Clinical and genetic associations with prostacyclin response in pulmonary arterial hypertension.

Pulmonary Circulation
Stephen J HallidayAnna R Hemnes

Abstract

Parenteral prostacyclin therapy is the most efficacious pharmacologic treatment for pulmonary arterial hypertension (PAH), but clinical response is variable. We sought to identify clinical, hemodynamic, and genetic associations with response to prostacyclin therapy. We performed a retrospective analysis of patients within a de-identified electronic health record and associated DNA biobank. Patients with PAH and a right heart catheterization (RHC) in the six months before initiation of a parenteral prostacyclin were included. Responders were defined a priori by attainment of World Health Organization (WHO) functional class (FC) 2 or better at the time of repeat RHC within two years. We performed exploratory analyses to identify genomic associations with prostacyclin response. Of 129 patients identified, 54 met our criteria for "responders." These patients were younger, more likely to be male, and were less likely to have connective tissue disease-related PAH. At follow-up, responders had improved hemodynamics, 6-min walk distance, and long-term survival. Baseline PA oxygen saturation (hazard ratio [HR] 0.568 [0.34-0.95]) and follow-up FC (HR = 2.57 [1.22-5.43]) were associated with survival. Prostacyclin responders were enriched...Continue Reading

References

Feb 1, 1996·The New England Journal of Medicine·R J BarstUNKNOWN Primary Pulmonary Hypertension Study Group
Jan 24, 2002·American Journal of Respiratory Cell and Molecular Biology·Lucie H ClappAndrew Tinker
Sep 3, 2002·Journal of the American College of Cardiology·Olivier SitbonGérald Simonneau
Sep 18, 2002·Circulation·Vallerie V McLaughlinStuart Rich
Nov 26, 2002·American Journal of Respiratory and Critical Care Medicine·Karl P KuhnIvan M Robbins
Sep 11, 2004·The European Respiratory Journal·M HumbertG Simonneau
Jun 28, 2005·Nucleic Acids Research·Bing ZhangJay Snoddy
May 27, 2008·Clinical Pharmacology and Therapeutics·D M RodenD R Masys
May 7, 2010·Clinical and Translational Science·Jill PulleyDaniel R Masys
Jul 14, 2010·American Journal of Respiratory and Critical Care Medicine·Emilia FalcettiLucie H Clapp
May 3, 2011·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Raymond L BenzaIrene M Lang
Nov 4, 2011·The New England Journal of Medicine·Bonnie W RamseyUNKNOWN VX08-770-102 Study Group
Sep 1, 2012·The European Respiratory Journal·James WestAnna R Hemnes
Mar 5, 2013·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ioana R PrestonIris Z Jaffe
May 25, 2013·Nucleic Acids Research·Jing WangBing Zhang
Dec 21, 2013·Journal of the American College of Cardiology·Vallerie V McLaughlinOlivier Sitbon
Nov 20, 2014·The New England Journal of Medicine·Alexandra SnyderTimothy A Chan
Dec 4, 2014·The New England Journal of Medicine·Benjamin J SolomonUNKNOWN PROFILE 1014 Investigators
Jan 31, 2015·The New England Journal of Medicine·Francis S Collins, Harold Varmus
Jun 13, 2015·Chest·Harrison W FarberRaymond L Benza
Dec 2, 2015·American Journal of Respiratory and Critical Care Medicine·Eric D Austin, James E Loyd
Dec 10, 2016·Journal of the American College of Cardiology·Tufik R AssadEvan L Brittain
Jun 10, 2017·Pulmonary Circulation·Stephen J Halliday, Anna R Hemnes

❮ Previous
Next ❯

Citations

Dec 28, 2019·British Journal of Pharmacology·Bradley A MaronAnna R Hemnes

❮ Previous
Next ❯

Methods Mentioned

BETA
chip
genotyping

Clinical Trials Mentioned

NCT02253394
NCT01712620

Software Mentioned

R Foundation for Statistical Computing
GTEx
ANNOVAR
WEB Gene Set Analysis Toolkit ( WebGestalt )
R

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.