JACC: CARDIOVASCULAR IMAGING
VOL. 8, NO. 2, 2015
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 1936-878X/$36.00
PUBLISHED BY ELSEVIER INC.
http://dx.doi.org/10.1016/j.jcmg.2014.12.004
EDITORIAL COMMENT
The Exercise Test Is Alive and Well When Coupled With Coronary Calcium Scoring* Leslee J. Shaw, PHD
I
n this issue of iJACC, Chang et al. (1) report on
outcomes at 7 years—well beyond the short-term
the long-term prognostic findings with coro-
findings often reported in many prognostic series.
nary artery calcification scoring (CACS) added
These data underscore the importance of CACS as a
to the more conventional exercise electrocardio-
marker of the natural history of atherosclerotic dis-
graphic (ECG) diagnostic testing. Although exercise
ease that persists for many years following index
testing is well established as a diagnostic tool for
testing.
coronary artery disease (CAD), CACS also has a well-
Conversely, exercise testing examines functional
developed evidence base in terms of risk stratifica-
capacity, and the predictive value of the stress ECG is
tion. However, often physicians have chosen one or
on the basis of the concept of demand ischemia. The
the other of these modalities and not evaluated the
primary aim of an exercise test is to provoke ischemia
interplay of their findings for risk-stratification pur-
whereby angina or other symptoms occurring with
poses. The report by Chang et al. (1) on long-term
arrhythmias or ECG abnormalities would be elicited
prognosis following combined CACS and exercise
during testing in the setting of a flow-limiting lesion.
ECG testing is quite intriguing.
The exercise ECG findings can be combined, with exertional symptoms and functional capacity, into
SEE PAGE 134
the Duke treadmill score, which effectively risk-
CACS has long been studied to examine the burden
stratifies patients but also identifies patients’ risk
of subclinical atherosclerosis in largely asymptom-
for severe or extensive CAD (5,6). The report by Chang
atic, apparently healthy adults (2). Calcified plaque is
et al. (1) states that, due to the improved prognosti-
considered a marker of stable but more advanced
cation with CACS, this procedure should be the front-
plaque, with recent evidence noting an inverse rela-
line test instead of the exercise ECG. An important
tionship between plaque density and cardiovascular
concept to note is that we no longer have the natural
events (3). This evidence supports the concept that
history of ECG ischemia, as its documentation initi-
advanced plaque often contains CAC and may also co-
ates a series of anti-ischemic therapies post-testing
occur
states.
that subsequently alter its natural history. These
Although this is a general pattern of how atheroscle-
concepts of identifying risk, altering risk with
rotic disease would progress, CAC does not uniformly
ischemia-guided management, and reducing the
with
progressive
obstructive
CAD
reflect an underlying obstructive stenosis (4). The
prognostic significance of the exercise ECG are the
findings in this report that CACS is a strong prog-
intended goals of testing for and treating stable
nosticator is no surprise given that it is a direct
ischemic heart disease within the diagnostic workup.
marker of the burden of atherosclerosis on the basis
In many ways, the fact that we can intervene in
of computed tomographic findings. Importantly, the
ischemia renders it integral for guided management.
findings from the registry of Chang et al. (1) reveal the
Missing from the discussion by Chang et al. (1) is that
strength of CAC findings in estimating long-term
we do not have a similar guided-management
*Editorials published in JACC: Cardiovascular Imaging reflect the views
long-term analysis. The lack of an established thera-
approach following CACS, which is the sole reason that it remains so prognostically significant in this
of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology. From the Department of Cardiology, Emory University, Atlanta, Georgia. Dr. Shaw has reported that she has no relationships relevant to the contents of this paper to disclose.
peutic strategy following CACS limits our enthusiasm for making CACS a front-line test. Moreover, it would then seem that these 2 markers provide disparate information that, when
146
Shaw
JACC: CARDIOVASCULAR IMAGING, VOL. 8, NO. 2, 2015 FEBRUARY 2015:145–7
Editorial Comment
combined, may prove optimal for prognostication.
an ischemia-guided strategy are poorly understood.
