Association of Angiopoetin-2 and TNF-α With Bleeding During Left Ventricular Assist Device Support: Analysis From the PREVENT Biorepository.

The purpose of this study was to describe the changes in plasma levels of angiogenic and inflammatory biomarkers, specifically Ang-2 and TNF-α, in patients receiving HeartMate II (HMII) left ventricular assist device (LVAD) and correlate them with nonsurgical bleeding. It has been shown that angiopoietin-2 (Ang-2) and tissue necrosis factor-α (TNF-α) may be linked to bleeding in LVAD patients. This study utilized biobanked samples prospectively collected from the PREVENT study, a prospective, multicenter, single-arm, nonrandomized study of patients implanted with HMII. Paired serum samples were obtained in 140 patients before implantation and at 90 days postimplantation. Baseline demographics were as follows: age 57 ± 13 years, 41% had ischemic etiology, 82% male, and 75% destination therapy indication. In the 17 patients with baseline elevation of both TNF-α and Ang-2, 10 (60%) experienced a significant bleeding event within 180 days postimplant compared with 37 of 98 (38%) patients with Ang-2 and TNF-α below the mean ( p = 0.02). The hazard ratio for a bleeding event was 2.3 (95% CI: 1.2-4.6) in patients with elevated levels of both TNF-α and Ang-2. In the PREVENT multicenter study, patients with elevations in serum Angiopoietin-2 and TNF-α at baseline before LVAD implantation demonstrated increased bleeding events after LVAD implantation.

Use of a Pulmonary Artery Pressure Sensor to Manage Patients With Left Ventricular Assist Devices.

BACKGROUND: Hemodynamic-guided management with a pulmonary artery pressure sensor (CardioMEMS) is effective in reducing heart failure hospitalization in patients with chronic heart failure. This study aims to determine the feasibility and clinical utility of the CardioMEMS heart failure system to manage patients supported with left ventricular assist devices (LVADs). METHODS: In this multicenter prospective study, we followed patients with HeartMate II (n=52) or HeartMate 3 (n=49) LVADs and with CardioMEMS PA Sensors and measured pulmonary artery pressure, 6-minute walk distance, quality of life (EQ-5D-5 L scores), and heart failure hospitalization rates through 6 months. Patients were stratified as responders (R) and nonresponders to reductions in pulmonary artery diastolic pressure (PAD). RESULTS: There were significant reductions in PAD from baseline to 6 months in R (21.5-16.5 mm Hg; P<0.001), compared with an increase in NR (18.0-20.3; P=0.002), and there was a significant increase in 6-minute walk distance among R (266 versus 322 meters; P=0.025) compared with no change in nonresponder. Patients who maintained PAD <20 compared with PAD ≥20 mm Hg for more than half the time throughout the study (averaging 15.6 versus 23.3 mm Hg) had a statistically significant lower rate of heart failure hospitalization (12.0% versus 38.9%; P=0.005). CONCLUSIONS: Patients with LVAD managed with CardioMEMS with a significant reduction in PAD at 6 months showed improvements in 6-minute walk distance. Maintaining PAD <20 mm Hg was associated with fewer heart failure hospitalizations. Hemodynamic-guided management of patients with LVAD with CardioMEMS is feasible and may result in functional and clinical benefits. Prospective evaluation of ambulatory hemodynamic management in patients with LVAD is warranted. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03247829.

Enhanced Thrombin Formation in Patients With Ventricular Assist Devices Experiencing Bleeding: Insights From the Multicenter PREVENT Study.

The aim of this investigation was to characterize the hemostatic status of heart failure patients with implanted left ventricular assist devices (LVADs) to propose a mechanism associated with bleeding. Patients (n = 300) from 23 US hospitals were enrolled in the PREVENtion of HeartMate II Pump Thrombosis through Clinical Management (PREVENT) study. A biobank was established with serum and plasma samples prospectively collected from a cohort of 175 patients preimplant baseline (BL) and 3 months (3M) postimplant. Outcomes were collected for 6 months. Thrombin (prothrombin fragment 1.2 [F1.2], functional thrombin generation [TG]) and fibrinolytic activity (D-dimer, plasminogen activator inhibitor-1 [PAI-1]), but not contact activation (complement C5a), were elevated in heart failure patients at BL. F1.2, TG, and PAI-1 levels decreased 3M after LVAD implantation ( p < 0.01) but did not revert to normal in all patients; conversely, D-dimer increased BL to 3M ( p < 0.01). Compared with patients without events, thrombin activity (F1.2) was increased in patients with late bleeding (3-4 months postimplant) ( p = 0.06) and in those with late gastrointestinal (GI) bleeding ( p = 0.01). Patients with 3M F1.2 levels above the cohort mean had a higher incidence of bleeding ( p < 0.001) and GI bleeding ( p < 0.001) compared with those with below mean F1.2. Patients experiencing multiple bleeding events were more likely to have 3M F1.2 greater than the cohort mean. Despite anticoagulation with aspirin and warfarin, LVAD implanted patients exhibit hemostatic activation. Excess thrombin formation, particularly shown by increased F1.2, was demonstrated in association with bleeding in LVAD implanted patients.

