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Objective To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.Design Registry based observational study.Setting 74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021Participants All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients).Main outcome measures Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.Results Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).Conclusions In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.

Background: Additional diagnostic means could be of added value when evaluating possible acute coronary syndrome (ACS) in primary care., Aim: To determine whether heart-type fatty acid-binding protein (H-FABP)-based point-of-care (POC) biomarker testing, embedded in a clinical decision rule (CDR), is helpful to the GP when evaluating possible ACS., Design & Setting: A prospective, non-randomised, double-blinded, diagnostic derivation study was undertaken, with a delayed-type cross-sectional diagnostic model among GPs in the Netherlands and Belgium., Method: Signs and symptoms predicting acute myocardial infarction (AMI) or ACS were identified using both logistic regression analysis, and classification and regression trees (CART). Diagnostic values of the POC H-FABP test (cut-off value 4 ng/ml) alone and as part of a CDR were determined., Results: A total of 303 participants (48.8% male) with chest pain or discomfort who had consulted a GP were enrolled. ACS was found in 32 (10.6%) of these 303 patients. For ACS, sensitivity and negative predictive value (NPV) of the POC H-FABP test was 25.8% (95% confidence interval [CI] = 12.5 to 44.9) and 91.6% (95% CI = 87.6% to 94.5%), respectively. The area under the receiver operating curve of the optimal CDR was 0.78 for ACS., Conclusion: Sensitivity of the current H-FABP POC test (cut-off value 4 ng/ml) as a stand-alone test is poor, either owing to limitations of the marker or of the test device. Usability of a CDR derived from these results is doubtful: the number of ACS cases missed by the GP is reduced but, as a consequence, disproportionally more ACS-negative patients are referred., (Copyright © 2019, The Authors.)

Atrial fibrillation (AF) affects more than 33 million individuals worldwide 1 and has a complex heritability 2 . We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.

Purpose: Pain sensation and extravasation are potential drawbacks of contrast media (CM) injection during computed tomographic angiography. The purpose was to evaluate safety and patient comfort of higher flow rates in different CM protocols during coronary computed tomographic angiography., Methods: Two hundred consecutive patients of a double-blind randomized controlled trial (NCT02462044) were analyzed. Patients were randomized to receive 94 mL of prewarmed iopromide 240 mg I/mL at 8.3 mL/s (group I), 75 mL of 300 mg I/mL at 6.7 mL/s (group II), or 61 mL of 370 mg I/mL at 5.4 mL/s (group III), respectively. Iodine delivery rate (2.0 g I/s) and total iodine load (22.5 g I) were kept identical. Outcome was defined as intravascular enhancement, patient comfort during injection, and injection safety, expressed as the occurrence of extravasation. Patients completed a questionnaire for comfort, pain, and stress during CM injection. Comfort was graded using a 5-point scale, 1 representing "very bad" and 5 "very well." Pain was graded using a 10-point scale, 0 representing "no pain" and 10 "severe pain." Stress was graded using a 5-point scale, 1 representing "no stress" and 5 "unsustainable stress.", Results: Mean enhancement levels within the coronary arteries were as follows: 437 ± 104 Hounsfield units (HU) (group I), 448 ± 111 HU (group II), and 447 ± 106 HU (group III), with P ≥ 0.18. Extravasation occurred in none of the patients. Median (interquartile range) for comfort, pain, and stress was, respectively, 4 (4-5), 0 (0-0), and 1 (1-2), with P ≥ 0.68., Conclusions: High flow rates of prewarmed CM were safely injected without discomfort, pain, or stress. Therefore, the use of high flow rates should not be considered a drawback for CM administration in clinical practice.

