Left Ventricular Assist Device Explantation Research Articles

Abstract 4134778: Myocardial Recovery and Survival after Weaning of Left Ventricular Assist Device Therapy in Patients with Toxic and non-Toxic Cardiomyopathy, A Canadian Experience

Left ventricular assist devices (LVAD) are increasingly used in refractory heart failure, mainly as a bridge to transplant or as destination therapy. LVAD unloading of the left ventricle (LV) can also promote myocardial recovery leading to improvement of the LV systolic function, allowing LVAD explantation. However, parameters associated with LVAD weaning and long-term outcomes are not well documented. The aim of this study was to assess the clinical and echocardiographic characteristics of weaned patients and to evaluate their event-free survival post-explantation. We conducted a single-center retrospective study recruiting patients who underwent a second or third generation LVAD implantation at a Canadian cardiology center between November 2009 and October 2021. A total of 98 patients underwent LVAD implantation during this period. All patients were on guideline-directed medical therapy (GDMT). Fourteen patients (14%) had significant LV recovery and were explanted/decommissioned after a median support time of 309 days (range 55-595 days). Toxic cardiomyopathy, defined as abuse of amphetamines (n=2), energy drinks (n=2) or multiple substances (n=6), was the most likely diagnosis in 10 of the weaned patients (71%). The LVEF was significantly higher and the left ventricular end-diastolic diameter (LVEDD) was significantly lower in weaned patients compared to unweaned patients after 3 months of support. Myocardial recovery manifested as pump thrombosis in 4 of the weaned patients (29%). Prior to explantation, 12 patients had a decrease in GDMT doses to minimize post explantation vasoplegia. After explantation, median follow-up time was 40 months (range 8-109 months) and the majority of patients were anticoagulated for 3 months. At last follow up, the LVEF was 44±6% and no patient had a LVEF below 35%. All patients were NYHA I or II and no death, heart transplant, or mechanical support initiation occurred. LVAD therapy can induce LV reverse remodeling leading to myocardial recovery in a significant proportion of patients, especially young patients with toxic and non-ischemic cardiomyopathies. Early reverse remodeling with decreasing LVEDD and improving LVEF at 3 months following implantation is associated with successful weaning. Pump thrombosis seems to be associated with LV reverse remodeling and weaning of mechanical support in certain patients. Weaned patients maintain satisfactory LVEF recovery after explantation and have good long-term event-free survival.

Subaortic Pannus Causing Complete Outlet Obstruction After Bioprosthetic Aortic Valve Replacement in a Patient with Left Ventricular Assist Device: A Case Report

Abstract Background Subaortic pannus formation complicates bioprosthetic aortic valve(AV) replacement. We report an extreme case in a continuous-flow left-ventricular-assist-device(LVAD) patient. Case Summary A 49-year-old Caucasian female with dilated cardiomyopathy was bridged-to-transplant with a HeartWare ventricular-assist-device(HVAD). Duration of support was prolonged, 6-years and 7-months, due to allosensitisation requiring desensitisation. Pump thrombosis occurred 2-years and 4-months post-LVAD requiring alteplase thrombolysis. The patient underwent bioprosthetic AV replacement 3-years and 10-months post-LVAD for symptomatic aortic incompetence. Transthoracic echocardiography(TTE) performed 1-year and 2-years post-bioprosthetic AV replacement repeatedly demonstrated an AV closed during all cardiac cycles without incompetence and nil flow through the left-ventricular-outflow-tract(LVOT). Following transplant, analysis of explanted heart revealed a fused AV. A pannus adherent to the underside of the AV had formed across the entire AV outlet, with complete obliteration of LVOT. This subaortic pannus was not visualised on previous TTE. Histologically, the pannus consisted of hypocellular fibrous tissue with chronic inflammatory cells, spindle histiocytes and myofibroblasts scattered throughout the loose fibromyxoid stroma, the latter highlighted on CD68 immunohistochemical stain(IHC). Partial endothelialisation on the pannus surface was highlighted on ERG & CD31 IHC. Neither calcification, nor signs of acute inflammation were noted. In contrast to previous cases, there was no evidence of associated thrombus macroscopically or microscopically. Discussion Prolonged LVAD support may facilitate subaortic pannus following bioprosthetic AV replacement due to AV closure and altered transvalvular flow. Due to the parallel LVAD circulation, subaortic pannus may develop asymptomatically, without haemodynamic compromise, allowing progression to total LVOT obstruction. This requires consideration prior to LVAD explantation in bridge-to-recovery patients.

