American Heart Association Cardiogenic Shock Registry: Design and Implementation.

BACKGROUND: Cardiogenic shock is a morbid complication of heart disease that claims the lives of more than 1 in 3 patients presenting with this syndrome. Supporting a unique collaboration across clinical specialties, federal regulators, payors, and industry, the American Heart Association volunteers and staff have launched a quality improvement registry to better understand the clinical manifestations of shock phenotypes, and to benchmark the management patterns, and outcomes of patients presenting with cardiogenic shock to hospitals across the United States. METHODS: Participating hospitals will enroll consecutive hospitalized patients with cardiogenic shock, regardless of etiology or severity. Data are collected through individual reviews of medical records of sequential adult patients with cardiogenic shock. The electronic case record form was collaboratively designed with a core minimum data structure and aligned with Shock Academic Research Consortium definitions. This registry will allow participating health systems to evaluate patient-level data including diagnostic approaches, therapeutics, use of advanced monitoring and circulatory support, processes of care, complications, and in-hospital survival. Participating sites can leverage these data for onsite monitoring of outcomes and benchmarking versus other institutions. The registry was concomitantly designed to provide a high-quality longitudinal research infrastructure for pragmatic randomized trials as well as translational, clinical, and implementation research. An aggregate deidentified data set will be made available to the research community on the American Heart Association's Precision Medicine Platform. On March 31, 2022, the American Heart Association Cardiogenic Shock Registry received its first clinical records. At the time of this submission, 100 centers are participating. CONCLUSIONS: The American Heart Association Cardiogenic Shock Registry will serve as a resource using consistent data structure and definitions for the medical and research community to accelerate scientific advancement through shared learning and research resulting in improved quality of care and outcomes of shock patients.

Standardized Definitions for Cardiogenic Shock Research and Mechanical Circulatory Support Devices: Scientific Expert Panel From the Shock Academic Research Consortium (SHARC).

The Shock Academic Research Consortium is a multi-stakeholder group, including representatives from the US Food and Drug Administration and other government agencies, industry, and payers, convened to develop pragmatic consensus definitions useful for the evaluation of clinical trials enrolling patients with cardiogenic shock, including trials evaluating mechanical circulatory support devices. Several in-person and virtual meetings were convened between 2020 and 2022 to discuss the need for developing the standardized definitions required for evaluation of mechanical circulatory support devices in clinical trials for cardiogenic shock patients. The expert panel identified key concepts and topics by performing literature reviews, including previous clinical trials, while recognizing current challenges and the need to advance evidence-based practice and statistical analysis to support future clinical trials. For each category, a lead (primary) author was assigned to perform a literature search and draft a proposed definition, which was presented to the subgroup. These definitions were further modified after feedback from the expert panel meetings until a consensus was reached. This manuscript summarizes the expert panel recommendations focused on outcome definitions, including efficacy and safety.

Correction: Understanding and Addressing Variation in Health Care-Associated Infections After Durable Ventricular Assist Device Therapy: Protocol for a Mixed Methods Study.

[This corrects the article DOI: 10.2196/14701.].

Hospitalization Patterns and Impact of a Magnetically-Levitated Left Ventricular Assist Device in the MOMENTUM 3 Trial.

