Heart Allocation Change and Multiple Temporary Circulatory Support as Bridge-to-Bridge.

INTRODUCTION: We investigated how the 2018 Organ Procurement and Transplantation Network heart allocation policy change was associated with changes in characteristics and outcomes of candidates receiving multiple temporary mechanical circulatory support (mtMCS) devices. MATERIALS AND METHODS: We included adult heart transplant candidates listed October 2014-January 2018 and October 2018-January 2022 in the United Network of Organ Sharing dataset. Prepolicy and postpolicy mtMCS recipients were compared at listing, transplant, 90-days, and 1-year post-transplant. Time between first and second devices and time between first device and transplant were modeled via multivariable linear regression. Transplantation likelihood was modeled using competing risks analysis. RESULTS: Postpolicy, a higher proportion of transplant candidates received mtMCS (4% versus 1%, P < 0.001), and received their second device an adjusted 49 d sooner versus prepolicy (P = 0.001). Time to transplant was also an adjusted 35 d shorter postpolicy, with an 80% increased transplantation likelihood versus prepolicy (95% confidence interval: 1.6-1.9, P < 0.001). Postpolicy patients experienced reduced waitlist mortality (8% versus 14%, P = 0.04) with marked improvements in 90-day (93% versus 85%, P < 0.001) and 1-year (88% versus 70%, P = 0.01) post-transplant survival. CONCLUSIONS: Postpolicy mtMCS recipients are more likely to progress to transplantation sooner on the waitlist and their shorter waitlist course together with earlier change to a secondary device was associated with improved post-transplant survival versus prepolicy.

Assessing the SAfety and FEasibility of bedside portable low-field brain Magnetic Resonance Imaging in patients on ECMO (SAFE-MRI ECMO study): study protocol and first case series experience.

BACKGROUND: To assess the safety and feasibility of imaging of the brain with a point-of-care (POC) magnetic resonance imaging (MRI) system in patients on extracorporeal membrane oxygenation (ECMO). Early detection of acute brain injury (ABI) is critical in improving survival for patients with ECMO support. METHODS: Patients from a single tertiary academic ECMO center who underwent head CT (HCT), followed by POC brain MRI examinations within 24 h following HCT while on ECMO. Primary outcomes were safety and feasibility, defined as completion of MRI examination without serious adverse events (SAEs). Secondary outcome was the quality of MR images in assessing ABIs. RESULTS: We report 3 consecutive adult patients (median age 47 years; 67% male) with veno-arterial (n = 1) and veno-venous ECMO (n = 2) (VA- and VV-ECMO) support. All patients were imaged successfully without SAEs. Times to complete POC brain MRI examinations were 34, 40, and 43 min. Two patients had ECMO suction events, resolved with fluid and repositioning. Two patients were found to have an unsuspected acute stroke, well visualized with MRI. CONCLUSIONS: Adult patients with VA- or VV-ECMO support can be safely imaged with low-field POC brain MRI in the intensive care unit, allowing for the assessment of presence and timing of ABI.

