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Background: The current incidence and outcomes of structural transcatheter procedures in heart transplant (HTx) recipients and left-ventricular assist devices (LVAD) carriers is unknown., Aims: To provide insights on structural transcatheter procedures performed across HTx and LVAD patients in Spain., Methods: Multicenter, ambispective, observational nationwide registry., Results: Until May/2023, 36 percutaneous structural interventions were performed (78% for HTx and 22% for LVAD) widely varying among centers (0%-1.4% and 0%-25%, respectively). Percutaneous mitral transcatheter edge-to-edge (TEER) was the most common (n = 12, 33.3%), followed by trancatheter aortic valve replacement (n = 11, 30.5%), and tricuspid procedures (n = 9, 25%). Mitral TEER resulted in mild residual mitral regurgitation in all but one case, mean gradient was <5 mmHg in 75% of them at 1-year, with no mortality and 8.3% re-admission rate. Tricuspid TEER resulted in 100% none/mild residual regurgitation with a 1-year mortality and readmission rates of 22% and 28.5%, respectively. Finally, trancatheter aortic valve replacement procedures (n = 8 in LVADs due to aortic regurgitation and n = 3 in HTx), were successful in all cases with one prosthesis degeneration leading to severe aortic regurgitation at 1-year, 18.2% mortality rate and no re-admissions. Globally, major bleeding rates were 7.9% and 12.5%, thromboembolic events 3.7% and 12.5%, readmissions 37% and 25%, and mortality 22% and 25%, in HTx and LVADs respectively. No death was related to the implanted transcatheter device., Conclusions: Most centers with HTx/LVAD programs perform structural percutaneous procedures but with very inconsistent incidence. They were associated with good safety and efficacy, but larger studies are required to provide formal recommendations., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction and Objectives: The impact of preoperative left ventricular (LV) unloading on postoperative outcomes in patients bridged with venoarterial extracorporeal membrane oxygenation (VA-ECMO) to heart transplantation (HT) is unknown. Our aim was to compare posttransplant outcomes in patients bridged to HT with VA-ECMO, with or without the use of different mechanical strategies for LV decompression., Methods: We conducted a retrospective analysis of the postoperative outcomes of consecutive HT candidates bridged with VA-ECMO, with or without concomitant LV unloading. Patients were included from 16 Spanish centers from 2010 to 2020. The primary endpoint was 1-year post-HT survival, which was assessed using Cox regression., Results: Overall, 245 patients underwent high-emergency HT while supported with VA-ECMO. A mechanical strategy for LV unloading was used in 133 (54.3%) patients, with the intra-aortic balloon pump being the most commonly used method (n = 112; 84.2%). One-year posttransplant survival was 74.4% in the LV unloading group and 59.8% in the control group (P = .025). In multivariate analyses, preoperative LV unloading was independently associated with lower 1-year mortality (adjusted HR, 0.50; 95%CI, 0.32-0.78; P = .003). This association was observed both in patients managed with an intra-aortic balloon pump alone (adjusted HR, 0.52; 95%CI, 0.32-0.84; P = .007) and with other strategies for mechanical LV unloading (adjusted HR, 0.43; 95%CI, 0.19-0.97; P = .042). No significant differences were found between groups regarding other postoperative complications., Conclusions: Preoperative LV unloading was independently associated with increased 1-year posttransplant survival in candidates bridged with VA-ECMO., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan., Methods: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain., Results: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients' clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958)., Conclusions: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: We aimed to describe the clinical outcomes of the use of the CentriMag acute circulatory support system as a bridge to emergency heart transplantation (HTx)., Methods: We conducted a descriptive analysis of the