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Whether pre left ventricular assist device (LVAD) sarcopenia is associated with higher incidence of gastrointestinal bleeding (GIB) on LVAD support remains unknown.To study the association between preoperative sarcopenia and post LVAD GIB events, we performed a retrospective, multi-centered study including patients with chest CTs performed ≤ 3 months prior to LVAD implantation at the University of Minnesota (n = 143) and Houston Methodist Hospital (n = 133). To quantify sarcopenia, unilateral pectoralis muscle mass indexed to body surface area (PMI) and attenuation (approximated by mean Hounsfield units; PHUThe study cohort included 276 LVAD recipients with 43 % designated as bridge to transplant at the time of LVAD implantation. High pectoralis muscle mass and tissue attenuation were both protective against GIB events. Each 5 unit increase in PHUPreoperative sarcopenia, as quantified by pectoralis muscle size and attenuation, was associated with the development of recurrent GI bleeding after LVAD implantation. These CT quantitative measures appear to predict not only early mortality but morbidity on LVAD as well.

Risk assessment for early, severe right heart failure (RHF) after LVAD implantation remains imperfect. We sought to define the differences in RV adaptation and load after axillary Impella support between patients who experienced RHF and those who did not. Seventeen of 18 patients included were deemed intermediate or high risk for RHF by EUROMACS-RHF score. Before Impella insertion, RV adaptation parameters (RAP, RAP:PCWP, PAPi) were worse in the non-RHF group compared to the RHF group. In both groups, RV load parameters (effective pulmonary arterial elastance, pulmonary vascular resistance, and pulmonary vascular compliance) improved after Impella insertion. Lesser improvements in RV adaptation were seen in the RHF group. Moreover, load-to-adaptation relationships (EA/RAP and EA/RAP:PCWP) worsened to a greater degree. In patients at intermediate or high risk for RHF after LVAD, assessment of RV adaptation and load during axillary Impella support may improve risk stratification.

BACKGROUND There is little insight into which patients can be weaned off right ventricular (RV) acute mechanical circulatory support (AMCS) after left ventricular assist device (LVAD) implantation. We hypothesize that concomitant RV AMCS insertion instead of postoperative implantation will improve 1-year survival and increase the likelihood of RV AMCS weaning. METHODS A multicenter retrospective database of 826 consecutive patients who received a HeartMate II or HVAD between January 2007 and December 2016 was analyzed. We identified 91 patients who had early RV AMCS on index admission. Cox proportional-hazards model was constructed to identify predictors of 1-year mortality post-RV AMCS implantation and competing risk modeling identified RV AMCS weaning predictors. RESULTS There were 91 of 826 patients (11%) who required RV AMCS after CF-LVAD implantation with 51 (56%) receiving a concomitant RV AMCS and 40 (44%) implanted with a postoperative RV AMCS during their ICU stay; 48 (53%) patients were weaned from RV AMCS support. Concomitant RV AMCS with CF-LVAD insertion was associated with lower mortality (HR 0.45 [95% CI 0.26-0.80], p = 0.01) in multivariable model (which included age, BMI, angiotensin-converting enzyme inhibitor use, and heart transplantation as a time-varying covariate). In the multivariate competing risk analysis, a TPG < 12 (SHR 2.19 [95% CI 1.02-4.70], p = 0.04) and concomitant RV AMCS insertion (SHR 3.35 [95% CI 1.73-6.48], p < 0.001) were associated with a successful wean. CONCLUSIONS In patients with RVF after LVAD implantation, concomitant RV AMCS insertion at the time of LVAD was associated with improved 1-year survival and increased chances of RV support weaning compared to postoperative insertion.

