HeartWare HVAD Research Articles

In silico Prediction of Thrombosis Risk in a Ventricular Assist Device Supported Right Heart: The Impact of Cannulation Site.

Right ventricular assist device (RVAD) associated thrombosis is a serious complication that may arise due to unfavorable blood flow dynamics (blood stasis) caused by RVAD cannula protrusion within the chambers. This study aims to investigate the thrombosis risk of cannulation via the right atrium (RA) and right ventricle (RV) (diaphragmatic) under full RVAD support using computational fluid dynamics. A HeartWare HVAD inflow cannula was virtually implanted in either the RA or RV of a rigid-walled right heart geometry (including RA, RV, superior, and inferior vena cava) extracted from computed tomography data of a biventricular support patient. Transient simulations, validated with particle image velocimetry, were performed with constant inflow. Thrombosis risk was predicted by analyzing the time-averaged blood velocity, blood stagnation volume, washout rate, and blood residence time (BRT). Results showed that RA cannulation disturbed the physiological swirling flow structure which can be found in an uncannulated RA. This led to a large low-velocity recirculation flow in the RV, increasing the thrombosis risk. Contrarily, RV diaphragmatic cannulation showed better preservation of swirling flow in the RA and flow ejection into the RV. Consequently, RV diaphragmatic cannulation exhibited a better washout rate (99% vs. 57% of old blood was replaced in 12 s), lower blood stagnation volume (0.13 ml vs. 32.85 ml), and BRT (4.2 s vs. 7.1 s) than the RA cannulation in this simulated non-pulsatile case. Our findings suggest that RV diaphragmatic cannulation had a lower thrombosis risk and might be more favorable in a full RVAD-supported setting.

Red Blood Cell Mechanical Fragility as a Potential Predictor of Long-Term Hemolysis from Ventricular Assist Devices

Introduction: Recent improvement in design and performance of Left Ventricular Assist Devices facilitate their use for destination therapy. The shear stresses in such devices can damage patients’ red blood cells (RBC), leading to increased hemolysis, which has been associated with pump thrombosis and patient mortality. Here we report an investigation assessing RBC mechanical fragility as a potential metric of blood damage and its potential utility in monitoring LVAD performance. Methods: Twenty subjects were recruited from the Center for Circulatory Support at the University of Michigan. Thirteen were implanted with the HeartWare HVAD (Medtronic, Inc.) and 7 with HeartMate 3® LVAD (HM3; Abbott Labs). Blood samples were obtained before surgery and at 1 hour, 24 hours, 1 week and 4 weeks after. Hemolysis biomarkers, total lactate dehydrogenase (LDH) and LDH isoenzymes, bilirubin, haptoglobin, and serum hemoglobin were determined through standard clinical tests. Mechanical fragility, as a metric of sub-hemolytic RBC damage, was determined using electromagnetically driven bead milling in a tube with a cylindrical bead, combined with non-invasive spectrophotometric analysis of induced hemolysis upon selected durations of the stress application. Certain variations of the stressing regime were employed for comparison. Results: RBC mechanical fragility, as assessed through some of the stress application regimes, was correlated with certain hemolysis metrics like bilirubin, LDH, and LDH1. Specifically, a subset of pre-surgery RBC mechanical fragility markers were strongly correlated with bilirubin levels measured 1 day, 1 week, and 1 month (though not immediately) after the surgery. While such correlation with unconjugated bilirubin declined in significance over time, the correlation to conjugated bilirubin reached significance at 1 month. Mechanical fragility values determined in albumin-supplemented medium at 1-day post-surgery, showed strong correlation to total LDH and LDH1 at 1-month post-surgery (p < 0.01, R2 up to 0.45), with the correlation with LDH1 stronger than with total LDH. Conclusions: These data demonstrate the potential for some RBC mechanical fragility metrics as predictive prognostic biomarkers for hemolysis induced by implantable circulatory support systems. With appropriate tailoring of testing parameters to best suit the application, mechanical fragility assays could help facilitate the transition to greater utilization of ventricular assist devices.

