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Abstract Background To evaluate the feasibility and value of first-pass contrast-enhanced dynamic and post-contrast 3D CMR in patients after transcatheter occlusion of left atrial appendage (LAA) to identify incorrect placement and persistent leaks. Methods 7 patients with different occluder systems (n = 4 PLAATO; n = 2 Watchman; n = 1 ACP) underwent 2 contrast-enhanced (Gd-DOTA) CMR sequences (2D TrueFISP first-pass perfusion and 3D-TurboFLASH) to assess localization, artifact size and potential leaks of the devices. Perfusion CMR was analyzed visually and semi-quantitatively to identify potential leaks. Results All occluders were positioned within the LAA. The ACP occluder presented the most extensive artifact size. Visual assessment revealed a residual perfusion of the LAA apex in 4 cases using first-pass perfusion and 3D-TurboFLASH indicating a suboptimal LAA occlusion. By assessing signal-to-time-curves the cases with a visually detected leak showed a 9-fold higher signal-peak in the LAA apex (567 ± 120% increase from baseline signal) than those without a leak (61 ± 22%; p < 0.03). In contrast, the signal increase in LAA proximal to the occluder showed no difference (leak 481 ± 201% vs. no leak 478 ± 125%; p = 0.48). Conclusion This CMR pilot study provides valuable non-invasive information in patients after transcatheter occlusion of the LAA to identify correct placement and potential leaks. We recommend incorporating CMR in future clinical studies to evaluate new device types.

Transcatheter therapies for the treatment of structural heart diseases (SHD) have expanded dramatically over the last years, thanks to the developments and improvements of devices and imaging techniques, along with the increasing expertise of operators. Imaging, in particular echocardiography, is pivotal during patient selection, procedural monitoring, and follow-up. The imaging assessment of patients undergoing transcatheter interventions places demands on imagers that differ from those of the routine evaluation of patients with SHD, and there is a need for specific expertise for those working in the cath lab. In the context of the current rapid developments and growing use of SHD therapies, this document intends to update the previous consensus document and address new advancements in interventional imaging for access routes and treatment of patients with aortic stenosis and regurgitation, and mitral stenosis and regurgitation., Competing Interests: Conflict of interest: E.A.: speaker and proctoring fees, research and educational grant from Philips, Edwards, Abbott, GE, and Siemens. E.B.: Proctoring fees from Abbott. M.D.: speaker fees from Pfizer and have participated on advisory boards for Novartis. F.F.: speaker's fees from Philips. P.M.-H.: Shareholder of Neumann Medical Ltd. M.S.: lecturer/proctor for Abbott Vascular, Boston Scientific, Philips Healthcare, and Bioventrix inc. R.S.V.B.: Trials (un-paid): IIT IZKS University of Go¨ttingen, Abbott Vascular, Bioventrix, Boston Scientific, Edwards Lifesciences, Medtronic; Speaker/ Advisory: Abbott Lifesciences, Bioventrix, Boston Scientific, Cardiac Dimensions, Edwards Lifesciences, and Philips. J.-L.Z.: research grants from Abbott. Speaker fee Daichii Sankio, Pfizer. B.A.P.: research grants and lecture fees from GE Healthcare and Hitachi-Aloka., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Three-dimensional transoesophageal echocardiography (3D TOE) has been rapidly developed in the last 15 years. Currently, 3D TOE is particularly useful as an additional imaging modality for the cardiac echocardiographers in the echo-lab, for cardiac interventionalists as a tool to guide complex catheter-based procedures cardiac, for surgeons to plan surgical strategies, and for cardiac anaesthesiologists and/or cardiologists, to assess intra-operative results. The authors of this document believe that acquiring 3D data set should become a 'standard part' of the TOE examination. This document provides (i) a basic understanding of the physic of 3D TOE technology which enables the echocardiographer to obtain new skills necessary to acquire, manipulate, and interpret 3D data sets, (ii) a description of valvular pathologies, and (iii) a description of non-valvular pathologies in which 3D TOE has shown to be a diagnostic tool particularly valuable. This document has a new format: instead of figures randomly positioned through the text, it has been organized in tables which include figures. We believe that this arrangement makes easier the lecture by clinical cardiologists and practising echocardiographers., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Tricuspid valve pathophysiology is not well-understood. Emergence of novel transcatheter tricuspid therapies has fueled the requirements for improved imaging visualization techniques and interventional imaging physician skillsets in guiding these complex transcatheter procedures. There is growing understanding on the clinical significance of tricuspid regurgitation which expanded the interest for percutaneous tricuspid valve interventions. The present review concentrates on three essential aspects of tricuspid valve pathophysiology: anatomical considerations for tricuspid interventions, optimal timing of tricuspid interventions by imaging guidance, and the role of interventional imaging physicians' skillset and knowledge in this field., Competing Interests: Author MS was proctor/lecturer for Abbott Vascular, Boston Scientific, Edwards Lifesciences, Philips Healthcare and Bioventrix Inc. Author DW has acted as a consultant for Abbott, Boston Scientific, Edwards Lifesciences, and has received a research grant support from Boston Scientific assigned to employer Henry Ford Health., (Copyright © 2022 Gheorghe, Hegeman, Vrijkorte, Wunderlich, Cavalcante, Wang, Rana, Vannan, Timmers and Swaans.)

