Research Projects

Immediate past and future research projects include the multipaper expert consensus statement on pediatric PH, normal reference values for non-invasive diagnostics, a survey and subsequent patient registry on children with both chronic (parenchymal) lung disease and pulmonary hypertension (e.g. bronchopulmonary dysplasia). Additional research projects are already in preparation or can be proposed by PVD network members.

Publications

In the last 30 years, rapid, accelerated knowledge gain due to an increasing number of publications on pathobiology and clinical trials have led to more tailored (“personalized”), goal oriented treatment modalities for PAH. From 2015-2020, new insights into metabolic dysregulation and previously unknown gene mutations, and high impact, high volume, longterm randomized controlled trials (RCT) using combined outcomes such as “first morbidity and mortality”, have been published, leading to the approval of more PAH drugs acting on previously known pathways. However, prospective studies in children and adolescents with PAH are largely lacking (only one RCT published by May, 2020). In 2020, the EPPVDN published the two first prospective observational studies on the use of selexipag (Hansmannn G et al., J Heart Lung Transpl, 2020; doi:…..) and macitentan (Schweintzger S et al. Cardivasc Diagn Ther, 2020; doi:….).

Meetings & Workshops

On April 7, 2016, the PVD Network conducted the worldwide first hands-on workshop on pediatric PH. The workshop included an introductory talk on echocardiography by Prof. Martin Köstenberger, hands-on teaching with live cases in the echo and cath labs, an ECMO circuit and specific ICU issues, including iNO and HFOV. Next day our PH Symposium took place in Hannover. Future PH workshops and scientific PH meetings are in preparation.

PVD Network Videos

For example: Video summary of the PAH-Genetics abstract by Dr. Juha Koskenvuo – presented at the Pulmonary Hypertension Symposium – Update 2016 in Hannover, Germany.

Research on PH and Heart Failure

In the last 30 years, rapid, accelerated knowledge gain due to an increasing number of publications on pathobiology and clinical trials have led to more tailored (“personalized”), goal oriented treatment modalities for PAH. New insights into metabolic dysregulation and previously unknown gene mutations, and high impact, high volume, longterm randomized controlled trials (RCT) using combined outcomes such as “first morbidity and mortality”, have been published, leading to the approval of more PAH drugs acting on previously known pathways. However, prospective studies in children and adolescents with PAH are largely lacking.

The number of publications addressing experimental therapies in PAH began to increase in 1995 after landmark studies in human PAH tissues and randomized controlled clinical PAH trials had been published.

Legend:

To evaluate the number of publications addressing experimental therapies in pulmonary arterial hypertension (PAH), the search engine Web of Science, which is a citation database of research literature, was used (www.webofknowledge.com). In the advanced search options we refined our outline query to Pulmonary Arterial Hypertension AND therapies and analyzed the Number of publications within the years 1990 and 2019.

In the last 30 years, rapid, accelerated knowledge gain due to an increasing number of publications on pathobiology and clinical trials have led to more tailored (“personalized”), goal oriented treatment modalities for PAH. New insights into metabolic dysregulation and previously unknown gene mutations, and high impact, high volume, longterm randomized controlled trials (RCT) using combined outcomes such as “first morbidity and mortality”, have been published, leading to the approval of more PAH drugs acting on previously known pathways. However, prospective studies in children and adolescents with PAH are largely lacking.

The number of publications addressing experimental therapies in PAH began to increase in 1995 after landmark studies in human PAH tissues and randomized controlled clinical PAH trials had been published.

Legend:

To evaluate the number of publications addressing experimental therapies in pulmonary arterial hypertension (PAH), the search engine Web of Science, which is a citation database of research literature, was used (www.webofknowledge.com). In the advanced search options we refined our outline query to Pulmonary Arterial Hypertension AND therapies and analyzed the Number of publications within the years 1990 and 2019.

Molecular Targets of Future Pulmonary Hypertension Therapies Adressing RV Dysfunction (2020)

By July 2020, more than 10 drugs have been approved for the treatment of adult PAH, all of which are primarily vasodilators. More than 35 randomized controlled trials (RCT) have shown a moderate effect of these agents (PDE5 inhibitors, ERA, prostacyclin analogues) – based on short-term improvement in functional capacity or longer time to clinical worsening. Hemodynamically, the drugs tend to increase cardiac output but have only little effect on elevated PA pressure and RV dysfunction. Although recent PAH studies on early combination therapy and new targets in classical signaling pathways (guanylate cyclase, IP receptor) have raised great hope for better composite outcomes, until today, no RCT lasting longer than 16 weeks has shown a decrease in mortality as single primary outcome.

Legend:

Summary of metabolic derangements identified in RV cardiomyocytes in PAH. Solid arrows denote pathways increased in PAH, and dashed arrows represent pathways decreased in PAH. RV, right ventricular; PAH, pulmonary arterial hypertension.

From: Vineet Agrawal, Tim Lahm, Georg Hansmann, Anna R. Hemnes. Molecular mechanisms of right ventricular dysfunction in pulmonary arterial hypertension: focus on the coronary vasculature, sex hormones, and glucose/lipid metabolism. Cardiovasc Diagn Ther 2020.

