Original Article
Influence of 99mTc-tetrofosmin SPECT myocardial perfusion imaging on the prediction of future adverse cardiac events

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Abstract

Background

The impact of myocardial perfusion imaging (MPI) on prediction of risk for future cardiac events was examined by comparing predictions based on clinical information alone and in combination with MPI findings.

Methods and Results

A 3-cardiologist Cardiac Event Prediction Panel (CEPP) estimated three-year cardiac event (non-fatal MI; aborted sudden cardiac death; cardiac death) risk based on clinical data (C) for 371 subjects. CEPP repeated this estimation after receiving Summed Stress Scores (SSS) and Summed Rest Scores (SRS) from blinded reading of rest-stress 99mTc-tetrofosmin MPI SPECT studies (C + MPI). The C and C + MPI estimates were then compared with three-year and total event rates. MPI was normal (SSS ≤ 3) in 227 patients (61%), mildly abnormal (SSS 4-8) in 31 (8%), moderately abnormal (SSS 9-13) in 36 (10%), and severely abnormal (SSS > 13) in 77 (21%). Eighteen cardiac events occurred within 3 years and 33 occurred during a mean follow-up of 3.9 years. C + MPI estimates of low risk (<1-1.5%/year) identified significantly more patients who did not have events than C. C + MPI three-year event-rate predictions were more accurate than those made with C (P < .01). C + MPI categorization also provided better delineation of incremental risk on time-to-event analyses.

Conclusions

99mTc-tetrofosmin MPI single photon emission computed tomography (SPECT) findings significantly improve accuracy of cardiac event rate prediction compared to those based on clinical information alone.

Introduction

The diagnostic value of myocardial perfusion imaging (MPI) for the assessment of functional severity of coronary artery disease (CAD) is well established in clinical practice.1, 2, 3, 4 MPI also provides important prognostic information, with the extent and severity of abnormalities on MPI allowing stratification of patients for future risk of adverse cardiac events. Numerous large studies have shown progressively greater incidence of myocardial infarction (MI), cardiac death, or need for revascularization with increasing size and severity of MPI defects.1,4, 5, 6, 7, 8 Conversely, normal MPI is associated with a low risk of future cardiac events.1,9,10 Even in the presence of CAD, patients with normal MPI have a lower incidence of adverse cardiac events compared to those with perfusion abnormalities.11,12

Several models have been developed for predicting the risk for future adverse cardiac events in patients with known or suspected CAD.13, 14, 15 These models are based on long-term, population-based observational studies and take into consideration the symptoms of angina, age, gender, body mass index, serum lipids, and other risk factors for CAD. While MPI is commonly used in clinical practice for adverse event risk assessment and treatment planning, the results of MPI have generally been investigated in terms of their association with future patient status rather than as a predictive tool. Clinicians incorporate MPI findings into their overall patient evaluation but are rarely required to provide an explicit numerical estimation of future event risk as part of developing a therapeutic strategy.

The objective of this study was to examine the impact of 99mTc-tetrofosmin MPI single photon emission computed tomography (SPECT) findings on the assessment of risk for subsequent adverse cardiac events. This was done by comparing an expert panel’s predictions based on clinical information alone and clinical information in combination with MPI with actual event rates for pre-specified cardiac endpoints: non-fatal MI, aborted sudden cardiac death (SCD), and cardiac death during follow-up. Aborted SCD was included as an endpoint because of the increasing utilization of implanted cardioverter-defibrillators (ICD), which can prevent arrhythmic deaths that were reflected in prognostic studies performed prior to widespread use of these devices for primary prevention.

Section snippets

Patient Population

This study examined outcomes in subjects who participated in three prospective Phase 3 research trials involving rest-stress 99mTc-tetrofosmin SPECT MPI between October 2000 and March 2002. Six hundred and fifty-five subjects with known or suspected CAD had 99mTc-tetrofosmin MPI SPECT perfusion imaging in the original trials: 319 (49%) undergoing pharmacological (dipyridamole or adenosine) stress and rest MPI, and 336 (51%) treadmill exercise and rest MPI. In order for a subject to be eligible

Results

Although follow-up data were collected for 406 subjects, 35 subjects were excluded from the analyses, 32 whose clinical data were incomplete (documenting status at a later date without information on earlier events) and three because of indeterminate results (no consensus) from the three image readers. Thirty-seven other subjects only had data to determine clinical status at <3 years post-MPI. Therefore, the population for the primary efficacy analysis, based on event rate estimates for the

Discussion

The results of this study show that the addition of MPI data significantly improves the prediction of adverse cardiac events in individual patients with known or suspected CAD, compared to that based upon clinical information alone. Addition of LVEF results from gated SPECT did not further improve cardiologists’ event prediction, most likely because the panel had already incorporated an expectation of the severity of LV dysfunction as part of the C + MPI assessment. The results of this study

Limitations

This study has a number of design and methodological limitations. Although the size of the population based on the original prospective studies was reasonable, the retrospective nature of the collection of follow-up information (this not having been envisioned in the original trial designs), especially the need to reconsent subjects, resulted in loss of more than a third of potential participants. This in turn resulted in the number of subjects included in the study and the number of outcome

Conclusions

In summary, the results of this study confirm numerous previous observational studies regarding the value of MPI SPECT results for defining low-risk cardiovascular patients. In spite of the modest number of patients in this study, the availability of data for a minimum of three years follow-up allowed achievement of results with statistical significance. Whereas the focus of MPI in clinical practice is usually on the diagnosis of CAD or ischemia, the results of this study reaffirm the

Acknowledgments

The authors would like to acknowledge the contribution of the following trial participants. Naomi Alazraki, MD, Atlanta VA Medical Center; Raye Bellinger, MD, Sacramento Heart & Vascular Research Center; Salvador Borges-Neto, MD, Duke University Medical Center; Veronica Covalesky, MD, Cardiology Consultants of Philadelphia; William Ganz, MD, Diagnostic Testing Group of Miami; Gary V. Heller, MD, PhD, Hartford Hospital; Ami E. Iskandrian, MD, The University of Alabama at Birmingham; Robert L.

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This study was performed by GE Healthcare.

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