Future growth and success of nuclear cardiology
Future growth and success of nuclear cardiology
George A. Beller 0
0 Reprint requests: George A. Beller, MD, Division of Cardiovascular Medicine, University of Virginia Health System , Box 800158, Charlottesville, VA 22903 , USA
1 Division of Cardiovascular Medicine, University of Virginia Health System , Charlottesville, VA , USA
About 6 months ago, I reviewed a manuscript, and
subsequently wrote an editorial,1 pertaining to a
retrospective study undertaken by Mayo Clinic investigators,
reporting a marked decline in the annual volume of
SPECT myocardial perfusion imaging (MPI) studies in
patients with known CAD, from 1425 in 2003, to 552 in
2012.2 This report followed a prior publication from the
same group in 2016, indicating that the volume of
SPECT MPI in patients without known CAD had
decreased from 2490 in 2003 to 1033, in 2012.3 In the
more recent report,2 the authors further showed that the
percentage of high-risk SPECT results also diminished
over time, from 47.8% of all studies in years 1991-1995,
to only 8.1% in years 2011-2012. This decrease in
highrisk SPECT imaging results occurred, even though the
prevalence of CAD risk factors, except for smoking, in
the tested population increased over this time period. A
similar observation was made by the Cedars Sinai
group,4 which reported a progressive decrease in
abnormal SPECT MPI studies from 40.9% in 1991 to
8.7% in 2009. The incidence of stress-induced ischemia
fell from 29.6% to 5.0% of imaging studies,
accompanied by a marked decrease in patients
manifesting moderate-to-severe ischemia.
Other studies in the literature confirm the Mayo
Clinic observation of a decrease in volume of SPECT
MPI in the past decade.5,6 Medicare data revealed that
the radionuclide MPI rate per 100 Medicare
beneficiaries rose from 63.4 in 2001, to a high of 88.0 in 2006,
but then significantly declined each year thereafter,
reaching a value of 10.8 in 2013.5 A Kaiser Permanente
database study revealed a 51% decline in the annual rate
of MPI procedures from 200
6 to 2011
.6 Other reports in
the literature also confirm the diminution over time of
abnormal test results.7,8 The average rate of abnormal
stress tests in 4 multicenter studies in which functional
stress testing was compared to coronary computed
tomography angiography (CTA) was only 14.5%.8 The
Prospective Multicenter Imaging Study for Evaluation
of Chest Pain (PROMISE) trial showed that just 12.6%
of patients in the functional testing arm had abnormal
tests.9 The risk of death, nonfatal myocardial infarction,
hospitalization for unstable angina, or major
complications related to diagnostic testing or cardiovascular
procedures after an abnormal functional test was only
3.0% at 25 months of follow-up.9 These data showed
that the prognosis in the population tested was quite
favorable, even after a positive test result. At the
University of Virginia, a total of 3302 SPECT MPI
studies, and 347 gated blood pool scan (MUGA) studies,
were performed in 2006. By 2017, the number of
SPECT MPI and MUGA procedures had decreased to
2021 and 103, respectively. However, this decrease in
SPECT MPI was attenuated by the performance of 365
PET MPI studies in 2017.
The possible explanations for the decrease in
volume in SPECT MPI and fewer high-risk imaging
findings are myriad, and were discussed in the editorial.1
Certainly, the emergence of Appropriate Use Criteria in
2005 had an impact on reducing referrals for SPECT
MPI, particularly in asymptomatic patients, and those
that had undergone uncomplicated revascularization
procedures. Routine functional stress testing after an
uncomplicated acute coronary syndrome, or 3-6 months
after percutaneous coronary intervention (PCI) or
coronary artery bypass surgery (CABG), was deemed to be
not indicated in AUC or practice guidelines. Barriers to
SPECT MPI were erected by insurance companies with
radiology benefits’ managers requiring pre-authorization
for testing. It is possible that more patients presenting
with typical angina were being referred directly to
invasive coronary angiography. Similarly, in recent
years, some patients are referred for CTA rather than
functional stress testing for the noninvasive evaluation
of chest pain. It is likely that more patients with atypical
symptoms and good exercise tolerance are undergoing
exercise stress testing without imaging as the first
diagnostic test. Because of more attention being paid to
the radiation exposure of diagnostic imaging, perhaps,
fewer young adults, particularly women, are being
referred for stress radionuclide imaging for testing.
