulmonary hypertension was associated with the presence of lung eggs and the local expression of cytokine mRNA in the lung. Treatment with praziquantel at 17 weeks prevented pulmonary hypertension and reversed pulmonary vascular remodelling, suggesting that eradication of the parasite might allow resolution of disease in patients. Some of this work was presented at the American Thoracic Society meeting in Denver in May 2011 and at the BTS.

Currently, the Cambridge branch is investigating the role of bone-marrow derived progenitor cells in pulmonary vascular remodelling in schistosomiasis. There is a serious attempt to discern whether mice that have a heterozygous null mutation in BMPR-II have an exaggerated pulmonary vascular response to S. mansoni infection. In addition, the Cambridge branch are exploring the effects of S. mansoni eggs in vitro on the proliferation, migration and cytokine expression on pulmonary artery smooth muscle and endothelial cells.


1. Continuation of the studies of the progenitor cells2. Exploration of the effects of S. mansoni eggs in vitro as

described above.

UNIVERSITY OF DENVER, COLORADO LAB ACTIVITIES

(Brian Graham, Rubin Tuder, USA)The Denver branch was involved in the following meetings in 2011:1. American Thoracic Society (Denver, CO).2. PVRI Annual Conference (Panama City).3. Grover Conference (Sedalia, CO).

With regards to publication, the taskforce members based in Denver submitted manuscript to Pulmonary Circulation regarding identification of Schistosoma antigens in human lung tissue.

Current research is focused on the continuation of the investigations regarding the pathogenic mechanism by which the host immune response contributes to pulmonary vascular remodeling in schistosomiasis-associated PAH using



an established mouse model of the disease. In particular, the Denver branch is interested in IL-4, IL-13, and TGF-beta signaling, and has been using knockout mice and inhibitors of these pathways. In addition, Dr. Graham and Professor Tuder are studying the whole lung transcriptome of mice with experimental Schistosoma-induced PH to identify alternative potentially pathogenic signaling pathways. Finally, the Denver branch recently submitted a manuscript to Pulmonary Circulation reporting the absence of a significant amount of identifiable Schistosoma antigen in human pulmonary tissue from individuals

who died of schistosomiasis-associated PAH, relying on tissue from collaborators Angela Bandeira (Recife, Brazil) and Luciano Espinheira (Salvador, Brazil).


1. Continuation of the studies of the signaling pathways 2. Potential expansion into new pathways identified by the

whole lung transcriptome analysis.

PVRI Pediatric TaskforceLeaders: Ian Adatia (Canada), Sheila Glennis Haworth (UK) and Maria J. del Cerro (Spain)

The Pediatric Taskforce was created in 2010 following the PVRI Annual General Meeting in Lisbon. There have been no changes in the leadership since then, though it has recruited several more members. Members include all the doctors who participated in the formation of the Pediatric Classification at the 5th PVRI AGM in Panama in 2011 and more, namely professors Steven Abman, Gabriel Diaz, Alexandra Heath Freudenthal, Franz Freudenthal, Harikrishnan S, Dunbar Ivy, Antonio Lopez, Usha Raj, Julio Sandoval, and Kurt Stenmark.

The Pediatric Taskforce has been involved in a number of conferences and initiatives this year, including the below:1. During the 2011 PVRI Panama meeting, the pediatric session

ended with the achievement of the consensus document on the pediatric classification of pediatric pulmonary vascular hypertensive disease and the functional classification. The classification and a report from the Pediatric Taskforce (A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease) was officially published in Pulmonary Circulation Vol 1, Issue 2. These consensus documents were presented at several meetings:

2. The 4th International Conference Neonatal & Childhood Pulmonary Vascular Disease, UCSF (San Francisco, March 11-12th 2011)

3. 45th annual Meeting of the Association for European Pediatric Cardiology, Granada, 18th-21st May 2011

4. American Thoracic Society Meeting, 16th May 2011 in Denver, Colorado, USA.

Taskforce publications for 2011 included:A consensus approach to the classification of pediatric pulmonary

hypertensive vascular disease: Report from the PVRI Pediatric Taskforce, Panama 2011.

Cerro MJ, Abman S, Diaz G, Freudenthal AH, Freudenthal F, Harikrishnan S, Haworth SG, Ivy D, Lopes AA, Raj JU, Sandoval J, Stenmark K, Adatia I.Pulm Circ. 2011;1(2):286-298.PMID: 21874158

Functional classification of pulmonary hypertension in children: Report from the PVRI pediatric Taskforce, Panama 2011.

Lammers AE, Adatia I, Cerro MJ, Diaz G, Freudenthal AH, Freudenthal F, Harikrishnan S, Ivy D, Lopes AA, Raj JU, Sandoval J, Stenmark K, Haworth SG.Pulm Circ. 2011 Aug 2;1(2):280-285.PMID: 21874157


• For 2012, the Taskforce prepares consensus documentson guidelines for pediatric catheterization in infants and children with PH, which will be discussed at the 6th PVRI AGM in Cape Town, February 2012

• Inaddition,an interviewwith thePediatricTaskforceonthe new classification will be published in PVRI Review in 2012

• Guidelines for cardiac catheterization of pediatricpulmonary hypertensive vascular disease for discussion at PVRI in Cape Town, SA 2012

• GlobalAspectsofPediatricpulmonaryhypertensivevasculardisease session at 5th International Conference of Neonatal and Childhood Pulmonary Vascular Disease.



PVRI PH-ARC TaskforceLeader: Stuart Rich (USA)

The PH-ARC is on schedule in the preparatory planning phase. It has created a steering committee, five working groups on various relevant topics, and a pediatric advisory committee. Likewise, the leaders have enlisted a full complement of leading academic authorities as members of each of these groups, along with members of the FDA, and employees of four different pharmaceutical companies: Pfizer, Gilead, Novartis, and Bayer. Collectively they have agreed support this initiative with unrestricted grants to the PVRI for a period of five years.


• Outlines of the tasks for eachworking grouphavebeencompleted, and are anticipated to be continued further over the next several months.

• Aface-to-facemeetingwillbeheldinWashingtonDConApril 30, 2012. The regulatory authorities from Mexico and Canada have also agreed to be participants in this project.

Pulmonary Hypertension Associated with Congenital Heart Disease Taskforce (PH-CHD TF) - 2011Leaders: Antonio A. Lopes (Brazil) and Marlene Rabinovitch (USA)

Recently invited new members (directly involved in the research project), not formally invited yet:• AnaMariaThomaz,M.D.(Brazil)• NairYukieMaeda,Pharmacist(Brazil)

The Taskforce’s general objective is to provide education and implement discussion and research on subjects related to the management of PH-CHD in pediatric patients and the adult population. This goal is pursued through a variety of means, including:

EDUCATIONAL ACTIVITIES

1. Internet videoconferenceTitle: “Combined clinical and surgical approaches to

congenital heart disease associated with pulmonary arterial hypertension”Data: June 1st, 2011Guest: Prof. Marcelo B. Jatene, Dept. of Pediatric Cardiology and Pediatric Cardiac Surgery, Heart Institute (InCor), São Paulo, BrazilSpeakers: Antonio A. Lopes and Marcelo B. Jatene

2. Daily practice revisedThis is a new educational session of the PH-CHD Taskforce page intended to inspire discussion regarding important (and sometimes controversial) issues on the routine management of patients with congenital heart disease associated with abnormalities in the pulmonary circulation. The topics are prepared and revised preferably by specialists from different institutions and

Current membersAlejandro Londono – Colombia Huili Gan - China Naveen Swami - QatarAlexandra H. Freudenthal - Bolivia Ian Adatia - Canada Paul Upton - UKAlexander S. Opotowsky – USA Irwin Reiss - The Netherlands Prannet Kumar - USAAnita Saxena – India Jeffrey Feinstein – USA Rolf Berger - The NetherlandsBaktybek Kojonazarov - Germany Jian Wang - USA Sachindra Joshi - USABernard Thébaud – Canada Julio Sandoval - Mexico Saleh Aldammas – Saudi ArabiaBhola kumar Dahal – Germany Katia Stewart - USA Shahin Moledina - UKChunli Liu – China Khalid Alnajashi – Saudi Arabia Sheila G. Haworth – UKDick Tibboel – Netherlands Konstantinos Dimopoulos - USA Shyam S.Kothari – IndiaDuncan J. Stewart – Canada Krishna Kumar - India Snehal Kulkarni - IndiaElena Krakhmalova - Ukraine Kurt Stenmark - USA Sophia Mohyuddin - GermanyFrantz Robert - USA Maha Al Dabbagh – Saudi Arabia Steve Abman - USAGeorg Hansmann - USA Maria Angélica Binotto - Brazil Tereza Pinheiro - BrazilHanaa Banjar – Saudi Arabia Michael Gatzoulis - UK Vera D. Aiello - BrazilHasan Asslan - Syria Michele D’Alto - Italy



countries. The topics are as follows:• Congenitalcardiacseptaldefectsassociatedwithpulmonary

hypertension. Bedside criteria of severity of the disease before the era of the new drugs for pulmonary arterial hypertension: A historical patient group

