Major achievements in nuclear cardiology: IIIPrognostic value of gated myocardial perfusion SPECT
Section snippets
Estimating risk versus disease
Although the focus of the current review is the estimation of prognosis with gated myocardial perfusion SPECT, recent evidence has been synthesized to reveal that gated myocardial perfusion SPECT is a highly sensitive test for the detection of a critical stenosis.5 In a recent meta-analysis organized by the United Kingdom's National Institute of Clinical Excellence, diagnostic sensitivity for myocardial perfusion imaging was 87% (n = 2,971/3,425).5 Specificity was lower (73%; n = 772/1,055) but
SPECT risk markers serve as intermediate outcome measures
Thus a shift in publications from diagnostic to prognostic accuracy should be considered a tremendous advance to the field and has the benefit of coordinating outcome estimation with therapeutic randomized controlled trial data. For example, one of our greatest prognosticators in cardiovascular medicine is left ventricular ejection fraction, which is commonly estimated by gated SPECT and is inversely related to cardiac survival. Integrative management decisions can be effectively initiated
Risk thresholds
One of the clear benefits of using risk estimation is that it can be coordinated within population-based risk thresholds. We do know that the underlying risk in the population varies with a patient's pretest risk, such that patients without coronary disease have lower rates of coronary disease events than those with disease (ie, approximately 1% vs 2%, on average). Population risk in those without disease may be estimated by use of one of many global risk scores (eg, Framingham risk32). In a
Bayesian theory
As evidenced by the prior discussion, optimal candidate selection depends on an understanding of the underlying risk in any given patient group. Extending this reasoning one additional step, appropriate patient selection for nuclear imaging will guide the added or incremental value of imaging in any pretest risk cohort. That is, by integrating risk factor, age, and symptom data into a global risk score (eg, Framingham risk score, European risk score), a patient's pretest risk may be estimated
Defining the effectiveness of cardiac imaging principles of risk stratification
A critical step in evaluating the utility of an imaging test is its impact on patient outcome and alterations in patient management.37 The evaluation of a test's ability to risk-stratify individuals has been proposed as an alternative to the challenges of assessing diagnostic accuracy.38 For any given test, risk stratification may be used as a method for defining high- and low-risk cohorts where treatment is allocated to those in greatest need.8 Furthermore, the intensity of management is
Outcome measures
The broad range of outcome measures that are applicable to the use of risk stratification include (1) intermediate clinical outcomes (eg, disease detected, cardiac event predicted), (2) major adverse cardiovascular events (eg, survival rates), (3) cumulative effects of test-driven strategy (eg, life years saved), (4) patient assessment of a test's value (eg, quality of life, patient preferences), and (5) combined quantity- and quality-of-life years (eg, quality-adjusted life years, healthy-year
Defining the interactive nature of risk with predictive models
Risk stratification may be defined statistically as the relative risk ratio (often with 95% CIs), in which a high-risk cohort is calculated as the ratio of increased risk of events. Relative risk ratios indicate the x-fold increase in event risk in high- versus low-risk patients where a statistical increase is noted when the CIs do not include 1.0. As cardiovascular risk is often interactive, additive, or multiplicative, multivariable regression models help to define the independent
Defining the added value of SPECT
The supportive rationale for the use of imaging is that symptoms, established risk factors, physical examination, and functional status measures are often insensitive to disease states.51 SPECT's incremental value may be calculated by quantifying the amount of added information, often called the test's incremental value. In general, tests that provide more added information would be favored over those that have less prognostic content. Diagnosis costs can be high when tests add little value
Concepts in linking risk assessment to tailored medical intervention
SPECT imaging provides not only information about the physiologic significance of flow-limiting disease and left ventricular function but also a global estimation of risk for major adverse cardiac events. As this is the threshold for evidence-based practice, gated SPECT is the tool optimally suited to provide information to guide patient management decisions. This concept, in terms of evidence-based medicine, is called empiric risk stratification, in which optimal improvement in outcome is
Risk of events in patients with normal or low-risk findings
By definition, principles of risk stratification would define a cohort with improved outcome (ie, low risk) and exhibit a clear separation in risk between higher-risk subsets of the population. In the case of patients with normal perfusion findings, numerous studies over the past decade have reported uniformly low rates of major adverse cardiac outcomes. Table 1 details the current evidence in 19 published series on normal or low-risk myocardial perfusion SPECT.8, 33, 54, 55, 56, 57, 58, 59, 60
Risk of events in patients with abnormal myocardial perfusion SPECT results
In the setting of moderate-severely abnormal myocardial perfusion SPECT, rates of “hard” cardiac events, notably cardiac death and nonfatal myocardial infarction, increase logarithmically over and above patients with low-risk findings. As previously noted, the relative increase (ie, x-fold) in risk is commonly calculated by use of a relative risk ratio. On average, relative risk ratios are increased 5- to 7-fold, with the results being highly dependent on the available sample size.8 In larger
Risk of events by poststress measures of left ventricular function
Although nuclear cardiology has been capable of obtaining measures of left ventricular function by first-pass and gated techniques for a number of decades, today rest and poststress estimations of systolic function are frequently performed as gated SPECT imaging. Estimates of left ventricular dysfunction are perhaps one of our greatest known prognosticators in cardiovascular medicine. In this era of gated SPECT imaging, a number of recent reports have provided an estimate of the current
Integrative management approaches
One of the benefits of the wealth of evidence on prognosis with SPECT imaging is that the data can be easily integrated into risk-based patient management algorithms. There are several examples of risk-based algorithms that have been developed in certain patient cohorts. For example, a recent taskforce of the American Society of Nuclear Cardiology has published an evidence-based guideline for at-risk women focusing on selecting candidates who receive the greatest incremental value from referral
High-risk findings and high-risk patient subsets
A review of evidence suggests that high-risk findings on SPECT imaging include patients whose expected rate of major adverse cardiac events is 3% to 5% or more and patients with moderately to severely abnormal perfusion abnormalities, multivessel perfusion abnormalities, or a summed stress score greater than 8. Patients with a high-risk poststress left ventricular ejection fraction lower than 45% are at an elevated risk of major adverse cardiac events. Other high-risk markers include transient
Optimal referral candidates based on added risk effectiveness
Although this review has focused on risk assessment in suspected or known coronary disease, there are specific subsets of patients for whom risk assessment is particularly valuable, with abundant evidence, including diabetics,75, 81, 91, 107, 108 women,109, 110 and patients referred to pharmacologic stress imaging.53, 55, 63, 67, 68, 69, 71, 72, 75, 78, 80, 82, 83, 85, 92 Figure 4 depicts a synthesis of evidence on the prognostic value of myocardial perfusion SPECT by sex and diabetes
Future applications of outcomes assessment in nuclear cardiology
Although the paradigm of estimating risk has added tremendous value to the use of nuclear imaging in guiding patient management decisions, its concept is largely based on the principle of defining the natural history of myocardial perfusion and ventricular function abnormalities. That is, we have defined SPECT risk markers as being associated with major adverse event rates of 4.8% to 8.5% (25th to 75th percentile) per year.50, 53, 57, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75,
Conclusion
This review provides a synopsis of available evidence on the prognostic value of gated myocardial perfusion SPECT. The magnitude of this evidence provides substantial documentation as to the maturity of this modality. As reported in 39 peer-reviewed articles, there is a clear separation in risk of major adverse cardiac events between patients with low- and high-risk perfusion imaging results over the ensuing 2 to 4 years of follow-up. From a total of 69,655 patients (including duplicates), the
Acknowledgements
The authors have indicated they have no financial conflicts of interest.
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