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[Abstract] Introduction and objectives: This report updates the annual data of the Spanish Heart Transplant Registry with the procedures performed in 2021. Methods: We describe the clinical profile, therapeutic characteristics and outcomes in terms of survival of the procedures performed in 2021. Their temporal trends are updated for the 2012 to 2020 period. Results: In 2021, 302 heart transplants were performed (8.6% increase versus 2020). The tendency in 2021 confirmed that of prior years, with fewer urgent transplants and a preference for the use of ventricular assist devices. The remaining characteristics and survival showed a clear trend toward stability in the last decade. Compared with 2019, the SARS-CoV-2 pandemic (2020 and 2021) did not affect short- or long-term survival. Conclusions: In 2021, transplant activity returned to prepandemic levels. The SARS-CoV-2 pandemic did not significantly affect transplant outcomes. The main transplant features and outcomes have clearly stabilized in the last decade. [Resumen] Introducción y objetivos. Se actualizan los datos anuales de Registro Español de Trasplante Cardiaco con los hallazgos de los procedimientos realizados en 2021. Métodos. Se describen las principales características clínicas, del tratamiento recibido y de los resultados en términos de supervivencia del año 2021 y las tendencias en el periodo 2012-2020. Resultados. En 2021 se han realizado 302 trasplantes cardiacos (un 8,6% más que el año anterior). En 2021 se ha confirmado la tendencia observada en años anteriores a una disminución de los trasplantes urgentes y a la realización de estos mayoritamente con dispositivos de asistencia ventricular. Las demás características y los resultados en términos de supervivencia muestran una clara tendencia a la estabilización en la última década. Respecto a 2019, en los años de la pandemia por SARS-CoV-2 (2020 y 2021) no se detecta un impacto relevante en los resultados en la fase aguda tras el trasplante y en la serie histórica. Conclusiones. En 2021 se ha recuperado la actividad de trasplante hasta cifras previas a la pandemia por SARS-CoV-2, que no ha tenido un impacto global significativo en los resultados. Las características del procedimiento y los resultados muestran una clara tendencia a la estabilización en la última década.

Monoclonal gammopathies (MGs) are a wide range of diseases that may evolve or progress over time. Comorbidity plays a critical role in this setting. The co-occurrence of two MGs is not a rare event. The evidence on the association of systemic light chain (AL) amyloidosis and multiple myeloma (MM) is scarce and controversial. Herein we aim to address this topic in a large series of patients of a referral center. All consecutive AL amyloidosis patients treated at our center from January 2005 to April 2023 were prospectively enrolled in a clinical and epidemiological registry. 141 patients diagnosed with AL amyloidosis were included, of which 7 (5%) had localized whereas 134 presented with systemic disease. The heart was the most frequently affected organ (90.3%). 25 patients (18.7%) fulfilled the IMWG diagnostic criteria of MM (AL/MM). Time-dependent association between AL and MM showed that the synchronous pattern is more frequent than the appearance of a second primary malignancy. The diagnostic delay was six months (m). Patients with AL/MM had a poorer median overall survival (OS) than AL-only patients (35.5 m, CI 95% 0–88.9, vs. 52.6 m, CI 95% 16.7–88.5), but this difference was not statistically significant. The prognosis in AL is dominated by the heart involvement, which is massive in this series. In our Cox regression model, only three prognostic variables remain as independent prognostic factors: age, N-terminal pro-brain natriuretic peptide (≥8500 ng/L), and undergoing an autologous stem cell transplant, whereas left ventricular ejection fraction shows a marginal effect. More and large studies focusing on the AL/MM association are needed to uncover the characteristics and prognostic impact of this association.

In this observational and multicenter study, that included all patients who underwent a heart transplantation (HT) in Spain from 1984 to 2018, we analyzed the incidence, management, and prognosis of colorectal cancer (CRC) after HT. Of 6,244 patients with a HT and a median follow-up of 8.8 years since the procedure, 116 CRC cases (11.5% of noncutaneous solid cancers other than lymphoma registered) were diagnosed, mainly adenocarcinomas, after a mean of 9.3 years post-HT. The incidence of CRC increased with age at HT from 56.6 per 100,000 person-years among under 45 year olds to 436.4 per 100,000 person-years among over 64 year olds. The incidence rates for age-at-diagnosis groups were significantly greater than those estimated for the general Spanish population. Curative surgery, performed for 62 of 74 operable tumors, increased the probability of patient survival since a diagnosis of CRC, from 31.6% to 75.7% at 2 years, and from 15.8% to 48.6% at 5 years, compared to patients with inoperable tumors. Our results suggest that the incidence of CRC among HT patients is greater than in the general population, increasing with age at HT.

BACKGROUND: Heart transplantation is an effective treatment offering the best recovery in both quality and quantity of life in those affected by refractory, severe heart failure. However, transplantation is limited by donor organ availability. The reintroduction of heart donation after the circulatory determination of death (DCD) in 2014 offered an uplift in transplant activity by 30%. Thoraco-abdominal normothermic regional perfusion (taNRP) enables in-situ reperfusion of the DCD heart. The objective of this paper is to assess the clinical outcomes of DCD donor hearts recovered and transplanted from donors undergoing taNRP. METHOD: This was a multicentre retrospective observational study. Outcomes included functional warm ischaemic time, use of mechanical support immediately following transplantation, perioperative and long-term actuarial survival and incidence of acute rejection requiring treatment. 157 taNRP DCD heart transplants, performed between February 2, 2015, and July 29, 2022, have been included from 15 major transplant centres worldwide including the UK, Spain, the USA and Belgium. 673 donations after the neurological determination of death (DBD) heart transplantations from the same centres were used as a comparison group for survival. FINDINGS: taNRP resulted in a 23% increase in heart transplantation activity. Survival was similar in the taNRP group when compared to DBD. 30-day survival was 96.8% ([92.5%-98.6%] 95% CI, n = 156), 1-year survival was 93.2% ([87.7%-96.3%] 95% CI, n = 72) and 5-year survival was 84.3% ([69.6%-92.2%] 95% CI, n = 13). INTERPRETATION: Our study suggests that taNRP provides a significant boost to heart transplantation activity. The survival rates of taNRP are comparable to those obtained for DBD transplantation in this study. The similar survival may in part be related to a short warm ischaemic time or through a possible selection bias of younger donors, this being an uncontrolled observational study. Therefore, our study suggests that taNRP offers an effective method of organ preservation and procurement. This early success of the technique warrants further investigation and use. FUNDING: None of the authors have a financial relationship with a commercial entity that has an interest in the subject. ispartof: ECLINICALMEDICINE vol:58 ispartof: location:England status: published

