Factors Associated With Lack of Long-Term Follow-Up Data After Global Cardiac Surgery Missions.

Background: Humanitarian medical missions attempt to lessen the burden of limited access to cardiac surgery in low- and middle-income countries. While organizations express difficulties obtaining follow-up information, there is currently little evidence to support the various assumptions for lack of data. This study examines the factors influencing long-term patient follow-ups on repeated short-term cardiac surgery missions across nine countries. Methods: A retrospective analysis of CardioStart International's database (RedCap) was conducted to investigate demographic, socioeconomic, and surgical factors associated with follow-ups. Results: A total of 550 pediatric (50%) and adult (50%) cardiac surgery patients displayed a follow-up rate of 14.7%, with no significant difference between populations (P = 1). Mean follow-up time was 1.5 years postoperative. Countries were highly variable, with Dominican Republic and Vietnam showing follow-up rates of 30.4% and 43.2%, respectively, while Brazil, Nepal, and Tanzania had no follow-ups (P < 0.0001). The 11 surrogate factors for socioeconomic status, including home amenities and technology access, were predominantly insignificant, with the exception of phone access showing an unexpectedly decreased follow-up rate (11.6%, P = 0.006). Surgical intervention was a significant factor (P = 0.009). No adult cardiac surgery trends were noted; however, congenital cases demonstrated increased follow-ups in patients with higher Risk Adjusted Congenital Heart Surgery scores, with ventricular septal defects (32.5%) exceeding atrial septal defects (7.3%). Conclusions: Follow-ups correlate with mission factors, including location and types of intervention, more so than previously assumed socioeconomic and technological factors. Thus, certain missions may require more allocation of resources and adapted organizational policies to overcome site-specific barriers to follow-up.

Esophageal Perforation by Fish Bone Ingestion Causing Purulent Pericarditis.

A previously healthy 38-year-old woman presented with new-onset sudden chest pain radiating to the back, associated with cough, dyspnea, nausea, vomiting, and gastric fullness after eating a bony fish. A diagnosis of gastroesophageal reflux disease was made. After a week of progressive worsening of her symptoms, she was referred to the specialist hospital. There, computed tomography imaging strongly suggested that a likely fishbone had penetrated the esophagus into the mediastinal structures; it seemed to have produced a pneumopericardium. Other tests suggested diffuse changes in ventricular repolarization, pericardial thickening, and diastolic restriction. Exploratory thoracotomy confirmed esophageal-pericardial perforation by the fishbone and purulent pericarditis. Despite appropriate surgical repair, the patient died on fifth postoperative day from an asystolic cardiac arrest that was refractory to repeated attempts to resuscitate her.

Profibrotic VEGFR3-Dependent Lymphatic Vessel Growth in Autoimmune Valvular Carditis.

BACKGROUND: Rheumatic heart disease is the major cause of valvular heart disease in developing nations. Endothelial cells (ECs) are considered crucial contributors to rheumatic heart disease, but greater insight into their roles in disease progression is needed. METHODS: We used a Cdh5-driven EC lineage-tracing approach to identify and track ECs in the K/B.g7 model of autoimmune valvular carditis. Single-cell RNA sequencing was used to characterize the EC populations in control and inflamed mitral valves. Immunostaining and conventional histology were used to evaluate lineage tracing and validate single-cell RNA-sequencing findings. The effects of VEGFR3 (vascular endothelial growth factor receptor 3) and VEGF-C (vascular endothelial growth factor C) inhibitors were tested in vivo. The functional impact of mitral valve disease in the K/B.g7 mouse was evaluated using echocardiography. Finally, to translate our findings, we analyzed valves from human patients with rheumatic heart disease undergoing mitral valve replacements. RESULTS: Lineage tracing in K/B.g7 mice revealed new capillary lymphatic vessels arising from valve surface ECs during the progression of disease in K/B.g7 mice. Unsupervised clustering of mitral valve single-cell RNA-sequencing data revealed novel lymphatic valve ECs that express a transcriptional profile distinct from other valve EC populations including the recently identified PROX1 (Prospero homeobox protein 1)+ lymphatic valve ECs. During disease progression, these newly identified lymphatic valve ECs expand and upregulate a profibrotic transcriptional profile. Inhibiting VEGFR3 through multiple approaches prevented expansion of this mitral valve lymphatic network. Echocardiography demonstrated that K/B.g7 mice have left ventricular dysfunction and mitral valve stenosis. Valve lymphatic density increased with age in K/B.g7 mice and correlated with worsened ventricular dysfunction. Importantly, human rheumatic valves contained similar lymphatics in greater numbers than nonrheumatic controls. CONCLUSIONS: These studies reveal a novel mode of inflammation-associated, VEGFR3-dependent postnatal lymphangiogenesis in murine autoimmune valvular carditis, with similarities to human rheumatic heart disease.