Elevated cancer biomarkers in patients with severe heart failure could be a potential predictor of mortality during LVAD support

Abstract Introduction Owing to increasing numbers of heart failure patients a search for new biomarkers predicting prognosis is desirable. Background The purpose of this study was to analyze levels of cancer biomarkers in patients with severe heart failure before or after left ventricular assist device (LVAD) implantation and estimate its impact on survival during LVAD support. Methods We retrospectively analyzed data of all consecutive 168 LVAD recipients (92.8%- male, mean age 53.3 years ( median - 56.6, SD 12.0 ), median INTERMACS profile- 3.0, ischemic etiology of heart failure- 52.4%, 41.0% post CRT-D and 54.8% post ICD implantation, 36.9 post IABP, 5.4% post ECMO%, 11.9% post CABG and 8.9% post other cardiac surgery before LVAD implantation) implanted with continuous-flow LVAD (59.5%-HeartMate3, 35.1%- HeartWare, 5.4%-Heart Mate II) in our institution within years 2009-2023. Among comorbidities 63% of patients had atrial fibrillation or flutter, 41.6%- diabetes, 37.5%- arterial hypertension, 48.8%-renal failure, 7.1% pulmonary obstructive disease, 56.5% had pulmonary hypertension with mean pulmonary artery pressure above 25 mm Hg in right heart catheterization and 47% of patients had a history of cardiac arrest or sustained ventricular arrythmia before LVAD implantation. The overall mortality was 44.0 %. 31% patients were transplanted during LVAD support and in 4 patients (2.3%) LVAD was explanted or deactivated. Patient were followed to death, heart transplantation, LVAD explantation or the end of observation in our institution. Mean time of LVAD support was 885 days (1-2570). 23% of patients had right ventricular failure (RVF) early post LVAD implantation while 7.7% had late form of RVF. Results Serum concentrations of cancer biomarkers: carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, carbohydrate antigen(CA)-125 and alpha fetoprotein (AFP) taken before (56 patients -33.3%) or after (24 patients-14.3%) LVAD implantation were analyzed. Mean values, rate of abnormal results and correlation of abnormal results of CEA, CA19-9, CA-125, AFP with mortality during LVAD support were depicted in Table 1. No statistically significant correlations were found between levels of abovementioned cancer biomarkers and mortality though a trend towards increased mortality could be observed for abnormal results of CEA and Ca 19-9 taken before LVAD implantation. No malignant neoplasms were found in all analyzed patients except of one in whom a recurrence of lymphoma was found 2 months after LVAD implantation. Conclusions Patients with severe heart failure before and after LVAD implantation may present abnormal values of cancer biomarkers despite no found neoplasms. Our observation suggests that elevated cancer biomarker levels could predict mortality in heart failure patients after LVAD implantation. Further research is needed to confirm this thesis and investigate mechanisms of this phenomenon.

The implantation of a left ventricular assist device causes changes in the aortic miRNome and proteome - an integrative analysis

Abstract Background Left ventricular assist devices (LVAD) have been widely used and accepted to treat patients with end-stage heart failure. LVAD non-physiological blood flow velocity, wall shear stress distribution, vorticity current intensity, and vorticity flow generation affect the pathophysiology of vascular changes in aortic tissue. Purpose In this study, we performed multi-omics-based analysis of the aorta to identify molecular markers that could clarify vascular remodeling during LVAD support. Methods Aortic specimens from 48 patients (pair matched samples N=96) were excised during implantation and explantation of LVAD. Small RNA-Seq screening using Next Generation Sequencing and proteomic profile using Data-Independent Acquisition mass spectroscopy were conducted. Experimental and computational approaches, proteomics and transcriptomics data, were integrated and bioinformatics analyses were performed. Results The principal component analysis of miRNome and permutational multivariate analysis of variance of proteomic profile clearly segregated samples before and after LVAD support. We identified a total of 113 differently expressed (DE) miRNAs (61 up-regulated; Padj<0.05 and log2 fold change>|0.5|) after long-term LVAD support. Proteomic analysis identified in total 93 protein significantly changed (47 increased; Padj<0.05 and log2 fold change>|0.5|). Correlation analysis identified strong association between 270 proteins and 66 DE-miRNAs (Padj<0.05 and correlation coefficient>|0.7|). Gene Set Enrichment Analysis revealed, that predicted target genes of DE-miRNAs were mainly engaged in axon guidance, regulation of actin cytoskeleton, endocytosis, and MAP signaling pathway (Padj<0.05). DE-proteins participated mainly in ECM-receptor interaction, focal adhesion, and platelet activation (Padj<0.05). Conclusion Our study presents a network-based method of integrating microRNAs and proteome data and reveals molecular signatures that reflects aortic vascular remodeling due to LVAD treatment.PCA of miRNA DESeq2PCA of protemic profile

