The Significance of Transient Ischemic Dilation in the Setting of Otherwise Normal SPECT Radionuclide Myocardial Perfusion Images

OBJECTIVES: 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.

PMID: 21327596

Cancer Risk Related to Low-Dose Ionizing Radiation from Cardiac Imaging in Patients After Acute Myocardial Infarction

OBJECTIVES: Patients exposed to low-dose ionizing radiation from cardiac imaging and therapeutic procedures after acute myocardial infarction may be at increased risk of cancer.

METHODS:  Using an administrative database, we selected a cohort of patients who had an acute myocardial infarction between April 1996 and March 2006 and no history of cancer. We documented all cardiac imaging and therapeutic procedures involving low-dose ionizing radiation. The primary outcome was risk of cancer. Statistical analyses were performed using a time-dependent Cox model adjusted for age, sex and exposure to low-dose ionizing radiation from noncardiac imaging to account for work-up of cancer.

RESULTS: Of the 82 861 patients included in the cohort, 77% underwent at least one cardiac imaging or therapeutic procedure involving low-dose ionizing radiation in the first year after acute myocardial infarction. The cumulative exposure to radiation from cardiac procedures was 5.3 milli Sieverts (mSv) per patient-year, of which 84% occurred during the first year after acute myocardial infarction. A total of 12 020 incident cancers were diagnosed during the follow-up period. There was a dose-dependent relation between exposure to radiation from cardiac procedures and subsequent risk of cancer. For every 10 mSv of low-dose ionizing radiation, there was a 3% increase in the risk of age- and sex-adjusted cancer over a mean follow-up period of five years (hazard ratio 1.003 per milliSievert, 95% confidence interval 1.002-1.004).

CONCLUSIONS: Exposure to low-dose ionizing radiation from cardiac imaging and therapeutic procedures after acute myocardial infarction is associated with an increased risk of cancer.

PMID: 21324846

Positron Emission Tomography Measurement of Periodontal (18)F-Fluorodeoxyglucose Uptake is Associated With Histologically Determined Carotid Plaque Inflammation

OBJECTIVES: This study aimed to test the hypothesis that metabolic activity within periodontal tissue (a possible surrogate for periodontal inflammation) predicts inflammation in a remote atherosclerotic vessel, utilizing (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging.  Several lines of evidence establish periodontal disease as an important risk factor for atherosclerosis. FDG-PET imaging is an established method for measuring metabolic activity in human tissues and blood vessels.

METHODS: One hundred twelve patients underwent FDG-PET imaging 92 ± 5 min after FDG administration (13 to 25 mCi). Periodontal FDG uptake was measured by obtaining standardized uptake values from the periodontal tissue of each patient, and the ratio of periodontal to background (blood) activity was determined (TBR). Standardized uptake value measurements were obtained in the carotid and aorta as well as in a venous structure. Localization of periodontal, carotid, and aortic activity was facilitated by PET coregistration with computed tomography or magnetic resonance imaging. A subset of 16 patients underwent carotid endarterectomy within 1 month of PET imaging, during which atherosclerotic plaques were removed and subsequently stained with anti-CD68 antibodies to quantify macrophage infiltration. Periodontal FDG uptake was compared with carotid plaque macrophage infiltration.

RESULTS: Periodontal FDG uptake (TBR) is associated with carotid TBR (R = 0.64, p < 0.0001), as well as aortic TBR (R = 0.38; p = 0.029). Moreover, a strong relationship was observed between periodontal TBR and histologically assessed inflammation within excised carotid artery plaques (R = 0.81, p < 0.001).

CONCLUSIONS: FDG-PET measurements of metabolic activity within periodontal tissue correlate with macrophage infiltration within carotid plaques. These findings provide direct evidence for an association between periodontal disease and atherosclerotic inflammation.

