Heart failure with preserved ejection fraction (HFpEF, EF≥45%) is of growing concern in the US as its prevalence has increased from 38% to 54% over the past 15 years [1]. Although the importance of HFpEF is well-recognized, its complex pathophysiology is poorly understood and a universally standardized diagnostic metric for HFpEF does not exist [2]. It is well known that HFpEF is caused primarily by increase in left ventricular (LV) myocardial stiffness (MS) that results in impaired LV relaxation [3]. Therefore, quantifying LV MS may assist in the diagnosis, treatment planning, and monitoring of HFpEF patients. Currently, passive LV MS can be measured using LV catheter-based pressure-volume loops [4]; however, catheterization is an invasive procedure, provides only a global measurement and does not estimate true intrinsic mechanical properties of the myocardium [5]. Therefore, there is a need for an alternative non-invasive technique to temporally and spatially estimate MS. Recently, with the advent of cardiac magnetic resonance elastography (cMRE), quantification of MS both temporally and spatially has become feasible [6-8]. This study exploits cMRE in a well-established HFpEF porcine model [9] to: 1) estimate LV MS temporally and over a 2 month period; 2) validate LV MS measurements against LV pressure measurements obtained from ventricular catheterization; and 3) compare alteration in LV MS measurements to changes in LV thickness, LV circumferential strain measurements and MRI relaxometry parameters (T2, T1, extra-cellular volume (ECV)) with disease progression.Renal wrapping surgery (a hypertension model) was performed to induce HFpEF in 8 pigs. LV catheterization (to measure mean LV pressure) and MRI (1.5-Tesla Avanto, Siemens Healthcare, Erlangen, Germany) was performed pre-surgery at baseline (Bx), and then post-surgery at month 1 (M1) and month 2 (M2). An in-house retrospective pulse-gated, segmented multi-phase GRE-based cMRE sequence was used to obtain short-axis slices covering the entire LV [6]. Imaging parameters for cMRE included: TE/TR=9.71/12.5 ms; field of view=384x384 mm2; imaging matrix=128x128; slice thickness=8mm; flip angle=15◦; cardiac phases=8; GRAPPA acceleration factor =2; excitation frequency=80Hz; phase offsets=4; and 160Hz motion encoding gradients were applied separately in all three directions to encode the in plane and through plane external motion. Other MR imaging (tagging, relaxometry parameter mapping) was performed using regular product sequences with imaging parameters similar to that used in the clinical imaging. cMRE wave images (Figure 1) were processed using custom built software (MRE-Lab, Mayo Clinic, Rochester, MN). Directional (8 directions) and band-pass filtering were performed to remove reflected and longitudinal waves respectively. A 3D local frequency estimation inversion [2] was then implemented to measure the 3D LV MS from all the slices. Regions with poor wave propagation were excluded from the final stiffness measurements. LV thickness was estimated from the center slice of the cMRE magnitude image. Circumferential Eulerian strain was estimated from the tagging images using the commercial software HARP (Diagnosoft, Palo Alto, California). T2, T1, and ECV fraction were calculated from the mid-ventricular region of the relaxometry maps. Statistical analysis was performed using SAS 9.4 software (SAS, Inc; Cary, NC). Longitudinal measures of end-diastolic (ED) and end-systolic (ES) LV MS were analyzed by mixed effect models. Correlations between both ED and ES LV MS and i) mean LV pressure, ii) LV thickness, iii) circumferential strain, iv) T2, T1, and ECV were assessed using Spearman’s correlation method.From Bx to M2, mean LV pressure, cMRE-derived ED and ES LV MS, and ED and ES LV thickness increased while circumferential strain decreased significantly (slope test, p≤0.05). MRI relaxometry parameters did not demonstrate any significant trend. Figure 2 shows variation in LV MS across the cardiac cycle, demonstrating an increase in LV MS with disease progression. Figure 3 shows variation in LV thickness across the cardiac cycle. The increase in LV thickness observed from the figure indicates that the animals developed LV hypertrophy over time. Figure 4 demonstrates that both mean LV pressure and LV thickness had good correlation with ED and ES cMRE-derived LV MS, indicating that LV hypertrophy secondary to hypertension caused increase in MS. Circumferential LV strain indicated a decrease only at M2 and showed a moderate negative correlation when compared to cMRE-derived MS (Figure 5). MRI relaxometry parameters did not demonstrate any significant change with disease progression and none of the parameters (T2, T1, and ECV measurements) showed any correlation with cMRE-derived MS.This study demonstrates that in an HFpEF model causing LV hypertrophy, cMRE-derived MS increases with increase in LV pressure and thickness. Therefore, cMRE has the potential to be used as a diagnostic tool to assess HFpEF inducing disease conditions.