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Background Left atrial substrate may have mechanistic relevance for ablation of atrial fibrillation (AF). We sought to analyze the relationship between low‐voltage zones (LVZs), transition zones, and AF recurrence in patients undergoing pulmonary vein isolation. Methods and Results We conducted a prospective multicenter study on consecutive patients undergoing pulmonary vein isolation‐only approach. LVZs and transition zones (0.5–1 mV) were analyzed offline on high‐density electroanatomical maps collected before pulmonary vein isolation. Overall, 262 patients (61±11 years, 31% female) with paroxysmal (130 pts) or persistent (132 pts) AF were included. After 28 months of follow‐up, 73 (28%) patients experienced recurrence. An extension of more than 5% LVZ in paroxysmal AF and more than 15% in persistent AF was associated with recurrence (hazard ratio [HR], 4.4 [95% CI, 2.0–9.8], P

Objectives: The aim of the present study was to determine the long-term prognostic value provided by the exercise electrocardiographic (ECG) response to nuclear myocardial perfusion imaging (MPI) in the evaluation of patients with chest pain, focusing on patients with a discrepancy between the two tests. Methods: A total of 1460 consecutive patients (777 female; 62.6±11.4 years) undergoing exercise myocardial single-photon emission computed tomography (SPECT) were included. The endpoint was the occurrence of acute coronary syndrome, heart failure or cardiac death during follow-up. Results: Ischemic ECG changes were observed during stress testing in 271 patients (18.5%) and 362 patients (24.7%) had positive (abnormal) exercise MPI results. There was a discrepancy between ECG and SPECT findings in 471 patients (32.2%). During the follow-up period (14.0-39.6 months), 224 patients (15.3%) presented cardiac events. The hazard ratios (HR) of ECG and MPI results to predict events were 1.506 (95% CI: 1.113-2.039) and 10.481 (95% CI: 7.799-14.080), respectively. In patients with negative MPI, the ECG response did not predict events (HR 1.214 [95% CI: 0.646-2.282]), the same as in patients with positive MPI (HR 1.203 [95% CI: 0.848-1.705]). Only in hypertensive patients with positive SPECT did the ECG show significant prognostic value (HR 1.937 [95% CI: 1.030-3.642]). In multivariate analysis, positive MPI proved an independent long-term prognostic factor (HR 10.536 [95% CI: 7.759-14.308]), but not ECG (HR 1.356 [95% CI: 0.994-1.850]). Conclusion: MPI results (normal vs. abnormal) had strong predictive value and discrepant ECG results had no significant additive prognostic value. Resumo: Objetivos: O objetivo do presente estudo foi determinar o valor prognóstico a longo prazo, fornecido pelo eletrocardiograma (ECG) em resposta ao esforço na cintigrafia de perfusão miocárdica (CPM) na avaliação de doentes com dor torácica, com ênfase para os grupos de doentes com discrepância entre os dois testes. Método: Foram incluídos 1460 doentes consecutivos (777 do sexo feminino; 62,6 ± 11,4 anos), submetidos a exercício na cintigrafia de perfusão miocárdica com SPECT. O endpoint foi a presença de síndrome coronária aguda, insuficiência cardíaca ou morte cardíaca durante o seguimento. Resultados: Duzentos e setenta e um doentes (18,5%) apresentaram alterações eletrocardiográficas de isquemia durante o teste de esforço e 362 doentes (24,7%) tinham resultados positivos (anormais) na CPM. A discrepância entre os resultados do ECG e CPM apareceu em 471 doentes (32,2%). Durante o período de seguimento (14,0-39,6 meses), 224 (15,3%) apresentaram eventos cardíacos. O hazard ratio (HR) para predizer eventos dos resultados do ECG e CPM foi de 1,506 (1,113-2,039) e 10,481 (7,799-14,080), respetivamente. No grupo de doentes com CPM negativo, o ECG não prediz eventos [HR 1,214 (0,646-2,282)],e o mesmo acontece no grupo de doentes com CPM positivo [HR 1,203 (0,848-1,705)]. Apenas em doentes hipertensos com CPM positivo, o ECG mostrou valor prognóstico significativo [HR 1,937 (1,030-3,642)]. Na análise multivariada, a CPM positiva foi um fator independente de prognóstico a longo prazo [HR 10,536 (7,759-14,308)], mas não o ECG [HR 1,356 (0,994-1,850)]. Conclusão: O resultado da CPM (normal versus anormal) teve um forte valor preditivo e o resultado discrepante no ECG não teve um valor prognóstico adicional significativo. Keywords: Electrocardiogram, Myocardial perfusion imaging, Stress test, Prognosis, Palavras-chave: Eletrocardiograma, Imagens de perfusão miocárdica, Prova de esforço, Prognóstico

Dilated cardiomyopathy (DCM) is a public health problem with no available curative treatment, and mitochondrial dysfunction plays a critical role in its development. The present study is the first to analyze the mitochondrial proteome in cardiac tissue of patients with DCM to identify potential molecular targets for its therapeutic intervention.16 left ventricular (LV) samples obtained from explanted human hearts with DCM (n = 8) and control donors (n = 8) were extracted to perform a proteomic approach to investigate the variations in mitochondrial protein expression. The proteome of the samples was analyzed by quantitative differential electrophoresis and Mass Spectrometry. These changes were validated by classical techniques and by novel and precise selected reaction monitoring analysis and RNA sequencing approach increasing the total heart samples up to 25. We found significant alterations in energy metabolism, especially in molecules involved in substrate utilization (ODPA, ETFD, DLDH), energy production (ATPA), other metabolic pathways (AL4A1) and protein synthesis (EFTU), obtaining considerable and specific relationships between the alterations detected in these processes. Importantly, we observed that the antioxidant PRDX3 overexpression is associated with impaired ventricular function. PRDX3 is significantly related to LV end systolic and diastolic diameter (r = 0.73, p value

Heart failure provokes alterations in the expression of nucleocytoplasmic transport-related genes. To elucidate the nucleocytoplasmic transport-linked functional network underlying the two major causes of heart failure, ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), we examined global transcriptome profiles of left ventricular myocardium tissue samples from 31 patients (ICM, n = 10; DCM, n = 13) undergoing heart transplantation and control donors (CNT, n = 8) using RNA-Sequencing and GeneMANIA. Comparative profiling of ICM versus control and DCM versus control showed 1081 and 2440 differentially expressed genes, respectively (>1.29-fold; P

Abstract Cardioneuroablation (CNA) represents a promising therapy for recurrent vasovagal syncope (VVS), extrinsically driven atrioventricular block (AVB) and sinus node dysfunction (SND). However, effectiveness in patients aged 50 and above is not well-established. In this prospective study of patients referred for CNA, we compared syncope and pacemaker implantation free survival, heart rate (HR) variability (HRV) and quality of life between two age groups: group A (

Sr. Editor: La canulación coronaria sigue siendo todo un desafío tras un implante percutáneo de válvula aórtica (TAVI). El alineamiento comisural de la prótesis valvular facilita la canulación coronaria, especialmente en prótesis autoexpandibles1. Además, para ciertos dispositivos, pueden hacerse necesarias diferentes técnicas de canulación coronaria si la prótesis valvular previamente implantada presenta un alineamiento comisural incorrecto2. Analizando las proyecciones de 3 cúspides y solapamiento de 2 cúspides izquierda a derecha (2 cúspides) tras el TAVI, es posible calcular el grado de alineamiento comisural de las prótesis valvulares con los postes comisurales identificables en la fluoroscopia3,4. El objetivo de este estudio fue describir las proyecciones óptimas para la canulación de la arteria coronaria izquierda (CI) y coronaria derecha (CD) en pacientes con TAVI previo. Se analizaron las imágenes tomográficas computarizadas pre-TAVI de 105 pacientes consecutivos derivados a nuestro centro para recibir un TAVI. Cinco casos fueron descartados por su mala calidad del estudio o por el reemplazo previo de la válvula aórtica. Las proyecciones óptimas para cateterizar la CI y la CD se identificaron con el software 3mensio (Pie Medical Imaging, Países Bajos) y definieron como proyecciones coplanares con el plano trasversal de la aorta a nivel de cada ostium coronario y ortogonales...

