Modified Langendorff Perfusion Method for Extended Perfusion Times of Rodent Cardiac Grafts.

Despite important advancements in the diagnosis and treatment of cardiovascular diseases (CVDs), the field is in urgent need of increased research and scientific advancement. As a result, innovation, improvement and/or repurposing of the available research toolset can provide improved testbeds for research advancement. Langendorff perfusion is an extremely valuable research technique for the field of CVD research that can be modified to accommodate a wide array of experimental needs. This tailoring can be achieved by personalizing a large number of perfusion parameters, including perfusion pressure, flow, perfusate, temperature, etc. This protocol demonstrates the versatility of Langendorff perfusion and the feasibility of achieving longer perfusion times (4 h) without graft function loss by utilizing lower perfusion pressures (30-35 mmHg). Achieving extended perfusion times without graft damage and/or function loss caused by the technique itself has the potential to eliminate confounding elements from experimental results. In effect, in scientific circumstances where longer perfusion times are relevant to the experimental needs (i.e., drug treatments, immunological response analysis, gene editing, graft preservation, etc.), lower perfusion pressures can be key for scientific success.

The Public Health Service "Increased Risk" 2020 Policy Change Has not Improved Organ Utilization in the United States: A Nationwide Cohort Study.

Objective: To assess the effects of the 2020 United States Public Health Service (PHS) "Increased Risk" Guidelines update. Background: Donors labeled as "Increased Risk" for transmission of infectious diseases have been found to have decreased organ utilization rates despite no significant impact on recipient survival. Recently, the PHS provided an updated guideline focused on "Increased Risk" organ donors, which included the removal of the "Increased Risk" label and the elimination of the separate informed consent form, although the actual increased risk status of donors is still ultimately transmitted to transplant physicians. We sought to analyze the effect of this update on organ utilization rates. Methods: This was a retrospective analysis of the Organ Procurement and Transplantation Network database which compared donor organ utilization in the 2 years before the June 2020 PHS Guideline update for increased-risk donor organs (June 2018-May 2020) versus the 2 years after the update (August 2020-July 2022). The organ utilization rate for each donor was determined by dividing the number of organs transplanted by the total number of organs available for procurement. Student t test and multivariable logistic regression models were used for analysis. Results: There were 17,272 donors in the preupdate cohort and 17,922 donors in the postupdate cohort; of these, 4,977 (28.8%) and 3,893 (21.7%) donors were considered "Increased Risk", respectively. There was a 2% decrease in overall organ utilization rates after the update, driven by a 3% decrease in liver utilization rates and a 2% decrease in lung utilization rates. After multivariable adjustment, donors in the postupdate cohort had 10% decreased odds of having all organs transplanted. Conclusions: The 2020 PHS "Increased Risk" Donor Guideline update was not associated with an increase in organ utilization rates in the first 2 years after its implementation, despite a decrease in the proportion of donors considered to be at higher risk. Further efforts to educate the community on the safe usage of high-risk organs are needed and may increase organ utilization.

Tracheostomy is associated with decreased vasoactive-inotropic score in postoperative cardiac surgery patients on prolonged mechanical ventilation.

Objective: We sought to quantify the influence that tracheostomy placement has on the hemodynamic stability of postoperative cardiac surgery patients with persistent ventilatory requirements. Methods: A retrospective, single-center, and observational analysis of postoperative cardiac surgery patients with prolonged mechanical ventilation who underwent tracheostomy placement from 2018 to 2022 was conducted. Patients were excluded if receiving mechanical circulatory support or if they had an unrelated significant complication 3 days surrounding tracheostomy placement. Vasoactive and inotropic requirements were quantified using the Vasoactive-Inotrope Score. Results: Sixty-one patients were identified, of whom 58 met inclusion criteria. The median vasoactive-inotrope score over the 3 days before tracheostomy compared with 3 days after decreased from 3.35 days (interquartile range, 0-8.79) to 0 days (interquartile range, 0-7.79 days) (P = .027). Graphic representation of this trend demonstrates a clear inflection point at the time of tracheostomy. Also, after tracheostomy placement, fewer patients were on vasoactive/inotropic infusions (67.2% [n = 39] pre vs 24.1% [n = 14] post; P < .001) and sedative infusions (62.1% [n = 36] pre vs 27.6% [n = 16] post; P < .001). The percent of patients on active mechanical ventilation did not differ. Conclusions: The median vasoactive-inotrope score in cardiac surgery patients with prolonged mechanical ventilation was significantly reduced after tracheostomy placement. There was also a significant reduction in the number of patients on vasoactive/inotropic and sedative infusions 3 days after tracheostomy. These data suggest that tracheostomy has a positive effect on the hemodynamic stability of patients after cardiac surgery and should be considered to facilitate postoperative recovery.

