Surgeons of the Future: A Novel Screening Tool for High-School Students.

INTRODUCTION: Given a looming shortage of surgeons and currently inadequate pipelines into our specialty for under-represented groups, there is an urgent need to identify and foster interest in young individuals who may have great potential as future surgeons. We aimed to explore the utility and feasibility of a novel survey instrument to identify high-school students well suited for careers in surgery based on personality profiling and grit. METHODS: An electronic screening tool was developed, combining components of the Myers-Briggs personality profile, the Big-Five Inventory 10, and the grit scale. This brief questionnaire was electronically distributed to surgeons and students across two academic institutions and three high schools (one private and two public). Wilcoxon rank-sum test and Chi-squared/Fisher's exact test were performed to evaluate variations between groups. RESULTS: Surgeons (n = 96) displayed mean Grit score of 4.03 (range: 3.08-4.92; standard deviation: 0.43), while high-schoolers' (n = 61) mean score was 3.38 (range: 2.08-4.58; standard deviation: 0.62) (P < 0.0001). Surgeons showed Myers-Brigg Type Indicator trait-dominance toward extroversion, intuition, thinking, and judging, while students displayed greater breadth of traits. Students were much less likely to show dominance in introversion versus extroversion (P < 0.0001) as well as perceiving versus judging (P < 0.0001). Big-Five Inventory 10 traits of neuroticism and conscientiousness were more prevalent among surgeons (P < 0.0001 for both). CONCLUSIONS: Importantly, there exists a subgroup of high-school students with personality and grit similar to those of surgeons. Moreover, we have demonstrated the feasibility of using this novel screening tool for future studies aimed to create pipelines for early exposure opportunities and mentorship.

An Analysis of Waitlist Inactivity Among Patients With Ventricular Assist Devices.

BACKGROUND: Ventricular assist devices (VADs) are commonly used mechanical circulatory support for bridge to transplant therapy in end-stage heart failure; however, it is not understood how VADs influence incidence of waitlist inactive status. We sought to characterize and compare waitlist inactivity among patients with and without VADs. METHODS: Using the Organ Procurement and Transplantation Network database, we investigated the VAD's impact on incidence and length of inactive periods for heart transplant candidates from 2005 through 2018. We compared median length of inactivity between patients with and without VADs and investigated inactivity risk with time-to-event regression models. RESULTS: Among 46,441 heart transplant candidates, 32% (n = 14,636) had a VAD. Thirty-eight percent (n = 17,873) of all patients experienced inactivity, of which 42% (7538/17,873) had a VAD. Median inactivity length was 31 d for patients without VADs and 62 d for VAD patients (P < 0.0005). Multivariable analysis showed no significant difference in risk of inactivity for deteriorating conditions between patients with and without VADs after controlling for demographic and baseline clinical variables. A larger proportion of patients without VADs were inactive for deteriorating conditions than VAD patients (54%, n = 8242/15,221 versus 32%, n = 3583/11,086, P < 0.001). Ten percent (1155/11,086) of VAD patients' inactive periods were for VAD-related complications. CONCLUSIONS: Although VAD patients were inactive longer and had an overall increased risk of any-cause inactivity, their risk of inactivity for deteriorating condition was not significantly different from patients without VADs. Furthermore, VAD patients had a smaller proportion of inactivity periods due to deteriorating conditions. Thus, VADs are protective from morbidity for waitlist patients.

High rates of de novo malignancy compromise post-heart transplantation survival.

