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Currently, the fully magnetically levitated left ventricular assist device (LVAD) HeartMate 3 (HM3) is the only commercially available device for advanced heart failure (HF) patients. However, the left ventricular (LV) functional and structural changes following mechanical unloading and circulatory support (MCS) with the HM3 have not been investigated. We compared the reverse remodeling induced by the HM3 to older generation continuous-flow LVADs. Chronic HF patients (n = 405) undergoing MCS with HeartWare Ventricular Assist Device (HVAD, n = 115), HM3 (n = 186), and HeartMate II (HM2, n = 104) at four programs were included. Echocardiograms were obtained preimplant and at 1, 3, 6, and 12 months following LVAD implantation. There were no differences in the postimplant serial LV ejection fraction (LVEF) between the devices. The postimplant LV internal diastolic diameter (LVIDd) was significantly lower for HM2 at 3 and 6 months compared with HVAD and HM3. The proportion of patients achieving "cardiac reverse remodeling responder" status (defined as LVEF improvement to ≥40% and LVIDD ≤5.9 cm) was 11.9%, and was similar between devices. HeartMate 3 appears to result in similar cardiac reverse remodeling as older generation CF-LVADs, suggesting that the fully magnetically levitated device technology could provide an effective platform to further study and promote cardiac reverse remodeling., Competing Interests: S.G.D. serves as a consultant for Abbott Laboratoriesand has received research support from Novartis. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

While notable improvements in survival, the incidence of hemocompatibility-related adverse events, hospitalizations, and cost have been demonstrated with the only commercially available durable left ventricular assist device, a category of pump malfunctions characterized by outflow graft obstruction has been noted with broader use and clinical follow-up of recipients of this technology. Of particular concern is the accumulation of acellular biodebris between the outflow graft and bend relief covering the outflow graft at its origin with the pump (which we term extrinsic outflow graft obstruction at the bend relief). This process tends to be insidious, occurs late in the postoperative course, can be challenging to diagnose, and can result in significant morbidity and mortality. Herein, we provide a review of this complication and outline diagnostic, treatment, and preventive strategies., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Patients have substantial variability in perioperative outcomes after left ventricular assist device (LVAD) implant. A perioperative multidimensional tool integrating mortality, adverse events (AEs), and patient-reported outcomes to assist in quality improvement initiatives is needed., Methods: Patients undergoing HeartMate 3 LVAD implant (January 1, 2017 to January 31, 2024) in the Society of Thoracic Surgeons' Intermacs registry were studied. Cox proportional hazard multivariable analyses incorporating AEs as time-varying covariates for mortality out to 180 days was used to generate the INtermacs Short term composITE quality score (INSITE score derivation), reflecting the adjusted hazard ratio (HR) for mortality contributed by each AE, applying the global ranking methodology. In those alive and on support at 6 months, multivariable logistic regression (odds ratio) was used to examine the impact of AEs on health-related quality of life (QOL) at 180 days, captured through the INSITE-QOL score. Failure to achieve ≥1 point increase in visual analog scale from baseline was the event., Results: Of 13,148 patients, 4,389 (33.4%) suffered at least 1 AE or death through 180 days. Stroke (survival: HR 13.1; QOL: HR 1.7), dialysis (survival: HR 31.4; QOL: HR 4.2), prolonged respiratory failure (survival: HR 5.7; QOL: HR 2.3), reoperation (survival: HR 3.4; QOL: HR 1.6), and right heart failure (survival: 5.0; QOL: HR 1.4), contributed to both mortality and failure to improve QOL at 180 days (all p < 0.05). The median INSITE and INSITE-QOL scores were 0.0 [0.0, 1.6] and 0.0 [0.0, 0.0], respectively. At 9.4% (n = 17) of centers, a high INSITE score (≥13) was present in 15% of patients, while the top 25% of centers had perfect INSITE-QOL scores in at least 75% of patients., Conclusions: AEs after LVAD confer differential impact on mortality and QOL, enabling the development of global rank outcome scores. Given the high mortality hazard conferred by 180-day AEs, center-specific quality interventions aimed at reducing early complications provide the greatest opportunity to improve long-term survival and QOL., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Hemocompatibility-related adverse events affect patients after left ventricular assist device (LVAD) implantation but are hard to predict., Objectives: Dynamic risk modeling with a multistate model can predict risk of gastrointestinal bleeding (GIB), stroke, or death in ambulatory patients., Methods: This was a secondary analysis of the MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial. HeartMate 3 LVAD recipients who survived to hospital discharge and were followed for up to 2 years. A total of 145 variables were included in the multistate model with multivariate logistic regression. Model performance was assessed with the area under the curve in a holdout validation cohort. A risk stratification tool was created by dividing patients into categories of predicted risk using the final model variables and associated OR., Results: Among 2,056 LVAD patients, the median age was 59.4 years (20.4% women, 28.6% Black). At 2 years, the incidence of GIB, stroke, and death was 25.6%, 6.0%, and 12.3%, respectively. The multistate model included 39 total variables to predict risk of GIB (16 variables), stroke (10 variables), and death (19 variables). When ambulatory patients were classified according to their risk category, the 30-day observed event rate in the highest risk group for GIB, stroke, or death was 26.9%, 1.8%, and 4.8%, respectively. The multistate model predicted GIB, stroke, and death at any 30-day period with an area under the curve of 0.70, 0.69, and 0.86, respectively., Conclusions: The multistate model informs 30-day risk in ambulatory LVAD recipients and allows recalculation of risk as new patient-specific data become available. The model allows for accurate risk stratification that predicts impending adverse events and may guide clinical decision making. (MOMENTUM 3 IDE Clinical Study Protocol; NCT02224755)., Competing Interests: Funding Support and Author Disclosures Abbott is the sponsor of the MOMENTUM 3 studies. Abbott supported an investigator-initiated grant paid to the Inova Heart and Vascular Institute to support this effort; and Abbott has filed a U.S. provisional patent (U.S. Patent Application No. 63/421,450) for the work presented in the paper. Dr Shah is supported by National Institutes of Health K23 Career Development Award 1K23HL143179; has received consulting fees from Procyrion, Merck, and Natera; and grant support has been paid to his institution from Abbott, Roche, Merck, and Bayer. Dr Sayer has received consulting fees from Abbott. Dr Kanwar is on the medical advisory board for Abiomed, CorWave, and CareDx. Dr Cowger has served as a consultant for Abbott, Medtronic, Bioventrix, Endotronix, Bivacor, and Procyrion; and has received grant support and speaker fees from Abbott. Dr Pagani has served as an AD hoc scientific advisor without compensation for FineHeart, Medtronic, CH Biomedical, and Abbott; has served as medical monitor for Abiomed; is a member of the data safety monitoring board for Carmat and the National Heart, Lung, and Blood Institute PumpKIN clinical trial; and is Chair of the Society of Thoracic Surgeons Intermacs Task Force. Dr Mehra has received travel support and consulting fees, paid to Brigham and Women’s Hospital, from Abbott; has received fees for serving on a steering committee from Medtronic and Janssen (Johnson and Johnson); has received fees for serving on a data and safety monitoring board from Mesoblast; has received consulting fees from Natera, Paragonix, Moderna, Baim Institute of Clinical Research, and Broadview Ventures; and has received fees for serving as a scientific board member from NuPulseCV, Leviticus, and FineHeart. Dr Cleveland has received fees from Abbott and Medtronic. Dr Desai is on the Speakers Bureau for Abbott. Drs Lu, Hu, Connolly, and Kormos are employees of Abbott. Dr Uriel is a medical advisory board member for Livemetric, Levitcus, and Revamp; and receives grant support from Abbott, Abiomed, and Fire 1. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Acute right ventricular failure (RVF) is prevalent in multiple disease states and is associated with poor clinical outcomes. Right-sided temporary mechanical circulatory support (tMCS) devices are used to unload RV congestion and increase cardiac output in cardiogenic shock (CS) with hemodynamically significant RVF. Several RV-tMCS device platforms are available; however consensus is lacking on patient selection, timing of escalation to RV-tMCS, device management, and device weaning. The purposes of this review are to 1) describe the current state of tMCS device therapies for acute RVF with CS, 2) discuss principles of escalation to RV-tMCS device therapy, 3) examine important aspects of clinical management for patients supported by RV-tMCS devices including volume management, anticoagulation, and positive pressure ventilation, and 4) provide a framework for RV-tMCS weaning., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The Impella 5.0 and 5.5 pumps (Abiomed, Danvers, MA) are large-bore transvalvular micro-axial assist devices used in cardiogenic shock (CS) for patients requiring high-capacity flow. Despite their increasing use, real-world data regarding indications, rates of utilization and clinical outcomes with this therapy are limited. The objective of our study was to examine clinical profiles and outcomes of patients in a contemporary, real-world CS registry of patients who received an Impella 5.0/5.5 alone or in combination with other temporary mechanical circulatory support (tMCS) devices., Methods: The CS Working Group (CSWG) Registry includes patients from 34 US hospitals. For this analysis, data from patients who received an Impella 5.0/5.5 between 2020-2023 were analyzed. Use of Impella 5.0/5.5 with or without additional tMCS therapies, duration of support, adverse events and outcomes at hospital discharge were studied. Adverse events including stroke, limb ischemia, bleeding and hemolysis were not standardized by the registry but reported per individual CSWG Primary Investigator discretion. For those who survived, rates of native heart recovery (NHR) or heart replacement therapy (HRT) including heart transplant (HT), or durable ventricular assist device (VAD) were recorded. We also assessed outcomes based on shock etiology (acute myocardial infarction or MI-CS vs. heart failure-related CS or HF-CS)., Results: Among 6,205 patients, 754 received an Impella 5.0/5.5 (12.1%), including 210 MI-CS (27.8%) and 484 HF-CS (64.1%) patients. Impella 5.0/5.5 was used as the sole tMCS device in 32% of patients, while 68% of patients received a combination of tMCS devices. Impella cannulation sites were available for 524/754 (69.4%) of patients, with 93.5% axillary configuration. Survival to hospital discharge for those supported with an Impella 5.0/5.5 was 67%, with 20.4% NHR and 45.5% HRT. Compared to HF-CS, patients with MI-CS supported on Impella 5.0/5.5 had higher in-hospital mortality (45.2% vs 26.2%, p < 0.001) and were less likely to receive HRT (22.4% vs 56.6%, p < 0.001. For patients receiving a combination of tMCS during hospitalization, this was associated with higher rates of limb ischemia (9% vs. 3%, p < 0.01), bleeding (52% vs 33%, p < 0.01), and mortality (38% vs 25%; p < 0.001) compared to Impella 5.0/5.5 alone. Among Impella 5.0/5.5 recipients, the median duration of pump support was 12.9 days (IQR: 6.8-22.9) and longer in patients bridged to HRT (14 days; IQR: 7.7-28.4)., Conclusions: In this multi-center cohort of patients with CS, use of Impella 5.0/5.5 was associated with an overall survival of 67.1% and high rates of HRT. Lower adverse event rates were observed when Impella 5.0/5.5 was the sole support device used. Further study is required to determine whether a strategy of early Impella 5.0/5.5 use for CS improves survival., Condensed Abstract: High capacity Impella heart pumps are capable of provide up to 5.5 liter/min of flow while upper body surgical placement allows for ambulation. Patients with advanced cardiogenic shock from acute myocardial infarction or heart failure requiring temporary mechanical circulatory support may benefit from upfront use of Impella 5.5 to improve overall survival, including native heart recovery or successful bridge to durable left ventricular assist device surgery or heart transplantation., (Copyright © 2024. Published by Elsevier Inc.)

