Over the past decade, extracorporeal life support (ECLS) has gained increasing utilization in the management of refractory cardiogenic shock (CS) with a class IIaC recommendation according to the latest European and US guidelines.¹ However, recent randomized controlled trials (RCTs) and meta-analyses can be considered inconclusive in demonstrating the benefit of ECLS compared with optimal medical treatment in patients with acute myocardial infarction complicated by CS.

Various factors may explain these neutral results but the inherent haemodynamic effect of the ECLS itself probably plays a major role. Due to its aortic retrograde flow principle, peripheral ECLS can lead to left ventricular (LV) overload and distension, increased myocardial workload and pulmonary oedema, compromising cardiac recovery, and diming the patient's prognosis. To optimize the chances of ECLS outcomes with good heart recovery, several left heart decompression (LHD) strategies have been proposed. However, all strategies are invasive, entail risks of bleeding, haemolysis and thromboembolic complications, and the risk–benefit ratio of their use remains unclear.² Despite limited available data, recent guidelines suggest early initiation of LHD after ECLS initiation (class IIaC) without further defining the preferred unloading technique or its implementation timing after ECLS.¹

Left heart decompression techniques aim to unload the left ventricle by increasing the forward flow, achieved either indirectly with the intra-aortic balloon pump (IABP) or directly through microaxial flow pumps, or through left atrial (LA) drainage (atrioseptostomy) or active transapical venting (Figure 1). Active LA venting implies the implementation of an atrioseptostomy in combination with a 21–23 Fr cannula inserted through the interatrial septum and connected in ‘Y’ to the venous ECLS circuit which remains in place for several days. Its achievement justifies multidisciplinary skills and expertise assuring safe septal defect realization and correct cannula positioning, but also close circuit monitoring during the ECLS run.

In this viewpoint around LA venting, we focus on two recent RCTs, EARLY-UNLOAD and EVOLVE-ECLS, conducted in patients with CS undergoing ECLS. In the EARLY-UNLOAD trial (n = 116; single centre), the comparison centred on early unloading through active LA venting within a 12-h window versus a rescue unloading strategy triggered by clinical indications of increased LV afterload.³ The EVOLVE-ECMO trial (n = 60; two centres) examined LHD via LA venting at the time of ECLS insertion (termed the early approach) versus the rescue unloading approach.⁴ Both trials yielded concordant findings, indicating the absence of significant differences in 30-day mortality rates. It is pertinent to acknowledge that the relatively modest sample sizes in both trials were insufficiently powered to adequately address their primary endpoints. Notably, the sample size calculation for the EARLY-UNLOAD trial was predicated on achieving a 50% reduction in relative mortality risk, assuming an initial unsuitable absolute mortality rate of 25% within the early intervention group. This assumption starkly contrasts with the 50–60% mortality rates reported in the literature for the CS population, underscoring the imperative need for more comprehensive investigations. Moreover, the interpretation of the EARLY-UNLOAD trial is complexified by a high rate of crossover with 41% of patients in the control group that finally underwent LA venting.³ This highlights the significant challenges associated with intention-to-treat analysis, adding a layer of complexity to interpreting the results. The difference in terms of timing of implantation (21.8 h in the control group vs. 1.1 h in the early LHD group) allows us to suggest that early discharge via LA venting is not superior to LHD based on signs of overload, but does not permit to conclude about the efficacy and superiority of LHD by LA venting.

Considering the findings of these two trials, two specific points deserve further attention.

First, it is essential to determine whether the use of LA venting is an effective unloading technique. Indeed, the utilization of LA venting for LV unloading prompts attention regarding its effectiveness, particularly in scenarios devoid of significant mitral regurgitation. This approach addresses the LV preload, but it disregards the intricate contributions of venous return via Thebesian veins, bronchial veins, and retro-aortic circulation, elements that contribute significantly in case of aortic insufficiency. Furthermore, this indirect method of LV unloading may compromise LV ejection efficiency, hindering adequate opening of the aortic valve and potentially exacerbating stasis, thereby increasing the incidence of LV and aortic thrombus formation. Therefore, the suggested technique may inadvertently overlook crucial facets of cardiac physiology and the intricate dynamics of the circulation. Additionally, the de-escalation process is compromised by the simultaneous withdrawal of LA venting and venoarterial extracorporeal membrane oxygenation (VA-ECMO), not only imposing physiological stress to the myocardium, but also resulting in a persistent septal defect in 17–100% of the survivors, requiring additional closure in up to 50% of cases.⁵

In opposite to LA venting, the mechanism of both Impella^TM and IABP offer physiological advantages. The Impella functions as an axial flow pump that actively unloads the left ventricle by propelling blood from the left ventricle into the ascending aorta. This actively assists in reducing myocardial workload and enhancing coronary perfusion. The IABP enhances diastolic coronary perfusion and reduces LV afterload, albeit at a lower extent as compared to the micro-axial flow pumps.⁶

