Hemocompatibility-related Adverse Events Research Articles

Abstract 4117646: The Ultimate Test in Hemocompatibility: HeartMate3 Restart After Prolonged Pump Shut Down

Introduction: The HeartMate 3 (HM3) LVAD, was shown to have a higher survival free of hemocompatibility related adverse events (HRAE) compared to its predecessors (HM2, HVAD). Superior HM3 outcomes are attributed to wide blood flow pathways coupled with frictionless movement and intrinsic pulsatility, reducing shear stress and blood stasis. It is unknown if improved hemocompatibility can withstand pump restart after prolonged shutdown. We herein report a case of HM3 pump stoppage without subsequent HRAE. Case Presentation: A 41-year-old male underwent HVAD implant in 2019 for advanced non-ischemic cardiomyopathy. This was exchanged to HM3 for recurrent neurological events despite therapeutic anticoagulation. Ten months after exchange, he awakened one morning to find his LVAD had been off for an unknown period but had not heard any device alarms (85dB if on battery power, 165dB if on wall power). Since he felt well he changed to battery power resulting in immediate pump restart. Log file analysis showed pump stoppage 2 am – 10 am, without preceding low flow alarms or power elevations. Management and Outcomes: In the ER INR was 1.5 (2.8 one week prior) and systemic heparin was started. Evaluation included: 1) CT brain without acute infarcts 2) echocardiogram without intracardiac thrombus 3) CT Angiography with patency of the inflow cannula and outflow graft 4) stable serial LDH measurements. The controller was exchanged, and analysis noted normal function. 1-year later the patient is maintained on warfarin and aspirin 325mg without further HRAE. Given the patient’s neurologic history and pump stoppage event, we did not invoke ARIES trial guidance and thus continued aspirin. Conclusion: Pump stoppage occurs when there is complete battery depletion, disconnection of both power leads, or the percutaneous lead from system controller. Our case is unique in that the duration of pump shutdown was 8 hours and INR subtherapeutic, without HRAE in the background of neurologic events on HVAD support. It has been previously reported that complete outflow graft thrombosis can occur shortly after LVAD decommissioning. The HM3 User Manual recommends restarting the pump immediately if off for a few minutes and using clinical judgment for longer durations due to increased risk for thromboembolic events. Our case adds to the paucity of existing data on improved hemocompatibility of the HM3 during rare circumstances of the ultimate test in hemocompatibility: complete pump shut down.

Preoperative anatomical landmarks and longitudinal HeartMate 3 pump position in X-rays: Relevance for adverse events.

Left ventricular assist device (LVAD) malposition has been linked to hemocompatibility-related adverse events (HRAEs). This study aimed to identify preoperative anatomical landmarks and postoperative pump position, associated with HRAEs during LVAD support. Pre- and postoperative chest X-ray measures (≤14 days pre-implantation, first postoperative standing, 6, 12, 18, and 24 months post-implantation) were analyzed for their association with HRAEs over 24 months in 33 HeartMate 3 (HM3) patients (15.2% female, age 66 (9.5) years). HM3 patients with any HRAE showed significantly lower preoperative distances between left ventricle and thoracic outline (dLVT) (25.3 ± 10.2 mm vs. 40.3 ± 15.5 mm, p = 0.004). A ROC-derived cutoff dLVT ≤ 29.2 mm provided 85.7% sensitivity and 72.2% specificity predicting any HRAE during HM3 support (76.2% (>29.2 mm) vs. 16.7% (≤29.2 mm) freedom from HRAE, p < 0.001) and significant differences in cardiothoracic ratio (0.58 ± 0.04 vs. 0.62 ± 0.04, p = 0.045). Postoperative X-rays indicated lower pump depths in patients with ischemic strokes (9.1 ± 16.2 mm vs. 38.0 ± 18.5 mm, p = 0.007), reduced freedom from any neurological event (pump depth ≤ 28.7 mm: 45.5% vs. 94.1%, p = 0.004), and a significant correlation between pump depth and inflow cannula angle (r = 0.66, p < 0.001). Longitudinal changes were observed in heart-pump width (F(4,60) = 5.61, p < 0.001). Preoperative X-ray markers are associated with postoperative HRAE occurrence. Applying this knowledge in clinical practice may enhance risk stratification, guide therapy optimization, and improve HM3 recipient management.

