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Viral cardiac infection represents a significant clinical challenge encompassing several etiological agents, disease stages, complex presentation, and a resulting lack of mechanistic understanding. Myocarditis is a leading cause of sudden cardiac death in young adults, where current knowledge in the field is dominated by later disease phases, and pathological host immune responses. However, little is known regarding how viral infection can acutely induce an arrhythmogenic substrate prior to the immune response. Adenovirus is a leading cause of myocarditis, but due to species-specificity, models of infection are lacking and it is not understood how adenoviral infection may underlie sudden cardiac arrest. Mouse Adenovirus Type-3 (MAdV-3) was previously reported as cardiotropic, yet has not been utilized to understand mechanisms of cardiac infection and pathology in the research setting. We have developed MAdV-3 infection as a model to investigate acute cardiac infection and molecular alterations to the infected heart prior to an appreciable immune response or gross cardiomyopathy. By optical mapping we find decreases in conduction velocity concomitant with increased phosphorylation of Cx43Ser368, a residue known to regulate gap junction channel function. Additional to changes in gap junctions, patch clamping of MAdV-3-infected adult mouse ventricular cardiomyocytes reveals prolonged action potential duration as a result of decreasedIK1andIKscurrent density. Turning to human systems, we find that human adenovirus type-5 (HAdV-5) increases phosphorylation of Cx43Ser368and disrupts calcium transients synchrony in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), indicating common mechanisms with our mouse whole heart and adult cardiomyocyte data. Together, these findings demonstrate that adenoviral infection creates an arrhythmogenic substrate through direct targeting of gap junction and ion channel function in the heart. Such alterations are known to precipitate arrhythmias and likely contribute to sudden cardiac death in acutely infected patients, while preceding the pathological remodeling of subsequent myocarditis disease progression.

Background Prior studies suggest similar efficacy between large-bore chest tube (CT) placement and small-bore pigtail catheter (PC) placement for the treatment of pleural space processes. This study examined reintervention rates of CT and PC in patients with pneumothorax, hemothorax, and pleural effusion. Methods This retrospective study examined patients from September 2015 through December 2020. Patients were identified using ICD codes for pneumothorax, hemothorax, or pleural effusion. Use of a pigtail catheter (≤14Fr) or surgical chest tube (≥20Fr) was noted. The primary outcome was overall reintervention rate within 30 days of tube insertion. Patients who died with a pleural drainage catheter in place, unrelated to complications from chest tube placement, were excluded. Results There were 1032 total patients in the study: 706 CT patients and 326 PC patients. The PC group was older with more comorbidities and more likely to have effusion as the indication for pleural drainage. Patients with PC were 2.35 times more likely to have the tube replaced or repositioned ( P < .0001), 1.77 times more likely to require any reintervention ( P = .001) and 2.09 times more likely to remain in the hospital >14 days ( P < .0001) compared to patients with CT. Conclusion PCs have a significantly higher reintervention rate compared to CT for the treatment of pneumothorax, hemothorax, and pleural effusion. Although PC are believed to cause less pain and tissue trauma, they do not necessarily drain the pleural space as well as CT. Decisions on which method of draining the chest should be made on a case-by-case basis.

Background Severe pulmonary hypertension (PH) and left ventricular diastolic dysfunction (LVDD) are independently associated with poor outcomes in cardiac surgery. We evaluated the relationship of several measures of LVDD, PH, and hemodynamic subtypes of PH including precapillary pulmonary hypertension(pcPH) and isolated post-capillary pulmonary hypertension(ipcPH) and combined pre and post capillary pulmonary hypertension(cpcPH) capillary PH to postoperative outcomes in a cohort of patients who underwent elective isolated-AVR.Methods We evaluated (n = 206) patients in our local STS database who underwent elective isolated-AVR between 2014 and 2018, with transthoracic echocardiogram (n = 177) or right heart catheterization (n = 183) within 1 year of operation (or both, n = 161). The primary outcome was a composite end point of death, prolonged ventilation, ICU readmission, and hospital stay >14 days.Results Severe PH was associated with worse outcomes (moderate: OR, 1.1, p = 0.09; severe: OR, 1.28, p = 0.01), but degree of LVDD was not associated with worse outcomes. Across hemodynamic subtypes of PH, odds of composite outcome were similar (p = 0.89), however, patients with cpcPH had more postoperative complications (67 vs. 36%, p = 0.06) and patients with ipcPH had greater all-cause mortality at 1 (8 vs. 1%, p = 0.03) and 3 years (27 vs. 4%, p = 0.008).Conclusion Severe PH conferred modestly greater risk of adverse events, and both LVDD grade and the combination of severe PH and LVDD were not associated with worse outcomes. However, hemodynamic stratification of PH revealed higher postoperative complications and worse long-term outcomes for those with cpcPH and ipcPH. Preoperative stratification of PH by hemodynamic subtype in valve replacement surgery may improve our risk stratification in this heterogenous condition. Further evaluation of the significance of LVDD and PH in other cardiac operations is warranted.

