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[Abstract] It is not clear to date whether a first admission in heart failure (HF) marks a worse evolution in patients not previously diagnosed with HF ("de novo HF") than those already diagnosed as outpatients ("acutely decompensated HF"). The aim of the study was to analyze whether survival in patients admitted for de novo HF differs from the survival in those admitted for a first episode of decompensation but with a previous diagnosis of HF. This study includes an analysis of 1,728 patients admitted for decompensated HF during 9 years. Readmissions and patients with left ventricular ejection fraction ≥50% were excluded (finally, 524 patients analyzed). We compared de novo HF (n = 186) in patients not diagnosed with HF, although their structural heart disease was defined, versus acutely decompensated HF (n = 338). The clinical profiles in both groups were similar. The de novo HF group more frequently presented with normal right ventricular function, with less presence of severe tricuspid regurgitation. The probability of survival was low in both groups. Thus, the median life in the de novo HF group was 2.1 years and in the acutely decompensated HF group, 3.5 years. There was a lower probability of long-term survival in the de novo HF group (p = 0.035). The variables associated with mortality were age (p

The outcomes of heart-lung transplant (HLT) are worse than those of heart transplant (HT) and lung transplant alone; this and the availability of mechanical assistance have meant that the indications for HLT have been changing. This study aims to analyze the evolution of indications for HLT in a country of 47 million inhabitants.We performed a retrospective observational study of all HLTs performed in Spain (performed in 2 centers) from 1990 to 2020. The total number of patients included was 1751 (HT 1673 and HLT 78). After clinical adjustment, overall survival was compared between the 2 groups. Seven etiological subgroups were considered within the HLT group: (1) cardiomyopathy with pulmonary hypertension (CM + PH);, (2) Eisenmenger syndrome, (3) congenital heart disease without Eisenmenger syndrome, (4) idiopathic pulmonary arterial hypertension (IPAH), (5) cystic fibrosis, (6) chronic obstructive pulmonary disease (COPD) and/or emphysema), and (7) diffuse interstitial lung disease.There were a large number of differences between patients with HLT vs HT. HLT had a 2.69-fold increased probability of death in the first year compared with HT. The indications for HLT have changed over the years. In the recent period the indications are mainly congenital heart disease and Eisenmenger syndrome, with some cases of CM + PH. Other indications for HLT have virtually disappeared, mainly lung diseases (IPAH, COPD, cystic fibrosis). Median survival was low in CM + PH (18 days), diffuse interstitial lung disease (29 days), and ischemic heart disease (114 days); intermediate in Eisenmenger syndrome (600 days); and longer in IPAH, COPD and/or emphysema, and cystic fibrosis.HLT is a procedure with high mortality. This and mechanical assists mean that the indications have changed over the years. Etiological analysis is of utmost interest to take advantage of organs and improve survival.

The age of heart transplant (HTx) donors and recipients is progressively increasing. The combination of donor-recipient ages has been shown to have prognostic implications. The objective of this study is to analyze survival in the first year and in the long-term based on the difference in age between donor and recipient of HTx.We performed a retrospective analysis of all consecutive HTxs performed in 1 center from 1987 to December 2021. Patients younger than 16 years, retransplants, and combined transplants were excluded. Three groups were considered according to the age of the donor and recipient: group 1: recipient and donor of the same age ± 10 years; group 2: donor10 years older than recipient; and group 3: donor10 years younger than recipient.A total of 841 HTxs were included (81% men, 31% urgent HTxs, donor mean (standard deviation) age 38.5 [12.3] years and recipient age 51.2 [12]). The most frequent group was group 3 with 476 patients (56%) followed by group 1 with 305 patients (36%). Figure 1 shows that long-term survival is similar in groups 1 and 2, being worse in group 3, P = .026. Mortality at the end of follow-up is 38.7% in group 1, 34.9% in group 2, and 71.9% in group 3 (P.0001). These differences occurred in the long-term without finding significant differences the first year after HTx. No differences were found in early graft failure between the 3 groups.Using donors of a different age from the recipient does not seem to have an impact on long-term survival, except when donors are used who are more than 10 years younger than the recipient, where survival is lower. This consolidates the concept that the use of elderly donors does not affect survival, allowing the pool of donors to be expanded.

Resumen Antecedentes y objetivos Las alteraciones del potasio constituyen un problema clinico de gran magnitud en la insuficiencia cardiaca (IC) descompensada. Este estudio pretende valorar las implicaciones pronosticas de la hipo e hiperpotasemia al ingreso por IC aguda en la mortalidad cardiovascular y reingresos hospitalarios. Material y metodo De enero de 2016 a junio de 2020 fueron ingresados 1.397 casos con diagnostico de IC aguda. Se excluyeron ingresos programados para estudio, terapias electivas y pacientes con fraccion de eyeccion del ventriculo izquierdo > 40%. El estudio se realizo sobre 689 pacientes, 45 con potasio (K+) 5,0 mmol/l y 595 K+ = 3,5-5,0 mmol/l. Se analizaron los antecedentes, perfil clinico basal, terapia farmacologica y niveles de potasio obtenidos al ingreso. Resultados La mortalidad anual por hipopotasemia (K+ Conclusiones En los pacientes ingresados por IC descompensada, tanto la hiperpotasemia como la hipopotasemia determinadas al ingreso tienen impacto pronostico negativo en la supervivencia. La creatinina y la edad son otros factores independientes asociados a la mortalidad. El efecto sobre la probabilidad de reingreso hospitalario al ano no se demuestra en este trabajo.

