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OBJECTIVE: To highlight recent developments in the utilization of mechanical circulatory support (MCS) devices as bridge-to-transplant strategies and to discuss trends in MCS use following the changes to the United Network for Organ Sharing (UNOS) heart allocation system. BACKGROUND: MCS devices have played an increasingly important role in the treatment of heart failure patients. Over the past several years, technological advancements have led to new developments in MCS devices and expanding indications for MCS use. In October of 2018, the UNOS heart allocation policy was revised to prioritize higher-urgency patients, including those supported with temporary MCS devices. Since then, changes in trends of MCS utilization have been observed. METHODS: Articles from the PubMed database regarding the use of MCS devices as bridge-to-transplant strategies were reviewed. CONCLUSIONS: Over the past decade, utilization of temporary MCS devices, which include the intra-aortic balloon pump (IABP), percutaneous ventricular assist devices (pVADs), and extracorporeal membrane oxygenation (ECMO), has become increasingly common. Recent advancements in MCS include the development of pVADs that can fully unload the left ventricle (LV) as well as devices designed to provide right-sided support. Technological advancements in durable left ventricular assist devices (LVADs) have also led to improved outcomes both on the device and following heart transplantation. Following the 2018 UNOS heart allocation policy revision, the utilization of temporary MCS in advanced heart failure patients has further increased and the proportion of patients bridged directly from a temporary MCS device has exponentially risen. However, following the start of the COVID-19 pandemic, the trends have reversed, with a decrease in the percentage of patients bridged from a temporary MCS device. As long-term data following the allocation policy revision becomes available, future studies should investigate how trends in MCS use for patients with advanced heart failure continue to evolve.

Ventricular assist devices (LVADs) are commonly used in end-stage heart failure for mechanical circulatory support as a bridge to heart transplantation. However, LVADs' long-term effects on posttransplant survival are unknown. We sought to compare long-term mortality after transplantation for patients with and without LVADs. Using the Organ Procurement and Transplantation Network database, we investigated LVADs' impact on long-term (3 month, 1 year, 2 years, 5 years, and 8 years) posttransplant mortality risk for all heart transplant recipients between 2010 and 2019. Time-to-event regression analysis quantified mortality risk by LVAD status in both unconditional and conditional survival analyses. Of 20,113 transplant recipients, 8,999 (45%) had a LVAD while on the waitlist. Among those who died after transplantation, patients with LVADs on average died sooner (1.8 years) than patients without LVADs (3.0 years; p < 0.01). On multivariable analysis, patients with LVADs had a 44% higher mortality risk within the first 3 months posttransplant (HR = 1.44, p = 0.03). There was no significant difference in mortality risk between patients who did and did not have pretransplant LVADs after 1, 2, and 5 years of posttransplant conditional survival. While LVAD patients have a survival disadvantage in the first year posttransplant, conditional survival analysis demonstrated no difference in mortality risk between patients with and without LVADs beyond 1 year of follow up. Of the patients who died posttransplant, patients with LVADs on average died sooner than patients without LVADs.

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.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.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.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.

Background Survival after heart transplantation is typically reported only in terms of overall survival. Conditional survival may provide prognostic information for patients after surviving a given period. This study sought to provide an analysis of conditional survival in heart transplantation. Methods Data from 29,000 patients who underwent heart transplantation between 2002 and 2016 were analyzed from the Organ Procurement and Transplantation Network database, and 5-year conditional survival rates were calculated according to age, sex, race, renal function, and hepatic function at transplantation. Results As time from transplantation increased from 0 to 5 years, the 5-year observed conditional survival changed from 74% to 82% for ages younger than 40 years, 79% to 82% for ages 40 to 49, 79% to 78% for ages 50 to 60, and 75% to 70% for ages older than 60 at transplantation. Conditional survival peaked at 1 and 2 years after transplantation for most subgroups. In recipients younger than 40 years, men had slightly higher conditional survival than women (absolute difference, 3%-4%). In recipients older than 60 years, women had slightly higher conditional survival (absolute difference, 1%-4%). Black recipients had lower survival than white and Hispanic recipients for nearly all time points. Recipients younger than 40 years with the worst renal (65% to 88%) and hepatic function (66% to 83%) at transplantation experienced the largest increase in conditional survival. Conclusions The conditional survival of patients who undergo heart transplantation changes substantially over time. The largest increases in conditional survival are in young patients with impaired renal and hepatic function. Conditional survival can provide more accurate prognostic information for heart recipients who survive a given period after transplantation.

