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Introduction: Since the 2018 change in the US adult heart allocation policy, more patients are bridged‐to‐transplant on temporary mechanical circulatory support (tMCS). Previous studies indicate that durable left ventricular assist devices (LVAD) may lead to allosensitization. The goal of this study was to assess whether tMCS implantation is associated with changes in sensitization. Methods: We included patients evaluated for heart transplants between 2015 and 2022 who had alloantibody measured before and after MCS implantation. Allosensitization was defined as development of new alloantibodies after tMCS implant. Results: A total of 41 patients received tMCS before transplant. Nine (22.0%) patients developed alloantibodies following tMCS implantation: 3 (12.0%) in the intra‐aortic balloon pump group (n = 25), 2 (28.6%) in the microaxial percutaneous LVAD group (n = 7), and 4 (44.4%) in the veno‐arterial extra‐corporeal membrane oxygenation group (n = 9)—p =.039. Sensitized patients were younger (44.7 ± 11.6 years vs. 54.3 ± 12.5 years, p =.044), were more likely to be sensitized at baseline ‐ 4 of 9 (44.4%) compared to 1 out of 32 (3.1%) (p =.001) and received more transfusions with red blood cells (6 (66.7%) vs. 8 (25%), p =.02) and platelets (6 (66.7%) vs. 5 (15.6%), p =.002). There was no significant difference in tMCS median duration of support (4 [3,15] days vs. 8.5 [5,14.5] days, p =.57). Importantly, out of the 11 patients who received a durable LVAD after tMCS, 5 (45.5%) became sensitized, compared to 4 out of 30 patients (13.3%) who only had tMCS—p =.028. Conclusions: Our findings suggest that patients bridged‐to‐transplant with tMCS, without significant blood product transfusions and a subsequent durable LVAD implant, have a low risk of allosensitization. Further studies are needed to confirm our findings and determine whether risk of sensitization varies by type of tMCS and duration of support. [ABSTRACT FROM AUTHOR]

Left ventricular hypertrophy is multifactorial and forecasts an increased risk of cardiovascular morbidity and mortality. Hypertrophic cardiomyopathy (HCM) is the most prevalent form of inherited cardiomyopathy. It results from mutations involving the genes encoding sarcomere proteins and is characterized by left ventricular hypertrophy and fibrosis. Cardiac amyloidosis (CA) is a disease where misfolded proteins accumulate in the extracellular cardiac tissue and is associated with poor prognosis. These cardiomyopathies share multiple features, and it can be challenging to differentiate between them. Timely diagnosis and differentiation between these cardiomyopathies is important. Advanced imaging modalities, namely cardiac magnetic resonance (CMR) is essential for accurate diagnosis and management. We compared 132 HCM patients, 62 CA & 20 healthy controls who completed a CMR (1.5 T or 3T) at the University of Utah Health. We examined the differences in multiple CMR parameters between these groups including left ventricular ejection fraction (LVEF), left atrial and right atrial size and emptying fraction (LAEF & RAEF), T1- tissue mapping and extracellular volume (ECV) measurement, CMR feature tracking (FT) peak segmental and global 2D and 3D strain. We used standard statistical descriptors and between-group analysis. On average, all three groups had preserved LVEF (64 ± 13) with the CA patients having low normal LVEF (52% ± 15). In comparison to HCM, the LAEF & RAEF were lower in CA (49 ± 11 vs 29 ± 15, P <0.001 & 52 ± 12.0 vs 34 ± 17, P <0.001). ECV was higher in CA when compared to HCM (53 ± 12 1.5 T & 51 ± 12 3T vs. 30 ± 7 1.5 T & 29 ± 5 3T, P<0.001). Regarding peak segmental strain, HCM exhibited lower absolute strain values compared to the control group, particularly in the basal septal segments. CA had significantly lower strain values across all segments. A relative apical sparing pattern was also noted (Figure 1). In HCM, only the global longitudinal strain was reduced, in both 2D & 3D, compared to controls (-9 ± 4 vs. -13 ± 4 2D & -7 ± 4 vs. -9 ± 4 3D, P<0.001). In CA, longitudinal, circumferential, and radial global strain, in both 2D and 3D, were reduced. CMR plays an important role in differentiating cardiomyopathies with increased left ventricular thickness. Among CMR parameters, LAEF, RAEF, ECV, peak global and regional strain, can be effective in distinguishing between HCM and CA. [ABSTRACT FROM AUTHOR]

