See Article by Tello et al

Over the last decade, there has been increasing appreciation for the importance of right ventricular (RV) coupling to the pulmonary arterial (PA) circulation. This relationship, so-called RV-PA coupling, is an application of the left-sided ventriculo-arterial coupling first described in the 1980s.¹ Whether it refers to the left or right, coupling describes the energy transfer between ventricular contractility and arterial afterload. Ventricular contractility is well characterized by end-systolic elastance (Ees), a load-independent measure of systolic function. Arterial afterload, on the other hand, can be thought of in terms of net vascular stiffness. Sunagawa et al^1,2 created a term in 1983 called effective arterial elastance (Ea), which encapsulates net stiffness by combining mean and pulsatile loading to yield a lumped parameter that reflects the load imposed upon the ventricle. An important breakthrough came in 1992 when Kelly et al³ found in humans that end-systolic pressure divided by stroke volume accurately represented Ea across a wide afterload range. Because Ea is conveniently measured using the same units as Ees, this allows the ratio of Ees to Ea to become a unit-less value that encapsulates ventriculo-arterial coupling. The ideal Ees/Ea ratio is estimated to be 1.0 to 2.0.² This ratio is seen in the healthy RV-PA unit and remains preserved even in the early phases of pulmonary hypertension (PH) because compensatory RV hypertrophy leads to an increase in RV Ees that matches increasing Ea. It is only with progressive RV decompensation that RV Ees begins to fall, Ees/Ea declines, and the RV-PA unit becomes uncoupled.⁴

RV-PA coupling is often talked about in academic circles and carefully measured in animal and human experimental studies of PH. Coupling can describe RV compensation not only in group I PH but also in PH secondary to a range of left-sided cardiac conditions. Its importance has risen alongside increasing recognition of the pivotal role that the RV plays in many cardiopulmonary conditions. But when was the last time any of us talked to a patient or clinical colleague about coupling? “Great news, your coupling ratio is 1.5!” Despite its common use in the literature and its ability to describe the full range of RV-PA performance, there is a surprising lack of correlation between coupling, as measured by Ees/Ea, and more clinically utilized parameters of RV dysfunction, such as RV dilation or RV ejection fraction (RVEF). This leads to an unfortunate disconnect between the research and clinical applications of RV-PA coupling.

In this issue of Circulation: Heart Failure, Tello et al⁵ lay out a much-needed blueprint that relates RV-PA coupling to more clinically accessible measures of RV performance in PH. In their study, they prospectively obtain pressure-volume loop measurements alongside right heart catheterization and cardiac magnetic resonance imaging in 42 human patients with PH. In this cohort, the PH patients with more severe disease demonstrated predictable increase in RV mass and end-diastolic volume , decrease in RVEF, as well as worsening PA stiffness, capacitance, and distensibility. Ees/Ea showed progressive decline alongside worsening RV end-diastolic volume, mass, and RVEF. By mapping out Ees/Ea across tertiles of each parameter, the authors show that Ees/Ea maintains a ratio of 0.89:1.09 in PH patients with compensated RVs (best tertile), drifts to 0.58:0.70 in early RV decompensation (middle tertile), and falls to 0.56:0.61 in the most decompensated tertile. Little is known about the clinical relevance of Ees/Ea, and so by using receiver operator curve analysis, the authors show that an Ees/Ea of <0.805 best predicted a cardiac magnetic resonance RVEF of <35%, the latter being an established indicator of RV decompensation in PH. Last, they show that RV stroke volume divided by end-systolic volume, a measure readily attainable from cardiac magnetic resonance, is at least as good at predicting RVEF <35% as Ees/Ea, if not better.

Using pressure-volume loops, the authors also calculate single-beat end-diastolic elastance (Eed), a coefficient of diastolic stiffness attainable from RV pressure-volume data. Eed indexes RV diastolic dysfunction, increases with diastolic stiffness, and has been shown to be predictive of outcomes in PH.^6,7 The authors show that Eed increases alongside worsening RV mass, volume, and ejection fraction, as well as worsening T1 mapping of RV fibrosis. Interestingly, Eed trends upward just as RV mass and end-diastolic volume increase and Ees/Ea declines, illustrating just how tightly interwoven coupling, mass, dilation, and diastolic dysfunction are in PH.⁵

