Predictors of ACEI/ARB therapy in patients with hypertrophic cardiomyopathy : results of a national registry

© The European Society of Cardiology 2018. All rights reserved. For Permissions, please e-mail: [email protected]: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are not considered disease-modifying drugs in hypertrophic cardiomyopathy (HCM) and their use is usually dependent on other clinical indications. Few data exist about the use of ACEI/ARB in HC in the real world, particularly in patients with intraventricular obstruction. Objective: In this study, we sought to determine the frequency of ACEI / ARB therapy in patients with HCM and the predictors for their use.info:eu-repo/semantics/publishedVersio

Polymorphism and Superconductivity in Bilayer Molecular Metals (CNB-EDT-TTF)4I3

Electrocrystallization from solutions of the dissymmetrical ET derivative cyanobenzene-ethylenedithio-tetrathiafulvalene (CNB-EDT-TTF) in the presence of triiodide I3 − affords two different polymorphs (β″ and κ) with the composition (CNB-EDT-TTF)4I3, both with a bilayer structure of the donors. These polymorphs differ in the packing patterns (β″- and κ-type) of the donor molecules in each layer, in both cases with bifurcated C−N···H interactions effectively coupling head-to-head donor molecules between layer pairs. Two β″ polymorphs can be obtained with different degrees of anionic ordering. In one disordered phase, β″d, with a smaller unit cell, the triiodide anions are disordered over two possible positions in a channel between the donor bilayers, while in the ordered phase, β″o, the triiodide anions occupy only one of those positions in this channel, leading to the doubling of the unit cell in the layer plane. These results for β″ phases contrast with the κ polymorph previously reported, for which weaker disorder of the triiodide anions, over two possible orientations with 94 and 6% occupation factors, was observed. While the β″ polymorphs remains metallic down to 1.5 K with a ρ300K/ρ4K resistivity ratio of 250, the κ polymorph presents a much smaller resistivity ratio in the range of 4−10 and superconductivity with an onset temperature of 3.5 K.This work was partially supported in Portugal by FCT under Contracts UID/Multi/04349/2013 and RECI/QEQ-QIN/ 0189/2012 and grants to S.O. (SFRH/BD/72722/2010) and S.R. (SFRH/BPD/113344/2015). Work in Bellaterra was supported by MINECO-Spain (Grant FIS2015-64886-C5-4- P) and Generalitat de Catalunya (2014SGR301). E.C. acknowledges the support of the Spanish MINECO through the Severo Ochoa Centers of Excellence Program under Grant SEV-2015-0496.Peer reviewe

DT-TTF Salts with [Cu(dcdmp)2]−: The Richness of Different Stoichiometries

(DT-TTF)[Cu(dcdmp)(2)] (1), (DT-TTF)(2)[Cu(dcdmp)(2)] (2), and (DT-TTF)(3)[Cu(dcdmp)(2)](2) (3) are three new charge transfer salts obtained by electrocrystallization of the donor DT-TTF (dithiophene-tetrathiafulvalene) with the diamagnetic copper complex [Cu(dcdmp)(2)](-) (dcdmp = 2,3-dicyano-5,6-dimercaptopyrazine). Compounds 1 and 3 crystallize in the triclinic system and consist of out-of-registry layers of mixed stacks of donor and acceptor molecules. (DT-TTF)(2)[Cu(dcdmp)(2)] presents a structure similar to the parent spin-ladder systems with donor stacks arranged in pairs; however, a magnetic spin-ladder behavior is not observed probably due to strong interactions between pairs. Compound 3, despite the mixed nature of the stacks, displays relatively high conductivity (7 S/cm) due to a one-dimensional network of interactions between donors.This work was supported by FCT (Portugal) through contracts PTDC/QEQ-SUP/1413/2012 and UID/Multi/04349/2013 and by DGI, Spain (CTQ2013-40480), the Generalitat de Catalunya (2014SGR0017), the CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), promoted by ISCIII, Spain. R. A. L. S. is thankful to FCT for the PhD grant SFRH/BD/86131/2012.Peer reviewe

