{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:26:33Z","timestamp":1793305593795,"version":"4.5.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/501100002386","name":"Cairo University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002386","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Am J Cardiovasc Drugs"],"published-print":{"date-parts":[[2024,1]]},"DOI":"10.1007\/s40256-023-00613-5","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T12:02:31Z","timestamp":1699531351000},"page":"39-54","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Systematic Review of Novel Therapies of Pulmonary Arterial Hypertension"],"prefix":"10.1007","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7959-9316","authenticated-orcid":false,"given":"Omnia Azmy","family":"Nabeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa I.","family":"Saud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basma","family":"Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira Samy","family":"Khedr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Amr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aml Medhat","family":"Faoosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eshraka","family":"Esmat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmeen Magdy","family":"Mahmoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Hatem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Osama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssef Mohamed Amin","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem Ibrahim","family":"Elkorashy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soha Aly","family":"Elmorsy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,9]]},"reference":[{"issue":"38","key":"613_CR1","first-page":"3618","volume":"43","author":"M Humbert","year":"2022","unstructured":"Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RM, Brida M, Carlsen J, Coats AJ, Escribano-Subias P, Ferrari P, Ferreira DS. 2022 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2022;43(38):3618\u2013731.","journal-title":"Eur Respir J"},{"issue":"4","key":"613_CR2","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1007\/s00408-020-00375-w","volume":"198","author":"ZG Vazquez","year":"2020","unstructured":"Vazquez ZG, Klinger JR. Guidelines for the treatment of pulmonary arterial hypertension. Lung. 2020;198(4):581\u201396.","journal-title":"Lung"},{"issue":"1","key":"613_CR3","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1080\/10717544.2021.1927243","volume":"28","author":"W Fu","year":"2021","unstructured":"Fu W, He W, Li Y, Chen Y, Liang J, Lei H, Fu L, Chen Y, Ren N, Jiang Q, Shen Y. Efficacy and safety of novel-targeted drugs in the treatment of pulmonary arterial hypertension: a Bayesian network meta-analysis. Drug Deliv. 2021;28(1):1007\u201319.","journal-title":"Drug Deliv"},{"issue":"1","key":"613_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep30060","volume":"6","author":"M Rysz-G\u00f3rzynska","year":"2016","unstructured":"Rysz-G\u00f3rzynska M, Gluba-Brz\u00f3zka A, Sahebkar A, Serban MC, Mikhailidis DP, Ursoniu S, Toth PP, Bittner V, Watts GF, Lip GY, Rysz J. Efficacy of statin therapy in pulmonary arterial hypertension: a systematic review and meta-analysis. Sci Rep. 2016;6(1):1.","journal-title":"Sci Rep"},{"issue":"4","key":"613_CR5","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.chest.2021.10.010","volume":"161","author":"DF Condon","year":"2022","unstructured":"Condon DF, Agarwal S, Chakraborty A, Auer N, Vazquez R, Patel H, Zamanian RT, de Jesus Perez VA. Novel mechanisms targeted by drug trials in pulmonary arterial hypertension. Chest. 2022;161(4):100\u20131072.","journal-title":"Chest"},{"issue":"11","key":"613_CR6","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.1093\/cvr\/cvaa350","volume":"117","author":"BJ Dunmore","year":"2021","unstructured":"Dunmore BJ, Jones RJ, Toshner MR, Upton PD, Morrell NW. Approaches to treat pulmonary arterial hypertension by targeting BMPR2: from cell membrane to nucleus. Cardiovasc Res. 2021;117(11):2309\u201325.","journal-title":"Cardiovasc Res"},{"issue":"2","key":"613_CR7","doi-asserted-by":"publisher","DOI":"10.1002\/pul2.12088","volume":"12","author":"HM Lazarus","year":"2022","unstructured":"Lazarus HM, Denning J, Wring S, Palacios M, Hoffman S, Crizer K, Kamau-Kelley W, Symonds W, Feldman J. A trial design to maximize knowledge of the effects of rodatristat ethyl in the treatment of pulmonary arterial hypertension (ELEVATE 2). Pulm Circ. 2022;12(2): e12088.","journal-title":"Pulm Circ."