Deciphering cell states and genealogies of human haematopoiesis.

The human blood system is maintained through the differentiation and massive amplification of a limited number of long-lived haematopoietic stem cells (HSCs)1. Perturbations to this process underlie diverse diseases, but the clonal contributions to human haematopoiesis and how this changes with age remain incompletely understood. Although recent insights have emerged from barcoding studies in model systems2-5, simultaneous detection of cell states and phylogenies from natural barcodes in humans remains challenging. Here we introduce an improved, single-cell lineage-tracing system based on deep detection of naturally occurring mitochondrial DNA mutations with simultaneous readout of transcriptional states and chromatin accessibility. We use this system to define the clonal architecture of HSCs and map the physiological state and output of clones. We uncover functional heterogeneity in HSC clones, which is stable over months and manifests as both differences in total HSC output and biases towards the production of different mature cell types. We also find that the diversity of HSC clones decreases markedly with age, leading to an oligoclonal structure with multiple distinct clonal expansions. Our study thus provides a clonally resolved and cell-state-aware atlas of human haematopoiesis at single-cell resolution, showing an unappreciated functional diversity of human HSC clones and, more broadly, paving the way for refined studies of clonal dynamics across a range of tissues in human health and disease.

Transplantation Outcomes with Donor Hearts after Circulatory Death.

BACKGROUND: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).

Multicenter evaluation of left ventricular assist device implantation with or without ECMO bridge in cardiogenic shock.

BACKGROUND: The efficacy of extracorporeal membrane oxygenation (ECMO) as a bridge to left ventricular assist device (LVAD) remains unclear, and recipients of the more contemporary HeartMate 3 (HM3) LVAD are not well represented in previous studies. We therefore undertook a multicenter, retrospective study of this population. METHODS AND RESULTS: INTERMACS 1 LVAD recipients from five U.S. centers were included. In-hospital and one-year outcomes were recorded. The primary outcome was the overall mortality hazard comparing ECMO versus non-ECMO patients by propensity-weighted survival analysis. Secondary outcomes included survival by LVAD type, as well as postoperative and one-year outcomes. One hundred and twenty-seven patients were included; 24 received ECMO as a bridge to LVAD. Mortality was higher in patients bridged with ECMO in the primary analysis (HR 3.22 [95%CI 1.06-9.77], p = 0.039). Right ventricular assist device was more common in the ECMO group (ECMO: 54.2% vs non-ECMO: 11.7%, p < 0.001). Ischemic stroke was higher at one year in the ECMO group (ECMO: 25.0% vs non-ECMO: 4.9%, p = 0.006). Among the study cohort, one-year mortality was lower in HM3 than in HeartMate II (HMII) or HeartWare HVAD (10.5% vs 46.9% vs 31.6%, respectively; p < 0.001) recipients. Pump thrombosis at one year was lower in HM3 than in HMII or HVAD (1.8% vs 16.1% vs 16.2%, respectively; p = 0.026) recipients. CONCLUSIONS: Higher mortality was observed with ECMO as a bridge to LVAD, likely due to higher acuity illness, yet acceptable one-year survival was seen compared with historical rates. The receipt of the HM3 was associated with improved survival compared with older generation devices.

Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients.

BACKGROUND: Hearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection. METHODS: We conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir-velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation. RESULTS: A total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders. CONCLUSIONS: In patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.).

Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure.

BACKGROUND: Mechanical circulatory support with a left ventricular assist device (LVAD) is an established treatment for patients with advanced heart failure. We compared a newer LVAD design (a small intrapericardial centrifugal-flow device) against existing technology (a commercially available axial-flow device) in patients with advanced heart failure who were ineligible for heart transplantation. METHODS: We conducted a multicenter randomized trial involving 446 patients who were assigned, in a 2:1 ratio, to the study (centrifugal-flow) device or the control (axial-flow) device. Adults who met contemporary criteria for LVAD implantation for permanent use were eligible to participate in the trial. The primary end point was survival at 2 years free from disabling stroke or device removal for malfunction or failure. The trial was powered to show noninferiority with a margin of 15 percentage points. RESULTS: The intention-to treat-population included 297 participants assigned to the study device and 148 participants assigned to the control device. The primary end point was achieved in 164 patients in the study group and 85 patients in the control group. The analysis of the primary end point showed noninferiority of the study device relative to the control device (estimated success rates, 55.4% and 59.1%, respectively, calculated by the Weibull model; absolute difference, 3.7 percentage points; 95% upper confidence limit, 12.56 percentage points; P=0.01 for noninferiority). More patients in the control group than in the study group had device malfunction or device failure requiring replacement (16.2% vs. 8.8%), and more patients in the study group had strokes (29.7% vs. 12.1%). Quality of life and functional capacity improved to a similar degree in the two groups. CONCLUSIONS: In this trial involving patients with advanced heart failure who were ineligible for heart transplantation, a small, intrapericardial, centrifugal-flow LVAD was found to be noninferior to an axial-flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure. (Funded by HeartWare; ENDURANCE ClinicalTrials.gov number, NCT01166347 .).