Accelerated Wean: A Novel 3 Day Berlin Heart Protocol in a Pediatric Patient.

We present the case of a 4 year old child who developed cardiogenic shock due to permanent junctional reciprocating tachycardia, requiring left ventricular assist device (LVAD) support. Despite the initial critical clinical presentation, successful myocardial recovery was achieved over 5 months, allowing for successful LVAD explantation. The patient's young age and behavioral issues were constraining factors for a prolonged LVAD wean trial. A modified wean protocol over a 3 day period with parameters for assessment of cardiac recovery before LVAD explantation is described.

A Case Report About Cardiac Arrest After Left Ventricular Assist Device Explantation.

Hemodynamic unloading by left ventricular assist devices (LVADs) in patients with advanced heart failure can result in reverse remodeling and cardiac recovery allowing pump removal. Ventriculoplasty during explantation may cause fibrosis and ventricular scars which can provide a substrate for reentry, a common cause of ventricular arrythmias. In this case report, we describe the clinical course of a patient who suffered a cardiac arrest in the following few months after undergoing LVAD explantation because of cardiac recovery. This case highlights a potential risk related to complete LVAD explantation with ventriculoplasty and patch repair of the apex.

Durable left ventricular assist device explantation following recovery in paediatric patients: Determinants and outcome after explantation.

Myocardial recovery in children supported by a durable left ventricular assist device is a rare, but highly desirable outcome because it could potentially eliminate the need for a cardiac transplant and the lifelong need for immunosuppressant therapy and the risk of complications. However, experience with this specific outcome is extremely limited. All patients < 19 years old supported by a durable left ventricular assist device from the European Registry for Patients with Mechanical Circulatory Support database were included. Participating centres were approached for additional follow-up data after explantation. Associated factors for explantation due to myocardial recovery were explored using Cox proportional hazard models. The incidence of recovery in children supported by a durable left ventricular assist device was 11.7% (52/445; median duration of support, 122.0 days). Multivariable analyses showed body surface area (hazard ratio 0.229; confidence interval 0.093-0.565; P = 0.001) and a primary diagnosis of myocarditis (hazard ratio 4.597; confidence interval 2.545-8.303; P < 0.001) to be associated with recovery. Left ventricular end-diastolic diameter in children with myocarditis was not associated with recovery. Follow-up after recovery was obtained for 46 patients (88.5%). Sustained myocardial recovery was reported in 33/46 (71.7%) at the end of the follow-up period (28/33; >2 year). Transplants were performed in 6/46 (11.4%) (in 5 after a ventricular assist device was reimplanted). Death occurred in 7/46 (15.2%). Myocardial recovery occurs in a substantial portion of paediatric patients supported with durable left ventricular assist devices, and sustainable recovery is seen in around three-quarters of them. Even children with severely dilated ventricles due to myocarditis can show recovery. Clinicians should be attentive to (developing) myocardial recovery. These results can be used to develop internationally approved paediatric weaning guidelines.

Socio-economic position, multimorbidity, and health care utilization among Danish left ventricular assist device patients.

