CHICAGO — In the Door-To-Unload in STEMI Pilot Trial, delaying reperfusion for 30 minutes after left ventricle unloading with the Impella CP device was safe and feasible in patients with anterior STEMI referred for primary PCI.
Preclinical testing has shown that mechanically unloading the LV before reperfusion, as opposed to after, reduces infarct size, which is directly associated with HF and mortality in STEMI, Navin K. Kapur, MD, FAHA, FACC, FSCAI, executive director of The CardioVascular Center for Research and Innovation at Tufts Medical Center, said during a presentation at the American Heart Association Scientific Sessions.
More recently, he noted, researchers have started to study a mechanism under this concept of LV unloading and identified that there is a critical need for delayed reperfusion after initiation of LV unloading. Preclinical testing has also indicated that a 30-minute delay between LV unloading and reperfusion is “necessary and sufficient for reduction in infarct size,” he said. This formed the basis of the phase 1, safety and feasibility, multicenter Door-to-Unload in STEMI Pilot Trial.
Kapur and colleagues randomly assigned 50 patients with anterior STEMI to LV unloading with the Impella CP device (Abiomed) followed by immediate reperfusion (n = 25) or delayed reperfusion after 30 minutes of unloading. Electrocardiographic, angiographic and cardiac magnetic resonance imaging (CMR) core labs were blinded during the analysis.
Primary study outcomes focused on safety, according to Kapur. Specifically, the researchers aimed to identify any differences in a composite of major adverse CV and cerebrovascular events, including mortality, reinfarction, stroke and major vascular events at 30 days. Additional safety and early efficacy outcomes were focused on between-group differences in infarct size measured as percent of total LV mass at 30 days.
Enrollment was successful and protocol was completed in all patients. Mean door-to-balloon times was 72 minutes in the unload and immediate reperfusion arm compared with 97 minutes in the unload and delayed reperfusion arm. Importantly, Kapur said, there was no bailout PCI in the delayed reperfusion arm.
“What this suggests is that when we look at operator behavior, operators were comfortable with initiating LV unloading and waiting 30 minutes. Operators were allowed at any moment to perform bailout PCI with a focus on patient safety and we didn’t see any of that in the delay arm,” he said.
In terms of primary safety outcomes, traditional 30-day MACCE rates were low and not significantly different in the immediate vs. delayed reperfusion groups (8% vs. 4%), according to Kapur. Rates of total composite MACCE that also included vascular complications were not different between the two study arms (8% vs. 12%; P = .99).
LV unloading with delayed reperfusion, compared with immediate reperfusion, also did not affect the 30-day mean infarct size (13% vs. 15%; P = .53), which was the primary efficacy endpoint of this trial.
Across the unloaded groups, 3- to 5-day CMR results showed relatively low infarct sizes normalized to total LV mass, according to Kapur. Myocardial salvage indices were elevated and microvascular obstruction rates were also low, suggesting that unloading and delaying reperfusion for 30 minutes did not increase infarct size.
Patient characteristics were well-balanced between groups and were representative of a typical population with large anterior STEMI, Kapur said.
This pilot trial “demonstrates for the first time that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is safe and feasible within a relatively short door-to-balloon time,” Kapur said. “The lessons we learned from the Door-to-Unload in STEMI Pilot Trial will now inform the development of the Door-to-Unload STEMI pivotal trial,” he said.
Despite these encouraging results, the study leaves some questions unanswered, Holger Thiele, MD, from the Heart Center Leipzig at the University of Leipzig, Leipzig, Germany, said during a discussion of the trial.
The trial lacked a control group that included standard of care for STEMI with radial access. Additionally, there was no adjustment for losses to follow-up and missing CMR, he said.
Thiele also raised concerns about whether the conclusion that LV unloading with delayed reperfusion does not lead to an increase in infarct size is true. He pointed out that symptom-to-unload time was 200 minutes with the immediate reperfusion strategy and the unload to PCI time was 11 minutes, meaning total ischemic time was 211 minutes, while total ischemic time in the delayed reperfusion arm was 210 minutes. Therefore, it might be unlikely that one would see any difference in infarct size between the two study arms, he said.
Finally, the study was not powered to look at safety endpoints and physicians should bear this in mind, Thiele added.
The data were simultaneously published in Circulation. – by Melissa Foster
Kapur NK, et al. LBS.04 – Preserving Brain and Heart in Acute Care Cardiology. Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.
Kapur N, et al. Circulation. 2018;doi:10.1161/CIRCULATIONAHA.118.038269.
Disclosures: This study was funded by Abiomed. Kapur reports he received research funding from Abiomed, Cardiac Assist and Maquet Cardiovascular. Thiele reports no relevant financial disclosures.