One Year Outcomes Following Transplantation with COVID-19-Positive Donor Hearts: A National Database Cohort Study.

The current understanding of the safety of heart transplantation from COVID-19+ donors is uncertain. Preliminary studies suggest that heart transplants from these donors may be feasible. We analyzed 1-year outcomes in COVID-19+ donor heart recipients using 1:3 propensity matching. The OPTN database was queried for adult heart transplant recipients between 1 January 2020 and 30 September 2022. COVID-19+ donors were defined as those who tested positive on NATs or antigen tests within 21 days prior to procurement. Multiorgan transplants, retransplants, donors without COVID-19 testing, and recipients allocated under the old heart allocation system were excluded. A total of 7211 heart transplant recipients met the inclusion criteria, including 316 COVID-19+ donor heart recipients. Further, 290 COVID-19+ donor heart recipients were matched to 870 COVID-19- donor heart recipients. Survival was similar between the groups at 30 days (p = 0.46), 6 months (p = 0.17), and 1 year (p = 0.07). Recipients from COVID-19+ donors in the matched cohort were less likely to experience postoperative acute rejection prior to discharge (p = 0.01). National COVID-19+ donor heart usage varied by region: region 11 transplanted the most COVID-19+ hearts (15.8%), and region 6 transplanted the fewest (3.2%). Our findings indicate that COVID-19+ heart transplantation can be performed with safe early outcomes. Further analyses are needed to determine if long-term outcomes are equivalent between groups.

Acute rejection in donation after circulatory death (DCD) heart transplants.

BACKGROUND: Donation after circulatory death (DCD) heart transplantation has promising early survival, but the effects on rejection remain unclear. METHODS: The United Network for Organ Sharing database was queried for adult heart transplants from December 1, 2019, to December 31, 2021. Multiorgan transplants and loss to follow-up were excluded. The primary outcome was acute rejection, comparing DCD and donation after brain death (DBD) transplants. RESULTS: A total of 292 DCD and 5,582 DBD transplants met study criteria. Most DCD transplants were transplanted at status 3-4 (61.0%) compared to 58.6% of DBD recipients at status 1-2. DCD recipients were less likely to be hospitalized at transplant (26.7% vs 58.3%, p < 0.001) and to require intra-aortic balloon pumping (IABP; 9.6% vs 28.9%, p < 0.001), extracorporeal membrane oxygenation (ECMO; 0.3% vs 5.9%, p < 0.001) or temporary left ventricular assist device (LVAD; 1.0% vs 2.7%, p < 0.001). DCD recipients were more likely to have acute rejection prior to discharge (23.3% vs 18.4%, p = 0.044) and to be hospitalized for rejection (23.4% vs 11.4%, p = 0.003) at a median follow-up of 15 months; the latter remained significant after propensity matching. On multivariable logistic regression, DCD donation was an independent predictor of acute rejection (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.00-2.15, p = 0.048) and hospitalization for rejection (OR 2.03, 95% CI 1.06-3.70, p = 0.026). On center-specific subgroup analysis, DCD recipients continued to have higher rates of hospitalization for rejection (23.4% vs 13.8%, p = 0.043). CONCLUSIONS: DCD recipients are more likely to experience acute rejection. Early survival is similar between DCD and DBD recipients, but long-term implications of increased early rejection in DCD recipients require further investigation.

