Transplantation Outcomes with Donor Hearts after Circulatory Death.

BACKGROUND: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).

Cost effectiveness of commercial portable ex vivo lung perfusion at a low-volume US lung transplant center.

BACKGROUND: Portable ex vivo lung perfusion during lung transplantation is a resource-intensive technology. In light of its increasing use, we evaluated the cost-effectiveness of ex vivo lung perfusion at a low-volume lung transplant center in the USA. METHODS: Patients listed for lung transplantation (2015-2021) in the United Network for Organ Sharing database were included. Quality-of-life was approximated by Karnofsky Performance Status scores 1-year post-transplant. Total transplantation encounter and 1-year follow-up costs accrued by our academic center for patients listed from 2018 to 2021 were obtained. Cost-effectiveness was calculated by evaluating the number of patients attaining various Karnofsky scores relative to cost. RESULTS: Of the 13 930 adult patients who underwent lung transplant in the United Network for Organ Sharing database, 13 477 (96.7%) used static cold storage and 453 (3.3%) used ex vivo lung perfusion, compared to 30/58 (51.7%) and 28/58 (48.3%), respectively, at our center. Compared to static cold storage, median total costs at 1 year were higher for ex vivo lung perfusion ($918 000 vs. $516 000; p = 0.007) along with the cost of living 1 year with a Karnofsky functional status of 100 after transplant ($1 290 000 vs. $841 000). In simulated scenarios, each Karnofsky-adjusted life year gained by ex vivo lung perfusion was 1.00-1.72 times more expensive. CONCLUSIONS: Portable ex vivo lung perfusion is not currently cost-effective at a low-volume transplant centers in the USA, being 1.53 times more expensive per Karnofsky-adjusted life year. Improving donor lung and/or recipient biology during ex vivo lung perfusion may improve its utility for routine transplantation.

Donation After Circulatory Death Heart Transplantation: A Narrative Review.

Heart transplantation is the definitive treatment for refractory, end-stage heart failure. The number of patients awaiting transplantation far exceeds available organs. In an effort to expand the donor pool, donation after circulatory death (DCD) heart transplantation has garnered renewed interest. Unlike donation after brain death, DCD donors do not meet the criteria for brain death and are dependent on life-sustaining therapies. Procurement can include a direct strategy or a normothermic regional perfusion, whereby there is restoration of perfusion to the organ before explantation. There are new developments in cold storage and ex vivo perfusion strategies. Since its inception, there has been a steady improvement in post-transplant outcomes, largely attributed to advancements in operative and procurement strategies. In this narrative review, the authors address the unique considerations of DCD heart transplantation, including withdrawal of care, the logistics of procuring and resuscitating organs, outcomes compared with standard donation after brain death, and ethical considerations.

The prognostic role of advanced hemodynamic variables in patients with left ventricular assist devices.

BACKGROUND: Invasive hemodynamic variables obtained from right heart catheterization have been used for risk-stratifying patients with advanced heart failure (HF). However, there is a paucity of data on the prognostic value of invasive hemodynamic variables in patients with left ventricular assist devices (LVAD). We hypothesized that cardiac power output (CPO), cardiac power efficiency (CPE), and left ventricular stroke work index (LVSWI) can serve as prognostic markers in patients with LVADs. METHODS: Baseline hemodynamic data from patients who had LVAD ramp studies at our institution from 4/2014 to 7/2018 were prospectively collected, from which advanced hemodynamic variables (CPO, CPE, and LVSWI) were retrospectively analyzed. Univariate and multivariable analyses were performed for hemocompatibility-related adverse events (HRAE), HF admissions, and mortality. RESULTS: Ninety-one participants (age 61 ± 11 years, 34% women, 40% Black or African American, and 38% ischemic cardiomyopathy) were analyzed. Low CPE was significantly associated with mortality (HR 2.42, 95% CI 1.02-5.74, p = 0.045) in univariate analysis and Kaplan-Meier analysis (p = 0.04). Low LVSWI was significantly associated with mortality (HR 2.13, 95% CI 1.09-4.17, p = 0.03) in univariate analysis and Kaplan-Meier analysis (p = 0.02). CPO was not associated with mortality. CPO, CPE, and LVSWI were not associated with HRAE or HF admissions. CONCLUSIONS: Advanced hemodynamic variables can serve as prognostic indicators for patients with LVADs. Low CPE and LVSWI are prognostic for higher mortality, but no variables were associated with HF admissions or HRAEs.

