Do we really need to look at volumetric measurements with 99mTc single photon emission computed tomography (SPECT) myocardial perfusion imaging?
Do we really need to look at volumetric 99m measurements with Tc single photon emission computed tomography (SPECT) myocardial perfusion imaging?
Dominik C. Benz 0 1
Andreas A. Giannopoulos 0
0 See related article, https://doi.org/10.1007/s12350-018-1253-4. Reprint requests: Andreas A. Giannopoulos, MD, Cardiac Imaging, Department of Nuclear Medicine, University Hospital Zurich , Raemistrasse 100, 8091 Zurich , Switzerland
1 Cardiac Imaging, Department of Nuclear Medicine, University Hospital Zurich , Switzerland
A little less than a century ago, in their classical
work, Tennant and Wiggers1 observed in open-chest
dogs that within 60 seconds of coronary occlusion
myocardial contractions in the ischemic zone change
from active shortening to passive systolic lengthening.
After restoration of myocardial blood flow, contractile
dysfunction was reversed. In later animal work,
Heyndrickx and colleagues2 demonstrated that while regional
electrocardiograms normalize within seconds,
contractile dysfunction lasts for up to 2 hours after a 5-minute
occlusion and for up to 24 hours after a 15-minute
occlusion. The functional effects in the ischemic
myocardium were shown to persist longer than one could
have been predicted by the rapid normalization of
coronary flow. The concept of myocardial stunning was
born—and defined as a state of prolonged contractile
dysfunction of post-ischemic myocardium in which
myocardial function is gradually restored over time.
Post-ischemic stunning can be quantified on single
photon emission computed tomography (SPECT)—
myocardial perfusion imaging (MPI) from regional
wall motion abnormalities or more globally as a
reduction in left ventricular ejection fraction (LVEF).
Another marker for myocardial stunning is the increase
in LV volumes after stress, namely transient ischemic
dilatation (TID) that is considered indicative of severe
and extensive coronary artery disease and a poor
prognostic sign.3,4 These parameters have been
investigated by a staggering number of studies and their
added diagnostic and prognostic value is undisputed.5–8
Reliable assessment and quantification of myocardial
stunning by SPECT-MPI pose however a series of
challenges on the applied imaging protocols. First, the
timing of the image acquisition is key. The time
elapsed between stress testing and image acquisition
determines the severity of post-stress LVEF decrease.9
Further, if the delay between stress and rest image
acquisition is too short to allow for recovery of
myocardial contractility, the post-stress EF decrease
may be underestimated.10 Second, the type of stress
agent may influence the severity of stress. Although the
initial investigations on TID were performed by
physical stress,4 more recent studies have confirmed these
results by vasodilator stress.7 Last but not least,
measurement of LVEF and LV volumes might be limited
by SPECT-MPI given its spatial resolution. The
pathophysiological mechanism of these phenomena is
also a highly debated subject. Some authors see it as
true increase in LV volume due to post-ischemic
stunning and offer several potential mechanisms for the
increased contractility (i.e., enhanced venous return via
Frank-Starling, increased myocardial blood flow via
Gregg mechanism and/or by higher heart rate).11,12
Others explain it by a stress-induced subendocardial
hypoperfusion giving the visual impression of
dilatation on ungated SPECT.13,14 Nonetheless, the severity
of post-ischemic stunning differs between the different
stress agents: it seems that myocardial dysfunction
persists much longer after dobutamine than after
adenosine stress.12,15,16 All these challenges may affect
the accurate and reliable estimation of myocardial
stunning and could result not only in high inter- and
intra-patient variability but also between different
SPECT scanners and image acquisition protocols.
In the current issue of the Journal of Nuclear
Cardiology, Camm et al.17 address some of these
challenges in a large retrospective study. The variation in
TID and LVEF decrease from rest to stress was analyzed
in a—rather normal—population including 661 gated
and 992 ungated patient studies without inducible
perfusion defects. Mean LVEF in gated SPECT images
decreased slightly but significantly from rest (62.4%) to
post-stress images (61.2%) resulting in a mean LVEF
difference of 1.2% (standard deviation of 5.2%). The
mean TID ratio was 1.00 with an overall upper 95%
confidence limit of 1.23. With lower volumes on
ungated rest images, the upper 95% confidence limit rose to
1.37. The authors, therefore, concluded that a fall in
LVEF of more than 11.6% (= 1.2% ? 2 9 5.2%) and
TID ratio of more than 1.23 is required for clinically
relevant myocardial stunning.
The authors should be commended for elaborating
on the normal limits of variation in LV volumes and EF
in a large patient population. However, the
generalizability of their results is limited due to the single-center
design (with a two-headed SPECT camera and one-day
stress-rest 99mTc-tetrofosmin acquisition protocol) and
due to the fact that about 30% of the initial patient
population was excluded from the analysis. Another
factor that confines the application of their results is the
fact that patients were stressed by exercise (56%) or by
regadenoson (42%). From a pathophysiological view, it
would have been of great interest whether these groups
differed with regard to LVEF decrease and TID ratio.
Without this subgroup analysis, the different stressors
rather appear to be a limitation than an advantage of this
study. The authors’ results highlight the enormous
variability of these parameters in apparently normal
SPECT-MPI studies. A strength of the study is the aim
to focus on patients without inducible perfusion defects.
Nonetheless, the authors included patients with fixed
perfusion defects and with balanced ischemia in their
analysis, something that could potentially explain the
large variability of their data. Besides this debatable
diagnostic reference standard, the study lacks information
on the outcome of these patients.
It is unclear whether it is safe to defer a patient with
an LVEF decrease from rest to stress of 9% and a TID of
1.15. Previous outcome studies have demonstrated that a
decrease in LVEF of more than 10% in patients without
inducible perfusion defects increases the risk for future
cardiac events.8,18 Hence, the threshold of 11.6% in the
present study reflects previous results relatively well and
adds valuable real-world data on volumetric
measurements like LVEF decrease in gated or TID in ungated
Gauging the clinical implications of these results,
the low sensitivity of TID deserves particular mention.
In view of the dramatic decrease in prevalence of
pathological SPECT-MPI scans,19 the issue of the
clinical value of markers for myocardial stunning like TID
should come into discussion. With non-invasive
assessment of coronary artery disease shifting towards
lower-risk patients, our tools need to have appropriate
sensitivity to be useful in clinical routine. In this new era
of non-invasive cardiovascular imaging, one could
suggest that such highly specific markers might
gradually lose significance—until the day that a SPECT-MPI
study pops up without inducible perfusion defect but a
fall in LVEF of 15% and a TID of 1.3. This patient with
severe three-vessel disease and balanced ischemia will
be grateful that you looked at the volumetric
measurements of his test.
The University Hospital Zurich holds a research contract
with GE Healthcare. Dr. Benz reports a research grant from
Theodor und Ida Herzog-Egli—Foundation, outside the
submitted work. Dr. Giannopoulos reports no conflict of interests
pertinent to this work.
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