LVAD Group Research Articles

Pre-operative pulmonary artery pulsatility index does not predict mortality post-cardiac transplantation.

The pulmonary artery pulsatility index (PAPi) is a novel haemodynamic marker that has previously been shown to predict right ventricular dysfunction and mortality in patients with pulmonary hypertension and advanced heart failure. Utility of the PAPi in predicting outcomes post-cardiac transplantation is unknown. The aim of this study was to compare the prognostic significance of PAPi against pulmonary vascular resistance (PVR) for the predication of morbidity and all-cause mortality post-transplantation. All patients who underwent cardiac transplantation over a 6year period were studied. Pre-operative right heart catheter data was obtained. The PAPi was calculated as follows: (systolic pulmonary artery pressure [sPAP]-diastolic pulmonary artery pressure [dPAP])/right atrial (RA) pressure. One hundred fifty-eight patients with a mean age of 49±14years were studied (43 with a pre-transplant left ventricular assist device [LVAD]). Three patients were excluded due to missing data. In the non-LVAD group, there was no significant difference in PAPi or PVR, nor was there any association with post-operative outcome (including stratification by natural history sub-type; all P>0.05). In the LVAD group, there was no association with PAPi and post-operative outcome; however, PVR was predictive of post-operative mortality (mortality: 2.8±1.3 WU vs. alive: 1.7±0.7 WU; P=0.005). The PAPi was not able to discriminate mortality outcomes for patients post-cardiac transplantation. Pulmonary vascular resistance remains a marker of mortality in an LVAD cohort bridged to transplant (central illustration).

The Effect of Age on Non-Invasive Hemodynamics in Chronic Heart Failure Patients on Left-Ventricular Assist Device Support: A Pilot Study.

Background: Implantation of continuous flow left ventricular assist devices (LVAD’s) has been increasingly used in patients with advanced heart failure (HF). Little is known about the non-invasive hemodynamics and the relationship with adverse events in this specific group of patients. We aimed to identify any differences in non-invasive hemodynamics in patients with an LVAD in different age categories and to investigate if there is an association with major adverse events. Methods: In this observational cross-sectional study, HF patients with a continuous flow LVAD were included. Non-invasive hemodynamic parameters were measured with a validated, automated oscillometric blood pressure monitor. The occurrences of adverse events were registered by reviewing the medical records of the patients. An independent-samples T-test and Chi-square test were used to compare different groups of patients. Results: Forty-seven patients were included; of these, only 12 (25.6%) had a successful measurement. Heart rate, heart rate-adjusted augmentation index, and pulse wave velocity were higher in the ≥55 years of age LVAD group compared to the <55 years of age LVAD group (all p < 0.05). Stroke volume was significantly lower in the ≥55 years of age LVAD group compared to the <55 years of age LVAD group (p = 0.015). Patients with adverse events such as cardiovascular events, GI-bleeding, or admission to a hospital had lower central pulse pressure (cPP) than patients without any adverse event. Conclusion: Older LVAD patients have a significantly higher heart rate, heart rate-adjusted augmentation index, and pulse wave velocity and a significantly lower stroke volume compared to participants aged < 55 years. The pulsatile component of blood pressure was decreased in patients with adverse events.

Advanced Heart Failure Therapy In The Middle East; Case Series, With Clinical, Imaging & Pathological Correlation, From A Nascent Program

