Evaluating the Reparative Potential of Secretome from Patient-Derived Induced Pluripotent Stem Cells during Ischemia-Reperfusion Injury in Human Cardiomyocytes.

During a heart attack, ischemia causes losses of billions of cells; this is especially concerning given the minimal regenerative capability of cardiomyocytes (CMs). Heart remuscularization utilizing stem cells has improved cardiac outcomes despite little cell engraftment, thereby shifting focus to cell-free therapies. Consequently, we chose induced pluripotent stem cells (iPSCs) given their pluripotent nature, efficacy in previous studies, and easy obtainability from minimally invasive techniques. Nonetheless, using iPSC secretome-based therapies for treating injured CMs in a clinical setting is ill-understood. We hypothesized that the iPSC secretome, regardless of donor health, would improve cardiovascular outcomes in the CM model of ischemia-reperfusion (IR) injury. Episomal-generated iPSCs from healthy and dilated cardiomyopathy (DCM) donors, passaged 6-10 times, underwent 24 h incubation in serum-free media. Protein content of the secretome was analyzed by mass spectroscopy and used to treat AC16 immortalized CMs during 5 h reperfusion following 24 h of hypoxia. IPSC-derived secretome content, independent of donor health status, had elevated expression of proteins involved in cell survival pathways. In IR conditions, iPSC-derived secretome increased cell survival as measured by metabolic activity (p < 0.05), cell viability (p < 0.001), and maladaptive cellular remodelling (p = 0.052). Healthy donor-derived secretome contained increased expression of proteins related to calcium contractility compared to DCM donors. Congruently, only healthy donor-derived secretomes improved CM intracellular calcium concentrations (p < 0.01). Heretofore, secretome studies mainly investigated differences relating to cell type rather than donor health. Our work suggests that healthy donors provide more efficacious iPSC-derived secretome compared to DCM donors in the context of IR injury in human CMs. These findings illustrate that the regenerative potential of the iPSC secretome varies due to donor-specific differences.

Spontaneous coronary artery dissection: a difficult journey from emergency coronary artery bypass grafting to left ventricular assist device.

Background: Excluding spontaneous coronary artery dissection (SCAD) as an aetiology of acute coronary syndrome in young adults is imperative. Case summary: A previously healthy 39-year-old woman experienced sudden severe chest pain, ST-segment elevation on electrocardiogram, necessitating high-dose aspirin and urgent transfer to a revascularization centre. Suffering ventricular tachycardia (VT) and ventricular fibrillation (VF), she underwent two rounds of advanced life support and venoarterial extracorporeal membrane oxygenation. Diagnosed with left main coronary artery (LMCA) SCAD, she was initially started on conservative therapy for declining left ventricular ejection fraction. However, she continued to experience an escalating anginal symptoms, worsening biomarkers, and LMCA SCAD progression, which urged the need for surgical intervention with coronary artery bypass graft surgery (CABG). Following her CABG, she experienced a worsening of her functional mitral regurgitating, which she underwent transcatheter edge-to-edge repair of her severe mitral regurgitation. Despite being listed for orthotopic heart transplantation (OHTx), her low body mass index and elevated antibodies necessitated the HeartMate III left ventricular assist device (LVAD) for bridge to transplant. After treating frequent VT episodes with medications, she eventually received a LVAD as a bridge to cardiac transplantation. Within 1 year of her receiving LVAD, she underwent a successful OHTx. Discussion: The pathogenesis of SCAD involves intramural haematoma formation through intimal tears or vasa vasorum haemorrhage. Adverse outcomes that could occur in SCAD patients include cardiac arrest, cardiogenic shock, reduced left ventricle systolic function, and occasionally serious cardiac arrhythmia-such as VF-which can lead to sudden cardiac death. Although most SCAD cases heal spontaneously, revascularization can be considered in case of worsening SCAD progression. Advanced therapeutic intervention including mechanical circulatory support and OHTx should be considered in refractory cases.

Significance of the Wnt signaling pathway in coronary artery atherosclerosis.

