Cardiovascular Imaging Research

JACC: CARDIOVASCULAR IMAGING

VOL. 8, NO. 8, 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.2015.06.009

EDITORIAL COMMENT

Cardiovascular Imaging Research Time to Think Beyond Risk Prediction?* Khurram Nasir, MD, MPHyzxk

“I

f we produce food that no one eats, we need

compounded in the context of asymptomatic in-

to consider different crops.” (1)

dividuals, considering the large population that it can affect, potential initial costs, lower risk of an

Hardly any other topic than the role of cardio-

adverse event (that can potentially be prevented) in

vascular (CV) imaging in how we manage our pa-

the short term, and the lack of clear-cut incentives

tients generates passionate debate among health

to project savings in the long term by our current

care stakeholders. Despite this, CV imaging con-

complicated landscape of a mixed form of private

tinues to play a major role in our clinical decision-

payers and governmental agencies. Coronary artery

making processes and is performed in more than 10

calcium (CAC) testing is a prime example of these

million patients each year for enhanced risk predic-

challenges. Despite the: 1) presence of an unprece-

tion and initiation of targeted therapies with ulti-

dented amount of evidence for superior risk pre-

mate goals of improving outcomes (2). Among the

diction; 2) potential to affect management decisions

spectrum of choices for CV imaging, established

and behavior; and 3) recent demonstration of being

modalities such as invasive angiography, echocardi-

cost-effective from a societal perspective, the use of

ography, and myocardial perfusion imaging are

CAC testing remains to be limited due to the lack of

deeply embedded in our standard of care processes,

consensus on guidelines and continued resistance by

especially for those with suspected and symptomatic

payers to reimburse costs (3).

CV disease. Due to the consideration of additional

Discussions on the appropriate future roles of

costs and potential undesired downstream implica-

emerging CV imaging modalities can be better facili-

tions, there is apprehension with regard to expand-

tated when examined in the context of our health

ing the horizon for newer modalities. Adding any

care

new CV imaging test in our clinical practice faces a

yglucose positron emission tomography (FDG-PET)

much more stringent task than its predecessors,

imaging with its ability to capture the differential rate

amidst demands of demonstrating value specifically

of tissue glycolysis is an established tool in clinical

in the form of improved outcomes. It is worthwhile

oncology for estimating tumor activity and for

constraints

considered

above.

Fluorodeox-

to note that although critically considering these

detection of occult infection in inflamed tissues. The

criteria, evidence is limited even for these estab-

potential utility of FDG-PET imaging to complement

lished CV imaging tests; however, this debate is

current CV imaging tools in humans rapidly pro-

unlikely to change the burden of proof asked of

gressed from observation of heightened PET activity

newer modalities. This issue becomes even more

in patients with vasculitis in 1987 to a point in 2001 where FDG uptake in the great vessels was clearly linked to atherosclerosis (4). In the past decade, the

*Editorials published in JACC: Cardiovascular Imaging reflect the views of

role of FDG-PET/computed tomography (CT) in

the authors and do not necessarily represent the views of JACC:

demonstrating the therapeutic antiatherosclerotic ef-

Cardiovascular Imaging or the American College of Cardiology. From the yCenter for Healthcare Advancement & Outcomes, Baptist Health South Florida, Miami, Florida; zMiami Cardiac & Vascular Institute (MCVI), Baptist Health South Florida, Miami, Florida; xThe

ficacy of proven treatments as well evaluating novel pharmacological agents for these purposes has added significant value to drug development processes. In

Johns Hopkins Ciccarone Center for the Prevention of Heart Disease,

recent years, investigators pointed out that arterial

Baltimore, Maryland; and the kDepartment of Medicine, Herbert

inflammation noted on routine FDG-PET CT scans

Wertheim College of Medicine, Department of Epidemiology, Robert

performed in active cancer patients and survivors can

Stempel College of Public Health, Florida International University, Miami, Florida. Dr. Nasir is on the Advisory Board of Quest Diagnostic;

enhance our ability to predict subsequent CV events in

and is a consultant for Regeneron.

this vulnerable population (5).

958

Nasir

JACC: CARDIOVASCULAR IMAGING, VOL. 8, NO. 8, 2015 AUGUST 2015:957–9

Editorial Comment

SEE PAGE 949

Considering our stakeholders’ demand for an accelerated drive toward value-based health care de-

In the current study in this issue of iJACC, Moon

livery, investigations that does not seek opportunities

et al. (6) demonstrated that the prognostic value

beyond mere risk prediction will unfortunately have

derived from measuring carotid arterial FDG extends

limited impact. So how do we navigate these chal-

to individuals free of established cancer or CV disease.

