Major Achievements in Nuclear Cardiology
Prognosis in the era of comparative effectiveness research: Where is nuclear cardiology now and where should it be?

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Introduction

Since our last review of the prognostic accuracy of stress myocardial perfusion SPECT,1 numerous advances in the field have promulgated tremendous (and oft characterized as excessive) growth in the utilization of nuclear cardiology services over the past few decades.2, 3, 4 The overall procedural utilization for stress myocardial perfusion imaging (MPI) reached its height in ~2008 with over 10 million procedures performed and Medicare expenditures in excess of $1 billion.3 Although many have focused culpability for growth on high reimbursement levels, the published evidence base also figured prominently in supporting healthcare coverage decisions and promoting utilization. Figure 1 plots the relationship between publications on nuclear cardiology and Medicare payments to physicians for stress MPI.

Most health policy experts agree that the practice of unconstrained imaging utilization that occurred in the last several decades was unsustainable.4,5 Additionally, the introduction and assimilation of new technology (without comparative information) has been identified as a dominant factor in the high costs of healthcare.6 This dramatic growth, with rates of increase that often exceeded 20% per annum,7,8 resulted in a number of healthcare policy initiatives aimed at cost containment including reimbursement cuts (by 30% or more) and prior authorization programs which has largely halted utilization growth in the field of nuclear cardiology. Recently, Medicare reported a nearly 18% decline in payments to physicians for stress MPI from 2009 to 2010.9

Advocacy and quality experts now call for comparative effectiveness research (CER) that compares nuclear cardiology procedures with different diagnostic strategies (including no testing options).3,4,10 The unfolding of novel medical delivery system options in healthcare reform will likely include a greater focus on patient-centeredness and efficient coordination and quality of care.11 For nuclear cardiology, the essence of this is to reduce or eliminate unwarranted testing while maintaining high quality care (i.e., the concept that “less is more”).12 Importantly, a greater evidence base of high quality research can only serve to support utilization within a given indication and create a sustainable practice for the field of nuclear cardiology.

The purpose of the current review is to provide an update on the evidence with stress MPI in patients with suspected and known coronary artery disease (CAD) published since 2004 and how this evidence has evolved to change our understanding of risk-based decision making. Moreover, we will also discuss gaps in research that could help to facilitate patient-centered imaging. It is also important to note that much of the focus of our prior review remains valid today and that the current report is an update on contemporary concepts in risk stratification with stress MPI.

Section snippets

The Role of Clinical Practice Guidelines and Appropriate Use Criteria (AUC) in Evidentiary Standards

Each day as a patient is referred for MPI, a physician must garner approval for the procedure through a Radiology Benefit’s Manager and justify the use of this procedure. On the part of private payers, there has been a strong focus on justification for cardiovascular imaging use that prompted the development of the American College of Cardiology Foundation’s (ACCF) AUC which now includes several documents on both coronary computed tomographic angiography (CCTA) and stress radionuclide MPI.13,14

Advances in Prognostic Accuracy Knowledge

Since our last review,1 an abundance of evidence has been published on the prognostic accuracy of stress MPI including several recent reviews on risk stratification.24, 25, 26, 27 Over the last two decades, much of the focus of research was aimed at creating larger and larger registries with validation across multiple centers and publishing evidence in unique patient subsets.28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 Much of the recent evidence in novel patient subgroups was

Normal MPI

The early and unfolding evidence base for a normal stress MPI reported a low risk of major adverse cardiac events averaging <1% annual risk.42, 43, 44, 45, 46, 47, 48 As this evidence has become more mature, we realized that within this average annual risk, there was significant variability that was driven by the degree of patient comorbidity and, more recently documented, by the burden of atherosclerosis (i.e., coronary artery calcification). Such that, for those patients with significant

Stress-Only SPECT Imaging

The growth in utilization has prompted a focus on radiation safety and not only on justification for appropriate use but also optimizing radiation dose reduction practices whenever possible.61, 62, 63, 64, 65, 66 Stress-only imaging, in the setting of normal findings, is one means to substantially reduce radiation exposure by ~1/3. This requires the use of initial stress imaging followed by selective rest imaging. Figure 3 reports the pooled annual event rate of 0.67% out of 10,436 patients