Increasing numbers of patients with advanced heart failure and significant comorbidity and social barriers are considered for left ventricular assist devices (LVADs). We sought to examine health care utilization post-LVAD implantation, including the influence of individual-level socio-economic position and multimorbidity. We conducted a Danish nationwide cohort study linking individual-level data from clinical LVAD databases, the Scandiatransplant Database, and Danish national medical and administrative registries. Socio-economic position included cohabitation status, educational level, and employment status. Multimorbidity was defined as two or more chronic conditions from at least two chronic disease groups. Health care utilization (hospital activity, general practice activity, and redeemed medical prescriptions) within 2years post-discharge after LVAD implantation was evaluated using descriptive statistics at 0.5year intervals. We identified 119 patients discharged alive with first-time LVAD implanted between 2006 and 2018. The median age of the patients was 56.1years, and 88.2% were male. Patients were followed until heart transplantation, LVAD explantation, death, 31 December 2018, or for 2years. The median follow-up was 0.8years. The highest median use of health care services was observed 0-0.5years post-LVAD discharge compared with the subsequent follow-up intervals: 0.5-1, 1-1.5, and 1.5-2years, respectively. The median (interquartile range) number of hospitalizations was 10 (7-14), bed days 14 (9-28), outpatient visits 8 (5-12), telephone contacts with a general practitioner 4 (2-8), and total redeemed medical prescriptions 26 (19-37) within 0-0.5years post-LVAD discharge compared with the median utilization within the consecutive follow-up periods [e.g. within 0.5-1year: hospitalizations 5 (3-8), bed days 8 (4-14), outpatient visits 5 (3-8), telephone contacts 2 (0-5), and redeemed medical prescriptions 24 (18-30)]. The median use of health care services was stable from 0.5years onwards. The median number of hospitalizations and bed days was slightly higher in patients living alone with a low educational level or low employment status within 0-0.5years post-LVAD implantation. Finally, the median number of in-hospital days and redeemed prescriptions was higher among patients with pre-existing multimorbidity. Among patients who underwent LVAD implantation, health care utilization was high in the early post-LVAD discharge phase and was influenced by socio-economic position. Multimorbidity influenced the number of in-hospital days and redeemed prescriptions during the 2year follow-up.

Incidence, Outcomes, and Opportunity for Left Ventricular Assist Device Weaning for Myocardial Recovery

BackgroundMyocardial recovery occurs in patients with advanced heart failure on left ventricular assist device (LVAD) support, but there is the premise that it is rare with uncertain results. ObjectivesThe goal of this study was to investigate the incidence and consequence of LVAD explant after myocardial recovery. MethodsUsing the United Network for Organ Sharing registry, LVAD implants in the United States between 2005 and 2020 were tracked until death, transplantation, or explant for myocardial recovery. The cohort undergoing explant was followed up for heart failure relapse (defined as relisting followed by delisting due to death, being too ill, or transplantation; or second durable LVAD implant). ResultsOf 15,728 LVAD implants, 126 patients underwent explant for recovery, which only occurred in 55 (38%) of 145 implanting centers. The crude cumulative incidence was 0.7% at 2 years, whereas the incidence reached 4.7% among designated centers in the selected young nonischemic cohort. Of 126 explanted patients, 76 (60%) were subsequently delisted for sustained recovery. Heart failure relapsing had a relatively higher hazard in the early phase, with a 30-day incidence of 6% (7 of 126) but tapered following with the freedom rate of 72.5% at 4 years. ConclusionsIn the United States, LVAD explant for myocardial recovery was underutilized, leading to a very low incidence at the national level despite a realistic rate being achieved in designated centers for selected patients. With follow-up extending up to 4 years after explant, more than one-half were successfully removed and stayed off the waitlist, and approximately 70% were free from heart failure relapse events.

Abstract 16737: Explantation of LVAD in Recovered Alcohol Induced Cardiomyopathy

Durable Left Ventricular Assist Device (LVAD) is an important modality for bridge or destination therapy for patients with end-stage heart failure. However, there is a paucity of evidence guiding management for LVAD explantation in patients with sufficient myocardial recovery as this only occurs in 1-3% of cases. We present a case of a patient with LVAD placement due to alcoholic cardiomyopathy with subsequent removal of his LVAD three years later. Description of Case: A 51-year-old male with a history of alcohol induced cardiomyopathy with an LV ejection fraction of 10% s/p Heartmate II LVAD implant 3 years ago was evaluated for LVAD explantation. Over the course of one year, LVAD speed was decreased and ejection fraction (EF), cardiac output (CO) and cardiac index (CI) were monitored. Prior to explantation, the patients EF was 50% with a CO of 5.6L/min and CI 2.7 L/min/m2. Following successful explantation, a repeat echocardiogram 3 months later revealed an EF of 45%. Right heart catheterization revealed CO of 5.3L/min and CI 2.6L/min/m2. Patient was discharged on guideline directed medical therapy with continued improvement. Discussion: Mechanical, histological, and biochemical myocardial improvement has been described in LVAD recipients. There is a paucity of data to guide recovery assessment and candidacy for explantation. The 2023 ISHLT guidelines have attempted to synthesize the available data and outline the major considerations. Assessment should be done at low LVAD speeds with incorporation of data from patient’s clinical status, echocardiography, right heart catheterization, and cardiopulmonary exercise testing. Utilization of LVAD as a bridge to recovery was feasible in our patient given careful assessment of recovered cardiac function as outlined by aforementioned criteria. LVAD explantation after heart recovery remains a rare phenomenon. As access to cardiac transplantation remains limited, consistent use of guideline directed medical therapy allows for the possibility of heart recovery along with explantation. We present a case of successful and maintained myocardial recovery after LVAD explantation. Cases such as this would benefit from standardization of LVAD explantation guidelines for optimal long-term survival for patients.

