Late-breaking PCI data challenge the 'time is muscle' paradigm
One of the key late-breaking trials presented ACC.26 in New Orleans was STEMI Door-to-Unload (DTU), which did not meet its primary endpoint. However, it did show that cath labs can buy more time in treating ST-elevated myocardial infarction (STEMI) patients and extend the door-to-balloon time window.
The study looked at using Impella CP pump hemodynamic support for 30 minutes prior to percutaneous coronary intervention (PCI) to unload the left ventricle prior to reperfusion. Animal studies showed how this approach could reduce reperfusiuon injury and reduce infarct size, but it fell short of offering any treatment advantages. Investigators said these findings could reshape how clinicians think about the timing of PCI, because waiting 30 minutes to perform PCI with Impella support did not increase infarct size.
Results from the STEMI DTU trial were presented by Gregg Stone, MD, of the Icahn School of Medicine at Mount Sinai, who spoke about the details of the data with Cardiovascular Business. He said the lessons learned from the trial could help refine another DTU trial.
This analysis enrolled 527 patients with large anterior STEMIs presenting within six hours of symptom onset and without cardiogenic shock. Patients were randomized to either undergo Impella-supported unloading with a built-in 30-minute delay before reperfusion, followed by continued support for several hours, or just undergo immediate PCI.
Stone said the trial was rooted in decades of preclinical research suggesting that reducing left ventricular workload prior to restoring blood flow could improve myocardial salvage.
“We've gotten very good as interventional cardiologists at performing primary PCI in patients with STEMI to open the infarct artery, which stops the infarct process. And we save a lot of lives. However, we're not as good as we'd like to be at salvaging myocardium. And it turns out that a lot of patients end up with a large heart attack and that leads to heart failure and death,” Stone explained.
Despite the biologic rationale, the study did not demonstrate a statistically significant reduction in infarct size at three to five days as measured by cardiac MRI. However, investigators also did not observe the expected increase in infarct size despite delaying reperfusion by an average of 47 minutes.
Stone emphasized that this finding challenges long-standing assumptions about the urgency of immediate reperfusion in all cases.
“So we've kind of broken this paradigm of 'time is muscle,' and that might give us more time to overcome some of the limitations that we learned in the trial,” he said.
Investigators identified several factors that may have limited the effectiveness of ventricular unloading in the study, including elevated blood pressure and prolonged device support times.
The trial also highlighted safety concerns, particularly bleeding and vascular complications associated with large-bore access. To make this this approach worthwhile, Stone noted, these complications need too be reduced.
Importantly, he said outcomes varied based on vascular closure strategies. Use of pre-closure devices were associated with fewer complications, while other closure approaches using the Manta device were linked to higher bleeding rates.
Researchers also noted that the average duration of Impella support—approximately 14 hours—may have been longer than necessary, potentially contributing to adverse events.
While some may interpret the results as negative, Stone characterized the findings differently.
“We call it a neutral trial as opposed to a negative trial, because we have kind of are breaking down that paradigm that 'time is myocardium' because we didn't see any signal towards an increase in infarct size,” he said.
Looking ahead, investigators believe the trial provides a roadmap for improving care strategies, including optimizing blood pressure control, refining patient selection, shortening device duration and improving vascular access techniques.
“I think we can make a new trial more effective and make it more safe at the same time, based on the lessons of this study,” Stone said.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: [email protected]