List For Heart Transplantation Research Articles

Abstract 17410: Geographic and Racial/ Ethnic Disparities in Heart Transplant Listing by County and Associated Risk Factors

Introduction: It is unknown if there are disparities in the transition from heart failure (HF) to listing for heart transplant (HT), although there are clear disparities in this transition in the transplant of other organs. Methods: We used CDC WONDER data and SRTR transplant data to identify county-level age-adjusted HF mortality and number of candidates listed for HT from 2006 to 2018 among racial/ ethnic subgroups. We determined rates of candidate listing and age-adjusted HF deaths (AAHFD) per 100,000 persons on aggregate and by racial/ ethnic subgroups. County-level demographic, socioeconomic, cardiovascular disease risk, and healthcare factors from public databases were used in multivariate models to determine factor groups explaining variation in candidates listed per AAHFD. Results: The median (IQR) candidates per AAHFD for the aggregated county cohort was 1.3 (0.75-2.0; 2558 counties reported data), the non-Hispanic white (NHW) county cohort was 1.5 (0.88-2.2; 2426 counties), the non-Hispanic black (NHB) county cohort was 1.1 (0.64-1.6; 860 counties), and the Hispanic county cohort was 1.1 (0.67-1.8; 254 counties) (p-value <0.001). The lowest candidates per AAHFD were in the South for NHW (median 1.3) and NHB (0.97), but in the West for Hispanic (0.84). Multivariate models with all county-level variables, explained (R 2 ) 28.7%, 38.7%, and 57.3% of variation in candidates listed per AAHFD for NHW, NHB, and Hispanic cohorts, respectively. Socioeconomic factors (R 2 0.14), healthcare factors (R 2 0.21), and cardiovascular disease risk factors (R 2 0.18), respectively, explained the greatest variation in models using variable subgroups. Conclusions: When age-adjusted rates of HF mortality by race/ ethnicity group is considered, HT candidate listing for NHB and Hispanic candidates is 27% lower than for NHW. County-level factors that explain variation in HT listing vary by racial/ ethnicity group, and explain more variation in NHB and Hispanic cohorts.

Abstract 13291: Impact of VAD Support Duration on Pediatric Heart Transplant Outcomes

Introduction: There is wide variability in the timing of heart transplant (HT) listing and consideration of organ offers after ventricular assist device (VAD) implant in children. While some centers wait weeks or months before proceeding with HT, others accept donor hearts within days of VAD surgery. We sought to determine if HT within 30 days of VAD implant impacts post-HT outcomes when compared to HT after ≥30 days of VAD support. Methods: Patients on VAD support prior to HT were extracted from the Pediatric Heart Transplant Study database. The primary endpoints were post-HT length of hospital stay (LOS) and one-year survival. Confounding was addressed by propensity score weighting using inverse probability of treatment. Propensity scores were calculated based on age at VAD implant, blood type, primary cardiac diagnosis, decade, VAD type, and allosensitization status. Group balance was verified with standardized differences. Results: A total of 1138 children underwent VAD implant prior to HT between 2000-2019 (Table 1). Most underwent HT ≥30 days after VAD (71%). The majority (70%) had an LVAD alone. Infants accounted for 22% of both groups, while those 1-11 years were 46% of the ≥30-day group and patients ≥12 years made up 42% of <30-day group (p=0.001). There was no difference in the prevalence of congenital heart disease vs. cardiomyopathy (p=0.7) or high allosensitization status (p=0.8) between groups. Post-HT LOS was similar between groups (23 vs. 21 days in <30 vs. ≥30 days, p=0.07). One-year survival was 90.5% in the <30-day group vs. 94.5% in ≥30 days (adjusted mortality HR 1.81, 95% CI 1.15-2.86, p=0.01). Conclusions: In this large study of children undergoing HT after VAD, we found lower one-year survival in patients on VAD support for <30 days prior to HT compared to those on VAD for ≥30 days before HT. These findings suggest that a strategy of delayed HT listing following VAD implant may favorably impact post-HT survival in the pediatric population.

Waiting list mortality and the potential of donation after circulatory death heart transplantations in the Netherlands.

