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1.  Endograft Sizing for Endovascular Aortic Repair and Incidence of Endoleak Type 1A 
PLoS ONE  2016;11(6):e0158042.
In endovascular aortic aneurysm repair (EVAR), proximal type 1A endoleaks can occur as a result of hostile neck anatomy or over- or undersizing of the endograft. As the current standard is based on the diameter or average of the short and long axes in a central lumen reconstruction image, it can falter in irregularly shaped aortic necks. An alternative method is circumference-based, therefore minimizing the measurement error. In this study we aimed to assess the degree of discrepancy between both methods and the association of this discrepancy with the occurrence of endoleak type 1A.
All patients with early (<30 days post-operative) endoleak type 1A after elective EVAR at our center between 2004 and 2016 were identified for a retrospective case-control study. Control patients were matched based on hostile neck anatomy, such as calcification, thrombus, reverse taper, and β-angulation. The aortic neck diameter was measured using the traditional, diameter-based method as well as an alternative method, based on the circumference of the aortic neck.
In 482 EVAR patients, 18 early endoleak type 1A cases were found (3.9%). After exclusion, 12 cases remained and 48 matching controls were found. No significant differences were found between the two measuring methods at any level below the renal arteries. The inter-observer variability was significant for the D(mean) (0.4 ± 1.69 mm, P = .02) and was larger than the D(circ) method (-0.1 ± 1.03 mm, P = .35). In only four out of 12 cases the endograft size was 10–20% larger than the D(mean) and D(circ) measurements. The differences between the diameter of the D(mean) and D(circ) and the chosen endograft were smaller for the case group (-8 ± 25.6% and -7 ± 24%) than for the control group. (-12.4 ± 12.4% and -11 ± 10.7%).
The difference between the D(mean) and D(circ) methods for aortic neck measurement was not large enough to play a significant role in the incidence of endoleak type 1A. Inadequate oversizing and considerable β-angulation of the aortic neck may have been the cause of endoleak type 1A in this population. Robust and well-investigated sizing methods are paramount for accurate endograft sizing and prevention of endoleak type 1A. Therefore the lack of studies in this field and a sizeable inter-observer variability do not justify the widespread reliance on the traditional diameter-based methods for endograft sizing.
PMCID: PMC4928836  PMID: 27359115
2.  Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets 
Molecular Imaging and Biology  2015;18:283-291.
In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated.
Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense™ 680 and imaged with IVIS® Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages.
There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and αSMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages.
MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 rather than M1 macrophages.
PMCID: PMC4783451  PMID: 26377769
Matrix metalloproteinase; Macrophage; Atherosclerotic plaque; Smooth muscle cell; MMPSense
3.  A comparison of Percutaneous femoral access in Endovascular Repair versus Open femoral access (PiERO): study protocol for a randomized controlled trial 
Trials  2015;16:408.
Access for endovascular repair of abdominal aortic aneurysms (EVAR) is obtained through surgical cutdown or percutaneously. The only devices suitable for percutaneous closure of the 20 French arteriotomies of the common femoral artery (CFA) are the Prostar™ and Proglide™ devices (Abbott Vascular). Positive effects of these devices seem to consist of a lower infection rate, and shorter operation time and hospital stay. This conclusion was published in previous reports comparing techniques in patients in two different groups (cohort or randomized). Access techniques were never compared in one and the same patient; this research simplifies comparison because patient characteristics will be similar in both groups.
Percutaneous access of the CFA is compared to surgical cutdown in a single patient; in EVAR surgery, access is necessary in both groins in each patient. Randomization is performed on the introduction site of the larger main device of the endoprosthesis. The contralateral device of the endoprosthesis is smaller. When we use this type of randomization, both groups will contain a similar number of main and contralateral devices. Preoperative nose cultures and perineal cultures are obtained, to compare colonization with postoperative wound cultures (in case of a surgical site infection). Furthermore, patient comfort will be considered, using VAS-scores (Visual analog scale). Punch biopsies of the groin will be harvested to retrospectively compare skin of patients who suffered a surgical site infection (SSI) to patients who did not have an SSI.
