Patients Awaiting Heart Transplantation Research Articles

Heart Transplantation Outcomes in Patients With Hypertrophic Cardiomyopathy in the Era of Mechanical Circulatory Support.

Mechanical circulatory support has emerged as a vital therapeutic modality for patients awaiting heart transplantation (HT). However, it is unknown how it affected the characteristics and post-HT outcomes of patients with hypertrophic cardiomyopathy (HCM). This retrospective cohort study analyzed adult HT recipients from the International Society for Heart and Lung Transplantation registry (1998-2017). Two equal-duration eras were defined: era 1 1998-2007 and era 2 2008-2017. Patients with HCM were compared across the two eras (n1 = 742 and n2 = 1,211) and within each era, they were contrasted with individuals with nonischemic (NICM) (n1 = 15,964 and n2 = 20,394) and ischemic cardiomyopathy (ICM) (n1 = 14,140 and n2 = 12,986). Across eras, the number of HTs among patients with HCM increased by 63%. The rate of recipients with HCM in the intensive care unit (ICU) supported with intra-aortic balloon pump (IABP) increased, yet their pre-HT functional status improved, and 5 year post-HT survival remained unchanged and favorable. In era 2, at the time of HT, patients with HCM were more frequently than their NICM and ICM counterparts in the ICU and supported with inotropes. In the same era, 1 and 5 year survival were more favorable in HCM compared to ICM and comparable to NICM.

Extracorporeal cardiopulmonary resuscitation for a patient awaiting heart transplantation: a case report

Extracorporeal cardiopulmonary resuscitation for a patient awaiting heart transplantation: a case report

Abstract Tu058: Reverse Remodeling with LVAD Therapy is Associated with Alternative Splicing of CAMK2D

Therapies for end-stage heart failure are lacking and the number of patients awaiting heart transplants far outweighs availability. Left ventricular assist devices (LVADs) take over cardiac pump function and are used as a bridge-to-transplant. Notably, some patients on LVADs experience recovery of cardiac function and reversal of pathological cardiac remodeling; however, the molecular mechanisms underlying these favorable outcomes are unknown. In this study, we studied 19 paired pre- and post-LVAD samples with 10 clinically categorized as responders and 9 as non-responders. Bulk mRNA sequencing identified 486 differentially expressed genes post-LVAD, including reduced pro-inflammatory gene expression and increased expression of genes involved in metal ion binding; however, just 23 total genes were differentially expressed between responders and non-responders. To determine whether LVAD differentially impacted the proteome in responders and non-responders, we next performed quantitative proteomics on post-LVAD samples. This analysis identified 154 differentially expressed proteins and revealed that factors involved in mRNA processing were higher expressed in LVAD responders. Re-analysis of our mRNA sequencing data for gene isoforms identified that alternative splicing of calcium and calmodulin-dependent protein kinase 2-delta ( CAMK2D ) was the most significantly impacted event with non-responders having increased inclusion of exon 14 (denoting the B isoform), which encodes a nuclear localization sequence. Notably, there was a strong negative correlation between exon 14 inclusion and ΔLVEF post-LVAD. We validated these findings using targeted exon-specific quantitative PCR, which confirmed that expression of CAMK2D B was higher both pre- and post-LVAD in non-responders, while responders had post-LVAD levels matching non-failing controls. We next investigated whether responders and non-responders differed at the phospho-proteome level via mass spectrometry and found three serines in CaMK2δ exon 14 were the only differentially abundant phosphosites and all increased in non-responders. Localization studies in vitro with adenoviruses expressing phospho-null or phospho-mimetic CaMK2D B constructs revealed that these phosphorylation events precluded nuclear localization. In conclusion, we identified differential alternative splicing and phosphorylation of CaMK2δ in LVAD responders, which may represent novel therapeutic targets for heart failure recovery.

