Left Ventricular Assist Device Caregiver Experiences and Health Outcomes: A Systematic Review of Qualitative and Quantitative Studies.

BACKGROUND: Knowledge synthesis is lacking regarding outcomes and experiences of caregivers of adult patients living with continuous flow left ventricular assist devices (CF-LVAD). The purpose of this systematic review was to summarize qualitative data related to the experience of caregivers of adult patients living with CF-LVAD as well as quantitative data related to health outcomes of caregivers. METHODS AND RESULTS: Multiple databases were systematically queried for studies of qualitative experiences and quantitative health outcomes for caregivers of adult CF-LVAD recipients. Search dates were constrained to articles published between 2004 and August of 2018 because CF-LVADs were not routinely implanted before 2004. Two authors independently screened 683 articles; 15 met predetermined inclusion criteria. Eligible articles reported results from 13 studies. Of those, 8 used either qualitative or mixed methods and 5 used quantitative methods. Caregivers were primarily female (81%) and their mean age was 59 years. Qualitative studies revealed 3 overarching themes related to the caregiver role, coping strategies, and LVAD decisions. Quantitative studies revealed caregiver strain peaked between 1 and 3 months after implantation, anxiety and depression were relatively stable, mental health status improved, and physical health status was stable from before to after implantation. CONCLUSIONS: CF-LVAD caregivers experience significant, sustained emotional strain for 3 months after implantation, reporting considerable stress in meeting their personal needs and those of their loved one.

Blending Evidence-Based Practice and Lean Six Sigma Methodology to Reduce Hospital-Acquired Pressure Injuries in a Progressive Care Unit.

BACKGROUND: Hospital-acquired pressure injuries (HAPIs) continue to challenge acute care facilities. Best practice to reduce HAPI includes assessment, documentation, positioning, and treatment. LOCAL PROBLEM: In spite of using evidence-based practices, the hospital's gastrointestinal/genitourinary progressive care unit had more HAPIs each month than the other units in the hospital. METHODS: A combination of Lean Six Sigma and evidence-based practice was used to decrease HAPIs. INTERVENTIONS: The T program (turn, touch, and tidy) was developed to address the areas of concern identified in the root cause analysis. RESULTS: HAPIs were reduced from 22 in the previous 2 quarters to zero for 3 consecutive quarters with a cost avoidance to $379 767. CONCLUSIONS: The successful implementation of the T program was the result of blending Lean Six Sigma and evidence-based practice.

A Computational Investigation of the Effects of Temporal Synchronization of Left Ventricular Assist Device Speed Modulation with the Cardiac Cycle on Intraventricular Hemodynamics.

Patients with advanced heart failure are implanted with a left ventricular assist device (LVAD) as a bridge-to-transplantation or destination therapy. Despite advances in pump design, the risk of stroke remains high. LVAD implantation significantly alters intraventricular hemodynamics, where regions of stagnation or elevated shear stresses promote thrombus formation. Third generation pumps incorporate a pulsatility mode that modulates rotational speed of the pump to enhance in-pump washout. We investigated how the timing of the pulsatility mode with the cardiac cycle affects intraventricular hemodynamic factors linked to thrombus formation. Computational fluid dynamics simulations with Lagrangian particle tracking to model platelet behavior in a patient-specific left ventricle captured altered intraventricular hemodynamics due to LVAD implantation. HeartMate 3 incorporates a pulsatility mode that modulates the speed of the pump every two seconds. Four different timings of this pulsatility mode with respect to the cardiac cycle were investigated. A strong jet formed between the mitral valve and inflow cannula. Blood stagnated in the left ventricular outflow tract beneath a closed aortic valve, in the near-wall regions off-axis of the jet, and in a large counterrotating vortex near the anterior wall. Computational results showed good agreement with particle image velocimetry results. Synchronization of the pulsatility mode with peak systole decreased stasis, reflected in the intraventricular washout of virtual contrast and Lagrangian particles over time. Temporal synchronization of HeartMate 3 pulsatility with the cardiac cycle reduces intraventricular stasis and could be beneficial for decreasing thrombogenicity.

