Original Article
The diagnostic and prognostic value of near-normal perfusion or borderline ischemia on stress myocardial perfusion imaging

https://doi.org/10.1007/s12350-020-02375-yGet rights and content

Abstract

Background

Data on the diagnostic and prognostic value of subtle abnormalities on myocardial perfusion imaging (MPI) are limited.

Methods and results

In a retrospective single-center cohort of patients who underwent regadenoson SPECT-MPI, near-normal MPI was defined as normal left ventricular ejection fraction (LVEF ≥ 50%) and a summed stress score (SSS) of 1-3 vs SSS = 0 in normal MPI. Borderline ischemia was defined as normal LVEF, SSS = 1-3, and a summed difference score (SDS) of 1 vs SDS = 0 in the absence of ischemia. Coronary angiography data within 6 months from MPI were tabulated. Patients were followed for cardiac death (CD), myocardial infarction (MI), coronary revascularization (CR), and Late CR (LCR) [> 90 days post MPI]. Among 6,802 patients (mean age, 62 ± 13 years; 42% men), followed for a mean of 2.5 ± 2.1 years, 4,398 had normal MPI, 2,404 had near-normal MPI, and 972 had borderline ischemia. Among patients who underwent angiography within 6 months, obstructive (≥ 70% or left main ≥ 50%) CAD was observed at higher rates among subjects with near-normal MPI (33.5% vs 25.5%; P = .049) and those with borderline ischemia (40.5% vs 25.8%; P = .004). During follow-up, 158 (2.3%) CD/MI, 246 (3.6%) CR, and 150 (2.2%) LCR were observed. Near-normal MPI (SSS = 1-3), compared to normal MPI (SSS = 0), was not associated with a significant difference in the risk of the composite endpoint of CD/MI (Hazard ratio [HR], 1.21; 95% confidence interval [CI], .88-1.66; P = .243) or LCR (HR 1.28; CI .93-1.78; P = .130), but was associated with a significant increase in the risk of CR (HR 1.91; CI 1.49-2.46; P < .001). Borderline ischemia (SDS = 1), compared to no ischemia (SDS = 0), was not associated with a significant difference in the risk of CD/MI [HR 1.09; CI .70-1.69; P = .693], but was associated with a significant increase in the risk of CR (HR 5.62; CI 3.08-10.25; P < .001) and LCR (HR 2.98; CI 1.36-6.53; P = .006).

Conclusion

Near-normal MPI and borderline ischemia on SPECT-MPI provide no significant prognostic information in predicting hard cardiac events but are associated with higher rates of obstructive angiographic CAD and coronary revascularizations.

Introduction

Stress myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT) is among the most commonly used methods in the assessment and risk stratification of patients with known or suspected coronary artery disease (CAD).1,2 The prognostic value of SPECT-MPI has been extensively studied, and data indicate that an abnormal scan is associated with a multi-fold increase in the risk of major adverse cardiac events (MACE).3,4 Conventionally, a SPECT-MPI scan with a summed stress score (SSS) ≥ 4 is defined as abnormal and a summed difference score (SDS) ≥ 2 is considered to represent myocardial ischemia.5, 6, 7, 8 While an SSS and SDS of 0 represent a “completely” normal perfusion, less than “perfectly normal” scans with SSS of 1-3 or SDS of 1 are considered within normal limits.5,6 Regadenoson, a selective A2A adenosine receptor agonist, is the most commonly used stress agent with SPECT-MPI in the U.S., owing to its favorable safety and tolerability profile.9, 10, 11 The prognostic value of abnormal regadenoson MPI has been previously evaluated,4,8,12,13 but data on the significance of near-normal MPI (SSS = 1-3) or borderline ischemia (SDS = 1), with otherwise normal scan, are lacking. In this study, we aimed at investigating the prognostic value of near-normal MPI and borderline myocardial ischemia in patients undergoing regadenoson SPECT-MPI.

Section snippets

Design and patient population

We implemented a retrospective cohort study design. This investigation was a sub-analysis of the database generated from a previously published investigation assessing the prognostic significance of regadenoson induced ST-segment changes. Data from this cohort have been published elsewhere.4,14,15 Cardiology information system at Rush University Medical Center was queried for all patients who underwent a clinically indicated regadenoson-stress SPECT-MPI during the period from July 1, 2009

Results

Among the 6,802 patients included in the analysis, 4,398 had normal MPI (SSS = 0) and 2,404 had near-normal scan (SSS = 1-3). Baseline characteristics of study subjects are summarized in Table 1. Notably, the mean age was 61.9 ± 13.4 years and the majority were women (58.1%). Patients with near-normal MPI had significantly more comorbid conditions and higher mean BMI when compared to those with normal scan. The mean TID was similar between the two groups. Within the study cohort, 6,229 patients

Discussion

This is one of the largest studies to evaluate the diagnostic and prognostic value of near-normal MPI or borderline ischemia in otherwise normal MPI. We demonstrated that patients with near-normal MPI (SSS = 1-3) and borderline ischemia (SDS = 1) were more likely to be referred for invasive coronary angiography within 6 month of the index MPI and they had higher rates of obstructive CAD. We also demonstrated that near-normal MPI is associated with increased risk of CR, while borderline

Limitations

Our investigation has several limitations. First, the study is inherently limited by the retrospective, single-center design. Second, the study was limited to patients undergoing regadenoson vasodilator stress, which may limit its generalizability to patients undergoing exercise stress MPI. Third, the cause of death in some patients was determined using death certificates which are not always accurate. In addition, death certificates issued outside the state of Illinois could not be obtained,

New knowledge gained

In this study, we demonstrated that near-normal MPI and borderline ischemia, in otherwise normal scan, are associated with higher prevalence of obstructive CAD and a statistically significant increase of CR compared to “completely” normal MPI. Borderline ischemia was even associated with severe/extensive CAD and increased risk of LCR. It is reassuring, however, that subtle perfusion abnormalities were not associated with a significant difference in the risk of the primary “hard” endpoint of

Conclusions

Near-normal SPECT-MPI and borderline ischemia, in otherwise normal scan, are associated with higher prevalence of obstructive CAD and increased risk of coronary revascularizations. Discriminating near-normal MPI or borderline ischemia from a perfectly normal scan can further refine identification of obstructive CAD and risk stratification. Close clinical surveillance, aggressive medical management, and additional imaging evaluation may be considered in these patients.

Funding

The study was partially funded by Astellas Pharma Global Development (Northbrook, IL).

Disclosure

No personal conflicts of interest to be reported by any of the authors.

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All editorial decisions for this article, including selection of reviewers and the final decision, were made by guest editor Randall Thompson, MD.

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