Although the number of clinical applications for fluorine-18 fluorodeoxyglucose (18F-FDG) cardiac positron emission tomography (PET) has continued to grow, there remains a lack of consensus regarding ...the ideal method of suppressing normal myocardial glucose utilization for image optimization. This review describes various patient preparation protocols that have been used as well as the success rates achieved in different studies. Collectively, the available literature supports using a high-fat, no-carbohydrate diet for at least two meals with a fast of 4-12 hours prior to 18F-FDG PET imaging and suggests that isolated fasting for less than 12 hours and supplementation with food or drink just prior to imaging should be avoided. Each institution should adopt a protocol and continuously monitor its effectiveness with a goal to achieve adequate myocardial suppression in greater than 80% of patients.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The goal of this study was to compare the economic outcomes of patients undergoing different noninvasive tests to evaluate suspected coronary artery disease (CAD).
Evaluation of noninvasive tests is ...shifting to an assessment of their effect on clinical outcomes rather than on their diagnostic accuracy. Economic outcomes of testing are particularly important in light of rising medical care costs.
We used an observational registry of 1,703 patients who underwent coronary computed tomography angiography (CTA) (n = 590), positron emission tomography (PET) (n = 548), or single-photon emission computed tomography (SPECT) (n = 565) for diagnosis of suspected CAD at 1 of 41 centers. We followed patients for 2 years, and documented resource use, medical costs for CAD, and clinical outcomes. We used multivariable analysis and propensity score matching to control for differences in baseline characteristics.
Two-year costs were highest after PET ($6,647, 95% confidence interval CI: $5,896 to $7,397), intermediate after CTA ($4,909, 95% CI: $4,378 to $5,440), and lowest after SPECT ($3,965, 95% CI: $3,520 to $4,411). After multivariable adjustment, CTA costs were 15% higher than SPECT (p < 0.01), and PET costs were 22% higher than SPECT (p < 0.0001). Two-year mortality was 0.7% after CTA, 1.6% after SPECT, and 5.5% after PET. The incremental cost-effectiveness ratio for CTA compared with SPECT was $11,700 per life-year added, but was uncertain, with higher costs and higher mortality in 13% of bootstrap replications. Patients undergoing PET had higher costs and higher mortality than patients undergoing SPECT in 98% of bootstrap replications.
Costs were significantly lower after using SPECT rather than CTA or PET in the evaluation of suspected coronary disease. SPECT was economically attractive compared with PET, whereas CTA was associated with higher costs and no significant difference in mortality compared with SPECT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives The goal of this study was to compare the economic outcomes of patients undergoing different noninvasive tests to evaluate suspected coronary artery disease (CAD). Background Evaluation of ...noninvasive tests is shifting to an assessment of their effect on clinical outcomes rather than on their diagnostic accuracy. Economic outcomes of testing are particularly important in light of rising medical care costs. Methods We used an observational registry of 1,703 patients who underwent coronary computed tomography angiography (CTA) (n = 590), positron emission tomography (PET) (n = 548), or single-photon emission computed tomography (SPECT) (n = 565) for diagnosis of suspected CAD at 1 of 41 centers. We followed patients for 2 years, and documented resource use, medical costs for CAD, and clinical outcomes. We used multivariable analysis and propensity score matching to control for differences in baseline characteristics. Results Two-year costs were highest after PET ($6,647, 95% confidence interval CI: $5,896 to $7,397), intermediate after CTA ($4,909, 95% CI: $4,378 to $5,440), and lowest after SPECT ($3,965, 95% CI: $3,520 to $4,411). After multivariable adjustment, CTA costs were 15% higher than SPECT (p < 0.01), and PET costs were 22% higher than SPECT (p < 0.0001). Two-year mortality was 0.7% after CTA, 1.6% after SPECT, and 5.5% after PET. The incremental cost-effectiveness ratio for CTA compared with SPECT was $11,700 per life-year added, but was uncertain, with higher costs and higher mortality in 13% of bootstrap replications. Patients undergoing PET had higher costs and higher mortality than patients undergoing SPECT in 98% of bootstrap replications. Conclusions Costs were significantly lower after using SPECT rather than CTA or PET in the evaluation of suspected coronary disease. SPECT was economically attractive compared with PET, whereas CTA was associated with higher costs and no significant difference in mortality compared with SPECT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
In rheumatoid arthritis (RA), there are limited data on risk factors for the clinical heart failure (HF) subtypes of HF with reduced ejection fraction (HFrEF) and HF with preserved ejection ...fraction (HFpEF). This study examined the association between inflammation and incident HF subtypes in RA. Because inflammation changes over time with disease activity, we hypothesized that the effect of inflammation may be stronger at the 5‐year follow‐up than at the standard 10‐year follow‐up from general population studies of cardiovascular risk.