PMID: 21329844

Prognostic Value of Cardiac Hybrid Imaging Integrating Single-Photon Emission Computed Tomography With Coronary Computed Tomography Angiography

OBJECTIVES:  Although cardiac hybrid imaging, fusing single-photon emission computed tomography (SPECT) myocardial perfusion imaging with coronary computed tomography angiography (CCTA), provides important complementary diagnostic information for coronary artery disease (CAD) assessment, no prognostic data exist on the predictive value of cardiac hybrid imaging. Hence, the aim of this study was to assess the prognostic value of hybrid SPECT/CCTA images.

PMID: 21320906

Appropriate Use Criteria for Stress Single-Photon Emission Computed Tomography Sestamibi Studies: A Quality Improvement Project

OBJECTIVES: We previously reported the application of the 2005 American College of Cardiology Foundation appropriate use criteria for stress single-photon emission computed tomography (SPECT) imaging to patients at Mayo Clinic (Rochester, MN) in 2005 and 2006. A subsequent internal quality improvement project focused on physician education in an attempt to reduce the rate of inappropriate SPECT studies.

METHODS: Our 2008 physician education effort, focused on 4 specific indications that accounted for 88% of the inappropriate SPECT studies, included a presentation at medical grand rounds, a publication in the staff newsletter, meetings with physician administrators, and focused presentations to departments/divisions with many ordering physicians. We then remeasured the appropriateness of SPECT studies using previously published methods.

RESULTS: The general categories of study indications, eg, after revascularization, were similar in 273 SPECT patients in 2008 and in our 2005 (n=284) and 2006 (n=284) cohorts. There was a trend suggesting a change in the overall classification of appropriateness over time (P=0.08) and a significant change in the rate of inappropriate studies over time (P=0.018). Inappropriate studies decreased from 14.4% in 2005 to 7.0% in 2006 before initiation of the quality improvement project. After completion of the quality improvement project, inappropriate studies increased to 11.7% (P=0.06). The 95% confidence limits for the 4.7% increase in inappropriate studies after the quality improvement project included a decrease of 0.2% and an increase of 9.6%.

CONCLUSIONS: This quality improvement project, focused on feedback, physician education, and remeasurement, did not reduce the rate of inappropriate stress SPECT studies in a single academic medical center. Similar limited interventions focused on physician education alone may have limited benefit. More extensive intervention may be necessary to improve the quality of care with appropriateness criteria.

PMID: 21262995

Ionizing Radiation Exposure to Patients Admitted With Acute Myocardial Infarction in the United States

OBJECTIVES: Invasive and noninvasive cardiovascular imaging is beneficial in the care of patients admitted with acute myocardial infarction. Little is known about patients’ cumulative radiation exposure.

METHODS: All patients admitted with an acute myocardial infarction to any of 49 University HealthSystem Consortium member hospitals from 2006 to 2009 were reviewed for inpatient procedures involving ionizing radiation that included chest radiograph, computed tomogram scans, radionuclide imaging, diagnostic cardiac catheterization, and percutaneous coronary intervention. The average cumulative effective radiation dose per patient was estimated on the basis of published typical effective radiation doses for imaging procedures.

RESULTS: Patients (n=64 071) admitted for acute myocardial infarction had a median age of 64.9 years. A total of 276 651 procedures involving ionizing radiation were performed during the study period, a median of 4.3 procedures per patient per admission. The majority of patients had invasive catheterization (77%), followed by computed tomogram scans (52%), mostly body examinations. The median cumulative effective radiation dose delivered was 15.02 mSv per patient per acute myocardial infarction admission. Postprocedural bleeding was a significant predictor of radiation exposure (odds ratio, 2.01; 95% confidence interval, 1.85 to 2.18), together with postprocedural mechanical complications resulting from device implantation (odds ratio, 2.86; 95% confidence interval, 2.61 to 3.13). Patients with higher underlying clinical complexity (defined by severity of illness scores) had higher radiation exposure and higher mortality (P<0.0001). There was also significant geographic variation in radiation exposure; patients in New England received the lowest cumulative exposure (odds ratio, 0.78; 95% confidence interval, 0.74 to 0.81).