clinical outcomes of consecutive HTx candidates included in a multicenter retrospective registry who were treated with the CentriMag device, configured either for left ventricular support (LVS) or biventricular support (BVS). All patients were listed for high-priority HTx. The study assessed the period 2010 to 2020 and involved 16 transplant centers around Spain. We excluded patients treated with isolated right ventricular support or venoarterial extracorporeal membrane oxygenation without LVS. The primary endpoint was 1-year post-HTx survival., Results: The study population comprised 213 emergency HTx candidates bridged on CentriMag LVS and 145 on CentriMag BVS. Overall, 303 (84.6%) patients received a transplant and 53 (14.8%) died without having an organ donor during the index hospitalization. Median time on the device was 15 days, with 66 (18.6%) patients being supported for> 30 days. One-year posttransplant survival was 77.6%. Univariable and multivariable analyses showed no statistically significant differences in pre- or post-HTx survival in patients managed with BVS vs LVS. Patients managed with BVS had higher rates of bleeding, need for transfusion, hemolysis and renal failure than patients managed with LVS, while the latter group showed a higher incidence of ischemic stroke., Conclusions: In a setting of candidate prioritization with short waiting list times, bridging to HTx with the CentriMag system was feasible and resulted in acceptable on-support and posttransplant outcomes., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

The bicaval transcatheter prosthesis (TricValve) allows the treatment of cava reflux in patients with severe tricuspid regurgitation and high surgical risk. It consists of the implantation of 2 self-expanding valves in both vena cava without directly approaching the native tricuspid valve. Heart transplantation in this setting may require some modifications compared with the conventional bicaval technique. We describe the clinical case of a 69-year-old woman with a background of rheumatic mitral valve disease who required a mitral valve replacement a few decades before. Ongoing clinical deterioration with biventricular dysfunction and severe tricuspid regurgitation was treated with a percutaneous bicaval heterotopic self-expanding valve system, with no clinical benefit. The patient underwent an elective heart transplantation. For the surgical approach, venous cannulation was performed percutaneously for both the right internal jugular and right femoral vein. Due to the impossibility of extracting percutaneous caval valves, the biatrial technique was selected for heart implantation. The postoperative course was difficult, but the patient was successfully discharged home 2 months postoperatively. She remains in good clinical condition with normal heart function 1 year after the transplant. To our knowledge, this is the first report describing a heart transplant in a patient with a bicaval transcatheter prosthesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Cardiac allograft vasculopathy (CAV) is a high-incident complication of heart transplant (HT) and is the leading cause of death beyond the first post-HT year. Traditional risk factors have been related to CAV development. Elevated lipoprotein (a) (Lp[a]) is an independent, genetic, and causal risk factor for cardiovascular disease; nonetheless, its association with the development or worsening of CAV in HT has not been firmly established., Methods: An observational nested case-control study including HT recipients under follow-up in a tertiary center. Lipoprotein (a) levels were determined at the time of inclusion. We considered elevated Lp(a) ≥30 mg/dL. We evaluated the association between Lp(a) levels and the presence and severity of CAV (The International Society For Heart And Lung Transplantation [ISHLT] Cardiac Allograft Vasculopathy Grading Scheme), dividing the sample between No or Mild CAV (0-1) and Moderate-Severe CAV (2-3). Routine coronary angiographies were performed the first year after the transplant and were subsequently symptom-driven., Results: One hundred fifty patients with HTs were included, with a mean follow-up of 110 ± 77 months. Patients with CAV 2 to 3 presented higher median Lp(a) levels (17 vs 86 mg/dL, P = 0.001). Elevated Lp(a) level was an independent risk factor for developing CAV 2 to 3 (odds ratio 8.57 [95% CI 2.82-26.04]; P < .001). Patients with Lp(a) ≥30 mg also showed an earlier onset compared with those with Lp(a) <30 mg/dL., Conclusions: Our study suggests that Lp(a) may play a role in the development of CAV. Lipoprotein (a) ≥30 mg/dL defines a subgroup of high-risk patients with HTs as portends to earlier onset and more severe CAV. Lipoprotein (a) determination should be a standard-of-care test in patients with HTs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: Patients with heart failure with reduced ejection fraction (HFrEF) have not been shown to benefit from statins. We hypothesized that, by limiting disease progression in stable HFrEF of ischaemic etiology, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab could reduce circulating troponin levels, a surrogate biomarker of myocyte injury and atherosclerosis progression., Methods and Results: The EVO-HF multicentre prospective randomized trial compared evolocumab (420 mg/month administered subcutaneously) plus guideline-directed medical therapy (GDMT; n = 17) versus GDMT alone (n = 22) for 1 year in patients with stable coronary artery disease and left ventricular ejection fraction (LVEF) <40%, ischaemic aetiology, New York Heart Association class II, N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥400 pg/ml, high-sensitivity troponin T (hs-TnT) >10 pg/ml, low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl. The primary endpoint was change in hs-TnT concentration. Secondary endpoints included NT-proBNP, interleukin-1 receptor-like 1 (ST2), high-sensitivity C-reactive protein (hs-CRP), LDL, low-density lipoprotein receptor (LDLR), high-density lipoprotein cholesterol (HDL-C), and PCSK9 levels at 1 year. Patients were mainly Caucasian (71.8%), male (79.5%), relatively young (mean age 68.1 ± 9.4 years), with a mean LVEF of 30.4 ± 6.5%, and managed with contemporary treatments. No significant changes in hs-TnT levels were observed in any group at 1 year. NT-proBNP and ST2 levels decreased in the GDMT plus evolocumab group (p = 0.045 and p = 0.008, respectively), without changes in hs-CRP, HDL-C, or LDLR. Total and LDL-C decreased in both groups, significantly higher in the intervention group (p = 0.003), and PCSK9 levels increased in the intervention group., Conclusions: This prospective randomized pilot trial, although with the limitation of the small sample size, does not support the benefit of evolocumab in reducing troponin levels in patients with elevated LDL-C levels, history of coronary artery disease, and stable HFrEF., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Worsening heart failure (HF) is associated with a high risk of death and rehospitalization. Despite that, real world evidence about the impact of worsening HF on clinical practice is scarce., Areas Covered: A narrative review about registries addressing recent worsening HF events in Spain, with special emphasis on patients recently hospitalized for HF was performed., Expert Opinion: Worsening HF can be defined as situations where the patient's HF deteriorates to the extent that it necessitates initiation or intensification of diuretic treatment (mainly intravenous). The events can occur at the outpatient level, generally in the day hospital, in the emergency department or even hospitalization. Early identification of worsening HF events is essential to establish appropriate treatment as soon as possible. In this context, robust clinical benefits have been reported for renin-angiotensin system inhibitors, sacubitril-valsartan, beta-blockers, mineralocorticoid receptor antagonists, SGLT2 inhibitors, and vericiguat. In Spain, several registries of patients with HF have been developed, some of them including patients recently hospitalized for HF, but not with recent worsening HF events. Therefore, registries addressing recent worsening events would be desirable. Using a practical approach, this review analyzes the importance of worsening HF events, with special emphasis on Spanish data.

