A multi-center trial on efficacy and safety of the LifeTech CeraFlexTM ASD occluder for transcatheter closure in patients with secundum atrial septal defects.

Background: The last decades have brought remarkable improvements in treatment strategy and occluder modification of secundum atrial septal defect (ASD) closure. Approval, efficacy and safety of ASD closure devices have previously been demonstrated. This study investigated the clinical efficacy and safety of the LifeTech CeraFlexTM ASD occluder for interventional closure of secundum ASD with a 6-month follow-up (FU). Methods: Procedure specific data was collected on patients considered for ASD closure with the CeraFlexTM occluder between April 2016 and December 2019 in three German centers. Efficacy and safety were assessed after device closure, at discharge, and at 6-month FU. Results: The primary endpoint (successful ASD closure without severe complications) was reached by 102/103 patients (99%). Device embolization occurred in two patients (one early and one late embolization). After early snare-retrieval of an embolized device, this ASD was closed surgically and in the other patient with late device embolization the defect was closed with a larger CeraFlexTM occluder. The secondary endpoint (clincal efficacy after 6 months) was reached by 94/98 patients since new onset of arrhythmia occurred in four patients. Three patients had withdrawn their study-participation and one patient had moderate residual shunt, but not related to the occluder. Incomplete right bundle branch block (iRBBB) was seen in 31 patients. At last FU only 17 patients had remaining iRBBB documenting effective volume unloading of the right ventricle. Conclusions: Catheter interventional closure of secundum ASDs with the CeraFlexTM ASD occluder was feasible, safe and effective in this study.

Catheter strategy to ease the procedure and reduce radiation exposure when requiring neck access.

OBJECTIVES: To assess the potential occupational radiation reduction and technical feasibility in patients rotated 180° (upside-down) when requiring neck access for transcervical or trans-subclavian catheterisation. METHODS: Upside-down positioning is defined as rotating patients in supine position by 180°, so that the feet come to rest where the head would otherwise be. We retrospectively evaluated all these procedures performed between March 2016 and May 2019. Furthermore, two different phantoms (paediatric and adult) were used prospectively to quantify the occupational dose between conventional or upside-down positioning. In this context, ambient dose equivalents were measured using real-time dosimeters. Three different projection angles were applied. RESULTS: 44 patients with median age and body weight of 1.0 year (range 0-56) and 9.5 kg (range 1.3-74.3) underwent 63 procedures positioned upside-down. This position proved advantageous for practical reasons, since the length of the examination table could be optimally used. Additionally, it resulted in a significantly lower overall ambient dose equivalent for the primary operator (PO) of 94.8% (mean: 2569±807 vs 135±23 nSv; p<0.01) in the adult, and of 65.5% (mean: 351±104 vs 121±56 nSv; p<0.01) in the paediatric phantom, respectively. CONCLUSION: Upside-down positioning facilitates handling in a straightforward manner when access from the neck is required. Moreover, it significantly reduces local radiation exposure for the PO in the paediatric and, most impressively, in the adult phantom.

Surgically placed radiopaque markers: Proof-of-concept of a novel technique to facilitate percutaneous interventions in neonates and infants.

OBJECTIVES: Aim of this study was to evaluate feasibility and benefit of self-designed, radiopaque markers as a novel technique in neonates and infants with shunt- or duct-dependent lesions. BACKGROUND: Surgically placed radiopaque markers have the potential to facilitate postoperative percutaneous interventions. METHODS: All consecutive children with surgically placed radiopaque markers involving systemic-to-pulmonary artery connections or arterial ducts in the context of hybrid palliation and subsequent cardiac catheterization between January 2013 and March 2019 were included in this analysis. Our primary endpoint was our concept's feasibility, which we defined as a combination of surgical feasibility and the percutaneous intervention's success. Secondary endpoint was the rate of complications resulting from the surgical procedure or during catheterization. RESULTS: Radiopaque markers that reveal the proximal entry of a surgical shunt or the arterial duct proved to be a feasible and beneficial approach in 25 postoperative catheterizations. The markers' high accuracy enabled easy probing and proper stent positioning in 13 neonates with a median age and weight of 121 days (range 9-356) and 4.7 kg (1.6-9.4) at the intervention. No procedural complications or unanticipated events associated with the radiopaque marker occurred. The markers were never lost, never migrated, and caused no local obstructive lesion. Surgical removal was straightforward in all patients. CONCLUSIONS: Radiopaque markers are a promising and refined technique to substantially facilitate target vessel access and enabling the accurate positioning of stents during postoperative percutaneous procedures.