Prospective Multicenter Study of Myocardial Recovery Using Left Ventricular Assist Devices (RESTAGE-HF [Remission from Stage D Heart Failure]): Medium-Term and Primary End Point Results.

BACKGROUND: Left ventricular assist device (LVAD) unloading and hemodynamic support in patients with advanced chronic heart failure can result in significant improvement in cardiac function allowing LVAD removal; however, the rate of this is generally considered to be low. This prospective multicenter nonrandomized study (RESTAGE-HF [Remission from Stage D Heart Failure]) investigated whether a protocol of optimized LVAD mechanical unloading, combined with standardized specific pharmacological therapy to induce reverse remodeling and regular testing of underlying myocardial function, could produce a higher incidence of LVAD explantation. METHODS: Forty patients with chronic advanced heart failure from nonischemic cardiomyopathy receiving the Heartmate II LVAD were enrolled from 6 centers. LVAD speed was optimized with an aggressive pharmacological regimen, and regular echocardiograms were performed at reduced LVAD speed (6000 rpm, no net flow) to test underlying myocardial function. The primary end point was the proportion of patients with sufficient improvement of myocardial function to reach criteria for explantation within 18 months with sustained remission from heart failure (freedom from transplant/ventricular assist device/death) at 12 months. RESULTS: Before LVAD, age was 35.1±10.8 years, 67.5% were men, heart failure mean duration was 20.8±20.6 months, 95% required inotropic and 20% temporary mechanical support, left ventricular ejection fraction was 14.5±5.3%, end-diastolic diameter was 7.33±0.89 cm, end-systolic diameter was 6.74±0.88 cm, pulmonary artery saturations were 46.7±9.2%, and pulmonary capillary wedge pressure was 26.2±7.6 mm Hg. Four enrolled patients did not undergo the protocol because of medical complications unrelated to the study procedures. Overall, 40% of all enrolled (16/40) patients achieved the primary end point, P<0.0001, with 50% (18/36) of patients receiving the protocol being explanted within 18 months (pre-explant left ventricular ejection fraction, 57±8%; end-diastolic diameter, 4.81±0.58 cm; end-systolic diameter, 3.53±0.51 cm; pulmonary capillary wedge pressure, 8.1±3.1 mm Hg; pulmonary artery saturations 63.6±6.8% at 6000 rpm). Overall, 19 patients were explanted (19/36, 52.3% of those receiving the protocol). The 15 ongoing explanted patients are now 2.26±0.97 years after explant. After explantation survival free from LVAD or transplantation was 90% at 1-year and 77% at 2 and 3 years. CONCLUSIONS: In this multicenter prospective study, this strategy of LVAD support combined with a standardized pharmacological and cardiac function monitoring protocol resulted in a high rate of LVAD explantation and was feasible and reproducible with explants occurring in all 6 participating sites. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01774656.

Optical tracking and laser-induced mortality of insects during flight.

Addressing the need for novel insect observation and control tools, the Photonic Fence detects and tracks mosquitoes and other flying insects and can apply lethal doses of laser light to them. Previously, we determined lethal exposure levels for a variety of lasers and pulse conditions on anesthetized Anopheles stephensi mosquitoes. In this work, similar studies were performed while the subjects were freely flying within transparent cages two meters from the optical system; a proof-of-principle demonstration of a 30 m system was also performed. From the dose-response curves of mortality data created as a function of various beam diameter, pulse width, and power conditions at visible and near-infrared wavelengths, the visible wavelengths required significantly lower laser exposure than near infrared wavelengths to disable subjects, though near infrared sources remain attractive given their cost and retina safety. The flight behavior of the subjects and the performance of the tracking system were found to have no impact on the mortality outcomes for pulse durations up to 25 ms, which appears to be the ideal duration to minimize required laser power. The results of this study affirm the practicality of using optical approaches to protect people and crops from pestilent flying insects.

Association of Clinical Outcomes With Left Ventricular Assist Device Use by Bridge to Transplant or Destination Therapy Intent: The Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) Randomized Clinical Trial.

