Centre for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands.
Experimental Cardiology, Department of Cardiology, University Medical Centre Groningen, University of Groningen, Antonius Deusinglaan 1, 9713AV Groningen, The Netherlands.
Eur Heart J. 2017 Jul 7;38(26):2034-2041. doi: 10.1093/eurheartj/ehx034.
Pulmonary arterial hypertension (PAH) is a progressive and lethal pulmonary vascular disease (PVD). Although in recent years outcome has improved by new treatments that delay disease progression, a cure has not yet been achieved. In PAH associated with congenital heart disease (CHD), remodeling of the pulmonary vasculature reaches an irreversible phenotype similar to all forms of end-stage PAH. In PAH-CHD, however, also an early stage is recognised, which can be completely reversible. This reversible phase has never been recognised in other forms of PAH, most likely because these patients are only diagnosed once advanced disease has developed. We propose that the clinical model of PAH-CHD, with an early reversible and advanced irreversible stage, offers unique opportunities to study pathophysiological and molecular mechanisms that orchestrate the transition from reversible medial hypertrophy into irreversible plexiform lesions. Comprehension of these mechanisms is not only pivotal in clinical assessment of disease progression and operability of patients with PAH-CHD; specific targeting of these mechanisms may also lead to pharmacological interventions that transform 'irreversible' plexiform lesions into a reversible PVD: one that is amenable for a cure. In recent years, significant steps have been made in the strive to 'reverse the irreversible'. This review provides an overview of current clinical and experimental knowledge on the reversibility of PAH, focussing on flow-associated mechanisms, and the near-future potential to advance this field.
肺动脉高压（PAH）是一种进行性和致命性的肺血管疾病（PVD）。尽管近年来新的治疗方法延缓了疾病进展，改善了预后，但仍未实现治愈。在与先天性心脏病（CHD）相关的 PAH 中，肺血管重构达到类似于所有终末期 PAH 形式的不可逆转表型。然而，在 PAH-CHD 中，还可以识别出一个早期阶段，该阶段可以完全逆转。在其他形式的 PAH 中从未认识到这种可逆阶段，这很可能是因为这些患者仅在出现晚期疾病时才被诊断出来。我们提出，PAH-CHD 的临床模型，具有早期可逆和晚期不可逆阶段，为研究调节从中度可复性向不可复性丛状病变转变的病理生理和分子机制提供了独特的机会。理解这些机制不仅对评估 PAH-CHD 患者疾病进展和手术可行性至关重要；针对这些机制的特定靶向也可能导致药物干预，将“不可逆转”的丛状病变转化为可逆转的 PVD：一种可以治愈的疾病。近年来，在努力“逆转不可逆转”方面取得了重大进展。这篇综述概述了当前关于 PAH 可逆性的临床和实验知识，重点介绍了与血流相关的机制，以及在推进这一领域方面的近期潜力。