Neurological Complications in COVID-19 Patients With ECMO Support: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with Coronavirus disease 2019 (COVID-19)-related acute respiratory disease (ARDS) increasingly receive extracorporeal membrane oxygenation (ECMO) support. While ECMO has been shown to increase risk of stroke, few studies have examined this association in COVID-19 patients. OBJECTIVE: We conducted a systematic review to characterise neurological events during ECMO support in COVID-19 patients. DESIGN: Systematic review of cohort and large case series of COVID-19 patients who received ECMO support. DATA SOURCES: Studies retrieved from PubMed, EMBASE, Cochrane, Cochrane COVID-19 Study Register, Web of Science, Scopus, Clinicaltrials.gov, and medRχiv from inception to November 11, 2020. ELIGIBILITY CRITERIA: Inclusion criteria were a) Adult population (>18 year old); b) Positive PCR test for SARS-CoV-2 with active COVID-19 disease; c) ECMO therapy due to COVID-19 ARDS; and d) Neurological events and outcome described while on ECMO support. We excluded articles when no details of neurologic events were available. RESULTS: 1,322 patients from 12 case series and retrospective cohort studies were included in our study. The median age was 49.2, and 75% (n=985) of the patients were male. Diabetes mellitus and dyslipidaemia were the most common comorbidities (24% and 20%, respectively). Most (95%, n=1,241) patients were on venovenous ECMO with a median P:F ratio at the time of ECMO cannulation of 69.1. The prevalence of intracranial haemorrhage (ICH), ischaemic stroke, and hypoxic ischaemic brain injury (HIBI) was 5.9% (n=78), 1.1% (n=15), and 0.3% (n=4), respectively. The overall mortality of the 1,296 ECMO patients in the 10 studies that reported death was 36% (n=477), and the mortality of the subset of patients who had a neurological event was 92%. CONCLUSIONS: Neurological injury is a concern for COVID-19 patients who receive ECMO. Further research is required to explore how neuromonitoring protocols can inform tailored anticoagulation management and improve survival in COVID-19 patients with ECMO support.

Risk Factors of Ischemic and Hemorrhagic Strokes During Venovenous Extracorporeal Membrane Oxygenation: Analysis of Data From the Extracorporeal Life Support Organization Registry.

OBJECTIVES: Stroke is commonly reported in patients receiving venovenous extracorporeal membrane oxygenation, but risk factors are not well described. We sought to determine preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors for both ischemic and hemorrhagic strokes in patients with venovenous extracorporeal membrane oxygenation support. DESIGN: Retrospective analysis. SETTING: Data reported to the Extracorporeal Life Support Organization by 366 extracorporeal membrane oxygenation centers from 2013 to 2019. PATIENTS: Patients older than 18 years supported with a single run of venovenous extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 15,872 venovenous extracorporeal membrane oxygenation patients, 812 (5.1%) had at least one type of acute brain injury, defined as ischemic stroke, hemorrhagic stroke, or brain death. Overall, 215 (1.4%) experienced ischemic stroke and 484 (3.1%) experienced hemorrhagic stroke. Overall inhospital mortality was 36%, but rates were higher in those with ischemic or hemorrhagic stroke (68% and 73%, respectively). In multivariable analysis, preextracorporeal membrane oxygenation pH (adjusted odds ratio = 0.10; 95% CI, 0.03-0.35; p < 0.001), hemolysis (adjusted odds ratio = 2.27; 95% CI, 1.22-4.24; p = 0.010), gastrointestinal hemorrhage (adjusted odds ratio = 2.01; 95% CI 1.12-3.59; p = 0.019), and disseminated intravascular coagulation (adjusted odds ratio = 3.61; 95% CI, 1.51-8.66; p = 0.004) were independently associated with ischemic stroke. Pre-extracorporeal membrane oxygenation pH (adjusted odds ratio = 0.28; 95% CI, 0.12-0.65; p = 0.003), preextracorporeal membrane oxygenation Po2 (adjusted odds ratio = 0.96; 95% CI, 0.93-0.99; p = 0.021), gastrointestinal hemorrhage (adjusted odds ratio = 1.70; 95% CI, 1.15-2.51; p = 0.008), and renal replacement therapy (adjusted odds ratio=1.57; 95% CI, 1.22-2.02; p < 0.001) were independently associated with hemorrhagic stroke. CONCLUSIONS: Among venovenous extracorporeal membrane oxygenation patients in the Extracorporeal Life Support Organization registry, approximately 5% had acute brain injury. Mortality rates increased two-fold when ischemic or hemorrhagic strokes occurred. Risk factors such as lower pH and hypoxemia during the pericannulation period and markers of coagulation disturbances were associated with acute brain injury. Further research on understanding preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors and the timing of acute brain injury is necessary to develop appropriate prevention and management strategies.

Patient Safety Indicators are an insufficient performance metric to track and grade outcomes of open aortic repair.