Percutaneous therapeutic options for an increasing variety of structural heart diseases (SHD) have grown dramatically. Within this context of continuous expansion of devices and procedures, there has been increased demand for physicians with specific knowledge, skills, and advanced training in multimodality cardiac imaging. As a consequence, a new subspecialty of 'Interventional Imaging' for SHD interventions and a new dedicated professional figure, the 'Interventional Imager' with specific competencies has emerged. The interventional imager is an integral part of the heart team and plays a central role in decision-making throughout the patient pathway, including the appropriateness and feasibility of a procedure, pre-procedural planning, intra-procedural guidance, and post-procedural follow-up. However, inherent challenges exist to develop a training programme for SHD imaging that differs from traditional cardiovascular imaging pathways. The purpose of this document is to provide the standard requirements for the training in SHD imaging, as well as a starting point for an official certification process for SHD interventional imager., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Mitral regurgitation is one of the most prevalent valvulopathies worldwide, and its surgical treatment is not feasible in all cases. The elderly and frail with several comorbidities and left ventricular dysfunction are often managed conservatively. Percutaneous treatment (repair or replacement) of the mitral valve has emerged as a potential option for those patients who are at a high risk for surgery. Mitral valve repair with the Mitraclip device proved both increased safety and mortality reduction in patients with severe mitral regurgitation. On the other hand, in the last decade, percutaneous mitral replacement opened new frontiers in the field of cardiac structural interventions. There are few mitral devices; some are in the early phase of development and some are waiting for CE mark of approval. The evolution of these devices was more complicated compared to the aortic technology due to the native mitral valve's complexity and access. This review aims to provide an overview of the current devices, their specific features, and their potential complications., Competing Interests: MS is a consultant for Abbott Vascular. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Gheorghe, Brouwer, Wang, Wunderlich, Rana, Rensing, Eefting, Timmers and Swaans.)

