Pulmonary Circulation Summer 2018 Update
Pulmonary Circulation receives its second Impact Factor of 2.283!
We are delighted to announce that Pulmonary Circulation received its second Impact Factor of 2.283 on 26 June 2018. The journal Impact Factor is the measure reflecting the yearly ratio of number of citations to recent articles published.
This is an increase from last year's Impact Factor of 2.178, indicating that authors know our journal is a forum for high quality research. Pulmonary Circulation is now ranked 37/59 journals (up from 40th) in Respiratory Systems, and 65/128 (up from 69th) in Cardiology.
This is an excellent achievement for a young journal, and it’s a tribute to our Editors-in-Chief Jason Yuan and Nick Morrell. Since the beginning of 2017, Dr. Yuan and Dr. Morrell have been supported by Deputy Editors Kurt Stenmark and Irene Lang. Congratulations to the editorial leadership team for this achievement!
Thank you to our authors, reviewers, and all who have cited Pulmonary Circulation articles in the past two years. We look forward to continuing to publish comprehensive review articles and high-quality original research articles in the coming years.
Increasing in Impact and in Influence
A journal's influence is indicated by its numbers of readers and our readership is growing at a staggering rate. Since launch, our articles have been downloaded over half a million times. Download numbers are currently increasing by 50% each year, evidence that Pulmonary Circulation is an increasingly important outlet for the most important research in pulmonary vascular disease.
Partnership with SAGE Publishing
Since January 2017, we have partnered with SAGE Publishing to publish and promote the journal online. SAGE is one of the world's leading journal publishers and has 50 years of experience publishing journals in medicine, science, technology, social sciences, and the humanities. Pulmonary Circulation beneﬁts from increased global visibility, faster publication times, and SAGE's wealth of knowledge and commitment to scholarship and innovation.
To submit your new manuscript to Pulmonary Circulation, use the SAGE submission portal: https://mc.manuscriptcentral.com/pulmonarycirculation
13th PVRI Annual World Congress on PVD, Barcelona – January 2019
Put the date in the diary: 31 January 2019 – 3 February 2019, Barcelona, Spain
Thank you to the Scientific Committee which is in charge of the program for this event: Joan-Albert Barbera, University of Barcelona; Sébastien Bonnet, Laval University; Anna Hemnes, Vanderbilt University; Christophe Guignabert, University of Paris-Sud; Steeve Provencher, Laval University; Soni Savai-Pullamsetti, University of Giessen. We are also thankful to our membership from all around the world for sending their suggestions for topics, all of which have been passed on to the committee for consideration.
See you in Barcelona!
PC Featured Articles
Tim Crowe, Geeshath Jayasekera, Andrew J. Peacock
First published December 28, 2017, Volume: 8, Issue: 1
Non-invasive tests of RV function to determine prognosis and response to treatment in patients with PH is essential. Although the right ventricle is the focus of attention, it is clear that cardiac interaction can cause left ventricular dysfunction, thus biventricular assessment is paramount. There is also focus on the atrial chambers in their contribution to cardiac function in PH. Furthermore, there is evidence of regional dysfunction of the two ventricles in PH, so it would be useful to understand both global and regional components of dysfunction. In order to understand global and regional cardiac function in PH, the most obvious non-invasive imaging techniques are echocardiography and cardiac magnetic resonance imaging (CMRI). Both techniques have their advantages and disadvantages. Echocardiography is widely available, relatively inexpensive, provides information regarding RV function, and can be used to estimate RV pressures. CMRI, although expensive and less accessible, is the gold standard of biventricular functional measurements. The advent of 3D echocardiography and techniques including strain analysis and stress echocardiography have improved the usefulness of echocardiography while new CMRI technology allows the measurement of strain and measuring cardiac function during stress including exercise. In this review, we have analyzed the advantages and disadvantages of the two techniques and discuss pre-existing and novel forms of analysis where echocardiography and CMRI can be used to examine atrial, ventricular, and interventricular function in patients with PH at rest and under stress.
