Disease‐Specific Ventricular Unloading Responses to Impella Support Revealed by Three‐Dimensional Pressure‐Volume‐Flow Landscape Analysis

Background Impella support alters left ventricular pressure‐volume (PV) relations, but disease‐specific unloading responses across the full support range remain incompletely characterized. We developed a three‐dimensional pressure‐volume‐flow landscape (3D‐PVL) framework to quantify and compare ventricular unloading in acute myocardial infarction (AMI), dilated cardiomyopathy (DCM), and DCM with mitral regurgitation (DCM + MR). Methods PV loops were simulated using a closed‐loop cardiovascular model at 51 Impella‐flow levels from 0 to 5.0 L/min. Loop‐centroid displacement and stroke work were normalized to their respective 0‐L/min values, and their unscaled direction‐sensitive derivatives were combined into a composite response. The response index (RI) quantified integrated response magnitude, while interior peak‐response flow (Qpeak) identified the flow level of maximal incremental response among interior flow points. Pressure‐volume area (PVA) provided energetic validation. Results Unloading trajectories differed among disease states despite baseline normalization. Integrated response magnitudes were similar across the three disease models (RI: 1.33, 1.37, and 1.35 for AMI, DCM, and DCM + MR, respectively), whereas interior Qpeak differed at 3.40, 2.90, and 2.70 L/min. DCM + MR showed a renewed response increase at high flow, with its overall maximum occurring at the 5.0‐L/min boundary. PVA‐based analysis preserved the higher‐flow response peak in AMI (3.60 vs. 3.10 and 2.90 L/min in DCM and DCM + MR). Conclusions The underlying disease substrate influenced the distribution of ventricular unloading across the Impella‐flow range despite similar integrated response magnitudes. The 3D‐PVL framework provides quantitative descriptors of disease‐specific unloading trajectories rather than clinically validated therapeutic targets.