RV Ees/Ea has been widely used in research; its clinical validity has generally been assumed. The current study thus does an important job of validating Ees/Ea, and even Eed, against multiple established clinical benchmarks of RV decompensation. Second, the authors verify that Ees/Ea maintains coupling at ≈1.0 in early PH and show us that Ees/Ea has to fall below 0.8 before we see RV dilation and overt worsening of RV systolic function. These values help us to understand the range of Ees/Ea in the context of known clinical markers of RV decompensation. Tello et al⁵ thus provide a much-needed link between the growing body of RV-PA coupling research to the bedside assessment of RV function in PH. One fly in the ointment, however, is the single-beat method by which Ees/Ea was determined. Ees is traditionally measured by altering RV preload, obtaining a family of pressure-volume loops, and measuring the slope of multiple end-systolic pressure points. This is known as the multi-beat method. The single-beat method determines Ees without need for filling changes to the RV. It was originally proposed by Sunagawa et al⁸ and Senzaki et al⁹ in the left ventricle and shown to be practical for the RV by Brimioulle et al.¹⁰ The single-beat method extrapolates a theoretical pressure of isovolumic contraction (P_isovol) and combines that with the end-systolic pressure point to calculate Ees. It should be noted that although RV P_isovol has been validated in animal models, it has not been validated in humans with severe PH,⁴ and a recent study failed to show correlation between single-beat and multi-beat measures of Ees in a human cohort with and without PH.¹¹ That said, both methodologies, on the whole, capture the same overall relationship of RV contractility to PA afterload, and Ea is measured the same either way. Also, the current study may help to bolster the validity of single-beat Ees/Ea by relating it to well-established metrics of RV decompensation.

Now that we have a blueprint with which to understand the clinical implications of Ees/Ea, where do we go from here? More work needs to be done to link Ees/Ea to the bedside. Despite its common use in research, Ees/Ea has never been shown to predict outcomes in PH patients. Does Ees/Ea even predict clinical events? It would be a much more relevant parameter if so. Also, the current study shows that readily available clinical metrics of RV performance serve as an adequate surrogate for reduced Ees/Ea. But is there perhaps a role for Ees/Ea in identifying early uncoupling in PH patients? Ees does remain a very sensitive measure of RV systolic function and captures declining RV contractility well before right heart catheterization or cardiac magnetic resonance can detect.^12,13 RV dilation, stroke volume/end-systolic volume, and reduced RVEF all capture the uncoupled RV, and so perhaps Ees/Ea can be better put to use in capturing earlier RV disease. Now that we are guided by Tello et al⁵ with a more robust clinical framework for RV-PA coupling, future studies in the field will hopefully provide more context and utility to the bedside application of Ees/Ea.

None.

The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.

Guest Editor for this article was Ryan J. Tedford, MD.

参见Tello等的文章

在过去的十年中，人们越来越认识到右心室（RV）耦合至肺动脉（PA）循环的重要性。这种关系称为RV-PA耦合，是1980年代首次描述的左侧心室-动脉耦合的一种应用。¹不管是指左侧还是右侧，耦合都描述了心室收缩力和动脉后负荷之间的能量转移。收缩末期弹性（Ees）很好地表征了心室收缩，收缩末期弹性是一种独立于负荷的收缩功能测量方法。另一方面，可以根据净血管刚度来考虑动脉后负荷。a川等人^1,21983年创建了一个术语，称为有效动脉弹性（Ea），该术语通过组合平均负荷和脉动负荷来产生净集总参数，从而反映出施加在心室上的负荷，从而封装了净刚度。一个重要的突破出现在1992年，当时Kelly等[ ^3]在人体中发现收缩末期压力除以中风量可在很宽的后负荷范围内准确代表Ea。因为使用与Ees相同的单位方便地测量Ea，所以这使得Ees与Ea的比率成为封装心室-动脉耦合的无单位值。理想的Ees / Ea比估计为1.0到2.0。^2个在健康的RV-PA单位中可以看到该比率，并且即使在肺动脉高压（PH）的早期阶段也可以保留该比率，因为代偿性RV肥大会导致RV Ees的增加与Ea的增加相匹配。只有通过渐进式RV失补偿，RV Ees才会开始下降，Ees / Ea下降，并且RV-PA单元将解耦。⁴

RV-PA偶联在学术界经常被谈论，并在动物和人类的PH实验研究中被仔细测量。耦合不仅可以描述I PH组中的RV补偿，而且还可以描述继发于左侧心脏疾病范围的PH中的RV补偿。随着越来越多的人认识到RV在许多心肺疾病中所起的关键作用，其重要性日益提高。但是，什么时候我们最后一次与患者或临床同事讨论耦合？“好消息，您的耦合比是1.5！” 尽管在文献中有普遍使用，并且具有描述整个RV-PA性能的能力，但是通过Ees / Ea测量的偶合与更广泛使用的RV功能障碍的临床参数（如RV）之间却缺乏令人惊讶的相关性。扩张或RV射血分数（RVEF）。

