Abstract Body: Objective: Myocardial stiffness is a primary determinant of left ventricular (LV) diastolic function and can be quantitatively described by the end-diastolic pressure-volume relationship (EDPVR). The EDPVR is traditionally derived by measuring LV end-diastolic pressure (EDP) and volume (EDV) during transient reductions in venous return (preload). However, the accuracy of this approach in predicting changes in LVEDP in response to a rise in LVEDV via rightward extrapolation has not been directly studied. Accordingly, we sought to assess the predictive accuracy of preload reduction-derived EDPVRs in estimating LV diastolic stiffness (ΔLVEDP/ΔLVEDV) in healthy swine.

Methods: LVEDP and LVEDV were measured in swine (n=6) at rest and during transient inferior vena cava (IVC) occlusion (reduced preload), transient aortic occlusion (increased afterload), and intravenous phenylephrine (PE; 0.5 mg/kg/hr; increased afterload and preload). Pressure-volume data collected during IVC occlusion were used to generate the EDPVR, the accuracy of which was determined via comparison to measurements of ΔLVEDP/ΔLVEDV during aortic occlusion and PE.

Results: The LV diastolic stiffness coefficient was greater when derived via aortic occlusion vs. IVC occlusion (0.057±0.013 vs. 0.022±0.004; p=0.03). As a result, IVC occlusion-derived EDPVRs underestimated the rise in LVEDP during aortic occlusion (7.6±2.2 vs. 13.5±2.1 mmHg; p=0.08). Similarly, ΔLVEDP/ΔLVEDV in response to aortic occlusion (0.96±0.28 mmHg/mL) tended to be higher than that predicted from the IVC occlusion-derived EDPVR (0.44±0.09 mmHg/mL; p=0.12). Compared with aortic occlusion, PE elicited a greater rise in LVEDV (31.5±5.4 vs.18.6±4.2 mL; p=0.08) and LVEDP (20.8±1.3 vs. 13.5±2.1 mmHg; p=0.01) but ΔLVEDP/ΔLVEDV was comparable between each condition (0.78±0.16 mmHg/mL vs. 0.96±0.28 mmHg/mL; p=0.60). However, ΔLVEDP/ΔLVEDV derived from PE tended to be higher than that from IVC occlusion (0.78±0.16 mmHg/mL vs. 0.44±0.09 mmHg/mL; p=0.10).

Conclusions: Rightward extrapolation of the EDPVR derived via IVC occlusion underestimates the rise in LVEDP when LVEDV is increased in the normal heart. This was observed with increased afterload as well as when afterload and preload were simultaneously increased via PE. These findings reinforce the importance of assessing the hemodynamic response to increased LV loading directly, rather than extrapolating from EDPVRs created via transient preload reduction.