BACKGROUND: Transplant patients are known to have increased risk of developing de novo malignancies (DNMs). As post-transplant survival increases, DNM represents an obstacle to further improving survival. We sought to examine the incidence, types, and risk factors for post-transplant DNM. METHODS: We studied adult heart transplant recipients from the Organ Procurement and Transplantation Network database (1987-2018). Kaplan-Meier survival analysis was performed to determine annual probabilities of developing DNM, excluding squamous and basal cell carcinoma. Rates were compared to the general population in the Surveillance, Epidemiology, and End Results database. Cox proportional hazards regression was performed to calculate hazard ratios for risk factors of DNM development, all-cause, and cancer-specific mortality. RESULTS: Over median follow-up of 6.9 years, 18% of the 49,361 patients developed DNM, which correlated with an incidence rate 3.8 times that of the general population. The most common malignancies were lung, post-transplant lymphoproliferative disorder, and prostate. Risk was most increased for female genital, tongue/throat, and renal cancers. Male gender, older age, smoking history, and impaired renal function were risk factors for developing DNM, whereas the use of MMF for immunosuppression was protective. Cigarette use, increasing age, the use of ATG for induction and calcineurin inhibitors for maintenance were risk factors for cancer-specific mortality. The development of a DNM increased the risk of death by 40% (p < .001). CONCLUSIONS: Heart transplant patients are at increased risk of malignancy, particularly rare cancers, which significantly increases their risk of death. Strict cancer surveillance and attention to immunosuppression are critical for prolonging post-transplant survival.

Gender and racial disparities in the transplant surgery workforce.

PURPOSE OF REVIEW: This review explores trends in the United States (US) transplant surgery workforce with a focus on historical demographics, post-fellowship job market, and quality of life reported by transplant surgeons. Ongoing efforts to improve women and racial/ethnic minority representation in transplant surgery are highlighted. Future directions to create a transplant workforce that reflects the diversity of the US population are discussed. RECENT FINDINGS: Representation of women and racial and ethnic minorities among transplant surgeons is minimal. Although recent data shows an improvement in the number of Black transplant surgeons from 2% to 5.5% and an increase in women to 12%, the White to Non-White transplant workforce ratio has increased 35% from 2000 to 2013. Transplant surgeons report an average of 4.3 call nights per week and less than five leisure days a month. Transplant ranks 1st among surgical sub-specialties in the prevalence of three well-studied facets of burnout. Concerns about lifestyle may contribute to the decreasing demand for advanced training in abdominal transplantation by US graduates. SUMMARY: Minimal improvements have been made in transplant surgery workforce diversity. Sustained and intentional recruitment and promotion efforts are needed to improve the representation of women and minority physicians and advanced practice providers in the field.

Persistent Racial and Sex Disparities in Outcomes After Coronary Artery Bypass Surgery: A Retrospective Clinical Registry Review in the Drug-eluting Stent Era.

OBJECTIVE: The purpose of this study was to assess the temporal trends in 30-day mortality by race group for patients undergoing coronary artery bypass grafting (CABG) between 2011 and 2018 and to investigate the effect of race and sex on postoperative outcomes after CABG. SUMMARY BACKGROUND DATA: Cardiovascular diseases remain a leading cause of death in the United States with studies demonstrating increased morbidity and mortality for black and female patients undergoing surgery. In the post drug-eluting stent era, studies of racial disparities CABG are outdated. METHODS: We performed a retrospective analysis of the Society for Thoracic Surgeons database for patients undergoing CABG between 2011 and 2018. Primary outcome was 30-day mortality. Secondary outcomes included postoperative length of stay, surgical site infection, sepsis, pneumonia, stroke, reoperation, reintervention, early extubation, and readmission. RESULTS: The study population was comprised of 1,042,506 patients who underwent isolated CABG between 2011 and 2018. Among all races, Black patients had higher rates of preoperative comorbidities. Compared with White patients, Black patients had higher overall mortality (2.76% vs 2.19%, P < 0.001). On univariable regression, Black patients had higher rates of death, infection, pneumonia, and postoperative stroke compared to White patients. On multivariable regression, Black patients had higher odds of 30-day mortality compared to white patients [odds ratio (OR) = 1.11, 95% confidence interval (CI) 1.05-1.18]. Similarly, female patients had higher odds of death compared to males (OR = 1.26, 95% CI 1.21-1.30). CONCLUSIONS: In the modern era, racial and sex disparities in mortality and postoperative morbidity after coronary bypass surgery persist with Black patients and female patients consistently experiencing worse outcomes than White male patients. Although there may be unknown or underappreciated biological mechanisms at play, future research should focus on socioeconomic, cultural, and multilevel factors.

Left Ventricular Assist Device Exchange Increases Heart Transplant Wait-List Mortality.