Importance: Left ventricular assist devices (LVADs) are well established in the treatment of advanced heart failure, but it is unclear whether outcomes are different based on the intended goal of therapy in patients who are eligible vs ineligible for heart transplant. Objective: To determine whether clinical outcomes in the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) trial differed by preoperative categories of bridge to transplant (BTT) or bridge to transplant candidacy (BTC) vs destination therapy (DT). Design, Setting, and Participants: This study was a prespecified secondary analysis of the MOMENTUM 3 trial, a multicenter randomized clinical trial comparing the magnetically levitated centrifugal-flow HeartMate 3 (HM3) LVAD to the axial-flow HeartMate II (HMII) pump. It was conducted in 69 centers with expertise in managing patients with advanced heart failure in the United States. Patients with advanced heart failure were randomized to an LVAD, irrespective of the intended goal of therapy (BTT/BTC or DT). Main Outcomes and Measures: The primary end point was survival free of disabling stroke or reoperation to remove or replace a malfunctioning device at 2 years. Secondary end points included adverse events, functional status, and quality of life. Results: Of the 1020 patients with implants (515 with HM3 devices [50.5%] and 505 with HMII devices [49.5%]), 396 (38.8%) were in the BTT/BTC group (mean [SD] age, 55 [12] years; 310 men [78.3%]) and 624 (61.2%) in the DT group (mean [SD] age, 63 [12] years; 513 men [82.2%]). Of the patients initially deemed as transplant ineligible, 84 of 624 patients (13.5%) underwent heart transplant within 2 years of LVAD implant. In the primary end point analysis, HM3 use was superior to HMII use in patients in the BTT/BTC group (76.8% vs 67.3% for survival free of disabling stroke and reoperation; hazard ratio, 0.62 [95% CI, 0.40-0.94]; log-rank P = .02) and patients in the DT group (73.2% vs 58.7%; hazard ratio, 0.61 [95% CI, 0.46-0.81]; log-rank P < .001). For patients in both BTT/BTC and DT groups, there were not significantly different reductions in rates of pump thrombosis, stroke, and gastrointestinal bleeding with HM3 use relative to HMII use. Improvements in quality of life and functional capacity for either pump were not significantly different regardless of preimplant strategy. Conclusions and Relevance: In this trial, the superior treatment effect of HM3 over HMII was similar for patients in the BTT/BTC or DT groups. It is possible that use of arbitrary categorizations based on current or future transplant eligibility should be clinically abandoned in favor of a single preimplant strategy: to extend the survival and improve the quality of life of patients with medically refractory heart failure. Trial Registration: ClinicalTrials.gov identifier: NCT02224755.

High Transpulmonary Artery Gradient Obtained at the Time of Left Ventricular Assist Device Implantation Negatively Affects Survival After Cardiac Transplantation.

AIM: Preoperatively elevated pulmonary vascular resistance (PVR) is a contraindication to heart transplantation (HT). Transpulmonary pressure gradient (TPG) is one of the main variables used in PVR determination (ie, PVR = TPG/cardiac output). Unlike PVR, which is subject to the shortcoming of cardiac output estimation, TPG is directly measured. We aimed to evaluate the relationship of TPG obtained before left ventricular assist device (LVAD) implantation on post-HT survival. METHODS AND RESULTS: A total of 490 patients were implanted with Heartmate II LVADs in the multicenter Heartmate II Bridge-to-Transplantation clinical trial, and 416/490 had pre-LVAD TPG data available. Outcomes during LVAD support and after HT stratified by both PVR and TPG were studied. The median pre-LVAD TPG was 10 mm Hg. Baseline demographic and clinical characteristics were similar for patients with and without TPG >10 mm Hg. Outcomes during LVAD support (ie, recovery to LVAD explantation, HT, or ongoing device support) for patients below and above the median TPG were similar. However, post-HT 1-year survival rate was significantly higher for patients with TPG ≤10 mm Hg compared with those with TPG >10 mm Hg (91% vs 80%; P = .016). Analysis based on the median PVR of 2.68 Wood units did not stratify post-HTx 1-year survival rates between the groups (89% vs 83%; P = .25). CONCLUSIONS: Elevated TPG, rather than high PVR, before LVAD implantation was associated with increased mortality following HT. Pre-LVAD TPG may be useful to identify a cohort that requires close follow-up with serial hemodynamic monitoring before HT.

Pump Position Impacts HeartMate II Left Ventricular Assist Device Thrombosis.

