Hemocompatibility Score Research Articles

Prognostic Value of Pressure-Volume Measures in Hemocompatibility-Related Clinical Adverse Events

<h3>Purpose</h3> Continuous-flow left ventricular assist device (cf-LVADs) can lead to hemocompatibility-related clinical adverse events (HRAEs) which are largely determined by mechanisms that underpin the pump-patient interaction. We assessed the association of pressure-volume (PV) measures [stroke work (SW) & pump arterial elastance (E_A)] with incidence of HRAEs. <h3>Methods</h3> Using a validated algorithm, brachial-pressure waveforms from oscillometric blood pressure cuff (SphygmoCor Xcel), echocardiography measures and Medtronic HVAD controller data were collected for estimation PV measures within the first 3 months. Patients (all Bridge-To-Transplantation) were divided into low, intermediate and high tertiles for each of SW (n=13, 14, 9) and E_A (n=12, 12, 12). HRAEs, including nonsurgical bleeding (NB), neurological (NE) and thromboembolic events (TE), was followed through a 12-month period post-implant. Hemocompatibility score (HCS) was calculated based on HRAEs in the 1^st year. Comparison between groups were conducted with one-way ANOVAs and Kruskal-Wallis analyses. Kaplan Meier survival analyses determined time-to-event. <h3>Results</h3> 36 HVAD patients (mean age 57±10, 83% males, 69% non-ischemic cardiomyopathy) were included. Baseline demographics and clinical parameters were comparable between SW and E_A tertile groups. Low E_A group had significantly higher rates of HRAEs in the 1^st year compared to intermediate and high groups (p=0.004). HRAE rates were marginally higher in the low SW group (p=0.080). There were no differences in HCS. Survival analysis showed significant differences in distribution of 1-year cumulative HRAE-free probabilities according to E_A tertiles (33.3%, 83.3% and 91.7% for low, intermediate and high E_A respectively, log-rank=0.003). <h3>Conclusion</h3> PV measures offer value in prognostication of LVAD patients. This study highlights the potential importance of assessing afterload and native ventricular contractility in circumventing HRAEs in cf-LVAD patients.

Functional Outcomes Not Significantly Impacted by Hemocompatibility-Related Adverse Event Burden among Different Devices

Landmark work has demonstrated that the hemocompatibility-related adverse event (HRAE) burden is significantly lower with the newest centrifugal flow pump; however, no study has specifically examined this HRAE burden on the prior commercially available pumps and the impact on functional outcomes. We performed a retrospective analysis of HRAE (non-surgical bleeding, thrombo-embolic event, pump thrombosis, or neurological event) burden in patients following surgical implantation of Heart-Mate II (HMII) or Heart-Ware (HW) devices through 1 year of clinical follow-up. An HRAE were categorized by the type and severity of an adverse event and then assigned a net Hemocompatibility Score (HCS) of 0 through 4 for no HRAE through life-ending or disabling HRAE. Statistical analysis included comparison of net HCS using proportional regression, as well as impact on functional outcomes [NYHA class, dyspnea score, 6-minute walk, and peak venous oxygen consumption (VO2)] RESULTS: The study cohort included a total of 331 patients, with 268 patients (81%) in the HMII group and 63 patients (19%) in HW group. The overall median age was 62.2 years; patients receiving HMII were older (median 63.5 versus 58.1years, p<0.001). Net HCS per patient in the HMII group was 0.7 (±1.4), reported as mean (± standard deviation). This was similar to the net HCS per patient of 0.5 (±1.2) in the HW group (p=0.36). A scatter-plot analysis demonstrates no significant impact on functional outcomes between the comparison groups for NYHA class (p=0.06), 6-minute walk distance (p=0.54), Borg dyspnea rating (p=0.12) or peak VO2 (p=0.83) (Figure 1). Burden of HRAE does not adversely affect measures of functional capacity after device implantation. Furthermore, this did not differ with the use of prior commercially-available devices. These findings indicate that overall functional quality of life may not be significantly impacted by burden of HRAE regardless of pump technology.

