The significance of transient ischemic dilation in the setting of otherwise normal SPECT radionuclide myocardial perfusion images

doi:10.1007/s12350-011-9343-6

Journal of Nuclear Cardiology

Volume 18, Issue 2, April 2011, Pages 220-229

https://doi.org/10.1007/s12350-011-9343-6 Get rights and content

Abstract

Background

Transient ischemic dilation (TID) in the setting of an abnormal SPECT radionuclide myocardial perfusion imaging (MPI) study is considered a marker of severe and extensive coronary artery disease (CAD). However, the clinical significance of TID and its association with CAD in patients with an otherwise normal MPI study is unclear.

Methods

From a database of patients who underwent MPI over a 9-year period, 96 without known cardiac history who had normal image perfusion patterns, and who underwent coronary angiography within 6 months, were identified. TID quantitative values were derived. To adjust for varying stress and image protocols, a TID index based on published threshold values was derived for each patient, with >1 considered as TID. We examined the relationship of TID to the presence/extent of CAD, and to a CAD prognostic index. TID was also correlated with patient survival. To address referral bias, survival in a separate cohort of 3,691 patients with a normal perfusion MPI who did not undergo angiography in the 6-month interval was correlated with the presence and severity of TID.

Results

For 28 (29.2%) patients with normal MPI perfusion patterns but with TID, there was no increased incidence of CAD, multivessel or left main disease, or a higher prognostic index compared with no TID. In addition, there was no increased mortality associated with TID in both the angiography cohort and in the patients who did not undergo immediate angiography.

Conclusions

TID in patients with an otherwise normal SPECT MPI study does not increase the likelihood of CAD, its extent or severity, and is not associated with worsened patient survival.

Introduction

Transient ischemic dilation (TID) of the left ventricle on a stress single-photon emission computed tomography (SPECT) radionuclide myocardial perfusion imaging (MPI) study is thought to reflect myocardial ischemia that is sufficiently severe and extensive to cause visually apparent LV enlargement on the post-stress relative to the post-rest images. Several pathophysiologic mechanisms have been proposed, including actual stress-induced transient cavity dilation,¹ a lack of subendocardial tracer uptake in the setting of extensive subendocardial ischemia without true anatomic cavity enlargement,² a stress induced decrease in LV systolic function from stunning that appears as TID in the summed SPECT images,³^,⁴ or perhaps various combinations of these. Regardless of the mechanism of the phenomenon, the presence of TID in patients with an abnormal MPI study has been shown to be a marker of severe and extensive CAD,¹^,5, 6, 7 and in a few studies to confer increased risk for cardiovascular events.8, 9, 10

Nevertheless, the significance of TID in patients with otherwise normal MPI images is not well understood as such patients have typically been excluded from investigative studies. One study did find an increased likelihood of a cardiac event in these patients, but most events were revascularization procedures rather than hard cardiac events, with therefore a potential bias from the image findings leading to the events rather than there being true increased patient risk.¹¹

Therefore, it remains unclear how best to approach patients with TID and otherwise normal SPECT images. While many people consider TID and normal SPECT to indicate a significant likelihood of balanced ischemia from multivessel coronary artery disease (CAD), to our knowledge there are no published manuscripts correlating TID as an isolated finding with the anatomic extent and severity of CAD. A recent editorial states that the finding of isolated TID is usually not associated with severe CAD and that it would not be appropriate to perform invasive coronary angiography on the basis of this observation alone, but then also suggests that in some clinical instances isolated TID could indicate high risk “balanced” ischemia.¹²

Therefore, to further investigate the significance of isolated TID on SPECT MPI, i.e., to specifically assess whether this SPECT image finding increases the likelihood of balanced ischemia from multivessel disease, we queried our nuclear cardiology database to find patients with normal perfusion images who underwent cardiac catheterization. We examined the relationship of the presence/absence and quantitative severity of TID to the extent/severity of CAD on coronary angiography and to patient survival. In addition, to account to some extent for catheterization referral bias, we assessed the survival of patients with normal perfusion images who did not undergo cardiac catheterization in relation to the presence/absence and quantitative severity of TID, with the reasoning being that the absence of a worsened prognosis suggests that balanced ischemia/multivessel disease was infrequent.