Keywords: pulmonary arterial hypertension, pulmonary hypertension, magnetic resonance imaging, echocardiography, right ventricle function and dysfunction
Original Research Article
Ting Wang, Mary E. Brown, Gabriel T. Kelly, Sara M. Camp, Joseph B. Mascarenhas, Xiaoguang Sun, Steven M. Dudek, Joe G.N. Garcia
First published March 9, 2018, Volume: 8, Issue: 1
Sphingosine 1-phosphate (S1P) is a potent bioactive endogenous lipid that signals a rearrangement of the actin cytoskeleton via the regulation of non-muscle myosin light chain kinase isoform (nmMLCK). S1P induces critical nmMLCK Y464 and Y471 phosphorylation resulting in translocation of nmMLCK to the periphery where spatially-directed increases in myosin light chain (MLC) phosphorylation and tension result in lamellipodia protrusion, increased cell-cell adhesion, and enhanced vascular barrier integrity. MYLK, the gene encoding nmMLCK, is a known candidate gene in lung inflammatory diseases, with coding genetic variants (Pro21His, Ser147Pro, Val261Ala) that confer risk for inflammatory lung injury and influence disease severity. The functional mechanisms by which these MYLK coding single nucleotide polymorphisms (SNPs) affect biologic processes to increase disease risk and severity remain elusive. In the current study, we utilized quantifiable cell immunofluorescence assays to determine the influence of MYLK coding SNPs on S1P-mediated nmMLCK phosphorylation and translocation to the human lung endothelial cell (EC) periphery . These disease-associated MYLK variants result in reduced levels of S1P-induced Y464 phosphorylation, a key site for nmMLCK enzymatic regulation and activation. Reduced Y464 phosphorylation resulted in attenuated nmMLCK protein translocation to the cell periphery. We further conducted EC kymographic assays which confirmed that lamellipodial protrusion in response to S1P challenge was retarded by expression of a MYLK transgene harboring the three MYLK coding SNPs. These data suggest that ARDS/severe asthma-associated MYLK SNPs functionally influence vascular barrier-regulatory cytoskeletal responses via direct alterations in the levels of nmMLCK tyrosine phosphorylation, spatial localization, and lamellipodial protrusions.
Keywords: sphingosine 1-phosphate, S1P, nmMLCK, SNP
Original Research Article
Valentina Mercurio, Grace Peloquin, Khalil I. Bourji, Nermin Diab, Takahiro Sato, Blessing Enobun, Traci Housten-Harris, Rachel Damico, Todd M. Kolb, Stephen C. Mathai, Ryan J. Tedford, Carlo G. Tocchetti, Paul M. Hassoun
First published April 17, 2018, Volume: 8, Issue: 1
Atrial arrhythmia (AA) occurrence in pulmonary arterial hypertension (PAH) may determine clinical deterioration and affect prognosis. In this study we assessed AA incidence in idiopathic (IPAH) and systemic sclerosis related PAH (SSc-PAH) and evaluated risk factors, management, and impact on mortality. We collected baseline data from consecutive IPAH or SSc-PAH patients prospectively enrolled in the Johns Hopkins Pulmonary Hypertension Registry between January 2000 and July 2016. During follow-up AA onset, treatment, and outcome were recorded. Among 317 patients (201 SSc-PAH, 116 IPAH), 42 developed AA (19 atrial fibrillation, 10 flutter-fibrillation, 9 atrial flutter, and 4 atrial ectopic tachycardia) with a 13.2% cumulative incidence. Most events were associated with hospitalization (90.5%). Electrical or pharmacological cardioversion was attempted in most cases. Patients with AA had higher right atrial pressure, pulmonary wedge pressure (P < 0.005), NT-proBNP (P < 0.05), and thyroid disease prevalence (P < 0.005). Higher mortality was observed in patients with AA, though not statistically significant (LogRank P = 0.323). Similar long-term mortality between IPAH with AA and SSc-PAH without AA was observed (LogRank P = 0.098). SSc-PAH with AA had the worst prognosis. In PAH patients AA occurrence is a matter of significant concern. Therapeutic strategies aimed at restoring sinus rhythm may represent an important goal.