Abstract 12373: Clinical Outcomes in Patients With Left Ventricular Assist Device on Guideline Directed Medical Therapy: A Propensity Score Matched Analysis

Introduction: We investigate the benefit of Guideline Directed Medical Therapy [GDMT] in patients with Left Ventricular Assist Device (LVAD) using an insurance claims database. Methods: We queried Trinetx US collaborative network for patients with LVAD and created two groups; those who received ≥2 prescriptions of any GDMT medication and who did not receive any GDMT after implantation. These were matched by Propensity Score Matching (PSM) for age, race, sex, BMI, LVEF, SBP, DBP, ischemic heart disease, hypertension, disorder of pulmonary circulation, chronic kidney disease (CKD) and acute kidney injury (AKI). All diagnosis were identified using ICD codes. Patient demographics, LVEF, BMI, SBP and DBP were recorded as reported by TriNetX. We looked at primary and secondary outcome measures starting 90 days until 10 years post implantation, primary being all cause mortality and secondary being risk of decompensated heart failure, hypotension, AKI, odds of receiving heart transplant and LVAD explant. Results: We had 4514 patients with LVAD on GDMT and 687 without GDMT. After PSM, we had 651 patients in each group. Both were matched by PSM with Standardized mean difference (SMD) &lt; 0.1 for all variables. Those with LVAD on GDMT had lower risk of all-cause mortality [233 (37.28%)] compared to those not on GDMT [157 (56.29%)] (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.24-0.37, P &lt; 0.0001) [Figure 1] but at a higher risk of decompensation (RR 2.74, 95% CI 2.19-3.42), hypotension (RR 3.58, 95% CI 2.73 - 4.69) and AKI (RR 2.64, 95% CI 2.23-3.18). Patients receiving heart transplant and LVAD explant had higher odds of being on GDMT [Odds Ratio [OR], 95% CI: 2.86, 1.87 - 4.37; 4.29, 2.13 - 8.63, respectively). Conclusions: LVAD patients on GDMT have lower all-cause mortality, higher odds of receiving heart transplant and LVAD explant starting 90 days post implant. However, for reasons not clear to us, they are also at higher risk of decompensation, hypotension and AKI.

Trans-aortic Valvular Ejection Fraction for Monitoring Recovery of Patients with Ventricular Systolic Heart Failure.

Durable mechanical circulatory support in the form of left ventricular (LV) assist device (LVAD) therapy is increasingly considered in the context of the recovery of native cardiac function. Progressive improvement in LV function may facilitate LVAD explantation and a resultant reduction in device-related risk. However, ascertaining LV recovery remains a challenge. In this study, we investigated the use of trans-aortic valvular flow rate and trans-LVAD flow rate to assess native LV systolic function using a well-established lumped parameter model of the mechanically assisted LV with pre-existing systolic dysfunction. Trans-aortic valvular ejection fraction (TAVEF) was specifically found to characterize the preload-independent contractility of the LV. It demonstrated excellent sensitivity to simulated pharmacodynamic stress tests and volume infusion tests. TAVEF may prove to be useful in the ascertainment of LV recovery in LVAD-supported LVs with pre-existing LV systolic dysfunction.