Isatis tinctoria L.-derived Petroleum Ether Extract Mediates Anti-inflammatory Effects via Inhibition of Interleukin-6, Interleukin-33 and Mast Cell Degranulation.

Isatis tinctoria L. (woad) has been used in medicine for centuries and has demonstrated anti-inflammatory effects. However, to date, no well-defined extracts with precise analysis of active substances have been developed. The aim of this study was to develop novel extracts of Isatis tinctoria L., and to characterize their active ingredients and anti-inflammatory properties. Various extracts of Isatis tinctoria L. were analysed for their active ingredients, and screened for anti-inflammatory effects using cyclooxygenase-2 activity assays. A petroleum ether extract was found to have the best effects, and was tested in a mouse model of acute allergic contact dermatitis. In the mouse model the petroleum ether extract resulted in significantly reduced ear swelling, oedema and inflammatory cell density. In mouse skin and human keratinocyte cultures, petroleum ether extract inhibited pro-inflammatory cytokine expression. Furthermore, human mast cell degranulation was significantly inhibited in LAD2 cell cultures. In conclusion, novel woad extracts were developed and shown to have anti-inflammatory properties in a contact hypersensitivity animal model and human keratinocytes. The production of such extracts and further characterization of their specific properties will enable determination of their potential dermatological effects in the treatment of inflamed and irritated skin.

Left recurrent laryngeal nerve palsy following aortic arch stenting: A case report.

BACKGROUND: Aortic arch stenting is continuously emerging as a safe and effective option to alleviate aortic arch stenosis and arterial hypertension. CASE SUMMARY: We present a 15-year-old girl with aortic arch hypoplasia who had undergone implantation of an uncovered 22 mm Cheatham-Platinum stent due to severe (native) aortic arch stenosis. On follow-up seven months later, she presented a significant re-stenosis of the aortic arch. A second stent (LD Max 26 mm) was implanted and both stents were dilated up to 16 mm. After an initially unremarkable post-interventional course, the patient presented with hoarseness five days after the intervention. MRI and CT scans ruled out an intracranial pathology, as well as thoracic hematoma, arterial dissection, and aneurysm around the intervention site. Laryngoscopy confirmed left vocal fold paresis attributable to an injury to the left recurrent laryngeal nerve (LRLN) during aortic arch stenting, as the nerve loops around the aortic arch in close proximity to the area of the implanted stents. Following a non-invasive therapeutic approach entailing regular speech therapy, the patient recovered and demonstrated no residual clinical symptoms of LRLN palsy after six months. CONCLUSION: Left recurrent laryngeal nerve palsy is a rare complication of aortic arch stenting not previously reported.

Collateral closure in congenital heart defects with Amplatzer vascular plugs: single-center experience and a simplified delivery technique for exceptional cases.

The study describes our experience with Amplatzer Vascular Plugs (AVP2 and 4) and highlights a more refindes telescopic technique for AVP2 delivery. AVPs are well-established occlusion devices for vascular anomalies in congenital heart disease (CHD). The AVP2 is sometimes preferred to the AVP4 due to its shorter length, flat-profiled retention disks, and the availability of larger diameters, but its profile requires a larger inner lumen for safe delivery. The latter may actually hamper access to target lesions. This is a retrospective analysis of all CHD patients treated with the AVP2 and AVP4 between 12/2012 and 12/2015. Target vessels were characterized, measured, and the device-to-vessel diameter ratio calculated. A modified pigtail technique for AVP2 delivery was frequently used: a floppy wire was simply reinforced by the curved tip of a pigtail catheter (instead of the long sheath's dilator) to guide the required delivery sheath towards the desired landing zone. 59 patients with a median age and bodyweight of 3.0 years (range 0.1-75) and 13.8 kg (range 2.5-80) underwent the implantation of 106 plug-devices (30 AVP2, 76 AVP4) in 91 target vessels. Indications for their use were ductus arteriosus (19%), aortopulmonary (43%) as well as venovenous collaterals (34%) and other miscellaneous lesions (4%). The pigtail-supported AVP2 delivery in six patients proved very convenient. No complications occurred. AVPs are excellent devices for embolizing shunt vessels in CHD patients. Here, we describe a simplified telescoping technique for AVP2 delivery to enter curvy target lesions gently and efficiently.

