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Long-term data on sex-differences in coronary plaque changes over time is lacking in a low-to-intermediate risk population of stable coronary artery disease (CAD). The aim of this study was to evaluate the role of sex on long-term plaque progression and evolution of plaque composition. Furthermore, the influence of menopause on plaque progression and composition was also evaluated. Patients that underwent a coronary computed tomography angiography (CTA) were prospectively included to undergo a follow-up coronary CTA. Total and compositional plaque volumes were normalized using the vessel volume to calculate a percentage atheroma volume (PAV). To investigate the influence of menopause on plaque progression, patients were divided into two groups, under and over 55 years of age. In total, 211 patients were included in this analysis, 146 (69%) men. The mean interscan period between baseline and follow-up coronary CTA was 6.2 ± 1.4 years. Women were older, had higher HDL levels and presented more often with atypical chest pain. Men had 434 plaque sites and women 156. On a per-lesion analysis, women had less fibro-fatty PAV compared to men (β -1.3 ± 0.4%; p

Objectives This study sought to evaluate whether right ventricular (RV) tissue heterogeneity on computed tomography (CT): 1) is associated with conduction delay in arrhythmogenic right ventricular cardiomyopathy (ARVC); and 2) distinguishes patients with ARVC from those with exercise-induced arrhythmogenic remodeling (EIAR) and control individuals. Background ARVC is characterized by fibrofatty replacement, related to conduction delay and ventricular tachycardias. Distinguishing ARVC from acquired, EIAR is challenging. Methods Patients with ARVC or EIAR and combined endocardial-epicardial electroanatomic voltage mapping for VT ablation with CT integration were enrolled. Patients without structural heart disease served as control individuals. Tissue heterogeneity on CT (CT heterogeneity) was automatically quantified within the 2-mm subepicardium of the entire RV free wall at normal sites and low voltage sites harboring late potentials (LP+) in ARVC/EIAR. Results Seventeen patients with ARVC (15 males; age: 50 ± 17 years), 9 patients with EIAR (7 males; age: 45 ± 14 years) and 17 control individuals (14 males; age: 50 ± 15 years) were enrolled. Of 5,215 ARVC mapping points, 560 (11%) showed LP+. CT heterogeneity was higher at sites with LP+ compared to normal sites (median: 31 HU/mm; IQR: 23 to 46 HU/mm vs. median: 16 HU/mm; IQR: 13 to 21 HU/mm; p Conclusions In patients with ARVC, tissue heterogeneity on CT can be used to identify LP+ as a surrogate for ventricular tachycardia substrate. The overall tissue heterogeneity on CT allows the distinguishing of patients with ARVC from those with EIAR and control individuals.

Perimyocarditis is a well-known acute inflammation of the pericardium and the underlying myocardium. Most commonly perimyocarditis is of viral aetiology, specifically the coxsackie B virus. However, nowadays SARS-CoV-2 associated with COVID-19 infections has emerged as a potential rare cause of perimyocarditis. This case report will demonstrate a case of a young female with perimyocarditis as diagnosed by magnetic resonance imaging (MRI) accompanied by antigens indicating a past COVID-19 infection. Clinical status as well as Findings at MRI, echocardiography and lab results will be reviewed.

Background and aims: Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) define a specific lipid profile associated with residual coronary artery disease (CAD) risk independently of total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Aim of the present study was to assess whether TG/ HDL-C ratio, coronary atherosclerosis and their change over time are characterized by a specific lipidomic profiling in stable patients with chronic coronary syndrome (CCS). Methods: TG/HDL-C ratio was calculated in 193 patients (57.8 +/- 7.6 years, 115 males) with CCS characterized by clinical, bio-humoral profiles and cardiac imaging. Patient-specific plasma targeted lipidomics was defined through a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) strategy. Patients underwent coronary computed tomography angiography (CTA) and an individual CTA risk score, combining extent, severity, composition, and location of plaques, was calculated. All patients entered a follow-up (6.39 +/- 1.17 years), including clinical, lipidomics and coronary CTA assessments. Results: Patients were divided in groups according to baseline TG/HDL-C quartiles: IQ (= 3.287). A specific pattern of altered lipids, characterized by reduced plasma levels of cholesterol esters, phosphatidylcholines and sphingomyelins, was associated with higher TG/HDL-C both at baseline and follow-up (IVQ vs IQ). The CTA risk score increased over time and this lipid signature was also associated with higher CTA score at follow-up. Conclusions: In stable CCS, a specific lipidomic signature identifies those patients with higher TG/HDL- C ratio and higher CTA score over time, suggesting possible molecular pathways of residual CAD risk not tackled by current optimal medical treatments.

Background Patients with Marfan syndrome (MFS) may develop aortic dissection due to progressive dilatation in the entire aorta. Increased aortic stiffness, i.e.a. decreased distensibility has been shown to often precede these dismal sequelae. Therefore, we investigated longitudinal changes in aortic distensibility throughout the entire aorta by means of Cardiac Magnetic Resonance (CMR) imaging in patients with MFS. Methods This retrospective study included all MFS patients with four CMR examinations performed between 1996 and 2012. Aortic distensibility was measured and calculated by a single analyst, in the ascending, proximal- and distal descending, and abdominal aorta. Changes in distensibility were studied using linear mixed-effects regression models. Furthermore, we investigated the association between distensibility and age, sex, blood pressure, medication use, FBN1 mutation type, and previous aortic root surgery. Results In total, 35 MFS patients (age at inclusion 28 [IQR 23–32] years, 54% male) were included. Mean aortic distensibility was low in the ascending and proximal descending aorta (resp. 3.25±1.87, 3.91±1.73x10–3 mmHg–1) at the first scan. Distensibility decreased significantly over time at level 2, 3, and 4 (resp. p=0.021, p=0.002, p=0.038) (Figure 1). The rate of distensibility loss per year (x10–3 mmHg–1/year) was respectively 0.04 and 0.06 in the proximal- and distal descending aorta. Men seemed to have a lower but more stable distensibility, whereas women showed a higher distensibility at younger age, but a faster deterioration rate over time (difference in distensibility loss per year between men and women: 0.08, p=0.038). Distensibility did not correlate significantly with medication use, FBN1 mutation type or previous aortic root surgery. Conclusion Patients with MFS have low distensibility at all levels of the aorta at young age, which keeps decreasing over time. Men had lower distensibility at younger age than women. Distensibility was stably low in men, while still deteriorating over time in women. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): AMC FoundationHorstingstuit Foundation

ObjectivesPatients with Marfan syndrome (MFS) are prone to develop aortic aneurysms due to fragmentation of elastic fibres, resulting in reduced distensibility of the aorta. Reduced distensibility was previously shown to predict progressive descending aorta dilatation. Here, we investigated longitudinal changes in distensibility, as a potential predictor of aortic events.MethodsThis retrospective study included all patients with MFS with at least four cardiac magnetic resonance examinations performed between 1996 and 2012. Aortic distensibility was assessed, in the ascending (level 1), proximal descending (level 2) and distal descending (level 3) aorta. Changes in distensibility were studied using linear mixed-effects regression models.ResultsIn total, 35 patients with MFS (age at inclusion 28 (IQR 23–32) years, 54% men) were included. Mean aortic distensibility was already low (between 2.9×10–3/mm Hg/year and 6.4×10–3/mm Hg/year) at all levels at baseline, and significantly decreased over time at levels 2 and 3 (respectively, p=0.012 and p=0.002). The rate of distensibility loss per year (×10-3/mm Hg/year) was 0.01, 0.03 and 0.06×10–3/mm Hg at levels 1, 2 and 3, respectively. At inclusion, men exhibited very low distensibility, whereas women showed moderately reduced distensibility, gradually decreasing with age.Aortic dilatation rate at level 2 was associated with reduced aortic distensibility. However, we could not demonstrate a direct correlation between distensibility and clinical events during a follow-up of 22 years.ConclusionPatients with MFS display reduced aortic distensibility already at an early age, inversely relating to aortic dilatation rate. However, in this selected patient group, distensibility seems less suitable as an individual predictor of aortic events.