To the Editor, Coronary re-access continues to be a challenge following transcatheter aortic valve implantation (TAVI). Commissural alignment of the prosthesis facilitates coronary re-access, especially in self-expanding prostheses.1 Additionally, for certain devices, different techniques for coronary cannulation might be necessary if the previously implanted prosthesis has commissural misalignment.2 By analyzing 3-cusp and left-to-right 2-cusp overlap (2-cusp) projections after TAVI, it is possible to estimate the degree of commissural alignment in prostheses with identifiable commissural posts on fluoroscopy.3,4 This study aimed to describe the optimal projections for left and right coronary artery (LCA, RCA) cannulation in patients with previous TAVI. We analyzed the pre-TAVI computed tomography scans of 105 consecutive patients referred to our center for TAVI implantation. Of these scans, 5 were excluded due to their poor quality or previous aortic valve replacement. The ideal projections for LCA and RCA catheterization were identified by using 3mensio software (Pie Medical Imaging, The Netherlands) and were defined as projections coplanar with the cross-sectional transverse plane of the aorta at the level of each coronary ostium and orthogonal to them, respectively. An en-face projection to the aortic annulus can be established intraprocedurally as a projection where the prosthesis is foreshortened, usually in a cranial (CRA)...

Introduction and objectives: Current epidemiological data on heart failure (HF) in Portugal derives from studies conducted two decades ago. The main aim of this study is to determine HF prevalence in the Portuguese population. Using current standards, this manuscript aims to describe the methodology and research protocol applied. Methods: The Portuguese Heart Failure Prevalence Observational Study (PORTHOS) is a large, three-stage, population-based, nationwide, cross-sectional study. Community-dwelling citizens aged 50 years and older will be randomly selected via stratified multistage sampling. Eligible participants will be invited to attend a screening visit at a mobile clinic for HF symptom assessment, anthropomorphic assessment, N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing, one-lead electrocardiogram (ECG) and a sociodemographic and health-related quality of life questionnaire (EQ-5D). All subjects with NT-proBNP ≥125 pg/mL or with a prior history of HF will undergo a diagnostic confirmatory assessment at the mobile clinic composed of a 12-lead ECG, comprehensive echocardiography, HF questionnaire (KCCQ) and blood sampling. To validate the screening procedure, a control group will undergo the same diagnostic assessment. Echocardiography results will be centrally validated, and HF diagnosis will be established according to the European Society of Cardiology HF guidelines. A random subsample of patients with an equivocal HF with preserved ejection fraction diagnosis based on the application of the Heart Failure Association preserved ejection fraction diagnostic algorithm will be invited to undergo an exercise echocardiography. Conclusions: Through the application of current standards, appropriate methodologies, and a strong research protocol, the PORTHOS study will determine the prevalence of HF in mainland Portugal and enable a comprehensive characterization of HF patients, leading to a better understanding of their clinical profile and health-related quality of life. Resumo: Introdução e objetivos: Os dados epidemiológicos atuais sobre insuficiência cardíaca (IC) em Portugal provêm de estudos realizados há mais de duas décadas. O objetivo principal deste estudo é determinar a prevalência da síndrome de IC na população portuguesa com 50 ou mais anos, sendo, especificamente, objetivo deste artigo descrever as abordagens metodológicas e o protocolo de investigação aplicados. Métodos: O Estudo de Prevalência de Insuficiência Cardíaca em Portugal (PORTHOS) é um estudo observacional transversal de grande dimensão, de base populacional, nacional, constituído por três fases. Serão selecionados aleatoriamente por amostragem estratificada multietapas cidadãos com 50 ou mais anos residentes na comunidade em Portugal. Os participantes elegíveis serão convidados a participar numa visita de triagem, que decorrerá numa clínica móvel, durante a qual serão submetidos a avaliação de sintomas de IC, avaliação antropomórfica, um teste de N-terminal pró-peptídeo natriurético tipo B (NT-proBNP), eletrocardiograma de 1 derivação, questionários sociodemográficos e questionário de qualidade de vida relacionada à saúde (EQ-5D). Todos os participantes com NT-proBNP ≥125 pg/mL ou história prévia de IC serão submetidos a uma avaliação diagnóstica confirmatória composta por eletrocardiograma de 12 derivações, ecocardiografia completa, questionário de IC (KCCQ) e colheita de sangue. Para validar o procedimento de triagem, um grupo controlo passará pela mesma avaliação diagnóstica. Os resultados dos ecocardiogramas realizados serão validados centralmente e o diagnóstico de IC será confirmado de acordo com as recomendações de IC da Sociedade Europeia de Cardiologia. Uma subamostra aleatória de participantes com diagnóstico questionável de IC com fração de ejeção preservada (ICFEp), após a aplicação do algoritmo de diagnóstico de fração de ejeção preservada da Heart Failure Association (HFA-PEFF) será convidada a realizar ecocardiografia de esforço. Conclusão: Através da aplicação das recomendações atuais e abordagens metodológicas adequadas, o estudo PORTHOS irá determinar a prevalência da IC em Portugal Continental e permitir uma caracterização abrangente dos doentes com IC, para melhor compreensão do seu perfil clínico e qualidade de vida relacionada com a saúde.

Abstract Aims This study aims to investigate the clinical and biochemical characteristics of patients with atrial fibrillation (AF) referred for ablation who develop arrhythmia‐induced cardiomyopathy (AiCM) as well as their long‐term outcomes after catheter ablation (CA). Methods and results A prospective multicentre study was conducted on consecutive AF patients who underwent CA. AiCM was defined as the development of heart failure in the presence of AF and an improvement of left ventricular fraction by at least 10% at 6 months after ablation. A subgroup of patients underwent peripheral and left atrial blood samples [galectin‐3, fatty acid‐binding protein 4 (FABP4), and soluble receptor for advanced glycation end products (sRAGE)] at the time of the procedure. Of the 769 patients who underwent AF ablation, 135 (17.56%) met the criteria for AiCM. Independent predictors of AiCM included persistent AF, male gender, left atrial volume, QRS width, active smoking, and chronic kidney disease (CKD). Biomarker analysis revealed that sRAGE, FABP4, and galectin‐3 levels were not predictive of AiCM development nor did they differ between groups or predict recurrence. There were no differences in AF recurrence between patients with and without AiCM (30.83% vs. 27.77%; P = 0.392) during a median follow‐up of 23.83 months (inter‐quartile range 9–36). Conclusions In the subset of patients referred for AF ablation, the development of AiCM was associated with persistent AF and CKD. Biomarker analysis was not different between groups nor predicted recurrence. Patients with AiCM benefited from ablation, with a significant improvement in left ventricular ejection fraction and similar AF recurrence rates to those without AiCM.