Fewer high-risk stress MPI results in imaging are
most likely contributed to by better treatment of CAD
risk factors and a decrease in smoking in the population.
Diabetic patients without overt heart disease are being
place on cholesterol-lowering drugs, resulting in fewer
high-risk SPECT MPI findings associated with better
outcomes even after an abnormal scan.10 The overall
observed reduction in the incidence of stress-induced
ischemia parallels the improved prognosis of patients on
optimal medical therapy, including statins and effective
blood pressure control.
For almost 40 years, the field of nuclear cardiology
has been dominated by perfusion imaging. Early in the
development of the field, enthusiasm was expressed for
infarct imaging with Tc-99m-pyrophosphate. This
dissipated with the emergence of biomarker testing for
detection of infarction in its early stages. First pass and
equilibrium gated cardiac blood pool imaging were
nuclear cardiology technologies that yielded accurate
measurement of left ventricular ejection fraction and
assessment of regional wall motion. One of these blood
pool imaging tests was often utilized for monitoring the
potential cardiac complications of cancer chemotherapy.
However, these radionuclide angiographic procedures
have also markedly declined in usage, in favor of
echocardiography and cardiac magnetic resonance
It is clear that thought leaders in the field of nuclear
cardiology, including the leadership of the American
Society of Nuclear Cardiology (ASNC), became
concerned with this declining volume of SPECT MPI, and
the need to provide relevant imaging strategies that
demonstrate their worth in a value-based healthcare
system. In June 2017, the ASNC Board of Directors
convened a meeting with industry representatives and
other stakeholders to ‘‘redefine the value of nuclear
cardiology and the priorities for future growth and
success.11’’ The ASNC board and their industry partners
proposed some ‘‘solutions-based’’ initiatives and
projects that were judged to propel the field of nuclear
cardiology into the future. These recommendations were
focused on the delivery of high-quality appropriate
imaging, promoting the unique benefits of cardiac PET,
modernizing the practice of cardiac SPECT, promoting
nonperfusion applications of nuclear cardiology, and
developing a road map to high-quality imaging.
Certainly, advocating for high-quality appropriate imaging
and modernizing SPECT practice are of paramount
importance, but this alone may not have a great impact
on expanding the field of nuclear cardiology with a
concomitant increase in volume and diversity of
procedures. Nevertheless, old SPECT cameras need to be
replaced by more sensitive solid state cameras that
permit lower doses of tracers without sacrificing quality.
Similarly, it appears that more and more practitioners
are adhering to AUC indications for imaging, with fewer
inappropriate tests being ordered.
What will truly make a difference in expanding
nuclear cardiology in the future are the Industry Forum
recommendations related to advancing cardiac PET and
developing new nonperfusion SPECT and PET
applications. The validation of these nonperfusion imaging
protocols is currently underway in the form of feasibility
studies, reports of small patient series, and carrying out
of outcomes studies to show their clinical value in
patient diagnosis and management. PET MPI has a
better resolution, a higher sensitivity, and specificity for
detection of CAD; is superior for detecting multivessel
disease; and has lower radiation exposure than SPECT
MPI.12 It allows for quantitative measurement of
myocardial blood coronary flow and coronary flow
reserve (CFR) using vasodilator stress. Measurement of
CFR is associated with improved detection of
multivessel disease and quantitating abnormal flow reserve
improves risk stratification compared to solely assessing
relative defects in tracer uptake. Abnormal CFR can be
seen in patients with nonobstructive CAD and patients
with microvascular dysfunction. These patients without
focal defects due to significant obstructive CAD, but
abnormal CFR have a worse prognosis than patients
with normal CFR and no inducible defects. Although
some nuclear cardiology laboratories have performed
more PET MPI studies in recent years, volumes are
limited by access to the instrumentation, which is often
shared with users in other specialties such as oncology.
Nuclear cardiology laboratories require dedicated PET
cameras to provide a better access to cameras. Many of
the nonperfusion applications of PET would also benefit
from enhanced access to PET instrumentation. Hybrid
imaging with PET/CT provides even greater information
pertaining to anatomy and physiology simultaneously
assessed. The Industry Forum report identifies the need
for educating third-party payers on the value of cardiac
PET imaging, which was deemed essential to helping
break down the barriers to access for PET. Presently, the
MPI radiotracer, F-18-flurpiridaz, is in Phase III trials.
