HTx Candidates Research Articles

An explainable machine learning approach using contemporary UNOS data to identify patients who fail to bridge to heart transplantation.

The use of Intra-aortic Balloon Pump (IABP) and Impella devices as a bridge to heart transplantation (HTx) has increased significantly in recent times. This study aimed to create and validate an explainable machine learning (ML) model that can predict the failure of status two listings and identify the clinical features that significantly impact this outcome. We used the UNOS registry database to identify HTx candidates listed as UNOS Status 2 between 2018 and 2022 and supported with either Impella (5.0 or 5.5) or IABP. We used the eXtreme Gradient Boosting (XGBoost) algorithm to build and validate ML models. We developed two models: (1) a comprehensive model that included all patients in our cohort and (2) separate models designed for each of the 11 UNOS regions. We analyzed data from 4,178 patients listed as Status 2. Out of them, 12% had primary outcomes indicating Status 2 failure. Our ML models were based on 19 variables from the UNOS data. The comprehensive model had an area under the curve (AUC) of 0.71 (±0.03), with a range between 0.44 (±0.08) and 0.74 (±0.01) across different regions. The models' specificity ranged from 0.75 to 0.96. The top five most important predictors were the number of inotropes, creatinine, sodium, BMI, and blood group. Using ML is clinically valuable for highlighting patients at risk, enabling healthcare providers to offer intensified monitoring, optimization, and care escalation selectively.

Cardiac transplantation in adult congenital heart disease: a narrative review.

As more children with congenital heart disease survive to adulthood, adult congenital heart disease (ACHD) prevalence will increase (currently ~1 million US patients). Heart failure (HF) accounts for 26-42% of ACHD deaths. The rate of ACHD heart transplantations (ACHD HTx) is also increasing. We describe the ACHD HTx recipient/candidate cohort, analyze ACHD HTx outcomes, identify ACHD HTx specific challenges, and discuss opportunities to better serve more patients with ACHD HF. PubMed literature search including articles published from 2010-2023. Reviewed 89 studies, 67 included. Our search focused on the challenges of ACHD HTx and potential solutions. ACHD HTx recipients are young [median age 35 years, interquartile range (IQR): 24-46 years]. 87-95% of ACHD HTx recipients had prior cardiac surgery. The most common underlying diagnoses include transposition of the great arteries (31%) and Fontan/Glenn circulation (28%). 63% of listed ACHD HTx candidates received a transplant within one year of listing. Post-transplant 1-year survival is 80%, 5-year survival 74%, and 10-year survival 59%. There are 4 unique ACHD HTx challenges: (I) difficulty in assessing pulmonary hypertension, resulting in some centers selecting oversized donor hearts. However, selecting oversized hearts does not improve post-operative mortality and could prolong waitlist time. (II) Increased immunologic sensitization, increasing rejection risk. Desensitization therapy has enabled sensitized HTx recipients to enjoy outcomes similar to non-sensitized recipients. (III) Procedural complexity with ~30% of cases requiring additional surgical reconstruction. Detailed multidisciplinary planning, extensive imaging, and transferring the patient into the operating room early can help manage the complexities and reduce organ ischemic time. (IV) Increased intraoperative bleeding due to patients' surgical histories and circulatory collaterals. Preoperative collateral coil embolization and select utilization of hypothermic circulatory arrest can help reduce bleeding. Additional Fontan specific challenges include extensive great artery repair, liver failure, plastic bronchitis, and protein loss enteropathy. Finally, given limited donor heart availability, mechanical circulatory support is a promising technology for patients with ACHD HF. The prevalence of ACHD HTx is slowly but steadily increasing. The operational complexity of ACHD HTx can be managed, and the majority of recipients have excellent outcomes (59% 10-year survival).

Graft preservation in heart transplantation: current approaches.

