Microaxial Flow Pump in Infarct-Related Cardiogenic Shock - DanGer Shock

Dec 23, 2024
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
Danish Heart Foundation and Abiomed
Date Presented:
04/07/2024
Date Published:
10/27/2024
Date Updated:
12/23/2024
Original Posted Date:
04/07/2024
References

Contribution To Literature:

Highlighted text has been updated as of December 23, 2024.

The DanGer Shock trial showed that routine implantation of Impella CP on top of standard care is superior to standard care alone in reducing 6-month mortality among patients presenting with STEMI and cardiogenic shock, despite a higher risk of complications.

Description:

The goal of the trial was to compare the safety and efficacy of Impella CP on top of standard care compared with standard care alone among patients with ST-segment elevation myocardial infarction (STEMI) and cardiogenic shock.

Study Design

Patients were randomized in a 1:1 fashion to either routine microaxial flow pump insertion (Impella CP) + standard care (n = 179) or standard care alone (n = 176).

Randomization was stratified according to the timing of randomization relative to the revascularization procedure and localization of STEMI (anterior vs. nonanterior). In the patients assigned to receive the microaxial flow pump, the device was to be placed immediately after randomization and run at the highest possible performance level for at least 48 hours unless complications occurred. In the event of hemodynamic instability, treatment could be escalated to additional mechanical circulatory support after randomization in either trial group. In the microaxial flow device group, treatment could be escalated to the placement of an Impella 5.0 Impella RP device or extracorporeal life support. In the standard care group, extracorporeal life support was recommended, although placement of an Impella 5.0 device was allowed.

  • Total screened: 1,211
  • Total randomized participants: 355
  • Median duration of follow-up: 6 months
  • Median patient age: 68 years
  • Percentage female: 21%

Inclusion criteria:

  • Age ≥18 years
  • STEMI
  • Cardiogenic shock, hypotension (systolic blood pressure <100 mm Hg or an ongoing need for vasopressor support), end-organ hypoperfusion with an arterial lactate level of ≥2.5 mmol/L, and a left ventricular ejection fraction of <45%)

Exclusion criteria:

  • Shock duration >24 hours
  • Other causes of shock; hypovolemia, sepsis, pulmonary embolism, or anaphylaxis
  • Shock due to mechanical complication to MI; papillary muscle rupture, rupture of the ventricular septum or rupture of ventricular free wall
  • Severe aorta valve regurgitation/stenosis
  • Severe peripheral arterial obstructive disease that would preclude Impella device placement
  • Mechanical aortic valve prosthesis
  • Already established mechanical circulatory support (Impella or venoarterial extracorporeal membrane oxygenation [VA-ECMO])
  • Left ventricular thrombus
  • Infective endocarditis
  • Shock due to right ventricular failure
  • Out-of-hospital cardiac arrest with persistent Glasgow coma scale <8 after return of spontaneous circulation. Cardiac arrest occurring in ambulance or after arrival to hospital is not an exclusion criterion.
  • Subject with documented heparin-induced thrombocytopenia
  • Life expectancy of <1 year due to comorbidities

Other salient features/characteristics:

  • Median arterial lactate: 4.5 mmol/L
  • Median left ventricular ejection fraction: 25%
  • Resuscitation prior to randomization: 20%
  • Anterior wall MI: 72%, SCAI-CSWG stage: C (56%), D (28%), E (16%)
  • Immediate percutaneous coronary intervention (PCI): 96%, nonculprit vessel PCI for multivessel disease: 44%
  • Randomization prior to revascularization: 57%
  • Median time from symptom onset to randomization: 4.3 hours
  • Duration between randomization and placement of Impella CP: 15 minutes
  • Median duration of Impella CP support: 60 hours
  • VA-ECMO use between Impella CP vs. standard care: 11.7% vs. 18.8%, use of Impella CP in standard care arm: 2%

Principal Findings:

The primary endpoint of all-cause mortality at 6 months for Impella CP + standard care vs. standard care alone was: 45.8% vs. 58.5% (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55-0.99, p = 0.04).

