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Background: Noninvasive monitoring of heart allograft health is important to improve clinical outcomes. MicroRNAs (miRs) are promising biomarkers of cardiovascular disease and limited studies suggest they can be used to noninvasively diagnose acute heart transplant rejection., Methods: The Genomic Research Alliance for Transplantation (GRAfT) is a multicenter prospective cohort study that phenotyped heart transplant patients from 5 mid-Atlantic centers. Patients who had no history of rejection after transplant were compared to patients with acute cellular rejection (ACR) or antibody-mediated rejection (AMR). Small RNA sequencing was performed on plasma samples collected at the time of an endomyocardial biopsy. Differential miR expression was performed with adjustment for clinical covariates. Regression was used to develop miR panels with high diagnostic accuracy for ACR and AMR. These panels were then validated in independent samples from GRAfT and Stanford University. Receiver operating characteristic curves were generated and area under the curve (AUC) statistics calculated. Distinct ACR and AMR clinical scores were developed to translate miR expression data for clinical use., Results: The GRAfT cohort had a median age of 52 years, with 35% females and 45% Black patients. Between GRAfT and Stanford, we included 157 heart transplant patients: 108 controls and 49 with rejection (50 ACR and 38 AMR episodes). After differential miR expression and regression analysis, we identified 12 miRs that accurately discriminate ACR and 17 miRs in AMR. Independent validation of the miR panels within GRAfT led to an ACR AUC 0.92 (95% confidence interval [CI]: 0.86-0.98) and AMR AUC 0.82 (95% CI: 0.74-0.90). The externally validated ACR AUC was 0.72 (95% CI: 0.59-0.82). We developed distinct ACR and AMR miR clinical scores (range 0-100), a score ≥ 65, identified ACR with 86% sensitivity, 76% specificity, and 98% negative predictive value, for AMR score performance was 82%, 84% and 97%, respectively., Conclusions: We identified novel miRs that had excellent performance to noninvasively diagnose acute rejection after heart transplantation. Once rigorously validated, the unique clinical ACR and AMR scores usher in an era whereby genomic biomarkers can be used to screen and diagnose the subtype of rejection. These novel biomarkers may potentially alleviate the need for an endomyocardial biopsy while facilitating the initiation of targeted therapy based on the noninvasive diagnosis of ACR or AMR., (Copyright © 2022 International Society for Heart and Lung Transplantation. All rights reserved.)

Black patients suffer higher rates of antibody-mediated rejection and have worse long-term graft survival after heart transplantation. Donor-derived cell free DNA (ddcfDNA) is released into the blood following allograft injury. This study analyzed %ddcfDNA in 63 heart transplant recipients categorized by Black and non-Black race, during the first 200 days after transplant. Immediately after transplant, %ddcfDNA was higher for Black patients (mean [SE]: 8.3% [1.3%] vs 3.2% [1.2%], p = 0.001). In the first week post-transplant, the rate of decay in %ddcfDNA was similar (0.7% [0.68] vs 0.7% [0.11], p = 0.78), and values declined in both groups to a comparable plateau at 7 days post-transplant (0.46% [0.03] vs 0.45% [0.04], p = 0.78). The proportion of Black patients experiencing AMR was higher than non-Black patients (21% vs 9% [hazard ratio of 2.61 [95% confidence interval: 0.651-10.43], p = 0.18). Black patients were more likely to receive a race mismatched organ than non-Black patients (69% vs 35%, p = 0.01), which may explain the higher levels of early allograft injury., (Copyright © 2022. Published by Elsevier Inc.)