BACKGROUND: The new heart transplant allocation criteria prioritize inpatients who require temporary mechanical circulatory support and give lower urgency to candidates on a durable left ventricular assist device (LVAD) who require a device exchange. This study explores whether the latter group should warrant higher priority to reduce wait-list mortality. METHODS: This is a retrospective observational study of 13,113 adult heart transplant candidates in the Organ Procurement and Transplantation Network database who underwent LVAD implantation between 2007 and 2017. It evaluates the impact of LVAD exchange on the composite endpoint of death or removal from the wait list owing to worsening medical condition 1 y after device implantation. RESULTS: There were 1085 pump exchanges in 954 patients (7% of candidates), of which 22% were women. The pump exchange rate was 5.92 events per 100 patient-years. One-year survival was lower for those who required a pump exchange (76.3% versus 88.5%, logrank P < 0.001). This was congruent with the risk-adjusted mortality 1-y after implantation (hazards ratio: 2.56, 95% confidence interval: 2.18-3.00, P < 0.001). CONCLUSIONS: These findings indicate that among candidates awaiting heart transplantation with a durable LVAD, undergoing pump exchange doubles the risk of 1-y mortality. Giving priority to these candidates may reduce wait-list mortality.

Effects of Systemic and Device-Related Complications in Patients Bridged to Transplantation With Left Ventricular Assist Devices.

BACKGROUND: The use of left ventricular assist devices (LVADs) as a bridge to heart transplantation has increased rapidly over the last 2 decades. We aim to explore the effect of pretransplant systemic and device-related complications on posttransplant survival for patients bridged with LVADs. MATERIALS AND METHODS: The United Network of Organ Sharing (Organ Procurement and Transplantation Network) database was queried for all adult heart transplant recipients (aged ≥ 18 y) transplanted from April 1, 2015, to June 31, 2018. Device-related complications included thrombosis, device infection, device malfunction, life-threatening arrhythmia, and other device complications. Systemic complications included a new dialysis need or ventilator dependence between the time of listing and transplantation, transfusion, or systemic infection requiring treatment with intravenous antibiotics within 2 wk of transplantation. RESULTS: A total of 2131 patients were identified as requiring LVAD support before transplantation. LVAD patients had high rates of preoperative systemic complications (53%) and high rates of device-related complications (42.7% experienced at least one device-related complication). Kaplan-Meier analysis revealed a significantly decreased 1-y survival for LVAD patients bridged to transplantation who experienced a pretransplant systemic complication (P = 0.041). Interestingly, preoperative device-related complications had no effect on 1-y posttransplantation survival (P = 0.93). Multivariate Cox modeling revealed that systemic complications were associated with a significantly increased risk of posttransplant mortality for LVAD patients (hazard ratio 1.45; P = 0.033). CONCLUSIONS: Recipients who suffered a systemic complication while awaiting heart transplantation experienced higher short-term mortality rates. Device-related complications do not appear to impact posttransplantation outcomes.

Impact of cytomegalovirus serologic status on heart transplantation.

BACKGROUND: Cytomegalovirus (CMV) infection has been associated with increased risk of mortality, cardiac allograft vasculopathy, and de novo malignancy following heart transplantation in prior institutional reports. This study examines the impact of the recipient and donor CMV status on heart recipients in the United States. METHODS: Adult heart transplant recipients were identified in the OPTN registry between 2005-2016. Recipients were stratified based on the recipient (R) and donor (D) CMV serologic status (+/-). The primary endpoint was survival 5-years after transplantation. The secondary endpoint was cardiac allograft vasculopathy 5-years after transplantation. Separate Cox proportional hazards regression models were developed to evaluate independent associations between CMV status and each of the study endpoints. RESULTS: A total of 21 878 recipients met the inclusion criteria. The breakdown of study arms by CMV serologic status was R-/D- = 3412, R+/D- = 4939; R-/D+ = 5230, and R+/D+ = 8,297. Five-year survival estimates were similar across groups (77-79%). CMV status was associated with increased mortality at 5-years (23%-41% increased risk) which was most evident in the first 3 months. The use of valganciclovir was associated with decreased risk of mortality (HR 0.56; 95% CI, 0.52-0.60). The cumulative incidence of cardiac allograft vasculopathy (R-/D- = 31%, R+/D- = 30%, R-/D+ = 31%, and R+/D+ = 30%) was similar across groups. CONCLUSIONS: CMV seropositivity at the time of transplantation is associated with increased long-term risk of mortality. Chemoprophylaxis with antivirals seems to mitigate this risk. There was no association with an increased risk of allograft vasculopathy.