Background 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). Methods and Results 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. Conclusions 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.

Objectives Degenerative thoracic aortic aneurysm (TAA) patients are known to be at risk of life-threatening acute aortic events. Guidelines recommend preemptive surgery at diameters of greater than 55 mm, although many patients with small aneurysms show only mild growth rates and more than half of complications occur in aneurysms below this threshold. Thus, assessment of hemodynamics using 4-dimensional flow magnetic resonance has been of interest to obtain more insights in aneurysm development. Nonetheless, the role of aberrant flow patterns in TAA patients is not yet fully understood. Materials and methods A total of 25 TAA patients and 22 controls underwent time-resolved 3-dimensional phase contrast magnetic resonance imaging with 3-directional velocity encoding (ie, 4-dimensional flow magnetic resonance imaging). Hemodynamic parameters such as vorticity, helicity, and wall shear stress (WSS) were calculated from velocity data in 3 anatomical segments of the ascending aorta (root, proximal, and distal). Regional WSS distribution was assessed for the full cardiac cycle. Results Flow vorticity and helicity were significantly lower for TAA patients in all segments. The proximal ascending aorta showed a significant increase in peak WSS in the outer curvature in TAA patients, whereas WSS values at the inner curvature were significantly lower as compared with controls. Furthermore, positive WSS gradients from sinotubular junction to midascending aorta were most prominent in the outer curvature, whereas from midascending aorta to brachiocephalic trunk, the outer curvature showed negative WSS gradients in the TAA group. Controls solely showed a positive gradient at the inner curvature for both segments. Conclusions Degenerative TAA patients show a decrease in flow vorticity and helicity, which is likely to cause perturbations in physiological flow patterns. The subsequent differing distribution of WSS might be a contributor to vessel wall remodeling and aneurysm formation.

Background Due to the malfunction of connective tissue, Marfan patients are at increased risk of aortic dissection. Uncomplicated acute type B dissection is usually managed with medical therapy. Retrograde progression or new type A dissection is a relatively rare but often fatal complication that occur most frequently in the first 6 months after acute type B dissection. Case summary We present a 31-year-old male with Marfan syndrome and a recent uncomplicated type B dissection from the left subclavian to the right common iliac artery who underwent 4D flow magnetic resonance imaging (MRI). The dissection had a large proximal intimal tear just distal to the left subclavian artery (15 mm) and large false lumen (35 mm). Aortic blood flow just distal to the left subclavian artery (3.6 L/min) was split disproportionately into the true (0.8 L/min, 22%) and false lumen (2.8 L/min, 78%). 4D flow streamlines revealed vortical flow in the proximal false lumen. Increased wall shear stress was observed at the sinotubular junction (STJ), inner wall of the ascending aorta and around the subclavian artery. Two weeks after MRI, the patient presented with jaw pain. Computed tomography showed a type A dissection with an entry tear at the STJ for which an acute valve-sparing root, ascending and arch replacement was performed. Discussion Better risk assessment of life-threatening complications in uncomplicated type B dissections could improve treatment strategies in these patients. Our case demonstrates that besides clinical and morphological parameters, flow derived parameters could aid in improved risk assessment for retrograde progression from uncomplicated type B dissection to acute type A dissection.

Pulse wave velocity (PWV) assessed by magnetic resonance imaging (MRI) is a prognostic marker for cardiovascular events. Prediction modelling could enable indirect PWV assessment based on clinical and anthropometric data. The aim was to calculate estimated-PWV (ePWV) based on clinical and anthropometric measures using linear ridge regression as well as a Deep Neural Network (DNN) and to determine the cut-off which provides optimal discriminative performance between lower and higher PWV values. In total 2254 participants from the Netherlands Epidemiology of Obesity study were included (age 45–65 years, 51% male). Both a basic and expanded prediction model were developed. PWV was estimated using linear ridge regression and DNN. External validation was performed in 114 participants (age 30–70 years, 54% female). Performance was compared between models and estimation accuracy was evaluated by ROC-curves. A cut-off for optimal discriminative performance was determined using Youden’s index. The basic ridge regression model provided an adjusted R2 of 0.33 and bias of 2: 0.29). All models showed good discriminative performance for PWV

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.

Myocardial perfusion scintigraphy (MPS) is based on visual qualitative interpretation and hence interobserver variability might affect clinical decision-making for the patient. Quantification of single photon emission computed tomography (SPECT) imaging enables absolute measurement of treatment efficacy. The aim of this experimental study is to assess quantitative accuracy and precision of iterative image reconstruction (Evolution; Q.Metrix package; GE Healthcare, Little Chalfont, UK), making use of both phantom and patient studies, for potential application of 99mTc-tetrofosmin SPECT/CT in coronary artery disease (CAD) patients. This research consists of a phantom study and an experimental validation study with patient data. An anthropomorphic torso phantom with cardiac insert was filled with technetium (99mTc) and acquired on a SPECT/CT gamma (Discovery 670 Pro; GE Healthcare). Seven sets of 6 acquisitions were evaluated containing a cardiac insert with various defect sizes and configurations. Subsequently, volumes‐of‐interest of the defects were manually drawn on CT to assess the recovery coefficient (RC). Bull’s eye plots were composed to evaluate the uptake per segment. Finally, 99mTc-tetrofosmin SPECT/CT scans were collected retrospectively in ten CAD patients after bone marrow cell treatment and evaluated using Evolution. The phantom study shows that the activity concentration converged after seven iterations (ten subsets) using Evolution. SPECT/CT data were reconstructed with and without Butterworth post-filtering. The average repeatability deviation of all configurations was 2.66% and 2.90% (%SD mean) for the filtered and unfiltered data, respectively. The accuracy after Butterworth post-filtering was lower compared to the unfiltered data with a mean(SD) RC of 0.66 ± 0.06 and 0.71 ± 0.05, respectively (p