Decoupling Between Diastolic Pulmonary Artery and Pulmonary Capillary Wedge Pressures Is Associated With Right Ventricular Dysfunction and Hemocompatibility-Related Adverse Events in Patients With Left Ventricular Assist Devices.

BackgroundDecoupling between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure is an index of pulmonary vascular damage. This study assessed the impact of decoupling on right heart function and hemocompatibility‐related adverse events.Methods and ResultsIn this prospective study, patients underwent invasive hemodynamic tests following left ventricular assist device implantation. Decoupling was defined as a difference of >5 mm Hg between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure. Among 92 patients with left ventricular assist devices (median age, 61 years; 57% male), 44 patients (48%) had decoupling. Right heart function and size by echocardiographic assessment worsened during a 1‐year observational period in the decoupling group as compared with the control group (P<0.05). The decoupling group had significantly lower 1‐year freedom from any hemocompatibility‐related adverse events (49% versus 79%; P=0.005), as well as a higher hemocompatibility score (2.14 versus 0.67; P=0.004). The scoring system depicts the severity of hemocompatibility‐related adverse events using 4 escalating tiers. Increased tier I scores (1–2 gastrointestinal bleedings or medically managed pump thrombosis; P=0.027) and tier IIIB scores (disabling stroke or hemocompatibility‐related adverse event–related death; P=0.041) occurred more frequently in the decoupling group.ConclusionsThe presence of decoupling between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure was associated with worsening of right heart function and hemocompatibility‐related adverse events in patients with left ventricular assist devices.

Hemocompatibility-related Adverse Events Following HeartMate II Left Ventricular Assist Device Implantation between Japan and United States.

Background: Left ventricular assist device (LVAD) therapy has improved the clinical outcomes in advanced heart failure patients, however, this may differ between countries. We aimed to compare outcomes between Japanese and US LVAD cohorts. Methods: For 416 consecutive LVAD patients who received HeartMate II LVAD implantation and completed a one-year follow-up, age-matched Japanese patients (the Japanese registry for mechanically assisted circulatory support (J-MACS) group) and the US patients were compared for their clinical outcomes. Results: 154 J-MACS patients and 77 US patients were compared. Survival, free from hemocompatibility-related adverse events (HRAEs) in the J-MACS was statistically comparable with the US (75% vs. 63%, p = 0.79). J-MACS had more disabling strokes than the US (0.221 vs. 0.052/patient-year, p = 0.005), whereas there was less nonsurgical bleeding (0.045 vs. 0.117/patient-year, p = 0.024). The net hemocompatibility score was statistically comparable between the groups (1.54 vs. 1.19 points/patient, p = 0.99). Post-LVAD prothrombin time with international normalized ratio (INR) <1.5 (odds ratio 4.07) was a risk factor for HRAEs in J-MACS, whereas INR >3.0 (odds ratio 5.71) was a risk factor in the US (p < 0.05 for both). Conclusion: In the age-matched cohorts, the J-MACS group experienced more strokes, while the US group had more bleedings. “Tailor-made” therapeutic strategy might be required for each country, given the unique variation of HRAE incidence among each country.

Omega-3 and hemocompatibility-related adverse events.

Hemocompatibility-related clinical adverse events (HRAEs) are major causes of readmission in patients with left ventricular assist devices (LVADs). Omega-3 is an unsaturated fatty acid that possesses anti-inflammatory and antiangiogenic properties. We aimed to investigate the impact of omega-3 therapy on HRAEs during LVAD support. Consecutive LVAD patients who were followed for 6 months were enrolled, and stratified by the use of omega-3. Freedom from any HRAEs and net burden of HRAEs, which was calculated by using a hemocompatibility score (using 4 escalating tiers of hierarchal severity to derive a total score for events), were compared between those with and without omega-3 therapy. Among 169 LVAD patients (57 years old and 124 males), 31 patients received 4 g/d of omega-3 therapy and 138 patients were in the control group. During the 6-month observational period, freedom from any HRAEs was 90% in the omega-3 group compared with 70% in the control group with a hazard ratio of 0.35 (95% confidence interval 0.11-0.87 and P = .042). The average hemocompatibility score in the omega-3 group was significantly lower compared with the control group (0.23 vs 0.91; P = .042), due to reduced Tier I scores (mild HRAE; P = .003) and Tier IIIB scores (severe HRAE; P < .001). The similar trends remained at propensity-matched populations. Omega-3 therapy was associated with reduced HRAEs including both bleeding and thromboembolic events in LVAD patients.