Resumen Introduccion y objetivos El retrasplante cardiaco (ReTC) representa un tema controvertido actualmente. Nuestro objetivo es describir y analizar los resultados del ReTC en Espana. Metodos Analisis retrospectivo del Registro Espanol de Trasplante Cardiaco de 1984 a 2018. Se recogieron datos sobre donante, receptor, cirugia, inmunosupresion y supervivencia. La mortalidad por todas las causas o la necesidad de ReTC postrasplante fueron el objetivo principal. Se estudiaron diferencias en supervivencia segun indicacion, tiempo entre trasplantes y epoca del ReTC. Resultados Se estudiaron en total 7.592 trasplantes cardiacos (TxC) y 173 (2,3%) ReTC (mediana de edad, 52,0 y 55,0 anos respectivamente). La enfermedad vascular del injerto fue la indicacion de ReTC mas frecuente (42,2%) y 59 pacientes (80,8%) recibieron el ReTC mas de 5 anos despues del trasplante inicial. El rechazo agudo y el fallo primario del injerto disminuyeron como indicaciones durante el periodo estudiado. La insuficiencia renal, la hipertension, la necesidad de ventilacion mecanica o balon intraaortico y la mayor duracion de la isquemia fria fueron mas frecuentes en el ReTC. La mediana de seguimiento del ReTC fue 5,8 anos. El ReTC tuvo peor supervivencia que el TxC (HR ponderado = 1,43; IC95%, 1,17-1,44; p Conclusiones El ReTC se asocio con mayor mortalidad que el TxC, especialmente por rechazo agudo. El pronostico del ReTC realizado mas de 5 anos despues es similar al del TxC primario.

[Abstract] Background. Primary graft dysfunction (PGD) still affects 2-28% of heart transplants (HT). Severe PGD requires mechanical circulatory support (MCS) and is the main cause of death early after HT. Earlier initiation has been suggested to improve prognosis but the best cannulation strategy is unknown. Methods. Analysis of all HT in Spain between 2010 and 2020. Early (

Resumen Introduccion y objetivos Se presentan las caracteristicas clinicas y los resultados de los trasplantes cardiacos realizados en Espana con la actualizacion correspondiente a 2019. Metodos Se describen las caracteristicas clinicas y los resultados de los trasplantes cardiacos realizados en 2019, asi como las tendencias de estos en el periodo 2010-2018. Resultados En 2019 se realizaron 300 trasplantes (8.794 desde 1984; 2.745 entre 2010 y 2019). Respecto a anos previos, los cambios mas llamativos son el descenso hasta el 38% de los trasplantes realizados en codigo urgente, y la consolidacion en el cambio de asistencia circulatoria pretrasplante, con la practica desaparicion del balon de contrapulsacion (0,7%), la estabilizacion del uso del oxigenador extracorporeo de membrana (9,6%) y el aumento de los dispositivos de asistencia ventricular (29%). La supervivencia en el trienio 2016-2018 es similar a la del trienio 2013-2015 (p = 0,34), y ambas mejores que la del trienio 2010-2012 (p = 0,002 y p = 0,01 respectivamente). Conclusiones Se mantienen estables tanto la actividad del trasplante cardiaco en Espana como los resultados en supervivencia en los ultimos 2 trienios. Hay una tendencia a realizar menos trasplantes urgentes, la mayoria con dispositivos de asistencia ventricular.

[Abstract] Background: We aimed to describe recent trends in the use and outcomes of temporary mechanical circulatory support (MCS) as a bridge to heart transplantation (HTx) in Spain. Methods: Retrospective case-by-case analysis of 1,036 patients listed for emergency HTx while on temporary MCS in 16 Spanish institutions from January 1st, 2010 to December 31st, 2020. Patients were classified in 3 eras according to changes in donor allocation criteria (Era 1: January 2010/May 2014; Era 2: June 2014/May 2017; Era 3: June 2017/December 2020). Results: Over time, the proportion of candidates listed with intra-aortic balloon pumps decreased (Era 1 = 55.9%, Era 2 = 32%, Era 3 = 0.9%; p < 0.001), while the proportion of candidates listed with surgical continuous-flow temporary VADs (Era 1 = 10.6%, Era 2 = 32%, Era 3 = 49.1%; p < 0.001) and percutaneous VADs (Era 1 = 0.3%, Era 2 = 6.3%; Era 3 = 17.2%; p < 0.001) increased. Rates of HTx increased from Era 1 (79.4%) to Era 2 (87.8%), and Era 3 (87%) (p = 0.004), while rates of death before HTx decreased (Era 1 = 17.7%; Era 2 = 11%, Era 3 = 12.4%; p = 0.037) Median time from listing to HTx increased in patients supported with intra-aortic balloon pumps (Era 1 = 8 days, Era 2 = 15 days; p < 0.001) but remained stable in other candidates (Era 1 = 6 days; Era 2 = 5 days; Era 3 = 6 days; p = 0.134). One-year post-transplant survival was 71.4% in Era 1, 79.3% in Era 2, and 76.5% in Era 3 (p = 0.112). Preoperative bridging with ECMO was associated with increased 1-year post-transplant mortality (adjusted HR=1.71; 95% CI 1.15-2.53; p = 0.008). Conclusions: During the period 2010 to 2020, successive changes in the Spanish organ allocation protocol were followed by a significant increase of the rate of HTx and a significant reduction of waiting list mortality in candidates supported with temporary MCS. One-year post-transplant survival rates remained acceptable.

[Abstract] Introduction and objectives: The Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score was derived and validated as a predictor of mortality after heart transplantation (HT). The primary objective of this work is to externally validate the IMPACT score in a contemporary Spanish cohort. Methods: Spanish Heart Transplant Registry data were used to identify adult (>16 years) HT patients between January 2000 and December 2015. Retransplantation, multiorgan transplantation and patients in whom at least one of the variables required to calculate the IMPACT score was missing were excluded from the analysis (N = 2810). Results: Median value of the IMPACT score was five points (IQR: 3, 8). Overall, 1-year survival rate was 79.1%. Kaplan-Meier 1-year survival rates by IMPACT score categories (0-2, 3-5, 6-9, 10-14, ≥15) were 84.4%, 81.5%, 79.3%, 77.3%, and 58.5%, respectively (Log-Rank test: p < .001). Performance analysis showed a good calibration (Hosmer-Lemeshow chi-square for 1 year was 7.56; p = .47) and poor discrimination ability (AUC-ROC .59) of the IMPACT score as a predictive model. Conclusions: In a contemporary Spanish cohort, the IMPACT score failed to accurately predict the risk of death after HT.

