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.

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.

Ischemic heart disease: Cellular and molecular immune contributions of the pericardium.

Ischemic heart disease promotes complex inflammatory and remodeling pathways which contribute to the development of chronic heart failure. Although blood-derived and local cardiac mediators have traditionally been linked with these processes, the pericardial space has more recently been noted as alternative contributor to the injury response in the heart. The pericardial space contains fluid rich in physiologically active mediators, and immunologically active adipose tissue, which are altered during myocardial infarction. Key immune cells in the pericardial fluid and adipose tissue have been identified which act as mediators for cell recruitment and function after myocardial infarction have been identified in experimental models. Here, we provide an overview of the current understanding of the inflammatory mechanisms of the pericardial space and their role in post-myocardial infarction remodeling and the potential for the use of the pericardial space as a delivery vehicle for treatments to modulate heart healing.

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.

Direct Effects of Empagliflozin on Extracellular Matrix Remodelling in Human Cardiac Myofibroblasts: Novel Translational Clues to Explain EMPA-REG OUTCOME Results.

BACKGROUND: Empagliflozin, an SGLT2 inhibitor, has shown remarkable reductions in cardiovascular mortality and heart failure admissions (EMPA-REG OUTCOME). However, the mechanism underlying the heart failure protective effects of empagliflozin remains largely unknown. Cardiac fibroblasts play an integral role in the progression of structural cardiac remodelling and heart failure, in part, by regulating extracellular matrix (ECM) homeostasis. The objective of this study was to determine if empagliflozin has a direct effect on human cardiac myofibroblast-mediated ECM remodelling. METHODS: Cardiac fibroblasts were isolated via explant culture from human atrial tissue obtained at open heart surgery. Collagen gel contraction assay was used to assess myofibroblast activity. Cell morphology and cell-mediated ECM remodelling was examined with the use of confocal microscopy. Gene expression of profibrotic markers was assessed with the use of reverse-transcription quantitative polymerase chain reaction. RESULTS: Empagliflozin significantly attenuated transforming growth factor ß1-induced fibroblast activation via collagen gel contraction after 72-hour exposure, with escalating concentrations (0.5 µmol/L, 1 µmol/L, and 5 µmol/L) resulting in greater attenuation. Morphologic assessment showed that myofibroblasts exposed to empagliflozin were smaller in size with shorter and fewer number of extensions, indicative of a more quiescent phenotype. Moreover, empagliflozin significantly attenuated cell-mediated ECM remodelling as measured by collagen fibre alignment index. Gene expression profiling revealed significant suppression of critical profibrotic markers by empagliflozin, including COL1A1, ACTA2, CTGF, FN1, and MMP-2. CONCLUSIONS: We provide novel data showing a direct effect of empagliflozin on human cardiac myofibroblast phenotype and function by attenuation of myofibroblast activity and cell-mediated collagen remodelling. These data provide critical insights into the profound effects of empagliflozin as noted in the EMPA-REG OUTCOME study.