Left Ventricular Assist Device Thrombosis: Combined Approach by Echocardiography and Logfiles Review for Diagnosis and Management

IntroductionLeft ventricular assist devices are an established therapy for end-stage heart failure. Follow-up of these patients showed complications, such as thrombosis. Our objective was to evaluate the contribution of echocardiography — in association with HeartWare HVAD online logfiles reviews and lactate dehydrogenase titration — for diagnosis and treatment of thrombosis.MethodsSeventeen episodes of thrombosis were diagnosed in 8/20 patients with HVAD. Diagnosis was made by trans-thoracic echocardiographic blood flow velocities, logfiles review of power consumption and pump flows, and titration of lactate dehydrogenase. Data were collected at baseline routine control (Group A), during thrombosis (Group B), after thrombolysis (Group C).ResultsThrombolysis was successful in all cases; one patient died of cerebral haemorrhage. Echocardiographic maximal blood flow velocity near the inflow cannula was 598±42 cm/sec (Group B), 379.41±21 cm/sec (Group C), and 378.24±28 cm/sec (Group A) (P<0.00001). In eight (47%) cases, thrombi were visualized in the left ventricle by three-dimensional modality. Logfiles recordings of blood flows were 9.52±0.9 L/min (Group B), 4.02±0.4 L/min (Group C), and 4.04±0.4 L/min (Group A) (P<00001). Power consumption was 5.01±0.7 W (Group B), 3.45±0.2 W (Group C), and 3.46±0.2 W (Group A) (P<0.00001). Lactate dehydrogenase was 756±54 IU (Group B), 234±22 IU (Group A), and 257±36 IU (Group C) (P<0.00001).ConclusionsEchocardiography of increased maximal velocity near the inflow cannula is a sign of HVAD obstruction. Logfile reviews provide a clear picture of HVAD obstruction. Combination of echocardiographic data and review of logfiles detects signs of left ventricular assist devices thrombosis leading to a successful treatment.

HVAD versus heartmate III bridge to heart transplantation: Waitlist and posttransplant outcomes

This study compared outcomes of patients bridged with either the Heartware HVAD or Heartmate 3 (HM3) device to orthotopic heart transplantation (OHT). The United Network of Organ Sharing registry was queried to perform two separate analyses of adult, isolated OHT candidates bridged with HVAD or HM3. First, waitlist outcomes were compared among patients waitlisted 1/1/2015-3/20/2020. Second, posttransplant survival was compared among those transplanted 1/1/2015-3/20/2020. Two thousand two hundred fifty-five candidates were waitlisted within the study period, 1587 (70.4%) bridged with HVAD and 668 (29.6%) with HM3. At 1 year from waitlisting, cumulative incidence of OHT higher in the HVAD cohort (p<.001). During the same time period, 2643 patients underwent OHT, 2154 (81.5%) with prior HVAD and 489 (18.5%) with HM3. Yearly proportions of patients bridged with HM3 increased across the study period and decreased for HVAD (p<.001). HM3-bridged recipients had shorter waitlist times, longer graft cold ischemic times, and experienced a higher rate of posttransplant dialysis requirement. Unadjusted and risk-adjusted posttransplant mortality rates were similar between both groups. Posttransplant survival is equivalent regardless of device type used for bridging. However, HM3 patients had lower likelihood of reaching transplantation, which may be a reflection of the recent heart allocation policy changes.

Abstract 11259: Promoting Discharges in Pediatric Patients with Congenital Heart Disease on Ventricular Assist Device Support: An ACTION Quality Improvement Project

Introduction: Discharge of pediatric ventricular assist device (VAD) patients is lagging behind adults, especially pediatric patients with concurrent congenital heart disease (CHD). This quality improvement project aimed to increase discharge rates and decrease time to discharge for pediatric patients with CHD on VAD support. Methods: Patients with CHD implanted with HeartWare HVAD or HeartMate 3 at participating Advanced Cardiac Therapies Improving Outcomes Network (ACTION) centers were included. Baseline demographics and outcomes including explant, transplant, or death, and time to outcome was collected from April 2018 until October 2019. QI interventions (VAD Flight Plan and Discharge Journey Map) were initiated in November 2019. Percentage discharged on VAD as well as time to outcome were compared before and after intervention. Results: Twenty-six patients with CHD (18 single ventricle physiology) were identified (14 pre-intervention and 12-post). The mean age was 16 years old with 27% implanted as Intermacs profile 1. Mortality on device was high at 38%. There were 77% (n=20) considered discharge eligible (alive on device &gt; 30 days) while 42% (n=11) achieved discharge (Table 1). Mean length of stay post-implant for discharged patients was 33 days. A higher percentage of biventricular physiology were discharged (63%) compared to univentricular (33%). QI interventions did not change discharge rate (43% vs 42%), mean time to discharge (46.3 vs 43.4 days), transplant before discharge (17% vs 21%), or death before discharge (42% vs 43%) in the post-intervention group. Conclusion: Discharging CHD patients on VAD support from the hospital remains a challenge largely due to the complex and heterogenous nature of this population at the time of implant. Interventions to address optimal timing of VAD implantation and patient selection could impact outcomes.