Resumen Introduccion y objetivos La mortalidad en shock cardiogenico (SC), sobre todo en casos refractarios donde se emplean dispositivos de soporte circulatorio mecanico (SCM), es muy elevada. El objetivo es analizar los resultados de un programa de atencion a pacientes en SC tras la implementacion de un equipo multidisciplinario en nuestro centro y la organizacion en red con los hospitales del area. Metodos Estudio observacional retrospectivo de los pacientes atendidos desde septiembre de 2014 a enero de 2019. Se incluyo a los pacientes en SC refractario que precisaron SCM y aquellos que por edad y ausencia de comorbilidades pueden ser candidatos a tratamientos avanzados. El objetivo principal es evaluar la supervivencia hospitalaria. Resultados En total se incluyo a 130 pacientes (69 locales y 61 trasladados). La media de edad era 52 ± 15 anos (el 72% varones). Las etiologias predominantes de SC fueron la insuficiencia cardiaca aguda descompensada (29%), el infarto agudo de miocardio (26%) y el shock tras cardiotomia (25%). En 105 pacientes (81%) se empleo SCM, mayoritariamente oxigenador extracorporeo de membrana (58%). La supervivencia al alta hospitalaria fue del 57% (74 de 130 pacientes). Los principales destinos fueron la recuperacion miocardica y el trasplante cardiaco. La puntuacion SAPS II, el lactato, el infarto como etiologia del SC y la puntuacion de inotropicos y vasoactivos resultaron predictores independientes de mortalidad hospitalaria. Conclusiones La creacion de equipos multidisciplinarios para la atencion de pacientes en SC mayoritariamente refractario y la coordinacion en red con los hospitales del area son factibles y consiguen una supervivencia hospitalaria de mas de la mitad de los pacientes atendidos.

Introducción y objetivos Se presentan las características clínicas y los resultados de los trasplantes cardiacos realizados en España con la actualización correspondiente a 2019. Métodos Se describen las características clínicas y los resultados de los trasplantes cardiacos realizados en 2019, así como las tendencias de estos en el periodo 2010-2018. Resultados En 2019 se realizaron 300 trasplantes (8.794 desde 1984; 2.745 entre 2010 y 2019). Respecto a años previos, los cambios más llamativos son el descenso hasta el 38% de los trasplantes realizados en código urgente, y la consolidación en el cambio de asistencia circulatoria pretrasplante, con la práctica desaparición del balón de contrapulsación (0, 7%), la estabilización del uso del oxigenador extracorpóreo de membrana (9, 6%) y el aumento de los dispositivos de asistencia ventricular (29%). La supervivencia en el trienio 2016-2018 es similar a la del trienio 2013-2015 (p = 0, 34), y ambas mejores que la del trienio 2010-2012 (p = 0, 002 y p = 0, 01 respectivamente). Conclusiones Se mantienen estables tanto la actividad del trasplante cardiaco en España como los resultados en supervivencia en los últimos 2 trienios. Hay una tendencia a realizar menos trasplantes urgentes, la mayoría con dispositivos de asistencia ventricular. Introduction and objectives: The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019. Methods: We describe the clinical characteristics and outcomes of heart transplants performed in Spain in 2019, as well as trends in this procedure from 2010 to 2018. Results: In 2019, 300 transplants were performed (8794 since 1984; 2745 between 2010 and 2019). Compared with previous years, the most notable findings were the decreasing rate of urgent transplants (38%), and the consolidation of the type of circulatory support prior to transplant, with an almost complete disappearance of counterpulsation balloon (0.7%), stabilization in the use of extracorporeal membrane oxygenation (9.6%), and an increase in the use of ventricular assist devices (29.0%). Survival from 2016 to 2018 was similar to that from 2013 to 2015 (P = .34). Survival in both these periods was better than that from 2010 to 2012 (P = .002 and P = .01, respectively). Conclusions: Heart transplant activity has remained stable during the last few years, as have outcomes (in terms of survival). There has been a trend to a lower rate of urgent transplants and to a higher use of ventricular assist devices prior to transplant.

This report presents the clinical characteristics, outcomes and complications of all consecutive patients implanted with a long-term mechanical circulatory support device in Spain between 2007 and 2020.Analysis of the Spanish Registry of durable ventricular assist devices (REGALAD) including data form Spanish centers with a mechanical circulatory support program.During the study period, 263 ventricular assist devices were implanted in 22 hospitals. The implanted device was an isolated continuous-flow left ventricular assist device in 182 patients (69%), a pulsatile-flow device (58 isolated left ventricular and 21 biventricular) in 79 (30%), and a total artificial heart in 2 patients (1%). The strategy of the implant was as bridge to heart transplant in 78 patients (30%), bridge to candidacy in 110 (42%), bridge to recovery in 3 (1%) and destination therapy in 72 patients (27%). Overall survival at 6, 12 and 24 months was 79%, 74% and 69%, respectively, and was better in continuous-flow left ventricular assist devices (84%, 80%, and 75%). The main adverse events related to this therapy were infections (37% of patients), bleeding (35%), neurological (29%), and device malfunction (17%).Durable ventricular assist devices have emerged in Spain in the last few years as a useful therapy for patients with advanced heart failure. As in other international registries, the current trend is to use continuous-flow intracorporeal left ventricular devices, which are associated with better results. Adverse events continue to be frequent and severe.

This report updates the annual data of the Spanish Heart Transplant Registry with the procedures performed in 2021.We describe the clinical profile, therapeutic characteristics and outcomes in terms of survival of the procedures performed in 2021. Their temporal trends are updated for the 2012 to 2020 period.In 2021, 302 heart transplants were performed (8.6% increase versus 2020). The tendency in 2021 confirmed that of prior years, with fewer urgent transplants and a preference for the use of ventricular assist devices. The remaining characteristics and survival showed a clear trend toward stability in the last decade. Compared with 2019, the SARS-CoV-2 pandemic (2020 and 2021) did not affect short- or long-term survival.In 2021, transplant activity returned to prepandemic levels. The SARS-CoV-2 pandemic did not significantly affect transplant outcomes. The main transplant features and outcomes have clearly stabilized in the last decade.

Resumen: La definición más actualizada de falla cardiaca avanzada incluye síntomas refractarios al tratamiento convencional, independiente de la fracción de eyección del ventrículo izquierdo, acompañados de elevación de péptidos natriuréticos. En esta nueva definición se destacan condiciones específicas como son la necesidad usual de diurético intravenoso, hospitalizaciones o consultas frecuentes por falla cardíaca, medicación inotrópica intermitente y arritmias malignas recurrentes.Esta condición está presente en aproximadamente 4 a 6% de los pacientes con falla cardiaca y se asocia a más síntomas, más comorbilidades y mayor mortalidad (hasta 75% a un año). En este punto, las terapias convencionales han fallado o son refractarias y se requiere la toma de decisiones para instaurar tratamientos más avanzados (p. ej.: inotrópicos, asistencia ventricular, trasplante cardiaco, cuidado paliativo, entre otras).El tratamiento representa un reto para los sistemas de salud de Colombia por la necesidad de optimizar y racionalizar el uso de estos recursos; por esto se debe considerar que estos pacientes, en algún momento de su evolución, que sean remitidos para valoración en las Clínicas de Falla Cardíaca ya que estos servicios cuentan con personal altamente calificado y una estructura administrativa, logística y tecnológica que garantizan el acceso a un tratamiento integral y multidisciplinario con estándares de calidad internacionales que es lo que finalmente se requiere en estas condiciones.En el “Consenso colombiano de falla cardiaca avanzada” se presentan diferentes opciones de tratamiento a considerar y un modelo de atención integral que inicia desde el momento del diagnóstico hasta etapas refractarias y avanzadas. Abstract: The most up-to-date definition of advanced heart failure includes symptoms refractory to conventional treatment (regardless of the left ventricular ejection fraction), accompanied by an elevation in natriuretic peptides. Specific conditions are highlighted in this new definition, such as the usual need of an intravenous diuretic, hospital admissions, or frequent consultations due to heart failure, intermittent inotropic medication, and recurrent malignant arrhythmias.This condition is present in approximately 4 to 6% of patients with heart failure and is associated with more symptoms, more comorbidities, and higher mortality (up to 75% at one year). On this point, the conventional treatments have failed, or are refractory, and decisions need to be taken to introduce more advanced treatments (for example: inotropic, ventricular assistance, palliative care, among others).The treatment represents a challenge for the Health Systems of Colombia due to the need to optimise and rationalise the use of these resources. For this reason, it must be considered that these patients, at any time during its course, may be sent for assessment in Heart Failure Clinics, as these services have highly qualified staff and an administrative, logistics, and technological structure that ensures access to an integral and multidisciplinary treatment with standards of international quality, which is what is finally required in these conditions.Different treatment options to consider are presented in the “Colombian consensus on advanced heart failure”, as well as an integral care model that begins from the time of the diagnosis until the refractory and advanced stages. Palabras clave: Avanzada, Tratamiento, Clínicas, Inotrópicos, Trasplante, Paliativo, Enfermería, Key words: Advanced, Treatments, Clinics, Inotropes, Transplant, Palliative, Nursing

