Platelet activation and aggregation in different centrifugal-flow left ventricular assist devices.

Left-ventricular assist devices (LVADs) improve outcomes in end-stage heart failure patients. Two centrifugal-flow LVAD systems are currently approved, HeartMate 3 (HM3) and Medtronic/Heartware HVAD (HVAD). Clinical findings suggest differences in thrombogenicity between both systems. We compared markers of platelet activation and aggregation between HM3 and HVAD. We prospectively included 59 LVAD patients (40 HM3, 19 HVAD). Platelet P-selectin expression, activated glycoprotein (GP) IIb/IIIa and monocyte-platelet aggregates (MPA) were assessed by flow-cytometry. Platelet aggregation was measured by light-transmission aggregometry (LTA) and multiple-electrode aggregometry (MEA). Von-Willebrand factor (VWF) antigen (VWF:Ag), VWF activity (VWF:Ac), and VWF multimer pattern analysis were determined. Soluble P-selectin (sP-selectin) was measured with an enzyme-linked immunoassay. P-selectin, GPIIb/IIIa and MPA levels in vivo and in response to arachidonic acid, adenosine diphosphate, and thrombin receptor activating peptide were similar between HM3 and HVAD (all p > .05). Likewise, agonist-inducible platelet aggregation by LTA and MEA did not differ between HM3 and HVAD (all p > .05). VWF:Ag levels and FVIII:C were similar between both systems (both p > .05), but patients with HVAD had significantly lower VWF:Ac (p = .011) and reduced large VWF multimers (p = .013). Finally, sP-selectin levels were similar in patients with HVAD and HM3 (p = .845). In conclusion, on-treatment platelet activation and aggregation are similar in HM3 and HVAD patients. Potential clinical implications of observed differences in VWF profiles between both LVAD systems need to be addressed in future clinical trials.

Left ventricular assist device implantation causes platelet dysfunction and proinflammatory platelet-neutrophil interaction.

Blood flow through left ventricular assist devices (LVAD) may induce activation and dysfunction of platelets. Dysfunctional platelets cause coagulation disturbances and form platelet-neutrophil conjugates (PNC), which contribute to inflammatory tissue damage. This prospective observational cohort study investigated patients, who underwent implantation of a LVAD (either HeartMate II (HM II) (n = 7) or HeartMate 3 (HM 3) (n = 6)) and as control patients undergoing coronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR) (n = 10). We performed platelet and leukocyte flow cytometry, analysis of platelet activation markers, and platelet aggregometry. Platelet CD42b expression was reduced at baseline and perioperatively in HM II/3 compared to CABG/AVR patients. After surgery the platelet activation marker ß-thromboglobulin and platelet microparticles increased in all groups while platelet aggregation decreased. Platelet aggregation was more significantly impaired in LVAD compared to CABG/AVR patients. PNC were higher in HM II compared to HM 3 patients. We conclude that LVAD implantation is associated with platelet dysfunction and proinflammatory platelet-leukocyte binding. These changes are less pronounced in patients treated with the newer generation LVAD HM 3. Future research should identify device-specific LVAD features, which are associated with the least amount of platelet activation to further improve LVAD therapy.

Device Therapy in Chronic Heart Failure: JACC State-of-the-Art Review.

The regulatory landscape for device-based heart failure (HF) therapies has seen a major shift in the last 7 years. In 2013, the U.S. Food and Drug Administration released guidance for early feasibility and first-in-human studies, thereby encouraging device innovation, and in 2016 the U.S. Congress authorized the Breakthrough Devices Program to expedite access for Americans to innovative devices indicated for diagnosis and treatment of serious illnesses, such as HF. Since December 2016, there has been an increase in the number of HF devices for which manufacturers are seeking approval through the breakthrough designation pathway. This has led to a rapid uptake in the development and evaluation of device-based HF therapies. This article reviews the current and future landscape of device therapies for chronic HF and associated comorbidities and the regulatory environment that is driving current and future innovation.

Hemolysis estimation in turbulent flow for the FDA critical path initiative centrifugal blood pump.