The PiERO trial is a multicenter randomized controlled clinical trial designed to show the consequences of using percutaneous access in EVAR surgery and focuses on the occurrence of surgical site infections.
Trial registration
NTR4257 10 November 2013, NL44578.042.13.
PMCID: PMC4570236  PMID: 26370286
4.  18F-Fluorodeoxyglucose Positron Emission Tomography/CT Scanning in Diagnosing Vascular Prosthetic Graft Infection 
BioMed Research International  2014;2014:471971.
Vascular prosthetic graft infection (VPGI) is a severe complication after vascular surgery. CT-scan is considered the diagnostic tool of choice in advanced VPGI. The incidence of a false-negative result using CT is relatively high, especially in the presence of low-grade infections. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scanning has been suggested as an alternative for the diagnosis and assessment of infectious processes. Hybrid 18F-FDG PET/CT has established the role of 18F-FDG PET for the assessment of suspected VPGI, providing accurate anatomic localization of the site of infection. However, there are no clear guidelines for the interpretation of the uptake patterns of 18F-FDG as clinical tool for VPGI. Based on the available literature it is suggested that a linear, diffuse, and homogeneous uptake should not be regarded as an infection whereas focal or heterogeneous uptake with a projection over the vessel on CT is highly suggestive of infection. Nevertheless, 18F-FDG PET and 18F-FDG PET/CT can play an important role in the detection of VPGI and monitoring response to treatment. However an accurate uptake and pattern recognition is warranted and cut-off uptake values and patterns need to be standardized before considering the technique to be the new standard.
PMCID: PMC4156987  PMID: 25210712
5.  Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm 
Gretarsdottir, Solveig | Baas, Annette F | Thorleifsson, Gudmar | Holm, Hilma | den Heijer, Martin | de Vries, Jean-Paul P M | Kranendonk, Steef E | Zeebregts, Clark J A M | van Sterkenburg, Steven M | Geelkerken, Robert H | van Rij, Andre M | Williams, Michael J A | Boll, Albert P M | Kostic, Jelena P | Jonasdottir, Adalbjorg | Jonasdottir, Aslaug | Walters, G Bragi | Masson, Gisli | Sulem, Patrick | Saemundsdottir, Jona | Mouy, Magali | Magnusson, Kristinn P | Tromp, Gerard | Elmore, James R | Sakalihasan, Natzi | Limet, Raymond | Defraigne, Jean-Olivier | Ferrell, Robert E | Ronkainen, Antti | Ruigrok, Ynte M | Wijmenga, Cisca | Grobbee, Diederick E | Shah, Svati H | Granger, Christopher B | Quyyumi, Arshed A | Vaccarino, Viola | Patel, Riyaz S | Zafari, A Maziar | Levey, Allan I | Austin, Harland | Girelli, Domenico | Pignatti, Pier Franco | Olivieri, Oliviero | Martinelli, Nicola | Malerba, Giovanni | Trabetti, Elisabetta | Becker, Lewis C | Becker, Diane M | Reilly, Muredach P | Rader, Daniel J | Mueller, Thomas | Dieplinger, Benjamin | Haltmayer, Meinhard | Urbonavicius, Sigitas | Lindblad, Bengt | Gottsäter, Anders | Gaetani, Eleonora | Pola, Roberto | Wells, Philip | Rodger, Marc | Forgie, Melissa | Langlois, Nicole | Corral, Javier | Vicente, Vicente | Fontcuberta, Jordi | España, Francisco | Grarup, Niels | Jørgensen, Torben | Witte, Daniel R | Hansen, Torben | Pedersen, Oluf | Aben, Katja K | de Graaf, Jacqueline | Holewijn, Suzanne | Folkersen, Lasse | Franco-Cereceda, Anders | Eriksson, Per | Collier, David A | Stefansson, Hreinn | Steinthorsdottir, Valgerdur | Rafnar, Thorunn | Valdimarsson, Einar M | Magnadottir, Hulda B | Sveinbjornsdottir, Sigurlaug | Olafsson, Isleifur | Magnusson, Magnus Karl | Palmason, Robert | Haraldsdottir, Vilhelmina | Andersen, Karl | Onundarson, Pall T | Thorgeirsson, Gudmundur | Kiemeney, Lambertus A | Powell, Janet T | Carey, David J | Kuivaniemi, Helena | Lindholt, Jes S | Jones, Gregory T | Kong, Augustine | Blankensteijn, Jan D | Matthiasson, Stefan E | Thorsteinsdottir, Unnur | Stefansson, Kari
Nature genetics  2010;42(8):692-697.
