Has anyone been listening? Post-SPECT MPI referral rates to catheterization
Has anyone been listening? Post-SPECT MPI referral rates to catheterization
Elizabeth Hill 0
Rory Hachamovitch 0
0 Reprint requests: Rory Hachamovitch, MD, MSc, Section of Cardio- vascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic , J1-5, 9500 Euclid Avenue, Cleveland, OH 44195
1 Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic , Cleveland, OH
Radionuclide single-photon emission computed
tomography (SPECT) myocardial perfusion imaging
(MPI) has retained its steadfast role in the assessment of
suspected or known coronary artery disease (CAD). Both
guidelines and appropriate use criteria continue to support
its role in numerous clinical settings.1,2 At a time when
there is increasing emphasis on quality and
appropriateness in testing, there is an ongoing need to scrutinize the
value of all cardiovascular imaging modalities. This
scrutiny has encompassed the continuum from patient
selection to correct image acquisition and interpretation
of the reporting of results to referring physicians.3 Indeed,
the importance of selecting the ‘‘right’’ patients for
testing and the importance of considering how test results will
change subsequent management have been embraced as a
mantra. Although they are infrequently reported, patterns
of post-SPECT MPI patient management are informative
for this purpose and likely represent the most pragmatic
insight we can gain with respect to the use of this modality
in daily practice. To this end, prior studies have examined
referral rates to catheterization, revascularization, and
medical therapy after exercise stress testing and stress
MPI, often focusing on whether systematic sex-related or
age-related posttest differences in patient management
On the basis of these studies, a number of
generalizations can be made. First, the likelihood of referral to
catheterization after MPI is overwhelmingly driven by
the results of the test. Further, the dominant drivers of
this referral are markers of ischemia—predominantly the
extent and severity of MPI-defined ischemia, but also
presenting symptoms, stress-induced symptoms, and ST
segment changes with stress.
Other factors, of unclear appropriateness, also inform
this decision. Referral rates vary among patient
populations. Despite the widely reported issues with sex-related
bias in cardiovascular care, catheterization rates remain
greater in men compared to women. These differences
remain after consideration of baseline patient
characteristics, site-related practice differences, and other factors.
Similarly, previous studies have also shown that in older
patients, absolute catheterization rates were lower in
patients aged [80 years compared to patients aged 50 to
64 years or 65 to 79 years.17 A 40 site prospective,
multicenter study—the Study of myocardial Perfusion and
coronary Anatomy imaging Roles in Coronary artery
disease (SPARC)—examined posttest patient
management in a cohort of 1703 patients with
intermediate-tohigh pretest likelihood of CAD who were referred for a
clinically ordered PET, SPECT, or CCTA in 40 sites.16,18
These results confirmed the impact of patient sex and age
on catheterization referral rates. Men were found to have a
significantly greater rate of referral to catheterization
compared to women after all other factors were
considered (odds ratio 1.82). Catheterization referral increased
progressively with increasing age—patients in their 50s,
60s, and 70s had greater catheterization rates compared to
patients aged younger than 40 years—but patients aged
[80 had a lower odds ratio compared to patients
\40 years of age. Hence, both these factors—patient age
and sex—appear to impact catheterization referral rates.
Whether the difference in referral rates related to these
two factors are clinically appropriate or not is a
Undoubtedly the most concerning finding in studies
to date is the relatively low absolute rate of referral to
catheterization after moderate-to-severe test
abnormalities. In the setting of the most profound test
abnormalities (and the greatest risk for adverse events),
the referral rates to 90-day catheterization are *40% to
60%.12,16,17 Although prior studies hypothesized that
those patients who were not referred for catheterization
were instead treated with aggressive medical
management, thus obviating the need for an initial invasive
approach, they did not collect pharmacotherapeutic data.
This information, collected in SPARC, revealed that
along with the *50% catheterization referral rate,
referring physicians also did not prescribe aggressive
medical therapy. Focusing on the use of aspirin, lipid
lowering agents, and beta-blockers, only one in five
patients with serious test abnormalities were on all three
of these medications, most were on one or two of them,
and there was no increase in the proportion of patients
with increased number of medications after testing.
Hence, half of the patients with the highest risk
noninvasive test findings received a catheterization, half
received a change in medical therapy, a quarter received
neither, and a quarter received both. These practice
patterns are difficult to comprehend and do not follow
what most clinicians would believe to be the
‘‘appropriate’’ pattern.19 Of note, no studies to date have
considered patient preferences, socioeconomic status,
insurance status, or refusal of procedure.