Background The global prevalence of heart failure continues to increase, with more patients presenting with advance heart failure that requires durable left ventricular (LVAD) placement and or orthotopic heart transplantation (OHT). Aim To describe the characteristics (clinical, imaging, pathological) and outcomes of patients undergoing LVAD or OHT at Cleveland Clinic Abu Dhabi (CCAD); a relatively new program from the UAE. Methods Retrospective chart review of all patients who had undergone LVAD or OHT at CCAD. The time period is May 2017 to current. Clinical data, imaging findings (echo, cardiac MRI, cardiac PET) and pathology findings were analyzed and correlated. Results Baseline characteristics and long term outcomes are shown in Table 1. Non Ischemic Cardiomyopathy was the predominant type of cardiomyopathy requiring LVAD or OHT. Ischemic Cardiomyopathy, as an etiology, was disproportionately noted in patients who received LVAD therapy compared to those who underwent OHT. Myocarditis was disproportionately noted in patients who underwent OHT, compared to the patients receiving LVAD. Table 2 shows the percentage of concordance or discordance between clinical, imaging and pathological diagnoses. The patients are separated by treatment strategy (LVAD, BTT or OHT). Importantly, clinical and imaging diagnoses of myocarditis were less likely to be corroborated on pathological examination. The concordance was excellent in the OHT group, modest in the LVAD group and poor in the BTT group. Conclusions We report the positive outcomes of patients seeking LVAD or OHT at our young program from the UAE. In spite of the low INTERMACS profiles, the outcomes are comparable to those reported to international databases. Concordance between clinical, imaging and pathological diagnoses of cardiomyopathy varied based on the treatment strategy. The global prevalence of heart failure continues to increase, with more patients presenting with advance heart failure that requires durable left ventricular (LVAD) placement and or orthotopic heart transplantation (OHT). To describe the characteristics (clinical, imaging, pathological) and outcomes of patients undergoing LVAD or OHT at Cleveland Clinic Abu Dhabi (CCAD); a relatively new program from the UAE. Retrospective chart review of all patients who had undergone LVAD or OHT at CCAD. The time period is May 2017 to current. Clinical data, imaging findings (echo, cardiac MRI, cardiac PET) and pathology findings were analyzed and correlated. Baseline characteristics and long term outcomes are shown in Table 1. Non Ischemic Cardiomyopathy was the predominant type of cardiomyopathy requiring LVAD or OHT. Ischemic Cardiomyopathy, as an etiology, was disproportionately noted in patients who received LVAD therapy compared to those who underwent OHT. Myocarditis was disproportionately noted in patients who underwent OHT, compared to the patients receiving LVAD. Table 2 shows the percentage of concordance or discordance between clinical, imaging and pathological diagnoses. The patients are separated by treatment strategy (LVAD, BTT or OHT). Importantly, clinical and imaging diagnoses of myocarditis were less likely to be corroborated on pathological examination. The concordance was excellent in the OHT group, modest in the LVAD group and poor in the BTT group. We report the positive outcomes of patients seeking LVAD or OHT at our young program from the UAE. In spite of the low INTERMACS profiles, the outcomes are comparable to those reported to international databases. Concordance between clinical, imaging and pathological diagnoses of cardiomyopathy varied based on the treatment strategy.

The growing role of designated communicators in the monitoring of patients with left ventricular assist device in the era of the COVID pandemic

Abstract Background Left ventricular assist devices (LVAD) are increasingly implanted in patients with end-stage heart failure. Patients require special care in terms of the safety and effectiveness of therapy, but during pandemic lockdown it is much more difficult to achieve. For many years at our institution, apart from routine personal visits, we have been using the REMEDIZER® internet communicator for remote care in LVAD group of patients. Objective - evaluation of the safety and effectiveness of remote monitoring in the care of patients with LVAD during the COVID pandemic – evaluation of the safety of remote monitoring with a designated communicator instead of personal visits Methods During the lockdown period (01/03/2020 - 31/12/2020), 72 patients (3 female) pts mean age 54.7±12,1 years with LVAD were monitored. For epidemiological reasons, the number of personal visits has been reduced in favor of telephone consultations and an increased volume of data entered into the REMEDIZER® internet communicator. The data collected in this period were compared with the data collected on 1 March 2019 - 31 December 2019, when: 53 pts (1 female) mean age 56,2±11,78 years were routinely, personally controlled at the Center for at least every 3 months and had blood, echo and LVAD examinations. Patients entered pump parameters: flow, motor speed, power consumption, pulse and blood pressure, body weight and temperature, at least twice a day (morning and evening) INR and dose of warfarin used were also reported. The number of complications during LVAD support was assessed: death or heart transplantation major complications: stroke, hemorrhage, pump thrombosis also other like arrhythmias requiring ICD intervention, hospitalization. Results Mean time of monitoring from hospital discharge after LVAD implantation to the end of observation in 2020 cohort was 651±486 days compared to 586±508, days in 2019 cohort In 2019, personal visits were performed significantly more often, 94 v. 17 (p&amp;lt;0.05), while remote visits (by phone or internet) were significantly more frequent in 2020 (2033 v. 1390). In 2019 patients were hospitalized significantly more often (28 vs. 10), but if we considered urgent hospitalizations, the differences were not statistically significant (9 vs. 8). In 2020, 5 patients (6,94%) died compared with 4 (7,55%) in 2019 (NS). In 2020, 9 patients (12,5%) were transplanted v. 3 (5,66%) in 2019. We observed 22 episodes of major complications in the 2020 cohort vs 20 in 2019 (NS); 11 ICD interventions vs 13 in 2019 (NS). Conclusions Replacing routine personal visits with increased patient self-control and constant remote contact with the center allowed a safe organization of patient care during COVID-19 pandemic The use of REMEDIZER® internet communicator dedicated for LVAD patients for remote care control proved to be effective and safe to control LVAD patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The study is funded by the National Center for Research and Development, Poland

The effect of paracorporeal pulsatile biventricular assist devices on allosensitization in adults: A comparison with left ventricular assist devices

