CF-LVAD Implantation Research Articles

Predictors of long-term success after successful explantation of continuous flow left ventricular assist device support.

Predictors and evaluations of continuous flow left ventricular assist device (cf-LVAD) explantation in recovered patients remains under discussion due to lack of evidence on long-term safety and efficacy. This study summarized our experiences regarding cf-LVAD explantation in non-ischaemic dilated cardiomyopathy patients and estimated a predictor for sufficient myocardial recovery allowing LVAD explant. We retrospectively identified 135 adult patients with cf-LVAD therapy as bridge to heart transplant due to non-ischaemic dilated cardiomyopathy. Of those, 13 patients underwent device explantation (recovery group) after myocardial recovery. 12 (92%) of the explanted patients were evaluated using our weaning protocol, and underwent surgical explantation. Meanwhile, the remaining 122 continued with cf-LVAD therapy (non- recovery group). Multivariate logistic regression analysis revealed time interval between the first heart failure event and cf-LVAD implantation as an independent predictor for successful explantation. The optimal time interval cutoff value to predict cf-LVAD explantation was 7 months, with a sensitivity of 91.0% and specificity of 84.6%. Echocardiography in patients with successful cf-LVAD explantation showed significant improvement of left ventricular function and dimensions at six months postoperatively. The 13 explanted patients are currently alive at a median of 30 (IQR; 18-58) months after explantation. The survival rate free from rehospitalization due to heart failure following explantation was 100%. Left ventricular function and remodelling after explantation were also preserved. In non-ischaemic dilated cardiomyopathy patients with a short interval between the first heart failure event and cf-LVAD therapy, left ventricular myocardium may recover in an early phase after device implantation.

Abstract 19044: Upfront Right Ventricular Assist Device at the Time of Lvad Implantation Reduces Mortality, Stroke, and Major Bleeding Risk

Introduction: Right ventricular failure (RVF) is a major cause for increased morbidity and mortality after continuous-flow left ventricular assist device (cf-LVAD) implantation. Patients who are high-risk for developing RVF would benefit from early support via right ventricular assist devices (RVADs) to improve hemodynamics and reduce RVF associated complications. However, current RVF prediction models have limited predictive value. To reduce RVF complications, select institutions have implemented upfront RVAD use in those deemed high-risk with mixed results. In this study, we examined our institutional cohort of high-risk RVF patients who received either emergent or upfront RVADs during LVAD implantation and associated one-year outcomes. Hypothesis: Does providing temporary RVAD support upfront to high-risk patients during LVAD implantation impact associated complications and outcomes. Goals/Aims: To assess one-year clinical outcomes for high-risk patients receiving RVADs during LVAD implantation. Methods: We retrospectively reviewed patients who underwent placement of both LVAD and upfront RVAD at our institution between January 2015 and August 2022. Patients were stratified by the type of RVAD placed (percutaneous vs central) and timing of support (upfront vs emergent). Outcomes were assessed up to one-year post-LVAD implantation. Results/Data: Of the 50 patients reviewed, 36 (72%) underwent upfront RVAD implantations and 14 (28%) underwent emergent RVAD implantations. The upfront cohort consisted of 16 of the total 19 INTERMACS 1 patients, 15 of total 21 INTERMACS 2 patients, 4 of total 9 INTERMACS 3 patients, and 1 of 1 INTERMACS 4 patients. Compared to emergent RVADs, patients who received upfront RVAD had significantly decreased one-year mortality (17.1% vs 50.0%, p=0.031), decreased cerebrovascular accidents (2.8% vs 28.6%, p=0.018), and decreased major bleeding (0% vs 40%, p=0.005). There was no significant difference in the length of stay, arrhythmias, gastrointestinal bleed, hemodialysis requirement, driveline infections or vasoplegia. Conclusion: Patients receiving upfront RVAD at the time of cf-LVAD implantation have improved survival and decreased incidence of cerebrovascular accidents.

Association of Nutritional Risk Index With Continuous Flow Left Ventricular Assist Device Complications

Studies revealing the relationship between major surgery outcomes and nutritional parameters are increasing daily. Publications demonstrating the relationship between early postoperative success and surgical complications in patients with chronic heart failure and continuous flow left ventricular assist device (cf-LVAD) are limited. The vast majority of patients with advanced chronic heart failure are cachexic, and the reason for this is multifactorial. The aim of this study is to investigate the link between the modified nutritional risk index (NRI) and 6-month survival and complication rates in patients with a cf-LVAD. This study included statistical analysis of NRI and postoperative parameters of 456 patients with advanced heart failure who had cf-LVAD implantation between 2010 and 2020. The results of this study showed a statistically significant difference between mean NRI values and postoperative parameters such as 6-month survival (P=.001), right ventricular failure (P=.003), infection (P=.001), driveline infection (P=.000), and sepsis (P=.000). This study revealed that 6-month postoperative complications and mortality rates of patients with advanced heart failure in patients with cf-LVAD are closely related to malnutrition status. In these patients, nutrition specialist use would be beneficial both preoperatively and postoperatively to increase surveillance and reduce postoperative complications.