Background Marfan syndrome (MFS) is a connective tissue disorder characterized by mutations in the fibrillin-1 (FBN1) gene. The most important manifestation is progressive enlargement of the aorta, ultimately leading to aortic dissection or rupture. Present day pharmacological treatment is based on drugs that decrease repetitive stress on the aorta and improve elastic properties and transport function of the aorta. Unfortunately, this is not sufficient for most patients and surgical resection and reconstruction of the enlarged part of the aorta is still necessary. We have shown earlier that the food supplement Resveratrol inhibits aortic growth and promotes aortic repair in a murine MFS model. Resveratrol is a natural polyphenol commonly found in the skin of berries and in nuts. Here, we hypothesize that Resveratrol treatment will also be protective against aortic dilatation and functional deterioration in humans with MFS. Methods/Design The RESVcue Marfan study is an investigator-initiated, prospective, pre-post observational, multicenter trial. Four specialized academic centers in the Netherlands will recruit 100 patients with genetically confirmed MFS. Patients will use Resveratrol for one year, on top of their ongoing medicinal regime. The primary endpoints consist of the following two main parameters; 1) aortic aneurysm expansion rate and 2) improvement of aortic functional indices. All indices will be measured before and after treatment by echocardiography and (4D flow) MRI. The 4D flow MRI allows for analysis of blood flow patterns and quantification of stresses on the aortic wall, distensibility and pulse wave velocity. Blood and skin samples will be taken to assess the effect of Resveratrol on potential biomarkers associated with Resveratrol metabolism and changes in the primary endpoints. Three psychological tests (The Well-being questionnaire (SF-12), the Hospital Depression and Anxiety Scales (HADS) questionnaire and the Checklist Individual Strength (CIS)) will be taken by the MFS patients to assess the effect of Resveratrol on their well-being. Discussion The RESVcue Marfan trial may provide sufficient data on beneficial effects of Resveratrol on aortic aneurysm expansion rate, aortic functional properties, and biomarkers in patients with MFS to justify a future randomized trial in a larger cohort for a longer study period.Trial registration NL66127.018.18, approved on 24 September 2018. https://www.toetsingonline.nl/ Resveratrol as potential aortic growth inhibitor in patients with Marfan syndrome.

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): The EVINCI study was supported by a grant from the European Union FP7-CP-FP506 2007 project (GA 222915). The SMARTool study was supported by a grant from the European Union H2020-PHC-30-2015 (GA 689068). This study was also partially supported by a grant from AMGEN (Protocol N. 20167781, 2017). Background. High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) characterize an atherosclerotic cardiovascular disease (CAD) risk condition defined as atherogenic dyslipidemia. Aim. To assess whether atherogenic dyslipidemia defined by TG/HDL-C ratio predicts CAD related outcomes in patients with stable angina, independently of other risk factors and treatments. Methods. We studied 355 patients (60 ± 9 y, 211m) with stable angina from the EVINCI Outcome study. Patients were characterized for clinical, bio-humoral and imaging profiles, managed clinically, and followed for 4.5 ± 0.9 years. A computed tomography angiography (CTA) coronary risk score was obtained at baseline in all patients, and at follow-up in 154 of them. The primary composite outcome was all-cause mortality and non-fatal myocardial infarction. CTA scan was repeated at follow-up in 154 patients to assess CAD progression. Results. The median value of TG/HDL-C ratio was 2.095 (2.079IQR). At baseline, the proportion of males, smoking, diabetes and metabolic syndrome, as well as circulating bio-markers of abnormal glucose metabolism and myocardial damage progressively increased across quartiles of TG/HDL-C ratio. The CTA score was significantly higher in the IV quartile of the TG/HDL-C ratio and both were the only independent predictors of the primary (CTA Score: HR 1.06, 95%CI 1.03-1.09, p = 0.001; TG/HDL-C IV quartile: HR 2.85, 95%CI 1.30-6.26, p Conclusions. In patients with stable angina, the TG/HDL-C ratio expresses a cardio-metabolic atherogenic disorder which is progressive over time and is associated with CAD related outcomes independently of LDL-C levels and treatments.

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. 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. 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 mm3 [760; 5627], p = 0.01) and hippocampal volume (β 72.5 mm3 [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. 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. • 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.

Quantitative flow ratio (QFR) is a novel technique to calculate fractional flow reserve (FFR), without hyperemia induction or a pressure wire, and has not yet been validated in patients with diabetes mellitus (DM), who are at increased risk of coronary microvascular dysfunction. The purpose of our study was to compare the diagnostic performance of QFR in diabetic and nondiabetic patients. Patients who underwent invasive coronary angiography and subsequent invasive FFR measurement within 6 months were included. QFR was determined in all coronary arteries in which invasive FFR was performed, using a dedicated software package. Diagnostic accuracy and the area under the receiver-operating characteristic curve (AUC) were determined for QFR, using an invasive FFR cut-off value of

Background Aortic stiffness, assessed through pulse wave velocity (PWV), is an independent predictor for cardiovascular disease risk. However, the scarce availability of normal and reference values for cardiovascular magnetic resonance imaging (CMR) based PWV is limiting clinical implementation. The aim of this study was to determine normal and reference values for CMR assessed PWV in the general population. Methods From the 2,484 participants of the Netherlands Epidemiology of Obesity (NEO) study that have available CMR-PWV data, 1,394 participants free from cardiovasculard disease, smokers or treatment for diabetes, hypertension or dyslipidaemia were selected (45–65 years, 51% female). Participants were divided into sex, age and blood pressure (BP) subgroups. Normal values were specified for participants with a BP Results Normal mean PWV was 6.0 m/s [95% CI 5.8–6.1]. PWV increased with advancing age and BP categories (both p 140/90 mmHg women had a higher PWV (p = 0.005). The interpercentile ranges were smaller for participants Conclusion This study provides normal and reference values for CMR-assessed PWV per sex, age and blood pressure category in the general population.

Background: coronary computed tomography angiography (CCTA) is a first line non-invasive imaging modality for detection of coronary atherosclerosis. Computational modeling with lipidomics analysis can be used for prediction of coronary atherosclerotic plaque progression. Methods: 187 patients (480 vessels) with stable coronary artery disease (CAD) undergoing CCTA scan at baseline and after 6.2 ± 1.4 years were selected from the SMARTool clinical study cohort (Clinicaltrial.gov Identifiers NCT04448691) according to a computed tomography (CT) scan image quality suitable for three-dimensional (3D) reconstruction of coronary arteries and the absence of implanted coronary stents. Clinical and biohumoral data were collected, and plasma lipidomics analysis was performed. Blood flow and low-density lipoprotein (LDL) transport were modeled using patient-specific data to estimate endothelial shear stress (ESS) and LDL accumulation based on a previously developed methodology. Additionally, non-invasive Fractional Flow Reserve (FFR) was calculated (SmartFFR). Plaque progression was defined as significant change of at least two of the morphological metrics: lumen area, plaque area, plaque burden. Results: a multi-parametric predictive model, including traditional risk factors, plasma lipids, 3D imaging parameters, and computational data demonstrated 88% accuracy to predict site-specific plaque progression, outperforming current computational models. Conclusions: Low ESS and LDL accumulation, estimated by computational modeling of CCTA imaging, can be used to predict site-specific progression of coronary atherosclerotic plaques.

Patients presenting with chronic and acute chest pain constitute a common and important diagnostic challenge. This has increased interest in using computerized tomography for non-invasive visualization of coronary artery disease in patients presenting with acute chest pain to the emergency department, particularly the subset of patients who are suspected of having an acute coronary syndrome, but without typical electrocardiographic changes and with normal troponin levels at presentation. As a result of rapid developments in coronary computerized tomography angiography technology, high diagnostic accuracies for excluding coronary artery disease can be obtained. It has been shown that these patients can be discharged safely. The accuracy for detecting a significant coronary artery stenosis is also high, but the presence of coronary artery atherosclerosis or stenosis does not imply necessarily that the cause of the chest pain is related to coronary artery disease. Moreover, non-invasive detection of coronary artery disease by computerized tomography has been shown to be related with an increased use of subsequent invasive coronary angiography and revascularization, and further studies are needed to define which patients benefit from invasive evaluation following coronary computerized tomography angiography. Conversely, implementation of coronary computerized tomography angiography can significantly reduce the length of hospital stay, with a significant cost reduction. Additionally, computerized tomography is an excellent modality in patients whose symptoms suggest other causes of acute chest pain such as aortic aneurysm, aortic dissection, or pulmonary embolism. Furthermore, acquisition of the coronary arteries, thoracic aorta, and pulmonary arteries in a single computerized tomography examination is feasible, allowing ‘triple rule-out’ (exclusion of aortic dissection, pulmonary embolism, and coronary artery disease). Finally, other applications, such as evaluation of coronary artery plaque composition, myocardial function and perfusion, and non-invasive assessment of fractional flow reserve from coronary computerized tomography angiography, are currently being developed and may also become valuable in the setting of chronic and acute chest pain in the future.