The HeartWare HVAD System (Medtronic) is a durable implantable left ventricular assist device that has been implanted in approximately 20,000 patients worldwide for bridge to transplant and destination therapy indications. In December 2020, Medtronic issued an Urgent Medical Device Communication informing clinicians of a critical device malfunction in which the HVAD may experience a delay or failure to restart after elective or accidental discontinuation of pump operation. Moreover, evolving retrospective comparative effectiveness studies of patients supported with the HVAD demonstrated a significantly higher risk of stroke and all-cause mortality when compared with a newer generation of a commercially available durable left ventricular assist device. Considering the totality of this new information on HVAD performance and the availability of an alternate commercially available device, Medtronic halted the sale and distribution of the HVAD System in June 2021. The decision to remove the HVAD from commercial distribution now requires the use of the HeartMate 3 left ventricular assist system (Abbott, Inc) if a patient previously implanted with an HVAD requires a pump exchange. The goal of this document is to review important differences in the design of the HVAD and HeartMate 3 that are relevant to the medical management of patients supported with these devices, and to assess the technical aspects of an HVAD-to-HeartMate 3 exchange. This document provides the best available evidence that supports best practices., (Copyright © 2022 The Society of Thoracic Surgeons, The American Association for Thoracic Surgery, and European Association for Cardio-Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Clinical Trials in Organ Transplantation-18 (CTOT-18) is a follow-up analysis of the 200-subject multicenter heart transplant CTOT-05 cohort. CTOT-18 aimed to identify clinical, epidemiologic, and biologic markers associated with adverse clinical events past 1 year posttransplantation. We examined various candidate biomarkers including serum antibodies, angiogenic proteins, blood gene expression profiles, and T cell alloreactivity. The composite endpoint (CE) included death, retransplantation, coronary stent, myocardial infarction, and cardiac allograft vasculopathy. The mean follow-up was 4.5 ± SD 1.1 years. Subjects with serum anti-cardiac myosin (CM) antibody detected at transplantation and at 12 months had a higher risk of meeting the CE compared to those without anti-CM antibody (hazard ratio [HR] = 2.9, P = .046). Plasma VEGF-A and VEGF-C levels pretransplant were associated with CE (odds ratio [OR] = 13.24, P = .029; and OR = 0.13, P = .037, respectively). Early intravascular ultrasound findings or other candidate biomarkers were not associated with the study outcomes. In conclusion, anti-CM antibody and plasma levels of VEGF-A and VEGF-C were associated with an increased risk of adverse events. Although this multicenter report supports further evaluation of the mechanisms through which anti-CM antibody and plasma angiogenesis proteins lead to allograft injury, we could not identify additional markers of adverse events or potential novel therapeutic targets., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: The feasibility of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) for the diagnosis of left ventricular assist device (LVAD) infection has been demonstrated. Beyond the diagnoses of LVAD infection, the authors hypothesized that the pattern and site of the infection along its various components may significantly impact clinical management and patient outcome., Background: In patients with end-stage heart failure, the clinical use of LVAD for destination therapy is on the rise, accompanied by a higher prevalence of infections and serious complications., Methods: FDG PET/CT was performed in 35 heart failure patients with LVAD, 24 with and 11 without clinical suspicion of infection. Microbiology and/or clinical follow-up were used as the final diagnosis standard. Survival rates were compared in patients with and without FDG evidence of infection, and in relation to peripheral (exit wound site or driveline) versus central (cannula or pump) device infection., Results: Of 35 patients, 28 (80%) showed metabolic evidence of LVAD infection: 5 limited to the periphery and 23 with extension to the central components of the device. The remaining 7 patients showed no metabolic evidence of infection, which was confirmed by microbiology and clinical follow-up. When CT images were interpreted independently from the FDG PET and clinical information, only 4 of 35 (11%) suggested the possibility of infection. Fourteen of 28 (50%) infected patients died during a mean of 23 months of follow-up after the diagnosis by FDG PET/CT: 12 (86%) with central infection and only 2 with peripheral infection. By contrast, none of the 7 (0%) noninfected patients died (p = 0.03)., Conclusions: FDG PET/CT is a useful technique for identifying LVAD infection and determining the site and pattern of the infection. The latter has clinical management and patient outcome implications., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: We previously investigated preoperative variables associated with qualitative inflow cannula malposition in the HeartMate II (Thoratec-Abbott, Abbott Park, IL) continuous-flow left ventricular assist device. In this report, we assess inflow cannula malposition quantitatively in recipients of both the HeartMate II and the HeartWare (Medtronic-HeartWare, Minneapolis, MN) and