Background: Interventricular interactions may be responsible for the decline in ventricular performance observed in various disease states that primarily affect the contralateral ventricle., Objectives: This study sought to quantify the impact of such interactions on right ventricular (RV) size and function using clinically stable individuals with left ventricular assist devices (LVADs) as a model for assessing RV hemodynamics while LV loading conditions were acutely manipulated by changing device speed during hemodynamic optimization studies (ie, ramp tests)., Methods: The investigators recorded RV pressure-volume loops with a conductance catheter at various speeds during ramp tests in 20 clinically stable HeartMate3 recipients., Results: With faster LVAD speeds and greater LV unloading, indexed RV end-diastolic volume increased (72.28 ± 15.07 mL at low speed vs 75.95 ± 16.90 at high speed; P = 0.04) whereas indexed end-systolic volumes remained neutral. This resulted in larger RV stroke volumes and shallower end-diastolic pressure-volume relationships. Concurrently, RV end-systolic pressure decreased (31.58 ± 9.75 mL at low speed vs 29.58 ± 9.41 mL at high speed; P = 0.02), but contractility, as measured by end-systolic elastance, did not change significantly. The reduction in RV end-systolic pressure was associated with a reduction in effective arterial elastance from 0.65 ± 0.43 mm Hg/mL at low speed to 0.54 ± 0.33 mm Hg/mL at high speed (P = 0.02)., Conclusions: Interventricular interactions resulted in improved RV compliance, diminished afterload, and did not reduce RV contractility. These data challenge the prevailing view that interventricular interactions compromise RV function, which has important implications for the understanding of RV-LV interactions in various disease states, including post-LVAD RV dysfunction., Competing Interests: Funding Support and Author Disclosures This project was supported, in part, by the American College of Cardiology and Merck Research Fellowship Award. Dr Brener has received consulting fees from Artract Medical and Osprey Medical. Dr Kanwar has served on the Medical Advisory Boards of Abiomed, CareDx, and CorWave. Dr Lander has served on the Medical Advisory Board of Abiomed. Dr Raina has received research support from United Therapeutics and Merck. Dr Sethi has received honoraria from Janssen and Chiessi; and has received institutional grant support from the American Heart Association’s COVID-19 Rapid Response Award. Dr Maurer has received funding from the National Institutes of Health (HL139671-01AL1 and AG K24AG036778); AD consulting income from Ionis, Alnylam, Eidos Therapeutics, Pfizer, Intellia, and Prothena; and his institution has also received funding for clinical trials for Ionis, Alnylam, Eidos Therapeutics, Pfizer, and Attralus. Dr Sayer has received consulting fees from Abbott. Dr Burkhoff has received an unrestricted institutional educational grant from Abiomed. Dr Uriel has received grant support from Abbott, Abiomed, and Fire1; and has served on the Medical Advisory Boards of Leviticus and Revamp. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Data regarding outcomes with Impella 5.5 are limited. The aim of this systematic review and meta-analysis was to summarize patient and treatment characteristics and early clinical outcomes among patients supported by Impella 5.5. A systematic literature search was conducted in PubMed, Scopus, and Cochrane databases from September 2019 to March 2023. Studies reporting outcomes in greater than or equal to 5 patients were included for review. Patient characteristics, treatment characteristics, and early clinical outcomes were extracted. Outcomes included adverse events, survival to hospital discharge, and 30 day survival. Random-effect models were used to estimate pooled effects for survival outcomes. Assessment for bias was performed using funnel plots and Egger's tests. Fifteen studies were included for qualitative review, representing 707 patients. Mean duration of support was 9.9 ± 8.2 days. On meta-analysis of 13 studies reporting survival outcomes, survival to hospital discharge was 68% (95% confidence interval [CI], 58-78%), and 30 day survival was 65% (95% CI, 56-74%) among patients with Impella devices predominantly supported by Impella 5.5 (>60%). There was significant study heterogeneity for these outcomes. Among 294 patients with Impella 5.5 only, survival to discharge was 78% (95% CI, 72-82%) with no significant study heterogeneity. This data present early benchmarks for outcomes with Impella 5.5 as clinical experience with these devices accrues., Competing Interests: Disclosure: A.K. is a speaker and consultant for Abiomed, 3ive, LivaNova, and Abbott. D.B. is employed by Abiomed. M.C. is a consultant for Abiomed. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Cardiogenic shock continues to portend poor outcomes, conferring short-term mortality rates of 30% to 50% despite recent scientific advances. Age is a nonmodifiable risk factor for mortality in patients with cardiogenic shock and is often considered in the decision-making process for eligibility for various therapies. Older adults have been largely excluded from analyses of therapeutic options in patients with cardiogenic shock. As a result, despite the association of advanced age with worse outcomes, focused strategies in the assessment and management of cardiogenic shock in this high-risk and growing population are lacking. Individual programs oftentimes develop upper age limits for various interventional strategies for their patients, including heart transplantation and durable left ventricular assist devices. However, age as a lone parameter should not be used to guide individual patient management decisions in cardiogenic shock. In the assessment of risk in older adults with cardiogenic shock, a comprehensive, interdisciplinary approach is central to developing best practices. In this American Heart Association scientific statement, we aim to summarize our contemporary understanding of the epidemiology, risk assessment, and in-hospital approach to management of cardiogenic shock, with a unique focus on older adults.

