Showing papers in "Asaio Journal in 2019"

Simultaneous Venoarterial Extracorporeal Membrane Oxygenation and Percutaneous Left Ventricular Decompression Therapy with Impella Is Associated with Improved Outcomes in Refractory Cardiogenic Shock.

Abstract: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been used for refractory cardiogenic shock; however, it is associated with increased left ventricular afterload. Outcomes associated with the combination of a percutaneous left ventricular assist device (Impella) and VA-ECMO remains largely unknown. We retrospectively reviewed patients treated for refractory cardiogenic shock with VA-ECMO (2014-2016). The primary outcome was all-cause mortality within 30 days of VA-ECMO implantation. Secondary outcomes included duration of support, stroke, major bleeding, hemolysis, inotropic score, and cardiac recovery. Outcomes were compared between the VA-ECMO cohort and VA-ECMO + Impella (ECPELLA cohort). Sixty-six patients were identified: 36 VA-ECMO and 30 ECPELLA. Fifty-eight percent of VA-ECMO patients (n = 21) had surgical venting, as compared to 100% of the ECPELLA cohort (n = 30) which had Impella (±surgical vent). Both cohorts demonstrated relatively similar baseline characteristics except for higher incidence of ST-elevation myocardial infarction (STEMI) and percutaneous coronary intervention (PCI) in the ECPELLA cohort. Thirty-day all-cause mortality was significantly lower in the ECPELLA cohort (57% vs. 78%; hazard ratio [HR] 0.51 [0.28-0.94], log rank p = 0.02), and this difference remained intact after correcting for STEMI and PCI. No difference between secondary outcomes was observed, except for the inotrope score which was greater in VA-ECMO group by day 2 (11 vs. 0; p = 0.001). In the largest US-based retrospective study, the addition of Impella to VA-ECMO for patients with refractory cardiogenic shock was associated with lower all-cause 30 day mortality, lower inotrope use, and comparable safety profiles as compared with VA-ECMO alone.

Left Ventricular Unloading During Veno-Arterial ECMO: A Simulation Study.

Abstract: Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is widely used in cardiogenic shock. It provides systemic perfusion, but left ventricular (LV) unloading is suboptimal. Using a closed-loop, real-time computer model of the human cardiovascular system, cardiogenic shock supported by peripheral VA ECMO was simulated, and effects of various adjunct LV unloading interventions were quantified. After VA ECMO initiation (4 L/min) in cardiogenic shock (baseline), hemodynamics improved (increased to 85 mm Hg), while LV overload occurred (10% increase in end-diastolic volume [EDV], and 5 mm Hg increase in pulmonary capillary wedge pressure [PCWP]). Decreasing afterload (65 mm Hg mean arterial pressure) and circulating volume (-800 mL) reduced LV overload (12% decrease in EDV and 37% decrease in PCWP) compared with baseline. Additional intra-aortic balloon pumping only marginally decreased cardiac loading. Instead, adjunct Impella™ enhanced LV unloading (23% decrease in EDV and 41% decrease in PCWP). Alternative interventions, for example, left atrial/ventricular venting, yielded substantial unloading. We conclude that real-time simulations may provide quantitative clinical measures of LV overload, depending on the degree of VA ECMO support and adjunct management. Simulations offer insights into individualized LV unloading interventions in cardiogenic shock supported by VA ECMO as a proof of concept for potential future applications in clinical decision support, which may help to improve individualized patient management in complex cardiovascular disease.

EC-VAD: Combined Use of Extracorporeal Membrane Oxygenation and Percutaneous Microaxial Pump Left Ventricular Assist Device.

Abstract: Combination of venoarterial extracorporeal membrane oxygenation (VA-ECMO) and a percutaneous microaxial left ventricular assist device (pLVAD), or "EC-VAD," has been reported in cases of left ventricular decompression with mixed results. We conducted a retrospective review of patients who received EC-VAD (n = 29) or isolated VA-ECMO therapy (ECMO-only; n = 196) for refractory cardiogenic shock between February 2011 and October 2014. Fourteen patients received VA-ECMO and then Impella pLVAD (E→EC-VAD), and 15 received the Impella pump then VA-ECMO (I→EC-VAD). E→EC-VAD patients demonstrated decreased pulmonary artery systolic (36.00 ± 16.84 mm Hg versus 30.63 ± 12.13 mm Hg; p = 0.049) and diastolic (24.25 ± 13.45 mm Hg versus 17.25 ± 7.96 mm Hg, p = 0.049) pressures by 24 hours post-EC-VAD implant. In the same period, I→EC-VAD patients demonstrated improved SvO2 (43.14 ± 16.75% versus 75.18 ± 13.88%, p = 0.043) and PaO2/FiO2 ratio (148.55 ± 67.69 mm Hg versus 374.51 ± 170.97 mm Hg, p = 0.043). Thirty-day survival rates were 42.9% in E→EC-VAD, 46.7% in I→EC-VAD, and 49.0% in ECMO-only (p = 0.913). Hemolysis occurred more in EC-VAD patients (44.83% versus 17.35% in ECMO-only, p = 0.002); however, there was no increased frequency of other adverse events including bleeding and lower limb ischemia. Despite increased hemolysis, combined use of VA-ECMO and pLVAD may improve or circumvent left ventricular distension in refractory cardiogenic shock while promoting adequate blood flow.