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported in part from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2020 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR) , no. GR 5002802 ,and by Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Assessment of coronary atherosclerosis: a new complete, anatomo-functional, morphological and biomechanical approach”, Project no. 504776 Background Computed Tomography Coronary Angiography (CTCA) is a non-invasive imaging modality, used effectively for anatomo-functional assessment of coronary artery disease (CAD). Machine learning (ML) processes can effectively allow the extraction of useful information from multidimensional feature spaces for evaluation of coronary lesions. Purpose To investigate the ability of ML for predicting impaired myocardial blood flow (MBF) by combining computational fluid dynamics (CFD) derived parameters with quantitative plaque burden, plaque morphology and anatomical characteristics obtained from CTCA. Methods 53 patients (31 male, mean age 64.7 ± 7.1 years) with intermediate pre-test likelihood of CAD who underwent CTCA and PET-MPI were included. PET was considered positive when > 1 contiguous segment demonstrated MBF ≤ 2.3 mL/g/min for 15O-water or ≤ 1.79 for 13N-ammonia respectively. CFD derived parameters such as a previously validated, virtual functional assessment index (vFAI), segmental endothelial shear stress (ESS), as well as anatomical and plaque characteristics were assessed. Seven classifiers were implemented and internally validated using 5-fold cross validation, repeated 1000 times. Using sequential forward selection (SFS), the highest rank features combination, based on appearances in the highest mean area under curve (AUC) classification scheme, was selected and features performance was evaluated following exhaustive search (ES). Results 92 coronary segments were analyzed and 34 features derived from CTCA were extracted. Classifiers performance are depicted in Figure A. k-NN was the best classifier with AUCmean = 0.791 (SENSmean= 0.622, SPECmean = 0.840, p Conclusion ML analysis is feasible for predicting with reasonable specificity abnormal MBF by PET, using a combination of CFD derived parameters and anatomical features. vFAI as a single characteristic was a specific predictor of impaired MBF, whilst in combination with stenosis severity, maintained almost the same AUC and specificity values and resulted in improved sensitivity. On the other hand, addition of lumen area to vFAI, increases the AUC and provides a relatively good specificity but low sensitivity. Abstract Figure 1

Cardiac sympathetic activity plays a key role in supporting cardiac function in both health and disease conditions, and nuclear cardiac imaging has always represented the only way for the non-invasive evaluation of the functional integrity of cardiac sympathetic terminals, mainly through the use of radiopharmaceuticals that are analogues of norepinephrine and, in particular, with the use of 123I-mIBG imaging. This technique demonstrates the presence of cardiac sympathetic dysfunction in different cardiac pathologies, linking the severity of sympathetic nervous system impairment to adverse patient’s prognosis. This article will outline the state-of-the-art of cardiac 123I-mIBG imaging and define the value and clinical applications in the different fields of cardiovascular diseases.

Aims The COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS). However, no significant effect was found on clinical endpoints, possibly due to a short follow-up period. The aim of the current study was therefore to investigate the long-term clinical outcomes after losartan treatment. Methods and results In the original COMPARE study (inclusion 2008–2009), adult patients with MFS (n = 233) were randomly allocated to either the angiotensin-II receptor blocker losartan® on top of regular treatment (β-blockers in 71% of the patients) or no additional medication. After the COMPARE trial period of 3 years, study subjects chose to continue their losartan medication or not. In a median follow-up period of 8 years, 75 patients continued losartan medication, whereas 78 patients, originally allocated to the control group, never used losartan after inclusion. No differences existed between baseline characteristics of the two groups except for age at inclusion [losartan 34 (interquartile range, IQR 26–43) years, control 41 (IQR 30–52) years; P = 0.031], and β-blocker use (losartan 81%, control 64%; P = 0.022). A pathological FBN1 mutation was present in 76% of patients and 58% of the patients were male. Clinical endpoints, defined as all-cause mortality, aortic dissection/rupture, elective aortic root replacement, reoperation, and vascular graft implantation beyond the aortic root, were compared between the two groups. A per-patient composite endpoint was also analysed. Five deaths, 14 aortic dissections, 23 aortic root replacements, 3 reoperations, and 3 vascular graft implantations beyond the aortic root occurred during follow-up. Except for aortic root replacement, all endpoints occurred in patients with an operated aortic root. Patients who used losartan during the entire follow-up period showed a reduced number of events compared to the control group (death: 0 vs. 5, P = 0.014; aortic dissection: 3 vs. 11, P = 0.013; elective aortic root replacement: 10 vs. 13, P = 0.264; reoperation: 1 vs. 2, P = 0.463; vascular graft implantations beyond the aortic root 0 vs. 3, P = 0.071; and composite endpoint: 14 vs. 26, P = 0.019). These results remained similar when corrected for age and β-blocker use in a multivariate analysis. Conclusion These results suggest a clinical benefit of combined losartan and β-blocker treatment in patients with MFS.

Background Sex related differences exist for coronary artery disease (CAD). Women tend to be older when presenting with CAD and have lower rates of obstructive disease. Invasive intravascular ultrasound studies have shown differences in plaque composition between males and females. However, these studies were performed in a high risk population needing invasive imaging. Coronary computed tomography angiography (CTA) allows for a fast and non-invasive quantification of CAD in low risk patients. Sex differences and quantitative analysis of plaque progression and changes in plaque composition have not been studied intensively. Purpose To evaluate the role of sex on long term plaque progression and on the change of plaque composition in a population with low-intermediate risk. Methods Patients that received a coronary CTA were prospectively included in the SMARTool study to receive a follow-up coronary CTA. In total, 275 patients from 5 European countries were recruited in 7 centers. Baseline and follow-up coronary CTA were quantitative analyzed on a per-lesion basis using dedicated software package. Patients without coronary plaques at follow-up or with uninterpretable coronary CTA results were excluded. Total plaque volume and compositional volumes, calcified or non-calcified (defined as fibrous, fibro-fatty or necrotic core), were normalized using the vessel volume to calculate a percentage atheroma volume (PAV). Lesions between males and females were compared using linear mixed models. We further classified patients into age groups Results In total, 211 patients were included in this analysis, 146 (69%) were male and 65 (31%) were female. Mean interscan period was 6.2±1.4 years. Females were older (64±7 vs 61±8 years; p0.05). When stratifying the patients in above and below 55 years old, females still had less fibro-fatty PAV compared to males in both age groups (p Conclusions Males have larger fibro-fatty PAV compared to females, however the rate of change did not differ. Younger women showed more regression of fibrous PAV and non-calcified PAV compared to males. No differences in the rate of plaque progression or plaque composition changes were seen between males and females in the older age group. Figure plaque progression and sex diff Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): EU H2020 research and innovation program