在本期《循环：心力衰竭》中，Tello等⁵提出了一个迫切需要的蓝图，该图将RV-PA偶联与PH中RV性能的更多临床可得性度量联系起来。在他们的研究中，他们前瞻性地获得了42例PH患者的压力-容积环测量结果以及右心导管检查和心脏磁共振成像。在该队列中，患有更严重疾病的PH患者表现出可预测的RV质量和舒张末期容积增加，RVEF下降以及PA僵硬，电容和扩张性恶化。Ees / Ea表现为进行性下降，同时右室舒张末期容积，质量和RVEF恶化。通过在每个参数的三分位数之间绘制Ees / Ea，作者显示，在具有RV补偿的PH患者（最佳三分位数）中，Ees / Ea维持0.89：1.09的比率，在早期RV失代偿（中三分位数）中漂移至0.58：0.70 ，在补偿最失调的三分位数中降至0.56：0.61。关于Ees / Ea的临床相关性知之甚少，因此，通过使用接收者操作符曲线分析，作者表明，Ees / Ea <0.805最佳预测了<35％的心脏磁共振RVEF，后者是确定的指标PH中的RV代偿失调。最后，他们表明，RV搏动量除以收缩末期容积（一种可从心脏磁共振轻松获得的指标），即使不是更好，在预测RVEF <35％方面也至少与Ees / Ea一样好。后者是RV中RV代偿失调的既定指标。最后，他们表明，RV搏动量除以收缩末期容积（一种可从心脏磁共振轻松获得的指标），即使不是更好，在预测RVEF <35％方面也至少与Ees / Ea一样好。后者是RV中RV代偿失调的既定指标。最后，他们表明，RV搏动量除以收缩末期容积（一种可从心脏磁共振轻松获得的指标），即使不是更好，在预测RVEF <35％方面也至少与Ees / Ea一样好。

使用压力-体积循环，作者还计算了单搏舒张末期弹性（Eed），这是从RV压力-体积数据可获得的舒张刚度系数。Eed指示RV舒张功能障碍，随舒张硬度增加而增加，并已显示出可预测PH的结果。^6,7作者表明，Eed增加，同时RV的质量，体积和射血分数变差，以及RV纤维化的T1定位变差。有趣的是，Eed随RV质量和舒张末期容积增加而Ees / Ea下降而上升，这说明了PH中交织耦合，质量，扩张和舒张功能障碍的紧密程度。⁵

RV Ees / Ea已被广泛用于研究中。一般认为其临床有效性。因此，当前的研究在针对多个既定的RV代偿失衡的临床基准进行Ees / Ea甚至Eed验证方面发挥了重要作用。其次，作者验证了在早期PH时Ees / Ea维持在≈1.0的耦合，并向我们证明Ees / Ea必须降到0.8以下，才能看到RV扩张和RV收缩功能的明显恶化。这些值有助于我们在RV代偿失调的已知临床指标的背景下了解Ees / Ea的范围。特洛等⁵因此，在RV-PA偶联研究的增长体与床旁评估PH的RV功能之间提供了急需的联系。然而，美中不足的是单搏方法，通过该方法可以确定Ees / Ea。传统上，Ees的测量是通过改变RV预载，获得一系列的压力-体积环以及测量多个收缩末期压力点的斜率来进行的。这就是所谓的多拍子方法。单拍方法无需填充RV即可确定Ees。它最初是由Sunagawa等人⁸和Senzaki等人⁹在左心室中提出的，并被Brimioulle等人证明对RV可行。¹⁰单搏法可推断等容收缩的理论压力（P_等静压）并将其与收缩末期压力点结合起来以计算Ees。应当指出的是，尽管RV P _isovol已在动物模型中得到验证，但尚未在具有严重PH的人中得到验证[ ^4]，并且最近的一项研究未能显示人的Ees的单搏和多搏测量之间的相关性。有和没有PH的队列。¹¹也就是说，总体而言，这两种方法均捕获了RV收缩力与PA后负荷的相同总体关系，并且任一方法均以相同的方式测量Ea。此外，当前的研究可能通过将其与完善的RV失代偿指标联系起来，来增强单搏Ees / Ea的有效性。

现在我们有了一个蓝图，可以用来了解Ees / Ea的临床意义，我们从这里去哪里呢？需要做更多的工作才能将Ees / Ea连接到床头。尽管在研究中普遍使用Ees / Ea，但从未证明它能预测PH患者的预后。Ees / Ea甚至可以预测临床事件吗？如果是这样，它将是一个更相关的参数。此外，当前的研究表明，RV性能的现成临床指标可作为降低Ees / Ea的适当替代方法。但是，Ees / Ea在确定PH患者的早期解偶联中可能发挥作用吗？Ees确实仍然是RV收缩功能的非常敏感的指标，并且可以在右心导管检查或心脏磁共振能够检测到之前捕获RV收缩力下降。^12,13RV扩张，中风量/收缩末期容积和RVEF降低均捕获了未偶合的RV，因此也许Ees / Ea可以更好地用于捕获较早的RV疾病。现在，在Tello等人^5的指导下，我们为RV-PA偶联提供了更强大的临床框架，该领域的未来研究有望为Ees / Ea的床旁应用提供更多的背景和实用性。

没有任何。

本文表达的观点不一定是编辑者或美国心脏协会的观点。

这篇文章的客座编辑是医学博士Ryan J. Tedford。