Porcine Model of Hypertrophy-Independent Left Ventricular Stiffening via Repetitive Pressure Overload.

Diastolic dysfunction arising from alterations in myocardial structure and/or function is a central component of several cardiovascular disorders, including heart failure with preserved ejection fraction (HFpEF). Basic research aimed at understanding underlying mechanisms contributing to the development of diastolic dysfunction has generally centered upon models of left ventricular (LV) hypertrophy arising from persistent and severe elevations in myocardial afterload (e.g., aortic banding). Mechanisms of hypertrophy-independent diastolic dysfunction, on the other hand, have received less attention, even though overt anatomic LV hypertrophy is absent in many HFpEF patients. Here, we describe the development of a novel porcine model of repetitive pressure overload (RPO) in which chronic, intermittent exposure to transient episodes of hypertension produces an increase in LV stiffness, interstitial fibrosis, cardiomyocyte hypertrophy, and capillary rarefaction without significant changes in LV mass. This model offers important insight into how diastolic dysfunction and HFpEF may develop in the absence of comorbidities, sustained hypertension, or LV hypertrophy, while also providing a useful translational research tool for investigation of novel therapeutic approaches to restore myocardial compliance and improve diastolic function.

Healthcare utilization and cost outcomes for a multicenter first seizure and new onset epilepsy clinic.

RATIONALE: A First Seizure/New Onset Epilepsy (FS/NOE) protocol was implemented to ensure proper evaluation by an epileptologist and improve overall care for patients. We compared healthcare utilization and cost incurred by patients pre and post protocol implementation. METHODS: Clinical data were retrospectively collected from the EMR and cost data from the financial database. Patients were identified by FS event and grouped into either the pre-implementation (pre-FSC) or post-implementation cohort (post-FSC). Pre-FSC patients were seen between January 2014-December 2015 and post-FSC between March 2016-January 2018. Utilization outcomes include time from FS to neurology appointment, MRI, and electroencephalogram (EEG). Cost outcomes included the annualized median difference in pre versus post costs for ER, inpatient, outpatient or ambulatory, and total hospital services. Cost and utilization outcomes were collected within 90 days or 6 months post first-seizure event. Pre and post cohorts were compared using Kaplan-Meier analysis and Cox proportional hazard models for time-to-event outcomes, multivariable median regression models for cost differences and negative binomial regression models for utilization analyses. Models were adjusted for age, sex, health insurance, and comorbidities. RESULTS: One-hundred and fifty six patients were included with 84 (53.8%) pre- and 72 (46.2%) post-FSC patients. Kaplan-Meier and Cox regression results indicated post-FSC patients had significantly faster time-to-first neurology appointment (5.0 vs. 20.9 days, p < .001; Adjusted Hazard Ratio (HR) = 5.98, p < .001), time-to-MRI (9.0 vs. 27.0 days; p = 0.005; HR = 1.88, p = .021) and EEG (3.6 vs. 48.6 days, p < .001; HR = 9.01, p < .001). A total of 138 patients had at least one cost in the financial database. For 6-month follow-up period, post-FSC patients had higher adjusted all-cause total median costs (+$830, p = 0.009) and outpatient costs (+$1203, p < .001) but lower ED costs (-245, p = 0.073), not significant. Results were similar for seizure-related costs. Similarly, Post-FSC patients had a significantly higher likelihood of all-cause (Adjusted Rate Ratio (ARR) = 1.41, p = .029) and outpatient utilization (ARR = 1.72, p = .008) but lower ED utilization (ARR = 0.54, p < .001). CONCLUSIONS: Implementation of the FSC decreased time to evaluation by a neurologist and time to diagnostic workup. Ultimately, total healthcare costs and ambulatory costs increased but ED costs and utilization were reduced. It is our hypothesis that faster access to initial care and diagnosis would result in better control of seizures and reduce long-term costs and utilization. Further research over a longer duration of time across a broader population is needed to evaluate the full implications of an epilepsy specialist-populated FSC.