BACKGROUND Retrograde autologous priming (RAP) before cardiopulmonary bypass (CPB) may minimize allogeneic red cell transfusion. We conducted a systematic review of the literature to examine the impact of RAP on perioperative allogeneic red cell transfusions in cardiac surgical patients. METHODS This study involved a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating the use of RAP in cardiac surgery involving CPB. The primary outcome was intraoperative allogeneic red cell transfusion. Secondary outcomes included whole hospital allogeneic transfusions and adverse events such as acute kidney injury (AKI) and stroke. RESULTS A total of 11 RCTs (n = 1337 patients) were included, comparing RAP patients (n = 674) to control (n = 663). In addition, 10 observational studies (n = 2327) were included, comparing RAP patients (n = 1257) to control (n = 1070). Overall, RAP was associated with a significantly reduced incidence of intraoperative red cell transfusion (n = 18 studies; odds ratio [OR] = 0.34; 95% confidence interval [CI], 0.22-0.55, P < .001) compared to controls. This effect was seen among RCTs (n = 10 studies; OR = 0.19; 95% CI, 0.08-0.45, P < .001) and observational studies (n = 8 studies; OR = 0.66; 95% CI, 0.50-0.87, P = .004) in isolation. RAP was also associated with a significantly reduced incidence of whole hospital red cell transfusion (n = 5 studies; OR = 0.28; 95% CI, 0.19-0.41, P < .001). Among the studies that reported AKI and stroke outcomes, there was no statistically significant increased odds of AKI or stroke in either RAP or control patients. CONCLUSIONS Based on the pooled results of the available literature, RAP is associated with a significant reduction in intraoperative and whole hospital allogeneic red cell transfusion. Use of RAP may prevent hemodilution of cardiac surgical patients and thus, lessen transfusions. Additional high-quality prospective studies are necessary to determine the ideal priming volume necessary to confer the greatest benefit without incurring organ injury.

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 ( 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

Background Transvenous lead extractions (TLEs) have increased in number due to an increased prevalence of cardiac implantable devices. Bleeding complications associated with TLEs can be catastrophic, and many institutions order blood components to be available in the procedure room. There are few studies supporting or refuting this practice. We evaluated transfusion rates for TLEs at a single, high-volume center to assess the need for having blood in the procedure room. Study design and methods Patients undergoing TLEs from April 2010 to February 2019 were identified from our institutional database. The percentage of patients transfused intraoperatively, the number of units transfused, and the reasons for transfusion were determined from the database and by manual chart review. Results A total of 473 patients underwent a TLE during this time frame. Of these, only 17 patients (3.6%) received a red blood cell (RBC) transfusion. Ten of the 17 patients received RBCs secondary to preoperative anemia. Of the remaining seven patients, only four patients received more than 2 RBC units, and only one received more than 10 RBC units. No patient received more than 2 RBC units or any plasma or platelets in the past 4 years. Conclusion Due to improvements in procedural techniques, advent of accessible remote blood allocation systems, and changes in transfusion practice (e.g., electronic crossmatch), routinely having blood components in the procedure room for every TLE may be an outdated practice for high-volume centers.

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.

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.

Background 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. Methods 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. Results During the study period, 20,052 adult patients underwent heart transplantation, of whom 9595 (47.9%) were phenotypically like 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 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 after stratification based on hospital transplant volume and initial waitlist status. Phenotypically like matched patients had longer waiting times compared with unlike matched patients overall (225 days vs 192 days, P Conclusions 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.

