Minimally Invasive Approaches to Mitral Valve Surgery: Where Are We Now? A Narrative Review.

Minimally invasive mitral valve surgery (MiMVS) has been increasing in prevalence. This review will focus on the approaches, the clinical outcomes, and patient selection for MiMVS. There are four minimally invasive approaches to the mitral valve: Right mini-thoracotomy, both video-assisted and fully endoscopic, robotic mitral surgery, and transapical, beating heart off-pump neochordal repair. Advantages over conventional surgery include less blood loss and transfusion, improved postoperative mobility, shorter length of stay, less postoperative atrial fibrillation, fewer surgical site infections, and improved cosmesis. This range of minimally invasive techniques will continue to evolve, providing options that are tailored for different patient populations.

Micronized Acellular Matrix Biomaterial Leverages Eosinophils for Postinfarct Cardiac Repair.

After ischemic injury, immune cells mediate maladaptive cardiac remodeling. Extracellular matrix biomaterials may redirect inflammation toward repair. Pericardial fluid contains pro-reparative immune cells, potentially leverageable by biomaterials. Herein, we explore how pericardial delivery of a micronized extracellular matrix biomaterial affects cardiac healing. In noninfarcted mice, pericardial delivery increases pericardial and myocardial eosinophil counts. This response is sustained after myocardial infarction, stimulating an interleukin 4 rich milieu. Ultimately, the biomaterial improves postinfarct vascularization and cardiac function; and eosinophil-knockout negates these benefits. For the first time, to our knowledge, we demonstrate the therapeutic potential of pericardial biomaterial delivery and the eosinophil's critical role in biomaterial-mediated postinfarct repair.

Acellular biomaterial modulates myocardial inflammation and promotes endogenous mechanisms of postinfarct cardiac repair.

OBJECTIVE: After myocardial infarction, we previously showed that epicardial implantation of porcine small intestinal submucosal extracellular matrix (SIS-ECM) improves postinfarct cardiac function through fibroblast-mediated angiogenic and antifibrotic pathways. Herein, we characterize how SIS-ECM also coordinates a reparative cardiac inflammatory response. METHODS: RNA sequencing and multiplex characterized modulation of fibroblast transcriptional and paracrine activity by SIS-ECM. Inhibitors of fibroblast growth factor 2 and toll-like receptor 9 elucidated mechanism. Mice received coronary ligation (infarction) and either SIS-ECM implantation (treatment) or sham surgery (control). Flow cytometry of SIS-ECM and the murine myocardium quantified monocytes, neutrophils, and proangiogenic subtypes. Microscopy tracked fibroblasts and immune cells, and characterized myocardial angiogenesis. RESULTS: SIS-ECM increased fibroblast transcription of inflammatory pathways and production of angiogenic vascular endothelial growth factor and inflammatory cytokines via fibroblast growth factor 2 and toll-like receptor 9-dependent pathways. Two-photon microscopy showed that SIS-ECM became engrafted by native fibroblasts and leukocytes, subsequently increasing release of inflammatory cytokines and angiogenic vascular endothelial growth factor. On flow cytometry, SIS-ECM implantation increased day-7 myocardial counts of neutrophils, inflammatory monocytes, and proangiogenic vascular endothelial growth factor recptor 1 subtypes. SIS-ECM has a higher proportion of proangiogenic leukocytes compared with the myocardium. Resonant confocal microscopy showed neovascularization near SIS-ECM. CONCLUSIONS: SIS-ECM promotes engraftment by native fibroblasts and leukocytes, and modulates fibroblast activity via fibroblast growth factor 2 and toll-like receptor 9 to potentiate a proangiogenic inflammatory response. Subsequently, the material increases myocardial counts of reparative proangiogenic leukocytes that can induce neovascularization. This reparative inflammatory response may explain previously reported functional improvements. Fibroblast growth factor 2 and toll-like receptor 9 mechanisms can be leveraged to design next-generation materials for postinfarct cardiac repair.

