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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

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.

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.

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.

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.

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.

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.