Author + information
- †Center for Healthcare Advancement & Outcomes, Baptist Health South Florida, Miami, Florida
- ‡Miami Cardiac & Vascular Institute (MCVI), Baptist Health South Florida, Miami, Florida
- §The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland
- ‖Department of Medicine, Herbert Wertheim College of Medicine, Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami, Florida
- ↵∗Reprint requests and correspondence:
Dr. Khurram Nasir, Center for Healthcare Advancement & Outcomes, Baptist Health South Florida, 1500 San Remo Avenue, Suite 340, Coral Gables, Florida 33139.
“If we produce food that no one eats, we need to consider different crops.” (1)
Hardly any other topic than the role of cardiovascular (CV) imaging in how we manage our patients generates passionate debate among health care stakeholders. Despite this, CV imaging continues to play a major role in our clinical decision-making processes and is performed in more than 10 million patients each year for enhanced risk prediction and initiation of targeted therapies with ultimate goals of improving outcomes (2). Among the spectrum of choices for CV imaging, established modalities such as invasive angiography, echocardiography, and myocardial perfusion imaging are deeply embedded in our standard of care processes, especially for those with suspected and symptomatic CV disease. Due to the consideration of additional costs and potential undesired downstream implications, there is apprehension with regard to expanding the horizon for newer modalities. Adding any new CV imaging test in our clinical practice faces a much more stringent task than its predecessors, amidst demands of demonstrating value specifically in the form of improved outcomes. It is worthwhile to note that although critically considering these criteria, evidence is limited even for these established CV imaging tests; however, this debate is unlikely to change the burden of proof asked of newer modalities. This issue becomes even more compounded in the context of asymptomatic individuals, considering the large population that it can affect, potential initial costs, lower risk of an adverse event (that can potentially be prevented) in the short term, and the lack of clear-cut incentives to project savings in the long term by our current complicated landscape of a mixed form of private payers and governmental agencies. Coronary artery calcium (CAC) testing is a prime example of these challenges. Despite the: 1) presence of an unprecedented amount of evidence for superior risk prediction; 2) potential to affect management decisions and behavior; and 3) recent demonstration of being cost-effective from a societal perspective, the use of CAC testing remains to be limited due to the lack of consensus on guidelines and continued resistance by payers to reimburse costs (3).
Discussions on the appropriate future roles of emerging CV imaging modalities can be better facilitated when examined in the context of our health care constraints considered above. Fluorodeoxyglucose positron emission tomography (FDG-PET) imaging with its ability to capture the differential rate of tissue glycolysis is an established tool in clinical oncology for estimating tumor activity and for detection of occult infection in inflamed tissues. The potential utility of FDG-PET imaging to complement current CV imaging tools in humans rapidly progressed from observation of heightened PET activity 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 role of FDG-PET/computed tomography (CT) in demonstrating the therapeutic antiatherosclerotic efficacy of proven treatments as well evaluating novel pharmacological agents for these purposes has added significant value to drug development processes. In recent years, investigators pointed out that arterial inflammation noted on routine FDG-PET CT scans performed in active cancer patients and survivors can enhance our ability to predict subsequent CV events in this vulnerable population (5).
In the current study in this issue of iJACC, Moon et al. (6) demonstrated that the prognostic value derived from measuring carotid arterial FDG extends to individuals free of established cancer or CV disease. The study investigators critically assessed the value of measuring the average FDG uptake of both carotid arteries normalized to the venous blood in nearly 1,000 asymptomatic individuals who underwent PET/CT for cancer screening. Overall, this was a low-risk population, with only 19 events (1.7%) noted in a mean follow-up of 4 years, notably half of them were anginal rather than atherothrombotic in nature. Two-thirds of events occurred in one-third of participants with the highest FDG uptake in carotid vessels. Surprisingly, as highlighted in Figure 1, even among those with the highest vessel wall FDG uptake, which may indicate plaque vulnerability, no events were noted in the first 2 years, with the majority of them occurring 4 years into the follow-up. This observation slightly conflicts with findings from Figuero et al. (7) who noted that those with elevated large arterial inflammation signals on PET were more likely to experience near-term CV disease. Irrespectively, robust statistical metrics used in the study demonstrated independent predictive value from arterial wall PET activity measurement beyond traditional risk factors and carotid intima-media thickness, an established surrogate for atherosclerotic disease burden.
These encouraging results add to the increasing recognition of potential predictive value of FDG-PET detection of inflammation for future adverse cardiac events. However, one needs to ask what is this added information worth? Would the results influence our stakeholders to adopt FDG-PET for risk assessment? Despite the promising results, the translational potential of FDG-PET for this specific purpose in an asymptomatic population, in my humble view, is limited. Among many considerations, one needs to take into account the significant cost, major radiation exposure, and lack of comparative data with more established imaging risk stratification tools such as CAC testing. Future research in this area needs to consider these issues in study designs. However, are there any clinical scenarios well suited for predicting CV risk with FDG-PET testing? Based on the current and recent studies, we are optimistic that significant information can be derived if additional measurement of arterial activity becomes a standard of care of those in whom FDG-PET imaging is routinely performed. This is a situation where clear value is added in how we can manage our patients without additional costs or radiation exposure.
Considering our stakeholders’ demand for an accelerated drive toward value-based health care delivery, investigations that does not seek opportunities beyond mere risk prediction will unfortunately have limited impact. So how do we navigate these challenges? For guidance, we need not look beyond the fantastic blueprint provided by the editors of iJACC, reminding us that CV imaging research needs concerted efforts to move beyond assessment of accuracy and prediction (2). These recommendations persuasively highlight practical steps for developing definitive evidence for any given modality with goals to improve “end results.” Encouragingly, comparative effectiveness research goals in the current era are not narrowly focused on realizing a reduction in clinical events, but also include additional worthy targets such as clarifying the role of CV imaging in the optimal management protocols for physicians, appropriate resource allocation for providers, and, more importantly, facilitating informed choices for our patients.
The challenges highlighted by a lack of clear downstream implications as noted in the current study are not limited to this specific situation or imaging modality. Each year, hundreds of CV imaging research studies continue to frame the question “does it improve risk prediction?” despite the fact that this knowledge will less likely cater to the broader health care needs. This singular approach in the past may have limited our ability to unlock the true value of CV imaging by not focusing on relevant research addressing our more urgent needs. This is not meant to discourage risk prediction research, but to redirect our energies so that we can place a higher value on evidence that needs to be generated. We acknowledge that these prediction specific investigations have played a pivotal role in clarifying pathophysiological disease mechanisms, disease specific associations, and risk among different clusters; however, it is worth contemplating whether it is time to shift our goals. This will not be an easy task and will require a major cultural shift. More importantly, we will have to rely on stakeholder consensus for defining ‘rational’ research that will cater to their specific needs. The entire CV imaging investigation community will be better served if we demand a greater return of investment by asking, “Is there anyone who would do something differently because of the results of the research?” (1).
↵∗ Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Dr. Nasir is on the Advisory Board of Quest Diagnostic; and is a consultant for Regeneron.
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