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., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: 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., Methods: Analysis of the Spanish Registry of durable ventricular assist devices (REGALAD) including data form Spanish centers with a mechanical circulatory support program., Results: 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%)., Conclusions: 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., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Introduction and Objectives: Short-term mechanical circulatory support is frequently used as a bridge to heart transplant in Spain. The epidemiology and prognostic impact of infectious complications in these patients are unknown., Methods: Systematic description of the epidemiology of infectious complications and analysis of their prognostic impact in a multicenter, retrospective registry of patients treated with short-term mechanical devices as a bridge to urgent heart transplant from 2010 to 2015 in 16 Spanish hospitals., Results: We studied 249 patients, of which 87 (34.9%) had a total of 102 infections. The most frequent site was the respiratory tract (n=47; 46.1%). Microbiological confirmation was obtained in 78 (76.5%) episodes, with a total of 100 causative agents, showing a predominance of gram-negative bacteria (n=58, 58%). Compared with patients without infection, those with infectious complications showed higher mortality during the support period (25.3% vs 12.3%, P=.009) and a lower probability of receiving a transplant (73.6% vs 85.2%, P=.025). In-hospital posttransplant mortality was similar in the 2 groups (with infection: 28.3%; without infection: 23.4%; P=.471)., Conclusions: Patients supported with temporary devices as a bridge to heart transplant are exposed to a high risk of infectious complications, which are associated with higher mortality during the organ waiting period., (Copyright © 2020 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Importance: Truncating variants in the gene encoding filamin C (FLNCtv) are associated with arrhythmogenic and dilated cardiomyopathies with a reportedly high risk of ventricular arrhythmia., Objective: To determine the frequency of and risk factors associated with adverse events among FLNCtv carriers compared with individuals carrying TTN truncating variants (TTNtv)., Design, Setting, and Participants: This cohort study recruited 167 consecutive FLNCtv carriers and a control cohort of 244 patients with TTNtv matched for left ventricular ejection fraction (LVEF) from 19 European cardiomyopathy referral units between 1990 and 2018. Data analyses were conducted between June and October, 2020., Main Outcomes and Measures: The primary end point was a composite of malignant ventricular arrhythmia (MVA) (sudden cardiac death, aborted sudden cardiac death, appropriate implantable cardioverter-defibrillator shock, and sustained ventricular tachycardia) and end-stage heart failure (heart transplant or mortality associated with end-stage heart failure). The secondary end point comprised MVA events only., Results: In total, 167 patients with FLNCtv were studied (55 probands [33%]; 89 men [53%]; mean [SD] age at baseline evaluation, 43 [18] years). For a median follow-up of 20 months (interquartile range, 7-60 months), 29 patients (17.4%) reached the primary end point (19 patients with MVA and 10 patients with end-stage heart failure). Eight (44%) arrhythmic events occurred among individuals with baseline mild to moderate left ventricular systolic dysfunction (LVSD) (LVEF = 36%-49%). Univariable risk factors associated with the primary end point included proband status, LVEF decrement per 10%, ventricular ectopy (≥500 in 24 hours) and myocardial fibrosis detected on cardiac magnetic resonance imaging. The LVEF decrement (hazard ratio [HR] per 10%, 1.83 [95% CI, 1.30-2.57]; P < .001) and proband status (HR, 3.18 [95% CI, 1.12-9.04]; P = .03) remained independent risk factors on multivariable analysis (excluding myocardial fibrosis and ventricular ectopy owing to case censoring). There was no difference in freedom from MVA between FLNCtv carriers with mild to moderate or severe (LVEF ≤35%) LVSD (HR, 1.29 [95% CI, 0.45-3.72]; P = .64). Carriers of FLNCtv with impaired LVEF at baseline evaluation (n = 69) had reduced freedom from MVA compared with 244 TTNtv carriers with similar baseline LVEF (for mild to moderate LVSD: HR, 16.41 [95% CI, 3.45-78.11]; P < .001; for severe LVSD: HR, 2.47 [95% CI, 1.04-5.87]; P = .03)., Conclusions and Relevance: The high frequency of MVA among patients with FLNCtv with mild to moderate LVSD suggests that higher LVEF values than those currently recommended should be considered for prophylactic implantable cardioverter-defibrillator therapy in FLNCtv carriers.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 García-Cosío, González-Vilchez, López-Vilella, Barge-Caballero, Gómez Bueno, Martínez-Selles, María Arizón, Rangel Sousa, González-Costello, Mirabet, Pérez-Villa, Molina, Rábago, Portolés Ocampo, de la Fuente Galán, Garrido and Delgado.)