Rilvani C. Gonçalves & Antonio A. Lopes• A proposed algorithm formanagement of patientswith

congenital cardiac defects associated with pulmonary hypertension

Antonio A. Lopes & Robyn J. Barst• HemodynamicrequirementsforsafelyindicatingaFontan

procedureMaria Angélica Binotto & Antonio A. Lopes

• ECHO-Doppler noninvasive assessment of pulmonaryhemodynamics in pulmonary arterial hypertension associated with congenital heart disease

Nasser Galal & Omar Tamimi & Maha Al Dabbagh• Current opinionon themanagementof congenital heart

disease complicated with pulmonary arterial hypertensionAntonio A. Lopes & Robyn Barst

ONGOING RESEARCh ACTIVITIES

Research projectTitle: Vasodilator Therapy for Pulmonary Arterial Hypertension Associated with Congenital Cardiac Defects

Authors: Congenital Heart Disease Taskforce – PVRIPurpose: To analyse the response to PAH therapies in borderline PAH-CHD patients (operable/inoperable) who might still be considered as possible candidates for surgical repair of their cardiac anomalies.Grant: Recently approved by FAPESP (Foundation for Research Support of the State of São Paulo, Brazil) #2011/09341-0.Amount: US$ 30,000.

Current status:• Mainstudygroup:18patients(1death)• Reference(untreated)studygroup:15patients(3deaths)• Historicalgroup:24patients(nodeaths)

Stored data/material: Complete pre- and postoperative hemodynamic data, intraoperative lung biopsy and extracted DNA.


1. To move forward with “Daily Practice Revised”2. To move forward with the Research Project3. To develop a review article on PAH-CHD for a possible

publication in Pulmonary Circulation4. To prepare a 2012 webinar – PAH-CHD updated (to be

confirmed depending on availabity of support).

PVRI Publications TaskforceThe year’s two main activities of the PVRI Publications Taskforce following the publication of the textbook of PVD were the premier publication of PVRI’s peer-reviewed journal Pulmonary Circulation and the continued publication of the PVRI Review.

PULMONARY CIRCULATION

The Publications Taskforce succeeded in bringing out Pulmonary Circulation, the peer-reviewed journal of the PVRI. PC is open-access and is available online, but also distributes print copies on demand. The first issue, Volume 1, Number 1, went online on March 16, 2011 (www.pulmonarycirculation.org). Between then and this report, two more issues were completed and posted. A fourth issue will be published in 2011, as we have planned the Journal as a quarterly. Pulmonary Circulation is an open-access journal and does not charge authors for anything, from submission to printing of color photographs. Even though the Journal is open-access, one has to subscribe to it to receive the print copy. The print version is distributed free to all PVRI Fellows. Figures 1 through 4 show the Journal’s global reach to date.

In 2011 the publisher of PC was Medknow Publications and Media, of Mumbai, India. All copies of Pulmonary Circulation were printed and distributed by Medknow, which published numerous other high-quality journals, including the PVRI’s other journal, PVRI Review. Late in 2011 Medknow was sold to publisher Wolters Kluwer, a 175-year-old global provider of information, software, and services that help professionals do

their work more quickly and efficiently. With 19,000 employees worldwide, Wolters Kluwer is headquartered in Alphen aan den Rijn, The Netherlands.

The Pulmonary Circulation journal project is supported for 3 years by, Cardio Medical Research and Education Fund (CMREF) (www.ipahresearch.org). The Editors-in-Chief are Professors Jason Yuan, Nicholas Morrell and Harikrishnan S. The Senior Editor is Professor Ghazwan Butrous, and the Executive Editor is Professor Harikrishnan S. The editorial assistants have been Karen Gordon,

Figure 1: The first three issue of Pulmonary Circulation



Figure 2: The statistics of the visits to the website of Pulmonary Circulation

Figure 4: Access to the PC website by city. This represents a near universal access

Figure 3: Access to the PC website by country. The darkest shade of green represents the maximum number of visits

Figure 5: Author Institution Mapping for 2011

based in USA and Nikki Krol in the UK. The Consulting Editor is Paul Soderberg.

An issue of Pulmonary Circulation always includes an editorial and a number of review and research articles. It sometimes also includes a guest editorial, a snapshot, guidelines and classifications, case studies, and historical viewpoints. The Journal has created its own style, thanks to the inputs by Paul Soderberg.

The editors and editorial staff were all involved in numerous

Skype meetings before the initiation of publication of the Journal. Several editors and staff also met in Panama City in February 2011 to discuss the imminent launch of PC. Another meeting was held in Denver on May 18, 2011.

The glad news for all those working with PC was received in October 2011 when Journal articles were cited in PubMed, a long cherished dream of all us. Our next aim is to receive an excellent impact factor, to demonstrate that Pulmonary Circulation has become the preferred medium of communication of all those who deal with pulmonary vascular disease.



PVRI ReviewAt the 5th PVRI AGM in Panama City, February 2011, it was decided that flagship journal PVRI Review would restrict itself to publication on a bi-annual basis. PVRI Review has been assigned a new role as the official newsletter of the PVRI. The content of the journal was altered to reflect a more PVRI-centric focus, whilst allowing original research articles and review articles the possibility of publication in Pulmonary Circulation. In addition to publishing all activities of the PVRI, PVRI Review also functions as a medium to publish perspectives, hypotheses, commentaries, overviews etc. At printing, PVRI Review has published two journals for 2011, both of which are open access available on the website www.pvrireview.org, as well as in print form. PVRI Fellows

and members receive a free printed copy of the journal, and subscription to the print form can be requested on the PVRI Review website.

With the shift in content, PVRI Review has published the PVRI Annual Report 2011, a report on the 4 day PVRI Panama conference, some review articles, commentaries and an interview with the PVRI Pediatric Taskforce on its work towards a new diagnostic classification for pediatric pulmonary hypertension. The journal continues to be well received and is settling into its new role.

However, the content is not the only change within PVRI Review. The Publication Taskforce announced late 2011 with regret that Dr. Harikrishnan will step down from his function as Editor-in-Chief of PVRI Review for the next year. The PVRI Review Board are very grateful for his tireless dedication, quality contributions and excellent work which has seen the PVRI Review blossom from its inception in January 2009 to the strong biannual non-peer reviewed voice of the PVRI. PVRI Review is embracing a new, more interactive model of management, which will see a far stronger presence of the Editorial Board, whilst the position of Editor-in-Chief will be opened anew each year for a nominated member of the Board. The convergence of this new board will be announced at the Annual General Meeting in Cape Town, 2012.

Dr. Harikrishnan has agreed to stay on in an assisting role for the first year, and the PVRI Review Editorial Board will consider applications from PVRI Fellows or members with experience in the world of scientific publishing and an interest in and enthusiasm for the execution of PVRI Review.

Figure 1: The thee issues of PVRI REVIEW (The green issue is the Portuguese supplement)



Administrative ActivitiesPVRI WebsiteThe PVRI website has been renewed to reflect recent changes in PVRI collaborations. As PVRI moves into the new year, the website has become more open and more individualised across the board in order to encourage easy interaction and collaboration amongst Fellows and members. The new website offers the following new features:• My PVRI - A individualised dashboard profile for each

Fellow or member, which allows user-friendly updates to address, details and disclosure, collects the PVRI-related RSS feeds as preferred by the individual, and produces a PVRI membership certificate upon demand. It also features a PVRI-centric email, allowing users simple communication.

