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Continuous-flow left ventricular assist device (CF-LVAD) support is a mainstay in the hemodynamic management of patients with end-stage heart failure refractory to optimal medical therapy. In this report we evaluated waitlist complications and competing outcomes for CF-LVAD patients compared with primary transplant candidates listed for orthotopic heart transplantation at a single center. All patients listed for orthotopic heart transplantation between 2006 and 2020 at our institution were retrospectively reviewed (CF-LVAD, 300; primary transplant, 244). Kaplan-Meier methodology with log-rank testing was used to evaluate survival outcomes. Terminal outcomes of death, delisting, and transplant were assessed as competing risks and compared between groups using Gray's test. Multivariable Fine-Gray regression was used to identify predictors of transplantation. One-year rates of transplant, delisting, and death were 48%, 8%, and 2%, respectively, for CF-LVAD patients and 45%, 15%, and 9%, respectively, for primary transplant (all P <.001). Waitlist mortality at 5 years was 4% among CF-LVAD patients and 13% for primary transplants. All-cause mortality after listing was lower for CF-LVAD patients (P =.017). There was no difference in posttransplant survival between groups (P =.250). On multivariable Fine-Gray regression stroke (P =.017), respiratory failure (P =.032), right ventricular failure (P =.019), and driveline infection (P =.050) were associated with decreased probability of transplantation. Posttransplant survival was not significantly worse for CF-LVAD patients who experienced device-related complications (P =.901). Although device-related complications were significantly associated with decreased rates of transplant, CF-LVAD patients had excellent waitlist outcomes overall. In light of the 2018 allocation score change the risk of complications should be taken into account when deciding whether to offer CF-LVAD as a bridge to transplant. [Display omitted] [ABSTRACT FROM AUTHOR]

Interleukin 1α (IL-1α) is capable of driving pro-inflammatory gene expression through both the initiation of transcription and by prolonging the half-life of short-lived mRNAs. Although the signaling events linking the IL-1 receptor to the activation of NFκB and the initiation of transcription have been well characterized, less is known about the signaling events linking to mRNA stabilization. As a model to study the control of mRNA stability we have used the mouse chemokine KC, expression of which requires both NFKB-driven transcription and stabilization of the constitutively unstable mRNA. We have evaluated the role of signaling adaptors known to play a role in IL-1α-driven NFαB activation in the generation of mRNA stability. Surprisingly, although TRAF6 is essential for NFκB activation, it is not required for IL-1α-induced mRNA stabilization. IRAK1, which is recognized to function upstream of TRAF6, is required for both mRNA stabilization and activation of NFB. Consistent with the previous findings, the TRAF6 interaction sites in IRAK1 are required for NFαB activation but do not play a role in mRNA stabilization. These findings indicate that signals from the IL-1 receptor segregate into at least two separate pathways at the level of IRAK1; one couples through TRAF6 to NFκB activation while a second utilizes a TRAF6-independent pathway that is responsible for mRNA stabilization. [ABSTRACT FROM AUTHOR]

The quality-adjusted life year (QALY) measures disease burden and treatment, combining overall survival and health-related quality of life (HRQOL). We estimated QALYs in 3 groups of older patients (60-80 years) with heart failure (HF) who underwent heart transplantation (HT, with pre-transplant mechanical circulatory support [HT MCS] or HT without pre-transplant MCS [HT Non-MCS]) or long-term MCS (destination therapy). We also identified factors associated with gains in QALYs through 24 months follow-up. Of 393 eligible patients enrolled (10/1/15-12/31/18) at 13 U.S. sites, 161 underwent HT (n = 68 HT MCS, n = 93 HT Non-MCS) and 144 underwent long-term MCS. Survival and HRQOL data were collected through 24 months. QALY health utilities were based on patient self-report of EQ-5D-3L dimensions. Mean-restricted QALYs were compared among groups using generalized linear models. For the entire cohort, mean age in years closest to surgery was 67 (standard deviation, SD: 4.7), 78% were male, and 83% were White. By 18 months post-surgery, sustained significant differences in adjusted average ± SD QALYs emerged across groups, with the HT Non-MCS group having the highest average QALYs (24-month window: HT Non-MCS = 22.58 ± 1.1, HT MCS = 19.53 ± 1.33, Long-term MCS = 19.49 ± 1.3, p = 0.003). At 24 months post-operatively, a lower gain in QALYs was associated with HT MCS, long-term MCS, a lower pre-operative LVEF, NYHA class III or IV before surgery, and an ischemic or other etiology of HF. Determination of QALYs may provide important information for policy makers and clinicians to consider regarding benefits of HT and long-term MCS as treatment options for older patients with HF. [ABSTRACT FROM AUTHOR]

