Cardiac outcomes in adults with supravalvar aortic stenosis

Aims Supravalvar aortic stenosis is a rare form of left ventricular outflow tract obstruction that is often progressive in childhood. Little data are available on outcomes in the adult population. Our aim was to define cardiac outcomes in adults with supravalvar aortic stenosis. Methods and results This is a multicentre retrospective study of cardiac outcomes in adults (≥18 years) with supravalvar aortic stenosis. We examined: (i) adverse cardiac events (cardiovascular death, myocardial infarction, stroke, heart failure, sustained arrhythmias, and infective endocarditis) and (ii) the need for cardiac surgery in adulthood. One hundred and thirteen adults (median age at first visit 19 years; 55% with Williams-Beuren syndrome; 67% with surgical repair in childhood) were identified. Adults without Williams-Beuren syndrome had more severe supravalvar aortic stenosis and more often associated left ventricular outflow tract obstructions (P < 0.001). In contrast, mitral valve regurgitation was more common in patients with Williams-Beuren syndrome. Eighty-five per cent of adults (96/113) had serial follow-up information (median follow-up 6.0 years). Of these patients, 13% (12/96) had an adverse cardiac event and 13% (12/96) had cardiac operations (7 valve repair or replacements, 4 supravalvar aortic stenosis repairs, 1 other). Cardiac surgery was more common in adults without Williams-Beuren syndrome (P = 0.007). Progression of supravalvar aortic stenosis during adulthood was rare. Conclusion Adults with supravalvar aortic stenosis remain at risk for cardiac complications and reoperations, while progression of supravalvar aortic stenosis in adulthood is rare. Valve surgery is the most common indication for cardiac surgery in adulthoo

Assisted Self-Assembly to Target Heterometallic Mn-Nd and Mn-Sm SMMs: Synthesis and Magnetic Characterisation of [Mn7_{7}Ln3_{3}(O)4_{4}(OH)4_{4}(mdea)3_{3}(piv)9_{9}(NO3_{3})3_{3}] (Ln=Nd, Sm, Eu, Gd)**

Assisted self-assembly by using a preformed [Mn$_{6}$O$_{2}$(piv)$_{10}$(4-Me-py)$_{2}$(pivH)$_{2}$] (1) (pivH=pivalic acid) cluster leads to 3 different outcomes of the reaction with Ln(NO$_{3}$)$_{3}$ ⋅ xH$_{2}$O (Ln=Pr−Ho and Y): Mn$_{7}$Ln$_{3}$ and in some cases the inverse butterfly Mn$_{2}$Ln$_{2}$ for Ln=Pr−Eu, Mn$_{5}$Ln$_{4}$ for Ln=Tb-Ho and in the special case of Gd all three possibilities can form. Whilst the magnetic properties for the Mn$_{5}$Ln$_{4}$ systems show the expected known SMM properties, for Mn$_{7}$Ln$_{3}$ two new examples of Nd- and Sm-containing SMMs have been discovered. in an assisted self-assembly approach starting from the [Mn$_{6}$O$_{2}$(piv)$_{10}$(4-Me-py)$_{2}$(pivH)$_{2}$] cluster a family of Mn−Ln compounds (Ln=Pr−Yb) was synthesised. The reaction of [Mn$_{6}$O$_{2}$(piv)$_{10}$(4-Me-py)$_{2}$(pivH)$_{2}$] (1) with N-methyldiethanolamine (mdeaH$_{2}$) and Ln(NO$_{3}$)$_{3}$ ⋅ 6H$_{2}$O in MeCN generally yields two main structure types: for Ln=Tb−Yb a previously reported Mn$_{5}$Ln$_{4}$ motif is obtained, whereas for Ln=Pr−Eu a series of Mn$_{7}$Ln$_{3}$ clusters is obtained. Within this series the Gd$^{III}$ analogue represents a special case because it shows both structural types as well as a third Mn$_{2}$Ln$_{2}$ inverse butterfly motif. Variation in reaction conditions allows access to different structure types across the whole series. This prompts further studies into the reaction mechanism of this cluster assisted self-assembly approach. For the Mn$_{7}$Ln$_{3}$ analogues reported here variable-temperature magnetic susceptibility measurements suggest that antiferromagnetic interactions between the spin carriers are dominant. Compounds incorporating Ln=Nd$^{III}$(2), Sm$^{III}$(3) and Gd$^{III}$ (5) display SMM behaviour. The slow relaxation of the magnetisation for these compounds was confirmed by ac measurements above 1.8 K