Section snippets

Study Population

The study patient selection process is detailed in Figure 1. To summarize, following IRB expedited review and approval, we reviewed a prospectively created database of over 20,000 consecutive patients who underwent stress radionuclide MPI at our institution between 2000 and 2009. We identified all patients without previously known cardiac history (no myocardial infarction, no coronary revascularization, no cardiomyopathy) who had normal or probably normal perfusion images on initial clinical

Patient Characteristics

Cohort 1 comprised a total of 96 patients. While one cannot say exactly why these patients with normal SPECT perfusion images were referred for cardiac catheterization within 6 months of nuclear testing, compared with the Cohort 2 patients who did not undergo cardiac catheterization in such close proximity to SPECT, the Cohort 1 patients more often had various clinical factors consistent with increased cardiac risk. These included a higher Diamond/Forrester pre-test likelihood of CAD.²²

Discussion

The presence of TID in patients with an abnormal SPECT MPI study is considered to be a marker of severe and extensive CAD that confers increased risk for cardiovascular events.¹^,5, 6, 7, 8, 9, 10 Such patients are therefore often referred for cardiac catheterization with intent to revascularize. However, despite the absence of clear data, such an approach is often extrapolated to patients who have TID in the presence of an otherwise normal MPI study, with these patients commonly also referred

Conclusions

The presence of TID in our cohort of patients with otherwise normal SPECT myocardial perfusion images did not predict extensive and severe CAD. In addition, the presence of TID in these patients did not increase the mortality risk when compared with those who did not have TID. Thus, the presence of TID as an isolated finding in stable patients with an otherwise normal SPECT MPI studies does not appear to indicate a need for invasive coronary angiography.

References (32)

IskandrianAS et al.
Left ventricular dilatation and pulmonary thallium uptake after single-photon emission computer tomography using thallium-201 during adenosine-induced coronary hyperemia
Am J Cardiol
(1990)
HungGU et al.
Relationship of transient ischemic dilation in dipyridamole myocardial perfusion imaging and stress-induced changes of functional parameters evaluated by Tl-201 gated SPECT
J Nucl Cardiol
(2005)
MazzantiM et al.
Identification of severe and extensive coronary artery disease by automatic measurement of transient ischemic dilation of the left ventricle in dual-isotope myocardial perfusion SPECT
J Am Coll Cardiol
(1996)
McClellanJR et al.
Prognostic importance of scintigraphic left ventricular cavity dilation during intravenous dipyridamole technetium-99m sestamibi myocardial tomographic imaging in predicting coronary events
Am J Cardiol
(1997)
LetteJ et al.
Long-term risk stratification with dipyridamole imaging
Am Heart J
(1995)
AbidovA et al.
Transient ischemic dilation ratio of the left ventricle is a significant predictor of future cardiac events in patients with otherwise normal myocardial perfusion SPECT
J Am Coll Cardiol
(2003)
AbidovA et al.
Transient ischemic dilation ratio: A universal high-risk diagnostic marker in myocardial perfusion imaging
J Nucl Cardiol
(2007)
BermanDS et al.
Incremental value of prognostic testing in patients with known or suspected heart disease: A basis for optimal utilization of exercise technetium-99 m sestamibi myocardial perfusion single-photon emission computed tomography
J Am Coll Cardiol
(1995)
BermanDS et al.
Comparative use of radionuclide stress testing, coronary artery calcium scanning, and noninvasive coronary angiography for diagnostic and prognostic cardiac assessment
Semin Nucl Med
(2007)
YoonAJ et al.
The effect of beta-blockers on the diagnostic accuracy of vasodilator pharmacologic SPECT myocardial perfusion imaging
J Nucl Cardiol
(2009)

McLaughlinMG et al.

Transient ischemic dilation: A powerful diagnostic and prognostic finding of stress myocardial perfusion imaging

J Nucl Cardiol

(2002)

SmelleyMP et al.

A hypertensive response to exercise is associated with transient ischemic dilation on myocardial perfusion SPECT imaging

J Nucl Cardiol

(2007)

HansenCL et al.