This long-acting PET tracer with excellent myocardial
extraction can be utilized in exercise PET MPI, and has
already been shown to have accuracy superior to SPECT
in Phase II trials.12
The acceptance and growth of nonperfusion cardiac
imaging applications are vital in widening the offerings
of nuclear cardiology going forward. Already, much
activity has been ongoing in validating the worth of
F18-flurodeoxyglucose (FDG) imaging for detecting and
quantitating focal inflammatory lesions in patients with
sarcoidosis.13,14 From 8 published studies, the pooled
sensitivity and specificity values for detecting cardiac
involvement with sarcoid were 89% and 78%,
respectively. Combining MPI with FDG imaging could even
enhance the accuracy of detection of sarcoid granulomas
in the heart. Even combining PET with MRI for showing
areas of delayed hyperenhancement in areas of
decreased perfusion without inflammation could be an
early manifestation of cardiac sarcoid.15
Hybrid imaging with PET/CT or SPECT/CT is
being evaluated for detection of cardiovascular implant
infection including surgically placed valvular
prostheses, transcatheter aortic valve implantations (TAVI),
pacemakers, pacemaker leads, implantable defibrillators,
and left ventricular assist devices.16 The clinical value of
neurocardiac imaging of the sympathetic nervous system
with SPECT or PET continues to be evaluated in clinical
trials.17,18 A new trial of
I-123-metaiodobenzylguanidine (MIBG) imaging involves randomizing patients
with LVEF values between 30% and 35%
(ADMIREICD) to determine if MIBG imaging useful for guiding
the decision for ICD implantation. This trial is scheduled
to be completed in 2019. Tc-99m-pyrophosphate (PYP)
imaging can be used for detection of transthyretin
cardiac amyloidosis.19 F-18-Florbetapir binds to cardiac
amyloid light-chain and transthyretin-related amyloid
deposits.20 This PET approach to early detection of this
pathology could be useful for more prompt treatment
before progression of the disease. Finally, work is
continuing to explore the clinical value in decision-making
for imaging vulnerable atherosclerotic plaques which are
inflamed.21 Atherosclerotic plaque uptake of FDG
correlates with macrophage infiltration, and increased
plaque FDG uptake in the arterial wall may identify a
higher risk for acute cardiac events. F-18-fluoride targets
microcalcifications in the fibrous caps of atherosclerotic
plaques.22 So far, plaque imaging has been found to
have a low positive predictive value but an excellent
negative predictive value for excluding lesions leading
to events.22 As with other nonperfusion imaging studies
under investigation, evidence for clinical value lies in
the ability of the imaging technique to predict hard
clinical endpoints and influencing outcomes.
In conclusion, the future growth and progress in
nuclear cardiology will include greater utilization of
PET for quantitative MPI with CFR measurement, and
for metabolic and molecular nonperfusion imaging
applications. This can be accomplished while still
adhering to the delivery of high-quality and appropriate
SPECT myocardial perfusion imaging, but with better
cameras and software applications. The use of
multimodality imaging in certain disease states will surely
provide even greater information that can yield an early
diagnosis, direct the most effective evidence-based
therapy, and improve outcomes. For nuclear cardiology
to grow and thrive, robust basic and clinical research
strategies are required for identifying new biologic
tracers for specific diseases, which, when translated to
clinical imaging protocols, will have an impact in
patient outcomes that can be measured. For too many
years, nuclear cardiology has been dependent on
perfusion imaging, which certainly has been of great clinical
value in the evaluation of patients with suspected or
known CAD. It is exciting to see that currently, many
innovative nonperfusion imaging procedures are being
evaluated in clinical research studies. Some are in
randomized trials. The ASNC Board of Directors with its
Industry partners and other stakeholders are diligently
working to identify a new road map to redefine the value
of nuclear cardiology, with support of new emerging
applications and innovations to enhance the field.
Personally, as someone who has witnessed the progress of
nuclear cardiology over more than 40 years, I remain
optimistic for the future. This optimism is predicated on
the assumption that we continue to attract the next
generation of academic imaging specialists to move the
field forward by engaging in translational research to
find new applications of nuclear cardiology that have a
positive impact on patient outcomes.
1. Beller GA. How should we interpret the decrease in annual
volume of stress imaging tests for evaluation of suspected or known
coronary artery disease with fewer high-risk tests? Circ
Cardiovasc Imaging. 2017. https://doi.org/10.1161/CIRCIMAGING.117.
The author declare that he has no conflict of interest.
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