Since the publication of the European Association of Nuclear Medicine (EANM) procedural guidelines for radionuclide myocardial perfusion imaging (MPI) in 2005, many small and some larger steps of ...progress have been made, improving MPI procedures. In this paper, the major changes from the updated 2015 procedural guidelines are highlighted, focusing on the important changes related to new instrumentation with improved image information and the possibility to reduce radiation exposure, which is further discussed in relation to the recent developments of new International Commission on Radiological Protection (ICRP) models. Introduction of the selective coronary vasodilator regadenoson and the use of coronary CT-contrast agents for hybrid imaging with SPECT/CT angiography are other important areas for nuclear cardiology that were not included in the previous guidelines. A large number of minor changes have been described in more detail in the fully revised version available at the EANM home page:
http://eanm.org/publications/guidelines/2015_07_EANM_FINAL_myocardial_perfusion_guideline.pdf
.
Cardiovascular disease (CVD) is the leading cause of death and disease burden worldwide. Nuclear myocardial perfusion imaging with either single-photon emission computed tomography or positron ...emission tomography has been used extensively to perform diagnosis, monitor therapies, and predict cardiovascular events. Several radiopharmaceutical tracers have recently been developed to evaluate CVD by targeting myocardial perfusion, metabolism, innervation, and inflammation. This article reviews old and newer used in nuclear cardiac imaging.
Abstract
Molecular markers are suggested to improve the diagnostic and prognostic accuracy in patients with coronary artery disease (CAD) beyond current clinical scores based on age, gender, symptoms ...and traditional risk factors. In this context, plasma lipids are emerging as predictors of both plaque composition and risk of future events. We aim to identify plasma lipid biomarkers associated to CAD indexes of stenosis severity, plaque lipid content and a comprensive score of CAD extent and its risk. We used a simple high performance liquid chromatography-tandem mass spectrometry method to identify 69 plasma lipids in 132 subjects referred to Coronary Computed Tomography Angiography (CCTA) for suspected CAD, all under statin treatment. Patients were stratified in groups using three different CCTA-based annotations: CTA-risk score, lipid plaque prevalence (LPP) ratio and the coronary artery disease-reporting and data system (CAD-RADS). We identified a common set of lipid biomarkers composed of 7 sphingomyelins and 3 phosphatidylethanolamines, which discriminates between high risk CAD patients and controls regardless of the CAD annotations used (CTA score, LPP ratio, or CAD-RADS). These results highlight the potential of circulating lipids as biomarkers of stenosis severity, non calcified plaque composition and overall plaque risk of events.
Coronary artery calcium (CAC) score has shown to provide incremental prognostic information when added to the Framingham risk score. Although the relation between CAC and myocardial ischemia has been ...evaluated, there has been little evaluation of the relationship between CAC score and inducible myocardial ischemia on computed tomography myocardial perfusion (CTP).
Patients who were referred with stable chest pain from the outpatient clinic and who underwent non-contrast computed tomography scan, coronary computed tomography angiography, and adenosine stress CTP were included in this study. CAC score was subdivided in four groups (1 to 99; 100 to 399, 400 to 999, and ≥ 1000). Inducible myocardial ischemia was considered when reversible perfusion defects were observed in ≥ 1 segment. A total of 131 patients (age 62 ± 9.4 years; 56% male) were included. The median CAC score was 241 (73 to 539). Forty-nine patients (37%) had evidence of inducible myocardial ischemia. The presence of inducible myocardial ischemia increased with increasing CAC score from 22% in the CAC score 1 to 99 subgroup to 35, 47, and 65% in the 100 to 399, 400 to 999, and ≥ 1000 CAC score subgroup, respectively. In multivariable analysis CAC score was the only determinant that significantly predicted the presence of inducible myocardial ischemia on CTP.
In a population of symptomatic patients, the majority of patients with extensive calcification had evidence of inducible myocardial ischemia on CTP. CAC score was the only independent predictor of inducible myocardial ischemia on CTP.
Coronary atherosclerosis is a chronic non-resolving inflammatory process wherein the interaction of innate immune cells and platelets plays a major role. Circulating neutrophils, in particular, ...adhere to the activated endothelium and migrate into the vascular wall, promoting monocyte recruitment and influencing plaque phenotype and stability at all stages of its evolution. We aimed to evaluate, by flow cytometry, if blood neutrophil number and phenotype-including their phenotypic relationships with platelets, monocytes and lymphocytes-have an association with lipid-rich necrotic core volume (LRNCV), a generic index of coronary plaque vulnerability, in a group of stable patients with chronic coronary syndrome (CCS).
In 55 patients, (68.53 ± 1.07 years of age, mean ± SEM; 71% male), the total LRNCV in each subject was assessed by a quantitative analysis of all coronary plaques detected by computed tomography coronary angiography (CTCA) and was normalized to the total plaque volume. The expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1, CXCR4 and CD41a cell surface markers was quantified by flow cytometry. Adhesion molecules, cytokines and chemokines, as well as MMP9 plasma levels, were measured by ELISA.