What Causes LVAD-Associated Ischemic Stroke? Surgery, Pump Thrombosis, Antithrombotics, and Infection

Abstract: Acute ischemic stroke (AIS) is a major complication in left ventricular assist device (LVAD) population. A better understanding of clinical risk factors associated with AIS may help mitigate risk of stroke. We reviewed prospectively collected data of 477 LVAD patients from a tertiary center from October 1, 2004 to December 31, 2016. Supplemental data abstraction was performed on patients with AIS. Fifty-seven (12%) developed 61 AIS. Of 61, 17 (28%) AIS occurred perioperatively. The median time from implant to perioperative AIS was 5 days (interquartile range: 3-9). Pump thrombosis accounted for 19 (31%) of 61 AIS, and 7 (37%) presented initially with AIS before the pump thrombosis. The median lactate dehydrogenase (LDH) at the time of AIS in the pump thrombosis group (806) was higher than LDH at 1 month (437, P = 0.27) at 3 months (334, P = 0.01), and 6 months (286, P = 0.001) before AIS. Thirty-three (54%) AIS occurred while receiving inadequate antithrombotic therapy. Acute infections were common (31, 51%) in AIS and 12 (20%) were associated with acute bloodstream infection. All AIS were explained by a combination of four clinical risk factors. All LVAD-associated AIS occurred perioperatively or in conjunction with pump thrombosis, subtherapeutic anticoagulation, and bloodstream infection. The common underlying thread is occurrence of a prothrombotic state. The results of this study underscore the potential consequences of disruption of delicate hemostatic balance in patients with LVAD.

Large Dual-Lumen Extracorporeal Membrane Oxygenation Cannulas Are Associated with More Intracranial Hemorrhage.

Abstract: Large dual-lumen veno-venous (VV) extracorporeal membrane oxygenation (ECMO) cannulas may increase venous pressure in the brain, contributing to intracranial hemorrhage (ICH). A retrospective cohort study was performed using the extracorporeal life support organization (ELSO) registry. Propensity score matching was used to control for confounding. The rate of ICH and rates of hemolysis, cannula complications, and mortality were compared between patients with a 27 French dual-lumen cannula and patients with a 31 French dual-lumen cannula. Seven hundred forty-four patients were included in the propensity score-matched cohort. Patients were well matched except there was some residual imbalance in body weight and sex. Patients with a 31 French cannula had an ICH rate of 4.3% compared with 1.6% in patients with a 27 French cannula (p = 0.03). There were no differences in hemolysis, cannula complications, or mortality between groups. After controlling for body weight and sex in the matched cohort, ICH odds remained higher in patients with a 31 French cannula; odds ratio = 2.74, (95% CI = 1.06-7.09, p = 0.03). Our study data suggest that large dual-lumen VV ECMO cannulas are associated with more ICH, and thus, smaller cannulas may be preferable when feasible.

Impact of Cannula Size on Clinical Outcomes in Peripheral Venoarterial Extracorporeal Membrane Oxygenation.

Abstract: Venoarterial extracorporeal membrane oxygenation (VA ECMO) is an effective mechanical circulatory support for cardiopulmonary failure. Conventionally, an arterial cannula over 15 Fr is inserted for full circulatory support in peripheral VA ECMO. However, limited data are available regarding the impa

Highlights from the Extracorporeal Life Support Organization Registry: 2006-2017.

Abstract: Extracorporeal membrane oxygenation (ECMO) is a supportive therapy for patients with severe cardiovascular or respiratory failure refractory to conventional medical therapy. Improvements in ECMO technology, easy access to ECMO devices, and a greater understanding of care of ECMO patients have led to increased utilization of ECMO. The Extracorporeal Life Support Organization (ELSO) registry was established in 1984, to collect data on patients receiving ECMO support to help improve outcomes of these patients. The registry has grown to include over 400 contributing centers from 60 countries with data for more than 90,000 patients. Many investigators have used the ELSO registry to answer clinical questions on outcomes and care of this vulnerable patient population. This report provides a brief summary of 16 peer-reviewed articles that have advanced the knowledge and treatment of neonates, children, and adults supported with ECMO using data from the ELSO registry.

Assessing Computational Model Credibility Using a Risk-Based Framework: Application to Hemolysis in Centrifugal Blood Pumps

Abstract: Medical device manufacturers using computational modeling to support their device designs have traditionally been guided by internally developed modeling best practices. A lack of consensus on the evidentiary bar for model validation has hindered broader acceptance, particularly in regulatory areas. This has motivated the US Food and Drug Administration and the American Society of Mechanical Engineers (ASME), in partnership with medical device companies and software providers, to develop a structured approach for establishing the credibility of computational models for a specific use. Charged with this mission, the ASME VV the main tenet of the framework is that the credibility requirements of a computational model should be commensurate with the risk associated with model use. This article provides an overview of the ASME V&V 40 standard and an example of the framework applied to a generic centrifugal blood pump, emphasizing how experimental evidence from in vitro testing can support computational modeling for device evaluation. Two different contexts of use for the same model are presented, which illustrate how model risk impacts the requirements on the V&V activities and outcomes.

Cannula-Related Infection in Patients Supported by Peripheral ECMO: Clinical and Microbiological Characteristics.