RENAL10: Urinary Vitamin D Binding Protein and Kidney Injury Molecule-1 May Predict the Risk of Acute Kidney Injury in Heart Failure Patients Undergoing CF-LVAD Implantation

Background: Renal dysfunction in advanced heart failure (HF) and durable mechanical circulatory support (MCS) is common and harmful, yet current tests are inaccurate and confounded by body composition, fluid status, and other factors. Newer biomarkers more directly reflecting specific aspects of renal health/function have been tested in other fields but have yet to be tested in this complex setting. Urine vitamin-D-binding protein (uVDBP) and urine kidney injury molecule-1 (uKIM-1) have been shown to identify and stage severity of parenchymal kidney injury in several settings. The purpose of our study is to explore the potential role of uVDBP and uKIM-1 as biomarkers of acute renal damage among HF patients receiving CF-LVAD support. Methods: Our cohort included 29 HF patients undergoing CF-LVAD implantation. Early morning voided urine was collected immediately pre-implantation. Measurements of uVDBP and uKIM-1 were performed with ELISA kits and data were normalized to urine creatinine (ng/mg Cr.). Relationships of uVDBP and uKIM-1 and important baseline clinical characteristics (presence of kidney dysfunction, defined as eGFR<60 ml/min/1.73m2, and hemodynamic instability, defined as INTERMACS 1/2) were assessed using the Wilcoxon test. Relationships of baseline uVDBP and uKIM-1 (log2 transformed) with risk of acute kidney Injury (AKI) developing within 90 days after CF-LVAD implant were assessed, using logistic regression with adjustment for baseline kidney function and for baseline hemodynamic stability. AKI was assessed using RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Results: The cohort (n=29), had mean (SD) age 58 (14) years, 17.2% were female, and destination therapy goal for 96.6%. Baseline kidney dysfunction and hemodynamic instability were present in 37.9% and 44.8% of patients respectively, and 44.8% had AKI within 90 days. Baseline uVDBP [median (IQR)] was 0.88 (0.20-2.3) ng/mg Cr., and baseline uKIM-1 [median (IQR)] was 0.013 (0.0032-0.042) ng/mg Cr. Baseline uVDBP was found to be significantly associated with baseline kidney risk category (p <0.001), with higher uVDBP associated with worse baseline kidney health/function risk (assessed by combination of baseline low kidney function and hemodynamic instability, Fig.1A). Baseline uKIM-1 was significantly associated with baseline kidney function but not with baseline kidney risk category (Fig.1B). Two-fold higher baseline uKIM-1 was associated with nearly two-fold increased odds of 90-day AKI (Table.1). Similar results were obtained for baseline uVDBP. Conclusions: We have demonstrated that both uVDBP and uKIM-1 may provide additional information about baseline kidney health beyond that provided by serum creatinine-based and hemodynamic instability-based measures, assessed by risk for adverse 90-day kidney outcomes. Further study in larger cohorts is needed. Table 1. - Association of baseline urine markers with post-implant AKI Odds ratios (95% confidence intervals) Unadjusted Model 1 Model 2 uKIM-1 Per two-fold greater uKIM-1 1.98 (1.28-3.71) 4.39 (1.79-22.2) 8.76 (2.03-311) uVDBP Per two-fold greater uVDBP 1.99 (1.27-3.68) 2.25 (1.23-4.90) 7.74 (2.07-296) Model 1 was adjusted for baseline kidney dysfunction;Model 2 was adjusted for baseline kidney dysfunction and baseline hemodynamic instability

Acquired blood platelet disorder in patients with end-stage heart failure after implantation of a continuous centrifugal-flow left ventricular assist device: A prospective cohort study

BackgroundContinuous-flow left ventricular assist devices (CF-LVADs) are an established therapy for advanced heart failure. Thrombosis and hemorrhage are common complications after CF-LVAD implantation, which may be explained by device-induced platelet activation. Few data on the effect of CF-LVAD implantation on platelets are available to date. ObjectivesThe aim of this study was to characterize the change in the platelet activation status after CF-LVAD. MethodsPlatelet phenotype and reactivity were determined with flow cytometry in 32 adults with end-stage heart failure before and 4 to 6 weeks after CF-LVAD implantation. Sixteen adults with a biological aortic valve prosthesis (AVP) using the same antiplatelet regimen were included to discriminate between the effects of CF-LVAD and the antiplatelet regimen. Plasma markers for platelet activation were determined with enzyme-linked immunosorbent assay. ResultsMedian (IQR) plasma levels of soluble P-selectin increased from 115.6 (79.1-142.7) ng/mL to 144.5 (100.4-197.5) ng/mL after CF-LVAD implantation (P < .001). Median (IQR) β-thromboglobulin levels were 60.5 (37.8-81.5) ng/mL before implantation and remained high after LVAD implantation [60.0 (42.0-69.5) ng/mL]. The platelet P-selectin expression after stimulation with ADP (30 and 60 μM) or PAR1-activating peptide (12.5 and 25 μM) was reduced by 17% to 21%, and fibrinogen binding was reduced by 37% to 86%. Platelet responses to agonists were similar in patients with a CF-LVAD and patients with an AVP, except for fibrinogen binding in response to 12.5 μM PAR1-AP, which was lower in patients with a CF-LVAD (P < .001). ConclusionsCombined, these data provide evidence for systemic platelet activation and an acquired platelet disorder after CF-LVAD implantation. This might contribute to the risk of both hemorrhage and thrombosis associated with CF-LVADs.