lenges? For guidance, we need not look beyond

The study investigators critically assessed the value of

the fantastic blueprint provided by the editors of

measuring the average FDG uptake of both carotid ar-

iJACC, reminding us that CV imaging research needs

teries normalized to the venous blood in nearly 1,000

concerted efforts to move beyond assessment of ac-

asymptomatic individuals who underwent PET/CT for

curacy and prediction (2). These recommendations

cancer screening. Overall, this was a low-risk popula-

persuasively highlight practical steps for developing

tion, with only 19 events (1.7%) noted in a mean follow-

definitive evidence for any given modality with goals

up of 4 years, notably half of them were anginal rather

to improve “end results.” Encouragingly, comparative

than atherothrombotic in nature. Two-thirds of events

effectiveness research goals in the current era are not

occurred in one-third of participants with the highest

narrowly focused on realizing a reduction in clinical

FDG uptake in carotid vessels. Surprisingly, as high-

events, but also include additional worthy targets such

lighted in Figure 1, even among those with the highest

as clarifying the role of CV imaging in the optimal

vessel wall FDG uptake, which may indicate plaque

management protocols for physicians, appropriate

vulnerability, no events were noted in the first 2 years,

resource allocation for providers, and, more impor-

with the majority of them occurring 4 years into the

tantly, facilitating informed choices for our patients.

follow-up. This observation slightly conflicts with

The challenges highlighted by a lack of clear down-

findings from Figuero et al. (7) who noted that those

stream implications as noted in the current study are

with elevated large arterial inflammation signals on

not limited to this specific situation or imaging mo-

PET were more likely to experience near-term CV dis-

dality. Each year, hundreds of CV imaging research

ease. Irrespectively, robust statistical metrics used in

studies continue to frame the question “does it

the study demonstrated independent predictive value

improve risk prediction?” despite the fact that this

from arterial wall PET activity measurement beyond

knowledge will less likely cater to the broader health

traditional risk factors and carotid intima-media

care needs. This singular approach in the past may

thickness, an established surrogate for atheroscle-

have limited our ability to unlock the true value of CV

rotic disease burden.

imaging

by

not

focusing

on

relevant

research

These encouraging results add to the increasing

addressing our more urgent needs. This is not meant to

recognition of potential predictive value of FDG-PET

discourage risk prediction research, but to redirect our

detection of inflammation for future adverse cardiac

energies so that we can place a higher value on evi-

events. However, one needs to ask what is this added

dence that needs to be generated. We acknowledge

information worth? Would the results influence our

that these prediction specific investigations have

stakeholders to adopt FDG-PET for risk assessment?

played a pivotal role in clarifying pathophysiological

Despite the promising results, the translational po-

disease mechanisms, disease specific associations, and

tential of FDG-PET for this specific purpose in an

risk among different clusters; however, it is worth

asymptomatic population, in my humble view, is

contemplating whether it is time to shift our goals. This

limited. Among many considerations, one needs to

will not be an easy task and will require a major cultural

take into account the significant cost, major radiation

shift. More importantly, we will have to rely on stake-

exposure, and lack of comparative data with more

holder consensus for defining ‘rational’ research that

established imaging risk stratification tools such as

will cater to their specific needs. The entire CV imaging

CAC testing. Future research in this area needs to

investigation community will be better served if we

consider these issues in study designs. However, are

demand a greater return of investment by asking, “Is

there any clinical scenarios well suited for predicting

there anyone who would do something differently

CV risk with FDG-PET testing? Based on the current

because of the results of the research?” (1).

and recent studies, we are optimistic that significant information can be derived if additional measure-

REPRINT REQUESTS AND CORRESPONDENCE: Dr.

ment of arterial activity becomes a standard of care of

Khurram Nasir, Center for Healthcare Advancement

those in whom FDG-PET imaging is routinely per-

& Outcomes, Baptist Health South Florida, 1500 San

formed. This is a situation where clear value is added

Remo Avenue, Suite 340, Coral Gables, Florida 33139.

in how we can manage our patients without addi-

E-mail: [email protected] OR knasir1@

tional costs or radiation exposure.

jhmi.edu.

Nasir

JACC: CARDIOVASCULAR IMAGING, VOL. 8, NO. 8, 2015 AUGUST 2015:957–9

Editorial Comment

REFERENCES 1. Krumholz HM. How do we know the value of our research? Circ Cardiovasc Qual Outcomes 2013;6: 371–2. 2. Shaw LJ, Min JK, Hachamovitch R, et al. Cardiovascular imaging research at the crossroads. J Am Coll Cardiol Img 2010;3:316–24. 3. Nasir K, Shaw LJ, Budoff MJ, Ridker PM, Peña JM. Coronary artery calcium scanning should be used for primary prevention: pros and cons. J Am Coll Cardiol Img 2012;5:111–8.

4. Chen W, Bural GG, Torigian DA, Rader DJ, Alavi A. Emerging role of FDG-PET/CT in assessing atherosclerosis in large arteries. Eur J Nucl Med Mol Imaging 2009;36:144–51. 5. Emami H, Tawakol A. Noninvasive imaging of arterial inflammation using FDG-PET/CT. Curr Opin Lipidol 2014;25:431–7. 6. Moon SH, Cho YS, Noh TS, Choi JY, Kim B-T, Lee K-H. Carotid FDG uptake improves prediction of future cardiovascular events in asymptomatic

individuals. J Am Coll Cardiol Img 2015;8: 949–56. 7. Figueroa AL, Abdelbaky A, Truong QA, et al. Measurement of arterial activity on routine FDG PET/CT images improves prediction of risk of future CV events. J Am Coll Cardiol Img 2013;6:1250–9.

KEY WORDS cardiovascular events, carotid artery, 18F-FDG, prognosis, risk prediction

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