Centrifugal Left Ventricular Assist Device Research Articles

Early Stroke Following Durable Left Ventricular Assist Device (LVAD) Implantation: An Analysis of The Society of Thoracic Surgeons Intermacs National Database

BackgroundStroke remains a devastating complication of durable left ventricular assist device (LVAD) therapy. This study evaluated the incidence and risk factors for early stroke within 7 days following LVAD implantation investigating both traditional pre-implant and new intraoperative variables collected by The Society of Thoracic Surgeons (STS) Intermacs National Database. MethodsSTS Intermacs was queried for patients undergoing implantation of a fully magnetically levitated centrifugal LVAD between 11/25/2020 and 6/30/2023. STS Intermacs stroke definitions were used to identify patients who suffered a stroke within the first 7 postoperative days (POD). A multivariable logistic regression model was created to generate adjusted odd ratios (OR) for variables associated with early stroke. ResultsAmong 6950 patients in the study cohort, 5.9% (413/6950) developed a stroke after a median follow-up of 11 months, with 50% (205/413) of strokes occurring within 7 days after LVAD implantation. Of the strokes occurring during POD 0-7, 70% (144/205) occurred on POD 0-2. By multivariable analysis, the following factors were associated with early stroke: older age (70 vs. 50; OR 1.4, P=0.0129), white race (OR 1.5, P=0.0078), pre-implant temporary MCS bridge (temporary LVAD only: OR 1.6, ECMO only: OR 1.7, combination of both devices: OR 3.3; P=0.0001) and presence of an unremoved left atrial clot (OR 8.0, P<0.0001). ConclusionA significant proportion of strokes occur within the first 7 days following LVAD implantation, particularly within the first 2 days. In addition to pre-implant variables, we identified modifiable intraoperative factors associated with stroke that provide an opportunity for further risk mitigation and improvement in quality of care.

Transient Performance Analysis of Centrifugal Left Ventricular Assist Devices Coupled With Windkessel Model: Large Eddy Simulations Study on Continuous and Pulsatile Flow Operation.

Computational fluid dynamics (CFD) simulations are widely used to develop and analyze blood-contacting medical devices such as left ventricular assist devices (LVADs). This work presents an analysis of the transient behavior of two centrifugal LVADs with different designs: HeartWare VAD and HeartMate3. A scale-resolving methodology is followed through Large Eddy Simulations, which allows for the visualization of turbulent structures. The three-dimensional (3D) LVAD models are coupled to a zero-dimensional (0D) 2-element Windkessel model, which accounts for the vascular resistance and compliance of the arterial system downstream of the device. Furthermore, both continuous- and pulsatile-flow operation modes are analyzed. For the pulsatile conditions, the artificial pulse of HeartMate3 is imposed, leading to a larger variation of performance variables in HeartWare VAD than in HeartMate3. Moreover, CFD results of pulsatile-flow simulations are compared to those obtained by accessing the quasi-steady maps of the pumps. The quasi-steady approach is a predictive tool used to provide a preliminary approximation of the pulsatile evolution of flow rate, pressure head, and power, by only imposing a speed pulse and vascular parameters. This preliminary quasi-steady solution can be useful for deciding the characteristics of the pulsatile speed law before running a transient CFD simulation, as the former entails a significant reduction in computational cost in comparison to the latter.

Inhospital outcomes of implantation of a centrifugal left ventricular assist device in patients with endstage heart failure: experience of the Chazov National Medical Research Center of Cardiology

