Temporal increases in oxidized phospholipids on plasminogen are associated with native heart survival in cardiogenic shock
I Taleb, T V Giannouchos, X Yang, S G Drakos, S TsimikasAbstract
Background
Oxidized phospholipids (OxPL) bind to circulating proteins, including plasminogen, apoB, and apo(a), with carrier-specific biological effects. While OxPL on apoB/apo(a) are linked to atherothrombosis, OxPL bound to plasminogen (OxPL-PLG) mediate faster fibrinolysis ex vivo and have been associated with lower risk of type I myocardial infarction and major cardiovascular events in human studies. Cardiogenic shock (CS) is characterized by oxidative stress and thrombo-inflammatory dysregulation that may persist despite temporary mechanical circulatory support (tMCS). Whether OxPL are pathophysiologically involved in CS remains unknown.
Purpose
To determine whether longitudinal changes in OxPL carriers and plasminogen are associated with native heart survival (NHS) in tMCS-treated CS.
Methods
Serial plasma samples (pre-tMCS, explant, discharge) were analyzed in 70 adults with tMCS-treated CS enrolled in a prospective registry. OxPL-PLG (primary biomarker), total plasminogen, OxPL-apoB, and OxPL-apo(a) were quantified by validated ELISAs. NHS was defined as survival to discharge without cardiac replacement therapy (NHS n=33; no NHS n=37 [death n=26, durable LVAD n=6, heart transplantation n=5]). Linear mixed-effects models assessed within-patient trajectories over time, allowing patterns to differ by NHS status. Models adjusted for age, chronic heart failure (HF), SCAI stage, and VA ECMO use.
Results
Baseline demographics, shock etiology, clinical and hemodynamic severity, and tMCS modality were comparable between groups. Chronic HF (40.5% vs 18.2%, p=0.038), CKD stage III-IV (24.3% vs 3%, p=0.027), and valvular heart disease (27% vs 3%, p=0.004) were more prevalent without NHS. Baseline OxPL-PLG levels were similar (NHS: 216.6 [152.0-281.2] vs no NHS: 235.4 [174.3-296.4] nmol/L). Over time, trajectories diverged: NHS patients demonstrated progressive increases (216.6 [152.0-281.2]->289.2 [221.4-357.0]->483.6 [406.2-561.1], p<0.001), whereas no NHS patients showed attenuated changes (235.4 [174.3-296.4]->266.7 [200.1-333.4]->323.3 [233.3-413.4], p=0.11). The time-by-NHS interaction was significant (p=0.002) and consistent across adjusted models. OxPL-apoB and OxPL-apo(a) showed no longitudinal association with NHS. Total plasminogen was higher at discharge in NHS patients (10.9 [8.4-13.4] vs 3.9 [1.0-6.9], p<0.001) but similar at baseline. After inclusion of total plasminogen, the time-by-NHS interaction was attenuated and no longer statistically significant, although the trajectory difference remained directionally consistent with similar magnitude.
Conclusions
In tMCS-treated CS, serial increases in OxPL-PLG were associated with NHS. The absence of similar trajectories in other OxPL carriers supports a carrier-specific association. Whether OxPL-PLG-associated fibrinolytic activity contributes to NHS warrants further mechanistic and multicenter validation.