• PVDImageGallery-Fellowsandmembersareencouraged

to upload their PVD related images with a caption, in an attempt to build a comprehensive image library on pulmonary vascular diseases.

• Contentuploads-thenewwebsiteallowsusertouploadcontent directly onto the server and to link to it, ensuring that taskforces can keep all relevant information in one universally accessible place on the website. The general public is not able to access these folders, allowing security and back-up of content.

• Content support - videos can now be uploaded tothe website, as well as documents and images as necessary.

• PVRIHelp-anyquestionswillbeansweredby theFAQ,which also has short instruction videos regarding use of the website.

• PVRIEventsDiary-MembersandFellowsareencouragedto upload information on upcoming events onto the website, using the events diary as well as the general content creation to post blogs and pages.

PVRI Educational WebsitePVRI has also created an e-learning website which will be released in 2012. The e-learning website features content such as lectures, slides and videos which allow students to learn on a virtual platform. It will be the vehicle for full certification in Pulmonary Vascular Diseases and CME/CPD credits.

PVRI AppsThe PVRI has created a smartphone app to allow easy access to the website and more for mobile phone users. The smartphone app will be available for download in the first quarter of 2012 for iPhone and iPad users. A Blackberry and Android app will be released later.

PVRI MembershipThe current PVRI membership totals 554 membership. This is an increase of 117 members and Fellows during the year 2011 at the time of printing.

PVRI RESEARCh GRANTS 2010

Animal Model of Pulmonary Hypertension for Identification of New TherapeuticDr. Kashif Hanif, Central Drug Research Institute, Lucknow.

Dr. Hanif was awarded a PVRI Travel grant in September 2010. He has now shown that an aqueous extract of pomegranate juice prevents the development of pulmonary hypertension in the monocrotaline rat model, reduces oxidative stress and inhibits a rise in ACE activity in the lungs. Dr. Hanif will begin training in Giessen from April 2012 onwards on the Animal Models of Pulmonary Hypertension for Identification of New Therapeutics.Figure 2: PVRI Research Grants: Progress Report

Figure 1: Front page of new Website



Genetic Determinants of Monge’s DiseaseJean-Paul Richalet1, Fabiola León-Velarde2, Maria Rivera2, Jose Espinoza2, Anne-Paule Gimenez-Roqueplo3

1Université Paris 13, Bobigny, France, 2Universidad Peruana Cayetano Heredia, Lima, Peru, 3INSERM, UMR 970, Laboratoire de génétique, Hôpital européen Georges Pompidou

Bioinformatic Analysis of Gene Expression Profiles of Pulmonary Arterial Hypertension Finding a Robust Gene Expression Signature for PAHSwapna MenonJawaharlal Nehru University (JNU), New Delhi, India, Host Institution PI: Dr. Andrew Lynn, Director, Communication & Information Services, Associate Professor, School of Computational & Integrative Sciences, JNU, New Delhi, India

Background: Permanent living at high altitude may provoke diseases characterized by an excessive number of red cells associated with pulmonary hypertension (Monge’s disease or Chronic Mountain Sickness- CMS), the prevalence of which is over 10% in the Altiplano. A genetic susceptibility has been suspected but never demonstrated for these diseases.

Various polymorphisms have been related to oxygen transport and/or oxygen sensing, as well as control of vascular tone and/or remodling in population suffering from acute or chronic exposure to hypoxia.

We proposed to perform a genone-wide association study in 2000 subjects (1000 patients vs 1000 controls) in population of high altitude cities of Peru (Cerro de Pasco, Puno, Cuzco). Polycythemic subjects will have a clinically-based diagnosis of CMS (CMS score > 20) and a Hb concentration > 21 g/dl.

Our objective is to propose a safe, efficient and low cost treatment for Monge’s disease, better characterize the physiopathology and genetic aspects of this disease and evaluate its socioeconomical consequences for Andean countries.

Background: Identification of genes that are consistently over or under expressed, across heritable and idiopathic PAH samples and, similarly regulated in animal models of disease to generate a molecular signature of PAH, independent of etiology. The goals included:1. Obtaining diverse microarray datasets2. Standardizing the microarray analysis workflow in

R/Bioconductor for preprocessing and differential expression analysis of microarray data and additional software tools for end stage analysis of significant genes/

Methods: Polycythemic (CMS) subjects and control normal subjects have been recruited in the city of Cerro de Pasco (4350m) Peru. For the moment, we have been able to include 215 subjects in the study (131 CMS and 84 controls). CMS patients had a clinically-based diagnosis of CMS (CMS score > 20) and a Hematocrit>61%. Control subjects had a hematocrit < 55%. DNA extraction has been performed in Peru (Genetics Laboratory, Universidad Cayetano Heredia, Lima) and genetic analysis in France (Laboratoire de Génétique, HEGP, Paris). Seven pairs of primers were designed to be used for the amplification of 215 DNA samples. Within the amplicons, we looked at 11 Single Nucleotide Polymorphisms (SNPs) of VEGFA that could be involved in CMS.

Results: Our preliminary results are very encouraging since we found a significant difference between the two groups for SNP rs3025033 A->G, confirming that VEGF could be differently expressed in normal and polycythemic subjects at high altitude.

Conclusions: Presently, the complete statistical analysis is being performed. In the next few months, new campaigns of patient recruitment will be performed to increase the number of patients and controls.

pathways3. Updation on current literature on the molecular

mechanisms underlying pulmonary arterial hypertension4. Updation on current literature on microarray techniques

and trends

The grant solely provided remunerative support to Ms. Swapna Menon, from October 2010- October 2011, the period of the grant award. The projected timeline for completion of the project is 3 years.

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Results and Conclusions: Results and findings were shown in academic output during the period of grant awards in the following publications and presentations:1. S. Menon, J. Fessel, J. West. Microarray studies in Pulmonary

arterial Hypertension. International Journal of Clinical Practice Special Issue: The Pulmonary Hypertension Reviews: an IJCP Companion Journal Vol 65, Issue Suppl s169, pages 19–28, January 2011

2. Eric D Austin*, Swapna Menon*, Anna R Hemnes, Linda R Robinson, Megha Talati, Kelly L Fox, Joy D Cogan, Rizwan Hamid, Lora K Hedges, Ivan Robbins, Kirk Lane, John H Newman, James E Loyd, and James West Idiopathic and heritable PAH have shared molecular etiology Pulmonary

Circulation, Jul-Sep 2011 (Austin, ED* and Menon, S* : equal contribution)

3. 6th PVRI AGM & Scientific Debates, Cape Town, South Africa, February 6-7, 2012. Gene expression profiling in human pulmonary arterial smooth muscle cells in response to bone morphogenetic proteins and transforming growth factor-β. Swapna Menon,Benjamin J Dunmore, Lu Long, Nicholas W Morrell.

Other academic work includes research summaries and other articles to every issue of PVRI Review, talks at local and national meetings of PVRI in India and contributions to http://pvri.info website.

Group providing data Data source Microarray analysisProf. Nicholas Morrell,Division of Respiratory Medicine Department of Medicine Cambridge University Addenbrooke's Hospital Cambridge, UK

Lobar pulmonary arterial smooth muscle cells (LPASMCs) from control and familial PAH patients stimulated with BMPR2 pathway ligands. Similar data also generated for commercially obtained human pulmonary arterial endothelial cells

R/ Bioconductor and supplementary software workflow devised for Affymetrix, short time course, multiseries experiment

Dr. James West, Assistant Professor of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

B cells from heritable PAH and idiopathic PAH patients and asymptomatic mutation carriers

Worked out R/Bioconductor workflow including preprocessing, quality control and differential expression for Affymetrix, pairwise comparison experiment

Does High Altitude Protect Against Irreversible Pulmonary Hypertension?Alexandra Heath1, Inge von Alvensleben1*, Brian Graham2, Rubin Tuder2**1Kardiozentrum – Pediatric Cardiologist, La Paz, Bolivia, PVRI Fellow, Former Resident, Aachen RWTH, Germany, 2Department of Medicine University of Colorado at Denver, *Pediatrician, La Paz, Bolivia, Former Resident University of Berlin,Germany, **Hart Family Professor of Medicine and Pathology Director, Program in Translational Lung Research Division of Pulmonary and Critical Care Medicine

Background: High altitude inhabitants with posttricuspidal shunts rarely develop severe pulmonary hypertension, and very late Eisenmenger Syndrome. The patients remain operable, and the pulmonary pressure remains reversible. We hypothesize thick pulmonary vessels are responsible for the stabilization of the vessel, which does not allow for the development of deformations, which are typical for the progressive disease of the vascular bed in pulmonary hypertension. Due to a continuous vasoconstriction, the muscular media does not allow the high flow to the pulmonary vessels, which is typical for this condition.