Aim. To study the inhospital outcomes of implantation of a centrifugal left ventricular assist device (LVAD) in patients with end-stage heart failure (HF).Material and methods. There were following inclusion criteria: estimated body surface area &gt;1,2 m2, end-stage HF, LV ejection fraction &lt;30%, cardiac index &lt;2,2 l/min, long-term optimal therapy for HF. Patients were considered for implantation of a centrifugal (LVAD) as part of the final therapy, but subsequent heart transplantation was not ruled out if appropriate.Results. LVAD was implanted in 23 patients. All patients were men (mean age, 59,1±10 years; mean body mass index, 26±4,6 kg/m2). Ten patients had dilated cardiomyopathy, while 13 — ischemic one. Diabetes was revealed on in 3 (13%) patients, while chronic kidney disease and cancer — in 3 (13%) and 4 (17%) patients, respectively. The mean value of the six-minute walk test (6MWT) upon admission to the hospital was 257±71 meters. In one patient with gastric cancer, the device was implanted as a part of bridging therapy strategy. Thirty-day mortality was 9% (n=2). One of the deceased patients had a long history of end-stage heart failure, body weight deficiency, and frailty with severe muscle weakness. The second death was the result of early postoperative right ventricular failure. At discharge, patients had optimal LVAD performance based on anthropometric characteristics and physical activity. According to echocardiography, the criteria for unloading the left heart chambers have been achieved. The distance of 6MWT at discharge was 298±78 meters.Conclusion. Inhospital outcomes of implantation of a centrifugal LVAD in patients with end-stage HF demonstrate high efficiency in supporting systemic hemodynamics with an acceptable safety profile in patients with extremely high perioperative risk.

Numerical simulation analysis of multi-scale computational fluid dynamics on hemodynamic parameters modulated by pulsatile working modes for the centrifugal and axial left ventricular assist devices

Continuous flow (CF) left ventricular assist devices (LVAD) operate at a constant speed mode, which could result in increased risk of adverse events due to reduced vascular pulsatility. Consequently, pump speed modulation algorithms have been proposed to augment vascular pulsatility. However, the quantitative local hemodynamic effects on the aorta when the pump is operating with speed modulation using different types of CF-LVADs are still under investigation. The computational fluid dynamics (CFD) study was conducted to quantitatively elucidate the hemodynamic effects on a clinical patient-specific aortic model under different speed patterns of CF-LVADs. Pressure distribution, wall shear stress (WSS), time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and velocity were calculated to compare their differences at constant and pulsatile speeds under centrifugal and axial LVAD support. Results showed that pulse pressure on the aorta was significantly larger under pulsatile speed mode than that under constant speed mode for both CF-LVADs, indicating enhanced aorta pulsatility, as well as the higher peak blood flow velocity on some representative slices of aorta. Pulsatile speed modulation enhanced peak WSS compared to constant speed; high TAWSS region appeared near the branch of left common carotid artery and distal aorta regardless of speed modes and CF-LVADs but these regions also had low OSI; RRT was almost the same for all the cases. This study may provide a basis for the scientific and reasonable selection of the pulsatile speed patterns of CF-LVADs for treating heart failure patients.

Treatment Strategies and Outcomes of Right Ventricular Failure Post Left Ventricular Assist Device Implantation: An INTERMACS Analysis.

Right heart failure (RHF) management after left ventricular assist device (LVAD) implantation includes inotropes, right ventricular mechanical support, and heart transplantation. The purpose of this study is to compare different RHF treatment strategies in patients with a magnetically levitated centrifugal LVAD. A total of 6,632 Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) patients from 2013 to 2020 were included. Of which, 769 (69.6%) patients (group 1) were supported with inotropes (≥14 days post-LVAD implantation), 233 (21.1%) patients (group 2) were supported with temporary right ventricular assist device (RVAD) that was implanted during LVAD implant, 77 (7.0%) patients (group 3) with durable centrifugal RVAD implanted during the LVAD implant, and 26 (2.4%) patients (group 4) were supported with RVAD (temporary or permanent), which was implanted at a later stage. Groups 1 and 4 had higher survival rates in comparison with group 2 (hazard ratio [HR] = 0.513, 95% confidence intervals [CIs] = 0.402-0.655, p < 0.001, versus group 1) and group 3 (HR = 0.461, 95% CIs = 0.320-0.666, p < 0.001, versus group 1). Patients in group 3 showed higher heart transplantation rates at 12 and 36 months as compared with group 1 (40.4% and 46.6% vs. 21.9% and 37.4%, respectively), group 2 (40.4% and 46.6% vs. 25.8% and 39.3%, respectively), and group 4 (40.4% and 46.6% vs. 3.8% and 12.0%, respectively). Severe RHF post-LVAD is associated with poor survival. Patients with LVAD who during the perioperative period are in need of right ventricular temporary or durable mechanical circulatory support constitute a group at particular risk. Improvement of devices tailored for right ventricular support is mandatory for further evolution of the field.

