By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
In this randomized controlled trial of patients presenting with ST-elevation myocardial infarction and cardiogenic shock, use of the Impella microaxial flow pump resulted in improved survival but also higher adverse safety events compared with standard care.
Møller JE, Engstrøm T, Jensen LO, et al. Microaxial flow pump or standard care in infarct-related cardiogenic shock. N Engl J Med 2024;390:1382-1393.
Cardiogenic shock (CS) complicates 5% to 10% of cases of ST-elevation myocardial infarction (STEMI). In those cases, approximately half of patients will die despite expedient revascularization and state-of-the-art care. Mechanical circulatory support (MCS) is one option for treating these patients. Prior randomized trials of intra-aortic balloon counterpulsation (IABP-SHOCK II) and extracorporeal life support (ECLS SHOCK) have failed to show an effect of these devices on short-term mortality. The Impella microaxial flow pump is a percutaneous ventricular assist device that has been available for this and other indications for more than 15 years. Three prior small, randomized trials of Impella in CS have failed to show benefit. Registry data have consistently demonstrated adverse events, including bleeding and vascular injury, that one would expect with large-bore femoral arterial access.
The Danish-German (DanGer) Shock Trial was designed to determine whether routine use of Impella in patients with acute MI and cardiogenic shock (AMI-CS) would affect mortality. To that end, 360 patients were enrolled at 14 centers in Denmark, Germany, and England over a period of more than 11 years between 2013 and 2023. Enrolled patients had a median age of 67 years, and the majority (79.2%) were men. Nearly all the patients were successfully revascularized, most by percutaneous coronary intervention (PCI).
The Impella device was placed successfully in 95% of patients assigned to the pump group, while only three patients in the standard care group crossed over to receive a microaxial flow pump. Approximately half of patients assigned to the Impella group received the device prior to PCI. In the pump group, 15.6% of patients were escalated to another form of mechanical circulatory support, while 21% of patients in the standard-care group received such escalation. Weaning and removal of the Impella device was guided by specific hemodynamic criteria designated by the trial.
At 180 days, all-cause death was significantly lower among patients assigned to the microaxial pump group (45.8% vs. 58.5%; hazard ratio, 0.74; 95% confidence interval, 0.55 to 0.99; P = 0.04). Put another way, the absolute risk reduction was nearly 13%, and the number needed to treat to prevent one death was eight. In subgroup analysis of the primary endpoint, the survival benefit was greatest in those with lower initial mean arterial pressures, while women treated with the device did not benefit.
A composite safety endpoint occurred in 24% of patients in the pump group vs. just 6% of the standard care group, translating to a number needed to harm of six. The relative risk was approximately 2 for severe bleeding and renal replacement therapy, greater than 5 for limb ischemia, and nearly 3 for sepsis with a positive blood culture.
The authors concluded that among patients with STEMI and cardiogenic shock, routine use of a microaxial flow pump resulted in significantly improved survival at 180 days compared with usual care, at the cost of a higher frequency of serious adverse events.
COMMENTARY
This is the first major randomized trial of any MCS device that has demonstrated an improvement in survival in cardiogenic shock associated with ST-elevation MI. The Impella device was first approved in the United States in 2008, and the current CP version used in the trial has been available since 2012. Use of this device in CS has been growing steadily in the United States despite its high cost and — until now — the lack of high-quality evidence.
Now that we have this evidence, how should it be applied? One essential point is that patients enrolled in this trial represent only a subset of AMI-CS patients. More than 1,200 patients were screened over more than a decade, and more than 70% were excluded. Determination of benefit in other subsets of patients optimally should be demonstrated by further randomized trials, but this is unlikely in the short term given the length of time and resources that were required to complete this study. Nevertheless, these results should not be automatically extrapolated to patients presenting late, patients without ST-segment elevation, patients with prominent right ventricular as well as left ventricular failure, and those who remain comatose after out-of-hospital cardiac arrest.
We also should remember that, despite the large relative effect size, nearly half of patients receiving pump support still died before 180 days. Whether upcoming smaller-bore iterations of the microaxial flow pump will improve safety and expand availability in peripheral arterial disease patients remains to be seen.
Another question is whether these results can be replicated outside of larger referral centers. Significant experience and care in the catheterization lab with large-bore vascular access and closure is essential, of course. However, the overall hospital approach is just as important, including experience with longitudinal management of patients with these devices, the implementation of a Shock Team paradigm to decide when devices are indicated and when and how they should be weaned, and the availability of escalating forms of MCS.
