The International Society of Heart and Lung Transplantation (ISHLT): 2024 infection definitions for durable and acute mechanical circulatory support devices.

Infections remain a significant concern in patients receiving mechanical circulatory support (MCS), encompassing both durable and acute devices. This consensus manuscript provides updated definitions for infections associated with durable MCS devices and new definitions for infections in acute MCS, integrating a comprehensive review of existing literature and collaborative discussions among multidisciplinary specialists. By establishing consensus definitions, we seek to enhance clinical care, facilitate consistent reporting in research studies, and ultimately improve outcomes for patients receiving MCS.

Use of percutaneous mechanical circulatory support for right ventricular failure.

BACKGROUND: Utilization of right ventricular mechanical circulatory support (RV-MCS) devices has been limited by a lack of recognition of RV failure as well as a lack of availability and experience with RV-MCS. AIMS: We report a single-center experience with the use of percutaneous RV-MCS and report predictors of adverse outcomes. METHODS: This was a single-center retrospective cohort study. Data from consecutive patients who received RV-MCS for any indication between June 2015 and January 2022 were included. Data on baseline comorbidities, hemodynamics, and laboratory values were collected. The primary outcome was in-hospital mortality analyzed as a logistic outcome in a multivariable model. These variables were further ranked by their predictive value. RESULTS: Among 58 consecutive patients enrolled, the median age was 66 years, 31% were female and 53% were white. The majority of the patients (48%) were hospitalized for acute on chronic heart failure. The majority of the patients were SCAI SHOCK Stage D (67%) and 34 (64%) patients had MCS placed within 24 h of the onset of shock. Before placement of RV-MCS, median central venous pressure (CVP) and RV stroke work index were 20 mmHg and 8.9 g m/m2, respectively. Median serum lactate was 3.5 (1.6, 6.2) mmol/L. Impella RP was implanted in 50% and ProtekDuo in the remaining 50%. Left ventricular MCS was concomitantly used in 66% of patients. Twenty-eight patients (48.3%) died. In these patients, median serum lactate was significantly higher (4.1 [2.3, 13.0] vs. 2.2 [1.4, 4.0] mmol/L, p = 0.007) and a trend toward higher median CVP (24 [18, 31] vs. 19 [14, 24] mmHg, p = 0.052). In the multivariable logistic model, both serum lactate and CVP before RV-MCS placement were independent predictors of in-hospital mortality. Serum lactate had the highest predictive value. CONCLUSION: In our real-world cohort, 52% of patients treated with RV-MCS survived their index hospitalization. Serum lactate at presentation and CVP were the strongest predictors of in-hospital mortality.

Early vs. Delayed Mechanical Circulatory Support in Patients with Acute Myocardial Infarction and Cardiogenic Shock.

BACKGROUND: Despite increased temporary mechanical circulatory support (tMCS) utilization for acute myocardial infarction complicated by cardiogenic shock (AMI-CS), data regarding efficacy and optimal timing for tMCS support are limited. This study aimed to describe outcomes based on tMCS timing in AMI-CS and to identify predictors of 30-day mortality and readmission. METHODS: Patients with AMI-CS identified in the National Readmissions Database were grouped according to the use of tMCS and early (<24 hours) vs. delayed (≥24 hours) tMCS. The correlation between tMCS timing and inpatient outcomes was evaluated using linear regression. Multivariate logistic regression was used to identify variables associated with 30-day mortality and readmission. RESULTS: Of 294,839 patients with AMI-CS, 109,148 patients were supported with tMCS (8,067 veno-arterial extracorporeal membrane oxygenation, 33,577 Impella, and 79,161 intra-aortic balloon pump). Of patients requiring tMCS, patients who received early tMCS (n = 79,906) had shorter lengths of stay (7 days vs. 15 days, p < 0.001) and lower rates of ischemic and bleeding complications than those with delayed tMCS (n = 32,241). Patients requiring tMCS had higher in-hospital mortality (OR [95% CI]) (1.7 [1.7-1.8], p < 0.001). Among patients requiring tMCS, early support was associated with fewer complications, lower mortality (0.90 [0.85-0.94], p < 0.001), and fewer 30-day readmissions (0.91 [0.85-0.97], p = 0.005) compared to patients with delayed tMCS. CONCLUSION: Among patients receiving tMCS for AMI-CS, early tMCS was associated with fewer complications, shorter lengths of stay, lower hospital costs, and fewer deaths and readmissions at 30 days.