A Fully Magnetically Levitated Left Ventricular Assist Device - Final Report.

BACKGROUND: In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device. METHODS: We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years. RESULTS: This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axial-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (relative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 for superiority). Pump replacement was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P<0.001). The numbers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, a fully magnetically levitated centrifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.).

Clinical outcomes of grafted vs. percutaneous axillary intra-aortic balloon pump support as a bridge to transplantation: a propensity score-matched analysis.

OBJECTIVES: The purpose of this study is to investigate the early and late outcomes of axillary intra-aortic balloon pump (IABP) implantation as a bridge to heart transplantation, comparing the grafted technique with the percutaneous technique. METHODS: Between July 2009 and January 2020, 163 patients underwent an axillary IABP insertion as a bridge to heart transplantation. Among them, 97 patients underwent axillary IABP implantation through a graft sutured onto the axillary artery (Group A) and 66 patients underwent percutaneously (Group B). Propensity matching identified 53 matched pairs for analysis (C-statistics 0.741). The primary outcomes of interest included IABP-related complications, success rate of a bridge to transplantation, in-hospital mortality, and late survival. RESULTS: In the propensity-score matched cohort, there were no significant differences in the baseline characteristics between the two groups. The operation time was significantly longer in Group A than in Group B (141.5 ± 38.3 min vs 42.7 ± 19.3 min, p < 0.01). The complication rates including stroke, re-exploration for bleeding, and aortic event were not significantly different between Group A and B. However, Group A required more transfusion and re-exploration for bleeding. The success rate of a bridge to transplantation was similar between Group A (47/53, 88.7%) and Group B (47/53, 88.7%). There were no significant differences in in-hospital mortality and late survival between two groups. CONCLUSION: In the propensity score matching analysis, there were not any significant differences between the two groups in IABP-related complications, in-hospital mortality, and late survival. The percutaneous technique provided a shorter operation time and less requirement of transfusion and re-exploration for bleeding compared to the grafted technique. The percutaneous technique might be favorable when feasible.

Decreasing blood wastage during ex vivo lung perfusion recovery through utilization of thermal control technology.

BACKGROUND: The Organ Care System (OCS) is a revolutionary ex vivo organ perfusion technology that can potentially expand the organ retrieval range. The OCS Lung device uses packed red blood cells (pRBC) with a proprietary solution. We report the ability to reduce blood waste during this procedure by using a thermal packaging solution in conjunction with the OCS platform. METHODS: We retrospectively reviewed all OCS Lung recoveries performed by our recovery team, using pRBCfrom May 2019 to January 2021. Initially, units were stored using passive refrigeration with the Performance cooler at a temperature range of 1-6°C for 4 h. Subsequently, thermal control technology with the ProMed cooler was utilized to maintain the same temperature range for 72 h. RESULTS: Twenty-three recoveries were initiated with 63 pRBC. The Performance cooler was used for 8, while the ProMed cooler for 13. 37.5% of pRBC transported with the Performance cooler was used within the validated time range, while 25.0% were used beyond the validated time range based on clinical judgment. In addition, 37.5% of pRBC transported with the Performance cooler were returned to the institution after canceled recoveries with an estimated loss of $1800; the ProMed cooler had no wastage. CONCLUSIONS: This study showed that using an advanced thermal packaging solution facilitates proper storage of pRBC and represents an advancement for extended donor lung preservation. The elimination of blood wastage in this initial study portends ongoing benefits for the limited blood supply and reduced cost.

Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices in the MOMENTUM 3 Randomized Trial.