},{"issue":"6","key":"613_CR8","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1253\/circj.CJ-15-0443","volume":"79","author":"K Odagiri","year":"2015","unstructured":"Odagiri K, Watanabe H. Effects of the Rho-kinase inhibitor, fasudil, on pulmonary hypertension. Circ J. 2015;79(6):1213\u20134.","journal-title":"Circ J"},{"issue":"1","key":"613_CR9","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.ijcard.2014.09.101","volume":"177","author":"X Jiang","year":"2014","unstructured":"Jiang X, Wang YF, Zhao QH, Jiang R, Wu Y, Peng FH, Xu XQ, Wang L, He J, Jing ZC. Acute hemodynamic response of infused fasudil in patients with pulmonary arterial hypertension: a randomized, controlled, crossover study. Int J Cardiol. 2014;177(1):61\u20135.","journal-title":"Int J Cardiol"},{"issue":"9","key":"613_CR10","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1253\/circj.CJ-09-0135","volume":"73","author":"Y Fukumoto","year":"2009","unstructured":"Fukumoto Y, Takaki A, Tawara S, Ohashi J, Nakano M, Tada T, Saji K, Sugimura K, Fujita H, Hoshikawa Y, Nawata J. Evidence for Rho-kinase activation in patients with pulmonary arterial hypertension. Circ J. 2009;73(9):1731\u20139.","journal-title":"Circ J"},{"issue":"2","key":"613_CR11","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1007\/s00380-009-1176-8","volume":"25","author":"H Fujita","year":"2010","unstructured":"Fujita H, Fukumoto Y, Saji K, Sugimura K, Demachi J, Nawata J, Shimokawa H. Acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, in patients with pulmonary arterial hypertension. Heart Vessels. 2010;25(2):144\u20139.","journal-title":"Heart Vessels"},{"key":"613_CR12","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1097\/00003086-199603000-00006","volume":"324","author":"EH Riley","year":"1996","unstructured":"Riley EH, Lane JM, Urist MR, Lyons KM, Lieberman JR. Bone morphogenetic protein-2: biology and applications. Clin Orthop Relat Res. 1996;324:39\u201346.","journal-title":"Clin Orthop Relat Res"},{"issue":"13","key":"613_CR13","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1056\/NEJMoa2024277","volume":"384","author":"M Humbert","year":"2021","unstructured":"Humbert M, McLaughlin V, Gibbs JS, Gomberg-Maitland M, Hoeper MM, Preston IR, et al. Sotatercept for the treatment of pulmonary arterial hypertension. N Engl J Med. 2021;384(13):1204\u201315.","journal-title":"N Engl J Med"},{"issue":"1","key":"613_CR14","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1083\/jcb.200806049","volume":"184","author":"VA de Jesus Perez","year":"2009","unstructured":"de Jesus Perez VA, Alastalo TP, Wu JC, Axelrod JD, Cooke JP, Amieva M, Rabinovitch M. Bone morphogenetic protein 2 induces pulmonary angiogenesis via Wnt\u2013\u03b2-catenin and Wnt\u2013RhoA\u2013Rac1 pathways. J Cell Biol. 2009;184(1):83\u201399.","journal-title":"J Cell Biol"},{"key":"613_CR15","doi-asserted-by":"crossref","unstructured":"Guignabert C, Humbert M. Targeting transforming growth factor-\u03b2 receptors in pulmonary hypertension. Eur Respir J. 2021;57(2).","DOI":"10.1183\/13993003.02341-2020"},{"issue":"8","key":"613_CR16","doi-asserted-by":"publisher","first-page":"3600","DOI":"10.1172\/JCI65592","volume":"123","author":"E Spiekerkoetter","year":"2013","unstructured":"Spiekerkoetter E, Tian X, Cai J, Hopper RK, Sudheendra D, Li CG, El-Bizri N, Sawada H, Haghighat R, Chan R, Haghighat L. FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension. J Clin Investig. 