Ventricular assist devices (VADs) have been associated with the development of anti-HLA antibodies (‘allosensitization’), but data on devices providing biventricular support in adults are limited. We sought to characterize differences in anti-HLA antibody formation in adult patients receiving left- (LVAD) versus biventricular- (BiVAD) assist devices as bridge to transplantation (BTT) by retrospectively reviewing the records of adult patients who have undergone VAD implantation at our institution. We assessed 82 patients supported with a pulsatile-flow paracorporeal BiVAD and compared them with 40 patients receiving LVAD till 2018. Forty-eight (58.5%) of the BiVAD and 23 (57.5%) of the LVAD patients were eventually transplanted (p = 0.91) with an average time to transplantation 559 and 598 days, respectively (p = 0.73). Evidence of sensitization pre-VAD was found in 11.0% of the BiVAD patients and 15.0% of the LVAD ones (p = 0.53); these percentages rose to 43.9% (p < 0.001) and 40.0% (p = 0.01), respectively. The post-VAD sensitization status was not significantly different between the BiVAD and the LVAD group (p = 0.68). De novo sensitization was comparable between the two groups (p = 0.55). Post-transplantation outcomes regarding rejections and cardiac allograft vasculopathy were also similar. Conclusively, BiVAD- and LVAD- induced allosensitization do not appear to differ significantly.

30 Years of Heart Transplant: Outcomes After Mechanical Circulatory Support From a Single Center

BackgroundSurvival after bridge to transplantation with mechanical circulatory support (MCS) has yielded varying outcomes on the basis of device type and baseline characteristics. Continuous-flow left ventricular assist devices (CF-LVADs) have significantly improved waitlist mortality, but recent changes to the transplantation listing criteria have dramatically altered the use of MCS for bridge to transplantation. MethodsOrthotopic heart transplantations from 1988 to 2019 at our institution (Washington University School of Medicine, Barnes-Jewish Hospital, St Louis, MO) were retrospectively reviewed and stratified by pretransplantation MCS status into CF-LVAD (n = 224), pulsatile LVAD (n = 49), temporary MCS (n = 71), and primary transplantation (n = 463) groups. Patients who underwent heart transplantation after the approval of CF-LVAD for bridge to transplantation and before the 2018 allocation policy changes underwent subgroup analysis to evaluate predictors of survival and complications in a contemporary cohort. ResultsRates of primary transplantation declined from 88% to 14% over the course of the study. No significant difference in survival was detected in the cohort stratified by MCS status (P = .18). In the modern era, survival of patients treated with CF-LVADs and temporary MCS was noninferior to that seen with primary transplantation (P = .22). Notable predictors of long-term mortality included lower body mass index, peripheral vascular disease, previous coronary artery bypass graft, ABO nonidentical transplant, and increased donor age (all P ≤ .02). There were no differences in major postoperative complications. ConclusionsCF-LVAD has grown to account for the majority of transplantations at our center in the last decade, with no adverse effect on survival or postoperative complications. Temporary MCS increased after the 2018 listing criteria change, with acceptable early outcomes.

Renal Function in Patients with or without a Left Ventricular Assist Device Implant During Listing for a Heart Transplant.

BackgroundLeft ventricular assist device (LVAD) implantation may improve kidney function, but in patients awaiting heart transplantation, the long-term effects of LVAD implantation on renal function and subsequent clinical outcome are unclear.Material/MethodsWe analyzed data in patients with LVAD implants (n=139) and without LVAD implants (n=1038) who were listed for a heart transplant at our institution between 2000 and 2019. The primary endpoint was an impairment in renal function (decrease of creatinine-based estimated glomerular filtration rate [eGFR] by ≥30%) up to a maximum of 2 years after listing. Secondary endpoints were chronic kidney disease stage 4 or 5, heart transplantation, survival during listing, and 1-year survival after transplantation.ResultsValues for eGFR increased after LVAD implantation (P=0.001) and were higher at the time of waitlisting in the LVAD group than in the non-LVAD group (P=0.002), but were similar between groups at the end of waitlisting (P=0.75). Two-year freedom from renal impairment was 50.6% and 66.7% in the LVAD and non-LVAD groups, respectively, with a multivariable-adjusted hazard ratio for the LVAD versus the non-LVAD group of 1.78 (95% confidence interval 1.19–2.68; P=0.005). Two-year freedom from chronic kidney disease stages 4–5 was similar between study groups (LVAD group: 83.5%; non-LVAD group: 80.1%; =0.50). The 2-year probability of transplantation was slightly lower in the LVAD group than in the non-LVAD group (50.0% and 55.8%, respectively, P=0.017). However, 2-year survival on the waiting list and 1-year survival after transplantation did not differ significantly between study groups (P-values >0.20).ConclusionsOur data indicate a transient improvement in creatinine-based eGFR values by LVAD implantation without influencing survival.