PVD Network – Featured Articles

You can open and download the following four featured articles in pdf format, recently published by members of the PVD Network.

„2019 Updated Consensus Statement on the Diagnosis and Treatment of Pediatric Pulmonary Hypertension“

The European Pediatric Pulmonary Vascular Disease Network (EPPVDN), endorsed by AEPC, ESPR and ISHLT
J Heart Lung Transplantation, 2019.

„Challenges and Special Aspects of Pulmonary Hypertension in Middle- to Low-Income Regions.“

European Pediatric Pulmonary Vascular Disease Network (EPPVDN), endorsed by endorsed by AEPC, CSC, PASCAR, PCS, and PCSI
Journal of the American College of Cardiology; 2020

„Selexipag for the treatment of children with pulmonary arterial hypertension: First multicenter experience in drug safety and efficacy.“

J Heart Lung Transplant. 2020 Jul;39(7):695-706. doi: 10.1016/​j.healun.​2020.03.029. Epub 2020 Apr 7

 „Pulmonary hypertension in bronchopulmonary dysplasia.“

Pediatr Res. 2020 Jun 10. doi: 10.1038/s41390-020-0993-4

Recent Publications of our PVD Network

Hansmann G, Meinel, K, Bukova M, Chouvarine P, Wåhlander H, Koestenberger M, on behalf of the European Pediatric Pulmonary Vascular Disease Network (EPPVDN).
Heart Lung Transplant 2020; in press
https://doi.org/10.1016/j.healun.2020.03.0
Schweintzger S, Koestenberger M, Schlagenhauf A, Gernot G, Burmas A, Kurath-Koller S, Pocivalnik M, Sallmon H, Baumgartner D, Hansmann G, Gamillscheg A.
Cardiovasc Diagn Ther 2020; in press. http://dx.doi.org/10.21037/cdt.2020.04.01
The European Pediatric Pulmonary Vascular Disease Network (EPPVDN). Koestenberger M, Avian A, Chouvarine P, Gamillscheg A, Cvirn G, Schweintzger S, Kurath-Koller S, Cantinotti M, Hohmann D, Hansmann G.
Pediatr Res. 2020 Jan 10. doi: 10.1038/s41390-020-0748-2. Online ahead of print. PMID: 31923914
Koestenberger M, Avian A, Cantinotti M, Meinel K, Hansmann G.
Pediatr Int. 2020 Apr 17. doi: 10.1111/ped.14163. Online ahead of print. PMID: 32304149 No abstract available.
Chouvarine P, Giera M, Kastenmüller G, Artati A, Adamski J, Bertram H, Hansmann G.
Heart. 2020 Feb 20:heartjnl-2019-315900. doi: 10.1136/heartjnl-2019-315900. Online ahead of print. PMID: 32079620 Free article.
Chouvarine P, Geldner J, Giagnorio R, Legchenko E, Bertram H, Hansmann G.
Pediatr Crit Care Med. 2020 Apr;21(4):340-349. doi: 10.1097/PCC.0000000000002207. PMID: 31876555
Koestenberger M, Sallmon H, Avian A, Cantinotti M, Gamillscheg A, Kurath-Koller S, Schweintzger S, Hansmann G.
Pulm Circ. 2019 Apr-Jun;9(2):2045894019854074. doi: 10.1177/2045894019854074. PMID: 31099302 Free PMC article.
Koestenberger M, Sallmon H, Hansmann G; European Pediatric Pulmonary Vascular Disease Network.
Int J Cardiol. 2019 Mar 1;278:242. doi: 10.1016/j.ijcard.2018.11.092. PMID: 30683328 No abstract available.
Koestenberger M, Avian A, Cantinotti M, Hansmann G; European Pediatric Pulmonary Vascular Disease Network.
Int J Cardiol. 2019 Jan 1;274:296-298. doi: 10.1016/j.ijcard.2018.07.013. Epub 2018 Jul 3. PMID: 30454722
Koestenberger M, Avian A, Gamillscheg A, Sallmon H, Grangl G, Burmas A, Schweintzger S, Kurath-Koller S, Cvirn G, Hansmann G.
Clin Cardiol. 2018 Sep;41(9):1144-1149. doi: 10.1002/clc.22994. Epub 2018 Aug 18. PMID: 29896859 Free PMC article. Clinical Trial.
Koestenberger M, Avian A, Sallmon H, Gamillscheg A, Grangl G, Kurath-Koller S, Schweintzger S, Burmas A, Hansmann G.
Echocardiography. 2018 Jun;35(6):841-848. doi: 10.1111/echo.13852. Epub 2018 Mar 5. PMID: 29505663
Koestenberger M, Grangl G, Avian A, Gamillscheg A, Grillitsch M, Cvirn G, Burmas A, Hansmann G.
Circ Cardiovasc Imaging. 2017 Jan;10(1):e005336. doi: 10.1161/CIRCIMAGING.116.005336. PMID: 28003222
Koestenberger M, Avian A, Grangl G, Burmas A, Kurath-Koller S, Hansmann G.
Int J Cardiol. 2016 Jun 1;212:274-6. doi: 10.1016/j.ijcard.2016.03.111. Epub 2016 Mar 24. PMID: 27057933 No abstract available.