Ventricular assist devices and middle age reduce heart transplantation rates for waitlist candidates.

BACKGROUND: Ventricular assist devices (VADs) are commonly employed as a bridge to transplantation for heart failure. The full effects of VADs on transplantation rates are not fully understood. We sought to compare transplantation rates stratified by age and VAD status. METHODS: Using the Organ Procurement and Transplantation Network (OPTN) database, we investigated the impact of age and VAD status on heart allocation rates among all transplant-eligible patients from January 2005 to September 2018. Patients were grouped based on the presence (+) or absence (-) of a VAD as well as age (<45, 45-65, and >65 years). Demographics were compared with a multivariate competing risk analysis that yielded risk-adjusted subdistribution hazard ratios (SHR). RESULTS: Among the 50 602 total waitlist candidates, 18 271 patients with a VAD had higher rates of diabetes and cerebrovascular disease at waitlist entry. Multivariate analysis found statistically significant lower rates of transplantation for all (+)VAD groups compared with age-matched (-)VAD counterparts, with the 45- to 65-year-old (+)VAD group having the lowest transplantation rate (SHR = 0.62; P < .0005). Among (-)VAD patients, transplantation rates increased with increase in age. CONCLUSIONS: There is a statistically significant reduced rate of transplantation for patients with a VAD compared with those without a VAD, with the lowest rate among those of ages 45 to 65 years with a VAD. The increasing prevalence of this demographic and the deprioritization of VADs in the new heart allocation criteria have the potential to further exacerbate this difference.

Geographic disparities in lung transplant rates.

In November 2017, in response to a lawsuit from a New York City lung transplant candidate, an emergency change to the lung allocation policy eliminated the donation service area (DSA) as the first geographic tier of allocation. The lawsuit claimed that DSA borders are arbitrary and that allocation should be based on medical priority. We investigated whether deceased-donor lung transplant (LT) rates differed substantially between DSAs in the United States before the policy change. We estimated LT rates per active person-year using multilevel Poisson regression and empirical Bayes methods. We found that the median incidence rate ratio (MIRR) of transplant rates between DSAs was 2.05, meaning a candidate could be expected to double their LT rate by changing their DSA. This can be compared directly to a 1.54-fold increase in LT rate that we found associated with an increase in lung allocation score (LAS) category from 38-42 to 42-50. Changing a candidate's DSA would have had a greater impact on the candidate's LT rate than changing LAS categories from 38-42 to 42-50. In summary, we found that the DSA of listing was a major determinant of LT rate for candidates across the country before the emergency lung allocation change.

Impact of Traumatically Brain-Injured Donors on Outcomes After Heart Transplantation.

BACKGROUND: Heart transplant recipients of traumatically brain-injured (TBI) donors have been reported to have inferior survival and increased rates of cardiac allograft vasculopathy in single-center studies. This study sought to examine the impact of TBI donors on outcomes after heart transplantation across all transplantation centers. METHODS: We identified all adult heart transplants performed during 2007-2016 in the OPTN database. Recipients were dichotomized based on donor cause of death (TBI versus non-TBI), propensity-scored across 22 variables with known associations with mortality, and matched 1:1 without replacement. The primary endpoint was all-cause mortality. Secondary endpoints were conditional survival and rates of cardiac allograft vasculopathy. RESULTS: In total, 20,244 patients underwent heart transplantation. TBI was the primary cause of death in 53.4% of donors (10,816/20,244), and among TBI donors, blunt injury (59.6%; 6443/10,816) and gunshot wound (35%; 3781/10,816) were the most common mechanisms of injury. Propensity matching generated 6919 pairs (all absolute mean differences < 0.07). Risk-adjusted survival was similar between recipients of TBI donors and non-TBI donors at 5 y (78.1% versus 77.5%, log-rank P = 0.34). Risk-adjusted survival conditional on 1-y survival was also similar at 5 y (86.2% versus 86.1%, log-rank P = 0.74). The 5-y risk-adjusted rates of cardiac allograft vasculopathy did not differ either (30.6% versus 30.4%; log-rank P = 0.78). CONCLUSIONS: In the largest analysis of TBI donors in heart transplantation, we found similar survival and rates of cardiac allograft vasculopathy to those who received hearts from non-TBI donors out to 5 y. These findings should allay concerns over continued transplantation with this unique donor population.