Novel hardening bone putty enhances sternal closure and accelerates postoperative recovery.

OBJECTIVES: Regaining and maintaining sternal stability are key to recovery after cardiac surgery and resuming baseline quality of life. Montage (ABYRX) is a moldable, calcium phosphate-based putty that adheres to bleeding bone, hardens after application, and is resorbed and replaced with bone during the remodeling process. We evaluate the feasibility, safety, and efficacy of enhanced sternal closure with this novel putty to accelerate recovery in patients after sternotomy. METHODS: A single-center, single-blinded, randomized controlled trial was performed (NCT03365843). Patients undergoing elective cardiac surgery via sternotomy received sternal closure with either Montage bone putty and wire cerclage (enhanced sternal closure; n = 33) or wire cerclage alone (control; n = 27). Standardized patient-reported outcomes assessed health-related quality of life (EQ-5D Index) and physical disability (Health Assessment Questionnaire). A Likert-type 11-point scale quantified pain. Spirometry assessed respiratory function. Patients reached 6-week follow-up, with 1-year follow-up for safety end points. RESULTS: There were no device-related adverse events. Enhanced sternal closure improved physical functional recovery (reduced Healthcare Index and Quality) and quality of life (increased EQ-5D Index) at day 5/discharge, week 2, and week 4. Enhanced sternal closure reduced incisional pain while resting, breathing, sleeping, and walking at day 5/discharge. Enhanced sternal closure reduced chest wall and back pain at day 3 and day 5 discharge. A higher proportion of patients with enhanced sternal closure recovered to 60% of their baseline forced vital capacity by day 5/discharge. Enhanced sternal closure shortened hospital stay. CONCLUSIONS: Enhanced sternal closure improves and accelerates postoperative recovery compared with conventional wire closure. Earlier discharge may provide substantial cost benefits for the healthcare system.

Sternum-Sparing Left Ventricular Assist Device Insertion Reduces Perioperative Transfusions and Blood Loss: A Single-Centre Canadian Experience.

Background: Left ventricular assist devices (LVADs) improve survival and quality of life, as either destination therapy or a bridge to transplantation. Although less-invasive hemisternotomy approaches for LVAD implantation are well studied, only a paucity of data is available in the literature on sternum-sparing bilateral minithoracotomy (BMT). Our centre has one of Canada's most extensive experiences with the BMT approach. Herein, we compared LVAD implantation via BMT with patients who received full median sternotomy or hemisternotomy. Methods: A single-centre retrospective review of data from Foothills Medical Centre (Calgary, Canada) was performed. Patients underwent LVAD insertion from 2012 to 2019, receiving either BMT (n = 11) or sternotomy (full median sternotomy or upper hemisternotomy with left minithoracotomy; n = 38). Intraoperative and early postoperative outcomes were assessed. Results: Patients who received BMT had significantly fewer transfusions of red blood cells, fresh frozen plasma, and platelets. The BMT group had lower chest-tube output in the first 12 hours. No significant differences occurred in ventilation time, intensive care unit length of stay, mortality, stroke, or reoperation for bleeding. Conclusions: Outcomes suggest that sternum-sparing LVAD implantation is a feasible alternative to sternotomy, leading to less postoperative blood loss and transfusion in the early postoperative period. Less transfusion is particularly valuable in this patient population, to reduce antigen-related sensitization prior to transplantation. Additional study is needed to assess potential benefits related to right heart function, postoperative mobility, and re-entry for transplantation.