Long-term medical treatment and adherence in patients with left ventricular assist devices: a Danish nationwide cohort study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Grant from Karen Elise Jensen Foundation and Helse Foundation. Introduction An increasing number of patients with advanced heart failure (HF) live with a left ventricular assist device (LVAD). Data regarding medical treatment after LVAD implantation is sparse, including the impact of socioeconomic factors and multimorbidity. Purpose To describe medication use and assess the influence of socioeconomic factors and multimorbidity on medication use in the first two years following LVAD implant. Methods We conducted a nationwide cohort study based on data from the Danish clinical LVAD databases, the Scandiatransplant Database, and Danish nationwide administrative and medical registries. We identified patients with LVAD implantation between January 1, 2008, and December 31, 2018, who were discharged with LVAD therapy. Patients were followed until heart transplantation, LVAD explant, death, or December 31, 2018. Medication use was defined as a redeemed prescription from the Danish National Prescription Registry using ATC codes. Socioeconomic factors included cohabitation status, highest education attained, employment status, and personal income. Multimorbidity was defined as two or more chronic conditions. Medical treatment 90 days before LVAD implant and 720 days post-LVAD were assessed using descriptive statistics in 90 days intervals. Results We identified 119 patients; 88.2% were male, and the mean age (standard deviation) was 52.6 (14.5) years. The median (IQR) follow-up time was 0.8 years (0.4;1.8 years). 44.5% of patients underwent heart transplantation, and 4.2% had the LVAD explanted during follow-up. 27.7% of the patients were living alone, 27.7% had a low educational level, 37.8% were unemployed, 15.1% were in the lowest income (25 percentile), and 16.8% were categorized with multimorbidity (without cardiovascular disease group). The proportion of medication users of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (88.7%), beta-blocker (67%), mineralocorticoid receptor antagonists (62.9%), warfarin (87.6%), and aspirin (55.7%) within 90 days post-LVAD were substantially higher than pre-LVAD and were stable during the follow-up (Figure 1). In contrast, the proportion of diuretic users was lower post-LVAD implant than pre-LVAD, decreased further, and plateaued up to 180 days after hospital discharge. Stratified analyses according to socioeconomic factors and multimorbidity showed no differences in medication use (Figure 2). Conclusions Guideline-derived medical therapies for HF increased after LVAD implantation and were stable during long-term follow-up. As expected, the proportion of warfarin users increased substantially after LVAD implantation. Surprisingly, the percentage of aspirin users was not at the same level as for warfarin users. Socioeconomic factors and comorbidity burden did not influence long-term medication use of guideline-derived HF therapies, warfarin and aspirin in LVAD recipients.

Left Ventricular Assist Device explantation using a new double patch technique.

There are several surgical approaches for explantation of an LVAD after recovery of cardiac function. Thus, remaining ventricular assist device components may bear significant risks of infection or thrombosis. We hereby report our technique and two-center experience with explantation of LVADs using a new double patch technique. From March 2019-April 2021, 5 patients underwent LVAD explantation after myocardial recovery (HVAD, n = 2; HeartMate 3, n = 3). Mean patient age was 50.3 years (100% male) and mean time on LVAD was 23.1 ± 20.8 months. Primary heart failure aetiology was dilated cardiomyopathy (n = 4) and myocarditis (n = 1).LVAD explantation was performed using a median sternotomy and cardiopulmonary bypass. The LVAD was stopped, and the outflow graft clamped. The outflow graft was ligated and sutured close to the aortic anastomosis. The driveline was clipped and removed. Under induced fibrillation, the attachment of the LVAD was released from the apical cuff and the LVAD was removed. A round pericardial patch was fixed from the inner of the ventricle. This already seals the apex of the heart. An additional Goretex patch is continuously sutured epicardially over the suture ring. The 5 cases showed technically uncomplicated explantation of the LVADs. During the follow-up of mean 16.4 ± 16.9 months, survival of 100% was observed. There were no bleeding complications or thromboembolic events during follow-up. LVAD explantation with the double patch technique is feasible and safe. This technique allows discontinuation of anticoagulation. There was a 30-day survival of 100%. Further studies are needed to provide better evidence for LVAD explantation and long-term follow-up.