Secondly, the ideal timing for LHD implementation is a crucial factor for optimizing its effectiveness. Unloading devices can be inserted before, together with, or shortly after the initiation of VA-ECMO. A proactive approach may safeguard the vulnerable ventricle and facilitate myocardial recovery by preventing exposure to elevated afterload, although this should be balanced against the potential risks of increased complications and costs. Based on a recent retrospective multicentre study, Schrage et al.⁷ showed that early LHD (within the first 2 h after ECLS initiation) was associated with a reduced risk of 30-day mortality (hazard ratio 0.64, 95% confidence interval [CI] 0.46–0.88) and an increased likelihood of successful weaning from mechanical ventilation (odds ratio 2.17, 95% CI 1.19–3.93). It is worth noting that this study specifically examined active LV unloading using the Impella^TM device. In contrast, despite the remarkably fast median time between randomization and transseptal LA cannulation in the early LHD group, the EARLY-UNLOAD and EVOLVE-ECLS trials failed to confirm the advantages of early LHD. This raises an important question: is the mechanism of unloading/device a contributing factor to the observed outcomes? Although current data suggest that prophylactic unloading after the initiation of VA-ECMO appears beneficial, we can only conclude that further prospective RCTs are needed to establish the optimal timing of LDH initiation. A tailored approach guided by individual haemodynamics and clinical criteria can individualize the unloading strategy and possibly improve outcomes.

The only clinical data comparing different unloading strategies rise from meta-analyses pooling retrospective studies.⁸ Results of these studies highlight the importance of further research in this field comparing different devices and timing of LHD initiation. Ongoing RCTs (UNLOAD-ECMO and REMAP-ECMO trials) are attempting to address the question whether early and/or systematic LHD initiation in CS patients treated with ECLS is beneficial or not. However, challenges in early LHD management and potential complications must be recognized, as they may hinder patient recruitment into RCTs, as seen in the premature termination of the REVERSE trial. Furthermore, additional RCTs comparing different LHD strategies, such as Impella^TM and IABP, are crucial to evaluate their impact on mortality, morbidity, and myocardial recovery, considering the limited availability and high cost of cardiac grafts and LV assist devices (Table 1). Awaiting randomized data to make firm recommendations on the preferred unloading methods, currently, decisions should be made on a case-by-case pragmatic base, guided by local expertise, and available strategies in the multidisciplinary shock team.

Conflict of interest: none declared.

在过去的十年中，体外生命支持 (ECLS) 在难治性心源性休克 (CS) 的治疗中得到了越来越多的应用，根据最新的欧洲和美国指南，其推荐为 IIaC 级。 ¹然而，最近的随机对照试验 (RCT) 和荟萃分析在证明 ECLS 与最佳药物治疗相比对急性心肌梗死并发 CS 患者的益处方面尚无定论。

有多种因素可以解释这些中性结果，但 ECLS 本身固有的血流动力学效应可能起着主要作用。由于其主动脉逆行血流原理，外周ECLS可导致左心室（LV）负荷过重和扩张、心肌负荷增加和肺水肿，损害心脏恢复并降低患者的预后。为了优化 ECLS 结果和良好心脏恢复的机会，已经提出了几种左心减压 (LHD) 策略。然而，所有策略都是侵入性的，都会带来出血、溶血和血栓栓塞并发症的风险，并且其使用的风险效益比仍不清楚。 ²尽管可用数据有限，但最近的指南建议在 ECLS 启动后尽早启动 LHD（IIaC 类），而无需进一步定义 ECLS 后的首选卸载技术或其实施时间。 ¹

左心减压技术旨在通过增加前向流量来减轻左心室负荷，可通过主动脉内球囊反搏泵 (IABP) 间接实现，或直接通过微轴流泵实现，或通过左心房 (LA) 引流（房间隔造口术）或主动经心尖导管实现通风（图1）。主动 LA 通气意味着实施房间隔造口术，并结合 21-23 Fr 插管插入房间隔，并以“Y”形连接至静脉 ECLS 回路，该回路可保留数天。其成就证明了多学科技能和专业知识的合理性，可确保安全的间隔缺损实现和正确的插管定位，而且还能在 ECLS 运行期间进行闭路监控。

