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Targeting Pulmonary Vascular Disease to Improve Global Health: Pulmonary Vascular Disease: The Global Perspective
This paper presents an argument for taking a global view of the problem of pulmonary vascular disease. Since pulmonary hypertension may be a marker for advanced cardiac and pulmonary diseases, it emphasizes the need to educate health care leaders to begin establishing regional centers of excellence so that a worldwide approach can be applied that will benefit all.
Citation
Rich S, Herskowitz A. Targeting pulmonary vascular disease to improve global health: pulmonary vascular disease: the global perspective. Chest. 2010 Jun;137(6 Suppl):1S-5S.Source: https://pubmed.ncbi.nlm.nih.gov/20522574/
Pulmonary Hypertension In Heart Failure With Preserved Ejection Fraction: A Community-based Study
This is one of the first studies to attempt to determine the prevalence of pulmonary hypertension in a community setting. The target population was patients diagnosed with HFpEF and followed over 3 years. They determined that pulmonary hypertension highly prevalent (83%), indicating the urgent need for a broader scale effort to screen for pulmonary hypertension. In addition, they show that pulmonary hypertension was strongly associated with mortality, underscoring the unmet need for therapies.
Citation
Lam CS, Roger VL, Rodeheffer RJ, Borlaug BA, Enders FT, Redfield MM. Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study. J Am Coll Cardiol. 2009 Mar 31;53(13):1119-26Source: https://pubmed.ncbi.nlm.nih.gov/19324256/
A Global View of Pulmonary Hypertension
This is one of the more in-depth reviews of the global burden of pulmonary hypertension. They estimate a prevalence of 1% of the world population having pulmonary hypertension from any cause. They also estimate that the large majority of these patients (80%) live in developing countries, which emphasizes the challenge for both preventive and treatment strategies that will be affordable and accessible.
Citation
Hoeper MM, Humbert M, Souza R, Idrees M, Kawut SM, Sliwa-Hahnle K, Jing ZC, Gibbs JS. A global view of pulmonary hypertension. Lancet Respir Med. 2016 Apr;4(4):306-22.Source: https://pubmed.ncbi.nlm.nih.gov/26975810/
Threshold Of Pulmonary Hypertension Associated With Increased Mortality
This screening study of more that 150,000 adults found a prevalence of pulmonary hypertension of greater than 18% ranging from mild to severe. In addition, they were able to show increasing mortality with the severity of pulmonary hypertension, beginning at the very lowest levels.
Citation
Strange G, Stewart S, Celermajer DS, Prior D, Scalia GM, Marwick TH, Gabbay E, Ilton M, Joseph M, Codde J, Playford D; NEDA Contributing Sites. Threshold of Pulmonary Hypertension Associated With Increased Mortality. J Am Coll Cardiol. 2019 Jun 4;73(21):2660-2672.Source: https://pubmed.ncbi.nlm.nih.gov/31146810/
Mild Pulmonary Hypertension and Premature Mortality Among 154 956 Men and Women Undergoing Routine Echocardiography
This large study of over 150,000 adults from the NEDA goes into deeper analysis to show how mild levels of elevation in pulmonary arterial pressure is associated with increased mortality in the general population. They conclude that notional screening strategies should be considered in as part of clinical surveillance programs.
Citation
Stewart S, Chan YK, Playford D, Strange GA; NEDA investigators. Mild pulmonary hypertension and premature mortality among 154 956 men and women undergoing routine echocardiography. Eur Respir J. 2021 May 28:2100832.Source: https://pubmed.ncbi.nlm.nih.gov/34049952/
Increasing Incidence and Prevalence of World Health Organization Groups 1 to 4 Pulmonary Hypertension: A Population-based Cohort Study in Ontario, Canada
This Canadian study includes a cohort of over 50,000 patients with pulmonary hypertension over a 10-year period. They confirm that the incidence and prevalence of pulmonary hypertension is increasing, with Group 2 and group 3 associated with the highest mortality.
Citation
Wijeratne DT, Lajkosz K, Brogly SB, Lougheed MD, Jiang L, Housin A, Barber D, Johnson A, Doliszny KM, Archer SL. Increasing Incidence and Prevalence of World Health Organization Groups 1 to 4 Pulmonary Hypertension: A Population-Based Cohort Study in Ontario, Canada. Circ Cardiovasc Qual Outcomes. 2018 Feb;11(2):e003973.Source: https://pubmed.ncbi.nlm.nih.gov/29444925/
Bmp Signaling Controls Pasmc Kv Channel Expression In Vitro And In Vivo
Interesting research demonstrating that the loss of BMPR2 signaling, an established fundamental mechanism underlying PAH, is mediated by downregulation of K+ channels of the voltage regulated family. This implies that K+ downregulation may be a cause of pulmonary vasoconstriction and that K+ channel activators may be a promising treatment.
Citation
Young KA, Ivester C, West J, Carr M, Rodman DM. BMP signaling controls PASMC KV channel expression in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L841-8.Source: https://pubmed.ncbi.nlm.nih.gov/16339782/
New Trial Designs and Potential Therapies for Pulmonary Artery Hypertension
This review focuses on the pitfalls of traditional randomized clinical trials, and suggest more modern approaches with new endpoints. Co-authored by members of the FDA, they also discuss newer treatments under development which may be better suited for these strategies.
Citation
Gomberg-Maitland M, Bull TM, Saggar R, Barst RJ, Elgazayerly A, Fleming TR, Grimminger F, Rainisio M, Stewart DJ, Stockbridge N, Ventura C, Ghofrani AH, Rubin LJ. New trial designs and potential therapies for pulmonary artery hypertension. J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D82-91.Source: https://pubmed.ncbi.nlm.nih.gov/24355645/
Building The Case for Novel Clinical Trials in Pulmonary Arterial Hypertension
This paper discusses the various possible clinical trial designs that are well suited for a disease like PAH. The authors point out that orphan diseases make the typical parallel design of randomized blinded trials difficult and often risky. Novel trial designs can result in smaller trials which are less costly, while at the same enriched to allow for larger treatment effects.
Citation
Ryan JJ, Rich JD, Maron BA. Building the case for novel clinical trials in pulmonary arterial hypertension. Circ Cardiovasc Qual Outcomes. 2015 Jan;8(1):114-23.Source: https://pubmed.ncbi.nlm.nih.gov/25604559/
Vasodilating Mechanisms of Levosimendan: Involvement of K+ Channels
A review of the known vascular effects of levosimendan via K+ ATP channel activation. The author discusses how levosimendan may be effective in heart failure outside of direct inotropic actions.