The twelfth annual report from The Society of Thoracic Surgeons (STS) Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) highlights outcomes for 26 688 continuous-flow left ventricular assist device (LVAD) patients over the past decade (2011-2020). In 2020, we observed the largest drop in yearly LVAD implant volumes since the registry's inception, which reflects the effects of the COVID-19 pandemic on cardiac surgical volumes in the United States. The 2018 heart transplant allocation policy change in the United States continues to affect LVAD implantation volumes and device strategy, with 78.1% of patients now receiving LVAD implants as destination therapy. Despite an older and sicker patient cohort, survival in the recent era (2016-2020) at 1 and 2 years continues to improve at 82.8% and 74.1%. Patient adverse event profile has also improved in the recent era, with significant reductions in stroke, gastrointestinal bleeding, infection, and device malfunction/pump thrombosis. Finally, we review the burden of readmissions after LVAD implant and highlight an opportunity to improve patient outcomes by reducing this frequent and vexing problem. [Display omitted] [ABSTRACT FROM AUTHOR]

The MAVERICK cohort of MAVA-LTE (NCT03723655), initiated in 2018, represents the longest study of patients with nonobstructive hypertrophic cardiomyopathy (HCM) receiving mavacamten. Eligible patients who completed MAVERICK-HCM (NCT03442764) were dosed to achieve one of two target concentrations (∼200 or ∼500 ng/mL) using 4 dose strengths (dose titration: week 6). Monitoring occurred every 12 weeks from week 24. Forty-four patients (mean age, 54 years; 64% female) enrolled; 37 patients (84%) remained on-treatment at data cutoff (May 31, 2022; 110 patient-years exposure). Compared with baseline, mavacamten treatment improved New York Heart Association (NYHA) class, N-terminal pro-B-type natriuretic peptide levels, left atrial volume index, and E/e' at week 120 with some exposure dependence observed (Table; Figure). Mean left ventricular ejection fraction (LVEF) reduction between groups corresponded with exposure but remained >50%. Of 12/44 patients (27%) with transient LVEF reductions <50% (range 29–49% between weeks 4–156), 9 resumed treatment; 3 discontinued. Treatment discontinuation reasons in 7/44 patients (16%) included stopping criteria (n=4), withdrawal (n=2) and nocturnal dyspnea (n=1). Since previous cutoff (October 30, 2020; 52 patient-years exposure), 3 serious adverse events (ankle fracture; brachial plexopathy; renal failure) were reported; exposure-adjusted cardiac failure incidence decreased between 2020 and 2022 cutoffs (1.91 and 0.91/100 patient-years, respectively). In patients with nonobstructive HCM, longer-term mavacamten treatment demonstrated improvements in NYHA class, NT-proBNP and echocardiographic measures. No unexpected safety signals were identified. Mavacamten was temporarily held in 27% of patients for LVEF <50%. Results helped inform the dosing strategy for ODYSSEY-HCM (NCT05582395). [ABSTRACT FROM AUTHOR]