Abstract: Little is known about cannula-related infection (CRI) in patients supported by extracorporeal membrane oxygenation (ECMO). The aim of this study was to assess the incidence, the risk factors, prognosis, and microbiological characteristics of CRI in patients supported by ECMO. This retrospective cohort study was conducted in one intensive care unit (ICU). Among 220 consecutive patients with peripheral ECMO, 39 (17.7%) developed CRI. The incidence of CRI was 17.2 per 1,000 ECMO days. The main isolated microorganisms were Enterobacteriaceae (38%), Staphylococcus spp. (28.2%; 8.5% were methicillin-sensitive Staphylococcus aureus and 19.7% were coagulase-negative staphylococci), and Pseudomonas aeruginosa (18.3%). Bacteremia was present in 23 cases (59.7%). In multivariate analysis, the risk factors for CRI were longer ECMO duration (p = 0.006) and higher Simplified Acute Physiology Score 2 (p = 0.004). Forty-one percentage of patients with CRI needed surgical management of the infected site. Cannula-related infection was not associated with higher in-hospital mortality (p = 0.73), but it was associated with a longer stay in ICU (p < 0.0001) and a longer stay in hospital (p = 0.002). In conclusion, CRI is frequent in patients with ECMO and associated with a longer stay in hospital. Risk factors for CRI were longer ECMO duration and higher Simplified Acute Physiology Score 2. Concomitant bacteremia was frequent (59.7%) and CRI should be strongly investigated in cases of positive blood culture.

Trends in Extracorporeal Membrane Oxygenation Growth in the United States, 2011-2014.

Abstract: The use of extracorporeal membrane oxygenation (ECMO) has grown rapidly in recent years. We sought to describe the rate of ECMO use in the United States, regional variation in ECMO use, the hospitals performing ECMO, and the primary payers for ECMO patients. Detailed data were obtained using the Healthcare Cost and Utilization Project (HCUPnet) summaries of State Inpatient Databases from 34 participating states for the years 2011-2014. The ECMO rates over time were modeled, overall and within subcategories of age group, bed size, hospital ownership, teaching status, and payer type. During the study period, the overall rate of ECMO use increased from 1.06 (1.01, 1.12) to 1.77 (1.72, 1.82) cases per 100,000 persons per year (p = 0.005). The rate of ECMO use varied significantly by region. Most ECMO patients are cared for at large hospitals, and at private, not-for-profit hospitals with teaching designation. The most common payer was private insurance; a minority of patient were uninsured. The use of ECMO increased significantly during the study period, but regional variation in the rate of ECMO use suggests that this technology is not being uniformly applied. Further research is warranted to determine why differences in ECMO use persist and what impact they have on patient outcomes.

Left Ventricular Distension in Veno-arterial Extracorporeal Membrane Oxygenation: From Mechanics to Therapies.

Abstract: Veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) is increasingly commonly used to treat acute cardiac or pulmonary failure because of a wide range of etiologies. However, despite progressively improving outcomes, the mortality associated with V-A ECMO, particularly when used to treat cardiac failure (its most common indication), continues to be high. Consistent with this, V-A ECMO is associated with numerous morbid complications. Left ventricular (LV) distension is a major complication of V-A ECMO, and is challenging both to treat and diagnose. The author review the pathophysiology underlying LV distension, and construct a systematic diagnostic and therapeutic approach.

What Is the Optimal Blood Pressure on Veno-Arterial Extracorporeal Membrane Oxygenation? Impact of Mean Arterial Pressure on Survival.

Abstract: Blood pressure management is crucial for patients on veno-arterial extracorporeal membrane oxygenation (VA ECMO). Lower pressure can lead to end-organ malperfusion, whereas higher pressure may compete with ECMO flow and cardiac output. The impact of mean arterial pressure (MAP) on outcomes of patients on VA ECMO was evaluated. Patients who were supported on VA ECMO from September 2010 to March 2016 were retrospectively analyzed for average MAP throughout their course on ECMO, excluding the first and last day. Survival and complications observed during ECMO were investigated by classifying patients into groups based on their average MAP. A total of 116 patients were identified. Average MAP was significantly higher in patients who survived to discharge (82 ± 5.6 vs. 78 ± 5.5 mm Hg, p = 0.0003). There was a positive association between MAP and survival. Survival was best with MAP higher than 90 mm Hg (71%) and worst with MAP less than 70 mm Hg, where no patient survived. MAP was an independent predictor of survival to discharge by multivariate analysis (odds ratio 1.17, p = 0.013). Vasopressors were used more frequently in patients with lower pressure (coefficient -3.14, p = 0.005) without affecting survival (odds ratio 0.95, p = 0.95). Although the MAP did not affect the probability of strokes or bleeding complications, patients with a higher MAP had a lower incidence of kidney injury (p = 0.007). In conclusion, survival of patients on VA ECMO was significantly greater with a higher MAP, without being affected by prolonged vasopressor use.

Medical Therapy As Compared To Surgical Device Exchange for Left Ventricular Assist Device Thrombosis: A Systematic Review and Meta-Analysis.