Background Coronavirus disease 2019 (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 virus that is affecting the entire world population. The objective of this study was to analyze the repercussion of the disease in a group of patients at risk such as heart transplant recipients. Methods From February 2020 to February 2021, heart transplant recipients diagnosed with COVID-19 were consecutively included. The total number of transplant recipients in outpatient follow-up at that time was 381. Three levels of infection were determined: group A: asymptomatic patients or with trivial symptoms without the need for hospital admission (6 patients); group B: patients admitted to the hospital for respiratory symptoms (12 patients); and group C: patients with severe symptoms and need for admission to the critical care unit (2 patients). At each risk level, medical performance was different: group A: close control, no therapeutic modification; group B: reduction of calcineurin inhibitor and substitution of mycophenolate mofetil for everolimus; group C: reduction of calcineurin inhibitor and withdrawal of mycophenolate mofetil. Results The prevalence of infection in the series was 5.2%. Most patients admitted had a pathologic chest x-ray with fever, cough, dyspnea, or vomiting. The change in immunosuppression performed in patients in group 2 was well tolerated and there was no graft rejection. Antiviral treatment was little used. However, boluses of steroids and some antibiotics were used frequently. The need for supplemental oxygen was 50% in group 2 and 100% in group 3. Conclusions A significant number of transplant recipients will be affected by COVID-19 (5.3%). Management of the infection will depend on the severity of the infection and must be based on a balance between reduction and adjustment of immunosuppression, strict control of the cardiologic situation, and treatment of the infection.

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.

The most common symptom in heart failure (HF) is congestion, which can be refractory to diuretic treatment. To verify whether, in patients with advanced HF and diuretic resistance, subcutaneous furosemide or furosemide in an oral solution can improve the clinical-analytical status. From 2018 to 2020, 27 consecutive outpatients with diuretic resistance, not candidates for other alternatives, were recruited. Patients were treated either with subcutaneous furosemide in elastomeric pump (n: 10) or with oral solution (n: 17) for 5 days. The functional status (NYHA) improved with subcutaneous administration (predose: 3.8 ± 0.5 vs. postdose: 3.1 ± 0.7; p: 0.02) and oral solution (predose: 3.7 ± 0.3 vs. postdose: 2.5 ± 0.7; p: 0.0001). Weight loss was greater with the oral solution (predose: 85.5 ± 19.5 vs. postdose: 81.3 ± 18.8Kg; p: 0.0001) than subcutaneous (predose: 81.6 ± 15.9 vs. postdose: 80.4 ± 15.1kg; p: 0.16). Creatinine showed a non-significant increase in both groups. The number of hospital visits showed no difference between both options. The administration of furosemide, both subcutaneously by elastomeric pump or drinking the oral solution, is effective for the treatment of congestion in advanced HF refractory to diuretic treatment.

Heart transplant (HTx) recipients constitute a group vulnerable to COVID-19 infection. Vaccination has been a turning point in the evolution of the pandemic. The objective was to analyze a series of HTx recipients with COVID-19 prior to vaccination and post vaccination.Inclusion: All HTx recipients diagnosed with COVID-19 (February 2020 to April 2022).HTx younger than 16 years. They were subdivided into prevaccination period (February 2020 to February 2021) and postvaccination period (March 2021 to April 2022). They were classified into 3 groups according to severity. Group 1: mild symptoms without admission. Group 2: admission for nonsevere pneumonia. Group 3: severe pneumonia according to American Thoracic Society/Infectious Diseases Society of America criteria. The general therapeutic attitude before and after vaccination was similar in both groups.A total of 65 HTx recipients have had COVID-19 to date (10.7% of the 374 HTx recipients alive). In the prevaccination period, 22 HTx recipients presented the disease (Fig 1A): 27% in group 1; 59% were admitted for nonsevere pneumonia (group 2), with favorable evolution and a mean stay of 16 days; and 14% in group 3 (criteria for severe pneumonia), with 2 HTx recipients dying in this group. In the postvaccination period, 43 HTx recipients have presented COVID-19 (Fig 1B), 49% in group 1, 42% in group 2, and 9% in group 3. The hospital stay is slightly reduced to 15 days and 3 of the 4 patients in group 3 have died (mortality rate 7%).A significant number of HTx recipients have been affected by COVID-19, associating high mortality in severe forms both in the pre- and postvaccination period. In our series of patients, vaccination has reduced the percentage of hospitalization for nonsevere pneumonia slightly below the average hospitalization and mortality.

In advanced heart failure (HF), each hospitalization for decompensation is a vulnerable moment, and it requires optimizing pharmacologic treatment. This study aimed to analyze changes in the pharmacologic treatment of HF before admission (P), during hospitalization (H), and at discharge (D) of patients with decompensated advanced HF.We performed an ambispective, cross-sectional, noninterventional study conducted from January 2020 to June 2020. There were 252 consecutive patients admitted for decompensated advanced HF. The following were excluded: de novo HF cases, deceased patients, and scheduled admissions. Finally, 134 patients were analyzed, compared in 3 subgroups: pulmonary congestion (n = 90), systemic congestion (n = 31), and low output (n = 13).In the global analysis, an increase was detected in angiotensin receptor and neprilysin inhibitors (P: 9.7%, H: 16.4, D: 22.4%; P.02), beta blockers (P: 67.2%, H: 77.6%, D: 84.3%; P.004), mineralocorticoid receptor antagonists (P: 29.9%, H: 44.4%, D: 46.3%; P.01), loop diuretics (P: 70.1%, H: 99.3%, D: 95.5%; P.001), and nitrates (P: 6.0%, H: 22.4%, D: 9.7%; P.001). Pulmonary congestion was predominant with a significant increase in beta blockers (P: 61.1%, H: 77.8%, D: 88.9%; P.001) and loop diuretics (P: 64.4%, H: 100%, D: 100%; P.001); diuretics were increased in the systemic congestion group (P: 80.6%, H: 100%, D: 100%; P.002), and 22.6% required 3% hypertonic saline solution. In patients with low output, beta blockers and diuretics were withdrawn (P: 84.6%, H: 76.9%, D: 46.1%; P.08 and P: 84.6%, H: 92.3%, D: 61.5%; P.1 respectively), without variation in the other pharmacologic groups.In daily clinical practice, HF drugs are increased and optimized in decompensated HF with a pulmonary or systemic congestion profile. When the profile is low output, beta blockers and diuretics are reduced.