Heart transplantation (HTx) represents the current best surgical treatment for patients affected by end-stage heart failure. However, with the improvement of medical and interventional therapies, the population of HTx candidates is increasingly old and at high-risk for mortality and complications. Moreover, the use of "extended donor criteria" to deal with the shortage of donors could increase the risk of worse outcomes after HTx. In this setting, the strategy of donor organ preservation could significantly affect HTx results. The most widely used technique for donor organ preservation is static cold storage in ice. New techniques that are clinically being used for donor heart preservation include static controlled hypothermia and machine perfusion (MP) systems. Controlled hypothermia allows for a monitored cold storage between 4°C and 8°C. This simple technique seems to better preserve the donor heart when compared to ice, probably avoiding tissue injury due to sub-zero °C temperatures. MP platforms are divided in normothermic and hypothermic, and continuously perfuse the donor heart, reducing ischemic time, a well-known independent risk factor for mortality after HTx. Also, normothermic MP permits to evaluate marginal donor grafts, and could represent a safe and effective technique to expand the available donor pool. However, despite the increasing number of donor hearts preserved with these new approaches, whether these techniques could be considered superior to traditional CS still represents a matter of debate. The aim of this review is to summarize and critically assess the available clinical data on donor heart preservation strategies employed for HTx.

Uso de un sistema extracorpóreo de asistencia circulatoria de flujo continuo, corta duración e inserción quirúrgica como puente a trasplante

Introduction and objectivesWe aimed to describe the clinical outcomes of the use of the CentriMag acute circulatory support system as a bridge to emergency heart transplantation (HTx). MethodsWe 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. ResultsThe 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. ConclusionsIn 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.

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

Introduction and objectivesWe aimed to describe the clinical outcomes of the use of the CentriMag acute circulatory support system as a bridge to emergency heart transplantation (HTx). MethodsWe 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. ResultsThe 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. ConclusionsIn 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.

Prioritizing the Sickest Among the Sickest: A Matter of Tact and Moderation, but the Game Is Worth the Candle.

Prioritizing the Sickest Among the Sickest: A Matter of Tact and Moderation, but the Game Is Worth the Candle.

Impact of the 2018 French allocation scheme on the profile of heart transplantation candidates, recipients and donors: Insights from a high-volume center

In 2018, a new cardiac allograft allocation scheme based on an individual scoring system considering both the risk of death on the waitlist and after heart transplantation (HTx) was implemented in France. We aimed to assess the impact of this new scheme on the profile of HTx candidates and recipients. In this single-center retrospective study, we included consecutive patients listed and/or transplanted between 01/01/2012 and 09/30/2021 at La Pitié-Salpêtrière hospital. Baseline characteristics of patients were retrieved from the national CRISTAL registry and were compared according to the type of allocation scheme (before or after 2018). A total of 1109 newly listed HTx candidates and 885 HTx recipients were included. One-year post-listing and post-transplant mortality were 14% and 19%, respectively. At listing, the proportion of candidates on inotropes significantly declined following the scheme update (26.3% compared to 20.8%, P = 0.037), reflecting a change in medical practice. At transplant, recipients had a worse renal function (estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2: old scheme = 30.3%; new scheme: 47.3%, P < 0.001), and were more likely to be on ECMO support (27.3% compared to 34.2%, P = 0.029) with the new scheme, reflecting the prioritization of more severe patients. Waitlist and post-transplant outcomes were not significantly influenced by the of the new allocation system. The implementation of the 2018 French allocation scheme had limited impact on the profiles of HTx candidates but selected more severe patients for HTx without significant impact on post-transplant outcomes.

The impact of the United Network of Organ Sharing allocation change on waitlist trajectories of inpatients listed with inotropic support: A single-center analysis.

In the United Network of Organ Sharing (UNOS) allocation scheme prior to October 18, 2018, heart transplant (HTx) candidates with extracorporeal membrane oxygenation (ECMO), temporary mechanical circulatory support (MCS), or pulmonary artery (PA) catheter inotropic support all received Status 1A priority. In revised scheme, patients with PA catheter and inotropic support are Status 3 after those on ECMO (Status 1) or temporary MCS (Status 2). We examined the impact of the allocation change on HTx candidates listed Status 1A versus Status 3 at a high-volume transplant center. Between January 2017 and January 2021, 75 patients were listed with a PA catheter and inotropic support prior to the allocation change (Era 1) and 48 were listed after (Era 2). Clinical characteristics and outcomes were compared for these 123 patients. Heart transplant (HTx) candidates in Era 2 had higher median inotrope doses at listing. There was no significant difference in inpatient wait list days (12vs. 20 days, P=.15), transition to temporary MCS (33.3%vs. 22.7%, P=.15), or wait list mortality (6.3%vs. 4.0%, P=.68). There was also no significant difference in survival to transplantation (91.7%vs. 94.7%, P=.71). There were no differences in post-transplant outcomes including 1-year survival (88.6%vs. 93.0%, P=.38). At a high-volume transplant center, the UNOS allocation change did not result in increased wait list time, use of temporary MCS, or mortality on the waitlist or post-transplant for candidates on inotropic support with continuous hemodynamic monitoring.