BackgroundWith more patients qualifying for heart transplantation (HT) and fewer hearts being transplanted, it is vital to look for other options. To date, only organs from brain-dead donors have been used for HT in the Netherlands. We investigated waiting list mortality in all Dutch HT centres and the potential of donation after circulatory death (DCD) HT in the Netherlands.MethodsTwo different cohorts were evaluated. One cohort was defined as patients who were newly listed or were already on the waiting list for HT between January 2013 and December 2017. Follow-up continued until September 2018 and waiting list mortality was calculated. A second cohort of all DCD donors in the Netherlands (lung, liver, kidney and pancreas) between January 2013 and December 2017 was used to calculate the potential of DCD HT.ResultsOut of 395 patients on the waiting list for HT, 196 (50%) received transplants after a median waiting time of 2.6 years. In total, 15% died while on the waiting list before a suitable donor heart became available. We identified 1006 DCD donors. After applying exclusion criteria and an age limit of 50 years, 122 potential heart donors remained. This number increased to 220 when the age limit was extended to 57 years.ConclusionWaiting list mortality in the Netherlands is high. HT using organs from DCD donors has great potential in the Netherlands and could lead to a reduction in waiting list mortality. Cardiac screening will eventually determine the true potential.

Coronary sinus catalase and ceruloplasmin levels predict all-cause mortality in patients with end-stage heart failure awaiting heart transplantation

Abstract Background, As a consequence of the worldwide increase in life expectancy and due to significant progress in the pharmacological and interventional treatment of heart failure (HF), the proportion of patients that reach an advanced phase of disease is steadily growing. Hence, more and more numerous group of patients is qualified to the heart transplantation (HT), whereas the number of potential heart donors has remained invariable since years. It contributes to deepening in disproportion between the demand for organs which can possibly be transplanted and number of patients awaiting on the HT list. Therefore, accurate identification of patients who are most likely to benefit from HT is imperative due to an organ shortage and perioperative complications. Purpose The aim of this study was to identify the factors associated with reduced survival during a 1.5-year follow-up in patients with end-stage HF awating HT. Method We propectively analysed 85 adult patients with end-stage HF, who were accepted for HT at our institution between 2015 and 2016. During right heart catheterization, 10 ml of coronary sinus blood was additionally collected to determine the panel of oxidative stress markers. Oxidative-antioxidant balance markers included glutathione reductase (GR), glutathione peroxidase (GPx), glutathione transferase (GST), superoxide dismutase (SOD) and its mitochondrial isoenzyme (MnSOD) and cytoplasmic (Cu/ZnSOD), catalase (CAT), malondialdehyde (MDA), hydroperoxides lipid (LPH), lipofuscin (LPS), sulfhydryl groups (SH-), ceruloplasmin (CR). The study protocol was approved by the ethics committee of the Medical University of Silesia in Katowice. The endpoint of the study was mortality from any cause during a 1.5 years follow-up. Results The median age of the patients was 53.0 (43.0–56.0) years and 90.6% of them were male. All included patients were treated optimally in accordance with the guidelines of the European Society of Cardiology. Mortality rate during the follow-up period was 40%. Multivariate logistic regression analysis showed that ceruloplasmin (odds ratio [OR] = 0.745 [0.565–0.981], p=0.0363), catalase (OR = 0.950 [0.915–0.98], p=0.0076), as well as high creatinine levels (OR = 1.071 [1.002–1.144], p=0.0422) were risk factors for death during 1.5 year follow-up. Conclusions Coronary sinus lower ceruloplasmin and catalase levels, as well as higher creatinine level are independently associated with death during 1.5 year follow-up. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical University of SIlesia, Katowice, POland

Survival After Heart Transplant Listing for Infants on Mechanical Circulatory Support

BackgroundInfants with heart failure remain at significant risk for wait list mortality, despite mechanical circulatory support (MCS). It is unclear if the outcomes are influenced by modality of support or underlying diagnosis. We sought to compare the outcomes of infants <10 kg, focusing on modality of support and underlying diagnosis.Methods and ResultsUsing the Pediatric Heart Transplant Society database, we evaluated survival following first MCS device in children <10 kg who were listed for heart transplant between 2010 and 2018. There were 2049 children <10 kg, with the predominant diagnosis being congenital heart disease (CHD) (59.8% [n=1226]) and 28.1% (n=577) requiring MCS. Extracorporeal membrane oxygenation (ECMO) was the most common form of MCS at listing, with ventricular assist device (VAD) more common after listing. There was no difference in the use of ECMO at or after listing for cardiomyopathy versus CHD (8.9% versus 7.2%; P=0.2; 5.4% versus 6.4%; P=0.4). However, there was a significant difference in the use of VAD both at listing (8% versus 2.4%; P<0.001) and after (22.8% versus 5.1%; P<0.001) between the 2 groups. When comparing these groups, patients with CHD were smaller and younger and had a higher proportion with previous cardiac surgery. Survival at 3 months demonstrated better survival for VAD therapy compared with ECMO (74.3% versus 48.6%; P<0.001). In patients <5 kg, survival did not differ between ECMO and VAD (P=0.01) for the CHD or the cardiomyopathy group (P=0.38), but patients with cardiomyopathy demonstrated better survival on both forms of support.ConclusionsSurvival for patients <10 kg on ECMO is inferior compared with VAD. Patients with cardiomyopathy <5 kg had better survival with both modes of MCS compared with those with CHD. These findings support the need for small, durable devices for neonates and infants, with particular focus in patients with CHD.