CONCLUSIONS: Acute myocardial infarction inpatients are exposed to an approximate median radiation dose of 15 mSv. This exposure is a result of multiple cardiovascular and noncardiovascular procedures. Efforts should be made to understand the risks and benefits of radiation exposure per episode of care for acute myocardial infarction.

PMID: 21060076

Assessment of Myocardial Ischaemia and Viability: Role of Positron Emission Tomography

In developed countries, coronary artery disease (CAD) continues to be a major cause of death and disability. Over the past two decades, positron emission tomography (PET) imaging has become more widely accessible for the management of ischemic heart disease. Positron emission tomography has also emerged as an important alternative perfusion imaging modality in the context of recent shortages of molybdenum-99/technetium-99m ((99m)Tc). The clinical application of PET in ischaemic heart disease falls into two main categories: first, it is a well-established modality for evaluation of myocardial blood flow (MBF); second, it enables assessment of myocardial metabolism and viability in patients with ischaemic left ventricular dysfunction. The combined study of MBF and metabolism by PET has led to a better understanding of the pathophysiology of ischaemic heart disease.

While there are potential future applications of PET for plaque and molecular imaging, as well as some clinical use in inflammatory conditions, this article provides an overview of the physical and biological principles behind PET imaging and its main clinical applications in cardiology, namely the assessment of MBF and metabolism.

PMID: 20965888

Gate-Keeper to Coronary Angiography: Comparison of Exercise Testing, Myocardial Perfusion SPECT and Individually Tailored Approach For Risk Stratification

OBJECTIVES: We aimed to evaluate the differences between exercise testing (ET), myocardial perfusion SPECT (MPS) and a combination of ET and MPS based risk assessment as outlined by the guidelines with respect to their “gate-keeper” role to coronary angiography (cath) and the associated diagnostic procedural costs if prognostic considerations, as those proposed by the current guidelines and the recent literature, were taken into account.

METHODS: The Duke-score and the summed difference score (SDS; extent of ischemia) were assessed in 955 consecutive patients referred for MPS combined with ET. According to the guidelines and the available literature, three different algorithms for risk stratification were retrospectively applied: (1) ET based risk stratification and cath if intermediate or high risk Duke-score; (2) MPS based risk stratification and cath if SDS ≥ 8; (3) combined approach with ET as first step and MPS in case of intermediate risk Duke-score. A cath would have been suggested in every patient with either high risk Duke-score or SDS ≥ 8 in patients with intermediate risk Duke-score.

RESULTS: The referral rate to cath was 27% according to the ET alone, 13% using MPS, and finally 12% applying the combined risk stratification. The cost of the diagnostic work-up including cath were: 615<euro>, 1’299<euro>, and 598<euro> per patient, respectively. The coronary angiography referral rate widely depends on the diagnostic modality used for risk stratification and according to the referral criteria provided by the guidelines.

CONCLUSIONS: In the present study, the use of a stress imaging modality (MPS) and published prognostic data was associated with a lower referral rate to cath as compared to exercise testing alone and thus underlines the advantage of a risk based approach applying stress imaging in patients with intermediate risk Duke-score.

PMID: 20411429

Cardiac Computed Tomography and Myocardial Perfusion Scintigraphy for Risk Stratification in Asymptomatic Individuals Without Known Cardiovascular Disease: A Position Statement of The Working Group on Nuclear Cardiology and Cardiac CT of the European Society of Cardiology

OBJECTIVES: Cardiovascular events remain one of the most frequent causes of mortality and morbidity worldwide. The majority of cardiac events occur in individuals without known coronary artery disease (CAD) and in low- to intermediate-risk subjects. Thus, the development of improved preventive strategies may substantially benefit from the identification, among apparently intermediate-risk subjects, of those who have a high probability for developing future cardiac events. Cardiac computed tomography and myocardial perfusion scintigraphy (MPS) by single photon emission computed tomography may play a role in this setting. In fact, absence of coronary calcium in cardiac computed tomography and inducible ischaemia in MPS are associated with a very low rate of major cardiac events in the next 3–5 years.

