PURPOSE:Human Leukocyte Antigen (HLA) sensitization can adversely impact heart transplant (HTx) outcomes. We evaluated the effect of panel-reactive antibody (PRA) and desensitization (DS) strategies on outcomes of pediatric HTx recipients using a unique linkage between clinical registry and administrative databases. METHODS:The Pediatric Heart Transplant Society (PHTS) registry was queried for all patients transplanted from January 2004 to March 2021 and linked by date of birth, HTx date, and center to the Pediatric Health Information System (PHIS). Class I and II PRA at listing, PRA at HTx, underlying diagnosis, age, gender, and graft loss were abstracted from PHTS. Inpatient DS therapy and associated charges were assessed via PHIS. Listed patients were divided by PRA into Low (< 10%), Medium (> 10% to less than median PRA for sensitized patients), and High (≥ median PRA for sensitized patients) cohorts for both Class I and II PRA. DS-related change in PRA category pre-HTx as well as 10-year graft survival were recorded. RESULTS:We linked 3229 HTx recipients (87.5% of total PHTS cohort) with PHIS (45% female, 51% congenital heart disease). Among those with PRA > 10%, median Class I and II PRA was 36% and 48%, respectively. There were 223 High Class I and 191 High Class II patients. Of those with PRA > 10%, 10.8% received some DS therapy, including IVIg, rituximab, bortezomib, and/or plasmapheresis pre-HTx. DS therapies did not significantly alter absolute PRA or drive a change in PRA category from High to Low (p > 0.05). Patients with Low PRAs at listing had greater 10-year graft survival than those with High PRA (p < 0.05). DS therapy did not improve graft survival among patients who were highly sensitized at listing (Figure). Median pharmacy DS charges were $9.9 K (IQR $3.9 K-$28.4 K). CONCLUSION:Elevated PRA adversely impacts graft survival in pediatric HTx recipients. Efficacy of the studied DS therapies in this limited cohort was inconsistent. In patients highly sensitized at listing, efforts at DS are not associated with improved outcomes. Given cost and morbidity associated with DS, careful assessment of risks and benefits for individual patients is warranted.

Background Arrhythmias can lead to cardiac arrest and heart failure. When intractable, heart transplantation (HTX) can become the only viable treatment. This rare high-risk cohort has not been reported as a distinct group. Objective The purpose of this study was to characterize the outcomes of pediatric patients listed for HTX with the primary indication being malignant arrhythmia (MA). Methods Using the Pediatric Heart Transplant Society prospective registry, we identified all patients younger than 18 years listed between 2014 and 2022. MA as the listing indication was categorized into primary tachyarrhythmia (PT), inherited arrhythmia (IA), congenital heart disease, and cardiomyopathy (CM) with secondary arrhythmia. Demographic, listing, and transplant data were analyzed. Results Among 4630 patients listed and 3317 transplanted, MA was the indication in 63 (1.4%) and 49 (1.5%), respectively. Patients with MA were categorized as PT in 11 (17%), IA in 4 (6%), congenital heart disease in 6 (10%), and CM in 42 (67%). Compared with the non-MA cohort, patients listed for MA were older (mean age 10.6 ± 6.2 years vs 6.1 ± 6.2 years; P < .01), more likely to present with cardiac arrest (43% vs 11%; P < .01), and less likely to be in the intensive care unit (40% vs 58%; P < .01) or on inotropes (30% vs 60%; P < .01) at the time of listing. Outcomes including waitlist mortality, transplantation, posttransplant survival, and freedom from rejection were comparable to those of the non-MA cohort. Conclusion Patients with MA constitute a small proportion of those listed for HTX in childhood. CM was the most common category, while IA and PT were rare. Their waitlist mortality and posttransplant outcomes were comparable to those of the non-MA cohort.

Purpose: 1 in 5 children with a ventricular assist device (VAD) remain on device for > 6 months. However, there are sparse data regarding outcomes in this group. We sought to characterize pre-implant characteristics, survival and frequency of adverse events (AE).