BACKGROUND: In the MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) pivotal trial, the HeartMate 3 (HM3) fully magnetically levitated left ventricular assist device (LVAD) demonstrated superiority over the axial-flow HeartMate II (HMII) LVAD. The patterns and predictors of hospitalizations with the HM3 LVAD have not been characterized. OBJECTIVES: This study sought to determine causes, predictors, and impact of hospitalizations during LVAD support. METHODS: Patients discharged after LVAD implantation were analyzed. In the pivotal trial, 485 recipients of HM3 were compared with 471 recipients of HMII. The pivotal trial HM3 group was also compared to 949 recipients of HM3 in the postapproval phase within the trial portfolio. Predictors of cause-specific rehospitalization were analyzed. RESULTS: The rates of rehospitalization were lower with HM3 LVAD than with HMII LVAD in the pivotal trial (225.7 vs 246.4 events per 100 patient-years; P < 0.05). Overall, rehospitalization rates and duration were similar in the HM3 postapproval phase and pivotal trial but prolonged hospitalizations (>7 days) were less frequent (rate ratio: 0.90 [95% CI: 0.80-0.98]; P < 0.05). In HM3 recipients, the most frequent causes of rehospitalization included infection, heart failure (HF)-related events, and bleeding. First rehospitalization caused by HF-related event versus other causes was associated with reduced survival (HR: 2.2 [95% CI: 1.3-3.9]; P = 0.0014). Male sex, non-White race, presence of cardiac resynchronization therapy/implantable cardioverter-defibrillator, obesity, higher right atrial pressure, smaller LV size, longer duration of index hospitalization, and lower estimated glomerular filtration rate at index discharge predicted HF hospitalizations. CONCLUSIONS: Contemporary support with the HM3 fully magnetically levitated LVAD is associated with a lower hospitalization burden than with prior pumps; however, rehospitalizations for infection, HF, and bleeding remain important challenges for progress in the patient journey. (MOMENTUM 3 IDE Clinical Study, NCT02224755; MOMENTUM 3 Continued Access Protocol [MOMENTUM 3 CAP], NCT02892955).

Center Variability in Patient Outcomes Following HeartMate 3 Implantation: An Analysis of the MOMENTUM 3 Trial.

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.

Outcomes With Phosphodiesterase-5 Inhibitor Use After Left Ventricular Assist Device: An STS-INTERMACS Analysis.

BACKGROUND: Elevated right ventricular afterload following continuous-flow left ventricular assist device (CF-LVAD) may contribute to late right heart failure (LRHF). PDE5i (phosphodiesterase-5 inhibitors) are used to treat pulmonary hypertension and right heart dysfunction after CF-LVAD, but their impact on outcomes is uncertain. METHODS: We queried Interagency Registry for Mechanically Assisted Circulatory Support from 2012 to 2017 for adults receiving a primary CF-LVAD and surviving ≥30 days from index discharge. Patients receiving early PDE5i (ePDE5i) at 1 month were propensity-matched 1:1 with controls. The primary outcome was the cumulative incidence of LRHF, defined using prevailing Interagency Registry for Mechanically Assisted Circulatory Support criteria; secondary outcomes included all-cause mortality and major bleeding. RESULTS: Among 9627 CF-LVAD recipients analyzed, 2463 (25.6%) received ePDE5i and 1600 were propensity-matched 1:1 with controls. Before implant, ePDE5i patients had more severe RV dysfunction (13.1% versus 9.6%) and higher pulmonary vascular resistance (2.8±2.7 versus 2.2±2.4 WU), both P<0.001, but clinical factors were well-balanced after propensity-matching. In the unmatched cohort, ePDE5i patients had a higher 3-year cumulative incidence of LRHF, mortality, and major bleeding, but these differences were attenuated in the propensity-matched cohort: LRHF 40.8% versus 35.7% (hazard ratio, 1.14 [95% CI, 0.99-1.32]; P=0.07); mortality 38.6% versus 35.8% (hazard ratio, 0.99 [95% CI, 0.86-1.15]; P=0.93); major bleeding 51.2% versus 46.0% (hazard ratio, 1.12 [95% CI, 0.99-1.27]; P=0.06). CONCLUSIONS: Compared with propensity-matched controls, adult CF-LVAD patients receiving ePDE5i had similar rates of LRHF, mortality, and major bleeding. While intrinsic patient risk factors likely account for more adverse outcomes with ePDE5i in the unmatched cohort, there is no obvious benefit of ePDE5i in the LVAD population.

