Managing Cardiogenic Shock & Cardiac Arrest: We’ll Get There

LONDON — Cardiogenic shock and recovering cardiac arrest have a checkered history when it comes to high-impact management strategies. Now, a new meta-analysis provides a clear steer on the value of mechanical circulatory devices for cardiogenic shock, while experts continue to stress the value of rapid cardiopulmonary resuscitation (CPR) for minimizing brain injury in out-of-hospital cardiac arrest (OHCA).

Giving the state-of-the-art lecture here at the European Society of Cardiology (ESC) Congress 2024 annual meeting, associate professor Carolina Malta Hansen, MD, PhD, from the University of Copenhagen, Copenhagen, Denmark, provided background on developments in the diagnosis and management of the two conditions.

“On cardiogenic shock, most recent research has revolved around mechanical circulatory devices,” she said. “It seems we’re making some progress in that we now have a device [Impella CP] that seems to work in the population with ST-elevation and myocardial infarction [MI], complicated by cardiogenic shock and a low risk of anoxic brain damage.” She added that there remains a high rate of complications, mostly bleeding and peripheral ischemia. “Also, we don’t really have good evidence-based options of how to treat the other phenotypes of cardiogenic shock.”

Cardiac arrest, however, may have some potentially interesting news with respect to an investigational neuroprotective drug called nelonemdaz, which aims to minimize brain damage. “It looks promising, but still needs to be tested in a large phase 3 trial, as in a cardiac arrest population,” said Malta Hansen.

All Cardiogenic Shock Is Not the Same

On cardiogenic shock, Malta Hansen said, “We have basically had unchanged survival for the last 20 years, and about half of the patients who are in cardiogenic shock end up dying.”

However, recently several significant trials have generated evidence to improve understanding of cardiogenic shock management. “There might not necessarily be better treatments yet, but trials are helping to improve understanding of the cardiogenic shock population, which is very heterogeneous.”

“For some reason, we’ve been talking about cardiogenic shock as one entity, and I think that it’s becoming increasingly clear that we need to better phenotype this condition,” she said.

Malta Hansen highlighted a meta-analysis on mechanical circulatory support (MCS) for cardiogenic shock presented at the ESC earlier in the day and published simultaneously in The Lancet.

She explained that the meta-analysis pooled all existing randomized controlled trials (RCTs) and showed that, altogether, MCS devices did not reduce 6-month survival in patients with acute myocardial infarction-related cardiogenic shock. However, there was a reduction in mortality in patients with ST-elevation and low risk for anoxic brain damage.

To provide some perspective on the evidence, she referred to a landmark study that compared early extracorporeal life support (ECLS) plus usual medical treatment with usual medical treatment alone in patients with acute MI complicated by cardiogenic shock.

Published in The New England Journal of Medicine (NEJM), she explained that the trial only included patients with MI — the largest subpopulation with cardiogenic shock — who then had cardiogenic shock, but that “no difference was found between patients who did and did not receive ECLS, and it showed a very large proportion of bleeding complications in the ECLS group compared with controls [23.4% vs 9.6%], which is really the problem with this type of mechanical support treatment.”

Malta Hansen added that patients who had been resuscitated after cardiac arrest had been included in the trial, and they have notoriously bad outcomes, possibly influencing results. Acknowledging the negative result, Malta Hansen said it remains that “we do not have evidence that ECLS in infarct-related cardiogenic shock increases survival in this population. However, such negative findings might mean we develop our measurements and diagnostics of complications and improve our use of, as well as outcomes, with these devices.”

She also drew attention to the Impella trial that gave half of patients with MI-related cardiogenic shock a microaxial flow pump (Impella CP) in addition to standard of care. “This is another landmark trial for being the first to show a benefit of the microaxial flow pump in this population.”

Published in the NEJM this year, the trial showed death within 180 days from any cause occurred in 45.8% in the microaxial flow pump group and in 58.5% of the standard-of-care group (P = .04), but adverse events were higher in the intervention arm. “The investigators still reported a very large risk of bleeding complications,” remarked Malta Hansen. “Importantly, this trial only included cardiac arrest patients who were not comatose.”