Textbook outcome: A novel metric in heart transplantation outcomes.

OBJECTIVE: Assessing heart transplant program quality using short-term survival is insufficient. We define and validate the composite metric textbook outcome and examine its association with overall survival. METHODS: We identified all primary, isolated adult heart transplants in the United Network for Organ Sharing/Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files from May 1, 2005, to December 31, 2017. Textbook outcome was defined as length of stay 30 days or less; ejection fraction greater than 50% during 1-year follow-up; functional status 80% to 100% at 1 year; freedom from acute rejection, dialysis, and stroke during the index hospitalization; and freedom from graft failure, dialysis, rejection, retransplantation, and mortality during the first year post-transplant. Univariate and multivariate analyses were performed. Factors independently associated with textbook outcome were used to create a predictive nomogram. Conditional survival at 1 year was measured. RESULTS: A total of 24,620 patients were identified with 11,169 (45.4%, 95% confidence interval, 44.7-46.0) experiencing textbook outcome. Patients with textbook outcome were more likely free from preoperative mechanical support (odds ratio, 3.504, 95% confidence interval, 2.766 to 4.439, P < .001), free from preoperative dialysis (odds ratio, 2.295, 95% confidence interval, 1.868-2.819, P < .001), to be not hospitalized (odds ratio, 1.264, 95% confidence interval, 1.183-1.349, P < .001), to be nondiabetic (odds ratio, 1.187, 95% confidence interval, 1.113-1.266, P < .001), and to be nonsmokers (odds ratio, 1.160, 95% confidence interval,1.097-1.228, P < .001). Patients with textbook outcome have improved long-term survival relative to patients without textbook outcome who survive at least 1 year (hazard ratio for death, 0.547, 95% confidence interval, 0.504-0.593, P < .001). CONCLUSIONS: Textbook outcome is an alternative means of examining heart transplant outcomes and is associated with long-term survival. The use of textbook outcome as an adjunctive metric provides a holistic view of patient and center outcomes.

Does Failure to Rescue Drive Race/Ethnicity-based Disparities in Survival After Heart Transplantation?

OBJECTIVE: The objective was to assess whether race/ethnicity is an independent predictor of failure to rescue (FTR) after orthotopic heart transplantation (OHT). SUMMARY BACKGROUND DATA: Outcomes following OHT vary by patient level factors; for example, non-White patients have worse outcomes than White patients after OHT. Failure to rescue is an important factor associated with cardiac surgery outcomes, but its relationship to demographic factors is unknown. METHODS: Using the United Network for Organ Sharing database, we included all adult patients who underwent primary isolated OHT between 1/1/2006 snd 6/30/2021. FTR was defined as the inability to prevent mortality after at least one of the UNOS-designated postoperative complications. Donor, recipient, and transplant characteristics, including complications and FTR, were compared across race/ethnicity. Logistic regression models were created to identify factors associated with complications and FTR. Kaplan Meier and adjusted Cox proportional hazards models evaluated the association between race/ethnicity and posttransplant survival. RESULTS: There were 33,244 adult, isolated heart transplant recipients included: the distribution of race/ethnicity was 66% (n=21,937) White, 21.2% (7,062) Black, 8.3% (2,768) Hispanic, and 3.3% (1,096) Asian. The frequency of complications and FTR differed significantly by race/ethnicity. After adjustment, Hispanic recipients were more likely to experience FTR than White recipients (OR 1.327, 95% CI[1.075-1.639], P =0.02). Black recipients had lower 5-year survival compared with other races/ethnicities (HR 1.276, 95% CI[1.207-1.348], P <0.0001). CONCLUSIONS: In the US, Black recipients have an increased risk of mortality after OHT compared with White recipients, without associated differences in FTR. In contrast, Hispanic recipients have an increased likelihood of FTR, but no significant mortality difference compared with White recipients. These findings highlight the need for tailored approaches to addressing race/ethnicity-based health inequities in the practice of heart transplantation.

