Safety and Efficacy of FAP iCDC in Acute Myocardial Infarction With Cardiogenic Shock

Background: Cardiogenic shock following acute myocardial infarction (AMI) remains a major unresolved clinical challenge. Despite advances in urgent revascularization and mechanical circulatory support, short-term mortality remains unacceptably high, approaching 40% within 30 days. Few evidence-based therapies have demonstrated a meaningful survival benefit, highlighting the urgent need for novel, mechanism-driven interventions. Growing clinical and experimental evidence indicates that a dysregulated systemic inflammatory response-manifested by hyperthermia, leukocytosis, and elevated proinflammatory mediators-plays a central role in the pathophysiology and progression of cardiogenic shock. Excessive inflammation exacerbates myocardial dysfunction, promotes multiorgan injury, and impairs recovery, suggesting that targeted immunomodulation may represent a complementary therapeutic strategy in this high-risk population. Dendritic cells (DCs), as professional antigen-presenting cells, occupy a pivotal position at the interface of innate and adaptive immunity and are uniquely suited to orchestrate context-dependent immune responses. In particular, tolerogenic DCs exert potent immunosuppressive effects through regulatory cytokine production, expression of co-inhibitory ligands, antigen-specific suppression of effector T cells, and induction of regulatory T cells. Collectively, these properties render DCs an attractive yet underexplored cellular platform for resolving excessive inflammation and promoting tissue repair in cardiogenic shock with AMI.

Purpose: In this prospective clinical study, the investigators engineered a stable, immunosuppressive, and fibrotic lesion-targeted DC therapy, termed immunosuppressive DCs (iCDC). This study was designed to evaluate the safety and preliminary efficacy of allogeneic fibroblast activation protein (FAP)-targeted iCDC therapy in patients with AMI complicated by cardiogenic shock.

Study design: This single-center, prospective, concurrent non-randomized controlled clinical trial enrolls patients aged 18-80 years presenting with acute myocardial infarction complicated by cardiogenic shock. Eligible patients are treated with allogeneic FAP-targeted immunosuppressive iCDC therapy.

Outcome measure: The primary outcome is the safety of FAP-targeted immunosuppressive iCDC therapy in patients with AMI complicated by cardiogenic shock. Secondary outcomes include 30-day all-cause mortality; hemodynamic parameters following iCDC therapy (systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate); time to hemodynamic stabilization; dose and duration of vasopressor and inotropic support; arterial lactate levels; changes in biomarkers (BNP, CRP, creatinine, ALT, AST, and inflammatory mediators); need for and duration of mechanical ventilation; need for and duration of left ventricular assist device implantation; intensive care unit and total hospital length of stay; left ventricular ejection fraction assessed by echocardiography; SAPS II score; SCAI shock classification; heart failure symptom burden assessed by NYHA functional class and the Kansas City Cardiomyopathy Questionnaire; incidence of major adverse cardiovascular events (MACE), including cardiac death and heart failure hospitalization; and incidence of adverse events.

• All-cause mortality [Time frame: 30 days after injection]
• Systolic blood pressure [Time frame: 24 hours、48 hours、72 hours、7 days after injection]
• Diastolic blood pressure [Time frame: 24 hours、48 hours、72 hours、7 days after injection]
• Mean arterial pressure [Time frame: 24 hours、48 hours、72 hours、7 days after injection]
• Time to hemodynamic stability [Time frame: From the end of the iCDC infusion to achievement of hemodynamic stability, assessed continuously until ICU discharge (up to 30 days).]
• Dose of vasopressors [Time frame: 24 hours、48 hours、72 hours、7 days after injection]
• Duration of vasopressor use [Time frame: From enrollment to hospital discharge (up to 30 days).]
• Dose of inotropic drugs [Time frame: 24 hours、48 hours、72 hours、7 days after injection]
• Duration of inotropic drugs use [Time frame: From enrollment to hospital discharge (up to 30 days).]
• Serum lactate level [Time frame: The measurement frequency is once every 8 hours for a duration of 48 hours.]
• Change in B-type natriuretic peptide (BNP) level from baseline [Time frame: 7 days，14 days，30 days after injection.]
• Change in C-reactive protein (CRP) level from baseline [Time frame: 24 hours, 72 hours, 7 days，14 days after injection.]