We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 × 10−10. In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 × 10−5), peripheral arterial disease (OR = 1.14, P = 3.9 × 10−5) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases—that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
PMCID: PMC4157066  PMID: 20622881
6.  Mechanochemical endovenous Ablation versus RADiOfrequeNcy Ablation in the treatment of primary great saphenous vein incompetence (MARADONA): study protocol for a randomized controlled trial 
Trials  2014;15:121.
Radiofrequency ablation (RFA) is associated with an excellent outcome in the treatment of great saphenous vein (GSV) incompetence. The use of thermal energy as a treatment source requires the instillation of tumescence anesthesia. Mechanochemical endovenous ablation (MOCA) combines mechanical endothelial damage, using a rotating wire, with the infusion of a liquid sclerosant. Tumescence anesthesia is not required. Preliminary experiences with MOCA showed good results and low post-procedural pain.
The MARADONA (Mechanochemical endovenous Ablation versus RADiOfrequeNcy Ablation) trial is a multicenter randomized controlled trial in which 460 patients will be randomly allocated to MOCA or RFA. All patients with primary GSV incompetence who meet the eligibility criteria will be invited to participate in this trial. The primary endpoints are anatomic and clinical success at a one-year follow-up, and post-procedural pain. The secondary endpoints are technical success, complications, operation time, procedural pain, disease-specific quality of life, time taken to return to daily activities and/or work, and cost-efficiency analyses after RFA or MOCA. Both groups will be evaluated on an intention to treat base.
The MARADONA trial is designed to show equal results in anatomic and clinical success after one year, comparing MOCA with RFA. In our hypothesis MOCA has an equal anatomic and clinical success compared with RFA, with less post-procedural pain.
Trial registration
Clinicaltrials NCT01936168
PMCID: PMC3996515  PMID: 24726004
Mechanochemical ablation; ClariVein; Radiofrequency ablation; Varicose vein; Therapy; Treatment; MOCA; Outcome
7.  Skin Autofluorescence, a Non-Invasive Marker for AGE Accumulation, Is Associated with the Degree of Atherosclerosis 
PLoS ONE  2013;8(12):e83084.
Advanced glycation endproducts (AGEs) may be involved in the development of atherosclerosis, beyond diabetes and renal disease. Skin autofluorescence (AF) is a non-invasive marker for AGEs. We examined whether skin AF is increased in (subclinical) atherosclerosis and associated with the degree of atherosclerosis independent of diabetes and renal function.
A cross-sectional study of 223 patients referred for primary (n = 163) or secondary (n = 60) prevention between 2006 and 2012 was performed. Skin AF was measured using the AGE-Reader. Ultrasonography was used to assess plaques in carotid and femoral arteries and computed tomography for the calculation of the coronary artery calcium score (CACS; in primary prevention only). Primary prevention patients were divided into a group with subclinical atherosclerosis defined as >1 plaque or CACS>100 (n = 67; age 53 year [interquartile range 48–56]; 49% male) and without (controls; 96; 43 [38–51]; 55%). Secondary prevention were patients with peripheral arterial disease (60; 64 [58–70]; 73%).