Background: CC chemokine ligands (CCLs) are elevated during acute coronary syndrome (ACS) and correlate with secondary events. Their involvement in plaque inflammation led us to investigate whether CCL3-5-18 are linked to the extent of coronary artery disease (CAD) and prognostic for primary events during follow-up., Methods: We measured CCL3-5-18 serum concentrations in 712 patients with chest discomfort referred for cardiac CT angiography. Obstructive CAD was defined as ≥50 % stenosis. The extent of CAD was measured by calcium score and segment involvement score (number of coronary segments with any CAD, range 0-16). Patients were followed up for all-cause mortality, ACS and revascularisation, for a mean 26 ± 7 months., Results: Patients with obstructive CAD had significantly higher CCL5 (p = 0.02), and borderline significantly elevated CCL18 plasma levels as compared with patients with <50 % stenosis (p = 0.06). CCL18 levels were associated with coronary calcification (p = 0.002) and segment involvement score (p = 0.007). Corrected for traditional risk factors, only CCL5 provided independent predictive value for obstructive CAD: odds ratio (OR) 1.27 (1.02-1.59), p = 0.04. CCL5 provided independent predictive value for primary events during follow-up: OR 1.62 (1.03-2.57), p = 0.04., Conclusions: While CCL18 serum levels correlated with extent of CAD, CCL5 demonstrated an independent association with the presence of obstructive CAD, and occurrence of primary cardiac events., Competing Interests: Conflict of interestM.O. Versteylen, M. Manca, I.A. Joosen, D.E. Schmidt, M. Das, L. Hofstra, H.J. Crijns, E.A. Biessen and B.L. Kietselaer state they have no competing interest.

Purpose: To evaluate image quality using reduced contrast media (CM) volume in pre-TAVI assessment., Methods: Forty-seven consecutive patients referred for pre-TAVI examination were evaluated. Patients were divided into two groups: group 1 BMI < 28 kg/m(2) (n = 29); and group 2 BMI > 28 kg/m(2) (n = 18). Patients received a combined scan protocol: retrospective ECG-gated helical CTA of the aortic root (80kVp) followed by a high-pitch spiral CTA (group 1: 70 kV; group 2: 80 kVp) from aortic arch to femoral arteries. All patients received one bolus of CM (300 mgI/ml): group 1: volume = 40 ml; flow rate = 3 ml/s, group 2: volume = 53 ml; flow rate = 4 ml/s. Attenuation values (HU) and contrast-to-noise ratio (CNR) were measured at the levels of the aortic root (helical) and peripheral arteries (high-pitch). Diagnostic image quality was considered sufficient at attenuation values > 250HU and CNR > 10., Results: Diagnostic image quality for TAVI measurements was obtained in 46 patients. Mean attenuation values and CNR (HU ± SD) at the aortic root (helical) were: group 1: 381 ± 65HU and 13 ± 8; group 2: 442 ± 68HU and 10 ± 5. At the peripheral arteries (high-pitch), mean values were: group 1: 430 ± 117HU and 11 ± 6; group 2: 389 ± 102HU and 13 ± 6., Conclusion: CM volume can be substantially reduced using low kVp protocols, while maintaining sufficient image quality for the evaluation of aortic root and peripheral access sites., Key Points: • Image quality could be maintained using low kVp scan protocols. • Low kVp protocols reduce contrast media volume by 34-67 %. • Less contrast media volume lowers the risk of contrast-induced nephropathy.