Graft Resistance Difference after HVAD to HeartMate 3 Left Ventricular Assist Device Exchange.

BACKGROUND: A likely consequence of the discontinued distribution and sale of the HVAD System (Medtronic, Minneapolis, MN) will be an increase in replacement with the HeartMate 3 (Abbott, Chicago, IL) left ventricular assist device when device exchange is necessary. If part or all of the HVAD 10-mm-diameter outflow graft is retained during replacement, the HeartMate 3 will have to run at a higher speed than it would with its 14-mm-diameter graft. METHODS: A steady-state, in vitro study was run with 250-mm-long samples of HVAD, HeartMate 3, and half-HVAD/half-HeartMate 3 grafts and additionally 125- and 375-mm-long samples of the HVAD graft. Flows of 3.0, 3.9, 4.3, 4.7, and 6.0 L/min were applied to encompass expected clinical conditions. RESULTS: At typical and high flow rates of 4.3 and 6.0 L/min, HeartMate 3 rotor speeds with the full HVAD graft had to be increased relative to those with the HeartMate 3 graft from 5350 to 5700 and 6350 to 6900 rpm, respectively, with power consumption increases from 3.7 to 4.3 W (16%) and 5.5 to 6.8 W (24%), respectively. CONCLUSIONS: The study did not elucidate a severe consequence of using a remnant HVAD graft during pump exchange, but the incremental risks of a higher rotor speed, disadvantage to the patient in battery runtime, and the general benefit of complete conversion to the HeartMate 3 graft should be balanced against other procedural considerations. Complete graft replacement during HVAD-to-HeartMate 3 conversion remains the preferred approach from an engineering point of view.

Adipose-derived stem cell sheet under an elastic patch improves cardiac function in rats after myocardial infarction.

OBJECTIVES: Although adipose-derived stem cells (ADSCs) have shown promise in cardiac regeneration, stable engraftment is still challenging. Acellular bioengineered cardiac patches have shown promise in positively altering ventricular remodeling in ischemic cardiomyopathy. We hypothesized that combining an ADSC sheet approach with a bioengineered patch would enhance ADSC engraftment and positively promote cardiac function compared with either therapy alone in a rat ischemic cardiomyopathy model. METHODS: Cardiac patches were generated from poly(ester carbonate urethane) urea and porcine decellularized cardiac extracellular matrix. ADSCs constitutively expressing green fluorescent protein were established from F344 rats and transplanted as a cell sheet over the left ventricle 3 days after left anterior descending artery ligation with or without an overlying cardiac patch. Cardiac function was serially evaluated using echocardiography for 8 weeks, comparing groups with combined cells and patch (group C, n = 9), ADSCs alone (group A, n = 7), patch alone (group P, n = 6) or sham groups (n = 7). RESULTS: Much greater numbers of ADSCs survived in the C versus A groups (P < .01). At 8 weeks posttransplant, the percentage fibrotic area was lower (P < .01) in groups C and P compared with the other groups and vasculature in the peri-infarct zone was greater in group C versus other groups (P < .01), and hepatocyte growth factor expression was higher in group C than in other groups (P < .05). Left ventricular ejection fraction was higher in group C versus other groups. CONCLUSIONS: A biodegradable cardiac patch enhanced ADSC engraftment, which was associated with greater cardiac function and neovascularization in the peri-infarct zone following subacute myocardial infarction.

Primary Graft Dysfunction in Heart Transplant Recipients-Risk Factors and Longitudinal Outcomes.