Background Elevated TG/HDL-C ratio is associated with CVD outcomes in high-risk populations presenting for coronary angiography, but studies were limited in gender-specific populations or in pts with ACS. Purpose Aim of this study was to evaluate the prognostic role of TG/HDL-C levels and their association with CAD progression in pts with suspected stable CAD. Methods TG/HDL-C ratio was calculated in 545 pts (60±9yrs,330males) with symptoms of stable CAD enrolled in the EVINCI study. 490 pts underwent coronary CTA to assess the presence of CAD (>50%stenosis) and entered a clinical follow up (4.5±0.9yrs). The CVD outcome measure included all cause mortality, non fatal MI, hospitalization for unstable angina or HF. After 6±1yrs, during the SMARTool study, a second CTA was obtained in 171 EVINCI pts and a CTA risk score (based on plaque extent, severity, composition, and location) was calculated at enrolment and at follow up to assess CAD progression (ΔCTA score). Results Pts were divided according to TG/HDL-C quartiles: IQ (3.33). As reported in Table, the frequency of male, diabetes, metabolic syndrome and obesity increased among quartiles. Glucidic biomarkers progressively increased from quartile I to IV, while LDL-C decreased. The prevalence of obstructive CAD at CTA did not differ among groups. The CVD endpoint occurred in 7% of pts. At multivariable analyses, high TG/HDL-C ratio (IVQ) was associated with the outcome endpoint independently from presence of obstructive CAD and treatment (HR 3.477, 95% CI 1.181–10.239, P=0.0237). CTA score was significantly higher in pts in IVQ compared to IQ at both SMARTool enrolment and follow up (Figure1). A significantly higher ΔCTA score was observed in pts in III-IVQ compared with those in I-IIQ (Figure2). Conclusion Elevated TG/HDL-C ratio is an independent predictor of outcome and it is associated with CAD progression in patients with stable CAD. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): “EValuation of INtegrated Cardiac Imaging” - EVINCI [GA number: 222915]; “Simulation Modeling of coronary ARTery disease: a tool for clinical decision support - SMARTool” [GA number: 689068]

Aims In patients with post-myocardial infarction (post-MI) ventricular tachycardia (VT), the presence of myocardial calcification (MC) may prevent heating of a subepicardial VT substrate contributing to endocardial ablation failure. The aims of this study were to assess the prevalence of MC in patients with post-MI VT and evaluate the impact of MC on outcome after endocardial ablation. Methods and results In 158 patients, the presence of MC was retrospectively assessed on fluoroscopy recordings in seven standard projections obtained during pre-procedural coronary angiograms. Myocardial calcification, defined as a distinct radiopaque area that moved synchronously with the cardiac contraction, was detected in 30 patients (19%). After endocardial ablation, only 6 patients (20%) with MC were rendered non-inducible compared with 56 (44%) without MC (P = 0.033) and of importance, 8 (27%) remained inducible for the clinical VT [compared with 9 (6%) patients without MC; P = 0.003] requiring therapy escalation. After a median follow-up of 31 months, 61 patients (39%) had VT recurrence and 47 (30%) died. Patients with MC had a lower survival free from the composite endpoint of VT recurrence or therapy escalation at 24-month follow-up (26% vs. 59%; P = 0.003). Presence of MC (HR 1.69; P = 0.046), a lower LV ejection fraction (HR 1.03 per 1% decrease; P = 0.017), and non-complete procedural success (HR 2.42; P = 0.002) were independently associated with a higher incidence of VT recurrence or therapy escalation. Conclusion Myocardial calcification was present in 19% of post-MI patients referred for VT ablation and was associated with a high incidence of endocardial ablation failure.

Contains fulltext : 220894.pdf (Publisher’s version ) (Closed access) AIMS: We aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores - which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) - and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders. METHODS: Out of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability. RESULTS: A total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265). CONCLUSION: Coronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone.

Aims We aimed to evaluate the associations of body fat distribution with cardiovascular function and geometry in the middle-aged general population. Methods and results Four thousand five hundred and ninety participants of the UK Biobank (54% female, mean age 61.1 ± 7.2 years) underwent cardiac magnetic resonance for assessment of left ventricular (LV) parameters [end-diastolic volume (EDV), ejection fraction (EF), cardiac output (CO), and index (CI)] and magnetic resonance imaging for body composition analysis [subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)]. Body fat percentage (BF%) was assessed by bioelectrical impedance. Linear regressions were performed to assess the impact of visceral (VAT) and general (SAT and BF%) obesity on cardiac function and geometry. Visceral obesity was associated with a smaller EDV [VAT: β −1.74 (−1.15 to −2.33)], lower EF [VAT: β −0.24 (−0.12 to −0.35), SAT: β 0.02 (−0.04 to 0.08), and BF%: β 0.02 (−0.02 to 0.06)] and the strongest negative association with CI [VAT: β −0.05 (−0.06 to −0.04), SAT: β −0.02 (−0.03 to −0.01), and BF% β −0.01 (−0.013 to −0.007)]. In contrast, general obesity was associated with a larger EDV [SAT: β 1.01 (0.72–1.30), BF%: β 0.37 (0.23–0.51)] and a higher CO [SAT: β 0.06 (0.05–0.07), BF%: β 0.02 (0.01–0.03)]. In the gender-specific analysis, only men had a significant association between VAT and EF [β −0.35 (−0.19 to −0.51)]. Conclusion Visceral obesity was associated with a smaller LV EDV and subclinical lower LV systolic function in men, suggesting that visceral obesity might play a more important role compared to general obesity in LV remodelling.

Background Progression of coronary artery disease using serial coronary computed tomography angiography (CTA) is of clinical interest. Our primary aim was to prospectively assess the impact of clinical characteristics and statin use on quantitatively assessed coronary plaque progression in a low-risk study population during long-term follow-up. Methods Patients who previously underwent coronary CTA for suspected coronary artery disease were prospectively included to undergo follow-up coronary CTA. The primary end point was coronary artery disease progression, defined as the absolute annual increase in total, calcified, and noncalcified plaque volume by quantitative CTA analysis. Results In total, 202 patients underwent serial coronary CTA with a mean interscan period of 6.2±1.4 years. On a per-plaque basis, increasing age (β=0.070; P =0.058) and hypertension (β=1.380; P =0.075) were nonsignificantly associated with annual total plaque progression. Male sex (β=1.676; P =0.009), diabetes mellitus (β=1.725; P =0.012), and statin use (β=1.498; P =0.046) showed an independent association with annual progression of calcified plaque. While hypertension (β=2.259; P =0.015) was an independent determinant of noncalcified plaque progression, statin use (β=−2.178; P =0.050) was borderline significantly associated with a reduced progression of noncalcified plaque. Conclusions Statin use was associated with an increased progression of calcified coronary plaque and a reduced progression of noncalcified coronary plaque, potentially reflecting calcification of the noncalcified plaque component. Whereas hypertension was the only modifiable risk factor predictive of noncalcified plaque progression, diabetes mellitus mainly led to an increase in calcified plaque. These findings could yield the need for intensified preventive treatment of patients with diabetes mellitus and hypertension to slow and stabilize coronary artery disease progression and improve clinical outcome.