Keywords: atrial arrhythmias, pulmonary arterial hypertension, systemic sclerosis
Original Research Article
Jules Hernández-Sánchez, Louise Harlow, Colin Church, Sean Gaine, Emily Knightbridge, Kate Bunclark, Dee Gor, Alun Bedding, Nicholas Morrell, Paul Corris, Mark Toshner
First published December 3, 2017, Volume: 8, Issue: 1
Our aim is to assess the safety and potential efficacy of a novel treatment paradigm in pulmonary arterial hypertension (PAH), immunomodulation by blocking interleukin-6 (IL6) signaling with the IL6 receptor antagonist, tocilizumab. Inflammation and autoimmunity are established as important in PAH pathophysiology. One of the most robust observations across multiple cohorts in PAH has been an increase in IL6, both in the lung and systemically. Tocilizumab is an IL-6 receptor antagonist established as safe and effective, primarily in rheumatoid arthritis, and has shown promise in scleroderma. In case reports where the underlying cause of PAH is an inflammatory process such as systemic lupus erythematosus, mixed connective tissue disease (MCTD), and Castleman’s disease, there have been case reports of regression of PAH with tocilizumab. TRANSFORM-UK is an open-label study of intravenous (IV) tocilizumab in patients with group 1 PAH. The co-primary outcome measures will be safety and the change in resting pulmonary vascular resistance (PVR). Clinically relevant secondary outcome measurements include 6-minute walk distance, WHO functional class, quality of life score, and N-terminal pro-brain natriuretic peptide (NT-proBNP). If the data support a potentially useful therapeutic effect with an acceptable risk profile, the study will be used to power a Phase III study to properly address efficacy.
Keywords: clinical studies, immunotherapy, pulmonary hypertension
A message from PVRI President, Paul Corris, M.D.
It is with a deep sense of responsibility, humility and pleasure that I take over the baton from Glennis in accepting the role of President of PVRI. Glennis has been an absolute bundle of efficient energy and in her two years of office has overseen a major transformation of PVRI from a club to a fully established scientific society. PVRI has grown from its childhood and teenage years into young adulthood and a transition from paediatric to adult care is now necessary.
In Rome, we launched our fantastic new website which has been built with the collaboration of the PVRI Head Office team, a specialist web-design agency and the energetic members of our Committee for Young Clinicians & Scientists. The considerable investment in time and resources this has required will provide a highly functioning platform for all our members and will greatly enhance the work of PVRI.
On that topic, 2016 sees a major launch of a web-based education programme, a focus on Pulmonary Circulation and a review of the structure of the various task forces.
The British relay teams have recently shown an annoying habit of dropping the baton in athletic finals, but I can assure all that I have no intention of dropping the PVRI baton. Seriously though, I have a tough act to follow, but rest assured that I will be working hard to maintain impetus and ensure that the PVRI’s adulthood continues in the right direction.
Many thanks to Glennis for her competent captaincy and commitment and if you think I employ too much alliteration in my writing, you’re absolutely correct!
PVRI Membership - Join or Renew today!
If you haven’t already renewed your PVRI membership, it’s now time to log-in and do so.
If you're not already a member of the PVRI, there are many benefits in joining. Our new website has all the latest information on pulmonary hypertension and PVD available to you and with over 800 e-learning materials, Pulmonary Circulation articles and PVRI Chronicle articles, there is something of interest for everyone. Only paid members can now view the e-learning content, so it is important you sign up. You have a 30-day free membership trial, just in case you change your mind.
A conversation with Dustin R. Fraidenburg, M.D., Chief Fellow in Pulmonary, Critical Care Medicine at the University of Illinois at Chicago.
Dr. Dustin Fraidenburg earned his M.D. at Wayne State University in Detroit, Michigan and did his residency in Internal Medicine at the University of Illinois at Chicago. He is in his final year of fellowship training in Pulmonary, Critical Care medicine at the University of Illinois at Chicago, where he has served as Chief Fellow since 2015. Dr. Fraidenburg serves on the Pulmonary Circulation Writing and Consulting Committee.
PC: What is your area of research interest and what projects are you currently involved in?