Introduction: Les dispositifs d'assistance ventriculaire gauche (DAVG) contribuent à améliorer la survie et la qualité de vie, soit en traitement définitif ou en attente d'une transplantation. Bien que des approches d'hémisternotomie moins invasives lors de l'implantation d'un DAVG font l'objet d'un bon nombre d'études, seules de rares données sont disponibles dans la littérature sur la minithoracotomie bilatérale (MTB) sans ouverture du sternum. Notre centre possède l'une des expériences les plus approfondies au Canada de l'approche par MTB. Dans le présent article, nous avons comparé l'implantation du DAVG par MTB chez les patients qui avaient subi une sternotomie médiane complète ou une hémisternotomie. Méthodes: Nous avons réalisé une revue rétrospective unicentrique des données du Foothills Medical Centre (Calgary, Canada). Les patients avaient subi l'insertion d'un DAVG de 2012 à 2019, soit par MTB (n = 11) ou par sternotomie (sternotomie médiane complète ou hémisternotomie supérieure associée à une minithoracotomie gauche ; n = 38). Nous avons évalué les résultats peropératoires et postopératoires précoces. Résultats: Les patients qui avaient subi une MTB avaient eu significativement moins de transfusions de globules rouges, de plasma frais congelé et de plaquettes. Le groupe de MTB avait un plus faible débit du drain thoracique dans les 12 premières heures. Aucune différence significative dans la durée de ventilation, la durée du séjour aux soins intensifs, la mortalité, l'accident vasculaire cérébral ou la réopération en raison d'un saignement n'a été observée. Conclusions: Les résultats montrent que l'implantation de DAVG sans ouverture du sternum est une alternative à la sternotomie, qui entraîne moins de pertes de sang postopératoires et de transfusions en phase postopératoire précoce. Un moins grand nombre de transfusions est particulièrement important au sein de cette population de patients afin de réduire la sensibilisation aux antigènes avant la transplantation. D'autres études sont nécessaires pour évaluer les avantages potentiels liés à la fonction du cœur droit, la mobilité après l'opération et la réadmission pour une transplantation.

Dye-Mediated Photo-Oxidation Biomaterial Fixation: Analysis of Bioinductivity and Mechanical Properties of Bovine Pericardium for Use in Cardiac Surgery.

Extracellular matrix bioscaffolds can influence the cardiac microenvironment and modulate endogenous cellular mechanisms. These materials can optimize cardiac surgery for repair and reconstruction. We investigated the biocompatibility and bioinductivity of bovine pericardium fixed via dye-mediated photo-oxidation on human cardiac fibroblast activity. We compared a dye-mediated photo-oxidation fixed bioscaffold to glutaraldehyde-fixed and non-fixed bioscaffolds reported in contemporary literature in cardiac surgery. Human cardiac fibroblasts from consenting patients were seeded on to bioscaffold materials to assess the biocompatibility and bioinductivity. Human cardiac fibroblast gene expression, secretome, morphology and viability were studied. Dye-mediated photo-oxidation fixed acellular bovine pericardium preserves human cardiac fibroblast phenotype and viability; and potentiates a pro-vasculogenic paracrine response. Material tensile properties were compared with biomechanical testing. Dye-mediated photo-oxidation fixed acellular bovine pericardium had higher compliance compared to glutaraldehyde-fixed bioscaffold in response to tensile force. The biocompatibility, bioinductivity, and biomechanical properties of dye-mediated photo-oxidation fixed bovine pericardium demonstrate its feasibility as a bioscaffold for use in cardiac surgery. As a fixed yet bioinductive solution, this bioscaffold demonstrates enhanced compliance and retains bioinductive properties that may leverage endogenous reparative pathways. Dye-mediated photo-oxidation fixed bioscaffold warrants further investigation as a viable tool for cardiac repair and reconstruction.

An Intact Pericardium Ischemic Rodent Model.

This protocol has shown that the pericardium and its contents play an essential anti-fibrotic role in the ischemic rodent model (coronary ligation to induce myocardial injury). The majority of pre-clinical myocardial infarction models require the disruption of pericardial integrity with loss of the homeostatic cellular milieu. However, recently a methodology has been developed by us to induce myocardial infarction, which minimizes pericardial damage and retains the heart's resident immune cell population. An improved cardiac functional recovery in mice with an intact pericardial space following coronary ligation has been observed. This method provides an opportunity to study inflammatory responses in the pericardial space following myocardial infarction. Further development of the labeling techniques can be combined with this model to understand the fate and function of pericardial immune cells in regulating the inflammatory mechanisms that drive remodeling in the heart, including fibrosis.