Background and Aims. Atherosclerosis is an inflammatory disease with long-lasting activation of innate immunity and monocytes are the main blood cellular effectors. We aimed to investigate monocyte phenotype (subset fraction and marker expression) at different stages of coronary atherosclerosis in stable coronary artery disease (CAD) patients. Methods. 73 patients with chronic coronary syndrome were evaluated by CT coronary angiography (CTCA) and classified by maximal diameter stenosis of major vessels into three groups of CAD severity: CAD1 (no CAD/minimal CAD, n°=30), CAD2 (non-obstructive CAD, n°=21), and CAD3 (obstructive CAD, n°=22). Flow cytometry for CD14, CD16, and CCR2 was used to quantify Mon1, Mon2, and Mon3 subsets. Expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1, and CXCR4 was also measured. Adhesion molecules and cytokines were quantified by ELISA. Results. Total cell count and fraction of Mon2 were higher in CAD2 and CAD3 compared to CAD1. By multivariate regression analysis, Mon2 cell fraction and Mon2 expression of CX3CR1, CD18, and CD16 showed a statistically significant and independent increase, parallel to stenosis severity, from CAD1 to CAD2 and CAD3 groups. A similar trend was also present for CX3CR1 and HLA-DR expressions on total monocyte population. A less calcified plaque composition was associated to a higher Mon2 expression of CD16 and higher TNF-α levels. IL-10 levels were lower at greater stenosis severity, while the IFN-γ/IL-10 ratio, a marker of a systemic pro-inflammatory imbalance, was directly correlated to stenosis degree and number of noncalcified plaques. Conclusions. The results of this study suggest that a specific pattern of inflammation-correlated monocyte marker expression is associated to higher stenosis severity and less calcified lesions in stable CAD. The clinical trial Identifier is NCT04448691.

Regrettably the original version of the above article contained errors in the three chemical structures presented in the ‘Atherosclerosis imaging’ section of Table 5, namely: 99mTc annexin V, 68Ga DOTATATE, and 64Cu DOTATATE; the chemical structures have been corrected in Table presented here. In addition, the radiopharmaceutical for isotope 67Ga has been corrected to 67Ga citrate, and many of the radiopharmaceuticals presented at the end of the table have been corrected.

Objectives: To analyse the implementation, applicability and accuracy of the pretest probability calculation provided by NICE clinical guideline 95 for decision making about imaging in patients with chest pain of recent onset. Methods: The definitions for pretest probability calculation in the original Duke clinical score and the NICE guideline were compared. We also calculated the agreement and disagreement in pretest probability and the resulting imaging and management groups based on individual patient data from the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT). Results: 4,673 individual patient data from the CoMe-CCT Consortium were analysed. Major differences in definitions in the Duke clinical score and NICE guideline were found for the predictors age and number of risk factors. Pretest probability calculation using guideline criteria was only possible for 30.8 % (1,439/4,673) of patients despite availability of all required data due to ambiguity in guideline definitions for risk factors and age groups. Agreement regarding patient management groups was found in only 70 % (366/523) of patients in whom pretest probability calculation was possible according to both models. Conclusions: Our results suggest that pretest probability calculation for clinical decision making about cardiac imaging as implemented in the NICE clinical guideline for patients has relevant limitations. Key Points: • Duke clinical score is not implemented correctly in NICE guideline 95. • Pretest probability assessment in NICE guideline 95 is impossible for most patients. • Improved clinical decision making requires accurate pretest probability calculation. • These refinements are essential for appropriate use of cardiac CT.

Combined CT angiography and CT myocardial perfusion enables similar prediction of 2-year major adverse cardiovascular event–free survival, including the need for myocardial revascularization procedures, similar to that achieved with standard invasive coronary angiography and single photon emission CT perfusion imaging.

Contains fulltext : 182860.pdf (Publisher’s version ) (Open Access) Fractional flow reserve (FFR) guided percutaneous coronary intervention (PCI) is associated with favourable outcome compared with revascularization based on angiographic stenosis severity alone. The feasibility of the new image-based quantitative flow ratio (QFR) assessed from 3D quantitative coronary angiography (QCA) and thrombolysis in myocardial infarction (TIMI) frame count using three different flow models has been reported recently. The aim of the current study was to assess the accuracy, and in particular, the reproducibility of these three QFR techniques when compared with invasive FFR. QFR was derived (1) from adenosine induced hyperaemic coronary angiography images (adenosine-flow QFR [aQFR]), (2) from non-hyperemic images (contrast-flow QFR [cQFR]) and (3) using a fixed empiric hyperaemic flow [fixed-flow QFR (fQFR)]. The three QFR values were calculated in 17 patients who prospectively underwent invasive FFR measurement in 20 vessels. Two independent observers performed the QFR analyses. Mean difference, standard deviation and 95% limits of agreement (LOA) between invasive FFR and aQFR, cQFR and fQFR for observer 1 were: 0.01 +/- 0.04 (95% LOA: -0.07; 0.10), 0.01 +/- 0.05 (95% LOA: -0.08; 0.10), 0.01 +/- 0.04 (95% LOA: -0.06; 0.08) and for observer 2: 0.00 +/- 0.03 (95% LOA: -0.06; 0.07), -0.01 +/- 0.03 (95% LOA: -0.07; 0.05), 0.00 +/- 0.03 (95% LOA: -0.06; 0.05). Values between the 2 observers were (to assess reproducibility) for aQFR: 0.01 +/- 0.04 (95% LOA: -0.07; 0.09), for cQFR: 0.02 +/- 0.04 (95% LOA: -0.06; 0.09) and for fQFR: 0.01 +/- 0.05 (95% LOA: -0.07; 0.10). In a small number of patients we showed good accuracy of three QFR techniques (aQFR, cQFR and fQFR) to predict invasive FFR. Furthermore, good inter-observer agreement of the QFR values was observed between two independent observers.

Background Spinal cord stimulation (SCS) reduces sympathetic activity in animal models of heart failure with reduced ejection fraction (HF) but limited data exist of SCS in patients with HF. The aim of the present study was to test the primary hypothesis that SCS reduces cardiac sympathetic nerve activity in HF patients. Secondary hypotheses were that SCS improves left ventricular function and dimension, exercise capacity, and clinical variables relevant to HF. Methods HF patients with a SCS device previously participating in the DEFEAT-HF trial were included in this crossover study with 6-week intervention periods (SCS-ON and SCS-OFF). SCS (50 Hz, 210-μs pulse duration, aiming at T2–T4 segments) was delivered for 12 hours daily. Indices of myocardial sympathetic neuronal function (heart-to-mediastinum ratio, HMR) and activity (washout rate, WR) were assessed using 123I-metaiodobenzylguanidine (MIBG) scintigraphy. Echocardiography, exercise testing, and clinical data collection were also performed. Results We included 13 patients (65.3 ± 8.0 years, nine males) and MIBG scintigraphy data were available in 10. HMR was not different comparing SCS-ON (1.37 ± 0.16) and SCS-OFF (1.41 ± 0.21, P = 0.46). WR was also unchanged comparing SCS-ON (41.5 ± 5.3) and SCS-OFF (39.1 ± 5.8, P = 0.30). Similarly, average New York Heart Association class (2.4 ± 0.5 vs 2.3 ± 0.6, P = 0.34), quality of life score (24 ± 16 vs 24 ± 16, P = 0.94), and left ventricular dimension and function as well as exercise capacity were all unchanged comparing SCS-ON and SCS-OFF. Conclusion In patients with HF, SCS (12 hours daily, targeting the T2–T4 segments of the spinal cord) does not appear to influence cardiac sympathetic neuronal activity or function as assessed by MIBG scintigraphy.