It is for this reason that the presentation of the
We often view ischemic findings as a checklist or as a
combined ECG and CACS findings from the Chang
gatekeeper to drive anti-ischemic management de-
et al. (1) series is compelling. First, the combination
cisions but not as a factor that should be a part of the
of exercise testing with CACS has only recently been
patient’s clinical history for years to come. Perhaps
evaluated but is intriguing given that these variable
this has to do with our current knowledge base from
risk markers for atherosclerosis and ischemia may
clinical trials in stable ischemic heart disease, which
improve prognostication. From a practical view-
treated the angiographic burden of disease and not
point, combining CACS and exercise testing would
targeted ischemic findings such as that guided by
be inexpensive and yet each risk component would
fractional flow measurements (8–10). On the basis of
be additive and improve the precision of the diag-
the findings from Chang et al. (1), one may envision
nostic evaluation (7). Second, the authors (1) present
the development of a management strategy whereby
long-term data on the rate of ensuing major CAD
the burden of CAC may crudely reflect anatomic
events following index exercise ECG and CACS
burden and, coupled with exercise test findings,
findings. The median follow-up in this cohort was
preliminary ischemia-guided management strategies
lengthy with disease progression likely in many pa-
may be devised. The interplay between these 2
tients. This report (1) tests the limit of a “warranty
markers of ischemia and atherosclerosis could form
period” beyond our usual 2 to 3 years of follow-up.
the basis of a newly developed diagnostic strategy,
High-risk CACS and ECG findings would prompt
the focus of which would not end following the next
near-term preventive management decisions aimed
referral to an additional noninvasive or invasive
at reducing long-term risk. The extent to which both
imaging procedure. But these results, given their
of these factors predict long-term outcomes is
longevity in risk prediction, could form the basis of
interesting
of
intensive and serial risk evaluations for years
effective therapeutic strategies or the fact that index
following an index diagnostic evaluation. As we
CACS and ECG findings persistently accelerate dis-
progress toward personalized medicine, including
ease and risk throughout a patient’s remaining life
patient-centered imaging, guided diagnostic risk evi-
expectancy following index testing.
dence should form the basis of ensuing short- and
and
may
reflect
underutilization
We have rarely observed long-term data following
long-term management. We and others have advo-
CAD imaging, and the report by Chang et al. (1)
cated that the link between imaging and improving
illustrates the value of this information in estimating
outcomes is largely indirect, and that outcomes can be
the longevity of the findings of this test. Perhaps, we
improved only if imaging-guided therapeutic inter-
consider angiographic findings more often within the
vention is implemented (11). It is time for research to
concept of what was observed and our expectations
progress beyond the usual risk-prediction models and
of what a patient’s disease state and risk would be
to move toward the development of diagnostic-
years from now. For example, a patient may have had
management strategies on the basis of index test
a 40% lesion 5 years ago, and pondering his or her
markers, with the aim of long-term risk reduction.
current status, we may not view this prior informa-
This investigative group lists one coauthor, Maria
tion statically but understand the complex interplay
Frias, who passed away recently. She was a long-
between disease progression, adherence to therapy,
standing research coordinator working with this
and other factors that have an impact on the changing
investigative group, and we were blessed to have had
paradigm of evolving risk. Yet, for diagnostic testing,
her guide our community and contribute greatly to
we have very limited data on long-term prognosis
the field of cardiovascular imaging.
and often view test results in isolation, such as that the patient had an abnormal exercise test result 5
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
years ago, but what that means for the patient now
Leslee J. Shaw, Emory University, Department of
and how that underlying ischemic burden and
Cardiology, 1462 Clifton Road, Room 529, Atlanta,
breakthrough symptom burden affect the success of
Georgia 30342. E-mail: [email protected].
