Abstract Body (Do not enter title and authors here): Introduction: Post-myocardial infarction ventricular septal perforation (VSP) with cardiogenic shock often requires mechanical circulatory support (MCS) to stabilize hemodynamics. Devices such as the percutaneous left ventricular assist device (Impella), veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and their combination (ECPELLA) provide systemic support and left ventricular (LV) unloading. However, managing VSP with these advanced MCS remains challenging due to complex hemodynamics and oxygenation dynamics.

Hypothesis: We hypothesized that the balance between right ventricular (RV) and LV function has a significant impact on VSP flow patterns and oxygenation in patients with VSP under advanced MCS.

Methods: We developed a cardiovascular simulation using Simulink® (MathWorks, Inc.) based on a 5-element resistance–capacitance network. VSP was simulated as a Bernoulli-based orifice. Systemic oxygen delivery (DO₂) and LV oxygen saturation (LV-SO₂) were calculated using oxygen supply–demand balance (Fig. 1A). In severe LV dysfunction (end-systolic elastance, LV-Ees = 0.4 mmHg/mL), we assessed right and left atrial pressures (RAP, LAP) and shunt flows under RV systolic dysfunction (low RV-Ees), high pulmonary vascular resistance (PVR), and impaired diastolic compliance of both ventricles (modeled by steeper end-diastolic pressure–volume relationships), across varying Impella and VA-ECMO flows(Fig. 1B). We also evaluated DO₂ and LV-SO₂ in the combined setting of high PVR and low RV-Ees.

Results: In isolated LV systolic dysfunction, MCS improved hemodynamics and reduced left-to-right (LR) shunt flow in an Impella flow–dependent manner without significant right-to-left (RL) shunt. Similar trends occurred with LV diastolic dysfunction. In contrast, high PVR markedly increases RL shunt flow with higher Impella flow. RV systolic and diastolic dysfunction also increased RL shunt flow, though less than high PVR (Fig. 2). In severe biventricular failure with high PVR, increased Impella flow lowered LV-SO₂ and only modestly improved DO₂. The addition of VA-ECMO provided critical oxygenation support (Fig. 3).

Conclusion: RV function and PVR are key determinants of the pressure balance between the RV and LV and thus play a critical role in the development of RL shunt under high Impella flow conditions. Careful titration of MCS flow based on RV function and PVR is essential in managing patients with VSP with severe LV failure.