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      Use of left atrial appendage as an autologous tissue source for epicardial micrograft transplantation during LVAD implantation

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          Abstract

          We report here the first clinical use of the left atrial appendage (LAA) for epicardial micrograft transplantation during left ventricular assist device (LVAD) implantation. Previously, a sample from the right atrial appendage (RAA) has been available for processing and administering micrograft therapy in cardiac surgery. Both LAA and RAA are rich sources of various types of myocardial cells and are capable of providing both paracrine and cellular support to the failing myocardium. The surgical approach of LAA micrografting facilitates epicardial micrograft therapy dose escalation and treatment of larger myocardial areas than done previously. Moreover, as collection of treated vs. untreated tissues from the recipient heart is possible following LVAD implantation at the time of heart transplantation, the evaluation of the therapy's mechanism of action can be further deciphered at cellular and molecular levels. This LAA modification of the epicardial micrografting technique has the overall potential to facilitate the adoption of cardiac cell therapy during heart surgery.

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          Most cited references15

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          The left atrial appendage: our most lethal human attachment! Surgical implications.

          To prevent death from atrial fibrillation, a cardiac disease which kills by producing emboli. Atrial fibrillation causes about 25% of strokes and increases stroke rate by five times. Over 90% of these embolic strokes are from clots originating in the left atrial appendage. This study addresses the surgical feasibility of removing the appendage to prevent future deaths in two subcategories of patients. (1) Prophylactic removal during open-heart surgery to study its safety. Theoretically, as these patients age and some develop atrial fibrillation, protection from embolic strokes would already be present. (2) Therapeutic removal in chronic atrial fibrillation patients by means of a thorascopic approach. Its technical feasibility is demonstrated. Its actual stroke prevention potential awaits large studies. Appendectomy has been evaluated three ways. (1) Experimentally, thorascopic appendage removal was performed on 20 goats with endoscopic approach. Late studies showed a cleanly healed atrial closure after stapling, and no puckering of tissue as seen with the purse-string approach. (2) Safety of human appendectomy was demonstrated in 437 patients (1995-1997). Routine appendectomy was performed during open-heart surgery. Forty-three appendages were stapled, 391 sutured off. (3) Thorascopic appendectomy in seven patients with chronic atrial fibrillation has been successfully accomplished as an isolated surgical procedure. Stapling or suture closure provides a much cleaner, non-puckered suture line than a purse string. In prophylactic removal, no acute bleeding occurred. No late problems have been identified. Endoscopic removal of the appendage has been successful in seven atrial fibrillation patients. The left atrial appendage is a lethal source of emboli in atrial fibrillation patients. As patients age and often develop atrial fibrillation, prophylactic appendage removal whenever the chest is open is suggested as a method to prevent future strokes. In chronic atrial fibrillation patients, appendectomy can be done with a mini-thorascopic approach. Further studies are planned to demonstrate the effectiveness of appendectomy in preventing strokes in the chronic fibrillating patients.
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            A Prospective Multicentre Study of Myocardial Recovery Using Left Ventricular Assist Devices (REmission from Stage D Heart Failure: RESTAGE-HF): Medium Term and Primary Endpoint Results

