Shivaram Poigai Arunachalam1, Arvin Arani1, Dawn M Pedrotty2, Alan M Sugrue2, Suganti Shivaram1, Phillip J Rossman1, Joshua D Trzasko1, Kevin J Glaser1, Yi Sui1, Armando Manduca3, Kiaran P McGee1, Richard L Ehman1, Barry A Borlaug2, and Philip A Araoz1
1Radiology, Mayo Clinic, Rochester, MN, United States, 2Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States, 3Biomedical Engineering and Physiology, Mayo Clinic, Rochester, MN, United States
Synopsis
Heart
failure with preserved ejection fraction (HFpEF) is an increasingly common
clinical syndrome with diagnostic challenges and no effective treatment which
is characterized by increased cardiac filling pressures resulting in increased
myocardial stiffness. The purpose of this study was to assess changes in
myocardial stiffness after pericardiectomy in a pig model of HFpEF, and to demonstrate
the feasibility of Cardiac MR Elastography (CMRE) as a noninvasive tool to
monitor treatment in HFpEF. Results show
a significant decrease in myocardial stiffness aster pericardiectomy implying
the potential of CMRE for treatment design, planning and monitoring for HFpEF
in humans
Introduction
Heart failure with preserved ejection fraction (HFpEF)
is an increasingly common clinical syndrome with diagnostic challenges and no
effective treatment (1). HFpEF is also characterized by increased cardiac
filling pressures that cause dyspnea (2-5). Pericardiectomy can relieve
external restraint on the myocardium which may decrease filling pressures in
HFpEF. Cardiac MR elastography (CMRE) allows noninvasive in vivo measurement of the global effective myocardial stiffness,
which is determined by filling pressures and the biomechanical properties of
the myocardium (6-8). The purpose of this study was to assess changes
in myocardial stiffness after pericardiectomy in a pig model of HFpEF and to demonstrate
the feasibility of CMRE as a noninvasive tool to monitor treatment in HFpEF. Methods
HFpEF was induced in four pigs by renal artery coiling and feeding with
a high-fat diet (2% cholesterol, 15% lard) for 2 weeks. CMRE imaging was
performed prior to pericardiectomy (designated as Day 0) as follows. A
custom-made, passive, MRE driver was placed on the chest of
each pig. The pigs were imaged in the prone position to maximize shear-wave
penetration into the heart (Figure 1).
Imaging was conducted on a 1.5-Tesla, whole-body, MR imager (Signa
Excite HDxt; GE Healthcare) with a 4-channel coil using an ECG-gated, spin-echo echo-planar imaging
(SE-EPI) MRE sequence and 140-Hz vibrations.
Acquisitions were performed with 4 breath holds of approximately 25
seconds each, depending on the heart rate.
Systolic acquisitions were performed with a minimum delay from the
R-wave trigger. Diastolic, short-axis acquisitions were performed using time
delays that corresponded to the first 3 phases of early diastole observed from
a FIESTA cine scan. The following MRE acquisition parameters were used: 1 shot,
NEX = 1; TR/TE = 4600/52 ms; FOV = 28.8 cm; 96x96 acquisition matrix; 11 3-mm-thick
slices with 0-mm spacing located mid-ventricle; 2 motion-encoding gradient
(MEG) pairs; x, y, and z motion-encoding directions; ASSET= 2, and 4 phase offsets spaced evenly
over one vibration period.