(1084) - Safety and Efficacy of Semaglutide Therapy in Advanced Heart Failure Patients Awaiting Heart Transplantation

(1084) - Safety and Efficacy of Semaglutide Therapy in Advanced Heart Failure Patients Awaiting Heart Transplantation

(1349) - Machine Learning for Predicting Waitlist Survival in Pediatric Patients Awaiting Heart Transplantation

(1349) - Machine Learning for Predicting Waitlist Survival in Pediatric Patients Awaiting Heart Transplantation

(292) - Clinical Deterioration in Stage 1 and 2 Single Ventricle Patients Awaiting Heart Transplant

(292) - Clinical Deterioration in Stage 1 and 2 Single Ventricle Patients Awaiting Heart Transplant

Cirbp suppression compromises DHODH-mediated ferroptosis defense and attenuates hypothermic cardioprotection in an aged donor transplantation model.

Hypothermia is commonly used to protect donor hearts during transplantation. However, patients transplanted with aged donor hearts still have severe myocardial injury and decreased survival rates, but the underlying mechanism remains unknown. Because aged hearts are not considered suitable for donation, the number of patients awaiting heart transplants is increasing. In this study, we examined whether hypothermic cardioprotection was attenuated in aged donor hearts during transplantation and evaluated potential therapeutic targets. Using a rat heart transplantation model, we found that hypothermic cardioprotection was impaired in aged donor hearts but preserved in young donor hearts. RNA-Seq showed that cold-inducible RNA-binding protein (Cirbp) expression was decreased in aged donor hearts, and these hearts showed severe ferroptosis after transplantation. The young donor hearts from Cirbp-KO rats exhibited attenuated hypothermic cardioprotection, but Cirbp overexpression in aged donor hearts ameliorated hypothermic cardioprotection. Cardiac proteomes revealed that dihydroorotate dehydrogenase (DHODH) expression was significantly decreased in Cirbp-KO donor hearts during transplantation. Consequently, DHODH-mediated ubiquinone reduction was compromised, thereby exacerbating cardiac lipid peroxidation and triggering ferroptosis after transplantation. A cardioplegic solution supplemented with CIRBP agonists improved hypothermic cardioprotection in aged donor hearts, indicating that this method has the potential to broaden the indications for using aged donor hearts in transplantation.

Heart transplantation from COVID-positive donors with 6-month follow-up: A case series.

Data on long term outcomes in heart transplant recipients from Coronavirus disease 2019 (COVID-19) positive donors are limited. We present a series of nine patients who underwent heart transplants from COVID-19 PCR-positive donors between November 2021 to August 2022 with mean follow-up of 12.12±3 months. All the recipients received two doses of COVID-19 vaccine and had at least 6 months follow-up. Eight recipients had acceptable long-term outcomes; one patient died during index admission from primary graft dysfunction. Details regarding donor and recipient characteristics, management and outcomes are provided. Two patients developed deep vein thrombosis, and one patient underwent pacemaker implantation for sinus node dysfunction. Among the surviving eight patients, none developed COVID-19 infection during follow-up period. There was no significant difference in outcome parameters when compared to patients who received hearts from donors who tested negative for COVID-19 during the same time period at our center. Keeping in mind the significant waitlist mortality in patients awaiting heart transplantation, COVID-19-positive donors should be considered for heart transplantation to help expand the donor pool and potentially reduce waitlist mortality.

An in vitro comparison of intra-operative isohemagglutinin and human leukocyte antigen removal techniques in pediatric heart transplantation

Background: Highly sensitized pediatric patients awaiting heart transplantation experience longer wait times and thus higher waitlist mortality. Similarly, children less than 2 years of age have increased waitlist times and mortality when compared to their older peers. To improve the likelihood of successful transplantation in these patients, various strategies have been utilized, including peri-operative plasmapheresis. However, limited data exists comparing plasmapheresis techniques for antibody reduction. This study’s aim was to compare the in vitro magnitude of isohemagglutinin titers (IT) and human leukocyte antigen (HLA) antibody removal and the time required between membrane-based plasmapheresis (MP) and centrifuge-based plasmapheresis (CP) incorporated into the extracorporeal (EC) circuit. Methods: Two MP (Prismaflex) and two CP (Spectra Optia, Terumo BCT) circuits were incorporated into four separate EC circuits primed with high titer, highly sensitized type O donor whole blood. Assays were performed to determine baseline IT and anti-HLA antibodies and then at 30-minute increments until completion of the run (two plasma volume exchanges) at two hours. Results: There was a decrease in anti-A and anti-B IgM and IgG titers with both MP and CP. Mean anti-A and anti-B titer reduction was by 4.625 titers (93.7% change) and 4.375 titers (93.8% change) using MP and CP, respectively. At 2 h of apheresis, CP reduced 62.5% of all ITs to ≤ 1:4, while MP reduced 50% of ITs to ≤ 1:4. Additionally, reduction of anti-HLA class II antibody to mean fluorescence intensity (MFI) <3000 was achieved with both MP and CP. At 2 h of apheresis, CP reduced MFI by 2–3.5 fold and MP reduced MFI by 1.7–2.5 fold. Both demonstrated similar hemolytic and thrombotic profiles. Conclusions: In this in vitro plasmapheresis model of IT and anti-HLA antibody reduction, both MP and CP incorporated into the EC circuit can be used quickly and effectively to reduce circulating antibodies. While CP may have some greater efficiency, further study is necessary to verify this in vivo.