Introduction: The progression of coronary atherosclerosis is an active and regulated process. The Wnt signaling pathway is thought to play an active role in the pathogenesis of several cardiovascular diseases; however, a better understanding of this system in atherosclerosis is yet to be unraveled. Methods: In this study, real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting were used to quantify the expression of Wnt3a, Wnt5a, and Wnt5b in the human coronary plaque, and immunohistochemistry was used to identify sites of local expression. To determine the pathologic significance of increased Wnt, human vascular smooth muscle cells (vSMCs) were treated with Wnt3a, Wnt5a, and Wnt5b recombinant proteins and assessed for changes in cell differentiation and function. Results: RT-PCR and Western blotting showed a significant increase in the expression of Wnt3a, Wnt5a, Wnt5b, and their receptors in diseased coronary arteries compared with that in non-diseased coronary arteries. Immunohistochemistry revealed an abundant expression of Wnt3a and Wnt5b in diseased coronary arteries, which contrasted with little or no signals in normal coronary arteries. Immunostaining of Wnt3a and Wnt5b was found largely in inflammatory cells and myointimal cells. The treatment of vSMCs with Wnt3a, Wnt5a, and Wnt5b resulted in increased vSMC differentiation, migration, calcification, oxidative stress, and impaired cholesterol handling. Conclusions: This study demonstrates the upregulation of three important members of canonical and non-canonical Wnt signaling pathways and their receptors in coronary atherosclerosis and shows an important role for these molecules in plaque development through increased cellular remodeling and impaired cholesterol handling.

Recurrent giant cell myocarditis following orthotopic heart transplant resulting in urgent redo orthotopic heart transplantation: a case report.

Background: Giant cell myocarditis (GCM) is a severe and rapidly progressing condition that can lead to end-stage heart failure. We present a case of a 51-year-old male with a history of orthotopic heart transplantation (OHTx) for GCM, who experienced recurrent GCM in the allograft, leading to progressive heart failure and the need for a second heart transplant. Case summary: A 51-year-old male with a history of OHTx for GCM presented with rapidly worsening heart failure symptoms. Despite initial stability, he deteriorated to cardiogenic shock and required intensive support. His clinical course was complicated by recurrent COVID-19 infections, worsened left ventricular ejection fraction, and withdrawal of guideline-directed medical therapy. Imaging showed extensive scar burden, and subsequent investigations ruled out coronary artery disease. With declining functional status and worsening cardiogenic shock, he was re-listed for OHTx and successfully underwent a second heart transplant. Discussion: Giant cell myocarditis poses challenges due to its aggressive nature. Early, aggressive immunosuppression and mechanical circulatory support are crucial. The recurrence rate of GCM post-OHTx is notable, often within the first year, and the optimal immunosuppressive regimen remains uncertain. In this case, GCM recurrence following OHTx led to continued deterioration despite treatment, necessitating a second heart transplant. This unique case emphasizes the complexity of managing recurrent GCM post-OHTx.

Measuring Single-Cell Calcium Dynamics Using a Myofilament-Localized Optical Biosensor in hiPSC-CMs Derived from DCM Patients.

Synchronized contractions of cardiomyocytes within the heart are tightly coupled to electrical stimulation known as excitation-contraction coupling. Calcium plays a key role in this process and dysregulated calcium handling can significantly impair cardiac function and lead to the development of cardiomyopathies and heart failure. Here, we describe a method and analytical technique to study myofilament-localized calcium signaling using the intensity-based fluorescent biosensor, RGECO-TnT. Dilated cardiomyopathy is a heart muscle disease that negatively impacts the heart's contractile function following dilatation of the left ventricle. We demonstrate how this biosensor can be used to characterize 2D hiPSC-CMs monolayers generated from a healthy control subject compared to two patients diagnosed with dilated cardiomyopathy. Lastly, we provide a step-by-step guide for single-cell data analysis and describe a custom Transient Analysis application, specifically designed to quantify features of calcium transients. All in all, we explain how this analytical approach can be applied to phenotype hiPSC-CM behaviours and stratify patient responses to identify perturbations in calcium signaling.

Hyperelastic Modeling and Validation of Hybrid-Actuated Soft Robot with Pressure-Stiffening.