Abstract: Pump thrombosis is a major adverse event in patients supported on continuous-flow left ventricular assist devices (CF-LVAD). The aim of this systematic review and meta-analysis was to determine the outcomes of various treatment approaches for pump thrombosis, including surgical as compared to medical therapy. Electronic search was performed to identify all studies in the English literature addressing surgical and medical management of pump thrombosis in the modern CF-LVAD era. All identified articles were systematically assessed for inclusion and exclusion criteria. In the meta-analysis, because of significant overlap of the data, reports based on trials, registries, and individual cohort studies were analyzed separately. Forty-three studies were included in the analysis (2 trials, 4 registry reports, and 37 individual cohort studies). 2,281/28,728 (10.6%) patients developed pump thrombosis, of which 44.4% and 55.1% were supported on the HeartWare and HeartMate II, respectively. To avoid overlap in studies and to seek more granular data, pooled individual cohort studies were found to be representative of the entire population, and further in-depth analysis of this category was performed. Of the 610/5,545 (11.8%) patients with pump thrombosis in these individual cohort studies, 225 patients had surgical pump exchange, and 186 were treated medically. Surgical therapy resulted in higher success as compared to medical therapy (81.3% vs. 45.4%; p < 0.001), lower 30 day mortality rate (16.7% vs. 34.5%; p = 0.013) and recurrence rate (11.8% vs. 38.3%; p < 0.001). Meta-regression of all studies demonstrates a possible temporal increase of pump thrombosis rate (p = 0.040). Surgical pump exchange is superior to medical therapy with a higher success rate of pump thrombosis resolution, lower mortality rate, and lower recurrence rate. Randomized controlled prospective studies are needed to compare these clinical approaches and their resultant outcomes to guide decision-making for the management of CF-LVAD thrombosis.

The Impact of Infection and Elevated INR in LVAD-Associated Intracranial Hemorrhage: A Case-Crossover Study.

Abstract: Despite the common occurrence left ventricular assist device (LVAD)–associated intracranial hemorrhage, the etiology of intracranial hemorrhage is uncertain. We aim to explore the impact of infection and international normalized ratio (INR) on intracranial hemorrhage in a case-crossover study. We re

Improving Outcomes in INTERMACS Category 1 Patients with Pre-LVAD, Awake Venous-Arterial Extracorporeal Membrane Oxygenation Support.

Abstract: Effective strategies to optimize Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS 1) patients are in much need. A novel awake venous-arterial extracorporeal membrane oxygenation (aVA ECMO) allows for clinical assessments while temporarily supporting biventricular function and stabilizing end-organ functions. The aim of the study was to assess outcomes of patients with aVA ECMO support before durable left ventricular assist device (LVAD) implantation. We evaluated 83 patients who received durable LVAD in 2012-2015, of whom 19 received aVA ECMO support before durable LVAD. Kaplan-Meier and Cox proportional hazards analyses were conducted to assess post-LVAD survival. No complications were observed during the mean aVA ECMO support of 2.7 days. Unadjusted survival of aVA ECMO-supported patients and non-aVA ECMO INTERMACS 1 patients at 1 year were 84.2% and 66.7%, respectively (p = 0.15). Survival of aVA ECMO patients was comparable with that of non-aVA ECMO INTERMACS 2 cohort (84.2% vs. 80.8%) at 1 year. Multivariate analysis demonstrated a significant reduction in the risk of death in aVA ECMO group compared with INTERMACS 1 non-aVA ECMO group (hazard ratio [HR]: 0.17; p = 0.035). Awake venous-arterial (VA) ECMO allows bridge to next therapy and improves outcomes in INTERMACS category 1 patients with an effect comparable with downgrading the disease severity on the INTERMACS scale.

Small Left Ventricular Size Is an Independent Risk Factor for Ventricular Assist Device Thrombosis.

Abstract: The prevalence of ventricular assist device (VAD) therapy has continued to increase due to a stagnant donor supply and growing advanced heart failure (HF) population. We hypothesize that left ventricular (LV) size strongly influences biocompatibility and risk of thrombosis. Unsteady computational fluid dynamics (CFD) was used in conjunction with patient-derived computational modeling and virtual surgery with a standard, apically implanted inflow cannula. A dual-focus approach of evaluating thrombogenicity was employed: platelet-based metrics to characterize the platelet environment and flow-based metrics to investigate hemodynamics. Left ventricular end-diastolic dimensions (LVEDds) ranging from 4.5 to 6.5 cm were studied and ranked according to relative thrombogenic potential. Over 150,000 platelets were individually tracked in each LV model over 15 cardiac cycles. As LV size decreased, platelets experienced markedly increased shear stress histories (SHs), whereas platelet residence time (RT) in the LV increased with size. The complex interplay between increased SH and longer RT has profound implications on thrombogenicity, with a significantly higher proportion of platelets in small LVs having long RT times and being subjected to high SH, contributing to thrombus formation. Our data suggest that small LV size, rather than decreased VAD speed, is the primary pathologic mechanism responsible for the increased incidence of thrombosis observed in VAD patients with small LVs.

Association of Inflow Cannula Position with Left Ventricular Unloading and Clinical Outcomes in Patients with HeartMate II Left Ventricular Assist Device.