The aim of the clinical study is to assess if the patients with left to right shunts (ductus, VSD, ASD and AV channel) have a protective factor which impairs the development of pulmonary hypertension at early stages of the evolution of the disease at high altitude.

Methods: Prospective, consecutive, case based one year study with inclusion and exclusion criteria (VSD, PDA, or AV Channel patients older than 5 years with pulmonary hypertension and indication of surgical closure). All patients planned for (1) diagnostic catheter to assess operability and for invasive

pulmonary pressure measures. (2) Surgical correction of the CHD and lung biopsy and (3) Post OP catheter for invasive pulmonary pressure measures.

Results: 4 patients (Patient 1: 12 year old boy with VSD. Patient 2: 28 year old man with PDA. Patient 3: 11 year old girl with VSD and Patient 4: 10 year old boy with VSD) underwent cardiac catheterization with a hyperoxia test to assess operability. All 4 patients had pulmonary hypertension and the pulmonary pressures dropped with hyperoxia. All Patients are already operated on and recovered well. Histologic examination of three lung biopsies was suggestive of increased pulmonary artery medial thickness in all 3 cases but not more typical changes for advanced disease in the pulmonary vessels. Patient 4 biopsy is waiting for sending. Patient 1 completed the three steps. The post-operative catheterization showed normal values for pressure and vascular resistance.

Conclusion: High altitude exposure may be protective against severe irreversible congenital heart disease-associated pulmonary hypertension. The first study results are encouraging. We are looking forward to complete the series.



We have submitted a manuscript to Pulmonary Circulation reporting our investigations into S. mansoni antigens in the lungs of humans with schistosomiasis-associated pulmonary arterial hypertension, describing an absence of significant identifiable antigens using a validated custom-made antibody to soluble S. mansoni egg antigens. We also attempted to use

mass spectroscopy to identify unique S. mansoni peptides in the human tissue, but were unable to do so reliably due to (1) the limited quality of often decades-old formalin-fixed and paraffin-embedded tissue and (2) similar protein sequences between S. mansoni and H. sapiens for the most abundant proteins such as histones and actin.

Significant Intrapulmonary Schistosoma Egg Antigens are not Present in Schistosomiasis – Associated Pulmonary HypertensionBrian B. Graham, Jacob Chabon, Angela Bandeira, Luciano Espinheira, Ghazwan Butrous, Rubin M. TuderUniversity of Denver, Colorado, USA, Memorial S. Jose Hospital - Recife-pe PROCAPE, Brazil, University of Kent, UK

Background: Schistosomiasis-associated pulmonary arterial hypertension (PAH) is one of the most common causes of pulmonary hypertension worldwide. A potential contributing mechanism to the pathogenesis of this disease is a localized immune reaction to retained and persistent parasite-derived antigens. We sought to identify Schistosoma-derived egg antigens present in the lungs of individuals who died of the disease.

Methods: We obtained 18 lung samples collected at autopsy from individuals who died of schistosomiasis-associated PAH in Brazil. A rabbit polyclonal antibody was created to known S. mansoni soluble egg antigen (SEA). Histologic assessment and immunostaining of the human tissue was performed, along with immunostaining and immunoblotting of lung tissue from mice experimentally infected with S. mansoni.

Results: All 18 lung samples had evidence of pulmonary vascular remodeling with plexiform lesions and arterial medial thickening, but no visible eggs were seen. The anti-SEA antibody detected S. mansoni egg antigens in visible eggs in mouse lung and human intestine specimens, but did not identify a significant amount of egg antigen in the human lung specimens. In mouse granulomas containing degraded eggs, we observed co-localization of egg antigens and macrophage lysosomes.

Conclusions: There is unlikely to be a significant amount of persistent parasite-derived antigens within the lungs of individuals who die of schistosomiasis-associated PAH. This suggests that retained and persistent parasite proteins are not contributing to a localized immune response in the pathogenesis of this disease.

Identification of Schistosoma Mansoni Antigens in the Lungs of Humans with Schistosomiasis – Associated Pulmonary Arterial HypertensionBrian GrahamUniversity of Denver, Colorado, USA



Implementation of an International Registry of Pulmonary HypertensionKaren SliwaUniversity of Cape Town, Cape Town, South Africa

Background: The Pan African Pulmonary Hypertension Cohort study (PAPUCO), a prospective observational cohort study, was initiated by the Co-Leaders of the Sub-Saharan Taskforce Karen Sliwa and Friedrich Thienemann. The objective of the study is to describe the epidemiology and characteristics of pulmonary hypertension in Sub-Saharan Africa (N=500), over a period of 24 months. Participants are drawn from

17 cardiovascular specialist centres in 8 African countries, namely Cameroon (1), Kenya (1), Mozambique (2), Rwanda (1), Nigeria (7), South Africa (2), Sudan (1), Tanzania (1), and Uganda (1).

For more information on PAPUCO, please see the Sub-Saharan Taskforce report in this Annual Report.

A Message to the Pvri Fellows and MembersPVRI Review is an educational non-peer reviewed publication, which focused on the activities of the PVRI and published articles by a variety of authors and Fellows. PVRI Review was a success and an inspiration- so much so that last year, PVRI also founded Pulmonary Circulation, We at PVRI would like to direct the reader's attention here to the tireless contribution of Dr. Harikrishnan S., who has been heavily involved in the editorial process as a Chief Editor for the last three years. His leadership in PVRI Review was a great attribute to its successful launch, and he has worked very hard as its Editor-in-Chief for the past three years to establish the Journal and to ensure its standard and quality. I want to hereby thank Dr. Harikrishnan for his fantastic efforts.

At present, Dr. Harikrishnan's tenure as Editor-in-Chief of PVRI Review is coming to an end. Next year he will take on a new responsibility as the Vice President of the PVRI South East Asia Taskforce, and we will have to appoint a new Editor-in-Chief for PVRI Review.

The role of Editor-in-Chief is pivotal to the Journal's wellbeing. The PVRI Review Editor-in-Chief holds the final responsibility for meeting deadlines, establishing a renewed Editorial Board, soliciting articles and keeping up the standard of the Journal. Interested Fellows will be timely, inspirational and motivating, and I hereby ask any interested PVRI Fellows to come forward and contact me; if they are interested in the role of Chief Editor for the next three years.

Sincerely, Ghazwan Butrous FPVRIPVRI Managing [email protected]



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Does Non-regression of Pulmonary Hypertension Following Balloon Mitral Valvotomy Correlate with BMPR2 Mutations?Harikrishnan S, Renuka Nair1, Mukund A Prabhu2

Department of Cardiology, SCTIMST, Trivandrum, 1Scientist G, Division of Cellular and Molecular Cardiology, SCTIMST, 2Department of Cardiology, SCTIMST, Trivandrum, India

Background: Pulmonary hypertension (PH) is a rare disorder that may be heritable (HPH), idiopathic (IPH), or associated with either drug-toxin exposures or associated with some rare medical conditions. There are reports describing association of this disease with genetic mutations. The most common association of PH is found to be with mutations in the bone

morphogenetic protein receptor type 2 gene (BMPR2).

Rheumatic Heart Disease (RHD) is continuing to be a vexing problem in the developing world. PH is a common accompaniment of RHD, with 70% of the patients having evidence of different grades of PH. PH is found to be

Molecular Mechanisms of Pulmonary Microvascular Endothelial Dysfunction Under Fluid Shear StressCC Kartha, SS Binil RajRajiv Gandhi Center for Biotechnology, Trivandrum, India

Background: The objective of the project is to study the effect of fluid shear stress on rat pulmonary micro vascular endothelial cells (PMVEC) and to delineate molecular mechanism of PMVEC dysfunction in response to fluid shear stress. Presently we were able to isolate and characterize the rat PMVEC.

