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Online Appendix Rommel et al., T1 Mapping for Quantification of LV Stiffness
METHODS
CMR protocol
CMR was performed immediately before invasive catheterization. All scans were performed on an Intera 1.5-T
scanner (Koninklijke Philips N.V., Amsterdam, the Netherlands). Electrocardiographic tracing and triggering
were performed with the system’s built-in patient monitoring unit. Initially, contiguous short-axis steady-state
free precession sequences (SSFP) were obtained in 2- and 4-chamber views as well as a short-axis cine stack
(repetition time/echo time 3.8/1.6 ms, 30 phases, 10 mm slice thickness) extending from the mitral valve annulus
to the LV apex.
A modified Look-Locker inversion recovery (MOLLI) sequence (repetition time/echo time: 2.5/1.03 ms) with
SSFP readout performed before and 15 minutes after administration of 0.15 mmol/kg body weight of gadobutrol
in short-axis orientation, extending from the mitral valve annulus to the LV apex, and in 4- and 2-chamber views
as described previously (1). Late-gadolinium enhancement (LGE) was evaluated 15 min after gadubotrol
administration using a 2-dimensionalinversion recovery gradient echo sequence.
Regional fibrosis was identified by LGE within the myocardium, defined quantitatively by a myocardial postcontrast signal intensity 6 SDs above that within a reference region of remote myocardium within the same slice.
Evaluation of volumes, LGE, and T1 mapping data post-processing was performed offline on a remote
workstation using dedicated software (cmr42, Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada).
Pre- and post-contrast pixel-based T1 maps were created from MOLLI data sets in all short-axis slices. Basally,
analysis included the first segment capturing LV myocardium only throughout the cardiac cycle to ensure
exclusion of left atrial tissue. Apically, analysis included the last slide still allowing for clear delineation between
myocardium and cavity. LV endocardial and epicardial borders were semi-automatically delineated on respective
T1 maps and manually adjusted to exclude artifacts or regions of focal LGE. T1 values were corrected for heart
rate, following the equation corrected T1 = T1•(2.7 •[heart rate - 70]), and averaged over slices on pre- and
post-contrast T1 maps (1). Blood pool evaluation was based on a manually-placed region of interest within the
center of the ventricular cavity on each slice. Calculation of ECV was based on the combination of pre- and post-
contrast T1 mapping data according to the approach proposed by Arheden et al (2) using the formula: ECV =
(∆R1myocardium/∆R1blood) • (1-hematocrit), where R1 = 1/T1 time.
Cardiac catheterization protocol
Standard invasive coronary angiography was performed via right femoral artery access to exclude significant
coronary artery disease; patients were excluded if they had an indication for the treatment of epicardial stenosis.
A 7-F Conductance catheter (CD Leycom, Zoetermeer, Netherlands) was then advanced via the right femoral
artery into the left ventricle under fluoroscopy and connected to a pressure volume (PV) signal processor (Inca,
CD Leycom). Real-time continuous LV pressure and volume signals were recorded for 10 s at baseline, with
volume calibration performed using LV volumetric data from the preceding CMR scan. For reduction of preload,
transient occlusion of the inferior vena cava was achieved by inflation of an Amplatzer sizing balloon (St. Jude
Medical, Saint Paul, Minnesota). On average, 12 PV loops were acquired during balloon inflation and deflation.
The end-systolic elastance (Ees) was determined as the linear slope through the end-systolic pressure-volume
relations (ESPVR) and the load-independent LV stiffness constant (Beta) was extrapolated from the EDPVR
using the formula EDP = C•eBeta•EDV, where EDP is LV end-diastolic pressure (LVEDP), C is a fitting
constant, and EDV is LV end-diastolic volume (3). Loops were analyzed from the last heartbeat before the onset
of volume/pressure decline for a minimum of 5 beats without an increase in heart rate. Curve-fitting was
performed using Microsoft Excel (Version 14.0).
To increase afterload, patients were asked to perform handgrip exercise for 1 min, and PV data were acquired at
baseline and throughout peak exercise. The time constant of active relaxation, or tau, was calculated after the
method of Mirsky (4), which evaluates the time needed for LV pressure to fall to one-half of its value from peak
rate of LV pressure fall (dP/dtmin). Arterial elastance (Ea) was calculated as end-systolic pressure/stroke
volume, whereas ventricular arterial coupling was assessed by the formula of end-systolic volume/stroke
volume.
RESULTS
Reproducibility of PV-Loop Measurements
ONLINE APPENDIX FIGURE LEGEND
Figure 1: Bland-Altman-Plots for Pressure-Volume-Analysis
Bland-Altman-Plots with mean difference of measurements and limits of agreement for A: Endsystolic Pressure
Volume Relationship (ESPVR); B: Enddiastolic Pressure Volume Relationship (EDPVR); C: Left Ventricular
Elastance (Ees); D: Arterial Elastance (Ea); E: Left Ventricular Stiffness Constant (Beta); F: Time Constant of
Active LV Relaxation (Tau)
ONLINE APPENDIX REFERENCES
1) Messroghli DR, Plein S, Higgins DM, et al. Human myocardium: single-breath-hold MR T1
mappingwith high spatial resolution—reproducibility study. Radiology 2006;238:1004–12.
2) Arheden H, Saeed M, Higgins CB, et al. Measurement of the distribution volume of
gadopentetate dimeglumine at echo-planar MR imaging to quantify myocardial infarction:
comparison with 99mTc-DTPA autoradiography in rats. Radiology 1999;211:698–708.
3) Burkhoff D, Mirsky I, Suga H. Assessment of systolic and diastolic ventricular properties via
pressure-volume analysis: a guide for clinical, translational, and basic researchers. Am J
Physiol Heart Circ Physiol 2005;289:H501–12.
4) Mirsky I. Assessment of diastolic function: suggested methods and future considerations.
Circulation 1984;69:836–41.