DF: My research focuses primarily on studying the cellular and molecular mechanisms of hypoxic pulmonary vasoconstriction and my current project is concentrated on how acute lung inflammation and injury affects hypoxic pulmonary vasoconstriction. In particular, how upregulation of the NFAT transcription factor during acute lung inflammation can affect pulmonary artery vasoreactivity through its effects on functional and transcriptional regulation of calcium channels in pulmonary artery smooth muscle cells. My project takes a unique approach to tackling the ventilation-perfusion mismatch which leads to profound hypoxemia in patients with acute respiratory distress syndrome. I believe a better understanding of mechanisms that impair hypoxic pulmonary vasoconstriction, a product of evolution meant to protect the diseased lung, could very well lead to distinctive therapeutic targets in ARDS among many other lung diseases.
PC: Why did you specialize in PVD?
DF: Pulmonary vascular disease was and still is a rapidly expanding area of research in respiratory diseases and there have been such great strides recently in both basic science, translational, and clinical research that I knew there was abundant opportunity to do research to discover the disease mechanisms involved, help patients, and develop a solid academic career. The people that have been on my side throughout my training are definitely the reason that I have both enjoyed and prospered in research on pulmonary vascular disease. I have had the pleasure of working with some amazing mentors as well as colleagues that shared my desire to produce really great research.
PC: What is the most exciting new topic in PVD research right now?
DF: There are so many researchers doing great work in the field. One of the really interesting things out there to read about right now is the lung-on-a-chip coming out of Harvard. New technologies and innovative techniques are really going to revolutionize both drug development as well as our understanding of many disease processes.
PC: What’s “lung-on-a-chip”?
DF: The lung-on-a-chip is a really unique three dimensional model of the human lung. It is a small chip containing airway epithelial cells on one side of a membrane that are exposed to oxygenated gas and pulmonary vascular cells on the opposite side of the membrane with culture media or solutions mimicking blood that flow across it. Additionally, there is a vacuum to create stretching forces on each side to mimic the changes of respiration. This allows experimental modeling of various injuries or therapies which will have wide ranging implications in basic science and translational research. (For more information, see the Wyss Institute at Harvard's website.)
PC: Where do you hope to see the field of PVD research in five years?
DF: In 5 to 10 years from now I very much expect the divisions between basic science and clinical research to become further blurred. I fully expect that the continued challenges researchers are faced with (for example, securing research funding and the distribution of public dollars to science) will lead to a revolution in how research is now divided as a necessary step to improve our effectiveness. Additionally, with mobile technology and social media making the world ever smaller, collaboration will be essential to our efficiency as researchers. Removing the redundancy from the system and illuminating the strengths of each group will help everyone to focus on our ultimate goal, the eradication of human disease. For research on pulmonary vascular disease in particular, I feel that a new generation of therapeutic agents for pulmonary hypertension will become available. It will be interesting to see therapies that shift from the pulmonary vasodilators, which will remain mainstays in treatment, to focus on mechanisms of maladaptive right ventricular remodeling or reversal of vascular remodeling with unique cellular and genetic targets.
PVRI Report - 10th PVRI Annual World Congress on PVD
PVRI President's Blog
2016, No. 1, First Quarter Edition
Welcome to the first joint edition of PVRI/PC Journal News!
Pulmonary Circulation is proud to be the official journal of the Pulmonary Vascular Research Institute (PVRI), the only global medical research charity dedicated to the fight against pulmonary vascular diseases.
The PVRI’s three guiding principles are to Inform, Collaborate, and Combat.
PVRI informs its members and the wider research community by providing educational materials and a world-class journal dedicated to communicating research on pulmonary vascular disease; its members come together from all across the globe to collaborate in the search for a cure for PVD; and they bring together clinicians, research scientists, pharmaceutical companies, and regulatory bodies to find new ways to combat the disease.
It is our honor to be able to work in tandem with the PVRI to bring new insight, engagement and collaboration to the fight against pulmonary hypertension and pulmonary vascular diseases.
What's Inside This Issue
- President’s Blog - a message from the incoming president of the PVRI, Dr. Paul A. Corris;
- Featured Articles from the latest issue of Pulmonary Circulation;
- Researcher Spotlight - an interview with PC Writing & Consulting Committee member, Dr. Dustin Fraidenburg, on his research, interests and hopes for the future of PH and PVD research;
- PVRI Report - on the 10th PVRI Annual World Congress on PVD in Rome;
- PH in the News - our new regular feature by the PVRI Committee for Young Clinicians & Scientists;
- Mark Your Calendar! - announcements for exciting upcoming events.