P50: Heart and Kidney Transplant and Recovery after Left Ventricular Assist Device and Intermittent Hemodialysis: Systematic Review and Individual-Participant-Data Meta-analysis

Background: Patients with left ventricular assist devices (LVADs) who require chronic intermittent dialysis (iHD) are considered to have poor prognosis despite paucity of supportive evidence, most of which is limited to case reports and very small single-center cohorts. This systematic review and individual-participant-data meta-analysis aims to study the main outcomes of patients receiving iHD during durable LVAD support, including heart, kidney, and heart-kidney transplantation (HT, KT, HKT, respectively) and mortality. Methods: We retrieved citations from ClinicalTrials.gov, Cochrane, Embase, PubMed, and Web of Science through systematic searches. We selected cohort studies (with n ≥5) of patients who were started on iHD at any point during durable LVAD support, excluding patients who exclusively received continuous renal replacement therapy but no actual iHD. We conducted Kaplan-Meier survival estimations and graphs, and compared mortality data between groups using the Gehan-Breslow-Wilcoxon test. P <.05 was considered statistically significant. We did not pursue inputations for missing data. Results: Six studies with a total of 64 patients met selection criteria. Their median age was 57.5 (46-64.5) years, 49 (76.6%) were men, 46 (86.8%) patients had a HeartMate (HM) 2, whereas 5 (9.4%) had a HM3, and 2 (3.8%) had an HVAD. Twenty-eight (66.7%) patients had LVADs as bridge to HT, and 14 (33.3%) as destination therapy. Only 26 (65%) were reported to have a history of CKD. Patients were initiated on iHD at a median of 18 (7-48) days after LVAD implantation, and remained on iHD for 68 (36-185) days. Eleven (17.2%) patients received HT, and at least 1 additional patient achieved myocardial recovery with LVAD explantation. Four (4.3%) patients became recipients of HKT, including one patient who had recovered enough of their renal function as to stop needing iHD prior to transplantation. Twenty-seven (42.2%) experienced renal recovery. Thirty-one (48.4%) patients died at 103 (64-308) days after initiation of iHD. According to Kaplan-Meier survival calculations, median survival was estimated at 153 (SE 217.5; CI 65-835) days (Figure 1). Survival after initiation of iHD was statistically significantly longer for patients who received HT (mortality: 2 [6.4%] vs 16 [11.6%]; p=.0346; median survival: 1972 [SE 98.8; 799-] days vs 93 [SE 10.3; CI 57-404] days), as evidenced in Figure 2. Survival comparisons between groups stratified based on other outcomes (HKT, renal recovery, composite HKT/renal recovery) did not reach statistical significance. Conclusions: The 18.8% of patients who achieved dual heart and kidney recovery and/or transplantation after being supported with LVAD and iHD experienced a significantly longer median survival. Only one patient experienced dual heart-kidney recovery. Larger contemporary multicenter cohort studies are warranted on this topic.Figure 1. Kaplan-Meier Survival Estimate (for the whole sample)Figure 2. Kaplan-Meier Survival Estimate According to Heart Transplant Status

Cardiomyocyte nuclear remodeling after mechanical unloading.

Cardiomyocytes increase DNA content in response to stress in humans. DNA content is reported to decrease in association with increased markers of proliferation in cardiomyocytes following left ventricular assist device (LVAD) unloading. However, cardiac recovery resulting in LVAD explant is rare. Thus, we sought to test the hypothesis that changes in DNA content with mechanical unloading occurs independent of cardiomyocyte proliferation by quantifying cardiomyocyte nuclear number, cell size, DNA content, and the frequency of cell-cycling markers using a novel imaging flow cytometry methodology comparing human subjects undergoing LVAD implantation or primary transplantation. We found that cardiomyocyte size was 15% smaller in unloaded versus loaded samples without differences in the percentage of mono-, bi-, or multinuclear cells. DNA content per nucleus was significantly decreased in unloaded hearts versus loaded controls. Cell-cycle markers, Ki67 and phospho-histon3 (H3P), were not increased in unloaded samples. In conclusion, unloading of failing hearts is associated with decreased DNA content of nuclei independent of nucleation state within the cell. As these changes were associated with a trend to decreased cell size but not increased cell-cycle markers, they may represent a regression of hypertrophic nuclear remodeling and not proliferation.NEW & NOTEWORTHY Our data suggest that increases in DNA content that occur with cardiomyocyte hypertrophy in heart failure may reverse with mechanical unloading.