Hemodynamic markers of pulmonary vasculopathy for prediction of early right heart failure and mortality after heart transplantation

Elevated pulmonary vascular resistance (PVR) is broadly accepted as an imminent risk factor for mortality after heart transplantation (HTx). However, no current HTx recipient risk score includes PVR or other hemodynamic parameters. This study examined the utility of various hemodynamic parameters for risk stratification in a contemporary HTx population. Patients from seven German HTx centers undergoing HTx between 2011 and 2015 were included retrospectively. Established risk factors and complete hemodynamic datasets before HTx were analyzed. Outcome measures were overall all-cause mortality, 12-month mortality, and right heart failure (RHF) after HTx. The final analysis included 333 patients (28% female) with a median age of 54 (IQR 46-60) years. The median mean pulmonary artery pressure was 30 (IQR 23-38) mm Hg, transpulmonary gradient 8 (IQR 5-10) mm Hg, and PVR 2.1 (IQR 1.5-2.9) Wood units. Overall mortality was 35.7%, 12-month mortality was 23.7%, and the incidence of early RHF was 22.8%, which was significantly associated with overall mortality (log-rank HR 4.11, 95% CI 2.47-6.84; log-rank p < .0001). Pulmonary arterial elastance (Ea) was associated with overall mortality (HR 1.74, 95% CI 1.25-2.30; p < .001) independent of other non-hemodynamic risk factors. Ea values below a calculated cutoff represented a significantly reduced mortality risk (HR 0.38, 95% CI 0.19-0.76; p < .0001). PVR with the established cutoff of 3.0 WU was not significant. Ea was also significantly associated with 12-month mortality and RHF. Ea showed a strong impact on post-transplant mortality and RHF and should become part of the routine hemodynamic evaluation in HTx candidates.

THE TELL-TALE HEART. MACHINE PERFUSION IN HEART TRANSPLANTATION

Hear Transplantation (HTx) is the current best surgical treatment for patients affected by end-stage heart failure. However, the improvement of medical and interventional therapies has led to an increasingly old and high-risk population of HTx candidates. Moreover, the use of “extended” donor criteria to face the shortage of donors could increase the risk of worse outcomes after HTx. In this setting, donor organ preservation strategy could significantly affect HTx results. The cold storage (CS) represents the standard practice worldwide for donor graft preservation. However, prolonged ischemic time is known to be an independent risk factor for mortality after HTx. Machine perfusion (MP) systems continuously perfuse the donor heart, reducing ischemic time. Also, since MP permits to evaluate marginal donor organs, they could represent a safe and effective technique to expand the available donor pool. Despite the increasing number of donor hearts preserved with MP, whether MP could be considered superior to traditional CS still represents a matter of debate. The aim of this paper is to summarize and critically assess the available clinical data on MP employed for HTx.

Barriers and misconceptions of ex situ heart perfusion in pediatric donation.

Despite efforts, pediatric HTx candidates continue to have high waitlist mortality due to limited donor availability. However, there is a significant number of offered hearts not used due to concerns of viability. ESHP is a method for continuous perfusion of the donor heart that allows assessment and extended out-of-body time. It is imperative to understand healthcare stakeholders' perspectives on ESHP for implementation. Therefore, the aims of this qualitative study were to: (1) Explore pediatric stakeholders' perspectives toward ESHP; and (2) Identify barriers to widespread adoption of this technology. Virtual focus groups were completed with pediatric HTx healthcare professional stakeholders. Following transcription of audio-recordings, the material was analyzed using content analysis. Four focus groups were completed with 17 participants, representing 12 institutions and three countries. Focus groups revealed varied understanding of both current and potential uses of ESHP. Participants did see the potential benefits of extending out-of-body time for and the ability to evaluate donor heart quality. However, concerns were expressed relating to patient selection, wait-list times, post-HTx outcomes, adverse events, and technical issues. These were felt to be important to understand in order to justify the costs of ESHP and impact on the healthcare system. This project represents the first qualitative formative evaluation of ESHP in pediatrics. The knowledge gained from stakeholders will form the basis for education initiatives, clinical trial design, and roll-out of new ESHP technologies designed for pediatrics.