Key secondary outcomes for Impella CP + standard care vs. standard care alone:

  • Composite at 6 months (escalation of treatment to additional mechanical circulatory support [short- or long-term], heart transplantation, or death of any cause): 52.5% vs. 63.6% (HR 0.72, 95% CI 0.55-0.95)
  • Composite safety endpoint (occurrence of severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation): 24.0% vs. 6.2% (HR 4.74, 95% CI 2.36-9.55)
  • Moderate or severe bleeding: 21.8% vs. 11.9% (p < 0.05)
  • Limb ischemia: 5.6% vs. 1.1% (p < 0.05)
  • Need for renal replacement therapy (RRT): 41.9% vs. 26.7% (p < 0.05)
  • Sepsis with positive blood culture: 11.7% vs. 4.5% (p < 0.05)

Renal outcomes: Acute kidney injury (AKI) according to RIFLE criteria (Risk, Injury, Failure, Loss, and End-stage kidney disease ≥1) for Impella CP + standard care vs. standard care: 61% vs. 45% (p < 0.01).

Need for RRT: 42% vs. 27% (p < 0.01). Development of AKI was associated with a higher risk of all-cause mortality at 180 days: 51% vs. 68% (p = 0.017). In patients without AKI, the odds ratio (OR) for 180-day mortality when allocated to the Impella CP compared with standard care was 0.49 (95% CI 0.26–0.93); in patients with AKI, the OR was 0.55 (95% CI 0.29–0.98; p for interaction = 0.84).

Hemodynamic and metabolic effects: A vasoactive-hemodynamic score (VHS) was determined in 324 patients. The MAP was significantly higher at time 1 hour (T1) and T12 after admission in the Impella CP group and otherwise similar in the groups over time, with mean values above the targeted threshold of 65 mm Hg throughout the first 72 hours at admission. The Vasoactive Inotropic Score (VIS) within the first 6 hours demonstrated a steep increase for the standard-care group compared with the Impella CP group with a significant difference between groups at T3 and T6. No difference in arterial lactate level was found between groups at randomization, and the lactate level declined for both groups over time. The Impella CP group achieved lactate normalization (<2 mmol/L) 12 hours before the standard-care group.

Interpretation:

The results of this trial show that routine implantation of Impella CP on top of standard care is superior to standard care alone in reducing 6-month mortality among patients presenting with STEMI and cardiogenic shock. Risk of complications including bleeding, limb ischemia, need for RRT, and sepsis were all higher with Impella CP. Of note, in >50% of patients, Impella CP was placed prior to revascularization. Risk of AKI/RRT was higher with Impella CP but the benefit of Impella CP over standard care was maintained among those with AKI or who needed RRT. The use of Impella CP enabled a lower utilization of vasopressors and inotropes while maintaining hemodynamic stability and achieving faster normalization of lactate level.

This is an important trial in a population that has been challenging to study. Multiple observational studies have suggested harm with Impella CP use in this patient population. Other mechanical circulatory support devices such as IABP and VA-ECMO have failed to show a benefit with routine use in this patient population. One caveat is that it took the investigators 10 years to enroll 355 patients across three countries. Inclusion criteria were strict, and blinding was also not possible. Among patients who survive, complications such as limb loss, need for RRT, etc., may have an impact on long-term mortality. Utility analyses from a patient-centered standpoint will be helpful in the future. Smaller Impella CP sheaths may help reduce these complications in the future. Accordingly, this trial supports the judicious use of Impella CP among patients presenting with STEMI and cardiogenic shock.

References:

Zweck E, Hassager C, Beske RP, et al. Microaxial Flow Pump Use and Renal Outcomes in Infarct-Related Cardiogenic Shock: A Secondary Analysis of the DanGer Shock Trial. Circulation 2024;150:1990-2003.

Udesen NL, Beske RP, Hassager C, et al. Microaxial Flow Pump Hemodynamic and Metabolic Effects in Infarct-Related Cardiogenic Shock: A Substudy of the DanGer Shock Randomized Clinical Trial. JAMA Cardiol 2024;Oct 27:[Epublished].

Møller JE, Engstrøm T, Jensen LO, et al., on behalf of the DanGer Shock Investigators. Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock. N Engl J Med 2024;390:1382-93.

Editorial: Rao SV. Mechanical Circulatory Support in Cardiogenic Shock — Persistence and Progress. N Engl J Med 2024;390:1436-8.

Presented by Dr. Jacob Eifer Møller at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 7, 2024.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Interventions and ACS

Keywords: ACC24, ACC Annual Scientific Session, Acute Coronary Syndrome, Implantable Devices, Percutaneous Coronary Intervention


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