Sacubitril/valsartan (SV) is a new therapy in heart failure with reduced ejection fraction. Our aim was to determine the efficacy and safety of this drug daily clinical practice. We performed a multicenter registry in 10 hospitals. All patients who started SV from October 2016 to March 2017 on an outpatient basis were included. A total of 427 patients started treatment with SV. Mean follow-up was 7.0 ± 0.1 months. Forty-nine patients (11.5%) discontinued SV, and 12 (2.8%) died. SV discontinuation was associated with higher cardiovascular (hazard ratio 13.22, 95% confidence interval, 6.71-15.73, P < 0.001) and all-cause mortality (hazard ratio 13.51, 95% confidence interval 3.22-56.13, P < 0.001). Symptomatic hypotension occurred in 71 patients (16.6%). Baseline N-terminal pro-B-type natriuretic peptide levels, functional class, and left ventricular ejection fraction improved at the end of follow-up in patients who continued with SV (all P values ≤0.001). This improvement was not significant in patients with SV discontinuation. SV has a good tolerability in patients from daily clinical practice. SV withdrawal in patients with heart failure and reduced ejection fraction was independently associated with increased all-cause mortality. Patients who continued with SV presented an improvement in functional class left ventricular ejection fraction and N-terminal pro-B-type natriuretic peptide levels. Sin financiación 2.598 JCR (2019) Q2, 62/138 Cardiac & Cardiovascular Systems; Q3, 147/270 Pharmacology & Pharmacy 0.800 SJR (2019) Q2, 110/362 Cardiology and Cardiovascular Medicine, 112/331 Pharmacology No data IDR 2019 UEM

Aims Our objective was to better understand the genetic bases of dilated cardiomyopathy (DCM), a leading cause of systolic heart failure. Methods and results We conducted the largest genome-wide association study performed so far in DCM, with 2719 cases and 4440 controls in the discovery population. We identified and replicated two new DCM-associated loci on chromosome 3p25.1 [lead single-nucleotide polymorphism (SNP) rs62232870, P = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication steps, respectively] and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10−8 and 1.4 × 10−3 in the discovery and replication steps, respectively), while confirming two previously identified DCM loci on chromosomes 10 and 1, BAG3 and HSPB7. A genetic risk score constructed from the number of risk alleles at these four DCM loci revealed a 3-fold increased risk of DCM for individuals with 8 risk alleles compared to individuals with 5 risk alleles (median of the referral population). In silico annotation and functional 4C-sequencing analyses on iPSC-derived cardiomyocytes identify SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, in silico and data mining annotations, and to a lesser extent functional analysis, strongly suggest SMARCB1 as the candidate culprit gene. Conclusion This study provides a better understanding of the genetic architecture of DCM and sheds light on novel biological pathways underlying heart failure.

Introduction and objectives: The present report updates the main characteristics and outcomes of heart transplants in Spain to 2020. Methods: We describe the main features of recipients, donors, surgical procedure, and immunosuppression in 2020. We also analyze the temporal trends of these characteristics and outcomes (survival) for the period 2011 to 2019. Results: In 2020, 278 heart transplants were performed (7.3% decrease vs 2019). The findings in 2020 confirmed previous observations of an increase in pretransplant sternotomy, a slight decrease in urgent transplants carried out with ventricular assist devices, a slight decrease in donor age, an increase in the use of allografts with previous arrest, and a decrease in ischemia time. Survival continued to improve in recent triennia, reaching 82.0% at 1 year in the period 2017 to 2019. Conclusions: The slight decrease in the number of heart transplants performed in 2020 in Spain, most likely due to the SARS-CoV-2 pandemic, did not change the main characteristics of the procedure. No change was observed in the tendency to improved survival. (C) 2021 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

Introducción y objetivos La amiloidosis cardiaca (AC) se produce por depósito de fibras de amiloide en el miocardio. Las formas más frecuentes son la amiloidosis por cadenas ligeras (AL) y por transtiretina (ATTR). Nuestro objetivo es describir la experiencia en el diagnóstico, tratamiento y pronóstico en un centro especializado español. Métodos Se incluyeron todos los pacientes diagnosticados de AC en el XXXX1 desde mayo de 2008 a septiembre de 2018 y se analizaron sus características clínicas, evolución y supervivencia. Resultados Se incluyeron 180 pacientes con AC, de los cuales, 64 (36%) eran AL (50% varones;65±11 años) y 116 ATTR (72% varones;79±11 años, 19 con ATTR hereditaria). La forma de presentación más frecuente fue la insuficiencia cardiaca en ambos grupos (81% AL y 45% ATTR;p

