Faculty Bibliography

Introduction: CytoSorb is a cytokine adsorption device that received FDA Emergency Use Authorization (EUA) for use in critically ill COVID-19 patients. The CTC Registry was established to collect patient-level data from U.S. centers using CytoSorb under the EUA.
Method(s): Consecutive patients on ECMO treated with CytoSorb were included. Retrospective data collection included demographics, comorbidities, COVID-19 medications, inflammatory biomarkers, and details on ECMO and CytoSorb use. Study follow-up was to hospital death or discharge. Primary outcome was ICU mortality. Comparisons between survivors and non-survivors were performed to evaluate predictors of mortality. Up-to-date information from the international Extracorporeal Life Support Organization (ELSO) ECMO COVID-19 Registry was considered to help contextualize the results.
Result(s): Fifty-two ECMO patients treated under EUA from April 2020 to April 2021 were enrolled from 5 U.S. centers. Baseline characteristics were comparable to the ELSO Registry except for higher rates of obesity in the CTC cohort. ICU mortality rates in the CTC cohort were 17.3% at 30 days, 26.9% at 90 days, and 30.8% overall. Gender, age, baseline SOFA, baseline D-dimer levels, and CytoSorb use between survivors and non-survivors are shown in the Table. Regression analyses suggested a borderline association between baseline D-dimer levels and mortality, with 32% increase in the risk of death per 1 mug/ ml increase (p = 0.055). CytoSorb was generally well tolerated without any unanticipated device-related adverse events reported.
Conclusion(s): Combined use of ECMO and CytoSorb in critically ill COVID-19 patients was associated with mortality rates that compared favorably to international benchmarks. Elevated baseline D-dimer levels appeared to be associated with increased risk of mortality

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.

Worldwide, the majority of heart transplant organs are from donation after brain death. However, the shortage of suitable donors places severe limitations on this route. One option to increase the donor pool is to use organs from donation after circulatory death (DCD). Transplant centers for solid organs have been using DCD organs for years. At this time, 40% of solid organ transplantation in the United Kingdom uses organs from DCD. Use of DCD for solid organ transplants in Canada is also rising. Recently, there has been interest in using DCD organs for heart transplantation. The authors will discuss their experience of 4 heart transplants with organs from DCD donors after normothermic regional perfusion (NRP). The authors' first heart transplant using a DCD organ was in January 2020, and the fourth was in March 2020, just before the coronavirus disease 2019 (COVID-19) pandemic. The authors' protocol using NRP allows adequate evaluation of the donor heart to confidently determine organ acceptance. The co-location of the donor and the recipient in neighboring operating rooms limits ischemic times. Avoidance of an expensive ex vivo organ perfusion machine is an additional benefit for programs that may not have the resources required to purchase and maintain the machine. Some hospitals may not have the resources and space to be able to co-locate both the donor and recipient. Use of cold storage may be an option to transport the procured organ, similar to donation after brain death organs. The authors hope that this technique of NRP in DCD donors can help further increase the donor pool for heart transplantation in the United States.

BACKGROUND:Despite innovations in left ventricular assist devices (LVAD) technology, stroke remains a leading cause of morbidity and mortality in this population. Major clinical trials of LVAD have used various definitions and approaches to measuring stroke outcomes which may limit comparison of stroke risk between different devices. METHODS:Data from the five major LVAD randomized, controlled, trials was abstracted to compare definitions of stroke (composite, ischemic, hemorrhagic and disabling) and stroke event rates across trials. Methodological limitations and suggestions to improve research and clinical practices for stroke and LVAD were identified. RESULTS:Comparison of stroke events across LVAD clinical trials is confounded by methodological variability including heterogeneity in stroke definitions, non-standardized evaluation of stroke etiology, oversimplification of stroke severity classification, and inconsistent event rate reporting due to data censoring at the time of death or transplant. Variability in the study of stroke in LVAD patients limits the ability to compare devices and design prevention strategies to mitigate stroke risk. CONCLUSIONS:Based on this review, we propose that future clinical trials: 1) utilize standardized stroke definitions and define stroke subtypes, 2) ensure that neurologists are integrated in study design and event adjudication, 3) include more thorough evaluations of stroke etiology using multimodality techniques, and 4) adopt the National Institutes of Health Stroke Scale to define stroke severity.