Methods: PMVECs were isolated using enzymatic digestion, followed by density gradient centrifugation. Lungs were removed from Male Wistar rats by sterile techniques. Visceral pleura were first stripped from each lobe, and the outer 3 to 5 mm of the peripheral lung tissue were sharply dissected free from the remaining tissue. The pooled pieces of lung periphery were finely minced and digested with a mixture of 0.5 % collagenase and 0.5 % dispase for 1 hr. The cell suspension collected by centrifugation was layered on a 50% Percoll gradient and centrifuged at 600g for 10 minutes. The endothelial cell rich fraction was formed a band around the middle third of the gradient. The entire middle layer was collected from gradient. The cells were resuspended in modified DMEM medium (L-Valine substituted with D-Valine) and were seeded onto gelatin coated tissue culture flasks. Cells were allowed to attach and grow to monolayers at 37°C in a humidified atmosphere of 5% CO2 and 95% air.

Progress: The isolated cells were characterized by uptake of Dil labeled acetylated LDL [Figure 1] and the binding of FITC-labeled Bandeiraea simplicifolia I isolectin B4

confirmed the microvascular nature of isolated endothelial cells. FACS analysis (using anti-CD31- FITC staining) of the isolated cells culture confirmed that endothelial cells were the major population. Further we will be studying the effect of variations in fluid shear stress on PMVE cell function.

Figure 1: Labeling of pulmonary microvascular endothelial cells with Dil-Ac-LDL. Bright field image (BF), nuclear stain with Hoechst, Dil-Ac-LDL uptake and merged images



Telomeres in Adaptation and Maladaptation Under Hypobaric HypoxiaQadar PashaInstitute of Genomics and Integrative Biology, Delhi, India

Podt-doc fellow/GSK fellow: Soon to be appointed.

The project activity has been initiated in full earnestness. However, it could not be fully initiated as we could not recruit the GSK fellow in time due to miscommunication between the PVRI fund release office and our finance department. Now that the issue has been resolved, my office knows that the fund has been deposited in its account and the recruitment process has been restarted. The position is on the IGIB website. The interview is fixed for December 20, 2011 with the intention to allow the fellow to join from January 1, 2012. The tenure is for one year from the date of appointment.

As this project has been approved by the Institute and has been alloted a project code, OLP0017, I am bound by IGIB protocols to submit the report at IGIB for presentation and evaluation every six months in front of ‘Research Council’. The start and end date of this project are as follows: January 1 to December 31, 2012.

Background: Telomeres are DNA sequences and associated proteins that cap and stabilize the ends of linear chromosomes, thereby maintaining genome integrity and stability. Telomere length is not only related to the basic biology as a trigger of cellular senescence but also reflects the balance between oxidative stress and antioxidant defence mechanisms. Telomere attrition in circulating white blood cells has been proposed as a marker for cumulative oxidative stress, whereas longer length has

been associated with longevity. Both these phenotypes associate with high-altitude environment.

The major goal of this study is to investigate the association of telomere length, telomerase activity with adaptation and maladaptation/disease under hypobaric hypoxia of high altitude. In addition, we would perform various correlation analyses among telomere length, telomerase activity, biochemical and clinical parameters. To accomplish these objectives, three well defined groups, namely healthy highlanders (HLs), high-altitude pulmonary edema-patients (HAPE-p) & HAPE-resistant controls (HAPE-r), would be screened. Real-time PCRs, genotyping of few related genes and relevant bioassays will be performed. This study would help us understand the association of telomere length in severity of HAPE and longevity. Genotyping of few novel SNPs in telomere maintenance genes may strengthen our understanding of telomere functioning and thus predisposition to HAPE.

Methods: The work plan has been initiated and the necessary reagents have been procured. The primers have been designed and order has been placed for procurement. The samples that have to be screened have been marked and dilution of the DNA’s for the desired concentration has been completed.

Progress: This project was already designed by Dr. Pasha. Due to a lack of manpower, the activity has not been started so far, but this will chance once the Post-doc is appointed.

a prognostic factor influencing the outcome of the disease including even interventional and surgical therapy.

As described in other diseases like sickle cell disease or congenital heart disease, there can be an association of BMPR-2 mutation and PH in RHD also. It can be postulated that those patients who are at risk of non-regression of PAH may harbour BMPR-2 mutations. There is no published data regarding the prevalence of BMPR2 mutation in patients with rheumatic heart disease and PH.

We are working with the following hypothesis: Patients having BMPR2 mutations are likely to have delayed/non-regression of Pulmonary Hypertension even after successful Balloon Mitral Valvotomy.

The aim of the study is to find out whether there is an association

of BMPR-2 mutation and non-regression of PH in patients who are undergoing a successful balloon mitral valvotomy.

Methods: This study is planned as an observational study. The prevalence of BMPR2 mutation will be studied in patients with mitral stenosis, who undergo a successful BMV but have non-regression of PAH. The prevalence data will be compared to patients who have regression of PAH following valvotomy.

Progress:• InstitutionalEthicsCommitteeClearanceobtained• FundstransferredfromPVRIlastmonth• Startedidentifyingsubjects,calllettersbeingsent• First patient will be enrolled by 1st of January 2012.

Patient recruitment and sample collection to be over in 9 months


Conversation on the PVRI- Panama Classification of Pediatric Pulmonary Hypertensive Vascular Disease Published in Pulmonary Circulation(1,2)

Ghazwan Butrous, Ian Adatia, Maria del Cerro, Sheila Haworth

It has been nearly a year since the leaders of the PVRI Pediatric Taskforce first presented an outline for a pediatric classification of pulmonary hypertensive disease at the PVRI 5th Annual General Meeting in Panama, February 2011. PVRI’s Managing Director Ghazwan Butrous decided to follow up with an interview with Taskforce Leaders Ian Adatia, Maria del Cerro and Sheila Haworth, and discussed the Taskforce’s motivations for the classification, the difficulties and successes of its creation, its reception within the world of PH specialists and pediatricians, and how they see the classification being utilized and moving forward in coming years.

Ghazwan Butrous: How did the idea of a pediatric classification come up?

Ian Adatia: Ghazwan had asked for ideas for the Annual PVRI Meeting in Lisbon in 2010. A number of us thought that it would be interesting to debate the pros and cons of a Pediatric Classification of Pulmonary Hypertension. Sheila Haworth and I debated the issue of having a dedicated pediatric classification because so many points in the Dana Point Classification (DPC), despite being a comprehensive and excellent document, didn't always take care of the issues that we face on a day to day basis in pediatric practice. After that debate, there was a lot of interest expressed from people affiliated with both adult and pediatric hypertension. In particular, Maria [del Cerro] became interested in pursuing this debate further, and Ghazwan [Butrous] asked us to prepare more formally an outline of a pediatric classification of PH or pulmonary hypertensive vascular disease, as we prefer to call PH in children, for the PVRI 5th Annual General Meeting in Panama in February 2011. As a result of the discussion with the whole PVRI Task Force in Panama- Alexandra Heath-Freudenthal, Steve Abman, Gabriel Diaz, Franz Freudenthal, Harikrishnan S., Sheila Haworth, Dunbar Ivy, Antonio Augusto Lopes, Usha Raj, Julio Sandoval, Kurt Stenmark- we put together what has become known as the Panama Classification.

Maria del Cerro: I think Ian described perfectly what happened. Most of the pediatricians I know were not entirely satisfied with the Dana Point Classification as they felt it did not classify the illness properly in pediatric patients. I think the idea of a pediatric classification was suggested at a perfect time.

Ghazwan Butrous: Professor Haworth, you have been practising in the area of pediatric pulmonary hypertension for a long time. What are your thoughts regarding the need for a pediatric classification?

Sheila Haworth: I think there are two points to consider. The first is that physicians working with children and young people have recognized for a long time the need for both a diagnostic and a functional classification specifically designed for the young. We needed a diagnostic classification in children because it is simply illogical, based on the evidence, to think that adult treatments can work equally well in children and in the same way. Ian and Maria especially worked very hard in designing a diagnostic classification designed to help in the diagnosis and treatment of young people with pulmonary hypertension. The need for a functional classification is self evident . There’s not much point asking a baby to do a 6-minute walk test!

Ghazwan Butrous: Considering the rationale, we did indeed need a diagnostic classification, but we already have the Dana Point Classification. Rather than design an entirely new classification, is it not possible to make small modifications to the existing classification to make it relevant in pediatric pulmonary hypertension treatment?