Comparison of pulmonary uptake with transient cavity dilation after exercise thallium-201 perfusion imaging

J Am Coll Cardiol

(1999)

WeissAT et al.

Transient ischemic dilation of the left ventricle on stress thallium-201 scintigraphy: A marker of severe and extensive coronary artery disease

J Am Coll Cardiol

(1987)

HestonTF et al.

Quantifying transient ischemic dilation using gated SPECT

J Nucl Med

(2005)

TakeishiY et al.

Dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging: A new marker of triple-vessel disease

Am Heart J

(1991)

Cited by (37)

Clinical phenotypes among patients with normal cardiac perfusion using unsupervised learning: a retrospective observational study
2024, eBioMedicine
Myocardial perfusion imaging (MPI) is one of the most common cardiac scans and is used for diagnosis of coronary artery disease and assessment of cardiovascular risk. However, the large majority of MPI patients have normal results. We evaluated whether unsupervised machine learning could identify unique phenotypes among patients with normal scans and whether those phenotypes were associated with risk of death or myocardial infarction.
Patients from a large international multicenter MPI registry (10 sites) with normal perfusion by expert visual interpretation were included in this cohort analysis. The training population included 9849 patients, and external testing population 12,528 patients. Unsupervised cluster analysis was performed, with separate training and external testing cohorts, to identify clusters, with four distinct phenotypes. We evaluated the clinical and imaging features of clusters and their associations with death or myocardial infarction.
Patients in Clusters 1 and 2 almost exclusively underwent exercise stress, while patients in Clusters 3 and 4 mostly required pharmacologic stress. In external testing, the risk for Cluster 4 patients (20.2% of population, unadjusted hazard ratio [HR] 6.17, 95% confidence interval [CI] 4.64–8.20) was higher than the risk associated with pharmacologic stress (HR 3.03, 95% CI 2.53–3.63), or previous myocardial infarction (HR 1.82, 95% CI 1.40–2.36).
Unsupervised learning identified four distinct phenotypes of patients with normal perfusion scans, with a significant proportion of patients at very high risk of myocardial infarction or death. Our results suggest a potential role for patient phenotyping to improve risk stratification of patients with normal imaging results.
This work was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health [R35HL161195 to PS]. The REFINE SPECT database was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health [R01HL089765 to PS]. MCW was supported by the British Heart Foundation [FS/ICRF/20/26002].
Do we need a new definition for post-stress reduction in LVEF beyond the numerical values?
2020, Journal of Nuclear Cardiology
Prognostic impact of TID in regadenoson MPI: Some patients and certain events
2016, Journal of Nuclear Cardiology
Predictors of high-risk coronary artery disease in subjects with normal SPECT myocardial perfusion imaging
2016, Journal of Nuclear Cardiology
While uncommon, normal stress SPECT myocardial perfusion imaging (MPI) can be seen in patients with high-risk coronary artery disease (CAD) by invasive coronary angiography (ICA).The predictors of high-risk CAD in patients with normal SPECT-MPI have not been described.
We studied 580 patients (age 64 ± 12 years, 49% men) without known CAD who underwent stress-gated SPECT-MPI [exercise (41%) or vasodilator (59%)] <2 months before ICA and had summed stress score (SSS) <4. High-risk CAD was defined as 3 vessels with ≥70% stenosis, 2 vessels with ≥70% stenosis including proximal left anterior descending, or left main with ≥50% stenosis. Obstructive non-high-risk CAD was defined by the presence of a ≥70% stenosis but without having other high-risk criteria. Tenfold cross-validated receiver operating characteristic (ROC) estimates were obtained to assess the predictors of high-risk CAD.
Forty-two subjects (7.2%) had high-risk CAD and 168 (29.0%) had obstructive non-high-risk CAD. Variables associated with high-risk CAD were pretest probability of CAD ≥66% (Odds ratio [OR] 3.63, 95% CI 1.6-8.3, P = .002), SSS > 0 (OR 7.46, 95% CI 2.6-21.1, P < 0.001), and abnormal TID (OR 2.16, 95% CI 1.0-4.5, P = 0.044). When substituted for TID, EF change was also predictive of high-risk CAD (OR 0.93, 95% CI 0.9-1.0, P = 0.023). The prevalence of high-risk CAD increased as the number of these predictors increased. In a sub-analysis of patients in whom quantitative total perfusion deficit (TPD) was available, TPD > 0 was also a predictor of high-risk CAD (OR 6.01, 95% CI 1.5-22.2, P = 0.011).
