Pre-transplant immune cell function assay as a predictor of early cardiac allograft rejection.

INTRODUCTION: ImmuKnow, an immune cell function assay that quantifies overall immune system activity can assist in post-transplant immunosuppression adjustment. However, the utility of pre-transplant ImmuKnow results representing a patient's baseline immune system activity is unknown. This study sought to assess if pre-transplant ImmuKnow results are predictive of rejection at the time of first biopsy in our cardiac transplant population. METHODS: This is a single center, retrospective observational study of consecutive patients from January 1, 2018 to October 1, 2020 who underwent orthotopic cardiac transplantation at NYU Langone Health. Patients were excluded if a pre-transplant ImmuKnow assay was not performed. ImmuKnow results were categorized according to clinical interpretation ranges (low, moderate, and high activity), and patients were divided into two groups: a low activity group versus a combined moderate-high activity group. Pre-transplant clinical characteristics, induction immunosuppression use, early postoperative tacrolimus levels, and first endomyocardial biopsy results were collected for all patients. Rates of clinically significant early rejection (defined as rejection ≥ 1R/1B) were compared between pre-transplant ImmuKnow groups. RESULTS: Of 110 patients who underwent cardiac transplant, 81 had pre-transplant ImmuKnow results. The low ImmuKnow activity group was comprised of 15 patients, and 66 patients were in the combined moderate-high group. Baseline characteristics were similar between groups. Early rejection occurred in 0 (0%) patients with low pre-transplant ImmuKnow levels. Among the moderate- high pre-transplant ImmuKnow group, 16 (24.2%) patients experienced early rejection (P = .033). The mean ImmuKnow level in the non-rejection group was the 364.9 ng/ml of ATP compared to 499.3 ng/ml of ATP for those with rejection (P = .020). CONCLUSION: Patients with low pre-transplant ImmuKnow levels had lower risk of early rejection when compared with patients with moderate or high levels. Our study suggests a possible utility in performing pre-transplant ImmuKnow to identify patients at-risk for early rejection who may benefit from intensified upfront immunosuppression as well as to recognize those where slower calcineurin inhibitor initiation may be appropriate.

Hemoadsorption for management of patients on veno-venous ECMO support for severe COVID-19 acute respiratory distress syndrome.

BACKGROUND AND AIM: Patients with severe coronavirus disease 2019 (COVID-19) develop a profound cytokine-mediated pro-inflammatory response. This study reports outcomes in 10 patients with COVID-19 supported on veno-venous extracorporeal membrane oxygenation (VV-ECMO) who were selected for the emergency use of a hemoadsorption column integrated in the ECMO circuit. MATERIALS AND METHODS: Pre and posttreatment, clinical data, and inflammatory markers were assessed to determine the safety and feasibility of using this system and to evaluate the clinical effect. RESULTS: During hemoadsorption, median levels of interleukin (IL)-2R, IL-6, and IL-10 decreased by 54%, 86%, and 64%, respectively. Reductions in other markers were observed for lactate dehydrogenase (-49%), ferritin (-46%), d-dimer (-7%), C-reactive protein (-55%), procalcitonin (-76%), and lactate (-44%). Vasoactive-inotrope scores decreased significantly over the treatment interval (-80%). The median hospital length of stay was 53 days (36-85) and at 90-days post cannulation, survival was 90% which was similar to a group of patients without the use of hemoadsorption. CONCLUSIONS: Addition of hemoadsorption to VV-ECMO in patients with severe COVID-19 is feasible and reduces measured cytokine levels. However, in this small series, the precise impact on the overall clinical course and survival benefit still remains unknown.

Ethical and logistical concerns for establishing NRP-cDCD heart transplantation in the United States.

