Adult Patients Undergoing Heart Transplantation Research Articles

Duration of Bridge-to-Transplant Extracorporeal Membrane Oxygenation and Heart Transplant Survival

Background. The 2018 Organ Procurement and Transplantation Network (OPTN) heart allocation policy change prioritizes patients bridged to transplant with mechanical circulatory support (MCS) devices, including extracorporeal membrane oxygenation (ECMO). As a result, the use of ECMO has significantly increased. Methods. We reviewed the OPTN database for adult patients undergoing heart transplant after bridge with ECMO between January 1st 2000 and October 18th 2018. We excluded patients with ≥180 days of ECMO duration, prior transplants, and those using additional MCS devices. Survival and morbidity outcomes of patients with ≥7 days of pre-transplant ECMO were compared to those of patients with <7 days. Results. Of 362 eligible transplant recipients, 163 (45%) utilized <7 days of pre-transplant ECMO and 199 (55%) utilized ≥7 days. Those with ≥7 days were younger (median age: 43 [28–54] vs. 50 [36–57] years, p=0.006) and more likely to have temporary waitlist inactivity (18% vs. 7%, p=0.003) with significantly longer duration of ECMO use (median: 14 [9–24] vs. 4 [2–5] days, p < 0.001). Patients with ≥7 days of ECMO had comparable survival to those with <7 days at one year (81.1% vs. 79.4%, p=0.64) and five years (61.1% vs. 49.3%, p=0.27). After adjustment for clinically relevant variables, duration of ECMO ≥7 days did not increase mortality at five years (HR = 0.90, p=0.59). Conclusions. Longer duration of ECMO (≥7 days vs. <7 days) among patients successfully bridged to transplant is not associated with increased mortality or selected adverse outcome, including graft failure or rejection, at up to five years.

Non-inferior outcomes in lower urgency patients transplanted with extended criteria donor hearts

Recent work has suggested that outcomes among heart transplant patients listed at the lower-urgency (United Network for Organ Sharing Status 4 or 6) status may not be significantly impacted by donor comorbidities. The purpose of this study was to investigate outcomes of extended criteria donors (ECD) in lower vs. higher urgency patients undergoing heart transplantation. The United Network for Organ Sharing (UNOS) database was queried for all adult patients undergoing heart transplantation from 10/18/2018 through 12/31/2021. Patients were stratified by degree of urgency (higher urgency: UNOS 1 or 2 vs. lower urgency: UNOS 4 or 6) and receipt of ECD hearts, as defined by donor hearts failing to meet established acceptable use criteria. Outcomes were compared using propensity score matched cohorts. Among 9,160 patients included, 2,320 (25.4%) were low urgency. ECD hearts were used in 35.5% of HU patients and 39.2% of LU patients. While ECD hearts had an impact on survival among high-urgency patients (p<0.01), there was no difference in 1- and 2-year survival (p>0.05) found among low urgency patients receiving ECD vs. standard hearts. Neither ECDs nor individual ECD criteria were independently associated with mortality in low urgency patients (p>0.05). Post-transplant outcomes among low urgency patients are not adversely affected by receipt of ECD vs. standard hearts. Expanding the available donor pool by optimizing use of ECDs in this population may increase transplant frequency, decrease waitlist morbidity, and improve postoperative outcomes for the transplant community at large.

Heart transplantation after total artificial heart bridging-Outcomes over 15 years.

Data are limited on outcomes after heart transplantation in patients bridged-to-transplantation (BTT) with a total artificial heart (TAH-t). The UNOS database was used to identify 392 adult patients undergoing heart transplantation after TAH-t BTT between 2005 and 2020. They were compared with 11014 durable left ventricular assist device (LVAD) BTT patients and 22348 de novo heart transplants (without any durable VAD or TAH-t BTT) during the same period. TAH-t BTT patients had increased dialysis dependence compared to LVAD BTT and de novo transplants (24.7%vs. 2.7%vs. 3.8%) and higher levels of baseline creatinine and total bilirubin (all p<.001). After transplantation, TAH-t BTT patients were more likely to die from multiorgan failure in the first year (25.0%vs. 16.1%vs. 16.1%, p=.04). Ten-year survival was inferior in TAH-t BTT patients (TAH-t BTT 53.1%, LVAD BTT 61.8%, De Novo 62.6%, p<.001), while 10-year survival conditional on 1-year survival was similar (TAH-t BTT 66.8%, LVAD BTT 68.7%, De Novo 69.0%, all p>.20). Among TAH-t BTT patients, predictors of 1-year mortality included higher baseline creatinine and total bilirubin, mechanical ventilation, and cumulative center volume <20 cases of heart transplantation involving TAH-t BTT (all p<.05). Survival after TAH-t BTT is acceptable, and patients who survive the early postoperative phase experience similar hazards of mortality over time compared to de novo transplant patients and durable LVAD BTT patients.

