Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent aminopeptidase that is found in several places and is thought to be a cytosolic enzyme that helps break down peptides. Recent studies, however, have revealed its extensive therapeutic relevance upon release into circulation, functioning not only as a biomarker for cellular injury but also as an active modulator of cardiovascular homeostasis and critical disease. High levels of circulating DPP3 (cDPP3) have been linked to the causes of cardiogenic shock, septic shock, acute coronary syndromes, heart failure, and serious viral diseases like COVID-19. Its enzymatic breakdown of angiotensin II disrupts vascular tone and myocardial contractility, leading to hemodynamic instability and multi-organ failure. In numerous cohorts, cDPP3 levels reliably correspond with disease severity, acute renal damage, and death, but dynamic trajectories yield superior predictive information relative to single assessments. In addition to risk stratification, translational studies utilizing rodent and porcine models illustrate that antibody-mediated inhibition of cDPP3 with the humanized monoclonal antibody Procizumab reinstates cardiac function, stabilizes renal perfusion, diminishes oxidative stress and inflammation, and enhances survival. First-in-human experiences in patients with refractory septic cardiomyopathy have further emphasized its therapeutic promise. DPP3 is a good example of a biomarker and a mediator in cardiovascular and critical care. Its growing clinical and translational profile makes cDPP3 a strong predictor of bad outcomes and a prospective target for treatment. Ongoing clinical trials using Procizumab will determine if neutralizing cDPP3 can lead to enhanced outcomes in individuals with cardiogenic and septic shock. This review outlines the physiological mechanisms, clinical implications, and emerging therapeutic potential of DPP3 in cardiovascular and critical care. Ongoing trials with Procizumab will clarify whether neutralizing cDPP3 can improve outcomes in patients with cardiogenic and septic shock.

Hypertrophic cardiomyopathy (HCM) is a complex and heterogeneous cardiac disorder, often complicated by cardiogenic shock, a life-threatening condition marked by severe cardiac output failure. Managing cardiogenic shock in HCM patients presents unique challenges due to the distinct pathophysiology of the disease, which includes dynamic left ventricular outflow tract obstruction, diastolic dysfunction, and myocardial ischemia. This review discusses current and emerging therapeutic strategies tailored to address the complexities of HCM-associated cardiogenic shock and other diseases with similar pathophysiology that provoke left ventricular outflow tract obstruction. We explore the role of pharmacological interventions, including the use of vasopressors and inotropes, which are crucial in stabilizing hemodynamics but require careful selection to avoid exacerbating the outflow obstruction. Additionally, the review highlights advancements in mechanical circulatory support devices such as extracorporeal membrane oxygenation (ECMO) and left ventricular assist devices (LVADs), which have become vital in the acute management of cardiogenic shock. These devices provide temporary support and bridge patients to recovery, definitive therapy, or heart transplantation, which remains a critical option for those with end-stage disease. Furthermore, the review delves into the latest research and clinical trials that are refining these therapeutic approaches, ensuring they are optimized for HCM patients. The impact of these treatments on patient outcomes, including survival rates and quality of life, is also critically assessed. In conclusion, this review underscores the importance of a tailored therapeutic approach in managing cardiogenic shock in HCM patients, integrating pharmacological and mechanical support strategies to improve outcomes in this high-risk population.