Importance of social vulnerability on long-term outcomes after heart transplantation.

The relationship between social determinants of health and outcomes after heart transplantation has not been examined. The social vulnerability index (SVI) uses United States census data to determine the social vulnerability of every census tract based on 15 factors. This retrospective study seeks to examine the impact of SVI on outcomes after heart transplantation. Adult heart recipients who received a graft between 2012 and 2021 were stratified into SVI percentiles of <75% and SVI of ≥75%. The primary endpoint was survival. The median SVI was 48% (interquartile range: 30%-67%) among 23 700 recipients. One-year survival was similar between groups (91.4 vs 90.7%, log-rank P = .169); however, 5-year survival was lower among individuals living in vulnerable communities (74.8% vs 80.0%, P < .001). This finding persisted despite risk adjustment for other factors associated with mortality (survival time ratio 0.819, 95% confidence interval: 0.755-0.890, P < .001). The incidences of 5-year hospital readmission (81.4% vs 75.4%, P < .001) and graft rejection (40.3% vs 35.7%, P = .004) were higher among individuals living in vulnerable communities. Individuals living in vulnerable communities may be at increased risk of mortality after heart transplantation. These findings suggest there is an opportunity to focus on these recipients undergoing heart transplantation to improve survival.

Sounding the Alarm: What Clinicians Need to Know about Physical, Emotional, and Cognitive Recovery After Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVE: We summarize the existing data on the occurrence of physical, emotional, and cognitive dysfunction associated with postintensive care syndrome (PICS) in adult survivors of venoarterial extracorporeal membrane oxygenation (VA-ECMO). DATA SOURCES: MEDLINE, Cochrane Library, EMBASE, Web of Science, and CINAHL databases were searched. STUDY SELECTION: Peer-reviewed studies of adults receiving VA-ECMO for any reason with at least one measure of health-related quality of life outcomes or PICS at long-term follow-up of at least 6 months were included. DATA EXTRACTION: The participant demographics and baseline characteristics, in-hospital outcomes, long-term health outcomes, quality of life outcome measures, and prevalence of PICS were extracted. DATA SYNTHESIS: Twenty-seven studies met inclusion criteria encompassing 3,271 patients who were treated with VA-ECMO. The studies were limited to single- or two-center studies. Outcomes variables and follow-up time points evaluated were widely heterogeneous which limits comprehensive analysis of PICS after VA-ECMO. In general, the longer-term PICS-related outcomes of survivors of VA-ECMO were worse than the general population, and approaching that of patients with chronic disease. Available studies identified high rates of abnormal 6-minute walk distance, depression, anxiety, and posttraumatic stress disorder that persisted for years. Half or fewer survivors return to work years after discharge. Only 2 of 27 studies examined cognitive outcomes and no studies evaluated cognitive dysfunction within the first year of recovery. No studies evaluated the impact of targeted interventions on these outcomes. CONCLUSIONS: Survivors of VA-ECMO represent a population of critically ill patients at high risk for deficits in physical, emotional, and cognitive function related to PICS. This systematic review highlights the alarming reality that PICS and in particular, neurocognitive outcomes, in survivors of VA-ECMO are understudied, underrecognized, and thus likely undertreated. These results underscore the imperative that we look beyond survival to focus on understanding the burden of survivorship with the goal of optimizing recovery and outcomes after these life-saving interventions. Future prospective, multicenter, longitudinal studies in recovery after VA-ECMO are justified.

Quality and readability of online patient information on the left ventricular assist device.

BACKGROUND: As patients seek online health information to supplement their medical decision-making, the aim of this study is to assess the quality and readability of internet information on the left ventricular assist device (LVAD). METHODS: Three online search engines (Google, Bing, and Yahoo) were searched for "LVAD" and "Left ventricular assist device." Included websites were classified as academic, foundation/advocacy, hospital-affiliated, commercial, or unspecified. The quality of information was assessed using the JAMA benchmark criteria (0-4), DISCERN tool (16-80), and the presence of Health On the Net code (HONcode) accreditation. Readability was assessed using the Flesch Reading Ease score. RESULTS: A total of 38 unique websites were included. The average JAMA and DISCERN scores of all websites were 0.82 ± 1.11 and 52.45 ± 13.51, respectively. Academic sites had a significantly lower JAMA mean score than commercial (p < 0.001) and unspecified (p < 0.001) websites, as well as a significantly lower DISCERN, mean score than commercial sites (p = 0.002). HONcode certification was present in 6 (15%) websites analyzed, which had significantly higher JAMA (p < 0.001) and DISCERN (p < 0.016) mean scores than sites without HONcode certification. Readability was fairly difficult and at the level of high school students. CONCLUSIONS: The quality of online information on the LVAD is variable, and overall readability exceeds the recommended level for the public. Patients accessing online information on the LVAD should be referred to sites with HONcode accreditation. Academic institutions must provide higher quality online patient literature on LVADs.