BACKGROUND Multicenter data on long term survival following LVAD implantation that make use of contemporary definitions of RV failure are limited. Furthermore, traditional survival analyses censor patients who receive a bridge to heart transplant. Here we compare the outcomes of LVAD patients who develop post-operative RV failure accounting for the transitional probability of receiving an interim heart transplantation. METHODS We use a retrospective cohort of LVAD patients sourced from multiple high-volume centers based in the United States. Five- and ten-year survival accounting for transition probabilities of receiving a heart transplant were calculated using a multi-state Aalen Johansen survival model. RESULTS Of the 897 patients included in the study, 238 (26.5%) developed post-operative RV failure at index hospitalization. At 10 years the probability of death with post-op RV failure was 79.28% vs 61.70% in patients without (HR 2.10; 95% CI 1.72 - 2.57; p = < .001). Though not significant, patients with RV failure were less likely to be bridged to a heart transplant (HR 0.87, p = .4). Once transplanted the risk of death between both patient groups remained equivalent; the probability of death after a heart transplant was 3.97% in those with post-operative RV failure shortly after index LVAD implant, as compared to 14.71% in those without. CONCLUSIONS AND RELEVANCE Long-term durable mechanical circulatory support is associated with significantly higher mortality in patients who develop post-operative RV failure. Improving outcomes may necessitate expeditious bridge to heart transplant wherever appropriate, along with critical reassessment of organ allocation policies.

Purpose Prediction of right heart failure (RHF) after left ventricular assist device (LVAD) implant is a crucial step to improve outcomes. The EUROMACS Right-Sided Heart Failure (EUROMACS-RHF) risk score is one of the most recent derived scores for RHF prediction after LVAD but it lacks external validation. The aim of our study was to validate the EUROMACS-RHF risk score. Methods From 01/2007 to 12/2017, 878 continuous-flow LVADs were implanted at three tertiary care centers. We calculated the EUROMACS-RHF score in 662 patients with complete data. We evaluated the predictive performance of the score for early RHF defined as need for short- or long-term right-sided circulatory support, continuous inotropic support for ≥14 days or nitric oxide ventilation for ≥48 hours post-operatively. Results RHF occurred in 211 patients (32%). RHF patients had higher creatinine, bilirubin and right atrial pressure, more echocardiographic RV dysfunction and were more critically ill reflected in lower INTERMACS class (p Conclusion In an external validation, the EUROMACS-RHF had similar discrimination predicting RHF compared to the original derivation cohort, which was better than other published scores. The clinical utility of these scores in the decision to implant LVAD in prospective studies remains to be determined.

Purpose Deciding which patients can be weaned from an RVAD placed after LVAD implantation could help triage advanced heart failure device strategy. Therefore, we set out to determine the predictors of RVAD weaning. Methods A multi-center retrospective study of 826 consecutive patients who received either a HeartMate2 or HVAD between 1/2007 an 12/2007. We identified 91 patients who received an early RVAD insertion during their LVAD implant index admission. A Cox Proportional hazard model was constructed to identify predictors of RVAD weaning. Results There were 91 patients (11%) who required an RVAD after LVAD with 48 (52%) weaned from RVAD support and 43 (48%) not weaned. Patients who were weaned had a lower prevalence of hypertension, higher pre-operative ACE-inhibitor use, and lower pre-operative transpulmonary gradient (TPG), RA-PCWP ratio, and RVSWI; they were also more likely to receive concomitant RVAD at time of LVAD insertion and ultimately transplanted more often (Table 1). Our multivariable model for predictors of RVAD weaning included pre-operative creatinine (HR 0.32 [0.15, 0.70], p = 0.004), PVR (HR 1.23 [1.02, 1.48], p = 0.03), non-white ethnicity (HR 2.56 [1.19, 5.54], p = 0.02), COPD (HR 4.63 [1.32, 16.25], p = 0.02), and concomitant RVAD insertion (HR 2.87 [1.00, 8.21], p-value = 0.05) with a model c-statistic of 0.84. The survival curve demonstrates that patients who are weaned from RVAD have significantly improved 1-year mortality (Figure 1, p Conclusion In a multi-institutional continuous-flow LVAD cohort, we show novel predictors of RVAD weaning that can help triage mechanical support strategy.