Before the 33rd Annual International Society for Heart and Lung Transplantation conference, there was significant intercenter variability in definitions of primary graft dysfunction (PGD). The incidence, risk factors, and outcomes of consensus-defined PGD warrant further investigation. We retrospectively examined 448 adult cardiac transplant recipients at our institution from 2005 to 2017. Patient and procedural characteristics were compared between PGD cases and controls. Multivariable logistic regression was used to model PGD and immediate postoperative high-inotrope requirement for hypothesized risk factors. Patients were followed for a mean 5.3 years to determine longitudinal mortality. The incidence of PGD was 16.5%. No significant differences were found with respect to age, sex, race, body mass index, predicted heart mass mismatch, pretransplant amiodarone therapy, or pretransplant mechanical circulatory support (MCS) between recipients with PGD versus no PGD. Each 10 minute increase in ischemic time was associated with 5% greater odds of PGD (OR = 1.05 [95% CI, 1.00-1.10]; p = 0.049). Pretransplant MCS, predicted heart mass mismatch ≥30%, and pretransplant amiodarone therapy were associated with high-immediate postoperative inotropic requirement. The 30 day, 1 year, and 5 year mortality for patients with PGD were 28.4%, 38.0%, and 45.8%, respectively, compared with 1.9%, 7.1%, and 21.5% for those without PGD (log-rank, p < 0.0001). PGD heralded high 30 day, 1 year, and 5 year mortality. Pretransplant MCS, predicted heart mass mismatch, and amiodarone exposure were associated with high-inotrope requirement, while prolonged ischemic time and multiple perioperative transfusions were associated with consensus-defined PGD, which may have important clinical implications under the revised United Network for Organ Sharing allocation system.

Evolution of Late Right Heart Failure With Left Ventricular Assist Devices and Association With Outcomes.

BACKGROUND: A revised definition of right heart failure (RHF) for the Society of Thoracic Surgeons Intermacs database of left ventricular assist devices (LVADs) was introduced in June 2014. OBJECTIVES: The purpose of this study was to determine the prevalence and severity of RHF over time and the association of RHF status at 3 months with 12-month outcomes after LVAD. METHODS: All patients in Society of Thoracic Surgeons Intermacs with follow-up and supported at least 3 months with a continuous flow LVAD implanted between June 2, 2014 and March 31, 2017 without a simultaneous RVAD. RHF was defined as both documentation and manifestations of elevated central venous pressures. RESULTS: There were 6,118 patients included with an incidence of RHF at 3, 6, and 12 months postimplant categorized as mild in 5%, 6%, and 6% and moderate in 5%, 3%, and 3%, respectively. For those with no RHF at 3 months, there was a low incidence of subsequent RHF at 6 and 12 months. The lack of RHF at 3 months, compared with mild and moderate RHF, was associated with a lower 12-month cumulative incidence of mortality (6.9% vs 16.7% vs 28.1%; P < 0.0001) and a lower 12-month cumulative incidence of stroke (7.4% vs 9.5% vs 11.0%; P = 0.0095), gastrointestinal bleeding (14.8% vs 24.2% vs 23.6%; P < 0.0001), and rehospitalization (65.2% vs 73.2% vs 71.2%; P < 0.0001). CONCLUSIONS: In patients surviving 3 months with LVAD support alone, mild or moderate RHF occurred in nearly 1 of 10 patients at 12 months. Patients with late RHF had worse survival and a higher cumulative incidence of major adverse events.

Creation and Validation of a Novel Sex-Specific Mortality Risk Score in LVAD Recipients.