REFERENCES 1. Chang SM, Nabi F, Xu J, et al. Value of CACS compared with ETT and myocardial
patients at low risk for coronary disease: clinical implications in a multimodality imag-
2. Budoff MJ, Shaw LJ, Liu ST, et al. Long-term prognosis associated with coronary calcification:
perfusion imaging for predicting long-term cardiac outcome in asymptomatic and symptomatic
ing world. J Am Coll Cardiol Img 2015;8: 134–44.
observations from a registry of 25,253 patients. J Am Coll Cardiol 2007;49:1860–70.
Shaw
JACC: CARDIOVASCULAR IMAGING, VOL. 8, NO. 2, 2015 FEBRUARY 2015:145–7
3. Criqui MH, Denenberg JO, Ix JH, et al. Calcium density of coronary artery plaque and risk of incident cardiovascular events. JAMA 2014;311: 271–8. 4. O’Rourke RA, Brundage BH, Froelicher VF, et al. American College of Cardiology/American Heart Association expert consensus document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. J Am Coll Cardiol 2000;36:326–40. 5. Shaw LJ, Peterson ED, Shaw LK, et al. Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups. Circulation 1998;98: 1622–30.
Editorial Comment
6. Alexander KP, Shaw LJ, Shaw LK, et al. Value of exercise treadmill testing in women. J Am Coll Cardiol 1998;32:1657–64. 7. Rozanski A, Cohen R, Uretsky S. The coronary calcium treadmill test: a new approach to the initial workup of patients with suspected coronary artery disease. J Nucl Cardiol 2013;20:719–30. 8. Boden WE, O’Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503–16. 9. De Bruyne B, Fearon WF, Pijls NH, et al. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med 2014;371:1208–17.
10. Tonino PA, De Bruyne B, Pijls NH, et al., FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213–24. 11. Shaw LJ, Min JK, Hachamovitch R, et al. Cardiovascular imaging research at the crossroads. J Am Coll Cardiol Img 2010;3:316–24.
KEY WORDS asymptomatic patients, calcium score, coronary artery exercise treadmill test, risk stratification
147
VOL. 8, NO. 2, 2015
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 1936-878X/$36.00
PUBLISHED BY ELSEVIER INC.
http://dx.doi.org/10.1016/j.jcmg.2014.12.004
EDITORIAL COMMENT
The Exercise Test Is Alive and Well When Coupled With Coronary Calcium Scoring* Leslee J. Shaw, PHD
I
n this issue of iJACC, Chang et al. (1) report on
outcomes at 7 years—well beyond the short-term
the long-term prognostic findings with coro-
findings often reported in many prognostic series.
nary artery calcification scoring (CACS) added
These data underscore the importance of CACS as a
to the more conventional exercise electrocardio-
marker of the natural history of atherosclerotic dis-
graphic (ECG) diagnostic testing. Although exercise
ease that persists for many years following index
testing is well established as a diagnostic tool for
testing.
coronary artery disease (CAD), CACS also has a well-
Conversely, exercise testing examines functional
developed evidence base in terms of risk stratifica-
capacity, and the predictive value of the stress ECG is
tion. However, often physicians have chosen one or
on the basis of the concept of demand ischemia. The
the other of these modalities and not evaluated the
primary aim of an exercise test is to provoke ischemia
interplay of their findings for risk-stratification pur-
whereby angina or other symptoms occurring with
poses. The report by Chang et al. (1) on long-term
arrhythmias or ECG abnormalities would be elicited
prognosis following combined CACS and exercise
during testing in the setting of a flow-limiting lesion.
ECG testing is quite intriguing.