Amyloidosis, a condition of abnormal protein folding and deposition, is caused by over 30 proteins in the human body. Two main types affect the heart, transthyretin amyloidosis (ATTR) from the liver, and light chain amyloidosis (AL) from the bone marrow. Both can lead to a considerable reduction in patients; health status, symptoms, function and quality of life. The Kansas City Cardiomyopathy Questionnaire - 12 (KCCQ) is a validated disease-specific assessment of heart failure (HF)-related health status. We examined the association of the KCCQ with HF outcomes in patients with amyloidosis. The initial KCCQ scores among consecutive patients with cardiac amyloidosis who completed the KCCQ as part of their routine care from 11/2015 to 09/2022 were analyzed with Cox regression to predict the composite outcome of HF hospitalization and mortality. The association of KCCQ quartiles with the composite outcome was expressed as hazard ratio (HR) and 95% confidence interval (CI), using KCCQ 75-100 quartile as a reference group. Study cohort included 53 patients with AL amyloidosis (mean age: 63.9±10.3, sex: 58.5% male) with a median follow-up of 636 days, and 117 patients with ATTR amyloidosis (mean age: 76.9±8.3, sex: 91.5% male) with a median follow-up of 670 days. The majority in both groups had heart failure with preserved ejection fraction (HFpEF) (AL: 66.0%, ATTR: 53.9%) and mean ejection fraction (EF) of 58.2±11.7% and 51.1±12.9 %, respectively. Among the AL population, 67.9% had an event with a mean time to event of 293.4±411.0 days (Figure 1). In the ATTR cohort, 40.2% experienced an event with a mean time to event of 357.2±383.9 days (Figure 2). For patients in the lowest quartile (KCCQ<25), the HR was 7.54 [95% CI, 1.98-28.73] for AL (n=9) and 1.42 [95% CI, 0.56-3.61] for ATTR (n=18), while in the second quartile (25

Aims: Adjuvant heart failure (HF) drug therapy in patients undergoing chronic mechanical circulatory support (MCS) is often used in conjunction with a continuous-flow left ventricular assist device (LVAD), but its potential impact is not well defined. The objective of the present study was to examine the effects of conventional HF drug therapy on myocardial structure and function, peripheral organ function and the incidence of adverse events in the setting of MCS.Methods and Results: Patients with chronic HF requiring LVAD support were prospectively enrolled. Paired myocardial tissue samples were obtained prior to LVAD implantation and at transplantation for histopathology. The Meds group comprised patients treated with neurohormonal blocking therapy (concurrent beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and aldosterone antagonist), and the No Meds group comprised patients on none of these. Both the Meds (n = 37) and No Meds (n = 44) groups experienced significant improvements in cardiac structure and function over the 6 months following LVAD implantation. The degree of improvement was greater in the Meds group, including after adjustment for baseline differences. There were no differences between the two groups in arrhythmias, end-organ injury, or neurological events. In patients with high baseline pre-LVAD myocardial fibrosis, treatment with HF drug therapy was associated with a reduction in fibrosis.Conclusions: Clinical and histopathological evidence showed that adjuvant HF drug therapy was associated with additional favourable effects on the structure and function of the unloaded myocardium that extended beyond the beneficial effects attributed to LVAD-induced unloading alone. Adjuvant HF drug therapy did not influence the incidence of major post-LVAD adverse events during the follow-up period. [ABSTRACT FROM AUTHOR]

Adeno-associated viral vectors (AAV) are the leading platform for gene delivery to treat disease. Although AAVs are not known to be pathogenic, patients with high levels of pre-existing neutralizing antibodies (NAbs) to AAVs may fail to achieve desired transgene expression and/or be at increased risk of a systemic inflammatory response. Tenaya Therapeutics is developing TN-201, the first AAV9-mediated gene therapy for the treatment of MYBPC3-associated HCM. To date, there have been no studies to assess pre-existing AAV9 immunity to determine the percentage of MYBPC3-associated HCM patients who may be candidates for this one-time gene therapy treatment. To assess the prevalence of NAbs in MYBPC3-associated HCM patients, Tenaya initiated an observational seroprevalence study, enrolling participants at US HCM clinics. Sites collected medical histories and sera from participants. Serum from each participant was used in an AAV9 NAb assay to assess NAb titer to AAV9, the serotype used in TN-201. Participants with titers <1:20 were classified as seronegative (low pre-existing NAb) to AAV9. Total antibody titer to AAV9 was assessed to compare with NAb titers. As of June 2023, participants have enrolled in this seroprevalence study across 10 clinics. Interim results indicate that 33 of 45 (73%) MYBPC3-associated participants are AAV9 seronegative. AAV9 seronegativity did not vary by age, race, geography, or medical history. Results suggest that MYBPC3-associated HCM patients have low levels of pre-existing NAbs to AAV9 used in TN-201. This finding may indicate that the majority patients could be eligible for TN-201 in clinical trials. [ABSTRACT FROM AUTHOR]