Purpose: Tibial tubercle/tuberosity fractures are rare injuries in young patients accounting for less than one percent of physeal fractures. Bilateral simultaneous fractures are even rarer, with only a few case reports in literature. The purpose of our study was to describe the largest case series of bilateral simultaneous tibial tuberosity avulsion fractures and compare it with unilateral fractures. We also wanted to compare our bilateral fractures case series with all the cases reported in the last 65 years., Methods: IRB approved retrospective study involving patients under age 18 years with tibial tuberosity avulsion fractures. Bilateral simultaneous fractures were compared to a unilateral group including demographic data, mechanism of injury, clinical exam findings, complication rates, and outcomes including return to function. Statistical analysis was performed using Mann-Whitney and Fisher Exact tests to compare the different groups., Results: 138 patients (131 males, 7 females) from a tertiary children's hospital between 2012 and 2019 with tibial tuberosity avulsion fractures were included. 11 bilateral simultaneous fractures (BL Group) were identified and compared to age matched cohort from the 127 unilateral fracture patients (UL group). There was no significant difference found in BMI, height, weight, age, sex, mechanism of injury, return to functional range of motion, and return to sports between the groups. 7/11 (63%) of the patients in the BL group who sustained simultaneous fractures had to be home bound and could not attend school for an average of 8.3 weeks. There was a higher rate of complications in the BL group (63.3%) compared to the UL group (21.1%), which was statistically significant. The most common complications in the bilateral group were hardware removal and wound dehiscence., Conclusion: This first case series comparing unilateral versus bilateral simultaneous tibial tuberosity avulsion fractures suggests that the final outcomes of the two groups are similar, however it shows a significantly higher complication rate and hardware removal rate in the BL group. This study is also the first to highlight the significant initial morbidity in the BL fracture group with issues with regards to early mobility and loss of school-days. Keeping in mind the profound initial impact the bilateral injury poses to the patient; surgeons can possibly plan for rigid fixation for early mobilization to better prepare bilateral fracture patients for the early post-operative recovery process., Competing Interests: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. No conflict of interest is to be declared., (© 2020 Delhi Orthopedic Association. All rights reserved.)

Transcatheter therapies for the treatment of valve heart diseases have expanded dramatically over the last years. The new developments and improvements in devices and techniques, along with the increasing expertise of operators, have turned the catheter-based approaches for valvular disease into an established treatment option. Various imaging techniques are used during these procedures, but echocardiography plays an essential role during patient selection, intra-procedural monitoring, and post-procedure follow-up. The echocardiographic assessment of patients undergoing transcatheter interventions places demands on echocardiographers that differ from those of the routine evaluation of patients with valve disease, and there is a need for specific expertise for those working in the cath lab. In the context of the current rapid developments and growing use of transcatheter valve therapies, this document intends to update the previous recommendations and address new advancements in imaging, particularly for those involved in any stage of the treatment of patients with valvular heart diseases., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Studies have associated obesity with better outcomes in comparison to non-obese patients after elective and emergency coronary revascularization. However, these findings might have been influenced by patient selection. Therefore we thought to look into the obesity paradox in a consecutive network STEMI population., Methods: The database of two German myocardial infarction network registries were combined and data from a total of 890 consecutive patients admitted and treated for acute STEMI including cardiogenic shock and cardiopulmonary resuscitation according to standardized protocols were analyzed. Patients were categorized in normal weight (≤24.9 kg/m(2)), overweight (25-30 kg/m(2)) and obese (>30 kg/m(2)) according to BMI., Results: Baseline clinical parameters revealed a higher comorbidity index for overweight and obese patients; 1-year follow-up comparison between varying groups revealed similar rates of all-cause death (9.1 % vs. 8.3 % vs. 6.2 %; p = 0.50), major adverse cardiac and cerebrovascular [MACCE (15.1 % vs. 13.4 % vs. 10.2 %; p = 0.53)] and target vessel revascularization in survivors [TVR (7.0 % vs. 5.0 % vs. 4.0 %; p = 0.47)] with normal weight when compared to overweight or obese patients. These results persisted after risk-adjustment for heterogeneous baseline characteristics of groups. An analysis of patients suffering from cardiogenic shock showed no impact of BMI on clinical endpoints., Conclusion: Our data from two network systems in Germany revealed no evidence of an "obesity paradox"in an all-comer STEMI population including patients with cardiogenic shock.