Heart transplantation using donation after circulatory death in the United States

ObjectivesHeart donation after circulatory death was recently reintroduced in the United States with hopes of increasing donor heart availability. We examined its national use and outcomes. MethodsThe United Network for Organ Sharing database was used to identify validated adult patients undergoing heart transplantation using donation after circulatory death donors (n = 266) and donation after brain death donors (n = 5998) between December 1, 2019, and December 31, 2021, after excluding heart-lung transplants. Propensity score matching was used to create more balanced groups for comparison. ResultsThe monthly percentage of donation after circulatory death heart transplant increased from 2.5% in December 2019 to 6.8% in December 2021 (P < .001). Twenty-two centers performed donation after circulatory death heart transplants, ranging from 1 to 75 transplants per center. Four centers performed 70% of the national volume. Recipients of donation after circulatory death hearts were more likely to be clinically stable (80.4% vs 41.1% in status 3-6, P < .001), to have type O blood (58.3% vs 39.9%, P < .001), and to wait longer after listing (55, interquartile range, 15-180 days vs 32, interquartile range, 9-160 days, P = .003). Six-month survival was 92.1% (95% confidence interval, 91.3-92.8) after donation after brain death heart transplants and 92.6% (95% confidence interval, 88.1-95.4) after donation after circulatory death heart transplants (hazard ratio, 0.94, 95% confidence interval, 0.57-1.54, P = .79). Outcomes in propensity-matched patients were similar except for higher rates of treated acute rejection in donation after circulatory death transplants before discharge (14.4% vs 8.8%, P = .01). In donation after circulatory death heart recipients, outcomes did not differ based on the procurement technique (normothermic regional perfusion vs direct procurement and perfusion). ConclusionsHeart transplantation with donation after circulatory death donors has short-term survival comparable to donation after brain death transplants. Broader implementation could substantially increase donor organ availability.

Induction Therapy in Heart Transplantation: A Systematic Review and Network Meta-Analysis

<h3>Purpose</h3> The utility of immunosuppressive induction therapy (IT) following heart transplantation remains contested. In order to evaluate the effectiveness and safety of IT, we conducted a systematic review and network meta-analysis (NMA), evaluating outcomes at 1 year post-heart transplantation. <h3>Methods</h3> We searched bibliographic databases for studies published from January 2000 to July 2021, reporting on the impact of any IT agent in adult patients undergoing heart transplantation. We performed a frequentist NMA evaluating the impact of currently available agents on 1-year all-cause mortality and treated rejection. The analysis generated direct and/or indirect estimates on the effect of IT on outcomes as relative risks (RR). The GRADE framework informed the quality of evidence. <h3>Results</h3> Of the 3,913 publications identified, 23 full-text studies proved eligible, of which 10 reported mortality or rejection outcomes at 1-year, informing the comparison among basiliximab, thymoglobulin (ATG), and no IT. These studies included 7 randomized controlled trials (RCTs) and 3 observational studies with adjusted analyses. Compared to no IT, ATG (RR 0.87, 95% CI 0.80-0.94) was associated with a significantly decreased risk of rejection, while basiliximab was not (RR 1.02, 95% CI 0.89-1.16). Mortality at 1 year was similar with vs without IT - ATG: RR 4.82, 95% CI 0.63-36.71 and basiliximab: RR 4.26, 95% CI 0.57-32.02. The use of ATG was associated with a significantly lower risk of rejection compared to basiliximab (RR 0.85, 95% CI 0.77-0.94), but with similar mortality (RR 1.14, 95% CI 0.40-3.23). As compared to the full network, our sensitivity analysis of RCTs alone showed no significant differences in pooled estimates of rejection or mortality for any of the network comparisons. <h3>Conclusion</h3> With low certainty in the synthetized evidence, this NMA suggests that the use of IT does not confer mortality benefit at 1 year after heart transplantation. The risk of rejection may, however, be reduced by ATG compared to no IT or basiliximab, although this was not statistically significant when only evaluating data from RCTs, likely due to the small number of events and insufficient power. The utility of IT in specific patient populations, in the long-term, and on other outcomes such as infections, graft dysfunction, kidney dysfunction, and malignancies, remains to be explored.