Prolonged endurance-type exercise is associated with elevated cardiac troponin (cTn) levels in asymptomatic recreational athletes. It is unclear whether exercise-induced cTn release mirrors a physiological or pathological underlying process. The aim of this study was to provide a direct comparison of the release kinetics of high-sensitivity cTnI (hs-cTnI) and T (hs-cTnT) after endurance-type exercise. In addition, the effect of remote ischemic preconditioning (RIPC), a cardioprotective strategy that limits ischemia-reperfusion injury, was investigated in a randomized controlled crossover manner. Twenty-five healthy volunteers completed an outdoor 30-km running trial preceded by RIPC (4 × 5 min 220 mm Hg unilateral occlusion) or control intervention. hs-cTnT, hs-cTnI, and sensitive cTnI (s-cTnI) concentrations were examined before, immediately after, 2 and 5 hours after the trial. The completion of a 30-km run resulted in a significant increase in circulating cTn (time: all p <0.001), with maximum hs-cTnT, hs-cTnI, and s-cTnI levels of 47 ± 27, 69 ± 62, and 82 ± 64 ng/L (mean ± SD), respectively. Maximum hs-cTnT concentrations were measured in 60% of the participants at 2 hours after exercise, compared with maximum hs-cTnI and s-cTnI concentrations at 5 hours in 84% and 80% of the participants. Application of an RIPC stimulus did not reduce exercise-induced cTn release (time × trial: all p >0.5). In conclusion, in contrast to acute myocardial infarction, maximum hs-cTnT levels after exercise precede maximum hs-cTnI levels. Distinct release kinetics of hs-cTnT and hs-cTnI and the absence of an effect of RIPC favors the concept that exercise-induced cTn release may be mechanistically distinct from cTn release in acute myocardial infarction., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Management of patients with acute chest pain remains challenging. Cardiac biomarker testing reduces the likelihood of erroneously discharging patients with acute myocardial infarction (AMI). Despite normal contemporary troponins, physicians have still been reluctant to discharge patients without additional testing. Nowadays, the extremely high negative predictive value of current high-sensitivity cardiac troponin (hs-cTn) assays challenges this need. However, the decreased specificity of hs-cTn assays to diagnose AMI poses a new problem as noncoronary diseases (eg, pulmonary embolism, myocarditis, cardiomyopathies, hypertension, renal failure, etc) may also cause elevated hs-cTn levels. Subjecting patients with noncoronary diseases to unnecessary pharmacological therapy or invasive procedures must be prevented. Attempts to improve the positive predictive value to diagnose AMI by defining higher initial cutoff values or dynamic changes over time inherently lower the sensitivity of troponin assays. In this review, we anticipate a potential changing role of noninvasive imaging from ruling out myocardial disease when troponin values are normal toward characterizing myocardial disease when hs-cTn values are (mildly) abnormal., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose was to investigate optimal contrast media (CM) injection parameters for lower kVp settings, whilst maintaining diagnostic attenuation levels., Methods and Materials: First, a circulation phantom with physiological parameters (BP 120/80mmHg, HR 60bpm) was used. A fixed CM injection protocol was used for each kVp setting (300mgI/ml [Iopromide], volume=45ml, flow rate=6.0ml/s, iodine delivery rate [IDR]=1.8gI/s, iodine load=13.5gI; at 120, 100, 80 and 70kVp). Then, IDR was decreased by steps of 0.2gI/s for each kVp setting, until diagnostically insufficient attenuation values were reached (<325HU). In order to keep injection time constant (7.5s), total iodine load (TIL) was reduced accordingly. Second, clinical applicability at 120 and 100kVp was evaluated in patients (n=60) referred for coronary CT angiography. A standard and reduced (12% less) CM protocol was used based on weight classes and scan duration ('high-pitch': 1s; 'adaptive sequence' and 'helical': 7s). Attenuation levels of the coronary arteries were measured and compared between protocols., Results: Using a fixed CM injection at each kVp level resulted in the following HU values: 335HU±31 (120kVp); 425HU±30 (100kVp); 587HU±29 (80kVp); 666HU±27 (70kVp). Keeping diagnostic enhancement levels (353HU±28) CM could be reduced as follows: 12% for 100kVp; 45% for 80kVp and 56% for 70kVp. Diagnostic enhancement levels could be reproduced with concurrent CM reduction (-12% at 100kV) in the clinical setting (382HU±35)., Conclusion: CM injection parameters can be substantially reduced at low kVp settings (up to 56% at 70kVp), whilst maintaining diagnostic attenuation levels. This may play an important role in CT imaging of the coronary arteries as well as cerebral and peripheral circulations in the future., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Background: High-sensitivity cardiac troponins (hs-cTn) are the preferred biomarkers to detect myocardial injury, making them promising risk-stratifying tools for patients with symptoms of chest pain. However, circulating hs-cTn are also elevated in other conditions like renal dysfunction, complicating appropriate interpretation of low-level hs-cTn concentrations., Methods: A cross-sectional analysis was performed in 1864 patients with symptoms of chest discomfort from the cardiology outpatient department who underwent cardiac computed tomographic angiography (CCTA). Serum samples were analyzed using hs-cTnT and hs-cTnI assays. Renal function was measured by the estimated glomerular filtration rate (eGFR), established from serum creatinine and cystatin C. On follow-up, the incidence of adverse events was assessed., Results: Median hs-cTnT and hs-cTnI concentrations were 7.2(5.8-9.2) ng/L and 2.6(1.8-4.1) ng/L, respectively. Multivariable regression analysis revealed that both assay results were more strongly associated with eGFR (hs-cTnT:stβ:-0.290;hs-cTnI:stβ:-0.222) than with cardiac imaging parameters, such as coronary calcium score, CCTA plaque severity score and left ventricular mass (all p<0.01). Furthermore, survival analysis indicated lower relative risks in patients with normal compared to reduced renal function for hs-cTnT [HR(95%CI), 1.02(1.00-1.03) compared to 1.07(1.05-1.09)] and hs-cTnI [1.01(1.00-1.01) compared to 1.02(1.01-1.02)] (all p<0.001)., Conclusion: In patients with chest discomfort, we identified an independent influence of renal function on hs-cTn concentrations besides CAD, that affected the association of hs-cTn concentrations with adverse events. Estimating renal function is therefore warranted when interpreting baseline hs-cTn concentrations.