The Future of Durable Mechanical Circulatory Support: Emerging Technological Innovations and Considerations to Enable Evolution of the Field.

The field of durable mechanical circulatory support (MCS) has undergone an incredible evolution over the past few decades, resulting in significant improvements in longevity and quality of life for patients with advanced heart failure. Despite these successes, substantial opportunities for further improvements remain, including in pump design and ancillary technology, perioperative and postoperative management, and the overall patient experience. Ideally, durable MCS devices would be fully implantable, automatically controlled, and minimize the need for anticoagulation. Reliable and long-term total artificial hearts for biventricular support would be available; and surgical, perioperative, and postoperative management would be informed by the individual patient phenotype along with computational simulations. In this review, we summarize emerging technological innovations in these areas, focusing primarily on innovations in late preclinical or early clinical phases of study. We highlight important considerations that the MCS community of clinicians, engineers, industry partners, and venture capital investors should consider to sustain the evolution of the field.

Bridge to Weight Loss: A Case Series.

Durable left ventricular assist devices (LVADs) are a well-established therapeutic option for patients with advanced heart failure. These devices are often used to "bridge" patients to an orthotopic heart transplantation (HT). Unfortunately, many patients on LVAD support with a body mass index (BMI) above a certain value are not eligible for HT due a lack of suitable donors and the association between obesity and poor outcomes after HT. This case series describes three individuals on LVAD support who were able to successfully lose enough weight to qualify to be listed for an HT. We highlight a systematic, multidisciplinary approach to implementing guideline-driven weight loss strategies, including some aggressive methods (ie, meal replacements, weight loss medications, and bariatric surgery). In addition to describing the weight loss outcomes, we also discuss barriers and medical challenges during weight loss that are unique to this population.

Cardiogenic Shock in Older Adults: A Focus on Age-Associated Risks and Approach to Management: A Scientific Statement From the American Heart Association.

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.

Machine Learning Multicenter Risk Model to Predict Right Ventricular Failure After Mechanical Circulatory Support: The STOP-RVF Score.