Improving contemporary outcomes following heart transplantation for cardiac amyloidosis

The incidence of systemic amyloidosis is rising, and there is a concomitant rise in heart transplant for an indication of cardiac amyloidosis. We utilized the Organ Procurement and Transplantation Network (OPTN) database to retrospectively assess survival and outcomes in adult patients undergoing heart transplant for cardiac amyloidosis from 1999 to 2019. We also compared survival among four distinct time periods: 1999-2001, 2002-2008, 2008-2015, 2016-2019. Of 41,103 patients, 425 (1.03%) were transplanted for an indication of restrictive cardiomyopathy due to cardiac amyloidosis (RCM-Amyloidosis). The percent of all transplants occurring for RCM-Amyloidosis increased from 0.25% in the 1999-2001 era to 1.74% in the 2015-2019 era (p < .001). Across eras, Kaplan-Meier survival functions were comparable between RCM-Amyloidosis and non-RCM patients at 1 year (88% vs. 89%, p = .56) and at 5 years (72% vs. 77%, p = .092), but worse for RCM-Amyloidosis patients at 10 years (44% vs. 59%, p = .002). With adjustment for other clinical variables in multivariable Cox regression model, RCM-Amyloidosis was not associated with increased risk of death at 1 year (hazard ratio [HR] = 1.11, p = .56) or at 5 years (HR = 1.20, p = .18), but it was associated with increased risk of death at 10 years (HR = 1.35, p = .01). Cardiac amyloidosis was not associated with any morbidity outcomes following transplant, including graft failure, acute rejection, or hospitalization for infection or rejection. Our data suggest a trend of improving survival among RCM-Amyloidosis patients compared with non-RCM patients across transplant eras, with current similarities in 1- and 5-year survival but a persistent, increased risk of mortality at 10 years.

Assessing predicted heart mass size matching in obese heart transplant recipients

Predicted heart mass (PHM) is currently the most reliable metric for donor-recipient size matching in heart transplantation. Undersizing PHM donor-recipient match more than 20% independently predicts reduced survival. However, it is unclear if this is the case in obese recipients, in whom size matching can be challenging. We examined the use of PHM undersized hearts in obese recipients and assessed its impact on survival. The United Network for Organ Sharing database was queried for adult patients undergoing heart transplantation from 1995 to 2020. Obese recipients (BMI ≥ 30) were categorized based on donor-recipient PHM match ≤-20% (undersized) or >-20% (size-matched). Nearest-neighbor propensity score matching was performed to adjust for baseline differences between cohorts. Temporal outcomes were compared by Kaplan-Meier survival analysis. A total of 13,668 obese recipients met inclusion criteria, with 9.6% receiving undersized and 90.4% receiving size-matched hearts. The proportion of undersized donor hearts in obese recipients significantly decreased over the study period (16.2% [1995] to 7.4% [2019], NP-trend < 0.001). Propensity-score matching resulted in 984 well-matched pairs of undersized and size-matched obese recipients. Recipients of undersized hearts saw similar 30-day mortality (5.5% vs 6.0%, p= 0.11) and re-transplantation rates (1.2% vs 1.2%, p=1.00) as size-matched recipients. Survival at 1 year (88.4% vs 87.9%, p=0.14), and 15 years (35.1% vs 31.0%, p=0.12) was similar across cohorts. A decreasing proportion of PHM undersized hearts are being utilized in obese recipients. However, utilizing PHM undersized hearts in obese recipients was not associated with a detriment in survival.