Galectin-3 as a Prognostic Biomarker of Left Ventricular Assist Device Implantation Outcomes.

We assessed the prognostic potential of Galectin-3 in a sample of 159 heart failure patients who received a left ventricular assist device (LVAD) implant from 2012 to 2020. Clinical outcomes included hemodynamic data, right heart failure (RHF), hemocompatibility-related adverse events (HRAEs), and mortality. Galectin-3 was compounded into Michigan-RVF and EUROMACS-RHF risk scores and compared to the noncompounded risk scores. Right heart failure was significantly correlated with Galectin (p = 0.004) on a continuous spectrum. Inotrope duration was significantly correlated to Galectin-3 (interquartile range [IQR]: 7.58-8.65, p < 0.001) along with INTERMACS score (IQR: 2.14-1.90, p < 0.001). Intensive care unit length of stay (median 8 days, p = 0.02), blood urea nitrogen (p < 0.001), creatinine (p < 0.001), and pulmonary artery pulsatility index (p = 0.05) were also significantly correlated with Galectin-3. In our c-statistic analysis, the predictive value for RHF improved when Galectin-3 was included for both the Michigan-RVF (0.80-0.86) and EUROMACS-RHF (0.77-0.82) risk scores. When elevated over a binary cutoff of 18.2 ng/ml, Galectin-3 significantly correlated with HRAEs (p = 0.014) and mortality (p = 0.031). Galectin-3 shows great promise as a predictive biomarker in patients implanted with durable LVADs. In addition to significant correlation with key clinical outcomes, Galectin-3 enhanced the Michigan-RVF and EUROMACS-RHF risk scores in predicting progression to RHF.

Early Postoperative Changes in Von Willebrand Factor Activity Are Associated With Future Bleeding and Stroke in HeartMate 3 Patients.

Hemocompatibility-related adverse events (HRAEs), particularly gastrointestinal bleeding, remain a frequent complication after left ventricular assist device (LVAD) implantation. The current study sought to describe and analyze whether early (<60 days) postoperative von Willebrand factor (VWF) activity assays predict the risk of gastrointestinal bleeding and stroke. A prospective single-center study including 74 HeartMate 3 device recipients between 2016 and 2023 was undertaken. The postoperative trajectory of the VWF profile was analyzed using linear mixed-effect models and Cox models were used to quantify associations between an early postoperative dip (≤0.7) in VWF activity assay measurements and late outcomes. Preoperatively, the mean VWF:Activity (Act)/Antigen (Ag) and VWF:Collagen Binding (CB)/Ag ratios were 0.94 (95% confidence interval [CI] = 0.81-1.02) and 0.95 (95% CI = 0.80-1.03), respectively, decreasing to 0.66 (95% CI = 0.57-0.73) and 0.67 (95% CI = 0.58-0.74) within 40 days (p < 0.05). In patients with VWF:CB/Ag and VWF:Act/Ag ratios ≤0.7 significantly more gastrointestinal bleeding (hazard ratio [HR]: 2.53; 95% CI = 1.1-5.8, and HR: 3.7; 95% CI = 1.5-9.2, respectively) and hemorrhagic stroke events (HR: 3.5; 95% CI = 1.6-7.6 and HR: 4.9; 95% CI = 2.1-11.7, respectively) were observed throughout the entire late (>60 days) postoperative period. In patients with VWF:Act/Ag ratio ≤0.7 less ischemic stroke events were observed (HR: 0.11; 95% CI = 0.01-0.85). In conclusion, VWF:Act/Ag and VWF:CB/Ag ratios ≤0.7 in the early postoperative phase can be used as biomarkers to predict HRAEs during long-term LVAD support.

A case of destination therapy for post-fulminant myocarditis with myelodysplastic syndrome.