Background Prior studies have shown that women have worse 3-month survival after receiving a left ventricular assist device compared with men. Currently used prognostic scores, including the Heartmate II Risk Score, do not account for the increased residual risk in women. We used the IMACS (International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support) registry to create and validate a sex-specific risk score for early mortality in left ventricular assist device recipients. Methods and Results Adult patients with a continuous-flow LVAD from the IMACS registry were randomly divided into a derivation cohort (DC; n=9113; 21% female) and a validation cohort (VC; n=6074; 21% female). The IMACS Risk Score was developed in the DC to predict 3-month mortality, from preoperative candidate predictors selected using the Akaike information criterion, or significant sex × variable interaction. In the DC, age, cardiogenic shock at implantation, body mass index, blood urea nitrogen, bilirubin, hemoglobin, albumin, platelet count, left ventricular end-diastolic diameter, tricuspid regurgitation, dialysis, and major infection before implantation were retained as significant predictors of 3-month mortality. There was significant ischemic heart failure × sex and platelet count × sex interaction. For each quartile increase in IMACS risk score, men (odds ratio [OR], 1.86; 95% CI, 1.74-2.00; P<0.0001), and women (OR, 1.93; 95% CI, 1.47-2.59; P<0.0001) had higher odds of 3-month mortality. The IMACS risk score represented a significant improvement over Heartmate II Risk Score (IMACS risk score area under the receiver operating characteristic curve: men: DC, 0.71; 95% CI, 0.69-0.73; VC, 0.69; 95% CI, 0.66-0.72; women: DC, 0.73; 95% CI, 0.70-0.77; VC, 0.71 [95% CI, 0.66-0.76; P<0.01 for improvement in receiver operating characteristic) and provided excellent risk calibration in both sexes. Removal of sex-specific interaction terms resulted in significant loss of model fit. Conclusions A sex-specific risk score provides excellent risk prediction in LVAD recipients.

Clinical outcomes and healthcare expenditures in the real world with left ventricular assist devices - The CLEAR-LVAD study.

BACKGROUND: Several distinctly engineered left ventricular assist devices (LVADs) are in clinical use. However, contemporaneous real world comparisons have not been conducted, and clinical trials were not powered to evaluate differential survival outcomes across devices. OBJECTIVES: Determine real world survival outcomes and healthcare expenditures for commercially available durable LVADs. METHODS: Using a retrospective observational cohort design, Medicare claims files were linked to manufacturer device registration data to identify de-novo, durable LVAD implants performed between January 2014 and December 2018, with follow-up through December 2019. Survival outcomes were compared using a Cox proportional hazards model stratified by LVAD type and validated using propensity score matching. Healthcare resource utilization was analyzed across device types by using nonparametric bootstrap analysis methodology. Primary outcome was survival at 1-year and total Part A Medicare payments. RESULTS: A total of 4,195 de-novo LVAD implants were identified in fee-for-service Medicare beneficiaries (821 HeartMate 3; 1,840 HeartMate II; and 1,534 Other-VADs). The adjusted hazard ratio for mortality at 1-year (confirmed in a propensity score matched analysis) for the HeartMate 3 vs HeartMate II was 0.64 (95% CI; 0.52-0.79, p< 0.001) and for the HeartMate 3 vs Other-VADs was 0.51 (95% CI; 0.42-0.63, p < 0.001). The HeartMate 3 cohort experienced fewer hospitalizations per patient-year vs Other-VADs (respectively, 2.8 vs 3.2 EPPY hospitalizations, p < 0.01) and 6.1 fewer hospital days on average (respectively, 25.2 vs 31.3 days, p < 0.01). The difference in Medicare expenditures, conditional on survival, for HeartMate 3 vs HeartMate II was -$10,722, p < 0.001 (17.4% reduction) and for HeartMate 3 vs Other-VADs was -$17,947, p < 0.001 (26.1% reduction). CONCLUSIONS: In this analysis of a large, real world, United States. administrative dataset of durable LVADs, we observed that the HeartMate 3 had superior survival, reduced healthcare resource use, and lower healthcare expenditure compared to other contemporary commercially available LVADs.

Impact of Pre-Existing Mitral Regurgitation Following Left Ventricular Assist Device Implant.