Does CMV Status Affect Morbidity and Survival Following Heart Transplantation? A Large Multicentre Retrospective Study

<h3>Purpose</h3> Cytomegalovirus (CMV) infection following heart transplant is associated with increased morbidity and mortality. We evaluated the impact of CMV status on long term survival at all centres in the UK, each employing different approaches to managing CMV. <h3>Methods</h3> Adult patients undergoing heart transplantation and surviving >30 days between 1987 and 2018 were included. Data obtained from NHS Blood and Transplant included CMV donor (D) and recipient (R) status, R age, R sex, centre, treated rejection episodes and survival. Patients grouped by CMV status: D-ve R-ve (DN), D+ve R-ve (PM), D+ve R+ve (DP), D-ve R+ve (RM). 5 year survival, adjusted for age, sex and centre, was compared between groups. Adjusted survival between centres was also compared. Survival data was compared using Cox-proportional hazards. Treated rejection rates between CMV groups were compared using Chi² test. <h3>Results</h3> 2675 patients were included from 6 UK transplant centres; 2 use a pre-emptive strategy, 4 use valganciclovir in PM patients and high risk R+ve patients for 3-6 months. Five year survival per group CMV DN 629/750 (83.9%), PM 440/563 (78.1%) RM 655/773 (84.7%) DP 467/592 (78.8%). Compared to DN, both PM (HR 1.43 p=0.005) and DP (HR 1.34 p=0.025) associated with significantly higher mortality. There was no survival difference between centres, p=0.127 and no difference between centres for PM (p=0.69) or DP (0.23) groups. Rates of treated rejection at 12 months were higher in PM and DP patients (p=0.0033). <h3>Conclusion</h3> This is the first multicentre evaluation of the impact of CMV status on longer term survival following heart transplant. CMV mismatch and double positive statuses were associated with higher rates of rejection and reduced survival, irrespective of CMV prevention strategy. This should be considered when counselling patients, and in adjusted survival analyses. No differences in outcomes were seen between centres, although we were unable to account for changes in individual centre practice over time.

The Optimal Cumulative Dose of Rabbit Antithymocyte Globulin Induction in Adult Heart Transplantation

Purpose To determine the optimal cumulative dose of rabbit antithymocyte globulin (rATG) regarding its efficacy and safety and to evaluate the target level of CD3+ T cell count for induction therapy in adult heart transplantation. Methods This retrospective cohort study enrolled adult patients undergoing heart transplantation in a medical center between January 2016 and July 2019. The rATG induction was initiated postoperatively at a dose of 0.75-1 mg/kg/day for 3-5 days to maintain CD3+ counts Results A total of 62 patients with 189 doses of rATG were enrolled. The first dose and the cumulative dose of rATG were 0.67 ± 0.18 mg/kg and 1.44 ± 0.40 mg/kg. The cut-off point for the cumulative dose of rATG in achieving CD3+ count Conclusion A cumulative rATG dose of 1.2 mg/kg may be effective in achieving CD3+ counts

Trends in the use of hepatitis C viremic donor hearts

ObjectiveTo examine trends in utilization of hearts from hepatitis C virus (HCV) viremic donors for transplantation, a strategy to expand organ availability. MethodsThe United Network for Organ Sharing (UNOS) registry was queried for adult patients undergoing heart transplantation between 2015 and 2019. We excluded multiorgan transplants, incomplete data, and loss to follow-up. Nucleic acid testing (NAT) defined HCV status. ResultsBetween 2015 and 2019, a total of 11,393 adults underwent heart transplantation: 326 from HCV NAT+ donors and 11,067 from NAT− donors. The use of NAT+ hearts increased from 1 in 2015 to 137 in 2018 against a static number of NAT− organs. The use of NAT+ hearts varied significantly across regions and individual centers. More than 75% of NAT+ hearts were transplanted in the Northeast region, leading to further travel (mean, 299 miles vs 173 miles for NAT− transplantations; P < .001), with longer ischemic times (mean: 3.52 hours vs 3.10 hours; P < .001). More than one-half of NAT+ transplantations were performed by 5 individual centers, and a single institution accounted for >20% of all transplantations from viremic donors. Survival in the 2 groups did not differ by Kaplan-Meier analysis (P = .240), and multivariable regression showed no differences in acute rejection (P = .455) or 30-day mortality (P = .490). Of the 326 recipients of NAT+ hearts, 38 seroconverted and 14 became viremic within 1 year. Survival was 100% in the viremic patients and 97.4% in seroconverted patients at 1 year. ConclusionsHeart transplantation from HCV viremic donors continues to increase but varies significantly across UNOS regions and individual centers. Short-term outcomes are comparable, but effects of seroconversion and long-term outcomes remain unclear.