STUDY OBJECTIVES: To identify the association between insomnia symptoms and signs of prodromal neurodegeneration, including an analysis of potential differences between sleep-onset and sleep-maintenance insomnia. METHODS: We included those aged 45–85 years, living in 1 of 10 Canadian provinces between 2012 and 2015 (at the baseline), recruited via 3 population-based sampling methods. Insomnia symptoms were assessed using questions adapted/modified from the Pittsburgh Sleep Quality Index. A panel of potential prodromal neurodegenerative markers including self-reported symptoms and objective gait motor, cognitive, and autonomic variables were assessed cross sectionally. We compared those who endorsed insomnia symptoms ≥ 3 times per week to controls, adjusting for age, sex, and education via logistic regression. RESULTS: Overall, 2,051/30,097 people screened positive for sleep-onset insomnia alone and 4,333 for sleep-maintenance insomnia alone, while 2,371 endorsed both subtypes. On objective gait tests, participants with sleep-onset insomnia, but not sleep-maintenance insomnia, had worse balance (odds ratio [OR] = 1.33, 95% confidence interval = [1.16, 1.52]) and slower gait speed (OR = 1.52 [1.34, 1.73]). Although participants with any insomnia subtype endorsed more motor symptoms, these were more severe in those with sleep-onset insomnia (OR onset vs maintenance = 1.13 [1.07, 1.18]). On objective cognitive tests, those with sleep-maintenance insomnia scored normally. However, participants with sleep-onset insomnia performed worse on tests of verbal fluency (OR = 1.24 [1.06, 1.43]), immediate memory (OR = 1.23 [1.08, 1.41]), and prospective memory task (OR = 1.29 [1.11, 1.50]). The sleep-onset insomnia group also had lower heart rate variability (OR = 1.23 [1.07, 1.43]). Secondary analyses found generally similar results in young vs older age of insomnia development. CONCLUSIONS: Compared to maintenance insomnia, those with sleep-onset insomnia have more motor, cognitive, and autonomic signs/symptoms. When evaluating neurodegenerative risk, differentiating insomnia subtypes may increase precision. CITATION: Yao CW, Pelletier A, Fereshtehnejad S-M, Cross N, Dang-Vu T, Postuma RB. Insomnia symptom subtypes and manifestations of prodromal neurodegeneration: a population-based study in the Canadian Longitudinal Study on Aging. J Clin Sleep Med. 2022;18(2):345–359.

Background: Earlier detection of parkinsonism, specifically during its prodromal stage, may be key to preventing its progression. Previous studies have produced contradictory results on the association between sleep symptoms and prodromal parkinsonism. Objective: We conducted a prospective study within the Canadian Longitudinal Study on Aging (CLSA) to determine whether self-reported symptoms of insomnia, somnolence, apnea, and restless legs syndrome predate the diagnosis of parkinsonism after three years of follow-up. Methods: At baseline, amongst other information, participants completed a questionnaire for difficulty initiating or maintaining sleep, daytime somnolence, snoring or stopping breathing during sleep, and symptoms of restless legs syndrome. After 3 years of follow-up, baseline responses from participants who self-reported a new diagnosis of parkinsonism (cases) were compared to those who did not (controls). For each case, 10 controls were individually matched by age, sex, education, BMI, caffeine, smoking, and alcohol. Binary unconditional logistic regression models were used to estimate the association between sleep symptoms and new-onset parkinsonism, adjusting for age, sex, education, BMI, smoking, alcohol, and caffeine. Results: We identified 58 incident-parkinsonism cases and 580 matched controls (65.5%male, mean age = 69.60, SD = 8.0). Baseline symptoms of sleep-onset insomnia (12.1%vs. 13.0%, Adjusted OR[95%CI] = 0.87[0.32,2.33]), sleep-maintenance insomnia (24.1%vs. 20.2%, AOR = 1.01[0.46,2.20]), daytime somnolence (8.6%vs. 7.4%, AOR = 1.11[0.37,3.39]), obstructive sleep apnea (27.3%vs. 26.2%, AOR = 0.84[0.40,1.79]), and restless leg syndrome (20.6%vs. 9.9%, AOR = 1.34[0.42,4.25]) were similar among those who developed parkinsonism and those who did not. Conclusion: Symptoms of insomnia, somnolence, apnea, and restless legs did not predate a new diagnosis of parkinsonism over 3 years.