CARD10: Transapical Left Ventricular Assist Device Implantation Using a Novel Accessory in Swine

Background: Conventional left ventricular assist devices (LVADs) require an anastomosis of the outflow graft to the ascending aorta. We developed and tested a LVAD accessory, which combines pump in- and transaortic outflow in a dual lumen adapter, thus, allowing LVAD implantation solely via the left ventricular apex. Methods: The LVAD accessory (Fig. A) consisted of a 3D printed titanium inflow and a 12 mm outflow stent graft. The accessory in combination with a centrifugal LVAD (HeartMate 3, HM3, Abbott, USA) was implanted in 10 adult female Landrace pigs (104 ± 13 kg). A balloon catheter (14 mm Atlas Gold PTA Dilatation Catheter, BD, USA) was introduced via the left femoral artery and placed in the left ventricle. After lower partial sternotomy, pericardiotomy and fixation ring attachment, apical coring was performed in a standard fashion on the beating heart using cardiopulmonary bypass. The balloon was exteriorized, inflated in the outflow graft and both, the accessory with the attached outflow graft, were pulled into the left ventricle and the aorta. The accessory was attached to the fixation ring. The LVAD was connected and deaired, and the balloon catheter was removed. Results: After successful LVAD implantation in all animals, echocardiography revealed no signs of aortic or mitral regurgitation. In eight animals ramp testing was performed. The HM3 flow estimate increased from 3.7 ± 1.2 L/min at 4’500 rpm to 5.4 ± 1.2 L/min at 7’200 rpm (Fig. B). Post-mortem examination (Fig. C) revealed correct placement of the LVAD accessory with the inflow in the left ventricle (blue arrow) and the outflow graft across the aortic valve (yellow arrow). There were neither signs of damage of the aortic (*) or mitral valve (+) nor signs of thrombosis. Conclusion: The novel accessory in combination with a centrifugal LVAD allowed safe and less-invasive LVAD implantation. Ramp testing revealed effective left ventricular support in the acute swine model. Further testing in a chronic heart failure model will be performed to validate these results.

CARD33: Analyzing Off-Design Point Operation for LVADs Using Flexible Rotor Blades

Introduction: The use of left ventricular assist devices (LVADs) has exhibited clinical success in both destination and bridge-to-transplant therapy for patients suffering from end stage heart failure (HF). However, the operating speeds of the LVAD are often tuned to accommodate patient variability which might lead to operating the LVAD at off design points. This could cause a potential loss in efficiency and an increased risk of thrombosis/hemolysis. The flexible rotor blades will deform in response to the complex inflow conditions, and with an appropriate geometry and flexibility generate a flatter performance curve. This would not only improve the preload sensitivity of the LVAD but also offer a wider range of operation with optimal efficiencies. In this study, we investigate the hydraulic performance of varied impeller geometries for a centrifugal LVAD with flexible rotor blades at pediatric and adult pressure/flow conditions. Methods: The flexible rotor blades are manufactured by casting polyurethane resin (Easton, PA) of shore hardness 60A in a four-piece mold. These mold pieces were 3D printed using a J850 Pro (Stratasys Ltd, MN, USA). The inlet angle of the blades was set at 20o and the outlet angle was varied from 10o to 70o. The blade thickness was 1.2 mm and the blade height was 7 mm. These flexible rotor blades were evaluated on a hydrodynamic test setup with 40%wt glycerin solution as the working fluid. This setup consisted of a motor to drive the rotor, a flow probe, pressure transducers upstream and downstream of the rotor and a pinch valve to vary the downstream resistance. The mounted rotor is driven at 3000 RPM, and the flow produced by the rotor is measured as the pinch valve incrementally increases downstream resistance. The hydrodynamic results were then scaled to achieve pediatric and adult pressure/flow conditions of 70mmHg-2L/min and 90mmHg-5L/min respectively. To analyze the off-design point operation, the gradient of the pressure/flow curve at two operating conditions was calculated using the equation in Figure 1. Results: For a flexible rotor blade with an outlet angle of 30o, the operating speed for pediatric and adult pressure/flow conditions was found to be 2550 RPM and 3230 RPM respectively. The gradient at the pediatric and adult operating conditions was – 6.14 mmHg/ (L/min)-1 and – 11.12 mmHg/ (L/min)-1. Results for the remaining flexible rotor blades is currently being generated and will be presented at the conference. Conclusion: We successfully analyzed the hydraulic performance of a centrifugal LVAD with flexible rotor blades. The flexible rotor blades proposed in this study will be a positive step towards improving the off-design point operation of LVADs and thereby, reducing the blood damage associated with it.Figure 1. Equation used to calculate the gradient of the pressure/flow curve at two operating conditionsFigure 2. Hydrodynamic Test Setup SchematicFigure 3. Hydrodynamic Performance Results for Flexible Rotor Blade with 30o Outlet Angle