Background: The Heartmate 3 (HM3) risk score (HM3RS) was derived and validated internally from within the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) trial population and provides 1- and 2-year mortality risk prediction for patients in those before HM3 left ventricular assist device (LVAD) implantation. We aimed to evaluate the HM3RS in nontrial unselected patients, including those not meeting inclusion criteria for MOMENTUM 3 trial enrollment., Methods: Patients who underwent HM3 LVAD implant at 1 of 7 US centers between 2017 and 2021, with at least 1-year follow-up, were included in this analysis. Patients were retrospectively assessed for their eligibility for the MOMENTUM 3 trial based on study inclusion and exclusion criteria. HM3RS risk discrimination was evaluated using time-dependent receiver operating characteristic curve analysis for 1-year mortality for all patients and further stratified by MOMENTUM 3 trial eligibility. Kaplan-Meier curves were constructed using the HM3RS-based risk categories., Results: Of 521 patients included in the analysis, 266 (51.1%) would have met enrollment criteria for MOMENTUM 3. The 1- and 2-year survival for the total cohort was 85% and 81%, respectively. There was no statistically significant difference in survival between those who met and did not meet enrollment criteria at 1 (87% vs 83%; p = 0.21) and 2 years postimplant (80% vs 78%; p = 0.39). For the total cohort, HM3RS predicted 1-year survival with an area under the curve (AUC) of 0.63 (95% confidence interval [CI]: 0.57-0.69, p < 0.001). HM3RS performed better in the subset of patients meeting enrollment criteria: AUC 0.69 (95% CI:0.61-0.77, p < 0.001) compared to the subset that did not: AUC 0.58 (95% CI: 0.49-0.66, p = 0.078)., Conclusions: In this real-world evidence, multicenter cohort, 1- and 2-year survival after commercial HM3 LVAD implant was excellent, regardless of trial eligibility. The HM3RS provided adequate risk discrimination in "trial-like" patients, but predictive value was reduced in patients who did not meet trial criteria., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures None.

Importance: Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety., Objective: To determine whether excluding aspirin as part of the antithrombotic regimen with a fully magnetically levitated LVAD is safe and decreases bleeding., Design, Setting, and Participants: This international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/d) vs placebo with VKA therapy in patients with advanced heart failure with an LVAD was conducted across 51 centers with expertise in treating patients with advanced heart failure across 9 countries. The randomized population included 628 patients with advanced heart failure implanted with a fully magnetically levitated LVAD (314 in the placebo group and 314 in the aspirin group), of whom 296 patients in the placebo group and 293 in the aspirin group were in the primary analysis population, which informed the primary end point analysis. The study enrolled patients from July 2020 to September 2022; median follow-up was 14 months., Intervention: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg/d) or placebo in addition to an antithrombotic regimen., Main Outcomes and Measures: The composite primary end point, assessed for noninferiority (-10% margin) of placebo, was survival free of a major nonsurgical (>14 days after implant) hemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. The principal secondary end point was nonsurgical bleeding events., Results: Of the 589 analyzed patients, 77% were men; one-third were Black and 61% were White. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (74%) vs those taking aspirin (68%). Noninferiority of placebo was demonstrated (absolute between-group difference, 6.0% improvement in event-free survival with placebo [lower 1-sided 97.5% CI, -1.6%]; P < .001). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P = .002) with no increase in stroke or other thromboembolic events, a finding consistent among diverse subgroups of patient characteristics., Conclusions and Relevance: In patients with advanced heart failure treated with a fully magnetically levitated LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes VKA, is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events., Trial Registration: ClinicalTrials.gov Identifier: NCT04069156.