We encountered a 64-year-old woman who experienced fulminant myocarditis and underwent treatment with veno-arterial extracorporeal membrane oxygenation and Impella CP support. Subsequently, she underwent a device upgrade to Impella 5.5 and received continuous hemodiafiltration for 3 months. During mechanical circulatory support, she developed refractory anemia and thrombocytopenia, leading to a diagnosis of myelodysplastic syndrome. Following the removal of the devices, she no longer required blood transfusions. She received HeartMate 3 left ventricular assist device implantation as a destination therapy indication despite the presence of myelodysplastic syndrome. She was successfully managed by aspirin-free antithrombotic therapy without any hemocompatibility-related adverse events for 4 months after index discharge on foot. We present a patient with a unique and rare presentation, wherein HeartMate 3 was implanted and successfully managed without aspirin to prevent bleeding complications associated with myelodysplastic syndrome.

Omission of Antiplatelet Therapy in Patients With HeartMate 3 Left Ventricular Assist Devices: A Systematic Review and Meta-Analysis.

The HeartMate 3 (HM3) left ventricular assist device has decreased thromboembolic events and minimized the risk of pump thrombosis. However, bleeding complications due to combined antithrombotic therapy with a vitamin K antagonist (VKA) and aspirin remain high. Only limited data on the safety of VKA monotherapy in HM3 patients are available. A systematic search on the main databases was performed. Observational data and randomized trials were eligible for this analysis. As primary endpoint, we analyzed hemocompatibility-related adverse events (HRAE). As secondary endpoints, we investigated the individual components of the primary endpoint. The analysis was carried out using the odds ratio (OR) as outcome measure. A random-effects model was fitted to the data. Five manuscripts fulfilled the inclusion criteria. These trials included 785 patients (381 on VKA monotherapy, 404 on VKA and aspirin). VKA monotherapy significantly reduced HRAE (OR: 0.11 [95% confidence interval {CI}: 0.02-0.59], p = 0.01, I2 = 87%). The reduction was driven by a decrease in bleeding complications (OR: 0.12 [95% CI: 0.02-0.62], p = 0.01, I2 = 86%) without increasing the rates of thromboembolic events (OR: 0.69 [95% CI: 0.26-1.81], p = 0.45, I = 0%). Vitamin K antagonist monotherapy is associated with a significant reduction of bleeding events without increasing the risk of thromboembolic complications in HM3 patients.

Evaluation of the Hemocompatibility of the Direct Oral Anticoagulant Apixaban in Left Ventricular Assist Devices: The DOAC LVAD Study

BackgroundPatients receiving left ventricular assist device (LVAD) support require long-term anticoagulation to reduce the risk of thromboembolic complications. Apixaban is a direct oral anticoagulant that has become first-line therapy; however, its safety in LVAD recipients has not been well described. ObjectivesThis study sought to investigate whether, in patients with a fully magnetically levitated LVAD, treatment with apixaban would be feasible and comparable with respect to safety and freedom from the primary composite outcome of death or major hemocompatibility-related adverse events (HRAEs) (stroke, device thrombosis, major bleeding, aortic root thrombus, and arterial non–central nervous system thromboembolism) as compared with treatment with warfarin. MethodsThe DOAC LVAD (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices) trial was a phase 2, open label trial of LVAD recipients randomized 1:1 to either apixaban 5 mg twice daily or warfarin therapy. All patients were required to take low-dose aspirin. Patients were followed up for 24 weeks to evaluate the primary composite outcome. ResultsA total of 30 patients were randomized: 14 patients to warfarin and 16 patients to apixaban. The median patient age was 60 years (Q1-Q3: 52-71 years), and 47% were Black patients. The median time from LVAD implantation to randomization was 115 days (Q1-Q3: 56-859 days). At 24 weeks, the primary composite outcome occurred in no patients receiving apixaban and in 2 patients (14%) receiving warfarin (P = 0.12); these 2 patients experienced major bleeding from gastrointestinal sources. ConclusionsAnticoagulation with apixaban was feasible in patients with an LVAD without an excess of HRAEs or deaths. This study informs future pivotal clinical trials evaluating the safety and efficacy of apixaban in LVAD recipients. (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices [DOAC LVAD]; NCT04865978)