Prophylactic levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease.

BACKGROUND: Low cardiac output syndrome remains a serious complication, and accounts for substantial morbidity and mortality in the postoperative course of paediatric patients undergoing surgery for congenital heart disease. Standard prophylactic and therapeutic strategies for low cardiac output syndrome are based mainly on catecholamines, which are effective drugs, but have considerable side effects. Levosimendan, a calcium sensitiser, enhances the myocardial function by generating more energy-efficient myocardial contractility than achieved via adrenergic stimulation with catecholamines. Thus potentially, levosimendan is a beneficial alternative to standard medication for the prevention of low cardiac output syndrome in paediatric patients after open heart surgery. OBJECTIVES: To review the efficacy and safety of the postoperative prophylactic use of levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. SEARCH METHODS: We identified trials via systematic searches of CENTRAL, MEDLINE, Embase, and Web of Science, as well as clinical trial registries, in June 2016. Reference lists from primary studies and review articles were checked for additional references. SELECTION CRITERIA: We only included randomised controlled trials (RCT) in our analysis that compared prophylactic levosimendan with standard medication or placebo, in infants and children up to 18 years of age, who were undergoing surgery for congenital heart disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias according to a pre-defined protocol. We obtained additional information from all but one of the study authors of the included studies. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of evidence from the studies that contributed data to the meta-analyses for the prespecified outcomes. We created a 'Summary of findings' table to summarise the results and the quality of evidence for each outcome. MAIN RESULTS: We included five randomised controlled trials with a total of 212 participants in the analyses. All included participants were under five years of age. Using GRADE, we assessed there was low-quality evidence for all analysed outcomes. We assessed high risk of performance and detection bias for two studies due to their unblinded setting. Levosimendan showed no clear effect on risk of mortality (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.12 to 1.82; participants = 123; studies = 3) and no clear effect on low cardiac output syndrome (RR 0.64, 95% CI 0.39 to 1.04; participants = 83; studies = 2) compared to standard treatments. Data on time-to-death were not available from any of the included studies.There was no conclusive evidence on the effect of levosimendan on the secondary outcomes. The length of intensive care unit stays (mean difference (MD) 0.33 days, 95% CI -1.16 to 1.82; participants = 188; studies = 4), length of hospital stays (MD 0.26 days, 95% CI -3.50 to 4.03; participants = 75; studies = 2), duration of mechanical ventilation (MD -0.04 days, 95% CI -0.08 to 0.00; participants = 208; studies = 5), and the risk of mechanical circulatory support or cardiac transplantation (RR 1.49, 95% CI 0.19 to 11.37; participants = 60; studies = 2) did not clearly differ between the groups. Published data about adverse effects of levosimendan were limited. A meta-analysis of hypotension, one of the most feared side effects of levosimendan, was not feasible because of the heterogeneous expression of blood pressure values. AUTHORS' CONCLUSIONS: The current level of evidence is insufficient to judge whether prophylactic levosimendan prevents low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. So far, no significant differences have been detected between levosimendan and standard inotrope treatments in this setting.The authors evaluated the quality of evidence as low, using the GRADE approach. Reasons for downgrading were serious risk of bias (performance and detection bias due to unblinded setting of two RCTs), serious risk of inconsistency, and serious to very serious risk of imprecision (small number of included patients, low event rates).

Prophylactic levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease.