Temporary mechanical circulatory support (tMCS) devices are increasingly used for the management of patients experiencing cardiogenic shock despite a paucity of randomized controlled data on their clinical efficacy. Complications associated with these devices are a common, but poorly quantified, occurrence that may negatively affect outcomes in cardiogenic shock patients receiving tMCS. We sought to evaluate complication rates in patients with cardiogenic shock who receive tMCS and compare complication rates between different tMCS devices. Consecutive patients with cardiogenic shock managed at a tertiary academic medical center from May 2015 to December 2021 were retrospectively reviewed (N=1,162). Our final study cohort comprised patients who developed cardiogenic shock and received tMCS after admission to our institution (N=187). Primary outcomes studied were complications using STS-INTERMACS definitions: neurologic complications (ischemic or hemorrhagic stroke, transient ischemic attack [TIA]), major bleeding events (type 3 and 4), and hemolysis, as well as acute kidney injury (AKI) requiring renal replacement therapy (RRT) and vascular compromise requiring vascular repair or amputation. Chi-squared tests were used to compare complication rates. Our study comprised 187 patients of whom 55 received VA-ECMO, 72 intra-aortic balloon pump, and 60 percutaneous ventricular assist device (pVAD - 90% Impella CP, 6.6% Impella 5.5, 3.3% Impella 2.5) as first tMCS. Patients receiving VA-ECMO had a higher proportion of SCAI stage E and higher lactate prior to the initiation of tMCS (Table- Panel A). Our analysis showed a vascular complication rate of 20% for VA-ECMO vs 6.9% for IABP vs 5% for pVAD, p=0.015; neurologic complication rate of 12.7% vs 8.3% vs 5%, p=0.34; hemolysis rate of 22.2% vs 2.8% vs 36.7%, p<0.001; AKI requiring RRT of 25.5% vs 9.7% vs 13.3%, p=0.045; and major bleeding event rate of 85.5% vs 34.7%% vs 53.3%, p<0.001 (Table- Panel B). Overall complication rates increased from IABP to pVAD to VA-ECMO. VA-ECMO patients experienced more vascular complications, AKI requiring RRT, and major bleeding; pVAD patients had more hemolysis while the risk of stroke/TIA was comparable among the tMCS groups. Whether the observed differences are related to the specific device type and/or the different degrees of severity of shock warrants further investigation. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a leading cause of morbidity and mortality in the United States and worldwide. As a multifactorial syndrome with unpredictable clinical outcomes, identifying the common molecular underpinnings that drive HF pathogenesis remains a major focus of investigation. Disruption of cardiac gene expression has been shown to mediate a common final cascade of pathological hallmarks wherein the heart reactivates numerous developmental pathways. Although the central regulatory mechanisms that drive this cardiac transcriptional reprogramming remain unknown, epigenetic contributions are likely. In the current study, we examined whether the epigenome, specifically DNA methylation, is reprogrammed in HF to potentiate a pathological shift in cardiac gene expression. To accomplish this, we used pairedend whole genome bisulfite sequencing and next-generation RNA sequencing of left ventricle tissue obtained from seven patients with end-stage HF and three nonfailing donor hearts. We found that differential methylation was localized to promoter-associated cytosine- phosphate-guanine islands, which are established regulatory regions of downstream genes. Hypermethylated promoters were associated with genes involved in oxidative metabolism, whereas promoter hypomethylation enriched glycolytic pathways. Overexpression of plasmid-derived DNA methyltransferase 3A in vitro was sufficient to lower the expression of numerous oxidative metabolic genes in H9c2 rat cardiomyoblasts, further supporting the importance of epigenetic factors in the regulation of cardiac metabolism. Last, we identified binding-site competition via hypermethylation of the nuclear respiratory factor 1 (NRF1) motif, an established upstream regulator of mitochondrial biogenesis. These preliminary observations are the first to uncover an etiology-independent shift in cardiac DNA methylation that corresponds with altered metabolic gene expression in HF. [ABSTRACT FROM AUTHOR]