Objectives: Contrast media (CM) injection protocols should be customized to the individual patient. Aim of this study was to determine if software tailored CM injections result in diagnostic enhancement of the coronary arteries in computed tomography angiography (CTA) and if attenuation values were comparable between different weight categories., Materials and Methods: 265 consecutive patients referred for routine coronary CTA were scanned on a 2nd generation dual-source CT. Group 1 (n=141) received an individual CM bolus based on weight categories (39-59 kg; 60-74 kg; 75-94 kg; 95-109 kg) and scan duration ('high-pitch: 1s; "dual-step prospective triggering": 7s), as determined by contrast injection software (Certegra™ P3T, Bayer, Berlin, Germany). Group 2 (n=124) received a standard fixed CM bolus; Iopromide 300 mgI/ml; volume: 75 ml; flow rate: 7.2 ml/s. Contrast enhancement was measured in all proximal and distal coronary segments. Subjective and objective image quality was evaluated. Statistical analysis was performed using SPSS (IBM, version 20.0)., Results: For group 1, mean attenuation values of all segments were diagnostic (>325 HU) without statistical significant differences between different weight categories (p>0.17), proximal vs. distal: 449 ± 65-373 ± 58 HU (39-59 kg); 443 ± 69-367 ± 81 HU (60-74 kg); 427 ± 59-370 ± 61 HU (75-94 kg); 427 ± 73-347 ± 61 HU (95-109 kg). Mean CM volumes were: 55 ± 6 ml (39-59 kg); 61 ± 7 ml (60-74 kg); 71 ± 8 ml (75-94 kg); 84 ± 9 ml (95-109 kg). For group 2, mean attenuation values were not all diagnostic with differences between weight categories (p<0.01), proximal vs. distal: 611 ± 142-408 ± 69 HU (39-59 kg); 562 ± 135-389 ± 98 HU (60-74 kg); 481 ± 83-329 ± 81 HU (75-94 kg); 420 ± 73-305 ± 35 HU (95-109 kg). Comparable image noise and image quality were found between groups (p ≥ 0.330)., Conclusions: Individually tailored CM injection protocols yield diagnostic attenuation and a more homogeneous enhancement pattern between different weight groups. CM volumes could be reduced for the majority of patients utilizing individualized CM bolus application., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Unstable plaque characteristics on coronary CT angiography (CTA), serum high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) concentrations are associated with cardiovascular events., Objective: To investigate the association between coronary CTA defined quantifiable plaque characteristics, hs-cTnT and NT-proBNP., Methods: 81 consecutive stable chest pain patients with an intermediate-to-high risk were analyzed. Coronary CTA was performed using a 64-slice multidetector-row CT-scanner. Total coronary plaque volume, calcified volume, non-calcified volume, plaque burden, remodeling index (RI) and number of plaques were measured using dedicated software. A total plaque score ("Sum plaque score") incorporating total plaque volume, RI, plaque burden and number of plaques was defined. Hs-cTnT and NT-proBNP concentrations were measured in serum samples before coronary CTA., Results: Univariate regression analysis demonstrated significant associations of hs-cTnT and NT-proBNP with total plaque volume (r hs-cTnT = .256; r NT-proBNP = .270), calcified volume (r hs-cTnT = .344; r NT-proBNP = .344), RI (r hs-cTnT = .335; r NT-proBNP = .342) and number of plaques (r hs-cTnT = .355; r NT-proBNP = .301) (all P values ≤ .021). Non-calcified plaque volume showed no association with hs-cTnT and NT-proBNP (r hs-cTnT = .050; r NT-proBNP = .087; P value = .660 and P value = .442). The "Sum plaque score" showed the highest correlation compared to other plaque parameters (r hs-cTnT = .362; r NT-proBNP = .409; P value = .001 and P value ≤ .001)., Conclusion: Our data suggest that coronary plaque morphology parameters, derived by dedicated software, are associated with serum hs-cTnT and NT-proBNP concentrations., (Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Purpose: Aim of this study was to test the hypothesis that peak injection pressures and image quality using low concentrated contrast media (CM) (240 mg/mL) injected with high flow rates will be comparable to a standard injection protocol (CM: 300 mg/mL) in coronary computed tomographic angiography (CCTA)., Material and Methods: One hundred consecutive patients were scanned on a 2nd generation dual-source CT scanner. Group 1 (n=50) received prewarmed Iopromide 240 mg/mL at an injection rate of 9 mL/s, followed by a saline chaser. Group 2 (n=50) received the standard injection protocol: prewarmed Iopromide 300 mg/mL; flow rate: 7.2 mL/s. For both protocols, the iodine delivery rate (IDR, 2.16 gI/s) and the total iodine load (22.5 gI) were kept identical. Injection pressure (psi) was continuously monitored by a data acquisition program. Contrast enhancement was measured in the thoracic aorta and all proximal and distal coronary segments. Subjective and objective image quality was evaluated between both groups., Results: No significant differences in peak injection pressures were found between both CM groups (121 ± 5.6 psi vs. 120 ± 5.3 psi, p=0.54). Flow rates of 9 mL/s were safely injected without any complications. No significant differences in contrast-to-noise ratio, signal-to-noise ratio and subjective image quality were found (all p>0.05). No significant differences in attenuation levels were found in the thoracic aorta and all segments of the coronary arteries (all p>0.05)., Conclusion: Usage of low iodine concentration CM and injection with high flow rates is feasible. High flow rates (9 mL/s) of Iopromide 240 were safely injected without complications and should not be considered a drawback in clinical practice. No significant differences in peak pressure and image quality were found. This creates a doorway towards applicability of a broad variety in flow rates and IDRs and subsequently more individually tailored injection protocols., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Coronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis and is a strong and independent predictor of cardiovascular disease (CVD). Arterial calcification is caused by an imbalance in calcification regulatory mechanisms. An important inhibitor of calcification is vitamin K-dependent matrix Gla protein (MGP). Both preclinical and clinical studies have shown that inhibition of the vitamin K-cycle by vitamin K antagonists (VKA) results in elevated uncarboxylated MGP (ucMGP) and subsequently in extensive arterial calcification. This led us to hypothesize that vitamin K supplementation may slow down the progression of calcification. To test this, we designed the VitaK-CAC trial which analyses effects of menaquinone-7 (MK-7) supplementation on progression of CAC. The trial is a double-blind, randomized, placebo-controlled trial including patients with coronary artery disease (CAD). Patients with a baseline Agatston CAC-score between 50 and 400 will be randomized to an intervention-group (360 microgram MK-7) or a placebo group. Treatment duration will be 24 months. The primary endpoint is the difference in CAC-score progression between both groups. Secondary endpoints include changes in arterial structure and function, and associations with biomarkers. We hypothesize that treatment with MK-7 will slow down or arrest the progression of CAC and that this trial may lead to a treatment option for vascular calcification and subsequent CVD.