Abstract: The relationship between the HeartMate II left ventricular assist device (LVAD) position and pump thrombosis has been reported. However, further clinical implications of device position are unknown. This study aimed to investigate optimal device position for better left ventricular (LV) unloading and patient prognosis. Patients undergoing a ramp test with right heart catheterization after HeartMate II LVAD implantation were enrolled to this study. Device position was quantified from the chest X-ray obtained at the time of the ramp test: (1) inflow cannula angle relative to horizontal line, (2) pump angle relative to spine, (3) pump depth, (4) angle between inflow cannula and pump, and (5) angle between pump and outflow graft. LV unloading was assessed by pulmonary capillary wedge pressure at set LVAD speed. Fifty-four patients (60 years old and 34 male [63%]) were enrolled. Nobody experienced device malfunction during the study period. Increased LV unloading (i.e., lower pulmonary capillary wedge pressure) was associated with a narrower inflow cannula angle relative to horizontal line. Inflow cannula angle <75° was associated with higher 1 year heart failure readmission-free survival rate (p < 0.05, hazards ratio 7.56 [95% confidence interval 2.32-24.7]). In conclusion, HeartMate II LVAD inflow cannula position was associated with LV unloading and patient prognosis. Prospective studies to ensure optimal device positioning and target better clinical outcomes are warranted.

Left Ventricular Assist Device Outflow Graft Obstruction: A Complication Specific to Polytetrafluoroethylene Covering. A Word of Caution!

Abstract: Pump thrombosis is an established complication of left ventricular assist devices (LVADs). Outflow graft obstruction has been previously described as one cause of LVAD thrombosis. We identified four cases of outflow graft obstruction that were attributed to a commonly applied polytetrafluoroethylene (PTFE) covering of the outflow graft. In this set of patients, the outflow graft was obstructed by a thrombus which formed between the outflow graft and its external PTFE covering, leading to impingement of the outflow graft. Patients typically presented after a median duration of 26 months (range 23-41 months) of support with gradual increase of heart failure symptoms and low pump flows. Computed tomography angiography was found to be the best diagnostic modality. Treatments included surgical LVAD replacement as well as percutaneous intraluminal stenting of the outflow graft. Our findings indicate that PTFE graft covering of the LVAD outflow graft can lead to graft occlusion and should be reconsidered as a potentially harmful modification to the approved device implant technique.

Bivalirudin Dosing Requirements in Adult Patients on Extracorporeal Life Support With or Without Continuous Renal Replacement Therapy.

Abstract: Systemic anticoagulation with unfractionated heparin is standard of care for patients receiving extracorporeal life support (ECLS); however, an alternative anticoagulant may be necessary when challenges with heparin therapy arise. Evidence for alternative anticoagulation in ECLS patients is limited. This retrospective analysis evaluated the dosing and outcomes associated with bivalirudin use in 14 adult ECLS patients. Indications for bivalirudin included heparin-induced thrombocytopenia, heparin resistance, or persistent clotting or bleeding while on heparin. The median initial bivalirudin dose to achieve target activated partial thromboplastin time was 0.15 mg/kg/h (range 0.04-0.26 mg/kg/h). Dosing requirements increased by 75-125% when renal replacement was included. Median time on bivalirudin was 5.2 days (range 0.9-28 days). Five patients (36%) required a circuit change while on bivalirudin because of clotting or failing oxygenation, and four (28.6%) had bleeding significant enough to require either reduction in activated partial thromboplastin time goals or temporary holding of anticoagulation. Bivalirudin appears to be a potential option for adult patients on ECLS who are unable to receive or fail heparin therapy; however, the wide variation in dosing suggests the need for careful management.

Impact of Anticoagulation and Circuit Technology on Complications During Extracorporeal Membrane Oxygenation

Abstract: The objective of this study is to evaluate the impact a change in anticoagulation protocol and circuit technology had on bleeding and thrombotic complications in patients supported on extracorporeal membrane oxygenation (ECMO). A retrospective review at a tertiary, academic pediatric intensive care unit was undertaken. The anticoagulation protocol changed from targeting an activated clotting time (ACT) to anti-Xa level. Significant changes in the ECMO circuit were undertaken concurrently. One-hundred and fifty-two ECMO runs in 129 patients in the ACT target group were compared with 122 ECMO runs in 101 patients in the anti-Xa target group. Improved probability of survival by ECMO duration, decreased rate of surgical exploration, increased time to first surgical exploration, decreased incidence of intracranial hemorrhage, increased time to identification of intracranial hemorrhage, decreased blood loss and transfused product volumes, decreased rate of circuit changes, and increased time to first circuit change were all observed in the anti-Xa targeted group. Heparin dosing was similar in both groups with fewer bolus doses of heparin and fewer changes in the infusion rate in the anti-Xa targeted group. The change in anticoagulation protocol and circuit technology was associated with an improvement in survival, a decrease in hemorrhagic complications, and a decrease in circuit changes.

Clinical Outcomes of Impella Microaxial Devices Used to Salvage Cardiogenic Shock as a Bridge to Durable Circulatory Support or Cardiac Transplantation.