BACKGROUND: Impaired qualitative and quantitative left ventricular (LV) rotational mechanics predict cardiac remodeling progression and prognosis after myocardial infarction. We investigated whether cardiac rotational mechanics can predict cardiac recovery in chronic advanced cardiomyopathy patients. METHODS AND RESULTS: Sixty-three patients with advanced and chronic dilated cardiomyopathy undergoing implantation of LV assist device (LVAD) were prospectively investigated using speckle tracking echocardiography. Acute heart failure patients were prospectively excluded. We evaluated LV rotational mechanics (apical and basal LV twist, LV torsion) and deformational mechanics (circumferential and longitudinal strain) before LVAD implantation. Cardiac recovery post-LVAD implantation was defined as (1) final resulting LV ejection fraction ≥40%, (2) relative LV ejection fraction increase ≥50%, (iii) relative LV end-systolic volume decrease ≥50% (all 3 required). Twelve patients fulfilled the criteria for cardiac recovery (Rec Group). The Rec Group had significantly less impaired pre-LVAD peak LV torsion compared with the Non-Rec Group. Notably, both groups had similarly reduced pre-LVAD LV ejection fraction. By receiver operating characteristic curve analysis, pre-LVAD peak LV torsion of 0.35 degrees/cm had a 92% sensitivity and a 73% specificity in predicting cardiac recovery. Peak LV torsion before LVAD implantation was found to be an independent predictor of cardiac recovery after LVAD implantation (odds ratio, 0.65 per 0.1 degrees/cm [0.49-0.87]; P=0.014). CONCLUSIONS: LV rotational mechanics seem to be useful in selecting patients prone to cardiac recovery after mechanical unloading induced by LVADs. Future studies should investigate the utility of these markers in predicting durable cardiac recovery after the explantation of the cardiac assist device. [ABSTRACT FROM AUTHOR]

BACKGROUND: Current organ allocation policy and the rapid growth of mechanical support favor heart transplant (HT) candidates on left ventricular assist devices. HT candidates with hypertrophic cardiomyopathy (HCM) are usually not left ventricular assist device candidates and may have a disadvantage compared with dilated forms of cardiomyopathy. METHODS AND RESULTS: Adult HT candidates registered in the Scientific Registry of Transplant Recipients database between 1999 and 2016 were included. HCM candidates were compared with ischemic cardiomyopathy (ICM) and non-ICM patients. Two eras were defined on the basis of the approval date of the first continuous-flow left ventricular assist device for bridge-to-transplant in the United States (2008). Patients outcomes were evaluated while on the waitlist and after HT. The proportion of patients with HCM listed for HT increased by 44% in era 2 compared with era 1. Waitlist mortality in patients with ICM (15.5%-8.7%) and non-ICM (14.2%-8.2%) declined across eras, but minimal decline was observed in HCM patients (11.7%-9.6%; P=0.06). In era 2, the 12-month rate of HT in HCM (64.8%) was comparable to that of ICM (60.9%) and non-ICM (62.7%) patients (P=0.06). Post-transplant survival in HCM patients was the most favorable in the most recent era (1 year: 91.6% and 5 years: 82.5%; P<0.05 for all comparisons). CONCLUSIONS: The number of patients with HCM in need of HT is increasing. Although post-transplant survival in HCM is excellent, waitlist mortality is substantial and with minimal decline in the most recent era, despite the frequent use of listing status upgrade by exception in this patient cohort. Different strategies to improve the performance of the organ allocation system in patients with HCM are needed. [ABSTRACT FROM AUTHOR]