Does CMV Status Impact on Morbidity and Survival Following Heart Transplantation? A Large Multi-Centre Retrospective UK Study

Cytomegalovirus (CMV) infection following heart transplant is associated with increased morbidity and mortality. We evaluated the impact of CMV status on long term survival at all UK centres, employing different approaches to managing CMV. Adult patients undergoing heart transplantation and surviving >30 days between March 1987 and August 2018 included. Data obtained from NHS Blood and Transplant included CMV donor (D) and recipient (R) status, age, sex, centre, treated rejection episodes and survival. Patients grouped by CMV status: D-ve R-ve (DN), D+ve R-ve (PM), D+ve R+ve (DP), D-ve R+ve (RM). 5 year survival, adjusted for age, sex and centre, was compared between all CMV groups, with individual comparisons between DN patients and other statuses. Survival between centres, adjusted for age and sex also compared. Survival data compared using Cox-proportional hazards. Rates of treated rejection between CMV groups compared using Chi2 test. 2675 patients included from 6 UK transplant centres; 2 use a pre-emptive strategy, 4 use valganciclovir in PM patients and high risk R+ve patients for 3-6 months. Five year survival per group CMV DN 629/750 (83.9%), PM 440/563 (78.1%) RM 655/773 (84.7%) DP 467/592 (78.8%). Compared to DN, both PM (HR 1.43 p=0.005) and DP (HR 1.34 p=0.025) were associated with significantly higher mortality. There was no survival difference between centres, p= 0.127, and no difference between centres for PM (p=0.69) or DP (0.23) groups. Rates of treated rejection at 12 months were higher in PM and DP patients, difference between groups p=0.0033. To our knowledge, this is the first multicentre evaluation of the impact of CMV status on longer term survival following heart transplant. CMV mismatch and double positive statuses were associated with higher rates of rejection and reduced survival, irrespective of the CMV prevention strategy used. This should be considered when counselling patients, and in adjusted survival analyses.

Utilization of New Heart Preservation Technology in the Era of New Organ Allocation and Extended Ischemic Times

Current ice bag heart preservation technique is associated with wide fluctuations of organ temperature, resulting in sub-optimal preservation and freeze injury. These shortcomings may be particularly impactful with increased ischemic times given increasing retrieval distances associated with new organ allocation. In comparison, the SherpaPakTM Cardiac Transport System is designed for the static hypothermic preservation of donor hearts within a controlled temperature range. This method avoids excess cooling and optimizes preservation during transportation. The purpose of this study is to assess the outcomes of heart transplantation using the static hypothermic preservation (SHP) system as compared with conventional ice bag preservation (IP). Retrospective cohort analysis was performed on adult patients undergoing heart transplantation between 6/30/2018 and 09/02/2019 at a single institution. Donor and recipient baseline characteristics and post-transplant outcomes were compared between patients receiving organs with SHP versus IP for donor heart transport. Patients who underwent multiple organ transplantation were excluded. Of 48 consecutive patients undergoing heart transplantation, 20 (41.7%) organs were transported using SHP and 28 (58.3%) using IP. SHP was used for older recipients (61.5 vs 57.5 years, p=0.02), and longer donor heart cold ischemic times (4.35 vs 3.49 hours, Figure1, p=0.018). There were no 30-day mortalities. Despite longer ischemic times, there was no difference in the incidence of any primary graft dysfunction (PGD) (14.3% vs 15.0%, p=1) or severe PGD requiring extracorporeal membrane oxygenation (10.7% vs 5.0%, Table1, p=0.63) between SHP and IP. There was no worsening in clinical outcomes with SHP despite longer ischemic times and older recipient ages. With new heart allocation changes, SHP may be beneficial in cases with further transport distances, by mitigating the effect of prolonged ischemic times.