Given the central role of sarcomeric dysfunction in cardiomyocyte biology and sarcomere alterations described in endomyocardial biopsies of transplant patients with rejection, we hypothesized that the serum expression levels of genes encoding sarcomeric proteins were altered in acute cellular rejection (ACR). The aim of this study is to identify altered sarcomere-related molecules in serum and to evaluate their diagnostic accuracy for detecting rejection episodes.Serum samples from transplant recipients undergoing routine endomyocardial biopsies were included in an RNA sequencing analysis (n = 40). Protein concentrations of alpha-cardiac actin were determined using a specific enzyme-linked immunoassay (n = 80).We identified 17 sarcomeric genes differentially expressed in patients with clinically relevant rejection (grade ≥2R ACR). A receiver operating characteristic curve was done to assess their accuracy for ACR detection and found that 6 relevant actins, myosins, and other sarcomere-related genes showed great diagnostic capacity with an area under the curve (AUC)0.800. Specifically, the gene encoding alpha-cardiac actin (ACTC1) showed the best results (AUC = 1.000, P0.0001). We determine ACTC1 protein levels in a larger patient cohort, corroborating its overexpression and obtaining a significant diagnostic capacity for clinically relevant rejection (AUC = 0.702, P0.05).Sarcomeric alterations are reflected in peripheral blood of patients with allograft rejection. Because of their precision to detect ACR, we propose sarcomere ACTC1 serum expression levels as potential candidate for to be included in the development of molecular panel testing for noninvasive ACR detection.

Background Noninvasive detection of primary graft dysfunction (PGD) remains a major challenge. SERCA2a plays an important role in cardiac homeostasis and its dysregulation has been associated with ventricular dysfunction and rejection. This study aimed to determine the potential utility of plasma levels of SERCA2a as a biomarker of PGD. Methods 135 plasma samples were collected from adult recipients 2-6 hours prior to heart transplantation (HT). Plasma concentrations of SERCA2a were determined using a specific sandwich enzyme-linked immunosorbent assay. Variables related to the recipient, the donor, and the periprocedural were collected in order to determine a multivariate predictive model of PGD. Results Levels of SERCA2a were decreased in patients who developed PGD (median 0.430 ng/mL [IQR 0.260 - 0.945] versus 0.830 ng/mL [IQR 0.582 - 1.052]; p = 0.001). Receiver operating characteristic (ROC) curve analysis revealed that SERCA2a discriminated between patients with and without PGD (AUC = 0.682, p = 0.001), and a cutoff point ≥ 0.60 ng/ml was a protective independent predictor of PGD (odds ratio 0.215 [p = 0.004]). Three independent predictors of PGD in this study were reduced levels of pre-HT SERCA2a, increased bilirubin levels, and short-term mechanical circulatory support bridge to transplantation. The analysis of the ROC curve of the model obtained a significant AUC 0.788, p = 0.0001. Conclusions Our findings suggest that assessment of SERCA2a plasma levels may improve risk prediction for the occurrence of PGD, and could be considered as a novel noninvasive biomarker in patients undergoing HT.

Background Nucleocytoplasmic transport is a crucial process for cell function. Previous studies have observed alterations in different molecules involved in it, relating them to ventricular function. However, there are no published data evaluating possible differences in the expression of these molecules in heart transplantation (HT) recipients. Our objective is to evaluate whether its levels are related to the appearance of cellular rejection (CR) during the first year after HT. Methods A prospective clinical cohort that included patients undergoing HT between January 2017 and January 2019 (n = 46). Blood samples for the analysis of importin 5 (IMP5), nucleoporin 153 (Nup153); RAN-GTPaseAP1 (RanGAP1), and sarcoplasmic reticulum calcium ATPase (ATP-aseCaTransp) were collected approximately 2 months post-HT. The levels obtained were correlated with the incidence of at least moderate CR during the first year of follow-up. Results Results showed that 17.39% of the patients had at least moderate CR during the first year of follow-up. Higher levels of IMP5, Nup153, and RanGAP1 were observed in this group. This difference was statistically significant in the case of Nup153 and RanGAP1 (15.94 ± 14.00 vs 28.62 ± 23.61, P = .048; 21.95 ± 15.97 vs 40.90 ± 27.16, P = .026, respectively); there was an opposite trend in the ATP-aseCaTransp case. Conclusion Patients with at least a moderate degree of CR during follow-up showed higher serum levels of IMP5, Nup153, and RanGAP1. The prognostic usefulness of the determination of these biomarkers and whether their elevation during follow-up would facilitate early, noninvasive identification of patients with CR remains to be clarified.