Surgical Interventions for Late Aortic Valve Regurgitation Associated with Continuous Flow-Left Ventricular Assist Device Therapy: Experience Gained and Lessons Learned.

This study aimed to investigate the outcomes of surgical interventions for symptomatic moderate-to-severe aortic regurgitation (AR), including aortic valve replacement (AVR) and repair (AVP), in 184 patients who underwent continuous flow-left ventricular assist device (Cf-LVAD) implantation as a bridge-to-transplant (BTT) between November 2007 and April 2020. Ten patients (median age, 34 (25-41) years; 60% men) underwent surgical interventions (AVR, n = 6; AVP, n = 4) late after cf-LVAD implantation. The median duration after the device implantation was 34 (24-44) months. Three patients required additional tricuspid valve repair. Aortic valve suturing resulted in severe recurrent AR 6 months postoperatively, due to leaflet cutting in one patient. Seven patients with AVR survived without regurgitation during the study period, except for one non-survivor complicated by liver failure due to postoperative right heart failure. Therefore, six patients after AVP (n = 4) and AVR (n = 2) underwent successful heart transplantation 7 (4-13) months after aortic intervention. Kaplan-Meier analysis showed no significant difference in overall survival through 5 years after cf-LVAD implantation, regardless of the surgical AV intervention chosen (log-rank test, p = 0.86). In conclusion, surgical interventions (AVR or AVP) for patients with an ongoing cf-LVAD are safe, effective, and viable options.

Left Ventricular Assist Device Implantation in Cancer-Therapy-Related Heart Failure.

Objectives: Cancer-therapy-related heart failure (CTrHF) due to cardiotoxic drugs or radiation is a growing cause of end-stage heart failure. Limited knowledge is available concerning the use of continuous-flow left-ventricular-assist devices (cfLVAD) in this setting. Methods: The files of all 1334 patients who underwent cfLVAD implantation between December 2008 and December 2020 were screened for the cause of heart failure. All patients with CTrHF were included in the analysis. Results: A total of 32 patients with a median age of 58 years (IQR: 46–65) were included in the study; 15 (47%) were male. The median time from the first diagnosis of heart failure (HF) to cfLVAD implantation was 6 months (IQR 2–24), and from cancer treatment to cfLVAD implantation 40 months (IQR 5–144). Malignancies comprised non-Hodgkin lymphoma (n = 12, 37%), breast cancer (n = 9, 28%), sarcoma (n = 5, 16%), leukemia (n = 5, 16%), and others (n = 1, 3%). In 24 patients, chemotherapy included anthracyclines (others n = 2, unknown n = 6). Chest radiation was performed in 13 patients (39%). Moreover, 71% were classified as INTERMACS profile 1 or 2. The 30-day survival rate after LVAD implantation was 88%. Rethoracotomy was necessary in nine (29%), and a temporary right ventricular assist device in seven (21%) patients. The median survival was 29 months. There was no significant difference in survival or right HF between patients with CTrHF and a matched control group. Conclusions: CfLVAD implantation is feasible in high-risk patients with CTrHF with or without prior chest radiation.

CARD1: Impairment of Mitochondrial Oxidative Phosphorylation in Heart Failure Patients with History of Ischemic Stroke undergoing CF-LVAD Implantation

