Translational proteomics in cardiogenic shock: from benchmark to bedside

A n acute coronary syndrome can compromise blood flow to certain areas of the heart and cause ischemia and myocardial cell death, which can lead to ventricular dysfunction. If this myocardial injury is large and the ventricular dysfunction is severe, cardiogenic shock (CS) may develop, which results in a life-threatening state of hypoperfusion and critical hypoxia of vital organs. Acute myocardial infarction (AMI) with left ventricular dysfunction is the most common cause of CS (80% of the cases). Other possible causes of CS include myocarditis and acute decompensation of chronic heart failure (HF). The incidence of CS has increased notably during the last decade, in part due to important macrotrends, such as the aging of the population. The incidence of CS derived from AMI increased from 6.5% in 2003 to 10.1% in 2010, with similar trends observed in patients with congestive HF not preceded by AMI. Nonetheless, in-hospital mortality decreased from 62% in 2004 to 48% in 2014, probably due to significant advances in revascularization and supportive treatment, such as the use of mechanical circulatory support (MCS) devices. However, mortality remains unacceptably high, with one in two patients dying within ninety days. Overall, CS is estimated to affect between two million people and four million people in more developed countries (Table 1). The multiorgan failure associated with CS is the source of innumerable circulating molecules that has been of great value in the characterization of CS, since contemporary advances in “omic” technologies provide new insights into a more holistic molecular signature of CS, including the inflammatory response and the involvement of other vital organs (kidney, liver and intestine, among others) beyond the myocardial dysfunction. Indeed, MCS devices are transforming the management of HF and represent the first life-saving treatment in emergencies like CS. Unfortunately, the implantation of this type of device requires a specialized center and equipment, it is highly invasive, with serious risks for the patient and enormous associated costs. Therefore, deciding which patient needs an MCS and which patient could do well with only standard treatments becomes an absolute necessity. Moreover, this is worsened by the rapid downward spiral evolution of CS and sometimes decision-making can be subjective, which entails greater risks for patients and a greater economic burden for health system. Sadly, molecular tools for CS prognosis have not yet been developed to guide such therapies. In recent years, two clinical scores (CardShock and IABP-SHOCK II) have been developed to try to aid in the prognosis of CS. Both scores are calculated from clinical variables at baseline and associated with short-term mortality. However, the only laboratory parameters included in these risk scores come from classical biochemical tests, glucose and lactate, which are the only metabolic biomarkers used in this pathology since 1950s. In addition, in emergency situations such as CS, the time needed to make a decision is crucial for the patient, and classic clinical variables may take time to reflect alterations in their values, which in turn make the decisionmaking of the medical team more imprecise and late. Many studies have explored different predictive Journal of Geriatric Cardiology