The PREVENtion of HeartMate II pump Thrombosis through clinical management (PREVENT) study was a multicenter, prospective investigation to evaluate the rate of pump thrombosis (PT) with adoption of a uniform set of surgical and medical practices for left ventricular assist device implantation. We sought to quantify pump position at baseline and retrospectively define a pump position associated with poor clinical outcomes. Chest x-rays at baseline were prospectively obtained per protocol. Pump pocket depth, inflow cannula (IC) angle relative to the pump, and IC angle relative to the vertical were measured. Pumps falling in the tail-ends of the IC angle and pump pocket depth distributions were categorized as having an extreme pump position within the PREVENT study. Patients with extreme pump position had a significantly higher risk of confirmed and suspected PT, hemolysis, and elevated lactate dehydrogenase. In a multivariable analysis of survival free of confirmed PT, extreme pump position was an independent risk factor (hazard ratio = 3.6; 95% confidence interval = 1.5-8.9; p = 0.006) when adjusting for differences in pump speed and anticoagulation level. Our analysis shows that HeartMate II pump position at implant can significantly impact event-free survival and the incidence of adverse events at 6 months.

Changes in pulmonary artery pressure before and after left ventricular assist device implantation in patients utilizing remote haemodynamic monitoring.

AIMS: The time course of changes in pulmonary artery (PA) pressure due to left ventricular assist devices (LVADs) is not well understood. Here, we describe longitudinal haemodynamic trends during the peri-LVAD implantation period in patients previously implanted with a remote monitoring PA pressure sensor. METHODS AND RESULTS: We retrospectively studied PA pressure trends in patients implanted with CardioMEMS™ PA pressure sensor between October 2007 and March 2017 who subsequently had an LVAD procedure. Data are presented as mean ± standard deviation, and P-values are calculated using standard t-test with equal variance. Among 436 patients in cohort, 108 (age 58 ± 11 years, 82% male) received an LVAD and 328 (age 60 ± 13 years, 70% male) did not. The mean PA pressure at sensor implant was higher by 29% (P < 0.001) among patients who later received LVAD. Mean PA pressure 6 months prior to LVAD implant was 35.5 ± 8.5 mmHg, increasing to 39.4 ± 9.9 mmHg (P = 0.04) at 4 weeks before LVAD, and then decreasing 27% to 28.8 ± 8.4 mmHg (P < 0.001) at 3 months post-implant and stabilizing at 31.0 ± 9.4 mmHg at 1 year. CONCLUSIONS: Patients who later receive LVADs have higher PA pressures at sensor implant and show a further increase leading up to LVAD implantation. There is a significant reduction of PA pressures post-LVAD implantation that persists long term. PA pressure monitoring may aid in the clinical decision making of timing for LVAD implantation and in management of LVAD patients.

Novel Cardiac Coordinate Modeling System for Three-Dimensional Quantification of Inflow Cannula Malposition of HeartMate II LVADs.

Optimal function of left ventricular assist devices (LVADs) depends on proper alignment of the inflow cannula (IC). Quantitative guidelines for IC angulation are lacking because of variation in cardiac geometry and difficulty in analyzing three-dimensional (3D) cannula orientation relative to the left ventricle (LV). Based on contrast-enhanced computed tomography images from five normal and five clinically malpositioned IC cases in patients with HeartMate II LVADs, we developed a method for 3D quantification of IC malpositioning. Using Mimics image software (Materialise, Leuven, Belgium), the native heart, major arteries, and LVAD were segmented to create patient-specific 3D models, allowing LV cavity volume and long-axis length to be measured directly. The deviation of the IC was quantified in a cylindrical coordinate system at the IC insertion point relative to the mitral valve and septum, and IC occlusion was assessed by the distance between cannula inlet and the proximal endocardium. Compared with normal cases, patients with malpositioned pumps had shorter LV length (p = 0.03) and reduced pump pocket depth (p = 0.009). Malpositioned pumps may experience greater obstruction by the nearby myocardium. This quantitative 3D modeling tool may help identify different modes of pump malalignment and migration and may facilitate preoperative planning and minimally invasive approaches via virtual LVAD implantation.

Left ventricular assist devices versus medical management in ambulatory heart failure patients: An analysis of INTERMACS Profiles 4 and 5 to 7 from the ROADMAP study.