Abstract: Temporary mechanical circulatory support (MCS) can be a bridge to decision for patients in severe cardiogenic shock who may be eligible for durable support or transplantation. Outcomes with Impella microaxial devices for salvage of severe shock in the end-stage heart failure population are not well described. Patients who underwent Impella placement as a bridge to decision, durable MCS, or transplantation were included. Eighty Impella devices (2.5 [1.3%], CP [53.8%], and 5.0 [45.0%]) were placed in 64 patients. Implant age was 56.2 ± 12.5 years. Mean duration of assisted support was 13.2 ± 15.1 days, and median duration per device was 7 days (interquartile range: 3-14). A total of 48.4% were in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS 1) shock at implant, 51.6% in profile 2. Recent cardiopulmonary resuscitation (CPR) (26.7%), ventilator use (67.2%), and extracorporeal membrane oxygenation (ECMO) use (26.7%) were frequent. Forty four of sixty four (68.8%) survived to next therapy: durable MCS (40.9%), heart transplant (OHT) (36.4%), and recovery (22.7%). Overall 30 and 60 day survival were 67.2% and 65.6%, respectively. Thirty and 60 day survival conditional on having survived to next therapy were 94.1% and 91.2%, respectively. Survivors were less likely to be on ventilators (p = 0.049) or continuous renal replacement therapy (p < 0.001) but were otherwise not different from nonsurvivors by age, sex, INTERMACS profile, CPR, prevalence of ischemic cardiomyopathy, among other characteristics. Sixteen patients were directly bridged to heart transplantation, and all were alive at long-term follow-up. Impella devices can be used to salvage patients in severe heart failure as a bridge to decision, durable MCS, or transplantation. Baseline demographics are not predictive of survival. Their use for this indication is increasing and further investigations are warranted.

Improving Outcomes in Bridge-to-Transplant: Extended Extracorporeal Membrane Oxygenation Support to Obtain Optimal Donor Lungs for Marginal Recipients.

Abstract: The use of extracorporeal membrane oxygenation (ECMO) as bridge-to-lung transplantation has been discussed controversially because of discouraging results. We report our experience with this challenging strategy. This retrospective investigation includes all consecutive lung transplantations in our center between January 2012 and July 2017 (n = 88, median Lung Allocation Score 66). Data of patients on ECMO bridge-to-transplant (n = 34) were compared with patients without such support (n = 54). Patients requiring ECMO support underwent lung transplantation after median bridging time of 29 days (range, 0-129 days). Survival was superior if transplantation was performed within 29 days of ECMO (p = 0.04). Donor age and oxygenation (pO2/FiO2) were similar in recipients with ECMO (42.3 ± 15.2 years, 444.5 ± 68.9 mm·Hg) or without ECMO (43.1 ± 13.9 years, 454.5 ± 73.4 mm·Hg). Four patients required postoperative ECMO support >1 day. Survival at 1 year and 3 years was similar in recipients with ECMO support (79%, 63%) or without ECMO support (86%, 71%). Successful lung transplantation after ECMO as bridge-to-transplant can be achieved, even in patients with prolonged support times. Bridging time of less than 30 days, however, is crucial for success. Extracorporeal membrane oxygenation expertise and donor organ quality may be important factors for favorable outcome.

Survival and Functional Status after Bridge-to-Transplant with a Left Ventricular Assist Device

Abstract: The use left ventricular assist devices (LVAD) as a bridge-to-transplant (BTT) has become a common modality to treat end-stage heart failure. We sought to examine the impact of BTT on long-term survival and quality of life after heart transplant. The population was all adult patients undergoing isolated heart transplantation in the United States between 2007 and 2017. Inclusion criteria covered BTT patients with a LVAD (only Heartmate II [HMII] or HeartWare Ventricular Assist System [HVAD]) and compared these with patients undergoing de novo heart transplantation. Our primary end-point was survival at 1, 2, and 5 years. Secondary end-points were functional status, return to work, and rates of hospital readmission and graft rejection. Unconditional and conditional survival was estimated with the Kaplan-Meier method. The independent influence of BTT on risk-adjusted mortality was determined using Cox proportional hazards models. In this period, 5,584 patients were bridged with an LVAD and 12,295 underwent de novo transplantation. Unconditional survival was 2% higher in de novo patients at 1, 2, and 5 years. After risk adjustment, BTT was associated with increased mortality at each time point. Unadjusted 5 year survival, conditional on 90 day survival, was similar between groups (82.6% vs. 83.4%; p = 0.15). Functional status, return to work, and unadjusted rates of hospital readmission and graft rejection were similar at 1, 2, 5 years. Bridge-to-transplant with LVADs provides excellent survival and similar quality of life to that of patients undergoing de novo heart transplantation. Bridge-to-transplant patients experience a slightly higher mortality rate within 90 days of transplantation.

Antithrombin During Extracorporeal Membrane Oxygenation in Adults: National Survey and Retrospective Analysis.