Importance: The existing models predicting right ventricular failure (RVF) after durable left ventricular assist device (LVAD) support might be limited, partly due to lack of external validation, marginal predictive power, and absence of intraoperative characteristics. Objective: To derive and validate a risk model to predict RVF after LVAD implantation. Design, Setting, and Participants: This was a hybrid prospective-retrospective multicenter cohort study conducted from April 2008 to July 2019 of patients with advanced heart failure (HF) requiring continuous-flow LVAD. The derivation cohort included patients enrolled at 5 institutions. The external validation cohort included patients enrolled at a sixth institution within the same period. Study data were analyzed October 2022 to August 2023. Exposures: Study participants underwent chronic continuous-flow LVAD support. Main Outcome and Measures: The primary outcome was RVF incidence, defined as the need for RV assist device or intravenous inotropes for greater than 14 days. Bootstrap imputation and adaptive least absolute shrinkage and selection operator variable selection techniques were used to derive a predictive model. An RVF risk calculator (STOP-RVF) was then developed and subsequently externally validated, which can provide personalized quantification of the risk for LVAD candidates. Its predictive accuracy was compared with previously published RVF scores. Results: The derivation cohort included 798 patients (mean [SE] age, 56.1 [13.2] years; 668 male [83.7%]). The external validation cohort included 327 patients. RVF developed in 193 of 798 patients (24.2%) in the derivation cohort and 107 of 327 patients (32.7%) in the validation cohort. Preimplant variables associated with postoperative RVF included nonischemic cardiomyopathy, intra-aortic balloon pump, microaxial percutaneous left ventricular assist device/venoarterial extracorporeal membrane oxygenation, LVAD configuration, Interagency Registry for Mechanically Assisted Circulatory Support profiles 1 to 2, right atrial/pulmonary capillary wedge pressure ratio, use of angiotensin-converting enzyme inhibitors, platelet count, and serum sodium, albumin, and creatinine levels. Inclusion of intraoperative characteristics did not improve model performance. The calculator achieved a C statistic of 0.75 (95% CI, 0.71-0.79) in the derivation cohort and 0.73 (95% CI, 0.67-0.80) in the validation cohort. Cumulative survival was higher in patients composing the low-risk group (estimated <20% RVF risk) compared with those in the higher-risk groups. The STOP-RVF risk calculator exhibited a significantly better performance than commonly used risk scores proposed by Kormos et al (C statistic, 0.58; 95% CI, 0.53-0.63) and Drakos et al (C statistic, 0.62; 95% CI, 0.57-0.67). Conclusions and Relevance: Implementing routine clinical data, this multicenter cohort study derived and validated the STOP-RVF calculator as a personalized risk assessment tool for the prediction of RVF and RVF-associated all-cause mortality.

Heart failure related cardiogenic shock: An ISHLT consensus conference content summary.

In recent years, there have been significant advancements in the understanding, risk-stratification, and treatment of cardiogenic shock (CS). Despite improved pharmacologic and device-based therapies for CS, short-term mortality remains as high as 50%. Most recent efforts in research have focused on CS related to acute myocardial infarction, even though heart failure related CS (HF-CS) accounts for >50% of CS cases. There is a paucity of high-quality evidence to support standardized clinical practices in approach to HF-CS. In addition, there is an unmet need to identify disease-specific diagnostic and risk-stratification strategies upon admission, which might ultimately guide the choice of therapies, and thereby improve outcomes and optimize resource allocation. The heterogeneity in defining CS, patient phenotypes, treatment goals and therapies has resulted in difficulty comparing published reports and standardized treatment algorithms. An International Society for Heart and Lung Transplantation (ISHLT) consensus conference was organized to better define, diagnose, and manage HF-CS. There were 54 participants (advanced heart failure and interventional cardiologists, cardiothoracic surgeons, critical care cardiologists, intensivists, pharmacists, and allied health professionals), with vast clinical and published experience in CS, representing 42 centers worldwide. State-of-the-art HF-CS presentations occurred with subsequent breakout sessions planned in an attempt to reach consensus on various issues, including but not limited to models of CS care delivery, patient presentations in HF-CS, and strategies in HF-CS management. This consensus report summarizes the contemporary literature review on HF-CS presented in the first half of the conference (part 1), while the accompanying document (part 2) covers the breakout sessions where the previously agreed upon clinical issues were discussed with an aim to get to a consensus.

Consensus statements from the International Society for Heart and Lung Transplantation consensus conference: Heart failure-related cardiogenic shock.