Survival following lung transplantation: A population-based nested case-control study.

BACKGROUND: Lung transplantation is the mainstay of treatment for patients with end-stage respiratory failure. This study sought to evaluate survival following transplantation compared to the general population and quantify standardized mortality ratios (SMRs) using a nested case-control study design. METHODS: Control subjects were nonhospitalized inhabitants of the United States identified through the National Longitudinal Mortality Study. Case subjects were adults who underwent lung transplantation between 1990 and 2007 and identified through the Organ Procurement and Transplantation Network. Propensity-matching (5:1, nearest neighbor, caliper = 0.1) was utilized to identify suitable control subjects based on age, sex, race, and location of residency. The primary study endpoint was 10-year survival. RESULTS: About 14,977 lung transplant recipients were matched to 74,885 nonhospitalized US residents. The 10-year survival rate of lung transplant recipients was 28% (95% confidence interval [CI] = 27%-29%). The population expected mortality rate was 19 deaths/100 person-years while the observed ratio was 104 deaths/100 person-years (SMR = 5.39, 95% CI = 5.35-5.43). The largest discrepancies between observed and expected mortality rates were in females (SMR = 5.97), Hispanic (SMR = 10.70), and single lung recipients (SMR = 5.92). SMRs declined over time (1990-1995 = 5.79, 1996-2000 = 5.64, and 2001-2007 = 5.10). Standardized mortality peaks in the first year after transplant and decreases steadily over time. CONCLUSIONS: Lung transplant recipients experience a fivefold higher SMR compared to the nonhospitalized population. Long-term mortality rates have experienced consistent decline over time.

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.

NMDA Receptor Antagonism for Neuroprotection in a Canine Model of Hypothermic Circulatory Arrest.

BACKGROUND: Hypothermic circulatory arrest (HCA) is associated with neurologic morbidity, in part mediated by activation of the N-methyl-D-aspartate glutamate receptor causing excitotoxicity and neuronal apoptosis. Using a canine model, we hypothesized that the N-methyl-D-aspartate receptor antagonist MK801 would provide neuroprotection and that MK801 conjugation to dendrimer nanoparticles would improve efficacy. MATERIALS AND METHODS: Male hound dogs were placed on cardiopulmonary bypass, cooled to 18°C, and underwent 90 min of HCA. Dendrimer conjugates (d-MK801) were prepared by covalently linking dendrimer surface OH groups to MK801. Six experimental groups received either saline (control), medium- (0.15 mg/kg) or high-dose (1.56 mg/kg) MK801, or low- (0.05 mg/kg), medium-, or high-dose d-MK801. At 24, 48, and 72 h after HCA, animals were scored by a standardized neurobehavioral paradigm (higher scores indicate increasing deficits). Cerebrospinal fluid was obtained at baseline, eight, 24, 48, and 72 h after HCA. At 72 h, brains were examined for histopathologic injury in a blinded manner (higher scores indicate more injury). RESULTS: Neurobehavioral deficit scores were reduced by low-dose d-MK801 on postoperative day two (P < 0.05) and by medium-dose d-MK801 on postoperative day 3 (P = 0.05) compared with saline controls, but free drug had no effect. In contrast, high-dose free MK801 significantly improved histopathology scores compared with saline (P < 0.05) and altered biomarkers of injury in cerebrospinal fluid, with a significant reduction in phosphorylated neurofilament-H for high-dose MK801 versus saline (P < 0.05). CONCLUSIONS: Treatment with MK-801 demonstrated significant improvement in neurobehavioral and histopathology scores after HCA, although not consistently across doses and conjugates.

Time-Resolved Echo-Particle Image/Tracking Velocimetry Measurement of Interactions Between Native Cardiac Output and Veno-Arterial ECMO Flows.