Registo Português de Miocardiopatia Hipertrófica : resultados globais

© 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. Todos os direitos reservados.Introduction: We report the results of the Portuguese Registry of Hypertrophic Cardiomyopathy, an initiative that reflects the current spectrum of cardiology centers throughout the territory of Portugal. Methods: A direct invitation to participate was sent to cardiology departments. Baseline and outcome data were collected. Results: A total of 29 centers participated and 1042 patients were recruited. Four centers recruited 49% of the patients, of whom 59% were male, and mean age at diagnosis was 53±16 years. Hypertrophic cardiomyopathy (HCM) was identified as familial in 33%. The major reason for diagnosis was symptoms (53%). HCM was obstructive in 35% of cases and genetic testing was performed in 51%. Invasive septal reduction therapy was offered to 8% (23% of obstructive patients). Most patients (84%) had an estimated five-year risk of sudden death of <6%. Thirteen percent received an implantable cardioverter-defibrillator. After a median follow-up of 3.3 years (interquartile range [P25-P75] 1.3-6.5 years), 31% were asymptomatic. All-cause mortality was 1.19%/year and cardiovascular mortality 0.65%/year. The incidence of heart failure-related death was 0.25%/year, of sudden cardiac death 0.22%/year and of stroke-related death 0.04%/year. Heart failure-related death plus heart transplantation occurred in 0.27%/year and sudden cardiac death plus equivalents occurred in 0.53%/year. Conclusions: Contemporary HCM in Portugal is characterized by relatively advanced age at diagnosis, and a high proportion of invasive treatment of obstructive forms. Long-term mortality is low; heart failure is the most common cause of death followed by sudden cardiac death. However, the burden of morbidity remains considerable, emphasizing the need for diseasespecific treatments that impact the natural history of the disease.Objectivo: Apresentação dos resultados do Registo Português de Miocardiopatia Hipertrófica. Metodologia: Convite direto aos diferentes centros de cardiologia de Portugal, com análise de dados basais e de seguimento. Resultados: Foram 29 os centros participantes e 1042 doentes incluídos. Quatro centros incluíram 49% dos doentes, 59% do sexo masculino, idade média de diagnóstico 53 ± 16 anos. A doença foi considerada familiar em 33% e a presença de sintomas foi a principal causa de diagnóstico (53%). A miocardiopatia hipertrófica foi obstrutiva em 35%. O estudo genético foi efetuado em 51%. Oito por cento dos doentes fizeram terapêutica invasiva de redução septal (23% dos doentes com obstrução). A maioria dos doentes (84%) apresentava um risco estimado de morte súbita aos 5 anos < 6%. Em 13% foi colocado desfibrilhador cardioversor implantável. Após um seguimento de 3,3 anos, intervalo interquartil (P25-P75) 1,3-6,5 anos, 31% estavam assintomáticos. A mortalidade total foi de 1,19%/ano e a cardiovascular de 0,65%/ano. A incidência de morte por insuficiência cardiaca foi de 0,25%/ano, a de morte súbita de 0,22%/ano e a de morte por acidente vascular cerebal de 0,04%/ano. A mortalidade por insuficiência cardíaca e transplante cardíaco foi de 0,27%/ano e a de morte súbita e equivalentes de 0,53%/ano. Conclusões: A miocardiopatia hipertrófica em Portugal apresenta idade de diagnóstico elevada e é frequente o tratamento invasivo de formas obstrutivas. A mortalidade é baixa, a insuficiência cardíaca é a principal causa de morte, seguida pela morte súbita. A doença apresenta elevada morbilidade, realça a necessidade do desenvolvimento de tratamentos específicos com impacto na sua história natural.info:eu-repo/semantics/publishedVersio

Gold and nickel alkyl substituted bis-thiophenedithiolene complexes: anionic and neutral forms