Skin AF was higher in subclinical and clinical atherosclerosis compared with controls (skin AF 2.11 [interquartile range 1.83–2.46] and 2.71 [2.15–3.27] vs. 1.87 [1.68–2.12] respectively; P = 0.005 and <0.001). In a multivariate analysis, the association of skin AF with the atherosclerosis categories was independent of age, sex, diabetes, presence of the metabolic syndrome, Framingham Risk Score, and renal function. Skin AF correlated with most cardiovascular risk factors, Framingham risk score, and IMT and CACS.
Skin AF is increased in documented subclinical and clinical atherosclerosis, independent of known risk factors such as diabetes and renal disease. These data suggest that AGEs may be associated with the burden of atherosclerosis and warrant a prospective study to investigate its clinical usability as a risk assessment tool for primary prevention.
PMCID: PMC3871581  PMID: 24376641
9.  Characterization of coagulation factor synthesis in nine human primary cell types 
Scientific Reports  2012;2:787.
The coagulation/fibrinolysis system is essential for wound healing after vascular injury. According to the standard paradigm, the synthesis of most coagulation factors is restricted to liver, platelets and endothelium. We challenged this interpretation by measuring coagulation factors in nine human primary cell types. FX mRNA was expressed by fibroblasts, visceral preadipocytes/adipocytes and hepatocytes, but not in macrophages or other cells. All cells expressed FVIII except endothelial cells. Fibroblasts, endothelial cells and macrophages produced thrombomodulin but not FV. Interestingly, vascular-related cells (platelets/monocytes) that expressed FV did not express FX and vice versa. Monocytes expressed FV, FVIII and FXIIIA, which are positive regulators of clot formation, but these cells also contained thrombomodulin, a negative regulator of coagulation. Our data show that the expression of coagulation factors is much more complex than previously thought, and we speculate that this intricate regulation of coagulation factor expression is necessary for correct fine-tuning of fibrinogenesis versus fibrinolysis.
PMCID: PMC3494008  PMID: 23145311
10.  PET and MRI for the evaluation of regional myocardial perfusion and wall thickening after myocardial infarction 
Deterioration of left ventricular (LV) function after myocardial infarction (MI) is a major cause of heart failure. Myocardial perfusion performance may play an important role in deterioration or improvement in LV function after MI. The aim of this study was to evaluate the myocardial perfusion reserve (MPR) and stress perfusion in deteriorating and non-deteriorating LV segments in patients after MI by PET and MRI, respectively.
Regional wall thickening of 352 segments in 22 patients was assessed at 4 and 24 months after MI by cardiac MRI. PET was performed to evaluate MPR and adenosine stress 13N-ammonia perfusion 24 months after MI. Segments were divided into four groups according to deterioration or improvement in wall thickening.
Normal functional segments at 4 months after MI that remained stable had a significantly higher mean MPR and mean stress perfusion PET value than deteriorated segments (p < 0.001). Furthermore, dysfunctional segments that improved had a significantly higher mean stress perfusion PET value than dysfunctional segments that remained dysfunctional (p < 0.001).
This study demonstrated the additional value of myocardial perfusion assessment in relation to the functional integrity of the injured myocardium. Segmental functional LV improvement after MI was associated with better regional myocardial perfusion characteristics. Furthermore, the amount of wall thickening reduction was associated with regional myocardial perfusion abnormalities in patients after MI.
PMCID: PMC3342486  PMID: 22410839
Myocardial infarction; Left ventricular function; Myocardial perfusion imaging; Cardiac MRI; Medicine & Public Health; Nuclear Medicine; Oncology; Orthopedics; Cardiology; Imaging / Radiology
11.  Dichotomy in Hedgehog Signaling between Human Healthy Vessel and Atherosclerotic Plaques 
Molecular Medicine  2012;18(1):1122-1127.