Aims: Percutaneous treatment of mitral regurgitation (MR) has been shown to reduce MR severity and improve functional outcomes. Surgical treatment of MR usually includes mitral annulus reduction. The influence of the MitraClip on annulus geometry is not clear. We wanted to investigate whether the procedure itself reduces annulus diameter and if there may be differences between secondary or functional (SMR) and primary (PMR) MR., Methods and Results: We retrospectively assessed 3D echocardiography (3D-TEE) data of 55 patients acquired during the procedure shortly before and after clip placement for changes in annulus diameter and area. Measurements were done with QLAB software. Patients were categorized as having either SMR (n = 41) or PMR (n = 14). In SMR, we were able to demonstrate a significant reduction in annulus area (meanΔ 1.30 ± 1.44 cm2; P < 0.001), anterior-posterior (AP)-diameter (meanΔ 0.28 ± 0.32 cm; P < 0.001), tenting area (meanΔ 0.39 ± 0.49 cm2; P < 0.001). No significant change could be found for latero-medial (LM)-diameter. In contrast, we could not demonstrate significant changes in any of the parameters described above in patients with PMR., Conclusion: Percutaneous treatment with the MitraClip device can produce immediate reductions in mitral annulus size in SMR, probably supporting procedural success. It also reduces tenting, which may have prognostic implications. In contrast, these effects on mitral geometry cannot be demonstrated in PMR. Knowledge of this difference between SMR and PMR may be important to improve procedural strategies.

Background: Patent foramen ovale (PFO) with right-to-left shunt has a prevalence of 10% to 34% in the general population. It can cause an ischemic stroke, transient ischemic attack, and paradoxical peripheral or coronary embolization. Its influence on migraine and several other diseases and conditions is currently under debate. Attention has recently been turned to the correlation between PFO and obstructive sleep apnea. Thus far, studies on the prevalence of right-to-left shunts as a surrogate for PFO in these patients were limited by small sample sizes and the results have been conflicting. Here, we evaluate the prevalence of right-to-left shunting (RLS) through transcranial Doppler ultrasound (TCD) in a large patient group with obstructive sleep apnea (OSA)., Methods: One hundred consecutive patients (mean age 59.5 y) with OSA underwent TCD with intravenous injection of agitated saline. The grading of right-to-left-shunts was in accordance with the Spencer PFO Grading Scale., Results: RLS was detected in 72 of 100 patients (72%). Thirty-four out of these 72 patients (47%) had a shunt grade I or II; 15 (21%) had a shunt Grade III or IV; and 23 (32%) had a large shunt (Grade V or V+). In 47 of 72 patients (65%), a right-to-left shunt was detectable at rest without Valsalva maneuver., Conclusion: The prevalence of a RLS in patients with OSA is high. Provided other intracardiac or pulmonary shunts were absent, the high prevalence of a RLS suggests a high prevalence of PFO in patients with OSA.

Background: Advanced chronic obstructive pulmonary disease causes a significant reduction in functional capacity because of dyspnea and fatigue, partially related to hypoxemia and compromised oxygen delivery. Percutaneous creation of an arteriovenous shunt may increase oxygen delivery and, hence, improve patients' functional capacity., Methods and Results: This is a prospective, single-center, proof-of-concept pilot study. Patients with advanced chronic obstructive pulmonary disease underwent percutaneous arteriovenous shunt creation. End points were the change in 6-minute walking distance; quality of life, measured by St George's Respiratory Questionnaire; and physiological parameters at 12-week follow-up. Fifteen patients underwent percutaneous arteriovenous shunt creation. Cardiac output and oxygen delivery increased significantly from 4.1 L/min at baseline to 5.9 L/min at 12 weeks (P<0.01) and from 751 mL/min at baseline to 972 mL/min at 12 weeks (P<0.01), respectively; however, there was a trend toward a significant decrease in the 6-minute walking distance between baseline (338 m) and 12-week follow-up (294 m) (P=0.07). There was no significant difference in the St George's Respiratory Questionnaire score, oxygen saturation, or lung function tests. Lower extremity edema, venous stenosis, right heart failure, and deep venous thrombosis occurred in 10, 7, 4, and 4 patients, respectively., Conclusions: Though it causes a significant increase in cardiac output and oxygen delivery , the creation of an arteriovenous shunt in the setting of severe chronic obstructive pulmonary disease did not improve functional capacity or quality of life. A significant number of adverse events occurred. This concept cannot be recommended for routine clinical use in unselected patients with advanced chronic obstructive pulmonary disease.

