DanGer Shock

Published

Møller JE, et al. "Microaxial flow pump or standard care in infarct-related cardiogenic shock". The New England Journal of Medicine. 2024. 390(15):1382-1393.
PubMed • Full text • PDF • ClinicalTrials.gov

Clinical Question

Among adults with STEMI and cardiogenic shock, does use of the microaxial flow pump in addition to standard care lower 180 day all-cause mortality when compared to standard care alone?

Bottom Line

Among adults with STEMI and cardiogenic shock, use of the Impella microaxial flow pump in addition to standard care was associated with reduction of 180 day all-cause mortality when compared to standard care alone, though use of the flow pump was associated with greater risk of certain adverse events.

Major Points

Cardiogenic shock occurs in approximately 8% of MIs and is associated with substantial mortality, upwards of 50% at 1 year. In the early 2000s and 2010s, management for such events was limited to coronary revascularization and vasopressor support. Mechanical circulatory support has been hypothesized to potentially lower mortality, though pre-2024, there was little evidence supporting this practice. For example, but the IABP-SHOCK II trial (2012) found no mortality benefit with the use of intraaorta balloon pump in this population. A 2023 meta-analysis of ECMO trials found no benefit for this intervention in MI-related cardiogenic shock.

Microaxial flow pumps, such as the Impella, are tiny LVADs. These devices draw blood from the LV and releases it in the aorta, just distal to the AV. These devices can be placed percutaneously during the index catheterization. A case-control study from Denmark found lower mortality among persons with MI-associated cardiogenic shock who underwent Impella placement. An adequately-powered clinical trial was needed to support the use of microaxial flow pumps in this population, however.

Published in 2024, the Danish–German Cardiogenic Shock (DanGer Shock) trial randomized 355 adults with STEMI and cardiogenic shock to placement of a microaxial flow pump (Impella CP device) plus standard care versus standard care alone in an open-label fashion. The addition of the microaxial flow pump was associated with a 13% absolute reduction in 180-day all-cause mortality when compared to standard care alone (45.8% vs. 58.5%; HR 0.74; 95% CI 0.55 to 0.99; P=0.04; NNT=8). The mortality benefit from the microaxial flow pump was offset by a 17.8% greater absolute risk in the composite safety endpoint (severe bleeding, limb ischemia device failure, worsening aortic regurgitation; 24.0% vs. 6.2%; RR 4.74; 95% CI 2.36 to 9.55; NNH=6). There was perhaps a differential benefit for use of the microaxial flow pump among persons with lower MAPs.

The DanGer Shock trial provides evidence for the use of microaxial flow pumps to lower mortality among persons with STEMI complicated by cardiogenic shock.

Guidelines

As of December 2024, no guidelines have been published that reflect the results of this trial.

Design

• Multicenter, open label, randomized controlled trial
• N=355 (among 1,211 screened)
  • Microaxial flow pump plus standard care (n=179)
  • Standard care (n=176)
• Setting: 14 centers in Denmark, Germany, and the UK
• Enrollment: 2013-2023
• Follow-up: 180 days
• Analysis: Intention to treat
• Primary outcome: 180 day all-cause mortality

Population

Inclusion Criteria

• STEMI with cardiogenic shock
  • STEMI or STEMI equivalent <36h
    • STEMI equivalent defined as new ST segment depression or LBBB <36h and angiography with acute proximal coronary artery occlusion
  • Cardiogenic shock <24h, defined by all 3 of the following occurring prior to 12h post-revascularization:
    • Peripheral tissue hypoperfusion (lactate ≥2.5 mmol/L and/or SvO2 <55% with normal PaO2)
    • SBP <100 mm Hg and/or need for vasopressors, defined as dopamine/norepinephrine or epinephrine
    • LVEF <45%

Exclusion Criteria

• Cardiogenic shock >24 hours or shock from non-cardiogenic cuase
• Cardiogenic shock from mechanical complication following MI (e.g., papillary muscle rupture)
• GCS <8 after ROSC in out-of-hospital cardiac arrest
• Severe RV failure
• Severe AS or AR
• Severe PAD or aorta abnormalities precluding Impella placement
• Mechanical AV or heart constrictive device
• LV mural thrombus
• Endocarditis
• Life expectancy <1 year prior to MI
• Psychiatric issue or language barrier preventing informed consent

Baseline Characteristics

From the microaxial flow pump plus standard care group.