Supplemental Digital Content is available in the text., OBJECTIVES: Extracorporeal membrane oxygenation is a potentially life-saving intervention in refractory cardiopulmonary failure, but it requires anticoagulation to prevent circuit thromboses, which exposes the patient to hemorrhagic complications. Heparin has traditionally been the anticoagulant of choice, but the direct thrombin inhibitor bivalirudin is routinely used in cases of heparin-induced thrombocytopenia and has been suggested as a superior choice. We sought to examine the timing of hemorrhagic and thrombotic complications after extracorporeal membrane oxygenation cannulation and to compare the rates of such complications between patients anticoagulated with heparin versus bivalirudin. DESIGN: Retrospective cohort study. SETTING: Johns Hopkins Hospital patients between January 2016 and July 2019. PATIENTS: Adult (> 18 yr) extracorporeal membrane oxygenation patients. INTERVENTIONS: Patients were anticoagulated either with heparin or bivalirudin. MEASUREMENTS AND MAIN RESULTS: We compared rates of hemorrhagic and thrombotic complications by time on heparin versus bivalirudin and characterized the average time to each complication. Of 144 extracorporeal membrane oxygenation patients (mean age 55.3 yr; 58% male), 41% were on central venoarterial extracorporeal membrane oxygenation, 40% on peripheral venoarterial extracorporeal membrane oxygenation, and 19% on venovenous extracorporeal membrane oxygenation. Thirteen patients (9%) received bivalirudin during their extracorporeal membrane oxygenation run, due to concern for (n = 8) or diagnosis of (n = 4) heparin-induced thrombocytopenia or for heparin resistance (n = 1). The rate of hemorrhagic or thrombotic complications did not differ between heparin (0.13/d) and bivalirudin (0.06/d; p = 0.633), but patients on bivalirudin received significantly fewer blood transfusions (1.0 U of RBCs/d vs 2.9/d on heparin; p < 0.001). CONCLUSIONS: Our results confirm the safety and efficacy of bivalirudin as an alternative anticoagulant in extracorporeal membrane oxygenation and suggest a potential benefit in less blood product transfusion, although prospective studies are needed to evaluate the true effect of bivalirudin versus the disease processes that prompted its use in our study population.

The use left ventricular assist devices (LVAD) as a bridge-to-transplant (BTT) has become a common modality to treat end-stage heart failure. We sought to examine the impact of BTT on long-term survival and quality of life after heart transplant. The population was all adult patients undergoing isolated heart transplantation in the United States between 2007 and 2017. Inclusion criteria covered BTT patients with a LVAD (only Heartmate II [HMII] or HeartWare Ventricular Assist System [HVAD]) and compared these with patients undergoing de novo heart transplantation. Our primary end-point was survival at 1, 2, and 5 years. Secondary end-points were functional status, return to work, and rates of hospital readmission and graft rejection. Unconditional and conditional survival was estimated with the Kaplan-Meier method. The independent influence of BTT on risk-adjusted mortality was determined using Cox proportional hazards models. In this period, 5,584 patients were bridged with an LVAD and 12,295 underwent de novo transplantation. Unconditional survival was 2% higher in de novo patients at 1, 2, and 5 years. After risk adjustment, BTT was associated with increased mortality at each time point. Unadjusted 5 year survival, conditional on 90 day survival, was similar between groups (82.6% vs. 83.4%; p = 0.15). Functional status, return to work, and unadjusted rates of hospital readmission and graft rejection were similar at 1, 2, 5 years. Bridge-to-transplant with LVADs provides excellent survival and similar quality of life to that of patients undergoing de novo heart transplantation. Bridge-to-transplant patients experience a slightly higher mortality rate within 90 days of transplantation.

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

Left ventricular assist devices are increasingly used as bridge-to-transplantation in eligible patients. The HeartMate 3 (HM3; Abbott Laboratories, Abbot Park, IL) is the latest device to obtain US Food and Drug Administration approval as bridge-to-transplantation. This study examines early outcomes of transplant recipients after HM3 in comparison with recipients bridged with the HeartMate 2 (HM2; Abbott Laboratories) and HeartWare Ventricular Assist System (HVAD; Medtronic, Minneapolis, MN) devices.Using the Organ Procurement and Transplantation Network database, we identified all adult patients who were slated for bridge-to-transplantation with a continuous-flow left ventricular assist devices (HM2, HVAD, or HM3) between April 1, 2015 and January 31, 2018. The primary endpoint was all-cause mortality 6 months after transplantation. The independent influence of the bridging device on outcomes was determined using Cox proportional hazard models.Patients (N = 1,978) were successfully bridged to transplantation with the HM2 (n = 881), HVAD (n = 920), or HM3 (n = 177) device. Six-month mortality rates were similar across these devices (HM2, 5.9%; HVAD, 7.7%; HM3, 4.7%; log-rank p = 0.30). On average HM2 patients were on a left ventricular assist device for 2 months longer (p0.01). The HVAD had the lowest rate of device exchange before transplant (p = 0.01). The HM3 had no events of pump thrombosis (p0.01). HVAD patients had the lowest rate of device malfunction before to transplant (p0.01). Panel reactive antibodies at the time of transplantation were lower for HM3 patients (p0.01); however rates of graft rejection at 6 months were not different (p = 0.25).The HM3 device provides excellent early outcomes as a bridge to transplantation and may be associated with a reduction in comorbidities. Longer follow-up is needed to better define differences between durable left ventricular assist devices.