2013;123(8):3600\u201313.","journal-title":"J Clin Investig"},{"issue":"3","key":"613_CR17","doi-asserted-by":"publisher","first-page":"1602449","DOI":"10.1183\/13993003.02449-2016","volume":"50","author":"E Spiekerkoetter","year":"2017","unstructured":"Spiekerkoetter E, Sung YK, Sudheendra D, Scott V, Del Rosario P, Bill M, et al. Randomised placebo-controlled safety and tolerability trial of FK506 (tacrolimus) for pulmonary arterial hypertension. Eur Respir J. 2017;50(3):1602449.","journal-title":"Eur Respir J"},{"issue":"11","key":"613_CR18","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1161\/01.RES.84.11.1285","volume":"84","author":"N Harada","year":"1999","unstructured":"Harada N, Sasano H, Murakami H, Ohkuma T, Nagura H, Takagi Y. Localized expression of aromatase in human vascular tissues. Circ Res. 1999;84(11):1285\u201391.","journal-title":"Circ Res"},{"issue":"2","key":"613_CR19","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1378\/chest.09-1140","volume":"137","author":"DB Badesch","year":"2010","unstructured":"Badesch DB, Raskob GE, Elliott CG, Krichman AM, Farber HW, Frost AE, Barst RJ, Benza RL, Liou TG, Turner M, Giles S. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137(2):376\u201387.","journal-title":"Chest"},{"issue":"1","key":"613_CR20","doi-asserted-by":"publisher","first-page":"L7","DOI":"10.1152\/ajplung.00337.2013","volume":"307","author":"T Lahm","year":"2014","unstructured":"Lahm T, Tuder RM, Petrache I. Progress in solving the sex hormone paradox in pulmonary hypertension. Am J Physiol-Lung Cell Mol Physiol. 2014;307(1):L7-26.","journal-title":"Am J Physiol-Lung Cell Mol Physiol."},{"issue":"10","key":"613_CR21","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.steroids.2010.02.016","volume":"75","author":"AO Mueck","year":"2010","unstructured":"Mueck AO, Seeger H. 2-methoxyestradiol\u2014biology and mechanism of action. Steroids. 2010;75(10):625\u201331.","journal-title":"Steroids"},{"issue":"2","key":"613_CR22","doi-asserted-by":"publisher","first-page":"294","DOI":"10.4103\/2045-8932.114756","volume":"3","author":"ED Austin","year":"2013","unstructured":"Austin ED, Lahm T, West J, Tofovic SP, Johansen AK, MacLean MR, Alzoubi A, Oka M. Gender, sex hormones and pulmonary hypertension. Pulm Circ. 2013;3(2):294\u2013314.","journal-title":"Pulm Circ."},{"issue":"6","key":"613_CR23","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1097\/FJC.0b013e3181f9ea8d","volume":"56","author":"SP Tofovic","year":"2010","unstructured":"Tofovic SP. Estrogens and development of pulmonary hypertension-interaction of estradiol metabolism and pulmonary vascular disease. J Cardiovasc Pharmacol. 2010;56(6):696.","journal-title":"J Cardiovasc Pharmacol"},{"issue":"1","key":"613_CR24","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3390\/ijms21010116","volume":"21","author":"SP Tofovic","year":"2019","unstructured":"Tofovic SP, Jackson EK. Estradiol metabolism: crossroads in pulmonary arterial hypertension. Int J Mol Sci. 2019;21(1):116.","journal-title":"Int J Mol Sci"},{"issue":"9","key":"613_CR25","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1161\/CIRCULATIONAHA.111.062927","volume":"126","author":"K White","year":"2012","unstructured":"White K, Johansen AK, Nilsen M, Ciuclan L, Wallace E, Paton L, Campbell A, Morecroft I, Loughlin L, McClure JD, Thomas M. Activity of the estrogen-metabolizing enzyme cytochrome P450 1B1 influences the development of pulmonary arterial hypertension. Circulation. 2012;126(9):1087\u201398.","journal-title":"Circulation"},{"key":"613_CR26","first-page":"A5588","volume":"199","author":"A Hemnes","year":"2019","unstructured":"Hemnes A, Niswender K, Burke K, Fan R, Mallugari R, Newman JH, et al. Clinical trial of metformin in pulmonary arterial hypertension. American Thoracic Society International Conference Abstracts. C97. Don\u2019t stop believing: clinical trials in pulmonary vascular medicine. Am J Respir Crit Care Med. 2019;199:A5588.","journal-title":"Am J Respir Crit Care Med"},{"issue":"2","key":"613_CR27","doi-asserted-by":"publisher","first-page":"496","DOI":"10.2337\/diabetes.55.02.06.db05-1064","volume":"55","author":"BJ Davis","year":"2006","unstructured":"Davis BJ, Xie Z, Viollet B, Zou MH. Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. Diabetes. 