Background: Correction of valvular disease is often undertaken during left ventricular assist device (LVAD) implantation with uncertain benefit. We analyzed clinical outcomes with HeartMate 3 (HM3; Abbott) LVAD implantation in those with various concurrent valve procedures (HM3+VP) with those with an isolated LVAD implant (HM3 alone)., Methods: The study included 2200 patients with HM3 implanted within the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) trial portfolio who underwent 820 concurrent procedures among which 466 (21.8%) were HM3+VP. VPs included 101 aortic, 61 mitral, 163 tricuspid; 85 patients had multiple VPs. Perioperative complications, major adverse events, and survival were analyzed., Results: Patients who underwent HM3+VP had higher-acuity Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles (1-2: 41% vs 31%) compared with no VPs (P < .05). The cardiopulmonary bypass time (124 vs 76 minutes; P < .0001) and hospital length of stay (20 vs 18 days; P < .0001) were longer in HM3+VP. A higher incidence of stroke (4.9% vs 2.4%), bleeding (33.9% vs 23.8%), and right heart failure (41.5% vs 29.6%) was noted in HM3+VP at 0 to 30 days (P < .01), with no difference in 30-day mortality (3.9% vs 3.3%) or 2-year survival (81.7% vs 80.8%). Analysis of individual VP showed no differences in survival compared to HM3 alone. No differences were noted among patients with either significant mitral (moderate or worse) or tricuspid (moderate or worse) regurgitation with or without corrective surgery., Conclusions: Concurrent VPs, commonly performed during LVAD implantation, are associated with increased morbidity during the index hospitalization, with no effect on short- and long-term survival. There is sufficient equipoise to consider a randomized trial on the benefit of commonly performed VPs (such as mitral or tricuspid regurgitation correction), during LVAD implantation., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The INTERMACS Events data set contains an expansive collection of temporal evidence of the course of adverse events (AEs) of >15 000 patients that have received a left ventricular assist device (LVAD). The chronology of AEs may contain insightful information of the "AE journeys" of LVAD patients. The purpose of this study is to investigate the timelines of AEs within the INTERMACS database., Methods: Descriptive statistics were applied to 86 912 recorded AEs of 15 820 patients with a continuous flow-LVAD between 2008 to 2016, extracted from INTERMACS registry. The characteristics of the timelines of AE journeys were investigated by posing six descriptive research questions., Results: The analysis revealed several time-related characteristics and patterns of the AE journey after LVAD including the most common time of occurrences of AEs after surgery, duration of AEs journeys, the time of first and last AEs, and the time gaps between AEs., Conclusion: The INTERMACS Event dataset is a valuable resource for research about the timeline of AE journeys of patients who received an LVAD. It is necessary for future studies to first explore and consider the time-related characteristics of the data set such as diversity and sparsity to effectively choose an appropriate scope of time and time granularity and to acknowledge potential challenges., (© 2023 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

A redesigned surgically implanted heart pump incorporates several design changes from the prior device generation, but no published comparative data demonstrate if these changes translate to improved outcomes. We retrospectively compared clinical characteristics and outcomes, drawn from an FDA-mandated QA database, for contemporary patients treated with the Impella 5.5 or Impella 5.0 for acute myocardial infarction complicated by cardiogenic shock (AMICS), cardiomyopathy, or postcardiotomy cardiogenic shock (PCCS). A total of 1238 patients at 290 US sites were included for analysis. Patients receiving the Impella 5.5 had significantly higher survival through explant (i.e., successfully weaned or bridged to heart replacement therapy) than those receiving the Impella 5.0 in all 3 settings: AMICS (70.5% vs 56.8%; p = 0.005), cardiomyopathy (88.1% vs 76.9%; p = 0.001), and PCCS (76.1% vs 55.7%; p = 0.003). Duration of support was significantly longer for Impella 5.5 patients with AMICS (9.2 vs 6.1 days; p = 0.008) and cardiomyopathy (10.7 vs 8.1 days; p < 0.001)., Competing Interests: Disclosure statement D.R. reports honoraria from Abiomed, Medtronic, and Abbott. E.G. Soltesz reports honoraria from Abiomed. S.S. reports consulting fees from Abbott and Abiomed. M.D. reports funding for clinical trial work to the institution from Abiomed, Abbott, and TransMedics; travel support from Abbott and Abiomed for HM3 and Impella 5.5 Users Meetings, respsectively. M.K. reports consulting fees from Abiomed and CareDx. D.A.D'A. reports honoraria from Abiomed and Paragonix. Auxiliary medical writing services were provided by the device manufacturer (acknowledged above)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Multiple studies have shown better outcomes for simultaneous heart-kidney transplant (sHKT) than for isolated orthotopic heart transplant (iOHT) in recipients with chronic kidney disease (CKD). However, outcomes in patients supported by durable left ventricular assist devices (LVADs) have not been well studied., Methods: Patients with durable LVADs and stage 3 or higher CKD (eGFR < 60 mL/min/1.73 m 2 ) undergoing iOHT or sHKT between 2008 and 2020 were identified from the United Network for Organ Sharing registry. A Kaplan-Meier survival analysis with associated log-rank test was conducted to compare post-transplant survival rates. Multivariable modeling was used to identify risk-adjusted predictors of 1 year post-transplant mortality., Results: We identified 4375 patients; 366 underwent sHKT, and 4009 underwent iOHT. The frequency of sHKT increased during the study period. The 1-year post-transplant survival rate was worse in patients after sHKT than in patients after iOHT (80.3% vs 88.3%; P < 0.001) and persisted up to 5 years post-transplant (P = 0.001). sHKT recipients were more likely to require dialysis after transplantation and had longer hospital lengths of stay (P < 0.001). Multivariable analysis showed that sHKT remained an independent risk factor for mortality at 1 year (OR 1.58; P = 0.002)., Conclusions: sHKT is becoming more common in patients with durable LVADs. Compared with iOHT, patients with sHKTs have worse short- and long-term survival rates and are more likely to require post-transplant dialysis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose of Review: Left ventricular assist devices (LVADs) are life-saving therapies for patients in end-stage heart failure (HF) with reduced ejection fraction regardless of candidacy for heart transplantation. Multiple clinical trials have demonstrated improved morbidity and mortality with LVADs when compared to medical therapy alone. However, the uptake of LVADs as a therapeutic option in a larger section of end-stage HF patients remains limited, partly due to associated adverse events and re-hospitalization., Recent Findings: Accurate assessment and staging of HF patients is crucial to guide appropriate use of LVADs. Innovative methods to risk stratify patients and manage cardiac and noncardiac comorbidities can translate to improved outcomes in LVAD recipients. Inclusion of quality of life metrics and measurements of adverse events can better inform heart failure cardiologists to help identify ideal LVAD candidates. Addition of machine learning algorithms to this process may guide patient selection to improve outcomes., Summary: Patient selection and assessment of reversible medical comorbidities are critical to the postoperative success of LVAD implantation. Identifying patients most likely to benefit and least likely to experience adverse events should be a priority., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Left ventricular assist-device (LVAD) implantation is a life-saving therapy for patients with advanced heart failure (HF). With chronic unloading and circulatory support, LVAD-supported hearts often show significant reverse remodeling at the structural, cellular and molecular level. However, translation of these changes into meaningful cardiac recovery allowing LVAD explant is lagging. Part of the reason for this discrepancy is lack of anticipation and hence promotion and evaluation for recovery post LVAD implant. There is additional uncertainty about the long-term course of HF following LVAD explant. In selected patients, however, guided by the etiology of HF, duration of disease and other clinical factors, significant functional improvement and LVAD explantation with long-term freedom from recurrent HF events has been demonstrated to be feasible in a reproducible manner. The identified predictors of myocardial recovery suggest that the elective therapeutic use of potentially less invasive VADs for reversal of HF earlier in the disease process is a future goal that warrants further investigation. Hence, it is prudent to develop and implement tools to predict HF reversibility prior to LVAD implant, optimize unloading-promoted recovery with guideline directed medical therapy and monitor for myocardial improvement. This review article summarizes the clinical aspects of myocardial recovery and together with its companion review article focused on the biological aspects of recovery, they aim to provide a useful framework for clinicians and investigators., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: As left ventricular assist device (LVAD) survival rates continue to improve, evaluating site-specific variability in outcomes can facilitate identifying targets for quality-improvement initiative opportunities in the field., Methods: Deidentified center-specific outcomes were analyzed for HeartMate 3 (HM3) patients enrolled in the MOMENTUM 3 pivotal and continued access protocol trials. Centers < 25th percentile for HM3 volumes were excluded. Variability in risk-adjusted center mortality was assessed at 90 days and 2 years (conditional upon 90-day survival). Adverse event (AE) rates were compared across centers., Results: In the 48 included centers (1958 patients), study-implant volumes ranged between 17 and 106 HM3s. Despite similar trial-inclusion criteria, patient demographics varied across sites, including age quartile ((Q)1-Q3:57-62 years), sex (73%-85% male), destination therapy intent (60%-84%), and INTERMACS profile 1-2 (16%-48%). Center mortality was highly variable, nadiring at ≤ 3.6% (≤ 25th percentile) and peaking at ≥ 10.4% (≥ 75th percentile) at 90 days and ≤ 10.2% and ≥ 18.7%, respectively, at 2 years. Centers with low mortality rates tended to have lower 2-year AE rates, but no center was a top performer for all AEs studied., Conclusions: Mortality and AEs were highly variable across MOMENTUM 3 centers. Studies are needed to improve our understanding of the drivers of outcome variability and to ascertain best practices associated with high-performing centers across the continuum of intraoperative to chronic stages of LVAD support., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Preoperative variables can predict short term left ventricular assist device (LVAD) survival, but predictors of extended survival remain insufficiently characterized., Method: Patients undergoing LVAD implant (2012-2018) in the Intermacs registry were grouped according to time on support: short-term (<1 year, n = 7,483), mid-term (MT, 1-3 years, n = 5,976) and long-term (LT, ≥3 years, n = 3,015). Landmarked hazard analyses (adjusted hazard ratio, HR) were performed to identify correlates of survival after 1 and 3 years of support., Results: After surviving 1 year of support, additional LVAD survival was less likely in older (HR 1.15 per decade), Caucasian (HR 1.22) and unmarried (HR 1.16) patients (p < 0.05). After 3 years of support, only 3 preoperative characteristics (age, race, and history of bypass surgery, p < 0.05) correlated with extended survival. Postoperative events most negatively influenced achieving LT survival. In those alive at 1 year or 3 years, the occurrence of postoperative renal (creatinine HR MT = 1.09; LT HR = 1.10 per mg/dl) and hepatic dysfunction (AST HR MT = 1.29; LT HR = 1.34 per 100 IU), stroke (MT HR = 1.24; LT HR = 1.42), infection (MT HR = 1.13; LT HR = 1.10), and/or device malfunction (MT HR = 1.22; LT HR = 1.46) reduced extended survival (all p ≤ 0.03)., Conclusions: Success with LVAD therapy hinges on achieving long term survival in more recipients. After 1 year, extended survival is heavily constrained by the occurrence of adverse events and postoperative end-organ dysfunction. The growth of destination therapy intent mandates that future LVAD studies be designed with follow up sufficient for capturing outcomes beyond 24 months., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Interventricular interaction, which refers to the impact of left ventricular (LV) function on right ventricular (RV) function and vice versa, has been implicated in the pathogenesis of RV failure in LV assist device (LVAD) recipients. We sought to understand more about interventricular interaction by quantifying changes in the RV systolic and diastolic function with varying LVAD speeds., Methods and Results: Four patients (ages 22-69 years, 75% male, and 25% with ischemic cardiomyopathy) underwent a protocolized hemodynamic ramp test within 12 months of LVAD implantation where RV pressure-volume loops were recorded with a conductance catheter. The end-systolic PV relationship and end-diastolic PV relationship were compared using the V 20 and V 10 indices (volumes at which end-systolic PV relationship and end-diastolic PV relationship reach a pressure of 20 and 10 mm Hg, respectively). The ∆V 20 and ∆V 10 refer to the change in V 20 and V 10 from the minimum to maximum LVAD speeds. RV PV loops demonstrated variable changes in systolic and diastolic function with increasing LVAD speed. The end-systolic PV relationship changed in 1 patient (patient 2, ∆V 20  = 23.5 mL), reflecting a decrease in systolic function with increased speed, and was unchanged in 3 patients (average ∆V 20  = 7.4 mL). The end-diastolic PV relationship changed with increasing speed in 3 of 4 patients (average ∆V 10  = 12.5 mL), indicating an increase in ventricular compliance, and remained unchanged in one participant (patient 1; ∆V 10  = 4.0 mL)., Conclusions: Interventricular interaction can improve RV compliance and impair systolic function, but the overall effect on RV performance in this pilot investigation is heterogeneous. Further research is required to understand which patient characteristics and hemodynamic parameters influence the net impact of interventricular interaction., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Left ventricular assist devices (LVADs) have consistently and successfully improved mortality associated with end-stage heart failure. However, the definition of an "optimal" outcome post LVAD as a benchmark remains debatable. We retrospectively examined patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) between 2012 and 2016 to assess 1 year post-LVAD "optimal outcome" defined as a patient who was alive on device or transplanted, New York Heart Association functional class I/II, had no more than 2 hospitalizations at year 1, and no major adverse event. We identified the features predicting a nonoptimal outcome at 1 year. Finally, we focused on 3 years outcomes in patients implanted as destination therapy. Of the 12,566 patients in INTERMACS who received an LVAD, only 3,495 (27.8%) met our definition of optimal LVAD outcome at 1 year. These patients tended to be younger, male, and were four times more likely to be supported as bridge to transplantation. For those with optimal outcome at year 1, their chances of long-term survival were better than those who were alive at year 1, but did not meet criteria for an optimal outcome. In the destination therapy population, only 14% of patients met the definition of an optimal outcome at 3 years. Despite significantly improved survival in patients with end-stage heart failure treated with LVAD therapy, majority patients had nonoptimal outcomes at 1 and 3 years post implant, by our definition. There is a pressing need to create a benchmark to define optimal outcomes post LVAD, both in our clinical trials and practice., Competing Interests: Disclosures: The authors have no conflicts of interest to report., (Copyright © ASAIO 2020.)