Importance: Although durable left ventricular assist device (LVAD) therapy has emerged as an important treatment option for patients with advanced heart failure refractory to pharmacological support, outcomes, including survival, beyond 2 years remain poorly characterized. Objective: To report the composite end point of survival to transplant, recovery, or LVAD support free of debilitating stroke (Modified Rankin Scale score >3) or reoperation to replace the pump 5 years after the implant in participants who received the fully magnetically levitated centrifugal-flow HeartMate 3 or axial-flow HeartMate II LVAD in the MOMENTUM 3 randomized trial and were still receiving LVAD therapy at the 2-year follow-up. Design, Setting, and Participants: This observational study was a 5-year follow-up of the MOMENTUM 3 trial, conducted in 69 US centers, that demonstrated superiority of the centrifugal-flow LVAD to the axial-flow pump with respect to survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump at 2 years. A total of 295 patients were enrolled between June 2019 to April 2021 in the extended-phase study, with 5-year follow-up completed in September 2021. Exposures: Of 1020 patients in the investigational device exemption per-protocol population, 536 were still receiving LVAD support at 2 years, of whom 289 received the centrifugal-flow pump and 247 received the axial-flow pump. Main Outcomes and Measures: There were 10 end points evaluated at 5 years in the per-protocol population, including a composite of survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump between the centrifugal-flow and axial-flow pump groups and overall survival between the 2 groups. Results: A total of 477 patients (295 enrolled and 182 provided limited data) of 536 patients still receiving LVAD support at 2 years contributed to the extended-phase analysis (median age, 62 y; 86 [18%] women). The 5-year Kaplan-Meier estimate of survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump in the centrifugal-flow vs axial-flow group was 54.0% vs 29.7% (hazard ratio, 0.55 [95% CI, 0.45-0.67]; P < .001). Overall Kaplan-Meier survival was 58.4% in the centrifugal-flow group vs 43.7% in the axial-flow group (hazard ratio, 0.72 [95% CI, 0.58-0.89]; P = .003). Serious adverse events of stroke, bleeding, and pump thrombosis were less frequent in the centrifugal-flow pump group. Conclusions and Relevance: In this observational follow-up study of patients from the MOMENTUM 3 randomized trial, per-protocol analyses found that receipt of a fully magnetically levitated centrifugal-flow LVAD vs axial-flow LVAD was associated with a better composite outcome and higher likelihood of overall survival at 5 years. These findings support the use of the fully magnetically levitated LVAD. Trial Registration: ClinicalTrials.gov Identifier: NCT02224755 and NCT03982979.

Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure.

BACKGROUND: In an early analysis of this trial, use of a magnetically levitated centrifugal continuous-flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical-bearing axial continuous-flow pump, at 6 months in patients with advanced heart failure. METHODS: In a randomized noninferiority and superiority trial, we compared the centrifugal-flow pump with the axial-flow pump in patients with advanced heart failure, irrespective of the intended goal of support (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke (with disabling stroke indicated by a modified Rankin score of >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove a malfunctioning device. The noninferiority margin for the risk difference (centrifugal-flow pump group minus axial-flow pump group) was -10 percentage points. RESULTS: Of 366 patients, 190 were assigned to the centrifugal-flow pump group and 176 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 151 patients (79.5%) in the centrifugal-flow pump group, as compared with 106 (60.2%) in the axial-flow pump group (absolute difference, 19.2 percentage points; 95% lower confidence boundary, 9.8 percentage points [P<0.001 for noninferiority]; hazard ratio, 0.46; 95% confidence interval [CI], 0.31 to 0.69 [P<0.001 for superiority]). Reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (3 patients [1.6%] vs. 30 patients [17.0%]; hazard ratio, 0.08; 95% CI, 0.03 to 0.27; P<0.001). The rates of death and disabling stroke were similar in the two groups, but the overall rate of stroke was lower in the centrifugal-flow pump group than in the axial-flow pump group (10.1% vs. 19.2%; hazard ratio, 0.47; 95% CI, 0.27 to 0.84, P=0.02). CONCLUSIONS: In patients with advanced heart failure, a fully magnetically levitated centrifugal-flow pump was superior to a mechanical-bearing axial-flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).

Comprehensive Analysis of Stroke in the Long-Term Cohort of the MOMENTUM 3 Study.