The major cause for plaque instability in atherosclerotic disease is neoangiogenic revascularization, but the factors controlling this process remain only partly understood. Hedgehog (HH) is a morphogen with important functions in revascularization, but its function in human healthy vessel biology as well as in atherosclerotic plaques has not been well investigated. Hence, we determined the status of HH pathway activity both in healthy vessels and atherosclerotic plaques. A series of 10 healthy organ donor–derived human vessels, 17 coronary atherosclerotic plaques and 24 atherosclerotic carotid plaques were investigated for HH pathway activity. We show that a healthy vessel is characterized by a high level of HH pathway activity but that atherosclerotic plaques are devoid of HH signaling despite the presence of HH ligand in these pathological structures. Thus, a dichotomy between healthy vessels and atherosclerotic plaques with respect to the activation status of the HH pathway exists, and it is tempting to suggest that downregulation of HH signaling contributes to long-term plaque stability.
PMCID: PMC3474430  PMID: 22371306
12.  High-resolution imaging of human atherosclerotic carotid plaques with micro18F-FDG PET scanning exploring plaque vulnerability 
Journal of Nuclear Cardiology  2011;18(6):1066-1075.
FDG-PET can be used to identify vulnerable plaques in atherosclerotic disease. Clinical FDG-PET camera systems are restricted in terms of resolution for the visualization of detailed inflammation patterns in smaller vascular structures. The aim of the study is to evaluate the possible added value of a high-resolution microPET system in excised carotid plaques using FDG.
Methods and Results
In this study, 17 patients with planned carotid endarterectomy were included. Excised plaques were incubated in FDG and subsequently imaged with microPET. Macrophage presence in plaques was evaluated semi-quantitatively by immunohistochemistry. Plaque calcification was assessed additionally with CT and correlated to FDG uptake. Finally, FDG uptake and macrophage infiltration were compared with patient symptomatology. Heterogeneous distributions and variable intensities of FDG uptake were found within the plaques. A positive correlation between the distribution of macrophages and the FDG uptake (r = 0.68, P < .01) was found. A negative correlation was found between areas of calcifications and FDG uptake (r = −0.84, P < .001). Ratio FDGmax values as well as degree of CD68 accumulation were significantly higher in CVA patients compared with TIA or amaurosis fugax patients (P < .05) and CVA patients compared with asymptomatic patients (P < .05).
This ex vivo study demonstrates that excised carotid plaques can be visualized in detail using FDG microPET. Enhancement of clinical PET/CT resolution for similar imaging results in patients is needed.
PMCID: PMC3225624  PMID: 22002650
Atherosclerosis; carotid artery; FDG; microPET; vulnerable plaque
14.  SUrgical versus PERcutaneous Bypass: SUPERB-trial; Heparin-bonded endoluminal versus surgical femoro-popliteal bypass: study protocol for a randomized controlled trial 
Trials  2011;12:178.
Endovascular treatment options for the superficial femoral artery are evolving rapidly. For long lesions, the venous femoropopliteal bypass considered to be superior above the prosthetic bypass. An endoluminal bypass, however, may provide equal patency rates compared to the prosthetic above knee bypass. The introduction of heparin-bonded endografts may further improve patency rates. The SUrgical versus PERcutaneous Bypass (SuperB) study is designed to assess whether a heparin-bonded endoluminal bypass provides equal patency rates compared to the venous bypass and to prove that it is associated with improved quality of life, related to a decreased complication rate, or not.
Two-hundred-twenty-two patients with peripheral arterial occlusive disease, category 3-6 according to Rutherford, will be randomized in two treatment arms; 1. the surgical femoro-popliteal bypass, venous whenever possible, and 2. the heparin-bonded endoluminal bypass. The power analysis was based on a non-inferiority principle, with an effect size of 90% and 10% margins (alpha 5%, power 80%). Patients will be recruited from 5 teaching hospitals in the Netherlands during a 2-year period. The primary endpoint is primary patency and quality of life evaluated by the RAND-36 questionnaire and the Walking Impairment Questionnaire. Secondary endpoints include secondary patency, freedom-from-TLR and complications.
The SuperB trial is a multicentre randomized controlled trial designed to show non-inferiority in patency rates of the heparin-bonded endograft compared to the surgical bypass for treatment of long SFA lesions, and to prove a better quality of life using the heparin bonded-endograft compared to surgically treatment, related to a reduction in complications.