Repeat pediatric heart transplantation: A united network for organ sharing database analysis.

BACKGROUND: A history of congenital heart disease and previous transplantation are each independently associated with worse survival following pediatric heart transplantation. This study aimed to evaluate the characteristics and outcomes of children undergoing repeat heart transplantation in the United States based on the underlying diagnosis. METHODS: The United Network for Organ Sharing database was used to identify 8111 patients aged <18 years undergoing isolated heart transplantation from 2000 to 2021, including 435 (5.4%) repeat transplants. Restricted cubic spline analysis assessed the non-linear relationship between inter-transplant interval and the primary outcome of all-cause mortality or re-transplantation. Multivariable Cox regression assessed the impact of re-transplantation on the primary outcome. Median follow-up was 5.0 (interquartile range 1.9-9.9) years. RESULTS: Repeat transplant patients were older (median age 12 vs. 4 years; p < .001), and less likely to be in UNOS status 1A (66.0%, n = 287 vs. 81.0% n = 6217; p < .001) than primary transplant patients. Freedom from the primary outcome was 51.4% (95% confidence interval [CI] 45.5-57.2) among repeat transplants and 70.5% (95% CI 69.2-71.8) among primary transplants at 10 years (p < .001). Among repeat transplant patients, the relative hazard of the primary outcome became non-significant when the inter-transplant interval >3.6 years. Congenital heart disease was an independent predictor of mortality among primary (HR 1.8, 95% CI 1.6-1.9) but not repeat transplant (HR 1.1, 95% CI .8-1.6) patients. CONCLUSIONS: Long-term outcomes remain poor for patients undergoing repeat heart transplantation, particularly those with an inter-transplant interval <3.6 years. Underlying diagnosis does not impact outcomes after repeat transplantation, after accounting for other risk factors.

The effect of warm ischemia and donor ejection fraction on 30-day mortality after donation after circulatory death heart transplantation: A national database analysis.

Donation after circulatory death (DCD) donor hearts recovered using the direct procurement and perfusion method experience variable durations of warm ischemia at the time of procurement (WIP). We used the Organ Procurement and Transplantation Network database to assess the effect of WIP on 30-day mortality after DCD heart transplantation. The analysis evaluated outcomes in 237 recipients of DCD heart transplantation, demonstrating an optimal WIP cut point of <36 minutes. Multivariable logistic regression modeling identified donor left ventricular ejection fraction (LVEF) <60% as an independent predictor of 30-day mortality. The area under the receiver operating characteristic curve for predicting 30-day mortality based on WIP ≥36 minutes and donor LVEF <60% was 0.90. Based on these findings, we do not recommend proceeding with DCD heart transplantation for patients with WIP ≥36 minutes, particularly in donors with LVEF <60%.

Is Transplantation With Coronavirus Disease 2019-Positive Donor Lungs Safe? A US Nationwide Analysis.

BACKGROUND: Since the beginning of the pandemic, coronavirus disease 2019 (COVID-19) has caused debilitating lung failure in many patients. Practitioners have understandably been hesitant to use lungs from donors with COVID-19 for transplantation. This study aimed to analyze the characteristics and short-term outcomes of lung transplantation from donors with recent positive COVID-19 testing results. METHODS: Lung transplantations performed between January 2020 and June 2022 were queried from the United Network for Organ Sharing database. Pediatric, multiorgan, and repeat lung transplantations were excluded. Propensity scoring matched recipients of lungs from donors with recent positive COVID-19 testing results to recipients of lungs from donors with negative COVID-19 testing results, and comparisons of 30-day mortality, 3-month mortality, and perioperative outcomes were performed. RESULTS: A total of 5270 patients underwent lung transplantation during the study dates, including 51 patients who received lungs from donors with recent positive COVID-19 testing results. Forty-five recipients of lungs from donors with recent positive COVID-19 testing results were matched with 135 recipients of lungs from donors with negative COVID-19 testing results. After matching, there was no difference in 30-day (log-rank P = .42) and 3-month (log-rank P = .42) mortality. The incidence of other perioperative complications was similar between the groups. CONCLUSIONS: The 30-day and 3-month survival outcomes were similar between recipients of lungs from donors with recent positive COVID-19 testing results and recipients of lungs from donors with negative COVID-19 testing results. This finding suggests that highly selected COVID-19-positive donors without evidence of active infection may be safely considered for lung transplantation. Further studies should explore long-term outcomes to provide reassurance about the safety of this practice.