OBJECTIVES: Optimal management of significant mitral regurgitation (SMR) during left ventricular assist device (LVAD) placement remains uncertain. This study evaluates the effect of untreated preop SMR on outcomes following LVAD implant. METHODS: Adults undergoing primary LVAD placement from April 2004 to May 2017 were included. Most recent preop transthoracic echocardiogram (TTE) was used to divide patients into an SMR group with moderate or greater regurgitation, and a group without SMR. Patients underwent LVAD implant without correction of SMR. Primary endpoint was 3-year postoperative survival, with secondary endpoints of length of stay (LOS), resolution of SMR following LVAD on postdischarge (30 day) TTE, and 1-year TTE. RESULTS: LVAD placement was performed in 270 patients, 172 (63.7%) without SMR and 98 (36.3%) with SMR. There were no differences in comorbidities including diabetes, hypertension, and renal disease. Preop ejection fraction was similar, but a higher pulmonary vascular resistance was recorded in the SMR group (3.6 vs 3.0 Wood Units, P = 0.048). There was no difference in 3-year mortality between the 2 cohorts (log-rank P = 0.0.803). The SMR group had decreased LOS (median 19.5 vs 22 days, P = 0.009). Of the 98 SMR patients, 91 (92.9%) had resolution of SMR to less than moderate at 30 days. At 1 year, 15% of those with preoperative SMR had recurrent SMR. CONCLUSIONS: Patients undergoing LVAD placement with preop SMR experience no differences in mortality, and a majority experience resolution of MR after implant. Longer-term SMR recurrence and need for mitral intervention with LVAD implant warrant further investigation.

A comparison of air-cell and gel surgical table pads and an evaluation of the influence of pressure distribution and other factors on pressure injury prevention.

Guidelines for pressure injury prevention consider the use of pressure-redistributing pads to prevent tissue deformation. However, limited research exists to assess the pressure distribution provided by the operating tables and the effectiveness of pressure-redistributing pads in preventing pressure injuries. In this study, we compared the pressure distribution properties of two surgical table pads and identified parameters influencing pressure injury outcomes after a lengthy surgical procedure. Twenty-seven patients undergoing left ventricular assist device implantation surgery participated in the study. Participants were randomly assigned to use either an air cell-based pad or a gel pad. Interface pressure was recorded during the surgery. We analyzed the effect of surgical table pad type, interface pressure distribution and pressure injury outcomes and analyzed what characteristics of the patients and the interface pressure are most influential for the development of pressure injuries. Comparing the interface pressure parameters between the air-cell group and the gel group, only the peak pressure index x time was significantly different (p < 0.05). We used univariate logistic regression analysis to identify significant predictors for the pressure injury outcome. The support surface was not significant. And, among patient characteristics, only age and BMI were significant (p ≤ 0.05). Among the interface pressure parameters, pressure density maxima, peak pressure index x time, and coefficient of variation were significant for pressure injury outcome (p ≤ 0.05). Peak pressure index, average pressure, and the surgery length were not statistically significant for pressure injury outcomes.

Durable mechanical circulatory support device use in the United States by geographic region and minority status.

BACKGROUND: Durable mechanical circulatory support device (MCSD) therapy has experienced rapid dissemination in the United States. Few studies have evaluated geographic patterns of its dissemination based upon patient characteristics that could identify potential variation in its application. METHODS: A combined Interagency Registry for Mechanically Assisted Circulatory Support and Medicare dataset identified durable MCSD implants from 2008 through 2014. MCSD implant rates were estimated using yearly US Census population data, estimated from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database and stratified by age, race, and United Network for Organ Sharing (UNOS) region. RESULTS: Overall, 16,331 patients received an MCSD implant from 232 unique centers. Annual MCSD implant rate (per 1 million population) significantly increased in each UNOS region (absolute range of increase, 5.3-16.4) with UNOS Region 7 demonstrating the highest overall absolute rate (20.9) in 2014 and UNOS Region 11 demonstrating the greatest relative increase in rate (430.5%). Geographical differences in the rate of MCSD implants were observed among whites and minorities with higher rates of MCSD implants observed for minorities for nearly all UNOS regions across all years. Significantly greater relative increases in MCSD implants for minorities compared with whites were observed within UNOS Regions 2, 3, 6, 7, 8, 9, and 11 (P < .001). CONCLUSIONS: Geographical differences exist in rates of MCSD implantation among whites and minorities. The reasons for these differences are unknown, but may reflect underlying differences in disease burden or disparities in access to heart transplantation and warrant further study.