Hemodynamic Implications of Sildenafil in Candidates for Heart Transplantation with Group 2 Pulmonary Hypertension: A Single Latin-American Center Registry

<h3>Purpose</h3> Heart failure is the most common cause of Group 2 pulmonary hypertension (PH). When it becomes fixed, it increases morbidity and mortality in heart transplantation (HTx). Reversing this situation is difficult, but the use of selective pulmonary vasodilators such as sildenafil could be a simple pharmacological tool in this setting. <h3>Objectives</h3> To analyze the prevalence of PH and the effect of Sildenafil in HTx candidates and its impact on mortality. <h3>Methods</h3> Patients who had undergone HTx over a ten-year period were analyzed retrospectively. PH was defined as mean pulmonary artery pressure (PAP) ≥25mmHg and/or pulmonary vascular resistance (PVR) > 3UW. Among the P with PH those who received sildenafil (Group A) and those who did not (Group B) were compared. Quantitative variables were compared with t-test or Mann-Whitney, and nominals with Fisher's test. Survival was analyzed using the log-rank test. A p<0.05 was considered significant <h3>Results</h3> From 01/2008 to 12/2018, 294 P undergone HTx, 30 P (10%) with combined transplantation, pediatric, re-transplantation, and without data, were excluded. Of the 217 P analyzed, 153 P (70%) presented PH, of whom 77P (51%) received sildenafil. Baseline characteristics are described in Table 1a. The causes for which 76 P (49%) with PH did not receive treatment with sildenafil were: intolerance to vasodilators, treatment with vasopressors, pulmonary congestion, and a tendency to reserve selective pulmonary vasodilators for those patients under previous treatment with ACEIs, ARAII or ARNI. Table 1b describes the hemodynamic variables for both groups. Table 1a shows a decrease in MPAP, transpulmonary gradient, and PVR without changes in cardiac index in Group A. There was no difference in mortality between both groups (graphic 1) <h3>Conclusion</h3> The use of Sildenafil in P with Group 2 PH could be an effective strategy to improve the hemodynamic profile during the candidacy for HTx, without impact on survival.

Facilitators and Barriers of Ex Situ Heart Perfusion (ESHP) in Pediatric Donation

Purpose Despite medical advances, pediatric heart transplant (HTx) candidates are at significant risk for morbidity and mortality. Ex Situ Heart Perfusion (ESHP) is a method for continuous perfusion of the donor heart, allowing for extended out-of-body time and functional assessment of the organ. Currently available devices are targeted to adults and have been used in the context of neurological and circulatory determination of death. Pediatric-specific devices are in development, but before adoption, knowledge of stakeholder attitudes towards ESHP is needed. The aim of this study was to explore pediatric HTx stakeholders’ understanding and perspectives of ESHP. Methods A virtual focus group study was conducted international pediatric HTx stakeholders. Data was analyzed using qualitative content analysis. Results There were 17 participants from 12 institutions representing 3 countries. Findings were organized under the topics of: general knowledge, indications, risks, adoption/barriers, and pediatric-specific considerations. Knowledge ranged from limited grasp of the technology to first-hand experience in clinical practice. Discussions encircled the current use of ESHP in adult-sized HTx candidates, and potential future uses in infants and young children. In all focus groups, it was discussed that risks need to be considered regarding ESHP itself, including the potential of damaging the donor heart, subjecting recipients to unquantified risks, and potential adverse impacts on pediatric HTx programs if poor outcomes occur. Concerns surrounding the material costs and human resources associated with ESHP were also discussed. While all discussions highlighted the need for pediatric ESHP devices, participants emphasized the need for rigorous research and implementation oversight of ESHP to navigate ethical issues, program administration, and support best practices in the context of technological innovation. Conclusion For stakeholders to become adopters of ESHP, they must understand the goals, benefits, and risks. This project represents the first step in the adoption of new technology, and the knowledge gained will form the basis for future education, clinical trial design, and rollout of pediatric ESHP technologies. Despite medical advances, pediatric heart transplant (HTx) candidates are at significant risk for morbidity and mortality. Ex Situ Heart Perfusion (ESHP) is a method for continuous perfusion of the donor heart, allowing for extended out-of-body time and functional assessment of the organ. Currently available devices are targeted to adults and have been used in the context of neurological and circulatory determination of death. Pediatric-specific devices are in development, but before adoption, knowledge of stakeholder attitudes towards ESHP is needed. The aim of this study was to explore pediatric HTx stakeholders’ understanding and perspectives of ESHP. A virtual focus group study was conducted international pediatric HTx stakeholders. Data was analyzed using qualitative content analysis. There were 17 participants from 12 institutions representing 3 countries. Findings were organized under the topics of: general knowledge, indications, risks, adoption/barriers, and pediatric-specific considerations. Knowledge ranged from limited grasp of the technology to first-hand experience in clinical practice. Discussions encircled the current use of ESHP in adult-sized HTx candidates, and potential future uses in infants and young children. In all focus groups, it was discussed that risks need to be considered regarding ESHP itself, including the potential of damaging the donor heart, subjecting recipients to unquantified risks, and potential adverse impacts on pediatric HTx programs if poor outcomes occur. Concerns surrounding the material costs and human resources associated with ESHP were also discussed. While all discussions highlighted the need for pediatric ESHP devices, participants emphasized the need for rigorous research and implementation oversight of ESHP to navigate ethical issues, program administration, and support best practices in the context of technological innovation. For stakeholders to become adopters of ESHP, they must understand the goals, benefits, and risks. This project represents the first step in the adoption of new technology, and the knowledge gained will form the basis for future education, clinical trial design, and rollout of pediatric ESHP technologies.