Atrial fibrillation increases thrombogenicity of LVAD therapy.

BACKGROUND: This study investigates the hypothesis that presence of atrial fibrillation (AF) in LVAD patients increases thrombogenicity in the left ventricle (LV) and exacerbates stroke risk. METHODS: Using an anatomical LV model implanted with an LVAD inflow cannula, we analyze thrombogenic risk and blood flow patterns in either AF or sinus rhythm (SR) using unsteady computational fluid dynamics (CFD). To analyze platelet activation and thrombogenesis in the LV, hundreds of thousands of platelets are individually tracked to quantify platelet residence time (RT) and shear stress accumulation history (SH). RESULTS: The irregular and chaotic mitral inflow associated with AF results in markedly different intraventricular flow patterns, with profoundly negative impact on blood flow-induced stimuli experienced by platelets as they traverse the LV. Twice as many platelets accumulated very high SH in the LVAD + AF case, resulting in a 36% increase in thrombogenic potential score, relative to the LVAD + SR case. CONCLUSIONS: This supports the hypothesis that AF results in unfavorable blood flow patterns in the LV adding to an increased stroke risk for LVAD + AF patients. Quantification of thrombogenic risk associated with AF for LVAD patients may help guide clinical decision-making on interventions to mitigate the increased risk of thromboembolic events.

Discordance between aPTT and anti-Xa in monitoring heparin anticoagulation in mechanical circulatory support.

AIMS: It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance. METHODS AND RESULTS: aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning random forest model and a multivariate regression model were applied to patient demographics, device type, and 14 laboratory variables; 23 001 pairs of simultaneously measured aPTT/anti-Xa were collected from 699 MCS patients. aPTT and anti-Xa were concordant in 35.5% of paired observations and discordant in 64.5% (aPTT > antiXa 61.5%; aPTT < antiXa 3.0%). Discordance with a high aPTT relative to anti-Xa (aPTT > antiXa) was associated with high INR, eGFR, and total bilirubin, as well as low platelets, haemoglobin, pre-albumin, white blood cell count, and haptoglobin. Total artificial heart and durable ventricular assist devices were more likely to be associated with aPTT > anti-Xa than temporary MCS devices. CONCLUSIONS: aPTT and anti-Xa were frequently discordant in MCS patients receiving heparin anticoagulation. Clinical conditions common in MCS patients such as concurrent warfarin use, malnutrition, haemolysis, and thrombocytopenia, as well as durable type of MCS devices were associated with a high aPTT relative to anti-Xa.

In Vitro Investigation of the Effect of the Timing of Left Ventricular Assist Device Speed Modulation on Intraventricular Flow Patterns.

Thromboembolic events remain a common complication for left ventricular assist device (LVAD) patients. To prevent in-pump thrombosis, third-generation LVADs use speed modulation, which is not synchronized with the native left ventricle (LV) contractility. This study aims to investigate the effect of speed modulation on intraventricular flow patterns, and specifically, the impact of timing relative to pressure variations in the LV. Stereo-particle image velocimetry measurements were performed in a patient-derived LV implanted with an LVAD, for different timings of the speed modulation and speed. Speed modulation has a strong effect on instantaneous afterload and flowrate (-16% and +20%). The different timings of the speed modulation resulted in different flowrate waveforms, exhibiting different maxima (5.3-5.9 L/min, at constant average flowrate). Moreover, the timing of the speed modulation was found to strongly influence intraventricular flow patterns, specifically, stagnation areas within the LV. These experiments highlight, once more, the complex relationship between LVAD speed, hemodynamic resistance, and intraventricular pressure. Overall, this study demonstrates the importance of considering native LV contractility in future LVAD controls, to improve hemocompatibility and reduce the risk of thromboembolic complications.

Method for Visualization of Emergency Granulopoiesis in the Zebrafish Embryo.

Emergency granulopoiesis (EG) is a response to severe inflammation in which increased neutrophils are generated in the hematopoietic tissue. Photolabeling is utilized to distinguish newly developed neutrophils from existing neutrophils. However, this technique requires a strong laser line and labels subsets of the existing neutrophils. Here we create a transgenic zebrafish line that expresses a time-dependent switch from green fluorescent protein (GFP) to red fluorescent protein (RFP) in neutrophils, which allows quantification of EG using simple GFP/RFP ratiometric imaging.

