Integrated myocardial flow reserve (iMFR) assessment: diffuse atherosclerosis and microvascular dysfunction are more strongly associated with mortality than focally impaired perfusion.

BACKGROUND AND AIMS: Although treatment of ischemia-causing epicardial stenoses may improve symptoms of ischemia, current evidence does not suggest that revascularization improves survival. Conventional myocardial ischemia imaging does not uniquely identify diffuse atherosclerosis, microvascular dysfunction, or nonobstructive epicardial stenoses. We sought to evaluate the prognostic value of integrated myocardial flow reserve (iMFR), a novel noninvasive approach to distinguish the perfusion impact of focal atherosclerosis from diffuse coronary disease. METHODS: This study analyzed a large single-center registry of consecutive patients clinically referred for rest-stress myocardial perfusion positron emission tomography. Cox proportional hazards modeling was used to assess the association of two previously reported and two novel perfusion measures with mortality risk: global stress myocardial blood flow (MBF); global myocardial flow reserve (MFR); and two metrics derived from iMFR analysis: the extents of focal and diffusely impaired perfusion. RESULTS: In total, 6867 patients were included with a median follow-up of 3.4 years [1st-3rd quartiles, 1.9-5.0] and 1444 deaths (21%). Although all evaluated perfusion measures were independently associated with death, diffusely impaired perfusion extent (hazard ratio 2.65, 95%C.I. [2.37-2.97]) and global MFR (HR 2.29, 95%C.I. [2.08-2.52]) were consistently stronger predictors than stress MBF (HR 1.62, 95%C.I. [1.46-1.79]). Focally impaired perfusion extent (HR 1.09, 95%C.I. [1.03-1.16]) was only moderately related to mortality. Diffusely impaired perfusion extent remained a significant independent predictor of death when combined with global MFR (p < 0.0001), providing improved risk stratification (overall net reclassification improvement 0.246, 95%C.I. [0.183-0.310]). CONCLUSIONS: The extent of diffusely impaired perfusion is a strong independent and additive marker of mortality risk beyond traditional risk factors, standard perfusion imaging, and global MFR, while focally impaired perfusion is only moderately related to mortality.

Integrated myocardial flow reserve (iMFR) assessment: optimized PET blood flow quantification for diagnosis of coronary artery disease.

PURPOSE: Distinguishing obstructive epicardial coronary artery disease (CAD) from microvascular dysfunction and diffuse atherosclerosis would be of immense benefit clinically. However, quantitative measures of absolute myocardial blood flow (MBF) integrate the effects of focal epicardial stenosis, diffuse atherosclerosis, and microvascular dysfunction. In this study, MFR and relative perfusion quantification were combined to create integrated MFR (iMFR) which was evaluated using data from a large clinical registry and an international multi-center trial and validated against invasive coronary angiography (ICA). METHODS: This study included 1,044 clinical patients referred for 82Rb rest/stress positron emission tomography myocardial perfusion imaging and ICA, along with 231 patients from the Flurpiridaz 301 trial (clinicaltrials.gov NCT01347710). MFR and relative perfusion quantification were combined to create an iMFR map. The incremental value of iMFR was evaluated for diagnosis of obstructive stenosis, adjusted for patient demographics and pre-test probability of CAD. Models for high-risk anatomy (left main or three-vessel disease) were also constructed. RESULTS: iMFR parameters of focally impaired perfusion resulted in best fitting diagnostic models. Receiver-operating characteristic analysis showed a slight improvement compared to standard quantitative perfusion approaches (AUC 0.824 vs. 0.809). Focally impaired perfusion was also associated with high-risk CAD anatomy (OR 1.40 for extent, and OR 2.40 for decreasing mean MFR). Diffusely impaired perfusion was associated with lower likelihood of obstructive CAD, and, in the absence of transient ischemic dilation (TID), with lower likelihood of high-risk CAD anatomy. CONCLUSIONS: Focally impaired perfusion extent derived from iMFR assessment is a powerful incremental predictor of obstructive CAD while diffusely impaired perfusion extent can help rule out obstructive and high-risk CAD in the absence of TID.

Inter- and Intraobserver Agreement of 18F-FDG PET/CT Image Interpretation in Patients Referred for Assessment of Cardiac Sarcoidosis.

Recent studies have reported the usefulness of 18F-FDG PET in aiding with the diagnosis and management of patients with cardiac sarcoidosis (CS). However, image interpretation of 18F-FDG PET for CS is sometimes challenging. We sought to investigate the inter- and intraobserver agreement and explore factors that led to important discrepancies between readers. Methods: We studied consecutive patients with no significant coronary artery disease who were referred for assessment of CS. Two experienced readers masked to clinical information, imaging reports, independently reviewed 18F-FDG PET/CT images. 18F-FDG PET/CT images were interpreted according to a predefined standard operating procedure, with cardiac 18F-FDG uptake patterns categorized into 5 patterns: none, focal, focal on diffuse, diffuse, and isolated lateral wall or basal uptake. Overall image assessment was classified as either consistent with active CS or not. Results: One hundred scans were included from 71 patients. Of these, 46 underwent 18F-FDG PET/CT with a no-restriction diet (no-restriction group), and 54 underwent 18F-FDG PET/CT with a low-carbohydrate, high-fat and protein-permitted diet (low-carb group). There was agreement of the interpretation category in 74 of 100 scans. The κ-value of agreement among all 5 categories was 0.64, indicating moderate agreement. For overall clinical interpretation, there was agreement in 93 of 100 scans (κ = 0.85). When scans were divided into the preparation groups, there was a trend toward higher agreement in the low-carb group versus the no-restriction group (80% vs. 67%, P = 0.08). Regarding the overall clinical interpretation, there was also a trend toward greater agreement in the low-carb group versus the no-restriction group (96% vs. 89%, P = 0.08). Conclusion: The interobserver agreement of cardiac 18F-FDG uptake image patterns was moderate. However, agreement was better regarding overall interpretation of CS. Detailed prescan dietary preparation seemed to improve interobserver agreement.