Hemolysis in medical devices and implants has been a primary concern over the past fifty years. Turbulent flow in particular can cause cell trauma and hemolysis in such devices. In this work, the effects of turbulence on red blood cell (RBC) damage are examined by simulating the flow field through a centrifugal blood pump that has been identified as a case study through the critical path initiative of the US Food and Drug Administration (FDA). In this study, a new model was employed to predict hemolysis in the turbulent flow environment in the pump selected for the FDA critical path initiative. The operating conditions for a centrifugal blood pump were specified by the FDA for rotational speeds of 2500 and 3500 rpm. The model is based on the analysis of the smaller eddies within the turbulent flow field, since it is assumed that turbulent flow eddies with sizes comparable to the dimensions of the RBCs lead to cell trauma. The Kolmogorov length scale of the velocity field is used to identify such small eddies. Using model parameters obtained in prior work through comparisons to capillary and jet flow, it is found that hemolysis for the 2500-rpm pump was predicted well, while hemolysis for the 3500-rpm pump was overpredicted. Results indicate refinement of the model and empirical constants with better experimental data is needed.

Berlin Heart EXCOR and ACTION post-approval surveillance study report.

BACKGROUND: The Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device (VAD) was introduced in North America nearly 2 decades ago. The EXCOR was approved under Humanitarian Device Exemption status in 2011 and received post-market approval (PMA) in 2017 from Food and Drug Administration. Since the initial approval, the field of pediatric mechanical circulatory support has changed, specifically with regard to available devices, anticoagulation strategies, and the types of patients supported. This report summarizes the outcomes of patients supported with EXCOR from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. These data were part of the PMA surveillance study (PSS) required by the Food and Drug Administration. METHODS: ACTION is a learning collaborative of over 40 pediatric heart failure programs worldwide, which collects data for all VAD implantations as one of its initiatives. All patients in North America with EXCOR implants reported to ACTION from 2018 to 2020 (n = 72) who had met an outcome were included in the EXCOR PSS group. This was compared with a historical, previously reported Berlin Heart EXCOR study group (Berlin Heart study [BHS] group, n = 320, 2007‒2014). RESULTS: Patients in the PSS group were younger, were smaller in weight/body surface area, were more likely to have congenital heart disease, and were less likely to receive a bi-VAD than those in the BHS group. Patients in the PSS group were less likely to be in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 and were supported for a longer duration. The primary anticoagulation therapy for 92% of patients in the PSS group was bivalirudin. Success, defined as being transplanted, being weaned for recovery, or being alive on a device at 180 days after implantation, was 86% in the PSS group compared with 76% in the BHS group. Incidence of stroke was reduced by 44% and the frequency of pump exchange by 40% in the PSS group compared with those in the BHS group. Similarly, all other adverse events, including major bleeding, were reduced in the PSS group. CONCLUSIONS: The PSS data, collected through ACTION, highlight the improvement in outcomes for patients supported with EXCOR compared with the outcomes in a historical cohort. These findings may be the result of changes in patient care practices over time and collaborative learning.

Structural improvement study of streamline design method, conical hub, and auxiliary blades for axial blood pump.

The blood pump is a medical device used to assist or replace the diseased heart. Research on the structure of blood pumps has been committed to achieving better hemolysis and hydraulic performance. The purpose of this study was to find some effective ways to improve design methods and hydraulic structures. The research contents of improvement include: (1) improved blade streamline design method; (2) conical impeller hub; (3) additional auxiliary blades. Characteristic analysis and parameter design were carried out on the above three aspects. The methods used in this study included Dynamics (CFD) simulation, hydraulic experiments, and Particle Image Velocimetry (PIV) experiments. The results showed that this improved streamline design method could improve the distortion of blades and ensure a smaller impeller length. And, in the enhanced design of the hub, it is designed to be conical with inlet and outlet diameters of 7.5 and 12.8 mm, respectively. Furthermore, the auxiliary blades between the main blades are analyzed and designed. The results have the best performance optimization effect when the length of the auxiliary blades is 55% of the main blades. In general, the structural improvements in this study achieved the effect of improving hydraulic performance and avoiding increased hemolysis. These methods can be considered as an effective means of improving blood pump performance.

Safety and Efficacy of a Percutaneously Inserted Ventricular Support Device Purge Solution Heparin 25 U/mL.