Study: Abnormalities in systemic immune cell mitochondrial oxidative phosphorylation (OxPhos) found to be linked with ischemic stroke and post-stroke brain injury. It was unclear if prior ischemic stroke in patients undergoing continuous-flow left ventricular assist device(CF-LVAD) implantation were associated with OxPhos abnormalities which subsequently can be used to predict the increased risk of post-CF-LVAD stroke. In this study we investigated if prior ischemic stroke in patients receiving CF-LVAD had systemic OxPhos abnormalities compared to non-stroke patients and if OxPhos abnormalities was impaired more in stroke patients post-CF-LVAD implantation. Methods: During June 2020-January 2022, we performed 77 CF-LVAD implants and 32 patients signed informed consent to volunteer for this prospective study. Out of 32 patients, 20 had prior stroke(ST group) 30 days before CFLVAD implantation and 12 had no prior stroke(No-ST group). Blood samples were collected within 7 days pre-CFLVAD and on the day 7th post-CF-LVAD. OxPhos was measured via immunoblot of peripheral blood mononuclear cells(PBMCs) using a total OxPhos Complex kit, which quantifies 5 complex subunit proteins of mitochondria (C.I-C.V) after normalizing to porin. The data were displayed with violin plot distribution. Results and Conclusions: At baseline(Pre-CF-LVAD), the ST group had reduced (p<0.01) C.I, C.II and C.V expression in PBMCs when compared to the No-ST group (Fig.A,B,E). While the pre-CF-LVAD differences in C.III (p=0.07) and C.IV (p=0.21) were not significant between the two groups, there was more than 20% diminished expressions observed in the ST group (Fig.C,D). Our study found for the first time the existence of mitochondrial alterations at the peripheral level in the HF patients with prior ischemic stroke even before CF-LVAD implantation. The Post-CF-LVAD reduction in all 5 OxPhos markers were found to be significant in the ST group compared to the No-ST group. In ST group, severe reduction of OxPhos proteins were noticed at post-CF-LVAD compared to their corresponding pre-CFLVAD values, while in No-ST group these proteins were comparable between pre-and post-CF-LVAD values. During the post-CF-LVAD hospitalization period (median 29 days), there were no patients in the No-ST group developed post-CF-LVAD stroke while 3 patients in the ST group (3/20;15%) developed stroke at 7, 13 and 16 days after implantation. In the ST group, the percentage change in OxPhos proteins from pre-CF-LVAD to post-CF-LVAD ([(Pre–Post)/Post]x100) indicated 41% and 37% more decrease in C.II and C.III proteins respectively in those patients who developed new post-CF-LVAD stroke compared to non new stroke patients (p<0.05). This finding demonstrated that, the severe reduction of OxPhos appeared to be associated with the new onset of stroke after CF-LVAD implantation. The changes in OxPhos protein expression in the ST group may have a potential diagnostic role in predicting post-CF-LVAD strokes.

Risk of Infection, Endoplasmic Reticular Stress and Systemic Activation of NLRP3 Inflammasome in Patients Supported by Continuous Flow Left Ventricular Assist Devices

<h3>Purpose</h3> We investigated changes in stress-associated endoplasmic reticulum (ER) protein 1 (SERP1), ER-stress response proteins and inflammasome activation in heart failure (HF) patients before and after CF-LVAD implantation, and relationship to subsequent infection within 3 months. <h3>Methods</h3> We analyzed blood samples from 24 CF-LVAD patients (pre- and 1week post-VAD) and 10 non-HF controls. Culture positive Infections was confirmed (median 42 days post-VAD) from bloodstream, GI, respiratory tracts, or driveline. SARP1, ER-stress proteins (ATF-6, GRP78) and NLRP3 inflammasome (NLRP3, ASC, Caspase1) in peripheral blood mononuclear cells (PBMC) were assessed. <h3>Results</h3> HF patients had significantly (p<0.05) elevated baseline (pre-VAD) PBMC protein levels of ATF6 (0.41±0.05 vs. 0.54±0.11), GRP78 (0.20±0.07 vs. 0.33±0.18), NLRP3 (0.28±0.17 vs. 0.78±0.28), and ASC (0.27±0.13 vs. 0.44±0.15) compared to controls. Among CF-LVAD recipients, SERP1 declined in those without subsequent infection (Group1) but significantly increased in those with infection (Group2) (<i>Fig.A,B</i>). Baseline ATF6 and GRP78 differed between Group1 and 2 (<i>Fig.C,D</i>). In Group2, the post-VAD ATF6, GRP78, NLRP3 and ASC were significantly elevated compared to pre-VAD; while in group1, only the post-VAD GRP78 was significantly elevated (<i>Fig.C-G</i>). Post-VAD caspase1 increased but not-significant (0.36±0.07 vs. 0.43±1.2) in group2 compared to pre-VAD (<i>Fig.H</i>). Baseline SERP1 and NLRP3 among patients who developed infection were positively correlated with ATF6 and GRP78 (<i>Fig.I-L</i>). <h3>Conclusion</h3> Post-VAD upregulation of SERP1 may be associated with ER-stress response, which in turn may activate NLRP3 inflammasome and predispose to early infection. Post-VAD decrease in SERP1 in group1 may protect against ER stress and NLRP3 activation. Further investigation of the role of SERP1 in ER-stress and inflammasome activation in CF-LVAD recipients is needed.

Quality of life metrics in LVAD patients after hemocompatibility-related adverse events.

