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• W4378675304 abstract "Objective: Left ventricular (LV) stiffening is a key pathophysiological component of heart failure with preserved ejection fraction (HFpEF) and contributes to pulmonary congestion and exertional dyspnea. Accurate assessment of LV stiffness is commonly accomplished via construction of end-diastolic pressure-volume relationships (EDPVRs) during transient reductions in venous return (i.e., preload). However, the extent to which this method accurately predicts the rise in LV pressure in response to an increase in preload is unknown. Accordingly, we sought to assess the predictive accuracy of preload reduction-derived EDPVRs in a porcine model of repetitive pressure overload (RPO)-induced HFpEF. Methods: Swine (n=8) were subjected to 2-weeks of RPO via daily administration of phenylephrine (PE; 400 ug/min; 1 hour/day) through an indwelling jugular vein catheter. This model has previously been shown to produce a HFpEF-like cardiac phenotype characterized by a persistent hypertrophy-independent reduction in LV diastolic compliance. Admittance catheter-based PV analysis (Transonic, ADV500) was subsequently performed at rest and during transient preload reduction to construct the LV EDPVR. The predicted change in LV end-diastolic pressure (EDP) for a given change in LV end-diastolic volume (EDV) was compared to the actual change in LVEDP measured in response to an acute PE-mediated increase in preload. Results were compared to those from a series of size-matched control animals (n=8) that underwent the same physiological study protocol. Results: Construction of the EDPVR via transient preload reduction revealed an increase in the LV diastolic stiffness coefficient (ß) from 0.016±.003 in normal control animals to 0.047±.008 after RPO (p<0.01). As a result, the predicted increase in LVEDP for a 20% increase in LVEDV was significantly greater in RPO animals (22.0±4.3 mmHg) than normal controls (8.5±1.3 mmHg; p<0.01). However, administration of PE demonstrated that this was a significant underestimation, as the actual change in LVEDP in response to an increase in preload was nearly 2-fold higher in each group (RPO: 38.1±7.3 mmHg; Control: 15.3±2.2 mmHg; both p<0.05 vs. predicted change in LVEDP). As a result, LV diastolic stiffness (ΔLVEDP/ΔLVEDV) was significantly higher when measured in response to an increase in preload (RPO: 1.78±0.31 mmHg/mL; Control: 0.59±0.09 mmHg/mL) than when extrapolated from EDPVRs derived from the hemodynamic response to preload reduction (RPO: 1.08±0.23 mmHg/mL; Control: 0.33±0.05 mmHg/mL; both p<0.05). Conclusions: Traditional approaches to determine the LV EDPVR underestimate the actual rise in LVEDP for a given rise in LVEDV. These findings highlight challenges in quantifying myocardial stiffness and reinforce the importance of assessing the hemodynamic response to increased preload directly, rather than extrapolating from EDPVRs created via transient preload reduction. The National Heart Lung and Blood Institute, the National Center for Advancing Translational Sciences, and the Department of Veterans Affairs. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process." @default.
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• W4378675304 date "2023-05-01" @default.
• W4378675304 modified "2023-09-27" @default.
• W4378675304 title "Predictive Accuracy of Traditional Methods to Assess Left Ventricular Stiffness in a Porcine Model of Heart Failure with Preserved Ejection Fraction" @default.
• W4378675304 doi "https://doi.org/10.1152/physiol.2023.38.s1.5791639" @default.
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