(962) Redesign and Improvement of Hemodynamics in a Centrifugal Left Ventricular Assist Device Using Heuristic Aerodynamic Techniques on the Bladed Flow Domain

(962) Redesign and Improvement of Hemodynamics in a Centrifugal Left Ventricular Assist Device Using Heuristic Aerodynamic Techniques on the Bladed Flow Domain

Abstract 15045: Impact of Left Ventricular Assist Device (LVAD) Type on Arrhythmic Outcomes in Patients With Continuous Flow LVADs

Introduction: Cardiac arrhythmias are common in continuous flow left ventricular assist device (LVAD) recipients. The impact of axial vs. intrapericardial centrifugal LVAD pumps on arrhythmia incidence and associated clinical outcomes is unclear. Hypothesis: This multicenter study evaluated the impact of LVAD type (axial vs. centrifugal) on incidence of atrial and ventricular arrhythmias, ICD shocks and mortality in LVAD patients. Methods: Analysis was done on 536 patients who underwent LVAD implantation at 5 US centers from 2008 to 2016. The groups were divided based on their LVAD type (axial - HeartMate II [HMII, n=433] vs. centrifugal - HeartWare (HW, n=103). Baseline characteristics as well as incidence of post-LVAD atrial arrhythmias (PL-AA), ventricular arrhythmias (PL-VA) and ICD shocks were analyzed in these groups. Multivariable Cox Regression analysis was used to identify predictors of survival. Results: Of 536 patients, 433 had HMII axial LVAD and 103 had HW centrifugal VAD implant. At baseline, HMII group had more males, higher proportion of CRT-D and higher prevalence of AA (Table 1A). Left ventricular dimensions were similar between groups. During a median follow-up of 537 days of LVAD support, incidence of PL-VA and ICD shocks were significantly higher in the HM2 group compared to HW group whereas incidence of PL-AA was not significantly different (Table 1A). In multivariable Cox Regression analysis, LVAD indication was the only variable that predicted survival (Table 1B). Type of LVAD (axial vs. centrifugal) was not associated with survival (HMII vs. HW - HR 1.04, P=0.48). Conclusions: In this multi-center continuous flow LVAD cohort, axial HM2 VAD patients had a higher incidence of PL-VA and ICD shocks. Type of LVAD (axial vs. centrifugal) was not associated with survival.

Comparison of the Hemocompatibility of an Axial and a Centrifugal Left Ventricular Assist Device in an In Vitro Test Circuit.

Background: Hemocompatibility of left ventricular assist devices is essential for preventing adverse events. In this study, we compared the hemocompatibility of an axial-flow (Sputnik) to a centrifugal-flow (HeartMate 3) pump. Methods: Both pumps were integrated into identical in vitro test circuits, each filled with 75 mL heparinized human blood of the same donor. During each experiment (n = 7), the pumps were operated with equal flow for six hours. Blood sampling and analysis were performed on a regular schedule. The analytes were indicators of hemolysis, coagulation activation, platelet count and activation, as well as extracellular vesicles. Results: Sputnik induced higher hemolysis compared to the HeartMate 3 after 360 min. Furthermore, platelet activation was higher for Sputnik after 120 min onward. In the HeartMate 3 circuit, the platelet count was reduced within the first hour. Furthermore, Sputnik triggered a more pronounced increase in extracellular vesicles, a potential trigger for adverse events in left ventricular assist device application. Activation of coagulation showed a time-dependent increase, with no differences between both groups. Conclusions: This experimental study confirms the hypothesis that axial-flow pumps may induce stronger hemolysis compared to centrifugal pumps, coming along with larger amounts of circulating extracellular vesicles and a stronger PLT activation.