Background: This study delineates the sequences of adverse events (AEs) preceding mortality attributed to multisystem organ failure (MSOF) in patients with a left ventricular assist device (LVAD)., Methods: We analyzed 3765 AEs after 536 LVAD implants recorded in The Society of Thoracic Surgeons Intermacs data registry between 2006 and 2015 that resulted in MSOF death. Hierarchical clustering identified and visualized quantitatively unique clusters of patients with similar AE profiles. Markov modeling was used to illustrate the AE sequences that led to MSOF death within the clusters. Cox proportional hazard models determined the risk-adjusted, preimplant predictors of MSOF., Results: We identified 2 distinct MSOF clusters based on their proportion of AE types and survival time. The early-death cluster (418 patients, 2304 AEs) had a median survival of 1 month (interquartile range, 3-6 months), whereas the late-death cluster (118 patients, 1,461 AEs) had a median survival of 11 months (interquartile range, 6-22 months). The predominant AE sequences in the early-death and late-death clusters were renal failure, to respiratory failure, to death (62%) and bleeding, to infection, to respiratory failure, to death (45%), respectively. Significant risk-adjusted preimplant predictors of MSOF included line sepsis (hazard ratio [HR] 3.0; 95% confidence interval [CI], 1.1-8.2), extracorporeal membrane oxygenation (HR, 2.2; 95% CI, 1.2-3.9), and dialysis or ultrafiltration (HR, 2.1; 95% CI, 1.5-3.0)., Conclusions: This analysis identified 2 AE clusters and the predominant sequences that result in MSOF-associated mortality. MSOF develops in 1 cluster of patients after chronic bleeding and repeated infections but has prolonged survival, while another group dies early after renal and respiratory complications., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Left ventricular assist devices (LVADs) are an increasingly common therapy for patients with advanced heart failure. However, implantation of the LVAD increases the risk of stroke, infection, bleeding, and other serious adverse events (AEs). Most post-LVAD AEs studies have focused on individual AEs in isolation, neglecting the possible interrelation, or causality between AEs. This study is the first to conduct an exploratory analysis to discover common sequential chains of AEs following LVAD implantation that are correlated with important clinical outcomes. This analysis was derived from 58,575 recorded AEs for 13,192 patients in International Registry for Mechanical Circulatory Support (INTERMACS) who received a continuous-flow LVAD between 2006 and 2015. The pattern mining procedure involved three main steps: (1) creating a bank of AE sequences by converting the AEs for each patient into a single, chronologically sequenced record, (2) grouping patients with similar AE sequences using hierarchical clustering, and (3) extracting temporal chains of AEs for each group of patients using Markov modeling. The mined results indicate the existence of seven groups of sequential chains of AEs, characterized by common types of AEs that occurred in a unique order. The groups were identified as: GRP1: Recurrent bleeding, GRP2: Trajectory of device malfunction & explant, GRP3: Infection, GRP4: Trajectories to transplant, GRP5: Cardiac arrhythmia, GRP6: Trajectory of neurological dysfunction & death, and GRP7: Trajectory of respiratory failure, renal dysfunction & death. These patterns of sequential post-LVAD AEs disclose potential interdependence between AEs and may aid prediction, and prevention, of subsequent AEs in future studies.