Bariatric Surgery In Advanced Heart Failure Patients As A Bridge To Advanced Therapies (b2b)

Introduction Obesity poses significant challenges in advanced heart failure patients who otherwise meet criteria for either left ventricular assist devices (LVAD) or heart transplant (HT). Current guidelines suggest body mass index (BMI) cutoff for HT of Methods A retrospective single center analysis of patients in the dedicated Obesity Clinic at University Hospitals were examined, identifying patients with left ventricular ejection fraction (LVEF) Results Between 2010 and 2019, there were 191 patients with history of obesity (BMI > 35kg/m2) and heart failure who were referred to the Obesity Clinic for bariatric surgery as demonstrated in Figure 1. Of this group, 58 (30%) of patients had heart failure with reduced ejection fraction, in which 22 (38%) went directly to bariatric surgery, 8 (14%) recovered their LVEF prior to gastric surgery, 19 (33%) were pending gastric surgery, and 9 (16%) developed advanced heart failure requiring implantation of an LVAD as B2B. Of the LVAD group, 5 patients underwent bariatric surgery and successfully met the goal of desired BMI for HT listing. All 5 patients were listed for HT, with 3 proceeding successfully to HT and 2 awaiting offers. Compared to morbidly obese patients who proceeded directly to gastric bypass surgery, those who underwent B2B had a lower BMI (51.67 ± 11.39 vs 41.9 ± 4.45 kg/m2; p = 0.00163), lower LVEF (32.16 ± 6.83 vs 18.06 ± 7.68%, p Conclusions B2B offers a successful pathway for obese patients to undergo HT.

Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device: Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA)

BackgroundGeographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown. MethodsWe created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months. ResultsThe cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU. ConclusionsAlthough waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.

A 3year post-intervention follow-up on mortality in advanced heart failure (EVITA vitamin D supplementation trial).

AimsVitamin D supplementation is widely used in the clinical setting, but its effects on mortality and cardiovascular outcomes in patients with heart failure are unclear. This paper reports outcome data that were collected during follow‐up of 3 years after closure of the EVITA trial (a 3 year randomized, placebo‐controlled, intervention study with 4000 IU vitamin D daily in patients with advanced heart failure), to capture potential latency effects of vitamin D supplementation on clinical outcomes.Methods and resultsThe prespecified primary endpoint was overall mortality. Secondary endpoints included hospitalization, mechanical circulatory support implantation, high urgent listing for heart transplantation, and heart transplantation. For group comparisons, we used Cox regression models with a time‐dependent categorical covariate. The calculated net difference in circulating 25‐hydroxyvitamin D between the vitamin D and placebo groups dropped from 60.9 nmol/L at the end of the active study period to 3.2 nmol/L at the end of the post‐intervention period. During the entire 6 year period, 73 patients (36.5%) died in the placebo group and 76 (38.8%) in the vitamin D group. Out of these 149 patients, 36 and 39 died during the first 3 years, and 37 and 37 during the second 3 years, respectively. The hazard ratio (HR) for mortality in the vitamin D versus the placebo group was 1.06 [95% confidence interval (CI): 0.68–1.66] for the first 3 years and 1.07 (95% CI: 0.68–1.70) for the 3 year post‐intervention follow‐up. Compared with the placebo group, the HRs for hospitalization and for mechanical circulatory support implant were significantly higher in the vitamin D group during vitamin D supplementation (HR = 1.31, 95% CI: 1.01–1.68 and HR = 2.01, 95% CI: 1.08–3.76, respectively) but not after vitamin D discontinuation (HR = 1.10, 95% CI: 0.62–1.94 and HR = 0.99, 95% CI: 0.38–2.56, respectively). There was no significant time‐dependent effect on the risk of high urgent listing for heart transplantation and heart transplantation.ConclusionsNo beneficial latency effects of vitamin D supplementation on overall mortality could be demonstrated. Instead, the disappearance of unfavourable findings in the vitamin D group (higher HRs for hospitalization and for mechanical circulatory support implant) after vitamin D discontinuation supports the assumption of adverse vitamin D effects on the cardiovascular system at doses of 4000 IU daily.

