Klinke Anna, Schubert Torben, Müller Marion, Legchenko Ekaterina, Zelt Jason G E, Shimauchi Tsukasa, Napp L Christian, Rothman Alexander M K, Bonnet Sébastien, Stewart Duncan J, Hansmann Georg, Rudolph Volker
Clinic for General and Interventional Cardiology/Angiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
Department of Pediatric Cardiology and Critical Care, Hannover Medical School, Hannover, Germany.
Cardiovasc Diagn Ther. 2020 Oct;10(5):1735-1767. doi: 10.21037/cdt-20-592.
Therapeutic options for right ventricular (RV) dysfunction and failure are strongly limited. Right heart failure (RHF) has been mostly addressed in the context of pulmonary arterial hypertension (PAH), where it is not possible to discern pulmonary vascular- and RV-directed effects of therapeutic approaches. In part, opposing pathomechanisms in RV and pulmonary vasculature, i.e., regarding apoptosis, angiogenesis and proliferation, complicate addressing RHF in PAH. Therapy effective for left heart failure is not applicable to RHF, e.g., inhibition of adrenoceptor signaling and of the renin-angiotensin system had no or only limited success. A number of experimental studies employing animal models for PAH or RV dysfunction or failure have identified beneficial effects of novel pharmacological agents, with most promising results obtained with modulators of metabolism and reactive oxygen species or inflammation, respectively. In addition, established PAH agents, in particular phosphodiesterase-5 inhibitors and soluble guanylate cyclase stimulators, may directly address RV integrity. Promising results are furthermore derived with microRNA (miRNA) and long non-coding RNA (lncRNA) blocking or mimetic strategies, which can target microvascular rarefaction, inflammation, metabolism or fibrotic and hypertrophic remodeling in the dysfunctional RV. Likewise, pre-clinical data demonstrate that cell-based therapies using stem or progenitor cells have beneficial effects on the RV, mainly by improving the microvascular system, however clinical success will largely depend on delivery routes. A particular option for PAH is targeted denervation of the pulmonary vasculature, given the sympathetic overdrive in PAH patients. Finally, acute and durable mechanical circulatory support are available for the right heart, which however has been tested mostly in RHF with concomitant left heart disease. Here, we aim to review current pharmacological, RNA- and cell-based therapeutic options and their potential to directly target the RV and to review available data for pulmonary artery denervation and mechanical circulatory support.
右心室（RV）功能障碍和衰竭的治疗选择非常有限。右心衰竭（RHF）大多是在肺动脉高压（PAH）的背景下进行研究的，在这种情况下，无法区分治疗方法对肺血管和右心室的影响。部分原因是，右心室和肺血管中的相反病理机制，即细胞凋亡、血管生成和增殖方面的机制，使得在PAH中治疗RHF变得复杂。对左心衰竭有效的治疗方法不适用于RHF，例如，抑制肾上腺素能受体信号传导和肾素-血管紧张素系统没有取得成功或仅取得有限的成功。一些使用PAH或RV功能障碍或衰竭动物模型的实验研究已经确定了新型药物的有益作用，分别在代谢、活性氧或炎症调节剂方面取得了最有希望的结果。此外，已有的PAH药物，特别是磷酸二酯酶-5抑制剂和可溶性鸟苷酸环化酶刺激剂，可能直接作用于右心室的完整性。此外，微小RNA（miRNA）和长链非编码RNA（lncRNA）阻断或模拟策略也取得了有希望的结果，这些策略可以针对功能失调的右心室中的微血管稀疏、炎症、代谢或纤维化和肥厚性重塑。同样，临床前数据表明，使用干细胞或祖细胞的细胞疗法对右心室有有益作用，主要是通过改善微血管系统，然而临床成功很大程度上取决于递送途径。鉴于PAH患者存在交感神经过度兴奋，PAH的一种特殊选择是对肺血管进行靶向去神经支配。最后，右心可采用急性和持久的机械循环支持，然而这大多是在伴有左心疾病的RHF中进行测试的。在这里，我们旨在综述当前基于药理学、RNA和细胞的治疗选择及其直接靶向右心室的潜力，并综述肺去神经支配和机械循环支持的现有数据。