BACKGROUND: Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Despite being the leading cause of death in adult patients with SCD, current recommendations for treatment of ACS remain largely supportive, consisting of pain management, aggressive fluid resuscitation, respiratory support, and transfusion therapy. Despite these measures, it is not uncommon for patients to require intubation due to progression to acute respiratory distress syndrome (ARDS). Recently, there have been a number of case reports that have successfully utilized extracorporeal membrane oxygenation (ECMO) for the management of ACS in those patients who fail to respond to conventional therapy [Kuo et al., 2013, Sewaralthahab et al, 2018]. However, the use of ECMO in this patient population remains uncommon, and further evaluation of this intervention is needed. This case report details an unsuccessful attempt at the use of ECMO in the case of ARDS secondary to ACS, in an attempt to identify critical pitfalls. CASE REPORT: A 32-year-old African-American female with HbSS disease on hydroxyurea therapy was transferred from an outside hospital following 3 days of respiratory decompensation. Prior to arrival, patient coded once at the outside hospital and once on transfer. Veno-arterial ECMO was initiated with improving oxygen saturation and volume status with continuous renal replacement therapy. To maintain an ECMO-specific goal hemoglobin level of 10 g/dL, 1:1 manual exchange transfusions were performed due to an inability to access equipment for automated RBC exchange. Once stable enough for CT, patient was found to have gray-white inversion suggestive of irreversible severe brain damage. Following another 28 days of supportive care with no neurologic improvement, the family decided to withdraw care, and the patient expired. CONCLUSION: While unsuccessful, this patient's case revealed a need for defining parameters regarding the initiation of ECMO in SCD patients with severe ACS. A review of previously-published literature has shown that the use of ECMO for the management of ARDS in adults is more efficacious than conventional ventilation support [Peek et al., 2009]. In patients with SCD, this improvement in efficacy is not readily reproduced, likely due to unique challenges presented by the pathophysiology of the disease. Notably, patients with SCD face additional risks of venous thromboembolism and strokes while on prolonged bed rest due to a baseline prothrombotic state [Sewaralthahab et al., 2018]. A systematic review of available case reports is needed to develop a protocol for the management of severe ACS that takes SCD-specific risks into account. The present report also makes a case for the training of providers in the early recognition of severe ACS in SCD patients. SCD remains largely undertreated in the United States, likely due to a complex interplay of patient, physician, and institutional factors. Had this patient been transferred immediately to a facility better equipped to provide a higher level of care, her condition could have arguably taken a different course. Despite the aforementioned challenges, ECMO remains a feasible option for the management of severe ACS in patients with SCD, and efforts should be made to standardize current treatment protocols. REFERENCES: Kuo KW, Cornell TT, Shanley TP, Odetola FO, and Annich GM. The use of extracorporeal membrane oxygenation in pediatric patients with sickle cell disease. Perfusion. 2013 September; 28(5): 424-432. Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany M, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. The Lancet. 2009 October; 374(9698): 1351-1363. Sewaralthahab SS, Menaker J, Law JY. Successful use of veno-venous extracorporeal membrane oxygenation in an adult patient with sickle cell anemia and severe acute chest syndrome. Hemoglobin. 2018 42(1): 65-67. Disclosures No relevant conflicts of interest to declare.