ABSTRACT
BACKGROUND: Atrial fibrillation (AF) is a common comorbidity in patients with left ventricular assist devices (LVAD) with no defined guideline treatment strategy of rate versus rhythm control. The purpose of this study is to determine the effects of rate versus rhythm control for AF on the outcomes of patients with LVAD at our institution. METHODS: Consecutive patients who underwent LVAD implantation at St Vincent Hospital from January 1, 2015 to December 31, 2017 were retrospectively evaluated. Patients with AF were identified and divided into rate control or rhythm control groups. The primary outcome evaluated was a composite of death, heart failure admission, gastrointestinal bleed, ventricular tachycardia, cerebrovascular accident, hemolysis, and pump thrombosis. Secondary outcomes included the individual variables from the primary outcome. RESULTS: Out of 201 patients that underwent LVAD implantation, 81 had AF after implantation and were included with a median follow-up period of 384 days. The rate control group (n = 31; 38%) and the rhythm control group (n = 51; 62%) had no difference in composite outcomes (61% vs 59%, p = 0.83). When taken individually there was no difference in outcomes between the two groups. Thirteen patients underwent electrical cardioversion and successful conversion to normal sinus rhythm occurred in 71% of cases with a 60% recurrence rate. CONCLUSIONS: There was no difference in primary outcome between rate and rhythm control groups. These data suggest that maintenance of sinus rhythm may not be necessary in all patients with LVAD.
ABSTRACT
While much progress has been made in the war on cancer, highly invasive cancers such as pancreatic cancer remain difficult to treat and anti-cancer clinical trial success rates remain low. One shortcoming of the drug development process that underlies these problems is the lack of predictive, pathophysiologically relevant preclinical models of invasive tumor phenotypes. While present-day 3D spheroid invasion models more accurately recreate tumor invasion than traditional 2D models, their shortcomings include poor reproducibility and inability to interface with automated, high-throughput systems. To address this gap, a novel 3D tumor-tissue invasion model which supports rapid, reproducible setup and user-definition of tumor and surrounding tissue compartments was developed. High-cell density tumor compartments were created using a custom-designed fabrication system and standardized oligomeric type I collagen to define and modulate ECM physical properties. Pancreatic cancer cell lines used within this model showed expected differential invasive phenotypes. Low-passage, patient-derived pancreatic cancer cells and cancer-associated fibroblasts were used to increase model pathophysiologic relevance, yielding fibroblast-mediated tumor invasion and matrix alignment. Additionally, a proof-of-concept multiplex drug screening assay was applied to highlight this model's ability to interface with automated imaging systems and showcase its potential as a predictive tool for high-throughput, high-content drug screening.