Abstract 10901: Association of Fried's Frailty Score and Sarcopenia with Outcomes After Left Ventricular Assist Device Implantation

Introduction: Measures of frailty are predictive of morbidity and mortality in patients with left ventricular assist device (LVAD) placement. While Fried’s Frailty Assessment (FFA) is well-validated, sarcopenia has emerged as a powerful predictor. The additive value of sarcopenia to existing frailty assessments and its association with outcomes in patients undergoing LVAD implantation is not well-characterized. Hypothesis: We assessed the hypothesis that sarcopenia in addition to FFA improves the assessment of frailty and that patients identified as frail may experience worse outcomes after LVAD implantation. Methods: We evaluated 34 patients who underwent LVAD implantation at our medical center between January 2018 and December 2020. Perioperative FFA score ≥ 3 was defined as frail. Skeletal muscle indices were measured using perioperative computed tomography imaging of the psoas and pectoralis major and minor muscles areas. Sarcopenia was defined per the lowest skeletal muscle tertile with total psoas area index ≤4.45 and pectoralis muscle index ≤4.50. Results: Of the 34 patients who had LVAD placement, 12 received HeartWare HVAD and 22 received HeartMate III. Five patients met criteria for frailty based on FFA. When combined with frailty based on sarcopenia, 13 additional patients met criteria. There were no differences in age (57 vs 54.5 years, p = 0.49) or gender (89% vs 100% male, p = 0.62) between the frail and non-frail groups. On Kaplan-Meier analysis, the frail group had significantly higher rates of composite outcome of 30-day readmission and all-cause mortality (log-rank p = 0.027), (Figure 1). There was no difference in rates of transplantation. Conclusions: In conclusion, FFA is a commonly used tool for assessing frailty in patients with heart failure. The addition of sarcopenia assessment allows for higher sensitivity in identifying patients with frailty who are at risk for poor outcomes. Larger studies are needed to validate these findings.

Third generation continuous flow left ventricular assist devices; a comparative outcome analysis by device type

Abstract Background Continuous-flow left ventricular assist devices (CF-LVADs) have become a standard of care in end-stage heart failure (HF). Device-related complications remain high. Limited data exists comparing outcomes of the HeartMate 3 (HM3) and the HeartWare HVAD (HW). We aimed to analyze HM3 and HW devices implanted over the past 10 years with a focus on long-term clinical outcomes of respective patients. Methods Investigator-initiated comparative, retrospective observational analysis of all patients who underwent primary implantation of a centrifugal CF-LVAD at our tertiary care academic center between January 2010 and December 2020. Data derived from a prospective registry, and included all patients receiving a HM3 or HW device. Primary endpoint was overall (all-cause) mortality and heart transplantation. Secondary endpoints included device-related major adverse cardiac and cerebrovascular events (MACCE), as well right heart failure (RHF), gastrointestinal (GI) bleeding, driveline infections, and surgical re-interventions. Results Out of 106 primary CF-LVAD implantations, 36 (34%) received HM3 and 70 (66%) received HW. Median follow-up time was 1.48 years [interquartile range 0.67, 2.41] and did not differ between devices (p=0.739). HM3 was more often implanted in men (91.7% vs. 72.9%, p=0.024), patients were older (median 61 years [54, 66.5] vs. 52.5 years [43, 60], p&amp;lt;0.001), had a higher body mass index (BMI) (median 26.7 kg/m2 [23.4, 29.0] vs. 24.3 kg/m2 [20.7, 27.4], p=0.013), had more comorbidities and were more likely targeted for destination therapy (DT) (36.1% vs. 14.3%, p=0.010). Death occurred in 33.3% of HM3 patients, compared to 22.9% of HW patients, p=0.247 (probability of survival at 2 years 54.7% vs. 74.1%, p=0.296). After adjustment for confounders, we observed a significant 6-fold risk increase in device malfunctions for HW (hazard ratio (HR) 6.49, 95% CI [1.89, 22.32], p=0.003), but no significant differences between devices in pump thrombosis (p=0.173) or overall survival (p=0.801). Conclusions Comparing long-term outcomes between HeartMate 3 and HeartWare HVAD for LVAD support from a prospective registry, HeartWare HVAD patients had a significantly higher risk of device malfunctions. No significant differences were evident between devices in overall survival, and in respect to most clinical outcomes. Funding Acknowledgement Type of funding sources: None. KM Plot primary and secondary outcomesRisk analysis on all outcomes