Purpose: Primary graft failure (PGF) is a leading cause of early morbidity and mortality after heart transplant (HTx). It manifests as allograft dysfunction in the absence of other causes. While the impact of PGF on early mortality in pediatrics has been described, it is unclear if PGF also influences long-term survival and post-HTx complications.

Purpose: Stroke remains a devastating complication of durable LVAD therapy. Pre-implant patient factors have traditionally been used to predict the risk of post-implant stroke. The purpose of this study was to evaluate the incidence and risk factors for early stroke within 7 days following LVAD implantation with particular attention to the impact of intraoperative variables.

Purpose This study compared the adverse event profiles of patients with bridge-to-transplant or transplant candidacy (BTT/BTC) treatment intent using continuous-flow, fully magnetically levitated (CF-FML) LVADs during UNOS/OPTN pre- and post-allocation eras. Methods The STS-INTERMACS data was queried for all adult patients eligible for BTT/BTC with CF-FML devices between July 1, 2015 and December 31, 2021. This cohort was divided into PRE (before October 18, 2018) and POST (after October 18, 2018) UNOS/OPTN policy change. Patients with device implantation between October 1 and December 31, 2018 (period of policy implementation) were excluded. Demographics, perioperative characteristics, and Kaplan-Meier survival analyses were used to compare groups. Early (90-days) and late (1-year) adverse event (AE) rates were compared. Results In total, 2,280 patients received a CF-FML LVAD as BTT/BTC, 692 (PRE) and 1,588 (POST). The PRE patients were older (54.2 vs 53.2, p=0.05), more likely to be White (65.5% vs 58.8%, p=0.01), and had lower rates of severe diabetes (4.9 vs 9.1%, p< 0.01) and pulmonary hypertension (11.6% vs 24.4%, p< 0.01). The PRE group had fewer IABPs at implantation (24.0% vs 27.6%, p=0.07). Of the PRE group, 40.4% (n=280) received a heart transplant versus only 22.2% (n=353) in the POST group (p< 0.01). PRE were more likely to have early ischemic strokes (4.8% vs 2.8%, p=0.01), late GI bleeding (7.1% vs. 5.0%, p=0.01), device malfunction (1.9% vs 0.8%, p< 0.01), and hemorrhagic stroke (1.4% vs 0.7%, p=0.01). Readmission was more common in PRE in both early (31.9% vs 28.4%, p< 0.01) and late periods (50.7% vs 41.0%, p< 0.01) (see Table 1). Conclusion Following the UNOS/OPTN allocation change in heart transplantation, CF-FML LVAD patients were less likely to be transplanted. Regardless, they had equivalent or less adverse event burden compared to recipients in the pre-allocation era.

Purpose We developed 4 new measures: 1) Satisfaction with Treatment, 2) Being Bothered by Ventricular Assist Device (VAD) Self-care and Limitations, 3) VAD Team Communication, and 4) Self-efficacy Regarding VAD Self-care to assess adjustment of patients to living with a VAD. We aimed to evaluate the association of these new measures with health-related quality of life (HRQOL) 3 months after implant. Methods Patients with a left (L)VAD were recruited from 12 U.S. sites (10/26/16-9/9/19). HRQOL was measured pre- and 3 months post-implant using the EQ-5D Visual Analog Scale (VAS) and KCCQ-12 overall summary score (OSS). Covariates included the 4 new measures, pre-implant HRQOL, demographics, adverse events (within 3 months post-implant), implant strategy, and resources. Analyses included backward selection regressions using full information maximum likelihood estimation to account for missing values of covariates, p<0.05. Results Our sample, n=111 LVAD patients, were mean(SD) age=55(13) years, 21% female, 78% non-Hispanic White, and 47% destination therapy. Factors associated with worse 3-month VAS after adjustment for baseline VAS were female sex, adverse events within 3 months post-implant (cardiac arrhythmias, bleeding, and venous thrombosis), and chest pain (R2=0.229). None of the 4 new measures were independently associated with 3-month VAS. Satisfaction with Treatment was associated with better KCCQ-12 OSS; Being Bothered by VAD Self-care and Limitations, cardiac arrythmias, ≤ high school education, chest pain, and peripheral edema were associated with worse OSS (R2=0.501) (Table). Conclusion In addition to demographics, post-implant adverse events, and symptoms, 2 of our new measures (Treatment Satisfaction and Being Bothered by VAD Self-care and Limitations) were associated with post-LVAD KCCQ-12 OSS, but not EQ-5D VAS. Our study supports the importance of these new VAD self-report measures for understanding HRQOL.