BACKGROUND: Low cardiac output syndrome remains a serious complication, and accounts for substantial morbidity and mortality in the postoperative course of paediatric patients undergoing surgery for congenital heart disease. Standard prophylactic and therapeutic strategies for low cardiac output syndrome are based mainly on catecholamines, which are effective drugs, but have considerable side effects. Levosimendan, a calcium sensitiser, enhances the myocardial function by generating more energy-efficient myocardial contractility than achieved via adrenergic stimulation with catecholamines. Thus potentially, levosimendan is a beneficial alternative to standard medication for the prevention of low cardiac output syndrome in paediatric patients after open heart surgery. OBJECTIVES: To review the efficacy and safety of the postoperative prophylactic use of levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. SEARCH METHODS: We identified trials via systematic searches of CENTRAL, MEDLINE, Embase, and Web of Science, as well as clinical trial registries, in June 2016. Reference lists from primary studies and review articles were checked for additional references. SELECTION CRITERIA: We only included randomised controlled trials (RCT) in our analysis that compared prophylactic levosimendan with standard medication or placebo, in infants and children up to 18 years of age, who were undergoing surgery for congenital heart disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias according to a pre-defined protocol. We obtained additional information from all but one of the study authors of the included studies. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of evidence from the studies that contributed data to the meta-analyses for the prespecified outcomes. We created a 'Summary of findings' table to summarise the results and the quality of evidence for each outcome. MAIN RESULTS: We included five randomised controlled trials with a total of 212 participants in the analyses. All included participants were under five years of age. Using GRADE, we assessed there was low-quality evidence for all analysed outcomes. We assessed high risk of performance and detection bias for two studies due to their unblinded setting. Levosimendan showed no clear effect on risk of mortality (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.12 to 1.82; participants = 123; studies = 3) and no clear effect on low cardiac output syndrome (RR 0.64, 95% CI 0.39 to 1.04; participants = 83; studies = 2) compared to standard treatments. Data on time-to-death were not available from any of the included studies.There was no conclusive evidence on the effect of levosimendan on the secondary outcomes. The levosimendan groups had shorter length of intensive care unit stays (mean difference (MD) 0.33 days, 95% CI -1.16 to 1.82; participants = 188; studies = 4; I² = 35%), length of hospital stays (0.26 days, 95% CI -3.50 to 4.03; participants = 75; studies = 2), and duration of mechanical ventilation (MD -0.04 days, 95% CI -0.08 to 0.00; participants = 208; studies = 5; I² = 0%). The risk of mechanical circulatory support or cardiac transplantation favoured the levosimendan groups (RR 1.49, 95% CI 0.19 to 11.37; participants = 60; studies = 2). Published data about adverse effects of levosimendan were limited. A meta-analysis of hypotension, one of the most feared side effects of levosimendan, was not feasible because of the heterogeneous expression of blood pressure values. AUTHORS' CONCLUSIONS: The current level of evidence is insufficient to judge whether prophylactic levosimendan prevents low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. So far, no significant differences have been detected between levosimendan and standard inotrope treatments in this setting.The authors evaluated the quality of evidence as low, using the GRADE approach. Reasons for downgrading were serious risk of bias (performance and detection bias due to unblinded setting of two RCTs), serious risk of inconsistency, and serious to very serious risk of imprecision (small number of included patients, low event rates).

Photophysical properties and OLED performance of light-emitting platinum(II) complexes.

The synthesis, photophysical properties and application as emitters in solution-processed multi-layer organic light-emitting diodes (OLEDs) of a series of blue-green to red light-emitting phosphorescent platinum(II) complexes are reported. These complexes consist of phenylisoquinoline, substituted phenylpyridines or tetrahydroquinolines as C^N cyclometalating ligands and dipivaloylmethane as an ancillary ligand. Depending on both the structure of the C^N cyclometalating ligands and the dopant concentration in the matrix, these platinum(II) complexes exhibit different aggregation tendencies. This property affects the photoluminescence spectra of the investigated compounds and colour-stability of the fabricated OLEDs. Using the blue-green to yellow-green emitting complexes, the best results were obtained with the 2-(4-trifluoromethylphenyl)-5,6,7,8-tetrahydroquinoline based platinum(II) complex. A maximum luminous efficiency of 4.88 cd A(-1) and a power efficiency of 4.65 lm W(-1), respectively, were achieved. Employing the red emitting phenylisoquinoline based complex as an emitter, colour-stable and efficient (4.71 cd A(-1), 5.12 lm W(-1)) devices were obtained.