The last decade has brought tremendous interest in the problem of cardiogenic shock. However, the mortality rate of this syndrome approaches 50%, and other than prompt myocardial revascularization, there have been no treatments proven to improve the survival of these patients. The bulk of studies have been in patients with acute myocardial infarction, and there is little evidence to guide the clinician in those patients with heart failure cardiogenic shock (HF-CS). An International Society for Heart and Lung Transplant consensus conference was organized to better define, diagnose, and manage HF-CS. There were 54 participants (advanced heart failure and interventional cardiologists, cardiothoracic surgeons, critical care cardiologists, intensivists, pharmacists, and allied health professionals) with vast clinical and published experience in CS, representing 42 centers worldwide. This consensus report summarizes the results of a premeeting survey answered by participants and the breakout sessions where predefined clinical issues were discussed to achieve consensus in the absence of robust data. Key issues discussed include systems for CS management, including the "hub-and-spoke" model vs a tier-based network, minimum levels of data to communicate when considering transfer, disciplines that should be involved in a "shock team," goals for mechanical circulatory support device selection, and optimal flow on such devices. Overall, the document provides expert consensus on some important issues facing practitioners managing HF-CS. It is hoped that this will clarify areas where consensus has been reached and stimulate future research and registries to provide insight regarding other crucial knowledge gaps.

Cardiogenic shock in a young woman with SCAD: The importance of early access to VA-ECMO in the community.

Spontaneous coronary artery dissection (SCAD) is a common cause of myocardial infarction in young and middle-aged women. Patients with SCAD present rarely with hemodynamic collapse and cardiogenic shock, requiring immediate resuscitation and mechanical circulatory support. Percutaneous mechanical circulatory support may serve as a bridge to recovery, decision or heart transplantation. We present a case of a young woman with SCAD of the left main coronary artery, presenting with ST-elevation myocardial infarction, cardiac arrest and cardiogenic shock. She was stabilized emergently with Impella and early escalation with extracorporeal membrane oxygenation (ECPELLA) at a non-surgical community hospital. Despite revascularization with percutaneous coronary intervention (PCI), her left ventricular recovery was poor, and ultimately required cardiac transplantation on day 5 of her presentation.

Associations Between Preimplant Cancer Type and Left Ventricular Assist Device Outcomes: An INTERMACS Registry Analysis.

We used the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database to examine whether history of a solid versus hematologic malignancy impacts outcomes after left ventricular assist device (LVAD) implantation. We included LVAD recipients (2007-2017) with cancer history reported (N = 14,799, 21% female, 24% Black). Multivariate models examined the association between cancer type and post-LVAD mortality and adverse events. Competing risk analyses compared death and heart transplantation between cancer types and those without cancer in bridge-to-transplant (BTT) patients. A total of 909 (6.1%) patients had a history of cancer (4.9% solid tumor, 1.3% hematologic malignancy). Solid tumors were associated with higher mortality (adjusted hazard ratio [aHR] = 1.31, 95% confidence interval [CI] = 1.09-1.57), major bleeding (aHR = 1.15, 95% CI = 1.00-1.32), and pump thrombosis (aHR = 1.52, 95% CI = 1.09-2.13), whereas hematologic malignancies were associated with increased major infection (aHR = 1.43, 95% CI = 1.14-1.80). Compared to BTT patients without a history of cancer, solid tumor patients were less likely to undergo transplantation (adjusted subdistribution HR [aSHR] = 0.63, 95% CI = 0.45-0.89) and hematologic malignancy patients were as likely to experience death (aSHR = 1.16, 95% CI = 0.63-2.14) and transplantation (aSHR = 0.69, 95% CI = 0.44-1.08). Cancer history and type impact post-LVAD outcomes. As LVAD utilization in cancer survivors increases, we need strategies to improve post-LVAD outcomes in these patients.

Treatment Strategies and Outcomes of Right Ventricular Failure Post Left Ventricular Assist Device Implantation: An INTERMACS Analysis.