The non-invasive diagnosis of acute cellular rejection (ACR) is a major challenge. We performed a molecular study analyzing the predictive capacity of serum RanGTPase AP1 (RANGAP1) for diagnosing ACR during the first year after heart transplantation (HT). We included the serum samples of 75 consecutive HT patients, extracted after clinical stability, to determine the RANGAP1 levels through ELISA. In addition, various clinical, analytical, and echocardiographic variables, as well as endomyocardial biopsy results, were collected. RANGAP1 levels were higher in patients who developed ACR (median 63.15 ng/mL; (inter-quartile range (IQR), 36.61–105.69) vs. 35.33 ng/mL (IQR, 19.18–64.59); p = 0.02). Receiver operating characteristic (ROC) curve analysis confirmed that RANGAP1 differentiated between patients with and without ACR (area under curve (AUC), 0.70; p = 0.02), and a RANGAP1 level exceeding the cut-off point (≥90 ng/mL) was identified as a risk factor for the development of ACR (OR, 6.8; p = 0.006). Two independent predictors of ACR identified in this study were higher RANGAP1 and N-terminal pro-brain natriuretic peptide levels. The analysis of the ROC curve of the model showed a significant AUC of 0.77, p = 0.001. Our findings suggest that RANGAP1 quantification facilitates risk prediction for the occurrence of ACR and could be considered as a novel non-invasive biomarker of ACR.

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.

Rationale and objectives Imaging is important in the diagnosis and follow-up of patients with heart failure (HF). Several thoracic radiological features have been described in these patients. The nodules with halo sign are very rarely reported in HF patients. This sign can appear in several diseases and a clinical context is essential for a final diagnosis. Materials and methods We present two immunocompetent patients with advanced HF waiting for cardiac transplantation showing multiple transient lung nodules with halo sign on preoperative chest CT. Results Our patients showed mild interstitial pulmonary edema and more interestingly multiple transient pulmonary nodules with halo sign. These nodules didn't coalesce, they even appear and disappear rapidly during worsening of pulmonary edema and showed thick halos. Nodules with halo sign are rarely reported in heart failure and considered focal pulmonary edema. Conclusion Nodules with halo sign in patients with advanced heart failure are a not usual finding that could not be the result of focal pulmonary edema, but of hemorrhage.

Currently, a high percentage of patients with congenital heart disease (CHD) reach adulthood. The consequence is that more and more patients will require a heart transplant (HTx) or heart-lung transplant (HLTx). The objective of the study was to analyze the evolution and temporary trend of the number of HTxs and HLTxs in patients with and without CHD.We performed a retrospective analysis of all HTxs and HTLxs from a Spanish transplant hospital. Retransplant and other combined transplants were excluded. HTx and HLTx were divided into 2 groups (CHD or non-CHD). The number of procedures of each modality was grouped in 5 years.A total of 930 HTxs were analyzed between 1987 and 2020; 36 were CHD (18 HTxs and 18 HLTxs). HTx and HLTx in CHD showed a growing progressive trend, probably because of the greater number of these patients who reach adulthood and finally develop advanced heart failure. HTx in patients without CHD showed a very high rise in the first decade, reaching the maximum peak around the year 2000, with a poststabilization trend or even progressive reduction in the number of procedures. HLTx in patients without CHD showed a marked ascent during the first decade with a peak around 2005 and subsequent significant decline in recent years practically in disuse, probably because of the possibility of circulatory assistance in the case of right ventricular failure.The number of HTxs and HLTxs in CHD has a progressive rise. The number of HTx in patients without CHD remains relatively stable. HLTx in patients without CHD shows a marked decrease.

Background: Tricuspid valve disease is the most frequent valvulopathy after heart transplantation (HTx). Evidence for the negative effect of post-transplant tricuspid regurgitation (TR) on survival is contradictory. The aim of this study was to analyze the causes of post-transplant TR and its effect on overall mortality.Methods: This is a retrospective observational study of all transplants performed in two Spanish centers (1009 patients) between 2000 and 2019. Of the total number of patients, 809 had no TR or mild TR and 200 had moderate or severe TR. The etiology of TR was analyzed in all cases.Results: The prevalence of moderate and severe TR was 19.8%. The risk of mortality was greater when TR was caused by early primary graft failure (PGF) or rejection (p < 0.05). TR incidence was related to etiology: incidence of PGF-induced TR was higher in the first period, while TR due to rejection and undefined causes occurred more frequently in three periods: in the first year, in the 10–14-year period following HTx, and in the long term (16–18 years). In the multivariable analysis, TR was significantly associated with mortality/retransplantation (HR:1.04, 95% CI:1.01–1.07, p:0.02).Conclusion: The development of TR after HTx is relatively frequent. The annual incidence depends on TR severity and etiology. The risk of mortality is greater in severe TR due to PGF or rejection.

Arrhythmogenic left ventricular cardiomyopathy (ALVC) is a rare heritable heart-muscle disorder characterized by a progressive loss of left ventricular myocardium and its replacement by fibrofatty tissue. Myocarditis is an inflammatory disease of the heart that may occur secondary to infections, immune system activation or exposure to drugs. Hot phases of ALVC present with chest pain and troponin rise, mimicking acute viral myocarditis and indicate a progression of the disease. Recently, myocarditis has also been described as an infrequent complication of coronavirus disease 2019 (Covid-19) mRNA vaccines. We herein report for the first time a case of probable myocarditis induced by Covid-19 vaccine in a patient with previous medical history of ALVC. We aim to highlight the common characteristics of ALVC and Covid-19 vaccine myocarditis and work through the differential diagnosis of these two entities.