First-in-Man Use of a Modified Controller to Resolve HVAD Failure-to-Restart.

We report a case of Medtronic HeartWare ventricular assist device (HVAD) pump failure-to-restart. Despite HVAD withdrawal from the market in June 2021, up to 4,000 patients remain on HVAD support worldwide, and many are at high risk for this serious complication. This report describes the first-in-man use of a new HVAD controller that restarted a defective HVAD pump and avoided a fatal outcome. This new controller has the potential of preventing unnecessary VAD exchanges and saving lives.

The History of Durable Left Ventricular Assist Devices and Comparison of Outcomes: HeartWare, HeartMate II, HeartMate 3, and the Future of Mechanical Circulatory Support.

The utilization of left ventricular assist devices (LVADs) in end-stage heart failure has doubled in the past ten years and is bound to continue to increase. Since the first of these devices was approved in 1994, the technology has changed tremendously, and so has the medical and surgical management of these patients. In this review, we discuss the history of LVADs, evaluating survival and complications over time. We also aim to discuss practical aspects of the medical and surgical management of LVAD patients and future directions for outcome improvement in this population.

A Computational Hemodynamics Approach to Left Ventricular Assist Device (LVAD) Optimization Validated in a Large Patient Cohort.

With increasing use of left ventricular assist devices (LVAD) it is critical to devise strategies to optimize LVAD speed while controlling mean arterial pressure (MAP) and flow according to patient physiology. The complex interdependency between LVAD speed, MAP, and flow frequently makes optimization difficult under clinical conditions. We propose a method to guide this procedure in silico, narrowing the conditions to test clinically. A computational model of the circulatory network that simulates HF and LVAD support, incorporating LVAD pressure-flow curves was applied retrospectively to anonymized patient hemodynamics data from the University of Washington Medical Center. MAP management on 61 patient-specific computational models with a target of 70 mm Hg, resulting flow for a given LVAD speed was analyzed, and compared to a target output of 5 L/min. Before performing virtual MAP management, 51% had a MAP>70 mm Hg and CO>5 L/min, and 33% had a MAP>70 mm Hg and CO<5 L/min. After changing systemic resistance to meet the MAP target (without adjusting LVAD speed), 84% of cases resulted in CO higher than 5 L/min, with a median CO of 6.79 L/min, using the computational predictive model. Blood pressure management alone is insufficient in meeting both MAP and CO targets, due to the risk of hypervolemia, and requires appropriate LVAD speed optimization to achieve both targets, while preserving right heart health. Such computational tools can narrow down conditions to be tested for each patient, providing significant insight into the pump-patient interplay. LVAD hemodynamic optimization has the potential to reduce complications and improve outcomes.

In Vitro Investigation of the Effect of Left Ventricular Assist Device Speed and Pulsatility Mode on Intraventricular Hemodynamics.

Stroke has become the main cause of mortality and morbidity in patients treated with Left Ventricular Assist Devices (LVADs). The hemodynamics of the left ventricle are altered by the implantation of an LVAD, with the increase of thrombogenic flow patterns, such as stagnation regions. Time-resolved stereo particle image velocimetry (Stereo-PIV) measurements of the flow inside a patient-specific model of the left ventricle (LV) implanted with an LVAD were performed. The effects of LVAD speed, peripheral resistance and afterload were investigated. The impact of activating the LVAD pulsatility mode (periodic speed modulation) was also evaluated. Analysis of the velocity measurements in two orthogonal planes revealed stagnation zones which may be favorable to thrombus formation. Increasing LVAD speed, despite increasing the flow rate through the inflow cannula, does not automatically result in smaller stagnation regions. These results demonstrated the strong interdependence of peripheral resistance, afterload and flow through the LVAD. As a consequence, the pulsatility mode showed very limited effect on overall flow rate. However, it did reduce the size of high stagnation areas. This study showed how LVAD speed, peripheral resistance and afterload impact the complex intraventricular flow patterns in a ventricle implanted with an LVAD and quantify their thrombogenic risk.