The Impact of Donor Gender on Heart Transplantation Outcomes - A Study of over 60,000 Patients in the United States

The objective of this study was to evaluate the impact of donor gender on heart transplantation outcomes in the United States. From 1987 to March 2019, 63,775 adult patients underwent heart transplantation in the United States, and their data were prospectively collected by the United Network for Organ Sharing (UNOS). Patients without missing data were stratified by donor gender (female, N = 11,474; male, N = 27,509) and donor menopause status (pre-menopause, ages 35-40 years old, N = 1,783; post-menopause, ages 50-55 years old, N = 1,105). The groups were propensity matched 1:1 based on year of surgery, pre-transplant status, wait list time, human leukocyte antigen matching, donor demographics, and allograft ischemic time. Paired t-test, McNemor's tests and Kaplan-Meier survival analyses were performed. The primary endpoint was all cause mortality, and secondary endpoints were postoperative complications. Propensity matching generated 15,506 patients based on donor gender and 1,094 patients based on donor menopause status. Recipients who received female donor hearts were more likely to have acute rejection episodes (630/11.9% vs. 545/10.1%, p = .007) and require post-transplant dialysis (837/10.9% vs. 719/9.3%, p = .001) than those who received male donor hearts. No difference was observed between using female or male donor hearts in the rates of graft failure (551/8.2% vs. 641/9.5%) or stroke (179/2.4% vs. 199/2.6%) (p ≥ .34). Median survival using female vs. male donor hearts was 11.6 vs. 12.1 years (p = .34) with ten-year survival of 56.5% vs. 57.1%, respectively. Recipients who received pre- vs. post-menopausal female donor hearts had similar rates of acute rejection episodes (39/11% vs. 45/12.5%), graft failure (37/7.9% vs. 46/9.9%), stroke (10/1.8% vs. 15/2.8%), or requiring dialysis (67/12.3% vs. 81/14.9%) (p ≥ .09). Median survival using pre- vs. post-menopausal female donor hearts was 11.5 vs. 10.4 years (p = .23) with ten-year survival of 56.7% vs. 51.2%, respectively. Analysis of the UNOS database showed similar median survival using female vs. male donor hearts in adult heart transplantation, irrespective of donor menopause status. Currently, female donor hearts are used far less frequently, thus these results represent an opportunity to maximize usage by better utilization of suitable female donor organs.

Relationship Between Change in Heart Transplant Volume and Outcomes: A National Analysis

Although volume-outcome relationships in transplantation have been well-defined, the effects of large changes in center volume are less well understood. The purpose of the current study was to examine the impact of changes in center volume on outcomes after heart transplantation. Retrospective analysis was performed of adult patients undergoing heart transplant between 2000 and 2017 identified in the United Network for Organ Sharing database. Exclusions included annual volume <10. Patients were grouped according to percentage change in center volume from the previous year. Multivariable Cox regression models were adjusted for the significant preoperative variance identified on univariate analyses. Of the 29,851 transplants during the study period, 64% were at centers with stable volume (±25% annual change), whereas 10% were performed at contracting (-25% change or more) and 26% were performed at growing (+25% change or more) centers. Average volume was lower with contracting centers compared with stable or growing programs (21 vs 36, P< .001). Thirty-day mortality was greater in decreasing centers (6% vs 4%, P < .001), with more acute rejection treatments at 1y (27% vs 24% P < .001). The adjusted risk of mortality among contracting centers was 1.25 ([1.07-1.46], P= .004), whereas growing centers had unaffected risk (0.90 [0.79-1.02], P= .103). Causes of death were similar between groups. Rapid growth of transplant center volume has occurred at select centers in the United States without decrement in programmatic outcomes. Decreasing center volume has been associated with poorer outcomes, although the causative nature of this relationship requires further investigation.