Aortic Insufficiency and Hemocompatibility-related Adverse Events in Patients with Left Ventricular Assist Devices

Hemocompatibility-related adverse events (HRAE) are a major cause of readmissions in patients with left ventricular assist devices (LVAD). The impact of aortic insufficiency (AI) on HRAE remains uncertain. We aimed to investigate the impact of AI on HRAE. Patients who underwent LVAD implantation between August 2014 and July 2017 and had echocardiograms 3 months post-LVAD implantation were enrolled. AI severity was assessed by measuring the systolic/diastolic ratio of flow and the rate of diastolic flow acceleration using Doppler echocardiography of the outflow cannula. Regurgitation fraction was derived from these parameters. Significant AI was defined as regurgitation fraction > 30%. Among 105 patients (median age, 56 years; 76% male), 36 patients (34%) had significant AI. Baseline characteristics were statistically not significantly different between those with and without significant AI except for higher rates of ischemic etiology and atrial fibrillation in the significant AI group (P < 0.05 for both). One-year survival free from HRAE was 44% in patients with AI compared to 67% in patients without significant AI (P = 0.018). The average hemocompatibility score, which defines the net burden of HRAE, was higher in the AI group (1.72 vs 0.64; P = 0.009), due mostly to higher tier I (mild HRAE; P = 0.034) and tier IIIB scores (severe HRAE; P = 0.011). Significant AI, as assessed by Doppler echocardiographic parameters, was associated with HRAE during LVAD support.

Hemocompatibility Related Outcomes of Centrifugal and Axial Flow LVADs: An IMACS Registry Analysis

Purpose A novel hemocompatibility score (HCS) has been created to quantify hemocompatibility related adverse events (HRAE) of LVAD support. We sought to determine the HCS profile of centrifugal (CG) versus axial flow (AF) devices and predictors of HRAE at 6 months. Methods We conducted a retrospective review of primary, continuous-flow, durable LVADs reported to IMACS from 2013 to 2017 and ≥6-month follow-up. Death Results Of 12925 primary devices, 4456(34%) were CG and 8469(66%) were AF. A total of 2143 HRAEs occurred in 1444 (32%) CG pts vs 4655 HRAEs in 2854 (34%) AF pts. A neurologic event was the most common HRAE in the CG group, 999 (47%), vs 1449 (31%) in AF. Bleeding events were less common in the CG group compared to AF, 513 (24%) vs 1682 (36%). 234 (11%) and 856 (18%) suspected or confirmed pump thrombus events were identified in CG and AF respectively. Deaths attributed to HRAEs were similar-CG, 346 (16%), and AF, 574 (12%). Arterial non-CNS thromboembolic events were rare, CG, 51 (2%), and AF, 94 (2%). Distribution of HCS within the first 6 months is depicted in Fig 1. Mean HCS was not significantly different between AF (0.94±1.96) vs CG (0.98±1.96), p=0.30. CG was not significantly associated with developing HRAE at 6 months (OR 0.94,p=0.14). Factors associated with increased odds of HRAE included age>60(OR 1.5), ischemic etiology(OR 1.2), INTERMACS level≤2(OR 1.3), chronic renal disease(OR 1.3), and diabetes(OR 1.3). Male gender was protective of HRAE(OR 0.75). Conclusion The distribution of HCS within 6 months was similar between CG and AF devices. CG devices had a higher proportion of neurologic and death events while AF devices had a higher proportion of bleeding and pump thrombosis events. Further investigation into device specific HRAE is warranted.