Despite current treatments, which include renin angiotensin system blockers and SGLT2 inhibitors, the risk of progression of kidney disease among patients with diabetes and chronic kidney disease (CKD) remains unacceptably high. The pathogenesis of CKD in patients with diabetes is complex and includes hemodynamic and metabolic factors, as well as inflammation and fibrosis. Finerenone is a highly selective nonsteroidal mineralocorticoid antagonist that, in contrast to current therapies, may directly reduce inflammation and fibrosis, thus adding value in the management of these patients. In fact, finerenone decreases albuminuria and slows CKD progression in persons with diabetes. We now review the mechanisms of action of finerenone, the results of recent clinical trials, and the integration of the kidney and cardiovascular protection afforded by finerenone in the routine care of patients with diabetes and CKD. Resumen: A pesar de los tratamientos actuales, que incluyen los inhibidores del sistema renina angiotensina y los inhibidores SGLT2, el riesgo de progresión de la enfermedad renal en los sujetos con diabetes y enfermedad renal crónica (ERC) continúa inaceptablemente alto. La patogenia de la ERC en el paciente con diabetes es compleja, e incluiría factores hemodinámicos, metabólicos, y de inflamación y fibrosis. La finerenona es un antagonista no esteroideo altamente selectivo del receptor mineralocorticoide que, a diferencia de los tratamientos actuales, podría disminuir directamente la inflamación y la fibrosis, aportando un valor añadido al abordaje de estos pacientes. De hecho, finerenona disminuye la albuminuria y enlentece la progresión de la ERC en personas con diabetes. La presente revisión aborda el mecanismo de acción de la finerenona, los resultados de ensayos clínicos recientes y la integración en práctica clínica de la nefroprotección y cardioprotección de la finerenona en el abordaje terapéutico integral del paciente diabético con ERC.

Resumen: A pesar de los tratamientos actuales, que incluyen los inhibidores del sistema renina angiotensina y los inhibidores SGLT2, el riesgo de progresión de la enfermedad renal en los sujetos con diabetes y enfermedad renal crónica (ERC) continúa inaceptablemente alto. La patogenia de la ERC en el paciente con diabetes es compleja e incluiría factores hemodinámicos, metabólicos y de inflamación y fibrosis. La finerenona es un antagonista no esteroideo altamente selectivo del receptor mineralocorticoide que, a diferencia de los tratamientos actuales, podría disminuir directamente la inflamación y la fibrosis, aportando un valor añadido al abordaje de estos pacientes. De hecho, la finerenona disminuye la albuminuria y enlentece la progresión de la ERC en personas con diabetes. La presente revisión aborda el mecanismo de acción de la finerenona, los resultados de ensayos clínicos recientes y la integración en práctica clínica de la nefroprotección y cardioprotección de la finerenona en el abordaje terapéutico integral del paciente diabético con ERC. Abstract: Despite current treatments, that include renin angiotensin system blockers and SGLT2 inhibitors, the risk of renal disease progression among patients with diabetes and chronic kidney disease (CKD) remains unacceptably high. The pathogenesis of CKD in patients with diabetes is complex and includes hemodynamic and metabolic factors, as well as inflammation and fibrosis. Finerenone is a nonsteroidal highly selective mineralocorticoid antagonist that, in contrast to current therapies, may directly reduce inflammation and fibrosis, supporting an added value in the management of these patients. In fact, finerenone decreased albuminuria and slowed CKD progression in persons with diabetes. We now review the mechanisms of action of finerenone, the results of recent clinical trials and a practical approach to integrate the kidney and cardiovascular protection afforded by finerenone in the routine care of patients with diabetes and CKD.

Coronary artery segmentation from CT scans is a helpful tool for coronary artery diseases diagnosis, which is frequently characterised by a vessel narrowing (stenosis). This is a highly demanded and high time-consuming process, thus automated procedures are becoming increasingly necessary. In this work, we propose an extremely light computationally 2D UNet that uses transfer learning for the first time in CT images. We compare the results, using different architectures and backbones, of a 2D UNet and a 3D UNet trained from scratch (i.e. weights are randomly initialised) and a 2D EfficientUNet. Both the amount of input data, with a total of 88 patients, and the extension of the structure to be recognised, the aorta and the coronary arteries ( $A + C.A$ ), as well as the coronary arteries only ( $C.A$ ) are analysed. Network outputs in clinically identified stenotic lesion areas are also assessed. The results show the advantage of using transfer learning when data is scarce, improving the $F_{1}$ score by up to 0.6 points for the 2D UNet. On the other hand, when data is sufficient, $F_{1}$ score values are close to 0.9 for all the networks. Besides, the results reveal that the 2D UNet distinguishes the thinnest and most distal vessels, although in the presence of a lesion, there is a clear tendency to overestimate it. The network with the best accuracy is the 3D UNet, with values above 95% and 75% in $A+C.A$ and $C.A$ , respectively. Moreover, the proposed methods show dependence on the amount of training data and dataset structure ( $A + C.A$ or $C.A$ ).

Abstract Relaxin-2 exerts many favourable cardiovascular effects in pathological circumstances such as atrial fibrillation (AF) and heart failure, but the mechanisms underlying its actions are not completely understood. Since inflammation and fibrosis are pivotal processes in the pathogenesis of AF, our aim was to study the relationship between relaxin-2 plasma levels in left atrium (LA) and peripheral vein with molecules implicated in fibrosis, inflammation and oxidative stress in AF patients, and to evaluate the anti-fibrotic ability of relaxin-2 in normal human atrial cardiac fibroblasts (NHCF-A). Peripheral vein relaxin-2 plasma levels were higher than LA relaxin-2 plasma levels in men while, in women, peripheral vein relaxin-2 levels were increased compared to men. AF patients with higher levels of relaxin-2 exhibited a reduction in H2O2 plasma levels and in mRNA levels of alpha-defensin 3 (DEFA3) and IL-6 in leucocytes from LA plasma. Relaxin-2-in-vitro treatment inhibited NHCF-A migration and decreased mRNA and protein levels of the pro-fibrotic molecule transforming growth factor-β1 (TGF-β1). Our results support an association between relaxin-2 and molecules involved in fibrosis, inflammation and oxidative stress in AF patients, and reinforce an anti-fibrotic protective role of this hormone in NHCF-A; strengthening the relevance of relaxin-2 in AF physiopathology, diagnosis and treatment.

Resumen: Antecedentes y objetivo: El objetivo del estudio fue caracterizar el perfil clínico y terapéutico de los pacientes con cardiopatía isquémica en España en los pacientes (grupo 1) al alta tras un síndrome coronario agudo, (grupo 2) en primera visita post-alta y (grupo 3) entre uno o 2 años tras el síndrome coronario agudo. Materiales y métodos: Estudio observacional, multicéntrico, transversal, de ámbito nacional, realizado en condiciones de práctica clínica habitual. Resultados: Se incluyeron 1.018 pacientes: 354 (34,8%) del grupo 1, 326 (32,0%) del 2 y 338 (33,2%) del 3. En comparación con el grupo 3, en el grupo 1 había un porcentaje significativamente mayor de pacientes fumadores (32,2 contra 10,9%), que consumían alcohol (28,2 contra 19,5%), que no realizaba ejercicio físico (61,0 contra 38,2%) o que no seguían una dieta (57,1 contra 32,5%). El 65,4% de los pacientes del grupo 1 no fue derivado a un programa de rehabilitación cardiaca (PRC). Del grupo 2, el 53,1% no tenía cita prevista para comenzar un PRC. Respecto al grupo 3, al 58,3% no se le recomendó nunca hacer rehabilitación cardiaca. Las variables asociadas al control de los factores de riesgo cardiovascular fueron la ausencia de obesidad y la asistencia a un PRC. Conclusiones: En el momento actual, menos de la mitad de los pacientes con cardiopatía isquémica en España son remitidos a un PRC, aunque estos programas se asocian a un mejor control de los factores de riesgo cardiovascular. Abstract: Introduction and objectives: The objective of the study was to characterize the clinical and therapeutic profile of patients with ischemic cardiopathy (IC) in Spain in patients (group 1) at the time of hospital discharge after an acute coronary syndrome (ACS), (group 2) at the first post-discharge follow-up visit, and (group 3) after one year of the ACS. Patients and methods: Observational, multicenter, cross-sectional, nationwide, performed in conditions of routine clinical practice. Results: A total of 1018 patients were included: 354 (34.8%) in the group 1, 326 (32.0%) in the 2, and 338 (33.2%) in the 3. Compared with group 3, a higher percentage of patients from group 1 were smokers (32.2% versus 10.9%), consumed alcohol (28.2% versus 19.5%), did not do any physical exercise (61.0% versus 38.2%) or followed a diet (57.1% versus 32.5%). Of patients in group 1, 65.4% were referred to a cardiac rehabilitation program (CRP). Of those in group 2, 53.1% had not a scheduled appointment to initiate a CRP. Regarding group 3, 58.3% did not receive the recommendation of doing a CRP. Absence of obesity and attendance to a CRP were variables associated with the control of cardiovascular risk factors. Conclusions: Currently, less than 50% of patients with IC in Spain are remitted to a CRP despite being associated with an improved control of cardiovascular risk factors.