Soft robots have gained popularity, especially in intraluminal applications, because their soft bodies make them safer for surgical interventions than flexures with rigid backbones. This study investigates a pressure-regulating stiffness tendon-driven soft robot and provides a continuum mechanics model for it towards using that in adaptive stiffness applications. To this end, first, a central single-chamber pneumatic and tri-tendon-driven soft robot was designed and fabricated. Afterward, the classic Cosserat's rod model was adopted and augmented with the hyperelastic material model. The model was then formulated as a boundary-value problem and was solved using the shooting method. To identify the pressure-stiffening effect, a parameter-identification problem was formulated to identify the relationship between the flexural rigidity of the soft robot and internal pressure. The flexural rigidity of the robot at various pressures was optimized to match theoretical deformation and experiments. The theoretical findings of arbitrary pressures were then compared with the experiment for validation. The internal chamber pressure was in the range of 0 to 40 kPa and the tendon tensions were in the range of 0 to 3 N. The theoretical and experimental findings were in fair agreement for tip displacement with a maximum error of 6.40% of the flexure's length.

Outcomes in Patients Undergoing Surgical Aortic Valve Replacement With vs Without a Preoperative Heart Team Assessment.

Background: This study sought to compare characteristics and outcomes of patients who underwent surgical aortic valve replacement (SAVR) after being referred to a heart team (HT), to those of patients referred directly for SAVR. Methods: An analysis of patients who underwent SAVR from 2015 to 2020 was conducted. Patients were categorized into 3 groups, as follows: (i) H-HT: patients referred to the HT from 2015 to 2017 (historical cohort); (ii) C-HT: patients referred to the HT from 2018 to 2020 (contemporary cohort); and (iii) No-HT: patients referred directly to cardiac surgery from 2018 to 2020. Two subanalyses were performed: H-HT vs C-HT patients, and C-HT vs No-HT patients. The primary outcome was a composite of in-hospital mortality, prolonged intubation, reoperation, sternal wound infection, and stroke. Results: This study consisted of 288 patients, distributed as follows: H-HT (n = 45); C-HT (n = 51); and No-HT (n = 192). The mean ages of H-HT, C-HT, and No-HT patients was 76.3 ± 6.9 years, 73.3 ± 7.6 years, and 69.6 ± 9.7 years, respectively (P = 0.0001). H-HT, C-HT, and No-HT patients had average Society of Thoracic Surgeons scores of 4.8 ± 2.2, 3.2 ± 1.6, and 4.2 ± 2 (P = 0.002), respectively. The composite outcome rate was more than 5 times higher among H-HT patients compared to that among the C-HT patients (20.0 vs 3.9%, P = 0.02), and was numerically higher in No-HT compared to C-HT patients (13.0 vs 3.9%, P = 0.07). Conclusions: Referral to an HT appears to be primarily driven by higher chronological age rather than overall risk profile. Patients assessed by the HT prior to undergoing SAVR have a low incidence of complications, comparable to that among patients referred directly to cardiac surgery.

Contexte: Cette étude visait à comparer les caractéristiques et le devenir de patients ayant subi une chirurgie de remplacement valvulaire aortique après avoir été orientés vers une équipe de cardiologie (EC) à ceux de patients orientés directement en chirurgie cardiaque pour une chirurgie de remplacement valvulaire aortique. Méthodologie: Une analyse portant sur les patients ayant subi une chirurgie de remplacement valvulaire aortique de 2015 à 2020 a été effectuée. Les patients ont été divisés en trois groupes, à savoir : i) CH-POEC : patients orientés vers une EC de 2015 à 2017 (cohorte historique); ii) CC-POEC : patients orientés vers une EC de 2018 à 2020 (cohorte contemporaine); iii) PODC : patients orientés directement en chirurgie cardiaque de 2018 à 2020. Deux sous-analyses ont été effectuées : CH-POEC vs CC-POEC, et CC-POEC vs PODC. Le paramètre d'évaluation principal était composite. Il comprenait la mortalité hospitalière, l'intubation prolongée, la réopération, l'infection de la plaie sternale et l'accident vasculaire cérébral. Résultats: L'étude regroupait 288 patients, répartis comme suit : CH-POEC, n = 45; CC-POEC, n = 51; PODC, n = 192. L'âge moyen dans les groupes CH-POEC, CC-POEC et PODC était respectivement de 76,3 ± 6,9 ans, 73,3 ± 7,6 ans et 69,6 ± 9,7 ans (P = 0,0001). Les groupes CH-POEC, CC-POEC et PODC présentaient des indices STS (Society of Thoracic Surgeons) moyens de 4,8 ± 2,2, 3,2 ± 1,6 et 4,2 ± 2 (P = 0,002), respectivement. Le taux composite d'événements au sein du groupe CH-POEC était plus de cinq fois supérieur à celui noté dans le groupe CC-POEC (20,0 vs 3,9 %, P = 0,02). Il était aussi plus élevé au sein du groupe PODC comparativement au groupe CC-POEC (13,0 vs 3,9 %, P = 0,07). Conclusions: Le principal motif d'orientation vers une EC semble être un âge chronologique avancé plutôt que le profil de risque global. Chez les patients qui sont évalués par une EC avant de subir une chirurgie de remplacement valvulaire aortique, l'incidence de complications est faible et comparable à celle observée chez les patients orientés directement en chirurgie cardiaque.