We reported the induction of tumor-selective iodide uptake and therapeutic efficacy of (131)I in a hepatocellular carcinoma (HCC) xenograft mouse model, using novel polyplexes based on linear polyethylenimine (LPEI), shielded by polyethylene glycol (PEG), and coupled with the epidermal growth factor receptor-specific peptide GE11 (LPEI-PEG-GE11). The aim of the current study in the same HCC model was to evaluate the potential of biodegradable nanoparticle vectors based on pseudodendritic oligoamines (G2-HD-OEI) for systemic sodium iodide symporter (NIS) gene delivery and to compare efficiency and tumor specificity with LPEI-PEG-GE11. Transfection of HCC cells with NIS cDNA, using G2-HD-OEI, resulted in a 44-fold increase in iodide uptake in vitro as compared with a 22-fold increase using LPEI-PEG-GE11. After intravenous application of G2-HD-OEI/NIS HCC tumors accumulated 6-11% ID/g (123)I (percentage of the injected dose per gram tumor tissue) with an effective half-life of 10 hr (tumor-absorbed dose, 281 mGy/MBq) as measured by (123)I scintigraphic gamma camera or single-photon emission computed tomography computed tomography (SPECT CT) imaging, as compared with 6.5-9% ID/g with an effective half-life of only 6 hr (tumor-absorbed dose, 47 mGy/MBq) for LPEI-PEG-GE11. After only two cycles of G2-HD-OEI/NIS/(131)I application, a significant delay in tumor growth was observed with markedly improved survival. A similar degree of therapeutic efficacy had been observed after four cycles of LPEI-PEG-GE11/(131)I. These results clearly demonstrate that biodegradable nanoparticles based on OEI-grafted oligoamines show increased efficiency for systemic NIS gene transfer in an HCC model with similar tumor selectivity as compared with LPEI-PEG-GE11, and therefore represent a promising strategy for NIS-mediated radioiodine therapy of HCC.

We reported the therapeutic efficacy of (131)I in hepatocellular carcinoma (HCC) cells stably expressing the sodium iodide symporter (NIS) under the control of the tumor-specific α-fetoprotein (AFP) promoter. In the current study we investigated the efficacy of adenovirus-mediated in vivo NIS gene transfer followed by (131)I and (188)Re administration for the treatment of HCC xenografts. We used a replication-deficient adenovirus carrying the human NIS gene linked to the mouse AFP promoter (Ad5-AFP-NIS) for in vitro and in vivo NIS gene transfer. Functional NIS expression was confirmed by in vivo γ-camera imaging, followed by analysis of NIS protein and mRNA expression. Human HCC (HepG2) cells infected with Ad5-AFP-NIS concentrated 50% of the applied activity of (125)I, which was sufficiently high for a therapeutic effect in an in vitro clonogenic assay. Four days after intratumoral injection of Ad5-AFP-NIS (3×10(9) plaque-forming units) HepG2 xenografts accumulated 14.5% injected dose (ID)/g (123)I with an effective half-life of 13 hr (tumor-absorbed dose, 318 mGy/MBq (131)I). In comparison, 9.2% ID/g (188)Re was accumulated in tumors with an effective half-life of 12.8 hr (tumor-absorbed dose, 545 mGy/MBq). After adenovirus-mediated NIS gene transfer in HepG2 xenografts administration of a therapeutic dose of (131)I or (188)Re (55.5 MBq) resulted in a significant delay in tumor growth and improved survival without a significant difference between (188)Re and (131)I. In conclusion, a therapeutic effect of (131)I and (188)Re was demonstrated in HepG2 xenografts after tumor-specific adenovirus-mediated in vivo NIS gene transfer.