Objective: PCSK9 inhibitors have been shown to reduce LDLc by up to about 60% and 85% when used with high doses of statins and ezetimibe (2019 ESC/EAS Guidelines). These therapies may lead to very low levels of LDLc and have been associated with possible cognitive deterioration. No significant differences were found in the only specific study (EBBINGHAUS). The objective is to prospectively evaluate cognitive deterioration and its repercussion on quality of life and changes in LDLc in patients starting treatment with PCKS9 inhibitors.Method: It is a postauthorization, multicentre, non-randomized, prospective study. Patients starting treatment for the first time with PCSK9 inhibitors will be recruited in 11 Galician Hospitals over a period of 12 months and with 24 months of follow-up. The primary outcome will be to evaluate changes in cognitive function using the Montreal Cognitive Assessment (MOCA) questionnaire. The secondary outcome will be to evaluate changes in quality of life using the EuroQol-5D. Changes in LDLc will be assessed. The sample size will be 275 patients, taking into account a loss to follow-up of no more than 10%. The primary outcome will be studied through the dichotomous variable cognitive deterioration (0/1). Cognitive changes over the follow-up period will be analysed using the McNemar test. In addition, an analytical approach using logistic regression will be followed to identify patients at risk of cognitive deterioration. As a result, this analysis will obtain a frequency measurement: the odds ratio (OR). The specific objectives will be studied using bivariate analysis. Continuous contrast variables will be studied using the t-test or ANOVA and categorical variables will be studied using the chi- square test.Conclusions: The MEMOGAL study will provide information on safety in terms of cognitive deterioration in patients starting treatment with PCSK9 inhibitors.

Abstract Background Cardio myoblast generation from conventional approaches is laborious and time-consuming. We present a bioelectronics on-a-chip for stimulating cells cardio myoblast proliferation during culture. Method The bioelectronics chip fabrication methodology involves two different process. In the first step, an aluminum layer of 200 nm is deposited over a soda-lime glass substrate using physical vapor deposition and selectively removed using a Q-switched Nd:YVO4 laser to create the electric tracks. To perform the experiments, we developed a biochip composed of a cell culture chamber fabricated with polydimethylsiloxane (PDMS) with a glass coverslip or a cell culture dish placed over the electric circuit tracks. By using such a glass cover slip or cell culture dish we avoid any toxic reactions caused by electrodes in the culture or may be degraded by electrochemical reactions with the cell medium, which is crucial to determine the effective cell-device coupling. Results The chip was used to study the effect of electric field stimulation of Rat ventricular cardiomyoblasts cells (H9c2). Results shows a remarkable increase in the number of H9c2 cells for the stimulated samples, where after 72 h the cell density double the cell density of control samples. Conclusions Cell proliferation of Rat ventricular cardiomyoblasts cells (H9c2) using the bioelectronics-on-a-chip was enhanced upon the electrical stimulation. The dependence on the geometrical characteristics of the electric circuit on the peak value and homogeneity of the electric field generated are analyzed and proper parameters to ensure a homogeneous electric field at the cell culture chamber are obtained. It can also be observed a high dependence of the electric field on the geometry of the electrostimulator circuit tracks and envisage the potential applications on electrophysiology studies, monitoring and modulate cellular behavior through the application of electric fields.

RESUMEN Introducción y objetivos: Las lesiones coronarias calcificadas pueden impedir una correcta expansión del stent que en ocasiones conduce a eventos adversos. La litotricia intracoronaria es una nueva herramienta de modificación de la placa, cuyas seguridad y viabilidad en pacientes con enfermedad coronaria estable han sido evaluadas en el ensayo Disrupt CAD II. Aunque su uso ha aumentado rápidamente, hasta el momento solo se han comunicado casos aislados en escenarios concretos. Se presentan los resultados en pacientes clínicamente complejos de la vida real con calcificación coronaria grave. Métodos: Entre octubre de 2018 y marzo de 2019 se trató a 25 pacientes (37 lesiones) en 2 centros españoles, lo que representa el 2,7% de los pacientes tratados con intervención coronaria percutánea. Resultados: Las tasas de éxito clínico y del dispositivo fueron del 84 y el 95%, y no se observaron complicaciones relacionadas con el procedimiento. En todos los casos se consiguió cruzar la lesión con el balón de litotricia intracoronaria, si bien en el 8% de los casos se rompió el balón durante el inflado. Se trataron con éxito lesiones complejas, como oclusiones coronarias totales y estenosis del tronco común. En comparación con el estudio Disrupt CAD II, nuestros pacientes eran más jóvenes, pero tenían peor escenario clínico, con mayor prevalencia de diabetes (68%) e insuficiencia renal (22%), y hasta el 76% se presentó como síndrome coronario agudo. En 3 de 4 pacientes con infraexpansión de stent tratados con litotricia intracoronaria no se consiguió una expansión adecuada tras el procedimiento. No hubo complicaciones ni mortalidad hospitalaria. Un paciente falleció por causa no cardiaca a los 30 días de seguimiento. Conclusiones: La litotricia intracoronaria se ha demostrado efectiva y segura en una cohorte de pacientes complejos de la vida real con lesiones calcificadas.

ABSTRACT Introduction and objectives: Complex calcified lesions can affect stent expansion and lead to stent failure and adverse outcomes. Intracoronary lithotripsy (ICL) has emerged as a new tool that enables calcium modification. The Disrupt CAD II clinical trial has recently evaluated the safety and feasibility of ICL in patients with stable coronary disease and calcified coronary lesions. Although its use has increased rapidly, the experience already reported with this new device is limited. We report the results in real-life complex patients with heavy coronary calcification. Methods: From October 2018 to March 2019, 25 patients (37 calcified lesions) were treated in 2 Spanish centers, which accounted for 2.7% of the patients treated with percutaneous coronary intervention. Results: The device and clinical success rates were 84% and 95%, respectively. No procedure-related complications were seen. The crossing rate of the ICL balloon was 100% and balloon rupture during inflation occurred in 8%. The ICL was performed in a subset of highly complex lesions like left main coronary artery lesions and chronic total coronary occlusions. Compared to the Disrupt CAD II trial, our patients were younger but their clinical scenario was worse with a higher prevalence of diabetes (68%), renal failure (22%), and up to 76% suffered from acute coronary syndrome. The ICL failed to reach proper expansion in 3 out of 4 cases of stent underexpansion. The procedure was performed safely, and clinical and device success were high with no in-hospital mortality. One patient died of non-cardiac causes at the 30-day follow-up. Conclusions: The ICL-assisted percutaneous coronary intervention was performed safely and effectively in a real-life cohort of patients with calcified and highly complex lesions.