METHODS: Based on current evidence, the evaluation of coronary calcium in primary prevention subjects should be considered in patients classified as intermediate-risk based on traditional risk factors, since high calcium scores identify subjects at high-risk who may benefit from aggressive secondary prevention strategies. In addition, calcium scoring should be considered for asymptomatic type 2 diabetic patients without known CAD to select those in whom further functional testing by MPS or other stress imaging techniques may be considered to identify patients with significant inducible ischaemia.

RESULTS: From available data, the use of MPS as first line testing modality for risk stratification is not recommended in any category of primary prevention subjects with the possible exception of first-degree relatives of patients with premature CAD in whom MPS may be considered.

CONCLUCIONS: However, the Working Group recognizes that neither the use of computed tomography for calcium imaging nor of MPS have been proven to significantly improve clinical outcomes of primary prevention subjects in prospective controlled studies. This information would be crucial to adequately define the role of imaging approaches in cardiovascular preventive strategies.

PMID: 20630895

Cumulative Exposure to Ionizing Radiation from Diagnostic and Therapeutic Cardiac Imaging Procedures: A Population-Based Analysis

OBJECTIVES: The purpose of this study was to describe radiation exposure from cardiac imaging procedures over time in a general population. Cardiac imaging procedures frequently expose patients to ionizing radiation, but their contribution to effective doses of radiation in the general population is unknown.

METHODS: We used administrative claims to identify cardiac imaging procedures performed from 2005 to 2007 in 952,420 nonelderly insured adults in 5 U.S. health care markets. We estimated 3-year cumulative effective doses of radiation in millisieverts from these procedures We then calculated population-based annual rates of radiation exposure to effective doses 3 mSv/year (background level ofradiation from natural sources), >3 to 20 mSv/year, or >20 mSv/year (upper annual limit for occupational exposure averaged over 5 years).

RESULTS: A total of 90,121 (9.5%) individuals underwent at least 1 cardiac imaging procedure using radiation. Among patients who underwent 1 cardiac imaging procedures, the mean cumulative effective dose over 3 years was 16.4 mSv (range 1.5 to 189.5 mSv). Myocardial perfusion imaging accounted for 74% of the cumulative effective dose. Overall, 47.8% of cardiac imaging procedures were performed in physician offices; this proportion was higher for myocardial perfusion imaging (74.8%) and cardiac computed tomography studies (76.5%). The annual population-based rate of receiving an effective dose of >3 to 20 mSv/year was 89.0 per 1,000; and 3.3 per 1,000 for cumulative doses >20 mSv/year. Annual effective doses increased with age and were generally higher among men.

CONCLUSIONS: Cardiac imaging procedures lead to substantial radiation exposure and effective doses for many patients in the U.S.

PMID:

Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging and the Risk of Sudden Cardiac Death in Patients With Coronary Disease and Left Ventricular Ejection Fraction >35%

OBJECTIVES: The aim of this study was to determine whether single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is an effective method of risk stratification for sudden cardiac death (SCD) in patients with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) >35%. Most victims of SCD have an LVEF >35%.

METHODS: The study population included 4,865 patients with CAD and LVEF >35% who underwent gated SPECT MPI. We used Cox proportional hazard modeling to examine the relationship between patient characteristics and SCD.

RESULTS: The median age of the population was 63 years (25th, 75th percentile: 54, 71 years), and the median LVEF was 56% (25th, 75th percentile: 50%, 64%). The median follow-up for all patients was 6.5 years (25th, 75th percentile: 3.6, 9.3 years). During follow-up, there were 161 SCDs (3.3%). After multivariable adjustment, LVEF, the Charlson index, hypertension, smoking, antiarrhythmic drug therapy, and the summed stress score (SSS) were associated with SCD (all p < 0.05). For each 3-U increase in the SSS, the hazard ratio for SCD was 1.13 (95% confidence interval: 1.04 to 1.23). The addition of perfusion data to the clinical history and LVEF was associated with increased discrimination for SCD events (c-index 0.728). Risk stratification with a derived SPECT nomogram did not result in statistically significant net reclassification improvement (p = 0.26) or integrated discrimination improvement (p = 0.38).