BACKGROUND: The Impella is a percutaneous ventricular assist device (pVAD) that provides temporary hemodynamic support to patients with cardiogenic shock or for protected percutaneous coronary intervention. The manufacturer recommends a 50-U/mL concentration of heparin purge solution (or 25 U/mL as an alternative), with systemic heparin to maintain therapeutic anticoagulation during device support. Concomitant use of systemic heparin with the purge solution may increase the risk of bleeding. OBJECTIVES: The primary objective of this study was to describe the prevalence of thrombosis and bleeding using a less-concentrated heparin purge solution (25 U/mL) in combination with systemic heparin therapy. METHODS: This was a retrospective observational cohort study of patients who required at least 12 hours of pVAD support and received 25-U/mL concentration of heparin purge solution between January 1, 2014, and May 31, 2017. The primary end points were the rate of thrombotic and bleeding events. Secondary end points included the percentage of time within the therapeutic activated partial thromboplastin time (aPTT) range. Descriptive statistics were utilized for data analysis. RESULTS: Of the 161 patients screened, 100 met inclusion criteria; 63% of patients experienced a bleeding event, with Bleeding Academic Research Consortium (BARC) type 3a being the most common. Median percentages of subtherapeutic and supratherapeutic aPTT values were similar between the bleeding and nonbleeding groups. Two patients experienced thrombotic events. CONCLUSION AND RELEVANCE: Based on our findings, the device thrombosis rate was 2% and the rate of major bleeding (BARC 3a and higher) was 35%. This study provides descriptive outcomes data of a lower-concentration heparin purge solution.

Evaluation method and platform of vibrational disturbance test for ventricular assist devices.

OBJECTIVE: For ventricular assist devices utilizing levitation bearing technology, collision and wear of the rotor would occur if the bearing cannot resist disturbances from patient activities and vibration/shock impacts. The reliability of ventricular assist devices can be seriously affected, potentially impairing blood compatibility (e.g. thrombus generation) and threatening patient safety. In this article, we proposed a vibrational disturbance test protocol for ventricular assist devices. METHODS: Two kinds of vibrational disturbances-translational and rotational-were defined and the disturbance levels determined as 6G and 10 rad/s per possible patient activity impact. A test platform was built according to the disturbance level requirements. RESULTS: The test platform successfully generated the required disturbance. The vibration test evaluation criteria for ventricular assist device assistance (characterized by the pressure head, flow rate, and driving current waveform) were well verified. CONCLUSION: Compared with translational vibration, rotational vibration had a greater impact on the rotor. Accurate control of high-speed rotor is difficult because of the gyroscopic effect. As conventional random vibration tests cannot cover all risk situations, it is recommended that translational and rotational disturbance tests are carried out for levitation ventricular assist devices. We recommend that researchers and manufacturers pay attention to the vibrational impact of rotor-levitated ventricular assist devices.

Pulse assessment is important with blood pressure measurement in individuals with continuous flow left ventricular assist devices.

While Doppler and cuff blood pressure techniques are prevalent methods of assessing blood pressure in patients with continuous flow left ventricular assist devices, the impact of pulsatility on measurement is not well established. Retrospective chart analysis of clinical variables including pulse perception, blood pressure (Doppler and standard cuff), and aortic valve opening on echo at clinic visit were abstracted. Stable outpatients on continuous flow left ventricular assist devices support with concomitant portable echo assessment were included. Mean average difference was calculated and Pearson's correlation performed for all those patients who had both Doppler and cuff pressure obtained. In all, 74 Heartmate-II patients with a median time from implant of 380 days were analyzed. A pulse was perceived in 82% of patients with persistent aortic valve opening on portable echo and also in 30% of those who had a persistently closed aortic valve. The mean average difference between the Doppler and systolic cuff pressure was ~13 mmHg (r = 0.5, p = 0.004) when a pulse was present and ~11 mmHg when aortic valve was open (r = 0.68, p < 0.0001). Pulse presence seems to reflect aortic valve opening a majority of the time but not always. In the presence of a prominent pulse or persistent aortic valve opening, the Doppler pressure seems to be more reflective of a systolic pressure than mean perfusion pressure. Hence, assessment of pulsatility needs to be incorporated into blood pressure measurement methods for patients with continuous flow left ventricular assist devices.