Donation after circulatory death heart procurement strategy impacts utilization and outcomes of concurrently procured abdominal organs.

INTRODUCTION: The impact of donation after circulatory death (DCD) heart procurement techniques on the utilization and outcomes of concurrently procured DCD livers and kidneys remains unclear. METHODS: Using the United Network for Organ Sharing database, we identified 246 DCD donors whose heart was procured using direct procurement and ex-situ machine perfusion and 128 DCD donors whose heart was procured using in-situ thoracoabdominal normothermic regional perfusion (12/2019-03/2022). We evaluated the transplantation rate of concurrently procured DCD livers and kidneys (defined as the number of organs transplanted/total number of organs available for procurement) and their post-transplant outcomes. RESULTS: The transplantation rate of concurrently procured DCD livers was higher with in-situ perfusion compared to direct procurement (67.1% vs 56.5%, p = 0.045). After excluding pediatric, multiorgan, and repeat transplant recipients, there was no difference in 6-month liver graft failure rate (direct procurement 0.9% vs in-situ perfusion 0%, p > 0.99). Recipients of kidneys procured with in-situ perfusion had less delayed graft function (11.3% vs 41.5%, p < 0.0001) shorter length of stay, and lower serum creatinine at discharge (both p < 0.05). Six-month recipient survival in the direct procurement and in-situ perfusion group were similar after DCD liver and kidney transplantation (p = 0.24 and 0.79 respectively). CONCLUSIONS: Compared to direct procurement, DCD heart procurement with in-situ thoracoabdominal normothermic regional perfusion was associated with increased utilization of DCD livers and a lower incidence of delayed graft function in concurrently procured DCD kidneys. Broader implementation of DCD heart transplantation must maximize the transplant potential of concurrently procured abdominal organs and ensure their successful outcomes.

Intraoperative Red Blood Cell Transfusion and Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: In this international, multicenter study of patients undergoing lung transplantation (LT), we explored the association between the amount of intraoperative packed red blood cell (PRBC) transfusion and occurrence of primary graft dysfunction (PGD) and associated outcomes. METHODS: The Extracorporeal Life Support in LT Registry includes data on LT recipients from 9 high-volume (>40 transplants/y) transplant centers (2 from Europe, 7 from the United States). Adult patients who underwent bilateral orthotopic lung transplant from January 2016 to January 2020 were included. The primary outcome of interest was the occurrence of grade 3 PGD in the first 72 h after LT. RESULTS: We included 729 patients who underwent bilateral orthotopic lung transplant between January 2016 and November 2020. LT recipient population tertiles based on the amount of intraoperative PRBC transfusion (0, 1-4, and >4 units) were significantly different in terms of diagnosis, age, gender, body mass index, mean pulmonary artery pressure, lung allocation score, hemoglobin, prior chest surgery, preoperative hospitalization, and extracorporeal membrane oxygenation requirement. Inverse probability treatment weighting logistic regression showed that intraoperative PRBC transfusion of >4 units was significantly ( P < 0.001) associated with grade 3 PGD within 72 h (odds ratio [95% confidence interval], 2.2 [1.6-3.1]). Inverse probability treatment weighting analysis excluding patients with extracorporeal membrane oxygenation support produced similar findings (odds ratio [95% confidence interval], 2.4 [1.7-3.4], P < 0.001). CONCLUSIONS: In this multicenter, international registry study of LT patients, intraoperative transfusion of >4 units of PRBCs was associated with an increased risk of grade 3 PGD within 72 h. Efforts to improve post-LT outcomes should include perioperative blood conservation measures.