COVID-19 patient bridged to recovery with veno-venous extracorporeal membrane oxygenation.

BACKGROUND: In severe cases, the coronavirus disease 2019 (COVID-19) viral pathogen produces hypoxic respiratory failure unable to be adequately supported by mechanical ventilation. The role of extracorporeal membrane oxygenation (ECMO) remains unknown, with the few publications to date lacking detailed patient information or management algorithms all while reporting excessive mortality. METHODS: Case report from a prospectively maintained institutional ECMO database for COVID-19. RESULTS: We describe veno-venous (VV) ECMO in a COVID-19-positive woman with hypoxic respiratory dysfunction failing mechanical ventilation support while prone and receiving inhaled pulmonary vasodilator therapy. After 9 days of complex management secondary to her hyperdynamic circulation, ECMO support was successfully weaned to supine mechanical ventilation and the patient was ultimately discharged from the hospital. CONCLUSIONS: With proper patient selection and careful attention to hemodynamic management, ECMO remains a reasonable treatment option for patients with COVID-19.

Left ventricle unloading strategies in ECMO: A single-center experience.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a life-saving technology capable of restoring perfusion but is not without significant complications that limit its realizable therapeutic benefit. ECMO-induced hemodynamics increase cardiac afterload risking left ventricular distention and impaired cardiac recovery. To mitigate potentially harmful effects, multiple strategies to unload the left ventricle (LV) are used in clinical practice but data supporting the optimal approach is presently lacking. MATERIALS & METHODS: We reviewed outcomes of our ECMO population from September 2015 through January 2019 to determine if our LV unloading strategies were associated with patient outcomes. We compared reactive (Group 1, n = 30) versus immediate (Group 2, n = 33) LV unloading and then compared patients unloaded with an Impella CP (n = 19) versus an intra-aortic balloon pump (IABP, n = 16), analyzing survival and ECMO-related complications. RESULTS: Survival was similar between Groups 1 and 2 (33 vs 42%, P = .426) with Group 2 experiencing more clinically-significant hemorrhage (40 vs. 67%, P = .034). Survival and ECMO-related complications were similar between patients unloaded with an Impella versus an IABP. However, the Impella group exhibited a higher rate of survival (37%) than predicted by their median SAVE score (18%). DISCUSSION: Based on this analysis, reactive unloading appears to be a viable strategy while venting with the Impella CP provides better than anticipated survival. Our findings correlate with recent large cohort studies and motivate further work to design clinical guidelines and future trial design.

Management of a young patient with dextrocardia, atrial septal defect, and Eisenmenger syndrome with venous-venous extracorporeal membrane oxygenation and heart-lung transplantation.

Dextrocardia is a rare congenital condition which presents important challenges for surgical management. We discuss a patient with dextrocardia, atrial septal defect, and Eisenmenger syndrome, which ultimately led to decompensated end-stage lung disease and heart-lung transplant. Venous-venous extracorporeal membrane oxygenation was an important strategy to bridge the patient until donor organs became available. Transplantation of a heart-lung block allowed for the treatment of the patient's underlying congenital heart defect, anatomic reversal of dextrocardia with appropriate venous and arterial connections, and management of pulmonary damage from pulmonary hypertension.

Comparison of heart transplant outcomes between recipients with pulsatile- vs continuous-flow LVAD.