Patient-specific finite element analysis of heart failure and the impact of surgical intervention in pulmonary hypertension secondary to mitral valve disease.

Pulmonary hypertension (PH), a chronic and complex medical condition affecting 1% of the global population, requires clinical evaluation of right ventricular maladaptation patterns under various conditions. A particular challenge for clinicians is a proper quantitative assessment of the right ventricle (RV) owing to its intimate coupling to the left ventricle (LV). We, thus, proposed a patient-specific computational approach to simulate PH caused by left heart disease and its main adverse functional and structural effects on the whole heart. Information obtained from both prospective and retrospective studies of two patients with severe PH, a 72-year-old female and a 61-year-old male, is used to present patient-specific versions of the Living Heart Human Model (LHHM) for the pre-operative and post-operative cardiac surgery. Our findings suggest that before mitral and tricuspid valve repair, the patients were at risk of right ventricular dilatation which may progress to right ventricular failure secondary to their mitral valve disease and left ventricular dysfunction. Our analysis provides detailed evidence that mitral valve replacement and subsequent chamber pressure unloading are associated with a significant decrease in failure risk post-operatively in the context of pulmonary hypertension. In particular, right-sided strain markers, such as tricuspid annular plane systolic excursion (TAPSE) and circumferential and longitudinal strains, indicate a transition from a range representative of disease to within typical values after surgery. Furthermore, the wall stresses across the RV and the interventricular septum showed a notable decrease during the systolic phase after surgery, lessening the drive for further RV maladaptation and significantly reducing the risk of RV failure.

Extracellular Vesicles as a Cell-free Therapy for Cardiac Repair: a Systematic Review and Meta-analysis of Randomized Controlled Preclinical Trials in Animal Myocardial Infarction Models.

Stem cell therapy for cardiac regeneration has been gaining traction as a possible intervention for the reduction of the burden associated with MI and heart failure. However, stem cell therapies have several shortcomings, including poor engraftment, limited improvements in cardiac function, and possible teratogenicity. Recently, extracellular vesicles (EVs) from stem cell sources have been explored as a novel therapy to regenerate the injured myocardium in several animal MI trials. In this systematic review and meta-analysis, we investigate the use of stem cell-derived EVs for cardiac repair preclinical trials in animal MI models. Cochrane Library, Medline, Embase, PubMed, Scopus and Web of Science and grey literature (Canadian Agency for Drugs, Technologies in Health, and Google Scholar) were searched through August 20, 2020 and 37 articles were included in the final analysis. The overall effect size observed in EV-treated small animals after MI for ejection fraction (EF) was 10.85 [95 %CI: 8.79, 12.90] and for fractional shortening (FS) was 7.19 [95 %CI: 5.43, 8.96] compared to control-treated animals. The most abundant stem cell source used were mesenchymal stem cells which showed robust improvements in EF and FS (MD = 11.89 [95 % CI: 9.44, 14.34] and MD = 6.96 [95 % CI: 4.97, 8.96], respectively). Significant publication bias was detected for EF and FS outcomes. This study supports the use of EVs derived from stem cells as a novel therapy for cardiac repair after MI. Further investigation in larger animal studies may be necessary before clinical trials.PROSPERO registration number: CRD42019142218.