OBJECTIVE: National rankings of hospitals rely on outcomes-based evaluation to assess the performance of surgical programs, particularly those performing high-risk elective surgical procedures such as open aortic repair. Various classification systems exist for tracking outcomes, but increasingly the International Classification of Diseases, Tenth Revision-based Agency for Healthcare Research and Quality Patient Safety Indicators (PSIs) are used as a publicly reported comparison measure of hospital quality performance. We sought to critically evaluate the accuracy of the existing vehicles to assess open aortic repair outcomes in an established program. METHODS: This is a case-control study of patients who underwent open abdominal aortic aneurysm repair at the Johns Hopkins Medical Institutions from 2004 to 2018. Patients' characteristics and outcomes were collected as part of a prospectively maintained retrospective database. For each case, hemorrhagic, cardiac, respiratory, renal, wound, and thromboembolic complications were identified with the unique definitions used for open abdominal aortic aneurysm repair by the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, the Society for Vascular Surgery Vascular Quality Initiative (VQI) database, and the Agency for Healthcare Research and Quality PSI initiative. RESULTS: Of the 154 patients included in the study, 79 (51.0%) were identified as having a complication as defined by the VQI, 46 (29.7%) according to the NSQIP, and 15 (9.7%) according to the PSI system (P < .001). Patients most likely to incur a complication in the PSI system were those with a pararenal or more extensive aneurysm, with baseline congestive heart failure, requiring a supramesenteric clamp (all P < .01), or with an aneurysm >6.5 cm in diameter (P = .02). The NSQIP and VQI systems both identified more postoperative hemorrhagic, respiratory, renal, and wound complications than the PSI system did (P < .05). The VQI system identified the most renal complications (52; P < .001); factors unique to incurring a complication in the VQI include use of a suprarenal clamp and performance of an aortorenal bypass procedure as part of the repair (P < .01). Particularly weak correlation was noted between the PSI system and the VQI with respect to renal outcomes (ρ = 0.163). CONCLUSIONS: The PSI system identified fewer important complications than either of the clinically focused databases, with the VQI capturing the most postoperative events, mostly because of its stringent definition of renal injury. We conclude that the PSI system should not form the basis of grading hospital performance in comparing clinically relevant complications of open aortic surgery programs.

Poor concordance of contemporary performance measures in detecting complications in complex endovascular aortic repair.

BACKGROUND: The Agency for Healthcare Research and Quality Patient Safety Indicators (PSI) are quality improvement indicators used to determine hospital performance and, increasingly, to rank surgical programs. The American College of Surgeons National Surgical Quality Improvement Program and the Society for Vascular Surgery Vascular Quality Improvement databases are also frequently used to compare outcomes, but definitions of complications vary between the systems and the optimal system for tracking complications in complex endovascular repair remains unclear. Herein we assess the three outcome tracking systems and their ability to capture complications after fenestrated endovascular abdominal aortic aneurysm repair (FEVAR) and open aortic aneurysm repair in a large complex aortic program. METHODS: Demographic and operative data for patients undergoing repair of juxtarenal or pararenal aortic aneurysms between 2004 and 2018 via both open and FEVAR approaches at the Johns Hopkins Medical Institutions were compiled in a prospectively maintained retrospective database. Postoperative complications were defined according to a surgeon-defined system, the Society for Vascular Surgery Vascular Quality Initiative, the American College of Surgeons National Surgical Quality Improvement Program, and the Agency for Healthcare Research and Quality PSI data dictionaries and were compared between surgical approaches as well as eras before and after the introduction of FEVAR. Complication rates between the classification systems were compared using proportion testing and the strength of the correlation between the systems was evaluated with Spearman's rank test. RESULTS: Of 145 patients, 60 (41.4%) underwent FEVAR and 85 (58.6%) underwent open aortic aneurysm repair. The introduction of fenestrated technology was associated with a decrease in the overall number of complications from 37.2% to 20.6% by surgeon-defined classification system (P = .036). The VQI identified the most complications (39.9% of the entire cohort and 25% of FEVAR cases), followed by the NSQIP (29.0% and 33.3%, respectively) and PSI (4.1% and 5%). The two clinically focused databases were found to correlate well with a surgeon-designed classification system, as well as each other (Spearman ρ ≥ 0.735) but not with PSI (ρ < 0.23). Proportion testing demonstrated the rate of complications identified by PSI to be significantly less than either VQI or NSQIP (P < .001). Specifically, PSI did not effectively identify renal complications (1.4% vs 9.0% by NSQIP and 27.3% by VQI definitions; P < .001). CONCLUSIONS: The introduction of FEVAR is associated with an overall decrease in complications in this study. The clinically relevant VQI and NSQIP databases show good concordance in capturing complications; however, PSI did not correlate with either and captured significantly fewer complications. These data highlight the value of high scrutiny classification systems to track postoperative complications and suggest that PSI are insufficient to rank complex aortic programs with high levels of FEVAR use.