Objective: We wondered if a modification of the conventional transseptal puncture technique performed with an angioplasty wire could be useful in patients with contrast hypersensitivity or allergy-like reactions. Methods: This study comprised our initial experience in 22 patients with atrial fibrillation who were scheduled for an electrophysiology study (EPS) and pulmonary vein ablation and who had a contraindication for iodinated contrast administration. Results: Of the 22 patients, 16 were men and ages ranged from 27 to 74 years (mean 56 years). Overall successful transseptal access was achieved in all 22. A control echocardiogram was performed in all patients. There were no complications in any case and no significant differences were found from the conventional transseptal puncture technique regarding procedure or fluoroscopy time. Conclusions: A modification of the conventional transseptal puncture technique performed with fluoroscopy and EPS catheters for anatomical reference and an angioplasty wire is an option in cases with severe contrast hypersensitivity. Resumo: Objetivos: Questionámo-nos se uma modificação da técnica de punção transseptal tradicional realizada com fio guia de angioplastia poderia ser útil em doentes com hipersensibilidade ou outros tipos de reações alérgicas ao contraste. Métodos: Este estudo reflete a nossa experiência inicial com 22 doentes com fibrilhação auricular, programados para estudo eletrofisiológico e ablação da veia pulmonar, que tiveram contraindicação para injeção de contraste com iodo. Resultados: O acesso transseptal global bem-sucedido foi alcançado na totalidade dos 22 doentes (16 homens) entre os 27-74 anos (idade média 56). Foi realizado um ecocardiograma de controlo em todos os doentes. Não se registaram complicações nem diferenças significativas em relação à técnica de punção tradicional relativamente à duração do procedimento ou ao tempo de fluoroscopia. Conclusões: A modificação da técnica de punção transseptal tradicional com fluoroscopia, cateteres de EEF para referências anatómicas e fio guia de angioplastia pode constituir uma opção válida nos casos de hipersensibilidade grave ao contraste.

AimWhether Takotsubo syndrome (TTS) should be classified within myocardial infarction with non-obstructive coronary arteries (MINOCAs) is still controversial. The aim of this work was to evaluate the main differences between TTS and non-TTS MINOCAs.Methods and ResultsA cohort study based on two prospective registries: TTS from the RETAKO registry (N:1,015) and patients with non-TTS MINOCAs from contemporary records of acute myocardial infarction from five 5 national centers (N:1,080). Definitions and management recommended by the ESC were used. Survival analysis was based on the Cox regression analysis; propensity score matching (PS) was created to adjust prognostic variables. Takotsubo syndrome were more often women (85.9 vs. 51.9%; p < 0.001) and older (69.4 ± 12.5 vs. 64.5 ± 14.1 years; p < 0.001). Atrial fibrillation (AF) was more frequent in non-TTS MINOCAs (10.4 vs. 14.4%; p = 0.007). Psychiatric disorders were more prevalent in TTS (15.5 vs. 10.2%, p < 0.001). In-hospital mortality and complications were higher in TTS: 3.4 vs. 1.8%, (p = 0.015), and 25.8 vs. 11.5%, (p < 0.001). Global mortality before PS matching was 16.1% in non-TTS MINOCAs and 8.1% in TTS. Median follow-up was 32.4 months; after PS matching, TTS had fewer major adverse cardiovascular events (MACEs): hazard ratio (HR) 0.59; 95% CI 0.42–0.83. There were no differences in global mortality (HR 0.87; CI: 0.64–1.19), but TTS had lower cardiovascular mortality (HR 0.58; CI: 0.35–0.98).ConclusionCompared to the rest of MINOCAs, TTS presents a different patient profile and a more aggressive acute phase. However, its long-term cardiovascular prognosis is better. These results support that TTS should be considered a separate entity with unique characteristics and prognosis.

The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in patients with Type 2 Diabetes Mellitus (T2DM)) trial evidenced the potential of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of patients with diabetes and cardiovascular disease. Recent evidences have shown the benefits of the SGLT2 inhibitor empagliflozin on improving liver steatosis and fibrosis in patients with T2DM. Metabolomic studies have been shown to be very useful to improve the understanding of liver pathophysiology during the development and progression of metabolic hepatic diseases, and because the effects of empagliflozin and of other SGLT2 inhibitors on the complete metabolic profile of the liver has never been analysed before, we decided to study the impact on the liver of male Zucker diabetic fatty (ZDF) rats of a treatment for 6 weeks with empagliflozin using an untargeted metabolomics approach, with the purpose to help to clarify the benefits of the use of empagliflozin at hepatic level. We found that empagliflozin is able to change the hepatic lipidome towards a protective profile, through an increase of monounsaturated and polyunsaturated glycerides, phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylinositols and lysophosphatidylcholines. Empagliflozin also induces a decrease in the levels of the markers of inflammation IL-6, chemerin and chemerin receptor in the liver. Our results provide new evidences regarding the molecular pathways through which empagliflozin could exert hepatoprotector beneficial effects in T2DM.

Atrial fibrillation is the most prevalent tachyarrhythmia in clinical practice, with very high cardiovascular morbidity and mortality with a high-cost impact in health systems. Currently, it is one of the main causes of stroke and subsequent heart failure and sudden death. miRNAs mediate in several processes involved in cardiovascular disease, including fibrosis and electrical and structural remodeling. Several studies suggest a key role of miRNAs in the course and maintenance of atrial fibrillation. In our study, we aimed to identify the differential expression of circulating miRNAs and their predictive value as biomarkers of recurrence in atrial fibrillation patients undergoing catheter pulmonary vein ablation. To this effect, 42 atrial fibrillation patients were recruited for catheter ablation. We measured the expression of 84 miRNAs in non-recurrent and recurrent groups (45.2%), both in plasma from peripheral and left atrium blood. Expression analysis showed that miRNA-451a is downregulated in recurrent patients. Receiver operating characteristic curve analysis showed that miR-451a in left atrium plasma could predict atrial fibrillation recurrence after pulmonary vein isolation. In addition, atrial fibrillation recurrence is positively associated with the increment of scar percentage. Our data suggest that miRNA-451a expression plays an important role in AF recurrence by controlling fibrosis and progression.

In this review, the authors describe evolving alternative strategies for the management of AF, focusing on non-invasive and percutaneous autonomic modulation. This modulation can be achieved – among other approaches – via tragus stimulation, renal denervation, cardiac afferent denervation, alcohol injection in the vein of Marshall, baroreceptor activation therapy and endocardial ganglionated plexi ablation. Although promising, these therapies are currently under investigation but could play a role in the treatment of AF in combination with conventional pulmonary vein isolation in the near future.