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)., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2020 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Truncating variants in the TTN gene (TTNtv) are the commonest cause of heritable dilated cardiomyopathy. This study aimed to study the phenotypes and outcomes of TTNtv carriers., Methods: Five hundred thirty-seven individuals (61% men; 317 probands) with TTNtv were recruited in 14 centers (372 [69%] with baseline left ventricular systolic dysfunction [LVSD]). Baseline and longitudinal clinical data were obtained. The primary end point was a composite of malignant ventricular arrhythmia and end-stage heart failure. The secondary end point was left ventricular reverse remodeling (left ventricular ejection fraction increase by ≥10% or normalization to ≥50%)., Results: Median follow-up was 49 (18-105) months. Men developed LVSD more frequently and earlier than women (45±14 versus 49±16 years, respectively; P =0.04). By final evaluation, 31%, 45%, and 56% had atrial fibrillation, frequent ventricular ectopy, and nonsustained ventricular tachycardia, respectively. Seventy-six (14.2%) individuals reached the primary end point (52 [68%] end-stage heart failure events, 24 [32%] malignant ventricular arrhythmia events). Malignant ventricular arrhythmia end points most commonly occurred in patients with severe LVSD. Male sex (hazard ratio, 1.89 [95% CI, 1.04-3.44]; P =0.04) and left ventricular ejection fraction (per 10% decrement from left ventricular ejection fraction, 50%; hazard ratio, 1.63 [95% CI, 1.30-2.04]; P <0.001) were independent predictors of the primary end point. Two hundred seven of 300 (69%) patients with LVSD had evidence of left ventricular reverse remodeling. In a subgroup of 29 of 74 (39%) patients with initial left ventricular reverse remodeling, there was a subsequent left ventricular ejection fraction decrement. TTNtv location was not associated with statistically significant differences in baseline clinical characteristics, left ventricular reverse remodeling, or outcomes on multivariable analysis ( P =0.07)., Conclusions: TTNtv is characterized by frequent arrhythmia, but malignant ventricular arrhythmias are most commonly associated with severe LVSD. Male sex and LVSD are independent predictors of outcomes. Mutation location does not impact clinical phenotype or outcomes.

Evidence on the impact of MCS on pediatric heart transplant survival is still scarce related to congenital heart disease patients including univentricular physiology as well as the risk factors for complications. We performed a retrospective review of all urgent pediatric (aged ≤16 years) HT from 2004 to 2014 in the Spanish Pediatric Heart Transplant Registry Group. Patients were stratified into two groups: urgent 0 (MCS at HT) and urgent 1 (non-MCS at HT). The primary outcome measure was post-transplant survival; secondary outcome measures were complications and absence of infections and rejection during the first post-transplant year. One hundred twenty-one pediatric patients underwent urgent HT, 58 (47.9%) urgent 0 and 63 (52%) urgent 1. There were 30 (24.8%) deaths: 12 in the urgent 0 group and 18 in the urgent 1 group, P = n.s. Regarding the type of MCS, patients on ECMO had the highest rate of complications (80%) and mortality (40%). Patients in the urgent 1 group showed a higher risk of hospital re-admission for infection during the first year after transplantation (OR 2.31 [1.1-4.82]), P = .025. We did not identify a risk factor for mortality. MCS does not impact negatively on survival after HT. However, there is a significant increase in 30-day and 1-year mortality and complications in ECMO patients compared with VAD patients. Infants, congenital heart disease, and PediMACS were not found to be risk factors for mortality., (© 2020 Wiley Periodicals LLC.)