Controlled heart donation after circulatory determination of death (cDCD) is well established internationally with good outcomes and could be adopted in the United States to increase heart supply if ethical and logistical challenges are comprehensively addressed. The most effective and resource-efficient method for mitigating warm ischemia after circulatory arrest is normothermic regional perfusion (NRP) in situ. This strategy requires restarting circulation after declaration of death according to circulatory criteria, which appears to challenge the legal circulatory death definition requiring irreversible cessation. Permanent cessation for life-saving efforts must be achieved to assuage this concern and ligating principal vessels maintains no blood flow to the brain, which ensures natural progression to cessation of brain function. This practice-standard in some countries-raises unique concerns about prioritizing life-saving efforts, informed authorization from decision-makers, and the clinician's role in the patient's death. To preserve public trust, medical integrity, and respect for the donor, the donation conversation must not take place until after an un-coerced decision to withdraw life-sustaining treatment made in accordance with the patient's treatment goals. The decision-maker(s) must understand cDCD procedure well enough to provide genuine authorization and the preservation/procurement teams must be kept separate from the clinical care team.

Comparison of device-specific adverse event profiles between Impella platforms.

BACKGROUND: The Impella (Abiomed) ventricular support system is a family of temporary mechanical circulatory support (MCS) devices used to treat patients with cardiogenic shock, acute cardiogenic decompensation, and for high-risk percutaneous or surgical revascularization. These devices include the percutaneously implanted 2.5/cardiac power (CP) and the surgically implanted 5.0/left direct (LD). Despite the beneficial effects and increased usage of these devices, data to assess adverse outcomes and guide clinician decision-making between the Impella CP and 5.0/LD are limited. METHODS: This is a retrospective analysis of 91 consecutive patients who required at least 24 h of Impella support, from January 1, 2015 to December 31, 2019. Groups were stratified based on either initial Impella CP or 5.0/LD placement. Clinical outcomes and in-hospital complications were compared. RESULTS: Impella CP was implanted in 66 patients (mean age: 61 ± 15 years, male 71.2%) and Impella 5.0/LD was implanted in 25 patients (mean age: 62 ± 9 years, male 84.0%). There was greater stability of device position (p = .033), less incidence of hemolysis (p < .001), and less frequent need for additional MCS (p = .001) in patients implanted with the Impella 5.0/LD compared with Impella CP in this study cohort. Patients with Impella 5.0/LD were more likely to survive from Impella and survive to discharge. CONCLUSIONS: This study suggests that for patients who require temporary MCS for more than 24 h, the Impella 5.0/LD may have a more favorable device-specific adverse profile compared with the Impella CP.

Assessing donor organ quality according to recipient characteristics in lung transplantation.

OBJECTIVE: There is a shortage of donor lungs relative to need, but overall donor organ utilization remains low. The most common reason for refusal is organ quality, but the standards applied to selection vary. In this study we sought to characterize differences in lung utilization according to quality across several clinically distinct recipient pools. METHODS: Data on donor lungs recovered (April 2006 to September 2019) were extracted from the Scientific Registry of Transplant Recipients database. Organs were classified as ideal, standard, or extended quality according to their poorest metric among selected parameters. Subanalyses were performed on the basis of procedure type, age, lung allocation score, era, and alternative definitions of extended quality. Recipient traits and survival according to organ quality were assessed. RESULTS: Of 156,022 lungs analyzed during the study period, 25,777 (16.5%) were transplanted. There was no difference in quality distribution for single and bilateral transplants. Young candidates were more likely to receive ideal (14.7% vs 12.3%) or standard (9.5% vs 8.2%) lungs, but not extended lungs (75.9% vs 79.5%; all P < .01). Absolute differences in distribution according to lung allocation score quartile were small (<2%). Extended quality donor utilization increased over time. Survival according to donor category was similar at 1 and 3 years post transplant in unadjusted and Cox regression analyses. CONCLUSIONS: Extended quality lungs comprise an increasing share of transplants in a national sample. Organ selection varies according to recipient age and lung allocation score. However, absolute differences in quality distribution are small, and adverse effects on outcomes are limited to organs with multiple extended qualifying characteristics.