Matchmaking Just Got Easier: Impact of Phenotypic Donor-Recipient Likeness in Heart Transplantation

Phenotypic matching in heart transplantation, where donors and recipients are matched based on physical characteristics, has been previously limited to only analyzing individual variables such as sex and age. This study examines the effects of phenotypic matching utilizing multiple factors simultaneously. Adult patients undergoing heart transplantation between 2006 and 2016 were identified from the Organ Procurement and Transplantation Network database. Phenotypic matching was defined based on six factors: body mass index difference >30%, age difference >30%, height difference >7%, non-identical ABO blood grouping, race, and sex. A value between 0 and 1 mismatched characteristics was considered phenotypically like matching, whereas 2-6 mismatches was considered phenotypically unlike matching. The primary study endpoint was 1-year survival. Risk-adjusted mortality was examined with multivariable Cox regression models. During the study period, 20,052 adult patientsunderwent heart transplantation, of whom 9595 (47.9%) were phenotypically like and 10,457 (52.1%) were phenotypically unlike matched. No differencesin 1-year survival were seen between like and unlike matched patients (risk-adjusted odds ratio 1.05, 95% confidence interval 0.96-1.15, P= .305) after controlling for clinically relevant covariates. Subgroup analyses did not demonstrate survival differences afterstratification based on hospital transplant volumeand initial waitlist status. Phenotypically like matched patients had longer waiting times compared with unlike matched patients overall (225 days vs 192 days, P < .001). Waiting for a phenotypically matched heart provides no survival benefit and exposes patients to prolonged waitlist times. These findings challenge the notion that a perfect donor heart exists, when in fact this concept may be a misnomer.

Genetic variants identified by target next-generation sequencing in heart transplant patients with dilated cardiomyopathy

Introduction and ObjectivesDilated cardiomyopathy (DCM) is a myocardial disease that can progress to a terminal stage, requiring heart transplantation. In this work we aim to contribute to knowledge of genetic variants in adult patients undergoing heart transplantation due to end-stage DCM, reporting the results obtained in our single-center tertiary hospital series using target next-generation sequencing (NGS). Methods and ResultsGenetic variants were screened in 15 genes, preselected based on variants previously identified in DCM patients. Thirteen unrelated patients were included, nine (69%) male, mean age at diagnosis 33±13 years, eight (62%) with familial DCM. Nine genetic variants were identified in six (46%) patients: five in LMNA, two in LBD3, one in TNNT2 and one in TCAP. These variants were new in most patients. The majority were classified as of uncertain significance. Two patients were double and triple heterozygotes in the LBD3 and LMNA genes, respectively. ConclusionOur results highlight the potential of NGS in the genetic characterization of DCM patients. LMNA is one of the most frequently mutated genes and should be included in all target gene assessments of end-stage DCM patients until more data are available.

Matchmaking Just Got Easier: Impact of Phenotypic Donor-Recipient Likeness in Open Heart Transplantation

Purpose Phenotypic matching in heart transplantation , where donors and recipients are matched based on physical characteristics, has been previously limited to only analyzing gender, BMI, and age. This study examines the effects of phenotypic matching utilizing multiple factors. Methods Adult patients undergoing heart transplantation between 2006 and 2016 were identified from the Organ Procurement and Transplantation Network (OPTN) database. Phenotypic matching was defined based on six factors: Body mass index (BMI) difference >30%, age difference >30%, height difference >7%, non-identical ABO blood grouping , ethnicity, and gender. A value between 0-1 mismatched characteristics was considered phenotypically like matching, while 2-6 mismatches was considered phenotypically unlike matching. The primary study endpoint was one-year survival. Risk-adjusted mortality was examined with multivariable Cox regression models after controlling for donor and recipient covariates. Results During the study period, 20,052 adult patients underwent heart transplantation, of which 9,595 (47.9%) were phenotypically like matched and 10,457 (52.1%) were phenotypically unlike matched. No differences in 1-year survival were seen between like and unlike matched patients (risk-adjusted OR 1.05, 95% CI 0.96-1.15, p=0.305) after controlling for clinically relevant covariates (Figure.) Subgroup analyses did not demonstrate survival differences after stratification based on hospital volume and initial waitlist status. Phenotypically like matched patients had longer waiting times compared to unlike matched patients both overall (225 days versus 192 days, p Conclusion Waiting for a phenotypically matched heart provides no survival benefit and exposes patients to prolonged waitlist times. This challenges the belief that a perfect donor heart exists, and we should challenge ourselves to accept organs sooner for patients who are waiting for a heart transplant .