Reduction of Adverse Events With Phosphodiesterase 5 Inhibitors Post LVAD Implantation: Is It Time for a Randomized Trial?

The improved survival of patients with advanced heart failure after left ventricular assist device (LVAD) implantation together with the scarcity of donor hearts has significantly increased the population of LVAD-supported patients. However, despite the improvement in LVAD technology and the advent of third-generation continuous flow LVADs, complications such as those related to hemocompatibility and stroke rates remain ongoing clinical challenges. Thus, improvement in LVAD technology should be coupled with innovative medical management to further reduce adverse events. We have previously shown a strong association between post LVAD implant phosphodiesterase-5 inhibitors (PDE-5i) use and fewer thrombotic events, as well as improved survival in 2 observational studies. We caution, nevertheless, the use of PDE-5i based on these observations and encourage clinicians to support enrollment in a randomized control trial. A randomized control trial will determine the efficacy and safety of PDE-5i use after implantation in patients with a centrifugal flow LVAD.

In Vivo Evaluation of a Physiologic Control System for Rotary Blood Pumps Based on the Left Ventricular Pressure-Volume Loop.

Current generation continuous flow assist devices to operate at a fixed speed, which limits preload response and exercise capacity in left ventricular assist device (LVAD) patients. A feedback control system was developed to automatically adjust pump speed based on direct measurements of ventricular loading using a custom cannula tip with an integrated pressure sensor and volume-sensing conductance electrodes. The input to the control system is the integral of the left ventricular (LV) pressure versus conductance loop (PGA) over each cardiac cycle. The feedback control system adjusts pump speed based on the difference between the measured PGA and the desired PGA. The control system and cannula tip were tested in acute ovine studies (n = 5) using the HeartMate II LVAD. The preload response of the control system was evaluated by partially occluding and releasing the inferior vena cava using a vessel loop snare. The cannula tip was integrated onto a custom centrifugal flow LVAD and tested in a 14-day bovine study. The control system adjusted pump support to maintain constant ventricular loading: pump speed increased (decreased) following an increase (decrease) in preload. This study demonstrated in vivo the Starling-like response of an automatic pump control system based on direct measurements of LV loading.

Infectious complications following contemporary left ventricular assist device implantation.

The aim of this study is to evaluate the source of infectious complications following contemporary left ventricular assist device (LVAD) implantation and to determine the impact of infections on patient outcomes. All patients who underwent centrifugal LVAD implantation between 2014 and 2020 at a single center were retrospectively reviewed. Postimplant infections were categorized as VAD-specific, VAD-related, or non-VAD according to previously published definitions. Postoperative survival and freedom from readmission were assessed using Kaplan-Meier analysis. Univariable and multivariable analyses were performed to determine the risk factors for postoperative infectious complications. A total of 212 patients underwent centrifugal LVAD implantation (70 HeartMate 3, 142 HeartWare HVAD) during the study period. One hundred and two patients (48.1%) developed an infection, including 34 VAD-specific, 11 VAD-related, and 57 non-VAD. Staphylococcus species were the most common source of postoperative infection (n = 57, 33.7%). In multivariable analysis, diabetes significantly impacted overall postoperative infection rate. At 12 and 24 months, respectively, Kaplan-Meier survival was 81.1% and 61.6% in the infection group and 83.4% and 78.1% in the noninfection group (p = 0.006). Within the total cohort, 12- and 24-month freedom from infection were 46.2% and 31.9%, respectively. Patients with infectious complication had significantly lower rate of transplantation (16.4% vs. 43.6%; p < 0.001), increased overall mortality (46.3% vs. 17.3%, p < 0.001), and increased rates of noncardiac readmission (58.2% vs. 37.3%, p = 0.007). Infections are common following contemporary LVAD implantation and are most commonly non-VAD related. Patients with postoperative infectious complications have significantly reduced rates of transplantation, survival, and freedom from noncardiac readmission.