Item does not contain fulltext Cardiac sympathetic nervous system dysfunction is closely associated with risk of serious cardiac events in patients with heart failure (HF), including HF progression, pump-failure death, and sudden cardiac death by lethal ventricular arrhythmia. For cardiac sympathetic nervous system imaging, (123)I-meta-iodobenzylguanidine ((123)I-MIBG) was approved by the Japanese Ministry of Health, Labour and Welfare in 1992 and has therefore been widely used since in clinical settings. (123)I-MIBG was also later approved by the Food and Drug Administration (FDA) in the United States of America (USA) and it was expected to achieve broad acceptance. In Europe, (123)I-MIBG is currently used only for clinical research. This review article is based on a joint symposium of the Japanese Society of Nuclear Cardiology (JSNC) and the American Society of Nuclear Cardiology (ASNC), which was held in the annual meeting of JSNC in July 2016. JSNC members and a member of ASNC discussed the standardization of (123)I-MIBG parameters, and clinical aspects of (123)I-MIBG with a view to further promoting (123)I-MIBG imaging in Asia, the USA, Europe, and the rest of the world.

Item does not contain fulltext The aim of this study was to explore the association between various cardiovascular (CV) risk scores and coronary atherosclerotic burden on coronary computed tomography angiography (CTA) in South Asians with type 2 diabetes mellitus and matched whites. Asymptomatic type 2 diabetic South Asians and whites were matched for age, gender, body mass index, hypertension, and hypercholesterolemia. Ten-year CV risk was estimated using different risk scores (United Kingdom Prospective Diabetes Study [UKPDS], Framingham Risk Score [FRS], AtheroSclerotic CardioVascular Disease [ASCVD], and Joint British Societies for the prevention of CVD [JBS3]) and categorized into low- and high-risk groups. The presence of coronary artery calcium (CAC) and obstructive coronary artery disease (CAD; >/=50% stenosis) was assessed using coronary CTA. Finally, the relation between coronary atherosclerosis on CTA and the low- and high-risk groups was compared. UKPDS, FRS, and ASCVD showed no differences in estimated CV risk between 159 South Asians and 159 matched whites. JBS3 showed a significant greater absolute CV risk in South Asians (18.4% vs 14.2%, p 0 (69% vs 55%, p

Contains fulltext : 182888.pdf (Publisher’s version ) (Open Access) Two-dimensional echocardiographic left ventricular (LV) global longitudinal strain (GLS) after ST-segment elevation myocardial infarction (STEMI) is moderately correlated with infarct size and reflects the residual LV systolic function. This correlation may be influenced by the presence of myocardial ischemia. The present study investigated how myocardial ischemia modulates the correlation between LV GLS and infarct size determined with single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in patients with first STEMI treated with primary coronary intervention. A total of 1,128 patients (age 60 +/- 11 years) who underwent SPECT MPI for the evaluation of infarct size and residual ischemia were evaluated. LV GLS was measured on transthoracic echocardiography. The time interval between echocardiography and SPECT MPI was 1 +/- 1 month. A moderate correlation between echocardiographic LV GLS and infarct size on SPECT MPI was observed (r = 0.58, p

Objective Aim of this study was to evaluate the relationship of plasma PCSK9 with metabolic and inflammatory profile and coronary atherosclerotic burden in patients with suspected CAD enrolled in the EVINCI study. Methods PCSK9 was measured in 539 patients (60.3 ± 8.6 years, 256 males) with symptoms of CAD characterized by risk factors, bio-humoral profiles, and treatment. N = 412 patients underwent coronary computed tomography angiography (CTA) to assess the presence and characteristics of coronary atherosclerosis. A CTA score, combining extent, severity, composition, and location of plaques was computed. Results Patients were divided according to PCSK9 quartiles: I ( 266 ng/mL). Compared with patients in quartile IV, patients in quartile I had a higher prevalence of the metabolic syndrome and higher values of body mass index. LDL- and HDL-cholesterol were significantly lower in patients in the quartile I than in those in quartile IV. Coronary CTA documented normal vessels in 30% and obstructive CAD in 35% of cases without differences among PCSK9 quartiles. Compared with patients with the highest levels, patients with the lowest PCSK9 levels had a higher CTA score mainly due to higher number of mixed non-obstructive coronary plaques. At multivariable analysis including clinical, medications, and lipid variables, PCSK9 was an independent predictor of the CTA score (coefficient − 0.129, SE 0.03, P Conclusion In patients with stable CAD, low PCSK9 plasma levels are associated with a particular metabolic phenotype (low HDL cholesterol, the metabolic syndrome, obesity, insulin resistance and diabetes) and diffuse non-obstructive coronary atherosclerosis. Trial registration ClinicalTrials.gov NCT00979199. Registered September 17, 2009

Background Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of LDL cholesterol levels and has emerged as a new therapeutic target in coronary artery disease (CAD). Plasma PCSK9 levels have also been related to other components of the lipid profile associated with atherosclerotic risk. Purpose Aim of the present study was to evaluate the relationship of plasma PCSK9 levels with lipid profile and measures of coronary atherosclerotic burden and risk in patients with stable CAD enrolled in the European EValuation of INtegrated Cardiac Imaging (EVINCI) study. Methods PCSK9 was measured in 412 patients (60.3±8.6 years, 256 males) with symptoms of stable CAD fully characterized by clinical risk factors, bio-humoral profiles, and treatment. All patients underwent coronary computed tomography (CT) angiography to assess the presence and characteristics of coronary atherosclerosis. We calculated an individual CT risk score, expressing the coronary atherosclerotic burden, combining extent, severity, composition, and location of plaques. Results Patients were divided in groups according to PCSK9 quartiles: I (266 ng/mL). LDL and HDL-cholesterol levels were significantly lower while total/HDL-cholesterol ratio was significantly higher in patients in the quartile I than in those in quartile IV (Figure A). CT angiography documented normal vessels in 30 and obstructive CAD in 35% of cases. Compared with patients with the highest levels (quartile IV), patients with the lowest PCSK9 levels (quartile I) had a higher CT risk score, a higher number of mixed plaque and higher hs-cTnI plasma levels (Figure B). PCSK9 itself was not associated with obstructive CAD. At multivariable analysis including clinical variables, medications and lipid variables PCSK9 was an independent predictor of the CT risk score (Coefficient - 0.129 (SE 0.03), p Figure 1 Conclusion PCSK9 levels are independently and inversely associated with the coronary atherosclerotic burden in patients with stable CAD. Acknowledgement/Funding AMGEN grant, EU FP7-CP-FP506 2007 project (grant agreement no. 222915)