Inflammatory profile in a canine model of hypothermic circulatory arrest.

BACKGROUND: Hypothermic circulatory arrest (HCA) is a technique used for complex repair of the aorta, but it can be associated with neurologic morbidity. To better understand the molecular changes that underlie ischemic brain injury, we assessed gene expression and cytokine/chemokine polypeptide concentration in brain tissue and cerebrospinal fluid (CSF) of canines that underwent two hours of HCA. MATERIALS AND METHODS: Adult male canines were cannulated peripherally for cardiopulmonary bypass, cooled to 18°C, and arrested for two hours. Animals were euthanized two, eight, or 24 hours post-HCA (n = 8 per group), and their brains were compared to brains from eight normal canines, using gene expression microarray analysis, cytokine assay, and histopathology. RESULTS: Two to eight hours after HCA, pro-inflammatory cytokine mRNAs increased markedly, and gene expression was enriched within signaling pathways related to neuroinflammation or ischemic injury. Concentrations of pro-inflammatory cytokine polypeptides IL-6, IL-8, IL-1ß, and CCL2 were very low in normal canine brain, whereas anti-inflammatory IL-10 and TGF-ß1 were expressed at moderate levels. Pro-inflammatory cytokine concentrations rose robustly in cerebral tissue and CSF after HCA. IL-6 and IL-8 peaked at eight hours and declined at 24 hours, while IL-1ß and CCL2 remained elevated. Concentrations of anti-inflammatory IL-10 and TGF-ß1 were maintained after HCA, with a significant increase in TGF-ß1 at 24 hours. CONCLUSIONS: These cytokines represent potential diagnostic markers for ischemic neurologic injury that could be used to assess neurologic injury in patients undergoing HCA. The cellular mechanisms underlying this pro-inflammatory, ischemic-induced injury represent potential targets for neuroprotection in the future.

An Analysis of Waitlist Inactivity Among Patients With Ventricular Assist Devices.

BACKGROUND: Ventricular assist devices (VADs) are commonly used mechanical circulatory support for bridge to transplant therapy in end-stage heart failure; however, it is not understood how VADs influence incidence of waitlist inactive status. We sought to characterize and compare waitlist inactivity among patients with and without VADs. METHODS: Using the Organ Procurement and Transplantation Network database, we investigated the VAD's impact on incidence and length of inactive periods for heart transplant candidates from 2005 through 2018. We compared median length of inactivity between patients with and without VADs and investigated inactivity risk with time-to-event regression models. RESULTS: Among 46,441 heart transplant candidates, 32% (n = 14,636) had a VAD. Thirty-eight percent (n = 17,873) of all patients experienced inactivity, of which 42% (7538/17,873) had a VAD. Median inactivity length was 31 d for patients without VADs and 62 d for VAD patients (P < 0.0005). Multivariable analysis showed no significant difference in risk of inactivity for deteriorating conditions between patients with and without VADs after controlling for demographic and baseline clinical variables. A larger proportion of patients without VADs were inactive for deteriorating conditions than VAD patients (54%, n = 8242/15,221 versus 32%, n = 3583/11,086, P < 0.001). Ten percent (1155/11,086) of VAD patients' inactive periods were for VAD-related complications. CONCLUSIONS: Although VAD patients were inactive longer and had an overall increased risk of any-cause inactivity, their risk of inactivity for deteriorating condition was not significantly different from patients without VADs. Furthermore, VAD patients had a smaller proportion of inactivity periods due to deteriorating conditions. Thus, VADs are protective from morbidity for waitlist patients.