Early report from the Pediatric Heart Transplant Society on COVID-19 infections in pediatric heart transplant candidates and recipients

BackgroundReports focused on adult heart transplant (HTx) recipients with COVID-19 suggest an increased risk of severe disease, however; it is unclear if this holds true for pediatric HTx patients, given the typically milder course of illness in children in general with COVID-19. We sought to rapidly implement a system for multi-center data collection on pediatric HTx candidates and recipients, with the aim of describing the patient population and infection related outcomes.MethodsThe Pediatric Heart Transplant Society (PHTS) is a multi-center collaboration that seeks to improve the outcomes of children who are listed and undergo HTx. The society consists of pediatric HTx centers in North America (n = 53), UK (n = 2), and Brazil (n = 1). In response to the pandemic, PHTS developed a web-based platform to collect COVID-19 specific data on pediatric HTx candidates and recipients. Non-PHTS centers were also invited to submit data. Data fields included pre-and post-HTx patient characteristics, presumed versus documented infection, need for hospitalization (including ICU and ventilator use), treatments administered, and 30-day outcome (resolution, death, sequelae, and or unresolved)ResultsData collection was initiated on 4/30/20. As of 03/15/21 there were 225 patients [19 pre-HTx and 206 post-HTx, median age 14 years (IQR 7, 18)] reported from 41 centers. Hospitalization occurred in 42% (n = 8) of the pre-HTx and 21% (n=43) of the post-HTx patients. Among the patients listed for HTx, 21% (n = 4) required ICU and 10.5% (n = 2) were mechanically ventilated. Among post-HTx patients, 7% (n = 14) required ICU and 1% (n = 3) were mechanically ventilated. At 30 days, the majority of patients had resolution of symptoms (94.7% pre-HTx, 95.6% post-HTx). One death was reported in a post-HTx patient prior to 30 days from onset of COVID-19 illness.ConclusionsThese data demonstrate the ability to rapidly adapt the PHTS data collection infrastructure in response to a novel infection and represent the first known multi-center report of characteristics and early outcomes for patients listed and following pediatric HTx with COVID-19. Hospitalization appears to be more common for both candidates and recipients due to COVID-19 than for the general pediatric population though stays were short and mortality minimal.

Abstract 11240: Capillary Rarefaction and Right Ventricular Dysfunction in Advanced HFrEF: Human Tissue Histomorphometry Analysis