Pre-operative pulmonary artery pulsatility index does not predict mortality post cardiac transplantation but PVR is a prognostic tool in LVAD-bridged patients

Abstract The Pulmonary artery pulsatility index (PAPi) is a novel haemodynamic marker that has been shown to be a strong predictor of right heart failure and mortality in patients with pulmonary hypertension and advanced heart failure. Its utility in predicting post transplant outcomes is currently unknown. Aim To determine the prognostic significance of pre-transplant haemodynamic assessment of PAPi, right atrial pressure (RA), and pulmonary vascular resistance (PVR) in predicting mortality post cardiac transplant. Methods All patients who underwent cardiac transplantation between January 2010 and June 2016 were retrospectively analyzed. Pre-operative right heart catheter data was obtained. The PAPi was calculated as the systolic pulmonary artery pressure (sPAP)- diastolic pulmonary artery pressure (dPAP) divided by RA. Statistical analysis was carried out using SPSS v25. Results A total of 158 patients, with a mean age of 48.6±13.5 were studied (115 non- LVAD, 43 LVAD pre-transplant), and 3 patients were excluded due to missing data. There was no significant difference in the non-LVAD group in RA, PVR or PAPi for mortality post transplant. In the LVAD group there was no significant difference in RA, or PAPi with regards to mortality, however there was a significant difference in mean PVR between those that died post transplant (222±100) and those still alive (138±59) Conclusion Despite having a role in prognostication for right heart failure in pulmonary hypertension and post LVAD implantation, PAPi did not discriminate mortality outcomes for patients post cardiac transplantation. PVR remains a marker of mortality in an LVAD cohort bridged to transplant. Funding Acknowledgement Type of funding source: None

30 Day Survival in Heart Transplant Patients Bridged with Short Term Mechanical Circulatory Support: Are We Failing to Rescue?

UNOS heart allocation policy has changed with patients receiving temporary MCS being prioritized. Failure to rescue (FTR) describes a phenomenon where patients with in-hospital complications demonstrate increased 30 day mortality. We sought to identify 30 day mortality rates in BTT recipients supported with temporary MCS. International Society for Heart and Lung Transplantation (ISHLT) provided de-identified patient data. Between 2005 and 2018, 63,866 heart transplant recipients ≥18 years were identified. Of these, 658 (1.0%) were bridged with VA-ECMO, 1991 (3.1%) with IABP, 11960 (18.7%) with continuous-flow LVAD. Patients who underwent re-operative heart transplantation were excluded. Patients who were pre-operatively supported with VA-ECMO were younger when compared to the IABP or LVAD group. Donors were more likely to be older, female, and with a slightly longer ischemic time when transplanted into VA-ECMO recipients compared to IABP or LVAD recipients (Table 1). Kaplan-Meier analysis demonstrated a post-transplant survival of 81% (124/658 VA-ECMO), 95% (104/1991 IABP), 95% (552/11960 LVAD), at 30 days (p < 0.001). BTT with VA-ECMO is associated with decreased 30-day survival compared to IABP or LVADs. With the prioritization of patients transplanted from temporary MCS, multi-institutional collaborative efforts are necessary to define if FTR versus specific donor or recipient factors contribute to this survival differential.

534 Preoperative Pulmonary Artery Pulsatility Index Does not Predict Mortality Post Cardiac Transplantation but PVR is a Prognostic Tool in Patients LVAD-Bridged Patients

The Pulmonary artery pulsatility index (PAPi) is a novel haemodynamic marker that has been shown to be a strong predictor of right heart failure and mortality in patients with pulmonary hypertension and advanced heart failure. It’s utility in predicting post transplant outcomes is currently unknown. To determine the prognostic significance of pre-transplant haemodynamic assessment of PAPi, right atrial pressure (RA), and pulmonary vascular resistance (PVR) in predicting mortality post cardiac transplant. All patients who underwent cardiac transplantation between January 2010 and June 2016 were retrospectively analyzed. Preoperative right heart catheter data was obtained. The PAPi was calculated as the systolic pulmonary artery pressure (sPAP)- diastolic pulmonary artery pressure (dPAP) divided by RA. A total of 158 patients age of 48.6±13.5 were studied (115 no LVAD, 43 LVAD pre-transplant), and 3 patients were excluded due to missing data. Using a Mann-Whitney U test for comparison there was no significant difference in the non-LVAD group in RA, PVR or PAPi for mortality post transplant. In the LVAD group there was no significant difference in RA, or PAPi for mortality outcomes, however there was a significant difference in PVR between those that died post transplant (222±100) and those still alive (138±59). Despite having a role in prognostication for right heart failure in pulmonary hypertension and post LVAD implantation, PAPi was not able to discriminate mortality outcomes for patients post cardiac transplantation. PVR remains a marker of mortality in an LVAD cohort bridged to transplant.