2006;55(2):496\u2013505.","journal-title":"Diabetes"},{"issue":"2","key":"613_CR28","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1161\/HYPERTENSIONAHA.116.07353","volume":"68","author":"A Dean","year":"2016","unstructured":"Dean A, Nilsen M, Loughlin L, Salt IP, MacLean MR. Metformin reverses development of pulmonary hypertension via aromatase inhibition. Hypertension. 2016;68(2):446\u201354.","journal-title":"Hypertension"},{"issue":"10","key":"613_CR29","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.1253\/circj.CJ-13-0443","volume":"77","author":"Y Fukumoto","year":"2013","unstructured":"Fukumoto Y, Yamada N, Matsubara H, Mizoguchi M, Uchino K, Yao A, et al. Double-blind, placebo-controlled clinical trial with a Rho-kinase inhibitor in pulmonary arterial hypertension\u2014a pilot efficacy trial. Circ J. 2013;77(10):2619\u201325.","journal-title":"Circ J"},{"issue":"4","key":"613_CR30","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1111\/chd.12764","volume":"14","author":"H Ruan","year":"2019","unstructured":"Ruan H, Zhang Y, Liu R, Yang X. The acute effects of 30 mg vs 60 mg of intravenous Fasudil on patients with congenital heart defects and severe pulmonary arterial hypertension. Congenit Heart Dis. 2019;14(4):645\u201350.","journal-title":"Congenit Heart Dis"},{"issue":"1","key":"613_CR31","doi-asserted-by":"publisher","first-page":"2201347","DOI":"10.1183\/13993003.01347-2022","volume":"61","author":"M Humbert","year":"2023","unstructured":"Humbert M, McLaughlin V, Gibbs JS, Gomberg-Maitland M, Hoeper MM, Preston IR, et al. Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. Eur Respir J. 2023;61(1):2201347.","journal-title":"Eur Respir J"},{"issue":"3","key":"613_CR32","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1164\/rccm.201605-1024OC","volume":"195","author":"SM Kawut","year":"2017","unstructured":"Kawut SM, Archer-Chicko CL, DeMichele A, Fritz JS, Klinger JR, Ky B, Palevsky HI, Palmisciano AJ, Patel M, Pinder D, Propert KJ. Anastrozole in pulmonary arterial hypertension. A randomized, double-blind, placebo-controlled trial. Am J Respir Crit Care Med. 2017;195(3):360\u20138.","journal-title":"Am J Respir Crit Care Med"},{"key":"613_CR33","doi-asserted-by":"crossref","unstructured":"Liao S, Li D, Hui Z, McLachlan CS, Zhang Y. Metformin added to bosentan therapy in patients with pulmonary arterial hypertension associated with congenital heart defects: a pilot study. Erj Open Research. 2018;4(3).","DOI":"10.1183\/23120541.00060-2018"},{"issue":"5","key":"613_CR34","doi-asserted-by":"publisher","first-page":"657","DOI":"10.2217\/fca.11.51","volume":"7","author":"M Surma","year":"2011","unstructured":"Surma M, Wei L, Shi J. Rho kinase as a therapeutic target in cardiovascular disease. Future Cardiol. 2011;7(5):657\u201371.","journal-title":"Future Cardiol"},{"issue":"3","key":"613_CR35","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1097\/00005344-200203000-00001","volume":"39","author":"H Shimokawa","year":"2002","unstructured":"Shimokawa H. Rho-kinase as a novel therapeutic target in treatment of cardiovascular diseases. J Cardiovasc Pharmacol. 2002;39(3):319\u201327.","journal-title":"J Cardiovasc Pharmacol"},{"issue":"14","key":"613_CR36","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1016\/j.bmcl.2019.05.006","volume":"29","author":"L Qi","year":"2019","unstructured":"Qi L, Lv T, Cheng Y, Yu M, Han H, Kong H, et al. Fasudil dichloroacetate (FDCA), an orally available agent with potent therapeutic efficiency on monocrotaline-induced pulmonary arterial hypertension rats. Bioorg Med Chem Lett. 2019;29(14):1812\u20138.","journal-title":"Bioorg Med Chem Lett"},{"key":"613_CR37","first-page":"A4395","volume":"199","author":"SR Joshi","year":"2019","unstructured":"Joshi SR, Liu J, Pearsall RS, Li G, Kumar R. ACTRIIA-Fc (Sotatercept) reverses pulmonary vascular remodeling to attenuate pulmonary arterial hypertension (PAH) by rebalancing TGF-b\/BMP signaling in a preclinical model. American Thoracic Society International Conference Abstracts. C26. Let it bleed: endothelial injury and angiogenesis in pulmonary hypertension [poster]. Am J Respir Crit Care Med. 2019;199:A4395.","journal-title":"Am J Respir Crit Care Med"},{"issue":"10","key":"613_CR38","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1164\/rccm.201509-1785OC","volume":"193","author":"CE