Prevention of Post-Operative Adhesions: A Comprehensive Review of Present and Emerging Strategies.

Post-operative adhesions affect patients undergoing all types of surgeries. They are associated with serious complications, including higher risk of morbidity and mortality. Given increased hospitalization, longer operative times, and longer length of hospital stay, post-surgical adhesions also pose a great financial burden. Although our knowledge of some of the underlying mechanisms driving adhesion formation has significantly improved over the past two decades, literature has yet to fully explain the pathogenesis and etiology of post-surgical adhesions. As a result, finding an ideal preventative strategy and leveraging appropriate tissue engineering strategies has proven to be difficult. Different products have been developed and enjoyed various levels of success along the translational tissue engineering research spectrum, but their clinical translation has been limited. Herein, we comprehensively review the agents and products that have been developed to mitigate post-operative adhesion formation. We also assess emerging strategies that aid in facilitating precision and personalized medicine to improve outcomes for patients and our healthcare system.

The CorMatrix Cor™ PATCH for epicardial infarct repair.

Contemporary management of ischemic heart disease lacks strategies to directly access the heart and promote reparative cellular mechanisms to improve postinfarct cardiac remodeling. Epicardial infarct repair (EIR) is an emerging technique whereby bioactive materials are sewn over ischemic areas of the heart at the time of surgical revascularization to promote adaptive cardiac repair. The CorMatrix Cor™ PATCH (CorMatrix Cardiovascular Inc., GA, USA) is an acellular bioactive material compatible with EIR. Herein, we review current preclinical and clinical data for the CorMatrix Cor PATCH and its use in EIR.

Lay abstract Therapies for heart attacks include revascularization and medical therapy, but clinicians lack methods of stimulating cells to improve cardiac repair and reduce cardiac fibrosis. Epicardial infarct repair (EIR) is an emerging technique where biomaterials are sewn over areas of the heart damaged by heart attacks. These materials have properties to stimulate repair at a cellular level. This procedure can be performed by cardiac surgeons during coronary artery bypass surgery. The CorMatrix Cor™ PATCH (CorMatrix Cardiovascular Inc., GA, USA) is a biomaterial compatible with EIR. Herein, we review the CorMatrix Cor PATCH and discuss its use in EIR.

Promoting Cardiac Regeneration and Repair Using Acellular Biomaterials.

Ischemic heart disease is a common cause of end-stage heart failure and has persisted as one of the main causes of end stage heart failure requiring transplantation. Maladaptive myocardial remodeling due to ischemic injury involves multiple cell types and physiologic mechanisms. Pathogenic post-infarct remodeling involves collagen deposition, chamber dilatation and ventricular dysfunction. There have been significant improvements in medication and revascularization strategies. However, despite medical optimization and opportunities to restore blood flow, physicians lack therapies that directly access and manipulate the heart to promote healthy post-infarct myocardial remodeling. Strategies are now arising that use bioactive materials to promote cardiac regeneration by promoting angiogenesis and inhibiting cardiac fibrosis; and many of these strategies leverage the unique advantage of cardiac surgery to directly visualize and manipulate the heart. Although cellular-based strategies are emerging, multiple barriers exist for clinical translation. Acellular materials have also demonstrated preclinical therapeutic potential to promote angiogenesis and attenuate fibrosis and may be able to surmount these translational barriers. Within this review we outline various acellular biomaterials and we define epicardial infarct repair and intramyocardial injection, which focus on administering bioactive materials to the cardiac epicardium and myocardium respectively to promote cardiac regeneration. In conjunction with optimized medical therapy and revascularization, these techniques show promise to upregulate pathways of cardiac regeneration to preserve heart function.

