AIMS:

The aim of this trial was to compare the clinical effects of intraoperative haemoadsorption versus standard care in patients undergoing orthotopic heart transplantation (OHT).

METHODS AND RESULTS:

In a randomized, controlled trial, OHT recipients were randomized to receive intraoperative haemoadsorption or standard care. Outcomes were vasoactive-inotropic score (VIS), frequency of vasoplegic syndrome (VS) in the first 24 h; post-operative change in procalcitonin (PCT) and C-reactive protein (CRP) levels; intraoperative change in mycophenolic acid (MPA) concentration; frequency of post-operative organ dysfunction, major complications, adverse immunological events and length of in-hospital stay and 1-year survival. Sixty patients were randomized (haemoadsorption group N = 30, control group N = 25 plus 5 exclusions). Patients in the haemoadsorption group had a lower median VIS and rate of VS (VIS: 27.2 [14.6-47.7] vs. 41.9 [22.4-63.2], P = 0.046, and VS: 20.0% vs. 48.0%, P = 0.028, respectively), a 6.4-fold decrease in the odds of early VS (OR: 0.156, CI: 0.029-0.830, P = 0.029), lower PCT levels, shorter median mechanical ventilation (MV: 25 [19-68.8] hours vs. 65 [23-287] hours, P = 0.025, respectively) and intensive care unit stay (ICU stay: 8.5 [8.0-10.3] days vs. 12 [8.5-18.0] days, P = 0.022, respectively) than patients in the control group. Patients in the haemoadsorption versus control group experienced lower rates of acute kidney injury (AKI: 36.7% vs. 76.0%, P = 0.004, respectively), renal replacement therapy (RRT: 0% vs. 16.0%, P = 0.037, respectively) and lower median per cent change in bilirubin level (PCB: 2.5 [-24.6 to 71.1] % vs. 72.1 [11.2-191.4] %, P = 0.009, respectively) during the post-operative period. MPA concentrations measured at pre-defined time points were comparable in the haemoadsorption compared to control groups (MPA pre-cardiopulmonary bypass: 2.4 [1.15-3.60] μg/mL vs. 1.6 [1.20-3.20] μg/mL, P = 0.780, and MPA 120 min after cardiopulmonary bypass start: 1.1 [0.58-2.32] μg/mL vs. 0.9 [0.45-2.10] μg/mL, P = 0.786). The rates of cardiac allograft rejection, 30-day mortality and 1-year survival were similar between the groups.

CONCLUSIONS:

Intraoperative haemoadsorption was associated with better haemodynamic stability, mitigated PCT response, lower rates of post-operative AKI and RRT, more stable hepatic bilirubin excretion, and shorter durations of MV and ICU stay. Intraoperative haemoadsorption did not show any relevant adsorption effect on MPA. There was no increase in the frequency of early cardiac allograft rejection related to intraoperative haemoadsorption use.

Concerns related to bodily integrity, medical mistrust, superstition, and disgust with respect to organ transplantation remain commonly cited barriers among African American, Caucasian, and Hispanic non-donors. The current study examined two narrative strategies for mitigating these barriers by eliciting feelings of happiness or sadness. African American, Caucasian, and Hispanic non-donors (N = 576) were randomly assigned to a radio ad that communicated either a recipient narrative or a waiting list narrative. As expected, the recipient narrative elicited greater feelings of happiness whereas the waiting list narrative aroused greater feelings of sadness. Moderated mediation analyses revealed models in which happiness, not sadness, was the mediator, such that the narrative frame was associated with ad persuasiveness. Additionally, only medical mistrust interacted with happiness to predict ad persuasiveness The results are discussed with an emphasis on message design strategies to employ among reluctant adult African American, Caucasian, and Hispanic potential donors.

BACKGROUND:

The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population.

METHODS:

Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction-confirmed influenza and vaccine reactogenicity.

RESULTS:

A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12-1); P < .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16-1]; P < .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08-1]; P < .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild.

CONCLUSIONS:

In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate.

CLINICAL TRIALS REGISTRATION:

Clinicaltrials.gov NCT03699839.

BACKGROUND:

Heart transplant (HTx) is gold-standard therapy for patients with end-stage heart failure. Cardiac rehabilitation (CR) is a multidisciplinary intervention shown to improve cardiovascular prognosis and quality of life. The aim in this randomized controlled trial is to explore the safety and efficacy of cardiac telerehabilitation after HTx. In addition, biomarkers of rehabilitation outcomes will be identified, as data that will enable treatment to be tailored to patient phenotype.