OBJECTIVE: Continuous-flow (CF) left ventricular assist devices (LVADs) have replaced pulsatile flow (PF) LVADs irrespective of concerns from the physiologic changes/morbidity secondary to lack of pulsatility. Data comparing posttransplant outcomes in patients with CF vs PF LVADs are limited and conflicting. We used the Organ Procurement and Transplant Network database to compare posttransplant outcomes between CF and PF LVAD patients. METHODS: From 1 January 2005 to 31 December 2011, 3449 adult patients underwent primary heart alone transplantation. The cohort was restricted to 2741 recipients with LVAD at the time of transplant and divided into two groups: PF (Heartmate XVE) (n = 705) and CF (Heartmate II, HeartWare HVAD, and Jarvik 2000) (n = 2036). Endpoints were 30-day freedom from graft failure, 1-, and 5-year patient survival. Propensity score matching identified 705 pairs for adjusted comparisons. RESULTS: Among propensity-matched patients, 30-day freedom from graft failure after heart transplantation (PF = 94.8% vs CF = 95.2%, P > .7), and 1-, and 5-year patient survival (PF; 87.5% vs CF; 88.9%, P = .4, and PF;75.7% vs CF;77.5%, P = .3) were not different. CONCLUSION: Survival and freedom from graft failure after heart transplantation is similar between CF and PF LVADs. These findings are relevant as the use of CF devices increases despite physiologic changes related to the absence of pulsatility.

Safety and Feasibility of Open Chest Epicardial Mapping and Ablation of Ventricular Tachycardia During the Period of Left Ventricular Assist Device Implantation.

INTRODUCTION: Patients undergoing catheter ablation for ventricular tachycardia (VT) may require epicardial mapping. In patients with end-stage heart failure, hybrid surgical epicardial mapping and ablation during the period of left ventricular assist device (LVAD) implantation may be considered in select patients to reduce post-LVAD ventricular tachycardia. METHODS AND RESULTS: From March 2009 to October 2012, 5 patients (4 men and 1 woman, age range 52-73 years) underwent open chest electrophysiology study and epicardial mapping for recurrent ventricular tachycardia while the heart was exposed during the period of LVAD implantation. Epicardial mapping was considered if patients had recurrent VT despite failed prior endocardial ablation and/or electrocardiogram (EKG) features of an epicardial exit. Activation and/or a substrate mapping approach were employed during all procedures. Three of 5 patients (60%) had acute procedural success. In all patients, VT was either eliminated or significantly reduced with epicardial ablation. One patient had mediastinal bleeding delaying sternal closure. During a follow-up period of 363 ± 368 days, 4 patients died due to nonarrhythmic causes. CONCLUSIONS: Open-chest hybrid epicardial mapping and ablation for recurrent VT is feasible and can be considered in select patients during the period of LVAD implantation.

Predictors and outcomes of unplanned early rehospitalization in the first year following lung transplantation.

Unplanned early rehospitalization (UER), defined as an unscheduled admission within 30 days of a hospital discharge, is associated with graft loss and recipient mortality in some solid organ transplants but has not been investigated in lung transplant. In this retrospective study, we collected socio-demographic and clinical factors to determine predictors and outcomes of UER in the first year following lung transplantation. There were 193 patients who underwent lung transplantation and survived to discharge during the 7.9-year study period. There were 116 (60.1%) patients with at least one UER. Infections (32.8%) and post-surgical complications (11.8%) were the most common reasons for UER. On multivariate analysis, the strongest predictor of having an UER was discharge to a long-term acute care facility (odds ratio: 3.01, 95% confidence interval [CI] 1.46-6.20; P=.003). Patients with any UER in the first year following transplantation had worse adjusted survival (hazard ratio: 1.89, 95% CI 1.02-3.50; P=.04). It is unclear, however, to what extent UERs reflect preventable outcomes. Further large-scale, prospective research is needed to identify the extent to which certain types of UER are modifiable and to define patients at high-risk for preventable UER.

Through the Looking Glass: Real-Time Video Using 'Smart' Technology Provides Enhanced Intraoperative Logistics.

INTRODUCTION: In the setting of increasingly complex medical therapies and limited physician resources, the recent emergence of 'smart' technology offers tremendous potential for improved logistics, efficiency, and communication between medical team members. In an effort to harness these capabilities, we sought to evaluate the utility of this technology in surgical practice through the employment of a wearable camera device during cardiothoracic organ recovery. METHODS: A single procurement surgeon was trained for use of an Explorer Edition Google Glass (Google Inc., Mountain View, CA) during the recovery process. Live video feed of each procedure was securely broadcast to allow for members of the home transplant team to remotely participate in organ assessment. Primary outcomes involved demonstration of technological feasibility and validation of quality assurance through group assessment. RESULTS: The device was employed for the recovery of four organs: a right single lung, a left single lung, and two bilateral lung harvests. Live video of the visualization process was remotely accessed by the home transplant team, and supplemented final verification of organ quality. In each case, the organs were accepted for transplant without disruption of standard procurement protocols. Media files generated during the procedures were stored in a secure drive for future documentation, evaluation, and education purposes without preservation of patient identifiers. CONCLUSIONS: Live video streaming can improve quality assurance measures by allowing off-site members of the transplant team to participate in the final assessment of donor organ quality. While further studies are needed, this project suggests that the application of mobile 'smart' technology offers not just immediate value, but the potential to transform our approach to the practice of medicine.