Trial Registration
Clinicaltrials: NCT01220245
PMCID: PMC3157423  PMID: 21767371
superficial femoral artery; femoro-popliteal bypass; endoluminal; stentgraft; peripheral arterial occlusive disease
15.  Multispectral Optoacoustic Tomography of Matrix Metalloproteinase Activity in Vulnerable Human Carotid Plaques 
Molecular Imaging and Biology  2011;14(3):277-285.
Elevated expression of cathepsins, integrins and matrix metalloproteinases (MMPs) is typically associated with atherosclerotic plaque instability. While fluorescent tagging of such molecules has been amply demonstrated, no imaging method was so far shown capable of resolving these inflammation-associated tags with high fidelity and resolution beyond microscopic depths. This study is aimed at demonstrating a new method with high potential for noninvasive clinical cardiovascular diagnostics of vulnerable plaques using high-resolution deep-tissue multispectral optoacoustic tomography (MSOT) technology.
Methods and results
MMP-sensitive activatable fluorescent probe (MMPSense™ 680) was applied to human carotid plaques from symptomatic patients. Atherosclerotic activity was detected by tuning MSOT wavelengths to activation-dependent absorption changes of the molecules, structurally modified in the presence of enzymes. MSOT analysis simultaneously provided morphology along with heterogeneous MMP activity with better than 200 micron resolution throughout the intact plaque tissue. The results corresponded well with epi-fluorescence images made from thin cryosections. Elevated MMP activity was further confirmed by in situ zymography, accompanied by increased macrophage influx.
We demonstrated, for the first time to our knowledge, the ability of MSOT to provide volumetric images of activatable molecular probe distribution deep within optically diffuse tissues. High-resolution mapping of MMP activity was achieved deep in the vulnerable plaque of intact human carotid specimens. This performance directly relates to pre-clinical screening applications in animal models and to clinical decision potential as it might eventually allow for highly specific visualization and staging of plaque vulnerability thus impacting therapeutic clinical decision making.
PMCID: PMC3346936  PMID: 21720908
Atherosclerosis; Optoacoustic imaging; Carotid arteries; Plaque; Contrast media; Inflammation; Medicine & Public Health; Imaging / Radiology
16.  Skin autofluorescence is increased in patients with carotid artery stenosis and peripheral artery disease 
Advanced glycation end products (AGEs) have a pivotal role in atherosclerosis. We evaluated skin autofluorescence (SAF), a non-invasive measurement of tissue AGE accumulation, in patients with carotid artery stenosis with and without coexisting peripheral artery occlusive disease (PAOD). SAF was measured using the AGE Reader™ in 56 patients with carotid artery stenosis and in 56 age- and sex-matched healthy controls without diabetes, renal dysfunction or known atherosclerotic disease. SAF was higher in patients with carotid artery stenosis compared to the control group: mean 2.81 versus 2.46 (P = 0.002), but especially in the younger age group of 50–60 years old: mean 2.82 versus 1.94 (P = 0.000). Patients with carotid artery stenosis and PAOD proved to have an even higher SAF than patients with carotid artery stenosis only: mean 3.28 versus 2.66 (P = 0.003). Backward linear regression analysis showed that age, smoking, diabetes mellitus, renal function and the presence of PAOD were the determinants of SAF, but carotid artery stenosis was not. SAF is increased in patients with carotid artery stenosis and PAOD. The univariate and multivariate associations of SAF with age, smoking, diabetes, renal insufficiency and PAOD suggest that increased SAF can be seen as an indicator of widespread atherosclerosis.
PMCID: PMC3288376  PMID: 21336554
Carotid artery stenosis; Peripheral vascular disease; Advanced glycation end products; Skin autofluorescence
17.  Interposition Grafting of Large Extracranial Carotid Aneurysm 
Texas Heart Institute Journal  2011;38(1):52-55.
Extracranial carotid aneurysms are a rare entity and carry an inherent risk of thromboembolic complications. Treatment options consist of endovascular and conventional surgical techniques. We describe the cases of 3 patients who were treated with an interposition graft for a large extracranial carotid aneurysm.