BACKGROUND: The ROADMAP study showed survival with improved functional status was better with left ventricular assist device (LVAD) therapy compared with optimal medical management (OMM) in ambulatory, non-inotrope-dependent (INTERMACS [IM] Profile 4 to 7) patients. To study more balanced cohorts and better define which patients may benefit from implantation of an LVAD, we re-evaluated the patients enrolled in ROADMAP when stratified by INTERMACS profile (Profile 4 and Profiles 5 to 7). METHODS: The primary end-point (survival on original therapy with improvement in 6-minute walk distance ≥75 meters at 1 year), actuarial survival, adverse events (AEs) and health-related quality of life (HRQoL) were evaluated. RESULTS: For INTERMACS Profile 4 (IM4), more LVAD patients met the primary end-point compared with OMM patients (40% vs 15%; odds ratio = 3.9 [1.2 to 12.7], p = 0.024), but there was no statistically significant difference for INTERMACS Profiles IM 5 to 7 (IM5-7). Event-free survival on original therapy at 2 years was greater for LVAD than for OMM patients in both IM4 (67% vs 28%; p < 0.001) and IM5-7 (76% vs 49%; p = 0.025) profile groups. Composite end-points of survival on original therapy with improved HRQoL or depression were better with LVAD than OMM in IM4, but not IM5-7. AEs trended higher in LVAD compared with OMM patients in both profile groups. Rehospitalization rates for LVAD vs OMM were similar between treatment arms in IM4 (82% vs 86%; p = 0.780), but were higher for LVAD in IM5-7 (93% vs 71%; p = 0.016). CONCLUSIONS: LVAD patients in IM4, but not IM5-7, are more likely to meet the primary end-point and have improvements in HRQoL and depression compared with OMM, even with AEs generally being more frequent. LVAD therapy with current technology may be beneficial in select IM4 patients, but can be deferred for most IM5-7 patients, who should be followed closely due to the high frequency of treatment failures.

Early intervention for lactate dehydrogenase elevation improves clinical outcomes in patients with the HeartMate II left ventricular assist device: Insights from the PREVENT study.

BACKGROUND: Hemolysis, assessed by elevated serum lactate dehydrogenase (LDH), is strongly associated with HeartMate II pump thrombosis (PT). However, it is unknown whether early intervention for elevated LDH circumvents the risk of serious PT requiring pump exchange. We sought to evaluate the relationship between elevated LDH and clinical outcomes, the effectiveness of early medical intervention, and risk factors for elevated LDH. METHODS: We studied 268 patients in the prospective, multicenter PREVENT study who had 2 or more LDH measurements at ≥30 days post-implant. Elevated LDH was defined as LDH ≥2.5× upper limit of normal (ULN) for 2 consecutive measurements. RESULTS: Fourteen percent of patients had elevated LDH. Stroke-free survival at 6 months was lower in patients with elevated LDH vs patients with normal LDH (83 ± 6% vs 93 ± 2%, p = 0.035). Elevated LDH resolved without intervention in 19% of patients, with intensified medical therapy in 43% and required surgical intervention in 38%. For patients receiving only medical therapy, survival was 94 ± 6% at 6 months post-treatment. In this subgroup, resolution of symptoms with intensified medical therapy was sustained in 15 of 16 patients, with PT occurring in 1 patient at 171 days after initial treatment for elevated LDH (202 days post-implant). Early medical intervention at moderately elevated LDH (2.5× to 3.2× ULN), as compared with higher levels (>3.2× ULN), led to more sustained resolution of symptoms without subsequent PT or need for surgical intervention (91% vs 26% at 6 months post-treatment, p = 0.002). CONCLUSIONS: Early medical intervention can successfully resolve moderate LDH elevations (2.5× to 3.2× ULN) with a low incidence of death or PT at 6 months post-treatment.

Quality of life and functional capacity outcomes in the MOMENTUM 3 trial at 6 months: A call for new metrics for left ventricular assist device patients.

