Use of a microaxial flow pump (Impella CP) with standard care led to a lower risk for death than standard care alone in patients with ST-elevation myocardial infarction (STEMI)-related cardiogenic shock in the randomized DanGer Shock trial, although with more adverse events.

The Impella CP is a small percutaneous pump placed within the heart’s left chamber, where it expels oxygenated blood from the left ventricle to the body with a flow rate of up to 3.5 liters per minute.

“Overall, we have more complications, but we also save lives,” said lead author Jacob E. Møller, MD, PhD, a cardiology professor at the Odense University Hospital in Denmark and a consultant at the cardiac intensive care unit of Copenhagen University Hospital Rigshospitalet.

Møller presented the findings today at the American College of Cardiology (ACC) Scientific Session 2024. The study was simultaneously published online in the New England Journal of Medicine. 

Benefits at a Cost

Investigators randomly assigned patients with STEMI and cardiogenic shock to receive the Impella CP plus standard care or standard care alone. The primary endpoint was death from any cause at 180 days. The first secondary endpoint was a composite of treatment escalation to additional mechanical circulatory support, heart transplantation, or death from any cause, whichever came first. The second secondary endpoint was days alive and out of the hospital.

A composite safety endpoint included severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation.

Eligible patients had STEMI and cardiogenic shock, defined as sustained hypotension, end-organ hypoperfusion with arterial lactate level ≥ 2.5 mmol/L, and a left ventricular ejection fraction less than 45%. Patients could be randomly assigned before, while in, or up to 12 hours after leaving the cath lab, depending on when the shock was first diagnosed.

A total of 355 patients from 14 centers in Denmark, Germany, and the United Kingdom were included in the final analysis: 179 were randomly assigned to the microaxial-flow-pump (mAFP) and 176 to standard care only. The median age was 67 years, and 79% were men. 

Results at 180 days showed that mortality was significantly lower among patients in the mAFP group compared with those receiving standard care alone (45.8% vs 58.5%, respectively; hazard ratio, 0.74, P =.04).

There was also a reduction in the composite cardiac endpoint among those who received the pump (52.5% mAFP vs 63.6% standard of care). 

“There was no difference in days alive out of hospital,” Møller told meeting attendees. “In fact, there were more patients still in hospital at day 30 in the micro-axial flow pump group.” With regard to prespecified subgroups, patients with very low blood pressure, less than the median, and those with multivessel disease seemed to benefit most.

A composite safety endpoint event occurred in 24% of patients in the mAFP group vs only 6.2% in the standard-care group (relative risk, 4.74). Specifically, the relative risk (mAFP group vs standard care) of moderate or severe bleeding was 2.06; of limb ischemia, 5.15; of renal-replacement therapy, 1.98; and of sepsis with a positive blood culture, 2.79. 

Seventy-five patients (41.9%) in the pump group underwent renal replacement therapy vs 47 patients (26.7%) in the standard-care group (relative risk, 1.98).

The researchers were surprised that more patients in the mAFP group ended up on renal replacement therapy, Møller said. “We will look into whether this is device-related or could be related to survival bias.”

Patient Selection Key

Møller stressed that “we should be cautious not to extrapolate these results to other causes of cardiogenic shock. The results may not apply to the out-of-hospital cardiac arrest patient who is comatose or the patient with non-ischemic cardiogenic shock.”

During the panel discussion, Ajay Kirtane, MD, director of the Columbia Interventional Cardiovascular Care program and a professor at the Columbia University Irving Medical Center in New York City, said, “One of the reasons you were so successful was that patient selection. And yet, despite that, we see a residual mortality of 45% and increased rates of adverse events and complications. But that gives me hope, because it suggests that if we could reduce those events further, then we can even further improve the outcomes that you were able to observe.”

Møller agreed that the rate of complications is “a true concern. We’ve seen it in the registries and now we have it in a randomized trial. It’s something we have to take very, very seriously, especially when studying lower-risk populations.”

The pump was effective in the current trial, he said, “because the patients were so sick that the benefit kind of overshadows the risk. But if we don’t reduce the risk and start to investigate less sick patients, this will not work. The bleeding and renal function are at the top of the list of sub-studies we will be diving into.”

“Just The Beginning”

Sunil Rao, MD, director of interventional cardiology at NYU Langone Health System in New York City and editor-in-chief of Circulation: Cardiovascular Interventions, called the results “striking.”

“This is the first trial since 1999 that has shown a reduction in mortality in patients with acute MI cardiogenic shock, albeit it comes at a price of increased adverse events,” he told theheart.org | Medscape Cardiology in an interview.

Rao, who is also the author of a related editorial, acknowledged that he has been “an Impella skeptic.” 

Nevertheless, he said, “This is an important study. The data are actionable. My takeaway is that the Impella device does, in fact, reduce 180-day mortality compared with no mechanical support in patients with acute myocardial shock, as long as its use is within the context of a standardized weaning protocol and best practices in terms of vascular access — that is, making sure you avoid things like limb ischemia.”

To reduce some of the risks for adverse events, he suggested using ultrasound and micropuncture for femoral access, and antegrade catheterization to allow for blood flow in the leg when the device is in. 

Regarding nonvascular adverse events, he said, “I’m purely speculating, but are we seeing those adverse events because patients in the Impella arm actually survived long enough to experience them? There does seem to be a bimodal distribution of mortality, where patients die early on, and a little bit later as well. Early on, many of the deaths are directly related to the shock presentation, whereas maybe later on, they’re more related to things like infection.”

Overall, Rao said, “I suspect that this is just the beginning of what we’re going to see from this trial. It’s a rich database, and so I think that the authors will continue to examine different aspects of the data, which I look forward to.”

The study was supported by the Danish Heart Foundation and Abiomed/Johnson & Johnson, maker of the Impella CP. Møller discloses institutional research grants from Abiomed and Novo Nordisk Foundation, speakers’ fees from Abbott and Boehringer Ingelheim, and membership on the steering committee for Recover IV. Rao has no disclosures to report. 

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.