Introduction

Heart failure incidence is increasing, now reaching “epidemic” proportions (1). Heart failure with preserved ejection fraction (HFpEF) accounts for half of incident heart failure cases (2), disproportionately affects women (3), portends a 30% one year mortality rate (4), and is responsible for an estimated $18 billion in overall medical costs per year (5). HFpEF has been called “one of the greatest unmet needs in Cardiology” (1). Despite over twelve, large, randomized treatment trials of HFpEF, none have shown a survival benefit (6). Currently, the diagnostic reference standard is hemodynamic catheterization, which detects increased left-ventricular (LV) filling pressure. However, catheterization is invasive and cannot be widely applied for HFpEF diagnosis. One hypothesis is that elevated pressures are due to increased stiffness of the myocardium in patients with HFpEF. Recently, a high-frequency cardiac MR elastography (MRE) technique was developed that is capable of measuring myocardial stiffness noninvasively (7,8). The objective of this abstract was to evaluate if cardiac MRE can detect increased myocardial stiffness in patients with HFpEF.

Methods

Fifty-eight volunteers and 10 patients with HFpEF were enrolled in this study, after IRB approval and obtaining formal written consent. One volunteer and 5 patients were excluded from the study due to poor image quality as determined by a quantitative octahedral shear strain signal-to-noise ratio metric (9). All subjects were imaged feet first in the supine position in a 1.5-Tesla, wide-bore, MR imager (Optima MR450W; GE Healthcare, WI, USA). Cardiac MRE was used to measure myocardial stiffness in the left ventricle of each subject. The experimental setup is shown in Figure 1. A flow-compensated, cardiac-gated, spin-echo, single-shot, echo-planar imaging, MRE sequence was used with 140-Hz vibrations and a TR matched to each subject’s heart rate with ECG gating. Other imaging parameters included TE = 69ms; FOV = 32 cm; 64x64 acquisition matrix; parallel imaging acceleration factor = 2; 5 contiguous 5-mm-thick axial slices; 2 motion-encoding gradient (MEG) pairs on each side of the refocusing pulse matched to the vibration frequency; alternating x, y, z, and 0 MEG directions; and 4 phase offsets spaced evenly over one vibration period. For image processing purposes, the image matrix was reformatted to 256x256x20 to give an isotropic voxel size of 1.25 mm. Images were acquired at the minimum delay possible in the cardiac cycle (~100 ms) after the R-wave ECG trigger. A 3D local-frequency estimation algorithm was used to calculate the stiffness, which we defined to be the tissue density (assumed to be 1 g/cm3) times the square of the shear wave speed (i.e., shear wavelength times the motion frequency). Statistical analysis was done using a Mann-Whitney U test of significance using a commercial software package (OriginPro 2015, OriginLab Corporation, Northampton, MA) (10). A p-value of less than 0.05 was considered statistically significant.

Results

The left-ventricle myocardial stiffness of the 5 HFpEF patients (mean stiffness: 10.5 ± 1.7 kPa; age (years): mean = 62.4, range = 54-74, median = 65) was significantly higher (p = 0.002) than the 57 normal control subjects (mean stiffness: 8.0 ± 1.2 kPa; age (years): mean = 33.5, range: 18-87, median = 27), as shown in Figure 2. A typical short-axis, left-ventricle, stiffness map from a healthy volunteer and a patient with HFpEF are shown in Figure 3. The images show the global change in myocardial stiffness that occurs in these patients.

Conclusions

This study demonstrates the feasibility of 3D, high-frequency, cardiac MRE as a contrast-agent-free diagnostic imaging technique for quantitatively measuring myocardial stiffness in patients with heart failure with preserved ejection fraction. The positive outcomes of this study motivate further investigation into the use of cardiac MRE as a quantitative, noninvasive, and exogenous contrast-free imaging technique to assist in the diagnosis and therapy monitoring of patients with HFpEF.

Acknowledgements

This study was supported by National Institutes of Health (NIH) grants 5R01HL115144 and EB001981 and the American Heart Association - Midwest Affiliate. (16POST29900011).

References

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