Angiotensin receptor-neprilysin inhibitors (ARNIs) greatly benefit functional capacity and longevity in heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors remain underutilized and unstudied, however, in left ventricular assist device (LVAD) recipients, in spite of their underlying HFrEF. In this case series, we studied the feasibility and short-term efficacy of ARNI utilization in 21 LVAD patients. Angiotensin receptor-neprilysin inhibitor initiation was successful in most, resulting in significant consolidation of blood pressure (BP) medical management and marked improvements in both functional capacity and diuretic requirements. Angiotensin receptor-neprilysin inhibitors are safe, feasible, and within a short timeframe benefit BP and heart failure control in LVAD recipients.

BACKGROUND: Cerebral autoregulation monitoring is a proposed method to monitor perfusion during cardiac surgery. However, limited data exist from the ICU as prior studies have focused on intraoperative measurements. Our objective was to characterise cerebral autoregulation during surgery and early ICU care, and as a secondary analysis to explore associations with delirium. METHODS: In patients undergoing cardiac surgery (n=134), cerebral oximetry values and arterial BP were monitored and recorded until the morning after surgery. A moving Pearson's correlation coefficient between mean arterial proessure (MAP) and near-infrared spectroscopy signals generated the cerebral oximetry index (COx). Three metrics were derived: (1) globally impaired autoregulation, (2) MAP time and duration outside limits of autoregulation (MAP dose), and (3) average COx. Delirium was assessed using the 3-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM) and the Confusion Assessment Method for the ICU (CAM-ICU). Autoregulation metrics were compared using χ(2) and rank-sum tests, and associations with delirium were estimated using regression models, adjusted for age, bypass time, and logEuroSCORE. RESULTS: The prevalence of globally impaired autoregulation was higher in the operating room vs ICU (40% vs 13%, P

Introduction: Extracorporeal cardio-pulmonary resuscitation (ECPR) is being used more frequently for refractory cardiac arrest (rCA). Stroke remains a key determinant of outcomes in patients receiving ECPR. No studies have yet analyzed sex differences in the frequency of stroke in patients with rCA treated with ECPR. Methods: Retrospective analysis of ECPR cases for rCA identified in the Extracorporeal Life Support Organization (ELSO) International Registry. Age, sex, race/ethnicity and vascular risk factors were included. Stroke was defined as “Ischemic Stroke” and “Intracranial Hemorrhage” as detected by neuroimaging. Statistical analysis: level of significance was set to p≤0.05. To assess sex differences comparative tests were used as appropriate. Results: From 1992 to 2020 a total of 7,460 adult cases of ECPR for rCA were identified; 2,276 (30%) women vs. 5,184 (69%) men; Mean age 50.3 years (±SD 17) in women vs. 54.7 years (±SD 14) in men, (p Conclusions: This is the first study evaluating sex-related differences in the frequency of stroke in patients with ECPR from the largest contemporary ELSO registry. Women were younger than men at the time of rCI and had more intracranial hemorrhages. Men were older and had more ischemic strokes. Morality was high when stroke was present. Our study has implications for future development of sex-targeted treatment strategies when implementing ECPR to reduce neurological complications and to improve outcome.

This review assesses the comorbidities affecting the coronary artery disease (CAD) population to assess generalizability and applicability to individual conduit selection. We also examine the influence of procedural factors, including conduit dimensions, lesion severity, and target vessel location. By summarizing these topics, we hope to facilitate a better understanding of conduit choice for the cardiac anesthesiologist to support evidenced-based, patient-centered care.