Introduction: Right ventricular dysfunction (RVD) limits survival in heart failure (HF). Besides pulmonary hypertension (PH), load-independent mechanisms may contribute to RVD. In experimental PH, loss of myocardial capillary density (rarefaction) was implicated in the faster decline of RV function. Hypothesis: To elucidate the role of rarefaction in development of RVD in HFrEF. Methods: We examined RV fractional area change (RV FAC%) prior heart Tx (median -57 days) in 124 consecutive HTx candidates (non-LVAD) and harvested RV free wall at HTx from patients in the bottom (Q1: 10-17%) and top (Q4: 32-42%) quartiles of pre-HTx RV FAC%. As controls (Con), we obtained RV samples from 20 unused heart donors. Quantitative histomorphometry and mRNA gene expression were studied. Results: HF (65% non-ischemic) and Con were matched by similar age, gender and BMI. HF patients had larger and more dysfunctional RV (RVD1 46 vs 32 mm, p&lt;0.001, RV FAC 25±10%). Compared to Con, RV from HF displayed significant upregulation of genes for PDK4 (Pyruvate Dehydrogenase Kinase4), NPPA (Natriuretic peptide A), BDH1 (β-OH-butyrate dehydrogenase), and downregulation of MYH6 (Myosin Heavy Chain 6). In HF vs Con, RV CM diameter was increased (25±6 vs 15±4 μm, p&lt;0.001), but RV capillary density was lower (939±474 vs 1457±670 n/mm -2 , p=0.007), even if adjusted to CM diameter (39 vs 102 mm -1 , p=0.0005) or area (Fig). HF patients from Q1 and Q4 RV FAC differed by higher PH (mPA 37 vs 31 mmHg, p=0.01), larger RV size (48 vs 43 mm, p=0.01) and higher PCWP (27 vs 22, p=0.002), but there was no difference in capillary density (unadjusted or per CM diameter/area, Fig) or gene expression profile, HF etiology or comorbidities. Conclusions: Compared to Con, RV of HF patients shows reduced capillary density, metabolic and myofilament remodeling. Yet, HF patients with lower RV FAC% do not differ from those with less impaired RV function, suggesting that capillary rarefaction per se does not explain progression of RVD in HF.

Moderate acceptance of COVID-19 vaccination in patients pre- and post-heart transplantation: Experiences from a German Transplant Centre.

Introduction and objectivesPatients awaiting heart transplantation (HTx) are at increased risk developing severe coronavirus disease 2019 (COVID‐19). Patients supported by a left ventricular assist device (LVAD) face additional risks due to coagulopathies during COVID‐19. Following HTx, elevated risk factors for severe COVID‐19 persist due to chronic immunosuppression and frequent comorbidities. Taken together, COVID‐19 vaccination is of critical importance in all three patient cohorts. Here, we report our experience to deliver COVID‐19 vaccination in a German transplant center.Methods and resultsWe screened 211 patients for contraindications and offered the remaining 186 eligible patients COVID‐19 vaccination. Of those, 133 patients (71%) accepted the offer and were vaccinated. Acceptance of vaccination differed between HTx recipients (84 of 113, 74%), patients on the waiting list (34 of 47, 72%), and patients with LVAD support (28 of 50, 56%). The LVAD cohort demonstrated lower acceptance levels for vaccination compared to HTx recipients and patients awaiting HTx (74% vs. 56%; p = 0.028).ConclusionWe demonstrate for the first time only moderate acceptance levels of COVID‐19 vaccination in HTx recipients and candidates on the waiting list compared to general population, despite perceived high‐risk for severe disease. Additionally, those supported by LVAD have even lower adherence. Efforts may need to be made to increase acceptance in this vulnerable as well as cost‐intensive patient cohort.

Impact of Ventricular Assist Devices on Cardiac Transplant Recipient Survival Outcomes