Background: Treatment of acute myocardial infarction (AMI) patients with prior stroke is a common clinical dilemma. Currently, the application of optimal medical therapy (OMT) and its impact on clinical outcomes are not clear in this patient population. Methods: We retrieved 765 AMI patients with prior stroke who underwent percutaneous coronary intervention (PCI) during the index hospitalization from the international multicenter BleeMACS registry. All of the subjects were divided into two groups based on the prescription they were given prior to discharge. Baseline characteristics and procedural variables were compared between the OMT and non-OMT groups. Mortality, re-AMI, major adverse cardiovascular events (MACE), and bleeding were followed-up for 1 year. Results: Approximately 5% of all patients presenting with AMI were admitted to the hospital for ischemic stroke. Although the prescription rate of each OMT medication was reasonably high (73.3%–97.3%), 47.7% lacked at least one OMT medication. Patients receiving OMT showed a significantly decreased occurrence of mortality (4.5% vs 15.1%, p

Abstract Accumulating evidence has confirmed that the expression of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is downregulated in heart failure and cardiac allograft rejection. Although many SERCA2a-related genes and proteins involved in the regulation of myocardial Ca2+ fluxes have been explored, its related metabolites remain poorly studied. Our main objective was to identify circulating SERCA2a-related metabolites altered in cardiac allograft rejection and to determine whether these could serve as non-invasive biomarkers. Sixty plasma samples from adult heart transplant were included in a metabolomic analysis. Sphingosine-1 phosphate (S1P), metabolite closely related with SERCA, were increased in patients with cardiac rejection (p

Abstract Supraventricular arrhythmias are common in Brugada syndrome (BS), and notoriously difficult to manage with medical therapy secondary to associated risks. Pulmonary vein isolation (PVI) is often utilized instead, but its outcomes in this population are not well‐known. We aim to provide a holistic evaluation of interventional treatment for Atrial fibrillation (AF) in the BS population. Electronic databases Medline, Embase, Cinahl, Cochrane, and Scopus were systematically searched for publications between 01/01/1995 and 12/31/2017. Studies were screened based on predefined inclusion and exclusion criteria. A total of 49 patients with BS and AF were included. Age range from 28.8 to 64 years, and 77.5% were male. 38 patients were implanted with implantable cardioverter‐defibrillators (ICD) at baseline, and of them, 39% suffered inappropriate shocks for rapid AF. 34/49 (69%) of patients achieved remission following a single PVI procedure. Of the remaining, 13 patients underwent one or more repeat ablation procedures. Overall, 45/49 (91.8%) of patients remained in remission during long‐term follow‐up after one or more PVI procedures in the absence of antiarrhythmic drug (AAD) therapy. Postablation, no patients suffered inappropriate ICD shock. Furthermore, no major complications secondary to PVI occurred in any patient. AF ablation achieves acute and long‐term success in the vast majority of patients. It is effective in preventing inappropriate ICD therapy secondary to rapid AF. Complication rates of PVI in BS are low. Thus, in light of the risks of AADs and risk of inappropriate ICD shocks in the BS population, catheter ablation could represent an appropriate first‐line therapy for paroxysmal atrial fibrillation in BS patients.

Introduction: Today's healthcare policies rely heavily on data that has been gathered from multiple small studies in intrinsically varied populations. We sought to describe the prevalence, comorbidities and outcomes of atrial fibrillation (AF) in the population of a specific region where all healthcare centers have implemented a common information technology (IT) structure. Methods: The total number of inhabitants was obtained from the healthcare area's IT system. Information pertaining to AF was derived from various datasets in the data warehouse of the Galician regional health service. Results: In the healthcare area of Santiago de Compostela (n=383 000), the diagnosis of AF was coded in 7990 (2.08%) individuals in 2013. Mean age was 76.83±10.5 years, mean CHA2DS2-VASc score was 3.5, 4056 (50.8%) were female and 72.6% were receiving oral anticoagulants. Up until December 31, 2015, 1361 patients died from all causes (17%), 478 (6%) of them in-hospital, with 30 deaths secondary to intracranial bleeding (0.4%) and 125 to stroke (1.6%). On multivariate analysis, age, gender, heart failure, diabetes, previous thromboembolic events and dementia were independently associated with all-cause mortality. Similarly, age, gender and previous thromboembolic events were associated with future thromboembolic events. Oral anticoagulation was found to be protective against mortality and thromboembolic events. Conclusions: In this study, we report for the first time the true prevalence of diagnosed AF and its clinical characteristics, treatment and prognosis in a Spanish healthcare area, based on the systematic integration of data available from a universally adopted health IT system within the region. Resumo: Introdução: As políticas dos cuidados de saúde confiam essencialmente em dados provenientes de múltiplos pequenos estudos no âmbito de populações diversificadas. Desejamos descrever a prevalência, as comorbilidades e os resultados da fibrilhação auricular (FA) numa população pertencente a uma área específica onde os centros dos cuidados de saúde implementaram uma estrutura informática comum. Métodos: O número total de habitantes foi obtido através do sistema informático das áreas dos cuidados de saúde. A informação relativa à FA provém de diversos conjuntos de dados proveniente do banco de dados do Serviço Saúde da Galiza. Resultados: Na área dos cuidados de saúde de Santiago de Compostela (n = 348 985), ao longo de 2013, o diagnóstico de FA foi codificado em 7990 (2,08%) indivíduos. A idade média foi 76,83 ± 10,5 anos, valor médio CHA2DS2-VASc = 3,5, sendo 4056 (50,8%) mulheres, 72,6% das quais administradas com anticoagulantes orais. Até 31 de dezembro de 2015, 1361 doentes morreram de mortalidade geral (17%). Destes, 478 (6%) estavam internados, tendo sido registadas 30 mortes secundárias a hemorragia intracraneana (0,4%) e 125 acidentes vasculares cerebrais (1,6%). Numa análise multivariável, a idade, o sexo, a insuficiência cardíaca, a diabetes, os eventos tromboembólicos e a demência foram associados independentemente da mortalidade em geral. Do mesmo modo, a idade, o sexo e o(s) tromboembólico(s) prévio(s) foram associados à ocorrência de futuros eventos tromboembólicos. Considerou-se que a anticoagulação oral teve um efeito protetor na mortalidade e nos eventos tromboembólicos. Conclusões: Neste estudo, apresentamos pela primeira vez a prevalência real da FA diagnosticada, com as características clínicas, tratamento e prognóstico de uma área específica de cuidados de saúde em Espanha, em conformidade com a integração sistemática dos dados disponíveis num processamento informático sanitário adotado na região. Keywords: Big data, CHA2DS2-VASc, Atrial fibrillation, Palavras-chave: Bancos de dados, CHA2DS2-VASC2, Fibrilhação auricular

Background: Healthcare systems are under prominent stress due to the COVID-19 pandemic. A fast and simple triage is mandatory to screen patients who will benefit from early hospitalization, from those that can be managed as outpatients. There is a lack of all-comers scores, and no score has been proposed for western-world population. Aims: To develop a fast-track risk score valid for every COVID-19 patient at diagnosis. Methods: Single-center, retrospective study based on all the inhabitants of a healthcare area. Logistic regression was used to identify simple and wide-available risk factors for adverse events (death, intensive care admission, invasive mechanical ventilation, bleeding > BARC3, acute renal injury, respiratory insufficiency, myocardial infarction, acute heart failure, pulmonary emboli, or stroke). Results: Of the total healthcare area population, 447.979 inhabitants, 965 patients (0.22%), were diagnosed with COVID-19. A total of 124 patients (12.85%) experienced adverse events. The novel SODA score (based on sex, peripheral O2 saturation, presence of diabetes, and age) demonstrated good accuracy for adverse events prediction (area under ROC curve 0.858, CI: 0.82–0.98). A cut-off value of ≤2 points identifies patients with low risk (positive predictive value [PPV] for absence of events: 98.9%) and a cut-off of ≥5 points, high-risk patients (PPV 58.8% for adverse events). Conclusions: This quick and easy score allows fast-track triage at the moment of diagnosis for COVID-19 using four simple variables: age, sex, SpO2, and diabetes. SODA score could improve preventive measures taken at diagnosis in high-risk patients and also relieve resources by identifying very low-risk patients.