CONCLUSIONS: Among patients with CAD and LVEF >35%, the extent of stress MPI perfusion defects is associated with an increased risk of SCD. Future large prospective studies should address the role of perfusion imaging in the identification of high-risk patients with LVEF >35% who might benefit from ICD implantation.

PMID: 19808541

The Vascular Biology of Atherosclerosis and Imaging Targets

The growing worldwide health challenge of atherosclerosis, together with advances in imaging technologies, have stimulated considerable interest in novel approaches to gauging this disease. The last several decades have witnessed a burgeoning in understanding of the molecular pathways involved in atherogenesis, lesion progression, and the mechanisms underlying the complications of human atherosclerotic plaques. The imaging of atherosclerosis is reaching beyond anatomy to encompass assessment of aspects of plaque biology related to the pathogenesis and complication of the disease. The harnessing of these biologic insights promises to provide a plethora of new targets for molecular imaging of atherosclerosis. The goals for the years to come must include translation of the experimental work to visualization of these appealing biologic targets in humans.

PMID: 20395349

Cost-Effective Diagnostic Cardiovascular Imaging: When Does it Provide Good Value for the Money?

OBJECTIVES: To summarize the results of all original cost-utility analyses (CUAs) in diagnostic cardiovascular imaging (CVI) and characterize those technologies by estimates of their cost-effectiveness.

METHODS: We systematically searched the literature for original CVI CUAs published between 2000 and 2008. Studies were classified according to several variables including anatomy of interest (e.g. cerebrovascular, aorta, peripheral) and imaging modality under study (e.g. angiography, ultrasound). The results of each study, expressed as cost of the intervention to number of quality-adjusted life years saved ratio (cost/QALY) were additionally classified as favorable or not using $20,000, $50,000, and $100,000 per QALY thresholds. The distribution of results was assessed with Chi Square or Fisher exact test, as indicated.

RESULTS: Sixty-nine percent of all cardiovascular imaging CUAs were published between 2000 and 2008. Thirty-two studies reporting 82 cost/QALY ratios were included in the final sample. The most common vascular areas studied were cerebrovascular (n = 9) and cardiac (n = 8). Sixty-six percent (21/32) of studies focused on sonography, followed by conventional angiography and CT (25%, n = 8, each). Twenty-nine (35.4%), 42 (51.2%), and 53 (64.6%) ratios were favorable at WTP $20,000/QALY, $50,000/QALY, and $100,000/QALY, respectively. Thirty (36.6%) ratios compared one imaging test versus medical or surgical interventions; 26 (31.7%) ratios compared imaging to a different imaging test and another 26 (31.7%) to no intervention. Imaging interventions were more likely (P < 0.01) to be favorable when compared to observation, medical treatment or non-intervention than when compared to a different imaging test at WTP $100,000/QALY.

CONCLUSIONS: The diagnostic cardiovascular imaging literature has growth substantially. The studies available have, in general, favorable cost-effectiveness profiles with major determinants relating to being compared against observation, medical or no intervention instead of other imaging tests.

PMID: 20446040

Feasibility of FDG Imaging of the Coronary Arteries: Comparison Between Acute Coronary Syndrome and Stable Angina

OBJECTIVES: This study tested the hypothesis that fluorodeoxyglucose (FDG) uptake within the ascending aorta and left main coronary artery (LM), measured using positron emission tomography (PET), is greater in patients with recent acute coronary syndrome (ACS) than in patients with stable angina. Inflammation is known to play an important role in atherosclerosis. Positron emission tomography imaging with ¹⁸F-FDG provides a measure of plaque inflammation.

METHODS: Twenty-five patients (mean age 57.9 ± 9.8 years, 72% male, 10 ACS, and 15 stable angina) underwent cardiac computed tomographic angiography and PET imaging with ¹⁸F-FDG after invasive angiography. Images were coregistered, and FDG uptake was measured at locations of interest for calculation of target-to-background ratios (TBR). Additionally, FDG uptake was measured at the site of the lesion deemed clinically responsible for the presenting syndrome (culprit) by virtue of locating the stent deployed to treat the syndrome.