Inorganic Approach to Stabilizing Nanoscale Toroidicity in a Tetraicosanuclear Fe18_{18}Dy6_{6} Single Molecule Magnet

Cyclic coordination clusters (CCCs) are proving to provide an extra dimension in terms of exotic magnetic behavior as a result of their finite but cyclized chain structures. The Fe$_{18}$Dy$_{6}$ CCC is a Single Molecule Magnet with the highest nuclearity among Ln containing clusters. The three isostructural compounds [Fe$_{18}$Ln$_{6}$(μ-OH)$_{6}$(ampd)$_{12}$(Hampd)$_{12}$(PhCO$_{2}$)$_{24}$](NO$_{3}$)$_{6}$·38MeCN for Ln = Dy$^{III}$ (1), Lu$^{III}$ (2), or Y$^{III}$ (3), where H$_{2}^{-}$ampd = 2-amino-2-methyl-1,3-propanediol, are reported. These can be described in terms of the cyclization of six {Fe$_{3}$Ln(μOH)(ampd)$_{2}$(Hampd)$_{2}$(PhCO$_{2}$)$_{4}$}$^{+}$ units with six nitrate counterions to give the neutral cluster. The overall structure consists of two giant Dy$_{3}$ triangles sandwiching a strongly antiferromagnetically coupled Fe$_{18}$ ring, leading to a toroidal arrangement of the anisotropy axis of the Dy ions, making this the biggest toroidal arrangement on a molecular level known so far

A nested spin structure and single molecule magnet behaviour in an Fe8_8Dy12_{12} heterometallic cyclic coordination cluster

The 20-nuclearity compound [Fe$_8$Dy$_{12}$(tea)$_8$(teaH)$_{12}$(NO$_3$)$_{12}$]·8MeCN (where teaH$_3$ = triethanolamine) was synthesised and characterised through single crystal X-ray diffraction and magnetic measurements. The shape of the magnetic hysteresis in the microSQUID measurements was rationalised using the MAGELLAN program

Breaking Symmetry Relaxes Structural and Magnetic Restraints, Suppressing QTM in Enantiopure Butterfly Fe2_{2}Dy2_{2} SMMs**

These 2 coordination clusters are similar but different both in the fine details of their structures as well as their magnetic behaviour. [Fe$_{2}$Dy$_{2}$(μ$_{3}$-OH)$_{2}$(Me-teaH)$_{2}$(O$_{2}$CPh)$_{6}$], which normally forms with the racemic version of Me-teaH3 by using enantiopure ligand, allows access to the S-version, but for the R-version there is significant racemisation. Surprisingly, by using the synthesis of [Fe$_{2}$Dy$_{2}$(μ$_{3}$-OH)$_{2}$(Me-teaH)$_{2}$(O$_{2}$CPh)$_{4}$(NO$_{3}$)$_{2}$] both enantiopure R- and S-compounds were obtained. In both cases breaking the symmetry of the parent compounds leads to enhanced SMM behaviour. The {Fe$_{2}$Dy$_{2}$} butterfly systems can show single molecule magnet (SMM) behaviour, the nature of which depends on details of the electronic structure, as previously demonstrated for the [Fe$_{2}$Dy$_{2}$(μ$_{3}$-OH)$_{2}$(Me-teaH)$_{2}$(O$_{2}$CPh)$_{6}$] compound, where the [N,N-bis-(2-hydroxyethyl)-amino]-2-propanol (Me-teaH$_{3}$) ligand is usually used in its racemic form. Here, we describe the consequences for the SMM properties by using enantiopure versions of this ligand and present the first homochiral 3d/4 f SMM, which could only be obtained for the S enantiomer of the ligand for [Fe$_{2}$Dy$_{2}$(μ$_{3}$-OH)$_{2}$(Me-teaH)$_{2}$(O$_{2}$CPh)$_{6}$] since the R enantiomer underwent significant racemisation. To investigate this further, we prepared the [Fe$_{2}$Dy$_{2}$(μ$_{3}$-OH)$_{2}$(Me-teaH)$_{2}$(O$_{2}$CPh)$_{4}$(NO$_{3}$)$_{2}$] version, which could be obtained as the RS-, R- and S-compounds. Remarkably, the enantiopure versions show enhanced slow relaxation of magnetisation. The use of the enantiomerically pure ligand suppresses QTM, leading to the conclusion that use of enantiopure ligands is a “gamechanger” by breaking the cluster symmetry and altering the intimate details of the coordination cluster\u27s molecular structure