Andrade, Marta A. et al.The Au and Ni monoanionic complexes of ter-buthyl and diisopropyl substituted thiophedithiolate ligand [M(α-tb-tpdt)2] and [M(α-dp-tpdt)2], were synthesized and characterized namely by single crystal X-Ray diffraction and magnetic susceptibility measurements. These complexes, prepared in a first step as monoanioc species, are easier to oxidized than the related non-substituted thiophenedithiolates and could be obtained also as stable neutral species, As expected, the peripheral alkyl groups in the ligands confer also to the complexes an high solubility in common organic solvents, The neutral gold complex [Au(α-tbtpdt)2] presents a significant ligand asymmetry indicative of unpaired electron localization in one ligand at variance with [Au(α-dp-tpdt)2] that is within experimental uncertainty fully symmetric illustrating the role of the intermolecular interactions in the stabilization of SOMO…SOMO interactions. While in [Au(α-tbtpdt)2] a significantr intermolecular interaction between paramagnetic molecules is possible leading to diamagnetic dimers of molecules, in [Au(α-dp-tpdt)2] the bulkier substituents prevent the intermolecular interactions, leading to a regular stacking of molecules in symmetrical configuration. The regular stacks of paramagnetic [Au(α-dp-tpdt)2] units behave at high temperatures as an antiferromagnetic chains undergoing an AFM transition at ca. 25 K.This work was supported by FCT (Portugal) through contracts UID/Multi/04349/2013, PTDC/QEQ-SUP/1413/2012 and RECI/QEQ-QIN/0189/2012 and doctoral grants to J.T.C. (SFRH/BD/84628/2012) and R.A.L.S (SFRH/BD/86131/2012).Peer reviewe

Genetic characterization and genotype-phenotype associations in a large cohort of patients with hypertrophic cardiomyopathy : an ancillary study of the Portuguese registry of hypertrophic cardiomyopathy

© 2018 Elsevier B.V. All rights reserved.Background: We present an ancillary study of the Portuguese Registry of Hypertrophic Cardiomyopathy (PRo-HCM). This is one of the largest HCM genetic studies based on a registry. Methods and results: Collected genetic variants were re-analysed for pathogenicity. Demographic, clinical, imaging and outcome data were analysed for associations with genotype, focusing on comparisons between patients with (G+) vs without (G−) a pathogenic/likely pathogenic (P/LP) variant in one the 9 main causal sarcomeric genes. From the 1042 patients in the registry, 528 (51%) had genetic testing. 152 (28%) were G+ and 98 pts. (19%) had variants of unknown significance. From the patients with the 9 mentioned genes sequenced (424 pts), 14.6% had P/LP variants in MYBPC3, 8.7% MYH7, 4.5% TNNT2, 1.7% TNNI3. Patients were 51 ± 16 years-old, 59% males. Genotype was associated with the following: birthplace (p = 0.005); age (p b 0.001); family history of HCM (p b 0.0005); hypertension (p b 0.0005); chest pain (p = 0.015); pattern of hypertrophy (p = 0.006); left ventricular hypertrophy on the ECG (p b 0.0005); family history of sudden cardiac death (SCD) (p = 0.002). G+ patients more frequently had more than one risk factor for SCD (p = 0.002) and a higher ESC-SCD risk score (p = 0.003). In survival analysis, G+ was associated with SCD (p = 0.017) and MYH7+ with LV systolic dysfunction (p = 0.038). Conclusion: Half of the registry patients had genetic testing. Sarcomere-positive patients had distinct demographics, ECG, imaging characteristics and family history and are at increased risk of SCD. The presence of a MYH7 mutation was associated with evolution towards LV systolic dysfunction.The Portuguese Registry of Hypertrophic Cardiomyopathy was supported by the following companies (in alphabetical order): Jaba Recordati, Medinfar, Merck Serono, Sanofi Genzyme, Servier, and Shire Human Genetic Therapiesinfo:eu-repo/semantics/publishedVersio

Synthesis and characterization of the cyanobenzene-ethylenedithio-TTF donor

A dissymmetric TTF-type electron donor, cyanobenzene-ethylenedithio-tetrathiafulvalene (CNB-EDT-TTF), was obtained in high yield, by a cross-coupling reaction with triethyl phosphite between 2-thioxobenzo[d][1,3]dithiole-5-carbonitrile and 5,6-dihydro-[1,3]dithiolo[4,5-b][1,4]dithiin-2-one. This new donor was characterized namely by single crystal X-ray diffraction, cyclic voltammetry, NMR, UV-visible and IR spectroscopy