Background: Mitral regurgitation (MR) determines pathophysiology and outcome in advanced heart failure. The impact of left ventricular assist device (LVAD) placement on clinically significant MR and its contribution to long-term outcomes has been sparsely evaluated., Methods: We evaluated the effect of clinically significant MR on patients implanted in the MOMENTUM 3 trial with either the HeartMate II (HMII) or the HeartMate 3 (HM3) at 2 years. Clinical significance was defined as moderate or severe grade MR determined by site-based echocardiograms., Results: Of 927 patients with LVAD implants without a prior or concomitant mitral valve procedure, 403 (43.5%) had clinically significant MR at baseline. At 1-month of support, residual MR was present in 6.2% of patients with HM3 and 14.3% of patients with HMII (relative risk = 0.43; 95% CI, 0.22-0.84; p = 0.01) with a low rate of worsening at 2 years. Residual MR at 1-month post-implant did not impact 2-year mortality for either the HM3 (hazard ratio [HR],1.41; 95% CI, 0.52-3.89; p = 0.50) or HMII (HR, 0.91; 95% CI, 0.37-2.26; p = 0.84) LVAD. The presence or absence of baseline MR did not influence mortality (HM3 HR, 0.86; 95% CI, 0.56-1.33; p = 0.50; HMII HR, 0.81; 95% CI, 0.54-1.22; p = 0.32), major adverse events or functional capacity. In multivariate analysis, severe baseline MR (p = 0.001), larger left ventricular dimension (p = 0.002), and implantation with the HMII instead of the HM3 LVAD (p = 0.05) were independently associated with an increased likelihood of persistent MR post-implant., Conclusions: Hemodynamic unloading after LVAD implantation improves clinically significant MR early, sustainably, and to a greater extent with the HM3 LVAD. Neither baseline nor residual MR influence outcomes after LVAD implantation., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

New Findings: LVAD patients are predisposed to hypertension which may increase the risk of stroke. Hypertension may result from markedly elevated levels of sympathetic nerve activity, which occurs through a baroreceptor-mediated pathway in response to chronic exposure to a non-physiologic (and reduced) pulse. Cerebral autoregulatory processes appear to be preserved in the absence of a physiologic pulse. Nevertheless, the rate of ischemic/embolic and hemorrhagic stroke is unacceptably high and is a major cause of morbidity and mortality in these patients. Despite normalization of a resting cardiac output, LVAD patients suffer from persistent, severe reductions in functional capacity., Abstract: Current generation left ventricular assist devices (LVADs) have led to significant improvements in survival compared to medical therapy alone, when used for management of patients with advanced heart failure. However, there are a number of side-effects associated with LVAD use, including hypertension, gastrointestinal bleeding, stroke, as well as persistent and severe limitations in functional capacity despite normalization of a resting cardiac output. These issues are, in large part, related to chronic exposure to a non-physiologic pulse, which contributes to a hyperadrenergic environment characterized by markedly elevated levels of sympathetic nerve activity through a baroreceptor-mediated pathway. In addition, these machines are unable to participate in, or contribute to, normal cardiovascular/autonomic reflexes that attempt to modulate flow through the body. Efforts to advance device technology and develop biologically sensitive devices may resolve these issues, and lead to further improvements in quality-of-life, functional capacity, and ultimately, survival, for the patients they support., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

New Findings: What is the topic of this review? Right heart dysfunction remains a major adverse event in patients with end stage heart failure undergoing left ventricular assist device placement. This article reviews the pathophysiology and clinical considerations of right heart failure in this patient population. What advances does it highlight? This review highlights the anatomic and physiological peculiarities of the interplay between left and right heart function in patients undergoing LVAD therapy. These would allow us to further advance our understanding of right ventricular function., Abstract: The adaptation of the right ventricular (RV) output to a left ventricular assist device (LVAD) often determines the fate of patients with pulmonary hypertension secondary to left heart failure. Pre-existing right heart dysfunction in patients with advanced left heart failure is the consequence of increased (arterial) afterload and not simply the consequence of myocardial disease. If unaccounted for, it has the potential of accelerating into clinical right heart failure after LVAD, leading to significant morbidity and mortality. After LVAD implantation, the RV has to face increased flow generated by the LVAD, cardiac arrhythmias and exaggerated functional interactions between both ventricles. Understanding the key physiological mechanisms of RV dysfunction in patients with end-stage heart failure will allow us to predict and therefore prevent RV failure after LVAD implantation., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

New Findings: What is the topic of this review? This review discusses how implantation of continuous flow left ventricular assist devices impact arterial stiffness and outcome. What advances does it highlight? Not all patients implanted with continuous flow left ventricular assist devices show an increase in arterial stiffness. However, in those patients where arterial stiffness increases, levels of composite outcome (stroke, gastrointestinal bleeding, pump thrombosis and death) is significantly higher than those who's arterial stiffness does not increase., Abstract: In parallel with the major advances in clinical care, technological advancements and implantation of mechanical circulatory support in patients with severe heart failure have resulted in these patients living longer. However, these patients are still at increased risk of stroke and gastrointestinal bleeding. The unique continuous flow produced by various left ventricular assist devices (LVADs) has been suggested as one potential reason for this increased risk of stroke and gastrointestinal bleeding. Furthermore, these continuous-flow (CF) devices challenge our understanding of circulatory blood pressure and flow regulation in relationship to organ health. In healthy pulsatile and dynamic systems, arterial stiffness is a major independent risk factor for stroke. However, to date, there are limited data regarding the impact of CF-LVAD therapy on arterial stiffness. The purpose of this report is to discuss the variable impact of CF-LVAD therapy on arterial stiffness and attempt to highlight some potential mechanisms linking these associations in this unique population., (© 2020 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