Long-term outcomes of a novel fully magnetically levitated ventricular assist device for the treatment of advanced heart failure in China

PurposeLeft ventricular assist devices (LVADs) are well-established for treating end-stage heart failure, but this therapy is only available to Chinese patients in recent years. The CH-VAD is the first used fully magnetically levitated pump and the most widely used device in China. This study reports the long-term outcomes of a cohort supported by the CH-VAD for the first time. MethodsFrom June 2017 to August 2023, 50 consecutive patients received CH-VAD implantation in Fuwai Hospital. Clinical data were collected during follow-up and retrospectively analyzed. ResultsBaseline characteristics included a mean age of 47.9±13.9 years, 90% male, and 26% ischemic etiology. The INTERMACS profile revealed 12% Profile 1, 56% Profile 2, 26% Profile 3 and 6% Profile 4. Mean support duration was 868 ± 630 days (range 33 days-6.4 years). Kaplan-Meier survival rate was 96% (95% confidence interval [CI], 85 to 99) at 6 months, 93% (95% CI, 79-98) at 1 year, 93% (95% CI, 79-98) at 2 years and 89% (95% CI, 71-96) at 3 years. 40 patients (80%) currently remain on support, 3 were bridged to recovery, 2 received transplant, and 5 expired during support. Major adverse events included right heart failure (10%), surgical related bleeding (8%), arrhythmia (8%) and driveline infection (16%). Major hemocompatibility-related adverse events were limited to 3 non-disabling strokes and 1 gastrointestinal bleeding. There was no major device malfunction during the follow-up period. ConclusionsThe largest single-center experience with the leading LVAD in China shows high survival with low complication rates, demonstrating the CH-VAD is safe and efficient in providing long-term support for end-stage heart failure patients.

(576) - Assessment of Platelet Response to Aspirin Therapy and Hemocompatibility-Related Adverse Events in HeartMate 3 Left Ventricular Assist Device Recipients

(576) - Assessment of Platelet Response to Aspirin Therapy and Hemocompatibility-Related Adverse Events in HeartMate 3 Left Ventricular Assist Device Recipients

Computational investigation of outflow graft variation impact on hemocompatibility profile in LVADs.

Hemocompatibility-related adverse events (HRAE) occur commonly in patients with left ventricular assist devices (LVADs) and add to morbidity and mortality. It is unclear whether the outflow graft orientation can impact flow conditions leading to HRAE. This study presents a simulation-based approach using exact patient anatomy from medical images to investigate the influence of outflow cannula orientation in modulating flow conditions leading to HRAEs. A 3D model of a proximal aorta and outflow graft was reconstructed from a computed tomography (CT) scan of an LVAD patient and virtually modified to model multiple cannula orientations (n = 10) by varying polar (cranio-caudal) (n = 5) and off-set (anterior-posterior) (n = 2) angles. Time-dependent computational flow simulations were then performed for each anatomical orientation. Qualitative and quantitative hemodynamics metrics of thrombogenicity including time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), endothelial cell platelet activation potential (ECAP), particle residence time (PRT), and platelet activation potential (PLAP) were analyzed. Within the simulations performed, endothelial cell activation potential (ECAP) and particle residence time (PRT) were found to be lowest with a polar angle of 85°, regardless of offset angle. However, polar angles that produced parameters at levels least associated with thrombosis varied when the offset angle was changed from 0° to 12°. For offset angles of 0° and 12° respectively, flow shear was lowest at 65° and 75°, time averaged wall shear stress (TAWSS) was highest at 85° and 35°, and platelet activation potential (PLAP) was lowest at 65° and 45°. This study suggests that computational fluid dynamic modeling based on patient-specific anatomy can be a powerful analytical tool when identifying optimal positioning of an LVAD. Contrary to previous work, our findings suggest that there may be an "ideal" outflow cannula for each individual patient based on a CFD-based hemocompatibility profile.