Sympathetic vasoconstrictor activity before and after left ventricular assist device implantation in patients with end-stage heart failure.

Sympathetic overactivity, which predicts poor outcome in patients with heart failure, normalizes following cardiac transplantation. We tested the hypothesis that haemodynamic improvement following left ventricular assist device (LVAD) implantation is also associated with reductions in centrally generated sympathetic activity. In eight patients with heart failure (two women, six men, age 44-66 years), we continuously recorded electrocardiogram, beat-to-beat finger blood pressure, respiration, and muscle sympathetic nerve activity (MSNA) before and after implantation of the continuous-flow LVAD devices HeartWare HVAD (n= 4) and HeartMate II (n= 2), and the non-continuous-flow device HeartMate 3 (n= 2). LVAD implantation increased cardiac output by 1.29 ± 0.88 L/min (P= 0.060) and mean arterial pressure by 16.2± 7.9 mmHg (P< 0.001), while reducing pulse pressure by 25.3± 9.8 mmHg (P< 0.001). LVAD implantation did not change MSNA burst frequency (-1.3± 7.5 bursts/min, P= 0.636), total activity (+0.62 ± 1.83 au, P= 0.369), or normalized activity (+0.63 ± 4.23, P= 0.685). MSNA burst incidence was decreased (-7.8± 9.3 bursts/100 heart beats, P= 0.049). However, cardiac ectopy altered MSNA bursting patterns that could be mistaken for sympatholysis. Implantation of current design LVAD does not consistently normalize sympathetic activity in patients with end-stage heart failure despite haemodynamic improvement.

Time in Therapeutic Range Significantly Impacts Survival and Adverse Events in Destination Therapy Patients.

The study aim was to examine the impact time in therapeutic range (TTR, International Normalized Ratio [INR] 2.0-3.0) has on survival and adverse events in patients receiving the HeartWare HVAD System in the ENDURANCE and ENDURANCE Supplemental Trials. Evaluable subjects (n = 495) had >1 INR value recorded 1-24 months postimplant and were categorized as: low TTR (10-39%), moderate TTR (40-69%), and high TTR (≥70%). Baseline characteristics, adverse events, and survival were analyzed. Low TTR patients experienced higher rates of major bleeding (1.69 vs. 0.54 events per patient year [EPPY]; p < 0.001), GI bleeding (1.22 vs. 0.38 EPPY; p < 0.001), stroke (0.47 vs. 0.17 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.02), infection (1.44 vs. 0.69 EPPY; p < 0.001), and renal dysfunction (0.23 vs. 0.05 EPPY; p < 0.001) compared with high TTR. Moderate TTR had higher rates of major bleeding (0.75 vs. 0.54 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.007), cardiac arrhythmia (0.32 vs. 0.24 EPPY; p = 0.04), and infection (0.90 vs. 0.69 EPPY; p = 0.001) compared with high TTR. Two year survival was greater among moderate and high versus low cohorts (Log-rank p = 0.001). The significant reduction in morbidity and mortality in destination therapy (DT) HVAD patients with well-controlled TTR (≥70%) emphasizes the importance of vigilant anticoagulation management.

Cerebrovascular Events in Patients With Centrifugal-Flow Left Ventricular Assist Devices: Propensity Score-Matched Analysis From the Intermacs Registry.