Heart retransplantation (ReHT) is controversial in the current era. The aim of this study was to describe and analyze the results of ReHT in Spain. Methods We performed a retrospective cohort analysis from the Spanish Heart Transplant Registry from 1984 to 2018. Data were collected on donors, recipients, surgical procedure characteristics, immunosuppression, and survival. The main outcome was posttransplant all-cause mortality or need for ReHT. We studied differences in survival according to indication for ReHT, the time interval between transplants and era of ReHT. Results A total of 7592 heart transplants (HT) and 173 (2.3%) ReHT were studied (median age, 52.0 and 55.0 years, respectively). Cardiac allograft vasculopathy was the most frequent indication for ReHT (42.2%) and 59 patients (80.8%) received ReHT > 5 years after the initial transplant. Acute rejection and primary graft failure decreased as indications over the study period. Renal dysfunction, hypertension, need for mechanical ventilation or intra-aortic balloon pump and longer cold ischemia time were more frequent in ReHT. Median follow-up for ReHT was 5.8 years. ReHT had worse survival than HT (weighted HR, 1.43; 95%CI, 1.17-1.44; P < .001). The indication of acute rejection (HR, 2.49; 95%CI, 1.45-4.27; P < .001) was related to the worst outcome. ReHT beyond 5 years after initial HT portended similar results as primary HT (weighted HR, 1.14; 95%CI, 0.86-1.50; P < .001). Conclusions ReHT was associated with higher mortality than HT, especially when indicated for acute rejection. ReHT beyond 5 years had a similar prognosis to primary HT. El retrasplante cardiaco (ReTC) representa un tema controvertido actualmente. Nuestro objetivo es describir y analizar los resultados del ReTC en España. Métodos Análisis retrospectivo del Registro Español de Trasplante Cardiaco de 1984 a 2018. Se recogieron datos sobre donante, receptor, cirugía, inmunosupresión y supervivencia. La mortalidad por todas las causas o la necesidad de ReTC postrasplante fueron el objetivo principal. Se estudiaron diferencias en supervivencia según indicación, tiempo entre trasplantes y época del ReTC. Resultados Se estudiaron en total 7.592 trasplantes cardiacos (TxC) y 173 (2,3%) ReTC (mediana de edad, 52,0 y 55,0 años respectivamente). La enfermedad vascular del injerto fue la indicación de ReTC más frecuente (42,2%) y 59 pacientes (80,8%) recibieron el ReTC más de 5 años después del trasplante inicial. El rechazo agudo y el fallo primario del injerto disminuyeron como indicaciones durante el periodo estudiado. La insuficiencia renal, la hipertensión, la necesidad de ventilación mecánica o balón intraaórtico y la mayor duración de la isquemia fría fueron más frecuentes en el ReTC. La mediana de seguimiento del ReTC fue 5,8 años. El ReTC tuvo peor supervivencia que el TxC (HR ponderado = 1,43; IC95%, 1,17-1,44; p < 0,001). El rechazo agudo (HR = 2,49; IC95%, 1,45-4,27; p < 0,001) se relacionó con el peor resultado. El ReTC más allá de 5 años del trasplante inicial presagia resultados similares a los del TxC primario (HR ponderado = 1,14; IC95%, 0,86-1,50; p < 0,001). Conclusiones El ReTC se asoció con mayor mortalidad que el TxC, especialmente por rechazo agudo. El pronóstico del ReTC realizado más de 5 años después es similar al del TxC primario. Sin financiación No data JCR 2021 0.385 SJR (2021) Q3, 1499/2489 Medicine (miscellaneous) No data IDR 2021 UEM

Heart transplantation from controlled donation after the circulatory determination of death (cDCDD) may help to increase the availability of hearts for transplantation. During 2020, four heart transplants were performed at three different Spanish hospitals based on the use of thoraco-abdominal normothermic regional perfusion (TA-NRP) followed by cold storage (CS). All donors were young adults

Introduction and objectives Sacubitril/valsartan (SV) is recommended in patients with heart failure and reduced left ventricular ejection fraction. However, the characteristics of the centers included in the pivotal clinical trial differ from real life. The present study aims to analyze the clinical profile of patients treated with SV according to hospital type and the potential role of these differences in drug safety and effectivity. Methods Prospective multicenter registry that included outpatients treated with SV. We compared baseline characteristics and treatments, drug titration, and data at 7-months follow-up according to hospital type. Results From 427 patients, 81 (19%) were included in medium/small size hospitals, 204 (48%) in heart transplant program centers and 142 (33%) in hospitals with ≥1000 beds without heart transplant program. A low starting dose of SV (50 mg bid) was more frequent in medium/small size hospitals than in hospitals with ≥1000 beds (51 [63.0%] vs 151 [43.6%] patients, P = .008). At 7 months, SV had been withdrawn more frequently in medium/small size hospitals than in hospitals ≥1000 beds (15 [18.5%] vs 34 [9.8%] patients, P = .001], in spite of a similar rate of adverse events (23 [28.4%)] vs 99 [28.6%] patients, P = .94). Conclusion In our registry, the use of SV in real life showed a low rate of events during follow-up. The above suggests that this drug is safe and beneficial in different clinical profiles of patients but drug withdrawal is more frequent in medium/small size hospitals. Resumen Introducción y objetivos Se recomienda el sacubitrilo-valstartán (SV) en pacientes con insuficiencia cardiaca y fracción de eyección reducida.. Sin embargo, las características de los centros incluidos en los ensayos clínicos fundamentales son diferentes a las de los centros en la vida real. El objetivo del presente estudio fue analizar el perfil clínico de los pacientes tratados con SV según el tipo de hospital y el papel potencial de estas diferencias en la seguridad y la efectividad de este fármaco. Métodos Registro multicéntrico prospectivo que incluyó a pacientes ambulatorios tratados con SV. Se compararon las características basales y los tratamientos, la dosificación del fármaco y los datos a los 7 meses de seguimiento. Resultados De 427 pacientes, 81 (19,0%) fueron incluidos en hospitales de tamaño medio/pequeño, 204 (48%) en centros con programa de trasplante cardiaco y 142 (33%) en hospitales con ≥ 1.000 camas sin trasplante cardíaco. Una dosis de inicio baja de SV fue más frecuente en hospitales de tamaño medio/pequeño que en hospitales con ≥ 1.000 camas (51 [63,0%] frente a 151 [43,6%] pacientes, p = 0,008). A los 7 meses, el SV se había retirado con mayor frecuencia en hospitales de tamaño medio/pequeño que en hospitales ≥ 1.000 camas (15 [18,5%] frente a 34 [9,8%] pacientes, p = 0,001], a pesar de una tasa similar de eventos adversos (23 [28,4%)] frente a 99 [28,6%] pacientes, p = 0,94). Conclusión En nuestro estudio, el uso de SV en la vida real mostró una tasa baja de eventos en el seguimiento. Esto sugiere que este fármaco es seguro y beneficioso en diferentes perfiles clínicos de pacientes, si bien el fármaco se suspendió con mayor frecuencia en los hospitales de tamaño medio/pequeño. Sin financiación No data JCR (2021) 0.130 SJR (2021) Q4, 317/356 Cardiology and Cardiovascular Medicine No data IDR 2021 UEM

Altres ajuts: Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV); Instituto de Salud Carlos III (ISCIII); Ministerio de Economía y Competitividad (MINECO). Biological differences between males and females change the course of different diseases and affect therapeutic measures' responses. Heart failure is not an exception to these differences. Women account for a minority of patients on the waiting list for heart transplantation or other advanced heart failure therapies. The reason for this under-representation is unknown. Men have a worse cardiovascular risk profile and suffer more often from ischemic heart disease. Conversely, transplanted women are younger and more frequently have non-ischemic cardiac disorders. Women's poorer survival on the waiting list for heart transplantation has been previously described, but this trend has been corrected in recent years. The use of ventricular assist devices in women is progressively increasing, with comparable results than in men. The indication rate for a heart transplant in women (number of women on the waiting list for millions of habitants) has remained unchanged over the past 25 years. Long-term results of heart transplants are equal for both men and women. We have analyzed the data of a national registry of heart transplant patients to look for possible future directions for a more in-depth study of sex differences in this area. We have analyzed 1-year outcomes of heart transplant recipients. We found similar results in men and women and no sex-related interactions with any of the factors related to survival or differences in death causes between men and women. We should keep trying to approach sex differences in prospective studies to confirm if they deserve a different approach, which is not supported by current evidence.