GDF-15 (Growth Differentiation Factor 15) Is Associated With Hospitalization and Mortality in Patients With a Fontan Circulation.

BackgroundWe investigated serial serum levels of GDF‐15 (growth differentiation factor 15) in Fontan patients and their relation to outcome.Methods and ResultsIn this single‐center prospective study of consecutive Fontan patients, serial serum GDF‐15 measurement and clinical assessment was done at baseline (n=81) and after 2 years (n=51). The association between GDF‐15 and the combined end point of all‐cause mortality, heart transplant listing, and Fontan‐related hospitalization was investigated. Median age at baseline was 21 years (interquartile range: 15–28 years). Median GDF‐15 serum levels at baseline were 552 pg/mL (interquartile range: 453–729 pg/mL). GDF‐15 serum levels correlated positively with age, age at Fontan initiation, New York Heart Association class, and serum levels of NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) and ɣGT (γ‐glutamyltransferase) and negatively with exercise capacity. During a median follow‐up of 4.8 years (interquartile range: 3.3–5.5 years), the combined end point occurred in 30 patients (37%). Multivariate Cox regression showed that patients with the highest baseline GDF‐15 (n=20, defined as the upper quartile) had a higher risk of hospitalization or death than the lowest 3 quartiles (hazard ratio [HR], 2.76; 95% CI, 1.27–6.00; P=0.011). After 2 years of follow‐up, patients in whom serum level of GDF‐15 increased to >70 pg/mL (n=13) had a higher risk of hospitalization or death than the lowest 3 quartiles (HR, 2.69; 95% CI, 1.03–6.99; P=0.043).ConclusionsIn Fontan patients, elevated serum levels of GDF‐15 are associated with worse functional status and predict Fontan‐related events. Furthermore, serial measurements showed that an increase in GDF‐15 serum level was associated with increased risk for adverse outcome.

Effect of Sacubitril-Valsartan in reducing depression in patients with advanced heart failure

BackgroundDepression is highly prevalent in Heart Failure (HF). Treatment with sacubitril/valsartan improved quality of life and survival in HF patients. Aim of the study was to investigate prospectively the effect of sacubitril/valsartan on depression in advanced HF patients in waiting list for heart transplant (HT). Methods37 consecutive patients with advanced HF in waiting list for HT were treated with sacubitril/valsartan. We analyzed data derived from the assessment performed the year before the beginning of sacubitril/valsartan, at study entry, and at one year of follow-up. Depression was assessed with Beck Depression Inventory II (BDI) scale. Cognitive function were assessed with Mini-Mental State Examination (MMSE). Functioning was evaluated measuring meters at 6 Minute Walking Test (6MWT) and maximum rate of oxygen consumption (VO2 max). ResultsAt baseline, 64.9% of HF patients were in NYHA III and 35.1% NYHA IIIB, BDI was 15.2 ± 5.2 with 59.5% of patients with a score > 13. MMSE was 27.8 ± 2.6. After one year of follow-up NYHA class improved significantly, with 56.8% in NYHA II, 40.5% in NYHA III and 2.7% NYHA in IIIB (p < 0.001). VO2 max and 6MWT increased. Notably, BDI was 9.5 ± 3.9 with 21.6% of patients with a score > 13. MMSE remain stable (28.2 ± 2.1) (p = 0.104). No statistical differences are observed between data collected in the evaluation 1-year before and soon before treatment with sacubitril/valsartan. Multivariate regression analysis demonstrate a relationship between reduction in BDI-II score and improvement in six-minute walking test independently by the effect of sex, age, selective serotonin reuptake inhibitors, VO2 max, NT-proBNP, PAPs, NYHA class differences evaluated at follow-up versus baseline. ConclusionsOur study showed a reduction in depressive symptomatology in heart transplant waiting list patients treated with sacubitril/valsartan. The improvement in depressive symptomatology was paralleled by 6MWT increase in the follow-up.

