We evaluated the diagnostic and prognostic value of quantification of myocardial flow reserve (MFR) with positron emission tomography (PET) in orthotopic heart transplant patients.
We retrospectively ...identified orthotopic heart transplant patients who underwent rubidium-82 cardiac PET imaging. The primary outcome was the composite of cardiovascular death, acute coronary syndrome, coronary revascularization, and heart failure hospitalization. Cox regression was used to evaluate the association of MFR with the primary outcome. The relationship of MFR and cardiac allograft vasculopathy severity in patients with angiography within 1 year of PET imaging was assessed using Spearman rank correlation and logistic regression. A total of 117 patients (median age, 60 years; 71% men) were identified. Twenty-one of 62 patients (34%) who underwent angiography before PET had cardiac allograft vasculopathy. The median time from orthotopic heart transplant to PET imaging was 6.4 years (median global MFR, 2.31). After a median of 1.4 years, 22 patients (19%) experienced the primary outcome. On an unadjusted basis, global MFR (hazard ratio, 0.22 per unit increase; 95% confidence interval, 0.09-0.50;
<0.001) and stress myocardial blood flow (hazard ratio, 0.48 per unit increase; 95% confidence interval, 0.29-0.79;
=0.004) were associated with the primary outcome. Decreased MFR independently predicted the primary outcome after adjustment for other variables. In 42 patients who underwent angiography within 12 months of PET, MFR and stress myocardial blood flow were associated with moderate-severe cardiac allograft vasculopathy (International Society of Heart and Lung Transplantation grade 2-3).
MFR assessed by cardiac rubidium-82 PET imaging is a predictor of cardiovascular events after orthotopic heart transplant and is associated with cardiac allograft vasculopathy severity.
Objective
Genetic studies have suggested that the branched‐chain amino acids (BCAAs) valine, leucine, and isoleucine have a causal association with type 2 diabetes (T2D). However, inferences are ...based on a limited number of genetic loci associated with BCAAs.
Methods
Instrumental variables (IVs) for each BCAA were constructed and validated using large well‐powered data sets and their association with T2D was tested using a two‐sample inverse‐variance weighted Mendelian randomization approach. Sensitivity analyses were performed to ensure the accuracy of the findings. A reverse association was assessed using instrumental variables for T2D.
Results
Estimated effect sizes between BCAA IVs and T2D, excluding outliers, were as follows: valine (β = 0.14 change in log‐odds per SD change in valine, 95% CI: −0.06 to 0.33, p = 0.17), leucine (β = 0.15, 95% CI: −0.02 to 0.32, p = 0.09), and isoleucine (β = 0.13, 95% CI: −0.08 to 0.34, p = 0.24). In contrast, T2D IVs were positively associated with each BCAA, i.e., valine (β = 0.08 per SD change in levels per log‐odds change in T2D, 95% CI: 0.05 to 0.10, p = 1.8 × 10−9), leucine (β = 0.06, 95% CI: 0.04 to 0.09, p = 4.5 × 10−8), and isoleucine (β = 0.06, 95% CI: 0.04 to 0.08, p = 2.8 × 10−8).
Conclusions
These data suggest that the BCAAs are not mediators of T2D risk but are biomarkers of diabetes.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Circulating metabolites act as biomarkers of dysregulated metabolism and may inform disease pathophysiology. A portion of the inter-individual variability in circulating metabolites is influenced by ...common genetic variation. We evaluated whether a genetics-based "virtual" metabolomics approach can identify novel metabolite-disease associations.
We examined the association between polygenic scores for 724 metabolites with 1,247 clinical phenotypes in the BioVU DNA biobank, comprising 57,735 European ancestry and 15,754 African ancestry participants. We applied Mendelian randomization (MR) to probe significant relationships and validated significant MR associations using independent GWAS of candidate phenotypes.
We found significant associations between 336 metabolites and 168 phenotypes in European ancestry and 107 metabolites and 56 phenotypes in African ancestry. Of these metabolite-disease pairs, MR analyses confirmed associations between 73 metabolites and 53 phenotypes in European ancestry. Of 22 metabolitephenotype pairs evaluated for replication in independent GWAS, 16 were significant (false discovery rate p < 0.05). These included associations between bilirubin and X-21796 with cholelithiasis, phosphatidylcholine (16:0/22:5n3,18:1/20:4) and arachidonate with inflammatory bowel disease and Crohn's disease, and campesterol with coronary artery disease and myocardial infarction. These associations may represent biomarkers or potentially targetable mediators of disease risk.
The purpose of this study was to describe our experience with fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET/CT) in diagnosing left ventricular assist ...device (LVAD) infections and perform a meta-analysis of published studies to determine overall diagnostic accuracy.
Device-related infections are a common complication of LVADs and are linked to worse outcomes. Diagnosis of LVAD infections remains challenging. FDG PET/CT has demonstrated good diagnostic accuracy in several other infectious conditions.
This was a single-center, retrospective case series of FDG PET/CT scans in suspected LVAD infection between September 2015 and February 2018. A systematic review of PubMed from database inception through March 2018 was also conducted to identify additional studies.
Nineteen FDG PET/CT scans were identified for the retrospective case series. The systematic review identified an additional 3 publications, for a total of 4 studies involving 119 scans assessing diagnostic performance. Axial (n = 36) and centrifugal (n = 83) flow LVADs were represented. Pooled sensitivity was 92% (95% confidence interval CI: 82% to 97%) and specificity was 83% (95% CI: 24% to 99%) for FDG PET/CT in diagnosing LVAD infections. Summary receiver-operating characteristic curve analysis demonstrated an AUC of 0.94 (95% CI: 0.91 to 0.95).
FDG PET/CT for suspected LVAD infections demonstrates good diagnostic accuracy, with overall high sensitivity but variable specificity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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