Purpose Early insertion of an RVAD may help to mitigate post-LVAD implantation morbidity and mortality. We hypothesize that concomitant RVAD insertion at time of LVAD implantation improves 1-year mortality in comparison to post-operative insertion. Methods A multi-center retrospective study of 826 consecutive patients who received either a HeartMate2 or HVAD between 1/2007 an 12/2017. We identified 91 patients who either had an unplanned or planned early RVAD on index admission. A Cox proportional hazard model was constructed to identify predictors of 1-year mortality. Results There were 91 patients (11%) who required an RVAD after LVAD implantation with 51 (56%) receiving a concomitant RVAD and 40 (43%) post-operatively (Table 1). Concomitant RVAD with LVAD insertion was associated with lower mortality (HR 0.45 [0.27, 0.76], p-value = 0.002, Figure 1). Our multivariable model (which included age, BMI, and ACE-i use) found receiving transplant (HR 0.04 [0.01, 0.29], p = 0.001) and concomitant RVAD (HR 0.51 [0.29, 0.90], p = 0.004) to be independent predictors of 1-year mortality with a final model C-statistic of 0.77. Stratifying concomitant RVAD by intended approach, planned versus unplanned RVAD insertion had a similar survival rate as unplanned approach at 1 year (42.8% versus 28.6%, p-value = 0.08). Conclusion We show in a continuous-flow and multi-institutional cohort that concomitant RVAD insertion at time of LVAD is associated with improved survival at 1 year compared to post-operative insertion.

Purpose The 2016 ISHLT revised cardiac transplantation listing criteria has recommended patients to achieve a body mass index (BMI) 35 show poorer outcome post-transplant, there is limited data on the BMI group of 35-39.9. This study aims to determine the relationship between post-transplant outcomes and a pre-transplant listing BMI of 35-39.9 as compared to a BMI Methods A retrospective cohort analysis of patients stratified by BMI subgroup was performed of 23,009 adult heart transplant patients from 2009-2018 using the United Network for Organ sharing database. Patients with BMI of 35-39.9 post-transplant outcomes were compared to patients with BMI Results Patients with a BMI 35.0-39.9 had post-transplant survival of 92.4% at 90 days, 89.3% at 1 year and 74.5% at 5 years, compared to patients with a BMI Conclusion Although a statistically significant increase in mortality was observed between the BMI

Introduction Heart transplant candidates with allosensitization face higher waitlist mortality and may have inferior post-transplant outcomes. We present our experience with a multi-drug desensitization regimen including daratumumab, an anti-CD38 monoclonal antibody, in a 51-year-old female listed for heart transplant. Case Report The patient presented with heart failure due to NICMP with LMNA mutation. She was listed for heart transplant with 94% class I PRAs and 98% class II PRAs. Given level of sensitization, the decision was made to desensitize with plasmapheresis (5 sessions), IVIG (2 g/kg), bortezomib (4 doses), and tocilizumab (1 dose). During this treatment she experienced neutropenia requiring bortezomib dose reduction. Following these therapies her class I PRA decreased to 36%, but her class II PRA persisted at 99%. Immunodominant HLA antibodies are trended in Figure 1. She subsequently received additional plasmapheresis (6 sessions) with IVIG (2 g/kg) and rituximab (1 dose). PRAs remained consistent; HLA MFIs remained high (Figure 1). She was then treated with daratumumab weekly. She received 8 doses; the last dose was received the day prior to transplant. Her class I PRA decreased to 13% and class II PRA was 99% at the time of transplant. Her crossmatch was negative, and she received steroid induction alone. Maintenance immunosuppression consisted of tacrolimus, mycophenolate, and prednisone. Her tacrolimus was therapeutic by POD6 with a goal of 10-15 mcg/mL. By month 11 post-transplant she has had no episodes of cellular or antibody-mediated rejection. Graft function has been stable with ejection fraction >60%. All DSA screening has been negative and she has not developed any significant infections post-transplant. Summary Daratumumab, as part of a desensitization regimen, appears to be safe and effective in sensitized patients awaiting heart transplant and was not associated with post-op complications, and may have contributed to prevention of antibody-mediated rejection post-transplant.