Introduction and objectives The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019. Methods We describe the clinical characteristics and outcomes of heart transplants performed in Spain in 2019, as well as trends in this procedure from 2010 to 2018. Results In 2019, 300 transplants were performed (8794 since 1984; 2745 between 2010 and 2019). Compared with previous years, the most notable findings were the decreasing rate of urgent transplants (38%), and the consolidation of the type of circulatory support prior to transplant, with an almost complete disappearance of counterpulsation balloon (0.7%), stabilization in the use of extracorporeal membrane oxygenation (9.6%), and an increase in the use of ventricular assist devices (29.0%). Survival from 2016 to 2018 was similar to that from 2013 to 2015 (P=.34). Survival in both these periods was better than that from 2010 to 2012 (P=.002 and P=.01, respectively). Conclusions Heart transplant activity has remained stable during the last few years, as have outcomes (in terms of survival). There has been a trend to a lower rate of urgent transplants and to a higher use of ventricular assist devices prior to transplant.

Background: A significant number of heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF) experience ventricular function recovery during follow-up. We studied the variables associated with LVEF recovery in patients treated with sacubitril/valsartan (SV) in clinical practice. Methods: We analyzed data from a prospective and multicenter registry including 249 HF outpatients with reduced LVEF who started SV between October 2016 and March 2017. The patients were classified into 2 groups according to LVEF at the end of follow-up (>35%: group R, or ≤35%: group NR). Results: After a mean follow-up of 7 ± 0.1 months, 62 patients (24.8%) had LVEF >35%. They were older (71.3 ± 10.8 vs. 67.5 ± 12.1 years, p = 0.025), and suffered more often from hypertension (83.9 vs. 73.8%, p = 0.096) and higher blood pressure before and after SV (both, p < 0.01). They took more often high doses of beta-blockers (30.6 vs. 27.8%, p = 0.002), with a smaller proportion undergoing cardiac resynchronization therapy (14.8 vs. 29.0%, p = 0.028) and fewer implanted cardioverter defibrillators (ICD; 32.8 vs. 67.9%, p < 0.001), this being the only predictive variable of NR in the multivariate analysis (OR 0.26, 95% CI 0.13–0.47, p < 0.0001). At the end of follow-up, the mean LVEF in group R was 41.9 ± 8.1% (vs. 26.3 ± 4.7% in group NR, p < 0.001), with an improvement compared with the initial LVEF of 14.6 ± 10.8% (vs. 0.8 ± 4.5% in group NR, p < 0.0001). Functional class improved in both groups, mainly in group R (p = 0.035), with fewer visits to the emergency department (11.5 vs. 21.6%, p = 0.07). Conclusions: In patients with LVEF ≤35% treated with SV, not carrying an ICD was independently associated with LVEF recovery, which was related to greater improvement in functional class.

The study of gender differences may lead into improvement in patient care. We have aimed to identify the gender differences in heart transplantation (HT) of adult HT recipients in Spain and their evolution in a study covering the years 1993–2017 in which 6740 HT (20.6% in women) were performed. HT indication rate per million inhabitants was lower in women, remaining basically unchanged during the 25‐year study period. HT rate was higher in men, although this decreased over the 25‐year study period. Type of heart disease differed in men versus women (p < .001): ischemic heart disease 47.6% versus 22.5%, dilated cardiomyopathy 41.3% versus 34.6%, or other 36% versus 17.8%, respectively. Men were more frequently diabetics (18% vs. 13.1% p < .001), hypertensives (33.1% vs. 24% p < .001), and smokers (21.7% vs. 12.9% p < .001), respectively. Women had more pre‐HT malignancies (7.1% vs. 2.8% p < .001), and their clinical status was worse at HT due to renal function and mechanical ventilation. Adjusted survival (p = .198) and most of the mortality‐related variables were similar in men and women. Death occurred more frequently in women due to rejection (7.9% vs. 5.1% p < .001) and primary failure (18.2% vs. 12.5% p < .001) and in men due to malignancies (15.1% vs. 6.6% p < .001). Sin financiación 2.863 JCR (2020) Q2, 80/211 Surgery 0.918 SJR (2020) Q2, 15/42 Transplantation No data IDR 2020 UEM

Our aim is to describe the characteristics of the patients receiving sacubitril/valsartan (SV) in daily clinical practice. This is a prospective registry in 10 hospitals including all patients who started SV in everyday clinical practice. From October 2016 to March 2017, 427 patients started treatment with SV. The mean age was 68.1 ± 12.4 years, and 30.5% were women (22.0% in PARADIGM-HF, P < 0.001). Comparing our cohort with patients included in PARADIGM-HF, baseline treatment was different, with a lower ratio of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (2.7 vs. 3.5, P < 0.001), and a higher proportion of patients with implantable cardioverter defibrillator (53.8% vs. 15%, P < 0.001), and cardiac resynchronization therapy (25.8% vs. 5%, P < 0.001). Treatment with mineralocorticoid receptor antagonists was more frequent (76.7% vs. 60.0%, P < 0.001), and the use of beta-blockers was similar (94.6% vs. 93.0%, P = 0.43). We observed more patients in functional class III-IV (30.4 vs. 24.8, P = 0.015), higher levels of Nt pro-BNP [3421 (904-4161) vs. 1631 (885-3154) pg/mL] and worse renal function (creatinine level 1.3 ± 0.7 vs. 1.1 ± 0.3 mg/dL, P < 0.001). In real life, patients receiving SV have a higher risk profile than in the pivotal trial, poorer functional class, higher levels of natriuretic peptides, and worse renal function. Sin financiación 2.371 JCR (2018) Q3, 69/136 Cardiac & Cardiovascular Systems, 151/267 Pharmacology & Pharmacy 0.837 SJR (2018) Q2, 111/365 Cardiology and Cardiovascular Medicine, 114/365 Pharmacology No data IDR 2018 UEM