Five-Year Mortality Hazard Is Reduced In Chronic Obstructive Pulmonary Disease Patients Receiving Double- versus Single-Lung Transplants.

BACKGROUND: Previous studies suggest double-lung transplant (DLT) may be associated with superior survival compared to single-lung transplantation (SLT) in chronic obstructive pulmonary disease (COPD) recipients. The purpose of this study was to compare survival in patients with COPD undergoing DLT versus SLT since the inception of the lung allocation score. METHODS: We used the United Network for Organ Sharing database to retrospectively identify adult patients with COPD who underwent isolated lung transplantation from 5/4/2005-12/31/2014. We then separated patients into DLT versus SLT. Short-term (1 y) and long-term survival (5 y) were compared between DLT and SLT cohorts by the method of Kaplan-Meier, and Cox proportional hazards modeling was used to adjust for case mix. RESULTS: Four thousand eight hundred thirty-two COPD patients were listed, and 3554 underwent lung transplantation over the study period, including 1358 SLTs (38%) and 2196 DLTs (62%). Survival 1 y after listing was 93% for those remaining wait listed (n = 1892) versus 91% for SLT (n = 1093) versus 89% for DLT (n = 1847) (log-rank P < 0.01). Survival at 1 y after transplant was 88% for both SLT and DLT groups (log-rank P = 0.93); however, 5-y survival was significantly lower after SLT (51% versus 59%, log-rank P < 0.01). After risk adjustment, hazard for 1-y mortality after DLT was not significantly reduced compared to SLT (hazard ratio 0.89 [0.69-1.14], P = 0.36) but was significantly reduced 5 y after DLT (hazard ratio 0.88 [0.78-0.99], P = 0.04). CONCLUSIONS: In the largest survival analysis of COPD recipients since the inception of the lung allocation score, the hazard for 5-y mortality was significantly reduced in recipients who underwent DLT as compared to SLT.

Discrepancies in access and institutional risk tolerance in heart transplantation: A national open cohort study.

BACKGROUND: The impact of center volume on heart transplantation is widely recognized and serves as a benchmark for certification and reimbursement. STUDY AIMS: Study sociodemographic variables associated with access to high-volume centers and substantiate the importance of extending access to underserved populations. METHODS: This study focused on adults undergoing heart transplantation between 2006 and 2015. Centers were clustered into terciles (>25, 14-25, or <14 transplants per year) and factors associated with receiving care in different terciles were identified through multinomial regression. RESULTS: During the study period, 18 725 patients were transplanted at 145 centers. Younger age (<30 years) (P = .005), lower educational level (P < .001), and government-based insurance (P < .001) were associated to lower odds of receiving care at a high-volume center. These centers had higher risk recipients and accepted organs from higher risk donors, when compared to intermediate- and low-volume centers. Receiving care at high (odds ratio [OR], 1.212; P = .017) and intermediate-volume centers (OR, 1.304; P = .001) was associated with greater odds of 1-year survival when compared with low-volume centers. CONCLUSION: Social, demographic, and geographic factors affect access to high- and intermediate-volume centers. High-volume centers tolerate more risk while providing excellent survival. Awareness of this impact should prompt an extension of access to care for underserved patient populations.

Etiology-dependent impairment of relaxation kinetics in right ventricular end-stage failing human myocardium.