Clinical interpretation standards and quality assurance for the multicenter PET/CT trial rubidium-ARMI.

UNLABELLED: Rubidium-ARMI ((82)Rb as an Alternative Radiopharmaceutical for Myocardial Imaging) is a multicenter trial to evaluate the accuracy, outcomes, and cost-effectiveness of low-dose (82)Rb perfusion imaging using 3-dimensional (3D) PET/CT technology. Standardized imaging protocols are essential to ensure consistent interpretation. METHODS: Cardiac phantom qualifying scans were obtained at 7 recruiting centers. Low-dose (10 MBq/kg) rest and pharmacologic stress (82)Rb PET scans were obtained in 25 patients at each site. Summed stress scores, summed rest scores, and summed difference scores (SSS, SRS, and SDS [respectively] = SSS-SRS) were evaluated using 17-segment visual interpretation with a discretized color map. All scans were coread at the core lab (University of Ottawa Heart Institute) to assess agreement of scoring, clinical diagnosis, and image quality. Scoring differences greater than 3 underwent a third review to improve consensus. Scoring agreement was evaluated with intraclass correlation coefficient (ICC-r), concordance of clinical interpretation, and image quality using κ coefficient and percentage agreement. Patient (99m)Tc and (201)Tl SPECT scans (n = 25) from 2 centers were analyzed similarly for comparison to (82)Rb. RESULTS: Qualifying scores of SSS = 2, SDS = 2, were achieved uniformly at all imaging sites on 9 different 3D PET/CT scanners. Patient scores showed good agreement between core and recruiting sites: ICC-r = 0.92, 0.77 for SSS, SDS. Eighty-five and eighty-seven percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. After consensus review, scoring agreement improved to ICC-r = 0.97, 0.96 for SSS, SDS (P < 0.05). The agreement of normal versus abnormal (SSS ≥ 4) and nonischemic versus ischemic (SDS ≥ 2) studies was excellent: ICC-r = 0.90 and 0.88. Overall interpretation showed excellent agreement, with a κ = 0.94. Image quality was perceived differently by the site versus core reviewers (90% vs. 76% good or better; P < 0.05). By comparison, scoring agreement of the SPECT scans was ICC-r = 0.82, 0.72 for SSS, SDS. Seventy-six and eighty-eight percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. Consensus review again improved scoring agreement to ICC-r = 0.97, 0.90 for SSS, SDS (P < 0.05). CONCLUSION: (82)Rb myocardial perfusion imaging protocols were implemented with highly repeatable interpretation in centers using 3D PET/CT technology, through an effective standardization and quality assurance program. Site scoring of (82)Rb PET myocardial perfusion imaging scans was found to be in good agreement with core lab standards, suggesting that the data from these centers may be combined for analysis of the rubidium-ARMI endpoints.

In vivo assessment of myocardial glucose uptake by positron emission tomography in adults with the PRKAG2 cardiac syndrome.

BACKGROUND: The PRKAG2 cardiac syndrome is an inherited metabolic disease of the heart characterized by excessive myocardial glycogen deposition. The biochemical alterations associated with this condition remain controversial and have not previously been studied in affected humans. METHODS AND RESULTS: Positron emission tomography (PET) imaging was used to quantitatively assess myocardial glucose uptake (MGU) in 6 adult subjects with the PRKAG2 cardiac syndrome and 6 healthy, matched control subjects using the glucose analogue (18)F-Fluoro-2-deoxyglucose (FDG). Studies were performed under a euglycemic hyperinsulinemic clamp to ensure stable blood glucose levels. Rubidium-82 perfusion scans were performed to ensure that myocardial differences in myocardial glucose uptake were not the result of significant myocardial scar. In adult patients with phenotypic expression of disease, the median myocardial glucose uptake of the left ventricle was 0.18 mumol/min/g (interquartile range, 0.14, 0.24), compared with 0.40 mumol/min/g (interquartile range, 0.30 to 0.45) in the control group (P=0.01). The median blood glucose during FDG-PET imaging was 4.72 mmol/L (interquartile range, 4.32 to 4.97) in the PRKAG2 group and 4.38 mmol/L (interquartile range, 3.90, 4.79) in the control group (P=NS). The significant decrease observed in myocardial glucose uptake in affected patients occurred in the absence of significant myocardial scar. CONCLUSIONS: The PRKAG2 cardiac syndrome is associated with a reduction of glucose uptake in adult patients affected with this genetic condition. In this pilot study, (18)F-FDG-PET imaging is a useful tool to assess alterations in myocardial glucose transport in this inherited metabolic disease and provide insight into the biochemical pathophysiology of the diseased state.