METHODS:

Patients after HTx will be recruited at IRCCS S. Maria Nascente - Fondazione Don Gnocchi, Milan, Italy (n = 40). Consenting participants will be randomly allocated to either of two groups (1:1): an intervention group who will receive on-site CR followed by 12 weeks of telerehabilitation, or a control group who will receive on-site CR followed by standard homecare and exercise programme. Recruitment began on 20th May 2023 and is expected to continue until 20th May 2025. Socio-demographic characteristics, lifestyle, health status, cardiovascular events, cognitive function, anxiety and depression symptoms, and quality of life will be assessed, as well as exercise capacity and muscular endurance. Participants will be evaluated before the intervention, post-CR and after 6 months. In addition, analysis of circulating extracellular vesicles using Surface Plasmon Resonance imaging (SPRi), based on a rehabilomic approach, will be applied to both groups pre- and post-CR.

CONCLUSION:

This study will explore the safety and efficacy of cardiac telerehabilitation after HTx. In addition, a rehabilomic approach will be used to investigate biomolecular phenotypization in HTx patients.

TRIAL REGISTRATION NUMBER:

ClinicalTrials.gov Identifier: NCT05824364.

INTRODUCTION:

Ischaemic cold static storage (ICSS) is the gold standard in donor heart preservation. This ischaemic time frame renders a time constraint and risk for primary graft dysfunction. Cold oxygenated heart perfusion, known as non-ischaemic heart preservation (NIHP), theoretically limits the ischaemic time, while holding on to the known advantage of hypothermia and cardioplegia, a low metabolic rate.

METHODS AND ANALYSIS:

The NIHP 2019 study is an international, randomised, controlled, open, multicentre clinical trial in 15 heart transplantation centres in 8 European countries and includes 202 patients undergoing heart transplantation, allocated 1:1 to NIHP or ICSS. Enrolment is estimated to be 30 months after study initiation. The patients are followed for 12 months after transplantation.The primary objective is to evaluate the effect of NIHP on survival, allograft function and rejection episodes within the first 30 days after transplantation. The secondary objectives are to compare treatment groups with respect to survival, allograft function, cardiac biomarkers, rejection episodes, allograft vasculopathy, adverse events and adverse device effects within 12 months.

ETHICS AND DISSEMINATION:

This protocol was approved by the Ethics Committee (EC) for Research UZ/KU Leuven, Belgium, the coordinating EC in Germany (Bei Der LMU München), the coordinating EC in the UK (West Midlands-South Birmingham Research), the EC of Hospital Puerta de Hierro, Madrid, Spain, the EC of Göteborg, Sweden, the coordinating EC in France, the EC of Padova, Italy and the EC of the University of Vienna, Austria. This study will be conducted in accordance with current local regulations and international applicable regulatory requirements according to the principles of the Declaration of Helsinki and ISO14155:2020. Main primary and secondary outcomes will be published on modified intention-to-treat population and per-protocol population.

TRIAL REGISTRATION NUMBER:

NCT03991923.

IMPORTANCE:

The effectiveness of goal-directed care to reduce loss of brain-dead potential donors to cardiac arrest is unclear.

OBJECTIVE:

To evaluate the effectiveness of an evidence-based, goal-directed checklist in the clinical management of brain-dead potential donors in the intensive care unit (ICU).

DESIGN, SETTING, AND PARTICIPANTS:

The Donation Network to Optimize Organ Recovery Study (DONORS) was an open-label, parallel-group cluster randomized clinical trial in Brazil. Enrollment and follow-up were conducted from June 20, 2017, to November 30, 2019. Hospital ICUs that reported 10 or more brain deaths in the previous 2 years were included. Consecutive brain-dead potential donors in the ICU aged 14 to 90 years with a condition consistent with brain death after the first clinical examination were enrolled. Participants were randomized to either the intervention group or the control group. The intention-to-treat data analysis was conducted from June 15 to August 30, 2020.

INTERVENTIONS:

Hospital staff in the intervention group were instructed to administer to brain-dead potential donors in the intervention group an evidence-based checklist with 13 clinical goals and 14 corresponding actions to guide care, every 6 hours, from study enrollment to organ retrieval. The control group provided or received usual care.

MAIN OUTCOMES AND MEASURES:

The primary outcome was loss of brain-dead potential donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed the effect of adherence to the checklist in the intervention group.

RESULTS:

Among the 1771 brain-dead potential donors screened in 63 hospitals, 1535 were included. These patients included 673 males (59.2%) and had a median (IQR) age of 51 (36.3-62.0) years. The main cause of brain injury was stroke (877 [57.1%]), followed by trauma (485 [31.6%]). Of the 63 hospitals, 31 (49.2%) were assigned to the intervention group (743 [48.4%] brain-dead potential donors) and 32 (50.8%) to the control group (792 [51.6%] brain-dead potential donors). Seventy potential donors (9.4%) at intervention hospitals and 117 (14.8%) at control hospitals met the primary outcome (risk ratio [RR], 0.70; 95% CI, 0.46-1.08; P = .11). The primary outcome rate was lower in those with adherence higher than 79.0% than in the control group (5.3% vs 14.8%; RR, 0.41; 95% CI, 0.22-0.78; P = .006).