Purpose: Cardiac allograft vasculopathy (CAV) continues to hinder the long-term success of heart transplant recipients. Redo-transplantation is currently the only definitive treatment for advanced CAV. We examined whether these patients are at similar CAV-risk with the second transplant. Methods: Heart recipients from 1985 to 2011 at the UTAH program were included in the study and those with CAV as an indication for redo-transplantation were identified. CAV diagnosis was made by coronary angiography and based on the 2010 ISHLT standardized nomenclature for CAV. Patient demographics, rejection history, and CAV incidence were analyzed. Results: Of the 1,169 eligible patients, 135 (11.5%) developed CAV post their first transplant; 78 cases within 10 years and 54 beyond 10 years. The mean time to CAV was 6.58 years. Of the 135 patients who developed CAV, only 21 (15.5%) ended up requiring a redo-transplant. Of the 21 retransplanted patients, 4 (19.0%) developed CAV again; 2 patients within 10 years and 2 patients beyond 10 years indicating a similar risk for CAV occurrence for first and redo-transplant. Conclusions: Our results indicate that CAV is as likely to develop in redo-transplants despite recent advances in immunosuppression and the standardized use of lipid-lowering agents. Although outcomes in redo-transplantation for the indication of CAV are favorable, efforts to better understand and minimize CAV are needed, especially in the face of scarce donor organs. [ABSTRACT FROM AUTHOR]

Background Survival beyond 1 year after heart transplantation has remained without significant improvement for the last 2 decades. A more individualized approach to post-transplant care could result in a reduction of long-term mortality. Although recipient age has been associated with an increased incidence of certain post-transplant morbidities, its effect on cause-specific mortality has not been established. Methods We analyzed overall and cause-specific mortality of heart transplant recipients registered in the International Society for Heart and Lung Transplantation Registry between 1995 and 2011. Patients were grouped by recipient age: 18 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and ≥ 70 years. Multivariable regression models were used to examine the association between recipient age and leading causes of post-transplant mortality. We also compared immunosuppression (IS) use among the different recipient age groups. Results There were 52,995 recipients (78% male; median age [5th, 95th percentile]: 54 [27, 66] years). Survival through 10 years after transplant was lower in heart transplant recipients in the 2 more advanced age groups: 49% for 60 to 69 years and 36% for ≥ 70 years ( p < 0.01 for pairwise comparisons with remaining groups). The risk of death caused by acute rejection (hazard ratio [HR], 4.11; p < 0.01), cardiac allograft vasculopathy (HR, 2.85; p < 0.01), and graft failure (HR, 2.29; p < 0.01) was highest in the youngest recipients (18–29 years) compared with the reference grou p (50–59 years). However, the risk of death caused by infection (HR, 2.10; p < 0.01) and malignancy (HR, 2.23; p < 0.01) was highest in older recipients (≥ 70 years). Similarly, the risk of death caused by renal failure was lower in younger recipients than in the reference group (HR, 0.53; p < 0.01 for 18–49 years vs 50–59 years). The use of induction IS was similar among the different recipient age groups, and differences in maintenance IS were not clinically important. Conclusions Causes of death in this large cohort of heart transplant recipients varied significantly with recipient age at the time of transplant, with cause-specific mortality profiles suggesting a possible effect of inadequate IS in younger recipients and over-IS in older recipients. Thus, a more personalized approach, possibly including different IS strategies according to recipient age, might result in improved post-transplant survival. [ABSTRACT FROM AUTHOR]