Amniotic stromal stem cell-loaded hydrogel repairs cardiac tissue in infarcted rat hearts via paracrine mediators.

The use of stem cells to repair the heart after a myocardial infarction (MI) remains promising, yet clinical trials over the past 20 years suggest that cells fail to integrate into the native tissue, resulting in limited improvements in cardiac function. Here, we demonstrate the cardioprotective potential of a composite inserting human amniotic stromal mesenchymal stem cells (ASMCs) in a chitosan and hyaluronic acid (C/HA) based hydrogel in a rat MI model. Mechanical characterization of the C/HA platform indicated a swift elastic conversion at 40°C and a rapid sol-gel transition time at 37°C. Cell viability assay presented active and proliferating AMSCs in the C/HA. The ASMCs + C/HA injected composite significantly increased left ventricular ejection fraction, fractional shortening, and neovessel formation. The encapsulated AMSCs were abundantly detected in the infarcted myocardium 6 weeks post-administration and co-expressed cardiac proteins and notably proliferative markers. Proteomic profiling revealed that extracellular vesicles released from hypoxia preconditioned ASMCs contained proteins involved in cytoprotection, angiogenesis, cardiac differentiation and non-canonical Wnt-signaling. Independent activation of non-canonical Wnt-signaling pathways in ASMCs induced cardiogenesis. Despite a low injected cellular density at baseline, the encapsulated AMSCs were abundantly retained and increased cardiac function. Furthermore, the C/HA hydrogel provided an active milieu for the AMSCs to proliferate, co-express cardiac proteins, and induce new vessel formation. Hence, this novel composite of AMSCs + C/HA scaffold is a conceivable candidate that could restore cardiac function and reduce remodeling.

Bioactive Scaffolds in Stem Cell-Based Therapies for Myocardial Infarction: a Systematic Review and Meta-Analysis of Preclinical Trials.

The use of bioactive scaffolds in conjunction with stem cell therapies for cardiac repair after a myocardial infarction shows significant promise for clinical translation. We performed a systematic review and meta-analysis of preclinical trials that investigated the use of bioactive scaffolds to support stem cell-aided cardiac regeneration, in comparison to stem cell treatment alone. Cochrane Library, Medline, Embase, PubMed, Scopus, Web of Science, and grey literature were searched through April 23, 2020 and 60 articles were included in the final analysis. The overall effect size observed in scaffold and stem cell-treated small animals compared to stem cell-treated controls for ejection fraction (EF) was 7.98 [95% confidence interval (CI): 6.36, 9.59] and for fractional shortening (FS) was 5.50 [95% CI: 4.35, 6.65] in small animal models. The largest improvements in EF and FS were observed when hydrogels were used (MD = 8.45 [95% CI: 6.46, 10.45] and MD = 5.76 [95% CI: 4.46, 7.05], respectively). Subgroup analysis revealed that cardiac progenitor cells had the largest effect size for FS, and was significant from pluripotent, mesenchymal and endothelial stem cell types. In large animal studies, the overall improvement of EF favoured the use of stem cell-embedded scaffolds compared to direct injection of cells (MD = 10.49 [95% CI: 6.30, 14.67]). Significant publication bias was present in the small animal trials for EF and FS. This study supports the use of bioactive scaffolds to aid in stem cell-based cardiac regeneration. Hydrogels should be further investigated in larger animal models for clinical translation.

Treatment of device thrombus in the HeartWare HVAD: surgical exchange through thoracotomy.

Pump thrombosis can occur in patients with a left ventricular assist device (LVAD). It can be treated medically with thrombolytic agents or surgically. We present a case of a man who successfully underwent an LVAD swap via left anterior thoracotomy due to recurrent thromboses in the inflow cannula.

The Essential Frailty Toolset in Older Adults Undergoing Coronary Artery Bypass Surgery.