Women approached who did not enroll in SUSTAIN-IT were more likely than men to refuse to participate. Reasons for refusal varied for both women and men based on type of advanced HF therapy. Our novel findings may provide tailored guidance when recruiting men and women in clinical trials.

Only 60% of pediatric HT recipients had ideal BMI at 1 year and 5 year follow up. Obesity at HT predicts an increased risk of CAV and graft loss. Exploring metabolic risk factors that lead to CAV development and graft loss are important. Healthy lifestyle interventions pre-HT and during HT follow up may potentially reduce morbidity and mortality.

Contrary to prior reports, in this large series plastic bronchitis did not have a negative impact on survival to or after heart transplantation in Fontan patients. A 50% reduction in listing in the most recent era suggests improvement in medical management of this rare and life-threatening condition.

Muscle wasting and deconditioning are frequently present in advanced heart failure patients at the time of continuous flow left ventricular assist device (CF-LVAD) placement and may influence post LVAD outcomes and quality of life (QoL). We analyzed the contribution of muscular strength to functional capacity (FC) and QoL in patients supported by CF-LVAD. FC and QoL were measured with 6 minute walk test (6MWT) and Kansas City Quality Questionnaire (KCQQ). Maximum isometric strength of the elbow flexors and knee extensors was evaluated while EMG of the biceps brachii and rectus femoris were measured. A sit-to-stand test was performed using EMG to evaluate percentage of maximal knee strength required to sit and stand. Clinical, echocardiographic and hemodynamic information were obtained from clinical records. Eighteen patients with a mean age of 55±14 years were enrolled in this study, 79% were male and 50 % were African Americans. The median time of support was 15.5 months (6 - 36). Baseline characteristics are shown in Table 1. Of the variables examined (Table 2), only elbow flexor and knee extensor strength (adjusted to BMI) correlated significantly with both 6MWT and KCQQ. We conclude that isometric muscle strength measured in stable ambulatory LVAD patients is associated with FC and QoL.Tabled 1Basic clinical and functional characteristicsCharacteristicsValueEchocardiography-Left ventricular diastolic dimension (LVDD (cm)5.7±1.2-Left ventricular Ejection Fraction (LVEF) (%)23±11Hemodynamics (n=9)11±6-Right Atrial (RA) pressure (mmHg)24±6-Pulmonary artery (PA) mean pressure (mmHg)12±6-Pulmonary capillary wedge pressure (PCWP) (mmHg)2.6±0.4-Cardiac index (CI) (L/min/m2)87±7-Mean arterial pressure (MAP) (mmHg)75±10-HR (bpm)Functional Capacity-6MWTD (m)387±77-Gate Speed4.5±0.8-NYHA-FC9 (50%)I7 (38.9%)II2 (11.1%)IIIQuality of Life-KCCQ53.4±7Muscular Strength-Knee369.8±109.5-Elbow214±66.7-Stand-up54.2±24.8Univariable analysis with outcomes of FC and QoL6MWTKCCQAge−0.6 (0.01)nsBMIns0.73 (0.001)RA/PCWP/CI/MAPnsnsLVEF/LVDDnsnsElbow0.58 (0.01)0.56 (0.018)Knee0.47 (0.055)0.64 (0.007)Stand-upns−0.74 (0.001) Open table in a new tab