Background: Pulmonary arterial hypertension (PAH) represents a marker of bad prognosis in left heart disease. Nonetheless, the effect on survival after heart transplant remains controversial. The objective was to study the impact of preoperative PAH on survival in patients undergoing elective heart transplant., Methods: A retrospective study of 173 transplant recipients was conducted at a single hospital from January 2009 to December 2018. Congenital etiology and emergent heart transplant were exclusion criteria as well as those patients without enough data in the hemodynamic study. Two groups were considered: A (without PAH) and B (with HTP). PAH was classified as mild (mean pulmonary arterial pressure [mPAP] 25-34 mm Hg, pulmonary vascular resistance [PVR] 2.5-3.4 Wood units and/or transpulmonary gradient [TPG] 13-16 mm Hg), moderate (mPAP 35-44 mm Hg, PVR 3.5-4.9 Wood units and/or TPG 17-19 mm Hg), and severe (mPAP > 44 mm Hg, PVR > 4.9 Wood units and/or TPG > 19 mm Hg)., Results: A total of 102 patients were enrolled; 71.6% were male and average age was 52.3 (SD, 10.02) years. The main etiology was ischemic cardiomyopathy; 13.7% underwent previous heart operations. A total of 61 patients (59.8%) had PAH prior to heart transplant: 25 mild, 34 moderate, and 2 severe. Mean overall survival after transplant was 79.9 (SD, 5.68) months, without differences between the 2 groups (P = .82). One-month survival was 89% (the main cause of mortality was primary graft dysfunction), and 1-year survival was 78%. Four patients required mechanical circulatory support during early post-transplant period., Conclusions: Preoperative PAH does not have a significant impact on survival in elective heart transplant., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Anticoagulation in heart transplant (HT) recipients increases the risk of hemorrhagic complications, so correct reversal of anticoagulation is needed. Dabigatran, a direct thrombin inhibitor, is increasingly used for anticoagulation in patients with non-valvular atrial fibrillation (NVAF) whose effect can be reversed by idarucizumab., Aim: To present a nationwide experience using idarucizumab for the urgent reversal of dabigatran before HT., Methods: Multicenter observational study in 12 Spanish centers to analyze the clinical outcomes after using idarucizumab before HT surgery., Results: Fifty-three patients were included (81.1% male). 7.5% required re-operation in the immediate postoperative period to control bleeding and 66% transfusion of blood products. Median length of stay in the intensive care unit was 6 days and total hospital stay 24 days. 30-day survival was 92.4%. There were four deaths in the first month, all in the first 5 days post-HT. Only in one patient (transplanted due to a congenital heart disease, after sternotomy) who had surgical problems and right ventricular failure post-HT death was associated with bleeding., Conclusions: These results may support the use of dabigatran as an alternative to vitamin K antagonists in patients listed for HT requiring anticoagulation due to NVAF. More studies are needed to reaffirm these observations., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To investigate the potential clinical benefit of an intra-aortic balloon pump (IABP) in patients supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO) as a bridge to heart transplantation (HT)., Methods: We studied 169 patients who were listed for urgent HT under VA-ECMO support at 16 Spanish institutions from 2010 to 2015. The clinical outcomes of patients under simultaneous IABP support (n = 73) were compared to a control group of patients without IABP support (n = 96)., Results: There were no statistically significant differences between the IABP and control groups with regard to the cumulative rates of transplantation (71.2% vs 81.2%, P = 0.17), death during VA-ECMO support (20.6% vs 14.6%, P = 0.31), transition to a different mechanical circulatory support device (5.5% vs 5.2%, P = 0.94) or weaning from VA-ECMO support due to recovery (2.7% vs 0%, P = 0.10). There was a higher incidence of bleeding events in the IABP