Minimally Invasive Surgical Aortic Valve Replacement: An Overview of Recent Advances.

Aortic valve replacement (AVR) is the only definitive treatment for severe aortic stenosis. Options for valve replacement include surgical AVR (SAVR) and percutaneous transcatheter AVR. Although transcatheter AVR has recently been shown to be the optimal approach for high-risk patients, SAVR is the gold standard for patients with low and intermediate surgical risk. Advances in technique and innovations in rapid-deployment and sutureless valves have facilitated the development of a third alternative. Accumulating evidence suggests that minimally invasive SAVR can be performed as safely as conventional SAVR, and perhaps with less morbidity, allowing patients a quicker return to their productive lives. The following discussion outlines the surgical technique, patient selection and advances in valve design.

Perceval Valve Implantation: Technical Details and Echocardiographic Assessment.

The Perceval valve (LivaNova, London, United Kingdom) is a collapsible, sutureless bioprosthetic aortic valve. This novel design is well suited for minimally invasive approaches and has particular advantages for patients with small, calcified annuli. The implantation technique is unique, and echocardiographic assessments of valve cage shape, angulation, and height are essential. The following discussion provides a framework of technical and sonographic considerations to help surgical teams achieve reproducible success with Perceval valve deployment.

Initial Canadian Experience With Bilateral Minithoracotomy Approach for HeartMate 3 Left Ventricular Assist Device Implantation.

Left ventricular assist devices provide hemodynamic support to improve quality of life and long-term survival in patients with end-stage heart failure. The HeartMate 3 (Abbott, Abbott Park, IL) left ventricular assist device uses magnetically levitated impeller technology, improving durability and reducing pump thrombosis. Sternum-sparing implantation may reduce perioperative bleeding and infection, improve mobility, decrease hospitalization duration, and reduce right ventricular dysfunction. We describe the first Canadian HeartMate 3 implantation via bilateral minithoracotomy. Our case supports the compatibility of the HeartMate 3 device with sternum-sparing approaches and highlights the feasibility of intrapericardial tunnelling of the outflow graft.

Les dispositifs d'assistance ventriculaire gauche procurent un soutien hémodynamique permettant d'améliorer la qualité de vie et la survie à long terme chez les patients présentant une insuffisance cardiaque terminale. Le dispositif d'assistance ventriculaire gauche HeartMate 3 (Abbott, Abbott Park, IL) fait appel à une pompe à flux centrifuge à lévitation magnétique, qui rehausse la durabilité de l'appareil et réduit le risque de thrombose de la pompe. L'implantation sans sternotomie peut diminuer le risque d'hémorragie périopératoire et d'infection, favoriser la mobilité, réduire la durée de l'hospitalisation et atténuer la dysfonction ventriculaire droite. Nous décrivons la première implantation d'un dispositif HeartMate 3 réalisée au Canada par minithoracotomie bilatérale. Le cas présenté montre la possibilité d'implanter le dispositif HeartMate 3 sans sternotomie et met en lumière la faisabilité d'une tunnellisation intrapéricardique de la prothèse d'éjection.

Mechanical Mitral Valve Thrombosis Secondary to Tinzaparin as an Anticoagulation Bridging Strategy.

For patients with mechanical heart valves, oral vitamin K antagonists effectively reduce the risk of valve thrombosis. Bridging strategies that use intravenous unfractionated heparin or subcutaneous low molecular weight heparin (LMWH) are required when reversal of anticoagulation is needed for invasive procedures or bleeding complications. There is limited data comparing anticoagulation efficacy between subtypes of LMWH and dosing regimens in this context. This report describes the case of a 45-year-old man with acute mechanical mitral valve thrombosis and suggests that the use of once daily dosing of subcutaneous tinzaparin may be an inappropriate anticoagulation bridging strategy.