Hemocompatibility-Related Adverse Events: Is the Burden Different among Available Centrifugal Flow Pumps?

Purpose Landmark work has demonstrated that hemocompatibility-related adverse event (HRAE) burden is significant lower with the newest centrifugal flow pump compared to the established axial flow pump. No study has compared HRAE among the approved centrifugal and axial flow pumps. The objective of this study was to evaluate the burden of HRAE between HeartMate II (HMII) and HeartWare HVAD (HW). Methods We performed a retrospective analysis of hemocompatibility related adverse events (nonsurgical bleeding, thromboembolic event, pump thrombosis , or neurological event) in patients following implantation of HMII or HW through 6 months follow-up. HRAE were categorized by type and severity of adverse event and assigned a hemocompatibility score (HCS) of 0-4 for no HRAE through life ending or disabling HRAE, respectively. Statistical analysis included assessment of survival free from HRAE from implantation to 6-month follow-up using Kaplan-Meier and Cox proportional-hazard models and comparison of net hemocompatibility score using proportional odds regression. Results The study cohort included 331 patients with 268 patients (81%) in the HMII group and 63 patients (19%) in HW group. Overall median age was 62.2 years; HMII patients were older (median 63.5 versus 58.1years, p Conclusion Freedom from and burden of HRAE were not significantly different between the HeartMate II and HeartWare HVAD which is distinct from findings in the MOMENTUM trial. This indicates that hemocompatibility may differ significantly among available centrifugal flow technology and direct comparison of centrifugal flow pumps is required.

Decoupling between Pulmonary Artery and Wedge Pressure is Associated with Hemocompatibility-Related Adverse Events Following LVAD Implantation

Purpose Hemocompatibility-related adverse events (HRAEs) are major causes of readmission in LVAD patients. Decoupling between diastolic pulmonary artery pressure (dPAP) and pulmonary capillary wedge pressure (PCWP) is an index of pulmonary vascular damage. This study assessed the implication of decoupling on HRAEs in LVAD patients. Methods In this prospective study LVAD patients underwent invasive hemodynamic tests and were followed for 1 year. Decoupling was defined as a difference >5 mmHg between dPAP and PCWP. One-year freedom from any HRAEs and the net burden of HRAEs, which was calculated by using a hemocompatibility score (using 4 escalating tiers of hierarchal severity to derive a total score for events), were compared between those with and without decoupling. Results Among 92 LVAD patients (median age 61 years, 57% male), 44 patients (48%) had decoupling. One-year freedom from any HRAEs was 49% in the decoupling group compared with 79% in the decoupling-free group (p = 0.005; Figure 1A). The average hemocompatibility score in the decoupling group was significantly higher compared with the control group (2.14 vs. 0.67; p = 0.004; Figure 1B), due to reduced Tier I (1-2 gastrointestinal bleedings or medically managed pump thrombosis; p = 0.027) and Tier IIIB scores (HRAEs-related death; p = 0.041). Conclusion The presence of decoupling between dPAP and PCWP was associated with HRAEs in LVAD patients. Studies evaluating if a reduction in decoupling will also reduce HRAE's is warranted.

Aortic Insufficiency is Associated with Hemocompatibility-Related Adverse Events in LVAD Patients