Perceção da doença de Fabry em cardiologia : uma lacuna a preencher

© 2018 Sociedade Portuguesa de Cardiologia. Published by Elsevier Espana, ˜ S.L.U. All rights reserved.Introduction: In adults, unexplained left ventricular hypertrophy is usually due to sarcomeric hypertrophic cardiomyopathy (HCM). Fabry disease (FD) is rare but may mimic sarcomeric HCM, and has an adverse prognosis in the absence of specific treatment. We aimed to assess cardiologists’ awareness of FD based on data from the Portuguese Registry of Hypertrophic Cardiomyopathy. Methods: A total of 811 index patients, aged 55±16 years, 486 (59.9%) male, were included. Three groups were characterized: A - 128 patients, 74 (57.8%) male, with pathogenic or likely pathogenic mutation(s) in sarcomeric genes; B - 234 patients, 146 (62.4%) male, with negative genetic testing; and C - 449 patients, 266 (59.2%) male, no genetic testing performed. The groups were compared in terms of whether FD was excluded in the registry. Potential red flags for FD were also analyzed and compared between groups. Results: Patients in group A were younger and more frequently had familial HCM (A - 53.9% vs. B - 20.1% vs. C - 18.3%; p<0.001). FD was recorded as excluded in 217 (26.8%), similar in all groups; GLA gene testing was performed in only 50/217 patients (A - 48.6%, B - 25.7%, p=0.019; C - 13.4%, p=0.036 for B vs. C), mostly in women (p<0.001) in groups B and C. Alphagalactosidase A (-Gal A) activity was assessed in 39/217 (18%) patients, with no difference between groups, but more often in men (p=0.005). Among patients with potential red flags for FD, only 46.7% underwent specific tests (GLA gene testing and/or -Gal A activity). When GLA genotyping was performed no mutations were identified. Conclusions: There is a need to improve cardiologists’ alertness for the identification of FD among the Portuguese HCM population.Introdução: Em adultos, hipertrofia ventricular esquerda inexplicada é geralmente devida a miocardiopatia hipertrófica sarcomérica (MH). A doença de Fabry (DF), rara, pode mimetizar MH e tem prognóstico adverso na ausência de tratamento específico. Avaliámos a perceção dos cardiologistas para DF com base no Registo Português de Miocardiopatia Hipertrófica. Métodos: Incluímos 811 doentes-índice, 55 ± 16 anos, 486 (59,9%) homens (H). Caracterizámos três grupos: A-128 doentes, 74 (57,8%) H, com mutação patogénica/provavelmente patogénica em genes sarcoméricos; B-234 doentes, 146 (62,4%) H, com teste genético negativo; C-449 doentes, 266 (59,2%) H, sem teste genético efetuado. Os grupos foram comparados em relação à exclusão de DF, segundo a informação do registo. Sinais potenciais de alerta para DF foram também avaliados e comparados entre os três grupos. Resultados: Os doentes do grupo A eram mais novos e tinham mais frequentemente MH familiar (A-53,9% versus B-20,1% versus C-18,3%; p< 0,001) nos grupos B e C; atividade enzimática da -Gal A foi avaliada em 39/217 (18%) doentes, sem diferença entre grupos, mas predominantemente em H (p = 0,005). Dos doentes com sinais potenciais de alerta para DF, apenas 46,7% foram submetidos a testes específicos (GLA e/ou -Gal A). Quando o gene GLA foi estudado, o resultado foi negativo. Conclusões: É necessário melhorar a perceção dos cardiologistas para a identificação da DF na população portuguesa com MH.The Portuguese Registry of Hypertrophic Cardiomyopathy was supported by the following companies (in alphabetical order): Jaba Recordati, Medinfar, Merck Serono, Sanofi Genzyme, Servier, Shire Human Genetic Therapies. This article was sponsored by a grant from Sanofi Genzyme.info:eu-repo/semantics/publishedVersio