Bas L.J.H. Kietselaer

Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid-artery atherosclerosis.

To the Editor: Although progressive stenosis of the arterial lumen constitutes the basis for ischemic symptoms in atherosclerotic vascular disease, acute vascular events are for the most part assoc...

Elevated Levels of Circulating DNA and Chromatin Are Independently Associated With Severe Coronary Atherosclerosis and a Prothrombotic State

Objective—Aberrant neutrophil activation occurs during the advanced stages of atherosclerosis. Once primed, neutrophils can undergo apoptosis or release neutrophil extracellular traps. This extracellular DNA exerts potent proinflammatory, prothrombotic, and cytotoxic properties. The goal of this study was to examine the relationships among extracellular DNA formation, coronary atherosclerosis, and the presence of a prothrombotic state. Approach and Results—In a prospective, observational, cross-sectional cohort of 282 individuals with suspected coronary artery disease, we examined the severity, extent, and phenotype of coronary atherosclerosis using coronary computed tomographic angiography. Double-stranded DNA, nucleosomes, citrullinated histone H4, and myeloperoxidase–DNA complexes, considered in vivo markers of cell death and NETosis, respectively, were established. We further measured various plasma markers of coagulation activation and inflammation. Plasma double-stranded DNA, nucleosomes, and myeloperoxidase–DNA complexes were positively associated with thrombin generation and significantly elevated in patients with severe coronary atherosclerosis or extremely calcified coronary arteries. Multinomial regression analysis, adjusted for confounding factors, identified high plasma nucleosome levels as an independent risk factor of severe coronary stenosis (odds ratio, 2.14; 95% confidence interval, 1.26–3.63; P=0.005). Markers of neutrophil extracellular traps, such as myeloperoxidase–DNA complexes, predicted the number of atherosclerotic coronary vessels and the occurrence of major adverse cardiac events. Conclusions—Our report provides evidence demonstrating that markers of cell death and neutrophil extracellular trap formation are independently associated with coronary artery disease, prothrombotic state, and occurrence of adverse cardiac events. These biomarkers could potentially aid in the prediction of cardiovascular risk in patients with chest discomfort.

Noninvasive Detection of Programmed Cell Loss with 99mTc-Labeled Annexin A5 in Heart Failure

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. 99mTc-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.

Influence of Contrast Media Viscosity and Temperature on Injection Pressure in Computed Tomographic Angiography A Phantom Study

PurposeIodinated 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 MethodsInitially, 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). ResultsViscosities 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. ConclusionsLow 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.

Coronary CT angiography using low concentrated contrast media injected with high flow rates: Feasible in clinical practice.

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.

Calcific aortic valve stenosis: hard disease in the heartA biomolecular approach towards diagnosis and treatment

Abstract Calcific aortic valve stenosis (CAVS) is common in the ageing population and set to become an increasing economic and health burden. Once present, it inevitably progresses and has a poor prognosis in symptomatic patients. No medical therapies are proven to be effective in holding or reducing disease progression. Therefore, aortic valve replacement remains the only available treatment option. Improved knowledge of the mechanisms underlying disease progression has provided us with insights that CAVS is not a passive disease. Rather, CAVS is regulated by numerous mechanisms with a key role for calcification. Aortic valve calcification (AVC) is actively regulated involving cellular and humoral factors that may offer targets for diagnosis and intervention. The discovery that the vitamin K-dependent proteins are involved in the inhibition of AVC has boosted our mechanistic understanding of this process and has opened up novel avenues in disease exploration. This review discusses processes involved in CAVS progression, with an emphasis on recent insights into calcification, methods for imaging calcification activity, and potential therapeutic options.

Role of tetrahydrobiopterin (BH4) in hyperhomocysteinemia -induced endothelial dysfuction: New indication for this orphan-drug?

to the editor: He et al. ([3][1]) presented in the American Journal of Physiology - Endocrinology and Metabolism that chronic hyperhomocysteinemia (HHcy; plasma level of homocysteine >15 μmol/l) impairs coronary endothelial function and that plasma levels of nitric oxide (NO) and

Patient Comfort During Contrast Media Injection in Coronary Computed Tomographic Angiography Using Varying Contrast Media Concentrations and Flow Rates: Results From the EICAR Trial.

PurposePain 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. MethodsTwo 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.” ResultsMean 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. ConclusionsHigh 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.

Acute chest pain in the high-sensitivity cardiac troponin era: A changing role for noninvasive imaging?

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.

Severely Thrombosed Transcatheter Aortic Valve 9 Months After Implantation

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.