Epicardial fat thickness is associated with cardiovascular disease. Mineralocorticoid receptor antagonist (MRA), a pharmaceutical treatment for CVD, was found to have an effect on adipose tissue. Our aim was to analyse the main epicardial fat genesis and inflammation-involved cell markers and their regulation by risk factors and MRA. We included blood and epicardial or subcutaneous fat (EAT or SAT) from 71 patients undergoing heart surgery and blood from 66 patients with heart failure. Cell types (transcripts or proteins) were analysed by real-time polymerase chain reaction or immunohistochemistry. Plasma proteins were analysed by Luminex technology or enzyme-linked immunoassay. Our results showed an upregulation of fatty acid transporter levels after aldosterone-induced genesis. The MRA intake was the main factor associated with lower levels in epicardial fat. On the contrary, MRA upregulated the levels and its secretion of the anti-inflammatory marker intelectin 1 and reduced the proliferation of epicardial fibroblasts. Our results have shown the local MRA intake effect on fatty acid transporters and anti-inflammatory marker levels and the proliferation rate on epicardial fat fibroblasts. They suggest the role of MRA on epicardial fat genesis and remodelling in patients with cardiovascular disease. Translational perspective: the knowledge of epicardial fat genesis and its modulation by drugs might be useful for improving the treatments of cardiovascular disease.

2016 ESC GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF ACUTE AND CHRONIC HEART FAILURE.The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC).Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

This study aimed to analyze changes in the expression of autophagy- and phagocytosis-related genes in patients with dilated cardiomyopathy (DCM), especially in relation to left ventricular (LV) dysfunction. Furthermore, transmission electron microscopy of the diseased tissue was carried out to investigate if the gene expression changes are translated into ultrastructural alterations. LV tissue samples from patients with DCM (n = 13) and from controls (CNT; n = 10) were analyzed by RNA-sequencing, whereupon the altered expression (P < 0.05) of 13 autophagy- and 3 phagocytosis-related genes was observed. The expression changes of the autophagy-related genes NRBP2 and CALCOCO2 were associated with cardiac dysfunction and remodeling (P < 0.05). The affected patients had a higher activity of these degradation processes, as evidenced by the greater number of autophagic structures in the DCM tissue (P < 0.001). Differences in the ultrastructural distribution were also found between the DCM and CNT tissues. These results show that in patients with DCM, the altered expression of NRBP2 and CALCOCO2 is related to LV dysfunction and remodeling. Clarification of the molecular mechanisms of cardiac autophagy would help in the future development of therapies to improve LV performance.

BackgroundAssociation between obesity and cardiovascular diseases is well known, however increased susceptibility of obese patients to develop several cancer types is not so commonly known. Current data suggest that poorer overall survival in cancer patients might be associated to non-cancer-related causes such as higher risk of cardiotoxicity in obese patients treated with chemotherapeutic agents. Omentin, a novel adipokine decreased in obesity, is actually in the spotlight due to its favourable effects on inflammation, glucose homeostasis and cardiovascular diseases. Also, recent data showed that in vitro anthracycline-induced cardiomyocyte apoptosis is counteracted by omentin suggesting its cardioprotective role.ObjectiveOur aim was to evaluate omentin effects against docetaxel toxicity.ResultsOur data indicate that omentin inhibits docetaxel-induced viability loss and that increased viability is associated to decreased caspase-3 expression and cell death. Although omentin reduces NOX4 expression, it failed to reduce docetaxel-induced reactive oxygen species production. Our results indicate that omentin decreases docetaxel-induced endoplasmic reticulum stress, suggesting that cardioprotective role might be associated to ERS inhibition.ConclusionThese data suggest that omentin treatment may contribute to decrease susceptibility to DTX-induced cardiotoxicity.

The association between dilated cardiomyopathy (DCM) and low thyroid hormone (TH) levels has been previously described. In these patients abnormal thyroid function is significantly related to impaired left ventricular (LV) function and increased risk of death. Although TH was originally thought to be produced exclusively by the thyroid gland, we recently reported TH biosynthesis in the human ischemic heart.Based on these findings, we evaluated whether the genes required for TH production are also altered in patients with DCM.Twenty-three LV tissue samples were obtained from patients with DCM (n = 13) undergoing heart transplantation and control donors (n = 10), and used for RNA sequencing analysis. The number of LV DCM samples was increased to 23 to determine total T4 and T3 tissue levels by ELISA.We found that all components of TH biosynthesis are expressed in human dilated heart tissue. Expression of genes encoding thyroperoxidase (-2.57-fold, P < 0.05) and dual oxidase 2 (2.64-fold, P < 0.01), the main enzymatic system of TH production, was significantly altered in patients with DCM and significantly associated with LV remodeling parameters. Thyroxine (T4) cardiac tissue levels were significantly increased (P < 0.01), whilst triiodothyronine (T3) levels were significantly diminished (P < 0.05) in the patients.Expression of TH biosynthesis machinery in the heart and total tissue levels of T4 and T3, are altered in patients with DCM. Given the relevance of TH in cardiac pathology, our results provide a basis for new gene-based therapeutic strategies for treating DCM.

Background: The adipokine chemerin has been associated with cardiovascular disease. We investigated the effects of chemerin on viability and intracellular signalling in murine cardiomyocytes, and the effects of insulin and TNF-α on cardiomyocyte chemerin production. Methods: Hoechst dye vital staining and cell cycle analysis were used to analyse the viability of murine cardiac cells in culture. Western blot was used to explore the phosphorylation of AKT and caspase-9 activity in neonatal rat cardiomyocytes and HL-1 cells. Finally, RT-qPCR, ELISA and western blot were performed to examine chemerin and CMKLR1 expression after insulin and TNF-α treatment in cardiac cells. Results: Chemerin treatment increased apoptosis, reduced phosphorylation of AKT at Thr308 and increased caspase-9 activity in murine cardiomyocytes. Insulin treatment lowered chemerin and CMKLR1 mRNA and protein levels, and the amount of chemerin in the cell media, while TNF-α treatment increased chemerin mRNA and protein levels but decreased expression of the CMKLR1 gene. Conclusion: Chemerin induces apoptosis, reduces AKT phosphorylation and increases the cleavage of caspase-9 in murine cardiomyocytes. The expression of chemerin is regulated by important metabolic (insulin) and inflammatory (TNF-α) mediators at cardiac level. Our results suggest that chemerin could play a role in the physiopathology of cardiac diseases.

Objectives: Given the increasing focus on early mortality and readmission rates among patients with acute coronary syndrome (ACS), this study was designed to evaluate the accuracy of the GRACE risk score for identifying patients at high risk of 30-day post-discharge mortality and cardiovascular readmission. Methods: This was a retrospective study carried out in a single center with 4229 ACS patients discharged between 2004 and 2010. The study endpoint was the combination of 30-day post-discharge mortality and readmission due to reinfarction, heart failure or stroke. Results: One hundred and fourteen patients had 30-day events: 0.7% mortality, 1% reinfarction, 1.3% heart failure, and 0.2% stroke. After multivariate analysis, the six-month GRACE risk score was associated with an increased risk of 30-day events (HR 1.03, 95% CI 1.02–1.04; p

La publicación en Estados Unidos de la guía de 2013 de American College of Cardiology/American Heart Association para el tratamiento del colesterol elevado ha tenido gran impacto por el cambio de paradigma que supone. El Comité Español Interdisciplinario de Prevención Cardiovascular y la Sociedad Española de Cardiología han revisado esa guía, en comparación con la vigente guía europea de prevención cardiovascular y de dislipemias. El aspecto más destacable de la guía estadounidense es el abandono de los objetivos de colesterol unido a lipoproteínas de baja densidad, de modo que proponen el tratamiento con estatinas en cuatro grupos de riesgo aumentado. En pacientes con enfermedad cardiovascular establecida, ambas guías conducen a una estrategia terapéutica similar (estatinas potentes, dosis altas). Sin embargo, en prevención primaria, la aplicación de la guía estadounidense supondría tratar con estatinas a un número de personas excesivo, particularmente de edades avanzadas. Abandonar la estrategia según objetivos de colesterol, fuertemente arraigada en la comunidad científica, podría tener un impacto negativo en la práctica clínica y crear cierta confusión e inseguridad entre los profesionales y quizá menos seguimiento y adherencia de los pacientes. Por todo ello, el presente documento reafirma las recomendaciones de la guía europea. Ambas guías tienen aspectos positivos pero, en general y mientras no se resuelvan las dudas planteadas, la guía europea, además de utilizar tablas basadas en la población autóctona, ofrece mensajes más apropiados para el entorno español y previene del posible riesgo de sobretratamiento con estatinas en prevención primaria.