Cost-effectiveness of left ventricular assist devices as destination therapy in the United Kingdom.

AIMS: Continuous-flow left ventricular assist devices (LVADs) as destination therapy (DT) are a recommended treatment by National Institute for Health and Care Excellence England for end-stage heart failure patients ineligible for cardiac transplantation. Despite the fact that DT is frequently used as an LVAD indication across other major European countries and the United States, with consistent improvements in quality-of-life and longevity, National Health Service (NHS) England does not currently fund DT, mainly due to concerns over cost-effectiveness. On the basis of the recently published ENDURANCE Supplemental Trial studying DT patients, we assessed for the first time the cost-effectiveness of DT LVADs compared with medical management (MM) in the NHS England. METHODS AND RESULTS: We developed a Markov multiple-state economic model using NHS cost data. LVAD survival and adverse event rates were derived from the ENDURANCE Supplemental Trial. MM survival was based on Seattle Heart Failure Model estimates in the absence of contemporary clinical trials for this population. Incremental cost-effectiveness ratios (ICERs) were calculated over a lifetime horizon. A discount rate of 3.5% per year was applied to costs and benefits. Deterministic ICER was £46 207 per quality-adjusted life year (QALY). Costs and utilities were £204 022 and 3.27 QALYs for the LVAD arm vs. £77 790 and 0.54 QALYs for the MM arm. Sensitivity analyses confirmed robustness of the primary analysis. CONCLUSIONS: The implantation of the HeartWare™ HVAD™ System in patients ineligible for cardiac transplantation as DT is a cost-effective therapy in the NHS England healthcare system under the end-of-life willingness-to-pay threshold of £50 000/QALY, which applies for VAD patients.

Responding to Ventricular Assist Device Recalls: An Ethical Guide for Mechanical Circulatory Support Programs.

We discuss the ethical responsibilities of mechanical circulatory support (MCS) programs in the context of cardiac device recalls, particularly the near-simultaneous recalls of Abbott HeartMate 3 left ventricular assist device (VAD) and Medtronic HVAD devices in 2018. We consider MCS programs' ethical responsibilities toward patients who already have VADs and their caregivers, as well as the impact of recalls on informed consent and shared decision-making in patients under consideration for new VADs. Timely communication to affected patients is imperative throughout the recall process. MCS programs are required to notify existing VAD patients about the nature and likelihood of risk. A press release from the device manufacturer or other press reports may occur before MCS teams learn about the recall. This leads to a disclosure gap, where the programs are actively deciding on an appropriate action plan while simultaneously fielding patient concerns. From an ethics standpoint, if all device users are owed the recall information from the manufacturer, all patients are owed the information from their treating team. The question is what to disclose specifically, and how.

Cost-Effectiveness of Thoracotomy Approach for the Implantation of a Centrifugal Left Ventricular Assist Device.

This study reports the first analysis regarding cost-effectiveness of left ventricular assist device (LVAD) implantation via thoracotomy. Cost-effectiveness of LVADs implanted via the traditional surgical approach of sternotomy has been improved through the years because of technological advances, along with understanding the importance of patient selection and postimplant management have on positively affecting outcomes. Given the positive clinical outcomes of the thoracotomy approach, we seek to study the cost-effectiveness of a centrifugal LVAD via this less invasive approach. We developed a Markov model. Survival and quality of life inputs (QALY) for the LVAD arm were based on data from the LATERAL clinical trial. For the Medical Management arm, survival was derived from the Seattle Heart Failure Model. The heart transplant probability was derived from INTERMACS. Survival after heart transplantation used International Society for Heart and Lung Transplantation data. Cost inputs were calculated based on Medicare data and past literature. The incremental cost-effectiveness ratio was found to be $64,632 per quality adjusted life year and $57,891 per life year in the bridge to transplant indication. These results demonstrate further improvement in the overall cost-effectiveness of LVAD therapy and confirm implantation of LVADs via a less invasive approach as being cost-effective.

