ECLS Shock trial – Extra-corporeal support in Cardiogenic Shock post-MI

Extracorporeal Life Support in Cardiogenic Shock Complicating Acute Myocardial infarction: The ECLS SHOCK trial

Thiele, Holger et al. “Extracorporeal Life Support in Infarct-Related Cardiogenic Shock.” The New England journal of medicine vol. 389,14 (2023): 1286-1297. doi:10.1056/NEJMoa2307227

Blog written by Dr Jose Chacko

Background

Acute myocardial infarction is complicated by cardiogenic shock in approximately 10% of patients (1). Despite timely revascularization, the mortality remains high, around 40–50% (2). Mechanical support, especially veno-arterial extracorporeal membrane oxygenation, has been increasingly employed to attain hemodynamic stabilization and, thereby, improve clinical outcomes (3). The development of more compact systems and percutaneous cannulation techniques have facilitated the initiation and conduct of extracorporeal life support (ECLS). However, the evidence to support the clinical efficacy of ECLS in cardiogenic shock has been largely confined to three randomized controlled trials (RCTs) of small sample size.

Brunner et al. randomized 42 patients with cardiogenic shock complicating acute myocardial infarction to receive ECLS or conventional treatment alone. The left ventricular ejection fraction among survivors at 30 days, the primary outcome, was similar in both groups of patients. The 30-day all-cause mortality was lower with ECLS (19% vs. 33%), although the difference was not statistically significant (4).

The EURO SHOCK trial included patients with persisting cardiogenic shock 30 minutes following primary percutaneous coronary intervention. The study was ceased after enrollment of only 35 patients as the Covid-19 pandemic swept across Europe. The 30-day all-cause mortality was similar in the ECLS and control groups at the time of cessation of the study. Vascular and bleeding complications were more often encountered among patients who underwent ECLS (5).

The multicenter RCT by Ostadal et al. included 117 patients – 58 underwent “immediate” ECLS, while 57 received conventional care. Those in the conventional group could receive ECLS if they remained hemodynamically unstable. The composite primary outcome, including all-cause mortality, resuscitated circulatory arrest, and resort to another mechanical support device at 30 days, was similar in both groups. This study showed that immediate initiation of ECLS among patients with severe cardiogenic shock did not improve clinical outcomes compared with conventional treatment, followed by later use of ECLS as appropriate (6).

The ECLS-SHOCK investigators hypothesized that early ECLS could lead to improved survival among patients with acute myocardial infarction complicated by cardiogenic shock, in whom revascularization was planned.

Population and design

The ECLS-SHOCK trial was conducted between June 2019 through November 2022 across 44 centers in Germany and Slovenia (7). The study included patients aged 18–80 years with cardiogenic shock following acute myocardial infarction who were planned for early revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery. Cardiogenic shock was defined as a systolic BP of <90 mm Hg for >30 minutes, or catecholamine administration to maintain systolic BP >90 mm Hg, an arterial lactate level of >3 mmol/L, and signs of organ hypoperfusion including one of the following.

• Altered mental status
• Cold, clammy extremities
• Urine output <30 ml/hour

After angiographic evaluation of anatomy and following the decision to revascularize, patients were randomized in a 1:1 ratio to one of two groups – conventional therapy combined with ECLS or conventional therapy alone.

Excluded

• Cardiopulmonary resuscitation for more than 45 minutes
• Mechanical cause of cardiogenic shock
• Severe peripheral vascular disease that did not permit cannula insertion for ECLS

Conventional therapy combined with ECLS (ECLS group)

ECLS was commenced during the index cardiac catheterization, before PCI if feasible. A distal perfusion catheter was recommended to reduce the likelihood of limb ischemia. Techniques of left ventricular unloading and weaning of ECLS were protocolized.

Conventional therapy alone (control group)

Conventional therapy was based on current guidelines. The trial protocol discouraged crossover to ECLS. However, if hemodynamic deterioration occurred, other devices, including an intra-aortic balloon pump or micro-axial transvalvular flow pump, could be used. Hemodynamic deterioration was defined as impending hemodynamic collapse, arterial lactate level of >3 mmol/L in a 6-h period, or an increase in the vasopressor dose by >50% of baseline to maintain mean arterial pressure of >65 mm Hg. Crossover to ECLS was discouraged.

Sample size

The authors based the sample size calculation assuming a 30-day mortality of 35% in the ECLS group and 49% in the control group. The enrollment of 394 patients provided 80% power to disprove the null hypothesis at a two-sided alpha level of 0.048 in the final analysis. A total of 420 patients were recruited, allowing a withdrawal rate of 6%.

Results

Among the 420 enrolled patients, three were excluded due to lack of informed consent. The final analysis included 209 patients in the ECLS group and 208 in the control group.

The mean age of the study cohort was 63 years and predominantly male (81.3%). Two-thirds of patients presented with ST-elevation myocardial infarction. The most common culprit vessel was the left anterior descending artery (47.6%); most patients had multivessel disease. The majority of patients (77.7%) received cardiopulmonary resuscitation before randomization. Revascularization was through PCI in 96.6% of patients. ECLS therapy was performed for a median duration of 2.7 days. In the control group, 28 patients (15.4%) underwent other types of mechanical support, mainly using the microaxial transvalvular device.