Mechanical unloading and circulatory support with left ventricular assist devices (LVADs) leads to significant structural and functional myocardial improvement in a subset of advanced heart failure (HF) patients, but the interplay between clinical parameters and underlying biological phenomena driving these changes is not well understood. By applying novel machine learning (ML) techniques, we sought to identify transcriptomics and clinical characteristics before the LVAD intervention that associate with subsequent structural and functional cardiac improvement. In a multicenter collaboration, baseline clinical variables and left ventricular apical tissue were collected from HF patients at the time of LVAD implantation (n=208). RNA was isolated from the apical tissue and mRNA transcripts were identified through RNA sequencing. Next, we used ML based on 59 clinical variables and 22,373 mRNA transcripts for the prediction of combined structural and functional myocardial improvement using a cutoff for left ventricular ejection fraction (LVEF) ≥40% and left ventricular end-diastolic diameter (LVEDD) ≤5.9cm. We also independently assessed LVEF and LVEDD as continuous variables representative of functional and structural myocardial improvement respectively, within the year post-LVAD implant. Combining the RNA and clinical data resulted in a support vector machine (SVM) model with 80 variables achieving an AUC of 0.73±0.15 for predicting LVAD-mediated myocardial recovery (Figure). Clinical factors associated with myocardial recovery included HF symptoms duration, pre-LVAD LVEF, LVEDD, and HF pharmacologic therapy, as well as LVAD configuration (axial vs. centrifugal). Transcriptomics associated with myocardial recovery included expression of CYREN (DNA repair), ATF3 (cellular stress), DUSP5 (cellular proliferation), and LRRN4C (ligand binding and programmed cell death). Using ML, we revealed specific clinical and molecular drivers of LVAD-mediated myocardial recovery. We also identified mechanistic pathways that may have diagnostic, prognostic, and therapeutic implications for the entire spectrum of HF. [ABSTRACT FROM AUTHOR]

Background: The number of centers with left ventricular assist device (LVAD) research programs focused on cardiac recovery is very small. Therefore, this phenomenon has been reported in real-world multi-center registries as a rare event.Objectives: This study evaluated the incidence of cardiac recovery with an a priori LVAD implantation strategy of bridge-to-recovery (BTR) and constructed a recovery predictive model.Methods: The study included LVAD recipients registered in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). Cardiac recovery was evaluated in BTR and non-BTR patients. A weighted score was derived and externally validated in patients of the Utah Cardiac Recovery (UCAR) program.Results: Of 15,138 INTERMACS patients, cardiac recovery occurred in 192 (1.3%). The incidence of recovery was 11.2% (n = 14) in BTR compared with 1.2% (n = 178) in non-BTR patients (p < 0.0001). Independent predictors of recovery included: age <50 years, non-ischemic cardiomyopathy, time from cardiac diagnosis <2 years, absence of ICD, creatinine ≤1.2 mg/dl, and LVEDD <6.5 cm (c-index: 0.85; p < 0.0001). A weighted score termed I-CARS, effectively stratified patients based on their probability of recovery. I-CARS was validated in the UCAR cohort (n = 190) with good performance (AUC: 0.94; 95% CI: 0.91 to 0.98). One-year survival after LVAD explantation, available in INTERMACS for 21 (11%) patients, was 86%.Conclusions: The incidence of cardiac recovery is higher in patients implanted with an a priori BTR strategy. We developed a simple tool to help identify patients in whom recovery is feasible. In BTR patients with favorable characteristics, I-CARS suggests a 24% probability of successful LVAD explantation. Large-scale studies to better address post-explantation outcomes are warranted. [ABSTRACT FROM AUTHOR]