Coil-occlusion of the left ventricle as emergency treatment in failing stage I palliation for hypoplastic left heart syndrome with sinusoids.

We report on a patient with hypoplastic left heart syndrome (HLHS), ventricular septal defects, and coronary sinusoids who suffered recurrent myocardial ischemic events that required cardiopulmonary resuscitation after stage I palliation. We identified the main reason to be a steal phenomenon of blood from the left coronary artery via the sinusoids into the rudimentary left ventricle and across the septal defects into the right ventricle. To limit this coronary steal phenomenon, we successfully performed transcatheter closure of the left ventricle with implantation of three Microplex Terumo-Coils. This led to the patient's clinical stabilization. Stage II surgery took place at the age of 5 months without difficulty. In the setting of a symptomatic neonate with HLHS and ventriculocoronary connections, embolization of the left ventricle is a feasible interventional therapy.

Impact of chronic kidney disease on long-term clinical outcomes after percutaneous coronary intervention with drug-eluting or bare-metal stents.

Chronic kidney disease (CKD) is associated with adverse outcomes after coronary bare-metal stent (BMS) and drug-eluting stent (DES) implantation, but it is unclear which stent type is associated with lower risk for morbidity and mortality in this population. Uniform treatment standards during coronary stent implantation and a median follow-up period of 2.8 years characterize the FReIburg STent (FRIST) registry, designed as a long-term outcome evaluation of a single tertiary referral cardiovascular center. CKD, defined as creatinine clearance <60 mL/min, was present at baseline in 180 (12%) of 1502 consecutive patients undergoing coronary stent intervention. Patients received first-generation DES (n = 117) or BMS (n = 63). Kaplan-Meier and multivariate Cox model analyses were applied to compare survival rates and adjust for existing clinical, procedural, and angiographic differences between the patients. The primary end point was mortality (cardiac and noncardiac death) and secondary end points were recurrent myocardial infarction, stent thrombosis, target vessel revascularization, sepsis, and major bleeding. Patients with a glomerular filtration rate <60 mL/min had a higher mortality rate (28.3% vs. 10.1%, P < 0.001) than patients with a good renal function. In patients with CKD, there was no difference in mortality rates in the BMS vs. the DES group (hazard ratio, 0.971; 95% confidence interval, 0.48-1.954). In summary, patients with CKD have significantly higher rates of death, but there appears to be no difference in long-term clinical outcomes of first-generation DES compared with BMS implantation during primary percutaneous coronary intervention.

Oxygen and temperature sensitivity of blue to green to yellow light-emitting Pt(II) complexes.

The synthesis and photophysical properties of a series of yellow-green to blue-green emitting heteroleptic, cyclometalated Pt(II)(acac) complexes based on substituted phenylpyridine and tetrahydroquinoline ligands is reported. The luminescence intensities and lifetimes of these compounds were also studied in poly(styrene) films with respect to their responses to oxygen and temperature. Particularly, due to the insensitivity to oxygen quenching, these complexes are promising candidates as inert reference dyes in optical sensors. On the other hand, the Pt(II) complex with 2-(4-bromophenyl)-5,6,7,8-tetrahydroquinoline as C^N ligand, displays a strong temperature quenching effect. The distinct response to temperature was additionally calibrated after incorporation in poly(vinylidene chloride-co-acrylonitrile) serving as oxygen-blocking matrix copolymer. The resulting yellow-green-emitting temperature sensor signifies an interesting alternative to the available mostly red emitting temperature-sensitive probes.

Oligo(U-terpyridines) and their ruthenium(II) complexes: synthesis and structural properties.

A highly efficient domino reaction starting from tetrahydroquinolinone and a series of bisiminium salts provides the corresponding bis(U-terpyridines). These ligands have been treated with [(tpy)RuCl3] to afford novel dinuclear complexes [(tpy)Ru(L)Ru(tpy)]4+. The protocol is also applied for the synthesis of a star-shaped tris(U-terpyridine) and the trinuclear complex [{(tpy)Ru}3(L)]6+. In view of potential applications in the fields of metallopolymers and molecular devices, the electronic spectra, as well as the electrochemical potentials of all the complexes have been obtained. According to these data, no significant intermetal interaction has been observed for the ruthenium complexes presented here.