Right heart failure (RHF) management after left ventricular assist device (LVAD) implantation includes inotropes, right ventricular mechanical support, and heart transplantation. The purpose of this study is to compare different RHF treatment strategies in patients with a magnetically levitated centrifugal LVAD. A total of 6,632 Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) patients from 2013 to 2020 were included. Of which, 769 (69.6%) patients (group 1) were supported with inotropes (≥14 days post-LVAD implantation), 233 (21.1%) patients (group 2) were supported with temporary right ventricular assist device (RVAD) that was implanted during LVAD implant, 77 (7.0%) patients (group 3) with durable centrifugal RVAD implanted during the LVAD implant, and 26 (2.4%) patients (group 4) were supported with RVAD (temporary or permanent), which was implanted at a later stage. Groups 1 and 4 had higher survival rates in comparison with group 2 (hazard ratio [HR] = 0.513, 95% confidence intervals [CIs] = 0.402-0.655, p < 0.001, versus group 1) and group 3 (HR = 0.461, 95% CIs = 0.320-0.666, p < 0.001, versus group 1). Patients in group 3 showed higher heart transplantation rates at 12 and 36 months as compared with group 1 (40.4% and 46.6% vs. 21.9% and 37.4%, respectively), group 2 (40.4% and 46.6% vs. 25.8% and 39.3%, respectively), and group 4 (40.4% and 46.6% vs. 3.8% and 12.0%, respectively). Severe RHF post-LVAD is associated with poor survival. Patients with LVAD who during the perioperative period are in need of right ventricular temporary or durable mechanical circulatory support constitute a group at particular risk. Improvement of devices tailored for right ventricular support is mandatory for further evolution of the field.

Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure: The ARIES-HM3 Randomized Clinical Trial.

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.

Safety and Performance of the Aortix Device in Acute Decompensated Heart Failure and Cardiorenal Syndrome.

BACKGROUND: Cardiorenal syndrome (CRS) complicates 33% of acute decompensated heart failure (ADHF) admissions, and patients with persistent congestion at discharge have high 30-day event rates. OBJECTIVES: The purpose of this study was to evaluate a novel catheter-deployed intra-aortic entrainment pump (IAEP) in patients with ADHF with CRS and persistent congestion. METHODS: A multicenter (n = 14), nonrandomized, single-arm, safety and feasibility study of IAEP therapy was conducted. Within patient changes (post-pre IAEP therapy) in fluid loss, hemodynamics, patient-reported dyspnea, and serum biomarkers were assessed using Wilcoxon signed-rank testing. RESULTS: Of 21 enrolled patients, 18 received Aortix therapy. Mean ± SD patient age was 60.3 ± 7.9 years. The median left ventricular ejection fraction was 22.5% (25th-75th percentile: 10.0%-53.5%); 27.8% had a left ventricular ejection fraction ≥50%. Pre-therapy, patients received 8.7 ± 4.1 days of loop diuretic agents and 44% were on inotropes. Pump therapy averaged 4.6 ± 1.6 days, yielding net fluid losses of 10.7 ± 6.5 L (P < 0.001) and significant (P < 0.01) reductions in central venous pressure (change from baseline: -8.5 mm Hg [25th-75th percentile: -3.5 to -10.0 mm Hg]), pulmonary capillary wedge pressure (-11.0 mm Hg [25th-75th percentile: -5.0 to -14.0 mm Hg]), and serum creatinine (-0.2 mg/dL [25th-75th percentile: -0.1 to -0.5 mg/dL]) with improved estimated glomerular filtration rate (+5.0 mL/min/1.73 m2 [25th-75th percentile: 2.0-9.0 mL/min/1.73 m2]) and patient-reported dyspnea score (+16 [25th-75th percentile: 3-37]). Dyspnea scores, natriuretic peptides, and renal function improvements persisted through 30 days. CONCLUSIONS: This pilot study of patients with ADHF, persistent congestion, and worsening renal function due to CRS supports the potential for safely achieving decongestion using IAEP therapy. These initial promising results provide the basis for future randomized clinical trials of this novel pump. (An Evaluation of the Safety and Performance of the Aortix System for Intra-Aortic Mechanical Circulatory Support in Patients with Cardiorenal Syndrome [The Aortix CRS Pilot Study]; NCT04145635).

Durable Mechanical Circulatory Support: JACC Scientific Statement.