Background The Essential Frailty Toolset (EFT) was shown to be easy to use and predictive of adverse events in patients undergoing aortic valve replacement procedures. The objective of this study was to evaluate the EFT in patients undergoing coronary artery bypass grafting procedures. Methods and Results The McGill Frailty Registry prospectively included patients ≥60 years of age undergoing urgent or elective isolated coronary artery bypass grafting between 2011 and 2018 at 2 hospitals. The preoperative EFT was scored 0 to 5 points as a function of timed chair rises, Mini-Mental Status Examination, serum albumin, and hemoglobin. The primary outcome was all-cause mortality assessed by Cox proportional hazards regression. The cohort consisted of 500 patients with a mean age of 71.4 ± 6.4 years, of which 27% presented with acute coronary syndromes requiring urgent surgery. The mean EFT was 1.3 ± 1.1 points, 132 (26%) were nonfrail, 298 (60%) were prefrail, and 70 (14%) were frail. Over a median follow-up of 4.0 years, 78 deaths were observed. In nonfrail, prefrail, and frail patients, survival at 1 year was 98%, 95%, and 91%, and at 5 years was 89%, 83%, and 63% (P<0.001). After adjustment, each incremental EFT point was associated with a hazard ratio of 1.28 (95% CI, 1.05-1.56) and frail patients had a 3-fold increase in all-cause mortality. Conclusions The EFT is a pragmatic and highly prognostic tool to assess frailty and guide decisions for coronary artery bypass grafting in older adults. Furthermore, the EFT may be actionable through targeted interventions such as cardiac rehabilitation and nutritional optimization.

Postoperative Nosocomial COVID-19 Infection in Cardiac Surgery: An Uncommon Event With High Mortality Rate.

BACKGROUND: The COVID-19 pandemic has had a major impact on cardiac surgery patients. Significant reductions in access to surgical treatment have forced surgeons to prioritise patients and follow strict COVID-19 protocols to protect surgeons, staff, and patients. Adult cardiac surgery and the COVID-19 pandemic: aggressive infection mitigation strategies are necessary in the operating room and surgical recovery. Nosocomial infections among cardiac surgery patients have been reported and are associated with a high mortality rate. As a COVID-19 tertiary care centre and a tertiary cardiac centre, we tried to balance the need to operate on urgent cardiac cases while protecting patients and staff from COVID-19. METHODS: During the first wave of the pandemic, we performed 579 surgeries. We report findings from an outbreak of 4 nosocomial infections. RESULTS: All patients tested negative within 24 hours of surgery or admission. Three patients were positive after surgery, suggesting an overall nosocomial rate during the first wave of 0.5% (3/579). One patient admitted for evaluation tested positive during mass screening. Two of the 4 patients died after respiratory complications. No health care worker (HCW) or family member with direct contact with these patients tested positive for COVID-19. Nosocomial COVID-19 infection is uncommon when adhering to safety protocols. Although uncommon, the mortality rate is high (50%) in our series. CONCLUSIONS: As widespread vaccination of HCWs and high-risk individuals susceptible to COVID-19 is in progress, we suggest that cardiac surgery patients, when feasible, be vaccinated before surgery given this could prevent excess mortality, protect HCWs and reduce resource use.

CONTEXTE: La pandémie de COVID-19 a eu des répercussions importantes sur les patients en chirurgie cardiaque. Les réductions importantes de l'accès aux traitements chirurgicaux ont obligé les chirurgiens à classer les patients par ordre de priorité et à suivre des protocoles COVID-19 rigoureux pour protéger les chirurgiens, le personnel et les patients. En ce qui a trait à la chirurgie cardiaque chez les adultes pendant la pandémie de COVID-19, des stratégies énergiques d'atténuation des infections sont nécessaires en salle d'opération et pendant la convalescence. Des infections nosocomiales ont été signalées chez des patients de chirurgie cardiaque; elles sont associées à un taux de mortalité élevé. Comme notre centre de soins tertiaires traite à la fois des patients atteints de troubles cardiaques et des patients atteints de la COVID-19, nous avons essayé de trouver un équilibre entre la nécessité d'effectuer les opérations cardiaques urgentes et la protection des patients et du personnel contre la COVID-19. MÉTHODOLOGIE: Pendant la première vague de la pandémie, nous avons effectué 579 interventions chirurgicales. Nous rapportons les résultats d'une éclosion de quatre infections nosocomiales. RÉSULTATS: Tous les patients ont obtenu un résultat négatif au test de dépistage dans les 24 heures suivant l'intervention ou l'admission. Trois patients ont obtenu un résultat positif à ce test après l'intervention, ce qui indique un taux global d'infection nosocomiale de 0,5 % (3 / 579) au cours de la première vague. Un patient admis pour évaluation a obtenu un résultat positif au moment du dépistage de masse. Deux des quatre patients sont morts après des complications respiratoires. Aucun travailleur de la santé ou membre de la famille ayant eu un contact direct avec ces patients n'a obtenu un résultat positif au test de dépistage de la COVID-19. L'infection nosocomiale à la COVID-19 est rare quand les protocoles de sécurité sont respectés. Mais même si elle est peu fréquente, le taux de mortalité associé est élevé (50 %) dans notre série. CONCLUSIONS: Alors que la vaccination généralisée des travailleurs de la santé et des personnes à haut risque vulnérables à la COVID-19 est en cours, nous suggérons que les patients en chirurgie cardiaque soient vaccinés avant l'opération, si possible, car cela pourrait prévenir la surmortalité, protéger les travailleurs de la santé et réduire l'utilisation des ressources.