Due to its dual role as reporter and therapy gene, the sodium iodide symporter (NIS) allows noninvasive imaging of functional NIS expression by (123)I-scintigraphy or (124)I-PET imaging before the application of a therapeutic dose of (131)I. NIS expression provides a novel mechanism for the evaluation of mesenchymal stem cells (MSCs) as gene delivery vehicles for tumor therapy. In the current study, we stably transfected bone marrow-derived CD34(-) MSCs with NIS cDNA (NIS-MSC), which revealed high levels of functional NIS protein expression. In mixed populations of NIS-MSCs and hepatocellular cancer (HCC) cells, clonogenic assays showed a 55% reduction of HCC cell survival after (131)I application. We then investigated body distribution of NIS-MSCs by (123)I-scintigraphy and (124)I-PET imaging following intravenous (i.v.) injection of NIS-MSCs in a HCC xenograft mouse model demonstrating active MSC recruitment into the tumor stroma which was confirmed by immunohistochemistry and ex vivo γ-counter analysis. Three cycles of systemic MSC-mediated NIS gene delivery followed by (131)I application resulted in a significant delay in tumor growth. Our results demonstrate tumor-specific accumulation and therapeutic efficacy of radioiodine after MSC-mediated NIS gene delivery in HCC tumors, opening the prospect of NIS-mediated radionuclide therapy of metastatic cancer using MSCs as gene delivery vehicles.

Background: To evaluate the feasibility and value of first-pass contrast-enhanced dynamic and post-contrast 3D CMR in patients after transcatheter occlusion of left atrial appendage (LAA) to identify incorrect placement and persistent leaks., Methods: 7 patients with different occluder systems (n = 4 PLAATO; n = 2 Watchman; n = 1 ACP) underwent 2 contrast-enhanced (Gd-DOTA) CMR sequences (2D TrueFISP first-pass perfusion and 3D-TurboFLASH) to assess localization, artifact size and potential leaks of the devices. Perfusion CMR was analyzed visually and semi-quantitatively to identify potential leaks., Results: All occluders were positioned within the LAA. The ACP occluder presented the most extensive artifact size. Visual assessment revealed a residual perfusion of the LAA apex in 4 cases using first-pass perfusion and 3D-TurboFLASH indicating a suboptimal LAA occlusion.By assessing signal-to-time-curves the cases with a visually detected leak showed a 9-fold higher signal-peak in the LAA apex (567 ± 120% increase from baseline signal) than those without a leak (61 ± 22%; p < 0.03). In contrast, the signal increase in LAA proximal to the occluder showed no difference (leak 481 ± 201% vs. no leak 478 ± 125%; p = 0.48)., Conclusion: This CMR pilot study provides valuable non-invasive information in patients after transcatheter occlusion of the LAA to identify correct placement and potential leaks. We recommend incorporating CMR in future clinical studies to evaluate new device types.

We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of radioiodine in neuroblastoma tumors after systemic nonviral polyplex-mediated sodium iodide symporter (NIS) gene delivery. In the present study, we used novel polyplexes based on linear polyethylenimine (LPEI), polyethylene glycol (PEG), and the synthetic peptide GE11 as an epidermal growth factor receptor (EGFR)-specific ligand to target a NIS-expressing plasmid to hepatocellular carcinoma (HCC) (HuH7). Incubation of HuH7 cells with LPEI-PEG-GE11/NIS polyplexes resulted in a 22-fold increase in iodide uptake, which was confirmed in other cancer cell lines correlating well with EGFR expression levels. Using (123)I-scintigraphy and ex vivo γ-counting, HuH7 xenografts accumulated 6.5-9% injected dose per gram (ID/g) (123)I, resulting in a tumor-absorbed dose of 47 mGray/Megabecquerel (mGy/MBq) (131)Iodide ((131)I) after intravenous (i.v.) application of LPEI-PEG-GE11/NIS. No iodide uptake was observed in other tissues. After pretreatment with the EGFR-specific antibody cetuximab, tumoral iodide uptake was markedly reduced confirming the specificity of EGFR-targeted polyplexes. After three or four cycles of polyplex/(131)I application, a significant delay in tumor growth was observed associated with prolonged survival. These results demonstrate that systemic NIS gene transfer using polyplexes coupled with an EGFR-targeting ligand is capable of inducing tumor-specific iodide uptake, which represents a promising innovative strategy for systemic NIS gene therapy in metastatic cancers.