On a per-patient basis, LRNCV values were positively associated, by a multiple regression analysis, with the neutrophil count (
/µL) (
= 0.02), neutrophil/lymphocyte ratio (
= 0.007), neutrophil/platelet ratio (
= 0.01), neutrophil RFI CD11b expression (
= 0.02) and neutrophil-platelet adhesion index (
= 0.01). Significantly positive multiple regression associations of LRNCV values with phenotypic ratios between neutrophil RFI CD11b expression and several lymphocyte and monocyte surface markers were also observed. In the bivariate correlation analysis, a significantly positive association was found between RFI values of neutrophil-CD41a+ complexes and neutrophil RFI CD11b expression (
< 0.0001).
These preliminary findings suggest that a sustained increase in circulating neutrophils, together with the up-regulation of the integrin/activation membrane neutrophil marker CD11b may contribute, through the progressive intra-plaque accumulation of necrotic/apoptotic cells exceeding the efferocytosis/anti-inflammatory capacity of infiltrating macrophages and lymphocytes, to the relative enlargement of the lipid-rich necrotic core volume of coronary plaques in stable CAD patients, thus increasing their individual risk of acute complication.
Patients with Marfan syndrome have an increased risk of life-threatening aortic complications, mostly preceded by aortic dilatation. Treatment with losartan, an angiotensin-II receptor-1 blocker, may ...reduce aortic dilatation rate in Marfan patients.
In this multicentre, open-label, randomized controlled trial with blinded assessments, we compared losartan treatment with no additional treatment in operated and unoperated adults with Marfan syndrome. The primary endpoint was aortic dilatation rate at any predefined aortic level after 3 years of follow-up, as determined by magnetic resonance imaging. A total of 233 participants (47% female) underwent randomization to either losartan (n = 116) or no additional treatment (n = 117). Aortic root dilatation rate after 3.1 ± 0.4 years of follow-up was significantly lower in the losartan group than in controls (0.77 ± 1.36 vs. 1.35 ± 1.55 mm, P = 0.014). Aortic dilatation rate in the trajectory beyond the aortic root was not significantly reduced by losartan. In patients with prior aortic root replacement, aortic arch dilatation rate was significantly lower in the losartan group when compared with the control group (0.50 ± 1.26 vs. 1.01 ± 1.31 mm, P = 0.033). No significant differences in separate clinical endpoints or the composite endpoint (aortic dissection, elective aortic surgery, cardiovascular death) between the groups could be demonstrated.
In adult Marfan patients, losartan treatment reduces aortic root dilatation rate. After aortic root replacement, losartan treatment reduces dilatation rate of the aortic arch.
Objectives
Application of computational fluid dynamics (CFD) to three-dimensional CTCA datasets has been shown to provide accurate assessment of the hemodynamic significance of a coronary lesion. We ...aim to test the feasibility of calculating a novel CTCA-based virtual functional assessment index (vFAI) of coronary stenoses > 30% and ≤ 90% by using an automated in-house-developed software and to evaluate its efficacy as compared to the invasively measured fractional flow reserve (FFR).
Methods and results
In 63 patients with chest pain symptoms and intermediate (20–90%) pre-test likelihood of coronary artery disease undergoing CTCA and invasive coronary angiography with FFR measurement, vFAI calculations were performed after 3D reconstruction of the coronary vessels and flow simulations using the finite element method. A total of 74 vessels were analyzed. Mean CTCA processing time was 25(± 10) min. There was a strong correlation between vFAI and FFR, (
R
= 0.93,
p
< 0.001) and a very good agreement between the two parameters by the Bland–Altman method of analysis. The mean difference of measurements from the two methods was 0.03 (SD = 0.033), indicating a small systematic overestimation of the FFR by vFAI. Using a receiver-operating characteristic curve analysis, the optimal vFAI cutoff value for identifying an FFR threshold of ≤ 0.8 was ≤ 0.82 (95% CI 0.81 to 0.88).
Conclusions
vFAI can be effectively derived from the application of computational fluid dynamics to three-dimensional CTCA datasets. In patients with coronary stenosis severity > 30% and ≤ 90%, vFAI performs well against FFR and may efficiently distinguish between hemodynamically significant from non-significant lesions.
Key Points
Virtual functional assessment index (vFAI) can be effectively derived from 3D CTCA datasets.
In patients with coronary stenoses severity > 30% and ≤ 90%, vFAI performs well against FFR.
vFAI may efficiently distinguish between functionally significant from non-significant lesions.
Objectives
Impaired cardiovascular function has been associated with cognitive deterioration; however, to what extent cardiovascular dysfunction plays a role in structural cerebral changes remains ...unclear. We studied whether vascular and left ventricular (LV) functions are associated with measures of cerebral small vessel disease (cSVD) in the middle-aged general population.