Comparison of Six-Month Outcomes in Hypertrophic Cardiomyopathy Patients before and after UNOS Allocation System Change

HCM patients may have increased waitlist (WL) mortality. Given the recent change in prioritizing patients with restrictive and hypertrophic cardiomyopathy requiring mechanical support, we sought to assess whether the policy change would affect the waitlist and post-transplant outcomes in HCM pts. 59 pts were identified in UNOS registry that underwent heart transplant (HT) with a diagnosis of HCM during a 6-month period immediately before and after the UNOS policy change. Comparisons between pt characteristics in the pre (n=43) and post (n=16) policy-change cohorts are reported using standard statistical methods; survival analysis performed using Cox proportional hazards modeling. The WL statuses of the pre-policy change pts were 1A (n=22), 1B (n=11), 2 (n=10) while the WL statuses of the post pts were 1 (n=2), 2 (n=7), 3 (n=1), 4 (n=6). For both groups, the age, donor age, gender, ethnicity, DM status, and ischemic times were similar. The median wait list time was decreased following the policy change (24.5 vs. 43 days, p=0.01). There was greater use of IABP following the allocation system change (31% vs. 5%, p=0.01). There was a trend toward worse post-HT survival in HCM following the policy change (p=0.06). The policy change significantly decreased waiting times for HCM pts on the HT list with a trend towards increased mortality with decreased rates of transplant. Further study is warranted to understand the long-term implications of this policy change.

Comparison of Six-Month Outcomes in Restrictive Cardiomyopathy Patients before and after UNOS Allocation System Change

Restrictive cardiomyopathy (RCM) patients represent a spectrum of disorders. Given the greater emphasis for status exceptions for RCM pts in the new allocation system, we sought to assess whether this change in the allocation policy would affect the wait list and post-transplant outcomes in RCM pts. 89 RCM pts were identified in the UNOS registry that underwent heart transplant (HT) during a 6-mos period immediately before and after UNOS policy change. Comparisons between pt characteristics in the pre (n=62) and post (n=27) policy-change cohorts are reported using standard statistical methods; survival analysis performed using Cox proportional hazards modeling. The waitlist (WL) statuses of the pre pts were 1A (n=34), 1B (n=14), 2 (n=14) while the WL statuses of the post pts were 1 (n=2), 2 (n=13), 3 (n=5), 4 (n=4), 6 (n=2). For the pre and post policy groups, the age, gender, ethnicity, DM status, and ischemic times were similar. The RCM subtype (idiopathic, amyloid, sarcoid, chemo/XRT, and other) distribution was similar for the two groups. Donor age was greater following policy change (40.6 ± 13.0 vs 30.7± 13.0, p=<0.01). Median total days on WL trended towards fewer days for post group (16.0 days vs 33.0 days, p=0.06). IABP utilization was greater for the post policy change group (37% vs 5%, p=<0.01). There was no significant survival difference at 6 month. After UNOS policy change, the 6 months post HT mortality was unchanged in RCM pts as compared to pre-policy change. There was a trend towards shorter wait times and significantly greater utilization of IABP after policy change. Despite the emphasis on status exception for RCM pts, there were fewer overall HT done for RCM.

Run for It: Use of Cardiopulmonary Exercise Testing for Hemodynamic Assessment in Advanced Heart Failure

Cardiopulmonary exercise testing (CPET) is an underutilized resource in the assessment of advanced heart failure (HF) after listing for heart transplant (HT). Currently, the ISHLT recommends repeating right heart catheterization (RHC) periodically after HT listing. The objective of this study was to assess whether CPET metrics could reliably predict hemodynamic pressures. Patients with pre-transplant RHC and CPET measured within 3 months of each other were included. Pearson correlation between CPET and hemodynamic variables were calculated. We applied a Random Forest method to develop a prediction model with demographics and CPET metrics for each hemodynamic variable. In addition, we ranked the input variables in terms of their relative importance, defined as the relative reduction in accuracy or, equivalent relative increase in RMSE. 102 patients were included. Of those, 65 had a CI ≥2 and 37 had a CI< 2 LPM. Mean peak oxygen consumption (pVO2) was 12.2±2.8 ml/kg/min, with a %predicted 45.8%±11.4%, a respiratory exchange ratio (RER) 1.12±0.11 and a VE/VCO2 slope 41.4±10.4. When comparing HF etiologies, RER was lowest in those with ischemic cardiomyopathy (ICMP 1.08±0.1, DCMP 1.1±0.11, Other 1.16±0.11, p=0.029). There were no differences in pVO2, %predicted or VE/VCO2 slope. The cross-correlation analysis stratified by CI is shown in Fig 1A. We found modest correlations in the low CI group between VE/VCO2 slope and diastolic PA pressure (r=0.44), VE/VCO2 slope and mean PA pressure (r=0.42), and pVO2 and CI (r=0.37). When combining CPET data and demographic data, we were able to rank the importance of each predictor within in each model (Fig 1B). Using CPET data as a surrogate for invasive hemodynamics in those listed for HT is feasible. The use of serial exercise testing may allow a safer means to monitor patients and determine the timing of more aggressive support prior to HT.