Single- vs double-lung transplantation in patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis since the implementation of lung allocation based on medical need.

IMPORTANCE: Outcomes of single- and double-lung transplantation have not been rigorously assessed since the allocation of donor lungs according to medical need as quantified by the Lung Allocation Score, which began in 2005. OBJECTIVE: To compare outcomes in single- and double-lung transplant recipients since the Lung Allocation Score was implemented. DESIGN, SETTING, AND PARTICIPANTS: In this exploratory analysis, adults with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) who underwent lung transplantation in the United States between May 4, 2005, and December 31, 2012, were identified in the United Network for Organ Sharing thoracic registry, with follow-up to December 31, 2012. Posttransplantation graft survival was assessed with Kaplan-Meier analysis. Propensity scores were used to control for treatment selection bias. A multivariable flexible parametric prognostic model was used to characterize the time-varying hazard associated with single- vs double-lung transplantation. EXPOSURE: Single- or double-lung transplantation. MAIN OUTCOMES AND MEASURES: Composite of posttransplant death and graft failure (retransplantation). RESULTS: Patients with IPF (n = 4134, of whom 2010 underwent single-lung and 2124 underwent double-lung transplantation) or COPD (n = 3174, of whom 1299 underwent single-lung and 1875 underwent double-lung transplantation) were identified as having undergone lung transplantation since May 2005. Median follow-up was 23.5 months. Of the patients with IPF, 1380 (33.4%) died and 115 (2.8%) underwent retransplantation; of the patients with COPD, 1138 (34.0%) died and 59 (1.9%) underwent retransplantation. After confounders were controlled for with propensity score analysis, double-lung transplants were associated with better graft survival in patients with IPF (adjusted median survival, 65.2 months [interquartile range {IQR}, 21.4-91.3 months] vs 50.4 months [IQR, 17.0-87.5 months]; P < .001) but not in patients with COPD (adjusted median survival, 67.7 months [IQR, 25.2-89.6 months] vs 64.0 months [IQR, 25.2-88.7 months]; P = .23). The interaction between diagnosis type (COPD or IPF) and graft failure was significant (P = .049). Double-lung transplants had a time-varying association with graft survival; a decreased instantaneous late hazard for death or graft failure among patients with IPF was noted at 1 year and persisted at 5 years postoperatively (instantaneous hazard at 5 years, hazard ratio, 0.67 [95% CI, 0.52-0.84] in patients with IPF and 0.89 [95% CI, 0.71-1.13] in patients with COPD). CONCLUSIONS AND RELEVANCE: In an exploratory analysis of registry data since implementation of a medical need-based lung allocation system, double-lung transplantation was associated with better graft survival than single-lung transplantation in patients with IPF. In patients with COPD, there was no survival difference between single- and double-lung transplant recipients at 5 years.

Transplantation for idiopathic pulmonary arterial hypertension: improvement in the lung allocation score era.