Alterations in myocardial structure and reduced cardiomyocyte adhesions have been previously described in dilated cardiomyopathy (DCM). We studied the transcriptome of cell adhesion molecules in these patients and their relationships with left ventricular (LV) function decay. We also visualized the intercalated disc (ID) structure and organization. The transcriptomic profile of 23 explanted LV samples was analyzed using RNA-sequencing (13 DCM, 10 control [CNT]), focusing on cell adhesion genes. Electron microscopy analysis to visualize ID structural differences and immunohistochemistry experiments of ID proteins was also performed. RT-qPCR and western blot experiments were carried out on ID components. We found 29 differentially expressed genes, most of all, constituents of the ID structure. We found that the expression of GJA3, DSP and CTNNA3 was directly associated with LV ejection fraction (r = 0.741, P = 0.004; r = 0.674, P = 0.011 and r = 0.565, P = 0.044, respectively), LV systolic (P = 0.003, P = 0.003, P = 0.028, respectively) and diastolic dimensions (P = 0.006, P = 0.001, P = 0.025, respectively). Electron microscopy micrographs showed a reduced ID convolution index and immunogold labeling of connexin 46 (GJA gene), desmoplakin (DSP gene) and catenin α-3 (CTNNA3 gene) proteins in DCM patients. Moreover, we observed that protein and mRNA levels analyzed by RT-qPCR of these ID components were diminished in DCM group. In conclusion, we report significant gene and protein expression changes and found that the ID components GJA3, DSP and CTNNA3 were highly related to LV function. Microscopic observations indicated that ID is structurally compromised in these patients. These findings give new data for understanding the ventricular depression that characterizes DCM, opening new therapeutic perspectives for these critically diseased patients.

Introduction: Atherosclerosis is an active process and the inflammatory component appears to be particularly correlated with the development of acute coronary syndromes (ACS). C-reactive protein (CRP) is an acute phase protein that appears in the circulation in response to inflammatory cytokines. The present study investigated the association between high-sensitivity C-reactive protein (hsCRP) on admission and follow-up prognosis after an ACS. Methods: We included 151 consecutive patients admitted to the coronary care unit with a diagnosis of ACS (47% ST-segment elevation myocardial infarction [STEMI]). The primary endpoint was the combination of cardiac death and myocardial reinfarction during the follow-up period (median 19.8 months, interquartile range 16.3–23.7 months). Results: The occurrence of follow-up events was significantly related to admission hsCRP level, which was an excellent predictor of cardiac death and reinfarction during follow-up (HR 1.091, 95% CI 1.014–1.174; p=0.019). Stratifying the population based on type of ACS, adjusted by variables associated with cardiac events in univariate analysis (hsCRP, diabetes, depressed ejection fraction and GRACE risk score), hsCRP proved to be an independent predictor of follow-up outcomes only in non-STEMI patients (HR 1.217, 95% CI: 1.093–1.356, p

In dilated cardiomyopathy (DCM), cardiac failure is accompanied by profound alterations of extracellular matrix associated with the progression of cardiac dilation and left ventricular (LV) dysfunction. Recently, we reported alterations of non-fibrillar collagen expression in ischemic cardiomyopathy linked to fibrosis and cardiac remodeling. We suspect that expression changes in genes coding for non-fibrillar collagens may have a potential role in DCM development.This study sought to analyze changes in the expression profile of non-fibrillar collagen genes in patients with DCM and to examine relationships between cardiac remodeling parameters and the expression levels of these genes.Twenty-three human left ventricle tissue samples were obtained from DCM patients (n = 13) undergoing heart transplantation and control donors (n = 10) for RNA sequencing analysis. We found increased mRNA levels of six non-fibrillar collagen genes, such as COL4A5, COL9A1, COL21A1, and COL23A1 (P < 0.05 for all), not previously described in DCM. Protein levels of COL8A1 and COL16A1 (P < 0.05 for both), were correspondingly increased. We also identified TGF-β1 significantly upregulated and related to both COL8A1 and COL16A1. Interestingly, we found a significant relationship between LV mass index and the gene expression level of COL8A1 (r = 0.653, P < 0.05).In our research, we identified new non-fibrillar collagens with altered expression in DCM, being COL8A1 overexpression directly related to LV mass index, suggesting that they may be involved in the progression of cardiac dilation and remodeling.

Permanent junctional reciprocating tachycardia (PJRT) is an uncommon form of atrioventricular reentrant tachycardia due to an accessory pathway characterized by slow and decremental retrograde conduction. The majority of accessory pathways in PJRT are located in the posteroseptal zone. Few cases of atypical location have been described. We report a case of PJRT in a 72-year-old woman in whom the accessory pathway was located in the left lateral region and treated by radiofrequency catheter ablation. Resumo: A forma permanente de taquicardia juncional reciprocante é uma modalidade incomum de taquicardia auriculoventricular reentrante devida a via de acesso caracterizada por condução retrógada lenta e gradual. A maioria das vias acessórias na forma permanente da taquicardia juncional reciprocante está localizada na zona posterosseptal. Foram apresentados poucos casos de localização atípica1-4. Apresentamos o caso de forma permanente da taquicardia junctional reciprocante numa mulher de 72 anos na qual a via acessória foi colocada na região lateral esquerda sendo a ablação efetuada por cateter de radiofrequência. Keywords: Permanent junctional reciprocating tachycardia, Catheter ablation, Accessory pathway, Paroxysmal supraventricular tachycardia, Palavras-chave: Taquicardia permanente juncional reciprocante, Ablação por cateter, Via de acesso, Taquicardia supraventricular paroxística

La práctica clínica cardiológica requiere una organización compleja que influya en los resultados globales y puede diferir sustancialmente entre distintos hospitales y comunidades. El objetivo de este documento de consenso es definir indicadores de calidad en cardiología, incluidos los indicadores para medir la calidad de los resultados (indicadores de resultados) y los parámetros de calidad relacionados con mejores resultados en la práctica clínica (indicadores de práctica asistencial). El documento está destinado principalmente al sistema de asistencia sanitaria de España y puede servir de base para documentos similares en otros países.

Systemic sclerosis (SS) is a chronic disease in which there may be multisystem involvement. It is rare (estimated prevalence: 0.5–2/10 000) with high morbidity and mortality, and there is as yet no curative treatment.We report the case of a young woman newly diagnosed with SS, in whom decompensated heart failure was the main manifestation. Resumo: A esclerose sistémica (ES) é uma doença crónica com possível apresentação multi-sistémica. É considerada uma doença rara (prevalência estimada: 0.5-2/10,000) com alta morbilidade e mortalidade para a qual não há cura hoje em dia.Relatamos o caso de uma jovem mulher, recém diagnosticada de ES por afetação pleural e cutânea, com insuficiência cardíaca global no momento da consulta. Keywords: Systemic sclerosis, Cardiomyopathy, Heart failure, Palavras-chave: Esclerose sistémica, Cardiomiopatia, Insuficiência cardíaca