BACKGROUND: The development of noninvasive approaches for the early diagnosis of acute cellular rejection (ACR), an important complication of cardiac transplantation, is of great importance in clinical practice. We conducted a nontargeted transcriptomic study focused on identifying serum miRNAs to evaluate their diagnostic accuracy for detecting rejection episodes. METHODS: We included consecutive serum samples from transplant recipients undergoing routine endomyocardial biopsies. In the discovery phase (n = 40), an RNA sequencing analysis (Illumina HiSeq 2500 sequencer) was performed. We focused on the validation of miR-144-3p in a larger patient cohort (n = 212), selected based on the criteria of higher accuracy for ACR detection. ACR was assessed according to the International Society for Heart and Lung Transplantation. RESULTS: In the discovery phase, 26 altered miRNAs were identified as potential markers for detecting ACR. miR-144-3p showed the best results, it was the only molecule with an AUC greater than 0.95 to detect Grade =2R ACR and it showed significant differences in its levels when we compared Grade 1R ACR with the nonrejection group. In the validation phase, we confirmed this finding, and it had an excellent diagnostic capacity for clinically relevant rejection (Grade =2R AUC = 0.801, p < 0.0001), detecting mild rejection (Grade 1R AUC = 0.631, p < 0.01) and was an independent predictor for the presence of ACR (odds ratio of 14.538, p < 0.01). CONCLUSIONS: ACR is associated with the differential expression of specific serum miRNAs that correlate with the severity of the episode. Circulating miR-144-3p is a candidate noninvasive ACR biomarker that could contribute to improving the surveillance of cardiac transplanted patients.

OBJECTIVES: In recent years, the percentage of heart transplantation (HT) with short/medium-term assistance devices has increased. This study aims at analyzing primary graft failure and in-hospital mortality according to the type of care. MATERIAL AND METHODS: From January 2013 to December 2017 all patients undergoing urgent HT with circulatory/ventricular assistance were retrospectively and consecutively recruited. Combined transplants, retransplantations and pediatric transplants were excluded. The sample was divided in 10 groups according to the type of shot/medium term assistance devices. RESULTS: A total of 53 patients were recruited, 79% men, average age 49 ± 13 years. 26 patients (51%) had mechanical ventilation at the time of the HT. Primary graft failure occurred in 20 patients (38.5%), whilst it was more frequent in patients assisted with ECMO (8 patients in group 1 (45%) and 7 in group 2 (54%), p 0.5). 14 deaths (27%) were registered, whereas a higher mortality was observed in the group assisted with ECMO (6 patients in group 1 (34%) and 4 in group 2 (31%), p 0.6). Mortality was 17% in the group of non-urgent Levitronix. CONCLUSIONS: Despite not showing statistical significance due to the low number of patients in some subgroups, hospital mortality was high in HT patients with circulatory assistance. A trend towards a higher incidence of primary graft failure and mortality in patients assisted with ECMO was observed. The direct implantation of a centrifugal pump as a bridge to urgent transplantation could identify a subgroup with a better prognosis.

BACKGROUND To analyze the relationship of the antigen carbohydrate 125 (CA125) biomarker with the cellular rejection of the heart graft during the first year after transplantation. METHODS Retrospective study of consecutive heart transplant (HTx) patients for 1.5 years. The total number of patients included in the study was 23 with a total of 103 follow-ups. In all patients, CA125 was determined before HTx and determined post-HTx in every follow-up. These were performed during months 1, 2, 4, 6, 9, and 12. Endomyocardial biopsy was performed in all revisions to assess the degree of graft rejection in the pathologic study. The biopsy results were grouped into 1. absence of rejection and 2. presence of some degree of rejection. RESULTS The mean pretransplant CA125 value presented a median of 120 U/mL with an interquartile range of 28.8 U/mL. One month after transplantation, the value was reduced by 20% and at 2 months by 81%. In subsequent reviews, plasma values were always between 10 and 20 U/mL. When comparing the values by periods and according to the presence or absence of rejection, no significant differences were found other than a slight elevation at the 6-month checkup (P = .03) but without clinical relevance, because the CA125 value was slightly higher in biopsy results without rejection. CONCLUSION The rapid reduction of CA125 corroborates its usefulness as a marker of congestion in heart failure. This biomarker is not useful for predicting rejection. However, in cases of very severe rejections that occurred with systemic congestion, it could be raised. It would be necessary to corroborate this hypothesis in a larger study with a higher number of severe rejections.

The purpose of this study was to analyze whether the level of IgA is related to right ventricular function and systemic congestion in patients with decompensated heart failure (HF) and reduced ejection fraction (EF).This was a consecutive prospective and observational study of hospitalized patients diagnosed with decompensated HF with reduced EF. The recruitment period lasted 2 months. In the first 24 hours after admission, clinical assessment, general laboratory tests, determination of HF biomarkers, IgA and echocardiographic study were performed. Patients were classified into 2 groups according to whether the plasma IgA level was lower (n = 11) or higher than 300 mg/dL (n = 12).Significant differences in IgA levels were found in the peripheral congestion variables (no congestion: 232, interquartile range [IQR], 125-310 mg/dL vs congestion: 429, IQR, 308-520 mg/dL; P = .03). There were also differences in echocardiographic parameters of right ventricular function, with a greater deterioration of right ventricular function in the group with higher IgA levels (P.05). There was a highly significant correlation between tricuspid annulus systolic excursion values and IgA levels (P = .004).In decompensated HF, patients with greater clinical congestion and echocardiographic parameters of right ventricular dysfunction have higher plasma IgA levels. This study is a preliminary experience that will help to establish the basis of the cardiointestinal syndrome as a clinical picture of systemic congestion in HF.