Several clinical, stress, and SPECT-MPI findings are associated high-risk CAD among patients with normal SPECT-MPI. Consideration of these factors may improve the overall assessment of the likelihood of high-risk CAD in patients undergoing stress SPECT-MPI.
Contemporary relevance of TID: Based on the company it keeps
2015, Journal of Nuclear Cardiology
Cardiac radionuclide imaging to assess patients with heart failure
2014, Seminars in Nuclear Medicine
Citation Excerpt :
Berman et al32 found that 17% of patients with a significant left main stenosis have totally normal SPECT image findings. Ancillary markers, such as transient ischemic (LV cavity) dilatation, can potentially identify situations of balanced ischemia in higher risk patients,33,34 but these may not be reliable.35,36 Alternatively, there is much current interest in using quantitative blood flow techniques such as coronary flow reserve (CFR) to overcome potential underestimation of ischemia or CAD.
Heart failure (HF) is a major problem, with a high prevalence, morbidity, mortality, and cost, and is expected to become more widespread. Radionuclide imaging currently plays an important role in evaluating these patients, with much potential for increased utility. Myocardial perfusion imaging (MPI) with radiotracers is commonly used to differentiate an ischemic from a nonischemic etiology of HF and cardiomyopathy. In some instances, MPI effectively distinguishes among these, but often, standard MPI is deficient in that a nonischemic cardiomyopathy can have focal defects in tracer uptake and coronary artery disease with global balanced ischemia can result in a normal-appearing perfusion pattern. Developments in measuring quantitative blood flow promise to provide a more accurate determination of HF etiology. If coronary artery disease is established, MPI has long established use for assessment of myocardial viability and identification of patients likely to benefit from revascularization. Although a recent multicenter trial substudy has questioned the benefits of viability imaging, specific limitations of this study must be balanced against previously demonstrated utility. At the same time, viability imaging may need to be directed more skillfully toward carefully selected patients. In patients with HF who are not candidates for revascularization, myocardial remodeling often leads to poor patient outcome. Newer nuclear analyses of myocardial shape and of dyssynchronous contraction or relaxation can risk stratify patients and may help guide therapy. Investigative molecular imaging techniques promise to better understand underlying pathophysiology and guide therapy on an individual basis. Finally, recent approval of a tracer for cardiac autonomic innervation imaging should greatly expand the use of radionuclide imaging in HF, potentially guiding proper use of life saving but expensive and high-risk mechanical therapies. Given the molecular basis of much of the pathophysiology of HF, the contribution of cardiac radionuclide imaging to improve patient care should increase.

View all citing articles on Scopus

: Presented in part at the American College of Cardiology 59th Annual Scientific Session, March 2010, Atlanta, GA.

View full text

Original ArticleThe significance of transient ischemic dilation in the setting of otherwise normal SPECT radionuclide myocardial perfusion images

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Study Population

Patient Characteristics

Discussion

Conclusions

Am J Cardiol

J Nucl Cardiol

J Am Coll Cardiol

Am J Cardiol

Am Heart J

J Am Coll Cardiol

J Nucl Cardiol

J Am Coll Cardiol

Semin Nucl Med

J Nucl Cardiol

J Nucl Cardiol

J Nucl Cardiol

J Am Coll Cardiol

Transient ischemic dilation of the left ventricle on stress thallium-201 scintigraphy: A marker of severe and extensive coronary artery disease

J Am Coll Cardiol

Quantifying transient ischemic dilation using gated SPECT

J Nucl Med

Dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging: A new marker of triple-vessel disease

Am Heart J

Original Article
The significance of transient ischemic dilation in the setting of otherwise normal SPECT radionuclide myocardial perfusion images