Ian Adatia: Firstly, Sheila and Astrid deserve the credit for the functional classification which I think would stand alone from the WHO adult functional classification. As for combining the Panama diagnostic classification with the Dana Point classification, that would be a great goal, but in order for that to work we need to look at the specific developmental issues in the fetus, the neonate and the

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Figure 1: From top left to right:- Ian Adatia, Sheila Haworth, and bottom left to right:- Maria del Cerro, Ghazwan Butrous


Butrous, et al.: Interview - Calcifications

young child, and the way in which their pulmonary vascular disease manifests in different ways from those of adults. The most important thing is that it has become increasingly clear that many diseases have their origin in fetal and early life, think for example of Barker and his work on systemic hypertension. The same is true of pulmonary hypertension, probably even more so. The pulmonary circulation undergoes huge changes at birth as it adapts to extra-uterine life and morphological and physiological change continues in the first months of life. Many diseases of the pulmonary circulation have their origins in that time frame. It is important to acknowledge these features within a classification. It may well be that abnormalities arising in fetal and early life have an important bearing on the development of pulmonary vascular disease in adult life. I think those are the main features we need to recognize in a classification, before we can consider putting them together with the Dana Point Classification, if this is possible at all.

Ghazwan Butrous: Sheila, please expand and add your perspective on the need for another classification in addition to the Dana Point Classification.

Sheila Haworth: I believe that the DPC is not adequate: it does not meet the needs of those diagnosising pulmonary hypertension in children. The DPC is very much an adaption of the Dana Point adult classification. Pediatric diagnosis has its particular problems, particularly combinations of several anomalies in a small child with pulmonary hypertension. In short, I feel the Dana Point Classification, though useful, is inadequate. The Panama classification very much takes the developmental perspective seriously. This is crucial as, of course, children are in a constant state of physical development and such a classification can help pinpoint whether the condition is for example, primarily a genetic problem, a prenatal problem, or perhaps a toxic problem due to drug use by the mother. It allows an exploration of questions which otherwise might not be asked so readily. It should help us learn more about the aetiology of pulmonary hypertension.

Ghazwan Butrous: Obviously there is a need for another classification. What are the difficulties you faced in designing this new classification, and what was the role of the PVRI Pediatric Taskforce?

Maria del Cerro: The PVRI Pediatric Taskforce played a crucial role as it gave the pediatricians involved the opportunity to gather and exchange their views and experiences. I don't think the classification would be here today if the PVRI had not been involved. One of the main difficulties we faced was in navigating time zones and schedules, but this is true for any project which involves international communication. At the moment, the Panama classification looks very complex, but at its base it is simple. We found that once we established the basic scheme, there were only little arguments regarding the specifics and definitions, such as the definition of pulmonary vascular disease in pediatric patients with aFontan-type circulation. However, everyone agreed on the most important aspects.

Ghazwan Butrous: What are the difficulties you faced before the Panama meeting, and what are the elements that created the (so far) successful results of the classification?

Ian Adatia: Many people felt the same way about the DPC, namely that it was difficult to find a satisfactory category in which to place a child, particularly one with multiple associations with PHVD. It was expressed by a number of people that quite often one would have to shoehorn a child into a less than satisfactory category which to define a child's disease, yet it was necessary as quite often criteria for therapy included a Dana point category. However, it caused difficulties with regards to the deciding on the correct category. If you had a child with, for instance, a 22q11.2 deletion and pulmonary hypertension, was that pulmonary hypertension associated with the di George syndrome, or was the diagnosis idiopathic hypertension associated with the di George syndrome? One can find a number of such examples. One of our difficulties was that we didn't have an unified approach. There had been some attempt to make a diagnostic classification but I think people stayed away from it because it started to look too complex. So the most important thing about the Panama meeting was that people were for the most part very happy to come together and try to solve the problem, as everyone saw it as it being a necessary task to undertake. So we all put forward some ideas on the diagnostic classification, but at the end of the day what we need to do is use it and see whether it works and how it can be improved and refined. After all, the DPC is a refinement of at least three other classifications. We are just beginning but if the classification is a good one it will be able to absorb new data easily and make diagnosis and an approach to management easier to apply to children. If it is flawed, that will not be the case and we will have to make major changes.

Ghazwan Butrous: During the Panama conference, the PPH Taskforce spent several hours meeting and discussing with pediatricians and people with an interest in pediatric pulmonary hypertension on how to best go about defining the new classifications. During this time, were there any surprises?

Ian Adatia: One of the surprises was the enthusiasm that many of the adult PH doctors had for the classification: they really embraced it. The other surprising development was that at the European society of pediatric cardiology the Panama classification was received very well by the audience. We have always made it very clear that we had incorporated many ideas from the DPC, which is very sound, into our classification. The other thing that surprised me is that when we presented the new Panama classification at the American Thoracic Society meeting, there was a great deal of interest from representatives of the National Heart, Lung and Blood Institute of North America. I think this kind of interest is very welcome and will encourage research into pediatric PHVD as a result.

Ghazwan Butrous: I'd like to extend the same question to you Sheila, and particularly, how did you find the participation in Panama and was there, in your opinion, the right conglomeration of people to help us achieve the steps we have so far achieved?

Sheila Haworth: I think that the interaction in Panama was extremely good within the Pediatric Taskforce. I believe that all continents were represented but specifically South America, North America and Europe were well represented. I'm uncertain about China and South East Asia, but in general good representation and good diversity, which was great as this highlighted region-specific problems and the impact of location on pulmonary hypertension



, for example in high altitude locations. As Maria said, this was very helpful in developing the classification.

Maria del Cerro: As Sheila has mentioned, it is the diversity of representation that has helped make the classification so rich.

Ghazwan Butrous: Knowing that PH shows itself differently in developing countries as opposed to in developed countries, where you find more untreated congenital heart diseases and infectious diseases, how would you suggest the classification can be further developed, and what steps would you recommend so people can get together and improve this classification further?

Ian Adatia: I think we need to take on the classification in the registry The Pediatric Pulmonary Hypertension NETwork (PPHNet) of North America is chaired by Steve Abman and is planning on setting up a database for pediatric pulmonary hypertensive vascular disease (PHVD) and test the classifications, the Panama and Dana Point, side by side to see how useful it is and what modifications are necessary. I think the only way to develop the classification is by using it. As far as the diagnostic classification goes, it's pretty clear we wish to use it to help clinical practice. It doesn't have any initial secondary uses, though they may appear over time, but to begin with it is devised to help with clinical practice so that when one is presented with a baby with PHVD one could use the classification to consider a number of diagnoses and investigate, manage and treat the child appropriately. It should help us to think more carefully and rigorously.

Ghazwan Butrous: Sheila, you have a lot of collaboration and interaction with countries in South East Asia. How would you like the classification to be implemented in such countries where the pathology and clinical presentation of the diseases might be different for a variety of logistic reasons? Do you think that the idea of the registry, which is currently considered in the US, could be adopted globally?

Sheila Haworth: In answer to your last question, yes, I do think it can be extended globally. I'm thinking of the ways in which it could move forwards. Both the diagnostic and functional classifications can only be tested by using them on individual children. It may be possible to test it for, say, a year, and then review it at another PVRI meeting, and it would be helpful to collect feedback from pediatricians and PH specialists using the classification in their everyday practice. I think it would also be helpful to have a page on the PVRI website which allows people to make comments about the classifications. It would be a good way to collect feedback and see where people find the classification awkward and where it needs refining and revising. I would ,however say that we probably shouldn't modify it for at least two years, to allow feedback to accumulate and then review the agreements, disagreements and difficulties. And so I think that all those concerned should sit down together, discuss, take into account the accumulated experience using the new classifications and modify the classifications accordingly. I don't know if it would be sensible to suggest using the diagnostic classification in developing countries immediately: I am confident about it but I wouldn't like many in India for example, to pause between the two systems. When the new classification has been reconsidered and perhaps revised in the light of experience in say 2 years time when we can suggest that everyone can use it with confidence.

Ghazwan Butrous: Do you think the idea of a registry is of any value in countries such as India, China and the Mediterranean?

Sheila Haworth: Certainly it is of value, but the problem of registries in developing countries is a very complex one. The idea that one can just sit down in a developing country and make a registry is not real life at the moment. Using the diagnostic category with an up and running registry is one thing: starting a registry it is quite another.