The pigs then underwent a closed-chest, percutaneous,
pericardiectomy procedure. Follow-up CMRE imaging was performed after 7 and 30
days post-pericardiectomy to assess the effective myocardial stiffness. The left ventricle
(LV) was segmented using a commercially available clinical software package (Cir
42, Cardiovascular
Imaging, Calgary, Alberta). The MRE effective stiffness was obtained by applying the curl operator
to the 3D displacement field and performing a 3D local-frequency estimation
(LFE). The total effective myocardial stiffness was reported as the mean stiffness
within the LV myocardium. A statistical software package (OriginPro 2016, OriginLab
Corporation, Northampton, MA) was used for the statistical analysis and
plotting. The Wilcoxon
signed-rank test for
significance was used in this study by considering a p-value of less than 0.05
as statistically significant. Results & Discussion
The mean value of the total myocardial effective stiffness during
systole decreased from 4.98 kPa on Day 0 to 4.15 kPa on Day 7 post-pericardiectomy
(p<0.05) (Figure 2) . Figure 3 shows MRE images during systole from a pig on Day 0 (pre-pericardiectomy)
(top) and on Day 7 post-pericardiectomy (bottom). The mean stiffness during diastole
decreased from 4.22 kPa on Day 0 to 3.74 kPa on Day 7 post-pericardiectomy (p<0.05)
(Figure 4). Figure 5 shows MRE images during diastole from the same pig on Day 0 (pre-pericardiectomy)
(top) and on Day 7 post-pericardiectomy (bottom). There were no significant
changes in the stiffness between Day 7 and Day 30 in either systole or diastole.
The results suggest that changes in
total myocardial effective stiffness post-pericardiectomy can be tracked by
MRE. Because the intrinsic myocardial properties would not be expected to
change this rapidly, these data indicate that ~20% of the total myocardial
effective stiffness is related to the restraining effects of the intact
pericardium, which contribute to the elevation in filling pressures in HFpEF. Conclusions
This study is the first application of CMRE to
monitor pericardiectomy treatment for HFpEF and shows that 3D, high-frequency,
CMRE may be able to track the changes of the total myocardial effective stiffness
post-pericardiectomy, which would be beneficial for treatment design, planning
and monitoring for HFpEF in humans. Acknowledgements
This
work was supported by National Institutes of Health (NIH) grants 5R01HL115144
and EB001981 and Mayo Clinic
Department of Radiology internal funding.References
1. Zile MR, Baicu CF, Gaasch WH. Diastolic heart failure--abnormalities in
active relaxation and passive stiffness of the left ventricle. The New England
journal of medicine 2004;350(19):1953-1959.
2. Go,
A.S., et al., Executive summary: heart disease and stroke statistics--2014
update: a report from the American Heart Association. Circulation, 2014.
129(3): p. 399-410.
3. Ferrari, R., et al., Heart failure with preserved ejection fraction:
uncertainties and dilemmas. Eur J Heart Fail, 2015. 17(7): p. 665-71.
4. Braunwald, E., Heart failure. JACC Heart
Fail, 2013. 1(1): p. 1-20.
5. Paulus, W.J., et al., How to diagnose diastolic heart failure: a
consensus statement on the diagnosis of heart failure with normal left
ventricular ejection fraction by the Heart Failure and Echocardiography
Associations of the European Society of Cardiology. Eur Heart J, 2007.
6. Muthupillai, R., Lomas, D.J., Rossman, P.J. and Greenleaf, J.F., 1995.
Magnetic resonance elastography by direct visualization of propagating acoustic
strain waves. Science, 269(5232), p.1854.
7. Arunachalam
SP, Rossman PJ, Arani A, Lake DS, Glaser KJ, Trzasko JD, Manduca A, McGee KP,
Ehman RL, Araoz PA. Quantitative 3D magnetic resonance elastography: Comparison
with dynamic mechanical analysis. Magnetic resonance in medicine : official
journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic
Resonance in Medicine 2016.
8. Arani
A, Glaser KL, Arunachalam SP, Rossman PJ, Lake DS, Trzasko JD, Manduca A, McGee
KP, Ehman RL, Araoz PA. In vivo, high-frequency three-dimensional cardiac MR
elastography: Feasibility in normal volunteers. Magnetic resonance in medicine
: official journal of the Society of Magnetic Resonance in Medicine / Society
of Magnetic Resonance in Medicine 2016.