Objectives: The purpose of this study was to evaluate the safety and effectiveness of the SeptRx patent foramen ovale (PFO) closure device (SeptRx, Inc., Fremont, California)., Background: A PFO is a relatively common remnant of the fetal circulation that can be associated with cryptogenic stroke, transient ischemic attack, migraine, or decompression sickness. Percutaneous PFO closure with different devices has been performed for many years. However, most of the common devices leave a relatively large amount of material in the left and right atria. The SeptRx PFO device (SeptRx, Inc.) is the first PFO closure device designed to fit directly into the pocket of the PFO., Methods: From July 2006 to May 2007, 13 patients between 18 and 65 years of age with a history of cryptogenic stroke or transient ischemic attack were included into this first-in-man trial. All patients received 100 mg aspirin and 75 mg clopidogrel for 6 months. Follow-up was done at 1 and 6 months after procedure with transesophageal echocardiography and transcranial Doppler., Results: In 11 of 13 patients, PFO closure with the SeptRx device was successfully performed. In 2 patients, PFO closure with this device was not possible due to the anatomy of the PFO; 1 device was retrieved before release, and the other was recaptured with a snare. After 30 days, 6 of the 11 PFOs were closed; after 6 months, all were closed. No adverse events occurred., Conclusions: The SeptRx PFO closure device appears to be safe and effective. The advantage of this occluder is that there is only minimal foreign material on the left and right sides of the interatrial septum. This is the first such "in-tunnel" PFO closure device., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: We recently reported the significant therapeutic efficacy of radioiodine therapy in various tumor mouse models following transcriptionally targeted sodium iodide symporter (NIS) gene transfer. These studies showed the high potential of NIS as a novel diagnostic and therapeutic gene for the treatment of extrathyroidal tumors. As a next crucial step towards clinical application of NIS-mediated radionuclide therapy we aim at systemic delivery of the NIS gene to target extrathyroidal tumors even in the metastatic stage., Experimental Design: In the current study, we used synthetic polymeric vectors based on pseudodendritic oligoamines with high intrinsic tumor affinity (G2-HD-OEI) to target a NIS-expressing plasmid (CMV-NIS-pcDNA3) to neuroblastoma (Neuro2A) cells., Results: Incubation with NIS-containing polyplexes (G2-HD-OEI/NIS) resulted in a 51-fold increase in perchlorate-sensitive iodide uptake activity in Neuro2A cells in vitro. Through (123)I-scintigraphy and ex vivo gamma counting Neuro2A tumors in syngeneic A/J mice were shown to accumulate 8% to 13% ID/g (123)I with a biological half-life of 13 hours, resulting in a tumor-absorbed dose of 247 mGy/MBq (131)I after i.v. application of G2-HD-OEI/NIS. Nontarget organs, including liver, lung, kidneys, and spleen revealed no significant iodide uptake. Moreover, two cycles of systemic NIS gene transfer followed by (131)I application (55.5 MBq) resulted in a significant delay in tumor growth associated with markedly improved survival., Conclusions: In conclusion, our data clearly show the high potential of novel pseudodendritic polymers for tumor-specific NIS gene delivery after systemic application, opening the prospect of targeted NIS-mediated radionuclide therapy of nonthyroidal tumors even in metastatic disease.