In the current issue of Journal of Nuclear
Cardiology , Zeltser and colleagues present results from a
study examining age and gender bias in catheterization
referral rates after MPI at a tertiary referral center. Their
hypothesis was that post-MPI referral bias associated
with female patients and older patients result in lower
referral catheterization rates. Their data suggest that the
previously reported gender bias is not present, but that
the age bias was present evident in their data.
Full disclosure: What should be expected from
publications in this area? A number of issues specific to
this type of research must be considered. The greatest
challenge facing investigators seeking to assess
postMPI treatment patterns is that of bias and confounding.
Due to the many potential applications of MPI, the
cohorts referred to MPI are a remarkably diverse
population. No clear conclusions can be reached from the
collected data without careful risk adjustment for known
or suspected confounders of treatment. Unfortunately, as
the authors note in their limitations section, they did not
collect data on clinical history, risk factors, stress test
results, patient symptoms, and other key elements. What
data were available are not entirely clear, as the authors
were able to calculate an atherosclerosis risk score, but
the necessary variables were not included in their
analysis. The most striking aspect of this is the lack of
symptom data. In the SPARC study the presence of
angina was associated with a risk-adjusted odds ratio of
3.1 for catheterization referral. As symptom patterns
differ between men and women presenting to testing,
and the association of symptoms and CAD differ with
sex and age, the absence of the data undermines the
interpretation of the results.
Although numerous catheterizations occurred on
follow-up, only twelve degrees of freedom were used in
the modeling (six covariates but three with four
categories). This limited risk adjustment has been referred to
as ‘‘underfitting’’ the model.20 The most striking aspect
of the current study is the paucity of data presented. The
authors inform us about the observed referral rates to
catheterization in men and women, but do not describe
the results as a function of the test result. In their solitary
table, catheterization rates across categories of summed
stress score but not summed difference score are
presented, despite previous studies demonstrating the latter
rather than the former to drive catheterization referral.
Indeed, catheterization rates in patients without CAD
with normal, mild, moderate, and severe summed score
abnormalities are 6.7%, 51.5%, 57.1%, and 56.1%,
respectively. It is disappointing that the authors do not
mention that (in the absence of availability of ischemia
data) physicians appear to use the MPI results in a
dichotomous fashion and that these results confirm the
previous reports of only *40% to 60% of patients
referred to catheterization after abnormal testing.
The authors do not refer to most of the studies in the
area cited above. They interchange studies evaluating
sex- and age-related treatment patterns in cohorts who
did not undergo MPI. These populations differ
considerably in makeup. Also, studies able to account for
markers of extent of disease (coronary anatomy or MPI
data) may differ in results compared to studies without
this information. Finally, the authors conclude that their
results may suggest that previously described sex-related
referral biases may no longer be present. Unfortunately,
the authors do not consider the results of the recent
multicenter study that indicates that this bias is,
unfortunately, still present.
The authors highlight these issues in their
limitations section, the section of a manuscript intended as an
opportunity for the authors to address the challenges to
internal and external validity (generalizability) due to
study design and execution that may limit interpretation
of the findings. What is unstated, but is understood, is
that a flaw of design or execution may be sufficiently
profound to compromise the study such that it is no
longer a mere limitation—if a prognosis study followed
only half the cohort, it would be problematic to refer to
it as a limitation. Rather, the study is irretrievably
compromised. The inability to acquire critical data
relegates the study to, at best, a pilot study, potentially
laying the groundwork for further, more complete,
Nonetheless, the authors’ results remain important
in that the underlying phenomenon of how we are using
these test results remains largely undervalued. The
results of a think tank on quality in cardiovascular
imaging identified patient selection for testing, image
acquisition and interpretation, and results
communication to be the important components of imaging quality.3
In light of the results of studies to date, however, it is
unclear whether a test result fulfilling these criteria
would be considered a ‘quality’ study or clinically
useful if its results are not considered appropriately in
the formulation of subsequent treatment plans.16
Whether a test performed in an appropriate clinical setting
that is performed, interpreted, and reported correctly is a
quality study is questionable, if no action is taken by the
referring physician, despite the presence of new
abnormalities. In the context of increasing scrutiny of
noninvasive testing, the monitoring of post-MPI
resource utilization is a metric whose time has arrived.
The authors do not receive honoraria, have relationships
with any companies or products, ownership of stock,
membership on advisory councils, committees, or board of directors,
thus, have no conflicts to disclose.
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