PurposeLeft ventricular assist devices (LVAD) have become a viable option for patients with end stage heart failure waiting on the cardiac transplant list. Heartmate II (HMII) and III (HM III) are indicated for use for bridge-to-transplantation (BTT). Survival outcomes of patients undergoing BTT therapies were evaluated.MethodsA retrospective analysis at our single center database was performed on patients who received a HTx from March 2012 to October 2020 (n=161). Patients were placed into the following cohorts: 1) HTx only (n=96) 2) HMII + HTx later (BTT) (n=46) 3) HMIII + HTx later (BTT) (n=10) 4) Other VAD + HTx later (BTT) (n=9). Kaplan Meier and Cox Regression Analysis were completed. P-value<0.05 was considered significant.ResultsThere was no difference between patient groups in regards to warm ischemic time, CPB time, ischemic time, and length of stay. Compared to the HTx only group, the HMII + HTx group had a significantly higher XC time (p=0.008). In addition, the Other VAD + HTx group was significantly younger than the HTx Only and HMII + HTx group (p=0.0005; p=0.002). The Kaplan Meier analysis showed no significant difference in survival between all patient groups (p=0.407). Cox Regression analysis across all groups showed that longer CPB times (HR=1.01; p=0.002) and recipient race (HR=0.966; p=0.018), specifically Caucasians and Hispanics compared to African Americans (p=0.012; p=0.022), were associated with poorer survival outcomes. Through Cox Regression, different INTERMACS listing criteria also significantly affected survival in all patient groups (p<0.0001).ConclusionThe use of BTT therapies did not affect survival outcomes in between HTx recipients. INTERMACS listing criteria can be considered for identifying immediate HTx candidates. Left ventricular assist devices (LVAD) have become a viable option for patients with end stage heart failure waiting on the cardiac transplant list. Heartmate II (HMII) and III (HM III) are indicated for use for bridge-to-transplantation (BTT). Survival outcomes of patients undergoing BTT therapies were evaluated. A retrospective analysis at our single center database was performed on patients who received a HTx from March 2012 to October 2020 (n=161). Patients were placed into the following cohorts: 1) HTx only (n=96) 2) HMII + HTx later (BTT) (n=46) 3) HMIII + HTx later (BTT) (n=10) 4) Other VAD + HTx later (BTT) (n=9). Kaplan Meier and Cox Regression Analysis were completed. P-value<0.05 was considered significant. There was no difference between patient groups in regards to warm ischemic time, CPB time, ischemic time, and length of stay. Compared to the HTx only group, the HMII + HTx group had a significantly higher XC time (p=0.008). In addition, the Other VAD + HTx group was significantly younger than the HTx Only and HMII + HTx group (p=0.0005; p=0.002). The Kaplan Meier analysis showed no significant difference in survival between all patient groups (p=0.407). Cox Regression analysis across all groups showed that longer CPB times (HR=1.01; p=0.002) and recipient race (HR=0.966; p=0.018), specifically Caucasians and Hispanics compared to African Americans (p=0.012; p=0.022), were associated with poorer survival outcomes. Through Cox Regression, different INTERMACS listing criteria also significantly affected survival in all patient groups (p<0.0001). The use of BTT therapies did not affect survival outcomes in between HTx recipients. INTERMACS listing criteria can be considered for identifying immediate HTx candidates.

From Heart Failure via Biventricular Assist Device to Heart Transplantation

Purpose The Berlin Heart® EXCOR biventricular assist device (BVAD) can be used in pediatric as well as adult patients for bridge to heart transplantation (HTX). This study represents the largest population of BVAD implantations in adult patients reported so far. Methods Adult patients (>16 years) receiving a BVAD from 2006-2020 were included. Patient characteristics and outcomes were analyzed in a retrospective single center study. Results Out of the 54 patients, 45 (83%) were male, mean age of 47.4 ± 11.8 years. Mean body mass index (BMI) was 26 kg/m2 with 15 patients >30kg/m2 BMI. INTERMACS classifications were: I =23 patients (43%), II-III = 17 (31%) and IV-V= 14 (26%). Eight patients (14.8) had previous cardiac surgery before BVAD. 30% suffered from ischemic cardiomyopathy. Before BVAD 33 patients (61%) needed temporary MCS (IABP n=14, v-a ECMO n=26; with 7 patients (13%) receiving both). Mean ICU stay after BVAD was 30 days. 26 patients (48%) died on BVAD with mean time to death of 64.6 days. Causes of death were multiple organ failure (27%), septic shock (19%), cerebral hemorrhage (15%), bleeding (11%), cardiogenic shock (11%) and thrombembolic event (8%). In all 54 BVAD patients we performed 83 chamber exchanges. 28 patients were listed as high-urgency (HU) before HTX. Causes for HU-listing were VAD infections (46%, deteriorating HF under BVAD (18%), multiple VAD-related complications (14%), pump thrombosis (7%), stroke (7%), gastrointestinal bleeding (4%) and cardiac arrhythmia (4%). Complications after BVAD and HTX are listed in table 1. Mean time to HTX was 305 days. 30-day-survival after HTX was 96%. 1- and 3-year-mortality were 18 and 30% respectively. Post-HTX causes of death were cardiogenic (27%) and septic shock (36%). Conclusion These retrospective data show secondary organ failure and bleeding represented the main complications under BVAD support. Only 50% of BVAD patients were successfully transplanted but post HTX survival in BVAD patients was comparable to other HTX candidates.