Abnormal MPI

The evidence continues to unfold that not only abnormal stress images (incorporating both ischemic and fixed defects) are highly prognostic but also that the burden of ischemia and the resting perfusion abnormalities are also highly predictive of patient outcome.25,34,40,42, 43, 44,46,50,51,72, 73, 74, 75, 76, 77 In one recent report, the underlying burden of resting perfusion abnormalities augmented the cardiac event risk observable with more extensive and severe ischemia.51 In the setting of

Heart Rate Change with Vasodilator Stress

In addition to perfusion defects and LV function, novel predictors of risk have been derived from stress MPI over the last few years. Perhaps the most notable is the change in heart rate during vasodilator stress.108 Since the activation of adenosine receptors cause a direct stimulation of the autonomic nervous system and a resultant increase in heart rate, a blunted heart rate response to adenosine, dipyridamole, or regadenoson can be used to detect the presence of cardiac autonomic

Augmenting MPI with Computed Tomographic Imaging Results—Hybrid Imaging Techniques

There have been numerous investigations over the role of sequential testing using index coronary artery calcium scoring followed by stress MPI.74,113, 114, 115 In a recent meta-analysis, the frequency of inducible ischemia increased modestly for patients with detectable CAC (13%) but was higher (20%-25%) for patients with significant CAC ≥ 100-400.113 In a series of 695 intermediate likelihood patients undergoing both CAC scoring and stress Rb-82 PET, adjusted survival revealed a graded

Stress Myocardial Perfusion PET

More recently, there has been substantive growth in the utilization of stress Rb-82 myocardial perfusion PET; which has reduced radiation exposure estimated at ~3 mSv (as compared to ~12 mSv for SPECT).61,66,123,124 A number of reports have been published on prognosis with stress Rb-82 myocardial perfusion PET and were evaluated in a meta-analysis.101,125, 126, 127, 128, 129, 130, 131 Figure 5 reports the results from the published reports revealing a summary RR ratio that was elevated 5.1-fold

Does MFR Add to Risk Stratification?

A major benefit to the application of PET imaging is the ability to quantify myocardial blood flow. And, in the setting of normal or abnormal myocardial perfusion findings, there may be an additional incremental value in knowledge of altered MFR. The incremental value of stress-induced alterations in myocardial blood flow have been the focus of recent published research.16,24,25,126,133 When pooling the event-free survival from three series including a total of 1,245 patients, the overall

Recent Randomized Trial Evidence with Stress MPI

There are a growing number of randomized trials where MPI was a central portion of the ischemia assessment. Over the next few sections, we will cover a number of published and upcoming randomized trials that deal with comparisons of functional stress imaging with nuclear cardiology as compared to other diagnostic imaging modalities and including no testing options.

First, the Detection of Ischemia in Asymptomatic Diabetics (DIAD) trial was a randomized trial of 1,123 asymptomatic individuals

Comparative Accuracy—Where is the Data?

The focus on quality has led to the surge in interest in the development of comparative effectiveness evidence to guide decision making with regards to optimal diagnostic testing choices.148,149 This is particularly important for moderately expensive procedures such as stress SPECT or PET MPI where cost efficiencies may be realized for other less expensive procedures, such as with treadmill testing or stress echocardiography.

For cardiac imaging, there are a number of randomized trials which

Gaps in the Evidence—What Do We Need to Drive Effective Use?

A simple response to this question is that we need additional CER to more clearly define the value of stress nuclear cardiology procedures when compared to alternative approaches and to define a pathway for sustainable practices within a given set of indications. The area that has unfolded as a leading set of indications has to do with the value of functional imaging in the high risk patient including patients with stable ischemic heart disease; largely based on the expansive observational77,86,

Defining Effectiveness Research for Nuclear Cardiology (Figure 8)

The focus of this review was to highlight the evidence on risk stratification with stress MPI and, particularly, to update this information from our prior review that was published in 2004.1 In addition to the magnitude and expansiveness of this literature base on prognostic accuracy with nuclear cardiology, there has been an evolution in thought with regards to the changing terminology as well as the vital importance of other factors taken in concert with risk stratification. Now, the

Conclusions

Readers of this review may note the comprehensiveness of this subject since our first publication in 2004.1 So much so, that we had to further refine the presentation of the evidence to that dealing (largely) with stable ischemic heart disease evaluation for risk stratification purposes. However, the field of effectiveness research is rapidly evolving and there is a greater demand on the part of the cardiology and payer community for cardiac imaging to be held to higher and higher standards in

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    An erratum to this article can be found at http://dx.doi.org/10.1007/s12350-012-9605-y.

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