Introduction Sensitization is a challenge in heart transplant recipients, often increasing wait time and decreasing access to acceptable organs. We present a case of a highly sensitized 47-year-old female listed for re-do heart and kidney transplant who was desensitized utilizing ofatumumab and tocilizumab. Case Report The patient received her first heart transplant in 1992 (induction muromonab-CD3) for viral cardiomyopathy at an outside hospital; in 2015 she was treated for antibody mediated rejection with plasma exchange (PLEX), intravenous immunoglobulin (IVIG), and bortezomib. She later developed cardiac allograft vasculopathy. In 2018 she was brought to our center with cardiogenic shock and worsening renal function, required dual inotropic support, and evaluated and listed for a re-do heart and kidney transplant. Her peak PRA was 90% with several class I and II antibodies. She underwent desensitization therapy with PLEX, IVIG (2 g/kg), ofatumumab (1 dose), and monthly tocilizumab (3 doses). No adverse drug events were reported during therapy. Her PRA remained persistently ∼90%; MFI trends of her antibodies are presented in Figure 1. After her 3rd tocilizumab dose she received an offer which was crossmatch negative and no pre-existing antibodies. She received basiliximab induction and maintenance immunosuppression of tacrolimus, mycophenolate, and prednisone. During the 1 year follow-up post-transplant, she had excellent graft function with ejection fraction >60%, serum creatinine Summary Desensitization with ofatumumab and tocilizumab resulted in successful heart and kidney transplantation. Although PRA and MFI of pre-existing antibodies were not significantly altered, this regimen may have been helpful in reducing de novo donor specific antibodies and preventing acute rejection post-transplant.

Purpose It is well established that “high volume” centers have better outcomes for complex surgical care including transplantation. However, few studies have used data-driven methodology to establish clinically meaningful volume thresholds predictive of improved outcomes for centers performing orthotopic heart transplantation (OHT). Methods All OHT cases performed between 2005 and 2015 (with follow-up through 2016) within the United Network for Organ Sharing (UNOS) database were reviewed for potential eligibility. All patients ≥18 years of age undergoing isolated OHT were included. Stratum-specific likelihood ratio analysis (SSLR) was used to establish volume thresholds predictive of the primary outcome of mortality at 1-year. Preoperative characteristics and postoperative outcomes were compared between volume strata using χ2 tests (categorical) or ANOVA (continuous). Results A total of 21,800 recipients (mean age 52.6 ± 12.8 years; 25.2% female) were included in the final cohort. Three distinct center volume strata were identified from the analysis: low ( Conclusion The results of our study demonstrate that higher volume centers perform better than their lower volume counterparts in terms of early mortality after OHT. Our study adds to the existing literature by providing specific, data-driven volume thresholds predictive of improved early outcomes in the contemporary transplant and circulatory support landscape.

Purpose Advances in immunosuppression, bridging therapies, and ex vivo perfusion and ventilation have led to substantial advances in lung transplantation (LTx). Nevertheless, LTx is associated with substantial morbidity and mortality. Better outcomes have been demonstrated in “high volume” lung transplant centers, but the field lacks a definition of high volume. The present study aims to identify meaningful, data-driven volume thresholds predicting improved outcomes for LTx centers. Methods All single and double LTx cases performed on patients over the age of 18 between 2005 and 2015 in the United Network for Organ Sharing (UNOS) database were reviewed. Patients listed for other organs or transplants performed in centers that were active for less than three of the ten years of the study period were excluded. Under 1% of patients were excluded due to lack of follow-up data. Stratum-specific likelihood ratios (SSLR) were calculated to establish volume thresholds predictive of the primary outcome of 1 year mortality. Demographic and outcomes data were compared between volume strata. Results A total of 20,153 recipients were included in the final cohort. We identified two thresholds based on SSLR analysis at 12 and 28 LTx/year, which yielded three distinct volume strata: low (under 12), intermediate (12-27), and high volume (over 27). The majority of transplants are performed at high volume centers, which have shorter lengths of stay (24 days vs 29 for low-volume) and better 30-day and 1-year patient survival (96.7% and 86%, vs 94.2% and 80.3% for low-volume), despite older recipients, greater ischemic time, and increased use of extended-criteria donors. Conclusion The results of our study support that high volume centers outperform their low and intermediate volume counterparts and distinguish between the three volume levels. Our study adds to the existing literature by estimating targets for annual lung transplants at which centers may attain improvements in recipient outcomes.

