January 14, 2019Circulation
Unloading the Left Ventricle Before Reperfusion in Patients With Anterior ST-Segment–Elevation Myocardial Infarction
Navin K. KapurMohamad AlkhouliTony DeMartiniHaroon FarazZachary GeorgeMark GoodwinJaime Hernández-MontfortVijay IyerNoam JosephySanjog KalraAmir KakiRichard H. KarasCarey KimmelstielGerald KoenigEvan LauKapildeo LotunRyan D. MadderSalvatore ManninoPerwaiz MerajJason A. MorelandJeffrey W. MosesRaymond L. KimTheodore SchreiberJames E. UdelsonChristian WitzkeDavid WohnsWilliam W. O’Neill
Key result
LV unloading with delayed reperfusion proves safe in anterior STEMI with similar MACCE vs immediate reperfusion.
- P=0.99
- n=50
Why the study?
In STEMI, infarct size correlates with heart failure and mortality, and preclinical data suggest LV unloading before reperfusion reduces infarct size and reperfusion injury, but safety and feasibility in patients without cardiogenic shock were untested.
Does left ventricular unloading with a 30-minute delay before reperfusion improve safety and reduce infarct size compared to immediate reperfusion in patients with anterior STEMI without cardiogenic shock?
Key Points
- To assess the safety and feasibility of mechanically unloading the left ventricle with an Impella CP device and delaying reperfusion in patients presenting with anterior STEMI without cardiogenic shock.
- Multicenter, prospective, randomized exploratory safety and feasibility trial (DTU-STEMI; NCT03000270) enrolling 50 patients with anterior STEMI.
- Participants were randomly assigned 1:1 to left ventricular unloading with immediate reperfusion (U-IR, n=25) or unloading with reperfusion delayed by 30 minutes (U-DR, n=25).
- Safety was assessed via a 30-day composite of major adverse cardiovascular and cerebrovascular events (MACCE), and efficacy was measured by cardiac magnetic resonance imaging for infarct size.
- All 50 patients completed their assigned protocols, yielding mean door-to-balloon times of 72 minutes in the U-IR group versus 97 minutes in the U-DR group.
- The primary safety outcome of 30-day MACCE occurred in 8% (2/25) of the U-IR group versus 12% (3/25) of the U-DR group (P=0.99).
- Mean 30-day infarct size measured as a percentage of left ventricular mass was 15±12% in the U-IR group compared with 13±11% in the U-DR group (P=0.53).
Study Design
Type
RCT (n=50)
Randomization
randomized
Multicenter
Yes
Structured PICO
Does left ventricular unloading with a 30-minute delay before reperfusion improve safety and reduce infarct size compared to immediate reperfusion in patients with anterior STEMI without cardiogenic shock?
P
Population
50 patients with anterior STEMI without cardiogenic shock, randomized to immediate or delayed reperfusion after LV unloading, followed for 30 days.
I
Intervention
Left ventricular unloading using the Impella CP device with a 30-minute delay before reperfusion (U-DR)
C
Comparator
Left ventricular unloading using the Impella CP device followed by immediate reperfusion (U-IR)
O
Outcome
Composite of major adverse cardiovascular and cerebrovascular events at 30 dayssafety
Main Result
Absolute Event Rate: 12% vs 8%
p-value: p=0.99
Limitations
- Exploratory pilot trial requiring an appropriately powered pivotal trial to confirm efficacy and safety
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Results from this analysis are early, but promising, indicating that in STEMI patients, unloading the left ventricle with Impella CP for 30 minutes and delaying PCI could potentially help improve patient outcomes by reducing damage to the heart muscle and helping prevent heart failure.”
“If a reduction of infarct size from unloading before reperfusion is confirmed in a future trial, this concept would enhance the existing guidelines of immediate reperfusion for STEMI patients. 75 percent of patients experiencing their first heart attack will develop heart failure within five years, so new approaches are needed to reduce infarct size and prevent heart failure.”
“During the period between Impella CP insertion and PCI, operators could bail out and perform PCI at their discretion based on patient stability. However, there was never a clinical need to begin PCI during this waiting period. We had 100% compliance. Many of my patients began to snore, suggesting that they were clinically stable enough to fall asleep. This suggests that pre-PCI LV unloading rested the heart without worsening the infarction.”
Implication
Left ventricular unloading with Impella CP and a 30-minute delay before reperfusion is safe and feasible in anterior STEMI, warranting a larger pivotal trial.
Abstract
Background: In ST-segment–elevation myocardial infarction (STEMI), infarct size correlates directly with heart failure and mortality. Preclinical testing has shown that, in comparison with reperfusion alone, mechanically unloading the left ventricle (LV) before reperfusion reduces infarct size and that 30 minutes of unloading activates a cardioprotective program that limits reperfusion injury. The DTU-STEMI pilot trial (Door-To-Unload in STEMI Pilot Trial) represents the first exploratory study testing whether LV unloading and delayed reperfusion in patients with STEMI without cardiogenic shock is safe and feasible. Methods: In a multicenter, prospective, randomized exploratory safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events at 30 days. Efficacy parameters included the assessment of infarct size by using cardiac magnetic resonance imaging. Results: All patients completed the U-IR (n=25) or U-DR (n=25) protocols with respective mean door-to-balloon times of 72 versus 97 minutes. Major adverse cardiovascular and cerebrovascular event rates were not statistically different between the U-IR versus U-DR groups (8% versus 12%, respectively, P =0.99). In comparison with the U-IR group, delaying reperfusion in the U-DR group did not affect 30-day mean infarct size measured as a percentage of LV mass (15±12% versus 13±11%, U-IR versus U-DR, P =0.53). Conclusions: We report that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is feasible within a relatively short time period in anterior STEMI. The DTU-STEMI pilot trial did not identify prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion. An appropriately powered pivotal trial comparing LV unloading before reperfusion to the current standard of care is required. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03000270.
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Cite This Study
Kapur et al. (2019) conducted an RCT in Anterior ST-Segment-Elevation Myocardial Infarction (STEMI) (n=50). Left ventricular unloading using Impella CP with delayed reperfusion after 30 minutes (U-DR) vs. Left ventricular unloading using Impella CP with immediate reperfusion (U-IR) was evaluated on Composite of major adverse cardiovascular and cerebrovascular events at 30 days (p=0.99). Left ventricular unloading using the Impella CP with a 30-minute delay before reperfusion was feasible in anterior STEMI, with 30-day MACCE rates of 12% vs 8% for immediate reperfusion (P=0.99).