The patients had presented with an extracranial carotid aneurysm with a diameter of 30 to 43 mm. In all cases, the aneurysm was excluded by means of an interposition graft, without major perioperative complications. There was 1 case of temporary paresis of the facial nerve and another of temporary paresis of the vocal cord. After a mean follow-up period of 14 months, all patients were alive, and there were no neurologic deficits.
A retrospective analysis was performed of patients who had undergone conventional surgical treatment of extracranial carotid aneurysms. The patients' characteristics, symptoms, surgical interventions, complications, and deaths were all documented.
Carotid aneurysms can safely be excluded by interposition grafting, and this treatment should still be considered for most patients, although endovascular repair might provide a valid alternative.
PMCID: PMC3060756  PMID: 21423469
Aneurysm/surgery; carotid artery diseases; carotid artery, common/surgery; carotid artery, internal/surgery; cranial nerve injuries/etiology; graft, interposition; stents; treatment outcome
18.  Small-animal SPECT and SPECT/CT: application in cardiovascular research 
Preclinical cardiovascular research using noninvasive radionuclide and hybrid imaging systems has been extensively developed in recent years. Single photon emission computed tomography (SPECT) is based on the molecular tracer principle and is an established tool in noninvasive imaging. SPECT uses gamma cameras and collimators to form projection data that are used to estimate (dynamic) 3-D tracer distributions in vivo. Recent developments in multipinhole collimation and advanced image reconstruction have led to sub-millimetre and sub-half-millimetre resolution SPECT in rats and mice, respectively. In this article we review applications of microSPECT in cardiovascular research in which information about the function and pathology of the myocardium, vessels and neurons is obtained. We give examples on how diagnostic tracers, new therapeutic interventions, pre- and postcardiovascular event prognosis, and functional and pathophysiological heart conditions can be explored by microSPECT, using small-animal models of cardiovascular disease.
PMCID: PMC2918793  PMID: 20069298
microSPECT; microSPECT/CT; Cardiovascular imaging
19.  Fluorodeoxyglucose and 11C-Choline positron emission tomography for distinction of metastatic plexopathy and neuritis: a case report 
Cases Journal  2009;2:9323.
Fluorodeoxyglucose positron emission tomography scanning has an established role in the diagnostic work-up of many malignant diseases and also in the evaluation of cancer treatment response. Fluorodeoxyglucose positron emission tomography may, however be non-specific as infectious processes are depicted as well.
Case presentation
We present a patient with longstanding leg pain and weakness due to plexopathy developed a few years after treatment for prostate cancer. Prostate-specific antigen was raised and magnetic resonance imaging showed contrast uptake in thickened sacral nerves, suspicious for metastasis. While fluorodeoxyglucose positron emission tomography showed increased uptake in the plexus region, 11C-Choline- positron emission tomography did not show any uptake. It was concluded that the FDG uptake reflected plexus neuritis and no tumor. Treatment for pain relief was started.
11C-Choline- positron emission tomography can be used to detect metastasis in patients with plexopathy suspicious for malignancy, while fluorodeoxyglucose positron emission tomography is more sensitive to inflammatory processes.
PMCID: PMC2804720  PMID: 20066056
20.  Ischemic patterns assessed by positron emission tomography predict adverse outcome in patients with idiopathic dilated cardiomyopathy 
Journal of Nuclear Cardiology  2009;16(5):769-774.
Although patients with idiopathic dilated cardiomyopathy (DCM) have no coronary artery disease, regional impairment of myocardial perfusion combined with preserved metabolism has been found using positron emission tomography (PET). Our aim was to assess the prognostic relevance of PET-mismatch between stress myocardial perfusion and glucose uptake on clinical outcome in DCM.
In 24 patients with DCM who underwent both myocardial perfusion and metabolism PET scanning, “mismatch” was assessed and the association with clinical outcome (hospitalization, mortality, and heart transplantation) was investigated.