P3476High-resolution respirometry reveals enhanced myocardial mitochondrial ketone oxidation after fasting and ventricular unloading

Abstract Background Impairment of myocardial mitochondrial function is regarded as an established pathomechanism in heart failure. Enhanced oxidation of ketone bodies may potentially exert protective effects on myocardial function. High-resolution respirometry (HRR) resembles a gold-standard methodology to determine myocardial mitochondrial metabolism and oxidative function but has not been validated for ketone substrates yet. Purpose We hypothesized that (1) quantification of ketone body oxidative capacity (OC) in myocardium utilizing ex-vivo HRR is feasible and that (2) ketone-associated OC is elevated after fasting and under conditions of chronic mechanical ventricular unloading. Methods We established new HRR (Oxygraph-2k) protocols, measuring oxygen flux generated by oxidation of the ketone substrates beta-hydroxybutyrate (HBA) and acetoacetate (ACA). Ketone protocols were then applied to twelve C57BL/6 mice' (of which six were fasted for 16h) left ventricular and right liver lobe tissue, as well as to eleven terminal heart failure patients' left ventricular tissue, harvested at heart transplantation. Heart transplant recipients were subdivided into patients with left ventricular assist device prior to transplantation (LVAD group, n=6) or no unloading prior to transplantation (HTX group, n=5). Results In non-fasted rodent hearts, HBA yielded an OC of 25±4 pmol/(s*mg tissue) above basal respiration, when applied as sole substrate (21±11 pmol/(s*mg) in liver). ACA alone did not induce oxygen flux, but ACA+succinate yielded 229% higher oxygen flux than succinate alone in state III (146±32 vs 44±12 pmol/(s*mg); p=0.0003). When titrated after succinate, ACA increased OC by 93±25 pmol/(s*mg) (p=0.0003). In 16h-fasted rodent hearts, HBA-supported OC was 27% higher (41±3 vs 52±9 pmol/(s*mg); p=0.04), while OC with ACA+succinate was unchanged (p=0.60). In rodent liver, no oxygen flux was induced by ACA, reflecting absence of 3-oxoacid CoA-transferase. However, HBA-supported OC was 118% higher in fasted liver (37±13 vs 57±13 pmol/(s*mg); p=0.03). In humans, left ventricular unloading was not associated with altered myocardial OC for fatty acids and glycolytic substrates (standard protocol, p=0.13), but HBA-supported OC was 39% higher in the LVAD group compared to the HTX group (54±12 vs 39±9 pmol/(s*mg), p=0.04). Conclusion Quantification of ketone body OC with HRR is feasible in permeabilized myocardial fibers. Applying this novel method revealed increased HBA-supported myocardial mitochondrial respiration after fasting and chronic left ventricular unloading. These data support a concept of enhanced ketone oxidation following ventricular unloading in myocardial mitochondria. Our findings facilitate new studies on myocardial ketone turnover and the interaction of mitochondrial ketone metabolism with cardiac performance. Acknowledgement/Funding CRC 1116, Research commission of the University Hospital Düsseldorf

P6315Effects of chronic heart failure unconventional therapies on endothelial function

Abstract Introduction Endothelial Dysfunction (ED) of peripheral arteries in Chronic Heart Failure (CHF) subjects has been demonstrated. Purpose We assessed endothelial function in subjects undergoing unconventional treatments for CHF, namely Heart Transplantation (HTX), continuous-flow Left Ventricular Assist Device implantation (LVAD), and repeated levosimendan infusions (r-LEVO). Methods Twenty HTX recipients (median time from HTX 21 months), 20 patients supported with LVAD (median time from implant 39 months), and 20 patients receiving monthly Levosimendan infusions (median time on treatment 28 months) were enrolled and compared to a group of 20 healthy subjects. ED was evaluated with ultrasound assessment of the diameter before and after ischemic stress at the brachial artery level. The difference between the two diameters normalized for the baseline value (Flow Mediated Dilation – FMD) has been used for the analysis. All the patients were stable at the time of FMD assessment, with those on r-LEVO being evaluated prior to infusion. Results FMD was significantly lower in HTX and LVAD groups with respect to controls (9.8±7.4, 9.3±5.7, and 15.6±6.4% respectively, p=0.01), but not in r-LEVO group (12.5±6.9%). When patients were analyzed according to time from the operation or on treatment, (&lt; versus &gt; of the median value), no differences were seen in HTX and r-LEVO group, while in LVAD group FMD was borderline significantly higher in patients with longer follow-up (8.4±6.4% versus 10.2±5.2%, p=0.05). Conclusions Based on this preliminary data we can inference the following: 1- FMD is abnormal in HTX recipients, despite their good functional status, probably due to factors unrelated to CHF (e.g. hypertension, renal insufficiency, denervation, and drug effects); 2- LVAD patients also show ED, with possible better adaptation in very long-term survivors; 3- Near-normal FMD values in CHF patients who remain stable with r-LEVO suggest that pulsed treatment may obtain favorable effects at peripheral level, persisting after clearance of the drug and its metabolites. Acknowledgement/Funding None

Results of new-generation intrapericardial continuous flow left ventricular assist devices as a bridge-to-transplant.