Objectives: We sought to examine the acute and subacute results of carotid stenting performed during live transmissions., Background: Teaching courses focusing on live demonstrations of carotid interventions have been the key educational facility for physicians interested in learning state-of-the-art interventional techniques of carotid stenosis treatment. However, starting with the very first live demonstration of interventional procedures, there has been an ongoing discussion whether patients treated during live transmissions are at higher risk., Methods: Between March 1, 2001, and June 30, 2008, 186 high-grade lesions of the internal carotid artery in 186 patients have been treated by stent implantation during live transmissions to 22 interventional conferences at 3 high-volume centers. Technical success was defined as the ability to perform carotid stent implantation. The combined end point of death, major stroke, minor stroke, or myocardial infarction was defined as primary end point., Results: The procedure was technically successful in 185 of 186 (99.5%) interventions. Seventeen patients had 1 of the following acute in-hospital complications: major stroke in 2 (1.1%), minor stroke in 3 (1.6%), transient ischemic attack in 11 (5.9%), and amaurosis of the ipsilateral eye due to an occlusion of the retinal artery in 1 (0.5%). None of the patients died, and no myocardial infarctions occurred. The composite primary end point occurred in 6 (3.2%) patients., Conclusions: In this consecutive series of carotid stent cases performed by expert operators during live demonstration courses, the procedural and 30-day clinical outcomes were similar to the results appearing in the contemporary published data.

Patent foramen ovale (PFO) is a congenital, small tunnel-like connection between the right and left atria that usually closes spontaneously after birth. However, frequently (in up to 35% of the normal population) it persists into adulthood. It is associated with 'paradoxical' embolism from the venous to the arterial system and may result in stroke or peripheral embolism. One prophylactic treatment option is transcatheter closure of the PFO. Currently available closure devices extend into both atria and therefore occasionally cause complications, such as thrombus formation or erosion of adjacent structures. The Coherex FlatStent is a flat, self-expanding stent that is designed to be positioned within the PFO tunnel. It is a very small, low-mass device that minimizes the amount of implanted foreign material to reduce the risk of device-related complications. This article focuses on the anatomy of PFOs and compares the Coherex FlatStent with currently available and experimental PFO closure devices.

Background and Purpose: Microvascular basal lamina damage occurs after cerebral ischemia and is important for the development of hemorrhage. The aim of this study was to determine whether hypothermia could maintain microvascular integrity in ischemic stroke., Methods: Using the suture model, we subjected 12 rats to 3 hours of focal ischemia and 24 hours of reperfusion. Six rats received postischemic normothermia (37 degrees C) and 6 received hypothermia (32 degrees C to 34 degrees C) for the reperfusion period; a group of 6 sham-operated animals without ischemia was used as control. Collagen type IV and hemoglobin were measured by Western blot analysis, matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography, and urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) by plasminogen-casein zymography., Results: Hypothermia reduced basal lamina collagen type IV loss: 87+/-16% (hypothermia) versus 43+/-4% (normothermia) in basal ganglia and 74+/-16% versus 64+/-4% in cortex; hypothermia reduced hemorrhage from 431+/-65% (normothermia) to 241+/-28% (basal ganglia) (P<0.05). Hypothermia also reduced MMP-2, MMP-9, uPA, and tPA (basal ganglia: MMP-2: 71+/-20% [hypothermia] versus 109+/-3% [normothermia]; MMP-9: 38+/-12% versus 115+/-4%; uPA activity: 310+/-86% versus 1019+/-22%; tPA activity: 61+/-17% versus 111+/-13%; cortex: MMP-2: 53+/-6% versus 116+/-1%; MMP-9: 16+/-4% versus 123+/-3%; uPA: 180+/-27% versus 176+/-10%; tPA: 91+/-15% versus 101+/-8%; each difference: P<0.001) (nonischemic control side=100%)., Conclusions: Hypothermia maintains microvascular integrity and reduces hemorrhage and the activities of MMP-2, MMP-9, uPA, and tPA.