BACKGROUND The purpose of the study was to analyze postcardiac transplant complications in patients who received transplants with short-term mechanical ventricular assist devices and to compare complications according to the type of device. METHODS Ambispective and consecutive study of urgent heart transplants from 2015 to 2019. Pediatric transplants, retransplants, and combined transplants were excluded. A total of 45 patients were analyzed in 4 groups: (1) venoarterial extracorporeal membrane oxygenation (ECMO) implanted

Background Heart transplantation (HT) is the reference treatment for patients with terminal heart failure. In recent years there has been a progressive increase in HT procedures in patients who have a circulatory support (CS). Methods This is a retrospective single-center study of 293 consecutive patients who underwent HT from 2009 to 2018, analyzing the evolution of the 2 cohorts: patients with and without CS as a bridge to HT. Baseline and evolutionary clinical data collected following the usual follow-up protocol were recorded, including clinical events observed during the follow-up 1 year after the procedure. Results The subgroup of patients transplanted with CS showed a higher incidence of primary graft failure, frequent infection, and mortality. A tendency toward lower cardiac allograft vasculopathy was observed in this subgroup. Mechanical ventilation added to the CS resulted in a higher incidence of primary graft failure, infection, and renal dysfunction. The CS variable as a bridge to HT was shown to be predictive of 1-year mortality in both univariate (odds ratio, 1.84; 95% confidence interval, 1.03-3.3; P = .038) and multivariate (odds ratio, 2.1; 95% confidence interval, 1.01-4.3; P = .047) analyses. Conclusions In our experience, CS as a bridge to HT results in a higher incidence of primary graft failure, frequent infection, and mortality at 1-year follow-up. Mechanical ventilation added to CS has a clear unfavorable prognostic impact. CS as a bridge to HT was shown to be predictive of 1-year mortality in both univariate and multivariate analyses.

Background: Heart failure (HF) alters the nucleo-cytoplasmic transport of cardiomyocytes and reduces SERCA2a levels, essential for intracellular calcium homeostasis. We consider in this study whether the molecules involved in these processes can differentiate those patients with advanced HF and the need for mechanical circulatory support (MCS) as a bridge to recovery or urgent heart transplantation from those clinically stable and who are transplanted in an elective code. Material and method: Blood samples from patients with advanced HF were analyzed by ELISA and the plasma levels of Importin5, Nucleoporin153 kDa, RanGTPase-Activiting Protein 1 and sarcoplasmic reticulum Ca2 + ATPase were compared among patients that need MCS and patients without MCS. Results: SERCA2a showed significantly lower levels in patients who had MCS compared to those who did not require it (0.501 ± 0.530 ng / mL and 1,123 ± 0.661 ng / mL p = 0.01, respectively). By constructing the ROC curve with the SERCA2a values ​​(area under the curve of 0.812 ± 0.085, with a p of 0.004 and a 95% confidence interval between 0.646 and 0.979), we have established a cut-off point of 0.84 ng / mL with sensitivity of 92%, specificity of 62%, negative predictive value of 91% and positive predictive value of 67%. Conclusion: Patients with advanced HF and need for MCS have significantly lower levels of SERCA2a than stable patients without need for MCS. More studies are needed to validate these results. Trial registration: retrospectively registered

Heart failure (HF) is a clinical syndrome that causes high morbidity and mortality with a high number of admissions and sometimes prolonged admissions. This study aimed at assessing whether parameters detected during the first 24 h of admission may predict a prolonged hospital stay in patients admitted to hospital for decompensated HF.From January 2016 to December 2019, 2359 admissions of decompensated HF were recorded. In-hospital transfers,Univariate differences were found at admission in NT-ProBNP, creatinine, history of cardiac surgery, smoking and alcoholism, left and right ventricular ejection fraction, systolic blood pressure and heart rate. The ROC analysis showed significant areas under the curve for the NT-ProBNP (AUC: 0.63, 95% CI: 0.60-0.67;Variables such as creatinine and NT-ProBNP at hospital admission may define a subgroup of patients who will probably have a long hospital stay. Therefore, the planning of hospital care and transition to discharge may be enhanced.

BACKGROUND The purpose of this study was to compare early and late survival among patients who have undergone heart transplantation (HTx) with a short-term mechanical assist device. METHODS This was an ambispective, single-center, consecutive study of patients undergoing urgent HTx for 5 years. Pediatric transplants, retransplants, and combined transplants were excluded. Forty-five patients were included. Four groups were analyzed: those with venoarterial extracorporeal membrane oxygenation (ECMO) implanted 10 days; patients classified as INTERMACS 2 to 3 with Levitronix Centrimag implanted; and those classified as INTERMACS 2 with Levitronix Centrimag implanted. Survival and the influence of orotracheal intubation (OI) at the time of transplantation were compared. RESULTS There were differences in in-hospital mortality (P = .03) and total mortality (P = .06). The groups with the highest risk for mortality were those who carried ECMO for >10 days before transplantation or those classified as INTERMACS 2 with Levitronix Centrimag implanted. In these groups, the need for posttransplant circulatory support was also greater (P = .04) as was the length of stay in critical care (P = .02). The need for OI during the days of care and until transplantation had a negative effect on survival in all groups (P < .1). CONCLUSIONS There are different risk subgroups among patients who are transplanted with a circulatory/ventricular assist device. The lowest mortality occurs when the days of ECMO implantation are

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.