Design and Rationale for the Direct Oral Anticoagulant Apixaban in Left Ventricular Assist Devices (DOAC LVAD) Study

Implantable left ventricular assist devices (LVAD) therapy is used to improve quality of life, alleviate symptoms, and extend survival in patients with advanced heart failure (HF). LVAD patients require chronic anticoagulation to reduce the risk of thromboembolic complications and frequently experience bleeding events. Apixaban is a direct oral anticoagulant which has become first-line therapy for patients with non-valvular atrial fibrillation and venous thromboembolism; however, its safety in LVAD patients has not been well-characterized. The evaluation of the hemocompatibility of the Direct Oral Anti-Coagulant apixaban in Left Ventricular Assist Devices (DOAC LVAD) trial is a Phase 2, open label trial of LVAD patients randomized to either apixaban or warfarin therapy. Patients randomized to apixaban will be started on a dose of 5 mg twice daily, while those randomized to warfarin will be managed to an INR goal of 2.0-2.5. All patients will be treated with aspirin 81mg daily. We plan to randomize and follow up to 40 patients for 24 weeks to evaluate the primary outcome of freedom from death or hemocompatibility related adverse events (HRAEs) (stroke, device thrombosis, bleeding, aortic root thrombus, and arterial non-CNS thromboembolism). DOAC LVAD will establish the feasibility of apixaban anticoagulant therapy in LVAD patients.Clinicaltrials.gov: NCT04865978

Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure

Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety. To determine whether excluding aspirin as part of the antithrombotic regimen with a fully magnetically levitated LVAD is safe and decreases bleeding. This international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/d) vs placebo with VKA therapy in patients with advanced heart failure with an LVAD was conducted across 51 centers with expertise in treating patients with advanced heart failure across 9 countries. The randomized population included 628 patients with advanced heart failure implanted with a fully magnetically levitated LVAD (314 in the placebo group and 314 in the aspirin group), of whom 296 patients in the placebo group and 293 in the aspirin group were in the primary analysis population, which informed the primary end point analysis. The study enrolled patients from July 2020 to September 2022; median follow-up was 14 months. Patients were randomized in a 1:1 ratio to receive aspirin (100 mg/d) or placebo in addition to an antithrombotic regimen. The composite primary end point, assessed for noninferiority (-10% margin) of placebo, was survival free of a major nonsurgical (>14 days after implant) hemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. The principal secondary end point was nonsurgical bleeding events. Of the 589 analyzed patients, 77% were men; one-third were Black and 61% were White. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (74%) vs those taking aspirin (68%). Noninferiority of placebo was demonstrated (absolute between-group difference, 6.0% improvement in event-free survival with placebo [lower 1-sided 97.5% CI, -1.6%]; P < .001). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P = .002) with no increase in stroke or other thromboembolic events, a finding consistent among diverse subgroups of patient characteristics. In patients with advanced heart failure treated with a fully magnetically levitated LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes VKA, is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events. ClinicalTrials.gov Identifier: NCT04069156.

The role of innovative modeling and imaging techniques in improving outcomes in patients with LVAD.

Heart failure remains a significant cause of mortality in the United States and around the world. While organ transplantation is acknowledged as the gold standard treatment for end stage heart failure, supply is limited, and many patients are treated with left ventricular assist devices (LVADs). LVADs extend and improve patients' lives, but they are not without their own complications, particularly the hemocompatibility related adverse events (HRAE) including stroke, bleeding and pump thrombosis. Mainstream imaging techniques currently in use to assess appropriate device function and troubleshoot complications, such as echocardiography and cardiac computed tomography, provide some insight but do not provide a holistic understanding of pump induced flow alterations that leads to HRAEs. In contrast, there are technologies restricted to the benchtop-such as computational fluid dynamics and mock circulatory loops paired with methods like particle image velocimetry-that can assess flow metrics but have not been optimized for clinical care. In this review, we outline the potential role and current limitations of converging available technologies to produce novel imaging techniques, and the potential utility in evaluating hemodynamic flow to determine whether LVAD patients may be at higher risk of HRAEs. This addition to diagnostic and monitoring capabilities could improve prevention and treatment of LVAD-induced complications in heart failure patients.