BACKGROUND: The MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) has demonstrated that the HeartMate 3 (HM3) pump is associated with reduced strokes compared with the HeartMate II (HMII) device. We now perform a comprehensive analysis of stroke events to evaluate their longitudinal occurrence, clinical correlates, patterns, and impact on outcome across the 2-year duration of support. METHODS: MOMENTUM 3 is a randomized controlled trial of the HM3 centrifugal-flow pump versus the HMII axial-flow pump in patients with advanced heart failure, regardless of the intended goal of support (bridge to transplantation or destination therapy). Baseline and postimplantation clinical correlates of stroke events were assessed with multivariable analyses. Longitudinal patterns, including device association, type of stroke (hemorrhagic versus ischemic), changing severity of impairment assessed with the modified Rankin Scale (disabling [modified Rankin Scale score >3] versus nondisabling [modified Rankin Scale score ≤3]) over time, and association with outcome, were determined. RESULTS: In 361 patients with the intended implant (189 HM3 and 172 HMII), 65 strokes (40 ischemic strokes and 25 hemorrhagic strokes) occurred in 52 patients at a median of 131 (range, 1-733) days. No difference in stroke rate was noted between 0 and 180 days of follow-up between devices. However, stroke incidence in the long-term period (181-730 days after left ventricular assist device) was 3.3 times lower for the HM3 group (HM3: 0.04 versus HMII: 0.13 events per patient-year; odds ratio, 0.23; 95% CI, 0.08-0.63; P=0.01). Treatment with the HM3 pump was the only independent predictor of lower stroke events. We found no direct association of blood pressure or antithrombotic regimens with observed stroke rates. A stroke event significantly lowered 2-year postimplantation survival regardless of subtype or initial severity of neurological impairment compared with patients without a stroke (43±12% for hemorrhagic stroke, 57±9% for ischemic stroke, 51±11% for disabling, and 51±11% for nondisabling compared with 85±2% 2-year survival for patients without stroke). CONCLUSIONS: The HM3 pump is associated with a marked reduction in stroke rates compared with the HMII device, with benefits observed in the long-term period (>6 months). The occurrence of stroke of any type (hemorrhagic and ischemic) or of any functional severity (disabling and nondisabling) is predictive of a poor 2-year clinical outcome. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02224755.

A Fully Magnetically Levitated Circulatory Pump for Advanced Heart Failure.

BACKGROUND: Continuous-flow left ventricular assist systems increase the rate of survival among patients with advanced heart failure but are associated with the development of pump thrombosis. We investigated the effects of a new magnetically levitated centrifugal continuous-flow pump that was engineered to avert thrombosis. METHODS: We randomly assigned patients with advanced heart failure to receive either the new centrifugal continuous-flow pump or a commercially available axial continuous-flow pump. Patients could be enrolled irrespective of the intended goal of pump support (bridge to transplantation or destination therapy). The primary end point was a composite of survival free of disabling stroke (with disabling stroke indicated by a modified Rankin score >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove the device at 6 months after implantation. The trial was powered for noninferiority testing of the primary end point (noninferiority margin, -10 percentage points). RESULTS: Of 294 patients, 152 were assigned to the centrifugal-flow pump group and 142 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 131 patients (86.2%) in the centrifugal-flow pump group and in 109 (76.8%) in the axial-flow pump group (absolute difference, 9.4 percentage points; 95% lower confidence boundary, -2.1 [P<0.001 for noninferiority]; hazard ratio, 0.55; 95% confidence interval [CI], 0.32 to 0.95 [two-tailed P=0.04 for superiority]). There were no significant between-group differences in the rates of death or disabling stroke, but reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (1 [0.7%] vs. 11 [7.7%]; hazard ratio, 0.08; 95% CI, 0.01 to 0.60; P=0.002). Suspected or confirmed pump thrombosis occurred in no patients in the centrifugal-flow pump group and in 14 patients (10.1%) in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, implantation of a fully magnetically levitated centrifugal-flow pump was associated with better outcomes at 6 months than was implantation of an axial-flow pump, primarily because of the lower rate of reoperation for pump malfunction. (Funded by St. Jude Medical; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).

Hepatitis C donor viremic cardiac transplantation: A practical approach.

INTRODUCTION: Patients with end-stage heart failure eligible for orthotopic heart transplantation (OHT) exceed the number of available donor organs. With highly effective hepatitis C virus (HCV) antiviral therapy now available, HCV+ organs are increasingly utilized. We seek to describe our experience with patients receiving HCV viremic organs as compared to non-HCV transplant recipients. METHODS: Our center began utilizing HCV hearts in February 2018. We retrospectively reviewed baseline demographics, laboratory data and outcomes for those undergoing OHT with majority being from a viremic HCV donor. RESULTS: Twenty-three of 25 HCV recipients received hearts from NAT+ donors with 22 of 23 seroconverting within 7 days. Fifteen recipients have completed HCV treatment, with the longest duration of follow-up being 13 months. No differences in rates of rejection, hospitalizations or death were seen between non-HCV and HCV transplant patients. DISCUSSION: With the advent of available direct-acting antivirals (DAAs), viremic HCV hearts provide an opportunity to increase organ availability. Moreover, treatment for HCV in the setting of immunosuppression is well-tolerated and results in sustained viremic response. CONCLUSION: Viremic, discordant HCV OHT can be performed in a safe and effective manner utilizing a systematic, multidisciplinary approach without an effect on short-term outcomes.