Orthotopic Heart Transplant Volume Can Be Aggressively Increased While Maintaining Outcomes

Purpose While volume-outcome relationships in transplantation have been well-defined, the effects of large swings in center volume are less well understood. The purpose of the current study was to examine the impact of changes in center volume on outcomes after heart transplantation. We hypothesize that rapid growth may be achieved without having a deleterious effect on outcomes. Methods Retrospective analysis was performed of adult patients undergoing heart transplant between 2000-2017 identified in the UNOS database. Exclusions included annual volume Results Of the 29,851 transplants during the study period, 64% were at centers with stable volume (±25% annual change), 10% were performed at decreasing (-25% change or more) and 26% were performed at growing (+25% change or more) centers. Average volume was lower with decreasing compared to stable or growing programs (21 vs. 36, p Conclusion Rapid growth of center volume can occur without decrement in programmatic outcomes. Careful patient selection among centers with changing volume may improve outcomes. Large decreases in transplant center volume are independently associated with increased short and long-term mortality after heart transplantation.

Risk of severe primary graft dysfunction in patients bridged to heart transplantation with continuous-flow left ventricular assist devices.

Primary graft dysfunction (PGD) remains a significant cause of post-transplant morbidity and mortality. The exact mechanism and risk factors for this phenomenon remain unknown in the contemporary era. In this study we reviewed adult patients undergoing heart transplantation (HT) at our institution between 2009 and 2017. Severe PGD was defined as the need for mechanical circulatory support (MCS) within the first 24 hours after HT. Multivariate logistic regression analysis was used to identify risk factors for severe PGD, focusing on those bridged to transplant (BTT) with a continuous-flow left ventricular assist device (CF-LVAD). Fifty-six of 480 (11.7%) HT patients experienced severe PGD. Eighty percent of the severe PGD patients were BTT with a CF-LVAD (odds ratio [OR] 3.86, 95% confidence interval [CI] 1.94 to 7.68, p < 0.001). Among the BTT patients, significant associations between >1 year of CF-LVAD support (OR 2.48, 95% CI 1.14 to 5.40, p = 0.022), pre-HT creatinine (OR 3.35, 95% CI 1.42 to 7.92, p = 0.006), elevated central venous pressure/pulmonary capillary wedge pressure (CVP/PCWP) ratio (OR 3.32, 95% CI 1.04 to 10.60, p = 0.043), use of amiodarone before HT (OR 2.69, 95% CI 1.20 to 6.20, p = 0.022), and severe PGD were identified. RADIAL score did not accurately predict severe PGD in this contemporary cohort. Those patients who developed severe PGD had decreased 1-year post-transplant survival (78.3% vs 91.8%, p = 0.007). Use of CF-LVAD as BTT is associated with an increased risk of severe PGD. Increased time on device support, renal dysfunction, right ventricular dysfunction as assessed by CVP/PCWP ratio, and pre-transplant amiodarone may identify those patients at high risk. Further research is warranted focusing on optimal timing of device implantation and transplantation, as well as the underlying mechanisms of PGD.

Electrocardiographic Correlates of Acute Allograft Rejection Among Heart Transplant Recipients.

Acute allograft rejection appears to be associated with increases in QT/QTc intervals. To determine the relationship between acute allograft rejection and electrocardiogram changes in patients undergoing an orthotopic heart transplant. The study population comprised 220 adult patients undergoing heart transplant and enrolled in the NEW HEART study. Electrocardiograms obtained within 72 hours of endomyocardial biopsy were analyzed; electrocardiograms obtained fewer than 10 days after transplant surgery were excluded. Repeated-measures analysis was performed with statistical models including effects for rejection severity (mild and moderate/severe) and time trends independent of rejection status. The 151 male and 69 female transplant recipients (mean age [SD], 54 [13] years) had 969 biopsy/electrocardiogram pairs: 677 with no rejection, 280 with mild rejection, and 12 with moderate/severe rejection. Moderate to severe organ rejection was associated with significant increases in QRS duration (P < .001), QT (P = .009), QTc (P = .003), and PR interval (P = .03), as well as increased odds of right bundle block branch (P = .002) and fascicular block (P = .009) occurring. Moderate to severe acute allograft rejection was associated with electrocardiographic changes after transplant surgery. Studies are needed to assess the value of computerized electrocardiogram measurement algorithms for detecting acute allograft rejection.