Abstract: The impact of antithrombin replacement during extracorporeal membrane oxygenation (ECMO) in adults remains unclear. This work comprises a survey, showing that antithrombin is routinely supplemented in many Italian ECMO-Centers, and a retrospective analysis on 66 adults treated with veno-venous ECMO and unfractionated heparin at our Institution. Twenty-four to 72 h after the beginning of ECMO, antithrombin activity was ≤70% in 47/66 subjects and activated partial thromboplastin time (aPTT) ratio was <1.5 in 20/66 subjects. Activated partial thromboplastin time ratio <1.5 was associated not with lower antithrombin activity (61 ± 17 vs. 63 ± 22%; p = 0.983) but with higher circulating level of C-reactive protein (23 ± 8 vs. 11 ± 9 mg/dl; p < 0.001). In 34 subjects who received antithrombin concentrate, antithrombin activity increased (from 54 ± 9 to 84 ± 13%; p < 0.001); the proportion of subjects with aPTT ratio ≥1.5 increased (from 21/34 [62%] to 31/34 [91%]; p = 0.004); heparin dosage remained constant (from 19 ± 7 to 19 ± 6 IU/kg/h; p = 0.543); and C-reactive protein decreased (from 17 ± 10 to 13 ± 9 mg/dl; p = 0.013). Among those with aPTT ratio <1.5, aPTT ratio remained <1.5 in 3 out of 13 subjects. Antithrombin is frequently supplemented during veno-venous ECMO although low antithrombin activity does not constantly impede, and antithrombin replacement does not constantly ensure, reaching the target aPTT ratio. Inflammation possibly affects the individual response to heparin.

Trends in Mortality and Risk Characteristics of Congenital Diaphragmatic Hernia Treated With Extracorporeal Membrane Oxygenation.

Abstract: Although the mortality of infants with congenital diaphragmatic hernia (CDH) has been improving since the late 1990s, this observation has not been paralleled among the CDH cohort receiving extracorporeal membrane oxygenation (ECMO). We sought to elucidate why the mortality rate in the CDH-ECMO population has remained at approximately 50% despite consistent progress in the field by examining the baseline risk profile/characteristics of neonates with CDH before ECMO (pre-ECMO). Neonates with a diagnosis of CDH were identified in the Extracorporeal Life Support Organization (ELSO) Registry from 1992 to 2015. Individual pre-ECMO risk score (RS) for mortality was categorized to pre-ECMO risk-stratified cohorts. Temporal trends based on individual-level mortality by risk cohorts were assessed by logistic regression. We identified 6,696 neonates with CDH. The mortality rates during this time period were approximately 50%. The average baseline pre-ECMO RS increased during this period: mean increase of 0.35 (95% confidence interval [CI]: 0.324-0.380). In the low-risk cohort, the likelihood of mortality increased over time: each 5 year change was associated with a 7.3% increased likelihood of mortality (odds ratio [OR]: 1.0726; 95% CI: 1.0060-1.1437). For the moderate-risk cohort, the likelihood of mortality decreased by 7.05% (OR: 0.9295; 95% CI: 0.8822-0.9793). There was no change in the odds of mortality for the high-risk cohort (OR: 0.9650; 95% CI: 0.8915-1.0446). Although the overall mortality rate remained approximately constant over time, the individual likelihood of death has declined over time in the moderate-risk cohort, increased in the low-risk cohort, and remained unchanged in the high-risk cohort.

Veno-Venous Extracorporeal Membrane Oxygenation for Respiratory Failure: How Long Is Too Long?

Abstract: The use of veno-venous extracorporeal membrane oxygenation (VV ECMO) in adults with respiratory failure has steadily increased during the past decade. Recent literature has demonstrated variable outcomes with the use of extended ECMO. The purpose of this study is to evaluate survival to hospital discharge in patients with extended ECMO runs compared with patients with short ECMO runs at a tertiary care ECMO referral center. We retrospectively reviewed all patients on VV ECMO for respiratory failure between August 2014 and February 2017. Bridge to lung transplant, post-lung transplant, and post-cardiac surgery patients were excluded. Patients were stratified by duration of ECMO: extended ECMO, defined as >504 hours; short ECMO as ≤504 hours. Demographics, pre-ECMO data, ECMO-specific data, and outcomes were analyzed. One hundred and thirty-nine patients with respiratory failure were treated with VV ECMO. Overall survival to discharge was 76%. Thirty-one (22%) patients had extended ECMO runs with an 87% survival to discharge. When compared with patients with short ECMO runs, there was no difference in median age, body mass index (BMI), body surface area (BSA), partial pressure of oxygen (PaO2)/ fraction of inspired oxygen (FiO2) (P/F), and survival to discharge. However, time from intubation to cannulation for ECMO was significantly longer in patients with extended ECMO runs. (p = 0.008). Our data demonstrate that patients with extended ECMO runs have equivalent outcomes to those with short ECMO runs. Although the decision to continue ECMO support in this patient population is multifactorial, we suggest that time on ECMO should not be the sole factor in this challenging decision.

Chronic In Vivo Test of a Right Heart Replacement Blood Pump for Failed Fontan Circulation.

Abstract: An implantable rotary blood pump was developed to provide long-term mechanical right heart support for patients who have failing Fontan circulation. The objective of this study was to evaluate the pump in vivo in a 30 day sheep study. Pump speed was set at 3,900 rpm for the duration of the study, and pump power was between 4.3 and 4.6 W. The pump inlet pressures for the superior vena cava (SVC) and inferior vena cava (IVC) were 14 ± 15 and 11 ± 15 mm Hg, respectively, over the duration of the study. Hematocrit remained stable at 30% ± 4%. Partial thromboplastin time (PTT) steadily increased from 30 s preoperatively to a high of 59 s on postoperative day 20, while prothrombin time (PT) remained at 20 ± 2 s for the duration of the study. The implantation and postoperative recovery were successful, and the animal demonstrated normal physiologic pulmonary and venous pressures and cardiac output. On pump inspection, the IVC and SVC inlets were completely clear of any deposits, but there were small thrombi (approximately 0.5 mm diameter) between each of the three rotor blades and along 20% of the parting line of the two volute halves. A complete right heart bypass was performed, postoperative recovery was successful, and the pump demonstrated adequate circulatory support and normal physiologic pulmonary and venous pressures. This study was the first successful test of a right heart replacement device in a chronic animal study.