Proteomic Profiles Of Left Ventricular Assist Device Implantation

Introduction Left ventricular assist devices (LVADs) are widely used to support patients with advanced heart failure, but conversion from normal pulsatile flow is known to lead to vascular remodeling and ultimately may contribute to adverse vascular events. The underlying biology of such changes remains poorly understood. Hypothesis: High-throughput plasma proteomic profiling before and after LVAD implantation will identify novel biomarkers and protein mediators of LVAD cardiovascular effects. Methods Fifteen patients undergoing HeartMate II implantation at University of Colorado Hospital had serial plasma samples collected pre-LVAD (day 0) as well as days 14 and 60 after LVAD implant. Proteomic profiling was performed with 1,196 antibody-based proteomic probes on the Olink® platform. Linear mixed effects models of log2-scaled proteomic measurements, adjusted for renal function, compared protein levels between time points. GO Biological Pathway analysis was performed using both over-representation analysis (ORA) and gene set enrichment analysis (GSEA). A false discovery rate (FDR) of 5% adjusted for multiple comparisons within each analysis. Results The mean age was 57 years; 3 participants (20%) were female, 3 (20%) were Black, and 9 (60%) had a non-ischemic cardiomyopathy. At day 14, 300 proteins were significantly different from day 0 at FDR<5%. At day 60, 161 proteins differed from day 0 at FDR<5% (Figure 1a). Known biomarkers showed expected changes: B-type natriuretic peptide decreased significantly (day 14 vs day 0 β = -0.87 ± 0.26, p = 0.002; day 60 vs day 0 β = -1.19 ± 0.23, p = 1 × 10−5) as did ST2 (day 60 vs day 0 β = -0.72 ± 0.26, p = 0.01). Four proteins had statistically significant (FDR < 5%) differences at 0 vs 14 and 14 vs 60 days, highlighting novel findings (Figure 1b): CCN3, DSG3, THBS4, and COMP are all involved in extracellular matrix biology, and DSG3 and CCN3 are implicated in cell-cell communication in myocardium. Indeed, ORA and GSEA identified enrichment for blood vessel development (p = 4 × 10−6, p = 4 × 10−5, respectively) and cell adhesion (p = 9 × 10−5, p = 8 × 10−5). Conclusions Proteomic profiling identified novel protein changes following LVAD implantation, particularly among proteins involved in blood vessel development and cell adhesion. Further work is needed to understand biological implications and determine if these proteins also associate with clinical outcomes in larger cohorts and in axial compared to centrifugal flow LVADs. Left ventricular assist devices (LVADs) are widely used to support patients with advanced heart failure, but conversion from normal pulsatile flow is known to lead to vascular remodeling and ultimately may contribute to adverse vascular events. The underlying biology of such changes remains poorly understood. Hypothesis: High-throughput plasma proteomic profiling before and after LVAD implantation will identify novel biomarkers and protein mediators of LVAD cardiovascular effects. Fifteen patients undergoing HeartMate II implantation at University of Colorado Hospital had serial plasma samples collected pre-LVAD (day 0) as well as days 14 and 60 after LVAD implant. Proteomic profiling was performed with 1,196 antibody-based proteomic probes on the Olink® platform. Linear mixed effects models of log2-scaled proteomic measurements, adjusted for renal function, compared protein levels between time points. GO Biological Pathway analysis was performed using both over-representation analysis (ORA) and gene set enrichment analysis (GSEA). A false discovery rate (FDR) of 5% adjusted for multiple comparisons within each analysis. The mean age was 57 years; 3 participants (20%) were female, 3 (20%) were Black, and 9 (60%) had a non-ischemic cardiomyopathy. At day 14, 300 proteins were significantly different from day 0 at FDR<5%. At day 60, 161 proteins differed from day 0 at FDR<5% (Figure 1a). Known biomarkers showed expected changes: B-type natriuretic peptide decreased significantly (day 14 vs day 0 β = -0.87 ± 0.26, p = 0.002; day 60 vs day 0 β = -1.19 ± 0.23, p = 1 × 10−5) as did ST2 (day 60 vs day 0 β = -0.72 ± 0.26, p = 0.01). Four proteins had statistically significant (FDR < 5%) differences at 0 vs 14 and 14 vs 60 days, highlighting novel findings (Figure 1b): CCN3, DSG3, THBS4, and COMP are all involved in extracellular matrix biology, and DSG3 and CCN3 are implicated in cell-cell communication in myocardium. Indeed, ORA and GSEA identified enrichment for blood vessel development (p = 4 × 10−6, p = 4 × 10−5, respectively) and cell adhesion (p = 9 × 10−5, p = 8 × 10−5). Proteomic profiling identified novel protein changes following LVAD implantation, particularly among proteins involved in blood vessel development and cell adhesion. Further work is needed to understand biological implications and determine if these proteins also associate with clinical outcomes in larger cohorts and in axial compared to centrifugal flow LVADs.