Determination of optimal hemodynamic and pressure-volume loading conditions for patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) would benefit from understanding the impact of ECMO flow rates (QE) on the native cardiac output in the admixing zone, i.e., aortic root. This study characterizes the flow in the aortic root of a pig with severe myocardial ischemia using contrast-enhanced ultrasound particle image/tracking velocimetry (echo-PIV/PTV). New methods for data preprocessing are introduced, including autocontouring to remove surrounding tissues, followed by blind deconvolution to identify the centers of elongated bubble traces in images with low signal to noise ratio. Calibrations based on synthetic images show that this procedure increases the number of detected bubbles and reduces the error in their locations by 50%. Then, an optimized echo-PIV/PTV procedure, which integrates image enhancement with velocity measurements, is used for characterizing the time-resolved two-dimensional (2D) velocity distributions. Phase-averaged and instantaneous flow fields show that the ECMO flow rate influences the velocity and acceleration of the cardiac output during systole, and secondary flows during diastole. When QE is 3.0 L/min or higher, the cardiac ejection velocity, phase interval with open aortic valve, velocity-time integral (VTI), and mean arterial pressure (MAP) increase with decreasing QE, all indicating sufficient support. For lower QE, the MAP and VTI decrease as QE is reduced, and the deceleration during transition to diastole becomes milder. Hence, for this specific case, the optimal ECMO flow rate is 3.0 L/min.

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.

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.

Association of preoperative spinal drain placement with spinal cord ischemia among patients undergoing thoracic and thoracoabdominal endovascular aortic repair.

OBJECTIVE: Spinal cord ischemia (SCI) is among the most devastating complications of thoracic endovascular aortic repair (TEVAR). Spinal fluid drainage has been proposed as a viable means to reduce SCI, but few data exist to support its routine use. This study investigated the association of preoperative spinal fluid drainage with the risk of SCI after TEVAR. METHODS: The Vascular Quality Initiative TEVAR module was queried for adult patients (≥18 years) undergoing TEVAR (coverage of zones 0-5) between September 2014 and March 2018 (inclusive). Patients with preoperative spinal malperfusion, aortic rupture on presentation, and connective tissue disorders were excluded. One-to-one propensity matching was used to balance patients on 44 separate dimensions by the nearest neighbor principle to compare those with vs those without preoperative spinal drainage. The primary end point was SCI still present at the time of discharge. Secondary outcomes were 30-day mortality and prolonged intensive care unit stay (>7 days). RESULTS: Among 4287 patients who underwent TEVAR (mean age, 67.1 [standard deviation, 13.7] years; 1665 [38.8%] women and 2622 [61.2%] men), 2076 had a spinal drain placed. Propensity matching yielded 1292 pairs with adequate covariate balance (all 44 absolute standardized differences <0.1). In the 2584 propensity-matched patients, spinal drain placement was associated with a reduced risk of SCI (1.5% vs 2.5%; risk-adjusted odds ratio [OR], 0.47; 95% confidence interval [CI], 0.24-0.89; P = .02). The rates of 30-day mortality (4.5% vs 5.0%; risk-adjusted OR, 0.67; 95% CI, 0.44-1.01; P = .05) and prolonged intensive care unit stay (7.0% vs 5.7%; risk-adjusted OR, 1.10; 95% CI, 0.84-1.45; P = .48) did not differ on the basis of spinal drain placement. The crossover rate was 10% (127/1292), and those with postoperative drain placement had a 20% (26/127) SCI rate on discharge. CONCLUSIONS: Among patients undergoing thoracic and thoracoabdominal endovascular aortic repair, preoperative placement of a spinal drain, compared with no drain, was associated with reduced risk of SCI. Cerebrospinal fluid drainage as a rescue measure does not provide the same protection offered by routine preoperative placement. Further investigation, including randomized controlled trials, is needed to more definitively determine the role for spinal drainage in TEVAR.

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.

Outcomes after heart transplantation in sensitized patients bridged with ventricular assist devices.

