Review of Cardiogenic Shock After Acute Myocardial Infarction .pdf

To the Editor The recent Review on cardiogenic shock after acutemyocardial infarction described the lack of evidence supporting use of percutaneous mechanical circulatory support devices in these patients.

致编辑 最近关于急性心肌梗死后心源性休克的评论描述了缺乏证据支持在这些患者中使用经皮机械循环支持装置。

Although temporary percutaneous mechanical circulatory support is not a cure for cardiogenic shock, it is a strategy used solely to temporarily suspend imminent death to facilitate another clinical development or intervention that can improve prognosis. With reversible myocardial injury, successful coronary revascularization or sufficient recovery of stunnedmyocardiummay allow weaning of percutaneousmechanical circulatory support. If myocardial injury is irreversible, suitability for and successful implementation of a longterm left ventricular assist device (LVAD) or cardiac transplant will determine prognosis. Any form of percutaneousmechanical circulatory support can be deemed to have “failed” only if these exit strategies are clearly possible but not reached.

虽然临时经皮机械循环支持不能治愈心源性休克，但它是一种仅用于暂时中止即将死亡的策略，以促进可以改善预后的另一临床开发或干预措施。对于可逆性心肌损伤，成功的冠状动脉血运重建或震惊心肌的充分恢复可能允许撤机经皮机械循环支持。如果心肌损伤是不可逆的，长期左心室辅助装置 (LVAD) 或心脏移植的适用性和成功实施将决定预后。只有当这些退出策略显然可行但未达到时，任何形式的经皮机械循环支持都可以被视为“失败”。

All major cardiogenic shock trials to date have used allcause mortality at 30 days as a primary end point. Given that percutaneous mechanical circulatory support for 30 days is relatively rare, inclusion of patients at study onset without an exit strategy (those with irrecoverable myocardial injury who are not candidates for LVAD or cardiac transplant) could lead to erroneous conclusions. Death due to unavoidable planned withdrawal of percutaneous mechanical circulatory support because of the lack of an exit strategy meets primary end point criteria in such trials but does not support the conclusion that the percutaneous mechanical circulatory support was ineffectual. In these cases, it is the lethal combination of irrecoverable myocardial injury with no exit strategy that dictates prognosis.

迄今为止，所有主要心源性休克试验都将30天内的全因死亡率作为主要终点。考虑到30天的经皮机械循环支持相对较少，在研究开始时纳入没有退出策略的患者（那些不适合LVAD或心脏移植的无法恢复的心肌损伤患者）可能会导致错误的结论。由于缺乏退出策略而不可避免地计划退出经皮机械循环支持导致的死亡符合此类试验的主要终点标准，但不支持经皮机械循环支持无效的结论。在这些情况下，决定预后的是无法恢复的心肌损伤与无退出策略的致命组合。

International guidelines have essentially placed a moratorium on intra-aortic balloon pump (IABP) use based on results from the IABP-SHOCK II trial. In this study, the median length of time patients received IABP support was 3 days and the median age of randomized patients was 70 years, which is older than optimal for transplant, especially in the setting of salvaged cardiogenic shock. The current reality that IABPs remain frequently used suggests that clinicians continue to see benefits with IABP support on an individual patient basis despite the IABP-SHOCK II trial conclusions.

根据 IABP-SHOCK II 试验的结果，国际指南基本上已暂停使用主动脉内球囊泵 (IABP)。在这项研究中，患者接受 IABP 支持的中位时间为 3 天，随机患者的中位年龄为 70 岁，这比移植的最佳年龄要大，尤其是在挽救性心源性休克的情况下。IABP 仍然经常使用的当前现实表明，尽管 IABP-SHOCK II 试验得出结论，但临床医生继续看到基于个体患者的 IABP 支持的益处。

A 2019 study of the percutaneous LVAD Impella, which also used all-cause mortality at 30 days as a primary end point, similarly revealed negative results. Moreover, an ongoing trial of venoarterial extracorporeal membrane oxygenation for patients with cardiogenic shock is also using the same primary end point of all-cause mortality at 30 days (NCT03813134).

2019 年对经皮利瓦德·普韦拉的一项研究也以 30 天的全因死亡率作为主要终点，同样显示出阴性结果。此外，一项正在进行的心源性休克患者静脉动脉体外膜肺氧合试验也使用了相同的主要终点，即 30 天的全因死亡率 (NCT03813134)。

With ongoing use of all-cause mortality at 30 days as a primary end point, are we in danger of generating a plethora of spurious “antievidence” for all current and emerging percutaneous mechanical circulatory support devices for cardiogenic shock?