Ghazwan Butrous: You mentioned that there are a few ways to test the classification. Can you expand on this? Do they test whether any patient can fit comfortable within any of the categories?

Sheila Haworth: Any classification is tested by using it in everyday clinical practice .The classifications we suggested in Panama can be used alongside or instead of the conventional DPC.

Ghazwan Butrous: What is the discussion in North America about the idea of a global or American registry? Is there talk of a small registry to test the classification, or a larger one?

Sheila Haworth: Ian, I am assuming there is a North American registry for pediatric pulmonary hypertension already, or that you are making one at the moment. Is that correct?

Ian Adatia: Yes, there are 8 pediatric centres in the North American pediatric pulmonary hypertension network or PPHNet, which consists of a group interested in pulmonary vascular disease in children. We began modestly and have set up a database that will be residing in Denver Children's Hospital. The plan is to enroll any patient who is evaluated for pulmonary hypertension, as people want different things from the registry. One of the important things about the registry is that we want to trial the Panama classification to help us understand whether that's a useful way of classifying patients, and whether that helps with diagnoses in general. This does not apply to the whole of North America yet but we are only just starting out.

Ghazwan Butrous: Maria, would you like to make any comments on what has been said regarding ideas on how to test the classification, and how to use the registry from a European perspective?

Maria del Cerro: The main difficulty pertaining to the classification, and also in the making of pediatric registries, is the presence of more than one disease process. Using the example of the Spanish registry, we found that a significant proportion of children often have multifactorial diseases. This means that a patient can be in more than one category, which obviously makes classification more complicated. However, I believe that the Panama classification is flexible enough to allow patients to be in more than one category. The design of future registries should take this into account. Continuing with the example of the Spanish registry, the doctor will be able to put a patient into a number of different categories: this makes pediatric registries more complicated and is the reason pediatric classifications



are always more complex. Patients with multifactorial diseases generally comprise about 3% of the registry: in pediatric pulmonary hypertension they may comprise up to 30%.

Ghazwan Butrous: Regarding the classification, what do you expect or envisage from the next PVRI meeting in Cape Town? I know that many pediatricians, who were not present at Panama, have been excited about the new classification and have signed up for the Cape Town meeting. What have you prepared to discuss in Cape Town?

Ian Adatia: I would welcome as much interest as possible, and to document the suggestions people have. I think we did not have direct representation on the Taskforce from Africa, Australia, New Zealand, Japan, China, and for the classification to be universally applicable it is necessary to have feedback and suggestions from all over the world. I certainly think we need to hear from more people and discuss their suggestions. However, I do think that Sheila' point is sensible with regards to not rewriting the classification too early and too frequently. Too many modifications in a small timeframe will likely be too confusing, so I would prefer to let the classification be used for a while and then collect feedback.

In Cape Town, I am very interested in hearing the opinions from the South Africans, especially those who were not present in Panama. I would like to know whether they think more or less categories are necessary in order to improve care for children and include common causes of PHVD that they see in daily practice in Africa.

Sheila Haworth: I think it will be very important to go through this in Africa because I think the balance of causation will be different. It is very interesting: in India we get a high number of cases of Eisenmenger patients, yet in America it is much rarer. I know several American physicians who were shocked at the number of Eisenmenger cases in India. I think we may be in for a similar shock in South Africa when it comes to HIV. I think it is quite important to stress that this diagnostic classification is not just an academic exercise, but needs to function in day-to-day life. It should make it possible for the physicians to communicate very clearly about what type of pulmonary hypertension a child has, and therefore to indicate which expensive but specific medicine he or she needs. The functional classification describes the function of the child according to its age, stage of development, disease etc., so we can monitor the child's progress, and so determine the best continued course of action. It will help us to monitor the response to treatment. The practical usages of the classifications can not be stressed enough.

Ghazwan Butrous: Sheila, you recently returned from the PVRI India meeting. I'm certain some of the attendees read the article on the PH classifications in Pulmonary Circulation. Did they express any concerns, questions or feedback?

Sheila Haworth: No, although I believe that was mostly because we had a very packed programme. It was a two day meeting, and one day was directed almost entirely to the pathologists. In August 2012 we will meet in North India, where a lot of high altitude problems associated with PVD, so I

am certain that there will much discussion of the classifications at that meeting.

Ghazwan Butrous: Maria, you've presented several times on the classification in Europe: What is some of the feedback you received at the meetings?

Maria del Cerro: At most places where the diagnostic classification has been presented (4th International Conference of neonatal and childhood pulmonary vascular disease in San Franscisco, and at the European Society of Pediatric Cardiology), the attendees thought it highly important to have such a classification. Nobody said that it was too confusing or difficult. We have had mostly positive feedback. Of course it is not a perfect classification and will have to be improved. I hope we will have more feedback in the Cape Town. Dr. Gabriel Diaz wrote to me to say that he wanted to create a working group for PH at high altitude. I think this classification will encourage and facilitate more studies, more research, and more collaborative studies between doctors.

Ghazwan Butrous: Very good. As leaders of the Pediatric PH Taskforce, what is your plan to collect feedback regarding the classifications?

Ian Adatia: It would be ideal to ask you if we could have a session in two or three years time at the PVRI Annual Meeting and re-discuss the classification. Then, taking into account the information and suggestions that people made, we may come up with an improved modified classification.

Sheila Haworth: I think Cape Town would be too early to collect feedback and try to modify the classifications. However, I would like to e-mail all the PVRI Fellows involved in pediatric PH and ask them to use it and to let us know of any problems they encounter. We can take that into account when we assess the situation in a year or two.

Maria del Cerro: If in the next months or years we see the classification mentioned in different journals and papers, that will be the best indicator that people are interested in the classification and are getting to know it. In fact, I have already received several requests from different authors who would like to mention the classification in the papers, so it seems to be going in the right direction. I think we should certainly continue on this path.

Ghazwan Butrous: Do you think this classification will be of any clinical value in treatment or in prognosis, or is it only an academic exercise to concentrate our attention on the understanding of the disease?

Ian Adatia: By defining the disease better, we will be able to develop meaningful cohorts of patients in whom to assess therapy. If we don't have homogeneous representation we have no idea why a therapy does or doesn't work. Groups of cohort homogeneous patients with pulmonary hypertension are essential for a better understanding of the disease and the classification hopefully allows for more this more sophisticated approach.



Maria del Cerro: The classification never pretended to be an academic exercise. On the contrary, it focuses on gathering the clinical experiences of doctors treating patients. Therein lies its value. Perhaps it looks so complex because it isn't academic- rather, it is based in reality. It has enormous educational value: anyone who wants to treat children with pulmonary hypertension should read the classification. I learned a lot by working with the other people in the taskforce.

Sheila Haworth: I think the diagnostic classification is very important as it will perhaps oblige doctors to think very carefully about the aetiology of every case they see, and as a result to describe that case more accurately than they might otherwise have done. In its way, I think it is actually quite a rigorous academic exercise, and this matters because we need to understand why the child has pulmonary hypertension. That knowledge will aid us in therapy and is also very important for the design of future clinical trials, as we must actually know what the child is suffering from when entering a child into the trial. The importance of the functional classification is self-evident as you need a way of assessing a child’s exercise tolerance and wellbeing, and of describing and monitoring the natural history of the condition. A functional classification must take a developmental approach as you follow the maturation and changes of the child over the years- in that sense the classification should really allow for all the stages between small child and young adult.

GENERAL COMMENTS

Maria del Cerro: I would like to invite the readers to make any comments pertaining to the classifications or this interview in the PVRI website via a blog, or to communicate by e-mail so we can get feedback. I also hope that many of the Cape Town attendees will give us their ideas, speculation and feedback during and after the meeting.

Ian Adatia: I agree with Maria; we want to hear from as many people as possible to improve the classification. I hope that this project will help us understand adult pulmonary hypertension better as well. My bias is that many adults have had PH for much longer than we think, and the origins may be in prenatal life. The classification may be a tool in establishing this theory.

Sheila Haworth: Classifications should improve our understanding of a disease process and facilitate clear communication between all those caring for the patient. Only by listening to the experience of everyone using the Diagnostic and Functional Classifications we put forward in Panama can we improve the classifications and move forward to improve the care of children with pulmonary hypertension.

