Karen Y. Gulenchyn

Increasing benefit from revascularization is associated with increasing amounts of myocardial hibernation: a substudy of the PARR-2 trial.

OBJECTIVESnWe sought to determine: 1) whether F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) parameters identify high-risk patients who gain benefit from revascularization; 2) whether there is a cut point for such benefit; and 3) predictors of outcome in patients with severe left ventricular (LV) dysfunction due to coronary artery disease.nnnBACKGROUNDnPatients with ischemic LV dysfunction might benefit from revascularization but not without risk. The FDG PET imaging can detect viable myocardium that recovers after revascularization. In the PARR-2 (PET and Recovery Following Revascularization-2) trial, FDG PET imaging showed a nonsignificant trend for improved outcome compared with standard care. Understanding the predictors of outcome from this prospective trial should help better identify patients at risk and which patients most benefit from revascularization.nnnMETHODSnThis post hoc analysis included 182 patients with left ventricular ejection fraction (LVEF) <35% and coronary artery disease, being considered for revascularization work-up, and randomized to the PET arm of PARR-2. The primary outcome was a composite of cardiac death, myocardial infarction, or cardiac repeat hospital stay at 1 year.nnnRESULTSnThere is an interaction between PET mismatch and protocol revascularization such that higher mismatch, when combined with revascularization, yields fewer primary outcome events (p = 0.02). On the basis of adjusted Cox modeling, with reduced mismatch (<7%), the risk is not significantly different with or without revascularization. As mismatch increases above this mark, risk is reduced with revascularization. Increasing creatinine (for a 10-mumol/l increase: hazard ratio: 1.03, 95% confidence interval: 1.01 to 1.06, p = 0.010) is also associated with increased risk, whereas decreasing LVEF (for a 2% decrease: hazard ratio: 1.08, 95% confidence interval: 0.99 to 1.18, p = 0.087) trends toward an association with increased risk.nnnCONCLUSIONSnIn this post hoc analysis, patients with ischemic cardiomyopathy with larger amounts of mismatch have improved outcome with revascularization. Renal function was also an independent predictor of outcome. The FDG PET seems to define high-risk patients that gain benefit from revascularization. (PET and Recovery Following Revascularization [PARR 2]; NCT00385242).

CCS/CAR/CANM/CNCS/CanSCMR joint position statement on advanced noninvasive cardiac imaging using positron emission tomography, magnetic resonance imaging and multidetector computed tomographic angiography in the diagnosis and evaluation of ischemic heart disease – executive summary

BACKGROUNDnOver the past few decades, advanced imaging modalities with excellent diagnostic capabilities have emerged. The aim of the present position statement was to systematically review existing literature to define Canadian recommendations for their clinical use.nnnMETHODSnA systematic literature review to 2005 was conducted for positron emission tomography (PET), multidetector computed tomographic angiography and magnetic resonance imaging (MRI) in ischemic heart disease. Papers that met the criteria were reviewed for accuracy, prognosis data and study quality. Recommendations were presented to primary and secondary panels of experts, and consensus was achieved.nnnRESULTSnIndications for PET include detection of coronary artery disease (CAD) with perfusion imaging, and defining viability using fluorodeoxyglucose to determine left ventricular function recovery and/or prognosis after revascularization (class I). Detection of CAD in patients, vessel segments and grafts using computed tomographic angiography was considered class IIa at the time of the literature review. Dobutamine MRI is class I for CAD detection and, along with late gadolinium enhancement MRI, class I for viability detection to predict left ventricular function recovery. Imaging must be performed at institutions and interpreted by physicians with adequate experience and training.nnnCONCLUSIONSnCardiac imaging using advanced modalities (PET, multidetector computed tomographic angiography and MRI) is useful for CAD detection, viability definition and, in some cases, prognosis. These modalities complement the more widespread single photon emission computed tomography and echocardiography. Given the rapid evolution of technology, initial guidelines for clinical use will require regular updates. Evaluation of their integration in clinical practice should be ongoing; optimal use will require proper training. A joint effort among specialties is recommended to achieve these goals.