P225 Daratumumab-induced interference with HLA crossmatching in cardiac amyloidosis patients awaiting heart transplantation

P225 Daratumumab-induced interference with HLA crossmatching in cardiac amyloidosis patients awaiting heart transplantation

Emerging Racial Differences in Heart Transplant Waitlist Outcomes for Patients on Temporary Mechanical Circulatory Support

Temporary mechanical circulatory support (tMCS) is increasingly used for patients awaiting heart transplantation. Although examples of systemic inequity in cardiac care have been described, biases in tMCS use are not well characterized. This study explores the racial disparities in tMCS use and waitlist outcomes. The United Network for Organ Sharing database was used to identify adults listed for first-time heart transplantation from 2015 to 2021. White and non-White patients on extracorporeal membrane oxygenation, intra-aortic balloon pump, or temporary left ventricular assist device were identified. Waitlist outcomes of mortality, transplantation, and delisting were analyzed by race using competing risks regression. The effect of the new heart allocation system was also assessed. A total of 16,811 patients were included in this study, with 10,377 self-identifying as White and 6,434 as non-White. White patients were more often male, privately ensured, and had less co-morbidities (p <0.05). tMCS use was found to be significantly higher in non-White patients (p <0.001). Among those on tMCS, non-White patients were more likely to be delisted because of illness (subhazard ratio 1.34 [1.09 to 1.63]) and less likely to die while on the waitlist (subhazard ratio 0.76 [0.61 to 0.93]). This disparity was not present before the implementation of the new heart allocation system. tMCS use was proportional to the risk factors identified in the non-White cohort. After the implementation of the new heart allocation system, White patients were more likely to die, whereas non-White patients were more likely to be delisted. Further work is needed to determine the causes of and potential solutions for disparities in the waitlist outcomes.

Pediatric risk to orthotopic heart transplant (PRO) score: Insights from United Network for Organ Sharing (UNOS) waitlist mortality findings.

Pediatric heart transplant candidates on the waitlist have the highest mortality rate among all solid organ transplants. A risk score incorporating a candidate's individual risk factors may better predict mortality on the waitlist and optimize organ allocation to the sickest of those awaiting transplant. Using the United Network for Organ Sharing (UNOS) database, we evaluated a total of 5542 patients aged 0-18 years old on the waitlist for a single, first time, heart transplant from January 2010 to June 2019. We performed a univariate analysis on two-thirds (N = 3705) of these patients to derive the factors most associated with waitlist mortality or delisting secondary to deterioration within 1 year. Those with a p <0.2 underwent a multivariate analysis and the resulting factors were used to build a prediction model using the Fine-Grey model analysis. This predictive scoring model was then validated on the remaining one-third of the patients (N = 1852). The Pediatric Risk to OHT (PRO) scoring model utilizes the following unique patient variables: blood type, diagnosis of congenital heart disease, weight, presence of ventilator support, presence of inotropic support, extracorporeal membrane oxygenation (ecmo) status, creatinine level, and region. A higher score indicates an increased risk of mortality. The PRO score had a predictive strength of 0.762 as measured by area under the ROC curve at 1 year. The PRO score is an improved predictive model with the potential to better assess mortality for patients awaiting heart transplant.