Bioprosthetic aortic valve thrombosis is a rare complication after transcatheter aortic valve implantation; however, one with a high mortality. We describe the case of a patient with a completely thrombosed transcatheter aortic valve prosthesis 9 months after implantation and review the diagnosis and management of this complication., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the optimal imaging time point for transcatheter aortic valve implantation (TAVI) therapy planning by comprehensive evaluation of the aortic root., Methods: Multidetector-row CT (MDCT) examination with retrospective ECG gating was retrospectively performed in 64 consecutive patients referred for pre-TAVI assessment. Eighteen different parameters of the aortic root were evaluated at 11 different time points in the cardiac cycle. Time points at which maximal (or minimal) sizes were determined, and dimension differences to other time points were evaluated. Theoretical prosthesis sizing based on different measurements was compared., Results: Largest dimensions were found between 10 and 20% of the cardiac cycle for annular short diameter (10%); mean diameter (10%); effective diameter and circumference-derived diameter (20%); distance from the annulus to right coronary artery ostium (10%); aortic root at the left coronary artery level (20%); aortic root at the widest portion of coronary sinuses (20%); and right leaflet length (20%). Prosthesis size selection differed depending on the chosen measurements in 25-75% of cases., Conclusion: Significant changes in anatomical structures of the aortic root during the cardiac cycle are crucial for TAVI planning. Imaging in systole is mandatory to obtain maximal dimensions., Key Points: • Most aortic root structures undergo significant dimensional changes throughout the cardiac cycle. • The largest dimensions of aortic parameters should be determined to optimize TAVI. • Circumference-derived diameter showed maximum dimension at 20% of the cardiac cycle.