Evaluation of clinically relevant operating conditions for left ventricular assist device investigations.

Standardized boundary conditions for flow rate and pressure difference are currently not available for the development and certification process of ventricular assist devices. Thus, interdisciplinary studies lack comparability and quantitative assessment. Universally valid boundary conditions could be used for the application of numerical and experimental investigations and the approval procedure of ventricular assist devices. In order to define such boundaries, physiological data from INCOR® patients were evaluated. A total of 599 out of possible 627 ventricular assist device patients were analyzed regarding their cardiac demands of flow rate and pressure head. An analysis of long-term data was performed, in order to provide respective, static mean values for benchmark testing. Furthermore, the short-term data of 188 patients delivered field data-based dynamic flow and pressure curves. The results of the study revealed physiologically reasonable boundary conditions, which can be applied in numerical or experimental investigations of ventricular assist devices. For steady flow analysis, single values for flow rate (4.46 L/min) and pressure head (62 mmHg) are suggested. For the support of pulsatile and unsteady flow studies, seven typical patients and one representative dynamic curve for flow rate and pressure head are proposed.The standardized results provided in this article, can be used in favor of interdisciplinary comparability of future numerical computations or in vitro ventricular assist device tests in research, development, and approval.

Toward a Standard Practice to Quantify von Willebrand Factor Degradation During Left Ventricular Assist Device Support.

BACKGROUND: Continuous-flow left ventricular assist devices (LVADs) cause degradation of von Willebrand factor (VWF) multimers and bleeding. Multiple techniques exist to characterize VWF deficiency. However, a standard methodology has not been established in LVAD patients. Toward this goal, we evaluated 4 methods to quantify VWF multimers. METHODS: We collected paired blood samples from patients (n = 48) before and after 1 week of LVAD support. After 652 ± 59 days of support, patients were classified as bleeders (≥1 bleeding episode) or nonbleeders. VWF multimers were resolved with electrophoresis and immunoblotting, the gold-standard to evaluate VWF multimers. We evaluated 4 quantification methods. RESULTS: Each method demonstrated significant VWF degradation during LVAD support vs a paired, pre-LVAD sample (method 1, VWF length: 48 of 48 patients, -10% ± 1%, P < .0001; method 2, VWF density: 40 of 48, -34% (interquartile range, -46% to -8%), P < .0001; method 3, pre-LVAD to LVAD ratio: 46 of 48, 17 ± 5: 10 ± 1, P < .0001; method 4, LVAD/pre-LVAD index: 46 of 48, 57% (interquartile range, 50% to 73%), P < .0001). Bleeding occurred in 27 of 48 patients. Method 1 demonstrated significantly fewer VWF multimers in bleeders compared with nonbleeders (-11% ± 1% vs -8% ± 1%; P = .01). Other methods did not demonstrate this potentially important clinical relationship. CONCLUSIONS: A standardized methodology is needed to quantify VWF multimer degradation with mechanical circulatory support devices. Novel method 1 successfully quantified the patient-specific change in VWF multimer length during LVAD support and demonstrated a difference in VWF multimers between bleeders and nonbleeders. Adoption of consensus methodology will assist to standardize patient-specific bleeding risk, inform anticoagulation and antiplatelet therapy, and evaluate LVAD hemocompatibility.

Flying after left ventricular assist device implantation.

Literature on the air travel activities of patients supported by permanent mechanical assist devices is rare. To the best of our knowledge, no air travel guidelines or fitness prerequisites exist on whether and when ventricular assist device (VAD) patients are allowed to travel by plane after device implantation. In this study, we evaluated the topic of air travel after VAD implantation. This working group aimed to produce a report on air travel passengers supported by VADs, regarding their fitness to fly. Fifty left ventricular assist device (LVAD) patients were surveyed in a worldwide multicenter study. The single survey was performed with a multimethod design, including interviews conducted face-to-face, online, and on phone. Out of 50 patients, 97% described their traveling by aircraft as perfect and uneventful during the flight. Eighty-five percent of the study participants consulted their medical practitioner before the flight. No patient reported the occurrence of a severe condition associated with flying. LVAD alarms, especially low flow alarms, did not occur in any of the devices. Thirty-five percent of the surveyed patients, however, stated a major problem pertaining to the security check procedures at the airport. The results of this study suggest that commercial air travel is safe for stable patients on permanent VAD support and traveling can be resumed securely after VAD implantation. Conscientious preparation by packing necessary devices, fluids, medications, and careful preparation for the airport security check is recommended.

