ESC Andreas Grüntzig Lecture in Interventional Cardiology
Cardiogenic shock complicating acute myocardial infarction – current evidence and future strategies
31 Aug 2024
Professor Holger Thiele (Heart Center Leipzig at University of Leipzig - Leipzig, Germany) has shed much-needed light on the necessity for better management of cardiogenic shock, notably as a leading investigator in the largest randomised trials, such as IABP-SHOCK II, CULPRIT-SHOCK and ECLS-SHOCK. Today, he presents the ESC Andreas Grüntzig Lecture in Interventional Cardiology discussing the treatment landscape for myocardial infarction (MI) with cardiogenic shock.
What are the key themes of your lecture?
The focus is to see how far we have come in the treatment of cardiogenic shock and what we need to do to further improve progress. Cardiogenic shock is still one of the leading causes of hospital admission for patients with acute cardiovascular disorders. Unacceptably high mortality rates have remained unchanged for around three decades, with roughly every second patient with cardiogenic shock dying, and evidence for new approaches is limited. For 25 years it has been clear that early revascularisation effectively reduces mortality. In addition, restricting percutaneous coronary intervention (PCI) to the culprit vessel artery alone improves survival over multivessel PCI.1 However, beyond these two strategies, we still do not know what is the best treatment for patients.
What are the most important knowledge gaps?
There was expectation that mechanical circulatory support via intra-aortic balloon counterpulsation would be beneficial, but we found no advantage in the IABP-SHOCK II trial.2 More recently, similar hopes were placed on the use of extracorporeal life support (ECLS) in infarct-related cardiogenic shock, but the ECLS-SHOCK trial found that this also failed to reduce mortality,3 a finding that was confirmed by subsequent meta-analyses from four randomised trials.4 We do not really understand the reasons for the lack of benefit of these strategies. My Late-Breaking Science Session presentation on Monday, discussing the 12-month results from the ECLS-SHOCK trial, will provide some more insights.
Another approach – left ventricular (LV) unloading by implantation of catheter-mounted microaxial flow pumps, such as the Impella device – also did not succeed in reducing mortality in small randomised trials and in a broad series in a general population in clinical practice.5 However, the DanGer Shock trial showed efficacy of this strategy in a highly selected patient population with ST-elevation MI patients without risk of neurological deficit.6 There is a great deal of discussion surrounding these results and the finding that the complication rate was four-times higher with the flow pump than with standard treatment, and more studies are required to confirm the role of these devices. Crucially, we need to find ways to reduce, and preferably, prevent, the associated complications and define criteria to select the patients most likely to benefit from mechanical circulatory support. In another Late-Breaking presentation on Monday, I will discuss this in the context of an individual patient data meta-analysis involving all randomised trials performed to date on mechanical circulatory support.
What are the most promising avenues of research?
The most effective way to reduce mortality is to prevent the development of cardiogenic shock in the first place, and this is something that requires urgent attention. Future investigations should also look at tackling the systemic hyperinflammatory shock response – involving an influx of neutrophils, elevated interleukins, mainly interleukin-6, and elevated C-reactive protein levels – and there is the idea that interleukin-6 inhibition could reduce myocardial injury and even decrease mortality.7 This effect needs to be addressed in specific phenotypes of patients. Another promising avenue of research follows biomarkers, such as dipeptidyl peptidase-3 (DPP-3), an enzyme released during cardiogenic shock, which is predictive of mortality and inhibits myocardial function.8 Experimental study showing successful blockade of DPP-3 is promising and this now requires further exploration in clinical human trials.
Given the multifactorial nature of cardiogenic shock, it is likely that a combination of approaches, involving prevention, early revascularisation, LV unloading in selected patients and blockade of inflammatory factors mediating cardiogenic shock, will hold the answer to more effective management and improved survival.
Don't miss!
1 September 11:00-11:45, ESC Andreas Grüntzig Lecture in Interventional Cardiology: Cardiogenic shock complicating acute myocardial infarction – current evidence and future strategies
References
- Thiele H, et al. N Engl J Med. 2017;377:2419–2432.
- Thiele H, et al. N Engl J Med. 2012;367:1287–1296.
- Thiele H, et al. N Engl J Med. 2023;389:1286–1297.
- Zeymer U, et al. Lancet. 2023;402:1338–1346.
- Miller PE, et al. JAMA Intern Med. 2022;182:926–933.
- Møller JE, et al. N Engl J Med. 2024;390:1382–1393.
- Lüscher TF and Thiele H. Eur Heart J. 2024 Jul 10:ehae425.
- Wenzl FA, et al. Eur Heart J. 2023;44:3859–3871.
