Gender differences in heart transplantation: Twenty-five year trends in the nationwide Spanish heart transplant registry.

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).

Impact of mechanical circulatory support on survival in pediatric heart transplantation.

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.

Use of Idarucizumab to reverse the anticoagulant effect of dabigatran in cardiac transplant surgery. A multicentric experience in Spain.

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.

Use of a surgically implanted, nondischargeable, extracorporeal continuous flow circulatory support system as a bridge to heart transplant.

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.

Repetitive ambulatory levosimendan as a bridge to heart transplantation.

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.

Structural heart transcatheter interventions in orthotopic cardiac transplant and left ventricular assist devices recipients: A nationwide study.

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.

Elevated Lipoprotein A Levels and Development of Moderate or Severe Cardiac Allograft Vasculopathy in Patients with Heart Transplants.

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.

Heart Transplantation in a Patient With a Heterotopic Percutaneous Tricuspid Valve Prosthesis: A Case Report.

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.

Evolocumab has no effects on heart failure with reduced ejection fraction injury biomarkers: The EVO-HF trial.

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.

What do Spanish registries report about worsening events in chronic heart failure? Needs and challenges.

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.