CONCLUSIONS AND RELEVANCE:

This cluster randomized clinical trial was inconclusive in determining whether the overall use of an evidence-based, goal-directed checklist reduced brain-dead potential donor loss to cardiac arrest. The findings suggest that use of such a checklist has limited effectiveness without adherence to the actions recommended in this checklist.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier: NCT03179020.

BACKGROUND:

Refractory out-of-hospital cardiac arrest (OHCA) has a poor outcome. In patients, who cannot be rescued despite using advanced techniques like extracorporeal cardiopulmonary resuscitation (ECPR), organ donation may be considered. This study aims to evaluate, in refractory OHCA, how ECPR versus a standard-based approach allows organ donorship.

METHODS:

The Prague OHCA trial randomized adults with a witnessed refractory OHCA of presumed cardiac origin to either an ECPR-based or standard approach. Patients who died of brain death or those who died of primary circulatory reasons and were not candidates for cardiac transplantation or durable ventricle assist device were evaluated as potential organ donors by a transplant center. In this post-hoc analysis, the effect on organ donation rates and one-year organ survival in recipients was examined.

RESULTS:

Out of 256 enrolled patients, 75 (29%) died prehospitally or within 1 hour after admission and 107 (42%) during the hospital stay. From a total of 24 considered donors, 21 and 3 (p = 0.01) were recruited from the ECPR vs standard approach arm, respectively. Fifteen brain-dead and none cardiac-dead subjects were ultimately accepted, 13 from the ECPR and two from the standard strategy group. A total of 36 organs were harvested. The organs were successfully transplanted into 34 recipients. All transplanted organs were fully functional, and none of the recipients died due to graft failure within the one-year period post-transplant.

CONCLUSION:

The ECPR-based approach in the refractory OHCA trial is associated with increased organ donorship and an excellent outcome of transplanted organs.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier: NCT01511666. Registered January 19, 2012.

An ambulatory medication safety dashboard was developed to identify missing labs, concerning labs, drug interactions, nonadherence, and transitions in care. This system was tested in a 2-year, prospective, cluster-randomized, controlled multicenter study. Pharmacists at 5 intervention sites used the dashboard to address medication safety issues, compared with usual care provided at 5 control sites. A total of 2196 transplant events were included (1300 intervention vs 896 control). During the 2-year study, the intervention arm had a 11.3% (95% confidence interval, 7.1%-15.5%) absolute risk reduction of having ≥1 emergency department (ED) visit (44.2% vs 55.5%, respectively; P < .001, respectively) and a 12.3% (95% confidence interval, 8.2%-16.4%) absolute risk reduction of having ≥1 hospitalization (30.1% vs 42.4%, respectively; P < .001). In those with ≥1 event, the median ED visit rate (2 [interquartile range (IQR) 1, 5] vs 2 [IQR 1, 4]; P = .510) and hospitalization rate (2 [IQR 1, 3] vs 2 [IQR 1, 3]; P = .380) were similar. Treatment effect varied by comorbidity burden, previous ED visits or hospitalizations, and heart or lung recipients. A bioinformatics dashboard-enabled, pharmacist-led intervention reduced the risk of having at least one ED visit or hospitalization, predominantly demonstrated in lower risk patients.

BACKGROUND:

A significant number of pediatric heart transplant recipients and their families experience post-traumatic stress symptoms following transplantation, which can impact recipient behavioral and medical health outcomes. Preventive behavioral health interventions may improve outcomes, especially if interventions can be delivered at a distance to decrease barriers to mental health care. This pilot study examined the acceptability and accessibility of an evidence-informed resilience training program delivered using a video telehealth platform. A secondary aim was to assess the preliminary efficacy of the intervention on recipient behavioral health outcomes, perceived barriers to recipient medication adherence, parent behavioral health outcomes, and family functioning.

METHODS:

Seventeen heart transplant recipients (8-18 years old) and their families were recruited and randomly assigned to a treatment as usual (n = 8) or an intervention group (n = 9). Baseline assessment data collected included demographic information and validated behavioral health measures. Follow-up assessments included the validated measures and acceptability and satisfaction ratings.

RESULTS:

The study demonstrated that the program has high acceptability by recipients and parents, and a positive impact on recipients and parents, including significant reductions in youth behavioral difficulties as well as parent depression and post-traumatic stress symptoms.

CONCLUSIONS:

Results of this study are promising and call for further evaluation of hybrid delivery models for behavioral health screening and prevention interventions for pediatric heart transplant recipients and their families.