Ischemic and hemorrhagic cerebrovascular accidents remain common among patients with centrifugal-flow left ventricular assist devices, despite improvements in survival and device longevity. We compared the incidence of neurologic adverse events (NAEs) associated with 2 contemporary centrifugal-flow left ventricular assist devices: the Abbott HeartMate3 (HM3) and the Medtronic HeartWare HVAD (HVAD). Using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), we collected data on adult patients who received a centrifugal-flow left ventricular assist device as a primary isolated implant between January 1, 2017, and September 30, 2019. Major NAEs were defined as transient ischemic attack, ischemic cerebrovascular accident, or hemorrhagic cerebrovascular accident. The association of HVAD with risk of NAE in the first year after implant was evaluated using propensity score matching to balance for preimplant risk factors. After matching, freedom from first major NAE in the HM3 and HVAD cohorts was compared with Kaplan-Meier curves. A secondary analysis using multivariable multiphase hazard models was used to identify predictors of NAE, which uses a data-driven parametric fit of the early declining and constant phase hazards and the associations of risk factor with either phase. Of 6205 included patients, 3129 (50.4%) received the HM3 and 3076 (49.6%) received the HVAD. Median follow-up was 9 and 12 months (HM3 and HVAD, respectively). Patients receiving HVAD had more major NAEs (16.4% versus 6.4%, P<0.001) as well as each subtype (transient ischemic attack: 3.3% versus 1.0%, P<0.001; ischemic cerebrovascular accident: 7.7% versus 3.4%, P<0.001; hemorrhagic cerebrovascular accident: 7.2% versus 2.0%, P<0.001) than did patients receiving HM3. A propensity-matched cohort balanced for preimplant risk factors showed that HVAD was associated with higher probabilities of major NAEs (% freedom from NAE 82% versus 92%, P<0.001). Device type was not significantly associated with NAEs in the early hazard phase, but HVAD was associated with higher incidence of major NAEs during the constant hazard phase (hazard ratio, 5.71 [CI, 3.90-8.36]). HM3 is associated with lower hazard of major NAEs than is HVAD beyond the early postimplantation period and during the constant hazard phase. Defining the explanation for this observation will inform device selection for individual patients.

Cerebrovascular Events in Patients With Centrifugal-Flow Left Ventricular Assist Devices: Propensity Score-Matched Analysis From the Intermacs Registry.

Ischemic and hemorrhagic cerebrovascular accidents remain common among patients with centrifugal-flow left ventricular assist devices, despite improvements in survival and device longevity. We compared the incidence of neurologic adverse events (NAEs) associated with 2 contemporary centrifugal-flow left ventricular assist devices: the Abbott HeartMate3 (HM3) and the Medtronic HeartWare HVAD (HVAD). Using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), we collected data on adult patients who received a centrifugal-flow left ventricular assist device as a primary isolated implant between January 1, 2017, and September 30, 2019. Major NAEs were defined as transient ischemic attack, ischemic cerebrovascular accident, or hemorrhagic cerebrovascular accident. The association of HVAD with risk of NAE in the first year after implant was evaluated using propensity score matching to balance for preimplant risk factors. After matching, freedom from first major NAE in the HM3 and HVAD cohorts was compared with Kaplan-Meier curves. A secondary analysis using multivariable multiphase hazard models was used to identify predictors of NAE, which uses a data-driven parametric fit of the early declining and constant phase hazards and the associations of risk factor with either phase. Of 6205 included patients, 3129 (50.4%) received the HM3 and 3076 (49.6%) received the HVAD. Median follow-up was 9 and 12 months (HM3 and HVAD, respectively). Patients receiving HVAD had more major NAEs (16.4% versus 6.4%, P<0.001) as well as each subtype (transient ischemic attack: 3.3% versus 1.0%, P<0.001; ischemic cerebrovascular accident: 7.7% versus 3.4%, P<0.001; hemorrhagic cerebrovascular accident: 7.2% versus 2.0%, P<0.001) than did patients receiving HM3. A propensity-matched cohort balanced for preimplant risk factors showed that HVAD was associated with higher probabilities of major NAEs (% freedom from NAE 82% versus 92%, P<0.001). Device type was not significantly associated with NAEs in the early hazard phase, but HVAD was associated with higher incidence of major NAEs during the constant hazard phase (hazard ratio, 5.71 [CI, 3.90-8.36]). HM3 is associated with lower hazard of major NAEs than is HVAD beyond the early postimplantation period and during the constant hazard phase. Defining the explanation for this observation will inform device selection for individual patients.