Hemocompatibility-related adverse events (HRAE) negatively influence survival. However, no study has examined the impact of these events on health-related quality of life (HRQOL) and functional outcomes following continuous-flow left ventricular assist device implantation (CF-LVAD). We assessed the impact of HRAE events on HRQOL and hypothesized that HRAE's adversely impact HRQOL and functional outcomes. INTERMACS database identified patients undergoing primary CF-LVAD implantation from 2008 to 2017. HRAEs included stroke, non-surgical bleeding, hemolysis, and pump thrombosis and were identified as defined in the literature. HRAEs were further stratified as Tier 1-2 and disabling stroke events. Time-series analysis was executed for HRAE patients with values pre-HRAE, post-HRAE, and closest to 12 months follow up. Local polynomial regression curves modeling individual patients were superimposed into "spaghetti" plots. All HRQOL and functional metrics improved in patients over time, despite HRAE complications. However, these patient metrics were significantly reduced compared to the non-HRAE cohort. Advanced data visualization techniques noted a decline after experiencing an HRAE with a subsequent recovery to baseline levels or higher. Six-minute walk test (6MWT) was noted to be most affected in the post-HRAE period but recovered similar to other metrics. The burden of HRAE following CF-LVAD implantation did not negatively impact the quality of life. However, the 6MWT did not increase in the post-HRAE period in all HRAE patients. Improvement of heart failure symptoms after CF-LVAD coupled with optimal management following the HRAE act to preserve the enhanced quality of life.

Incidence of Blood Stream Infection and Impact on Survival in Patients on Left Ventricular Assist Device Support

<h3>Purpose</h3> Bloodstream infection (BSI) is a severe complication in patients with continuous flow left ventricular assist devices (CF-LVADs). In this study, we aimed to describe the incidence of BSI on contemporary LVAD support and its impact on subsequent survival. <h3>Methods</h3> This analysis included adult patients with first time CF LVAD implantation at a single center (June 2005-June 2020). BSI was defined as ≥1 positive blood culture with a likely pathogen (e.g. Staphylococcus aureus) or >1 positive blood culture with a low virulence skin organism (e.g. Staphylococcus epidermidis). Time to BSI was recorded for each patient. Survival-free of BSI was estimated using Kaplan-Meier method and compared among device types. Survival among patients who did and did not develop BSI by 9 months post implant was compared using Cox regression adjusting for medical and social factors. <h3>Results</h3> 502 patients were included in the analysis. Over a median follow up period of 1,468 days (IQR 454-3,081 days), 73 (14.5%) developed a BSI. Patients who developed BSI were more likely to have diabetes, implanted cardiac defibrillators, and to have a designation of destination therapy. Median time to BSI was 389 days (IQR 94-997). The most common organisms were enterococci (23%) and streptococci (23%). At the time of BSI, 53% of patients had a WBC count above 11 × 10⁹/L. Compared to the HeartMate 2, patients implanted with the HeartMate 3 had a lower rate of 1-year survival free of BSI (87% vs. 95 %, p=0.007). When comparing survival after 9 months among those with and without BSI, mortality was significantly higher in patients with BSI in both unadjusted (HR =1.96, 95% CI; 1.02 - 3.76) and adjusted models (2.00, 95% CI; 1.03 - 3.88). <h3>Conclusion</h3> BSI continues to occur in the contemporary era of LVAD therapy and is associated with significantly worse survival. The absence of elevated WBC count in LVAD patients with severe infections such as bacteremia raises the question of whether leukocytosis should be infection criteria for UNOS status increase.

Pulmonary Capillary Recruitment Is Attenuated Post Left Ventricular Assist Device Implantation

Intoduction There is limited knowledge of pulmonary physiology and pulmonary function following continuous flow-left ventricular assist device (CF-LVAD) implantation. Therefore, the present study investigated if CF-LVAD influenced the pulmonary circulation by assessing pulmonary capillary blood volume and alveolar- capillary conductance as well as pulmonary function in heart failure patients. Methods 17 patients with severe HF who were scheduled for CF-LVAD (Heart Mate II® or Heart Ware®) implantation participated in the study. They underwent pulmonary function testing (measures of lung volumes and flow rates) and more unique measures of pulmonary physiology using a rebreathe-technique that quantified the diffusing capacity of the lungs for carbon monoxide and nitric oxide (DLCO and DLNO, respectively) pre and 3 months post CF-LVAD implantation. Results After CF-LVAD, pulmonary function was not significantly changed (p>0.05). For lung diffusing capacity, DLCO was significantly reduced (p=0.04), however, alveolar volume (VA) was not changed (p=0.47). After DLCO was corrected by VA, DLCO/VA demonstrated a trend towards reduction (p=0.08). For the alveolar-capillary component, capillary blood volume (Vc) and alveolar membrane conductance (Dm) were significantly or trended towards a reduction (p<0.04, p=0.06, respectively). However, Dm/Vc was not altered (p=0.92). Conclusions Early post CF LVAD implantation, Vc is reduced likely as a result of pulmonary capillary de-recruitment which contributes to the fall in lung diffusing capacity. There is limited knowledge of pulmonary physiology and pulmonary function following continuous flow-left ventricular assist device (CF-LVAD) implantation. Therefore, the present study investigated if CF-LVAD influenced the pulmonary circulation by assessing pulmonary capillary blood volume and alveolar- capillary conductance as well as pulmonary function in heart failure patients. 17 patients with severe HF who were scheduled for CF-LVAD (Heart Mate II® or Heart Ware®) implantation participated in the study. They underwent pulmonary function testing (measures of lung volumes and flow rates) and more unique measures of pulmonary physiology using a rebreathe-technique that quantified the diffusing capacity of the lungs for carbon monoxide and nitric oxide (DLCO and DLNO, respectively) pre and 3 months post CF-LVAD implantation. After CF-LVAD, pulmonary function was not significantly changed (p>0.05). For lung diffusing capacity, DLCO was significantly reduced (p=0.04), however, alveolar volume (VA) was not changed (p=0.47). After DLCO was corrected by VA, DLCO/VA demonstrated a trend towards reduction (p=0.08). For the alveolar-capillary component, capillary blood volume (Vc) and alveolar membrane conductance (Dm) were significantly or trended towards a reduction (p<0.04, p=0.06, respectively). However, Dm/Vc was not altered (p=0.92). Early post CF LVAD implantation, Vc is reduced likely as a result of pulmonary capillary de-recruitment which contributes to the fall in lung diffusing capacity.