Development and Validation of a Life-Sized Mock Circulatory Loop of the Human Circulation for Fluid-Mechanical Studies.

Abstract: Mock circulatory loops (MCLs) are usually developed for assessment of ventricular assist devices and consist of abstracted anatomical structures represented by connecting tubing pipes and controllable actuators which could mimic oscillating flow processes. However, with increasing use of short-term peripheral mechanical support (extracorporeal life support [ECLS]) and the upcoming evidence of even counteracting flow processes between the failing native circulation and ECLS, MCLs incorporating the peripheral vascular system and preserved anatomical structures are becoming more important for systematic assessment of these processes. For reproducible and standardized fluid-mechanical studies using magnetic resonance imaging, Doppler ultrasound, and computational fluid dynamics measurements, we developed a MCL of the human circulation. Silicon-based life-sized dummies of the human aorta and vena cava (vascular module) were driven by paracorporeal pneumatic assist devices. The vascular module is placed in a housing with all arterial branches merging into peripheral resistance and compliances modules, and blood-mimicking fluid returns to the heart module through the venous dummy. Compliance and resistance chambers provide for an adequate simulation of the capillary system. Extracorporeal life support cannulation can be performed in the femoral and subclavian arteries and in the femoral and jugular veins. After adjusting vessel diameters using variable Hoffmann clamps, physiologic flow rates were achieved in the supraaortic branches, the renal and mesenteric arteries, and the limb arteries with physiologic blood pressure and cardiac output (4 L/min). This MCL provides a virtually physiologic platform beyond conventional abstracted MCLs for simulation of flow interactions between the human circulation and external circulation generated by ECLS.

A Versatile Hybrid Mock Circulation for Hydraulic Investigations of Active and Passive Cardiovascular Implants.

Abstract: During the development process of active or passive cardiovascular implants, such as ventricular assist devices or vascular grafts, extensive in-vitro testing is required. The aim of the study was to develop a versatile hybrid mock circulation (HMC) which can support the development of such implants that have a complex interaction with the circulation. The HMC operates based on the hardware-in-the-loop concept with a hydraulic interface of four pressure-controlled reservoirs allowing the interaction of the implant with a numerical model of the cardiovascular system. Three different conditions were investigated to highlight the versatility and the efficacy of the HMC during the development of such implants: 1) biventricular assist device (BiVAD) support with progressive aortic valve insufficiency, 2) total artificial heart (TAH) support with increasing pulmonary vascular resistance, and 3) flow distribution in a total cavopulmonary connection (TCPC) in a Fontan circulation during exercise. Realistic pathophysiologic waveforms were generated with the HMC and all hemodynamic conditions were simulated just by adapting the software. The results of the experiments indicated the potential of physiologic control during BiVAD or TAH support to prevent suction or congestion events, which may occur during constant-speed operation. The TCPC geometry influenced the flow distribution between the right and the left pulmonary artery, which was 10% higher in the latter and led to higher pressures. Together with rapid prototyping methods, the HMC may enhance the design of implants to achieve better hemodynamics. Validation of the models with clinical recordings is suggested for increasing the reliability of the HMC.

Sedative and Analgesic Drug Sequestration After a Single Bolus Injection in an Ex Vivo Extracorporeal Membrane Oxygenation Infant Circuit.

Abstract: Patient sedation and analgesia on extracorporeal membrane oxygenation (ECMO) is vital for safety and comfort. However, adsorption to the circuit may alter drug pharmacokinetics and remains poorly characterized. This study characterizes drug adsorption of morphine, fentanyl, midazolam, and dexmedetomidine in an ex vivo infant ECMO circuit utilizing polymethylpentene (PMP) membrane oxygenator (MO) with protein-bounded polyvinylchloride (PVC) tubing. Twelve closed-loop ex vivo ECMO circuits were prepared using P.h.i.s.i.o (phosphorylcholine)-coated PVC tubing (Sorin Group USA, Inc.) and a Quadrox-iD pediatric polymethylpentene MO (Maquet Cardiopulmonary AG). Once the circuits were primed and running, a single medication was injected as a bolus into the circuit with three circuits per drug. Drug samples were drawn following injection, at 2, 5, 15, 30, 60, 120 minutes and at 4, 12, 24, 36, and 48 hours and analyzed using ultra high-performance liquid chromatography with mass spectrometry. Compared with morphine, the other drugs are highly sequestered with fentanyl 68.5%, dexmedetomidine 50.8%, and midazolam 26.2% affecting the availability of free drug in the circuit. Sequestration of fentanyl, midazolam, and dexmedetomidine in an ECMO circuit with P.h.i.s.i.o-coated PVC tubing and PMP MO may limit drug delivery to infants. Future in vivo studies are needed to determine the clinical impact of sequestration.