Tumor-associated macrophages (TAMs) can exist in pro- and anti-inflammatory states. Anti-inflammatory TAMs (also referred to as M2-polarized) generally suppress antitumor immune responses and enhance the metastatic progression of cancer. To explore the mechanisms behind this phenomenon, we isolated macrophages from mice and humans, polarized them ex vivo, and examined their functional interaction with breast cancer cells in culture and in mice. We found that anti-inflammatory TAMs promoted a metabolic state in breast cancer cells that supported various protumorigenic phenotypes. Anti-inflammatory TAMs secreted the cytokine TGF-β that, upon engagement of its receptors in breast cancer cells, suppressed the abundance of the transcription factor STAT1 and, consequently, decreased that of the metabolic enzyme succinate dehydrogenase (SDH) in the tumor cells. The decrease in SDH levels in tumor cells resulted in an accumulation of succinate, which enhanced the stability of the transcription factor HIF1α and reprogrammed cell metabolism to a glycolytic state. TAM depletion-repletion experiments in a 4T1 mouse model additionally revealed that anti-inflammatory macrophages promoted HIF-associated vascularization and expression of the immunosuppressive protein PD-L1 in tumors. The findings suggest that anti-inflammatory TAMs promote tumor-associated angiogenesis and immunosuppression by altering metabolism in breast cancer cells.

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.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.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).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.

Background With the implementation of the new heart allocation system, heart transplantation teams are prompted to reevaluate management of patients requiring mechanical circulatory support. The purpose of our study is to compare the outcomes of patients supported with extracorporeal membrane oxygenation (ECMO) before transplantation. Methods The United Network for Organ Sharing database was queried for all adult patients (aged 18 years or more) who required support with ECMO before heart transplantation from 2001 to 2018. Patients were stratified into patients who did not require ECMO before transplantation, who were weaned off ECMO before transplantation, who were bridged immediately to transplantation from ECMO, and who were bridged to a left ventricular assist device (LVAD) before transplantation. Demographics and outcomes including 1-year survival, postoperative stroke, postoperative renal failure requiring dialysis, episodes of rejection, and graft failure were compared. Results Overall, 29,370 patients did not require ECMO before transplantation, 101 patients were weaned off ECMO before transplantation, 118 were bridged from ECMO directly to transplantation, and 55 patients were successfully bridged from ECMO to LVAD before transplantation. Kaplan-Meier survival estimates found a statistically significant decrease in 1-year survival for patients who were bridged from ECMO to transplantation compared with patients who were bridged to LVAD before subsequent transplantation (P Conclusions Our study suggests bridging ECMO patients to an LVAD before transplantation will result in improved 1-year survival compared with patients bridged to immediate transplantation. With the new heart allocation system, continued evaluation of outcomes is required to inform management strategies.

Background: Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition.Objective: We evaluated the effect of a 2-y CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m2) among participants enrolled in CALERIE-2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a multicenter, randomized controlled trial.Design: Participants were 218 nonobese (BMI: 21.9-28.0) adults aged 21-51 y who were randomly assigned to 25% CR (CR, n = 143) or ad libitum control (AL, n = 75) in a 2:1 ratio. Measures at baseline and 12 and 24 mo included body weight, waist circumference, fat mass (FM), fat-free mass (FFM), and appendicular mass by dual-energy X-ray absorptiometry; activity-related energy expenditure (AREE) by doubly labeled water; and dietary protein intake by self-report. Values are expressed as means ± SDs.Results: The CR group achieved 11.9% ± 0.7% CR over 2-y and had significant decreases in weight (-7.6 ± 0.3 compared with 0.4 ± 0.5 kg), waist circumference (-6.2 ± 0.4 compared with 0.9 ± 0.5 cm), FM (-5.4 ± 0.3 compared with 0.5 ± 0.4 kg), and FFM (-2.0 ± 0.2 compared with -0.0 ± 0.2 kg) at 24 mo relative to the AL group (all between-group P < 0.001). Moreover, FFM as a percentage of body weight at 24 mo was higher, and percentage of FM was lower in the CR group than in the AL. AREE, but not protein intake, predicted preservation of FFM during CR (P < 0.01). Men in the CR group lost significantly more trunk fat (P = 0.03) and FFM expressed as a percentage of weight loss (P < 0.001) than women in the CR group.Conclusions: Two years of CR had broadly favorable effects on both whole-body and regional adiposity that could facilitate health span in humans. The decrements in FFM were commensurate with the reduced body mass; although men in the CR group lost more FFM than the women did, the percentage of FFM in the men in the CR group was higher than at baseline. CALERIE was registered at clinicaltrials.gov as NCT00427193.