BACKGROUND: The Multicenter Study of MAGLEV Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) clinical trial demonstrated improved 6-month event-free survival, but a detailed analysis of health-related quality of life (HR-QOL) and functional capacity (FC) was not presented. Further, the effect of early serious adverse events (SAEs) on these metrics and on the general ability to live well while supported with a left ventricular assist system (LVAS) warrants evaluation. METHODS: FC (New York Heart Association [NYHA] and 6-minute walk test [6MWT]) and HR-QOL (European Quality of Life [EQ-5D-5L] and the Kansas City Cardiomyopathy [KCCQ]) assessments were obtained at baseline and 6 months after HeartMate 3 (HM3, n = 151; Abbott, Abbott Park, IL) or HeartMate II (HMII, n = 138; Abbott) implant as part of the MOMENTUM 3 clinical trial. Metrics were compared between devices and in those with and without events. The proportion of patients "living well on an LVAS" at 6 months, defined as alive with satisfactory FC (NYHA I/II or 6MWT > 300 meters) and HR-QOL (overall KCCQ > 50), was evaluated. RESULTS: Although the median (25th-75th percentile) patient KCCQ (change for HM3: +28 [10-46]; HMII: +29 [9-48]) and EQ-5D-5L (change for HM3: -1 [-5 to 0]; HMII: -2 [-6 to 0]) scores improved from baseline to 6 months (p < 0.05), there were no differences between devices (p > 0.05). Likewise, there was an equivalent improvement in 6MWT distance at 6 months in HM3 (+94 [1-274] meters] and HMII (+188[43-340 meters]) from baseline. In patients with SAEs (n = 188), 6MWTs increased from baseline (p < 0.001), but gains for both devices were less than those without SAE (HM3: +74 [-9 to 183] meters with SAE vs +140 [35-329] meters without SAE; HMII: +177 [47-356] meters with SAE vs +192 [23-337] meters without SAE, both p < 0.003). SAEs did not affect the 6-month HR-QOL scores. The "living well" end point was achieved in 145 HM3 (63%) and 120 HMII (68%) patients (p = 0.44). CONCLUSIONS: Gains in HR-QOL and FC were similar early after HM3 and HMII implant. 6MWT improvements were attenuated in patients experiencing SAEs, but HR-QOL metrics did not change. The development of left ventricular assist device-specific HR-QOL tools is needed to better characterize the effect of SAEs on a patient's well-being. CLINICAL TRIAL NO: MOMENTUM 3 clinical trial #NCT02224755.

Multicenter Evaluation of Octreotide as Secondary Prophylaxis in Patients With Left Ventricular Assist Devices and Gastrointestinal Bleeding.

BACKGROUND: Gastrointestinal (GI) bleeding is one of the most common complications after continuous-flow left ventricular assist device implantation. More than one third of patients with incident bleed go on to develop recurrent GI bleeding. Octreotide, a somatostatin analog, is proposed to reduce the risk of recurrent GI bleeding in this population. METHODS AND RESULTS: This multicenter, retrospective analysis evaluated 51 continuous-flow left ventricular assist device patients who received secondary prophylaxis with octreotide after their index GI bleed from 2009 to 2015. All patients had a hospitalization for GI bleed and received octreotide after discharge. Patient demographics, medical and medication history, and clinical characteristics of patients who rebled after receiving octreotide were compared with non-rebleeders. These data were also compared with matched historical control patients previously enrolled in the HMII (HeartMate II) clinical trials, none of whom received octreotide, to provide a context for the bleeding rates. Twelve patients (24%) who received secondary octreotide prophylaxis developed another GI bleed, whereas 39 (76%) did not. There were similar intergroup demographics; however, significantly more bleeders had a previous GI bleeding history before left ventricular assist device placement (33% versus 5%; P=0.02) and greater frequency of angiodysplasia confirmed during endoscopy (58% versus 23%; P=0.03). Fewer patients in this study experienced a recurrent GI bleed compared with a matched historical control group that did not receive octreotide (24% versus 43%; P=0.04). CONCLUSIONS: Patients with continuous-flow left ventricular assist device receiving secondary prophylaxis with octreotide had a significantly lower GI bleed recurrence compared with historical controls not treated with octreotide. Additional prospective studies are needed to confirm these data.

Patient-Reported Health-Related Quality of Life Is a Predictor of Outcomes in Ambulatory Heart Failure Patients Treated With Left Ventricular Assist Device Compared With Medical Management: Results From the ROADMAP Study (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management).

BACKGROUND: The prospective observational ROADMAP study (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management) demonstrated that ambulatory advanced heart failure patients selected for left ventricular assist device (LVAD) were more likely to be alive at 1 year on original therapy with ≥75-m improvement in 6-minute walk distance compared with patients assigned to optimal medical management. Whether baseline health-related quality of life (hrQoL) resulted in a heterogeneity of this treatment benefit is unknown. METHODS AND RESULTS: Patient-reported hrQoL was assessed with EuroQol questionnaire and visual analogue scale (VAS). We aimed to identify predictors of event-free survival and survival with acceptable hrQoL (VAS≥60). LVAD patients had significant improvement in 3 of 5 EuroQol dimensions (P<0.05), but no significant changes were observed with optimal medical management. Among patients with baseline VAS<55, survival on original treatment was lower for optimal medical management patients compared with those assigned to LVAD (58±7% versus 82±5%; P=0.004). No such difference was seen if baseline VAS was ≥55 (70±7% versus 75±9%; P=0.79). Survival on original therapy with acceptable quality of life was also more likely with LVAD versus optimal medical management if baseline VAS was <55, whereas outcomes in patients with higher baseline VAS scores were similar regardless of treatment assignment (P=0.046 for treatment arm and baseline VAS interaction). CONCLUSIONS: LVAD therapy resulted in improvement of patient health status in heart failure patients with low self-reported hrQoL, but not in patients with acceptable quality of life at the time of LVAD implantation. Patient-reported hrQoL should be integrated into decision making concerning the use and timing of LVAD therapy in heart failure patients who are symptom limited but remain ambulatory. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01452802.