We analysed the outcomes with the use of a new-generation continuous-flow left ventricular assist device (CF-LVAD) as a bridge-to-transplant (BTT). We included all patients implanted with an intrapericardial CF-LVAD as BTT, between January 2012 and December 2016. Primary outcomes were overall survival, survival on waiting list and postheart transplant (HTx) survival. The outcomes after HTx were compared with those of a contemporary cohort of patients transplanted without previous CF-LVAD (No-LVAD group, n = 73). We included 53 patients with a median age of 52 years (interquartile range: 43-59 years). Seventy-two percent were in INTERMACS profile 1-2 before implant; all entered the HTx waiting list after receiving the CF-LVAD. HTx was performed in 42 (79%) cases (LVAD group). Overall estimated survival (considering both pre-HTx and post-HTx) was 89% [95% confidence interval (CI) 81-98%] at 1 year and 80% (CI 70-92%) at 2 years. The estimated survival on waiting list was 91% (CI 80-100%) at 6 months, whereas the 1-year estimated post-HTx survival was 88% (CI 79-98%). The Kaplan-Meier curves of survival after HTx of LVAD versus No-LVAD group were comparable (log-rank P = 0.54), as well as the rates of post-HTx adverse events. A multivariable model of survival after HTx, accounting for the most relevant patient characteristics, identified LVAD use as a significant protective factor [LVAD versus No-LVAD hazard ratio 0.22 (CI 0.06-0.91)]. The use of new-generation intrapericardial CF-LVADs as a BTT resulted, in our series, in satisfactory pre-HTx and post-HTx outcomes.

OC34 IMPACT OF CONTINUOUS FLOW LEFT VENTRICULAR ASSIST DEVICES AS BRIDGE TO TRANSPLANT ON GRAFT REJECTION AND DEVELOPMENT OF DONOR-SPECIFIC ANTIBODIES

Abstract Background and Aim: We analysed patients transplanted with and without previous continuous-flow left ventricular assist devices (CF-LVADs) to compare survival and rates of acute rejection, development of donor-specific antibodies (DSA) and chronic allograft vasculopathy (CAV). Methods: All consecutive patients aged&gt;18 years, who underwent HTx at our Institution from Jan-2012 to Dec-2017 were included. Patients assisted with pulsatile LVADs or total artificial heart were excluded. Cellular rejection score – CRS and antibody rejection score – ARS (total number of rejections divided by the number of endo-myocardial biopsies performed) were calculated at 3, 6 and 12 months after HTx. Results: We included 149 patients with a mean age of 54 ± 12 years. Among these, 47 (32%) were implanted with a CF-LVAD (25 HeartWare, 20 Jarvik 2000 and 2 HeartMate III) before HTx (LVAD group) and 102 (68%) were not (No-LVAD group). Pre-HTx allo-sensitization records were comparable among groups. Mean time of follow up was 25 ± 18 months in LVAD group and 24 ± 22 months in No-LVAD (p = 0.58). Overall mortality was comparable among groups (19% LVAD vs 18% No-LVAD, p = 0.83; Kaplan-Meier log-rank p = 0.98). Cellular and antibody-mediated rejection occurred similarly among groups. Incidence of CAV was comparable (p = 0.77), as well. De-novo DSA developed in a significantly higher number of bridged cases (29% vs 9%, p = 0.03). Conclusions: Patients supported with a CF-LVAD showed similar rates of cellular and antibody-mediated rejection and CAV after heart transplant, compared with non-bridged patients. Despite development of de-novo DSA was more frequent in assisted patients, this did not translate in worsened clinical outcomes.

Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients: The ROADMAP Study 2-Year Results