Association Between Center Level Characteristics And 1-Month Post-LVAD Implant Risk Standardized Mortality Rates

<h3>Background</h3> As more durable continuous flow (CF) left ventricular assist device (LVAD) are implanted, the number of implanting centers has increased. Whether center level characteristics influence post-implantation outcomes is not fully defined. Therefore, we sought to determine center level characteristics associated with risk standardized mortality rates (RSMR) at 1-month post-implant. <h3>Methods</h3> Data from 167 centers that implanted CF-LVADs in 19,503 patients between 2008-2017 in the INTERMACS were analyzed. The 1-month post-implantation center RSMR was generated with a multivariable logistic regression model adjusting for 50 patient-level characteristics at implantation for all LVAD treatment strategies. Data from patients who were transplanted within 1-month or who had ≥5 missing variables were excluded. RSMR estimates underwent Bayesian correction to account for the influence of unbalanced inter-center CF LVAD volumes. Center-level characteristics were compared by the Cochran-Armitage trend or Chi-square tests across tertiles of the 1-month RSMR where appropriate. <h3>Results</h3> The overall median [25-75^th quartile] 1-month RSMR was 4% (1-6%). Median 1-month RSMR by center tertiles was 0% (0-1%), 4% (3-4%), and 7% (6-9%) respectively. Both greater annual and greater cumulative center LVAD volume were associated with lower 1-month RSMR (P <0.04 for both, figure A-B). Higher annual destination therapy CF-LVAD implantation volume (P=0.03), but not bridge-to-transplant CF-LVAD implantation volume (P=0.14) was associated with a lower 1-month RSMR. An implanting center's percentage of destination therapy or bridge-to-transplant strategy CF-LVAD devices implanted was also not associated with 1-month RSMR (Figure C-F). Higher rates of a concomitant mitral valve repair, a sternal implant approach, and intraoperative ECMO or IABP removal were each associated with a lower 1-month RSMR (P<0.05 for all). Less cardiopulmonary bypass time (P<0.01), but not total surgical time (P=0.43) was associated with a lower 1-month RSMR. Lastly, there was no association with the percentage of patients with INTERMACs profile 1 and 1-month RSMR (P=0.80). <h3>Conclusions</h3> When controlling for patient-level characteristics, higher LVAD implantation volumes, higher absolute rates of DT LVAD volumes, and certain patient-management strategies by center were associated with lower 1-month RSMR. These data identify potential patterns of care by center that may influence short-term post-LVAD outcomes.

Surgical left atrial appendage occlusion in patients with left ventricular assist device.

Thromboembolic (TE) events are among the most common and devastating adverse events in patients with continuous-flow left ventricular assist device (cf-LVAD). Given the high burden of AF among cf-LVAD patients, we sought to evaluate the effect of concomitant surgical LAAO in patients receiving cf-LVAD. A systematic search using electronic databases was performed using the keywords: "left atrial appendage occlusion" and "left ventricular assist device." Statistical analysis was performed using metapackage for R version 4.0 and Rstudio version 1.2. Mantel-Haenszel risk ratio (RR) random-effects model was used to summarize data between two groups. The primary outcomes included: (a) stroke; (b) LVAD pump thrombosis; (c) all-cause mortality RESULTS: Three studies with a total of 305 patients (LAAO=68 and No-LAAO=237) were included in the analysis. HeartMate II (39%) and Heartware (27.5%) were the two most common cf-LVADs utilized, while only 5% received HeartMate III. At a mean follow up of 1.47 years, LAAO group had a lower risk of stroke (8.8%vs. 15.2%, RR 0.64; 95% CI 0.28-1.49), LVAD pump thrombosis (1.5%vs. 3.8%, RR 0.28; 95% CI 0.05-1.55) and all-cause mortality (5.9%vs. 20.2%, RR 0.69; 95% CI 0.19-2.52) when compared with no-LAAO group, but the difference did not reach statistical significance. Concomitant surgical LAAO at the time of cf-LVAD implantation demonstrated a trend toward positive outcomes and was not associated with adverse outcomes during the follow-up period, though the results were not statistically significant.