Postimplant Phosphodiesterase-5 Inhibitor Use in Centrifugal Flow Left Ventricular Assist Devices

ObjectivesThis study examined the association between phosphodiesterase-5 inhibitor (PDE-5i) use and outcomes in patients with contemporary centrifugal flow left ventricular assist devices (LVADs). BackgroundPDE-5i use may affect outcomes in patients with continuous flow LVADs. MethodsPatients enrolled in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support), with HeartMate 3 (n = 4,628) or HeartWare Ventricular Assist Device (HVAD) (n = 2,601) implant were included in the analysis. The mean duration of follow-up was 11.94 ± 8.65 months. PDE-5is were used in 2,173 patients. The primary endpoint was the composite of all-cause mortality, ischemic stroke, and pump thrombosis. Propensity matching and stabilized inverse probability of treatment weights were used to adjust for baseline differences between patients receiving and not receiving PDE-5i. Adjusted Cox proportional hazards analysis was performed for each outcome. ResultsThe primary endpoint was lower in the PDE-5i group (adjusted HR: 0.77; 95% CI: 0.69-0.86; P < 0.0001; HeartMate 3: adjusted HR: 0.77; 95% CI: 0.64-0.92; P = 0.0044; HVAD: adjusted HR: 0.76; 95% CI: 0.66-0.88; P = 0.0002). All-cause mortality was lower with PDE-5is (adjusted HR: 0.75; 95% CI: 0.65-0.86; P < 0.0001; HeartMate 3: adjusted HR: 0.70; 95% CI: 0.57-0.86; P = 0.0007; HVAD: adjusted HR: 0.78; 95% CI: 0.65-0.94; P = 0.0098) and fewer ischemic strokes with PDE-5is were observed (adjusted HR: 0.71; 95% CI: 0.56-0.89; P = 0.003; HeartMate 3: adjusted HR: 0.67; 95% CI: 0.45-0.99; P = 0.045; HVAD: adjusted HR: 0.73; 95% CI: 0.56-0.97; P = 0.03). LVAD thrombosis was unchanged with PDE-5is, with overall low event rates observed. ConclusionsPostimplant PDE-5i use was associated with lower mortality and ischemic strokes in patients with centrifugal flow LVADs.

Echo-guided LVAD speed optimization for exercise maximization

Abstract Background Continuous-flow left ventricular assist devices (LVAD) are becoming a destination therapy in patients with end-stage left ventricular dysfunction and a competitive method for heart transplantation. Current generation pumps operate with a fixed rotation speed and do not have the automatic speed adjustment capability. However, it was shown that acceleration of the pump speed during stress test increases the maximum exercise tolerance. Purpose The study aimed to evaluate the concept of dynamic pump speed optimization based on the echocardiographic assessment of aortic valve opening (AVO) during the cardiopulmonary exercise test (CPET). Methods Patients with implanted third-generation centrifugal continuous-flow LVAD's with hydrodynamic bearing were prospectively included. Two CPET's were performed after resting speed optimization. The first one with maintained baseline pump speed settings, and the second one with gradually increased speed depending on live echocardiographic imaging. The sequence of tests was random. Results Exercise AVO was apparent in all 22 included patients. The resting pump speed was 2691 RPM and incremented on average by 566 RPM (20%). Pump power and flow raised from 5.6 to 9.8 Watts (p&amp;lt;0.0001) and from 5.8 to 7.3 l/min (p&amp;lt;0.0001), respectively. Peak VO2 increased from 11.1 to 12.8 ml/kg/min (p=0.0003) and maximum workload from 1.1 to 1.2 W/kg (p=0.03). The Borg scale exertion level decreased from 15.2 to 13.5 (p=0.0049). There was a visible trend towards longer exercise time (36s) but no statistical significance was achieved (p=0.1). Conclusion Ultrasonographic AVO analysis is possible during CPET's in patients supported with LVAD. Dynamic echo-guided pump speed adjustment based on the AVO improves exercise tolerance, augments peak VO2 consumption and maximal workload. An automatic speed adjustment in the next generations of LVAD controllers might improve functional capacity and requires further basic, technological and clinical research. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): 1. Cor Aegrum Foundation of Cardiac Surgery Development in Cracow2. Medtronic Poland Sp. z o.o.