Accuracy of Seattle Heart Failure Model and HeartMate II Risk Score in Non-Inotrope-Dependent Advanced Heart Failure Patients: Insights From the ROADMAP Study (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients).

BACKGROUND: Timing of left ventricular assist device (LVAD) implantation in advanced heart failure patients not on inotropes is unclear. Relevant prediction models exist (SHFM [Seattle Heart Failure Model] and HMRS [HeartMate II Risk Score]), but use in this group is not established. METHODS AND RESULTS: ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) is a prospective, multicenter, nonrandomized study of 200 advanced heart failure patients not on inotropes who met indications for LVAD implantation, comparing the effectiveness of HeartMate II support versus optimal medical management. We compared SHFM-predicted versus observed survival (overall survival and LVAD-free survival) in the optimal medical management arm (n=103) and HMRS-predicted versus observed survival in all LVAD patients (n=111) using Cox modeling, receiver-operator characteristic (ROC) curves, and calibration plots. In the optimal medical management cohort, the SHFM was a significant predictor of survival (hazard ratio=2.98; P<0.001; ROC area under the curve=0.71; P<0.001) but not LVAD-free survival (hazard ratio=1.41; P=0.097; ROC area under the curve=0.56; P=0.314). SHFM showed adequate calibration for survival but overestimated LVAD-free survival. In the LVAD cohort, the HMRS had marginal discrimination at 3 (Cox P=0.23; ROC area under the curve=0.71; P=0.026) and 12 months (Cox P=0.036; ROC area under the curve=0.62; P=0.122), but calibration was poor, underestimating survival across time and risk subgroups. CONCLUSIONS: In non-inotrope-dependent advanced heart failure patients receiving optimal medical management, the SHFM was predictive of overall survival but underestimated the risk of clinical worsening and LVAD implantation. Among LVAD patients, the HMRS had marginal discrimination and underestimated survival post-LVAD implantation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01452802.

Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients: The ROADMAP Study 2-Year Results.

OBJECTIVES: The authors sought to provide the pre-specified primary endpoint of the ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) trial at 2 years. BACKGROUND: The ROADMAP trial was a prospective nonrandomized observational study of 200 patients (97 with a left ventricular assist device [LVAD], 103 on optimal medical management [OMM]) that showed that survival with improved functional status at 1 year was better with LVADs compared with OMM in a patient population of ambulatory New York Heart Association functional class IIIb/IV patients. METHODS: The primary composite endpoint was survival on original therapy with improvement in 6-min walk distance ≥75 m. RESULTS: Patients receiving LVAD versus OMM had lower baseline health-related quality of life, reduced Seattle Heart Failure Model 1-year survival (78% vs. 84%; p = 0.012), and were predominantly INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 4 (65% vs. 34%; p < 0.001) versus profiles 5 to 7. More LVAD patients met the primary endpoint at 2 years: 30% LVAD versus 12% OMM (odds ratio: 3.2 [95% confidence interval: 1.3 to 7.7]; p = 0.012). Survival as treated on original therapy at 2 years was greater for LVAD versus OMM (70 ± 5% vs. 41 ± 5%; p < 0.001), but there was no difference in intent-to-treat survival (70 ± 5% vs. 63 ± 5%; p = 0.307). In the OMM arm, 23 of 103 (22%) received delayed LVADs (18 within 12 months; 5 from 12 to 24 months). LVAD adverse events declined after year 1 for bleeding (primarily gastrointestinal) and arrhythmias. CONCLUSIONS: Survival on original therapy with improvement in 6-min walk distance was superior with LVAD compared with OMM at 2 years. Reduction in key adverse events beyond 1 year was observed in the LVAD group. The ROADMAP trial provides risk-benefit information to guide patient- and physician-shared decision making for elective LVAD therapy as a treatment for heart failure. (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients [ROADMAP]; NCT01452802).

Outcomes in HeartMate II Patients With No Antiplatelet Therapy: 2-Year Results From the European TRACE Study.

