Project Summary/Abstract Heart failure (HF) significantly impairs quality of life and contributes to over 1 million hospital admissions per year. Cardiac decompensation remains the most frequent cause of hospitalization. The Centers for Medicare and Medicaid Services has thus identified decreasing heart failure hospitalizations as a key priority. Identifying precipitants of HF exacerbation could provide actionable targets for reducing HF admissions and improving QOL. Psychological stress can precipitate myocardial ischemia, cardiac arrhythmia, and left ventricular dysfunction - even in patients with HF, and we have identified a high-risk profile. Furthermore, targeting this profile in clinical trials has reduced event risk. Studies also show that chronic psychological stress may increase overall risk for HF hospitalization. The absence of a non-invasive metric that captures cardiac decompensation in HF patients has however, impeded the identification of psychological experiences as acute precipitants that contribute to HF decompensation and hospitalization. The imperative to reduce HF hospitalizations has spurred technological innovations to capture early stages of decompensation and more rapid outpatient interventions. The wireless hemodynamic monitor (e.g., CardioMEMS,) is one such innovation. These monitors are implanted in the pulmonary artery and directly measure pulmonary artery pressure (PAP), providing a metric of decompensation and hospitalization risk. Our preliminary data suggest that PAP is higher in situations of high sympathetic activity, and that anxiety and stress are also associated with higher PAP. The increasing use of these monitors thus provides a unique opportunity to identify and risk stratify HF patients for whom stress may contribute to HF exacerbation. We propose to leverage this new technology in a mechanistic clinical trial to: (Aim 1a) determine the effect of acute laboratory stress on momentary PAP, and (Aim 1b) determine the relationship of daily stress and negative emotion to daily PAP as captured by ecological momentary assessment (EMA). For Aim 2 we will determine the relationship of stress- induced PAP increase to HF exacerbation; and for Aim 3 we will explore markers of heterogeneity in the PAP response to stress, including markers of disease severity, sleep quality, and psychosocial factors to identify a risk profile. CardioMEMS-implanted HF patients will be randomized within the laboratory stress protocol that we have developed, during which PAP will be measured continuously. Patients will then complete our smartphone 'app' based, daily EMA for stress exposures and negative experiences over a six-month period during clinically prescribed daily measurement of PAP. Patients will also complete assessment of psychosocial factors and related biomarkers of stress susceptibility. Clinical trials targeting stress induced cardiac syndromes have shown promise for reducing morbidity and mortality. This study will demons...