Methods
We studied an electronic health record (EHR)–based RA cohort with data pre‐ and post‐RA incidence. We applied a validated approach to identify HF and extract ejection fraction to classify HFrEF and HFpEF. Follow‐up started from the RA incidence date (index date) to the earliest occurrence of incident HF, death, last EHR encounter, or 10 years. Baseline inflammation was assessed using erythrocyte sedimentation rate or C‐reactive protein values. Covariates included demographic characteristics, established HF risk factors, and RA‐related factors. We tested the association between baseline inflammation with incident HF and its subtypes using Cox proportional hazards models.
Results
We studied 9,087 patients with RA; 8.2% developed HF during 10 years of follow‐up. Elevated inflammation was associated with increased risk for HF at both 5‐ and 10‐year follow‐ups (hazard ratio HR 1.66, 95% confidence interval 95% CI 1.12–2.46 and HR 1.46, 95% CI 1.13–1.90, respectively), which is also seen for HFpEF at 5 years (HR 1.72, 95% CI 1.09–2.70) and 10 years (HR 1.45, 95% CI 1.07–1.94). HFrEF was not associated with inflammation for either follow‐up time.
Conclusion
Elevated inflammation early in RA diagnosis was associated with HF; this association was driven by HFpEF and not HFrEF, suggesting a window of opportunity for prevention of HFpEF in RA.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Optimal risk stratification with machine learning (ML) from myocardial perfusion imaging (MPI) includes both clinical and imaging data. While most imaging variables can be derived automatically, ...clinical variables require manual collection, which is time-consuming and prone to error. We determined the fewest manually input and imaging variables required to maintain the prognostic accuracy for major adverse cardiac events (MACE) in patients undergoing a single-photon emission computed tomography (SPECT) MPI.
This study included 20 414 patients from the multicentre REFINE SPECT registry and 2984 from the University of Calgary for training and external testing of the ML models, respectively. ML models were trained using all variables (ML-All) and all image-derived variables (including age and sex, ML-Image). Next, ML models were sequentially trained by incrementally adding manually input and imaging variables to baseline ML models based on their importance ranking. The fewest variables were determined as the ML models (ML-Reduced, ML-Minimum, and ML-Image-Reduced) that achieved comparable prognostic performance to ML-All and ML-Image. Prognostic accuracy of the ML models was compared with visual diagnosis, stress total perfusion deficit (TPD), and traditional multivariable models using area under the receiver-operating characteristic curve (AUC). ML-Minimum (AUC 0.798) obtained comparable prognostic accuracy to ML-All (AUC 0.799, P = 0.19) by including 12 of 40 manually input variables and 11 of 58 imaging variables. ML-Reduced achieved comparable accuracy (AUC 0.796) with a reduced set of manually input variables and all imaging variables. In external validation, the ML models also obtained comparable or higher prognostic accuracy than traditional multivariable models.
Reduced ML models, including a minimum set of manually collected or imaging variables, achieved slightly lower accuracy compared to a full ML model but outperformed standard interpretation methods and risk models. ML models with fewer collected variables may be more practical for clinical implementation.