Is a Fixed Value for the Least Significant Change Appropriate

The least significant change (LSC) represents the smallest difference between successive measurements of bone mineral density (BMD) that can be considered to be a real change and not attributable to chance. The LSC is derived from same-day in vivo BMD precision measurements. Our first objective was to determine if the LSC differs between technologists. Our second objective was to determine if patient body size influenced the LSC. Each of 8 technologists measured same-day precision in groups of 30 patients for the lumbar spine and the total trochanter and neck regions of the proximal femur. At the spine, precision ranged from 0.008 to 0.011g/cm(2) and did not differ between technologists. Precision for the total region of the left proximal femur ranged from 0.006 to 0.016g/cm(2) and did differ between technologists. For the trochanter and neck regions, precision ranged from 0.008 to 0.013g/cm(2) for the former and from 0.010 to 0.020g/cm(2) for the latter, again, with inter-technologist differences. The LSC for the lumbar spine increased linearly from 0.022 to 0.031g/cm(2) when body mass index (BMI) increased from 19.5 to 31.3kg/m(2). In contrast, there was no discernable impact of BMI on the LSC for any of the proximal femur regions. The LSC at the spine is determined by the patient, whereas the LSC at the femur is determined by the technologist. Use of a single value for the LSC will lead to misinterpretations of the significance of BMD changes at both the spine and the proximal femur.

Characterization of 3D PET systems for accurate quantification of myocardial blood flow

Three-dimensional (3D) mode imaging is the current standard for PET/CT systems. Dynamic imaging for quantification of myocardial blood flow with short-lived tracers, such as 82Rb-chloride, requires accuracy to be maintained over a wide range of isotope activities and scanner counting rates. We proposed new performance standard measurements to characterize the dynamic range of PET systems for accurate quantitative imaging. Methods: 82Rb or 13N-ammonia (1,100–3,000 MBq) was injected into the heart wall insert of an anthropomorphic torso phantom. A decaying isotope scan was obtained over 5 half-lives on 9 different 3D PET/CT systems and 1 3D/2-dimensional PET-only system. Dynamic images (28 × 15 s) were reconstructed using iterative algorithms with all corrections enabled. Dynamic range was defined as the maximum activity in the myocardial wall with less than 10% bias, from which corresponding dead-time, counting rates, and/or injected activity limits were established for each scanner. Scatter correction residual bias was estimated as the maximum cavity blood–to–myocardium activity ratio. Image quality was assessed via the coefficient of variation measuring nonuniformity of the left ventricular myocardium activity distribution. Results: Maximum recommended injected activity/body weight, peak dead-time correction factor, counting rates, and residual scatter bias for accurate cardiac myocardial blood flow imaging were 3–14 MBq/kg, 1.5–4.0, 22–64 Mcps singles and 4–14 Mcps prompt coincidence counting rates, and 2%–10% on the investigated scanners. Nonuniformity of the myocardial activity distribution varied from 3% to 16%. Conclusion: Accurate dynamic imaging is possible on the 10 3D PET systems if the maximum injected MBq/kg values are respected to limit peak dead-time losses during the bolus first-pass transit.

Does FDG PET-Assisted Management of Patients With Left Ventricular Dysfunction Improve Quality of Life? A Substudy of the PARR-2 Trial

BACKGROUNDnPatients with left ventricular dysfunction whose management is directed by F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging may have a quality of life (QOL) benefit over standard care.nnnMETHODSnAmong 430 patients randomized in the PET and Recovery Following Revascularization (PARR)-2 trial to FDG PET-assisted management vs standard, QOL scores were obtained using the European Quality of Life-5 Dimensions (EQ-5D) in 427 patients at baseline (FDG PET n = 216; standard n = 211) and 355 patients at 12-month follow-up (FDG PET n = 184; standard n = 171). EQ-5D scores between FDG PET and standard arms were compared using mixed model repeated measures (MMRM). Subgroup analysis compared EQ-5D scores between patients in FDG PET who adhered to PET recommendations (Adherence) vs standard using MMRM. Interaction of revascularization with management was assessed using a general linear model.nnnRESULTSnA trend toward higher EQ-5D scores in FDG PET was observed (P = 0.056). Subgroup analysis showed a significant difference favouring adherence (P = 0.04). Higher QOL at 6 months for FDG PET (P = 0.02) and Adherence (P = 0.02) were observed. For revascularization, an interaction with management (FDG PET vs standard) for QOL was observed (6 months: P = 0.01; 12 months: P = 0.1); Adherence (6 months: P = 0.01; 12 months: P = 0.1).nnnCONCLUSIONSnFDG PET-directed management improves QOL, at least in the short-term and with adherence to recommendations. This may relate to revascularization, and may indicate better treatment selection using FDG PET.