Background Heart transplantation is the mainstay of treatment for patients in end-stage heart failure. This study sought to contrast survival after transplantation with that of the general population to quantify standardized mortality rates using a nested case-control study design. Methods Control subjects were noninstitutionalized inhabitants of the United States identified through the National Longitudinal Mortality study. Case subjects were adults who underwent heart 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 state of permanent residency. The primary study endpoint was 10-year survival. Results In all, 31,883 heart transplant recipients were matched to 159,415 noninstitutionalized residents of the United States. The 10-year survival of heart transplant recipients was 53%. The population expected mortality rate was 15.9 deaths per 100 person-years with an observed rate of 45.1 deaths per 100 person-years (standardized mortality rate [SMR] 2.84; 95% confidence interval, 2.82 to 2.87). The broadest gaps between observed and expected survival were evident in female (SMR 3.63), black (SMR 3.67), and Hispanic (SMR 4.12) recipients. Standardized mortality ratios declined over time (1990 to 1995, 3.09; 1996 to 2000, 2.90; 2001 to 2007, 2.58). The long-term standardized survival of older recipients was closest to that expected for their age. Conclusions Heart transplant recipients have considerable long-term survival and have a threefold higher standardized long-term mortality rate than that of the noninstitutionalized population. Long-term mortality rates have consistently declined over time and will likely continue to decrease.

Despite the 6000 patients treated with extracorporeal membrane oxygenation (ECMO) annually, there is a paucity of data regarding the nutritional management of these patients.We performed a prospective, observational study of nutrition in postcardiotomy shock patients at our institution. Over a 3.5-year study period, we identified 50 ECMO patients and 225 non-ECMO patients. We identified type, amount, duration, and disruption of nutritional delivery by cohort. The primary outcome was percent of caloric goal met, and secondary outcome was gastrointestinal complications.ECMO patients met less of their caloric (29% versus 40%, P = 0.017) and protein goals (34% versus 55%, P 0.001) compared with non-ECMO patients. Tube feeds were administered more slowly (26 versus 37 mL/h, P 0.001) and held for longer (8.3 versus 4.5 h/d, P 0.001) in ECMO patients because of procedures (60%) and high-dose pressors (20% versus 7%, P 0.001). Multivariate analysis demonstrated that ECMO decreased caloric intake by 14%, with no detected increased risk of gastrointestinal complications.-ECMO patients received significantly less nutrition support compared with a non-ECMO population. Tube feed hold deficits could potentially be avoided by utilizing postpyloric tubes to feed through procedures, by eliminating holds for vasopressors/inotropes in hemodynamically stable patients, or by establishing volume-based feeding protocols. Further clinical studies are needed to establish efficacy of these interventions and to understand the impact of nutrition on outcomes in ECMO patients.

Left ventricular assist devices (LVADs) are the most common mode of circulatory support for patients awaiting heart transplantation. Unfortunately, a fraction of these patients require pump exchange during their course for pump-related adverse events. This study examined whether LVAD exchanges affect posttransplantation outcomes.This study focused on adult patients in the Organ Procurement and Transplantation Network database who were bridged to transplant with a LVAD implanted between 2007 and 2017. Patients who underwent LVAD exchange were compared with those supported with a single device. The primary end point was all-cause mortality at 1, 2, and 5 years after transplantation. The impact of device exchange on risk-adjusted outcomes was examined using Cox proportional hazards models.Among 8239 patients who met the inclusion criteria, there were 611 pump exchanges in 560 patients (7% of recipients). The pump exchange rate was 6.24 events per 100 patient-years. Survival at 5 years was lower for those who underwent LVAD exchange (69.4% vs 77.5%, log-rank P = .027). This finding was similar for risk-adjusted 5-year mortality (hazard ratio, 1.36; 95% confidence interval, 1.11 to 1.67; P = .003). Subgroup analysis revealed lower 5-year survival for female recipients who underwent LVAD exchange (55.4% vs 79.7%, log-rank P.001). The interaction between female sex and LVAD exchange was associated with increased risk-adjusted 5-year mortality (hazard ratio, 1.65; 95% confidence interval, 1.05 to 2.59; P = .030).Recipients who underwent pump exchange while awaiting heart transplantation had a higher mortality compared with those on a primary device. Subgroup analysis revealed a marked increase in mortality of female recipients who experienced LVAD exchange.

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.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.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).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.