OBJECTIVE: Sensitization has been associated with worse outcomes following heart transplantation (HTx). The use of ventricular assist devices (VAD) is a risk factor for the development of sensitization. We investigated the impact of left ventricular assist devices (LVAD) and sensitization in HTx recipients. METHODS: We queried the UNOS database for all heart transplants performed from January 2000 through December 2016. Patients were considered highly sensitized and included if panel-reactive antibody (PRA) activity was 25% or higher. Patients were separated by pretransplant LVAD utilization and subgroup analysis was performed by device type (HeartMate II or HeartWare). Outcomes included Kaplan-Meier survival and episodes of rejection within 1 year of HTx. RESULTS: Of 18 009 recipients, 2434 (14%) were highly sensitized. 1055 (43.3%) were bridged with a VAD. In multivariate analysis, LVAD use did not impact 1-year (hazards ratio [HR], 1.30; P = 0.052) or 5-year survival (HR, 1.18; P = 0.112) in highly sensitized recipients. Furthermore, episodes of rejection were not affected by LVAD status (P = 0.765). Of the 1055 sensitized LVAD-bridged transplant recipients, 624 (59%) were implanted with a HeartMate II and 99 (9.4%) were bridged with a HeartWare device. In multivariate analysis, no differences were observed in 1-year survival (HR, 0.86; P = 0.664), 5-year survival (HR, 1.35; P = 0.209), or episodes of rejection (P = 0.497). CONCLUSIONS: The use of ventricular assist devices did not impact survival or rejection within 1 year of HTx in highly sensitized patients. Highly sensitized recipients have similar outcomes regardless of prior LVAD support or type of LVAD used as a bridge to transplantation.

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.

Predictors of operative mortality among cardiac surgery patients with prolonged ventilation.

BACKGROUND: Prolonged ventilation after cardiac surgery affects survival and increases morbidity. Previous studies have focused on predicting this complication preoperatively; however, indicators of poor outcome in those requiring prolonged ventilation remain ill-defined. We sought to identify predictors of operative mortality in cardiac surgery patients who experience prolonged mechanical ventilation. METHODS: 1698 patients who underwent cardiac surgery (CAB, aortic valve replacement ± CAB, or mitral valve repair/replacement ± CAB) required prolonged postoperative mechanical ventilation (>24 hours) between 2012 to 2016 in a statewide consortium. Perioperative factors were evaluated to identify the association with operative mortality. Covariates were selected through bootstrap aggregation to fit multivariable logistic regression models. The relative strength of association was determined by the Wald chi-square statistic. RESULTS: Median patient age was 68 years [IQR 61 to 76], 38% (644/1,698) were female, median duration of mechanical ventilation was 65 hours [IQR 38 to 143], median STS predicted risk of mortality was 3.1% [IQR 1.4 to 6.9%], and 15.7% (266/1698) suffered operative mortality. Among preoperative and operative characteristics, patient age and intraoperative initiation of extracorporeal membrane oxygenation (ECMO) were the strongest correlates of operative mortality on the multivariate analysis. Among postoperative factors, cardiac arrest and renal failure requiring dialysis were the strongest predictors of risk-adjusted operative mortality. Type of operation or surgical center had no association to mortality after risk adjustment. CONCLUSION: Prolonged ventilation following cardiac surgery is associated with a five-fold increase in operative mortality. In these patients, operative mortality is associated with older age, intraoperative initiation of ECMO, postoperative cardiac arrest, and renal failure requiring dialysis.

Superior diastolic function with KATP channel opener diazoxide in a novel mouse Langendorff model.

BACKGROUND: Adenosine triphosphate-sensitive potassium (KATP) channel openers have been found to be cardioprotective in multiple animal models via an unknown mechanism. Mouse models allow genetic manipulation of KATP channel components for the investigation of this mechanism. Mouse Langendorff models using 30 min of global ischemia are known to induce measurable myocardial infarction and injury. Prolongation of global ischemia in a mouse Langendorff model could allow the determination of the mechanisms involved in KATP channel opener cardioprotection. METHODS: Mouse hearts (C57BL/6) underwent baseline perfusion with Krebs-Henseleit buffer (30 min), assessment of function using a left ventricular balloon, delivery of test solution, and prolonged global ischemia (90 min). Hearts underwent reperfusion (30 min) and functional assessment. Coronary flow was measured using an inline probe. Test solutions included were as follows: hyperkalemic cardioplegia alone (CPG, n = 11) or with diazoxide (CPG + DZX, n = 12). RESULTS: Although the CPG + DZX group had greater percent recovery of developed pressure and coronary flow, this was not statistically significant. Following a mean of 74 min (CPG) and 77 min (CPG + DZX), an additional increase in end-diastolic pressure was noted (plateau), which was significantly higher in the CPG group. Similarly, the end-diastolic pressure (at reperfusion and at the end of experiment) was significantly higher in the CPG group. CONCLUSIONS: Prolongation of global ischemia demonstrated added benefit when DZX was added to traditional hyperkalemic CPG. This model will allow the investigation of DZX mechanism of cardioprotection following manipulation of targeted KATP channel components. This model will also allow translation to prolonged ischemic episodes associated with cardiac surgery.