Purpose: It is unclear if prolonged contrast media injection, to improve right ventricular visualization during coronary CT angiography, leads to increased detection of right ventricle pathology. The purpose of this study was to evaluate right ventricle enhancement and subsequent detection of right ventricle disease during coronary CT angiography., Materials and Methods: 472 consecutive patients referred for screening coronary CT angiography were retrospectively evaluated. Every patient underwent multidetector-row CT of the coronary arteries: 128x 0.6mm coll., 100-120kV, rot. time 0.28s, ref. mAs 350 and received an individualized (P3T) contrast bolus injection of iodinated contrast medium (300 mgI/ml). Patient data were analyzed to assess right ventricle enhancement (HU) and right ventricle pathology. Image quality was defined good when right ventricle enhancement >200HU, moderate when 140-200HU and poor when <140HU., Results: Good image quality was found in 372 patients, moderate in 80 patients and poor in 20 patients. Mean enhancement of the right ventricle cavity was 268HU±102. Patients received an average bolus of 108±24 ml at an average peak flow rate of 6.1±2.2 ml/s. In only three out of 472 patients (0.63%) pathology of the right ventricle was found (dilatation) No other right ventricle pathology was detected., Conclusion: Right ventricle pathology was detected in three out of 472 patients; the dilatation observed in these three cases may have been picked up even without dedicated enhancement of the right ventricle. Based on our findings, right ventricle enhancement can be omitted during screening coronary CT angiography.

Purpose: Iodinated contrast media (CM) in computed tomographic angiography is characterized by its concentration and, consecutively, by its viscosity. Viscosity itself is directly influenced by temperature, which will furthermore affect injection pressure. Therefore, the purposes of this study were to systematically evaluate the viscosity of different CM at different temperatures and to assess their impact on injection pressure in a circulation phantom., Materials and Methods: Initially, viscosity of different contrast media concentrations (240, 300, 370, and 400 mgI/mL) was measured at different temperatures (20°C-40°C) with a commercially available viscosimeter. In the next step, a circulation phantom with physical conditions was used. Contrast media were prepared at different temperatures (20°C, 30°C, 37°C) and injected through a standard 18-gauge needle. All other relevant parameters were kept constant (iodine delivery rate, 1.9 g I/s; total amount of iodine, 15 g I). Peak flow rate (in milliliter per second) and injection pressure (psi) were monitored. Differences in significance were tested using the Kruskal-Wallis test (Statistical Package for the Social Sciences)., Results: Viscosities for iodinated CM of 240, 300, 370, and 400 mg I/mL at 20°C were 5.1, 9.1, 21.2, and 28.8 mPa.s, respectively, whereas, at 40°C, these were substantially lower (2.8, 4.4, 8.7, and 11.2 mPa.s). In the circulation phantom, mean (SD) peak pressures for CM of 240 mg I/mL at 20°C, 30°C, and 37°C were 107 (1.5), 95 (0.6), and 92 (2.1) psi; for CM of 300 mg I/mL, 119 (1.5), 104 (0.6), and 100 (3.6) psi; for CM of 370 mg I/mL, 150 (0.6), 133 (4.4), and 120 (3.5) psi; and for CM of 400 mg I/mL, 169 (1.0), 140 (2.1), and 135 (2.9) psi, respectively, with all P values less than 0.05., Conclusions: Low concentration, low viscosity, and high temperatures of CM are beneficial in terms of injection pressure. This should also be considered for individually tailored contrast protocols in daily routine scanning.