New Findings: What is the topic of this review? Patients with advanced heart failure who are implanted with left ventricular assist devices (LVADs) present an opportunity to understand the human circulation under extreme conditions. What advances does it highlight? LVAD patients have a unique circulation that is characterized by a reduced or even absent arterial pulse. The remarkable survival of these patients is accompanied by circulatory complications, including stroke, gastrointestinal bleeding and right-heart failure. Understanding the mechanisms related to the complications in LVAD patients will help the patients and also advance our fundamental understanding of the human circulation in general., Abstract: Some humans with chronic, advanced heart failure are surgically implanted with a left ventricular assist device (LVAD). Because the LVAD produces a continuous flow, a palpable pulse is often absent in these patients. This allows for a unique investigation of the human circulation and has created a controversy around the 'need' for a pulse. The medical debate has also generated a more generic, fundamental discussion into what is 'normal' arterial physiology and health. The comprehensive study and understanding of the arterial responses to drastically altered haemodynamics due to continuous-flow LVADs, at rest and during activity, presents an opportunity to significantly increase our current understanding of the fundamental components of arterial regulation (flow, blood pressure, sympathetic activity, endothelial function, pulsatility) in a way that could never have been studied previously. In a series of four articles, we summarize the talks presented at the symposium entitled 'Bionic women and men - Physiology lessons from implantable cardiac devices' presented at the 2019 Annual Meeting of The Physiological Society in Aberdeen, UK. The articles highlight the novel questions generated by physiological phenomena observed in LVAD patients and propose future areas of interest within the field of cardiovascular physiology., (© 2020 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Women comprise approximately one-third of the advanced heart failure population but may receive fewer advanced heart failure therapies including left ventricular assist devices (LVADs). During the early pulsatile-flow device era, women had higher post-LVAD mortality and increased complications. However, knowledge about these differences in the continuous-flow device era is limited. Therefore, we sought to explore temporal trends in LVAD utilization and post-LVAD mortality by sex., Methods and Results: Patients with LVAD implantation from 2004 to 2016 were identified using the Nationwide Inpatient Sample. Trends in LVAD utilization and post-LVAD inpatient mortality were compared by sex and device era. Although LVADs are being increasingly utilized for patients with advanced systolic heart failure, women continue to represent a smaller proportion of LVAD recipients-25.8% in 2004 to 21.9% in 2016 ( P for trend, 0.91). Women had increased inpatient mortality after LVAD implantation compared with men in the pulsatile-flow era (46.9% versus 31.1%, P <0.0001) but not in the continuous-flow era (13.3% versus 12.1%, P =0.27; P for interaction=0.0002). Inpatient mortality decreased for both sexes over time after LVAD, with a sharp fall in 2008 to 2009. Female sex was independently associated with increased post-LVAD inpatient mortality beyond adjustment for demographics and risk factors during the pulsatile-flow era (odds ratio, 2.13; 95% CI, 1.45-3.10; P <0.0001) but not during the continuous-flow era (1.18; 0.93-1.48; P =0.16)., Conclusions: Although utilization of LVAD therapy increased over time for both sexes, LVAD implantation remains stably lower in women, which may suggest a potential underutilization of this potentially life-saving therapy. Prospective studies are needed to confirm these findings.

Current risk stratification models to predict outcomes after a left ventricular assist device (LVAD) are limited in scope. We assessed the performance of Bayesian models to stratify post-LVAD mortality across various International Registry for Mechanically Assisted Circulatory Support (INTERMACS or IM) Profiles, device types, and implant strategies. We performed a retrospective analysis of 10,206 LVAD patients recorded in the IM registry from 2012 to 2016. Using derived Bayesian algorithms from 8,222 patients (derivation cohort), we applied the risk-prediction algorithms to the remaining 2,055 patients (validation cohort). Risk of mortality was assessed at 1, 3, and 12 months post implant according to disease severity (IM profiles), device type (axial versus centrifugal) and strategy (bridge to transplantation or destination therapy). Fifteen percentage (n = 308) were categorized as IM profile 1, 36% (n = 752) as profile 2, 33% (n = 672) as profile 3, and 15% (n = 311) as profile 4-7 in the validation cohort. The Bayesian algorithms showed good discrimination for both short-term (1 and 3 months) and long-term (1 year) mortality for patients with severe HF (Profiles 1-3), with the receiver operating characteristic area under the curve (AUC) between 0.63 and 0.74. The algorithms performed reasonably well in both axial and centrifugal devices (AUC, 0.68-0.74), as well as bridge to transplantation or destination therapy indication (AUC, 0.66-0.73). The performance of the Bayesian models at 1 year was superior to the existing risk models. Bayesian algorithms allow for risk stratification after LVAD implantation across different IM profiles, device types, and implant strategies.

Objectives: This study investigates the use of a Bayesian statistical models to predict survival at various time points in patients undergoing left ventricular assist device (LVAD) implantation., Background: LVADs are being increasingly used in patients with end-stage heart failure. Appropriate patient selection continues to be key in optimizing post-LVAD outcomes., Methods: Data used for this study were derived from 10,277 adult patients from the INTERMACS (Inter-Agency Registry for Mechanically Assisted Circulatory Support) who had a primary LVAD implanted between January 2012 and December 2015. Risk for mortality was calculated retrospectively for various time points (1, 3, and 12 months) after LVAD implantation, using multiple pre-implantation variables. For each of these endpoints, a separate tree-augmented naïve Bayes model was constructed using the most predictive variables., Results: A set of 29, 26, and 31 pre-LVAD variables were found to be predictive at 1, 3, and 12 months, respectively. Predictors of 1-month mortality included low Inter-Agency Registry for Mechanically Assisted Circulatory Support profile, number of acute events in the 48 h before surgery, temporary mechanical circulatory support, and renal and hepatic dysfunction. Variables predicting 12-month mortality included advanced age, frailty, device strategy, and chronic renal disease. The accuracy of all Bayesian models was between 76% and 87%, with an area under the receiver operative characteristics curve of between 0.70 and 0.71., Conclusions: A Bayesian prognostic model for predicting survival based on the comprehensive INTERMACS registry provided highly accurate predictions of mortality based on pre-operative variables. These models may facilitate clinical decision-making while screening candidates for LVAD therapy., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The clinical use of left ventricular assist devices (LVADs) in the growing epidemic of heart failure has improved quality of life and long-term survival for this otherwise devastating disease. The current generation of commercially available devices offers a smaller profile that simplifies surgical implantation, a design that optimizes blood flow characteristics, with less adverse events and improved durability than their predecessors. Despite this, the risk for adverse events remains significant, as do burdens for patients and their caregivers. Appropriate patient selection remains key to optimal LVAD outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (© 2017 American Heart Association, Inc.)