Incidence and Variables Predictive of Pressure Injuries in Patients Undergoing Ventricular Assist Device and Total Artificial Heart Surgeries: An 8-Year Retrospective Cohort Study.

OBJECTIVE: To investigate the incidence and risk factors of pressure injury (PI) development after ventricular assist device (VAD) or total artificial heart (TAH) surgery. METHODS: The investigator reviewed all VAD-TAH surgeries performed between 2010 and 2018 in a large academic health system. The PIs were reported by case incidence, patient incidence, and incidence density for each of the respective 1,000 patient days during the study period. Statistics on four different VAD-TAH devices were assessed; variables significant in bivariate analysis were entered into a stepwise logistic regression model to identify significant predictors of PI. RESULTS: The sample included 292 independent VAD-TAH surgeries among 265 patients. Thirty-two patients developed 45 PIs. The PI incidence was 11% (32/292), with a PI incidence per patient of 12% (32/265). Incidence density was 10 per 1,000 patient days (1%) for 2010-2012, 12 per 1,000 patient days (1.2%) for 2013-2015, and 10 per 920 patient days (1.1%) for 2016-2018. Logistic regression revealed that significant predictor variables for PI were age, mechanical ventilation time, and preoperative Braden Scale score. The mean time to PI was 23 days after admission and over 14 days after surgery, indicating a low rate of intraoperative and ICU-associated PI. CONCLUSIONS: The incidence of PI was lower than anticipated given historic rates. Potential mechanisms by which these patients were protected from PI are discussed. Prospective studies to further investigate significant risk factors and effective prevention measures are warranted.

Protein C Pathway, Inflammation, and Pump Thrombosis in Patients With Left Ventricular Assist Devices.

Use of left ventricular assist devices (LVADs) for management of advanced heart failure is becoming increasingly common; however, device associated thrombosis remains an important cause of mortality in this patient population. We hypothesize that inflammation in LVAD implanted patients dysregulates the protein C pathway, creating a hypercoagulable state leading to thrombosis. Plasma samples from 22 patients implanted with the Thoratec HeartMate II LVAD were analyzed by commercial ELISAs. Retrospective sample selection included those collected 1-3 months prior to and within 1 month after a thrombotic or bleeding event. Unrelated to warfarin dosing, total protein S and free protein S (p = 0.033) levels were 20% lower in patients with LVAD-thrombosis than in patients with LVAD-bleeding. Levels of protein C, soluble endothelial cell protein C receptor, and soluble thrombomodulin were similar in both groups before and after the event. Compared to normal, C-reactive protein levels were 25-fold elevated in LVAD-thrombosis patients but only 9-fold elevated in LVAD-bleeding patients. This study suggests that protein S, influenced by the inflammatory state, is a gatekeeper for the function of protein C in patients with LVAD-associated thrombosis.

An International Study on Ventricular Assist Device Program Models.

BACKGROUND: Advanced technology and improved outcomes have led to rapid growth of ventricular assist devices (VADs) throughout the world, but little exists regarding their structure. We sought to study trends in VAD programs on a global level. METHODS: We distributed a 26-question online survey to 321 individuals who work within those programs. Four categories of questions were formed: patient management, coordinator role, multidisciplinary support, and leadership. RESULTS: Fifty-eight surveys (47 United States, 11 international) were analyzed. The majority of programs cared for 26 to 100 device-assisted patients (62%), 26% cared for ≤25 patients, and 12% cared for ≥100 patients. Advanced practice providers (APPs) were used in 69% of programs as a device coordinator. In-hospital rounding was performed equally among the APPs and registered nurses. Most programs used a social worker (90%), nutritionist (74%), pharmacist (72%), palliative care (66%), and finance coordinator (64%). Less than half (43%) included a case manager and only 33% used a pharmacist. The program leader was identified as a cardiologist (31%) or surgeon (26%) or both equally (43%). CONCLUSION: This study demonstrates differences and similarities between VAD program structures. Additional research is warranted to evaluate the effect of program structure on outcomes, job satisfaction, and retention regions.