The Preimplantation Psychosocial Evaluation and Prediction of Clinical Outcomes During Mechanical Circulatory Support: What Information Is Most Prognostic?

BACKGROUND: Psychosocial evaluations are required for long-term mechanical circulatory support (MCS) candidates, no matter whether MCS will be destination therapy (DT) or a bridge to heart transplantation. Although guidelines specify psychosocial contraindications to MCS, there is no comprehensive examination of which psychosocial evaluation domains are most prognostic for clinical outcomes. We evaluated whether overall psychosocial risk, determined across all psychosocial domains, predicted outcomes, and which specific domains appeared responsible for any effects. METHODS: A single-site retrospective analysis was performed for adults receiving MCS between April 2004 and December 2017. Using an established rating system, we coded psychosocial evaluations to identify patients at low, moderate, or high overall risk. We similarly determined risk within each of 10 individual psychosocial domains. Multivariable analyses evaluated whether psychosocial risk predicted clinical decisions about MCS use (DT versus bridge), and postimplantation mortality, transplantation, rehospitalization, MCS pump exchange, and standardly defined adverse medical events (AEs). RESULTS: In 241 MCS recipients, greater overall psychosocial risk increased the likelihood of a DT decision (odds ratio, 1.76; P = 0.017); and postimplantation pump exchange and occurrence of AEs (hazard ratios [HRs] ≥ 1.25; P ≤ 0.042). The individual AEs most strongly predicted were cardiac arrhythmias and device malfunctions (HRs ≥ 1.39; P ≤ 0.032). The specific psychosocial domains predicting at least 1 study outcome were mental health problem severity, poorer medical adherence, and substance use (odds ratios and HRs ≥ 1.32; P ≤ 0.010). CONCLUSIONS: The psychosocial evaluation predicts not only clinical decisions about MCS use (DT versus bridge) but important postimplantation outcomes. Strategies to address psychosocial risk factors before or soon after implantation may help to reduce postimplantation clinical risks.

Gender Differences in Mortality After Left Ventricular Assist Device Implant: A Causal Mediation Analysis Approach.

We used the International Society for Heart and Lung Transplantation (ISHLT) Registry for Mechanically Assisted Circulatory Support (IMACS) database to examine 1) gender differences in post-left ventricular assist device (LVAD) mortality in the contemporary era and 2) preimplant clinical factors that might mediate any observed differences. Adults who received continuous-flow (CF)-LVAD from January 2013 to September 2017 (n = 9,565, age: 56.2 ± 13.2 years, 21.6% female, 31.1% centrifugal pumps) were analyzed. An inverse probability weighted Cox proportional hazards model was used to estimate association of female gender with all-cause mortality, adjusting for known covariates. Causal mediation analysis was performed to test plausible preimplant mediators mechanistically underlying any association between female gender and mortality. Females had higher mortality after LVAD (adjusted hazard ratio [HR]: 1.36; p < 0.0001), with significant gender × time interaction (p = 0.02). An early period of increased risk was identified, with females experiencing a higher risk of mortality during the first 4 months after implant (adjusted HR: 1.74; p < 0.0001), but not after (adjusted HR: 1.18; p = 0.16). More severe tricuspid regurgitation and smaller left ventricular end-diastolic diameter at baseline mediated ≈21.9% of the increased early hazard of death in females; however, most of the underlying mechanisms remain unexplained. Therefore, females have increased mortality only in the first 4 months after LVAD implantation, partially driven by worsening right ventricular dysfunction and LV-LVAD size mismatch.

Delineating Pathways to Death by Multisystem Organ Failure in Patients With a Left Ventricular Assist Device.

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.