Item does not contain fulltext OBJECTIVES: This study was designed to assess the prognostic value of a new comprehensive coronary computed tomography angiography (CTA) score compared with the stenosis severity component of the Coronary Artery Disease-Reporting and Data System (CAD-RADS). BACKGROUND: Current risk assessment with coronary CTA is mainly focused on maximal stenosis severity. Integration of plaque extent, location, and composition in a comprehensive model may improve risk stratification. METHODS: A total of 2,134 patients with suspected but without known CAD were included. The predictive value of the comprehensive CTA score (ranging from 0 to 42 and divided into 3 groups: 0 to 5, 6 to 20, and >20) was compared with the CAD-RADS combined into 3 groups (0% to 30%, 30% to 70% and >/=70% stenosis). Its predictive performance was internally and externally validated (using the 5-year follow-up dataset of the CONFIRM [Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry], n = 1,971). RESULTS: The mean age of patients was 55 +/- 13 years, mean follow-up 3.6 +/- 2.8 years, and 130 events (myocardial infarction or death) occurred. The new, comprehensive CTA score showed strong and independent predictive value using the Cox proportional hazard analysis. A model including clinical variables plus comprehensive CTA score showed better discrimination of events compared with a model consisting of clinical variables plus CAD-RADS (0.768 vs. 0.742, p = 0.001). Also, the comprehensive CTA score correctly reclassified a significant proportion of patients compared with the CAD-RADS (net reclassification improvement 12.4%, p < 0.001). Good predictive accuracy was reproduced in the external validation cohort. CONCLUSIONS: The new comprehensive CTA score provides better discrimination and reclassification of events compared with the CAD-RADS score based on stenosis severity only. The score retained similar prognostic accuracy when externally validated. Anatomic risk scores can be improved with the addition of extent, location, and compositional measures of atherosclerotic plaque. (Comprehensive CTA risk score calculator is available at: http://18.224.14.19/calcApp/).

Background Leptin is an adipokine involved in energy homeostasis and has been related with established vascular risk factors. However, studies on the association of leptin plasma levels with coronary artery disease (CAD) have yielded conflicting results. Purpose Aim of the present study was to evaluate the association between leptin plasma levels and presence, severity and progression of coronary atherosclerosis in patients with suspected stable CAD. Methods In a cohort of 257 patients with symptoms of stable CAD enrolled in the SMARTool study, coronary computed tomography angiography (CTA), plasma leptin levels and clinical and bio-humoral CAD risk profile (including glucose, lipid and inflammation variables) were obtained at enrolment and after 6±1yrs of follow-up. Sixty-four patients were revascularized and the remaining 193 represent the population for the present study. CTA findings were categorised as no-minimal CAD ( Results CTA findings showed obstructive CAD in 11% of patients at baseline and in 15% at follow-up (p Figure 1 Conclusion Plasma leptin is inversely associated with coronary atherosclerotic burden and disease progression in patients with stable CAD. This association is independent of known factors affecting leptin levels. These results could prompt further investigations on the pathophysiological mechanisms of this association. Acknowledgement/Funding EU H2020 research and innovation program under grant agreement No 689068

Aims To test the hypothesis that virtual functional assessment index (vFAI) is related with regional flow parameters derived by quantitative positron emission tomography (PET) and can be used to assess abnormal vasodilating capability in coronary vessels with stenotic lesions at coronary computed tomography angiography (CCTA). Methods and results vFAI, stress myocardial blood flow (MBF), and myocardial flow reserve (MFR) were assessed in 78 patients (mean age 62.2 ± 7.7 years) with intermediate pre-test likelihood of coronary artery disease (CAD). Coronary stenoses ≥50% were considered angiographically significant. PET was considered positive for significant CAD, when more than one contiguous segments showed stress MBF ≤2.3 mL/g/min for15O-water or 13N-ammonia. MFR thresholds were ≤2.5 and ≤2.0, respectively. vFAI was lower in vessels with abnormal stress MBF (0.76 ± 0.10 vs. 0.89 ± 0.07,P P 15O-water and 82.7% and 71.2% in13N-ammonia studies, respectively. Addition of vFAI to anatomical CCTA data increased the ability for predicting abnormal stress MBF and MFR in15O-water studies [AUCccta + vfai = 0.866, 95% confidence interval (CI) 0.783–0.949;P = 0.013 and AUCccta + vfai = 0.737, 95% CI 0.648–0.825;P = 0.007, respectively]. An incremental value was also demonstrated for prediction of stress MBF (AUCccta + vfai = 0.887, 95% CI 0.799–0.974;P = 0.001) in13N-ammonia studies. A similar trend was recorded for MFR (AUCccta + vfai = 0.780, 95% CI 0.632–0.929;P = 0.13). Conclusion vFAI identifies accurately the presence of impaired vasodilating capability. In combination with anatomical data, vFAI enhances the diagnostic performance of CCTA.

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., This is the pre-final version.

Background The predictive value of coronary artery calcium ( CAC ) has been widely studied; however, little is known about specific characteristics of CAC that are most predictive. We aimed to determine the independent associations of Agatston score, CAC volume, CAC area, CAC mass, and CAC density score with major adverse cardiac events in patients with suspected coronary artery disease. Methods and Results A total of 379 symptomatic participants, aged 45 to 85 years, referred for invasive coronary angiography, who underwent coronary calcium scanning and computed tomography angiography as part of the CORE 320 (Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography) study, were included. Agatston score, CAC volume, area, mass, and density were computed on noncontrast images. Stenosis measurements were made on contrast‐enhanced images. The primary outcome of 2‐year major adverse cardiac events (30 revascularizations [>182 days of index catheterization], 5 myocardial infarctions, 1 cardiac death, 9 hospitalizations, and 1 arrhythmia) occurred in 32 patients (8.4%). Associations were estimated using multivariable proportional means models. Median age was 62 (interquartile range, 56–68) years, 34% were women, and 56% were white. In separate models, the Agatston, volume, and density scores were all significantly associated with higher risk of major adverse cardiac events after adjustment for age, sex, race, and statin use; density was the strongest predictor in all CAC models. CAC density did not provide incremental value over Agatston score after adjustment for diameter stenosis, age, sex, and race. Conclusions In symptomatic patients, CAC density was the strongest independent predictor of major adverse cardiac events among CAC scores, but it did not provide incremental value beyond the Agatston score after adjustment for diameter stenosis.

Background The posterior wall of the left atrium (LA) is a well‐known substrate for atrial fibrillation (AF) maintenance. Isolation of the posterior wall between the pulmonary veins (box lesion) may improve ablation success. Box lesion surface area size varies depending on the individual anatomy. This retrospective study evaluates the influence of box lesion surface area as a ratio of total LA surface area (box surface ratio) on arrhythmia recurrence. Methods Seventy consecutive patients with persistent AF (63 ± 11 years, 53 men) undergoing computed tomography (CT) imaging and ablation procedure consisting of a first box lesion were included in this study. Box lesion surface area was measured on electroanatomical maps and total LA surface area was derived from CT. Patients were followed with 24‐h electrocardiography and exercise tests at 3, 6, and 12 months after AF ablation. Arrhythmia recurrence was defined as any AF/atrial tachycardia (AT) beyond 3 months without antiarrhythmic drugs. Results During a median follow‐up of 13 (interquartile range = 10‐17) months, 42 (60%) patients had AF/AT recurrence. Multivariate Cox proportional regression analysis showed that a larger box surface ratio protected against recurrence (hazard ratio [HR] = 0.81; 95% confidence interval [CI] = 0.690‐0.955; P = 0.012). Left atrial volume index (HR = 1.01 [0.990‐1.024, P = 0.427] and a history of mitral valve surgery (HR = 2.90; 95% CI = 0.970‐8.693; P = 0.057) were not associated with AF recurrence in multivariate analysis. Conclusion A larger box lesion surface area as a ratio of total LA surface area is protective for AF/AT recurrence after ablation for persistent AF.