There are many treatments that can improve how long and how well people live with heart failure when they are outside the hospital. However, the investigators know less about how to effectively treat hospitalized heart failure patients so that they do not have to return to the hospital after they go home. Part of the problem is that the investigators don't understand all of the causes of worsening heart failure. Previous studies by other researchers suggest that white blood cells called monocytes are over-active in heart failure. Under normal conditions monocytes help fight infections in the body, but over-active monocytes release chemicals that could cause abnormal function of the heart and blood vessels. The investigators' research group believes that over-active monocytes may be an important reason that heart failure worsens before hospitalization. In this study the investigators will collect blood samples on the day a patient comes into the hospital, the day they return home, and the day they come back to the clinic for a follow-up appointment. The investigators will measure the inflammation in the bloodstream and the activity of monocytes from the patients' blood to see if there are changes in these measurements as heart failure improves. The investigators will also call each patient several times after they return home to ask questions about how they are doing.
With over 5 million Americans having heart failure (HF) today and an incidence approaching 10 per 1000 population among persons over the age of 65, HF is a major source or morbidity and mortality and a significant public health concern facing developed nations. In the US, decompensated heart failure is the most common reason for hospital admission among persons older than 65. Yet despite significant advances in the treatment of chronic heart failure, currently there are very few evidence-based strategies to treat acutely decompensated heart failure. The incidence of heart failure will likely continue to rise with the increasing prevalence of HF risk factors (advanced age, hypertension, obesity, diabetes, and other metabolic diseases). Accordingly, substantial efforts are underway to identify and treat populations at risk and to understand the molecular drivers of this heterogeneous disease. The investigators understanding of the pathophysiology of heart failure has evolved from a 'cardiocentric' view focused on mechanical dysfunction to a more global view. Heart failure is now understood as a complex blend of structural, functional, and neurohormonal abnormalities manifested both locally and systemically. More recently, several groups have demonstrated abnormalities in the inflammatory cascade associated with both the initiation and the progression of heart failure. The innate immune system appears to modulate the inflammatory component of HF through several mechanisms including the production of inflammatory cytokines (tumor necrosis factor-α,TNFα; interleukin-6, IL6), reactive oxygen species, activation of the complement system, as well as through functional modification of endothelial cells and myeloid cell trafficking. Monocytes and macrophages are two of the key myeloid mediators of acute and chronic inflammatory responses. Myeloid dysregulation has been implicated in the pathogenesis of diverse diseases including diabetes, tumor metastasis, pulmonary fibrosis, myocardial infarction, and atherosclerosis. Accumulating evidence suggests that myeloid subsets have distinct functional properties reflecting their polarization patterns and their interaction with the local microenvironment. As a framework to study their role in models of clinical diseases, myeloid populations have been broadly categorized as "inflammatory" and "anti-inflammatory" based on specific surface markers, cytokine potential, and other functional properties. Although the role of myeloid populations in inflammatory disease is now appreciated, the molecular mechanisms linking these cells to clinical heart failure syndromes remain largely unknown. The investigators hypothesize that distinct myeloid subsets drive different phases of acute and chronic heart failure syndromes, and that identification of these subsets and their functional properties will provide further insight into the pathophysiology of clinical heart failure. In order to initially characterize the roles that monocytes play across the spectrum of heart failure, the investigators will obtain whole-blood samples from acutely decompensated patients on the date of hospitalization, the date of transfer from the intensive care unit (ICU) to the general-care telemetry floor (if relevant), the date of hospital discharge, and at their first outpatient follow-up visit. Subjects will be recruited from the University of Michigan inpatient heart failure service, which admits approximately 75 patients for decompensated heart failure each month. Once the samples are obtained, the investigators will perform flow cytometry to characterize monocyte subsets and their flux in response to treatment. The investigators will also look at the production of reactive oxygen species by monocytes and will examine how cytokines and chemokines skew monocyte population subsets and their gene expression profiles. The investigators will also investigate the energetic state and flux (aerobic vs. anaerobic metabolic status) of the monocytes.
Study Type
OBSERVATIONAL
Enrollment
60
University of Michigan Health System
Ann Arbor, Michigan, United States
Change in IL-6 between hospital admission and discharge
Cytokine
Time frame: All scheduled blood draws - hospital admission, discharge (3-14 days after admission), and first post-discharge appointment (5-10 days following discharge)
Lys6c Hi and Lo, Mannose Receptor
Cell Surface Markers
Time frame: All scheduled blood draws - hospital admission, discharge (3-14 days after admission), and first post-discharge appointment (5-10 days following discharge)
IL-10, IL-13
Cytokine
Time frame: All scheduled blood draws - hospital admission, discharge (3-14 days after admission), and first post-discharge appointment (5-10 days following discharge)
Gene Expression (iNOS, CCL2, Ym1, Fizz, VEGF, MMP2/9)
Monocyte gene expression
Time frame: All scheduled blood draws - hospital admission, discharge (3-14 days after admission), and first post-discharge appointment (5-10 days following discharge)
microRNA
miR155, let7, mir-33a
Time frame: All scheduled blood draws - hospital admission, discharge (3-14 days after admission), and first post-discharge appointment (5-10 days following discharge)
Monocyte/macrophage morphology
Macrophages/monocytes will be classified based on their morphology
Time frame: All scheduled blood draws - hospital admission, discharge (3-14 days after admission), and first post-discharge appointment (5-10 days following discharge)
Serum F-2 Isoprostanes
Oxidative stress marker
Time frame: All scheduled blood draws - hospital admission, discharge (3-14 days after admission), and first post-discharge appointment (5-10 days following discharge)
TNF-alpha
Marker of inflammation
Time frame: All scheduled blood draws - hospital admission, discharge (3-14 days after admission), and first post-discharge appointment (5-10 days following discharge)
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