A multi-institutional retrospective analysis on impact of RV acute mechanical support timing after LVAD implantation on 1-year mortality and predictors of RV acute mechanical support weaning

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. 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. 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. 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.

Association of bleeding with serotonergic antidepressants in patients receiving left ventricular assist device support.

This study sought to determine whether SA use is associated with bleeding in patients receiving CF-LVAD support. A retrospective cohort analysis was conducted of all adult patients who received CF-LVAD implantation at our institution. Barnes-Jewish Hospital between July 1, 2009, and October 1, 2018. Patients at least 18 years of age who received a HVAD™ (HeartWare Corp.), HeartMate II™ (St. Jude Medical), or HeartMate 3™ (St. Jude Medical) CF-LVAD and survived for at least 30 days postoperatively were included. Patients who received SAs (n=203) were compared to those who did not (n=391) from 30days to 18months following implantation. The primary outcome was the incidence of first bleeding events including gastrointestinal bleed (GIB), epistaxis, or intracerebral hemorrhage (ICH). During follow-up, 219 patients had bleeding events: 93 of 203 (45.8%) in the SA group versus 126 of 391 (32.2%) in the control group (p=0.001). After adjustment for age, angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) use, history of bleeding events, history of smoking, and CF-LVAD type, SA use remained associated with bleeding (adjusted odds ratio: 1.75, 95% confidence interval: 1.22-2.51, p=0.002). HeartMate 3™ patients experienced less bleeding than HeartMate II™ patients (adjusted odds ratio 0.46, 95% confidence interval: 0.23-0.90, p=0.024). In this single-center, retrospective cohort of patients supported with CF-LVADs, SA use was associated with the incidence of first bleeding events, primarily driven by GIB. Further studies are needed to assess any differential risk of bleeding among SA agents and to assess the utility of altering antithrombotic strategies.

Third generation continuous flow left ventricular assist devices; a comparative outcome analysis by device type

Abstract Background Continuous-flow left ventricular assist devices (CF-LVADs) have become a standard of care in end-stage heart failure (HF). Device-related complications remain high. Limited data exists comparing outcomes of the HeartMate 3 (HM3) and the HeartWare HVAD (HW). We aimed to analyze HM3 and HW devices implanted over the past 10 years with a focus on long-term clinical outcomes of respective patients. Methods Investigator-initiated comparative, retrospective observational analysis of all patients who underwent primary implantation of a centrifugal CF-LVAD at our tertiary care academic center between January 2010 and December 2020. Data derived from a prospective registry, and included all patients receiving a HM3 or HW device. Primary endpoint was overall (all-cause) mortality and heart transplantation. Secondary endpoints included device-related major adverse cardiac and cerebrovascular events (MACCE), as well right heart failure (RHF), gastrointestinal (GI) bleeding, driveline infections, and surgical re-interventions. Results Out of 106 primary CF-LVAD implantations, 36 (34%) received HM3 and 70 (66%) received HW. Median follow-up time was 1.48 years [interquartile range 0.67, 2.41] and did not differ between devices (p=0.739). HM3 was more often implanted in men (91.7% vs. 72.9%, p=0.024), patients were older (median 61 years [54, 66.5] vs. 52.5 years [43, 60], p&amp;lt;0.001), had a higher body mass index (BMI) (median 26.7 kg/m2 [23.4, 29.0] vs. 24.3 kg/m2 [20.7, 27.4], p=0.013), had more comorbidities and were more likely targeted for destination therapy (DT) (36.1% vs. 14.3%, p=0.010). Death occurred in 33.3% of HM3 patients, compared to 22.9% of HW patients, p=0.247 (probability of survival at 2 years 54.7% vs. 74.1%, p=0.296). After adjustment for confounders, we observed a significant 6-fold risk increase in device malfunctions for HW (hazard ratio (HR) 6.49, 95% CI [1.89, 22.32], p=0.003), but no significant differences between devices in pump thrombosis (p=0.173) or overall survival (p=0.801). Conclusions Comparing long-term outcomes between HeartMate 3 and HeartWare HVAD for LVAD support from a prospective registry, HeartWare HVAD patients had a significantly higher risk of device malfunctions. No significant differences were evident between devices in overall survival, and in respect to most clinical outcomes. Funding Acknowledgement Type of funding sources: None. KM Plot primary and secondary outcomesRisk analysis on all outcomes

Prevalence and management of driveline infections in mechanical circulatory support - a single center analysis