One-Year Outcomes With Venovenous Extracorporeal Membrane Oxygenation Support for Severe COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can cause acute respiratory failure requiring mechanical ventilation. Venovenous (VV) extracorporeal membrane oxygenation (ECMO) has been used in patients in whom conventional mechanical ventilatory support has failed. To date, published data have focused on survival from ECMO and survival to discharge. In addition to survival to discharge, this study reports 1-year follow-up data for patients who were successfully discharged from the hospital. METHODS: A single-institution, retrospective review of all patients with severe COVID-19 who were cannulated for VV-ECMO between March 10, 2020 and May 1, 2020 was performed. A multidisciplinary ECMO team evaluated, selected, and managed patients with ECMO support. The primary outcome of this study was survival to discharge. Available 1-year follow-up data are also reported. RESULTS: A total of 30 patients were supported with VV-ECMO, and 27 patients (90%) survived to discharge. All patients were discharged home or to acute rehabilitation on room air, except for 1 patient (3.7%), who required supplemental oxygen therapy. At a median follow-up of 10.8 months (interquartile range [IQR], 8.9-14.4 months) since ECMO cannulation, survival was 86.7%, including 1 patient who underwent lung transplantation. Of the patients discharged from the hospital, 44.4% (12/27) had pulmonary function testing, with a median percent predicted forced expiratory volume of 100% (IQR, 91%-110%). For survivors, a 6-minute walk test was performed in 59.3% (16/27), with a median value of 350 m (IQR, 286-379 m). CONCLUSIONS: A well-defined patient selection and management strategy of VV-ECMO support in patients with severe COVID-19 resulted in exceptional survival to discharge that was sustained at 1-year after ECMO cannulation.

Early experience with donation after circulatory death heart transplantation using normothermic regional perfusion in the United States.

OBJECTIVE: This pilot study sought to evaluate the feasibility of our donation after circulatory death (DCD) heart transplantation protocol using cardiopulmonary bypass (CPB) for normothermic regional reperfusion (NRP). METHODS: Suitable local DCD candidates were transferred to our institution. Life support was withdrawn in the operating room (OR). On declaration of circulatory death, sternotomy was performed, and the aortic arch vessels were ligated. CPB was initiated with left ventricular venting. The heart was reperfused, with correction of any metabolic abnormalities. CPB was weaned, and cardiac function was assessed at 30-minute intervals. If accepted, the heart was procured with cold preservation and transplanted into recipients in a nearby OR. RESULTS: Between January 2020 and January 2021, a total of 8 DCD heart transplants were performed: 6 isolated hearts, 1 heart-lung, and 1 combined heart and kidney. All donor hearts were successfully resuscitated and weaned from CPB without inotropic support. Average lactate and potassium levels decreased from 9.39 ± 1.47 mmol/L to 7.20 ± 0.13 mmol/L and 7.49 ± 1.32 mmol/L to 4.36 ± 0.67 mmol/L, respectively. Post-transplantation, the heart-lung transplant recipient required venoarterial extracorporeal membrane oxygenation for primary lung graft dysfunction but was decannulated on postoperative day 3 and recovered uneventfully. All other recipients required minimal inotropic support without mechanical circulatory support. Survival was 100% with a median follow-up of 304 days (interquartile range, 105-371 days). CONCLUSIONS: DCD heart transplantation outcomes have been excellent. Our DCD protocol is adoptable for more widespread use and will increase donor heart availability in the United States.

Efficacy of proning in acute respiratory distress syndrome on extracorporeal membrane oxygenation.