Autoimmune Valvular Carditis Requires Endothelial Cell TNFR1 Expression.

BACKGROUND: Inflammation is a key driver of cardiovascular pathology, and many systemic autoimmune/rheumatic diseases are accompanied by increased cardiac risk. In the K/B.g7 mouse model of coexisting systemic autoantibody-mediated arthritis and valvular carditis, valve inflammation depends on macrophage production of TNF (tumor necrosis factor) and IL-6 (interleukin-6). Here, we sought to determine if other canonical inflammatory pathways participate and to determine whether TNF signaling through TNFR1 (tumor necrosis factor receptor 1) on endothelial cells is required for valvular carditis. METHODS: We first asked if type 1, 2, or 3 inflammatory cytokine systems (typified by IFNγ, IL-4, and IL-17, respectively) were critical for valvular carditis in K/B.g7 mice, using a combination of in vivo monoclonal antibody blockade and targeted genetic ablation studies. To define the key cellular targets of TNF, we conditionally deleted its main proinflammatory receptor, TNFR1, in endothelial cells. We analyzed how the absence of endothelial cell TNFR1 affected valve inflammation, lymphangiogenesis, and the expression of proinflammatory genes and molecules. RESULTS: We found that typical type 1, 2, and 3 inflammatory cytokine systems were not required for valvular carditis, apart from a known initial requirement of IL-4 for autoantibody production. Despite expression of TNFR1 on a wide variety of cell types in the cardiac valve, deleting TNFR1 specifically on endothelial cells protected K/B.g7 mice from valvular carditis. This protection was accompanied by reduced expression of VCAM-1 (vascular cell adhesion molecule), fewer valve-infiltrating macrophages, reduced pathogenic lymphangiogenesis, and diminished proinflammatory gene expression. CONCLUSIONS: TNF and IL-6 are the main cytokines driving valvular carditis in K/B.g7 mice. The interaction of TNF with TNFR1 specifically on endothelial cells promotes cardiovascular pathology in the setting of systemic autoimmune/rheumatic disease, suggesting that therapeutic targeting of the TNF:TNFR1 interaction could be beneficial in this clinical context.

CD47 Promotes Autoimmune Valvular Carditis by Impairing Macrophage Efferocytosis and Enhancing Cytokine Production.

Systemic autoantibody-mediated diseases accelerate chronic cardiovascular disease in humans. In the K/B.g7 mouse model of spontaneous autoantibody-mediated inflammatory arthritis, valvular carditis arises in part because of Fc receptor-mediated activation of macrophages, leading to production of pathogenic TNF and IL-6. In this study, we explored whether impaired efferocytosis mediated by the interaction of CD47-expressing apoptotic cells with signal regulatory protein α (SIRPα) on macrophages contributes to disease progression in this model. CD47-expressing apoptotic cells and SIRPα+ macrophages were abundant in inflamed/rheumatic cardiac valves from both mice and humans. In vivo anti-CD47 blockade both prevented and treated valvular carditis in K/B.g7 mice. Blocking CD47 enhanced macrophage efferocytosis and reduced macrophage production of TNF and IL-6. These studies highlight the CD47:SIRPα interaction as a key driver of chronic cardiac valve inflammation and suggest these molecules as potential therapeutic targets to reduce cardiovascular disease risk in autoantibody-driven inflammatory diseases.

Surviving the Struggle of COVID-19: Practical Recommendations for Pediatric/Adult Cardiology and Cardiac Surgical Programs in Resource-Limited Settings: a Review.

INTRODUCTION: The primary aim of this systematic review is to provide perioperative strategies to help restore or preserve cardiovascular services under threat from financial and personnel constraints imposed by the coronavirus disease 2019 (COVID-19) pandemic. METHODS: The Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, Cochrane Central Register of Controlled Trials/CCTR, and Google Scholar were systematically searched using the search terms "(cardiac OR cardiology OR cardiothoracic OR surgery) AND (COVID-19 or coronavirus OR SARS-CoV-2 OR 2019-nCoV OR 2019 novel coronavirus OR pandemic)". Additionally, the webpages of relevant medical societies, including the World Federation Society of Anesthesiologists, the Cardiothoracic Surgery Network, and the Society of Thoracic Surgeons, were screened for relevant information. RESULTS: Whereas cardiac surgery and cardiology practices were reduced by 50-75% during the pandemic, mortality of patients with COVID-19 increased significantly. Healthcare workers are among those at high risk of infection with COVID-19. CONCLUSION: Hospitals must provide maximum protective equipment and training on how to use it to healthcare workers for their mutual protection. Triage management of patients - which accounts for patient's clinical status and risk-factor profile relatable to which services are available during the COVID-19 pandemic - is recommended. A strict reorganization of the hospital resources including preoperative, intraoperative, and postoperative detailed protective measures is necessary to reduce probability of vector contamination, to protect patients and the cardiovascular teams, and to permit safe resumption of cardiological and cardiac surgical activity.

