Two Major Trials Present Findings on Left Ventricular Unloading in Percutaneous Coronary Intervention

Recent clinical trials, STEMI-DTU and CHIP-BCIS3, have investigated the use of left ventricular (LV) unloading devices during percutaneous coronary intervention (PCI) in different patient populations. The STEMI-DTU trial reported that LV unloading with an Impella CP device did not reduce infarct size in anterior ST-elevation myocardial infarction (STEMI) patients without cardiogenic shock, and was associated with increased bleeding and vascular complications. Conversely, the CHIP-BCIS3 trial found that elective LV unloading with a microaxial flow pump during complex PCI in patients with severe LV dysfunction did not reduce major adverse clinical outcomes and was associated with increased mortality. Both sets of findings were presented at ACC.26.

STEMI-DTU Trial: LV Unloading in Anterior STEMI Patients

The STEMI-DTU (ST-Elevation Myocardial Infarction Door-to-Unload) trial aimed to determine if mechanical LV unloading using a transvalvular micro-axial flow pump (Impella CP) combined with a 30-minute delay before PCI could reduce infarct size compared to immediate PCI alone.

The study involved 527 adults with anterior STEMI who were not experiencing cardiogenic shock. Participants had no prior myocardial infarction and were enrolled across 55 hospitals internationally. The average age of patients was 61 years, with 79.1% being male. Patients were randomized to either receive the Impella CP device for 30 minutes prior to PCI or undergo immediate PCI.

The median time from hospital arrival to PCI was 40 minutes longer in the Impella group, resulting in a total ischemic time that was 47 minutes longer for these patients.

The primary outcome, infarct size normalized to LV mass (assessed by cardiac magnetic resonance imaging 3-5 days post-PCI), showed no statistically significant difference between the two groups. Infarct size was 30.8% in the Impella CP group versus 31.9% in the control group.

Regarding safety, the intervention group experienced a 30.8% rate of device-related major bleeding or blood vessel complications within 30 days, which exceeded the pre-defined performance goal of 26.5%. Bleeding rates were 34% in the Impella CP group compared to 6% in the PCI-only group. One proposed factor for the higher bleeding was prolonged exposure to high-dose peri-procedural anticoagulation due to the protocolized delay to PCI.

One-year mortality rates were 3.6% in the Impella CP group and 5.1% in the control group, a difference that was not statistically significant.

Co-author Gregg W. Stone, MD, stated that the findings do not support the routine use of an Impella CP with a 30-minute waiting period before PCI, as opposed to immediate PCI, in this patient population.

Sanjit Jolly, MD, an investigator, suggested that reducing infarct size might be beyond the device's current application in this context, while acknowledging its efficacy in cardiogenic shock.

David Kandzari, MD, not involved in the trial, noted that the risk-benefit ratio for Impella CP in this specific setting is clear due to increased complications without clinical benefit.

Researchers suggested future studies could explore improving pump effectiveness by pre-treating patients with intravenous medications to lower blood pressure, as most participants had elevated blood pressure and the pump's efficiency can be affected by blood pressure levels. Additionally, reducing the duration of pump support might mitigate bleeding complications.

These findings do not alter the observed benefits of Impella in patients with acute MI complicated by cardiogenic shock, as demonstrated in other studies. The STEMI-DTU results were published in JACC.

CHIP-BCIS3 Trial: LV Unloading in Complex PCI Patients

The CHIP-BCIS3 trial investigated the use of elective left ventricular (LV) unloading with a microaxial flow pump during complex percutaneous coronary intervention (PCI) in a different patient cohort.

This prospective, open-label trial was conducted across 21 sites in the UK, randomizing 300 patients. Participants had severe LV dysfunction (left ventricular ejection fraction <35%) and extensive coronary heart disease. They were assigned to either a strategy of elective LV unloading with a microaxial flow pump (148 patients) or standard care (152 patients) during a planned complex PCI. The average patient age was 73 years, with 17% women. The median LVEF was 27%.

At a median follow-up of 22 months, the primary endpoint, a hierarchical composite of all-cause death, disabling stroke, spontaneous myocardial infarction, cardiovascular hospitalization, and periprocedural myocardial injury, showed no significant benefit for the microaxial flow pump group. The win ratio was 0.85 (p=0.30), with 36.6% of pairwise comparisons favoring the microaxial flow pump and 43.0% favoring standard care.

Secondary outcomes revealed an increased risk of mortality in the intervention group:

• Death from any cause occurred in 32.6% of patients in the microaxial flow pump group compared to 23.4% in the standard care group (hazard ratio, 1.54).
• Cardiovascular death was observed in 26.7% of the microaxial flow pump group versus 14.5% in the standard care group.
• Periprocedural myocardial injury occurred in 61.7% of patients in the microaxial flow pump group compared to 50.0% in the control group.
• There were no significant differences in the risk of bleeding or vascular complications between the groups in this trial.

Divaka Perera, MD, the first author of the study, noted that the findings suggested patients assigned to LV unloading experienced more damage to the LV than those receiving standard care.

The results indicate that the routine use of this device without further evidence of benefit should be reevaluated.

An accompanying editorial in NEJM emphasized that the data supports a more selective approach to mechanical circulatory support in high-risk PCI, particularly in situations without clear hemodynamic instability.

The CHIP-BCIS3 trial results were published in NEJM.