Mohammadi Asma, Matos Wanessa F, Intriago Cesar, Thakkar Keval, Jahan Nasrin, Shah Heeya, Nishu Rifath I, Marzban Sima
Division of Research & Academic Affairs, Larkin Community Hospital, South Miami, USA.
Cureus. 2021 Sep 22;13(9):e18191. doi: 10.7759/cureus.18191. eCollection 2021 Sep.
Pulmonary Hypertension (PH) is defined as a disorder in which the mean Pulmonary Arterial Pressure (mPAP) is greater than 20 mmHg at rest. Pulmonary Arterial Hypertension (PAH) is considered when mPAP is > 20 mmHg and pulmonary vascular resistance (PVR) is ⩾ 3 WU. PAH is a chronic progressive disease resulting in right heart failure and premature death. It is postulated to be due to an inactivating mutation of a gene named bone morphogenetic protein receptor type 2 (BMPR2), whose predominant function is halting vascular proliferation. It has a lamentable prognosis if not rapidly diagnosed and adequately treated. Treatment of PAH has evolved in the past few decades since many related pathways and potential therapeutic targets have been explored. Parenteral prostanoids are the most effective therapeutic options for PAH. Epoprostenol is a synthetic analog of prostacyclin and a potent vasodilator that was Food and Drug Administration (FDA)-approved in December 1995 for intravenous use to treat PAH. It has also been used to treat different PAH subtypes, including connective tissue-related PAH like lupus and systemic sclerosis, congenital heart disease, and drug-induced PAH. It is effective in reducing mortality rates and improving survival rates. Although the use of Epoprostenol for PAH is challenging, it has been one of the most successful therapies used. In this manuscript, we review the pathophysiology of PAH and the risk stratification tool. We also discuss the mechanism of action of PAH-targeted therapies while focusing on the role of epoprostenol that has been investigated in many clinical trials. Finally, we discuss two ongoing clinical trials which highlight some potential therapeutic options.
肺动脉高压(PH)被定义为一种静息时平均肺动脉压(mPAP)大于20 mmHg的病症。当mPAP>20 mmHg且肺血管阻力(PVR)≥3 Wood单位(WU)时,则考虑为肺动脉高压(PAH)。PAH是一种慢性进行性疾病,可导致右心衰竭和过早死亡。据推测,这是由于一种名为骨形态发生蛋白受体2型(BMPR2)的基因发生失活突变所致,其主要功能是阻止血管增殖。如果不迅速诊断和进行充分治疗,其预后不佳。在过去几十年中,由于探索了许多相关途径和潜在治疗靶点,PAH的治疗有了进展。胃肠外前列腺素类药物是PAH最有效的治疗选择。依前列醇是前列环素的合成类似物,是一种强效血管扩张剂,于1995年12月获得美国食品药品监督管理局(FDA)批准用于静脉注射治疗PAH。它也被用于治疗不同的PAH亚型,包括与结缔组织相关的PAH,如狼疮和系统性硬化症、先天性心脏病以及药物性PAH。它在降低死亡率和提高生存率方面有效。尽管使用依前列醇治疗PAH具有挑战性,但它一直是最成功的治疗方法之一。在本手稿中,我们回顾了PAH的病理生理学和风险分层工具。我们还讨论了PAH靶向治疗的作用机制,同时重点关注在许多临床试验中研究过的依前列醇的作用。最后,我们讨论了两项正在进行的临床试验,它们突出了一些潜在的治疗选择。