Despite advances in medical therapy for patients with stage C heart failure (HF), survival for patients with advanced HF is <20% at 5 years. Durable left ventricular assist device (dLVAD) support is an important treatment option for patients with advanced HF. Innovations in dLVAD technology have reduced the risk of several adverse events, including pump thrombosis, stroke, and bleeding. Average patient survival is now similar to that of heart transplantation at 2 years, with 5-year dLVAD survival now approaching 60%. Unfortunately, greater adoption of dLVAD therapy has not been realized due to delayed referral of patients to advanced HF centers, insufficient clinician knowledge of contemporary dLVAD outcomes (including gains in quality of life), and deprioritization of patients with dLVAD support waiting for heart transplantation. Despite these challenges, novel devices are on the horizon of clinical investigation, offering smaller size, permitting less invasive surgical implantation, and eliminating the percutaneous lead for power supply.

Emerging Individualized Approaches in the Management of Acute Cardiorenal Syndrome With Renal Assist Devices.

Growing insights into the pathophysiology of acute cardiorenal syndrome (CRS) in acute decompensated heart failure have indicated that not every rise in creatinine is associated with adverse outcomes. Detection of persistent volume overload and diuretic resistance associated with creatinine rise may identify patients with true acute CRS. More in-depth phenotyping is needed to identify pathologic processes in renal arterial perfusion, venous outflow, and microcirculatory-interstitial-lymphatic axis alterations that can contribute to acute CRS. Recently, various novel device-based interventions designed to target different pathophysiologic components of acute CRS are in early feasibility and proof-of-concept studies. However, appropriate trial endpoints that reflect improvement in cardiorenal trajectories remain elusive and highly debated. In this review the authors describe the variety of physiological derangements leading to acute CRS and the opportunity to individualize the management of acute CRS with novel renal assist devices that can target specific components of these alterations.

Predictors of 5-Year Mortality in Patients Managed With a Magnetically Levitated Left Ventricular Assist Device.

BACKGROUND: In advanced heart failure patients implanted with a fully magnetically levitated HeartMate 3 (HM3, Abbott) left ventricular assist device (LVAD), it is unknown how preimplant factors and postimplant index hospitalization events influence 5-year mortality in those able to be discharged. OBJECTIVES: The goal was to identify risk predictors of mortality through 5 years among HM3 LVAD recipients conditional on discharge from index hospitalization in the MOMENTUM 3 pivotal trial. METHODS: This analysis evaluated 485 of 515 (94%) patients discharged after implantation of the HM3 LVAD. Preimplant (baseline), implant surgery, and index hospitalization characteristics were analyzed individually, and as multivariable predictors for mortality risk through 5 years. RESULTS: Cumulative 5-year mortality in the cohort (median age: 62 years, 80% male, 65% White, 61% destination therapy due to transplant ineligibility) was 38%. Two preimplant characteristics (elevated blood urea nitrogen and prior coronary artery bypass graft or valve procedure) and 3 postimplant characteristics (hemocompatibility-related adverse events, ventricular arrhythmias, and estimated glomerular filtration rate <60 mL/min/1.73 m2 at discharge) were predictors of 5-year mortality. In 171 of 485 patients (35.3%) without any risk predictors, 5-year mortality was reduced to 22.6% (95% CI: 15.4%-32.7%). Even among those with 1 or more predictors, mortality was <50% at 5 years (45.7% [95% CI: 39.0%-52.8%]). CONCLUSIONS: Long-term survival in successfully discharged HM3 LVAD recipients is largely influenced by clinical events experienced during the index surgical hospitalization in tandem with baseline factors, with mortality of <50% at 5 years. In patients without identified predictors of risk, long-term 5-year mortality is low and rivals that achieved with heart transplantation, even though most were implanted with destination therapy intent. (MOMENTUM 3 IDE Clinical Study Protocol, NCT02224755; MOMENTUM 3 Pivotal Cohort Extended Follow-up PAS, NCT03982979).