Minimal invasive temporary percutaneous right ventricular circulatory support after left ventricular assist device implantation.

Cardiogenic shock is a life-threatening situation with high mortality rates. Mechanical unloading of the left ventricle may be achieved via left ventricular assist device (LVAD) implantation. Postoperative right ventricular (RV) failure, however, has very limited therapeutic options and is associated with increased postoperative mortality. In this paper, we describe a percutaneous right heart bypass for temporary postoperative RV support. We retrospectively examined all patients receiving percutaneous RV mechanical support after LVAD implantation. All patients receiving trans-jugular mechanical right heart bypass during or after LVAD implantation in our tertiary medical centre between November 2014 and December 2019 were examined retrospectively. The venous draining cannula was placed in the femoral vein; the pulmonary cannula was placed in the pulmonary artery using fluoroscopy. In total, 14 patients received RV support using the trans-jugular technique. Mean age was 48.4 ± 14.9 years. Nine patients were treated with mechanical circulatory support before LVAD implantation. Biventricular support was done in 7 patients. All patients were treated with an Heartware HVAD . Mean postoperative intensive care unit stay was 46.3 ± 32.4 days. Mean right heart bypass support time was 10.6 ± 4.3 days. Twelve patients (86%) could be bridged to RV recovery, RV assist device implantation or heart transplantation. Percutaneous RV mechanical support is feasible, safe and shows acceptable outcome. Early implantation of RV support may contribute to successful outcome after LVAD implantation.

The impact of socioeconomic status in patients with left ventricular assist devices (LVADs).

Socioeconomic status (SES) can be a powerful predictor of adverse outcomes among heart failure patients but its impact on survival and readmission following left ventricular assist device (LVAD) implantation surgery is poorly understood. We investigated if the LVAD recipients from more deprived neighborhoods experienced higher mortality and readmission rate after device implantation as compared to those from less deprived areas. This is a single center, retrospective analysis evaluating adults who received Heartmate III and Heartware HVAD implants between 2009 and 2018. SES indicators were area of deprivation index (ADI), race and income. Our cohort was grouped by ADI quartiles from least deprived (Q1), Q2, Q3 to the most deprived (Q4). Outcomes included overall mortality and readmission following surgery. A total of 191 patients were included in the study. Demographics by SES indicators demonstrated that least deprived (Q1) patients were older than the most deprived (65 vs. 57, p < .01), African-American patients originated from more deprived neighborhoods than Caucasians (ADI 87 vs. 62, p < .001), and high-income patients had higher preoperative BUN and creatinine. Outcome differences included a decreased risk of death in most deprived patients (Q4) compared to the least deprived (Q1), however after adjusting for age, LVAD indication, and INTERMACS profile this was no longer significant. No differences in survival or readmission by race or income was observed CONCLUSION: SES does not independently impact survival and readmission after Heartware HVAD and Heartmate III LVAD implantation. More studies are needed to evaluate if other SES factors affect these outcomes.

Ex Vivo Assessment of Different Oral Anticoagulant Regimens on Pump Thrombosis in a HeartWare Ventricular Assist Device

In light of decreased intracranial hemorrhage with direct oral anticoagulants and concerns about their safety in continuous flow left ventricular assist devices, we conducted an ex vivo study of thrombus formation using multiple anticoagulation agents. A continuous flow left ventricular assist device (HeartWare ventricular assist device) hemocompatibility loop was run using human blood under 7 conditions: control (no anticoagulation or antiplatelet); in vitro addition of aspirin; in vitro addition of apixaban at low dose (equivalent 2.5 mg twice daily); addition of apixaban at high dose (equivalent 5 mg twice daily); patients on warfarin; patients on apixaban (5 mg twice daily); and patients on dabigatran (150 mg twice daily). The primary outcome was time to formation of intrapump thrombosis. Secondary outcomes were reduction in clotting times over 1 hour, hemolysis, reduced platelet aggregation, and von Willebrand activity. Twenty-one runs were completed. Times to thrombosis in median (interquartile range) were control, 131 (127-134.5); in vitro aspirin, 124 (114.5-137); and patients on dabigatran, 131 (130.5-135.5) minutes, respectively. Times in patients on warfarin were, 137 (136.5-143.5); in vitro low-dose apixaban, 141 (138.5-142); and patients on apixaban, 140 (138-142.5) minutes, respectively. No thrombus formed in the in vitro high-dose apixaban group. There were no significant differences between the individual groups. When all apixaban groups were compared with nonapixaban groups, the time to thrombosis formation was significantly longer, 143 (137-150) versus 133.5 (128.5-140) minutes, P=0.02. There were similar changes in lactate dehydrogenase levels and other secondary end points. In an in vitro study of anticoagulation using human blood in a mock loop with a HeartWare HVAD, we demonstrated similar thrombosis times for apixaban and warfarin. Time to clotting was longer in the combined apixaban groups compared with combined other groups, but thrombosis times between individual groups were not significantly different.