Healthcare Resource Use and Cost Implications in the MOMENTUM 3 Long-Term Outcome Study.

BACKGROUND: The MOMENTUM 3 trial compares the centrifugal HeartMate 3 (HM3) with the axial HeartMate II (HMII) continuous-flow left ventricular assist system in patients with advanced heart failure, irrespective of the intended goal of therapy. The trial's 2-year clinical outcome (n=366) demonstrated superiority of the HM3 for the primary end point (survival free of a disabling stroke or reoperation to replace or remove a malfunctioning pump). This analysis evaluates health resource use and cost implications of the observed differences between the 2 devices while patients were enrolled in the trial. METHODS: We analyzed all hospitalizations and their associated costs occurring after discharge from the implant hospitalization until censoring (study withdrawal, heart transplantation, and pump exchange with a nonstudy device or death). Each adjudicated episode of hospital-based care was used to calculate costs (device-attributable and non-device-attributable event costs), estimated by using trial data and payer administrative claims databases. Cost savings stratified by subgroups (study outcome [transplant, death, or ongoing on device], intended goal of therapy, type of insurance, or sex) were also assessed. RESULTS: In 366 randomly assigned patients, 361 comprised the as-treated group (189 in the HM3 group and 172 in the HMII group), of whom 337 (177 in the HM3 group and 160 in the HMII group) were successfully discharged following implantation. The HM3 arm experienced fewer total hospitalizations per patient-year (HM3: 2.1±0.2 versus HMII: 2.7±0.2; P=0.015) and 8.3 fewer hospital days per patient-year on average (HM3: 17.1 days versus HMII: 25.5 days; P=0.003). These differences were driven by patients hospitalized for suspected pump thrombosis (HM3: 0.6% versus HMII: 12.5%; P<0.001) and stroke (HM3: 2.8% versus HMII: 11.3%; P=0.002). Controlled for time spent in the study (average cumulative cost per patient-year), postdischarge HM3 arm costs were 51% lower than with the HMII (HM3: $37 685±4251 versus HMII: $76 599±11 889, P<0.001) and similar in either bridge to transplant or destination therapy intent. CONCLUSIONS: In this 2-year outcome economic analysis of the MOMENTUM 3 trial, the HM3 demonstrated a reduction in rehospitalizations, hospital days spent during rehospitalizations, and a significant cost savings following discharge in comparison with the HMII left ventricular assist system, irrespective of the intended goal of therapy. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02224755.

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.

BACKGROUND: The HeartMate 3 (HM3) Left Ventricular Assist System (LVAS) (Abbott) is a centrifugal, fully magnetically levitated, continuous-flow blood pump engineered to enhance hemocompatibility and reduce shear stress on blood components. The MOMENTUM 3 trial (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) compares the HM3 LVAS with the HeartMate II (HMII) LVAS (Abbott) in advanced heart failure refractory to medical management, irrespective of therapeutic intention (bridge to transplant versus destination therapy). This investigation reported its primary outcome in the short-term cohort (n=294; 6-month follow-up), demonstrating superiority of the HM3 for the trial primary end point (survival free of a disabling stroke or reoperation to replace the pump for malfunction), driven by a reduced need for reoperations. The aim of this analysis was to evaluate the aggregate of hemocompatibility-related clinical adverse events (HRAEs) between the 2 LVAS. METHODS: We conducted a secondary end point evaluation of HRAE (survival free of any nonsurgical bleeding, thromboembolic event, pump thrombosis, or neurological event) in the short-term cohort (as-treated cohort n=289) at 6 months. The net burden of HRAE was also assessed by using a previously described hemocompatibility score, which uses 4 escalating tiers of hierarchal severity to derive a total score for events encountered during the entire follow-up experience for each patient. RESULTS: In 289 patients in the as-treated group (151 the HM3 and 138 the HMII), survival free of any HRAE was achieved in 69% of the HM3 group and in 55% of the HMII group (hazard ratio, 0.62; confidence interval, 0.42-0.91; P=0.012). Using the hemocompatibility score, the HM3 group demonstrated less pump thrombosis requiring reoperation (0 versus 36 points, P<0.001) or medically managed pump thrombosis (0 versus 5 points, P=0.02), and fewer nondisabling strokes (6 versus 24 points, P=0.026) than the control HMII LVAS. The net hemocompatibility score in the HM3 in comparison with the HMII patients was 101 (0.67±1.50 points/patient) versus 137 (0.99±1.79 points/patient) (odds ratio, 0.64; confidence interval, 0.39-1.03; P=0.065). CONCLUSIONS: In this secondary analysis of the MOMENTUM 3 trial, the HM3 LVAS demonstrated greater freedom from HRAEs in comparison with the HMII LVAS at 6 months. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT02224755.