Correlating Oxygen Delivery During Cardiopulmonary Bypass With the Neurologic Injury Biomarker Ubiquitin C-Terminal Hydrolase L1 (UCH-L1).

OBJECTIVE: The authors sought to assess the relationship between low oxygen delivery (DO2) during cardiopulmonary bypass (CPB) and a neuron-specific biomarker of neurologic injury, ubiquitin C-terminal hydrolase L1 (UCH-L1). DESIGN: Retrospective analysis of patient charts and prospectively collected blood samples. SETTING: University-affiliated tertiary care hospital. PARTICIPANTS: Adult patients undergoing cardiac surgery on CPB. INTERVENTIONS: Serum UCH-L1 levels were drawn at baseline and 6 and 24 hours after CPB cessation. DO2 was computed from perfusion records, with area-under-the-curve (AUC) computations performed to account for distance of DO2 excursions below predefined DO2 thresholds and the amount of time spent below them. Strokes were defined radiographically using computed tomography and magnetic resonance imaging. MEASUREMENTS AND MAIN RESULTS: Forty-three adults were included (median age 65 y, interquartile range 59-72). Three patients experienced strokes (imaged at 2, 7, and 8 d postoperatively). Most patients underwent isolated coronary artery bypass grafting (41%, 18 patients) or isolated aortic valve replacement (30%, 13). Median UCH-L1 levels differed from baseline to 6 and 24 hours after CPB (40, 232, and 166 pg/mL, respectively; p < 0.001). On multivariable linear regression analysis controlling for baseline and surgical variables, only DO2 AUC <225 was significantly associated with 6-hour UCH-L1 levels (p = 0.001), whereas only DO2 AUC <300 was significantly associated with 24- hour levels (p < 0.001). The 3 patients who experienced radiographic strokes had nonsignificantly elevated 24-hour UCH-L1 levels compared with control patients (585 v 151 pg/mL, p = 0.11). CONCLUSIONS: This is the first study to demonstrate an independent association between DO2 during CPB and elevations of a brain injury biomarker; additional study is needed to clarify the clinical significance of these results.

A Novel Risk Score to Predict New Onset Atrial Fibrillation in Patients Undergoing Isolated Coronary Artery Bypass Grafting.

BACKGROUND: Atrial fibrillation (AF) is common after cardiac surgery and contributes to increased morbidity and mortality. Our objective was to derive and validate a predictive model for AF after CABG in patients, incorporating novel echocardiographic and laboratory values. METHODS: We retrospectively reviewed patients at our institution without preexisting dysrhythmia who underwent on-pump, isolated CABG from 2011-2015. The primary outcome was new onset AF lasting >1 hour on continuous telemetry or requiring medical treatment. Patients with a preoperative echocardiographic measurement of left atrial diameter were included in a risk model, and were randomly divided into derivation (80%) and validation (20%) cohorts. The predictors of AF after CABG (PAFAC) score was derived from a multivariable logistic regression model by multiplying the adjusted odds ratios of significant risk factors (P < .05) by a factor of 4 to derive an integer point system. RESULTS: 1307 patients underwent isolated CABG, including 762/1307 patients with a preoperative left atrial diameter measurement. 209/762 patients (27%) developed new onset AF including 165/611 (27%) in the derivation cohort. We identified four risk factors independently associated with postoperative AF which comprised the PAFAC score: age > 60 years (5 points), White race (5 points), baseline GFR < 90 mL/min (4 points) and left atrial diameter > 4.5 cm (4 points). Scores ranged from 0-18. The PAFAC score was then applied to the validation cohort and predicted incidence of AF strongly correlated with observed incidence (r = 0.92). CONCLUSION: The PAFAC score is easy to calculate and can be used upon ICU admission to reliably identify patients at high risk of developing AF after isolated CABG.