Evaluation of a Health Care Performance Improvement Initiative to Facilitate Optimal Clinical Outcomes in Patients Receiving Ventricular Assist Device Support.

BACKGROUND: Ventricular assist device (VAD) patients are at high risk for morbidities and mortality. One potentially beneficial component of the Joint Commission VAD Certification process is the requirement that individual VAD programs select 4 performance measures to improve and optimize patients' clinical outcomes. PROBLEM STATEMENT: Review of patient data after our program's first certification visit in 2008 showed that, compared to national recommendations and published reports, our patients had suboptimal outcomes in 4 areas after device implantation: length of hospital stay, receipt of early (<48 hours) postsurgical physical therapy, driveline infection incidence, and adequacy of nutritional status (prealbumin ≥18 mg/dL). METHODS: Plan-Do-Study-Act processes were implemented to shorten length of stay, increase patient receipt of early physical therapy, decrease driveline infection incidence, and improve nutritional status. With 2008 as our baseline, we deployed interventions for each outcome area across 2009 to 2017. Performance improvement activities included staff, patient, and family didactic, one-on-one, and hands-on education; procedural changes; and outcomes monitoring with feedback to staff on progress. Descriptive and inferential statistics were examined to document change in the outcomes. OUTCOMES: Across the performance improvement period, length of stay decreased from 40 to 23 days; physical therapy consults increased from 87% to 100% of patients; 1-year driveline infection incidence went from 38% to 23.5%; and the percentage of patients with prealbumin within the normal range increased from 84% to 90%. IMPLICATIONS: Performance improvement interventions may enhance ventricular assist device patient outcomes. Interventions' sustainability should be evaluated to ensure that gains are not lost over time.

Management of Right Ventricular Failure in Pulmonary Embolism.

Acute right ventricular failure remains the leading cause of mortality associated with acute pulmonary embolism (PE). This article reviews the pathophysiology behind acute right ventricular failure and strategies for managing right ventricular failure in acute PE. Immediate clot reduction via systemic thrombolytics, catheter based procedures, or surgery is always advocated for unstable patients. While waiting to mobilize these resources, it often becomes necessary to support the RV with vasoactive medications. Clinicians should carefully assess volume status and use caution with volume resuscitation. Right ventricular assist devices may have an expanding role in the future.

Decision Aid Implementation among Left Ventricular Assist Device Programs Participating in the DECIDE-LVAD Stepped-Wedge Trial.

Background. Despite demonstrated efficacy, patient decision aids (DAs) are rarely used in clinical practice in the absence of coverage mandates. Deciding whether to pursue a left ventricular assist device (LVAD) is a major, preference-sensitive decision-ideal for exploring implementation of a DA. Methods. We conducted a type II effectiveness-implementation hybrid trial at 6 LVAD programs using a stepped-wedge cluster-randomized design. Using the RE-AIM framework, we collected both quantitative and qualitative outcomes, including a checklist collected by study staff for each enrolled patient regarding DA use and interviews with LVAD program clinicians preintervention, 6 months postintervention, and at the conclusion of the study. Results. From June 2015 to January 2017, 248 patients and their caregivers were enrolled. A total of 69 interviews were conducted with 48 clinicians at 3 time points. The DA reached 95% of eligible patients. Adoption was 100%, as all sites approached agreed to participate in the trial. Interviews revealed several themes related to the implementation of the DA: clinicians had a strong desire to ensure patients were informed and embraced the DA. Despite this, they reported communication challenges among their team that impeded implementation. Five of the 6 sites have maintained use of the DA following the trial; 1 site reported concerns about decreased procedural volume with use of the DA as a reason for discontinuation. Conclusions. In this hybrid trial, a DA for patients considering LVADs and their caregivers demonstrated high reach. Adoption and implementation were facilitated by a strong desire to ensure that patients were well informed. Future dissemination research and practice should attend to concerns about procedure volume and coverage mandates and facilitate ongoing communication at sites using the DA.