CE-452777-1 INCIDENCE, PREDICTORS AND CLINICAL SIGNIFICANCE OF LATE VENTRICULAR ARRHYTHMIAS AFTER LVAD IMPLANTATION

Long-term survival after durable left ventricular assist device (LVAD) is improving. Ventricular arrhythmias are a driver of patient morbidity following implantation. Predictors of late ventricular arrhythmias (LVA) and their prognostic significance remain uncertain. We sought to determine the incidence of LVA, risk factors associated with their development and their clinical impact on patients in patients after LVAD implantation in long-term follow-up. A single-center retrospective analysis was performed including patients who underwent LVAD implantation from 2007-2022. We compared clinical characteristics and outcomes between patients who developed LVA to those patients without LVA. LVAs were defined as an episode of sustained ventricular tachycardia or ventricular fibrillation identified on ECG, telemetry and/or CIED occurring >30 days after LVAD implantation. Transplant-free survival was defined as time from index LVAD implantation to transplantation, LVAD explantation, death or most-recent follow-up. Of the 788 patients who underwent LVAD implantation during the study period, 141 patients (21.9%) had LVA >30 days after LVAD implantation. There was no significant difference between ages of patients with LVA and those without ventricular arrhythmia following LVAD implantation (LVA vs no LVA: 63.2 vs 62.3 years; p = 0.556). The majority of patients were male (78.7% vs 71.8%; p = 0.102) and self-identified as black (70.9% vs 71.8%; p = 0.875). Patients with LVAs more often had a history of preoperative presence of CRT (22.9% vs 12.5%; p = 0.002), history of ventricular tachycardia (49.3% vs 30.0%; p = <0.001), history of atrial flutter ablation (10.7% vs 3.7%; 0.001), appropriate ICD therapy prior to implantation (15.7% vs 5.5%; p = <0.001), taking amiodarone (31.8% vs 21.9%; p = 0.023), larger LVEDD (7.0 cm ± 1.0 vs 6.8 cm ± 1.0; p = 0.013) and QTc prolongation (504.8 ms ± 56.5 vs 518.2 ms ± 50.3; p = 0.017). The strongest independent predictors of LVA were a history of atrial flutter ablation (OR 3.52; CI 1.43-8.62; p = 0.006) and appropriate ICD shock in 7 days prior to implantation (OR 3.22; CI 1.49-6.99; p = 0.003). There was no difference between transplant-free survival time in patients with and without LVAs (p = 0.062, Figure 1). Despite being a common event after LVAD therapy, the development of LVA does not adversely impact transplant-free survival time. Future studies are warranted to determine the impact of LVA on quality-of-life in LVAD patients.

Patient-tailored silicone plug for HeartMate 3™ left ventricular assist device explantation

Patient-tailored silicone plug for HeartMate 3™ left ventricular assist device explantation in two successive males proceeded successfully. Given medical therapeutic advancements, FDA-approved plug systems designed by LVAD manufacturers themselves will be necessary for the near future to provide a safe and simple device explantation alternative that fulfills all regulatory standards.

(1025) Myocardial Recovery Profile in Patients Following Left Ventricular Assist Device Explantation

(1025) Myocardial Recovery Profile in Patients Following Left Ventricular Assist Device Explantation

Effect of mechanical unloading on genome-wide DNA methylation profile of the failing human heart.

Heart failure (HF) is characterized by global alterations in myocardial DNA methylation, yet little is known about the epigenetic regulation of the noncoding genome and potential reversibility of DNA methylation with left ventricular assist device (LVAD) therapy. Genome-wide mapping of myocardial DNA methylation in 36 patients with HF at LVAD implantation, 8 patients at LVAD explantation, and 7 nonfailing (NF) donors using a high-density bead array platform identified 2,079 differentially methylated positions (DMPs) in ischemic cardiomyopathy (ICM) and 261 DMPs in nonischemic cardiomyopathy (NICM). LVAD support resulted in normalization of 3.2% of HF-associated DMPs. Methylation-expression correlation analysis yielded several protein-coding genes that are hypomethylated and upregulated (HTRA1, FBXO16, EFCAB13, and AKAP13) or hypermethylated and downregulated (TBX3) in HF. A potentially novel cardiac-specific super-enhancer long noncoding RNA (lncRNA) (LINC00881) is hypermethylated and downregulated in human HF. LINC00881 is an upstream regulator of sarcomere and calcium channel gene expression including MYH6, CACNA1C, and RYR2. LINC00881 knockdown reduces peak calcium amplitude in the beating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). These data suggest that HF-associated changes in myocardial DNA methylation within coding and noncoding genomes are minimally reversible with mechanical unloading. Epigenetic reprogramming strategies may be necessary to achieve sustained clinical recovery from heart failure.