Review of anticoagulation considerations in extracorporeal membrane oxygenation support.

Since its first success in 1975, extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency for pulmonary and cardiopulmonary bypass. Use in adults has increased exponentially since the early 2000s, but despite thousands of international cannulations using both veno-arterial (VA) and veno-venous (VV) ECMO, there are still significant hemocompatibility-related adverse events. Current management of anticoagulation has been based on the Extracorporeal Life Support Organization guidance published in 2014 with recent updates published in 2022. Despite this guidance, there is still limited international consensus on how to manage anticoagulation in ECMO. For this review, we completed a comprehensive search of multiple electronic databases to identify studies pertaining to anticoagulation of adult patients on VV or VA-ECMO. The highest priority was given to sources that were prospective, randomized, controlled studies, but in the absence of such resources, observational studies, retrospective uncontrolled studies, and case series/reports were considered for inclusion. This document serves to provide a comprehensive review of the current understanding of management pertaining to anticoagulation relating to ECMO.

Predictors of 5-Year Mortality in Patients Managed With a Magnetically Levitated Left Ventricular Assist Device

BackgroundIn advanced heart failure patients implanted with a fully magnetically levitated HeartMate 3 (HM3, Abbott) left ventricular assist device (LVAD), it is unknown how preimplant factors and postimplant index hospitalization events influence 5-year mortality in those able to be discharged. ObjectivesThe goal was to identify risk predictors of mortality through 5 years among HM3 LVAD recipients conditional on discharge from index hospitalization in the MOMENTUM 3 pivotal trial. MethodsThis analysis evaluated 485 of 515 (94%) patients discharged after implantation of the HM3 LVAD. Preimplant (baseline), implant surgery, and index hospitalization characteristics were analyzed individually, and as multivariable predictors for mortality risk through 5 years. ResultsCumulative 5-year mortality in the cohort (median age: 62 years, 80% male, 65% White, 61% destination therapy due to transplant ineligibility) was 38%. Two preimplant characteristics (elevated blood urea nitrogen and prior coronary artery bypass graft or valve procedure) and 3 postimplant characteristics (hemocompatibility-related adverse events, ventricular arrhythmias, and estimated glomerular filtration rate <60 mL/min/1.73 m2 at discharge) were predictors of 5-year mortality. In 171 of 485 patients (35.3%) without any risk predictors, 5-year mortality was reduced to 22.6% (95% CI: 15.4%-32.7%). Even among those with 1 or more predictors, mortality was <50% at 5 years (45.7% [95% CI: 39.0%-52.8%]). ConclusionsLong-term survival in successfully discharged HM3 LVAD recipients is largely influenced by clinical events experienced during the index surgical hospitalization in tandem with baseline factors, with mortality of <50% at 5 years. In patients without identified predictors of risk, long-term 5-year mortality is low and rivals that achieved with heart transplantation, even though most were implanted with destination therapy intent. (MOMENTUM 3 IDE Clinical Study Protocol, NCT02224755; MOMENTUM 3 Pivotal Cohort Extended Follow-up PAS, NCT03982979)

CARC13: Evaluation of Response to Aspirin Platelet Therapy and Hemocompatibility-Related Adverse Events with the HeartMate 3 Left Ventricular Assist Device