Diuretic dose is a strong prognostic factor in ambulatory patients awaiting heart transplantation.

The prognostic value of 'high dose' loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients awaiting heart transplantation (HT). All ambulatory patients (n=700, median age 55years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into 'low dose', 'intermediate dose', and 'high dose' loop diuretics corresponding to furosemide equivalent doses of ≤40, 40-250, and >250mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N-terminal pro-B-type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P=0.001) for 'low dose', 'intermediate dose', and 'high dose' patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the 'high dose' group was associated with increased waitlist mortality or urgent HT [adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P=0.002] and a six-fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P<0.001) when compared with the 'low dose' group. 'Intermediate doses' were not significantly associated with these two outcomes in adjusted models (P>0.05). A 'high dose' of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre-HT patients.

New UNOS allocation system associated with no added benefit in waitlist outcomes and worse post-transplant survival in heart–kidney patients

The 2018 United Network for Organ Sharing (UNOS) heart transplant policy change (PC) sought to improve waitlist risk stratification to decrease waitlist mortality and promote geographically broader sharing for high-acuity patients awaiting heart transplantation. Our analysis sought to determine the effect of the UNOS PC on outcomes in patients waiting for, or who have received, a heart-kidney transplantation. We analyzed adult (≥18 years old), first-time, heart-only and heart-kidney transplant candidates and recipients from the UNOS Registry. Patients were divided into pre-PC (PRE: October 18, 2016-May 30, 2018) and post-PC (POST: October18, 2018-May30, 2020) groups for comparison. Competing risks analysis (subdistribution and cause-specific hazards analyses) was performed to assess for differences in waitlist death/deterioration or heart transplantation. One-year post-transplant survival was assessed with Kaplan-Meier and Cox analyses. We included an interaction term (policy era × heart ± kidney) in our analyses to evaluate the effect of PC on outcomes in heart-kidney patients. One-year post-transplant survival was similar (p=0.83) for PRE heart-kidney and heart-only recipients, but worse (p<0.001) for POST heart-kidney vs heart-only recipients. There was a policy-era interaction between heart-kidney and heart-only recipients (HR 1.92[1.04,3.55], p=0.038) indicating a detrimental effect of policy on 1-year survival in POST vs PRE heart-kidney recipients. No added beneficial effect of PC on waitlist outcomes in heart-kidney vs heart-only candidates was observed. There was no added policy-era benefit on waitlist outcomes for heart-kidney candidates when compared to heart-only candidates. POST heart-kidney recipients experienced worse 1-year survival compared to PRE heart-kidney recipients with no policy effect on heart-only recipients.

“I Just Wanted Nothing More Than to Get in a Real Shower”: Patient Experience of the Inpatient Wait for a Heart Transplant

BackgroundPatients waiting for heart transplant may be hospitalized for weeks to months before undergoing transplantation. This high-stress period is further complicated by restrictions of daily privileges including diet, rooming, access to the outdoors, and hygiene (eg, limited in ability to shower). However, there is a paucity of research on the experience of this waiting period. We sought to describe the inpatient experience among patients awaiting heart transplantation and to better understand the needs of inpatients waiting for heart transplant. Methods and ResultsWe conducted in-depth, semistructured phone interviews with a purposeful sample of patients who received a heart transplant in the past 10 years and waited in the hospital for at least 2 weeks before surgery. Using the prior literature, the lived experience of the lead author, and input from qualitative experts, we developed an interview guide. Interviews were recorded, transcribed, and analyzed in an iterative process until theoretical saturation was achieved. A 3-person coding team identified, discussed, and reconciled emergent themes. We conducted interviews with 15 patients. Overarching themes included food, hygiene, relationship with health care professionals, living environment, and stressors. Patients reported that strong bonds were formed between the patients and the staff, and the overwhelming majority only had positive comments about these relationships. However, many expressed negative comments about the experience of the food and limitations in personal hygiene. Other stressors included the unknown length of the waiting period, lack of communication about position on the transplant list, worry about family, and concerns that their life must be saved by the death of another. Many participants described that they would benefit from more interaction with recent heart transplant recipients. ConclusionsHospitals and care units have the opportunity to make small changes that could greatly benefit the experience of waiting for a heart transplant, as well as the experience of hospitalization more generally.