在围绕 LA 通气的观点中，我们重点关注最近在接受 ECLS 的 CS 患者中进行的两项随机对照试验，即 EARLY-UNLOAD 和 EVOLVE-ECLS。在 EARLY-UNLOAD 试验（ n = 116；单中心）中，比较集中在通过 12 小时窗口内主动左心室通气进行早期卸载与由左心室后负荷增加的临床指征触发的救援卸载策略。 ³ EVOLVE-ECMO 试验（ n = 60；两个中心）检查了 ECLS 插入时通过 LA 通气的 LHD（称为早期方法）与救援卸载方法。 ⁴两项试验得出了一致的结果，表明 30 天死亡率没有显着差异。需要承认的是，这两项试验的样本量相对较小，不足以充分解决其主要终点问题。值得注意的是，EARLY-UNLOAD 试验的样本量计算是以实现相对死亡风险降低 50% 为基础的，假设早期干预组中初始不合适的绝对死亡率为 25%。这一假设与文献报道的 CS 人群 50-60% 的死亡率形成鲜明对比，强调了进行更全面调查的迫切需要。此外，对 EARLY-UNLOAD 试验的解释因高交叉率而变得复杂，对照组中有 41% 的患者最终接受了 LA 通气。 ³这凸显了与意向治疗分析相关的重大挑战，增加了解释结果的复杂性。植入时间方面的差异（对照组为 21.8 小时，对照组为 21.8 小时） 早期 LHD 组中的 1.1 小时）使我们能够根据过载迹象表明通过 LA 通气提前出院并不优于 LHD，但不允许得出通过 LA 通气进行 LHD 的功效和优越性的结论。

考虑到这两项试验的结果，有两个具体点值得进一步关注。

首先，必须确定使用 LA 通风是否是一种有效的卸载技术。事实上，利用左心室通气进行左心室卸载引起了人们对其有效性的关注，特别是在没有明显二尖瓣反流的情况下。这种方法解决了左心室前负荷的问题，但它忽略了通过底比斯静脉、支气管静脉和主动脉后循环的静脉回流的复杂贡献，这些因素在主动脉瓣关闭不全的情况下发挥着重要作用。此外，这种间接的左心室卸载方法可能会损害左心室射血效率，阻碍主动脉瓣充分打开，并可能加剧瘀滞，从而增加左心室和主动脉血栓形成的发生率。因此，所建议的技术可能会无意中忽视心脏生理学和复杂的循环动力学的关键方面。此外，降级过程因 LA 通气和静脉动脉体外膜氧合 (VA-ECMO) 的同时撤出而受到损害，不仅对心肌施加生理应激，而且还会导致 17-100% 的患者出现持续性间隔缺损。幸存者，最多 50% 的案件需要额外关闭。 ⁵

与 LA 通气相反，Impella ^TM和 IABP 的机制都具有生理优势。 Impella 充当轴流泵，通过将血液从左心室推进到升主动脉来主动卸载左心室。这积极有助于减少心肌负荷和增强冠状动脉灌注。 IABP 增强舒张期冠状动脉灌注并减少左心室后负荷，尽管与微轴流泵相比程度较低。 ⁶

其次，LHD实施的理想时机是优化其有效性的关键因素。卸载装置可以在 VA-ECMO 启动之前、同时或启动后不久插入。积极主动的方法可以通过防止后负荷升高来保护脆弱的心室并促进心肌恢复，尽管这应该与并发症和费用增加的潜在风险相权衡。 Schrage等人根据最近的一项回顾性多中心研究。^{图 7}显示，早期 LHD（ECLS 开始后的前 2 小时内）与 30 天死亡率风险降低相关（风险比 0.64，95% 置信区间 [CI] 0.46-0.88），并且成功脱机的可能性增加。机械通气（比值比 2.17，95% CI 1.19–3.93）。值得注意的是，这项研究专门检查了使用 Impella ^TM装置的主动左室卸载。相比之下，尽管早期 LHD 组中随机化和房间隔 LA 插管之间的中位时间非常快，但 EARLY-UNLOAD 和 EVOLVE-ECLS 试验未能证实早期 LHD 的优势。这就提出了一个重要的问题：卸载/设备的机制是观察到的结果的影响因素吗？尽管目前的数据表明，开始 VA-ECMO 后预防性卸载似乎是有益的，但我们只能得出结论，需要进一步的前瞻性随机对照试验来确定 LDH 开始的最佳时机。以个体血流动力学和临床标准为指导的定制方法可以个性化卸载策略并可能改善结果。

比较不同卸载策略的唯一临床数据来自汇总回顾性研究的荟萃分析。 ⁸这些研究的结果强调了在该领域进一步研究比较不同设备和 LHD 启动时间的重要性。正在进行的随机对照试验（UNLOAD-ECMO 和 REMAP-ECMO 试验）试图解决接受 ECLS 治疗的 CS 患者早期和/或系统性 LHD 是否有益的问题。然而，必须认识到早期 LHD 管理的挑战和潜在的并发症，因为它们可能会阻碍患者纳入随机对照试验，正如 REVERSE 试验的提前终止所示。此外，考虑到心脏移植物和左心室辅助装置的可用性有限且成本高昂，比较不同 LHD 策略（例如 Impella ^TM和 IABP）的额外随机对照试验对于评估其对死亡率、发病率和心肌恢复的影响至关重要（表1）。目前，正在等待随机数据对首选卸载方法提出明确建议，目前应在当地专业知识和多学科休克团队可用策略的指导下，根据具体情况务实做出决定。

利益冲突：未声明。