Objectives: Proning patients with acute respiratory distress syndrome (ARDS) has been associated with increased survival, although few data exist evaluating the safety and feasibility of proning patients with ARDS on extracorporeal membrane oxygenation (ECMO). Methods: A single-institution retrospective review of all patients with ARDS placed on ECMO between March 1 and May 31, 2020, was performed. All proning events were evaluated for complications, as well as change in compliance, sweep, oxygenation, and flow. The primary outcome of this study was the rate major morbidity associated with proning while on ECMO. Results: In total, 30 patients were placed on ECMO for ARDS, with 12 patients (40%) proned while on ECMO. A total of 83 proning episodes occurred, with a median of 7 per patient (interquartile range, 3-9). No ECMO cannula-associated bleeding, cannula displacement, or endotracheal tune dislodgements occurred (0%). Oropharyngeal bleeding occurred twice (50%). Four patients were proned with chest tubes in place, and none had complications (0%). Lung compliance improved after proning in 70 events (84%), from a mean of 15.4 mL/mm Hg preproning to 20.6 mL/mm Hg postproning (P < .0001). Sweep requirement decreased in 36 events (43%). Oxygenation improved in 63 events (76%), from a mean partial pressure of oxygen of 86 preproning to 103 postproning (P < .0001). Mean ECMO flow was unchanged. Conclusions: Proning in patients with ARDS on ECMO is safe with an associated improvement in lung mechanics. With careful planning and coordination, these data support the practice of appropriately proning patients with severe ARDS, even if they are on ECMO.

Extracorporeal Membrane Oxygenation Support in Severe COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) remains a worldwide pandemic with a high mortality rate among patients requiring mechanical ventilation. The limited data that exist regarding the utility of extracorporeal membrane oxygenation (ECMO) in these critically ill patients show poor overall outcomes. This report describes our institutional practice regarding the application and management of ECMO support for patients with COVID-19 and reports promising early outcomes. METHODS: All critically ill patients with confirmed COVID-19 evaluated for ECMO support from March 10, 2020, to April 24, 2020, were retrospectively reviewed. Patients were evaluated for ECMO support based on a partial pressure of arterial oxygen/fraction of inspired oxygen ratio of less than 150 mm Hg or pH of less than 7.25 with a partial pressure of arterial carbon dioxide exceeding 60 mm Hg with no life-limiting comorbidities. Patients were cannulated at bedside and were managed with protective lung ventilation, early tracheostomy, bronchoscopies, and proning, as clinically indicated. RESULTS: Among 321 patients intubated for COVID-19, 77 patients (24%) were evaluated for ECMO support, and 27 patients (8.4%) were placed on ECMO. All patients were supported with venovenous ECMO. Current survival is 96.3%, with only 1 death to date in more than 350 days of total ECMO support. Thirteen patients (48.1%) remain on ECMO support, and 13 patients (48.1%) have been successfully decannulated. Seven patients (25.9%) have been discharged from the hospital. Six patients (22.2%) remain in the hospital, of which 4 are on room air. No health care workers who participated in ECMO cannulation developed symptoms of or tested positive for COVID-19. CONCLUSIONS: The early outcomes presented here suggest that the judicious use of ECMO support in severe COVID-19 may be clinically beneficial.

A Simple Prioritization Change to Lung Transplant Allocation May Result in Improved Outcomes.

BACKGROUND: The lung allocation score (LAS) significantly improved outcomes and wait list mortality in lung transplantation. However, mortality remains high for the sickest wait list candidates despite additional changes to allocation distance. Regulatory considerations of overhauling the current lung allocation system have met significant resistance, and changes would require years to implement. This study evaluates whether a modest change to the current system by prioritization of only high-LAS lung transplant candidates would result in lowered wait list mortality. METHODS: The Thoracic Simulated Allocation Model was used to evaluate all lung transplant candidates and donor lungs recovered between July 1, 2009 and June 30, 2011. Current lung allocation rules (initial offer within a 250-nautical mile radius for ABO-identical then compatible offers) were run. Allocation was then changed for only patients with an LAS of50 or higher (high-LAS) to be prioritized within a 500-nautical mile radius with no stratification between ABO-identical and compatible offers. Ten iterations of each model were run. Primary end points were wait list mortality and posttransplant 1-year survival. RESULTS: A total of 6538 wait list candidates and transplant recipients were evaluated per iteration, for a total of 130,760 simulated patients. Compared with current allocation, the adjusted model had a 23.3% decrease in wait list mortality. Posttransplant 1-year survival was minimally affected. CONCLUSIONS: Without overhauling the entire system, simple prioritization changes to the allocation system for high-LAS candidates may lead to decreased wait list mortality and increased organ use. Importantly, these changes do not appear to lead to clinically significant changes in posttransplant 1-year survival.