Complications of left ventricular assist devices causing high urgency status on waiting list: impact on outcome after heart transplantation

AimsHeart transplantation (HTx) represents optimal care for advanced heart failure. Left ventricular assist devices (LVADs) are often needed as a bridge‐to‐transplant (BTT) therapy to support patients during the wait for a donor organ. Prolonged support increases the risk for LVAD complications that may affect the outcome after HTx.Methods and resultsA total of 342 patients undergoing HTx after LVAD as BTT in a 10‐year period in two German high‐volume HTx centres were retrospectively analysed. While 73 patients were transplanted without LVAD complications and with regular waiting list status (T, n = 73), the remaining 269 patients were transplanted with high urgency status (HU) and further divided with regard to the observed leading LVAD complications (infection: HU1, n = 91; thrombosis: HU2, n = 32; stroke: HU3, n = 38; right heart failure: HU4, n = 41; arrhythmia: HU5, n = 23; bleeding: HU6, n = 18; device malfunction: HU7, n = 26). Postoperative hospitalization was prolonged in patients with LVAD complications. Analyses of perioperative morbidity revealed no differences regarding primary graft dysfunction, renal failure, and neurological events except postoperative infections. Short‐term survival, as well as Kaplan–Meier survival analysis, indicated comparable results between the different study groups without disadvantages for patients with LVAD complications.ConclusionsLeft ventricular assist device therapy can impair the outcome after HTx. However, the occurrence of LVAD complications may not impact on outcome after HTx. Thus, we cannot support the prioritization or discrimination of HTx candidates according to distinct mechanical circulatory support‐associated complications. Future allocation strategies have to respect that device‐related complications may define urgency but do not impact on the outcome after HTx.

Changes in Heart Transplant Allocation Policy: "unintended" Consequences but Maybe Not so "unexpected…".

To the Editor: We read with great interest the article of JR Trivedi & MS Slaughter, which reported a dramatic increase in the number of patients listed and transplanted on acute mechanical support and in posttransplant mortality following the implementation of the new US heart transplantation (HTx) allocation scheme.1 Although not intended, these results may not be unexpected. Allocation schemes that prioritize patients according to the medical therapy they receive have always influenced medical practice. Gaming the waitlist by using unnecessary multiple inotrope therapy has already been demonstrated in the United States.2 Whereas its hemodynamic impact is minimal and it has not been shown to have any survival benefit in cardiogenic shock, the intraaortic balloon pump (IABP) has been given a high priority status in the new scheme.3 We believe that IABP represents a prototypal candidate for gaming the waitlist since the benefits in prioritization clearly outweigh the risks associated with this minimally invasive support. On reflection, the proportion of patients transplanted with IABP increased from 9% to 33%. The prioritization of HTx candidates based on an individual score, not taking into account medical practices but keeping the same principle of the “sickest first,” as has been the case in France since 2018, may be an attractive approach to avoid these drifts.4 A remaining key challenge for allocation is to estimate posttransplant mortality to avoid futile transplantations. The high scrutiny of US agencies has always been effective in maintaining excellent posttransplant results,5 but the recent scheme changes may have increased the number of high-risk HTx. In France, the high priority status given to patients on extracorporeal membrane oxygenator (ECMO) has been initially associated with very high-risk transplantations with unacceptably high posttransplant mortality.6 This has led to HTx being contraindicated for ECMO patients with a glomerular filtration rate below 40 ml/min. In our current allocation scheme, an individual scoring system allows the stratification of the risk of early posttransplant death and contraindicates very high-risk HTx.7 We believe that cardiac transplantation in patients previously stabilized with ECMO should not be seen as the devil, and the concept is different from bridging stable patients to transplantation with ECMO support, with the letter making no sense. Carefully selected ECMO patients can be excellent candidates for a direct HTx strategy. After the implementation of a specific ECMO protocol, which includes systematic reperfusion, percutaneous cannulation, IABP to unload the left ventricle, and an awake strategy, we reported favorable posttransplant outcomes for pre-HTx ECMO patients, comparable to those of patients without ECMO.8 In addition, survival benefit (the difference between survival after HTx and waiting list survival without HTx), which appears to be a more clinically relevant metric than the standard one-year posttransplant survival, is maximal for these patients.9,10 We think that the field of organ allocation would greatly benefit from international collaborative research, not only at the level of national agencies, but especially at the level of centers, which can provide both the heterogeneity between cohorts and highly phenotyped databases that are required to improve risk stratification and allocations schemes.