Racial Disparities in Coronavirus Disease 2019 Mortality Are Present in Heart Transplant Recipients.

BACKGROUND: Studies have demonstrated the devastating effects of coronavirus disease 2019 (COVID-19) on vulnerable populations. Although they receive close follow-up, heart transplant recipients represent a particularly vulnerable population, given long-term immunosuppression and comorbid conditions. We sought to investigate the association between race/ethnicity and the probability of death due to COVID-19 in adult heart transplant recipients in the United States. METHODS: Adult isolated heart transplant recipients were identified using the Organ Procurement and Transplantation Network database. Recipients who were described as deceased or lost to follow-up before January 2020 were excluded. Recipients were stratified into 4 cohorts by race/ethnicity. The primary outcome of interest was death due to COVID-19. RESULTS: A total of 22 157 adult recipients were identified. During the course of follow-up, 153 recipients had COVID-19 reported as the primary cause of death. COVID-19 mortality was significantly different between race/ethnicity cohorts (Black, n = 34 [0.79%]; Hispanic, n = 23 [1.33%]; White, n = 92 [0.60%]; other, n = 4 [0.44%]; P = .007). COVID-19 was listed as a contributing cause of mortality in 0.12% of Black, 0.23% of Hispanic, 0.04% of White, and 0.33% of other recipients (P = .002). No significant difference in non-COVID mortality or all-cause mortality was observed. After multivariable adjustment, Black (hazard ratio, 2.78 [1.40-5.52]; P = .003) and Hispanic (hazard ratio, 3.92 [1.88-8.16]; P < .001) recipients were at higher risk of death due to COVID-19 compared with White recipients. CONCLUSIONS: Compared with White recipients, Black and Hispanic recipients experienced higher rates of COVID-19 mortality after transplantation. These findings suggest that racial/ethnic disparities of COVID-19 mortality in the general population persist in adult heart transplant recipients.

Hemodynamic and Clinical Performance of Hearts Donated After Circulatory Death.

BACKGROUND: Donor organ demand continues to outpace supply in heart transplantation. Utilization of donation after circulatory death (DCD) hearts could significantly increase heart donor availability for patients with advanced heart failure. OBJECTIVES: The purpose of this study was to describe hemodynamic and clinical profiles of DCD hearts in comparison to standard of care (SOC) hearts donated after brain death (DBD). METHODS: This single-center retrospective cohort study of consecutive heart transplant recipients analyzed right heart catheterization measurements, inotrope scores, echocardiograms, and clinical outcomes between DCD and DBD heart recipients. RESULTS: Between April 2016 and February 2022, 47 DCD and 166 SOC hearts were transplanted. Median time from DCD consent to transplant was significantly shorter compared with SOC waiting list time (17 days [6-28 days] vs 70 days [23-240 days]; P < 0.001). Right heart function was significantly impaired in DCD recipients compared with SOC recipients 1 week post-transplant (higher median right atrial pressure (10 mm Hg [8-13 mm Hg] vs 7 mm Hg [5-11 mm Hg]; P < 0.001), higher right atrial pressure to pulmonary capillary wedge pressure ratio (0.64 [0.54-0.82] vs 0.57 [0.43-0.73]; P = 0.016), and lower pulmonary arterial pulsatility index (1.66 [1.27-2.50] vs 2.52 [1.63-3.82]; P < 0.001), but was similar between groups by 3 weeks post-transplant. DCD and SOC recipient mortality was similar at 30 days (DCD 0 vs SOC 2%; P = 0.29) and 1 year post-transplant (DCD 3% vs SOC 8%; P = 0.16). CONCLUSIONS: DCD heart utilization is associated with transient post-transplant right heart dysfunction and short-term clinical outcomes otherwise similar to transplantation using DBD hearts.