The exercise ECG findings can be combined, with exertional symptoms and functional capacity, into
SEE PAGE 134
the Duke treadmill score, which effectively risk-
CACS has long been studied to examine the burden
stratifies patients but also identifies patients’ risk
of subclinical atherosclerosis in largely asymptom-
for severe or extensive CAD (5,6). The report by Chang
atic, apparently healthy adults (2). Calcified plaque is
et al. (1) states that, due to the improved prognosti-
considered a marker of stable but more advanced
cation with CACS, this procedure should be the front-
plaque, with recent evidence noting an inverse rela-
line test instead of the exercise ECG. An important
tionship between plaque density and cardiovascular
concept to note is that we no longer have the natural
events (3). This evidence supports the concept that
history of ECG ischemia, as its documentation initi-
advanced plaque often contains CAC and may also co-
ates a series of anti-ischemic therapies post-testing
occur
states.
that subsequently alter its natural history. These
Although this is a general pattern of how atheroscle-
concepts of identifying risk, altering risk with
rotic disease would progress, CAC does not uniformly
ischemia-guided management, and reducing the
with
progressive
obstructive
CAD
reflect an underlying obstructive stenosis (4). The
prognostic significance of the exercise ECG are the
findings in this report that CACS is a strong prog-
intended goals of testing for and treating stable
nosticator is no surprise given that it is a direct
ischemic heart disease within the diagnostic workup.
marker of the burden of atherosclerosis on the basis
In many ways, the fact that we can intervene in
of computed tomographic findings. Importantly, the
ischemia renders it integral for guided management.
findings from the registry of Chang et al. (1) reveal the
Missing from the discussion by Chang et al. (1) is that
strength of CAC findings in estimating long-term
we do not have a similar guided-management
*Editorials published in JACC: Cardiovascular Imaging reflect the views
long-term analysis. The lack of an established thera-
approach following CACS, which is the sole reason that it remains so prognostically significant in this
of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology. From the Department of Cardiology, Emory University, Atlanta, Georgia. Dr. Shaw has reported that she has no relationships relevant to the contents of this paper to disclose.
peutic strategy following CACS limits our enthusiasm for making CACS a front-line test. Moreover, it would then seem that these 2 markers provide disparate information that, when
146
Shaw
JACC: CARDIOVASCULAR IMAGING, VOL. 8, NO. 2, 2015 FEBRUARY 2015:145–7
Editorial Comment
combined, may prove optimal for prognostication.
an ischemia-guided strategy are poorly understood.
It is for this reason that the presentation of the
We often view ischemic findings as a checklist or as a
combined ECG and CACS findings from the Chang
gatekeeper to drive anti-ischemic management de-
et al. (1) series is compelling. First, the combination
cisions but not as a factor that should be a part of the
of exercise testing with CACS has only recently been
patient’s clinical history for years to come. Perhaps
evaluated but is intriguing given that these variable
this has to do with our current knowledge base from
risk markers for atherosclerosis and ischemia may
clinical trials in stable ischemic heart disease, which
improve prognostication. From a practical view-
treated the angiographic burden of disease and not
point, combining CACS and exercise testing would
targeted ischemic findings such as that guided by
be inexpensive and yet each risk component would
fractional flow measurements (8–10). On the basis of
be additive and improve the precision of the diag-
the findings from Chang et al. (1), one may envision
nostic evaluation (7). Second, the authors (1) present
the development of a management strategy whereby
long-term data on the rate of ensuing major CAD
the burden of CAC may crudely reflect anatomic
events following index exercise ECG and CACS
burden and, coupled with exercise test findings,
findings. The median follow-up in this cohort was
preliminary ischemia-guided management strategies
lengthy with disease progression likely in many pa-
may be devised. The interplay between these 2
tients. This report (1) tests the limit of a “warranty
markers of ischemia and atherosclerosis could form
period” beyond our usual 2 to 3 years of follow-up.
the basis of a newly developed diagnostic strategy,
High-risk CACS and ECG findings would prompt
the focus of which would not end following the next
near-term preventive management decisions aimed
referral to an additional noninvasive or invasive
at reducing long-term risk. The extent to which both
imaging procedure. But these results, given their
of these factors predict long-term outcomes is
longevity in risk prediction, could form the basis of
interesting
of
intensive and serial risk evaluations for years
effective therapeutic strategies or the fact that index
following an index diagnostic evaluation. As we
CACS and ECG findings persistently accelerate dis-
progress toward personalized medicine, including
ease and risk throughout a patient’s remaining life
patient-centered imaging, guided diagnostic risk evi-
expectancy following index testing.