BACKGROUND: In patients with end-stage heart failure, the primary etiology often originates in the left ventricle, and eventually the contractile function of the right ventricle (RV) also becomes compromised. RV tissue-level deficits in contractile force and/or kinetics need quantification to understand involvement in ischemic and non-ischemic failing human myocardium. METHODS AND RESULTS: The human population suffering from heart failure is diverse, requiring many subjects to be studied in order to perform an adequately powered statistical analysis. From 2009-present we assessed live tissue-level contractile force and kinetics in isolated myocardial RV trabeculae from 44 non-failing and 41 failing human hearts. At 1 Hz stimulation rate (in vivo resting state) the developed active force was not different in non-failing compared to failing ischemic nor non-ischemic failing trabeculae. In sharp contrast, the kinetics of relaxation were significantly impacted by disease, with 50% relaxation time being significantly shorter in non-failing vs. non-ischemic failing, while the latter was still significantly shorter than ischemic failing. Gender did not significantly impact kinetics. Length-dependent activation was not impacted. Although baseline force was not impacted, contractile reserve was critically blunted. The force-frequency relation was positive in non-failing myocardium, but negative in both ischemic and non-ischemic myocardium, while the ß-adrenergic response to isoproterenol was depressed in both pathologies. CONCLUSIONS: Force development at resting heart rate is not impacted by cardiac pathology, but kinetics are impaired and the magnitude of the impairment depends on the underlying etiology. Focusing on restoration of myocardial kinetics will likely have greater therapeutic potential than targeting force of contraction.

A Contemporary Analysis of Heart Transplantation and Bridge-to-Transplant Mechanical Circulatory Support Outcomes in Cardiac Sarcoidosis.

BACKGROUND: Patients with end-stage cardiomyopathy due to cardiac sarcoidosis (CS) may be referred for mechanical circulatory support (MCS) and heart transplantation (HT). We describe outcomes of patients with CS undergoing HT, focusing on the use of MCS as a bridge to transplant (BTT). METHODS: Using the United Network for Organ Sharing Scientific Registry of Transplant Recipients, we identified all adult waitlisted patients and isolated HT recipients from 2006 to 2015. These were divided into those with and without CS and further divided into those who did or did not receive MCS as BTT. Outcomes included 1- and 5-year post-transplantation freedom from mortality and 5-year freedom from primary graft failure. RESULTS: Over the study period, 31,528 patients were listed for HT, 148 (0.4%) of whom had CS. Among the CS patients, 34 (23%) received MCS as BTT. 18,348 patients (58%) eventually underwent HT, including 67 (0.4%) with CS, 20 (30%) of whom had received BTT MCS. Compared with non-CS diagnoses, CS patients had similar 1-year (91% vs 90%; log rank P = .88) and 5-year (83% vs 77%; log rank P = .46) freedom from mortality. Survival was also similar between CS BTT and non-CS BTT groups at 1 year (89% vs 89%; log-rank P = .92) and 5 years (72% vs 75%; log-rank P = .77). CONCLUSIONS: Survivals after HT were similar between CS and non-CS patients out to 5 years, and were also similar between CS and non-CS BTT cohorts. Both HT and BTT MCS should be considered in patients with CS.

SCN5A variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia.

Nav channels are essential for metazoan membrane depolarization, and Nav channel dysfunction is directly linked with epilepsy, ataxia, pain, arrhythmia, myotonia, and irritable bowel syndrome. Human Nav channelopathies are primarily caused by variants that directly affect Nav channel permeability or gating. However, a new class of human Nav channelopathies has emerged based on channel variants that alter regulation by intracellular signaling or cytoskeletal proteins. Fibroblast growth factor homologous factors (FHFs) are a family of intracellular signaling proteins linked with Nav channel regulation in neurons and myocytes. However, to date, there is surprisingly little evidence linking Nav channel gene variants with FHFs and human disease. Here, we provide, to our knowledge, the first evidence that mutations in SCN5A (encodes primary cardiac Nav channel Nav1.5) that alter FHF binding result in human cardiovascular disease. We describe a five*generation kindred with a history of atrial and ventricular arrhythmias, cardiac arrest, and sudden cardiac death. Affected family members harbor a novel SCN5A variant resulting in p.H1849R. p.H1849R is localized in the central binding core on Nav1.5 for FHFs. Consistent with these data, Nav1.5 p.H1849R affected interaction with FHFs. Further, electrophysiological analysis identified Nav1.5 p.H1849R as a gain-of-function for INa by altering steady-state inactivation and slowing the rate of Nav1.5 inactivation. In line with these data and consistent with human cardiac phenotypes, myocytes expressing Nav1.5 p.H1849R displayed prolonged action potential duration and arrhythmogenic afterdepolarizations. Together, these findings identify a previously unexplored mechanism for human Nav channelopathy based on altered Nav1.5 association with FHF proteins.