Pyroglutamate-3 Aβ (pGlu-3 Aβ) is an N-terminally truncated and post-translationally modified Aβ species found in Alzheimer's disease (AD) brain. Its increased peptide aggregation propensity and ...toxicity make it an attractive emerging treatment strategy for AD. We address the question of how the effector function of an anti-pGlu-3 Aβ antibody influences the efficacy of immunotherapy in mouse models with AD-like pathology.
We compared two different immunoglobulin (Ig) isotypes of the same murine anti-pGlu-3 Aβ mAb (07/1 IgG1 and 07/2a IgG2a) and a general N-terminal Aβ mAb (3A1 IgG1) for their ability to clear Aβ and protect cognition in a therapeutic passive immunotherapy study in aged, plaque-rich APP
/PS1ΔE9 transgenic (Tg) mice. We also compared the ability of these antibodies and a CDC-mutant form of 07/2a (07/2a-k), engineered to avoid complement activation, to clear Aβ in an ex vivo phagocytosis assay and following treatment in APP
xhQC double Tg mice, and to activate microglia using longitudinal microPET imaging with TSPO-specific
F-GE180 tracer following a single bolus antibody injection in young and old Tg mice.
We demonstrated significant cognitive improvement, better plaque clearance, and more plaque-associated microglia in the absence of microhemorrhage in aged APP
/PS1ΔE9 Tg mice treated with 07/2a, but not 07/1 or 3A1, compared to PBS in our first in vivo study. All mAbs cleared plaques in an ex vivo assay, although 07/2a promoted the highest phagocytic activity. Compared with 07/2a, 07/2a-k showed slightly reduced affinity to Fcγ receptors CD32 and CD64, although the two antibodies had similar binding affinities to pGlu-3 Aβ. Treatment of APP
xhQC mice with 07/2a and 07/2a-k mAbs in our second in vivo study showed significant plaque-lowering with both mAbs. Longitudinal
F-GE180 microPET imaging revealed different temporal patterns of microglial activation for 3A1, 07/1, and 07/2a mAbs and no difference between 07/2a-k and PBS-treated Tg mice.
Our results suggest that attenuation of behavioral deficits and clearance of amyloid is associated with strong effector function of the anti-pGlu-3 Aβ mAb in a therapeutic treatment paradigm. We present evidence that antibody engineering to reduce CDC-mediated complement binding facilitates phagocytosis of plaques without inducing neuroinflammation in vivo. Hence, the results provide implications for tailoring effector function of humanized antibodies for clinical development.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Among persons presenting to the emergency department with suspected acute myocardial infarction (MI), cardiac troponin (cTn) testing is commonly used to detect acute myocardial injury. Accelerated ...diagnostic protocols (ADPs) guide clinicians to integrate cTn results with other clinical information to decide whether to order further diagnostic testing.
To determine the change in the rate and yield of stress test or coronary CT angiogram following cTn measurement in patients with chest pain presenting to the emergency department pre- and post-transition to a high-sensitivity (hs-cTn) assay in an updated ADP.
Using electronic health records, we examined visits for chest pain at five emergency departments affiliated with an integrated academic health system 1-year pre- and post-hs-cTn assay transition. Outcomes included stress test or coronary imaging frequency, ADP compliance among those with additional testing, and diagnostic yield (ratio of positive tests to total tests).
There were 7564 patient-visits for chest pain, including 3665 in the pre- and 3899 in the post-period. Following the updated ADP using hs-cTn, 862 (23.5 per 100 patient visits) visits led to subsequent testing versus 1085 (27.8 per 100 patient visits) in the pre-hs-cTn period, (P < 0.001). Among those who were tested, the protocol-compliant rate fell from 80.9% to 46.5% (P < 0.001), but the yield of those tests rose from 24.5% to 29.2% (P = 0.07). Among tests that were noncompliant with ADP guidance, yield was similar pre- and post-updated hs-cTn ADP implementation (pre 13.0%, post 15.4% (P = 0.43).
Implementation of hs-cTn supported by an updated ADP was associated with a lower rate of stress testing and coronary CT angiogram.
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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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