(807) The Impact of Axillary Mechanical Circulatory Support in Patients Awaiting Heart Transplantation with Pulmonary Hypertension

(807) The Impact of Axillary Mechanical Circulatory Support in Patients Awaiting Heart Transplantation with Pulmonary Hypertension

Prognosis value of Forrester's classification in advanced heart failure patients awaiting heart transplantation

Prognosis value of Forrester's classification in advanced heart failure patients awaiting heart transplantation

Assessing the Reversibility of Renal Impairment in Patients Awaiting Heart Transplantation.

Assessing the Reversibility of Renal Impairment in Patients Awaiting Heart Transplantation.

Comparative prognostic value of parameters of right ventricular pulsatile afterload in patients with advanced heart failure awaiting heart transplantation

Abstract Background Right ventricular (RV) function demonstrated a strong impact on survival of patients with advanced heart failure with reduced ejection fraction (HFrEF). In particular, increased RV pulsatile afterload (RVPA) was associated with poor prognosis. Several right heart catheterization-derived parameters have been proposed to characterize RVPA, including pulmonary artery compliance (PAC), elastance (PAE) and pulsatile index (PAPi). However, among these indices, the best prognostic indicator is undetermined. Purpose To assess the prognostic relevance of RVPA parameters in patients with advanced HFrEF evaluated for heart transplantation. Methods 149 patients with end-stage HFrEF underwent right heart catheterization during the evaluation for heart transplantation. All patients were clinically followed up until death or any censoring events including heart transplantation, left ventricular assist device (LVAD) and hospitalization for acute heart failure. Cox regression and ROC-curve analysis were used to test the prognostic value of RVPA determinants. Multivariate regression models with C-statistics were used to test the independent predictive value of RVPA indices. Results The mean age of the study population was 56.6±10.1 years and 85.2% were male. The most frequent aetiology of HFrEF was ischemic cardiomyopathy (52.3%). Mean LV ejection fraction was 25.7±10.2%. During a mean follow up time of 17±15 months, 29 (19.5%) patients met the primary endpoint: 9 (6%) patients died, 4 (2.68%) patients underwent an urgent heart transplantation, 11 (7.3%) patients underwent urgent LVAD implantation (as bridge to transplantation therapy) and 5 (3.3%) were hospitalized for HF. Patients who met the primary endpoint were significantly older patients (61.2±7.8 vs 55.4±10.2, p=0.006) and with worse hemodynamic profile than event-free survivors (PAC [1.8±0.8 vs. 2.7±2.0, p=0.01], mPAP [33.5±11.3 vs. 29.3±11.0, p=0.05], PVR [3.0±1.6 vs. 2.6±2.0, p=0.09] and PAE [1.12±0.5 vs. 0.98±0.6, p=0.04]). Among the RVPA parameters PAC&amp;lt;1.9 mL/mmHg (HR 4.0, CI 1.3–6.0, p=0.007) and PAE&amp;gt;0.9 mmHg/mL (HR 2.5, 95% CI 1.1–5.2, p=0.02) were associated with the primary endpoint. On the contrary, PAPi was not significantly associated with the outcome. PAC demonstrated a superior predictive value for the composite adverse outcome compared with pulmonary vascular resistances (PVR) (AUC comparison p=0.019) and PAPi (p=0.03) but similar compared with PAE (p=0.19) and mPAP (p=0.51). In multivariable regression models, PAC, but not PAE showed incremental prognostic value compared with cardiac index (p=0.02). Conclusions Hemodynamic indices of RVPA are associated with worse survival in patients with end-stage heart failure. In particular, PAC and PAE demonstrated superior prognostic value compared with PAPi and steady-state PVR. Moreover, PAC showed incremental prognostic value compared with cardiac index in patients awaiting heart transplantation. Funding Acknowledgement Type of funding sources: None.

TCT-92 Cardiogenic Shock by SCAI Classification in Patients Awaiting Heart Transplantation

TCT-92 Cardiogenic Shock by SCAI Classification in Patients Awaiting Heart Transplantation