dence should form the basis of ensuing short- and
and
may
reflect
underutilization
We have rarely observed long-term data following
long-term management. We and others have advo-
CAD imaging, and the report by Chang et al. (1)
cated that the link between imaging and improving
illustrates the value of this information in estimating
outcomes is largely indirect, and that outcomes can be
the longevity of the findings of this test. Perhaps, we
improved only if imaging-guided therapeutic inter-
consider angiographic findings more often within the
vention is implemented (11). It is time for research to
concept of what was observed and our expectations
progress beyond the usual risk-prediction models and
of what a patient’s disease state and risk would be
to move toward the development of diagnostic-
years from now. For example, a patient may have had
management strategies on the basis of index test
a 40% lesion 5 years ago, and pondering his or her
markers, with the aim of long-term risk reduction.
current status, we may not view this prior informa-
This investigative group lists one coauthor, Maria
tion statically but understand the complex interplay
Frias, who passed away recently. She was a long-
between disease progression, adherence to therapy,
standing research coordinator working with this
and other factors that have an impact on the changing
investigative group, and we were blessed to have had
paradigm of evolving risk. Yet, for diagnostic testing,
her guide our community and contribute greatly to
we have very limited data on long-term prognosis
the field of cardiovascular imaging.
and often view test results in isolation, such as that the patient had an abnormal exercise test result 5
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
years ago, but what that means for the patient now
Leslee J. Shaw, Emory University, Department of
and how that underlying ischemic burden and
Cardiology, 1462 Clifton Road, Room 529, Atlanta,
breakthrough symptom burden affect the success of
Georgia 30342. E-mail: [email protected].
REFERENCES 1. Chang SM, Nabi F, Xu J, et al. Value of CACS compared with ETT and myocardial
patients at low risk for coronary disease: clinical implications in a multimodality imag-
2. Budoff MJ, Shaw LJ, Liu ST, et al. Long-term prognosis associated with coronary calcification:
perfusion imaging for predicting long-term cardiac outcome in asymptomatic and symptomatic
ing world. J Am Coll Cardiol Img 2015;8: 134–44.
observations from a registry of 25,253 patients. J Am Coll Cardiol 2007;49:1860–70.
Shaw
JACC: CARDIOVASCULAR IMAGING, VOL. 8, NO. 2, 2015 FEBRUARY 2015:145–7
3. Criqui MH, Denenberg JO, Ix JH, et al. Calcium density of coronary artery plaque and risk of incident cardiovascular events. JAMA 2014;311: 271–8. 4. O’Rourke RA, Brundage BH, Froelicher VF, et al. American College of Cardiology/American Heart Association expert consensus document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. J Am Coll Cardiol 2000;36:326–40. 5. Shaw LJ, Peterson ED, Shaw LK, et al. Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups. Circulation 1998;98: 1622–30.
Editorial Comment
6. Alexander KP, Shaw LJ, Shaw LK, et al. Value of exercise treadmill testing in women. J Am Coll Cardiol 1998;32:1657–64. 7. Rozanski A, Cohen R, Uretsky S. The coronary calcium treadmill test: a new approach to the initial workup of patients with suspected coronary artery disease. J Nucl Cardiol 2013;20:719–30. 8. Boden WE, O’Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503–16. 9. De Bruyne B, Fearon WF, Pijls NH, et al. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med 2014;371:1208–17.
10. Tonino PA, De Bruyne B, Pijls NH, et al., FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213–24. 11. Shaw LJ, Min JK, Hachamovitch R, et al. Cardiovascular imaging research at the crossroads. J Am Coll Cardiol Img 2010;3:316–24.
KEY WORDS asymptomatic patients, calcium score, coronary artery exercise treadmill test, risk stratification
147