Surviving the Struggle of COVID-19: Practical Recommendations for Pediatric/Adult Cardiology and Cardiac Surgical Programs in Resource-Limited Settings: a Review

ABSTRACT Introduction: The primary aim of this systematic review is to provide perioperative strategies to help restore or preserve cardiovascular services under threat from financial and personnel constraints imposed by the coronavirus disease 2019 (COVID-19) pandemic. Methods: The Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, Cochrane Central Register of Controlled Trials/CCTR, and Google Scholar were systematically searched using the search terms "(cardiac OR cardiology OR cardiothoracic OR surgery) AND (COVID-19 or coronavirus OR SARS-CoV-2 OR 2019-nCoV OR 2019 novel coronavirus OR pandemic)". Additionally, the webpages of relevant medical societies, including the World Federation Society of Anesthesiologists, the Cardiothoracic Surgery Network, and the Society of Thoracic Surgeons, were screened for relevant information. Results: Whereas cardiac surgery and cardiology practices were reduced by 50-75% during the pandemic, mortality of patients with COVID-19 increased significantly. Healthcare workers are among those at high risk of infection with COVID-19. Conclusion: Hospitals must provide maximum protective equipment and training on how to use it to healthcare workers for their mutual protection. Triage management of patients — which accounts for patient's clinical status and risk-factor profile relatable to which services are available during the COVID-19 pandemic — is recommended. A strict reorganization of the hospital resources including preoperative, intraoperative, and postoperative detailed protective measures is necessary to reduce probability of vector contamination, to protect patients and the cardiovascular teams, and to permit safe resumption of cardiological and cardiac surgical activity.

Applicability of the Disruptions in Surgery Index in the Cardiovascular Management Scenarios - A Marker for Developing Functionally Efficient Teams.

INTRODUCTION: To support the development of practices and guidelines that might help to reduce adverse events related to human factors, we aimed to study the response and perception by members of a cardiovascular surgery team of various error-driven or adverse features that might arise in the operating room (OR). METHODS: A previously validated Disruptions in Surgery Index (DiSI) questionnaire was completed by individuals working together in a cardiovascular surgical unit. Results were submitted to reliability analysis by calculating the Cronbach's alpha coefficient. Non-parametric Kruskal-Wallis test and Dunn's post-test were performed to estimate differences in perceptions of adverse events or outcomes between the groups (surgeons, nurses, anesthesiologists, and technicians). P<0.05 was considered statistically significant. RESULTS: Cronbach's alpha reliability coefficients showed consistency within the recommended range for all disruption types assessed in DiSI: an individual's skill (0.85), OR environment (0.88), communication (0.81), situational awareness (0.92), patient-related disruption (0.89), team cohesion (0.83), and organizational disruption (0.83). Nurses (27.4%) demonstrated significantly higher perception of disruptions than surgeons (25.4%), anesthetists (23.3%), and technicians (23.0%) (P=0.005). Study participants were more observant of their colleagues' disruptive behaviors than their own (P=0.0001). CONCLUSION: Our results revealed that there is a tendency among participants to hold a positive self-perception position. DiSI appears to be a reliable and useful tool to assess surgical disruptions in cardiovascular OR teams, identifying negative features that might imperil teamwork and safety in the OR. And human factors training interventions are available to develop team skills and improve safety and efficiency in the cardiovascular OR.

Applicability of the Disruptions in Surgery Index in the Cardiovascular Management Scenarios - A Marker for Developing Functionally Efficient Teams

Abstract Introduction: To support the development of practices and guidelines that might help to reduce adverse events related to human factors, we aimed to study the response and perception by members of a cardiovascular surgery team of various error-driven or adverse features that might arise in the operating room (OR). Methods: A previously validated Disruptions in Surgery Index (DiSI) questionnaire was completed by individuals working together in a cardiovascular surgical unit. Results were submitted to reliability analysis by calculating the Cronbach's alpha coefficient. Non-parametric Kruskal-Wallis test and Dunn's post-test were performed to estimate differences in perceptions of adverse events or outcomes between the groups (surgeons, nurses, anesthesiologists, and technicians). P<0.05 was considered statistically significant. Results: Cronbach's alpha reliability coefficients showed consistency within the recommended range for all disruption types assessed in DiSI: an individual's skill (0.85), OR environment (0.88), communication (0.81), situational awareness (0.92), patient-related disruption (0.89), team cohesion (0.83), and organizational disruption (0.83). Nurses (27.4%) demonstrated significantly higher perception of disruptions than surgeons (25.4%), anesthetists (23.3%), and technicians (23.0%) (P=0.005). Study participants were more observant of their colleagues' disruptive behaviors than their own (P=0.0001). Conclusion: Our results revealed that there is a tendency among participants to hold a positive self-perception position. DiSI appears to be a reliable and useful tool to assess surgical disruptions in cardiovascular OR teams, identifying negative features that might imperil teamwork and safety in the OR. And human factors training interventions are available to develop team skills and improve safety and efficiency in the cardiovascular OR.