Evaluation of aspirin platelet inhibition in left ventricular assist device population.

Aspirin therapy is recommended in durable left ventricular assist device (LVAD) patients to prevent thromboembolic complications. Up to 30% of patients treated with aspirin may demonstrate aspirin resistance, which has been related to thrombotic complications. However, it is unknown whether individual patients exhibit temporal alterations in aspirin sensitivity during LVAD support. We hypothesized that aspirin platelet inhibition would wane after the initial postimplant period. This was a retrospective, observational, single center study conducted at an academic medical center. This study evaluated changes in aspirin platelet inhibition over the first 6 months of LVAD support. Patients who underwent placement of centrifugal LVAD with aspirin platelet sensitivity assays were included for analysis. Aspirin responsiveness was assessed postimplant after 5 days, 3 months, and 6 months. A total of 28 patients were included for analysis of which 7% of patients were aspirin resistant initially. At 3 months, 32% (odds ratio [OR], 6.1, p = .03) of patients were aspirin resistant and 28% (OR, 4.1, p = .1) at 6 months. Over the first 3 months postimplant, the odds of aspirin resistance increased sixfold and remained relatively constant at 6 months. Patients who were aspirin resistant and received an increase in aspirin dose at 3 months subsequently had a sensitive ARU at 6 months. Aspirin responsiveness not only varies between patients but can significantly wane within individual LVAD patients over time. Additional study is needed to determine if monitoring aspirin resistance may prevent thrombotic complications after LVAD implantation.

The ever-changing field of mechanical circulatory support: new challenges at the advent of the 'single device era'.

The ever-changing field of mechanical circulatory support: new challenges at the advent of the 'single device era'.

ELSO Interim Guidelines for Venoarterial Extracorporeal Membrane Oxygenation in Adult Cardiac Patients.

ELSO Interim Guidelines for Venoarterial Extracorporeal Membrane Oxygenation in Adult Cardiac Patients.

Exercise capacity following ventricular assist device implantation via thoracotomy with outflow cannula anastomosis to the descending aorta.

Left ventricular assist device (LVAD) implantation via left lateral thoracotomy with outflow cannula anastomosis to the descending aorta is an alternative technique that avoids anterior mediastinal planes and requires a single incision. This study compares changes in exercise capacity following LVAD implantation with outflow cannula anastomosis to the descending aorta versus ascending aorta. Adult patients who received a continuous flow centrifugal LVAD implantation and completed both pre- and postimplantation cardiopulmonary exercise tests (CPETs) and or 6-minute walk tests (6MWT) were included. Change in CPET parameters (maximum oxygen intake: vO2 max, oxygen uptake efficiency ratio: OUES, ventilatory efficiency ratio: vE/vCO2 Slope) and 6MWT distance were compared between ascending and descending aorta anastomosis groups. Ascending and descending aorta anastomosis cohorts included 59 and 14 patients, respectively. Pre- and postimplantation CPETs were performed 63±12days before and 216±17days following implantation. The improvement in CPET parameters (vO2 max, OUES, vE/vCO2 Slope) or 6MWT distance was not significantly different between the ascending and descending aorta anastomosis groups. This study found no significant difference in the improvement of CPET parameters or 6MWT distance between LVAD implantation via thoracotomy with outflow cannula anastomosis to descending aorta and standard implantation via sternotomy with outflow cannula anastomosis to ascending aorta.