RESULTS: The FDG uptake was higher in the ACS versus the stable angina groups in the ascending aorta (median [interquartile ranges] TBR 3.30 [2.69 to 4.12] vs. 2.43 [2.00 to 2.86], p = 0.02), as well as the LM (2.48 [2.30 to 2.93] vs. 2.00 [1.71 to 2.44], p = 0.03, respectively). The TBR was greater for culprit lesions associated with ACS than for lesions stented for stable coronary syndromes (2.61 vs. 1.74, p = 0.02). Furthermore, the TBR in the stented lesions (in ACS and stable angina groups) correlated with C-reactive protein (r = 0.58, p = 0.04).

CONCLUSIONS: This study shows that in patients with recent ACS, FDG accumulation is increased both within the culprit lesion as well as in the ascending aorta and LM. This observation suggests inflammatory activity within atherosclerotic plaques in acute coronary syndromes and supports intensification of efforts to refine PET methods for molecular imaging of coronary plaques.

PMID: http://imaging.onlinejacc.org/cgi/content/abstract/3/4/388

18F-FDG PET Imaging of Myocardial Viability in an Experienced Center With Access to 18F-FDG and Integration With Clinical Management teams: The Ottawa-FIVE Substudy of the PARR 2 Trial

OBJECTIVES: (18)F-FDG PET may assist decision making in ischemic cardiomyopathy. The PET and Recovery Following Revascularization (PARR 2) trial demonstrated a trend toward beneficial outcomes with PET-assisted management. The substudy of PARR 2 that we call Ottawa-FIVE, described here, was a post hoc analysis to determine the benefit of PET in a center with experience, ready access to (18)F-FDG, and integration with clinical teams.

METHODS: Included were patients with left ventricular dysfunction and suspected coronary artery disease being considered for revascularization. The patients had been randomized in PARR 2 to PET-assisted management (group 1) or standard care (group 2) and had been enrolled in Ottawa after August 1, 2002 (the date that on-site (18)F-FDG was initiated) (n = 111). The primary outcome was the composite endpoint of cardiac death, myocardial infarction, or cardiac rehospitalization within 1 y. Data were compared with the rest of PARR 2 (PET-assisted management [group 3] or standard care [group 4]).

RESULTS: In the Ottawa-FIVE subgroup of PARR 2, the cumulative proportion of patients experiencing the composite event was 19% (group 1), versus 41% (group 2). Multivariable Cox proportional hazards regression showed a benefit for the PET-assisted strategy (hazard ratio, 0.34; 95% confidence interval, 0.16-0.72; P = 0.005). Compared with other patients in PARR 2, Ottawa-FIVE patients had a lower ejection fraction (25% +/- 7% vs. 27% +/- 8%, P = 0.04), were more often female (24% vs. 13%, P = 0.006), tended to be older (64 +/- 10 y vs. 62 +/- 10 y, P = 0.07), and had less previous coronary artery bypass grafting (13% vs. 21%, P = 0.07). For patients in the rest of PARR 2, there was no significant difference in events between groups 3 and 4. The observed effect of (18)F-FDG PET-assisted management in the 4 groups in the context of adjusted survival curves demonstrated a significant interaction (P = 0.016). Comparisons of the 2 arms in Ottawa-FIVE to the 2 arms in the rest of PARR 2 demonstrated a trend toward significance (standard care, P = 0.145; PET-assisted management, P = 0.057).

CONCLUSIONS: In this post hoc group analysis, a significant reduction in cardiac events was observed in patients with (18)F-FDG PET-assisted management, compared with patients who received standard care. The results suggest that outcome may be benefited using (18)F-FDG PET in an experienced center with ready access to (18)F-FDG and integration with imaging, heart failure, and revascularization teams.

PMID: 20237039