As always, if you have any thoughts, ideas, or suggestions concerning Pulmonary Circulation, or would like to submit a reader’s comment to appear in the next issue of PC/PVRI News, please contact Managing Editor, Annisa Westcott at firstname.lastname@example.org.
The 10th PVRI Annual World Congress on Pulmonary Vascular Disease was held in the beautiful city of Rome, Italy on 14-17 January 2016.
This year's conference took place at the Rome Cavalieri, Waldorf-Astoria, atop the highest of Rome's seven hills, Monte Mario. With its breathtaking views of the city of Rome, the venue was a unique setting in which our over two hundred attendees came together with great enthusiasm to share knowledge, make new connections and solidify previous collaborative relationships.
The scientific programme was put together through the diligent efforts of many members of the PVRI, chief among them former PVRI president, Sheila Glennis Haworth, North American Task Force leader, Kurt Stenmark, and European Task Force leaders, Dario Vizza and Stefano Ghio. We extend our most sincere thanks for their hard work.
Logistically speaking, we have PVRI Operational Team members Andrea Rich, Stephanie Barwick, Aaron Shefras and Margaret Carver to thank for their extraordinary efforts in arranging the venue, the sightseeing tours and the Gala Dinner. Their above-and-beyond attitude, can-do spirit and healthy sense of humour made the event a phenomenal success.
The conference sessions and task force breakout meetings provided many hours of engaging discussion on the most up-to-the-minute and important topics in the field of pulmonary hypertension and pulmonary vascular disease. Each of the sessions will be available for viewing on the PVRI website shortly.
The PVRI Annual General Meeting and the semi-annual Pulmonary Circulation Editorial Board Meeting were also held during the congress. Both meetings were met with much enthusiasm and elicited great ideas for our future from all participants.
- 223 attendees from 28 different countries from around the world
- 53 speakers, chairs and facilitators
- First PVRI event that received CME registration. The event was accredited by the ECCME (European Council for Continuous Medical Education) and received a total of 17 CME credits.
- Overwhelming positive feedback
2016 PVRI Award Winners
As is our tradition, several awards were presented during the Gala Dinner to members of the PVRI who have made outstanding contributions to the field of PVD and to the PVRI. We again extend congratulations to all our prize winners.
- Lewis Rubin received the Lifetime Achievement Award in recognition of his distinguished contributions to advances in patient care and research in PVD.
- Nick Morrell received the 2015 Achievement Award for his outstanding contribution to medical research, to the PVRI and to its journal Pulmonary Circulation as co-Editor-in-Chief.
- Ian Adatia and the PVRI Paediatric Task Force received the 2015 Certificate of Achievement in recognition of their outstanding contributions to the PVRI. Unfortunately, Ian could not make it to the Gala Dinner to accept this award.
In conclusion, the 10th PVRI Annual World Congress on Pulmonary Vascular Disease was an overwhelming success, our largest conference to date, and a magnificent opportunity for the advancement of our understanding of the pathobiology and treatment of pulmonary hypertension and pulmonary vascular disease. We may not have a cure yet, but each time we bring together the great minds working on PVD we create a fertile environment from which curative strategies and options may grow.
Please join us next year in Miami, Florida for our 11th PVRI Annual World Congress, on 26-29 January 2017!
PH in the News
Study Reports an Association Between Pulmonary Hypertension and Non-Dialysis Dependent Chronic Kidney Disease
Mariella Vélez Martínez
PVRI Committee for Young Clinicians & Scientists
Chronic kidney disease (CKD) carries an increased risk for incurring cardiovascular disease morbidity and mortality. Traditional factors influencing an elevated risk in CKD patients include hypertension, diabetes, and hypercholesterolemia. Pulmonary hypertension (PH) is also an important contributor to cardiovascular disease morbidity, and has not yet been fully studied in the non-dialysis dependent CKD population. However, authors from a recently published article in theJournal of the American Society of Nephrology concluded that PH is an independent predictor of cardiovascular and all-cause mortality in non-dialysis dependent CKD. (Navaneethan S, et al. Journal of the American Society of Nephrology, published online before print September 18, 2015, doi: 10.1681/ASN.2014111111).