ObjectivesThe authors sought to provide the pre-specified primary endpoint of the ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) trial at 2 years. BackgroundThe ROADMAP trial was a prospective nonrandomized observational study of 200 patients (97 with a left ventricular assist device [LVAD], 103 on optimal medical management [OMM]) that showed that survival with improved functional status at 1 year was better with LVADs compared with OMM in a patient population of ambulatory New York Heart Association functional class IIIb/IV patients. MethodsThe primary composite endpoint was survival on original therapy with improvement in 6-min walk distance ≥75 m. ResultsPatients receiving LVAD versus OMM had lower baseline health-related quality of life, reduced Seattle Heart Failure Model 1-year survival (78% vs. 84%; p = 0.012), and were predominantly INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 4 (65% vs. 34%; p < 0.001) versus profiles 5 to 7. More LVAD patients met the primary endpoint at 2 years: 30% LVAD versus 12% OMM (odds ratio: 3.2 [95% confidence interval: 1.3 to 7.7]; p = 0.012). Survival as treated on original therapy at 2 years was greater for LVAD versus OMM (70 ± 5% vs. 41 ± 5%; p < 0.001), but there was no difference in intent-to-treat survival (70 ± 5% vs. 63 ± 5%; p = 0.307). In the OMM arm, 23 of 103 (22%) received delayed LVADs (18 within 12 months; 5 from 12 to 24 months). LVAD adverse events declined after year 1 for bleeding (primarily gastrointestinal) and arrhythmias. ConclusionsSurvival on original therapy with improvement in 6-min walk distance was superior with LVAD compared with OMM at 2 years. Reduction in key adverse events beyond 1 year was observed in the LVAD group. The ROADMAP trial provides risk-benefit information to guide patient- and physician-shared decision making for elective LVAD therapy as a treatment for heart failure. (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients [ROADMAP]; NCT01452802)

Does stroke etiology play a role in predicting outcome of acute stroke patients who underwent endovascular treatment with stent retrievers?

AimsThe goal of the study was to identify whether the stroke etiology play a role in the recanalization and outcome of patients who underwent mechanical thrombectomy with stent retrievers. Methods and resultsA retrospective analysis of a prospectively collected database included consecutive patients treated with stent retrievers. We included patients with cardioembolic stroke and large vessel atherosclerotic disease and compared risk factors for stroke, baseline NIHSS and Alberta Stroke Program Early CT scores (ASPECTS), stroke outcome, recanalization rate, onset-to-recanalization, onset-to-groin puncture time and the procedural time between two groups. Male sex was statistically more common in patients with large vessel atherosclerotic disease. Mean time from symptom onset- to the achievement of recanalization in patients with LVAD was 242±72.4 compared with cardioembolic stroke patients (301±70.7; p=0.014). Time for groin puncture to recanalization was longer in patients with cardioembolic stroke compared to LVAD group (97.5±44.3 vs 58.2±21.8; p=0.002). Time for microcatheter to successful recanalization or procedural termination was longer in patients with cardioembolic stroke compared to LVAD group (63.6±30.2 vs 34.2±19.4; p<0.001) with cardioembolic stroke had significantly worse long-term outcome (mRS 3–6) compared to those with LVAD (60.6% vs 26.3%; p=0.036). ConclusionStroke etiology may play a role in the outcome of acute stroke patients who underwent endovascular stroke therapy. Cardioembolic strokes may be more resistant to endovascular acute stroke treatment.

Association of Nasal Mucosal Vascular Alterations, Gastrointestinal Arteriovenous Malformations, and Bleeding in Patients With Continuous-Flow Left Ventricular Assist Devices

ObjectivesThis study sought to determine whether the nasal mucosa can serve as a surrogate for evaluating arteriovenous malformations (AVMs) related gastrointestinal (GI) bleeding in patients supported by continuous-flow left ventricular assist devices (CF LVADs). BackgroundBleeding from the mucosal surfaces of GI tract, particularly AVMs, is the most common complication of CF LVAD support. The pathophysiology of AVM formation during CF LVAD support is of critical interest yet poorly understood; in large part because of the length and accessibility of the GI tract. Nasal endoscopy is a minimally invasive, bedside test giving access to a mucosal surface possibly representative of the GI tract. MethodsEighty subjects (35 with CF LVAD, 30 with heart failure reduced ejection fraction [HFrEF], and 15 controls without heart failure) underwent nasal endoscopy for systematic evaluation of the intranasal mucosa for the presence of hypervascularity (HV). Patient records were reviewed for episodes and etiology of GI bleeding. ResultsNasal HV was present in 63%, 57%, and 20% of the LVAD, HFrEF, and control groups, respectively (p = 0.018). Although the prevalence was similar, the severity of nasal HV was significantly higher in the CF LVAD group compared with the HFrEF group. Of the baseline characteristics in the entire cohort, only a history of heart failure was associated with HV (odds ratio: 4.8; 95% confidence interval: 1.02 to 22.31; p = 0.040) in adjusted logistic regression modeling. HV was strongly associated with GI bleeding in the CF LVAD cohort: the incidence was 32% in subjects with HV compared with 0% in subjects with normal mucosa (p = 0.023). ConclusionsIn this pilot study, HV of the nasal mucosa was associated with GI bleeding in subjects with CF LVADs. Nasal endoscopy has significant potential to further investigation into mechanisms of bleeding and risk stratification during CF LVAD support.

