Extending the ‘host response’ paradigm from sepsis to cardiogenic shock: evidence, limitations and opportunities

Abstract

Recent clinical and research efforts in cardiogenic shock (CS) have largely focussed on the restoration of the low cardiac output state that is the conditio sine qua non of the clinical syndrome. This approach has failed to translate into improved outcomes, and mortality has remained static at 30–50%. There is an unmet need to better delineate the pathobiology of CS to understand the observed heterogeneity of presentation and treatment effect and to identify novel therapeutic targets. Despite data in other critical illness syndromes, specifically sepsis, the role of dysregulated inflammation and immunity is hitherto poorly described in CS. High-dimensional molecular profiling, particularly through leukocyte transcriptomics, may afford opportunity to better characterise subgroups of patients with shared mechanisms of immune dysregulation. In this state-of-the-art review, we outline the rationale for considering molecular subtypes of CS. We describe how high-dimensional molecular technologies can be used to identify these subtypes, and whether they share biological features with sepsis and other critical illness states. Finally, we propose how the identification of molecular subtypes of patients may enrich future clinical trial design and identification of novel therapies for CS. Graphical Abstract

Early physical rehabilitation dosage in the intensive care unit associates with hospital outcomes after critical COVID-19

“…Precision exercise, dose–response, and individual response heterogeneity are concepts in exercise dosing that are known to impact outcomes in older adults and diverse patient populations [ 14 – 16 ]. The intra-individual variations have also been recognized in critical care with ventilatory and pharmaceutical interventions [ 17 , 18 ]. To improve the ICU rehabilitation field, it is imperative that clinicians and researchers examine the dose–response.…”

Future for cardiogenic shock research

“…Proteomics and metabolomics may further unravel the complex molecular mechanisms in cardiogenic shock [13]. By analyzing the proteome of cardiac tissues or circulating proteins, it is possible to identify biomarkers indicative of myocardial injury, inflammation, or stress response [14], thus potentially aiding prediction of cardiogenic shock development and risk prediction of cardiogenic shock [15].…”