Faculty Bibliography

OBJECTIVE:Preliminary data suggest that nonalcoholic fatty liver disease is associated with early heart failure (HF). However, whether nonalcoholic steatohepatitis (NASH) is directly associated with echocardiographic changes in cardiac structure or function remains unknown. METHODS:A retrospective cohort was identified of individuals (N = 65) without known heart disease, undergoing elective bariatric surgery with perioperative liver biopsy, and available recent transthoracic echocardiography (TTE). TTE measures were evaluated by NASH status using correlation coefficients, ANOVA, and linear regression, accounting for cardiometabolic factors. RESULTS: = -0.89, P = 0.047, respectively). CONCLUSIONS:In this bariatric cohort, NASH was associated with changes in myocardial structure and in load-dependent indices of LV diastolic function, suggestive of subclinical HF.

BACKGROUND: Randomized control trials (RCTs) have established the use of Coronary Computed Tomography Angiography (CCTA) for the evaluation of low to intermediate risk patients presenting with acute chest pain to the emergency department (ED). However, concerns remain regarding the downstream resource utilization and the clinical impact of such strategy. METHODS: We performed a meta-analysis of existing studies to compare CCTA to the standard of care (SOC) strategies in the low to intermediate risk chest pain patients. We abstracted the reported incidence of acute coronary syndromes (ACS), the total number of invasive coronary angiography (ICA) and subsequent revascularization procedures, the rates of hospital readmissions and repeat ED visits. We stratified the results according to the type of the studies (randomized or not) and used random effect analysis for the studied outcomes. RESULTS: Four RCTs and 3 case-control studies with 3306 patients undergoing CCTA and 2752 assigned to SOC were included in the analysis. Following the index visit, we observed a significant reduction in the risk of ACS (RR: 0.26, 95% CI, 0.08 to 0.87; p=0.03) and in the rates of repeat ED visits (RR: 0.58, 95% CI: 0.36 to 0.94; p=0.03). In addition, a trend toward less hospital readmission (p=0.07) was noted. There was no difference in ICA (p=0.99) but an increase in revascularization procedures (RR: 1.46, 95% CI: 1.09 to 1.94; p=0.01). CONCLUSION: CCTA use in the ED for the triage of low to intermediate risk patients reduces the risk of future ACS and subsequent ED visits for chest pain.

Background. Brugada syndrome accounts for 4-12% of all sudden deaths worldwide and at least 20% of sudden deaths in patients with structurally normal hearts. Case Report. A 48-year-old female presented to the emergency department after two witnessed syncopal episodes. While awaiting discharge had a third collapse followed by cardiac arrest with shockable rhythm. Initial electrocardiogram showed wide QRS complex with left axis deviation, ST-segment elevation of <1 mm in V1 and V2, and flattening of T waves in V1. The angiogram did not demonstrate obstructive coronary disease. The electrocardiogram obtained two days after these events showed a right bundle branch block with ST-segment elevation of >2 mm followed by a negative T wave with no isoelectric separation, suggestive of spontaneous intermittent Brugada type 1 pattern. Cardiac magnetic resonance imaging demonstrated neither structural heart disease nor abnormal myocardium. After placement of an implantable cardioverter defibrillator the patient was discharged. Why should an emergency physician be aware of this? Brugada syndrome is an infrequently encountered clinical entity which may have a fatal outcome. This syndrome primarily presents with syncope. It should be considered as a component of differential diagnosis in patients with family history of syncope and sudden cardiac death.

Apoptosis repressor with caspase recruitment domain (ARC) inhibits both death receptor- and mitochondrial/ER-mediated pathways of apoptosis. Although expressed mainly in terminally differentiated cells, ARC is markedly upregulated in a variety of human cancers, where its potential contributions have not yet been defined. In this study, we provide evidence of multiple critical pathophysiologic functions for ARC in breast carcinogenesis. In the polyoma middle T-antigen (PyMT) transgenic mouse model of breast cancer, in which endogenous ARC is strongly upregulated, deletion of the ARC-encoding gene nol3 decreased primary tumor burden without affecting tumor onset or multiplicity. More notably, ARC deficiency also limited tumor cell invasion and the number of circulating cancer cells, markedly reducing the number of lung metastases. Conversely, ectopic overexpression of ARC in a PyMT-derived metastatic breast cancer cell line increased invasion in vitro and lung metastasis in vivo. We confirmed these results in a humanized orthotopic model based on MDA-MB-231-derived LM2 metastatic breast cancer cells, in which RNAi-mediated knockdown of ARC levels was shown to reduce tumor volume, local invasion, and lung metastases. Lastly, we found that endogenous levels of ARC conferred chemoresistance in primary tumors and invading cell populations. Our results establish that ARC promotes breast carcinogenesis by driving primary tumor growth, invasion, and metastasis as well as by promoting chemoresistance in invasive cells.