Background: Left ventricular assist device (LVAD) patients usually are prescribed a combination of anticoagulation and aspirin (ASA) therapy. HeartMate 3 (HM3) demonstrates reduced hemocompatibility-related adverse events (HRAEs) including stroke, thrombosis and bleeding. However, it’s not known whether ASA responders vs. non-responders are non-inferior in the incidence of HRAEs, and whether there are temporal changes in ASA sensitivity during HM3 support. Methods: This prospective, observational, single-center cohort study included 21 HM3 LVAD patients (Age: 59.0±11.1 years, female: 4.8%, BMI: 29.6±6.1kg/m2) implanted between 2019 and 2021, with serial ASA platelet sensitivity assays (VerifyNow Assay). ASA platelet therapy resistance was defined by ASA reactivity units (ARU) > 550. Primary endpoint was the incidence of HRAEs (ASA responders vs. non-responders) 6 months before initial assessment and until the next outpatient follow-up visit (3 months ± 30 days). Secondary endpoint was the temporal change in ASA resistance. Results: Eight (38.1%) patients were ASA resistant at the first ARU assessment (426 days after HM3 implantation) and 21.1% (p=0.38) during follow-up, without ARU changes over time (512±64 vs. 491±53, p=0.22). ASA responders and non-responders received a comparable ASA daily dose per-protocol (108±28mg vs. 100±28mg, p=0.43), without significant differences in baseline demographics (age: 62±9 vs. 55±14 years, p=0.17; female: 0% vs. 12.5%, p=0.38; BMI: 29±7 vs. 32±3, p=0.55; ischemic heart failure: 46.2% vs. 25.0%, p=0.45) or risk factors (Atrial fibrillation: 30.8% vs. 25.0%, diabetes: 30.8% vs. 37.5% and stroke history: 15.4% vs. 12.5%, p>0.99). The incidence of HRAEs was comparable between ASA responders and non-responders 6 months before the first measurement (15.4% vs. 0.0%, p=0.26) and between the two ARU measurements (0.0% vs. 12.5%, p=0.22). Conclusion: Although the ASA resistance varies considerably between LVAD outpatients, without significant changes over time, the HM3 demonstrated excellent hemocompatibility. Further large-scale multicenter studies are needed to confirm the findings of this study that ASA plays only a minor role in antithrombotic treatment with HM3 and can be safely removed.

PEDS4: Postoperative anticoagulation with bivalirudin versus heparin for HeartMate 3 in children

Background: Bivalirudin has become the standard of care for paracorporeal VAD support in children, although its utilization and outcomes in children with intracorporeal VADs have not been thoroughly studied. We compared the outcomes in children receiving bivalirudin versus unfractionated heparin (UFH) for early (<14 days) post-operative thromboprophylaxis. Methods: Using the ACTION network registry, we conducted a multicenter, retrospective analysis with all patients receiving bivalirudin or UFH for HeartMate 3 (HM3). Survival and adverse events in 14 days post VAD implantation were compared between patients receiving bivalirudin, UFH, or both agents. Results: Between 4/1/18-7/31/22, 171 patients with median age 15.3 years (IQR 12.9-17.3) and weight 62 kg (IQR 45-81) underwent HM3 implantation. Of these, 65 (38%) received bivalirudin, 91 (53%) received UFH and 15 (8.7%) received both agents. At 2 weeks, there was 100% survival in the bivalirudin group, 98% survival in the UFH group, and 100% survival in the bivalirudin/UFH group (p=0.65). Stroke incidence was similar across all anticoagulation agents [4 (6.1%) bivalirudin, 5 (5.5%) UFH, 1 (6.7%) bivalirudin/UFH, p=0.99]. Major bleeding incidence was similar across the anticoagulation agents [2 (3%) bivalirudin, 5 (5.5%) UFH, 1 (6.7%) bivalirudin/UFH, p=0.6). Hemolysis was lower in patients treated with bivalirudin [3 (4.6%)] versus UFH [7 (7.6%)] and bivalirudin/UFH [3 (33%)], p=0.006. Conclusions: In pediatric patients with a HeartMate3, anticoagulation with bivalirudin resulted in similar survival, stroke-free survival, and bleeding-free survival compared to UFH, with lower hemolysis with bivalirudin. More evaluation is required to understand the burden of post-operative hemocompatibility related adverse events.