Purpose Hemocompatibility-related clinical adverse events (HRAEs) are major causes of readmission and reduce quality of life in LVAD patients. The impact of aortic insufficiency (AI) on HRAEs remains uncertain. This study assessed the impact of AI, which was graded by using novel Doppler echocardiographic parameters obtained at the LVAD outflow cannula , on HRAEs. Methods LVAD patients with varying degrees of AI underwent Doppler echocardiography of the LVAD outflow cannula. AI regurgitation fraction (RF) was calculated from the systolic/diastolic velocity ratio and the rate of diastolic flow acceleration of the LVAD outflow cannula (Figure 1A). RF >30% defined as significant AI. Freedom from any HRAEs and the net burden of HRAEs, which was calculated by using a hemocompatibility score (with 4 escalating tiers of hierarchal severity), were compared between those with/without significant AI during a 1-year observational period. Results Among 105 patients (median age 56 years, 76% male), 36 patients (34%) had significant AI. Baseline characteristics were comparable between two groups (p >0.05 for all). One-year survival free from HRAEs was 44% in the significant AI group compared with 67% in the non-significant AI group (p = 0.018; Figure 1B). The average hemocompatibility score in the significant AI group was higher compared with the non-significant AI group (1.72 vs. 0.64; p = 0.009; Figure 1C), due to higher tier I (gastrointestinal bleedings or medically managed pump thrombosis ; p = 0.034) and tier IIIB scores (HRAE-related death; p = 0.011). Conclusion Significant AI, which was assessed by using novel Doppler echocardiographic parameters, was associated with an increased rate of HRAEs in LVAD patients.

HeartMate 3 Surgical Implant Technique and Outcomes in the MOMENTUM 3 Trial

Purpose The HeartMate 3 (HM3) Left Ventricular Assist System is a fully magnetically levitated, centrifugal, continuous-flow pump. In the MOMENTUM 3 trial, the HM3 apical cuff could be attached with two different Methods Cut then Sew or Sew then Cut. This analysis describes the surgical techniques used in the trial and evaluates their impact on outcomes. Methods 189 patients in the Long Term (LT) cohort were implanted with the HM3 pump. Patients were divided into groups based on the technique used to attach the apical cuff at implant. Survival and adverse events at 2 years of follow-up were compared between the groups. The burden of hemocompatibility related adverse events (HRAE) was evaluated with a previously defined hemocompatibility score (Mehra. Eur Heart J. 2017). Continuous and categorical data were compared with the Wilcoxon rank sum and chi-square tests. The log-rank test was used to compare survival. This analysis will be updated to the 515 patients implanted with HM3 in the Full Cohort, which will be available in March 2019. Results 189 patients were implanted with HM3 by 68 surgeons at 52 centers. The median implant and bypass times were 261 and 83 minutes respectively. The majority of implants used the Cut then Sew apical attachment method (64%), true apical inflow cannula insertion (79%), silicone to skin driveline interface (90%), and right-sided driveline exit (54%). Cut then Sew was associated with longer median bypass times when compared to Sew then Cut (86 vs 77.5 minutes, p = 0.033). In the LT Cohort, there were no significant differences in 2-year survival between the groups (log-rank P=0.16). However, there was a trend for Cut then Sew to have a higher risk of stroke compared to Sew then Cut (Figure). Patients implanted with Cut then Sew vs Sew then Cut were also more likely to have a hemocompatibility score>1 (27% vs 15%, p=0.048). Conclusion We demonstrate that the Cut then Sew method used additional bypass time and may confer a higher stroke risk and HRAE net burden compared to Sew then Cut pump implantation technique.

Long-Term Burden of Hemocompatibility Related Adverse Events in the MOMENTUM 3 Trial: Final Analysis of the 1028 Patient Cohort