Post-Transplant Outcomes for Patients Based on Their Duration of Smoking Cessation at the Time of Heart Transplant (HT) Listing

Smoking cessation is a prerequisite prior to listing for HT, however the optimal duration of smoking cessation prior to listing is unknown and there is variability amongst HT programs on an acceptable abstinence period. We sought to evaluate the long-term post-transplant outcomes of patients based on duration of smoking cessation. We evaluated the UNOS registry for all HT recipients from 2005 to 2019. We compared patient characteristics in the group with smoking cessation duration less than or equal to 12 months from the time of listing (N=2800) to the group with cessation duration greater than 12 months (N=9524). The differences were analyzed using standard statistical methods including Cox proportional hazards regression for survival analysis. Recipient mean age (57.3 ± 9.9 vs 50.5 ± 11.8, p<0.001), proportion of male recipients (81.1% vs. 78.9%, p=0.009), and donor age (32.4 ± 11.5 vs. 31.6 ± 11.3, p = 0.002) were significantly greater in the >12 month group. Diabetes (33.1% vs. 24.0%, p<0.001) and history of prior cardiac surgery (45.9% vs. 40.4%, p<0.001) were more common in the >12 month group. Recipients were less likely to require ventricular assist device (VAD) support (43.4% vs. 50.2%, p<0.001) and mechanical ventilation (1 vs. 1.5%, p=0.026) prior to transplant in the >12 month group. Median (IQR) time on the wait list was significantly longer for the >12 month group [97.0 (29.0, 264.0) days vs. 81.0 (25.0, 231.0) days, p<0.001]. There was a lower total (19.1% vs. 21.4%) and cardiovascular (7.1% vs. 10.5%) post-transplant mortality in the >12 month group (p<0.001). Despite being an older group with higher prevalence of diabetes, prior cardiac surgery, higher donor age, and longer organ wait time, patients with longer (>12 month) duration of smoking cessation have improved survival post-HT with less need for ventilator and VAD support. These findings may have implications for patient selection.

Impact of Histidine-Tryptophan-Ketoglutarate Preservation Solution in Heart Transplantation with Extended Distance

In countries with such continental dimensions, and low rates of organs donations and recovery, strategies to shorten the waiting time in heart transplantation (HT) list are still required. A prolonged ischemic time (pISQT, >240 min) has been reported to be a significant factor leading to primary graft dysfunction (PGD). Thus, optimal heart preservation is mandatory for transplant procedures with pISQT. Use of Histidine-Tryptophan-Ketoglutarate (HTK) solution has been suggested to improve extended organ preservations up to 180 min. This study investigated the impact of the donor distance (DD) from transplantation center and pISQT on PGD after HT using preservation with HTK solution. Between January 2017 and December 2018, all 92 consecutive patients underwent HT at our institution after preservation with HTK solution were retrospectively evaluated divided into 2 groups according to the DD: (G1) 46 patients underwent HT with a DD <100km, and (G2) 46 patients after HT with a DD >100km. No significant differences were observed with regard to gender, age, diagnosis, donor inotropic support, and donor-recipient weight ratio among patients in G2 when compared with G1. The PGD was characterized using the ISHLT defined criteria. Descriptive analyses of the results are presented as mean values and standard deviations. The analytical studies were performed with the Fisher exact test. Kaplan-Meier and log-rank tests were performed to investigate survivals. All analyses were performed using R and p<0.05 was considered to be significant. The incidence of PGD was similar in both groups (p=0.81). After risk adjustment, longer DD were associated with a significantly lower risk of mortality at both 60 days (p=0.05, Figure 1). This study illustrates that HTK solution may help to expand donor acceptance criteria to include more distant donor heart locations and accepting longer allograft ischemic times without increase in PGD and mortality after transplantation.

Prevalence of Cognitive Impairment in Heart Transplant Waiting-List Patients in a Developing Country