This study used the data from the Chronic Renal Insufficiency Cohort (CRIC) Study to evaluate the prevalence, risk factors and clinical outcomes of pulmonary hypertension, as measured by echocardiography (pulmonary artery systolic pressure [PASP] > 35 mmHg and/or tricuspid regurgitant velocity [TRV] >2.5 m/s), in this patient population. The CRIC Study was established in 2003 and enrolled approximately 3000 patients, with a broad spectrum of renal disease severity, at seven sites and followed participants for up to 5 years.
The investigators found a prevalence of PH of 21% in this population. They also identified the following risk factors associated with PH in this patient population: older age, non-Hispanic blacks, a lower estimated glomerular filtration rate (eGFR), and comorbid conditions, such as obesity and diabetes. In a cross-sectional multivariable model, those patients who were older, with anemia, lower left ventricular ejection fraction, and left ventricular hypertrophy had a higher chance of having PH as measured at the year 1 CRIC study visit.
After a median follow up of approximately 4 years and adjusting for confounders, the investigators found that the presence of PH was associated with an elevated risk for all-cause mortality and cardiovascular outcomes. In addition, higher ranges of TRV and PASP were shown to predict a higher risk of cardiovascular events and all-cause mortality, including a higher risk for congestive heart failure, even in those without preexisting heart failure.
The authors concluded having used an echo-based definition of PH in their study is a well-known limitation, given that “the sensitivity and specificity of echocardiography to diagnose PH are modest (83% and 72% respectively).” They did perform sensitivity analyses in light of this known limitation. The analyses indeed confirmed that a TRV > 2.9 m/sec imparts a higher risk of cardiovascular events and mortality. The investigators also noted that their study did not determine the etiology of the association between PH and poor outcomes in this population, due to the epidemiologic nature of the investigation. Finally, the authors concluded that more mechanistic studies are needed in order to further investigate the etiology of this association.
Mark Your Calendar!
PVRI Chronicle - February
Keep an eye out for the next edition of the PVRI Chronicle, Volume 3, Issue 1. It will be available via the PVRI website by end of February, 2016.
PVRI Charity Dinner and Auction of Promises - April
The PVRI will be holding a Charity Dinner and Auction at the Foundling Museum in London, 19 April, 2016. There will be lots of exciting auction prizes to bid on and all proceeds go to charity. Watch the PVRI website for further information.
ATS 2016 Get-Together in San Francisco - May
Following the success of last year's event, we are planning to hold another PVRI Get-Together during the ATS in San Francisco, 13-18 May, 2016. Watch the PVRI website for registration details.
3rd Annual PVRI Drug Discovery & Development Symposium in Bethesda, USA - July
Save the date in your diary: 11-12 July, 2016, at the Bethesda North Marriott Hotel & Conference Center - 5701 Marinelli Road North, Bethesda, MD 20852. We are delighted to announce that the FDA is a co-sponsor of the meeting. Click here to download the full scientific agenda. More information can be found on the PVRI website, here.
Registration is now open!
We have a new website!
Pulmonary Circulation is proud to announce the launch of the new PVRI website at www.pvri.info. A joint effort between PVRI and PC, the Pulmonary Circulation side of the website features free access to all articles published in the journal, plus journal information and news, and on the PVRI side you will find all the specialised educational and collaborative content available to the general public, alongside even richer content and features in its members-only site. The website is rich with valuable content produced through collaboration with all of our members and numerous experts in pulmonary vascular disease.
On the journal side, you will soon be able to access all of the articles published in PC since its inception in 2011, along with our freshest articles, ahead of print. Please visit “Explore the Journal” to read PC, the “Info for Authors” page for information relating to the submission of articles, our “About” page for information about our editors and editorial board, and, of course, the “News” page for journal news and press releases.
The new website offers users a new, friendlier experience and a richer forum for collaboration in the fight against pulmonary vascular disease.
We are proud to be the official peer-reviewed journal of the Pulmonary Vascular Research Institute.