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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/
Association Of Borderline Pulmonary Hypertension With Mortality And Hospitalization In A Large Patient Cohort: Insights From The Veterans Affairs Clinical Assessment, Reporting, And Tracking Program
This is a retrospective study of over 20,000 patients with pulmonary hypertension confirmed by cardiac catheterization, from any cause who were followed for clinical outcomes. Like other studies it confirmed the increasing mortality beginning at the mildest levels of increased pulmonary artery pressure. The case can be made for screening programs to detect early disease to initiate treatments.
Citation
Maron BA, Hess E, Maddox TM, Opotowsky AR, Tedford RJ, Lahm T, Joynt KE, Kass DJ, Stephens T, Stanislawski MA, Swenson ER, Goldstein RH, Leopold JA, Zamanian RT, Elwing JM, Plomondon ME, Grunwald GK, Barón AE, Rumsfeld JS, Choudhary G. Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. Circulation. 2016 Mar 29;133(13):1240-8Source: https://pubmed.ncbi.nlm.nih.gov/26873944/
Atp-dependent Potassium Channels As A Key Target For The Treatment Of Myocardial And Vascular Dysfunction
This is a review of the role of K+ATP channels in the cardiovascular system, and the potential of K+ channel opener drugs. Included in the review is the finding that myocardial ischemia may be prevented from K+ATP channel activators, including levosimendan, via effects on cardiac mitochondria.
Citation
Pollesello P, Mebazaa A. ATP-dependent potassium channels as a key target for the treatment of myocardial and vascular dysfunction. Curr Opin Crit Care. 2004 Dec;10(6):436-41.Source: https://pubmed.ncbi.nlm.nih.gov/15616383/
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.
Citation
Yildiz O. Vasodilating mechanisms of levosimendan: involvement of K+ channels. J Pharmacol Sci. 2007 May;104(1):1-5.Source: https://pubmed.ncbi.nlm.nih.gov/17452812/
Uncovered Contribution of Kv7 Channels to Pulmonary Vascular Tone in Pulmonary Arterial Hypertension
This is a report of preclinical research that studied the role of K+(V.7) channels in PAH. Unlike other K+ channels that appear to be downregulated in PAH, the Kv7 channel function was preserved whereas the KCNE4 subunit was upregulated. This research highlights the complexities behind K+ channel control over the pulmonary circulation and the impact of their actions.
