O. Chioncel et al. Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus-driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high-quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in-hospital management.

Background: Cardiogenic shock (CS) is a life-threatening state of tissue hypoperfusion, associated to a very high risk of mortality, despite intensive monitoring and modern treatment modalities. Present review aims to describe the therapeutic advances in the management of CS. Areas of Uncertainty: Many uncertainties about CS management remain in clinical practice, and these relate to intensity of invasive monitoring, the type and timing of vasoactive therapies, the risk-benefit ratio of mechanical circulatory support (MCS) therapy and optimal ventilation mode. Furthermore, most of the data is coming from CS in setting of acute myocardial infarction (AMI), while for nonAMI-CS patients there are very few evidences for etiological or MCS therapies. Data Sources: The prospective multicentric acute heart failure registries that specifically presented characteristics of patients with CS, distinct to other phenotypes, were included in the present review. Relevant clinical trials investigating therapeutic strategies in post AMI-CS patients were added as source information. Several trials investigating vasoactive medications and metaanalysis providing information about benefits and risks of MCS were reviewed in the manuscript.

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