BACKGROUND: Current recommendations of antithrombotic therapy for HeartMate II (HMII) patients include the use of both an anticoagulant and an antiplatelet agent. Because bleeding is still the most frequent adverse event, the TRACE (STudy of Reduced Anti-Coagulation/Anti-platelet Therapy in Patients with the HeartMatE II) study was initiated to evaluate the incidence of adverse events in HMII patients on reduced antithrombotic (RT) therapy. METHODS: HMII patients (n = 101) from nine centers were enrolled in the European arm of TRACE and were managed on a single anticoagulant (vitamin K antagonist) with no antiplatelet agents. An analysis of bleeding and thrombotic adverse events from all 101 patients with 2-year follow-up after initiation of RT therapy is reported here. RESULTS: Median age was 56 years (range, 18 to 72 years), 93% were men, 70% had an Interagency Registry for Mechanically Assisted Circulatory Support profile 1 to 3, and 82% received the HMII as a bridge to transplantation. Ninety-two percent were placed on RT therapy as a center standard of care or due to physician preference and 6% as a response to bleeding. Median HMII support duration on RT therapy was 25 months (range, 1 to 93 months). Median international normalized ratio was 2.31 [quartile 1 to quartile 3: 2.07 to 2.60]. At 2 years, freedom from bleeding, ischemic stroke, hemorrhagic stroke, and pump thrombosis after initiation of RT therapy was 81% ± 6%, 96% ± 2%, 94% ± 3%, and 94% ± 3%, respectively. CONCLUSIONS: The 2-year analysis of the observational European TRACE study suggests that managing HMII patients with a vitamin K antagonist with a target international normalized ratio of 2.3 without antiplatelet therapy may help to reduce the incidence of major bleeding without increasing the risk of thromboembolic events, including ischemic stroke and pump thrombosis.

PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management: The PREVENT multi-center study.

BACKGROUND: Recommended structured clinical practices including implant technique, anti-coagulation strategy, and pump speed management (PREVENT [PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management] recommendations) were developed to address risk of early (<3 months) pump thrombosis (PT) risk with HeartMate II (HMII; St. Jude Medical, Inc. [Thoratec Corporation], Pleasanton, CA). We prospectively assessed the HMII PT rate in the current era when participating centers adhered to the PREVENT recommendations. METHODS: PREVENT was a prospective, multi-center, single-arm, non-randomized study of 300 patients implanted with HMII at 24 participating sites. Confirmed PT (any suspected PT confirmed visually and/or adjudicated by an independent assessor) was evaluated at 3 months (primary end-point) and at 6 months after implantation. RESULTS: The population included 83% men (age 57 years ± 13), 78% destination therapy, and 83% Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profile 1-3. Primary end-point analysis showed a confirmed PT of 2.9% at 3 months and 4.8% at 6 months. Adherence to key recommendations included 78% to surgical recommendations, 95% to heparin bridging, and 79% to pump speeds ≥9,000 RPMs (92% >8,600 RPMs). Full adherence to implant techniques, heparin bridging, and pump speeds ≥9,000 RPMs resulted in a significantly lower risk of PT (1.9% vs 8.9%; p < 0.01) and lower composite risk of suspected thrombosis, hemolysis, and ischemic stroke (5.7% vs 17.7%; p < 0.01) at 6 months. CONCLUSIONS: Adoption of all components of a structured surgical implant technique and clinical management strategy (PREVENT recommendations) is associated with low rates of confirmed PT.

Outcomes of Adult Patients with Small Body Size Supported with a Continuous-Flow Left Ventricular Assist Device.

There is insufficient data on patients with small body size to determine if this should be considered a risk factor for continuous-flow left ventricular assist device (CF-LVAD) support. We sought to evaluate survival outcomes, adverse events, and functional status of CF-LVAD patients with body surface area (BSA) <1.5 m in a large national registry. Adults with BSA < 1.5 m (n = 128) implanted with a HeartMate II (HMII)-LVAD from the Interagency Registry for Mechanically Assisted Circulatory Support registry from April 2008 to December 2012 formed this cohort. Outcomes were compared with HMII bridge to transplant (BTT) and destination therapy (DT) post approval studies. The majority of patients were female (n = 106, 83%). A total of 64% (n = 82) were implanted for BTT and 36% (n = 46) for DT. The median BSA (range) was 1.44 (1.19-1.49) and 1.45 (1.25-1.49) m for BTT and DT, respectively. Overall survival 1 year post implant was 81% ± 5% for BTT and 84% ± 6% for DT. The most common adverse events for BTT and DT patients were bleeding (0.91, 0.88 events/patient year) and driveline infection (16%, 0.28 events/patient year). Six months post implantation, 87% of BTT and 77% of DT patients were New York Heart Association functional class I or II. Post implant survival, functional status improvement, and adverse event profile for adult BTT and DT HMII patients with BSA < 1.5 m are favorable and comparable with outcomes published in the overall patient population.