In-vitro investigation of endothelial monolayer retention on an inflow VAD cannula inside a beating heart phantom

Ventricular assist devices (VADs) provide an alternative solution to heart transplantation for patients with end-stage heart failure. Insufficient hemocompatibility of VAD components can result in severe adverse events, such as thromboembolic stroke, and readmissions. To enhance VAD hemocompatibility, and avoid thrombus formation, surface modification techniques and endothelialization strategies are employed.In this work, a free form patterning topography is selected to facilitate the endothelialization of the outer surface of the inflow cannula (IC) of a commercial VAD. An endothelialization protocol for convoluted surfaces such as the IC is produced, and the retainment of the endothelial cell (EC) monolayer is evaluated. To allow this evaluation, a dedicated experimental setup is developed to simulate realistic flow phenomena inside an artificial, beating heart phantom with a VAD implanted on its apex. The procedural steps of mounting the system result to the impairment of the EC monolayer, which is further compromised by the developed flow and pressure conditions, as well as by the contact with the moving inner structures of the heart phantom. Importantly, the EC monolayer is better maintained in the lower part of the IC, which is more susceptible to thrombus formation and may therefore aid in minimizing the hemocompatibility related adverse events after the VAD implantation.

Implication to Prevent Tachyarrhythmia by Amiodarone Therapy During Durable Left Ventricular Assist Device Supports.

To the Editor: Graboyes et al.1 demonstrated that prophylactic amiodarone therapy was associated with a reduction in the incidence of postoperative arrhythmias, particularly atrial arrhythmias, without incremental incidence of amiodarone-related adverse events among those receiving durable continuous-flow left ventricular assist devices (CF-LVAD). Several concerns have been raised. The implication to prevent all postoperative tachyarrhythmias following CF-LVAD implantation is uncertain.1 Ventricular arrhythmias was not associated with in-hospital mortality and morbidity in patients receiving CF-LVAD supports in the US nationwide database.2 In another study conducted in Japan, the existence of atrial fibrillation was not associated with the development of hemocompatibility-related adverse events during CF-LVAD supports.3 On the contrary, the frequent low-flow alerts were managed by catheter ablation to treat ventricular tachyarrhythmias in a case report.4 It might be of great interest to investigate tachyarrhythmia-induced hemodynamic deterioration as a primary outcome. The definition of prophylactic treatment is unclear. In the authors’ study, some patients had history of arrhythmias and others received antiarrhythmic agents during CF-LVAD supports.1 The concomitant use of renin-angiotensin-aldosterone system inhibitors, which might also suppress the development of tachyarrhythmias, is unclear. The authors followed liver and thyroid function during amiodarone therapy for the safety analyses but did not investigate the incidence of interstitial pneumonia, which is one of the most fatal drug-related adverse events.1 How was associated biomarkers such as KL-6 and SP-D during amiodarone therapy? Although it did not reach statistical significance, more patients receiving amiodarone trended to encounter death or CF-LVAD exchange. Could the authors clarify the causes of their death?

The prognostic role of advanced hemodynamic variables in patients with left ventricular assist devices.

Invasive hemodynamic variables obtained from right heart catheterization have been used for risk-stratifying patients with advanced heart failure (HF). However, there is a paucity of data on the prognostic value of invasive hemodynamic variables in patients with left ventricular assist devices (LVAD). We hypothesized that cardiac power output (CPO), cardiac power efficiency (CPE), and left ventricular stroke work index (LVSWI) can serve as prognostic markers in patients with LVADs. Baseline hemodynamic data from patients who had LVAD ramp studies at our institution from 4/2014 to 7/2018 were prospectively collected, from which advanced hemodynamic variables (CPO, CPE, and LVSWI) were retrospectively analyzed. Univariate and multivariable analyses were performed for hemocompatibility-related adverse events (HRAE), HF admissions, and mortality. Ninety-one participants (age 61 ± 11 years, 34% women, 40% Black or African American, and 38% ischemic cardiomyopathy) were analyzed. Low CPE was significantly associated with mortality (HR 2.42, 95% CI 1.02-5.74, p=0.045) in univariate analysis and Kaplan-Meier analysis (p=0.04). Low LVSWI was significantly associated with mortality (HR 2.13, 95% CI 1.09-4.17, p=0.03) in univariate analysis and Kaplan-Meier analysis (p=0.02). CPO was not associated with mortality. CPO, CPE, and LVSWI were not associated with HRAE or HF admissions. Advanced hemodynamic variables can serve as prognostic indicators for patients with LVADs. Low CPE and LVSWI are prognostic for higher mortality, but no variables were associated with HF admissions or HRAEs.