examine its association with device thrombosis., Methods: Malposition was quantified based on angular deviation from a hypothetic ideal inflow cannula position in two orthogonal computed tomography imaging planes. Ideal position lies on a line from the apex to the center of the mitral valve. Positive anterior plane angulation indicates deviation toward the superior free wall; negative, toward the inferior wall. Positive lateral plane angulation indicates deviation toward the septum; negative, toward the lateral wall. Device thrombosis was assessed based on clinical criteria., Results: Fifty-four HeartMate II patients and 68 HeartWare patients were analyzed. Inflow cannula deviation was significantly higher for HeartMate II than for HeartWare (anterior plane angle 36.7 ± 16.8 versus -18.7 ± 11.6 degrees, p < 0.001; lateral plane angle 23.7 ± 20.1 versus 0.2 ± 15.0 degrees, p < 0.001. Pump thrombosis occurred in 31% of HeartMate II patients and 2.9% of HeartWare patients (p < 0.001). In a multivariate model, HeartMate II and increasing inflow cannula deviation toward the septum were associated with higher thrombosis risk (odds ratio 1.35 per 10-degree increase)., Conclusions: We found distinct device-dependent differences in inflow cannula positioning and thrombosis, with HeartWare showing both less malposition and less thrombosis. Malposition toward the ventricular septum may contribute to pump thrombosis through a vicious cycle of suction events, low flow, and speed reduction., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The Jarvik 2000, an axial flow ventricular assist device (VAD), is currently under investigation for bridge to transplant (BTT) indications. The principal advantage of the Jarvik device is intraventricular pump placement. This eliminates the inflow cannula and pump pocket and allows for uncomplicated left ventricular implantation without sternotomy. Here we describe the evolution of our surgical implantation and explantation technique., Methods: Data for all patients undergoing implantation of a left VAD (LVAD) (n=35) at the University of Maryland between September 2002 and September 2010 were retrospectively reviewed. Preoperative patient demographics and clinical status and operative technique and outcomes were reviewed., Results: A simple technique for enclosing the pump and outflow graft greatly simplifies the explantation procedure and reduces the risk of lung adhesions and injury. Off-pump implantation reduces operative time and intraoperative red cell transfusions but carries a risk of incomplete ventricular coring, which may precipitate pump thrombosis. The benefits of the left thoracotomy approach were seen in the reduced need for intraoperative red cell transfusion and reduced total intensive care unit (ICU) stay for patients who had undergone previous sternotomy., Conclusions: The Jarvik 2000 has several distinctive features that simplify surgical management and permit flexible application in an expanded range of candidates for LVAD implantation, particularly in patients who have undergone previous sternotomy., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Despite concerns about the adequacy of support provided by continuous-flow left ventricular assist devices (LVADs), direct comparisons of patient characteristics and outcomes between first-generation pulsatile and second-generation nonpulsatile LVADs are absent. We hypothesized that a nonpulsatile Jarvik 2000 LVAD (Jarvik Heart, Inc, New York, NY) would result in comparable outcomes to those of similarly ill patients implanted with a pulsatile LVAD (Novacor, WorldHeart Inc, Oakland, CA; and HeartMate XVE, Thoratec, Pleasanton, CA)., Methods: We retrospectively compared common pre-LVAD clinical characteristics and indicators of heart failure severity between 13 pulsatile and 14 nonpulsatile LVAD recipients. The outcomes analyzed were either heart transplantation, if the LVAD was intended as a bridge to transplantation, or hospital discharge if the intention was destination therapy., Results: There was no significant difference between groups in pre-LVAD disease severity indicators. Nonpulsatile LVAD recipients had a significantly smaller body surface area (1.9 +/- 0.2 m2 versus 2.1 +/- 0.2 m2, p = 0.04) and cardiopulmonary bypass time was also significantly shorter (61 +/- 34 minutes versus 110 +/- 49 minutes, p = 0.01). Aside from duration of initial intensive care unit stay (nonpulsatile, 10 +/- 16 days; pulsatile, 14 +/- 11 days; p = 0.02), there was no difference in post-LVAD outcomes: 10 of 14 nonpulsatile and 8 of 13 pulsatile LVAD patients achieved the combined end point (p = 0.69)., Conclusions: Similarly ill congestive heart failure patients benefited equally well from either a nonpulsatile or a pulsatile LVAD. This may support an expanded role for nonpulsatile LVADs in the treatment of severe heart failure.

Acute heart failure and cardiogenic pulmonary edema is a common cause of respiratory distress among patients presenting to the emergency department. The emergency department is frequently the primary entry point into the health care system for these patients and is the site of initial stabilization, evaluation, and management of the patient.Emergency physicians, alongside cardiologists, play a critical role as these patients are treated in the emergency department and transferred to the cardiac ICU. The approach to the critically ill patient who has heart failure should be multidisciplinary and involve the emergency physician and the cardiologist who will care for the patient.