Selection is a key determinant of clinical outcomes after left ventricular assist device (LVAD) placement in patients with end-stage heart failure. The HeartMate II risk score (HMRS) has been proposed to facilitate risk stratification and patient selection for continuous flow pumps. This study retrospectively assessed the performance of HMRS in predicting 90 day and 1 year mortality in patients within the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). A total of 11,523 INTERMACS patients who received a continuous flow LVAD between 2010 and 2015 were retrospectively categorized per their calculated HMRS to predict their 90 day and 1 year risk of mortality. The performance of the score was evaluated by the area under curve (AUC) of the receiver operator characteristic. We also performed multiple regression analysis using variables from the HMRS calculation on the INTERMACS data. The HMRS model showed moderate discrimination for both 90 day and 1 year mortality prediction with AUCs of 61% and 59%, respectively. The predictions had similar accuracy irrespective of whether the pump was axial or centrifugal flow. Multivariable analysis using independent variables used in the original HMRS analysis revealed different set of variables to be predictive of 90 day mortality than those used to calculate HMRS. HMRS predicts both 90 day and 1 year mortality with poor discrimination when applied to a large cohort of LVAD patients. Newer risk prediction models are therefore needed to optimize the therapeutic application of LVAD therapy. Patient selection for appropriate use of LVADs is critical. Currently available risk stratification tools (HMRS) continue to be limited in their ability to accurately predict mortality after LVAD. This study highlights these limitations when applied to a large, comprehensive, multicenter database. HMRS predicts mortality with only modest discrimination when applied to a large cohort of LVAD patients. Better risk stratification tools are needed to optimize outcomes.

Objectives: This study hypothesized that the presence of residual mitral regurgitation (MR) post-continuous flow (CF) left ventricular assist device (LVAD) implantation based on quantitative assessment would be negatively associated with right ventricular (RV) size and function and clinical outcomes., Background: MR is associated with elevated left atrial pressure, secondary pulmonary hypertension and RV dysfunction. Implantation of a LVAD leads to mechanical unloading of the left ventricle and generally improves MR. The clinical significance of residual MR in patients supported with CF LVADs is uncertain. Most studies evaluating the presence of MR in LVAD patients have utilized predominantly qualitative assessments of MR., Methods: We retrospectively identified patients implanted with CF LVADs at our institution from 2007 to 2013 who had a pre-operative transthoracic echocardiogram (TTE) within 3 months of LVAD implant and who had a post-operative TTE at least 1 month post-LVAD. MR was assessed quantitatively using the ratio of MR color jet area (CJA)/left atrial area (LAA) in apical views. We also compared quantitative RV metrics, hospitalizations, and mortality in patients with and without significant residual MR (defined as MR CJA/LAA >0.2) on post-implantation TTE., Results: Sixty-nine patients were included in this study. Post-LVAD implantation, 55 patients (80%) had mild or less MR (mean MR CJA/LAA 0.08) but 14 (20%) had significant residual MR (mean MR CJA/LAA 0.34). Patients with residual MR had significantly larger RV size (right ventricular end diastolic dimension 49 mm vs. 45 mm; p = 0.04) and worse RV function (tricuspid annular plane systolic excursion 10 mm vs. 12 mm; p = 0.02; and right ventricular fractional area change 29% vs. 34%; p = 0.02). Post-implantation pulmonary artery pressures were higher in patients with residual MR (pulmonary artery systolic 43 mm Hg vs. 35 mm Hg; p = 0.05). In patients with residual MR there was slightly greater posterior displacement of the mitral coaptation point on pre-operative TTE (28 mm vs. 26 mm; p = 0.16) but this difference was not significant. Time from LVAD implantation to first hospitalization was shorter in patients with residual MR (62 days vs. 103 days; p = 0.05) as was time from LVAD implantation to death (80 days vs. 421 days; p = 0.03)., Conclusions: Significant residual MR post-LVAD implantation assessed by a quantitative measure is associated with persistent pulmonary hypertension, worse RV function, and significantly shorter time to hospitalization and death. MR post-LVAD implantation may serve as a surrogate for adverse outcomes post-LVAD implantation., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study investigates the use of a Bayesian statistical model to address the limited predictive capacity of existing risk scores derived from multivariate analyses. This is based on the hypothesis that it is necessary to consider the interrelationships and conditional probabilities among independent variables to achieve sufficient statistical accuracy., Background: Right ventricular failure (RVF) continues to be a major adverse event following left ventricular assist device (LVAD) implantation., Methods: Data used for this study were derived from 10,909 adult patients from the Inter-Agency Registry for Mechanically Assisted Circulatory Support (INTERMACS) who had a primary LVAD implanted between December 2006 and March 2014. An initial set of 176 pre-implantation variables were considered. RVF post-implant was categorized as acute (<48 h), early (48 h to 14 daysays), and late (>14 days) in onset. For each of these endpoints, a separate tree-augmented naïve Bayes model was constructed using the most predictive variables employing an open source Bayesian inference engine., Results: The acute RVF model consisted of 33 variables including systolic pulmonary artery pressure (PAP), white blood cell count, left ventricular ejection fraction, cardiac index, sodium levels, and lymphocyte percentage. The early RVF model consisted of 34 variables, including systolic PAP, pre-albumin, lactate dehydrogenase level, INTERMACS profile, right ventricular ejection fraction, pro-B-type natriuretic peptide, age, heart rate, tricuspid regurgitation, and body mass index. The late RVF model included 33 variables and was predicted mostly by peripheral vascular resistance, model for end-stage liver disease score, albumin level, lymphocyte percentage, and mean and diastolic PAP. The accuracy of all Bayesian models was between 91% and 97%, with an area under the receiver operator characteristics curve between 0.83 and 0.90, sensitivity of 90%, and specificity between 98% and 99%, significantly outperforming previously published risk scores., Conclusions: A Bayesian prognostic model of RVF based on the large, multicenter INTERMACS registry provided highly accurate predictions of acute, early, and late RVF on the basis of pre-operative variables. These models may facilitate clinical decision making while screening candidates for LVAD therapy., Competing Interests: None of the authors have any financial relationship with any commercial entities that have an interest in the subject of the presented manuscript or other conflicts of interest to disclose., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Existing risk assessment tools for patient selection for left ventricular assist devices (LVADs) such as the Destination Therapy Risk Score and HeartMate II Risk Score (HMRS) have limited predictive ability. This study aims to overcome the limitations of traditional statistical methods by performing the first application of Bayesian analysis to the comprehensive Interagency Registry for Mechanically Assisted Circulatory Support dataset and comparing it to HMRS. We retrospectively analyzed 8,050 continuous flow LVAD patients and 226 preimplant variables. We then derived Bayesian models for mortality at each of five time end-points postimplant (30 days, 90 days, 6 month, 1 year, and 2 years), achieving accuracies of 95%, 90%, 90%, 83%, and 78%, Kappa values of 0.43, 0.37, 0.37, 0.45, and 0.43, and area under the receiver operator characteristic (ROC) of 91%, 82%, 82%, 80%, and 81%, respectively. This was in comparison to the HMRS with an ROC of 57% and 60% at 90 days and 1 year, respectively. Preimplant interventions, such as dialysis, ECMO, and ventilators were major contributing risk markers. Bayesian models have the ability to reliably represent the complex causal relations of multiple variables on clinical outcomes. Their potential to develop a reliable risk stratification tool for use in clinical decision making on LVAD patients encourages further investigation.

Management for continuous flow left ventricular assist device (LVAD) thrombosis often relies on speculation of individual clinical risk factors and integration of indirect evidence for device dysfunction. There are no comprehensive guidelines for treatment of this serious complication, and most of our current knowledge comes from anecdotal experience or observational study. More data on effective treatment, both with aggressive pharmacologic and device-based interventions, are needed for improving our understanding of mechanisms driving device thrombosis and for preventing future events. We present a case of LVAD thrombosis with emphasis on recognition and treatment of acute pump thrombosis, and discuss a potentially novel strategy using percutaneous mechanical circulatory support for pump salvage.