随着 30 天全因死亡率作为主要终点的持续使用，我们是否有可能为所有当前和新兴的心源性休克经皮机械循环支持装置产生过多的虚假“反证据”？

In Reply In his Letter to the Editor about our recent Review, Dr Dalzell makes a case for continued use of temporary percutaneous mechanical circulatory support devices and questions the utility of using 30-daymortality as an end point in trials of these devices. We agree that percutaneous mechanical circulatory support devices are neither a definitive treatment nor a cure for cardiogenic shock. These devices are deployed to temporarily augment systemic perfusion while the etiology of clinical decompensation (in the case of acute myocardial infarction, an occluded epicardial coronary artery) is identified and treated so that the shock state can be reversed. As noted, percutaneous mechanical circulatory support devices can be removed when the acute shock state has resolved and after demonstrating that the heart can maintain adequate systemic perfusion. Alternatively, removal of a percutaneous mechanical circulatory support device should be considered if a patient experiences a device-related complication and the risk of continued use outweighs potential benefit.

回复达尔泽尔博士在致编辑关于我们最近的评论的信中提出了继续使用临时经皮机械循环支持装置的理由，并质疑使用 30 天死亡率作为这些装置试验的终点的效用。我们同意经皮机械循环支持装置既不是最终的治疗方法，也不是心源性休克的治愈方法。这些装置用于临时增加全身灌注，同时识别和治疗临床失代偿（在急性心肌梗塞的情况下，闭塞的心外膜冠状动脉）的病因，从而可以逆转休克状态。如前所述，当急性休克状态消退并且证明心脏可以维持足够的全身灌注后，可以移除经皮机械循环支持装置。或者，如果患者出现与装置相关的并发症并且继续使用的风险超过潜在的益处，则应考虑移除经皮机械循环支持装置。

It appears that the crux of the proposal put forth by Dalzell is 2-fold: (1) the use of mortality alone as an end point in randomized trials may obscure the benefit of temporary percutaneous mechanical circulatory support if the trial does not also include some “exit strategy,” such as LVAD placement or cardiac transplant and (2) the inclusion of patients who may not be candidates for advanced therapies such as LVAD or cardiac transplant in randomized trials diminishes the potential benefit of percutaneous mechanical circulatory support because it does not allow for the assessment of these devices as a “bridge” to these advanced therapies.

达尔泽尔提出的建议的关键似乎有 2 倍：(1) 如果试验不包括一些随机试验，单独使用死亡率作为终点可能会掩盖临时经皮机械循环支持的益处。“退出策略”，例如 LVAD 植入或心脏移植，以及 (2) 在随机试验中纳入可能不适合 LVAD 或心脏移植等先进疗法的患者降低了经皮机械循环支持的潜在益处，因为它不 允许评估这些设备作为这些先进疗法的“桥梁”。

We agree in part with the argument put forth by Dalzell but offer these important caveats.Mortality from cardiogenic shock is still high, and any device therapy that carries riskmust prove that it reduces mortality before it is widely implemented. If a device shows that it improves survival or, at the very least, does not reduce survival, then other outcomes such as hospital/ intensive care unit length of stay or surrogate outcomes can be studied. Moreover, the use of a 30-day mortality end point would include patients who survive to receive advanced therapies. Dalzell’s comment about the inclusion of patients who are not candidates for advanced therapies is well taken; however, older patients may be at higher risk of developing cardiogenic shock, and there is a dearth of evidence for effective therapies in older patients. Systematic exclusion of a specific patient subgroup with a potentially worse outcome would limit external validity and study generalizability. We propose that any trial of percutaneous mechanical circulatory support should strive to oversample patient groups in whom the evidence base is particularly sparse.

我们部分同意达尔泽尔提出的论点，但提出了这些重要的警告。心源性休克的死亡率仍然很高，任何具有风险的器械疗法都必须证明它可以在广泛实施之前降低死亡率。如果设备显示它可以提高生存率，或者至少不会降低生存率，则可以研究其他结果，例如住院/重症监护病房的住院时间或替代结果。此外，使用 30 天死亡率终点将包括存活并接受高级治疗的患者。达尔泽尔关于纳入不适合接受高级治疗的患者的评论得到了很好的采纳；然而，老年患者发生心源性休克的风险可能更高，并且缺乏对老年患者进行有效治疗的证据。系统排除具有潜在更差结果的特定患者亚组将限制外部有效性和研究的普遍性。我们建议，任何经皮机械循环支持试验都应努力对证据基础特别稀少的患者群体进行过度抽样。