Background This study evaluated current trends in incidence and outcomes of left ventricular assist device (LVAD)-related thromboembolic (LVAD-TE) and LVAD malfunction (LVAD-M) complications among heart transplant (HT) candidates supported with continuous-flow LVADs. LVAD-TE and LVAD-M are potentially catastrophic complications that may require status upgrade on the HT waiting list. An increased incidence of device thrombosis has been recently observed; however, whether similar trends of LVAD-TE and LVAD-M are observed on the HT waiting list and their effect on outcomes is unknown. Methods We analyzed 3,821 HT candidates on continuous-flow LVADs who were registered on the United States waiting list from 2008 to 2014. We evaluated the incidence of LVAD-TE and LVAD-M as well as survival before and after HT. Results LVAD-TE occurred in 249 patients (6.5%) and LVAD-M in 210 patients (5.5%). The incidence of LVAD-TE was highest in regions 1, 2, and 9, whereas LVAD-M was highest in regions 9, 1, and 7. The incidence of LVAD-TE and LVAD-M increased after 2011 from 0.04 to 0.10 and from 0.03 to 0.08 events per patient-year ( p < 0.0001 for both comparisons). Survival on the waiting list at 2 years was lower in candidates with LVAD-TE (45% vs 72%, p < 0.0001) and LVAD-M (56% vs 71%, p = 0.003) compared with candidates without complications. Post-HT survival was similar between patients with and without LVAD-TE and LVAD-M ( p > 0.43 for both outcomes). In patients with LVAD-TE, mortality risk was highest among candidates managed conservatively (hazard ratio, 8.07; p < 0.0001), whereas patients who underwent HT only (hazard ratio, 0.10; p < 0.0001) had the lowest mortality risk and similar to that of patients without LVAD-TE ( p = 0.34). Conclusions The incidence of LVAD-TE and LVAD-M on the United States waiting list has increased since 2011, with significant regional variation. LVAD-TE and LVAD-M have a detrimental effect on waiting list survival and transplant candidacy. In candidates who develop an LVAD-TE, a conservative approach, without LVAD exchange or HT, carries the highest risk of death. These results should be considered in the ongoing efforts to optimize the allocation of donor hearts. [ABSTRACT FROM AUTHOR]

Background: Our current understanding of right heart failure (RHF) post-left ventricular assist device (LVAD) is lacking. Recently, a new Interagency Registry for Mechanically Assisted Circulatory Support definition of RHF was introduced. Based on this definition, we investigated natural history, risk factors, and outcomes of post-LVAD RHF. Methods: Patients implanted with continuous flow LVAD between June 2, 2014, and June 30, 2016 and registered in the Interagency Registry for Mechanically Assisted Circulatory Support/Society of Thoracic Surgeons Database were included. RHF incidence and predictors, and survival after RHF were assessed. The manifestations of RHF which were separately analyzed were elevated central venous pressure, peripheral edema, ascites, and use of inotropes. Results: Among 5537 LVAD recipients (mean 57±13 years, 49% destination therapy, support 18.9 months) prevalence of 1-month RHF was 24%. Of these, RHF persisted at 12 months in 5.3%. In contrast, de novo RHF, first identified at 3 months, occurred in 5.1% and persisted at 12 months in 17% of these, and at 6 months occurred in 4.8% and persisted at 12 months in 25%. Higher preimplant blood urea nitrogen (ORs,1.03–1.09 per 5 mg/dL increase; P <0.0001), previous tricuspid valve repair/replacement (ORs, 2.01–10.09; P <0.001), severely depressed right ventricular systolic function (ORs,1.17–2.20; P =0.004); and centrifugal versus axial LVAD (ORs,1.15–1.78; P =0.001) represented risk factors for RHC incidence at 3 months. Patients with persistent RHF at 3 months had the lowest 2-year survival (57%) while patients with de novo RHF or RHF which resolved by 3 months had more favorable survival outcomes (75% and 78% at 2 years, respectively; P <0.001). Conclusions: RHF at 1 or 3 months post-LVAD was a common and frequently transient condition, which, if resolved, was associated with relatively favorable prognosis. Conversely, de novo, late RHF post-LVAD (>6 months) was more frequently a persistent disorder and associated with increased mortality. The 1-, 3-, and 6-month time points may be used for RHF assessment and risk stratification in LVAD recipients. [ABSTRACT FROM AUTHOR]