Complete Heart Block Causing Takotsubo Syndrome: A Case Report.

The association of complete atrioventricular (AV) block with Takotsubo syndrome (TTS) is well known, but the cause-and-effect relationship has not been determined. We present the case of a 91-year-old female with complete AV block who went untreated for over a year and later developed Takotsubo syndrome. Reversal of wall movement defects was seen after a permanent pacemaker was implanted, and routine follow-up showed that the implanted pacemaker worked normally.

Index Case of COVID-19 Myocarditis Requiring BiV-ICD for Primary Prevention of Sudden Cardiac Death.

INTRODUCTION: The severity of clinical presentation of COVID-19 myocarditis ranges from incidental identification of depressed left ventricular ejection fraction, cardiogenic shock requiring percutaneous mechanical circulatory support, to fatal fulminant myocarditis. In previously reported cases, surviving patients experienced improvement in left ventricular ejection fraction with the use of glucocorticoids and antivirals (+/- intravenous immunoglobulin/ convalescent plasma). We report the first case of COVID-myocarditis in a surviving patient where a persistently depressed left ventricular ejection fraction (less than 35 percent) despite optimal therapy prompted implantable cardioverter-defibrillator (ICD) implantation for primary prevention of sudden cardiac death. CASE PRESENTATION: A previously healthy 67-year-old man, diagnosed with mild COVID-19 pneumonia five days prior, presented to the emergency department with suspected STEMI (hypoxia, substernal chest pain and known left bundle branch block). Left heart catheterization showed patent coronary arteries. Transthoracic echocardiogram showed severely depressed ejection fraction (15-20 percent). CT showed bilateral infiltrates: treatment was started with dexamethasone, remdesivir and convalescent plasma for acute hypoxic respiratory failure due to COVID-19 pneumonia. After a four-day hospitalization, guideline-directed medical therapy at maximum tolerated doses over three months did not improve left ventricular ejection fraction. CONCLUSION: This is the index case of COVID-19 myocarditis-mediated heart failure with reduced ejection fraction requiring ICD for primary prevention of sudden cardiac death.

Bioengineering the Oxygen-Deprived Tumor Microenvironment Within a Three-Dimensional Platform for Studying Tumor-Immune Interactions.

Oxygen deprivation within tumors is one of the most prevalent causes of resilient cancer cell survival and increased immune evasion in breast cancer (BCa). Current in vitro models do not adequately mimic physiological oxygen levels relevant to breast tissue and its tumor-immune interactions. In this study, we propose an approach to engineer a three-dimensional (3D) model (named 3D engineered oxygen, 3D-O) that supports the growth of BCa cells and generates physio- and pathophysiological oxygen levels to understand the role of oxygen availability in tumor-immune interactions. BCa cells (MDA-MB-231 and MCF-7) were embedded into plasma-derived 3D-O scaffolds that reflected physio- and pathophysiological oxygen levels relevant to the healthy and cancerous breast tissue. BCa cells grown within 3D-O scaffolds were analyzed by flow cytometry, confocal imaging, immunohistochemistry/immunofluorescence for cell proliferation, extracellular matrix protein expression, and alterations in immune evasive outcomes. Exosome secretion from 3D-O scaffolds were evaluated using the NanoSight particle analyzer. Peripheral blood mononuclear cells were incorporated on the top of 3D-O scaffolds and the difference in tumor-infiltrating capabilities as a result of different oxygen content were assessed by flow cytometry and confocal imaging. Lastly, hypoxia and Programmed death-ligand 1 (PD-L1) inhibition were validated as targets to sensitize BCa cells in order to overcome immune evasion. Low oxygen-induced adaptations within 3D-O scaffolds validated known tumor hypoxia characteristics such as reduced BCa cell proliferation, increased extracellular matrix protein expression, increased extracellular vesicle secretion and enhanced immune surface marker expression on BCa cells. We further demonstrated that low oxygen in 3D-O scaffolds significantly influence immune infiltration. CD8+ T cell infiltration was impaired under pathophysiological oxygen levels and we were also able to establish that hypoxia and PD-L1 inhibition re-sensitized BCa cells to cytotoxic CD8+ T cells. Bioengineering the oxygen-deprived BCa tumor microenvironment in our engineered 3D-O physiological and tumorous scaffolds supported known intra-tumoral hypoxia characteristics allowing the study of the role of oxygen availability in tumor-immune interactions. The 3D-O model could serve as a promising platform for the evaluation of immunological events and as a drug-screening platform tool to overcome hypoxia-driven immune evasion.