The Role of Wnt/ß-Catenin Pathway Mediators in Aortic Valve Stenosis.

Aortic valve stenosis (AVS) is a prevailing and life-threatening cardiovascular disease in adults over 75 years of age. However, the molecular mechanisms governing the pathogenesis of AVS are yet to be fully unraveled. With accumulating evidence that Wnt signaling plays a key role in the development of AVS, the involvement of Wnt molecules has become an integral study target in AVS pathogenesis. Thus, we hypothesized that the Wnt/ß-catenin pathway mediators, SFRP2, DVL2, GSK3ß and ß-catenin are dysregulated in patients with AVS. Using immunohistochemistry, Real-Time qPCR and Western blotting, we investigated the presence of SFRP2, GSK-3ß, DVL2, and ß-catenin in normal and stenotic human aortic valves. Markedly higher mRNA and protein expression of GSK-3ß, DVL2, ß-catenin and SFRP2 were found in stenotic aortic valves. This was further corroborated by observation of their abundant immunostaining, which displayed strong immunoreactivity in diseased aortic valves. Proteomic analyses of selective GSK3b inhibition in calcifying human aortic valve interstitial cells (HAVICs) revealed enrichment of proteins involved organophosphate metabolism, while reducing the activation of pathogenic biomolecular processes. Lastly, use of the potent calcification inhibitor, Fetuin A, in calcifying HAVICs significantly reduced the expression of Wnt signaling genes Wnt3a, Wnt5a, Wnt5b, and Wnt11. The current findings of altered expression of canonical Wnt signaling in AVS suggest a possible role for regulatory Wnts in AVS. Hence, future studies focused on targeting these molecules are warranted to underline their role in the pathogenesis of the disease.

Bioactive scaffolds in stem-cell-based therapies for cardiac repair: protocol for a meta-analysis of randomized controlled preclinical trials in animal myocardial infarction models.

BACKGROUND: Acute myocardial infarction (MI) remains one of the leading causes of death worldwide with no curative therapy available. Stem cell therapies have been gaining interest as a means to repair the cardiac tissue after MI and prevent the onset of heart failure. Many in vivo reports suggest that the use of stem cells is promising, yet clinical trials suggest that the cells fail to integrate into the native tissue, resulting in limited improvements in cardiac function and repair. To battle this limitation, the combination of using stem cells embedded in a bioactive scaffold that promotes cell retention is growing in interest. Yet, a systematic review of the literature on the use of stem cells embedded in bioactive scaffolds for cardiac repair has not yet been performed. In this protocol, we outline a systematic review and meta-analysis of preclinical trials in animal MI models that utilize stem cell-embedded scaffolds for cardiac repair and compare their effects to stem cell-treated animals without the use of a scaffold. METHODS/DESIGN: We will search the following electronic databases: Cochrane Library, MEDLINE, Embase, PubMed, Scopus and Web of Science, and gray literature: Canadian Agency for Drugs and Technologies in Health and Google Scholar. We will only include randomly controlled preclinical trials that have directly investigated the effects of stem cells embedded in a scaffold for cardiac repair in an animal MI model. Two investigators will independently review each article included in the final analysis. The primary endpoint that will be investigated is left ventricular ejection fraction. Secondary endpoints will include infarct size, end systolic volume, end diastolic volume, fractional shortening and left ventricular wall thickness. Pooled analyses will be conducted using the DerSimonian-Laird random effects and Mantel-Haenszel fixed-effect models. Between-studies heterogeneity will be quantified and determined using the Tau2 and I2 statistics. Publication bias will be assessed using visual inspection of funnel plots and complemented by Begg's and Egger's statistical tests. Possible sources of heterogeneity will be assessed using subgroup-meta analysis and meta-regression. DISCUSSION: To date, the use of scaffolds in myocardial repair has not yet been systematically reviewed. The results of this meta-analysis will aid in determining the efficacy of stem cell-embedded scaffolds for cardiac repair and help bring this therapy to the clinic.