INTRODUCTION AND OBJECTIVES The present report updates the characteristics and results of heart transplantation in Spain, mainly focused in the 2008-2017 period. METHODS We describe the recipient and donor characteristics, surgical procedures, and outcomes of heart transplants performed in 2017. The 2017 data were compared with those obtained from 2008 to 2016. RESULTS A total of 304 cardiac transplants were performed in 2017. Between 1984 and 2017, 8173 procedures were performed, 2689 of them after 2008. Significant temporal trends were observed in recipient characteristics (lower pulmonary vascular resistance, lower use of mechanical ventilation, and a higher percentage of diabetic patients and those with previous cardiac surgery), donor characteristics (older donor age and a higher percentage of female donors and those with a prior cardiac arrest) and procedures (lower ischemia time). In 2017, 27% of patients were transplanted after undergoing mechanical ventricular assistance (P

Resumen Introduccion y objetivos El tacrolimus de liberacion prolongada (TLP) permite una dosificacion unica diaria, lo que simplifica el regimen inmunosupresor. El presente estudio describe la eficacia y la seguridad del uso de TLP de novo y precoz para el trasplante cardiaco. Metodos Se realizo un estudio observacional, retrospectivo y multicentrico para comparar el uso de novo de TLP (grupo de TLP; n = 94), tacrolimus de liberacion estandar (grupo de TLE; n = 42) y la conversion precoz (CP) de TLP a TLE (grupo de CP; n = 44). El TLP se uso entre 2007 y 2012. Se analizaron la tasa de incidencia de rechazo agudo, infeccion e infeccion por citomegalovirus al primer ano tras el trasplante, asi como parametros de seguridad. Resultados Entre los grupos no hubo diferencias significativas en la dosis diaria y las concentraciones sericas de tacrolimus durante el primer ano tras el trasplante. La incidencia de rechazo fue de 1,05 (IC95%, 0,51-1,54), 1,39 (IC95%, 1,00-1,78) y 1,11 (IC95%, 0,58-1,65) eventos/pacientes-anos en los grupos de TLE, TLP y CP respectivamente (p = 0,48). La incidencia de infeccion fue de 0,75 (IC95%, 0,60-0,86), 0,62 (IC95%, 0,52-0,71) y 0,55 (IC95%, 0,40-0,68) en los grupos de TLE, TLP y CP respectivamente (p = 0,46). Se produjo infeccion por citomegalovirus en el 23,8, el 20,2 y el 18,2% respectivamente (p = 0,86). No hubo diferencias significativas entre los grupos en los parametros de seguridad o la funcion del injerto. Fallecio 1 paciente del grupo de TLE y 2 del grupo de TLP. Conclusiones Parece que el uso de novo de TLP o la CP de TLP a TLE tienen similares eficacia y seguridad que el TLE en el trasplante cardiaco.

Introduction and objectives The extended-release formulation of tacrolimus (ERT) allows once-daily dosage, thus simplifying the immunosuppressive regimen. This study aimed to describe the safety and efficacy of the de novo and early use of ERT in heart transplantation. Methods This was an observational, retrospective, multicenter study comparing the safety and efficacy of the de novo use of ERT (ERT group [n = 94]), standard-release tacrolimus (SRT group [n = 42]) and early conversion (EC) from SRT to ERT (EC group [n = 44]). Extended-release tacrolimus was used between 2007 and 2012. One-year incidence rates of acute rejection, infection, and cytomegalovirus infection were analyzed. Safety parameters were also evaluated. Results There were no significant between-group differences in the daily dose or trough levels of tacrolimus during the first year after transplantation. The rejection incidence rates were 1.05 (95%CI, 0.51-1.54), 1.39 (95%CI, 1.00-1.78), and 1.11 (95%CI, 0.58-1.65) episodes per patient-years in the SRT group, ERT group, and EC group, respectively (P = .48). The infection incidence rates were 0.75 (95%CI, 0.60-0.86), 0.62 (95%CI, 0.52-0.71), and 0.55 (95%CI, 0.40-0.68) in the SRT group, ERT group, and EC group, respectively (P = .46). Cytomegalovirus infection occurred in 23.8%, 20.2%, and 18.2% of the patients, respectively (P = .86). No significant between-group differences were found in laboratory tests or in allograft function. There was 1 death in the SRT group and 2 in the ERT group. Conclusions Both de novo and early use of ERT seem to have similar safety and efficacy profiles to conventional SRT-based immunosuppression.

Background: Heart failure (HF) alters the nucleo-cytoplasmic transport of cardiomyocytes and reduces SERCA2a levels, essential for intracellular calcium homeostasis. We consider in this study whether the molecules involved in these processes can differentiate those patients with advanced HF and the need for mechanical circulatory support (MCS) as a bridge to recovery or urgent heart transplantation from those who are clinically stable and who are transplanted in an elective code. Material and method: Blood samples from 29 patients with advanced HF were analysed by ELISA, and the plasma levels of Importin5, Nucleoporin153 kDa, RanGTPase-Activating Protein 1 and sarcoplasmic reticulum Ca2+ ATPase were compared between patients requiring MCS and those patients without a MCS need prior to heart transplantation. Results: SERCA2a showed significantly lower levels in patients who had MCS compared to those who did not require it (0.501 ± 0.530 ng/mL vs. 1.123 ± 0.661 ng/mL, p = 0.01). A SERCA2a cut-off point of 0.84 ng/mL (AUC 0.812 ± 0.085, 95% CI: 0.646–0.979, p = 0.004) provided a 92% sensitivity, 62% specificity, 91% negative predictive value and 67% positive predictive value. Conclusions: In this cohort, patients with advanced HF and a need for MCS have shown significantly lower levels of SERCA2a as compared to stable patients without a need for MCS prior to heart transplantation. This is a small study with preliminary findings, and larger-powered dedicated studies are required to confirm and validate these results.

