The ECLS-Shock trial did not demonstrate improved mortality with ECMO compared to medical therapy alone in patients with acute myocardial infarction complicated by cardiogenic shock. However, the lack of benefit in that trial may have been due to poor patient selection and the delayed initiation of ECMO.
Percutaneous microaxial flow pumps are another type of mechanical circulatory support. This device drains blood from the left ventricle and expels it into the ascending aorta (i.e. unloads the left ventricle). In order for this device to work appropriately, blood needs to be well oxygenated and the right ventricular function has to be adequate. No RCT to date has shown a mortality benefit with the use of these devices and existing data shows a higher rate of excess bleeding.
Paper: Moller JE et al. Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock. NEJM 2024. PMID: 38587239
Clinical Question: In adult patients with STEMI complicated by cardiogenic shock does the use of microaxial flow pumps in addition to standard medical care improve 180d mortality compared to standard medical care alone?
What They Did:
- The Danish-German Cardiogenic Shock (DanGer Shock) Trial
- International, multicenter, randomized, open-label trial
- Performed in Denmark, Germany, and the UK
- Originally trial was intended to be conducted in one country (DanShock), however due to slow enrollment, the trial was expanded to Germany (2019) and the UK (2021)
- Patients with STEMI and cardiogenic shock with planned emergency revascularization randomized to:
- Microaxial flow pump (Impella CP) plus standard care
- Standard care alone
- Randomization occurred in the cath lab, either before or after revascularization or up to 12 hours after leaving the cardiac catheterization lab, depending on when cardiogenic shock was recognized
- In the event of hemodynamic instability, treatment could be escalated to additional mechanical circulatory support after randomization in either trial group (i.e. Impella 5.0, Impella RP, or ECMO)
Outcomes:
- Primary: Death from any cause at 180 days
- Secondary:
- Composite: Escalation of treatment to additional mechanical circulatory support, heart transplantation, or death from any cause
- Days alive and out of hospital
- Safety:
- Composite of severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation
- Need for RRT
- Sepsis with positive blood cultures
Inclusion:
- Adult patients (≥18 years of age)
- STEMI and cardiogenic shock
- Cardiogenic shock = hypotension (SBP <100mmHg or an ongoing need for vasopressor support, end-organ hypoperfusion with an arterial lactate ≥2.5mmol/L, and LVEF <45%
Exclusion:
- Patients who had been resuscitated from OHCA and remained comatose on arrival to the cardiac catheterization lab
- Overt RV failure
Results:
- 360 patients underwent randomization
- 355 included in the final analysis
- Median SBP 82mmHg
- Median Lactate 4.5 mmol/L
- Median LVEF 25% (Range 15 to 30%)
- Anterior MI ≈70%
- SCAI Stage at Admission
- C (Pt with clinical evidence of hypoperfusion that initially requires pharmacologic or mechanical support) ≈55%
- D (Pt with clinical evidence of shock that worsens or fails to improve despite escalation of therapy) ≈28%
- E (Pt with refractory shock or actual/impending circulatory collapse) ≈ 16%
- Median time from symptom onset to randomization ≈4hrs
- Placement of microaxial flow pump support
- Impella 95%
- Control 1.7%
- Escalation to ECMO
- Impella 11.7%
- Control 18.8%
- Any escalation to additional MCS
- Impella 15.6%
- Control 21.0%
- Death from any cause at 180d:
- Impella: 82/179 (45.8%)
- Control: 103/176 (58.8%)
- HR 0.74; 95% CI 0.55 to 0.99; p = 0.04
- NNT = 8
- Composite Safety Outcome
- Impella: 24.0%
- Control: 6.2%
- RR 4.74; 95% CI 2.36 to 9.55
- NNH = 6
- Moderate or Severe Bleeding
- Impella: 21.8%
- Control 11.9%
- RR 2.06; 95% CI 1.15 to 3.66
- Limb Ischemia
- Impella: 5.6%
- Control: 1.1%
- RR 5.15; 95% CI 1.11 to 23.84
- RRT
- Impella: 41.9%
- Control: 26.7%
- RR 1.98; 95% CI 1.27 to 3.09
- Sepsis with Positive Blood Culture
- Impella: 11.7%
- Control: 4.5%
- RR 2.79; 95% CI 1.20 to 6.48
Strengths:
- Asks a clinically important question about a device that has not been previously shown to have mortality benefit
- Multicenter, randomized, controlled trial increases generalizability of results
- An independent data and safety monitoring committee oversaw patient safety and performed interim analyses after enrollment
- Funders did not take part in the trial design and did not participate in the analysis or interpretation of data or in the writing of the manuscript
- Patients fairly well balanced at baseline (Control group had slightly more HTN and DM at baseline)
Limitations:
- Study was funded by Danish heart Foundation and Abiomed (maker of impella)
- Representatives of Abiomed had an opportunity to review and comment on the final manuscript
- Strict inclusion/exclusion criteria would make it difficult to extrapolate results of this trial to patients with cardiogenic shock who remain comatose after cardiac arrest, NSTEMI patients, and patients with SCAI stage C shock without elevation in arterial lactate level
- Unblinded trial (i.e. open-label) which could affect other therapeutic decisions made by treating physicians that might have an impact on mortality
- Trial conducted over a period of 10 years, but most patients underwent randomization after 2019
Discussion:
- Lack of blinding in this study is an important point to bring up. If the group strongly believed in a benefit from mechanical circulatory support, this could influence care delivery outside of microaxial flow pumps:
- More vasoactive medications used in the microaxial flow pump group compared to control (88.8% vs 83.0%)
- More mechanical ventilation used in microaxial flow pump group ( 74.3% vs 65.9%)
- In subgroup analyses of the primary outcome the following subgroups seemed to benefit more from the use of MCS:
- Males
- MAP ≤63mmHg
- Diseased Coronary Vessels ≥2
- Patients who remained comatose after cardiac arrest were excluded due to the fact that it is impossible to differentiate between metabolic derangements caused by cardiac arrest and that caused by underlying LV failure due to MI
- Additionally, patients with cardiac arrest, hypoxic brain injury is the leading cause of death, whereas patients without cardiac arrest where persistent cardiac failure is the leading cause of death
- Patients in the microaxial flow pump group required more RRT than the control group. This could simply be due to the fact that more patients died early in control group which could cause a survival bias. This finding could also be due to increased hemolysis from the microaxial flow pump inducing nephropathy.
- Although microaxial flow pumps had more complications, it does not appear that these complications overshadowed the primary outcome of mortality benefit
Author Conclusion: “The routine use of microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump.”
Clinical Take Home Point: In this multicenter, randomized clinical trial of adult patients having STEMI complicated by cardiogenic shock microaxial flow pumps plus standard medical care led to a lower mortality at 180days compared to standard care alone. Although the incidence of adverse events was higher with the use of microaxial flow pumps, this did not seem to overshadow the mortality benefit seen. This is the first RCT to show a mortality benefit with the routine use of MCS.
References:
- Moller JE et al. Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock. NEJM 2024. PMID: 38587239
Post Peer Reviewed By: Anand Swaminathan, MD (Twitter/X: @EMSwami)