Cognitive impairment and mood deviation often occurs in patients with heart failure. Frailty and sarcopenia have been widely studied in patients with heart disease, but cognitive frailty has been little explored. High complexity of patients referred for heart transplantation connected with socioeconomic characteristics in a developing country underlines the importance to investigate cognitive and mood conditions in this population. The aim of the study is to evaluate the prevalence of cognitive impairment and depression symptoms in patients with heart failure in waiting list for heart transplantation (HTx). Cognition was assessed with the Montreal Cognitive Assessment (MoCA) and Wechsler Abbreviated Scale of Intelligence (WASI), depression symptoms was assessed with Beck Depression Inventory (BDI). Patients included in waiting-list from Nov/2018 to Sep/2019 in our institution had its cognitive assessment in four weeks. 36 patients were evaluated; 28 (77%) were male; 45,6 was the average age; Chagas disease was the main etiology (36%), followed by dilated cardiomyopathy (25%), ischemic cardiomyopathy (11%) and other etiologies (28%). 9,1 was the average of school years; 20 (55,5%) belong to social class "E" according to monthly family income and 9 (25%) reported history of mental health treatment or psychotropic use. Considering scales described above, 14 (38,8%) had mild symptons for depression; 31 (86,1%) denoted frailty on the brief cognitive screening test (MoCA) and 32 (88,8%) in the global intelligence scale (WASI), with emphasis on lower scores on non-verbal tasks over verbal tasks. In our cohort, the prevalence of cognitive frailty in patients in heart transplant waiting list was alarming. Socioeconomic conditions seem to be a crucial issue in worse performance of candidates reflecting specific features and challenges regarding heart transplantation in a developing country.

Impact of the Revised Heart Allocation System at a Large Volume Center

In October of 2018, the United Network for Organ Sharing (UNOS) instituted a revised allocation system (RAS) for heart transplantation (HT). We sought to explore how these changes impacted our own center's listing and bridging strategies and rates of adult HT. We performed a retrospective review comparing adult patients transplanted at our center between October 1, 2017 and October 17, 2018 (prior to RAS, Cohort A) with those transplanted between October 18, 2018 and August 1, 2019 (following RAS, Cohort B). Among the characteristics we explored were patient blood type, status at time of listing and HT, status justification, and for patients listed by exception, reason for exception request RESULTS: Between October 1, 2017 and August 1, 2019, a total of 178 adults underwent HT at our institution, including 98 patients in Cohort A and 80 patients in Cohort B. Relative to patients in Cohort A, patients in Cohort B were more likely to be bridged to HT with temporary mechanical circulatory support (MCS) (9 (11%) vs 2 (2%), less likely to be bridged with durable LVAD (21 (26%) vs 39 (40%)) and equally likely to be listed by status exception request (23 (29%) vs 28 (29%)). Among 21 patients in Cohort B bridged with durable LVAD, only 4 (19%) underwent HT at status 4 whereas 17 (81%) required upgrade to status 3 using their '30-day time' (n=15) or due to complications (n=2), in order to achieve HT. By comparison, among 39 patients in Cohort A bridged with durable LVAD, 18 (46%) underwent HT at Status 1B (equivalent to status 4 in the RAS). Nineteen (49%) transplanted LVADs in Cohort A had ABO O blood type, compared to only 6 (29%) in Cohort B. While implementation of the RAS did not significantly impact our center's rate of HT, it influenced decision-making at time of HT listing in favor of temporary MCS when justified, and against durable MCS, especially in patients with O blood type. Moreover, despite RAS changes aimed at reducing status exception requests, requests made by our center remain equally likely now as they were prior to RAS implementation.

Blood Urea Nitrogen to Creatinine Ratio at Listing is Associated with Poor Outcomes in Heart Transplant Recipients with Stage 3 Chronic Kidney Disease

Non-dialysis dependent patients with renal impairment undergoing heart transplantation (HT) alone are at significantly higher risk of mortality and poor renal outcomes compared with those undergoing heart-kidney transplantation (HKT). It remains unclear what parameters might identify patients who may benefit from HKT compared to HT alone. We investigated whether blood urea nitrogen to creatinine ratio (BCR) at time of HT listing among those with stage 3 chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) between 30 and 59 ml/min/1.73 m2) is associated with higher risk of post-HT death or dialysis. We identified 159 patients who underwent HT alone at our institution between 1/2009 and 2/2018. Univariate and multivariate Cox-proportional regression analyses were used to investigate the association between BCR and composite risk of post-HT death or dialysis at 1 year. At listing, average age was 55±10 years (74% male and 28% African American) and eGFR was 47 ± 8. Mean eGFR did not differ between those with the composite outcome (46 ± 8) and those without (47 ± 8; p = 0.60). Overall, 14 patients (9%) died and 25 (16%) needed dialysis by 1 year post-HT. The univariate and multivariate adjusted hazard ratios for continuous variable BCR as a predictor of the composite outcome were 1.05 [95% confidence interval (CI): 1.02, 1.09; p < 0.01) and 1.04 [95% CI: 1.01, 1.09; p = 0.02), respectively. Additional regression analyses and Kaplan-Meier survival curves are shown in the figure. Heart transplant candidates with stage 3 CKD and elevated BCR at time of listing are at increased risk of post-HT mortality or dialysis. Further investigation of HKT outcomes among those with stage 3 CKD and elevated BCR at listing is warranted.

