LAUSR

Cardiogenic shock is a low-cardiac output condition due to primary cardiac dysfunction, resulting in inadequate peripheral tissue oxygen delivery.1 Despite efforts to improve cardiogenic shock interventions, including mechanical circulatory support and reperfusion therapy for myocardial infarction, outcomes still remain poor.2 The haemodynamic profile of cardiogenic shock is characterized by low cardiac output, low blood pressure, high filling pressures (central venous pressure and pulmonary capillary wedge pressure) and elevated systemic vascular resistance.3 The oxygen demand–delivery imbalance of cardiogenic shock results in reduced mixed venous oxygen saturation and increased lactate levels, together with worsening of renal and liver function, and altered mental status. Cardiogenic shock triggers a plethora of endogenous responses, including activation of the sympathetic nervous system and the renin–angiotensin–aldosterone system (RAAS) in the attempt to increase cardiac output by increasing heart rate and cardiac contractility. At the same time, counter-regulatory systems, such as the natriuretic peptide system, are activated to reduce high filling pressures and ventricular loading and to counteract peripheral vasoconstriction to increase forward blood. Accordingly, circulating levels of most cardiovascular biomarkers are markedly increased in cardiogenic shock,4 but most are considered epiphenomena and not causal factors in the pathophysiology of cardiogenic shock. The observation made by Deniau et al.5 in this issue of the Journal that the cytosolic enzyme dipeptidyl peptidase 3 (DPP3) not only represents a novel prognostic biomarker but also may be a potential candidate as a bio-target in cardiogenic shock is therefore intriguing. DPP3, like other members of the dipeptidyl peptidase family, is devoted to the cleavage of vasoactive peptides including angiotensin II and enkephalins (Table 1). The limited experimental data that have