Induction therapy in lung transplantation: A contemporary analysis of trends and outcomes.

OBJECTIVES: We provide a contemporary consideration of long-term outcomes and trends of induction therapy use following lung transplantation in the United States. METHODS: We reviewed the United Network for Organ Sharing registry from 2006 to 2018 for first-time, adult, lung-only transplant recipients. Long-term survival was compared between induction classes (Interleukin-2 inhibitors, monoclonal or polyclonal cell-depleting agents, and no induction therapy). A 1:1 propensity score match was performed, pairing patients who received basiliximab with similar risk recipients who did not receive induction therapy. Outcomes in matched populations were compared using Cox, Kaplan-Meier and Logistic regression modeling. MEASUREMENTS AND MAIN RESULTS: 22 025 recipients were identified; 8003 (36.34%) were treated with no induction therapy, 11 045 (50.15%) with basiliximab, 1556 (7.06%) with alemtuzumab and 1421 (6.45%) with anti-thymocyte globulin. Compared with those who received no induction, patients receiving basiliximab, alemtuzumab or anti-thymocyte globulin were found on multivariable Cox-regression analyses to have lower long-term mortality (all p < .05). Following propensity score matching of basiliximab and no induction populations, analyses demonstrated a statistically significant association between basiliximab use and long- term survival (p < .001). Basiliximab was also associated with a lower risk of acute rejection (p < .001) and renal failure (p = .002). CONCLUSION: Induction therapy for lung transplant recipients-specifically basiliximab-is associated with improved long-term survival and a lower risk of renal failure or acute rejection.

Interventional Therapies for Acute Pulmonary Embolism.

Pulmonary embolism (PE) is the third leading cause of cardiovascular mortality in the United States. Unfortunately, significant gaps exist in outcome data around many interventional therapies, a fact that is reflected in the low strength of management recommendations found in consensus major society guidelines. In addition to careful risk stratification, therapeutic anticoagulation generally should be an early part of PE management in all cases. For patients presenting with acute high-risk PE or intermediate-risk PE with higher risk features, consideration should be given to systemic thrombolysis after careful evaluation for potential bleeding complications. In patients with contraindications to systemic thrombolysis, failure of this therapy, or significant ongoing cardiopulmonary distress, consideration should be given to interventional therapies like catheter-directed lysis, catheter-directed embolectomy, surgical embolectomy, and mechanical circulatory support. Until more robust comparative outcome data are put forward, pulmonary embolism response teams (PERT) should be considered for multi-disciplinary patient evaluation and management.

Rationale and Design of the Randomized Controlled Trial of New Oral Anticoagulants Versus Warfarin for Post Cardiac Surgery Atrial Fibrillation: The NEW-AF Trial.

OBJECTIVE: This manuscript describes the rationale and design of a randomized, controlled trial comparing outcomes with Warfarin vs Novel Oral Anticoagulant (NOAC) therapy in patients with new onset atrial fibrillation after cardiac surgery. BACKGROUND: New onset atrial fibrillation commonly occurs after cardiac surgery and is associated with increased rates of stroke and mortality. in nonsurgical patients with atrial fibrillation, NOACs have been shown to confer equivalent benefits for stroke prevention with less bleeding risk and less tedious monitoring requirements compared with Warfarin. However, NOAC use has yet to be adopted widely in cardiac surgery patients. METHODS: The NEW-AF study has been designed as a pragmatic, prospective, randomized controlled trial that will compare financial, convenience and safety outcomes for patients with new onset atrial fibrillation after cardiac surgery that are treated with NOACs versus Warfarin. RESULTS: Study results may contribute to optimizing the options for stroke prophylaxis in cardiac surgery patients and catalyze more widespread application of NOAC therapy in this patient population. CONCLUSIONS: The study is ongoing and actively enrolling at the time of the publication. The trial is registered with clinicaltrials.gov under registration number NCT03702582.