Periprocedural Risk and Survival Associated With Implantable Cardioverter-Defibrillator Placement in Older Patients With Advanced Heart Failure

Little is known about the utilization rates and outcomes of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D) placement among patients with advanced heart failure (HF). To examine utilization rates, patient characteristics, and outcomes of ICD and CRT-D placements among patients with advanced HF. This cohort study was a post hoc analysis of 81 492 Medicare fee-for-service beneficiaries enrolled in the National Cardiovascular Data Registry ICD Registry between January 2010 and December 2014. Inclusion criteria were patients who had received an HF diagnosis, had a left ventricular ejection fraction of 35% or lower, and showed evidence of advanced HF, which was defined as New York Heart Association (NYHA) class IV symptoms, inotrope use within the last 60 days, left ventricular assist device in situ, or orthotopic heart transplant listing. The comparator group included patients with NYHA class II and no HF hospitalization within the last 12 months, no left ventricular assist device, no orthotopic heart transplant listing, and no current or recent inotrope use. All eligible patients underwent first-time ICD or CRT-D placement for primary prevention of sudden cardiac death. Data were analyzed from January 2010 to December 2014. All-cause mortality and periprocedural complications. Of 81 492 Medicare patients, 3343 had advanced HF (4.1%) and 19 424 were in the comparator group (23.8%). Among the advanced HF population, the mean (SD) age of patients was 74 (9) years, and patients were predominantly white individuals (81.5%) and men (71.1%). The all-cause mortality rate at 30 days was 3.1% (95% CI, 2.6%-3.8%) in the advanced HF group vs 0.5% (0.4%-0.6%) in the comparator group (P < .001). In the advanced HF population, the aggregate in-hospital periprocedural complication rate was 3.74% (95% CI, 3.12%-4.44%) vs 1.10% (95% CI, 0.95%-1.25%) in the comparator group (P < .001). Most adverse events in this group were in-hospital fatality (1.82%; 95% CI, 1.40%-2.34%) and resuscitated cardiac arrest (1.05%; 95% CI, 0.73%-1.45%). Patients with NYHA class IV (hazard ratio, 1.40; 95% CI, 1.02-1.93; P = .04), ischemic heart disease (hazard ratio, 1.24; 95% CI, 1.04-1.48; P = .02), or diabetes (hazard ratio, 1.17; 95% CI, 1.04-1.33; P = .01) had a higher risk of death. Among patients undergoing ICD or CRT-D placement for primary prevention of sudden cardiac death, only a small proportion had advanced HF. These patients experienced clinically important periprocedural complication rates associated with in-hospital death and cardiac arrest relative to patients with nonadvanced HF.

Cardiovascular progenitor cells and tissue plasticity are reduced in a myocardium affected by Becker muscular dystrophy

We describe the association of Becker muscular dystrophy (BMD) derived heart failure with the impairment of tissue homeostasis and remodeling capabilities of the affected heart tissue. We report that BMD heart failure is associated with a significantly decreased number of cardiovascular progenitor cells, reduced cardiac fibroblast migration, and ex vivo survival.BackgroundBecker muscular dystrophy belongs to a class of genetically inherited dystrophin deficiencies. It affects male patients and results in progressive skeletal muscle degeneration and dilated cardiomyopathy leading to heart failure. It is a relatively mild form of dystrophin deficiency, which allows patients to be on a heart transplant list. In this unique situation, the explanted heart is a rare opportunity to study the degenerative process of dystrophin-deficient cardiac tissue. Heart tissue was excised, dissociated, and analyzed. The fractional content of c-kit+/CD45− cardiovascular progenitor cells (CVPCs) and cardiac fibroblast migration were compared to control samples of atrial tissue. Control tissue was obtained from the hearts of healthy organ donor’s during heart transplantation procedures.ResultsWe report significantly decreased CVPCs (c-kit+/CD45−) throughout the heart tissue of a BMD patient, and reduced numbers of phase-bright cells presenting c-kit positivity in the dystrophin-deficient cultured explants. In addition, ex vivo CVPCs survival and cardiac fibroblasts migration were significantly reduced, suggesting reduced homeostatic support and irreversible tissue remodeling.ConclusionsOur findings associate genetically derived heart failure in a dystrophin-deficient patient with decreased c-kit+/CD45− CVPCs and their resilience, possibly hinting at a lack of cardioprotective capability and/or reduced homeostatic support. This also correlates with reduced plasticity of the explanted cardiac tissue, related to the process of irreversible remodeling in the BMD patient’s heart.