(787) - Left Ventricular Assist Device-Associated Allosensitization - Much More Than a Nuisance

The impact of immune allosensitization induced by continuous flow left ventricular assist devices (CF LVAD) on post-transplant outcomes is still controversial. And, whether LVAD allosensitization carries a different importance than allosensitization due to other etiologies is also not known. Alloantibodies were detected with single-antigen beads on Luminex platform in all patients who received heart transplant in our program from 2006 to 2014. Allosensitization was defined as calculated panel reactive antibody (cPRA) >10%. In patients receiving CF LVADs as a bridge to transplant, cPRA was determined before CF LVAD implant and at the time of transplant, and in patients without CF LVAD at transplant listing and at the time of transplant. Antibody mediated rejection was defined as 3 or more episodes of pAMR≥2 detected on endomyocardial biopsies. 197 patients were transplanted between 2006 and 2014, of which 78 (40%) were bridged with CF LVADs. The mean age was 52±12 years, 18% were female and 92% of women were previously pregnant. Twenty patients were sensitized at baseline, and additional 12 patients became sensitized before transplant. Among all patients, those who became newly sensitized were at the highest risk of AMR, followed by patients already sensitized at baseline - p=0.02. In the CF LVAD group, sensitization was strongly associated with AMR (p<0.001, Figure 1A), but not in the non-LVAD group alone (p=NS, Figure 1B). Cardiovascular mortality and all-cause mortality were numerically higher in the sensitized patients, but this relationship was not statistically significant, perhaps due to the limited number of events. CF LVADs lead to a high risk of AMR after transplant in the 10% of patients who developed alloantibodies after LVAD implant. CF LVAD associated sensitization appears to be of higher clinical significance than sensitization of other etiologies, possibly due to the temporal closeness of the newly triggered antibody production to the transplant.

ProBNP serum levels and mRNA expression decrease after VAD implantation

Objectives: ProBNP is an established diagnostic and prognostic marker of cardiac insufficiency. It correlates to myocardial stretch and volume load, but is also influenced by metabolic and renal clearance, immunologic processes and other. ProBNP data for adult patients with ventricular assist devices (VAD) are scarce. Methods: We analyzed VAD patients retrospectively for proBNP (normal: < 125 pg/ml) and creatinine in serum before implantation (n = 32) as well as 28 ± 7 days (n = 15) and 60 ± 14 days (n = 32) postoperatively. 24 patients had left-ventricular (LVAD) and 8 had biventricular (BVAD) support. In addition, left-ventricular myocardial samples were taken at VAD implantation and explantation for heart transplantation. BNP mRNA expression of 10 patients was quantified by qPCR and normalized for 106 copies of Rps29. Data are given as mean ± standard deviation (median). SPSS version 19 was used for Wilcoxon tests and univariate regression analysis. Results: ProBNP decreased from 8696 ± 11454 (4637) before VAD implantation to 2898 ± 2521 pg/ml (2148 pg/ml) after one month and to 3034 ± 3619 pg/ml (1677 pg/ml) after two months on VAD. There was a decrease within the first month (28 days versus preop, p = 0.008), but not in the second month anymore. The LVAD and BVAD groups did not differ before or after VAD implant. Further, BNP mRNA expression decreased during VAD support from 80 ± 78 (55) to 9 ± 13 (34) copies (p = 0.005). Creatinine values developed similar to proBNP with a decrease within the first 4 weeks from 1.4 ± 0.6 (1.2) to 0.8 ± 0.3 (0.7) mg/dl (p = 0.002), but not in the second month (p = 0.272). However, creatinine did not explain proBNP values according to regression analysis. Conclusion: ProBNP values in serum declined within one month after VAD implantation. A decrease of mRNA expression was observed during VAD support. A relation of proBNP with cardiac unloading could be possible, but this association remains to be elucidated.

Comparison of Costs, Readmissions and Days out of Hospital at One Year between Heart Transplantation and Continuous Flow LVAD

Purpose With healthcare cost reform firmly on the horizon, it is critical to understand costs associated with new technologies like continuous flow LVAD (CFLVAD) vis-s-vis well established treatments for advanced heart failure like heart transplantation (HT). Scarce data exists describing costs of these two therapies after 1 year of support. Methods and Materials 20 consecutive pts who underwent implantation of a CFLVAD and 20 consecutive pts who underwent HT who were discharged following index surgery and survived at least 1 year represent the study populations. All medical costs incl organ acquisition and device costs, and all direct and indirect costs from day of operation through 365 days were calculated. Hospital charges were converted to costs using hospital specific cost-to-charge ratios. Results Total costs for 1 yr are shown in Figure 1 . Median index LOS was 14 and 23 days for HT and LVAD groups respectively(p Conclusions Costs for 1 yr of care are modestly higher for LVAD than for HT patients. Difference attributable to more hospital days and higher surgical costs unrelated to device cost. Reducing index LOS and readmissions for LVAD pts would render these 2 therapies cost equivalent.