The results from the newly published meta-analysis, which pooled patient-level data from nine RCTs of MCS used for patients with cardiogenic shock, reinforced the previous findings, Malta Hansen pointed out. “Taken together, the results show that the addition of mechanical circulatory support to standard care in patients with myocardial infarction complicated by cardiogenic shock does not improve survival at 6 months and increases the risk of complications. However, patients with an ST-elevation infarction and with low risk of anoxic brain damage seem to benefit from this treatment.”

Minimizing Brain Damage in OHCA

Turning to OHCA and the associated brain damage if the patient is not resuscitated within the first 10 minutes, Malta Hansen said, “We have not yet figured out how to reverse this brain damage.”

However, she referred to an abstract presentation during the ESC on new phase 2 data on the neuroprotective drug nelonemdaz, which has the potential to reduce hypoxic brain injury in OHCA.

“Most patients who are resuscitated from cardiac arrest die from brain damage,” she explained. “Once they come into the hospital, most patients are stabilized, but their brain has suffered very significant damage during the downtime of cardiac arrest. We have not figured out how to deal with this, so any new developments of relevance are important.”

The double-blind, placebo-controlled, randomized, multicenter AWAKE trial compared patients given a high or low dose of nelonemdaz with placebo. Nelonemdaz is a moderate NR2B-selective N-methyl-D-aspartate receptor antagonist that also exhibits potent free radical scavenger properties.

Jin-Ho Choi, associate professor at Samsung Medical Center’s Division of Cardiology Heart Vascular and Stroke Institute, South Korea, presented the findings during Malta Hansen’s session and reported that the drug did not reduce blood serum neuron-specific enolase levels of patients with OHCA. However, patients on the high dose of nelonemdaz showed better fractional anisotropy, suggestive of reduced cerebral white matter damage, and showed a favorable tendency of neurologic recovery at day 90 without significant adverse effects. The drug should now move to a phase 3 trial.

“The trial did not show a benefit of nelonemdaz treatment according to the primary biomarker endpoint, and there was no difference in efficacy based on high- and low-dose nelonemdaz. However, the secondary outcome of fractional anisotropy was significantly lower in the high-dose group, and functional assessment showed a trend toward improved clinical outcomes, although they were statistically insignificant,” reported Choi.

At a session the day before, Claudio Sandroni, MD, professor of intensive care at the Catholic University School of Medicine and consultant at the Agostino Gemelli University Hospital, Rome, Italy, gave a state-of-the-art lecture on brain protection after cardiac arrest.

“It’s important that we avoid brain injury after cardiac arrest to improve both neurological outcome and survival,” he began.

Referring to 20 years of investigation related to hypothermia after cardiac arrest, he explained that there is no convincing evidence that there is a benefit to lowering the body temperature of comatose patients following cardiac arrest to 32 °C-34 °C compared with management by avoiding fever. Accordingly, the current European Resuscitation Council-European Society of Intensive Medicine do not recommend lowering the body temperature and instead focus on fever prevention for at least 72 hours and continuous monitoring of core temperature.

However, Sandroni added that, in 2022, an observational study demonstrated some potential benefit from temperature control at 33 °C vs 36 °C in patients with moderate postanoxic encephalopathy assessed using EEG, while no benefit was observed in patients with mild or severe encephalopathy.

Commenting on neuroprotective drugs, Sandroni said that, until recently, there had been no clinical evidence in favor of any drug. “But in recent years, gases such as xenon and hydrogen have shown potential beneficial effects. In 2016, a clinical trial showed that inhaled xenon, which has shown a consistent benefit in various preclinical models of brain injury, resulted in less white matter damage measured using MRI in comatose survivors of out-of-hospital cardiac arrest.”

In 2023, the HYBRID-II trial showed that inhalation of 2% hydrogen for 18 hours was associated with higher rates of survival with good neurologic outcome in patients with OHCA from cardiac origin. However, the difference was not significant, and the trial was stopped early because of the COVID-19 pandemic. Further studies are needed.

In her final remarks, Malta Hansen asserted that “What we do know is that to prevent brain injury, CPR has to be initiated within the first minutes after cardiac arrest.”

“This takes training emergency dispatchers and call handlers to recognize cardiac arrest and provide dispatch-assisted CPR, training the population in CPR, and disseminating publicly accessible automated external defibrillators,” she stressed.

“To improve in-hospital care, we need to improve prehospital care. That calls for action from public health authorities and stakeholders across all communities,” she concluded.

Malta Hansen, Sandroni, and Choi had no relevant disclosures to declare.