Mismatch was found in 16 patients (66.7%). Univariate analysis showed that the presence of mismatch was associated with adverse outcome (P = 0.03). After adjustment for sex and age, the association remained significant with an adjusted relative risk of 10.4 (95% CI 1.1-103; P = 0.04) for death, heart transplant, or hospitalization. Univariate analysis also showed that a higher extent of mismatch was significantly associated with adverse outcome (P = 0.02). After adjusting for sex and age, the association remained significant with an adjusted relative risk of 6.5 [95% CI 1.2-36; P = 0.03] for death, heart transplantation, or hospitalization.
PET stress perfusion-metabolism mismatch, indicative for ischemia, is frequently found in DCM patients and related to a poorer outcome.
PMCID: PMC2746307  PMID: 19649680
Heart failure; dilated cardiomyopathy; positron emission tomography; myocardial perfusion; myocardial ischemia
21.  Endovascular Abdominal Aortic Aneurysm Repair in Nonagenarians—Beyond Limits? 
Texas Heart Institute Journal  2009;36(4):345-348.
Herein, we report a single institution's experience with endovascular abdominal aortic aneurysm repair in nonagenarians, over a 4-year period of time. We performed a retrospective study of cases, in which we documented patient demographics, symptoms, physical findings, surgical interventions, complications, and deaths. The survivors answered a questionnaire.
Endovascular abdominal aneurysm repair was performed in 4 male nonagenarians (age range, 90–92 yr): 2 underwent repair of asymptomatic aneurysm and 2 underwent repair of symptomatic aneurysm. There was no in-hospital death, and patients were discharged after a median time of 11 days. Both patients with symptomatic abdominal aortic aneurysm died within 30 days, 1 of an occluded left femoral artery and the other of unknown cause. After follow-ups of 6 and 54 months, both survivors were in good physical condition and patient satisfaction appeared to be very high.
We have shown that elective endovascular abdominal aneurysm repair in a small, selected group of nonagenarians was feasible and afforded acceptable short-term survival. In patients with symptomatic disease, however, the early postprocedural mortality rate appears to be high. Decision-making should focus chiefly on comorbidities, on subjective issues such as fear of rupture, and on ethical and financial considerations.
PMCID: PMC2720286  PMID: 19693313
Aged, 80 and over; aortic aneurysm, abdominal/rupture, spontaneous/surgery; blood vessel prosthesis implantation; comorbidity; patient selection; outcome assessment (health care); stents; surgical procedures, elective; survival rate; vascular surgical procedures/adverse effects
22.  The role of coronary artery calcification score in clinical practice 
Coronary artery calcification (CAC) measured by electron-beam computed tomography (EBCT) has been well studied in the prediction of coronary artery disease (CAD). We sought to evaluate the impact of the CAC score in the diagnostic process immediately after its introduction in a large tertiary referral centre.
598 patients with no history of CAD who underwent EBCT for evaluation of CAD were retrospectively included into the study. Ischemia detection test results (exercise stress test, single photon emission computed tomography or ST segment analysis on 24 hours ECG detection), as well as the results of coronary angiography (CAG) were collected.
The mean age of the patients was 55 ± 11 years (57% male). Patients were divided according to CAC scores; group A < 10, B 10 – 99, C 100 – 399 and D ≥ 400 (304, 135, 89 and 70 patients respectively). Ischemia detection tests were performed in 531 (89%) patients; negative ischemia results were found in 362 patients (183 in group A, 87 in B, 58 in C, 34 in D). Eighty-eight percent of the patients in group D underwent CAG despite negative ischemia test results, against 6% in group A, 16% in group B and 29% in group C. A positive ischemia test was found in 74 patients (25 in group A, 17 in B, 16 in C, 16 in D). In group D 88% (N = 14) of the patients with a positive ischemia test were referred for CAG, whereas 38 – 47% in group A-C.
Our study showed that patients with a high CAC score are more often referred for CAG. The CAC scores can be used as an aid in daily cardiology practice to determine further decision making.
PMCID: PMC2628861  PMID: 19091061

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