Impact of concomitant mitral valve repair for severe mitral regurgitation at the time of continuous-flow left ventricular assist device insertion.

OBJECTIVES: Mitral regurgitation (MR) is common in patients with end-stage heart failure. We assessed the effect of performing concomitant mitral valve repair during continuous-flow left ventricular assist device (CF-LVAD) implantation in patients with severe preoperative MR. METHODS: We performed a single-centre, retrospective review of all patients who underwent CF-LVAD implantation between December 1999 and December 2013 (n = 469). Patients with severe preoperative MR (n = 78) were identified and then stratified according to whether they underwent concomitant valve repair. Univariate and survival analyses were performed, and multivariable regression was used to determine predictors of survival. RESULTS: Of the 78 patients with severe MR, 21 underwent valve repair at the time of CF-LVAD implantation (repair group) and 57 did not (non-repair group). A comparison of the 2 groups showed significant differences between groups: INTERMACS I 16.985 vs 9.52%, (P = 0.039), cardiopulmonary bypass time 82.09 vs 109.4 min (P = 0.0042) and the use of HeartMate II 63.16 vs 100% (P = 0.001). Survival analysis suggested trends towards improved survival and a lower incidence of heart failure-related readmissions in the repair group. Multivariable regression analysis showed no significant independent predictors of survival (mitral valve repair: odds ratio 0.4, 95% confidence interval 0.8-1.5; P = 0.2). CONCLUSIONS: Despite the lack of statistical significance, trends towards improved survival and a lower incidence of heart failure events suggest that mitral valve repair may be beneficial in patients undergoing CF-LVAD implantation. Given the known relationship between severe MR and mortality, further study is encouraged to confirm the value of mitral valve repair in these patients.

The Stent Is Not to Blame: Lessons Learned With a Simplified US Version of the Frozen Elephant Trunk.

BACKGROUND: We analyzed trends, assessed outcomes and lessons learned, and investigated whether using a simplified US version of the frozen elephant trunk (FET) technique to treat complex arch pathology poses additional risk. METHODS: From 2010 to 2015, we performed 129 consecutive ET procedures (traditional ET [t-ET], n = 92 [71.3%]; FET, n = 37 [28.7%]) for chronic dissecting (n = 62 [48.1%]) and atherosclerotic aneurysms (n = 67 [51.9%]). A stepwise logistic regression model using preoperative and intraoperative variables was created to analyze the outcomes. RESULTS: Thirty-day mortality was 12.4% (t-ET, n = 9 [9.8%]; FET, n = 7 [18.9%]; p = 0.24). The rate of persistent (at the time of discharge) stroke was 5.4% (t-ET, n = 5 [5.4%]; FET, n = 2 [5.4%]; p =1.00). The rate of persistent spinal cord deficit was 3.9% (t-ET, n = 3 [3.3%]; FET, n = 2 [5.4%]; p = 0.62). In the multivariable analyses, the addition of FET was not an independent predictor of mortality, permanent stroke, or spinal cord deficit. CONCLUSIONS: With the advent of endovascular technology, there is a clinical shift toward increased use of FET to eliminate or facilitate the second surgical stage in treating patients with extensive aortic pathology. The addition of FET to the surgical armamentarium does not seem to pose additional risk (although larger studies are needed), but judicious use is advised nonetheless. A single-piece endoprosthesis for FET instead of a customized one should be considered.