Gastrointestinal bleeding (GIB) is a frequent cause of re-hospitalization in left ventricular assist device (LVAD) patients. Changes in the composition of the intestinal microbiota have been associated with inflammation and bleeding in conditions such as inflammatory bowel disease. We hypothesized that changes in the composition of the intestinal microbiota may be associated with GIB in LVAD patients. We analyzed paired samples of the intestinal microbiome in two patients supported by LVAD at baseline (prior to GIB) and during active GIB. Fecal DNA was prepared and PCR primers were used to amplify the V4 region of the 16s rRNA gene. The amplified DNA was analyzed by Illumina MiSeq DNA sequencing to an average read depth of 100,000 reads per sample. Bioinformatic analysis was performed using the QIIME package to obtain microbial taxa and compare the alpha and beta diversity between the pre and post GIB samples. The alpha diversity (distribution within the sample) in both patients after GIB increased on average 12%. Consistent with the alpha analysis, the top 50 most abundant genera for all samples revealed that after GIB, several similar taxa were found to be changing in both samples (correlation 0.46). Nine out of top 10 genera showed similar pattern of increase or decrease after GIB. Specifically, following GIB, Bacteriodes, Ruminococcus, Blautia, and Escherichia decreased in abundance whereas Faecalibacterium, Oscillospora, Sutterella, Parabacteroides, Binfidobacterium increased (figure 1). Analysis of beta diversity (dissimilarity between each paired sample test) revealed differences between pre and post GIB samples. Acute Gastrointestinal bleeding in patients supported with LVAD is associated with changes in the composition of the intestinal microbiota. Further studies are ongoing to expand this novel description and to evaluate the therapeutic potential to alter the microbiota to prevent or treat GIB in this population.

An overall outcome of children bridged to heart transplant (HT) with VAD at the time of transplant is associated with superior post-transplant survival than ECMO support. Limited outcomes information is available on mechanical circulatory support device (MCSD) in patients with single ventricle (SV). We analyzed data from the Pediatric Heart Transplant Study (PHTS) registry to evaluate the outcome of children with SV physiology who are supported with MCSD as a bridge to HT and their post-HT outcomes. Of the 3631 PHTS patients listed for HT between 2005 and 2014, 1825 (50%) had congenital heart disease (CHD) [SV= 1381 (76%) and biventricular (Bi-V) = 444 (24%)]. Of these, 906 (65%) SV patients and 298 (67%) Bi-V underwent HT; 233 (17%) and 80 (18%) died while waiting. 57% of all SV patients had hypoplastic left heart syndrome. MCSD support was more prevalent in Bi-V patients (46%: 24% ECMO & 22% VAD) compared to SV (14%: 9% ECMO & 5% VAD) (p<.01). Overall, 40% of SV patients (45.3% of VAD group & 38.6% of ECMO group) with MCSD received transplantation by 6 months compared to 59% of those without MCSD. SV waitlist mortality was 11% among no-MCSD support, 35% in VAD group, and 47% in ECMO group at 6 months (p <.01). SV patients on MCSD were more likely to remain on support until HT if they received VAD 22/60 (36%) compared to ECMO 10/127 (8%); p<.01. After HT, 12 month survival was significantly different between SV groups with no MCSD at listing or while listed (88%), VAD (78%) and ECMO (69%); p<.01. However, there was no difference in survival between SV patients on VAD at the time of HT (74%) vs those on ECMO (80%); p=0.9 (figure). Waitlist mortality for SV patients supported with MCSD remains unacceptably high. SV patients receiving MCSD are more likely to stay on support until HT if they had VAD compared to ECMO. However, for those SV patients on MCSD support at HT, there was no significant difference in survival outcomes between ECMO and VAD.

LATE BREAKING CLINICAL TRIAL. Completion Date: February 2009. Sponsor: Ventracor, Inc. Summary of Objectives: The VentrAssist™ implantable left ventricular assist device (LVAD) is a third generation centrifugal pump with no mechanical bearings (it uses a hydronamically suspended impeller) designed to enhance reliability and decrease adverse events. This trial evaluates the efficacy and safety of the VentrAssist LVAD in BTT patients. The results of this trial will constitute the first report of a major trial of a centrifugal LVAD in the U.S.

Detailed information regarding social support and its relationship with quality of life (QOL) 5 to 10 years (yrs) after heart transplantation (HT) is unknown. The purposes of this longitudinal study were to examine demographic, physiologic, and psychosocial characteristics and their relationship to social support after HT, and identify if perceived satisfaction with social support is a predictor of QOL post HT.