Background: Testosterone deficiency is associated with heart failure (HF) progression and poor prognosis. Testosterone therapy has been shown to improve exercise capacity in patients with chronic HF, but no trial has evaluated the impact of replacement in patients with demonstrated testosterone deficiency. Methods: Prospective, randomized, double-blind, placebo-controlled, and parallel-group trial comparing testosterone replacement with placebo in males with chronic HF with reduced ejection fraction (HFrEF) and testosterone deficiency (NCT01813201). Long-acting undecanoate testosterone at a fixed dose of 1000 mg was supplied by intramuscular injection at inclusion and then every 3 months. The placebo group received isotonic saline serum. Patients were randomly allocated 1:1 to testosterone or placebo while receiving optimal medical therapy, and the study was conducted for 12 months. Results: The final sample comprised 29 patients, 15 in the placebo group and 14 in the testosterone group (aged 65 ± 8, 62% with an ischemic etiology, left ventricular ejection fraction [LVEF] 30% ± 6%, 69% New York Heart Association functional [NYHA II]). After 12 months, testosterone replacement increased testosterone levels ( P = .002) but was not associated with benefit in terms of clinical symptoms and functional capacity including NYHA class, Framingham score, Minnesota Living Heart Failure Questionnaire, 6-minute walk test, or LVEF and N-terminal pro-B-type natriuretic peptide levels. No significant side effects associated with testosterone treatment were observed. No effects were found in other hormonal, metabolic, and bone turnover biomarkers. Conclusion: In patients with HFrEF and testosterone deficiency, replacement therapy was not associated with any significant improvement.

Resumen Introduccion y objetivos El presente articulo presenta las caracteristicas y resultados del trasplante cardiaco en Espana, desde que empezo su actividad en mayo de 1984. Metodos Se realiza un analisis descriptivo de las caracteristicas de los receptores, donantes, procedimiento quirurgico y resultados de los trasplantes cardiacos realizados en Espana hasta el 31 de diciembre de 2016. Resultados Durante 2016 se han realizado 281 procedimientos, con lo que la serie historica consta de 7.869 trasplantes. Las caracteristicas generales del procedimiento son similares a las observadas en los ultimos anos y destacan el alto porcentaje de procedimientos realizados en codigo urgente y, sobre todo, la extension del uso de dispositivos de asistencia circulatoria, particularmente de asistencia ventricular de flujo continuo (el 19,1% del total de trasplantes). La supervivencia ha aumentado significativamente en la ultima decada con respecto a periodos anteriores. Conclusiones La actividad de trasplante cardiaco en Espana permanece estable en los ultimos anos, con alrededor de 250-300 procedimientos al ano. A pesar de la mayor complejidad del contexto clinico, se observa una mejoria de la supervivencia en los ultimos anos.

A ventricular septal defect (VSD) is a rare complication of blunt chest trauma. This report presents the case of a 44-year-old man who developed a VSD as a result of high-energy closed chest trauma. We describe the initial surgical and medical management of the cardiac rupture. After failed repair surgery, extracorporeal membrane oxygenation (ECMO) was used as a bridge to heart transplantation. We discuss the successful use of ECMO to improve the prognosis results in this rare and complex entity.

Background The assessment of vascular remodeling using optical coherence tomography (OCT) has been previously described in some types of pulmonary hypertension. However, evidence about its feasibility and clinical utility for evaluation of pulmonary arterial vasculopathy in advanced heart failure (HF) is scarce. Optical Coherence Tomography Observation of Pulmonary Ultra-Structural Changes in Heart Failure (OCTOPUS-CHF) study is designed to study the correlation between OCT-morphometric parameters and hemodynamic data measured or derived from right heart catheterization (RHC). Methods OCTOPUS-CHF is an observational, prospective, multicentre study aiming to recruit 100 patients with advanced HF referred for heart transplantation (HTx) evaluation. As part of such evaluation, all patients will undergo RHC in order to rule out severe pulmonary hypertension. After RHC, a Dragonfly™ OPTIS™ imaging catheter will be used to perform OCT evaluation of a right-lower-lobe pulmonary artery with a luminal diameter ≤ 5 mm. The primary objective is to study the correlation of OCT parameters with hemodynamic RHC data. The secondary objective is to determine if OCT parameters improve prognostic stratification. Conclusions The OCTOPUS-CHF study will investigate the feasibility and clinical utility of pulmonary arterial vasculopathy evaluation with OCT in advanced HF patients and its correlation with hemodynamic RHC data. The ability of OCT-morphometric parameters to improve prognostic stratification will also be tested. Sin financiación 4.164 JCR (2020) Q2, 56/142 Cardiac & Cardiovascular Systems 1.406 SJR (2020) Q1, 62/349 Cardiology and Cardiovascular Medicine No data IDR 2020 UEM

[Abstract] Background Lifelong adherence with post-transplant immunosuppression is challenging, with nonadherence associated with greater acute rejection (AR) risk. Methods This retrospective study evaluated conversion from immediate-release tacrolimus (IRT) to prolonged-release tacrolimus (PRT), between January 2008 and December 2012 in stable adult heart transplant recipients. Cumulative incidence rate (IR) of AR and infection pre- and postconversion, safety, tacrolimus dose and trough levels, concomitant immunosuppression, and PRT discontinuation were analyzed (intention-to-treat population). Results Overall, 467 patients (mean age, 59.3 [SD, 13.3] years) converted to PRT at 5.1 (SD, 4.9) years post transplant and were followed for 3.4 (SD, 1.5) years. During the 6 months post conversion, 5 patients (1.1%; 95% CI, 0.35%–2.48%) had an AR episode and IR was 2.2/100 patient-years (95% CI, 0.91–5.26). Incidence of rejection preconversion varied by time from transplant to conversion. Infection IR was similar post- and preconversion (9.2/100 patient-years [95% CI, 7.4–11.3] vs 10.6/100 patient-years [95% CI, 8.8–12.3], respectively; P = .20). Safety variables remained similar post conversion. The IR of mortality/graft loss was 2.3/100 patient-years (95% CI, 1.7–3.1). Conclusions Conversion from IRT to PRT in heart transplant recipients in Spain was associated with no new safety concerns and appropriate immunosuppressive effectiveness.