Methods
In this cross-sectional analysis of the UK Biobank, 4366 participants (54% female, mean age 61 years) underwent magnetic resonance imaging to assess LV function (ejection fraction EF and cardiac index CI) and cSVD measures (total brain volume, grey and white matter volumes, hippocampal volume and white matter hyperintensities WMH). Augmentation index (AIx) was used as a measure of arterial stiffness. Linear and non-linear associations were evaluated using cardiovascular function measures as determinants and cSVD measures as outcomes.
Results
EF was non-linearly associated with total brain volume and grey matter volume, with the largest brain volume for an EF between 55 and 60% (both
p
< 0.001). EF showed a negative linear association with WMH (- 0.23% - 0.44; - 0.02,
p
= 0.03), yet no associations were found with white matter or hippocampal volume. CI showed a positive linear association with white matter (β 3194 mm
3
760; 5627,
p
= 0.01) and hippocampal volume (β 72.5 mm
3
23.0; 122.0,
p
= 0.004). No associations were found for CI with total brain volume, grey matter volume or WMH. No significant associations were found between AIx and cSVD measures.
Conclusions
This study provides novel insights into the complex associations between the heart and the brain, which could potentially guide early interventions aimed at improving cardiovascular function and the prevention of cSVD.
Key Points
• Ejection fraction is non-linearly and cardiac index is linearly associated with MRI-derived measures of cerebral small vessel disease.
• No associations were found for arterial stiffness with cSVD measures.
Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the Fibrillin-1 gene (FBN1). Here, we undertook the first epigenome-wide association study (EWAS) in patients with MFS ...aiming at identifying DNA methylation loci associated with MFS phenotypes that may shed light on the disease process.
The Illumina 450 k DNA-methylation array was used on stored peripheral whole-blood samples of 190 patients with MFS originally included in the COMPARE trial. An unbiased genome-wide approach was used, and methylation of CpG-sites across the entire genome was evaluated. Additionally, we investigated CpG-sites across the FBN1-locus (15q21.1) more closely, since this is the gene defective in MFS. Differentially Methylated Positions (DMPs) and Differentially Methylated Regions (DMRs) were identified through regression analysis. Associations between methylation levels and aortic diameters and presence or absence of 21 clinical features of MFS at baseline were analyzed. Moreover, associations between aortic diameter change, and the occurrence of clinical events (death any cause, type-A or -B dissection/rupture, or aortic surgery) and methylation levels were analyzed.
We identified 28 DMPs that are significantly associated with aortic diameters in patients with MFS. Seven of these DMPs (25%) could be allocated to a gene that was previously associated with cardiovascular diseases (HDAC4, IGF2BP3, CASZ1, SDK1, PCDHGA1, DIO3, PTPRN2). Moreover, we identified seven DMPs that were significantly associated with aortic diameter change and five DMP's that associated with clinical events. No significant associations at p < 10
or p < 10
were found with any of the non-cardiovascular phenotypic MFS features. Investigating DMRs, clusters were seen mostly on X- and Y, and chromosome 18-22. The remaining DMRs indicated involvement of a large family of protocadherins on chromosome 5, which were not reported in MFS before.
This EWAS in patients with MFS has identified a number of methylation loci significantly associated with aortic diameters, aortic dilatation rate and aortic events. Our findings add to the slowly growing literature on the regulation of gene expression in MFS patients.
The added value of computed tomography (CT) follow-up after elective proximal aortic surgery is unclear. We evaluated the benefit of CT follow-up by assessing the incidence of aorta-related ...complications and reinterventions detected during routine CT follow-up.
Data on 314 patients undergoing first time elective proximal aortic surgery between 2000 and 2015 were collected. The primary study end points were aorta-related complications and reinterventions, detected during routine CT follow-up. Secondary study endpoints included all aorta-related complications and reinterventions, irrespective of the mode of detection and survival.
Median CT follow-up time was 6.8 (IQR 4.1-9.8) years, during which a total of 1303 routine follow-up CT-scans (median 4, IQR 3-5) were performed. During CT follow-up, aorta-related complications were detected in 18 (5.7%) patients, of which 6 (1.6%) underwent reintervention. In total, 28 aorta-related complications were observed in 23 (7.3%) patients, of which 9 led to reintervention. In order to detect 1 aorta-related complication leading to reintervention, 218 routine follow-up CT-scans were required. The unadjusted and EuroSCORE II adjusted hazard ratios of not undergoing CT follow-up on mortality were 1.260 (95% CI 0.705-2.251) and 0.830 (95% CI 0.430-1.605), respectively.
Following first time elective proximal aortic surgery, aorta-related complications are uncommon, are not always detected during CT follow-up and, if detected, often do not result in reintervention. Therefore, a more conservative CT follow-up protocol could be considered in selected patients to reduce lifetime radiation burden and health care costs.
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