Study paves way for larger trial on ventricular unloading before PCI

The Door-to-Unload pilot study concluded without any “prohibitive safety signals,” researchers reported at the American Heart Association 2018 Scientific Sessions, clearing the path for a larger trial to test the hypothesis that ventricular unloading prior to PCI with the Impella CP heart pump can reduce reperfusion injury.

That hypothesis is based on preclinical studies which showed that mechanically unloading the left ventricle for 30 minutes before reperfusion for ST-segment elevation myocardial infarction (STEMI) can reduce infarct size and limit reperfusion injury. But delaying reperfusion in the setting of STEMI isn’t currently recommended, and the Impella CP is only indicated for support during high-risk coronary interventions with cardiogenic shock.

To test the feasibility of this delayed reperfusion approach in STEMI patients without cardiogenic shock, lead author Navin K. Kapur, MD, and colleagues conducted a tightly controlled randomized trial of 50 patients. All underwent left ventricular unloading with the Impella CP, but half were randomized to then undergo immediate reperfusion while the other half received PCI after 30 minutes of unloading.

There was one cardiovascular death in each group at 30 days and the treatment arms had similarly low rates of major adverse cardiovascular and cerebrovascular events—three in the delayed reperfusion group (12 percent) and two in the immediate reperfusion group (8 percent). Average infarct sizes upon cardiac magnetic resonance imaging at 30 days were also similar.

“The DTU-STEMI pilot trial did not identify any prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion,” wrote Kapur, with Tufts Medical Center in Boston, and coauthors in Circulation. “Based on results from this pilot trial, an appropriately powered pivotal trial comparing LV unloading and delayed reperfusion with the current standard of care is currently in development.

“The finding that LV unloading and delaying reperfusion is feasible potentially opens many new doors for further exploration by suggesting that other adjunct interventions (i.e. pharmacologic) may now be considered during that ‘window-period’ where the coronary artery is occluded, but the LV is mechanically unloaded in a STEMI.”

The pivotal trial of this delayed reperfusion approach is slated to begin next year, according to an announcement from Abiomed, the manufacturer of the Impella CP.

The average door-to-balloon times for patients in the delayed reperfusion group were 97 minutes, compared to 72 minutes in the immediate reperfusion group.

However, the author of an accompanying editorial pointed out ischemic times were similar between the two groups, despite PCI being delayed in one of them.

“It should be noted that by randomized chance that the ischemic time from symptom onset to unloading was 24 minutes longer in the immediate reperfusion group making the total ischemic time in the two arms, even after unloading and delayed reperfusion, similar between groups,” wrote Manesh R. Patel, MD, with Duke Clinical Research Institute. “Unfortunately, due the randomization differences in ischemic times mentioned, it is not possible to make any substantive interpretations around the infarct size associated with delay.”

Still, Patel congratulated the researchers on executing a “difficult to perform” pilot trial. Another limitation of the study, he said, is the lack of a control arm which undergoes primary PCI without LV unloading, but Kapur et al. indicated such a group would be included in their pivotal study scheduled to begin in 2019.