Temporal Differences in Outcomes During Long-Term Mechanical Circulatory Support.

BACKGROUND: Device indications have changed for placement of continuous-flow left ventricular assist devices (CF-LVADs). We performed a multicenter analysis evaluating temporal variations in outcomes after CF-LVAD implantation. METHODS & RESULTS: We retrospectively defined 3 time intervals to reflect changes in CF-LVAD technology (period 1, 2004-2009; period 2, 2010-2012; and period 3, 2012-2014). A total of 1,064 patients (Heartmate II [HMII] = 835; Heartware [HVAD] = 229) underwent CF-LVAD implantation from May 2004 to October 2014. Device utilization was different between periods: period 1: HMII = 134 (100%); period 2: HMII = 480 (88%) and HW = 63 (12%); and period 3: HMII = 221 (57%) and HW = 166 (43%); P < .001. Despite few baseline group differences, adjusted survivals were similar among the time periods (P = .96). Adjusted multivariable analysis revealed age (per 10-year increase) and Interagency Registry for Mechanically Assisted Circulatory Support category (1 vs all others) as the only independent predictors of mortality: P < .001 and P = .008, respectively. Furthermore, it also showed the later periods to be at an increased risk of adverse events: 1) pump thrombosis (periods 2 and 3); and 2) gastrointestinal bleeding (period 3). CONCLUSIONS: Despite significant differences in device types, indications, and patient characteristics, post-implantation survivals were similar across time intervals. The most recent cohort seems to be at an increased risk of gastrointestinal bleeding and pump thrombosis.

Ventricular Assist Device Therapy in Older Patients With Heart Failure: Characteristics and Outcomes.

BACKGROUND: Limited data exist on outcomes in patients ≥70 years of age supported with the use of continuous-flow left ventricular assist devices (LVADs). METHODS: Data on 1149 continuous-flow LVAD recipients was queried from the Mechanical Circulatory Support Research Network. Groups were assigned based on age: ≥70 years ("older patients") and <70 years. The primary outcome was survival at one-year based on age grouping. RESULTS: Compared with younger patients (54.3 ± 11.2 y; n = 986), older patients (73.4 ± 3.0 y) constituted only 14% of LVAD implants. Older patients had similar rates of device thrombosis (P = .47) and stroke (P = .44), but survival-free of gastrointestinal bleeding (GIB) at 1 year was lower compared with younger patients (58% vs 69%; P < .01). Unadjusted survival at 1 year in older patients was 75% compared with 84% in younger patients, and at 2 years 65% versus 73% (P = .18). Age ≥70 years was not associated with increased mortality (adjusted hazard ratio [aHR] 0.94, 95% confidence interval [CI] 0.70-1.26; P = .67). Preoperative creatinine (aHR 1.57, 95% CI: 1.30-1.89, P < .0001), bilirubin (aHR 1.22, 95% CI 1.05-1.42; P = .010), and ischemic cardiomyopathy (aHR 1.43, 95% CI 1.11-1.84; P = .005) portended increased risk of death. In older patients, the only predictor of mortality was creatinine (HR 2.1, 95% CI 1.2-3.4; P = .007). Creatinine ≥1.4 mg/dL was associated with a 1-year survival of 65%, compared with 84% when the creatinine was <1.4 mg/dL (P = .009). CONCLUSION: Age >70 years is an important consideration when assessing LVAD risk, but other correlates may be more predictive of LVAD survival. Older patients without renal dysfunction have survival similar to younger patients. Older patients should be counseled about age-correlated risks, including higher rates of GIB.