BACKGROUND: Lung transplantation and heart-lung transplantation represent surgical options for treatment of medically refractory idiopathic pulmonary arterial hypertension. The effect of the lung allocation score on wait-list and transplantation outcomes in patients with idiopathic pulmonary arterial hypertension is poorly described. METHODS AND RESULTS: Adults diagnosed with idiopathic pulmonary arterial hypertension and listed for transplantation in the 80 months before and after the lung allocation score algorithm was implemented (n=1430) were identified in the United Network for Organ Sharing thoracic registry. Patients were stratified by organ listed and pre- and post-lung allocation score era. The cumulative incidences of transplantation and mortality for wait-listed patients in both eras were appraised with competing outcomes analysis. Posttransplantation survival was assessed with the Kaplan-Meier method. These analyses were repeated in propensity-matched subgroups. Cox proportional hazards analysis evaluated the effect of prelisting and pretransplantation characteristics on mortality. We found that patients in the post-lung allocation score era had significantly worse comorbidities; nevertheless, both lung transplantation and heart-lung transplantation candidates in this era enjoyed lower wait-list mortality and a higher incidence of transplantation in unmatched and propensity-matched analyses. On multivariable analysis, heart-lung transplantation and double-lung transplantation were associated with improved survival from the time of wait-listing, as was being listed at a medium- to high-volume institution. Donor/recipient sex matching predicted posttransplantation survival. CONCLUSIONS: The incidence of transplantation has increased while wait-list mortality has decreased in patients with idiopathic pulmonary arterial hypertension wait-listed for transplantation in the post-lung allocation score era. Both heart-lung transplantation and double-lung transplantation are predictive of survival in transplantation candidates with idiopathic pulmonary arterial hypertension, as is being listed at a medium- to high-volume institution. Donor/recipient sex matching is associated with better posttransplantation survival.

HeartMate II left ventricular assist device implantation in patients with advanced hepatic dysfunction.

BACKGROUND: We sought to determine the outcomes for patients with advanced hepatic dysfunction undergoing HeartMate II left ventricular assist device (LVAD) implantation. METHODS: Between November 1, 2003 and December 1, 2012, we implanted the HeartMate II continuous-flow LVAD in 338 patients, either for bridging to heart transplantation or for destination therapy. Twenty-three of these patients (19 men and 4 women; mean age, 47 ± 16 years) had advanced hepatic dysfunction, as characterized by alanine aminotransferase (ALT) or aspartate transaminase (AST) levels five times normal; serum total bilirubin levels three times normal; and/or necessity for a liver biopsy before or during device implantation. Of this group, 17 patients received the LVAD as a bridge to transplantation, and six patients received it for destination therapy. RESULTS: Nine of the 23 patients required either a transjugular or a core liver biopsy during LVAD implantation. Three patients died within the first postoperative month; the 20 surviving patients had significant improvements in their hepatic parameters. The ALT decreased from 238 ± 296 to 27 ± 13 U/L (p = 0.022), AST decreased from 209 ± 199 to 29 ± 8 U/L (p = 0.009), and total bilirubin level decreased from 6.9 ± 6.0 to 0.6 ± 0.1 mg/dL (p = 0.044). The serum albumin level increased from 3.2 ± 0.6 to 4.3 ± 0.3 g/dL (p = 0.003), and creatinine clearance increased from 77.6 ± 35.2 to 110.2 ± 35.7 mL/min/1.73 m2 (p = 0.101). CONCLUSION: Continuous-flow LVAD support may significantly improve hepatic function, allowing patients with poor preimplant liver function to become better candidates for heart transplantation.

Lower socioeconomic status is associated with worse outcomes after both listing and transplanting children with heart failure.

The relationship between SES and outcomes surrounding pediatric cardiac transplantation is complex and influenced by recipient race. Broad-based studies of SES have not been performed. A retrospective review of all 5125 primary pediatric heart transplants performed in the United States between 2000 and 2011. Patients were stratified by SES based on zip code of residence and U.S. census data (low SES: 1637; mid-SES: 2253; high SES: 1235). Survival following listing and transplantation was compared across strata. Risk-adjusted long-term mortality on the waitlist was higher among low SES patients (hazard 1.32, CI 1.07-1.63). The relationship between SES and outcomes varied by race. Early risk-adjusted post-transplant outcomes were worst among high SES patients (10.8% vs. low SES: 8.9%, p < 0.05). The incidence of non-compliance was higher among low SES patients (p < 0.0001). Long-term risk-adjusted patient survival was poorer among low (hazard 1.41, CI 1.10-1.80) and mid-SES (1.29, 1.04-1.59) groups. Low SES is associated with worse outcomes on both the waitlist and late following transplantation. Higher SES patients had more complex transplants with higher early mortality. Further research should be directed at identifying and addressing underlying causal factors for these disparities.