Ventetuolo","year":"2016","unstructured":"Ventetuolo CE, Baird GL, Barr RG, Bluemke DA, Fritz JS, Hill NS, Klinger JR, Lima JA, Ouyang P, Palevsky HI, Palmisciano AJ. Higher estradiol and lower dehydroepiandrosterone-sulfate levels are associated with pulmonary arterial hypertension in men. Am J Respir Crit Care Med. 2016;193(10):1168\u201375.","journal-title":"Am J Respir Crit Care Med"},{"issue":"11","key":"613_CR39","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1513\/AnnalsATS.201904-328RL","volume":"16","author":"SM Kawut","year":"2019","unstructured":"Kawut SM, Pinder D, Al-Naamani N, McCormick A, Palevsky HI, Fritz J, Smith KA, Mazurek JA, Doyle MF, MacLean MR, DeMichele A. Fulvestrant for the treatment of pulmonary arterial hypertension. Ann Am Thorac Soc. 2019;16(11):1456\u20139.","journal-title":"Ann Am Thorac Soc"},{"key":"613_CR40","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.ejphar.2016.09.003","volume":"791","author":"L Liu","year":"2016","unstructured":"Liu L, Pan Y, Song Y, Su X, Ke R, Yang L, Gao L, Li M. Activation of AMPK \u03b12 inhibits airway smooth muscle cells proliferation. Eur J Pharmacol. 2016;791:235\u201343.","journal-title":"Eur J Pharmacol"},{"key":"613_CR41","doi-asserted-by":"publisher","first-page":"635","DOI":"10.3389\/fphar.2020.00635","volume":"11","author":"M Deng","year":"2020","unstructured":"Deng M, Su D, Xu S, Little PJ, Feng X, Tang L, Shen A. Metformin and vascular diseases: a focused review on smooth muscle cell function. Front Pharmacol. 2020;11:635.","journal-title":"Front Pharmacol"},{"key":"613_CR42","unstructured":"Scherger JE. Is Metformin a Wonder Drug?. Int Med Alert. 2021;43(8)."},{"issue":"19","key":"613_CR43","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1001\/jama.2019.3805","volume":"321","author":"J Flory","year":"2019","unstructured":"Flory J, Lipska K. Metformin in 2019. JAMA. 2019;321(19):1926\u20137.","journal-title":"JAMA"},{"issue":"4","key":"613_CR44","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/S0735-1097(02)02012-0","volume":"40","author":"O Sitbon","year":"2002","unstructured":"Sitbon O, Humbert M, Nunes H, Parent F, Garcia G, Herv\u00e9 P, Rainisio M, Simonneau G\u00c9. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol. 2002;40(4):780\u20138.","journal-title":"J Am Coll Cardiol"},{"issue":"123","key":"613_CR45","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1183\/09059180.00009011","volume":"21","author":"JL Vachiery","year":"2012","unstructured":"Vachiery JL, Yerly P, Huez S. How to detect disease progression in pulmonary arterial hypertension. Eur Respir Rev. 2012;21(123):40\u20137.","journal-title":"Eur Respir Rev"},{"issue":"3","key":"613_CR46","doi-asserted-by":"publisher","first-page":"249","DOI":"10.5152\/akd.2015.5834","volume":"15","author":"R Demir","year":"2015","unstructured":"Demir R, K\u00fc\u00e7\u00fcko\u011flu MS. Six-minute walk test in pulmonary arterial hypertension. Anatol J Cardiol. 2015;15(3):249.","journal-title":"Anatol J Cardiol"},{"issue":"1","key":"613_CR47","doi-asserted-by":"publisher","first-page":"2200879","DOI":"10.1183\/13993003.00879-2022","volume":"61","author":"M Humbert","year":"2023","unstructured":"Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RM, Brida M, Carlsen J, Coats AJ, Escribano-Subias P, Ferrari P, Ferreira DS. 2022 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2023;61(1):2200879.","journal-title":"Eur Respir J"},{"issue":"3","key":"613_CR48","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.healun.2014.08.020","volume":"34","author":"HW Farber","year":"2015","unstructured":"Farber HW, Miller DP, McGoon MD, Frost AE, Benton WW, Benza RL. Predicting outcomes in pulmonary arterial hypertension based on the 6-minute walk distance. J Heart Lung Transplant. 2015;34(3):362\u20138.","journal-title":"J Heart Lung Transplant"},{"issue":"13","key":"613_CR49","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1016\/j.jacc.2012.01.083","volume":"60","author":"G Savarese","year":"2012","unstructured":"Savarese G, Paolillo S, Costanzo P, D\u2019Amore C, Cecere M, Losco T, et al. Do changes of 6-minute walk distance predict clinical events in patients with pulmonary arterial hypertension? A meta-analysis of 22 randomized trials. J Am Coll Cardiol. 