BackgroundDriveline infections in continuous-flow left ventricular assist devices (cf-LVAD) remain the most common adverse event. This single-center retrospective study investigated the risk factors, prevalence and management of driveline infections.MethodsPatients treated after cf-LVAD implantation from December 2014 to January 2020 were enrolled. Baseline data were collected and potential risk factors were elaborated. The multi-modal treatment was based on antibiotic therapy, daily wound care, surgical driveline reposition, and heart transplantation. Time of infection development, freedom of reinfection, freedom of heart transplantation, and death in the follow-up time were investigated.ResultsOf 75 observed patients, 26 (34.7%) developed a driveline infection. The mean time from implantation to infection diagnosis was 463 (±399; range, 35–1400) days. The most common pathogen was Staphylococcus aureus (n = 15, 60%). First-line therapy was based on antibiotics, with a primary success rate of 27%. The majority of patients (n = 19; 73.1%) were treated with surgical reposition after initial antibiotic therapy. During the follow-up time of 569 (±506; range 32–2093) days, the reinfection freedom after surgical transposition was 57.9%. Heart transplantation was performed in eight patients due to resistant infection. The overall mortality for driveline infection was 11.5%.ConclusionsDriveline infections are frequent in patients with implanted cf-LVAD, and treatment does not efficiently avoid reinfection, leading to moderate mortality rates. Only about a quarter of the infected patients were cured with antibiotics alone. Surgical driveline reposition is a reasonable treatment option and does not preclude subsequent heart transplantation due to limited reinfection freedom.

B-AB23-05 OUTCOMES AND COMPLICATIONS OF CARDIAC RESYNCHRONIZATION THERAPY IN PATIENTS WITH CONTINUOUS-FLOW LEFT VENTRICULAR ASSIST DEVICES

The effect of CRT on clinical outcomes and complications in patients with CF-LVAD is currently not well understood. To evaluate the outcomes and complications of CRT in patients with Continuous-Flow LVAD. We conducted a single-center retrospective analysis of a cohort of 478 subjects who underwent CF-LVAD implantation at the University of Rochester, Rochester, NY between May 2008 and January 2020. The study cohort was divided into three groups: no ICD, ICD only, and ICD+CRT (at LVAD implantation). The endpoints were all-cause mortality, and device complications. There were 166 of 478 (35%) LVAD patients implanted with a CRT, 191 implanted with ICD only (40%), and 121 (25%) had no ICD before LVAD implantation. During the mean follow-up of 2.7 years, there was no significant difference in the cumulative probability of all-cause mortality in patients with CRT, ICD-only, or no device (Figure, log-rank p=0.439). In the multivariate model there was no significant difference in death in patients with CRT vs. no device (HR= 1.18, 95% CI: 0.80-1.75, p=0.40), or in patients with an ICD vs. no device (HR=1.17, 95%CI: 0.79-1.74, p=0.44). In the CRT group, 31 (22%) of the 141 patients had device-related complications, 4 patients (12.5%) had device infection, 4 (12.5%) had lead infection, 15 (47%) had lead dislodgment or high threshold, and 9 (28%) had other complications. In CF-LVAD patients, CRT was not associated with improved survival. Device-related complications were frequently observed in patients with CRT. Further studies are warranted to investigate the risk-benefit ratio of an implanted CRT in patients with CF-LVADs.

Serotonergic antidepressants and hospitalization for bleeding in patients supported with a continuous flow left ventricular assist device

Continuous flow left ventricular assist devices (CF -LVAD) improve survival in patients with advanced heart failure, but confer risk of bleeding complications. Serotonergic antidepressants (SA) are commonly used in heart failure patients receiving LVADs, but their inhibitory effect on platelet function may contribute to bleeding risk. We performed a retrospective analysis of LVAD patients at our institution from 2016 -2019 comparing patients treated with SA after LVAD to those without SA. Demographic and clinical variables related to bleeding were collected on discharge from index hospitalization for CF-LVAD implantation and on admission for any bleeding event. The primary endpoint was incidence of bleeding requiring hospitalization after discharge. Secondary endpoints included overall number of admissions for bleeding, time to first hospitalization for a bleeding event, and incidence rate of hospitalizations for bleeding per patient year. 100 patients met inclusion criteria for the study. A total of 5 patients without a history of SA use and 31 patients who were prescribed SA after CF -LVAD implant were readmitted for a bleeding event after initial implant hospitalization (15% vs 46%, p=0.004). Bleeding rate per person year (0.3 vs 0.61, p=0.01) were significantly less in patients without SA use. Age-adjusted multivariable analysis found SA use to be associated with a hospitalization for bleeding (HR 2.3, 95% CI 0.99 -5.4). The higher incidence of hospitalization for bleeding was driven by non-gastrointestinal anatomical sites (6% vs 28%, p=0.02) with a HR 7.7 (95% CI 0.96 -62). SA treatment after CF-LVAD implantation was associated with an increased risk for bleeding complications requiring hospitalization, particularly non-gastrointestinal bleeding.