Left Ventricular Assist Device Inflow Cannula Insertion Depth Influences Thrombosis Risk.

Left ventricular assist device (LVAD) use has continued to grow. Despite recent advances in technology, LVAD patients continue to suffer from devastating complications, including stroke and device thrombosis. Among several variables affecting thrombogenicity, we hypothesize that insertion depth of the inflow cannula into the left ventricle (LV) influences hemodynamics and thrombosis risk. Blood flow patterns were studied in a patient-derived computational model of the LV, mitral valve (MV), and LVAD inflow cannula using unsteady computational fluid dynamics (CFD). Hundreds of thousands of platelets were tracked individually, for two inflow cannula insertion depth configurations (12 mm-reduced and 27 mm-conventional) using platelet-level (Lagrangian) metrics to quantify thrombogenicity. Particularly in patients with small LV dimensions, the deeper inflow cannula insertion resulted in much higher platelet shear stress histories (SH), consistent with markedly abnormal intraventricular hemodynamics. A larger proportion of platelets in this deeper insertion configuration was found to linger in the domain for long residence times (RT) and also accumulated much higher SH. The reduced inflow depth configuration promoted LV washout and reduced platelet SH. The increase of both SH and RT in the LV demonstrates the impact of inflow cannula depth on platelet activation and increased stroke risk in these patients. Inflow cannula depth of insertion should be considered as an opportunity to optimize surgical planning of LVAD therapy.

Comparison of Neurologic Event Rates Among HeartMate II, HeartMate 3, and HVAD.

Strokes remain a leading cause of morbidity and mortality in patients with ventricular assist devices (VADs). Varying study populations, event definitions, and reporting methods make direct comparison of neurologic event risk across clinical trials and registries challenging. We aim to highlight important differences among major VAD studies and standardize rates of neurologic events to facilitate a comprehensive and objective comparison. We systematically identified and analyzed key clinical trials and registries evaluating the HeartMate II (HMII), HeartMate 3 (HM3), and HVAD devices. Reported neurologic events were nonexclusively categorized into ischemic stroke, hemorrhagic stroke, disabling stroke, fatal stroke, and other neurologic events per the studies' definitions. Event rates were standardized to events per patient-year (EPPY) and freedom from event formats. Seven key clinical trials and registries were included in our analysis. There is significant variation and overlap in neurologic event rates for the three VAD platforms across clinical trials (all neurologic events [EPPY]: HM3 0.17-0.21; HMII 0.19-0.26; HVAD 0.16-0.28). None performs consistently better for all types of neurologic events. Furthermore, stroke rates among VAD trials correlated with baseline stroke risk factors including ischemic etiology, history of atrial fibrillation, and history of prior stroke.

Accuracy of Doppler blood pressure measurement in HeartMate 3 ventricular assist device patients.

AIMS: Optimal blood pressure (BP) control is imperative to reduce complications, especially strokes, in continuous flow ventricular assist device (VAD) patients. Doppler BP has been shown to be an accurate and reliable non-invasive BP measurement method in HeartMate II and HVAD patients. We examined whether Doppler BP is also accurate in patients with the HeartMate 3 VAD. METHODS AND RESULTS: In a prospective, longitudinal cohort of HeartMate 3 patients, arterial line BP and simultaneously measured Doppler opening pressure were obtained. Correlation and agreement between Doppler opening pressure and arterial line mean arterial pressure (MAP) versus systolic blood pressure (SBP) were analysed, as well as the effect of pulse pressure on the accuracy of Doppler opening pressure. A total of 589 pairs of simultaneous Doppler opening pressure and arterial line pressure readings were obtained in 43 patients. Doppler opening pressure had good correlation with intra-arterial MAP (r = 0.754) and more closely approximated MAP than SBP (mean error 2.0 vs. -8.6 mmHg). Pulse pressure did not have a clinically significant impact on the accuracy of the Doppler BP method. These results in HeartMate 3 patients are very similar to previous results in HeartMate II and HVAD patients. CONCLUSIONS: Doppler BP method should be the default non-invasive BP measurement method in continuous flow VAD patients including patients implanted with the HeartMate 3.

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

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.