2012;60(13):1192\u2013201.","journal-title":"J Am Coll Cardiol"},{"issue":"14","key":"613_CR50","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1161\/CIRCULATIONAHA.106.618397","volume":"114","author":"D Mereles","year":"2006","unstructured":"Mereles D, Ehlken N, Kreuscher S, Ghofrani S, Hoeper MM, Halank M, Meyer FJ, Karger G, Buss J, Juenger J, Holzapfel N. Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation. 2006;114(14):1482\u20139.","journal-title":"Circulation"},{"key":"613_CR51","doi-asserted-by":"crossref","unstructured":"Lewis RA, Durrington C, Condliffe R, Kiely DG. BNP\/NT-proBNP in pulmonary arterial hypertension: time for point-of-care testing?. Eur Resp Rev. 2020;29(156).","DOI":"10.1183\/16000617.0009-2020"},{"key":"613_CR52","doi-asserted-by":"crossref","unstructured":"Ghio S, Mercurio V, Fortuni F, Forfia PR, Gall H, Ghofrani A, Mathai SC, Mazurek JA, Mukherjee M, Richter M, Scelsi L. A comprehensive echocardiographic method for risk stratification in pulmonary arterial hypertension. Eur Resp J. 2020;56(3).","DOI":"10.1183\/13993003.00513-2020"},{"issue":"1","key":"613_CR53","doi-asserted-by":"publisher","DOI":"10.1136\/openhrt-2016-000408","volume":"3","author":"S Ghio","year":"2016","unstructured":"Ghio S, Pica S, Klersy C, Guzzafame E, Scelsi L, Raineri C, Turco A, Schirinzi S, Visconti LO. Prognostic value of TAPSE after therapy optimisation in patients with pulmonary arterial hypertension is independent of the haemodynamic effects of therapy. Open heart. 2016;3(1): e000408.","journal-title":"Open heart."},{"issue":"8","key":"613_CR54","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1111\/j.1445-5994.2008.01880.x","volume":"39","author":"T Rasekaba","year":"2009","unstructured":"Rasekaba T, Lee AL, Naughton MT, Williams TJ, Holland AE. The six-minute walk test: a useful metric for the cardiopulmonary patient. Intern Med J. 2009;39(8):495\u2013501.","journal-title":"Intern Med J"},{"issue":"138","key":"613_CR55","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1183\/16000617.0062-2015","volume":"24","author":"S Rosenkranz","year":"2015","unstructured":"Rosenkranz S, Preston IR. Right heart catheterisation: best practice and pitfalls in pulmonary hypertension. Eur Respir Rev. 2015;24(138):642\u201352.","journal-title":"Eur Respir Rev"}],"container-title":["American Journal of Cardiovascular Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40256-023-00613-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40256-023-00613-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40256-023-00613-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T08:31:10Z","timestamp":1705998670000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40256-023-00613-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,9]]},"references-count":55,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["613"],"URL":"https:\/\/doi.org\/10.1007\/s40256-023-00613-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2575826\/v1","asserted-by":"object"}]},"ISSN":["1175-3277","1179-187X"],"issn-type":[{"value":"1175-3277","type":"print"},{"value":"1179-187X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,9]]},"assertion":[{"value":"22 September 2023","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 November 2023","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Omnia Azmy Nabeh, Alaa I. Saud, Basma Amin, Amira Samy Khedr, Alaa Amr, Aml Medhat Faoosa, Eshraka Esmat, Yasmeen Magdy Mahmoud, Aya Hatem, Mariam Mohamed, Alaa Osama, Youssef Mohamed Amin Soliman, Reem Ibrahim Elkorashy, and Soha Aly Elmorsy declare they have no potential conflicts of interest that might be relevant to the contents of this manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"All authors contributed to the study conception, design, data collection, analysis and writing, and read and approved the final manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and materials"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}}]}}