• Demographics: Age 67y, male sex 79%
• Medical problems: HTN 50%, DM 18%, MI 16%, HF 9%, CKD 10%
• Vital signs: SBP 84, MAP 63, HR 94
• Labs: Lactate 4.6 mmol/L
• LVEF: 25%
• Pre-randomization details: Resuscitation: 39%, intubation 35%, transfer from outside hospital 51%
• Randomization timing details: Time since onset 5 hours, randomization prior to revascularization 55%, randomization in cath lab 27%, randomization ≤12 after leaving cath lab 18%
• MI details: Anterior 70%
  • SCAI-CSWG stage: C 56%, D 28%, E 16%
  • # diseased vessels: None 1%, one 29%, two 39%, three 31%
• Revascularization details: PCI 96%, non-culprit vessel PCI 46%, CABG 1%, door to balloon time 58 minutes
• Mechanical circulatory support:
  • Placement of Impella CP 95% (vs. 2%/N=3 in standard group)
  • Placement of flow pump prior to PCI among those randomized before PCI 85% (vs 100%/N=3 in standard group)
  • Time from randomization to placement of flow pump: 14 min
  • Duration of flow pump support: 59h
  • Mechanical hemolysis: 12%
  • Malfunction of device: 1%
  • Successful weaning from flow pump: 81%

Interventions

• Participants were randomized to a group in the cath lab or in the 12 hours following a trip to the cath lab to a group:
  • Microaxial flow pump plus standard care - Placement of the Impella CP immediately post-randomization and run at the highest possible level for ≥48 hours unless there were complications requiring change in settings. If needed, an Impella 5.0, Impella RP, or ECMO could be used instead.
  • Standard care - If needed, ECMO could be added. Placement of an Impella 5.0 was allowed.
• All participants received revascularization if indicated and were also treated with vasopressor support.

Outcomes

Presented as microaxial flow pump plus standard care vs. standard care.

Primary Outcome

180 day all-cause mortality

45.8% vs. 58.5% (HR 0.74; 95% CI 0.55 to 0.99; P=0.04; NNT=8)

Secondary Outcomes

Many of the planned secondary outcomes are not presented in this manuscript. See planned secondary outcomes on PDF page 46 of the protocol.

Escalation to additional short or long-term mechanical circulatory support, heart transplant, or all-cause mortality

This was termed "composite cardiac endpoint". For unclear reasons, this endpoint was different in this manuscript than as it was planned to be performed in the protocol (see PDF page 46). The protocol's version did not include all-cause mortality and instead also included (a) unplanned revascularization, (b) cardiac mortality, and (c) cardiac hospitalization. It is unclear why the authors changed from their planned analysis.

52.5% vs. 63.6% (HR 0.72; 95% CI 0.55 to 0.95)

Days alive and out of hospital

82 vs. 73 days (mean between-group difference 8 days; 95% CI -8 to 25)

Additional Outcomes

Mechanical circulatory support escalation

Placement of Impella 5.0: 4% vs. 3%

Placement of Impella CP for venting during VA ECMO: 0% vs. 2%

Placement of Impella 2.5: 0% vs. 1%

Placement of Impella RP: 0% vs. 0%

VA ECMO: 12% vs. 19%

Time from randomization to placement of VA ECMO: 14h vs. 2h

Placement of permanent LVAD: 6% vs. 2%

Any mechanical circulatory support escalation: 16% vs. 21%

Intensive care details

Mechanical ventilation: 74% vs. 66%

Duration of ventilation: 5 vs. 3 days

ICU duration: 6 vs. 3 days

≥30 days: 12% vs. 6%

Hospital duration: 12 vs. 7 days

≥30 days: 23% vs. 11%

Medications:

Vasopressors: 89% vs. 83%

Norepinephrine: 87% vs. 81%

Dopamine: 28% vs. 23%

" Epinephrine: 37% vs. 38%

Inotropes: 69% vs. 62%

Dobutamine: 35% vs. 34%

Milronone: 35% vs. 33%

Levosimendan: 22% vs. 22%

Staged revascularization while in-hospital

PCI: 4% vs. 6%

CABG: 0 vs. 2%

Subgroup Analysis

Subgroups for the primary outcome are shown in Figure 2. There was perhaps a different effect among men (who benefited from the intervention) than women (who did not), but this observation is difficult to interpret given the relatively small proportion of women in the trial (~20% of the population were women). There was perhaps differential benefit by blood pressure, where persons with MAP ≤63 mm Hg might have gained greater benefit than persons with higher MAP. Finally, there was perhaps differential benefit for persons with ≥2 diseased vessels.

Adverse Events

Severe bleeding, limb ischemia device failure, worsening aortic regurgitation

This was the composite safety endpoint.

24.0% vs. 6.2% (RR 4.74; 95% CI 2.36 to 9.55; NNH=6)

Moderate or severe bleeding, per GUSTO criteria: 21.8% vs. 11.9% (RR 2.06; 95% CI 1.15 to 3.66)

Limb ischemia: 5.6% vs. 1.1% (RR 5.15; 95% CI 1.11 to 23.84)

RRT: 41.9% vs. 26.7% (RR 1.98; 95% CI 1.27 to 3.09)

Stroke: 3.9% vs. 2.3% (RR 1.75; 95% CI 0.50 to 6.01)

Cardioversion for VT or Vfib: 33.0% vs. 29.5% (RR 1.17; 95% CI 0.75 to 1.83)

Blood culture positive sepsis: 11.7% vs. 4.5% (RR 2.79; 95% CI 1.20 to 6.48)

Criticisms

• Open label.
• Women are underrepresented. No reporting by race/ethnic group.
• >70% of screened participants were excluded.

Funding

• Danish Heart Foundation
• Abiomed, who sells the Impella device, via unrestricted research grant in order to allow the expansion of the study to German sites.