Vertebral fracture prevalence in a referral population of 750 Canadian men and women

AIMnTo establish the prevalence of vertebral fracture (VF) in a representative sample of 750 Canadians and to examine the relationships between VF prevalence and bone mineral density (BMD) at the spine and proximal femur.nnnMATERIALS AND METHODSnX-ray-based dual-photon absorptiometry (DXA) was used to perform measurements of lumbar spine BMD, proximal femur BMD, and VF assessment (VFA).nnnRESULTSnTwo hundred and fifty-nine VFs were identified in 156 patients and the prevalence of unknown or unsuspected VF was 18.7%. For premenopausal women and for men, there was no difference in BMD at either the spine or the hip whether or not there was at least one VF. For postmenopausal women, BMD of the total region of the proximal femur was statistically lower (p < 0.001) in women with at least one VF whereas spine BMD only tended to be less (0.10 > p > 0.05). Proximal femur BMD was lower for postmenopausal women with more VF, while spine BMD was virtually unchanged as the number of VF increased. Neither spine nor hip BMD was lower for men with more VF. A strong association was observed in postmenopausal women between an age-dependent increase in VF prevalence and a reduction in femoral BMD. Such an association was not present in men.nnnCONCLUSIONnVFs are common, are often independent of either spine or hip BMD, and frequently go unnoticed. Therefore, VFA should be part of a routine assessment of fracture risk.

Treating the right patient at the right time: Access to cardiovascular nuclear imaging

Cardiovascular nuclear medicine uses agents labelled with radioisotopes that can be imaged with cameras (single-photon emission tomography [SPECT] or positron emission tomography [PET]) capable of detecting gamma photons to show physiological parameters such as myocardial perfusion, myocardial viability or ventricular function. There is a growing body of literature providing guidelines for the appropriate use of these techniques, but there are little data regarding the appropriate timeframe during which the procedures should be accessed. An expert working group composed of cardiologists and nuclear medicine specialists conducted an Internet search to identify current wait times and recommendations for wait times for a number of cardiac diagnostic tools and procedures, including cardiac catheterization and angioplasty, bypass grafting and vascular surgery. These data were used to estimate appropriate wait times for cardiovascular nuclear medicine procedures. The estimated times were compared with current wait times in each province. Wait time benchmarks were developed for the following: myocardial perfusion with either exercise or pharmacological stress and SPECT or PET imaging; myocardial viability assessment with either fluorodeoxyglucose SPECT or PET imaging, or thallium-201 SPECT imaging; and radionuclide angiography. Emergent, urgent and nonurgent indications were defined for each clinical examination. In each case, appropriate wait time benchmarks were defined as within 24 h for emergent indications, within three days for urgent indications and within 14 days for nonurgent indications. Substantial variability was noted from province to province with respect to access for these procedures. For myocardial perfusion imaging, mean emergent/urgent wait times varied from four to 24 days, and mean nonurgent wait times varied from 15 to 158 days. Only Ontario provided limited access to viability assessment, with fluorodeoxyglucose available in one centre. Mean emergent/urgent wait times for access to viability assessment with thallium-201 SPECT imaging varied from three to eight days, with the exception of Newfoundland, where an emergent/urgent assessment was not available; mean nonurgent wait times varied from seven to 85 days. Finally, for radionuclide angiography, mean emergent/urgent wait times varied from two to 20 days, and nonurgent wait times varied from eight to 36 days. Again, Newfoundland centres were unable to provide emergent/urgent access. The publication of these data and proposed wait times as national targets is a step toward the validation of these recommendations through consultation with clinicians caring for cardiac patients across Canada.

Biological Response of Positron Emission Tomography Scan Exposure and Adaptive Response in Humans

The biological effects of exposure to radioactive fluorodeoxyglucose (18F-FDG) were investigated in the lymphocytes of patients undergoing positron emission tomography (PET) procedures. Low-dose, radiation-induced cellular responses were measured using 3 different end points: (1) apoptosis; (2) chromosome aberrations; and (3) γH2AX foci formation. The results showed no significant change in lymphocyte apoptosis, or chromosome aberrations, as a result of in vivo 18F-FDG exposure, and there was no evidence the PET scan modified the apoptotic response of lymphocytes to a subsequent 2 Gy in vitro challenge irradiation. However, lymphocytes sampled from patients following a PET scan showed an average of 22.86% fewer chromosome breaks and 39.16% fewer dicentrics after a subsequent 2 Gy in vitro challenge irradiation. The effect of 18F-FDG exposure on phosphorylation of histone H2AX (γH2AX) in lymphocytes of patients showed a varied response between individuals. The relationship between γH2AX foci formation and increasing activity of 18F-FDG was not directly proportional to dose. This variation is most likely attributed to differences in the factors that combine to constitute an individual’s radiation response. In summary, the results of this study indicate18F-FDG PET scans may not be detrimental but can elicit variable responses between individuals and can modify cellular response to subsequent radiation exposures.