Emotional quality-of-life and patient-reported limitation in sports participation in children with uncorrected congenital and acquired heart disease in healthcare-restricted settings in low- and middle-income countries.

BACKGROUND: Little is known about emotional quality-of-life in paediatric heart disease in low- and middle-income countries where the prevalence of uncorrected lesions is high. Research on emotional quality-of-life and its predictors in these settings is key to planning interventions. METHODS: Ten-year retrospective cross-sectional study of children aged 6-17 years with uncorrected congenital or acquired heart disease in 12 low- and middle-income countries was conducted. Emotional functioning score of the PedsQL TM 4.0 generic core scale and data on patient-reported limitation in sports participation were collected via in-person interview and analysed using regression analyses. RESULTS: Ninety-four children reported mean emotional functioning scores of 71.94 (SD 25.32) [95% CI 66.75-77.13] with lower scores independently associated with having a parent with a chronic illness or who had died (p = 0.005), having less than three siblings (p = 0.007), and reporting a subjective limitation in carrying an item equivalent to a 4 lb load (p = 0.021). Patient-reported limitation in sports participation at least "sometimes" was present in 69% and was independently associated with experiencing symptoms at least once a month (p < 0.001). CONCLUSION: Some of the factors which were associated with better emotional quality-of-life were similar to those identified in previous studies in patients with corrected defects. Patient-reported limitation in sports participation is common. In addition to corrective surgery and exercise, numerous other interventions which are practicable during surgical missions might improve emotional quality-of-life.

CD301b/MGL2+ Mononuclear Phagocytes Orchestrate Autoimmune Cardiac Valve Inflammation and Fibrosis.

BACKGROUND: Valvular heart disease is common and affects the mitral valve (MV) most frequently. Despite the prevalence of MV disease (MVD), the cellular and molecular pathways that initiate and perpetuate it are not well understood. METHODS: K/B.g7 T-cell receptor transgenic mice spontaneously develop systemic autoantibody-associated autoimmunity, leading to fully penetrant fibroinflammatory MVD and arthritis. We used multiparameter flow cytometry, intracellular cytokine staining, and immunofluorescent staining to characterize the cells in inflamed K/B.g7 MVs. We used genetic approaches to study the contribution of mononuclear phagocytes (MNPs) to MVD in this model. Specifically, we generated K/B.g7 mice in which either CX3CR1 or CD301b/macrophage galactose N-acetylgalactosamine-specific lectin 2 (MGL2)-expressing MNPs were ablated. Using K/B.g7 mice expressing Cx3Cr1-Cre, we conditionally deleted critical inflammatory molecules from MNPs, including the Fc-receptor signal-transducing tyrosine kinase Syk and the cell adhesion molecule very late antigen-4. We performed complementary studies using monoclonal antibodies to block key inflammatory molecules. We generated bone marrow chimeric mice to define the origin of the inflammatory cells present in the MV and to determine which valve cells respond to the proinflammatory cytokine tumor necrosis factor (TNF). Finally, we examined specimens from patients with rheumatic heart disease to correlate our findings to human pathology. RESULTS: MNPs comprised the vast majority of MV-infiltrating cells; these MNPs expressed CX3CR1 and CD301b/MGL2. Analogous cells were present in human rheumatic heart disease valves. K/B.g7 mice lacking CX3CR1 or in which CD301b/MGL2-expressing MNPs were ablated were protected from MVD. The valve-infiltrating CD301b/MGL2+ MNPs expressed tissue-reparative molecules including arginase-1 and resistin-like molecule α. These MNPs also expressed the proinflammatory cytokines TNF and interleukin-6, and antibody blockade of these cytokines prevented MVD. Deleting Syk from CX3CR1-expressing MNPs reduced their TNF and interleukin-6 production and also prevented MVD. TNF acted through TNF receptor-1 expressed on valve-resident cells to increase the expression of vascular cell adhesion molecule-1. Conditionally deleting the vascular cell adhesion molecule-1 ligand very late antigen-4 from CX3CR1-expressing MNPs prevented MVD. CONCLUSIONS: CD301b/MGL2+ MNPs are key drivers of autoimmune MVD in K/B.g7 mice and are also present in human rheumatic heart disease. We define key inflammatory molecules that drive MVD in this model, including Syk, TNF, interleukin-6, very late antigen-4, and vascular cell adhesion molecule-1.