BACKGROUND:Increased utilization of hepatitis C virus (HCV)-positive donors has increased transplantation rates. However, high levels of viremia have been documented in recipients of viremic donors. There is a knowledge gap in how transient viremia may impact acute cellular rejections (ACRs). METHODS:In this study, 50 subjects received hearts from either viremic or non-viremic donors. The recipients of viremic donors were classified as nucleic acid amplification testing (NAT)+ group, and the remaining were classified as NAT-. All patients were monitored for viremia levels. Endomyocardial biopsies were performed through 180 days, evaluating the incidence of ACRs. RESULTS:A total of 50 HCV-naive recipients received hearts between 2018 and 2019. A total of 22 patients (44%) who received transplants from viremic donors developed viremia at a mean period of 7.2 ± 0.2 days. At that time, glecaprevir/pibrentasvir was initiated. In the viremia period (<56 days), 14 of 22 NAT+ recipients (64%) had ACR vs 5 of 28 NAT- group (18%) (p = 0.001). Through 180 days, 17 of 22 NAT+ recipients (77%) had a repeat rejection biopsy vs 12 of 28 NAT- recipients (43%) (p = 0.02). NAT+ biopsies demonstrated disparity of ACR distribution: negative, low-grade, and high-grade ACR in 84%, 12%, and 4%, respectively, vs 96%, 3%, and 1%, respectively, in the NAT- group (p = 0.03). The median time to first event was 26 (interquartile range [IQR]: 8-45) in the NAT+ group vs 65 (IQR: 44-84) days in the NAT-. Time to first event risk model revealed that NAT+ recipients had a significantly higher rate of ACR occurrences, adjusting for demographics (p = 0.004). CONCLUSIONS:Transient levels of viremia contributed to higher rates and severity of ACRs. Further investigation into the mechanisms of early immune activation in NAT+ recipients is required.

We conducted a retrospective review of thoracic transplant recipients (22 heart and 16 lung transplant recipients) prospectively enrolled in a single-center observational study of HCV NAT+ organ transplantation in HCV NAT- recipients. All recipients were treated with 8 weeks of glecaprevir-pibrentasvir (GP) for HCV viremia in addition to standard triple immunosuppression post-transplant. Thoracic transplant recipients of HCV NAT- organs were used as a control (24 heart and 22 lung transplant recipients). Our primary outcome was to assess the effect of GP on tacrolimus dose requirements. Secondary objectives included assessing drug interactions with common post-transplant medications, adverse effects, and the need to hold or discontinue GP therapy. The median tacrolimus concentration-to-dose (CDR) in the cohort was 184 (99-260) during GP therapy and 154 (78-304) over the first month after GP (p=0.79). Trends in median tacrolimus CDR were similar on a per-week basis and per-patient basis. In three instances, concomitant posaconazole and GP led to hyperbilirubinemia and interruption of posaconazole. GP therapy was held in one heart transplant recipient, and discontinued in another, due to unresolving hyperbilirubinemia. Utilization of GP to treat HCV viremia post-thoracic transplant is feasible and safe, but requires modifications to post-transplant pharmacotherapy and careful monitoring for adverse effects.

Study: Despite advances in design and hemocompatibility, pump thrombosis remains a significant cause of morbidity for patients implanted with durable left ventricular assist devices (LVAD). Pharmacologic fibrinolysis may be preferred as initial therapy because it obviates a surgical procedure. Yet, it historically has been associated with a significant risk of secondary intracerebral hemorrhage (ICH).
Method(s): We implemented a novel protocol to treat HVAD pump thrombosis and minimize risk of ICH that consisted of the following: initiation of a non-titrating heparin infusion at 500 units/hr; normalization of international normalized ratio (INR) by giving a flat dose of 1,000 units of four-factor prothrombin complex concentration (4F-PCC); and administration of alteplase as a 10 mg bolus followed by 40 mg given over 3 hours.
Result(s): Two patients underwent treatment with the above protocol for presumed HVAD pump thrombosis based on clinical signs of hemolysis and elevations of power on log-file analysis. One patient was 2 months from HVAD implant and the other 13 months. Both patients had subtherapeutic INR in the preceding weeks. Following administration of alteplase, log-file analysis demonstrated immediate resolution of power elevations (Fig. 1). Both patients had a subsequent rise in power requiring repeat alteplase dosing. No bleeding or thrombotic events occurred with treatment. One patient underwent heart transplant a month after treatment and is doing well; the second patient is stable on HVAD support 4 months following alteplase. Combining 4F-PCC to temporarily normalize the INR with repeat dosing of alteplase was effective at resolving HVAD pump thrombosis without bleeding complications and should be investigated further