ACKNOwLEDGMENT

We are grateful to Ms. Nikki Krol, for the help in the transcription of this interview.

Footnote:(1) Lammers AE, Adatia I, Cerro MJ, Diaz G, Freudenthal AH, Freudenthal F, Harikrishnan S, Ivy D, Lopes AA, Raj JU, Sandoval J, Stenmark K, Haworth SG., Functional classification of pulmonary hypertension in children: Report from the PVRI pediatric taskforce, Panama 2011. Pulm Circ. 2011 Aug 2;1(2):280-285.http://www.pulmonarycirculation.org/article.asp?issn=2045-8932;year=2011;volume=1;issue=2;spage=280;epage=285;aulast=Lammers(2) Cerro MJ, Abman S, Diaz G, Freudenthal AH, Freudenthal F, Harikrishnan S, Haworth SG, Ivy D, Lopes AA, Raj JU, Sandoval J, Stenmark K, Adatia I.; A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: Report from the PVRI Pediatric Taskforce, Panama 2011.Pulm Circ. 2011;1(2):286-298.http://www.pulmonarycirculation.org/article.asp?issn=2045-8932;year=2011;volume=1;issue=2;spage=286;epage=298;aulast=del

Figure 2: Imaged during the video conference interview top Ian Adatia, inset Ghazwan butrous) left bottom: Nikki Krol, midddle bitton Ian Adatia, middle right: Maria del Cerro:

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iEw Pulmonary Hypertension in Children:

The First Book Written in SpanishAuthors: Gabriel F Diaz, Julio Sandoval, Augusto Sola 1a. edición; 2011 ISBN 978958837935-7 DINSA 55,00 €

“Hipertensión pulmonar en niños” (Pulmonary hypertension in children) is presented as the first book written in Spanish that focuses on that pathology related to paediatric patients. This monograph, whose chief editor is Professor Gabriel F. Diaz (FPVRI) from the National University of Colombia, follows the premise that a child is not a small adult, and provides an updated view into the clinical features that differentiate pulmonary hypertension in paediatrics. The book details the definition and the treatment of the illness, and recounts the difficulty of extending and improving patients’ lives, as the treatment is dependent on an early diagnosis. This presents an additional challenge in children, and Prof. Diaz gathers experts from around the world to discuss the process and its various difficulties in detail in an attempt to identify and fill knowledge gaps regarding pulmonary hypertension in children. Though not all information is equally valuable, the aim is to give doctors all the necessary tools to manage the disease.

In that sense, the book is a triumph. There is no doubt that the manuscript as edited by Dr. Diaz FPVRI, Dr. Sandoval FPVRI and Dr. Sola, has great value within the field- it directly addresses the problem that most of our knowledge of pulmonary vascular diseases has been obtained in studies with adults, which often does not apply to treatment in children. As the aim is to move quickly and effectively, and also considering the ethical implications, clinicians often find themselves left with little choice but to try and apply that knowledge to the child patient. Throughout the work, the authors take an extensive tour that covers everything from general aspects that define the disease to the recent scientific advances regarding the pathogenesis, genetics, diagnosis, classification, and treatment including transplantation and future perspectives. In addition, unlike many other works it also focuses on discussing the issues related to altitude. Since both the altitude and the resulting hypoxia are two important factors for the development of the disease, especially in children, this is a refreshing approach considering most of paediatric hypertension studies have been conducted at low altitudes close to the sea level.

The book is not unique in its efforts, but it does stand out. The Spanish language is one of the most widely used languages on the planet, but much of the literature regarding pulmonary vascular diseases is predominantly written in English. This book bucks the trend and so taps into a large audience of interested non-English speakers, which is crucial for the development of better treatments for children with PVDs.

“Hipertensión pulmonar en niños” is also versatile. The early chapters feature an interesting historical journey that tracks the first mention of the disease as pulmonary arterial sclerosis around 1851 to the latest developments in the Dana Point, as presented at the Fourth International Symposium on Pulmonary Hypertension. Regrettably, the book precedes the recent advances presented at the 5th annual meeting of the Pulmonary Vascular Research Institute in Panama City (2011). However, it does discuss the issues related to the different classifications. Chapter Two focuses in more detail on criticism of the current classification, leaving us "with a mouth watering feeling", and bringing to our attention a classification made by Dr. MJ del Cerro et al., which was presented in Panama City and later published in August’11 in Pulmonary Circulation (Vol 1: Issue 2). The book’s body provides an in-depth description of the genetic aspects and associated risk factors, the molecular pathogenesis of the disease and the histopathological features characteristic of each type of patient according to the group in which they are classified. Moreover, an important part of the book focuses on the origin of the disease in children native to moderate and high altitudes. The hypoxia that these patients are subjected to from their birth and throughout their lives has an important role in the appearance and development of pulmonary hypertension yet is often overlooked in the literature. This specific perspective is well served in this excellent and versatile manuscript.

At this point the book invites us to consider several main features in the treatment of pediatric patients. From fetus to adulthood, this manuscript speaks not only about mechanical, biochemical, enzymatic, molecular and genetics factors, but also about the epidemiology and the clinical manifestations; in short, everything a paediatrician needs to successful diagnose and treat his patients.

The last chapters review the current methods of diagnosis, from clinical examination to the analysis of biomarkers but also regarding chest radiograph, electrocardiogram, ultrasound, MRI or catheterization, among others. As a coda, a final chapter talks about the different treatments (including surgery and transplantation), only to conclude that, despite the progress made to date, the therapeutic resources available now are still insufficient. This allows the editors to engage with the continuing research into new ways, redefined targets and novel molecules that may reduce functional limitations of pulmonary hypertension patients and, consequently, improve the bad prognosis.


Oliver: PH in children – The Spanish book

Beyond its implications for clinical use, the book also delivers from an educational point of view. For example, Chapter Six was especially useful in its discussion on histopathological aspects, which collects an extensive classification based on these characteristics. This includes a wide range of color images showing lung sections and the different lesions – important tools, not only for diagnosis, but also for researchers.

One minor point is that the very inclusiveness of “Hipertensión pulmonar en niños” sometimes turns repetitive, especially at points in the main chapters that specifically focus on the children. These could be better summarized at the beginning of the book and only referred to throughout to avoid repetition. In rare parts, the work sometimes appears more like a collection of translated reviews instead of a new monograph. Yet it is unparalleled in the achievement of its aim to gather current information regarding PVDs in children in one place, and so provide pediatricians with a more complete set of tools. From a clinical point of view, the final chapters are especially relevant in their focus on methods of diagnosis, as well as the chapter that looks at catheterization

and includes examples on how to do hemodynamic calculations. The benefits of the manuscript certainly outweigh its small beauty flaws.

In short, “Hipertensión pulmonar en niños” is an interesting book which captures vast amounts of necessary information in relation to pulmonary hypertension. The work is not only useful to the pediatrician, but also to any other health professional dedicated to this disease. It is beneficial both for clinical use as a guide for the management of the disease, and also for those like me, who are dedicated to basic research but do not want to forget that at the end of all it is still the patient and its clinical consequences. Just be aware that people interested to read this recommended monograph must be familiar with the language of Cervantes.

Eduardo OliverDivision of Experimental Medicine. Centre for Pharmacology &

Therapeutics. Imperial College London, E-504, Burlington Danes Building, Hammersmith Campus, Du Cane Road, W12 0NN

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M "Impaired oxidative metabolism and enhanced glycolysis in right ventricular hypertrophy: The Warburg effect", published in PVRI Review, Disease mechanisms in PVD. 2009 vol.1, issue 3, pp: 163-166, authored by: Lin Piao, Peter T. Toth, Dalia Urboniene, Stephen L. Archer.

The M-mode images for the Figure 2(a) in the published version (2009) were incorrect. The correct version contains all new images for the figure 2(a). The images for the PAAT (Doppler) were changed to match the images for RVFW (M-mode). The current images have been recorded using the high resolution ultrasound system Vevo770 (VisualSonics).

Figure 2: The properties of RVH induced by monocrotaline (MCT). (a) Right ventricular free wall (RVFW, <-> in green) is thickened and pulmonary artery acceleration time (PAAT, - in red) is shortened in the MCT group vs control (CTR) by applying M-mode with two-dimensional guidance (RVFW) and pulsed-wave Doppler (PAAT) echocardiography


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PVRI Review 3:2 2011