Muscle Mass and Mortality After Cardiac Transplantation.

BACKGROUND: Frailty assessment is recommended to evaluate the candidacy of adults referred for orthotopic heart transplantation (OHT). Psoas muscle area (PMA) is an easily measured biomarker for frailty. There has yet to be a study examining the prognostic impact of PMA in OHT patients. METHODS: In this retrospective study, preoperative and postoperative computed tomography (CT) scans were retrieved for adults transplanted between 2000 and 2015 at a tertiary care hospital. Psoas muscle area was measured on a single axial image. Outcomes of interest were all-cause mortality over 6 years and a composite of in-hospital mortality or major morbidity (prolonged ventilation, stroke, dialysis, mediastinitis, or reoperation). RESULTS: Of 161 adult patients transplanted, 82 had at least 1 abdominal CT scan. At baseline, mean PMA was 25.7 ± 5.8 cm in men and 16.0 ± 3.6 cm in women, and decreased by 8% from the first to the last available CT scan. Adjusting for age, sex, body mass index, and cardiomyopathy etiology, every 1-cm increase in PMA was found to be associated with a 9% reduction in long-term mortality (hazard ratio, 0.91; 95% confidence interval [CI], 0.83-0.99; P = 0.031) and a 17% reduction in in-hospital mortality or major morbidity (odds ratio, 0.83; 95% CI, 0.72-0.96; P = 0.014). When PMA was smaller than the sex-specific median, the risk of mortality or major morbidity increased fourfold (odds ratio, 4.29; 95% CI, 1.19-15.46; P = 0.026). CONCLUSIONS: Muscle mass is an independent predictor of mortality and major morbidity after OHT. Further research is needed to determine whether frail OHT patients with low PMA may benefit from muscle-building interventions to improve outcomes.

Pathological significance of lipoprotein(a) in aortic valve stenosis.

BACKGROUND AND AIMS: Aortic valve stenosis (AVS) affects a significant percentage of our elderly population and younger subjects with familial hypercholesterolemia. Lipoprotein(a) [Lp(a)] has been associated with AVS in recent genetic studies. The purpose of this study was to determine the effects of Lp(a) on human aortic valve interstitial cells (HAVICs), and to identify apolipoproteins and phospholipids in diseased human aortic valves. METHODS: We examined the effects of Lp(a) on HAVICs mineralization and oxidant formation. Proteomic analyses were used to determine the effects of Lp(a) on downstream intracellular markers. We also used mass spectroscopy to identify the different lipoproteins and oxidized phospholipids in calcified aortic valves. RESULTS: HAVICs incubated with either LDL or Lp(a) had significantly higher calcium deposition, compared to control (p<0.001), with Lp(a) having the most significant effect (p<0.01) compared to LDL. Proteomic analysis after 10 days of treatment with Lp(a) resulted in enrichment of proteins involved in calcium deposition and vesicle biogenesis. Treatment of HAVICs with Lp(a) significantly increased ROS formation (p<0.05). Patients with calcific aortic stenosis had higher plasma Lp(a) concentrations compared to non-CAD individuals (p<0.001). LC-MS/MS revealed the presence of apolipoproteins and phospholipids in calcified human aortic valves. CONCLUSIONS: The present study outlines an association between Lp(a) and AVS, and suggests that Lp(a) may serve as a potential target for therapeutic purposes to manage the progression of AVS.