Left ventricular (LV) dysfunction is the most common reason that potential donor hearts are not allocated. However, a significant proportion of brain-dead donors (BDDs) have transient LV dysfunction, and these allocated hearts have equivalent post-transplant outcomes. It is difficult to determine which potential donors with cardiac dysfunction on initial assessment are likely to recover. Stress-induced cardiomyopathy (SIC) patterns, specifically reverse takatsubo's- LV basal hypokinesis with apical hyperkinesis, are often observed in BDDs, however its association with donor LV recovery remains unclear. We retrospectively reviewed echocardiograms from our OPO's recovery center to determine if specific strain patterns predict functional recovery. All BDDs managed at a single OPO recovery center between 1/1/2015-6/1/2018 with reduced initial LV ejection fraction (LVEF) ≤ 40% were included. Initial echocardiograms were adjudicated for image quality, with donors with poor quality or inability to obtain longitudinal strain (LS) excluded. All echocardiograms were interpreted by a single reader, with segmental and global longitudinal strain (SLS and GLS) analysis conducted in apical views. Composite LV apical and basal SLS obtained in each view were used to quantify apical-to-basal strain ratio. LV recovery was defined as an LVEF ≥ 50% on a subsequent echocardiogram during the evaluation process. 54 donors were included in this analysis, 29 (54%) had LV recovery and 25 (46%) donors did not have LV recovery. Donors with LV recovery had higher initial LVEF and greater overall LVEF improvement, with greater average overall LV and RV GLS (Table 1). The LV recovery group also had higher average LV apical and basal LS. However, LV, RV, apical, and basal LS were not independently associated with LV recovery when normalized for initial LVEF. Among all donors, the LV apical-to-basal LS ratio was 2.11 ± 1.7. There was no difference in apical-to-basal strain ratio between LV recovery and no recovery groups. Reverse takatsubo's-type pattern with elevated apical-to-basal LS ratio was generally observed among all BDDs with LV dysfunction, however this ratio was not associated with LV recovery. Multiple echocardiographic measures were associated with recovery, including initial LVEF, LV GLS and SLS. However, strain does not appear to provide added predictive value for recovery when accounting for initial LVEF. Additional work, combining imaging and clinical data, is needed to better predict donor LV recovery and thus expand the cardiac donor pool. [ABSTRACT FROM AUTHOR]

Heart transplantation (HT) and mechanical circulatory support (MCS) as destination therapy (DT) are life-saving options for 60-80 year-old patients (pts) with advanced heart failure (HF). We compared pt health-related quality of life (HRQOL) before and 1 year (yr) after surgery in pts undergoing HT (with or without MCS) and DT MCS. Among 393 pts at 13 US sites awaiting HT (n=239; 118 awaiting HT with MCS, 121 awaiting HT without MCS; 66% transplanted) and DT MCS (n=154) between 10/1/15-12/31/18, we collected self-report data on: HRQOL (EQ-5D-3L Visual Analog Scale [VAS]: 0-100=worst to best) and (KCCQ-12: 0-100=lowest to highest), depressive symptoms (PHQ-8: 0-24=fewer to more) and anxiety (STAI-state: 20-80=lower to higher]). There were 337 pts at 1 year follow up. Statistical analyses included paired t-tests, chi-square tests, and baseline-adjusted linear regression models. The majority of pts were white and male. DT pts were older than HT pts (DT = 68.6±5.2 vs HT with MCS = 64.4±3.3 vs HT without MCS = 64.0±2.9 years, p<0.001) and had more co-morbidities (DT = 4.7±2.0 vs HT with MCS = 4.0±1.8 vs HT without MCS = 3.6±1.6, p<0.001). Baseline HRQOL scores were worse in DT MCS pts vs HT with MCS (p<0.001) and without MCS pts (p≤0.003). HRQOL improved in all 3 groups from before to 1 yr post-surgery (p<0.0001), but 1 yr HRQOL scores were lower in the DT MCS group than both HT groups (p≤0.003). Depressive symptoms and anxiety decreased over time in all 3 groups (p≤0.0025), but DT pt scores were worse than HT pt scores at 1 yr (p≤0.007) (Figure). HRQOL and mood improved in all 3 groups over time with better overall 1-yr scores observed in those undergoing HT. These unique findings may guide HRQOL-related therapeutic strategies. [ABSTRACT FROM AUTHOR]