A Power Tracking Algorithm for Early Detection of Centrifugal Flow Pump Thrombosis.

Logfiles from the HeartWare HVAD System provide operational pump trend data to aid in patient management. Pump thrombosis is commonly associated with increases in the logfile power that may precede the clinical presentation. A Power Tracking algorithm was developed to detect significant deviations in pump power that may be associated with pump thrombus (PT). The Power Tracking algorithm was applied retrospectively to logfiles captured in the ENDURANCE, ENDURANCE Supplemental, and LATERAL clinical trials. From a combined dataset of 896 patients, available logfiles with suspected PT (n = 70 events in 60 patients) and available logfiles from patients without adverse events (AEs) (n = 106 patients, consisting of 27.4 patient-years of monitoring) were organized into two cohorts. The Power Tracking algorithm detected PT cases on or before the recorded AE date with a sensitivity of 85.7%, with detection occurring an average of 3.9 days before clinical presentation. The algorithm averaged one false alarm for every 6.85 patient-years of monitoring from logfiles without AEs. The favorable performance of the Power Tracking algorithm may enable earlier detection of pump thrombosis and allow early medical management versus surgical intervention.

Instructions for Use and Patient Manual for HeartWare HVAD System

Instructions for Use and Patient Manual for HeartWare HVAD System

Analysis of the HeartWare HVAD pump characteristics under pulsatile operation

Rotary blood pumps (RBPs) are clinically utilised to support patients suffering from later stage heart failure and although the development of these devices has led to vast improvements, they still lack a physiological pulse. To overcome the drawbacks of the absence of pulsatility in RBPs, physiological control systems have been developed which introduce pulsatility by rapid speed modulation. Much of the research introducing pulsatility in patients supported by a HeartWare HVAD has focussed on haemodynamic output with no investigations on the limitations of the pump’s electrical characteristics. Accordingly, the aim of the present study was to investigate the effect of rapid speed modulation on the accuracy of the flow estimator and power consumption as well as analysis of the shape of the flow and pressure waveforms when speed modulation was performed with quantised sine and square waves. The accuracy of the flow estimator was shown to be dependent on flow rate and independent of fluid viscosity, base speed or pulse amplitude. The average power consumption was shown not to differ greatly when pulsatility was introduced increasing by 0.72 ± 0.31 W per 1000 RPM of peak-to-peak speed modulation. However, the instantaneous power draw was shown to increase by up to three times, particularly at low base speeds. Speed modulation using a quantised sine wave qualitatively demonstrated reductions in overshoot from the target speed when compared to speed modulation using a square wave. Information contained in this article will assist researchers in the development of physiological control systems employing rapid speed modulation techniques.

Impact of extra-corporeal life support (ECLS) cannulation strategy on outcome after durable mechanical circulation support system implantation on behalf of durable MCS after ECLS Study Group.