Post-transplant lymphoproliferative disorders (PTLD) are a rare complication after both solid organ (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this single center retrospective study, we compared clinical, biological, and histological features, and outcomes of PTLD after both types of transplant. We identified 82 PTLD (61 after SOT and 21 after allo-HSCT). The presence of B symptoms, Waldeyer ring, spleen, central nervous system, and liver involvement, and advanced Ann-Arbor stage were more frequent in allo-HSCT recipients. PTLD had an earlier onset in allo-HSCT than in SOT cohort (4 vs. 64 months, p .0001). PTLD was EBV-positive in 100% of allo-HSCT, in contrast to 47% of SOT (p = .0002). Four years after PTLD diagnosis, median overall survival was 32% (95% CI, 22-48) and 10% (95% CI, 2-49) in SOT and allo-HSCT recipients, respectively (p = .002). In conclusion, the clinical presentation and the outcome of PTLD varies greatly depending on the type of transplant.

Objectives To evaluate whether the levels of some molecules implicated in nucleocytoplasmic transport in human cardiomyocytes are related to the severity of heart failure (HF) in patients on the heart transplantation (HT) waiting list, and to determine whether there is a differential pattern of molecular alteration between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (DCM). Methods Sixty-three blood samples collected before HT were analyzed to identify the levels of IMPORTIN5 (IMP5); IMPORTINalpha2; ATPaseCaTransp (ATPCa); NUCLEOPORIN153kDa (Nup153); NUCLEOPORIN160kDa (Nup160); RANGTPaseAP1 (RanGAP1) and EXPORTIN4 (EXP4). These data were then compared between patients with advanced HF with or without the need for ventricular support with extracorporeal membrane oxygenation (ECMO) as a bridge for HT, as well as between patients with non-ischemic DCM and patients with ICM. Results Thirty-three patients had ICM, 26 had non-ischemic DCM, and 4 had heart disease. Seventeen patients required ventricular assistance as a bridge to HT. The levels of ATPCa, RanGAP1, and IMP5 were significantly higher in patients with ECMO, while EXP4 was significantly higher in patients without ECMO. Patients with DCM showed higher levels of IMP5, RanGAP1, and Nup153 than those with ICM. Conclusion Patients with advanced HF in critical condition (with ECMO as a bridge for HT) presented with significantly higher levels of ATPCa, RanGAP1, and IMP5, while patients with DCM had significantly higher levels of RanGAP1, IMP5, and Nup153. It remains to be clarified whether the determination of these molecules would facilitate the early identification of this group or if their alteration occurs as consequence of circulatory support with ECMO.

Background Acute renal dysfunction (ARD) may appear in heart transplant (HTx) patients both in the early postoperative period and during follow-up, even after several years. CD25 is a subunit of the interleukin-2 receptor which is found exclusively on activated CD4 T lymphocytes. CD25 is crucial for clonal expansion of anti-allograft host lymphocytes that mediate in acute rejection. There are experiences supporting the use of Anti-CD25 monoclonal antibodies (MAb) immediately after HTx in patients with ARD as a bridge to renal function recovery, allowing the temporary suspension of treatment with CNI. Methods In this study we report two cases of successful use of weekly MAb (basiliximab) in HTx patients who developed late ARD after HTx. Conclusions In coclusion, we think that in cases of ARD where CNI therapy plays a key role, the use of weekly doses of basiliximab allows CNI discontinuation until the restoration of renal function is achieved.

The objective of the present work is to describe the experience with intravenous (IV) sildenafil in heart transplant (HT) patients with reactive pulmonary hypertension (PH) who developed right ventricular dysfunction (RVD) in the immediate postoperative period. The first 5 patients who received IV sildenafil followinga HT are presented. The HTs took place between March 2011 and September 2012 in patients aged 37 to 64 years; all patients were male. Prior to the HT, mean pulmonary artery pressure (mPAP) was 32-56 mmHg. In all cases, the hemodynamic study demonstrated PH reactivity (positive vasodilator test with nitric oxide). All 5 patients developed RVD with hemodynamic instability immediately after the HT, despite the administration of nitric oxide from the time of intubation prior to the implant, optimal medical treatment in all cases, and a ventricular assist in 2 cases. In all patients, IV sildenafil was initiated at 10 mg/8 h for 48 h and was subsequently increased to 20 mg/8 h. in its oral formulation until discharge from the hospital. The change in pulmonary pressure was assessed using a Swan-Ganz catheter. Ventricular function was assessed using echocardiography. Length of stay in the Resuscitation Unit and mid-term survival were also assessed. Average time of extracorporeal circulation was 200 ± 110 min and organ ischemic time was 210 ± 95 min. All of the patients demonstrated pulmonary and systemic hemodynamic improvement, as well as recovery of right ventricular function after completing the treatment with IV sildenafil. The stay in the Resuscitation Unit lasted 3-25 days. All the patients were discharged from hospital with no mortality to date. Intravenous sildenafil improves right ventricle hemodynamics associated with pulmonary hypertension post-HT. Prophylactic prevention with this drug could be indicated for patients with reactive PH who are about to receive a transplant.