Adverse Outcomes Associated With Atrial Arrhythmias After Veno-Venous Extracorporeal Membrane Oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) is used as a treatment modality in those who fail to respond to conventional care. Hypoxia and medications used in the intensive care unit may increase risk for atrial arrhythmias (AA). This study aims to evaluate the impact of AA on post-VV ECMO outcome. A retrospective review of patients who were placed on VV ECMO between October 2016 and October 2021. One hundred forty-five patients were divided into two groups, AA and no AA. Baseline characteristic and potential risk factors were assessed. Uni- and multivariate analysis using logistic regression models were constructed to evaluate the predictors of mortality between groups. Survival between groups was estimated by the Kaplan-Meier method using the log-rank test. Advanced age with history of coronary artery disease and hypertension were associated with increased risk to develop AA post-VV ECMO placement ( p value < 0.05). Length on ECMO, time intubated, hospital length of stay, and sepsis were significantly increased in patients in the AA group ( p value < 0.05). There was no difference in the overall mortality between the two groups. AAs were associated with worse hospital course and complications but no difference in overall mortality rate. Age and cardiovascular disease seem to be predisposing risk factors for this. Further studies are needed to investigate potential strategies to prevent AAs development in this population.

Limited Effect of Prevention Strategies on Incidence of Clinically Detectable Venous Thromboembolism After Lung Transplantation.

BACKGROUND: Thromboembolic complications are common post-lung transplant, leading to significant morbidity. We instituted multiple interventions because of an observed 36.8% incidence of venous thromboembolism (VTE) (Incidence rate (IR) 5.74/1000 pt days) in our recipients. METHODS: Our initiative commenced January 2015 with enoxaparin initiation within 6-8 hours of intensive care unit arrival and continuation for 4-6 weeks. We evaluated the IR of VTE in lung transplant recipients within 90 days of transplant. In 2017, the protocol was modified to extend the time to initiation of prophylaxis to within 72 hours of ICU arrival. In 2019, we further amended our intraoperative vascular access strategy. RESULTS: Eighteen of 26 lung transplant recipients (LTR) met inclusion criteria in the 2015 cohort. Six of 18 (33.3%) developed VTE, 50% of which were upper extremity (UE), line associated. Fifty two of 75 LTR were eligible for enoxaparin prophylaxis in the 2017 cohort. Fifteen of 52 subjects (28.8%) developed VTE, 77.8% of which were UE and line associated. Despite improved adherence in 2017, there was little change in VTE IR (3.90/1000 pt days compared with 3.85/1000 pt days). Twenty six of 43 LTR met protocol inclusion criteria in the 2019 cohort. Ten subjects (38.5%) developed VTE, 67% of which were UE and line associated (IR 5.18/1000 pt days). CONCLUSION: Our prospective study found that LTR remain at high risk for VTE despite aggressive prophylaxis with 4-6 weeks of enoxaparin and adjustment of vascular access approach. Alternative interventions should be investigated to minimize VTE development in this vulnerable population.

The Cost-effectiveness of Transplanting Hearts From Hepatitis C-infected Donors Into Uninfected Recipients.

BACKGROUND: The DONATE HCV trial demonstrated the safety and efficacy of transplanting hearts from hepatitis C viremic (HCV+) donors. In this report, we examine the cost-effectiveness and impact of universal HCV+ heart donor eligibility in the United States on transplant waitlist time and life expectancy. METHODS: We developed a microsimulation model to compare 2 waitlist strategies for heart transplant candidates in 2018: (1) status quo (SQ) and (2) SQ plus HCV+ donors (SQ + HCV). From the DONATE HCV trial and published national datasets, we modeled mean age (53 years), male sex (75%), probabilities of waitlist mortality (0.01-0.10/month) and transplant (0.03-0.21/month) stratified by medical urgency, and posttransplant mortality (0.003-0.052/month). We assumed a 23% increase in transplant volume with SQ + HCV compared with SQ. Costs (2018 United States dollar) included waitlist care ($2200-190 000/month), transplant ($213 400), 4-wk HCV treatment ($26 000), and posttransplant care ($2500-11 300/month). We projected waitlist time, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs [$/QALY, discounted 3%/year]; threshold ≤$100 000/QALY). RESULTS: Compared with SQ, SQ + HCV decreased waitlist time from 8.7 to 6.7 months, increased undiscounted life expectancy from 8.9 to 9.2 QALYs, and increased discounted lifetime costs from $671 400/person to $690 000/person. Four-week HCV treatment comprised 0.5% of lifetime costs. The ICER of SQ + HCV compared with SQ was $74 100/QALY and remained ≤$100 000/QALY with up to 30% increases in transplant and posttransplant costs. CONCLUSIONS: Transplanting hearts from HCV-infected donors could decrease waitlist times, increase life expectancy, and be cost-effective. These findings were robust within the context of current high HCV treatment costs.