In cardiology, diagnostic tools for ruling acute coronary syndrome (ACS) in or out are becoming more and more sensitive. In general practice, diagnostic means to discriminate between ACS and less demanding causes of chest complaints remain poor. Both situations challenge physicians working in their respective fields. Cardiologists have to deal with a decrease in specificity due to the increasing sensitivity of high-sensitivity troponin and face the dilemma of whether or not to perform invasive coronary angiography in cases of doubt. General practitioners on the other hand are still lacking adequate diagnostic tools. These difficulties are illustrated in three cases where patients present chest complaints in primary care and are eventually referred to a cardiologist. Notwithstanding the presence of the aforementioned dilemmas, combining clinical reasoning with current definitions of ACS and myocardial infarction leads to an unambiguous diagnosis in all three cases.

Background: Although high-sensitivity cardiac troponin (hs-cTn) substantially improves the early detection of myocardial injury, it lacks specificity for acute myocardial infarction (MI). In suspected non-ST-elevation MI, invasive coronary angiography (ICA) remains necessary to distinguish between acute MI and noncoronary myocardial disease (eg, myocarditis), unnecessarily subjecting the latter to ICA and associated complications. This trial investigates whether implementing cardiovascular magnetic resonance (CMR) or computed tomography angiography (CTA) early in the diagnostic process may help to differentiate between coronary and noncoronary myocardial disease, thereby preventing unnecessary ICA., Study Design: In this prospective, single-center, randomized controlled clinical trial, 321 consecutive patients with acute chest pain, elevated hs-cTnT, and nondiagnostic electrocardiogram are randomized to 1 of 3 strategies: (1) CMR, or (2) CTA early in the diagnostic process, or (3) routine clinical management. In the 2 investigational arms of the study, results of CMR or CTA will guide further clinical management. It is expected that noncoronary myocardial disease is detected more frequently after early noninvasive imaging as compared with routine clinical management, and unnecessary ICA will be prevented. The primary end point is the total number of patients undergoing ICA during initial admission. Secondary end points are 30-day and 1-year clinical outcome (major adverse cardiac events and major procedure-related complications), time to final diagnosis, quality of life, and cost-effectiveness., Conclusion: The CARMENTA trial investigates whether implementing CTA or CMR early in the diagnostic process in suspected non-ST-elevation MI based on elevated hs-cTnT can prevent unnecessary ICA as compared with routine clinical management, with no detrimental effect on clinical outcome., (© 2013.)

Objectives: The purpose of this study was to investigate whether the use of a semiautomated plaque quantification algorithm (reporting volumetric and geometric plaque properties) provides additional prognostic value for the development of acute coronary syndromes (ACS) as compared with conventional reading from cardiac computed tomography angiography (CCTA)., Background: CCTA enables the visualization of coronary plaque characteristics, of which some have been shown to predict ACS., Methods: A total of 1,650 patients underwent 64-slice CCTA and were followed up for ACS for a mean 26 ± 10 months. In 25 patients who had ACS and 101 random controls (selected from 993 patients with coronary artery disease but without coronary event), coronary artery disease was evaluated using conventional reading (calcium score, luminal stenosis, morphology), and then independently quantified using semiautomated software (plaque volume, burden area [plaque area divided by vessel area times 100%], noncalcified percentage, attenuation, remodeling). Clinical risk profile was calculated with Framingham risk score (FRS)., Results: There were no significant differences in conventional reading parameters between controls and patients who had ACS. Semiautomated plaque quantification showed that compared to controls, ACS patients had higher total plaque volume (median: 94 mm(3) vs. 29 mm(3)) and total noncalcified volume (28 mm(3) vs. 4 mm(3), p ≤ 0.001 for both). In addition, per-plaque maximal volume (median: 56 mm(3) vs. 24 mm(3)), noncalcified percentage (62% vs. 26%), and plaque burden (57% vs. 36%) in ACS patients were significantly higher (p < 0.01 for all). A receiver-operating characteristic model predicting for ACS incorporating FRS and conventional CCTA reading had an area under the curve of 0.64; a second model also incorporating semiautomated plaque quantification had an area under the curve of 0.79 (p < 0.05)., Conclusions: The semiautomated plaque quantification algorithm identified several parameters predictive for ACS and provided incremental prognostic value over clinical risk profile and conventional CT reading. The application of this tool may improve risk stratification in patients undergoing CCTA., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Apoptosis, or programmed cell death (PCD), contributes to the decline in ventricular function in heart failure. Because apoptosis comprises a programmed cascade of events, it is potentially reversible, and timely intervention should delay the development of cardiomyopathy. (99m)Tc-Labeled annexin A5 has successfully been used for the noninvasive detection of PCD in myocardial infarction and heart transplant rejection. The present study evaluated the role of annexin A5 imaging for detection of PCD in heart failure patients., Methods: Annexin A5 imaging was performed on 9 consecutive heart failure patients with advanced nonischemic cardiomyopathy (dilated, n = 8; hypertrophic, n = 1) and in 2 relatives having the same genetic background as the hypertrophic cardiomyopathy patient but no heart failure., Results: Four of the patients with dilated cardiomyopathy and the 1 with hypertrophic cardiomyopathy and heart failure showed focal, multifocal, or global left ventricular uptake of annexin A5. No uptake was visualized in the remaining 4 patients or in the 2 controls. All cases showing annexin A5 uptake within the left ventricle experienced significant reduction in left ventricular function or functional class. In cases with no annexin A5 uptake, left ventricular function and clinical status remained stable., Conclusion: These data indicate the feasibility of noninvasive PCD detection with annexin imaging in heart failure patients. Annexin A5 uptake is associated with deterioration in left ventricular function, and this association may lend itself to the development of novel management strategies.