NMDA Receptor Antagonism for Neuroprotection in a Canine Model of Hypothermic Circulatory Arrest.

BACKGROUND: Hypothermic circulatory arrest (HCA) is associated with neurologic morbidity, in part mediated by activation of the N-methyl-D-aspartate glutamate receptor causing excitotoxicity and neuronal apoptosis. Using a canine model, we hypothesized that the N-methyl-D-aspartate receptor antagonist MK801 would provide neuroprotection and that MK801 conjugation to dendrimer nanoparticles would improve efficacy. MATERIALS AND METHODS: Male hound dogs were placed on cardiopulmonary bypass, cooled to 18°C, and underwent 90 min of HCA. Dendrimer conjugates (d-MK801) were prepared by covalently linking dendrimer surface OH groups to MK801. Six experimental groups received either saline (control), medium- (0.15 mg/kg) or high-dose (1.56 mg/kg) MK801, or low- (0.05 mg/kg), medium-, or high-dose d-MK801. At 24, 48, and 72 h after HCA, animals were scored by a standardized neurobehavioral paradigm (higher scores indicate increasing deficits). Cerebrospinal fluid was obtained at baseline, eight, 24, 48, and 72 h after HCA. At 72 h, brains were examined for histopathologic injury in a blinded manner (higher scores indicate more injury). RESULTS: Neurobehavioral deficit scores were reduced by low-dose d-MK801 on postoperative day two (P < 0.05) and by medium-dose d-MK801 on postoperative day 3 (P = 0.05) compared with saline controls, but free drug had no effect. In contrast, high-dose free MK801 significantly improved histopathology scores compared with saline (P < 0.05) and altered biomarkers of injury in cerebrospinal fluid, with a significant reduction in phosphorylated neurofilament-H for high-dose MK801 versus saline (P < 0.05). CONCLUSIONS: Treatment with MK-801 demonstrated significant improvement in neurobehavioral and histopathology scores after HCA, although not consistently across doses and conjugates.

Acute Brain Injury in Postcardiotomy Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVE: Acute brain injury (ABI) is common in venoarterial extracorporeal membrane oxygenation (VA-ECMO). One of the most common indications for use of VA-ECMO is postcardiotomy shock (PCS). The authors aimed to characterize the prevalence of ABI and its association with outcomes in this population. DESIGN: prospective observational. SETTING: Single-center tertiary care university hospital. PARTICIPANTS: Fifty-two consecutive patients treated for PCS with VA-ECMO from November 2017 to March 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median age of patients was 64 (interquartile range 44-84), 62% were male. Of 52 PCS patients treated with extracorporeal membrane oxygenation, 38% (n = 20) experienced acute brain injury. Ischemic stroke was the most common (n = 13, 25%). Patients with central versus peripheral cannulation experienced more ischemic and hemorrhagic strokes (8% v 38%, p = 0.04). Patients with intracardiac thrombus experienced more brain injury (n = 4, 8% p = 0.02). The in-hospital mortality in patients with brain injury was 90% (n = 18/20) compared to 78% (n = 25/32) in patients without brain injury. CONCLUSIONS: ABI is common in postcardiotomy VA-ECMO and associated with worse outcome. Patients with central recanalization experienced the majority of acute strokes. Intracardiac thrombus was significantly associated with acute brain injury.