Heart failure and obesity are two growing epidemics in the United States with significant overlap in patient populations. Morbid obesity is currently a relative contraindication to cardiac transplantation as previous data has shown decreased survival with extremes of body mass index (BMI). However, there is limited data that explores the relationship between BMI and adverse outcomes following left ventricular assist device (LVAD) implantation. This study aims to determine if there is an association between higher BMI and exchange-free survival at one year post LVAD implantation. This was a single-center, retrospective cohort study with patients who had undergone LVAD implantation at Barnes-Jewish Hospital between 2005 and 2018. Patients with age<18, BMI<18.5, or no available BMI information were excluded. Patients were divided into four groups: 18.5≤BMI<30 (BMI<30 group), 30≤BMI<35 (BMI 30-35 group), 35≤BMI<40 (BMI 35-40 group), and BMI≥ 40 group. Subjects were censored for heart transplant. The groups were compared for death or LVAD exchange using the log-rank test. We examined 734 patients who underwent LVAD implantation, including 574 HeartMate II devices (78%), 124 HeartWare HVAD devices (17%), and 36 HeartMate III devices (5%). Compared to BMI<30 group, higher BMI groups were more likely to be younger, female, black race, and have diabetes mellitus. Higher BMI groups also had more HVAD and HeartMate III models (57% and 33%, respectively, in BMI≥40 group). Cumulative exchange-free LVAD survival was worse for higher BMI categories (one year exchange free survival BMI <30 = 75%, BMI 30-35 = 69%, BMI 35-40 = 66%, BMI≥40 = 66%, p-value for trend 0.034) (Figure 1). In this cohort, higher BMI is associated with decreased exchange-free survival in LVAD patients. Further studies are needed to clarify impact of BMI on adverse clinical outcomes. [ABSTRACT FROM AUTHOR]

Caregiving for heart failure (HF) patients is burdensome. We examined differences in caregiver burden for 3 groups of older advanced HF patients: (1) supported with mechanical circulatory support (MCS) before heart transplantation (HT MCS), (2) awaiting transplant without MCS (HT non-MCS), and (3) prior to long-term MCS and factors associated with burden. From October 1, 2015 to December 31, 2018, we enrolled 276 caregivers for HF patients from 13 U.S. sites: 85 HT MCS, 96 HT non-MCS, and 95 prior to long-term MCS. At enrollment, caregivers completed the Oberst Caregiving Burden Scale (15 items, 2 subscales: time (range = 1-5; higher score = more time spent on task) and difficulty (range = 1-5; higher score = higher difficulty of task) and other measures. Statistical analyses included descriptive statistics, ANOVA, chi-square tests, and linear regression. Overall, caregivers were aged 60.8 ± 9.8 years and predominantly white, female, spouses, well educated, and reported ≥1 comorbidities. Caregivers overall reported a moderate amount of time spent on tasks and slight task difficulty. Caregivers for HT non-MCS candidates reported significantly less perceived time spent on tasks than caregivers for HT MCS candidates and caregivers for patients prior to long-term MCS (2.2 ± 0.74 vs 2.4 ± 0.74 vs 2.5 ± 0.71, respectively, p = 0.02) and less perceived difficulty of tasks (1.2 ± 0.33 vs 1.4 ± 0.53 vs 1.4 ± 0.54, respectively, p = 0.01). Caregiver and patient factors were associated with caregiver burden. Prior to HT and long-term MCS, caregiver burden was low to moderate. Caregiver factors were predominantly associated with caregiver burden. Understanding caregiver burden and factors affecting caregiver burden may enhance preoperative advanced therapies discussions and guide caregiver support. [ABSTRACT FROM AUTHOR]