The literature on outcomes of patients requiring durable mechanical circulatory support (MCS) after extra-corporeal life support (ECLS) is limited. The aim of this study was to investigate the impact of preoperative ECLS cannulation on postoperative outcome after durable MCS implantation. The durable MCS after ECLS registry is a multicenter retrospective study that gathered data on consecutive patients who underwent durable MCS implantation after ECLS between January 2010 and August 2018 in eleven high volume European centers. Patients who underwent the implantation of total artificial heart, pulsatile pumps, or first-generation pumps after ECLS were excluded from the analysis. The remaining patients were divided into two groups; central ECLS group (cECLS) and peripheral ECLS group (pECLS). A 1:1 propensity score analysis was performed to identify two matched groups. The outcome of these two groups was compared. A total of 531 durable MCS after ECLS were implanted during this period. The ECLS cannulation site was peripheral in 87% (n=462) and central in 13% (n=69) of the patients. After excluding pulsatile pumps and total artificial heart patients, a total of 494 patients remained (pECLS =434 patients, cECLS =60 patients). A 1:1 propensity score analysis resulted in 2 matched groups (each 55 patients) with median age of 54 years (48-60 years) in cECLS group and 54 years (43-60 years) in pECLS group. HeartWare HVAD (Medtronic, Minneapolis, MN) was implanted in the majority of the patients (cECLS =71% vs. pECLS =76%, P=0.67). All postoperative morbidities were comparable between the groups. The thirty-day, one year and long-term survival was comparable between the groups (P=0.73). The cannulation strategy of ECLS appears to have no impact on the post-operative outcome after durable MCS implantation.

Development of tricuspid regurgitation and right ventricular performance after implantation of centrifugal left ventricular assist devices.

Tricuspid regurgitation (TR) after left ventricular assist device (LVAD) implantation is associated with a poor prognosis. This study evaluates the development of TR and right ventricular (RV) performance after LVAD implantation. Retrospective analysis of patients who underwent LVAD implantation between March 2018 and June 2019. Patients who underwent concomitant tricuspid valve surgery and patients with congenital heart disease were excluded. A total of 155 patients underwent LVAD implantation. Fourteen patients were excluded. Of the remaining patients, thirty-one died during the first six months, six were lost to follow-up and two underwent transplantation. 102 patients presented at 6.3 months (5.8 to 7.0). Patients were supported with HeartWare HVAD (74%) or HeartMate 3 (26%). 50.4% were rated as INTERMACS profile 1 or 2. At six months, systolic pulmonary artery pressure dropped from 36 to 21 mmHg (P<0.001). Tricuspid annular plane systolic excursion decreased from 17.3 to 14.3 mm (P<0.001), RV fractional area change did not change (P=0.839). Twenty-two patients (22%) presented with moderate-to-severe or severe (ms-s) TR pre-operatively. Of these, eighteen (81%) showed improvement to ≤ moderate TR. At follow-up twelve patients presented with ms-s TR. Of these, only four patients (33%) had been diagnosed with ms-s TR pre-operatively. There were no differences in pre-operative echocardiographic or clinical parameters between the twelve patients with ms-s late TR and the other ninety patients in the cohort. TR can show an impressive improvement with LVAD support. Longitudinal RV function decreases; this appears to be compensated by transverse shortening. Late TR can develop independently from pre-operative parameters including TR.

A Tale of Two Centrifugal-Flow Ventricular Assist Devices As Bridge to Heart Transplant

BackgroundUse of continuous-flow left ventricular assist devices (LVAD) has increased over the years as a bridge to transplant. The HeartWare HVAD (Medtronic, Minneapolis, MN) and HeartMate III (HM3, Abbott, Abbott Park, IL) are currently approved centrifugal-flow devices used for bridge to transplant. We sought to evaluate outcomes of the patients listed and who received a transplant after receiving these 2 devices. MethodsThe United Network of Organ Sharing thoracic transplant database was queried after August 23, 2017, until December 2018 to identify patients aged older than 18 years listed for heart transplant and supported by the HVAD or HM3. Patient characteristics were evaluated at the time of listing and transplant. The primary study end point was 1-year mortality after LVAD implantation. Nonparametric tests were used to evaluate the device groups. ResultsOf 569 patients listed for heart transplant during the study period, 226 had HM3 and 343 had HVAD. The HM3 group had more men (82% vs 74%, P = .02), patients with diabetes (38% vs 29%, P = .02), and the body mass index was higher (28 vs 27 kg/m2, P = .04) at listing. Between the HM3 and HVAD groups, the 1-year mortality was 20% vs 17%, respectively (log-rank P = .28; Figure 1), and the posttransplant survival at 1 year was 97% and 94%, respectively (P = .1). ConclusionsIn a relatively well-matched group of patients listed for heart transplant with a centrifugal-flow LVAD, the 6-month and 1-year mortality on the waiting list as well as after transplant were not statistically different. Additional real-world experience or a randomized trial would be needed to determine whether one LVAD is superior.