Summary of Objectives The MOMENTUM 3 trial has demonstrated superiority of the centrifugal HeartMate 3 (HM3) device to the mechanical bearing axial HeartMate II (HMII) continuous-flow cardiac pump, in patients with advanced heart failure refractory to medical management. In this final analysis of the full trial cohort, we evaluate the net burden of hemocompatibility related adverse events between the two LVAS in the long-term and identified risk factors associated with the development of hemocompatibility related adverse events (HRAE's). Methods MOMENTUM 3 is a randomized controlled trial of the HM3 pump versus the HMII pump, irrespective of intended goal of support. This large adaptive trial is designed to have 3 prespecified end points of which the short term (n=294, 6-months) and long-term (n=366, 2-years) primary end points have been reported; we now present this analysis from the full of all 1028 randomized patients. To assess the aggregate of HRAEs, we evaluate the endpoint of 2-year survival free of any non-surgical bleeding, thromboembolic event, pump thrombosis or any neurological event. The net burden of HRAEs will be assessed using a previously defined and validated severity tiered hemocompatibility score, which separates clinical events into four escalating tiers of severity to derive a total score for HRAE events encountered during the entire experience for each patient to death, transplantation or study end. Furthermore, we will identify risk factors for the development of HRAEs. The analysis will be performed with the full cohort of MOMENTUM 3: n=1028 patients. The last patient completed 2 years of follow-up in August 2018; the data lock will be accomplished in November 2018 and final results will be analyzed and available by March 2019. Endpoints This will be the first comprehensive analysis of the long-term outcomes for an aggregate hemocompatibility related adverse endpoint and tiered severity score to evaluate the net burden of bleeding and thrombotic complications experienced by patients treated with either the HM3 or HMII LVAS in the pivotal MOMENTUM 3 trial. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.)

OC30 HEMOCOMPATIBILITY-RELATED ADVERSE EVENTS AND PHYSIOLOGICAL CIRCULATORY INTERFACE OF DIFFERENT GENERATION LEFT VENTRICULAR ASSIST DEVICES

Abstract Background and Aim: Aim of this study has been to assess the rate of hemocompatibility-related adverse events (HRAEs) of current generation centrifugal pumps and older axial continuous-flow (CF) left ventricular assist devices (LVADs). Methods: We identified 193 CF LVAD recipients at three institutions. We studied the quantitative estimates of freedom from HRAEs between 3 types of pumps, the HeartMate II (HMII,n = 56), the HeartMate 3 (HM3,n = 38) and the HeartWare HVAD (HVAD,n = 99). The net burden of HRAE was assessed by using the MOMENTUM 3 hemocompatibility score. Results: Survival free of any HRAE was achieved in 86% of the HM3 group, 64% of the HMII group and 52% in HVAD group (hazard ratio, 0.64; confidence interval, 0.40–0.95; p = 0.014). Using the hemocompatibility score, the HM3 group demonstrated less pump thrombosis requiring reoperation (0 versus 6 and 14 points, for HMII and HVAD, respectively, p = 0.002) or medically managed pump thrombosis (0 versus 4 points and 17 points, for HMII and HVAD, respectively, p = 0.001), and fewer nondisabling strokes (6 versus 14 and 30 points, for HMII and HVAD, respectively, p = 0.002). The net hemocompatibility score in the HM3 in comparison with the HMII and HVAD patients was 71 (0.66 ± 1.45 points/patient) versus 103 (0.86 ± 1.59 points/patient) and 157 (0.96 ± 1.71 points/patient), respectively (odds ratio, 0.66; confidence interval, 0.38–1.01; p = 0.063). Conclusions: In this analysis, HM3 had a more favorable physiological circulatory interface at 36 months in comparison with HMII and HVAD. This confirms the need to develop different clinical monitorings and coagulation management protocols when facing with various device platforms.

Letter by Maltais et al Regarding Article, “Hemocompatibility-Related Outcomes in the MOMENTUM 3 Trial at 6 Months: A Randomized Controlled Study of a Fully Magnetically Levitated Pump in Advanced Heart Failure”

In the article by Uriel et al,1 the authors evaluated a composite end point defined as hemocompatibility-related clinical adverse events (HRAEs) between the HeartMate 3 and the HeartMate II left ventricular assist device. The authors proposed a new hemocompatibility score (HCS) to describe the HRAE burden experienced by patients within the trial period. Mehra et al2 proposed the suggested HCS, which identified the need for a clinical score to quantify a burden of hemocompatibility. The grading system developed by Uriel et al1 relates more to a traditional rating because it consists of individual cutoff points derived from intuitive clinical reasoning. The …