Aims Sacubitril/valsartan is safe when initiated during hospitalization in a clinical trial setting. Its safety in real‐life population is not stablished. We compared the initiation of sacubitril/valsartan during hospitalization in a non‐selected population, in the PIONEER‐HF trial, and in non‐selected outpatients. Methods and results Multicentre registry included 527 patients: 100 were started on sacubitril/valsartan during hospitalization (19.0%) and 427 as outpatients (81.0%). Compared with those in the pivotal trial, inpatients in our cohort were older (71 ± 12 vs. 61 ± 14 years; P < 0.001); had more frequently Functional Class II (41 [41.0%] vs. 100 [22.7%]; P < 0.001), higher levels of N‐terminal pro‐B type natriuretic peptide (4044 [1630–8680] vs. 2013 [1002–4132] pg/mL; P < 0.001), better glomerular filtration rate (63.5 [51.0–80.0] vs. 58.4 [47.5–71.5] mL/min; P = 0.01), and higher systolic blood pressure (121 [110–136] vs. 118 [110–133] mmHg; P = 0.03); and received angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers more frequently (92 [92.0%] vs. 208 [52.7%]; P < 0.001). Compared with non‐selected outpatients, inpatients were older (71 ± 12 vs. 68 ± 12 years, P = 0.02), had more frequent Functional Class III–IV (58 [58.0%] vs. 129 [30.3%], P < 0.001), had higher levels of N‐terminal pro‐B type natriuretic peptide (4044 [1630–8680] vs. 2182 [1134–4172]; P < 0.001), and were receiving angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers target dose less frequently (55 [55.0%] vs. 335 [78.5%]; P < 0.001). They also started sacubitril/valsartan with a low dose (50 mg/12 h) more frequently (80 [80.0%] vs. 209 [48.8%], P < 0.001). The initiation of sacubitril/valsartan in outpatients was an independent predictor of high‐dose use (OR 3.1; 95% confidence interval 1.7–5.6, P < 0.001). The follow‐up time in both cohorts, including all patients enrolled, was similar (7.0 ± 0.1 vs. 7.2 ± 2.6 months, P = 0.72). All‐cause admissions during follow‐up were more frequent in inpatients (30 [30.0%] vs. 68 outpatients [15.9%], P = 0.001), with no relevant differences in all‐cause mortality. There was no significant difference in sacubitril/valsartan withdrawal rate (17 inpatients [17.0%] vs. 49 outpatients [11.5%], P = 0.13). The incidence of adverse effects was also similar: hypotension (16 inpatients [16.0%] vs. 71 outpatients [16.7%], P = 0.88), worsening renal function (7 inpatients [7.0%] vs. 29 outpatients [6.8%], P = 0.94), and hyperkalaemia (1 inpatient [1.0%] vs. 21 outpatients [4.9%], P = 0.09). We did not register any case of angioedema. Conclusions It is safe to initiate sacubitril/valsartan during hospitalization in daily clinical practice. Inpatients have a higher risk profile and receive low starting doses more frequently than outpatients. Sin financiación 3.902 JCR (2019) Q2, 44/138 Cardiac & Cardiovascular Systems 0.640 SJR (2019) Q2, 145/362 Cardiology and Cardiovascular Medicine No data IDR 2019 UEM

Background: Women are underrepresented in sacubitril/valsartan (SV) clinical trials. The aim of this study was to assess sex-specific differences in efficacy, tolerability, and safety of SV in real-world heart failure with reduced ejection fraction (HFrEF) patients. Methods: A prospective registry in 10 centers including all patients who started SV during the last 6 months was analyzed in this study. Results: A total of 427 patients were included, 126 (29.5%) were women. There were no substantial differences in HFrEF treatment before SV initiation, although fewer women than men carried an implantable cardioverter defibrillator (57 [45.2%] vs. 173 [58.1%], p = 0.02). SV starting dose was 24/26 mg b.i.d. in 206 patients (48.2%), 49/51 mg b.i.d. in 184 (43.1%), and 97/103 mg b.i.d. in 34 (8.2%), without relevant differences associated to sex. There were no losses during a mean follow-up of 7.0 ± 0.1 months. The proportion of patients who discontinued the drug (16 [12.7%] women vs. 33 [11.0%] men, p = 0.66) or presented SV-related adverse effects (31 [24.6%] women vs. 79 [26.5%] men, p = 0.72) was also similar in both sexes. However, female sex was an independent predictor of functional class improvement in the multivariate analysis (odds ratio 2.33, 95% confidence interval: 1.24–4.38, p = 0.04). Conclusions: SV in women with HFrEF has a similar tolerability as in men. Females seem to have a more frequent functional class improvement than males.

[Background] The BAG3 (BLC2-associated athanogene 3) gene codes for an antiapoptotic protein located on the sarcomere Z-disc. Mutations in BAG3 are associated with dilated cardiomyopathy (DCM), but only a small number of cases have been reported to date, and the natural history of BAG3 cardiomyopathy is poorly understood. [Objectives] This study sought to describe the phenotype and prognosis of BAG3 mutations in a large multicenter DCM cohort. [Methods] The study cohort comprised 129 individuals with a BAG3 mutation (62% males, 35.1 ± 15.0 years of age) followed at 18 European centers. Localization of BAG3 in cardiac tissue was analyzed in patients with truncating BAG3 mutations using immunohistochemistry. [Results] At first evaluation, 57.4% of patients had DCM. After a median follow-up of 38 months (interquartile range: 7 to 95 months), 68.4% of patients had DCM and 26.1% who were initially phenotype-negative developed DCM. Disease penetrance in individuals >40 years of age was 80% at last evaluation, and there was a trend towards an earlier onset of DCM in men (age 34.6 ± 13.2 years vs. 40.7 ± 12.2 years; p = 0.053). The incidence of adverse cardiac events (death, left ventricular assist device, heart transplantation, and sustained ventricular arrhythmia) was 5.1% per year among individuals with DCM. Male sex, decreased left ventricular ejection fraction. and increased left ventricular end-diastolic diameter were associated with adverse cardiac events. Myocardial tissue from patients with a BAG3 mutation showed myofibril disarray and a relocation of BAG3 protein in the sarcomeric Z-disc. [Conclusions] DCM caused by mutations in BAG3 is characterized by high penetrance in carriers >40 years of age and a high risk of progressive heart failure. Male sex, decreased left ventricular ejection fraction, and enlarged left ventricular end-diastolic diameter are associated with adverse outcomes in patients with BAG3 mutations., This work was supported by grants from the following institutions: Instituto de Salud Carlos III (ISCIII) (PI14/ 0967, PI15/01551, AC16/0014), CIBERCV (CB16/11/00403), Progreso and Salud Foundation (Junta de Andalucia) (PI-0011/201), Ministry of Economy, Industry and Competitiveness (IJCI-2016-29393), Mutual Medical (Research Award 2017), ERA-CVD Joint Transnational Call 2016 (Genprovic), British Heart Foundation (SP/10/10/28431), Wellcome Trust (107469/Z/15/), NIHR Royal Brompton Cardiovascular Biomedical Research Unit, NIHR Imperial Biomedical Research Center, Health Innovation Challenge Fund award from the Wellcome Trust and Department of Health, U.K. (HICF-R6-373), Danish Heart Foundation (16-R107-A6617), University of Southern Denmark, the Region of Southern Denmark, Odense University Hospital, German Competence Network Heart Failure, (TP9, FKZ 01GI0205), DETECTIN-HF project (ERA-CVD framework), and PROMEX Charitable Foundation. UCL Hospitals NIHR Biomedical Research Center and Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2015-12 eDETECT and CVON2014-40 DOSIS. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Grants from ISCIII and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de IþDþI 2013-2016 – European Regional Development Fund (FEDER) “A way of making Europe.” The Hospital Universitario Puerta de Hierro Majadahonda, Hôpital PitiéSalpêtrière, and Saint Bartholomews’ Hospital are members of the European Reference Network for rare, low-prevalence, and complex diseases of the heart (ERN GUARD-Heart). Drs. Ochoa, Cicerchia, and Salazar-Mendiguchia are employees of Health In Code.