Racial disparities in outcomes of adult heart transplantation.

BACKGROUND: This study evaluated whether minority orthotopic heart transplant (OHT) recipients tend to be transplanted at worse performing centers. METHODS AND RESULTS: OHT recipients between 2000 and 2010 were identified in the United Network for Organ Sharing database and stratified by race. Center performance was evaluated using observed-to-expected mortality ratios that were calculated using validated indexes for recipient and donor risk in OHT. The primary outcome was 1-year post-OHT mortality. A total of 102 centers performed OHT in 18 085 patients. Blacks had higher unadjusted 1-year mortality, which was confirmed after risk adjustment. Blacks had increased risk-adjusted mortality at poor performing centers (observed-to-expected mortality ratio, >1.2; odds ratio, 1.37 [95% confidence interval, 1.12-1.69]; P=0.002) and a strong trend toward increased mortality at excellent performing centers (observed-to-expected mortality ratio, <0.8; odds ratio, 1.42 [95% confidence interval, 0.99-2.02]; P=0.06). A higher proportion of blacks were treated at centers with higher-than-expected mortality (56.4% versus 47.1% whites versus 48.1% Hispanics; P<0.001), a finding that persisted after adjusting for insurance type and highest education level. In addition, there was a positive correlation between the percentage of blacks and observed-to-expected mortality ratios at the center level (r=0.32; P=0.001). In multivariable analysis incorporating immunologic and socioeconomic variables, there was no clear dominant source for the disparities in outcomes of OHT between races. CONCLUSIONS: Blacks have a propensity to be transplanted at worse performing centers; however, center effect alone does not explain the mortality difference between ethnicities. Although referral of minorities to better performing centers would improve absolute survival, it would not likely eliminate the racial disparities that exist in OHT outcomes.

Dysfunction in the ßII spectrin-dependent cytoskeleton underlies human arrhythmia.

BACKGROUND: The cardiac cytoskeleton plays key roles in maintaining myocyte structural integrity in health and disease. In fact, human mutations in cardiac cytoskeletal elements are tightly linked to cardiac pathologies, including myopathies, aortopathies, and dystrophies. Conversely, the link between cytoskeletal protein dysfunction and cardiac electric activity is not well understood and often overlooked in the cardiac arrhythmia field. METHODS AND RESULTS: Here, we uncover a new mechanism for the regulation of cardiac membrane excitability. We report that ßII spectrin, an actin-associated molecule, is essential for the posttranslational targeting and localization of critical membrane proteins in heart. ßII spectrin recruits ankyrin-B to the cardiac dyad, and a novel human mutation in the ankyrin-B gene disrupts the ankyrin-B/ßII spectrin interaction, leading to severe human arrhythmia phenotypes. Mice lacking cardiac ßII spectrin display lethal arrhythmias, aberrant electric and calcium handling phenotypes, and abnormal expression/localization of cardiac membrane proteins. Mechanistically, ßII spectrin regulates the localization of cytoskeletal and plasma membrane/sarcoplasmic reticulum protein complexes, including the Na/Ca exchanger, ryanodine receptor 2, ankyrin-B, actin, and αII spectrin. Finally, we observe accelerated heart failure phenotypes in ßII spectrin-deficient mice. CONCLUSIONS: Our findings identify ßII spectrin as critical for normal myocyte electric activity, link this molecule to human disease, and provide new insight into the mechanisms underlying cardiac myocyte biology.