In the control group, 26 patients crossed over to receive ECLS, 22 within 24 hours of randomization.

The primary outcome: all-cause mortality at 30 days

The 30-day all-cause mortality was comparable in both groups – 100/209 (47.8%) in the ECLS group and 102/208 (49%) in the control group (relative risk, 0.98; 95% CI, 0.80–1.19; p = 0.81). The results of sensitivity analysis, allowing for patients who had crossed over from the control to the ECLS group, were similar.

Secondary outcomes

The secondary outcomes studied were similar in both groups (Table 1)

Table 1. Secondary outcomes

Safety outcomes

Moderate or severe bleeding was significantly higher in the ECLS (23.4%) compared to the control group (9.6%) (relative risk, 2.44; 95% CI, 1.50–3.95). Other complications, including peripheral vascular complications requiring intervention and stroke or systemic embolization, were also higher in the ECLS group.

Subgroup analysis

The authors performed a predefined subgroup analysis of the primary outcome based on age (<65 vs. ≥65 years), gender, presence of diabetes, presence of ST-segment elevation, anterior wall myocardial infarction, arterial lactate levels (3–6 mmol/L vs. >6 mmol/L), and receipt of cardiopulmonary resuscitation. The 30-day mortality was similar in the ECLS and the control groups on subgroup analysis.

Study conclusions

ECLS therapy, compared with conventional treatment alone, did not improve clinical outcomes, including 30-day all-cause mortality, among patients with acute myocardial infarction complicated by cardiogenic shock, who were planned for early revascularization. Complications, including moderate to severe bleeding, were more common with ECLS.

Comments

• The ECLS-SHOCK trial addressed an important, clinically relevant question: whether extracorporeal support improves outcomes in cardiogenic shock following acute myocardial infarction. The study is timely and pertinent considering lack of benefit of ECLS observed in previous small RCTs.
• In contrast to previous RCTs, the ECLS-SHOCK trial was adequately powered to address the clinical question.
• Patients in both groups were well-matched at baseline.
• ECLS was carried out using a standardized protocol.
• The study could not be blinded; hence, clinicians were aware of the study arm, which could have led to bias in management.
• Although crossover was discouraged, among patients who were randomized to conventional care, 26 underwent ECLS, including 22 within the first 24 hours of randomization. However, the primary outcome was similar on analysis by actual treatment received.
• Patients were severely ill; 77.7% had undergone cardiopulmonary resuscitation before randomization. The question remains whether ECLS would be more efficacious in a less severely ill patient population.
• Left ventricular unloading techniques were used sparingly – this could potentially have reduced the likelihood of myocardial recovery.
• No information was available regarding the transition to durable assist devices and cardiac transplantation.
• Evaluation of outcome was limited to 30 days; longer-term outcomes may be relevant, especially considering the large number of patients who received cardiopulmonary resuscitation and potentially adverse neurological outcomes.

References

1. Thiele H, Ohman EM, de Waha-Thiele S, Zeymer U, Desch S. Management of cardiogenic shock complicating myocardial infarction: an update 2019. Eur Heart J. 2019 Aug 21;40(32):2671–83.
2. Thiele H, Akin I, Sandri M, de Waha-Thiele S, Meyer-Saraei R, Fuernau G, et al. One-Year Outcomes after PCI Strategies in Cardiogenic Shock. N Engl J Med. 2018 Nov 1;379(18):1699–710.
3. Becher PM, Schrage B, Sinning CR, Schmack B, Fluschnik N, Schwarzl M, et al. Venoarterial Extracorporeal Membrane Oxygenation for Cardiopulmonary Support. Circulation. 2018 Nov 13;138(20):2298–300.
4. Brunner S, Guenther SPW, Lackermair K, Peterss S, Orban M, Boulesteix AL, et al. Extracorporeal Life Support in Cardiogenic Shock Complicating Acute Myocardial Infarction. J Am Coll Cardiol. 2019 May 14;73(18):2355–7.
5. Banning AS, Sabaté M, Orban M, Gracey J, López-Sobrino T, Massberg S, et al. Venoarterial extracorporeal membrane oxygenation or standard care in patients with cardiogenic shock complicating acute myocardial infarction: the multicentre, randomised EURO SHOCK trial. EuroIntervention J Eur Collab Work Group Interv Cardiol Eur Soc Cardiol. 2023 Aug 21;19(6):482–92.
6. Ostadal P, Rokyta R, Karasek J, Kruger A, Vondrakova D, Janotka M, et al. Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock: Results of the ECMO-CS Randomized Clinical Trial. Circulation. 2023 Feb 7;147(6):454–64.
7. Thiele H, Zeymer U, Akin I, Behnes M, Rassaf T, Mahabadi AA, et al. Extracorporeal Life Support in Infarct-Related Cardiogenic Shock. N Engl J Med. 2023 Oct 5;389(14):1286–97.