Department of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam.
Section of Systems Physiology, Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Curr Opin Pulm Med. 2019 Sep;25(5):410-417. doi: 10.1097/MCP.0000000000000610.
Right ventricular (RV) function is an important determinant of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although substantial progress has been made in understanding the development of RV failure in the last decennia, this has not yet resulted in the development of RV selective therapies. In this review, we will discuss the current status on the treatment of RV failure and potential novel therapeutic strategies that are currently being investigated in clinical trials.
Increased afterload results in elevated wall tension. Consequences of increased wall tension include autonomic disbalance, metabolic shift and inflammation, negatively affecting RV contractility. Compromised RV systolic function and low cardiac output activate renin-angiotensin aldosterone system, which leads to fluid retention and further increase in RV wall tension. This vicious circle can be interrupted by directly targeting the determinants of RV wall tension; preload and afterload by PAH-medications and diuretics, but is also possibly by restoring neurohormonal and metabolic disbalance, and inhibiting maladaptive inflammation. A variety of RV selective drugs are currently being studied in clinical trials.
Nowadays, afterload reduction is still the cornerstone in treatment of PAH. New treatments targeting important pathobiological determinants of RV failure directly are emerging.
右心室(RV)功能是肺动脉高压(PAH)患者发病率和死亡率的重要决定因素。尽管在过去几十年中,人们对 RV 衰竭的发展有了更深入的了解,但这并未导致 RV 选择性治疗的发展。在这篇综述中,我们将讨论 RV 衰竭治疗的现状和目前正在临床试验中研究的潜在新治疗策略。
后负荷增加会导致壁张力升高。壁张力增加的后果包括自主神经失衡、代谢转移和炎症,这些都会对 RV 收缩功能产生负面影响。RV 收缩功能受损和心输出量降低会激活肾素-血管紧张素-醛固酮系统,导致液体潴留和 RV 壁张力进一步增加。这种恶性循环可以通过直接针对 RV 壁张力的决定因素来阻断,通过 PAH 药物和利尿剂来降低前负荷和后负荷,但也可能通过恢复神经激素和代谢失衡以及抑制适应性炎症来阻断。目前正在临床试验中研究多种 RV 选择性药物。
目前,降低后负荷仍然是 PAH 治疗的基石。针对 RV 衰竭重要病理生理决定因素的新治疗方法正在出现。