Purpose Mechanical circulatory support (MCS) has been considered a “bridge to decision/therapy” alternative to ameliorate compromised hemodynamic condition in patients whom conventional medical therapy is insufficient to maintain the adequate organ perfusion and function. Outcomes of patients after temporary mechanical support depend on various factors and can range from mortality to recovery to a bridge to cardiac replacement like heart transplant or long term ventricular assist devices. We aim to retrospectively analyze medical record information and clinical outcomes from patients with axillary Impella 5.0 seen at our institution. Methods This retrospective analysis study was designed to gather information about patients that were implanted with an axillary Impella 5.0 at The Methodist Hospital between 2010 and 2019. Subjects were identified and selected through chart review and physician referrals. Results Through the span of about a decade, we have placed about 48 axillary Impella 5.0 devices in a wide range of patients divided into 42 men and 6 women. 24 patients were over the age of 60, 15 patients between 41 and 60 years old, and 9 patients between 29-40 years of age. Of those patients, about 26 patients were upgraded from an Intra-aortic balloon pump, 10 patients had no previous MCS, and the rest either had ECMO or other impella devices. About 44 patients met their hemodynamic needs via the axillary impella device. The 4 remaining patient had either concurrent ECMO and/or RVAD. In regards to outcomes, 22 patients were able to be bridged to OHT or LVAD, 18 patients expired and were not candidates for advanced HF therapy, and 8 patients were able to have the impella weaned off. Conclusion Our single center retrospective study shows that axillary impella 5.0 devices are a viable device for bridge to recovery and/or bridge to cardiac replacement. Over 62% of our patients were able to be bridged to heart transplant/LVAD or have the impella weaned off due to cardiac recovery. Our rate of success is largely due to the increased support provided by the Impella 5.0 devices, but also with the added benefit allowing these patients to be ambulatory to help reduced critical illness morbidity and mortality.

Malfunction of a continuous-flow left ventricular assist device (CF-LVAD) due to device thrombosis is a potentially life-threatening event that currently presents a diagnostic challenge. We aimed to propose a practical echocardiographic assessment to diagnose LVAD malfunction secondary to pump thrombosis.Among 52 patients implanted with a CF-LVAD from a single center who underwent echocardiographic pump speed-change testing, 12 had suspected pump thrombosis as determined by clinical, laboratory, and/or device parameters. Comprehensive echocardiographic evaluation was performed at baseline pump speed and at each 1,000-rpm interval from the low setting of 8,000 rpm to the high setting of 11,000 rpm in 11 of these patients.Receiver operating characteristic curves and stepwise logistic regression analyses showed that the best diagnostic parameters included changes in the LV end-diastolic diameter (0.6 cm), aortic valve opening time (80 msec), and deceleration time of mitral inflow (70 msec) from lowest to highest pump speed. One parameter was predictive of pump malfunction, with 100% sensitivity and 89% specificity, whereas 2 of 3 parameters increased the sensitivity to 100% and specificity to 95%.The 3 echocardiographic variables of measured changes in LV end-diastolic diameter, aortic valve opening time, and deceleration time of mitral inflow between the lowest (8,000 rpm) and highest pump speed settings (11,000 rpm) during echo-guided pump speed-change testing appear highly accurate in diagnosing device malfunction in the setting of pump thrombosis among patients supported with CF-LVAD. Further investigation is warranted to create and validate a prediction score.