Factors Related to Pump Thrombosis With the Heartmate II Left Ventricular Assist Device.

BACKGROUND: Recent reports suggested that HeartMate II (HMII) thrombosis rates may be higher in implants after 2011. We characterize events at HMII centers (>100 HMII implants) whose device thrombosis rates are equivalent or lower than reported by INTERMACS. METHODS: Seven centers pooled implants from 2011 through June 2013 to examine pump thrombus and identify characteristics and clinical strategies that potentially mitigate the risk. A total of 666 patients (age 59 ± 13 years; 81% male) were studied (support duration: 13.7 ± 8.3 months, cumulative: 759 patient years). Median target INR was 2.25 (range 2.0 to 2.5), and median pump speed was 9200 rpm (range 8600 to 9600). Pump thrombus was suspected with clinical evidence (e.g., hemolysis, positive ramp test) requiring intervention (e.g., anticoagulation therapy, pump exchange) or patient death. RESULTS: Suspected pump thrombus occurred in 24/666 (3.6%) patients within three months of implant. At six months, 38/666 (5.7%) had suspected pump thrombus including 24 (3.6%) resulting in pump exchange or death. Stroke (hemorrhagic: 0.049, and ischemic: 0.048 events/patient year) and survival (six months: 88 ± 1%; 1 year: 81 ± 2%) were consistent with national averages. Suspected pump thrombus patients were younger (55 ± 13 vs. 59 ± 13, p = 0.046) and had more females (31.6% vs. 18.3%, p = 0.054). There was no difference in indication, etiology of heart failure, or body size. CONCLUSIONS: This analysis demonstrates low HMII thrombus events. Minimization of risk factors by uniform implant techniques and consistent post-op management may reduce device thrombosis. A larger scale multicenter evaluation may better elucidate the difference in thrombus events between centers.

A single-center experience with the Sorin Mitroflow pericardial aortic valve: hemodynamics up to five years.

BACKGROUND AND AIM OF THE STUDY: The authors' institution participated in a 28-center FDA Investigational Device Exemption study to evaluate the Sorin Mitroflow pericardial aortic bioprosthesis. Six high-enrolling sites evaluated patients on an annual basis as part of an ongoing hemodynamic study. These data represent patients followed for an average of five years after implant, with annual echocardiography. METHODS: Seventy-one patients were entered into the study and constitute the basis of this review. Mean follow up was 3.3 +/- 2.0 years (range: 0-5.5 years), with a cumulative follow up of 233 patient-years. The mean patient age was 73.8 years (range: 45-89 years), and 52% were males. The majority of aortic valve lesions were stenosis (63%) or mixed (30%), and nine patients (12.7%) were reoperations. Sixty-one patients (86%) had concomitant procedures, the most common being coronary artery bypass grafting (70%). RESULTS: A total of 281 echocardiograms was obtained from the patients over a five-year period. The largest number of echocardiograms was obtained with 23-mm valve implants (n = 122), followed by 25 mm valve implants (n = 87). The early baseline (30-day) mean gradient was < or = 10 mm in all patients. The mean gradient decreased as the valve size increased (21 mm valve gradient = 10.0 +/- 5.6 mmHg; 27 mm valve gradient = 6.2 +/- 2.2 mmHg). The mean increase in gradient at five years was < 7 mmHg, with a trend towards increased gradients at smaller valve sizes. The effective orifice area (EOA) showed a trend to decline slightly with 21 mm valves (from 1.5 to 1.2 cm2) and 23 mm valves (1.4 to 1.2 cm2), but there was either no change or a slight increase in larger-size valves. Left ventricular mass regression occurred mainly within the first year (18.9%), but then remained stable throughout the study period. No greater than mild prosthetic aortic valve regurgitation was observed over the study period. CONCLUSION: The Sorin Mitroflow aortic valve provides excellent hemodynamic results up to five years, with minimal increase in mean gradients, acceptable peak gradients, and good EOAs with all valves sizes.