Jacob Macdonald1, Omid Forouzan2, Naomi Chesler2, Christopher Francois3, and Oliver Wieben1,3
1Medical Physics, University of Wisconsin - Madison, Madison, WI, United States, 2Biomedical Engineering, University of Wisconsin - Madison, Madison, WI, United States, 3Radiology, University of Wisconsin - Madison, Madison, WI, United States
Synopsis
Cardiopulmonary exercise testing is gaining increased
recognition as a useful tool for assessing pulmonary hypertension (PH). Using
an MRI-compatible exercise device that allows subjects to exercise in the bore
of the magnet, we investigated the effects of exercise stress on blood flow in
the ascending aorta in healthy controls and patients with PH. The measurements
we obtained demonstrated a decreased exercise capacity in PH subjects and in
older controls. Some parameters, such as cardiac output, demonstrated
statistically significant changes between rest and stress, while others were
unclear due to the relatively low exercise power tolerated by the PH patients.Purpose
Cardiopulmonary exercise testing is gaining increased
recognition as a useful tool for assessing pulmonary hypertension (PH)
1.
The increased pulmonary artery pressure associated with the disease can shift
the ventricular septum, resulting in decreased left ventricular (LV) filling
and aortic flow. This response becomes more pronounced when stressed through
exercise. Due to its increased accuracy in measuring cardiopulmonary function,
MRI is preferred to echocardiography for assessing such physiologic responses.
Traditionally, however, MRI relies on pharmacologically induced stress due to
inherent constraints within the MRI bore. Previously we demonstrated the use of
MRI-compatible exercise equipment
2 to assess aortic flow and LV
function in healthy subjects
3,4. In this study, we aim to determine
if changes to aortic flow caused by PH are detectable using MRI following
exercise stress.
Methods
Three subject cohorts were imaged: 20 young, healthy
controls (26±4 years,8M,12F), 8 older, age-matched controls (58±10 years,1M,7F),
and 6 PH patients (60±9 years,1M,5F). Imaging was performed on a clinical 1.5 T
system (HDx/Discovery 450w, GE Healthcare, Waukesha, WI). A custom-built MRI-compatible
stepping device was used which allowed subjects to exercise in a supine
position in the scanner bore (Figure 1). Figure 2 shows the exercise/scanning
protocol for each cohort. A low power of 30W was targeted for the PH patients
whose exercise capacity can be greatly compromised. The control groups
exercised at slightly higher powers to induce measurable responses. Each
exercise stage was followed immediately by an ECG-gated 2D cine PC acquisition
(TR/TE=6.1/3.7ms; FA=30
o; ASSET=2; VENC=200cm/s; resolution=256x256)
with 20 cardiac phases in the ascending aorta across a 15s breath hold. Changes
in heart rate, stroke volume, cardiac output, peak systolic velocity and flow,
relative aorta area change, and pulse wave velocity (using the QA method
5)
were analyzed with CV Flow (Version 3.3, Medis, Leiden, Netherlands) and MATLAB
(Mathworks,Natick,NJ). A paired t-test and 1-way ANOVA with Tukey’s HSD test were
used to determine the statistical significance (p<0.05) of intra-group and
inter-group changes respectively between exercise and baseline. To reduce the
effect of varying exercise power between subjects, the exercise stage measuring
closest to 30 W was analyzed for each subject.
Results
The average exercise powers were 36±8 W, 33±6 W, and 30±9 W
with an average increase in heart rate of 35%, 39%, and 65% (Figure 3) for the
young controls, older controls, and PH subjects respectively, all of which were
statistically significant. Figure 4 displays boxplots comparing the results for
each group for the remaining parameters investigated. A bracket between two
boxplots indicates the two groups have a statistically significant difference.
Discussion
The increase in heart rate was much higher for the PH
subjects than the control groups, indicating a higher stress level for this
modest exercise. The results for stroke volume and cardiac output indicated
that younger, healthy subjects showed a greater ability to increase blood
supply in response to exercise stress. For many of the parameters measured at
stress the older controls and PH groups showed a wider range of values than the
younger controls. We hypothesize this is due to a greater perceived difficulty
for each exercise challenge to these groups, resulting in higher respiratory
and cardiac motion compromising image quality, making ROI measurements more
difficult. Differing degrees of PH and age-related loss of CV function could
also be responsible for the spread found in these subjects. Many of the
parameters investigated did not show strong intra-group statistical
significance between rest and stress. This may be a result of low statistical
power from the small sample size for the PH subjects, and work-rates that were
too low to elicit a strong cardiopulmonary response, as evidenced by the lower
heart rates, in the healthy controls. Future studies may benefit from
standardizing comparisons based on heart rate instead of exercise power. The
implementation of improved motion-correction and real-time imaging would also
allow for more accurate measurements, possibly allowing us to detect more
subtle hemodynamic changes brought on by exercise.
Conclusion
This study demonstrates the use of MRI to measure the effect
of modest exercise stress on aortic flow in both healthy controls and patients
with pulmonary hypertension. The PH patients showed a good response to the
exercise challenge (an average 65% increase in heart rate), yet their response
was heterogeneous for measures of cardiac output and stroke volume, likely
reflecting different stages of loss of CV function. The response to the exercise challenge was
less pronounced for the control groups due to the low exercise power. Future
studies comparing larger cohorts of subjects based off of heart-rate instead of
work-rate may provide comparisons with more statistical power.
Acknowledgements
We gratefully acknowledge funding by NIH grant R01HL105598
and GE Healthcare for their research support.References
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exercise testing in patients with pulmonary arterial hypertension: An
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Cardiac Stress Tests. Journal of Medical Devices. 2014;8(4).
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Journal of Cardiovascular Magnetic Resonance. 2015; 17(Suppl 1): M2.
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