group (45.2% vs 25%, P = 0.006; adjusted odds ratio 2.18, 95% confidence interval 1.02-4.67). In-hospital postoperative mortality after HT was 34.6% in the IABP group and 32.5% in the control group (P = 0.80). One-year survival after listing for urgent HT was 53.3% in the IABP group and 52.2% in the control group (log rank P = 0.75). Multivariate adjustment for potential confounders did not change this result (adjusted hazard ratio 0.94, 95% confidence interval 0.56-1.58)., Conclusions: In our study, simultaneous IABP therapy in transplant candidates under VA-ECMO support did not significantly reduce morbidity or mortality., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction and Objectives: In Spain, intra-aortic balloon pump (IABP) has been used frequently as a bridge to urgent heart transplant (HT). We sought to analyze the clinical outcomes of this strategy., Methods: We conducted a case-by-case, retrospective review of clinical records of 281 adult patients listed for urgent HT under IABP support in 16 Spanish institutions from 2010 to 2015. Pre- and post-transplant survival and adverse clinical events were analyzed., Results: A total of 194 (69%, 95%CI, 63.3-74.4) patients were transplanted and 20 (7.1%, 95%CI, 4.4-10.8) died during a mean period of IABP support of 10.9±9.7 days. IABP support was withdrawn before an organ became available in 32 (11.4%) patients. Thirty-five (12.5%, 95%CI, 8.8-16.9) patients transitioned from IABP to full-support mechanical devices. Mean urgent waiting list time increased from 5.9±6.3 days in 2010 to 15±11.7 days in 2015 (P=.001). Post-transplant survival rates at 30-days, 1-year, and 5-years were 88.1% (95%CI, 85.7-90.5), 76% (95%CI, 72.9-79.1), and 67.8% (95%CI, 63.7-71.9), respectively. The incidence rate of major adverse clinical outcomes-device dysfunction, stroke, bleeding or infection-during IABP support was 26 (95%CI, 20.6-32.4) episodes per 1000 patient-days. The incidence rate of IABP explantation due to complications was 7.2 (95%CI, 4.5-10.8) cases per 1000 patient-days., Conclusions: In a setting of short waiting list times, IABP can be used to bridge candidates to urgent HT with acceptable postoperative results, but there were significant rates of adverse clinical events during support., (Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: To study the prognostic value of serum lactate in patients under temporary preoperative mechanical circulatory support who underwent urgent heart transplant., Methods: We conducted a subanalysis of a Spanish multicenter registry recording data on patients under temporary mechanical circulatory support listed for highly urgent heart transplant from 2010 to 2015. Participants selected for the present study were those who received a transplant and who had known preoperative serum lactate levels. The main study outcome was 1-year survival after transplant., Results: A total of 177 heart transplant recipients were studied; preoperatively, 90 were supported on venoarterial extracorporeal membrane oxygenation, 51 on temporary left ventricular assist devices, and 36 on temporary biventricular assist devices. Preoperative hyperlactatemia (≥ 2 mmol/L) was present in 44 (25%) patients. On multivariable analysis, pretransplant serum lactate was identified as an independent predictor of 1-year posttransplant survival (adjusted HR per 0.1 mmol/L, 1.02; 95%CI, 1.01-1.03; P = .007). One-year posttransplant survival was 53.1% (95%CI, 45.3-60.9) in patients with preoperative hyperlactatemia and 75.6% (95%CI, 71.8-79.4) in those without preoperative hyperlactatemia (adjusted HR, 1.94; 95%CI, 1.04-3.63; P = .039). Preoperative hyperlactatemia correlated with adverse outcomes in patients supported with extracorporeal membrane oxygenation, but not in patients supported on ventricular assist devices., Conclusions: Preoperative serum lactate is a strong independent predictor of worse outcomes in patients undergoing urgent heart transplant on short-term mechanical circulatory support., (Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2018 American College of Cardiology Foundation. All rights reserved.)