Background: Endothelial to Mesenchymal Transition (EndMT) and the reverse phenomenon of mesenchymal to endothelial transitioning (MET) has been shown to contribute to fibrosis in rodent models of heart failure. There are no studies documenting the same in human cardiac tissue. Methods: We performed immunofluorescence dual staining on end stage heart failure myocardial samples obtained from our bio repository. Staining for endothelial and mesenchymal markers were performed with Anti-VE-Cadherin (Santa Cruz Biotechnologies) and anti-Fibroblast specific protein 1 (Dako Antibodies) respectively using standard immunofluoresence techniques. Presence of dual staining on fluorescence microscopy was considered as positive for the presence of EndMT. Vascular density was assessed using a DAB (3-3’ Diaminobenzidine) technique with Anti-CD31 (PECAM, Abcam). Results: Of the end stage heart failure samples, 18 were from left ventricular core during LVAD implant and 5 during a direct transplant as status 1A (axillary intraaortic balloon pump). 10 hearts of patients bridged to transplant with a continuous flow LVAD (Days under support 3436228) were also studied. Mean age was 55y with 82% males and 74% white. 70% of all samples had evidence of EndMT. The number of cells ranged from 1 to 5 per high power field. There was no significant difference between patient characteristics between those with evidence of EndMT versus not, except a higher prevalence of diabetes in the latter group. (Fig 1B) 74% of the end-stage heart failure samples and 60% of the post-VAD samples showed the presence of EndMT cells. Vascular Density was higher in the samples exhibiting EndMT phenomenon. (Figure 1A). Conclusion: We have documented for the first time, the existence of endothelial-mesenchymal transition in human end stage myocardial samples corroborating earlier pioneering studies in rodents. Interestingly the existence of such dual staining cells in end stage hearts (which is highly fibrotic) suggests a possible role of ongoing fibrosis with endothelial to mesenchymal transitioning or potential antifibrotic mechanism though mesenchymal to endothelial transitioning. Further studies of the later process will be warranted to explore potential anti-fibrotic therapeutic implications.

Purpose Acute right heart failure following LVAD implantation continues to be a challenging post-operative problem. Although medical management can be helpful, biventricular support is sometimes required. There is much debate about whether tricuspid valve repair (TVR) should be performed in those patients with significant tricuspid valve regurgitation undergoing device implantation. Methods and Materials A total of 30 patients who underwent LVAD placement were included in the study. All had moderate to severe tricuspid regurgitation (TR) by pre-op 2D echocardiography. 21 of these patients received a TVR during HMII placement and 9 did not (control). Outcome measures were analyzed for age, survival, acute RVF, need for biventricular support, and other hemodynamic parameters. Results In the TVR group, central venous pressure (CVP) was significantly reduced pre- vs postop (17.3±4.2 vs 11.1±4.2 mmHg) than the control group (p≤0.01). Acute RVF was significantly lower in the TVR group, occurring in 1/21 patient (4.5%). In contrast, 3/9 (33%) patients who did not have repair had onset of RVF (p≤0.02). 2/9 patients in the control group required RVAD support, as compared 1/21 in the TVR group (p=0.08). The 30-day mortality rate was 28% lower in the TVR group compared to the control group (p=0.03) when assessed by Kaplan Meier curve. The event-free survival curve demonstrated a significant increase in survival in the TVR group (p=0.03). Conclusions Tricuspid valve regurgitation is a common finding at preoperative assessment for LVAD placement. If moderate to severe tricuspid valve regurgitation is observed, our experience suggests that concomitant TVR may reduce onset of acute RVF. [ figure 1 ]

Purpose As functionality improves for mechanical support, the ethical challenges are becoming more complex. In the case of assist devices, this clinical-ethical complexity can primarily be attributed to the increase in number of DT patients. One major clinical-ethical challenge for these devices involves patients’ and surrogates’ requests for deactivation of the device at a time clinicians feel is premature. Methods and Materials 4 patients underwent device implant for severe heart failure and eventually recovered but requested discontinuation of device support: 3 patients with LVADs and 1 with a Syncardia TAH. Surrogates made these requests on behalf of incapacitated patients in two cases, whereas awake, alert patients made the request in the other two cases. Results In our approach to these four patients, we addressed two main ethical and practical issues. The first is whether it is ethically permissible to deactivate the device. In consultation with our hospital’s ethics consultants, we concluded that, while there are ethically relevant distinctions between the two types of devices, it was ethically permissible to deactivate both types based on the ethical precept allowing informed refusal of life-sustaining therapies. The second is whether there are countervailing ethical considerations that suggest that it should not be performed in a given case (e.g., depression, surrogate motives, or inconsistencies in patient preferences). In consultation with ancillary services Psychiatry, Ethics, and Palliative Care, we determined there were none and all patients’ devices were deactivated. Conclusions Using the collaboration of various ancillary services, we ensured a compassionate and respectful implementation process. From these experiences, we learned preventive ethics strategies, including how and when to involve ancillary services pre-implantation for the purpose of elucidating goals, expectations, and preferences, managing the complexities associated with surrogate decision making, and facilitating advance care planning.