            Background: Left ventricular assist device (LVAD) unloading and hemodynamic support in patients with advanced chronic heart failure can result in significant improvement in cardiac function allowing LVAD removal, however the rate of this is generally considered to be low. This prospective multicenter non-randomized study (RESTAGE-HF) investigated whether a protocol of optimized LVAD mechanical unloading, combined with standardized specific pharmacological therapy to induce reverse remodeling and regular testing of underlying myocardial function, could produce a higher incidence of LVAD explantation. Methods: Forty patients with chronic advanced heart failure from non-ischemic cardiomyopathy receiving the Heartmate II LVAD were enrolled from 6 centers. LVAD speed was optimized with an aggressive pharmacological regimen and regular echocardiograms were performed at reduced LVAD speed (6000rpm, no net flow) to test underlying myocardial function. The primary endpoint was the proportion of patients with sufficient improvement of myocardial function to reach criteria for explantation within 18 months with sustained remission from HF (freedom from transplant/VAD/death) at 12 months. Results: Prior to LVAD age was 35.1±10.8 years, 67.5% were male, heart failure mean duration was 20.8±20.6 months, 95% required inotropic and 20% temporary mechanical support, left ventricular ejection fraction (LVEF) was 14.5±5.3%, end-diastolic diameter (LVEDD) 7.33±0.89cm, end-systolic diameter (LVESD) 6.74±0.88cm, PA saturations were 46.7±9.2% and pulmonary capillary wedge pressure (PCWP) was 26.2±7.6mmHg. Four enrolled patients did not undergo the protocol due to medical complications unrelated to the study procedures. Overall 40% of all enrolled (16/40) patients achieved the primary endpoint, p<0.0001, with 50% (18/36) of patients receiving the protocol being explanted within 18 months (pre-explant LVEF 57±8%; LVEDD 4.81±0.58cm; LVESD 3.53±0.51cm; PCWP 8.1±3.1mmHg; PA sats 63.6±6.8% at 6000rpm). Overall 19 patients were explanted (19/36, 52.3% of those receiving the protocol). The fifteen ongoing explanted patients are now 2.26±0.97years post explant. Post-explantation survival free from LVAD or transplantation was 90% at 1-year and 77% at 2 and 3 years. Conclusions: In this multicenter prospective study, this strategy of LVAD support combined with a standardized pharmacologic and cardiac function monitoring protocol resulted in a high rate of LVAD explantation and was feasible and reproducible with explants occurred in all six participating sites.
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              Myocardial Recovery in Patients Receiving Contemporary Left Ventricular Assist Devices: Results From the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS).

              Time course and predictors of myocardial recovery on contemporary left ventricular assist device support are poorly defined because of limited number of recovery patients at any implanting center. This study sought to investigate myocardial recovery using multicenter data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS).
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                Author and article information

                Contributors
                Journal
                Front Cardiovasc Med
                Front Cardiovasc Med
                Front. Cardiovasc. Med.
                Frontiers in Cardiovascular Medicine
                Frontiers Media S.A.
                2297-055X
                28 April 2023
                2023
                : 10
                : 1143886
                Affiliations
                [ 1 ]Department of Cardiac-, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany
                [ 2 ]EpiHeart Oy , Helsinki, Finland
                [ 3 ]Department of Neuroscience and Biomedical Engineering, Aalto University , Espoo, Finland
                [ 4 ]Department of Pharmacology, Faculty of Medicine, University of Helsinki , Helsinki, Finland
                Author notes

                Edited by: Tomasz Zieliński, National Institute of Cardiology, Poland

                Reviewed by: Peter Lee, Brown University, United States Philippe Menasché, Assistance Publique Hopitaux De Paris, France

                [* ] Correspondence: Esko Kankuri esko.kankuri@ 123456helsinki.fi

                Abbreviations CABG, coronary artery bypass grafting; LVAD, left ventricular assist device.

                Article
                10.3389/fcvm.2023.1143886
                10176448
                37187792
                768860ff-0d8b-46e7-8b26-6942b3cab97a
                © 2023 Schmitto, Kuuva, Kronström, Hanke and Kankuri.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 13 January 2023
                : 10 April 2023
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 15, Pages: 0, Words: 0
                Funding
                Funded by: Helsinki University Library
                EpiHeart Oy and HBW srl contributed materials to this study. Open access funding was received from EpiHeart Oy. EpiHeart Oy were not involved in the study design, collection, analysis, interpretation of data, the writing of the article or the decision to submit it for publication.
                Categories
                Cardiovascular Medicine
                Brief Research Report
                Custom metadata
                Heart Failure and Transplantation

                autologous cardiac micrografts,cell therapy,epicardial transplantation,left ventricular assist device (lvad),left atrial appendage (laa),heart failure

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