Background: In Spain, listing for high-urgent heart transplantation is allowed for critically ill candidates not weanable from temporary mechanical circulatory support (T-MCS). We sought to analyse the clinical outcomes of this strategy., Methods and Results: We conducted a case-by-case, retrospective review of clinical records of 291 adult patients listed for high-urgent heart transplantation under temporary devices from 2010 to 2015 in 16 Spanish institutions. Survival after listing and adverse clinical events were studied. At the time of listing, 169 (58%) patients were supported on veno-arterial extracorporeal membrane oxygenation (VA-ECMO), 70 (24%) on temporary left ventricular assist devices (T-LVAD) and 52 (18%) on temporary biventricular assist devices (T-BiVAD). Seven patients transitioned from VA-ECMO to temporary ventricular assist devices while on the waiting list. Mean time on T-MCS was 13.1 ± 12.6 days. Mean time from listing to transplantation was 7.6 ± 8.5 days. Overall, 230 (79%) patients were transplanted and 54 (18.6%) died during MCS. In-hospital postoperative mortality after transplantation was 33.3%, 11.9% and 26.2% for patients bridged on VA-ECMO, T-LVAD and T-BiVAD, respectively (P = 0.008). Overall survival from listing to hospital discharge was 54.4%, 78.6% and 55.8%, respectively (P = 0.002). T-LVAD support was independently associated with a lower risk of death over the first year after listing (hazard ratio 0.52, 95% confidence interval 0.30-0.92). Patients treated with VA-ECMO showed the highest incidence rate of adverse clinical events associated with T-MCS., Conclusion: Temporary devices may be used to bridge critically ill candidates directly to heart transplantation in a setting of short waiting list times, as is the case of Spain. In our series, bridging with T-LVAD was associated with more favourable outcomes than bridging with T-BiVAD or VA-ECMO., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Background: It's unclear whether pre-transplant T. gondii seropositivity is associated with impaired survival in heart transplant recipients., Objectives: To test the above-mentioned hypothesis in the Spanish Heart Transplantation Registry., Methods: Post-transplant outcomes of 4048 patients aged >16years who underwent first, single-organ heart transplantation in 17 Spanish institutions from 1984 to 2014 were studied. Long-term post-transplant survival and survival free of cardiac death or retransplantation of 2434 (60%) T. gondii seropositive recipients and 1614 (40%) T. gondii seronegative recipients were compared., Results: T. gondii seropositive recipients were older, had higher body mass index, and presented higher prevalence of hypertension, hypercholesterolemia, COPD and Cytomegalovirus seropositivity than T. gondii seronegative recipients. In univariable analysis, pre-transplant T. gondii seropositivity was associated with increased post-transplant all-cause mortality (non-adjusted HR 1.15; 95% CI 1.04-1.26). However, this effect was no longer statistically significant after multivariable adjustment by recipient's age and sex (adjusted HR 1.01, 95% CI 0.92-1.11). Extended multivariable adjustment by other potential confounders showed similar results (adjusted HR 0.99, 95% CI 0.89-1.11). T. gondii seropositivity had no significant effect on the composite outcome cardiac death or retransplantation (non-adjusted HR 1.08, 95% CI 0.95-1.24, p=0.235). The distribution of the causes of death was comparable in T. gondii seropositive and T. gondii seronegative recipients. No statistically significant impact of donor's T. gondii serostatus or donor-recipient T. gondii serostatus matching on post-transplant survival was observed., Conclusions: Our analysis did not show a significant independent effect of preoperative T. gondii serostatus on long-term outcomes after heart transplantation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminal-prohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: To evaluate the possible relationship between high levels of CA-125 and long-term prognosis in chronic heart failure patients after they undergo a cardiac transplantation (CT)., Materials & Methods: We retrospectively studied all patients who underwent a CT and had a previous determination of CA-125. Congestive patients and those whose survival was <1 year after CT were excluded., Results: Of 55 patients, 23 had elevated CA-125 levels (>35 U/ml). After CT, survival was significantly inferior in this group (96.3 vs 81%, 84.9 vs 64%, 70.7 vs 32.9% at 2, 5 and 8 years, p = 0.014). CA-125 >35 U/ml was the only factor independently associated to long-term mortality (OR: 3.94; 95% CI: 1.2-12.82; p = 0.023)., Conclusion: Noncongestive patients with high levels of CA-125 had inferior long-term survival after CT.