In this article, we review the clinical aspects of imaging with the programmed cell-detecting protein annexin A5 (anxA5). AnxA5 binds to phosphatidylserine, which is one of the "eat me" signals at the surface of the apoptotic cell. This biologic property forms the basis for the development of anxA5 as a diagnostic tool. Within this context, the clinical relevance, limitations, and future perspectives of this approach of visualizing cell death are discussed in this article, as are other potential applications of anxA5. Furthermore, the biologic properties and the radiopharmaceutical, pharmacologic, and biodistribution aspects of anxA5 are reviewed and discussed in this article. Radiolabeled anxA5 bears the promise of becoming a clinically applied radiopharmaceutical with potential applications in cardiology and oncology. Visualization of cell death is important in pathologies such as myocardial infarction, atherosclerosis, and cancer. Furthermore, radiolabeled anxA5 may be developed as a tool for monitoring cell death-inducing or cell death-preventing therapies. In addition, experiences with radiolabeled anxA5 open novel avenues for drug targeting with anxA5 as a biologic "cruise missile."

Programmed cell death plays a critical role in embryology, homeostasis and disease. However, until recently no non-invasive imaging modality has been able to visualize this process directly. Annexin A5 binds to cells undergoing programmed cell death. When labeling this protein, Annexin A5 becomes a tool for the detection of programmed cell death in vitro and in vivo. Labeled Annexin A5 has enabled our group and others to detect programmed cell death non-invasively in animals and patients. This review will highlight the development of this imaging modality in cellular and animal models. Furthermore, we will discuss Annexin A5 imaging in human disease. We will focus on the clinical applications and their relevance, limitations and future perspectives of non-invasive imaging of programmed cell death using labeled Annexin A5.

Background: Primary endocardial tumours are rare, but may impose a difficult clinical problem. The definite diagnosis regarding the nature of the tumour is often made after surgery. This is due to the fact that current non-invasive imaging techniques are unable to inform us about the nature of the tumour. In addition, invasive techniques can not be used to obtain biological information of the tumour in these cases, because they carry a high risk of embolic complications., Objective: To assess the possibility of a novel modality of imaging, molecular imaging, in the diagnosis of primary intracardiac tumours., Methods: We evaluated two patients with a primary cardiac tumour. Prior to therapy, we infused human recombinant annexin-V Tc99-m and thallium 201. We used a dual isotope single photon emission computed tomography technique. This allowed us to obtain information about the relation between the anatomical position of the left ventricle and the uptake of the labelled annexin-V within the thoracic cavity., Results: The patient with a malignant primary cardiac tumour showed uptake of labelled annexin-V within the area of the tumour. After surgery, the malignant nature was confirmed by histological analysis. The patient with a benignant intracardiac tumour showed no uptake of annexin-V within the area of the tumour., Conclusion: This novel imaging technique, molecular imaging, may be of help to differentiate non-invasively between a malignant and benignant primary intracardiac tumour.