Evaluation of contraceptive methods in women with congenital heart disease in Germany, Hungary and Japan

Aims For women with congenital heart defects (CHD), pregnancy may pose a health risk. Sexually active women with CHD without the desire for own children or for whom pregnancy would imply considerable health risks require adequate counselling regarding appropriate contraception. This study gathers data on the contraceptive behaviour of women with CHD from three different cultural regions. Methods and results 634 women with CHD from Germany, Hungary and Japan were surveyed regarding contraception and contraceptive methods (CM) used. The patients were divided into groups according to different criteria such as pregnancy associated cardiovascular risk or "safety" of the contraceptive methods used. 59% of the study participants had already gained experience with CM. The average age at the first time of use was 18.4 years; the German patients were significantly younger at the first time of using a CM than those from Hungary and Japan. Overall the condom was the method used the most (38%), followed by oral contraceptives (30%) and coitus interruptus (11%). The range of CM used in Japan was much smaller than that in Germany or Hungary. Unsafe contraceptives were currently, or had previously been used, by 29% of the surveyed patients (Germany: 25%, Hungary: 37%, Japan: 32%). Conclusion Most women with CHD use CM. There are differences between the participating countries. Adequate contraceptive counselling of women with CHD requires considering the individual characteristics of each patient, including potential contraindications. For choosing an appropriate CM, both the methods' "safety", as well as the maternal cardiovascular risk, are important. © 2015 Elsevier Ireland Ltd

Influence of socioeconomic factors on pregnancy outcome in women with structural heart disease

OBJECTIVE: Cardiac disease is the leading cause of indirect maternal mortality. The aim of this study was to analyse to what extent socioeconomic factors influence the outcome of pregnancy in women with heart disease.  METHODS: The Registry of Pregnancy and Cardiac disease is a global prospective registry. For this analysis, countries that enrolled ≥10 patients were included. A combined cardiac endpoint included maternal cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, hospitalisation for cardiac reason or intervention. Associations between patient characteristics, country characteristics (income inequality expressed as Gini coefficient, health expenditure, schooling, gross domestic product, birth rate and hospital beds) and cardiac endpoints were checked in a three-level model (patient-centre-country).  RESULTS: A total of 30 countries enrolled 2924 patients from 89 centres. At least one endpoint occurred in 645 women (22.1%). Maternal age, New York Heart Association classification and modified WHO risk classification were associated with the combined endpoint and explained 37% of variance in outcome. Gini coefficient and country-specific birth rate explained an additional 4%. There were large differences between the individual countries, but the need for multilevel modelling to account for these differences disappeared after adjustment for patient characteristics, Gini and country-specific birth rate.  CONCLUSION: While there are definite interregional differences in pregnancy outcome in women with cardiac disease, these differences seem to be mainly driven by individual patient characteristics. Adjustment for country characteristics refined the results to a limited extent, but maternal condition seems to be the main determinant of outcome

Is Ectopic Cushing Syndrome Commonly Associated with Small Cell Lung Cancer (SCLC)? Critical Review of the Literature and ACTH Expression in Resected SCLC

The literature emphasizes that pulmonary ectopic Cushing syndrome (ECS) is associated not only with neuroendocrine tumors (NETs), but also with small cell lung carcinomas (SCLCs). This statement is debatable, because extrapulmonary ECS is associated with NETs in the vast majority of cases and very rarely with neuroendocrine carcinomas (NECs). Therefore, we critically reviewed the literature on SCLCs associated with ECS (ECS-SCLC) and performed immunohistochemical analysis of ACTH expression in 155 resected SCLCs and 158 pulmonary NETs. The literature search revealed that 90% of the 205 ECS-SCLC patients identified between 1952 and 2023 had no or poor-quality histologic images, so the diagnosis of SCLC could not be confirmed. Review of the 20 reports (10%) with histologic images revealed that 18/20 (90%) had to be reclassified as "probable NET", of which 5/18 (28%) showed spindle cell morphology, while only 2 cases were qualified as "SCLC compatible" due to their pleomorphic cell features. Immunohistochemically, 5/155 (3%) resected SCLCs, all without ECS, showed weak single cell ACTH expression, whereas in the NET cohort, 61/158 (39%) tumors expressed ACTH, of which 4 (3%) were associated with ECS. Both observations, the literature review, which casts doubt on previously reported data regarding the frequency of SCLC in ECS, and the immunohistochemical study, suggest that there is limited evidence that SCLC is the cause of ECS